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Alison Judd measuring her cardiac output by impedance cardiograph. "listologii without Tears": Sean Fitzsimons with his tutorial software for the Acorn Archimedes, which uses multiple choice questions and powerful graphics, many derived roin electronmicroscopic images.

SOUTHAMPTON DEMONSTRATIONS Photorraphs by Ander McIntyre

David Andrew (seated) with (left to right)Hyun Son, Tim Amess and Bruce "The Bionic Frog":Jeff Bagust's computerprogran emulatinga frog sciatic nerve Matthews demonstratingthe recordingoflaser Dopplerbloodflow signals from practical,using actual recordings made during an in vitro experiment, human teeth. Ii1 Physiology at King's College, London - Peter McNaoghton ...... I Southam pton Revisited - lan Brown & Dic Williams ...... 3 Letters & Reports Con nection mach ines - Denis N oble ...... 4 Physiology in Southam pton - E M Sed wick ...... 4 Anonymous assessment of large classes - Mayank Dutia ...... 4 H idden energy and w ork - W ilfred W iddas ...... 5 Views IUPS Congress, Glasgow The wider social and political implications of the Congress - Denis Noble ...... 7 A postcard from G lasgow - PeterM oore ...... 9 Behind the scenes at G lasgow - Ron Baxendalh ...... 12 Animals in Research M anager's headaches - Georgina Watson ...... 14 The 1986 Act: the view of a "Day-to-Day Care Person" - Rick Ski/ton ...... 15 The Research for Health Charities Group - Myc Riggulsford ...... 17 Articles The initiation of parturition: molecular and neural messages - P eter W Nathaniels:...... 19 Development of ovarian follicles in vitro and after transplantation - Roger Gosden & Nicola Boland ...... 22 Events Designated Sessions at the Kiqg's College Meeting Epithelia & M embrane Transport - Barry Hirst ...... 24 Human Physiology - Ron Maughan ...... 24 N euroendocrinology - M ary Forsling ...... 24 R espiratory Physiology - Piers Nye ...... 24 Designated Sessions at the Southampton Meeting Cellular Neurophysiology - Alex Thomson ...... 25 Comparative Physiology and Comparative & Invertebrate Neuroscience - Ted Taylor ...... 25 Developm ental N euroscience - Simon M iller ...... 25 R enal Physiology - David Potts ...... 26 Special Interest Group News Sensorim otor C ontrol - Roger Lemon ...... 26 Undergraduate symposium 26

Notices 27 Journal Contents The Journal of Physiology ...... 28 Experimental Physiology ...... 32 Extra Grey Book Page 35

Grants and Funding Schemes 36

Affiliation Form 37

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Opinions expressed in articles and letters submitted by or commissioned from Members, Affiliates or outside bodies are not necessarily those of the Society. The PhVsiological Society is registered in England as a company limited by guarantee, No 323575. Registered office: PO Box 506, Oxford OXI 3XE. Registered Charity No 211585.

printed by Lynx Offset Limited, Unit 35A Monument Industrial Park, Chalgrove, Oxfordshire, OX44 7RW Physiology. All is change at present in medical Muscle, Endocrinology, Microvascular and teaching, with a thorough-going curriculum review, Endothelium, Cardiovascular Control, Human instigated by the recent GMC recommendations in Physiology, Epithelia and Membrane Transport, undergraduate teaching, currently in progress at Heart/Cardiac Muscle and Respiratory Physiology. King's. As a recent arrival at King's, I admire the way More than 250 abstracts have been submitted. Five in which clinicians and basic medical scientists have sessions will run simultaneously throughout much of buckled down to this difficult and contentious task the Meeting, but as all the lecture theatres are adjacent with an obvious determination to create the best to one another transferring between sessions should possible medical curriculum. In a nutshell, we plan to present little problem. Tea, Demonstrations and a integrate clinical and preclinical teaching intoa single large Trade Exhibition will be in our Multi-Purpose five-year core curriculum. Some areas currently taught Laboratories, on theground floor ofthe Main Building in the preclinical course will move up to what are at at Strand. present the clinical years and there will be a Finally, King's College hosts an annual McDowall corresponding downward move of some areas of lecture, in honourof a former Head of Department, to clinical science particularly relevant to the basic which a distinguished overseas speaker is traditionally medical sciences. Teaching in the core course will be invited. As no Physiological Society Lecture was organised around systems (egCellularand Molecular; scheduled for the King's Meeting we have arranged Cardiovascular and Respiratory; Neuroscience) and for our McDowall Lecture to be given at 5.30 pm on will span departmental boundaries. The core course Thursday 16 December, during the Meeting. Professor will be drastically pruned to occupy only 60% of a RWTsienof theDepartmentof Cellularand Molecular medical student's time. The remainder will be taken Physiology, Stanford University, has kindly agreed up with a selection from a range of modules designed to give the lecture entitled "Mechanisms of Short- and to encourage study in depth. The range of choice in Long-Term Modulation of Synaptic Transmission". this area of the course will be as broad as possible and We are delighted that Dick Tsien, who has close links we plan that it will include courses currently offered with British Physiology, hasagreed to givethis lecture. to science and humanities students as well as a range The lecture will be followed by the Society Dinner in of more obviously medically-related subjects. The resulting medical curriculum will offer a degree of ou eently refurbished Great Hall. We have tried to flexibility which I think medical students will find to keep the price of the Dinner down, by subsidy from a be a very attractive and refreshing alternative to the variety of nefarious sources, and at £20, including rigovro butrctis at oe-ensh ional m oeda wine, it should be excellent value for money. We can m soolsin accommodate 280 and hope the Great Hall will be courses currently on offer in most medical schools in packed. Great Britain. Postgraduate taught courses have always been aenodbya.Welcome to King's, and we hope the Meeting is all. strength at King's, with the unique MSc in Human & enjoyed by Applied Physiology justly well-known among UK PeterMcNaughton physiologists. Stella Rowlands has poured her energy into this course for nearly 20 years, and a highly- ­ selected group of students receive a varied education both at King's and at a variety of other well-equipped research centres such as the RAF Institute of Aviation Medicine at Farnborough. This well-established MSc has recently been joined by a new MSc in Biomedical Research Methods, introduced three years ago by Joan Abbott. This MSc offers a variety of taught courses, training workshops and research projects, and from the first attracted a full house of well­ qualified applicants. Both MScs will readily be adapted to serve as stepping stones to a PhD, as envisaged in the recent Science White Paper. Peter The King's Meeting McNaughton The Physiological Society returns to King's after an absence of four years. This is the first Meeting I have See the Events section fordetailsof DesignatedSessions to been involved in organising, and the signs at the time be held at the King's Meeting of writing are that it will be one to remember. There are three symposia, on "Physiology and Molecular Biology - A Symbiosis", organised by myself; on "Signal Transduction Pathways in Epithelium", organised by Jeremy Pearson and Giovanni Mann of our Vascular Biology Research Centre; and on "The Physiological Consequences of Ageing" organised by Ron Maughan from Aberdeen. There will in addition be eight Designated Sessions on Smooth SOUTHAMPTON REVISITED Tuesday started with coffee () and Thanks to: another full day of Corn- AD Instruments Ltd ltwaswithpleasurethattheDepartmentofPhysiology munications and Demonstrations Confocal Technologies Ltd and Pharmacology at Southampton welcomed The was enjoyed by all. The evening Digitimer PhysiologicalSociety. Monday saw an intensivestart to was spent at Rhinefield House Gould Electronics the Meeting with two Communications sessions and Hotel in theheart oftheNew Forest Harvard Apparatus no fewerthan three symposia. The highlights included where the Society dined on smoked Leica UK plenary talks by Professors I A Selverston and R salmon and guinea fowl. After a Linton Instruments Laprade and concluded with the Stephen Paget scientific sprint finish on Moor Instruments Memorial Lecture given by Salvador Moncada. The Wednesday morning, our guests Nikon UK Poster session which followed was extremely well departed with our good wishes and Sigma Chemicals attended and was accompanied by a wine reception our hope that we could all do it Silicon Graphics and followed by a very well received evening of good again soon. Spindler &Hoyer food, wine and excellent jazz in the company of the and Wise Press Mardi Gras Band, only possible because of the Ian Brown Williams World Precision Instruments generous support of the Trade Exhibitors. Dic (R G)

Assessing a poster lan Brown (left) and Dic Williams (second from right)at the end of a full day, with (left to right) Alan Thomas, Den Wisdon, Jaipaul Singh

Photographsbi Brian Chapman

The Trade Inormal Exhibition area discussion between Sessions

living to the jazz of the MardiGras Band Robert Walker (right),head of the host department, with Ton Ridge Connection Machines A notable first non-invasive recording of the lumbar Dear Sir cord dorsum potential in man was work begun in the Department of Physiology by E M Sedgwick but The inside cover colour illustration (Fig 2) for the continued, as in all the above, in the Clinical valuable article by Conrad Murphy and Max Lab Neurological Sciences Group. [Issue No 10, September 19931 was provided before the reference for the relevant publication explaining the The Physiological Society is interested in good illustration could be provided. The paper dealing physiology which is being done increasingly outside with it has now appeared and its full reference is preclinical departments. Indeed, much of the exciting R L Winslow, A L Kimball, A Varghese & D Noble work, especially in man, is done in other environments. (1993) Simulating cardiac sinus and atrial network E M Sedgwick dynamics on the Connection Machine, PhysicaD,64: President,BritishSociety for 281-298. ClinicalNeurophysiology The Connection Machine used for this work is currently the most powerful machine in the world ANONYMOUS ASSESSMENT OF and is installed at the University of Minnesota. The LARGE CLASSES senior author of this work, Rai Winslow, is at the Department of Biomedical Engineering at Johns Like other universities in the UK, Edinburgh has Hopkins University. experienced a substantial increase in undergraduate The This is a suitable opportunity to say that at the time student numbers over the past few years. when this work was started (three years ago) there(computer­ or was no suitable computer in the United Kingdom. aided learning) -particularly where this replaces laboratory sessions- isseen as Even now there is only one Connection Machine supplements practical installed (at Edinburgh University) for the whole of a meansof accommodating larger classes, asdiscussed the UK. The work would therefore have been by Robin Orchardson in the September issue of the impossiblewithoutthecollaborationofmyAmerican Magazine. However - and predictably, perhaps ­ colleagues and the generous provision of time by the actually teaching more students is only part of the Army High Performance Computer Center at problem. Minnesota. The administrative demands on course organisers Massively parallelcomputersareexpensive(theentry (COs) have increased disproportionately, thanks Massvelcmpuers paalll re xpesiv (te etrychiefly to developments involving the greater use of price starts at £200k and state-of-the-art machines are continuous assessment and the modularisation of several million) but it is extremely likely that parallel co u s smn an the mdul a ati comptinfolowthehisory wil f cmpuing courses, both of which have resulted in dramatic computing will follow the history of computing increases in the total number of examinable items of generally: the price will eventually tumble as usage work submitted by each student. In addition, the becomes widespread. dealwithcomplexnonlinearsystems,Physiology, withwillthenbenefit its need to requirements that each examinable item is greatly. anonymously marked (ie with the identity of the student withheld from the examiners, to avoid possible Denis Noble bias) and the need to return statistical analyses of Physiology inSouthampton students' performance for the purposes of academic audit, have meant that new procedures for encoding Dear Sir students' identities during the assessment process We would not like Members to think that the whole of are necessary. These clearly must be able to cope Physiology in Southampton was covered by Professor efficiently with large classes and large numbers of R Walker's article with that title. He says clearly that examinable items. his article covers only the Department of Physiology To meet these demands, about two years ago we and Pharmacology. The Medical School has several developed a computer program, now called vigorous groups producing excellent physiological "Barmark", which provides an efficient method of research, training and teaching postgraduate scientists reading into a computer the marks from, for example, and medics. essays, practical reports or script books after they One can mention the classic physiological and have been assessed and exporting this data to a philosophical study of a man without proprioception spreadsheet for calculation of final marks. by Jonathan Cole, Pride and a Daily Marathon, To do this, we adapted a very well-established Duckworth 1991; studies on the nature of CSF technology: bar code labelling of items. The essential circulation by Professor R Weller in Neuropathology; working of the Barmark software is very simple and on the hypothalamo-hypophyseal portal system by centres around a set of sticky labels issued to each Mr P Lees, neurosurgeon; and work on the student on a particular course (Figs I and 2). Each mechanisms of ischaemic brain damage and protection label contains the student's matriculation number from it by Mr F lannotti, also a neurosurgeon. printed as a bar code, and the last five digits of the Neurologists have contributed with L S Illis's work matriculation number printed in plain text (Fig 1). on spinal cord stimulation and H Katifi's studies on The first label in the set carries the student's name, nerve conduction in compressed spinal roots. The while the others do not: the only function of the first work of Professor N Saunders in developmental label is to allow the student to identify his/her own physiology is known to most Members. set of labels when s/he receives them and confirm Fig 2 Eiaminatlon Utle and date Clas list file Contains the names and matriculationnumbers The steps Candidate's name(first label only) ofstudents enrmoledon the course Downloaded fromcentralrecords lved'it I preparingeusingarmarn and PHYSIOLOGY3. JUNEEXAMINATION or a art car Print1 Ibelsper f Named label- the candidate Atulent for a particular confar time SOMENAME,A.B. ac-.ded where N is the number colrse and matriculation of examinable items to matlculation " 3tg 43 number be handed in for number upon Prepare a Work-disk receipt assessment dedicated to this Icourse ANormaity thisis a floppy PYSIOLOGY3. JUNEEXAMINATION Matriculation Distribute labels to dik whichcan be locked 28thJUNE 1993 nutmber(text: clans away after use year ofentry Any convnient Havinga separate disk ~Aoayle oa stared out) ehd, as k for eachcourse each St r minimizes the chances of manyas thecorrec setof labels mix-ups between re=uredforeachone "*539455359 43 -... _._ classFOaCOreSerIal Fora wrtten courses exatidnale IIIIIIII III 1 enrolment exameatiaon, tabe Item) IEIEIIIIhlllll i nortber may be placed nthe desksin alphabetical order with are question PHYSIOLOGY3. JUNEEXAMINATION paper 28thJUNE 1993 Scan In the mark awarded for each Item, after assessment Is complete

5535 5 4t3 Illl lExport text file to spreadsheet forcalculationoffinalmark, printng of rankedlits, etc

Fig I Clearly the rapid processing of items after assessment Example ofa set of sticky labels issued to one student. Thefirst label is named, the is dependent on the preparation beforehand of labels rest anonymous. Each label carries the student's matriculation number printed as a and a work disk. Of these, preparing a work disk bar code, as u'ell as the last fivedigits in plain text (the first two digits represent the takes less than a minute. Printing of labels can be student's year of entry to the universityand are starred out). The top two lines oit performed at a rate of some 700 per hour using a 24­ the label are inplain text and normally indicate the course and the component on pin dot matrix printer (cost perlabel about0.03 pence), wihich the label is to be used (eg practical report, essay etc; inthis case, the two an dot matrix cost, hignte anonymous labels were to be used ott script books ina written examination). The serial class enrolment number is used to sort the examinable items by candidate (eg using a laser printer. The Barmark program does not all the script books belonging to one student) after assessment is complete. So as not require Windows and so runs happily on olderslower to compromise anonymity, this number need not startfrom I nor increment by +1; machines (note, though, that bar code readers are not more adventurous course organisers may even use hexadecimal numbers. available for all types of machines). The bar code reader of choice is a "keyboard wedge" type, which that the details are correct. Subsequently, each of the interposes itself between anonymous labels is fixed by the student to items that the computer and the s/he hands in for assessment. The steps involved in keyboard so that the preparing Barmark for use in a particular course are characters read by thebar shown in Fig 2, along with some of the practical code reader appear as if details. The bar code on each book is scanned using a they had been typed in at hand-held reader, and the mark awarded is typed in the keyboard. These cost at the keyboard. Alternatively, to speed up the process about £350, and in our further and to eliminate keyboard typing errors, the case a single computer mark awarded can also be scanned in, from a printed equipped with a reader sheet of bar codes representing integer numbers from has been sufficient to deal 0 to 100. Barmark produces a text file containing the with all the courses run candidates' names, matriculation numbers and the in the Department. marks awarded for each component ofthe course (Fig Mayank Dutia 2). The text file can then be imported into a spreadsheet program such as Microsoft's Excel or Borland's HIDDEN WORK AND ENERGY Quattro Pro. The permeability of cellular membranes has been In the minority of cases where the printed labels are extensively studied in human red cells which have a damaged, lost or unreadable, the matriculation very fast transfer system for glucose (and other number is typed in at the keyboard and the mark monosaccharides) and for anion exchanges (chloride, awarded is read in as normal. This can either be the bicarbonate and hydroxyl ions). Neither of these full matriculation number, if the student was classes of molecules would be able to penetrate a instructed to write it on his work in the absence of a simple bimolecular lipid membrane at the rates label, or the last five digits from the plain text entry on observed experimentally. Their penetration is possible a damaged label (Fig 1). Inthe latter case, the possibility only because ofthe presence in the red cell membrane of confusing two candidates is extremely small; in our of 250,000 protein transporters specific for sugars on experience no course has had a pair of students with the one hand and ca 300,000 band 3 proteins for anion matriculation numbers differing only in their first exchanges on the other. two digits. Glucose is transferred inwards and outwards at a evolved which can use this above-average energy turnover rate of ca 1,000 per second on each either (i) in a cascade arrangement (the anion transporter. The exchange rate for anions is ten times exchanger) or (ii) to produce evaporation (the glucose faster, ca 10,000 per second. They both work transporter). That evaporation has a cooling effect is reciprocally but by different detailed mechanisms. well known and the mechanical work done by the Further, since there is no heat evolved, no CO 2 is protein in transporting the glucose molecules will be produced nor any ATP hydrolysed, the transfers degraded back into heat, also locally (Joule effect). As have been regarded as "passive" in the literature, the cooling and heating balance, there are none of the However, it has been calculated that in five litres of accepted physiological attributes of work to be blood the glucose transporters are doing ten times as observed. much work as that derived from resting metabolism It is important to realise that the large amount of (8.7 kJ/min).The anion exchanger isprobably carrying hidden work being done isalways reciprocal in nature. out an amount of work more than 100 times that of Thus, kinetic energy can be harnessed by appropriate resting metabolism, submicroscopic mechanisms to do a large amount of The calculations are based on the estimate of the work essential for the rapid permeability of cell energy available to - and probably used by - the membranes. Such mechanisms cannot do vectorial postulated mechanism when carrying out a single work, ie repetitive work performed in one direction transfer. Multiplication ofthis energy by the turnover only. In the absence of ATP, a muscle can still do one rate per second, by the number of transporter stroke of work as it goes into rigor but repetitive molecules in one red cell membrane, by the numberof contractions and relaxations are impossible. It is for cells in five litres of blood and by 60 as the number of vectorial work that physiological mechanisms use seconds in one minute gives a measure of the work ATP. It would appear that nature uses ATP sparingly done per minute. and uses kinetic energy wherever possible. The energy available is that of the thermal energy of Wilfred Faraday Widdas the molecules. In some collisions, energy greater than Reference average is available, and functional proteins have Widdas, W F (1993) Biomedical Letters, 48: 15-26.

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ADInstrumenis Limited, 9 Provost Road, London NW3 WE1'UK Fax: (44)-71 - 586 7121 THE WIDER SOCIAL AND of the huge welcome posters around the city - not POLITICAL IMPLICATIONS OF THE even a demonstration, let alone any media coverage CONGRESS for them. TheOrganisingCommitteeoftheGlasgowCongress No-one can be certain, of course, but my own has received a marvellous postbag since the meeting interpretation ofthis particular "dog thatdidn't bark" itself, with colleagues from all over the world writing is that we, for once, had taken the initiative. Virtually in to say how much they enjoyed the event andg all the press of relevance were at our Congress takingg appreciated the work that went into organising it. A stories forpublication.Anyclaimbytheantivivisection few also combined their praise with some helpful side that we were secretive, afraid to let the public see commentsandcriticismforfutureCongressorganisers what we were doing (a recurrent theme of to consider. Not surprisingly, the main issues in their antivivisection propaganda) would have looked minds were the scientific programme, the Congress ludicrous to the hardened journalists in our press structure and the social programme. office. There was also an underlying mood of confidence that expressed itself in different ways and which was also identifiable at the Congress itself. This is that the subject had clearly, persuasively and loudly spoken out for itself. People left Glasgow feeling proud to be physiologists and confident that the meeting had succeeded in communicating the nature and 2July SundayTimes importance of our discipline to vastly more than the nearly 5,000 who attended it. EThe Times Th Times i flIES ! The daily Congress Newsletter helped to J IIEWLEFTEI? communicate some ofthewiderimpact ("the 29 July T Guardian ...... _ World has its eye on us" was one of the 30 July The Herald e Haue Lift Of, Newsletter headlines). Even so, very few The Scotsman people at the Congress can have known just 1 August Observer how wide -and, hopefully, influential -this Scotland on Sunday impact was. Sunday Times To start with, the welcome letter from the 2 August Daily Express Alzeimer's Disease E Science Minister, Mr William Waldegrave, Daily Mail Artificial placenta TheWrkl Eye are...u ..... was more than a mere formality. It arose Daily Telegraph Russian plans for space clinics from substantial correspondence that Ihad Herald with MrWaldegrave and the Cabinet Office Independent on tne importance and significance of the event. Mr Reuters Waldegrave is a classicist. He, and many of his Scotsman colleagues in government, will know nothing of our 3 August Daily Express Neurolab subject unless we inform them. The Congress gave us Daily Record Stress and homosexuality a valuable opportunity to do this in extenso. There Evening Times were other spin-off effects in government, too. At a Herald subsequent Cabinet Office meeting of an advisory Scotsman group, reference to the Society's role in developing The Times joint meetings and scientific contact with East Asia was not only well justified but will also mean that we 4 August Evening Times Pre-birthlearning are taken by this advisory group as a role model for Herald Exercis and immunity such international collaboration. Scotsman Anylin and diabetes Thisimpact "behind closed doors" was complemented 5 August Dailye press Seals and diving by the coverage achieved via the media. The Minister Herald responsible for an official government reception at the Congress (Lord Fraser) commented that he could "hardly go to sleep without hearingabout theCongress OTHER RADIO AND TELEVISION on the radio"! We should be more aware than we are that, to Daily radio coverage: BBC Radio networked news programmes and politicians, one measure of a subject's political regional programmes, plus various other pieces on BBC Radio significance is how much of their time is taken up by BBC Radio special: half an hour on Science Now it. Our opponents in the antivivisection movements BBC World Service: half-hour interview are well aware of this golden rule and we should also Sky News/STV: interviews take advantage of this knowledge. Radio Scotland Newsweek: six minutes This takes me to a most important point. Despite a BBC TV: Scotland Today interview major presence of these movements in Glasgow, there ABC (Australia): HealthReport science show were noattempts to disrupt ourCongress, nodefacing ABC TV: Good MorningAmerica LJSJAE..ILLAA ~ty ,,.,~- ~ ~ ibnple test is ~-"~' rst fr Ah " hailed infight = - . 1-'ble'F- against disease uch a fine body !ft ",'" ""' ' ' -' f evidence Coni5T - -:.~ce ~ e ­1fol . ".6...

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A selection of The same argument applies to the MPs who attended and biological science. The Logic of Life was in fact cuttings from the the Congress. Not only were they free to walk around circulated quite widely to selected politicians and British press the posters, listen to papers and meet physiologists, other opinion formers before the Congress itself. One they were also given an opportunity for an open must also hope that this, and the scientific success of A-entinly goode Ovr7 atoswr press officedebate on two issues: the free international the Congress itself, will eventually influence the way movement of scientists and the social and political medical science is funded. There is an inevitable implications of the Congress Book The Logic of Life. tendency for grant committees to follow fashions, Those particular press conferences did not actually particularly in hard times when money is short. It is lead to any major newspaper or radio/TV coverage hard to estimate the impact of high profile events like (perhaps the nearly full page coverage of some of the congresses in influencing fashions in science. issues in the Guardian and Observer had already filled Nevertheless, who would have predicted, even a that particular slot) but, even so, imagine the impact yearago, that thelnternationalCongress of Physiology of that experience on those MPs when they next meet in Glasgow would attract more than twice as many with less enlightened colleagues in the corridors and scientists as the Genetics Congress held a little later in tea rooms of Westminster repeating some of the Birmingham? The last time (four years ago) the figures "saloon bar" misapprehensions about our work. were the other way round. Sometimes when MPs are invited to a meeting at Politicians talk a lot about the "chattering classes". Society and Committee dinners, for example, one has There are chattering classes in science, too, and the the feeling that we may be talking to the converted perceived success or failure of high profile meetings (why else did they accept the invitation?) and, is part of their stock-in-trade. This is not just a matter doubtless, that was also true of those MPs who of numbers (I'm told, for example, that the Genetics attended Glasgow (two of them in fact were medically Congress was very good despite the small turnout). qualified) but of course even the converted need Finally, Ihave no doubt that Glasgow did us a lot of ammunition and I have no doubt that Glasgow go nentoal.Oe 0ntoswr provided it abundantly. represented. We made them very welcome (in most One of the features of Glasgow that impressed the cases in theirown languages) and they will remember politicians on both sides was that we were willing to that. Everyone will have his or her own story from the enter into the public debate on the nature of medical Congress on this aspect. My own include: an evening where the Koreans sang their national anthem to its A POSTCARD FROM GLASGOW: original melody (believe it or not, the pre-war Korean A DELEGATE'S PERSPECTIVE nationalists used the tune of "Auld Lang Syne"); a toast drunk with enthusiasm with the entire Ukrainian The arrival (Saturday) delegation at the Society evening reception; the Saturday morning, the sun was shining, the plane amusement of my French colleagues on finding that one was only one hour late and I'd managed to find a bus ofthe welcome posters used a flag of a nation in southern into the centre of Glasgow, having bought my ticket France (the Langue d'Oc region) that never existed (hence from a slightly over-zealous bus conductor. All was one of the difficulties involved in winning the bottle of going well. I simply needed to find my accom­ Champagne offered to anyone who could decipher all modation, drop off my bags and head down to the the nations and languages); the St Petersburg 1997 Scottish Exhibition and Conference Centre (SECC) to organisers inviting the Princess Royal to be patron of pick up the abstracts. their Congress, too (protocol requires that I should not print her exact reply - I think I can say, though, that it was Glasgow is a large city and, just because I'dgot to the main bus station, it was somewhat foolish of me a most polite refusal - the Russians were happy anyway, to for what they really wanted was a publicity photograph); expect a sign directing me to my hall of residence. A for hatheywntedwasa ealy pulicty hotorap); uick change of plan and a taxi ride an Israeli colleague who couldn't believe that "Ilkley quick T geefficienc of the registatinand I wasprocedure at the Moorbar t'hat" was English; and those who thought that s Therefien of the registrat cu the Langue d'Oc songs in Stirling Castle were in Scottish was impressive, as was the load of material that was Gaelic. Such misunderstandings, however, are neither handed over. Given that my delegate's pack weighed here nor there. The real thing is that the rest of the world almo 5 t ere wrmor han 5,000 of u -which has, after all, to learn our language to participate few hours. at all in international science - has known that we respect fwhus and know something of their cultures too and that, at An enquiry at the Scottish information desk to find least, is one way of meeting their hearts and minds, out where my accommodation was took a bit longer Denis Noble as they were snowed under with delegates trying to Chairman of the Organising Committee their rooms. One person was complaining about being placed ten miles out of town. Once again, history recorded that there were no rooms at the inn. Seated in the main concourse, slowly making sense of the set of abstracts, Istarted to get an impression of the vast scale of the Congress. People from every corner of the world poured in, greeting longstanding friends and colleagues and it was delightful to meet friends I normally associate with other societies who had travelled to Glasgow.

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Members of the CongressExecutive Committee. Left to right,back row:John Gillespie,CharlesMichel, Lynn Bindman, Cecil Kidd; front row': lan McGrath, Denis Noble, Su Walton, EricFlitneY

The mele of physiologists arrivingat the SECC Getting around (Sunday) from Japan the night before, presented results from a Like so many new kids on the block, we set off after series of trials in which his group is trying to develop breakfast withourindex, mapsand Sunday's abstracts, an artiiilpaet.Drntificial placenta. During theh ensuingnun discussion,icsin "where", "which" and "how" featuring prominently it became apparent just how far this project has still to amongst the opening words of conversations, go, but nevertheless it is important that the Society is involved in the developments that will shape the Where was the bus going to take us and where were future. One of the great strengths of the Congress was the oral sessions to be held? For that matter, which of not only the depth of knowledge represented by the the 21 symposia now under way did you want to go delegates but also the breadth over which their to? By the afternoon we were faced with the added experience was spread. problem of choosing which of the 180 posters we wanted to see. How would we all meet up for lunch? In the afternoon, we discussed foetal growth and Deciding which wmetabolism, before considering the effects of hypoxia syposium to and asphyxia on foetal reflex control mechanisms and data presented was attend neuronal outcome. Whilst the - Ilargely based on animal research, it was interesting to compare it with some examples of clinical observations of similar conditions. The need for basic animal research to support - and at times lead the way for ­ medical practice could not have been shown more clearly.

' Speaker's corner (Monday) By now, most of us had mastered the buses and knew how to get around. The new hazard was the torrential rain. I returned to the second half of the Fetal Physiology symposium, whilst other members ofthe group went

- .$ to hear reviews onareas ofsomatosensory, respiratory and cardiovascular physiology. The only problem now was trying to make a choice, as all the talks had interest and importance to our work. It is perhaps unfair to pick on one symposium, but consistently high praise was coming from everyone I met who had been to the symposium on the global aspects of regulation of breathing and focal brain function. They were particularly grateful for some clear reviews, given by people who obviously understood the area. Owing to the distance between lecture theatres, it was My fear was that we were about to embark on a week difficult to pick individual talks from different lists, a of traipsing around endlessly looking for the problem that was occasionally compounded by appropriate lecture theatre only to find it packed to sessions running over time. the seams when we eventually arrived. However, but Monday afternoon, the pace increased as speakers for a few poorly signed routes around Glasgow were given ten minutes to present theirdata anda five University, including one that seemed to indicate that minute discussion followed. This was my opportunity you needed to dig a hole in order to find the theatre, to speak and, although the theatre was less packed my fears were without foundation. The lecture theatres than in the morning, it was a privilege to present my seemed to be excellently chosen for the numbers of work to such a knowledgeable audience and the people who wished to attend each session, with discussion which followed my presentation was most enough space to accommodate all the bags and books rewarding. that we had accumulated, but not so big that the room The day finished with the foetal physiology special felt uncomfortably empty. interest group dinner. A bus ride through the rain My first port of call was at the Fetal Physiology took us to Ross Priory, a large old house on the banks symposium, which kicked off with a discussion of the of Loch Lomond. My favourite malt was on offer as various roles of the placenta. The first talk, given by we arrived and an excellent meal followed. During an Geoffrey Thorburn from Monash University, one of after-dinner speech, John Challis from Canada the most senior workers in the field, elegantly showed announced the intention of starting a much needed how involved the placenta is in dictating the review journal to cater for foetal and neonatal physiological state of the fetus and, in particular, physiology. The idea is to take short pithy reviews, of stressed the involvement ofPGE 2.As if todemonstrate about 2,000 words, that will help everyone keep up how varied the conference was going to be, the next with the pace of new ideas within developmental speaker, Professor Y Kuwabara, who had flown in physiology. Poster Maze (Tuesday) The Press (Wednesday)

The organisers stressed that the theme of this Congress Hg/h Elder, would be the need for integrative book that accompanied our abstracts,physiology The Logic and of Life, the dealingwitiZedia the

gave a forceful argument in favour ofthis. The opening quote in the book comes from James Black, indicating that, in his view, the future of science will be of "the progressive triumph of physiology over molecular biology". Whilst that was the spoken theme, in the event the conference theme for me was one of integrative discussion. There was an environment that seemed to stimulate discussion and the correct space and pace, giving people who had previously only been names on the top of papers the opportunity to introduce themselves. This was particularly important for the new entrants to physiology research, the PhD students. One example serves to show how easily discussions started between different generations. Looking for a table to sit at for lunch, I, a recent PhD graduate and Wilfred Widdas a PhD student invaded the one currently occupied by (seated, left) in a Wilfred Widdas. Widdas, who attended his first bhiitioie Congress in 1950 in Copenhagen, has missed only discussion with two since. Explaining the secret of a happy retirement, some yoiunger he pointed out that he had published 17 papers before physiologists he retired and 25 since retiring.

Behind the scenes, a large media effort was under way. BBC television and radio came along and the major daily newspapers sent their regional reporters. Press conferences were arranged and one of the three immaculate green Rover cars whisked delegates to the press centre, temporarily converting bench scientists into international VIPs. The press conferences allowed journalists to ask the sort of questions that each felt their readers would like to ask themselves. The task of the scientist was then to explain the significance of their work without resorting to complex language or jargon. Making use of press opportunities is something that is very close to the heart of the Society, as any regular Respondingto The tabled area in the middle of the Exhibition Centre readeroftheMagazinewillappreciate. becameaquiet oasiswherepeoplefrommanydifferent a question, Professor Denis Noble, Chairman of the disciplines sat to discuss ideas. Around this nucleus Congress, said, "The way a democracy to influence of relative calm, the massed ranks of poster boards stood like strings of messenger RNA, whilst the I attended a few of the press conferences to see what ribosomal RNA delegates passed up and down went on. Through this I got to know a few of the stopping to decode the information, to discuss the reporters and began to understand many of the findings and, from time to time, to argue vehemently problems they have in finding stories and then making with the authors. them both understandable and interesting. On the whole, they were looking for stories with a "people I had some fascinating discussions with different interest",liketheproposed testforAlzheimer'sdisease presenters, including one with Martin Rosenberg, that was announced at the Congress. from Queen Mary & Westfield College, London, about his work on the effect that exercise has on auditory The scientists who came over well were those who function. The work showed that exercise reduces our had obviously thought carefully about the ability to determine the spatial origin of a sound implications of their work and answered questions occurring behind our heads; watch out if you cycle without speaking down to the questioners. After all, through London - you may not detect a bus wemustneverforgetthatmanyjournaliststhemselves approaching from behind! hold PhDs in science. Logic for the future (Thursday) BEHIND THE SCENES: By Thursday there was a feeling that for many the A LOCAL ORGANISER'S VIEW Congress was coming to an end; indeed, some had It was fitting that the XXXIInd Congress of the IUPS already left. However, discussion centred around the in Glasgow should provide the location for the Ian posters was still as lively as ever and the oral sessions Boyd Symposium on Proprioception and the Afferent were still packed, and for some the Congress was just Control of Movement, since he was instrumental in starting as their symposium was scheduled for that bringing the Congress to Glasgow. He was also a day. strong believer in the revised format which Delegates from my group took the opportunity to concentrates the symposia in one city, thereby look at areas of physiology they knew little about but allowing much greater interaction between felt held areas of mutual interest. The symposium on participants. Unfortunately, he died suddenly in 1987 metabolism presented some fascinatingdata ondiving just a few weeks before the decision was taken to base mammals, some of which go to depths in excess of the Congress in Glasgow. We were proud to name the any achieved by the most sophisticated submarines, symposium in his honour. holding their breath for many hours in the process. It lan is often said that there are many similarities between Boyd the mammalian foetal responses to hypoxia and those shown by diving mammals, so this session gave much food for thought. Few delegates actually saw Princess Anne as she toured the Congress earlier in the week and fewer still spoke with her but, even in days when the role of the monarchy is under question, her presence was a hallmark of the importance of the event, for which everyone who was present should take credit. Taking stock of the Congress, and looking to the future, it is interesting to see where a vast number of delegates came from. There were 500 Japanese and 50 Korean delegates, compared to only 250 from Germany and 120 from France. Denis Noble, in speaking to the press, said that the "centre of gravity of science is following the centre of gravity of economics". Comparing the up and coming eastern countries with the west, he added that "the big gap lies in the investment from industry. We need to ensure that we are more efficient at exploiting our knowledge". In four years' time we meet in St Petersburg where it will be interesting to see which Bill Ferrell was the driving force behind the players in the study of symposium. He quickly recruited the help of a more the logic of life, experienced physiologist, Uwe Proske, in drawing up a programme of speakers who could do justice to XXXIII PeterMoore this extensive topic. Uwe is a migratory physiologist INTERNATIONAL CONGRESSOF who finds comfort inavoiding the Australian summer PHYSIOLOGICAL by travelling regularly to Europe. Several years of SCIENCES diligent work assembled the speakers and found the ST PETERSBURG financial backing and by the spring of this year J, Ll everything seemed to be going smoothly. The real work started the week before the Congress FIRST and by the morning of Sunday 1 August things ANNOINCEMENT looked a little less organised. I spent most of that week running a daily marathon round the SECC sorting out a few of the problems some 5,000 distinguished scientific visitors had brought with them. I did not make it to the opening session of the symposia but Iremember the portable phone calling W me to the conference hotel to see to the hall lights. One large hall had been divided into three and it was possible from the front of one hall to gain control of the lights in all three sections by injudicious button pushing. All three rooms then darkened or lit up as one. It took a long time to find the hotel electrician on Animated a Sunday morning in themiddleof a holiday weekend. discussion on one of the GlaSgow Many unusual requests for audiovisual aids were Congressbuses made during the Congress. Ian McCloskey's request for a sweeping brush was the strangest, though his subsequent use of it was masterly. Another surprise was how often speakers addressing the topic of how fine manipulative tasks might be controlled found it ­ necessary to make expansive hand movements which dislodged the microphones from their stands. It was interesting to see how speakers reacted to the stress. The memory of one very eminent speaker being redirected away from his chosen route and out My final memory of the week was attending a into very heavy rain some minutes before his lecture receptionr hosted byy thet Russians who represented by a security guard doing his best to protect the the St Petersburg organising committee. How Princess Royal from unwelcome attentions will linger generous they are with vodka. Rather like the Scots, for a long time. the Russians are a very emotional people and after a The symposium dinner came as a welcome relief. Bill few glasses of vodka the languages seemed strangely Ferrell and I had travelled across Loch Lomond some similar. This was probably the effect of sleep months before to the lovely island of Inchmurrin in deprivation catching up with all of us. glorious sunshine. It was unfortunate that on the In summary then, it was a most enjoyable experience; evening of the symposium the rain was heavy and to remember Ian Boyd, to bring together old friends, visibility almost zero. Scots know not to apologise to make new friends, to hear new ideas. What new about the weather and anyway the bagpipes sounded joys await us in 1997? better through a Highland Mist.The return trip across the loch afforded better views by moonlight and was Ron Baxendale chiefly memorable for Dick Stein's patience as contemporary Scots political history was explained to him in great detail by the boatman whilst the rest of the passengers sang Brave Lochnagar with just a hint of a Japanese accent. The party returned to Glasgow by bus a little later than intended due to an oversight by the organisers. The driver had not been given a drop-off route round the conference hotels. The symposium participants showed remarkable ingenuity and surprising sobriety in organising this unassisted.

Pathophysiology of the Gut and Airways: An Introduction Edited by Paul Andrews and John Widdicombe Published on behalf of the Physiological Society by Portland Press This book examines the pathophysiological basis of a number of relatively common clinical problems and summarises the more difficult concepts. The two systems share many similar physiological features which are reflected in the patho­ physiological basis of the diseases and disorders reviewed. Chapters are paired dealing with the same or similar problems in the gut and airways and are selected to illustrate the clinical impact ofan understanding of normal physiological processes. Contents: Respiratory and gastro-intestinal parallels: real or contrived? G Burnstock; Non-adrenergic, non-cholinergic nerves in airways, PJBarn, Non-adrenergic, non-cholinergic motor systems in the gastro-intestina tract, GJSanger The pathophysiology of cystic fibrosis in the airways, DM Geddes and EAton; The pathophysiology of cystic fibrosis in the gastro-intestinal tract, JHardcastleet at; Hypersecretion in the airways, N Mygind; Diarrhoea and intestinal hyper­ secretion, N WRead; The pathophysiology of airway inflammation and mucosal damage in asthma, S E Webber and D R Corfield The pathophysiology of gastric and duodenal ulcer, J L Walace et al; Coughing: An airway defensive reflex, G SantAmbrogio;Vomiting: A gastro-intestinal tract defensive reflex, PAndrews; Glossary; Index. ISBN I 85578 022 4 Paper 130 pages June 1993 £ 16.951US$27.50 Physiological Society member price £ I2.70/US$20.62 Articles in this section were commissionedby Tilli Tansey In the second series of articlesabout animalsin researchGeorgina Watson, the managerof an animalfacility, outlines some of the currentproblemsfaced by such managers.Rick Skilton, managerofanothersuchfacility,elaboratesthesubstantialchangesinduced by the 1986 (Animals) Scientific Procedures Act, especially in the managementof animalfacilities, which stressesthe welfare and care components of working with living animals.Finally,Myc Riggulsford, the Information Officer of the Research for Health CharitiesGroupdescribes the establishmentof the organisation,and outlines the main activitiesit currently undertakes. Independently, severalarticleson this issue have indicatededucationalstrategiesto which physiologists can - and, indeed, must -contribute if thereareto be futurephysiologists,animaltechniciansandinformed members of society. We hopethese articlesmay prompt even more Members to make their propercontributionto this importantdebate. Tilli Tansey

MANAGER'S HEADACHIES samplingand collection, injection oftumour cell lines, and As the manager of a large, multispecies animal facility harvesting monoclonal antibodies, harvesting in a university, I feel that, in addition to the current implanting embryos. laws, the problems encountered in facility Thesemanipulationstaketime, whichmustbecharged management can be classified in the following groups: back to the requesting research team, which enables to be generated. * finance some income greater the need for funding * politics The more time elapses, the bodies to understand that the full staff costs must be • personnel borne by the research. This not only includes the " communication animal technicians in direct care of the animals, but Finance the overtime for weekends, public holidays and emergency call-outs. The funding must also cover a Inmost universities where theanimal accommodation proportion of secretarial, managerial, supervisory is a central facility, funding may now not be as and day-to-day care persons' salaries. forthcoming as it was up to some five years ago. Until Some grant holders have, in order to avoid some of fairly recently, animal accommodation was fully theadministration costs, lodged their funds in private funded in exactly the same way that academic accounts or with health authorities, which do not departments were. Since that time, many services "top slice" the funds as greatly as universities. These have had to incorporate full cost recovery into their accounts are very difficult to secure payment from charging systems.requredtocrryoutte Evennrmathe costs hubandytehniues of the consumables and, in order to reduce overheads being incurred, in required t carry out the normal husbandry techniques our facility we insist that, as far as possible, all goods, must be re-charged. The increase in costs tothe user in animals and services are paid for before the work can order to achieve full cost recovery has been commence. These users additionally incur 17.5% VAT, approximately 500%. This has had a twofold effect: which is "dead money". Current grants have run out before the research has been completed; because funding authorities will not Politics "top up" and cover the shortfall, this has led to loss of Internal politics must play a major role in the style of revenue and unnecessary loss of animal life. management of the institution. In some universities, The funding of smaller projects is now so costly that the attitude of those in the higher echelons is less than much proposed research is not undertaken because of supportive of the work carried out by the dedicated the lack of capital. animal technicians and research workers. This is often These two effects have led to a general reduction in the shielded from the technicians by the management rightly) quantity of research being undertaken and the staff of the animal unit, who (probably quite prevent such attendant reduction inthestaffing levels ofthe facilities. feel that the establishment would like to research from being undertaken. This has been Some university facilities have successfully marketed particularly evident with those universities (at least their expertise and now undertake research on behalf Liverpool, Leeds and Sheffield) who have declined to of non-university research teams. Many of them have hold the annual three-day congress of the Institute of been so successful at this that the staff on site now find Animal Technology on their premises. This attitude is it difficult to secure accommodation for their animals, deplored by animal technicians, who feel that it is the once they can afford to undertake work. Where dutyoftheleadersoftheseseatsoflearningtosupport departments have been prevented from carrying out and encourage them in their endeavours to improve this type of contract work, the staff levels have been the care and well being of animals, not to depress it drastically reduced. Reductions in staff have led to further. reduction in costs but when major projects do materialise suitable staff to support the work are Personnel almost impossible to find. Overall reduction in staff levels reduces staff morale In order to offset some of the staff costs, some animal very greatly. This in turn leads to poor quality work, technicians undertake the more straightforward work which results in greater pressure by the supervisors, on behalf of the research personnel. These procedures who try to improve the situation, which in turn lowers include: inoculation of animals with antigen, blood morale still further. The loss of posts has resulted in fewer trainee ANIMALS (SCIENTIFIC technicians being employed and this means there are PROCEDURES) ACT 1986: fewer and fewer newly qualified staff emerging. THE VIEW OF Reduction in numbers has drastically reduced the A "DAY-TO-DAY CARE PERSON" numbers of training courses available for animal technicians, so those that are lucky enough to be The Animals (Scientific Procedures)Act 1986 relates appointed either cannot find a suitable course or have to the breeding, procurement and use of experimental to travel long distances to attend one. animals for research in the United Kingdom. As well The people who make good animal technicians are magentoaialhunglscmsudras the operation of the Act, the design, structure and fewandfarbeteean hae aver secil atitde management of animal housing also comes under few and far between and have a very special attitude Home Office regulations. Having been responsible towards animals. Universities that suggest one year for laboratory animal house facilities for more than 30 fillingfillingheseposts these posts with qualifequalifiedtechnicians technicians, , unlessuh esso tayears, hI believeret thatoAiasAt17the current law is morenmkn effective l reponile they are surrounded by other research facilities and anse Credth to animals are bleto emptpeoleway Anialsarever those concerned with laboratory animals responsible are able to tempt people away. Animals are very and accountable. sensitive to change and tend to suffer high levels of stress when handled by new or untrained technicians; Researchers and animal technicians are nowworking this can be partly alleviated by the special caring more closely than ever to advance knowledge of caringnabiochemical, physiological, behavioural and disease processes. In particular, both groups have worked Communication together to develop training programmes and in many Research is liable to fluctuation and sudden changes animal houses induction courses are now provided of direction; this is nomoresothan in our universities, for all new animal users, regardless of previous where changes seem tooccur overnight. It can be very experience and rank.This clearly results in theanimal difficult to predict what will be happening in the next technicians and care assistants becoming an accepted sixmonthsandthiscanleadtowhatcouldbeconstrued part of the research team. as serious errors of judgement. These errors may In February of this year the Home Office set out its include building accommodation that is suitable for policy on the education and training of all personnel the housing of rodents and other small mammals and under the Animals (Scientific Procedures) Act 1986. subsequently having several groups intending to use From 1 April 1994, Personal Licence applicants will large laboratory and farm species for their research, have to offer proof of attendance at an accredited New staff are regularly appointed to research posts training course before the Home Office will process and these often have a direct impact on the animal theirlicence. Each licensee is individually responsible services; unfortunately, no-one considers asking if for the welfare of all animals on which they carry out therequiredfacilitiesareavailable.Thisusuallyresults regulated procedures. Similar conditions will apply, in requests for facilities that are, sometimes, very from 1 April 1995, to applicants for Project Licences, difficult to achieve. It is not unknown for requests for which will continue to be issued only to persons specialist equipment, to be made by the new member properly able to direct a well-justified programme of of staff on the day s/he arrives on the animal unit work. Project licenceapplications must explicitly take door step. So much time, effort and cost could be into account all reasonable possibilities for the three saved by a little negotiation at the appointment stage. "R's" -reduction, refinement and replacement of the Communication between research staff and animal experimental animals. technicians sometimes leaves much to be desired. Additionally, and unlike the 1876 Cruelty to Animals Experience has shown that if the animal technician is Act, the present Act requires three named persons to told about the work, its objectives and procedural accept overall responsibility for each establishment. methods then the response is to take even greater care They are: and interest in the work. The research worker is then 0 Holder of Certificate of Designation viewed much more favourably, rather than as the 0 Named Day to Day Care Person ogre who takes the technician's animals away. 0 Named Veterinary Surgeon In conclusion, the central animal IThe Certificate of Designation is issued to a person facility cares for animals from a variety of different disciplines, each representing the authority of the establishment, and he or she is ultimately responsible to the Home Office research group having its own that all conditions of the Act are observed. The specific requirements. It would be Certificate Holder may be the Secretary of a medical show favouritism to certain fields of school or faculty; in the commercial sector it is usually sho faourtist cetai fildsofthe lega drcoof the research. This should not be allowed gal director o company. to occur: each and every research The Certificate Holder must nominate a person to group deserves equal care and assume responsibility for the day-to-day care of attention. This should be animals, normally the manager of the animal facility, remembered by all personnel,before and also a Veterinary Surgeon. These people must they are tempted to start asking for ensure a complete, round-the-clock cover for animal favours, welfare and normally carry aircall bleeps, in order to GeorginaWatson give a quick response to problems at any time of the day or night. Naturally, the Certificate Holder, the is working and how animals are maintained and Day-to-Day Care Person and the Veterinary Surgeon cared for in a busy animal facility. Naturally, all such need to be in regularcontact and toestablisha working events need to be handled with diplomacy and tact. rapport. It has been argued that, whilst both the cost ofanimals The Named Day-to-Day Care Person and the bureaucratic requirements pertaining to their use have mushroomed, these have little relevance to The Home Office have intimated that the role of the their humane treatment. I strongly disagree with this Named Person should be performed by a suitably view. The current Act and its educational and training qualified and experienced animal technician. The requirements constantly remind all who use animals Institute of Animal Technology set up a Registration thatConsideration, Welfareand Accountability, must Board in 1985, which ensures a high standard of be in our minds, as well as Reduction, Refinement professionalism, and members signified by the and Replacement, when using animals. designation RAnTech adhere to a code of professional Finally, how many readers of this article this might conduct. The administrative responsibilities of the Day-to-Day medicalconsider research?giving talks Animal to schoolsrights groups about andanimals similar in r satih fia eagr and sionab Care Person include everything pertaining to animal organisationsm find an eager and impressionable use, welfare and environmental conditions such as audience in schools and colleges. As the manager of the fabric and security of the building. A considerable an animal facility, I am often asked to talk to schools, amount of time and thought is spent on staffing especially after antivivisectionists have made matters, to ensure that the animals are checked every presentations. Considering the enormous amount of single day of the year and that working rotas and interest in the subject, it is perhaps surprising that the standard operational procedures are effective. national curriculum does not specifically consider Members of the public and the media are generally the use of animals in medical research. Animals are ignorant of this "care ingredient" of laboratory animal included to some extent in the science curriculum, but experimentation and welfare. I believe that if this in the context of the care and welfare of school and aspect werebetter publicised and understood,a change home pets. Iurge you to consider becoming a school of attitudes might gradually occur. speaker. Contact the Research Defence Society, who Parallel with the Animals (Scientific Procedures) Act can help with training and provide a presentation are other laws relating to animals that those in charge pack of slides and information. If each reader gave of laboratory animals need to know. The use of large justone hour peryear in talking to schools farmanimals, forexample, requires movement licences and colleges about the positive side of and recording procedures as directed by the Ministry using animals in medical research, I of Agriculture Fisheries & Food. The same Ministry believe that within a decade public also controls quarantine regulations, relating to the opinion would become more informed importation and exportation of all livestock, which and tolerant. Helping young people to include some laboratory species. understand why the welfare of all During the course of a typical day of the Named Day- laboratory animals is an important to-Day Care Person, discussion and activities take consideration in medical research is only place on a wide range of subjects, including all those one reason why education about this mentioned above. The overriding necessity is, of subject is important. It is often overlooked & k4' course, to stay within the framework of the Act at all that school pupils of today become the times and to ensure that the departmental chairperson animal care and research employees of j:'/ 3 is kept up to date with all current demands from the tomorrow. research teams. One of an animal department's most Rick Skilton urgent current problems is to ensure that senior research members of staff (normally Project Licence Holders) liaise with animal house staff before requesting changes to their Project Licences. The Home Office Inspector's immediate contact person for clarification of all problems and requests is usually the Named Day-to-Day Care Person and it is clearly vital that this person is kept up to date on any matter that the Htome Office may query. Animal Research From time to time, contact and liaison with local .Fac-igt, Police and the CID (especially the Animal Rights Public,1 thet'stand National Index, ARNI) is also required, with regard to org'anised by the security in the light of local and national activities of Animal Weltare the ALF and other groups of protesters. make-Coiigrcss The responsibilities and activities of the Care Person delegates awareof and the animal facility may extend further. To give the iaterM just one example, during the past year I have had to available to hel arrange visits for MPs and others, including overseas the to visitors, who wish to see at first hand how the new Act communicate with the public THE RESEARCH FOR HEALTH Secondly, because of the need to promote understanding ¢ 3 CHARITIES GROUP role of animals in medicalof research,A2this vital R C dare ec g Scientists, and medical scientists in particular, are membersmem of the ofthe RHCG are encouraged A~ e ' I notoriouslybad communicators. One wit,disparaging to take part in media events. ACTIN 4 the notion of communication courses run by senior Spokesmen and women are available doctors tobreakbad news (of death and the possibility to debate this issue in the media and Action Rerch of organ donation for transplantation) said, "Being to speak to schools and other s a tons here anducther taught communication skills by a consultant is like or holders to being taught to fly by a pastry chef". obligation on all grant Inan effort to combat the more outrageous allegations explain the purpose and the nature of of the animal rights groups, and in recognition of the their work. If members of the public V obligation to promote public awareness ofthe method are togo on funding this work through Arthritis&Rheumatism Council and relevance of medical research, the major medical charitable subscriptions they have a research charities launched the Research for Health right to know how and why the money Charities Group in November 1991. There are now 15 is spent. If we are to attract students to members of the RHCG, which between them fund become our next generation of £303 million of medical research annually (compared biomedical researchers we must with the government's £220m through the Medical explain the nature and importance of Research Council). OfthisE303m, approximately£7m the work. All RHCG grant holders British Diabetic Association is spent on animal based studies, which includes the have been encouraged to volunteer to maintenance and welfare of the animals, vets and speak to schools (for which the technicians' salaries. Research Defence Society offers a free There are three main activities of the RHCG: training course) and to undertake TV, firstly, to provide information explaining radio and debating discussions (for the essential role of research involving which media training courses have British Heart Foundation animals in the development of our beenorganisedthroughtheWellcome C ncer understanding of and treatment for various Trust and Imperial Cancer Research R r diseases. The animal rights activists have Fund). a targeted school children in particular. They Thirdly, the RHCG makes a stand on U: r nPign have the resou rces to distribute widely a th e p ro mo tio n o f g o od p ractice C. ctr s ea,rch Capti.g great variety of literature with the aim of amongst grant-giving charities for Cancer Research Campaig persuading the coming generation that researchinvolvinganimals. Members medical research can advance in the are encouraged to keep careful and complete absence of work with animals. accurate records ofusage in the grants This lack of balanced argument has serious they award. All members ensure that CYSTIC consequences for all of us, for our health now and for the licence requirements of the 1986 FIBROSIS TRUST future generations. The RHCG has produced and Actare fulfilled by grant holders. They Cyc Fibrosis Research Trust distributed leaflets suitable for 12-15 year olds and arealso encouraged to investigate the also a school textbook The Search for Health - Medical case for animal usage at a level of Research In Action, published in association with enquiry that exceeds the requirements 4V Hobson's Scientific. This book does not seek to of the Act. This includes careful Imperial Cancer promote animal-based medical research but places it analysis of applications involving the Research Fund within the context of all medical research, showing use of animals and refusal when the the small but vital part which it plays. scientific case does not merit animal pe41l Cancer Reearch Fund use as proposed by the applicant. 9 Janice Wilkins of These aims have been assisted by the THHE INSTTUTE Of the ICRFspeaking establishment of the RHCG office, CANCER at the Society's which conducts vigorous debate with RE SEARCH joint symposium representatives of the animal rights with the RDS movements. It is vital that a climate of Institute of Cancer Research

informed and concerned discussion is fostered, so that researchers as well as the public can express their doubts and misgivings about thecontribution of animals in our society and the uses Mli l ce o i o i t to which we put them. Multiple Sclerosis Society At this year's Edinburgh Science Festival, we had a debate opened for the scientific community by Dr Mark M Matfield of the Research Defence MUSCULAR 0YSTROPHY Society. He was supported by Judy RSEAR ,COUNSELLINCARE MacArthur Clarke, president of the Muscular Dystrophy Group Royal Veterinary College; Professor Stephen Rose, scientist and refuting shoddy thinking wherever it appears. At the NATIONAL philosopher; and Professor Stuart RHCG office we have monitored over 200 letters in Cobbe, clinician and British Heart local newspapers this year alone. Where are the local Foundation grantholder, representing doctors, scientists and teachers writing in reply? Where the RHCG. In opposition was Mr Les are you? It is your children and neighbours who read RESEARCH Ward of Advocates for Animals, a and believe these claims. Because of the unbalanced National Kidney Reearch Fund Scottish antivivisection society. He argument against the use of animals in medical was supported by Professor Michael research, charities must speak out about the need for A V Balls of FRAME, Dr Gill Langley of further research to find treatments for crippling and the Dr Hadwen Trust and Richard fatal diseases. Wemustspeak oftheenormous benefits . gelng Ryder of the Political Animal Lobby, which past research, much of which has involved w itha "jury" orpanelofdistinguished animals, has brought. Without this voice the general have no Plesserah Into P41ng experts. public and especially schoolchildren will on which to base their own LThedebate centred on theethicalright accurate information of humans to use animals in medical ethical and moral decisions. Furthermore, public science; the humanitarian obligations support will be lost by failure to reply to the critics (no to reduce or remove pain, suffering matter how unfair or inaccurate that criticism is) and * U and distress; and the possible eventually and inevitably effective medical research hindered. Trust advances in techniques not requiring in this country will be Walloo.e animals which could be made inthe With this in mind the Research for Health near or immediate future. These Charities Group wishes to ensure that advances, especially in the field of children in particular, who have been WORMA toxicistoxicity testing, will onlysonly be adopted inundated with information fromaccurate animal TRUST if current legislation and scientific rights groups, have access to accurate WeuaS I--Medical Trust prejudice can be altered and some information provided by the scientific replacement tests properly validated community.Thiswouldencourageinformed to show that they provide better debate by increasing the public indicators than the current tests understanding of medical science. involving interpretation of results Individuals can then be left to make up their from live animals. own minds about the needs and benefits of 1578. 1657 medical research. Wiliam Havey Rarch Insitute It is time that all of us, especially those not directly involved in the animal Myc Riggulsford aspects of medical research, started

or ofrlinesoeisty pen yber to enable te m to travel betw e an kee in

nte USAforresearch or lectue purposes, between 1Octoberand 31 May (with possible blackouts over certain peak holiday periods such as Christmas and Easter). TheCom~te ha ageedthat thse Flwhips will be awarded by theGrants Sub-~Committee, in conjunction wi Northwest Airlines. Foreaef dmnitrtincadiats il be considered in conucto witheDle and Ruhtn ns an Aflit Travel Grant wll beaked to indicate to for a Nortwest hip.,whiThese

opes that Fellowships to a the younger age group.

Norhwet irlnesisnow offring prferential ratesAcademito all MebrFaresof the Society to facilitate aae-i rvl sflos * avn h ee day minumstay restriction on all pbihdAPEX fares from Lodn(Gatwick) and Glasgow. This represents an average saving of 30% on the unrestricted fare. 0 complimentary upgrade to Business Class when travelling on an unretriced Full Fare Economy ticket (Yclass). For example, a Society Membervould travel round-trip inBusiness Class between London (Gatwick) and Boston on a fare of £756 instead of the usual £2,122 - a saving of over 60%. For further information on Academic Fares or reservations, call Northwest Airlines on the following numbers: For travel from London: (0293) 561000 For travel from Glasgow: (041) 226 4175 Northwest Airlines has a current fleet of 371 aircraft, serving 242 cities (including 105 American airports), with 1,390 daily flights. There are daily flights from Gatwick and Glasgow, with connections to most major cities in the USA. THE INITIATION OF PARTURITION: enzymes, there is also an increase in availability of MOLECU LAR AND N EU RAL receptors forACTH on the foetal ovine adrenal cortex. MESSAGES The increased activity of the foetal adrenal cortex, as demonstrated by elevation of foetal plasma cortisol Historic studies on the role of the foetus levels in the lamb, is parallelled in non-human Parturition is an integrated multifactorial process primates by an increase in circulating concentrations involving diverse mechanisms in both the foetal and of foetal androgens (Fig3). We will return to this point maternal nervous systems, as well as several foetal later. and maternal endocrine organs. Recent studies, particularly those conducted in pregnant sheep, have 100. demonstrated that the foetus plays a major role in A initiating the signals that terminate pregnancy. The 75. focus of this review is to identify and evaluate the E nature of the neural and molecular messages that are , 50. used to convert a situation of stable maintenance of z / pregnancy, accompanied by minimal myometrial ! 25 " ?"? , activity, to one in which the cervix dilates and the myometrium contracts efficiently, with the resultant 0 • safe expulsion of the foetus. In a short review it is . 8B impossible to deal with all the studies by the many 9 investigators worldwide who have contributed to the 404 development of the detailed understanding of the -, interconnected sequence of events that precipitate - 20 parturition. A large number of excellent, focused * studies have been carried out in sheep and non- 0 human primateanimal species. Iwill focus particularly - 3o c * on the contributions with which I have had the good . 0_ fortune to be personally involved with my colleagues " in the Physiological Laboratory at Cambridge 20 University, the University of California at Los Angeles ' and, most recently, at the College of Veterinary tOo Medicine at Cornell University, Ithaca, New York. a. 9. In 1993, Percy Malpas reported that encephalic human 0 -20I -15I -10ei -5 i TERM +5 +10 I foetuses are invariably born postmature, provided that no complications, such as polyhydramnios, exist. TIME (days) In the 1960s it was observed that variousabnormalities that result in hypofunction of the hypothalamo- Fig I hypophyseal-adrenocortical-placental axis (HHAPA) A plasma ACTH concentrationsand B plasma cortisoloffetal sheep with bilateral in foetal sheep and calves prolong pregnancy. These lesionsof the hypothalamic paraventricularnucleus (lesion group, '!) or sham observations set the stage forthe precise experimental lesion (shamgroup,) from term - 22 days' gestation to term + 10 days' gestation studies directed at elucidating the critical molecular (term 146.5 ± 0.9 days' gestation,mean ± SEM in sham group). C, Plasma and neural messages involved in initiating and progesteroneconcentrationsof ewes bearingfetuses of lesion group C.') orsham delivering the signals that bring pregnancy to an end. group (e). *p < 0.05 when compared with sham group at term. Reproducedwith Sir Graham "Mont" Liggins performed a series of permissionfrom McDonald,T I & Nathanielsz,P W (1991) Am J Obstet 1653: 764-770 classical studies in which interruption of the foetal Gynecol, HHAPA at any one ofseveral levelsled to prolongation Fig 2 of pregnancy. In the converse experiments, infusion Adrenal mRNA of ACTH or cortisol to the lamb foetus resulted in , concentrations premature delivery. These experiments clearly (arbitraryunits) demonstrated the involvement of the foetal HHAPA 40. from fetal and in delivering the signals to parturition in sheep. Using neonatal(NEO) specific and sensitive assays to measure cortisol in L lambs for P4 5 0 7, foetal ovine plasma over the last 30 days of gestation, sdchain we demonstrated that the risein foetal plasma cortisol S Barsle with begins around 125-130 days ofpregnancy (Fig 1). This -C 20 different letters increased activity of the foetal adrenal cortex at this I are significantly stage of developmentstg o eelpetcorrelatesorlae wellwl withit theh 0 l bnt different. demonstration of increased activity of key adrenal 0Reproduced with cytochrome P450 hydroxylases, such as side-chain . permissionfrom cleavageand 17a hydroxylase within the foetaladrenal 0 7777" Myers, D A, cortical cells (Fig 2). In contrast, other foetal adrenal 105 120 128 136 NEO McDonald,T I & P450 hydroxylases such as the 110 hydroxylase do Gestational Age (Days) Nathanielsz, P W not appear to be regulated according to gestational (ocn2 y Endocrinology, age. Just prior to the increased activity of these adrenal 1329-1335 Foetal hypothalamic and pituitary function increases over the last 10-15% of gestation. A similar The increased activity of the foetal adrenal cortex is rise in oestrogen production occurs in ruminants as a driven by increased secretion of ACTH by the foetal result of the stimulation of the enzymatic conversion pituitary. It hasbeen demonstrated that themolecular of progesterone to oestrogen by cortisol. message for proopiomelanocortin (POMC), the precursor of ACTH, in the foetal pituitary, rises at around 120-125 days gestation. This is exactly the : 8000 100 stage of foetal development that is consistent with a ±

key role for ACTH in the drive to increased adrenal 0 06 function. Plasma ACTH increases in foetal plasma at a the same stage of development (Fig 1). 0 ( In adult mammals, it is well known that arginine = 4000 150 vasopressin (AVP), and corticotropin releasing V) 0 hormone (CRH) from the hypothalamus, particularly , 2000 25 the paraventricular nucleus (PVN), are the key / U regulators of ACTH secretion. Immunostaining of i ...... 0­ the foetal ovine hypothalamus shows abundant CRH 70% 85% BIRTH 0 and AVP in the foetal PVN throughout the last third of gestation. When both foetal PVN are lesioned in Percentage of pregnancy the sheep, pregnancy is prolonged. Bilateral foetal PVN lesions prevent the normal foetal hormonal changes that occur in the three weeks prior to delivery Fig3 (Fig 1). Comparisonof the main adrenalhormone, DHEAS, in fetal monkey blood and Following bilateral PVN lesions in foetal lambs, CRH cortisol in thefetal sheep blood in late fetal life, shows the similarityin the rise of the staining is absent from the median eminence of the blood concentrationsof thesefetal adrenalproducts.Reproduced with permission from Nathanielsz, P W (1992) Life Before Birth and A Time to be Born, ~Perinatologfoetal hypothalamus. Thus, it appears that the drive y Press, Ithaca, New7 York to the foetal HHAPA either originates in or passes through the foetal PVN. When in situ hybridisation It has been proposed that the increased activity of the histochemistry techniques are used to evaluate the foetal HHAPA results from a decrease in the negative distribution of CRH message in the PVN, marked feedbackof cortisol on the HHAPA, thereby resulting heterogeneity of this neural structure is clearly in progressively increasing secretion of ACTH. As a observed. Preliminary studies suggest that there are result, cortisol secretion continues to increase, even in potentially important regional changes in CRH the presence of plasma levels which, in adult sheep, synthesis in different areas of the PVN at this critical would feed back to inhibit the system. We have period of preparationregionaltrdifferenceshwithinethetPVN for birth. These mayacorrelate findings of demonstrated that the placement of dexamethasone regional differences within the PVN may correlate crystals adjacent to the foetal PVN will switch off the with different inputs to the PVN from various foetal CRHr gene. This negative feedback was more neural structures such as the medulla oblongata pronounced at 120 than at 130 days gestation, thus Catecholaminergic inputs from the hind brain supporting the negative feedback hypothesis. innervate the adult PVN very richly. Further studies remaining questions are many. The central issueThe is are necessary to determine which, if any, of these whether the increased activity of the neurones of the inputs regulate the increased activity of the HHAPA foetal PVN represents an autonomous clock within that triggers delivery, the PVN, or whether there is an increased input to the Controversy exists as to whether the non-human PVN from other areas of the foetal brain. primate foetus has a predelivery increase in foetal HHAP anfuctiowhtheranysuchchage~ These studies in ruminant species have produced a actii playsioanimilarhrletortatyd tate i fairly clear picture of thedegree activity plays a similar role of foetal involvement to that demonstrated to asa wellel asa theh naturea u e ofo theh foetalotl signals.sg as Threeh e bring about the initiation of parturition in sheep. The studies have been conducted in rhesus monkeys to studies described above, in which the foetal ovine determine the duration of placental retention HHAPA is manipulated both surgically and following removal of the foetus, and with it, any pharmacologically, are much more difficult to conduct . . inphman imaes,a nd tuchoedataifro the few signals the foetus may provide that initiate delivery. in non-human primates, and the data from the few One early study suggested that when the placenta relevant experiments in foetal non-human primates was left in situ it was not retained past normal term is open to conflicting interpretation. In the foetal after the foetus was removed. A second independent baboon, our preliminary data suggests that there is a study tended to contradict this first study. In a recent rise in foetal ACTH prior to the time of delivery, attempt to resolve these conflicting findings, we have Foetal rhesus monkey plasma androgens have been demonstrated that the removal of the rhesus monkey shown to rise in relation to the onset of delivery foetus at 120 days of gestation (term 168 in the rhesus according to a profile very similar to the rise in foetal monkey) resulted in retention of the placenta in situ cortisol in the sheep (Fig 3). The androgens secreted for up to 220 days of gestation. Thus it appears that in by the non-human primate foetal adrenal are the non-human primate the foetus is also responsible converted by theplacenta into oestrogens. As a result, for the initial signal to start the birth process. in non-human primates maternal plasma oestrogen 30 A 20 A

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Fig 4(i) Fig4ii) Contractureactivity datafrom a pregnantsheep showing A intra-amniotic Contraction activitydatafrom a pregnantsheep showingA intra-anmiotic pressure,B myometrial electromyogram, C pozwer spectrum of intra-amniotic pressure,B inyometrialelectromyogram, C power spectrum of intra-alniotic pressurerecorded in A andD power spectrumof myometrial electromyogram pressurerecorded in A and D power spectrumof myometrial electromyogram recorded in B. recordedin B. The potential role of adrenal innervation Recent studies by several groups of researchers have birth. The non neuroendocrine, neural signals that demonstrated that steroid hormone secretion is may help to mature the foetal HHAPA in lategestation modulated by innervation in the testes, the adrenal, remain to be elucidated. and the ovary. The role of the splanchnic innervation in the initiation of the increased function of the foetal foetalUterine HHAPA contractility as a stimulus to the adrenal cortex that occurs at the time of birth remains to be analysed. The demonstration of marked effects Myometrial activity occurs throughout pregnancy. of splanchnic innervation on the regulation of The epochs of activity observed in mid pregnancy in adrenocortical function in newborn calves suggest all mammalian species studied to date are long lasting thatsimilarmechanismsmayoccurinthefoetalsheep. (greater than three minutes) and generate only Splanchnic nerve section in foetal sheep modulates relatively small increments in intrauterine pressure. the foetal adrenocortical response to ACTH, afinding These epochs have been called contractures to that suggests a possible role forsplanchnic innervation distinguish them from the short, less than one minute, in the increased secretion offoetalcortisol that initiates well co-ordinated contractions oflabour and delivery (Fig 4). Contractures have been shown to stimulate

- ACTH secretion by the foetus. There are two routes by which contractures affect foetal ACTH secretion: E i N firstly, sensory stimulation of the foetus; secondly, H moderate foetal hypoxemia (Fig 5). These potential H interactions between foetus and mother remain to be "-­ explored. 10 010 2 J Fig 5 H A fetal carotidarterialPO,from baseline (averagcof two preoxiitocin ijection values); andchange in fetal carotidarterialACTt I before and after 70 n L oxyitocin - N administrationto fit' maternaljugularv ein at tinme 0 oier5 seconds, when oxi.gen was administeredto the ewe vi a a trachealcatheter to maintainfetal ,,xy.ge,,(N, M) andwhen no oxilgen was administered(t,o). Reproduced with permissionfroni 0!( ,n. Woudstra, B R,Kim, C, Aarnoudse, IG and Nathanielsz, P W (1991) Endocrinology, 129: 1709-1713 Biological significance of a foetal role in DEVELOPMENT OF OVARIAN the initiation of parturition FOLLICLES TO MATURITY IN VITRO What is the relevance of these studies in foetal sheep AND AFTER TRANSPLANTATION to the mechanisms of parturition in other species? The developmental biology of mammalian oocytes Clearly, monotocous and polytocous speciesare likely has been difficult to investigate because they are to differentially utilise signals from a single foetus at sequestrated behind follicular epithelial cells upon the time of birth. Similarly, foetuses of altricial and which they depend for normal growth, metabolism precocial species are likely to differ in the degree of and maturation. Oocytes from immature follicles foetal involvement in triggering parturition since the neither grow nor differentiate in nutrient culture readiness for the challenges of extrauterine lifediffers media when isolated from their granulosa cells. We in altricial and precocial species. However, in briefly describe here new methods for culturing and monotocous, precocial species, the concept that the transplanting whole follicles and granulosa-oocyte foetal brain plays a central role in the initiation of complexes with the aim of providing greater delivery clearly has considerable potential advantages experimental access to all follicular cells. This progress for the foetus. If the foetus determines A Time to be could also lead to applications for animal breeding Born, s/he can regulate the development of their technology and reproductive medicine. critical organs, such as the lung, while using the same Follicles are developmental units consisting ofa central processescirumsancsa to initiate mismatch parturition. between Thus, under vital normalorgan oocyte, enveloping layer(s) of granulosa epithelial circumstances,a mim atuitin vital not cells resting on a basement membrane and a peripheral maturationtheca. These structures are particularly well suited to occur. Whether foetal mechanisms similar to those a Tstture re paulr ellie to involving the foetal HHAPA observed in foetal sheep a culr environnpas oliclemal initiate parturition in primates such as the monkey, avascular and, thus, non-physiological chemical baboon and human remains to be resolved. However, gradients need not be presentduring their incubation. theparallel increase in foetal adrenal function between Small, preantralfollicles from mouse ovaries can now sheep and non-human primate species in late foetal be grown to maturity in vitro and the ultimate goal of life, suggests similarities. Further studies will be continuous growth from primordial stages appears necessary to elucidate the inputs to the foetal PVN to understand the molecular messages that are utilised Preantral follicles measuring 180 gim are dissected to activate parturition and to determine the extent to and transferred either to hydrophobic membranes or which different species employ these systems in to microwells of Minimal Essential Medium under different fashions. mineral oil containing follicle-stimulating hormone Peter W Nathanielsz (FSH) and homologous serum (2-5%). Onthe first two days of culture, the oocytes complete growth to full size (70 Im) and additional layers of granulosa cells are produced. The following day, an antral cavity forms and secretion ofoestradiol-17b begins. Neither of these changes occurs in the absence of FSH or by substitution with luteinising hormone (LH). Being formed in vitro, development of the antrum cannot be accounted for by the original hypothesis of

450-

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Suggested Reading R, 79-89.E30Bloom, S Edwards, A V and Jones, C T (1989) 1Physiol, 417:

Liggins,G C, Fairclough, SA, Grieves, JZ, and Knox, BS(1973) Recent Prog Horm Res, 29:111-149 Fig I McDonald, T J and Nathanielsz, P W (1991) Am I Obstet I 250 Primary follicles Gynecol, 165: 764-70 / ANTRUM FORMATION isolatedfii Myers, D A, Robertshaw, D, and Nathanielsz (1990) 3 mouse ovaries Endocrinology, 127:2328-2335 0 Nathanielsz, P W (1992) Life BeforeBirthand A Time to be Born. LL200F and rown in Promethean Press, Ithaca, New York, 14853, USA vitro forinan Nathanielsz, P W, Jansen, C A M, Yu, H K, and Cabalum, T antruni on the (1984).FetalPhysiologyandMedicine,TheBasisofPerinatoloy,ed 150 third day and R W Beard and P W Nathanielsz. Marcel Dekker, Inc, a 1 2 3 4 5 6 reach mature Butterworths, New York and Basel, London, 629-653. DAY OF CULTURE Graafiansize three days later. transudation from capillaries, and mechanisms of the resulting embryos develop to full term after water transport are now open to study. Oestrogen is transfer to pseudopregnant animals. Alternatively, evidently not required for follicular cell growth and the complexes can be transplanted after isolation in differentiation since development proceeds normally vitro to the evacuated ovarian capsule of a sterilised withoutatresia eitherwhenits production isinhibited animal after reaggregating them with stroma-theca by antibodies to thecal androgens or its actions are cells in a collagen gel or fibrin vehicle. Follicular competitively inhibited by oestrogen receptor growth from primordial to Graafian stages resumes antagonists. A theca layer is obligatory for full in the grafts, restoring oestrogen secretion and development and its removal halts growth at a ovulatory cycles and reversing host sterility. Table I preantral stage and prevents oestrogen production. Table indicating Growing follicles consume large amounts of glucose Starting Graafn Nuclear Ovulating the developmental and produce much lactate, requiring frequent numnber maturation capacity of replenishment of the miniature culture wells. The 30 19 (60%) 22 (73%) 10 (33%) preantralniouse ratio of glucose: lactate is 1:2 indicating that follicles follicles in culture utilise a predominantly glycolytic pathway of energy production, which is driven by gonadotrophic Storage of small follicles at very low temperatures is these hormonestimulation. That folliclesderivetheirenergy also feasible and increases the flexibility of from aerobic glycolysis was demonstrated by their techniques. The procedures are similar to those being ability to continue growth and steroidogenesis after used for mature oocytes and preimplantation in a inhibitionofoxidative phosphorylation with malonate embryos. The follicles are cooled slowly impaired development under anaerobic programmable freezer at a rate of 0.30'C/ min to and by their 0 conditions. The character of follicular energy -400'C and then at 1 C/ mi to liquid nitrogen metabolism therefore resembles that of tumours, temperatures in a medium containing dimethyl­ which also grow rapidly and competitively. sulphoxide. Whenthey are restoredby rapid warming By the fifth day, full preovulatory morphology is ittesgsfcluaand washed to remove theaae cryoprotectant rzntae there is rearag Foe-ane achieved and addition of LH to the medium inhibits imordialgn in vitro and produce fertile oocytes after oestradiol production and stimulates ovulation in development trnsl ntin to animals. about a third of each cohort of follicles. These FSH-dependent physiological responses indicate that LH receptors can be acquired and follicle rupture In conclusion, the complex, evolving character of mechanisms established during culture. Furthermore, ovarian follicles need not be a hindrance to germinal vesicle oocytes respond to stimulation by experimental investigations. Apparently normal resuming nuclear maturation and reach metaphase II development can occur in culture, providing new of meiosis within a mucified mass of cumulus cells at opportunities to study the role of intercellular the time of recovery. The fertility ofthese oocytes now molecular signalling and the control of follicular needs to be tested. secretion and morphogenesis. Furthermore, experimental access to the early stages of oogenesis is Fig2 300- increasing and with it the dawning prospect of Productionof - +,P "farming" oocytesR for practicalG& purposes.aB oestradiol-17b by Roger G Gosden & Nicola I Boland follicles during CONTROL MEDIUM daysgofSuggestedesix reading culturein the Boland NI, Humpherson PG, Leese HJ &Gosden RG (1993) presenceof FSH e200" Biol Reprod, 48: 798-806. and with the a ­ Carroll J& Gosden R G (1993) Hum Reprod (in press). addition of LH on E Eppig, J J, Wigglesworth K &O'Brien M J (1993) Mol Reprod the fifth day to jDe, 32: 33-40. G (1990) umtonReprod, 5: 499-504. 0 Gosden, R induce ovulation. 0 ­ Gosden R G &Boland N 1(1992) In Infertility, eds Templeton A A & Drife JO: 263-275. Springer-Verlag, London. - Nayudu P L &Osborn S M (1992) 1 Reprod Fert, 95: 349-362. 0 +LH

0 1 2 3 4 5 6 DAY OF CULTURE

A much larger yield of small follicles can be obtained by disaggregating ovaries with collagenase rather than by manual dissection, but they do not grow to Graafian sizes in vitro because they are denuded of theca cells. However, when these granulosa-oocyte , Left: complexes are cultured for ten days on collagen-j RogerGosden impregnated membranes, the oocytes become capable Right: of meiotic maturation and fertilisation, and some of , Nicola Boland DESIGNATED SESSIONS Neuroendocrinology AT THE KING'S COLLEGE MEETING The main activity of the Special Interest Group for Epithelia & Membrane Transport Neuroendocrinology this year was the organisation of five days devoted to neuroendocrine topics at the Sergio Grinstein obtained the PhD degree in very successful IUPS Congress in Glasgow. This Physiology at the Polytechnical Institute of Mexico centred on two symposia, one devoted to molecular City in 1975, under the supervision of Dr David Erlij. endocrinology and one to oxytocin. There were also He next trained for two years in the laboratory of Dr symposia on gonadotrophin releasing hormone, Aser Rothstein in Toronto and for one year with Dr reproductive behaviour, fever as a Giorgio Semenza at the ETH in Zurich. In 1980 Dr neuroimmunological endocrine phenomenon, as well Grinstein was appointed to the Research Institute of as physiology of stress and neural control of the Hospital for SickChildren in Toronto, where he is immunological responses. These sessions were currently a Senior Scientist and Head of the Division centred on the university campus and were very well of Cell Biology. He is cross-appointed to the attended; indeed, there was standing room only for Department of Biochemistry of the University of the Mortyn Jones Memorial Lecture (organised by the Toronto and is an International Scholar ofthe Howard British Neuroendocrine Group) given by Dr Colin Hughes Medical Institute. Ingram on central oxytocin and the milk ejection The lecture will describe the processes that challenge reflex. It was generally agreed that another high point intracellular pH homeostasis in leukocytes and some of the neuroendocrine sessions was the poster session of the mechanisms involved in its regulation. The on the Wednesday evening run in conjunction with a primary sources of metabolic acid generation during buffet supper and an ample supply of wine. the microbicidal response will be discussed. Next, the The next event to be organised by the Group will be role and properties of the Na*/H* antiport will be a Designated Session at the King's College Meeting. briefly summarised. In addition, recent evidence There will be a full day, Friday 17 December, devoted concerning the activation of vacuolar-type proton to Neuroendocrine topics. There will be 16 Oral pumps and proton-selective "channels" will be Communications, precededby a plenarylecture tobe discussed in detail. Finally, the notion that the acid- given by Professor Fred Karsch on the subject of producing and acid-extruding processes are coupled neuroendocrine rhythms. Professor Karsch received throughcommonsignallingeventswillbeconsidered. his undergraduate degree in Biology from Juniata Barry Hirst College in Pennsylvania before embarking on postgraduate training at the Universities of Maine Human Physiology and Illinois. He has had two distinguished mentors, There will be a symposium and Designated Session completing his PhD in Animal Science under the for the Group at the King's College London Meeting guidanceof thelateA V Nalbandovand a postdoctoral to be held on 15-17 December. The topic of the fellowship on the neuroendocrine control of the symposium is "The Physiological Consequences of primate menstrual cycle with Ernst Knobil at the Ageing" and the programme is as follows: University ofPittsburgh. In 1972 he moved to a faculty he is * A Young (London): the muscle cell and position at the University of Michigan where external force production currently Professor in the Department of Physiology and Research Scientist in the interdisciplinary * S A Ward (London): the respiratory response to Reproductive Sciences programme. In this exercise environment he has inspired many pre- and 9 E Lakatta (Baltimore): the circulatory response to postdoctoral students with his enthusiasm for studies exercise on the neuroendocrine regulation of reproduction in * W J Evans (Boston): time-dependent changes in a seasonally breeding species, the ewe. At present he physiological function and responses to training is on sabbatical leaveat the AFRC Babraham Institute. * E J Bassey (Nottingham): customary physical There will be a lunchtime poster session and, after the activity: the chicken or the egg? approval of posters in the afternoon, a short Business The symposium will be followed by a Business Meeting to discuss future plans of the Group. It is Meeting of the Group. One of the main items for planned to hold a symposium in the autumn of 1994 bring them discussion is the programme of activities for next but if you have any other ideas please year, and members are encouraged to give some along. If there are any particular items you would like fordiscussed, please contact me. thought to suggestions for symposium topics and for Designated Lectures. Mary Forsling Anyone wishing to have details of the Biochemistry Respiratory Physiology of Exercise Conference to be held in Aberdeen in July A Designated Session of the Respiratory Physiology 1994 should contact Ron Maughan. The deadline for Special Interest Group will be held at the King's receipt of abstracts will be the end of January. College Meeting of the Society in December. The Ron Maughan Meeting is heavily subscribed so there will be a poster session to absorb the overflow. The Oral Communications will emphasise the subject of "Hypoxia". We will be hosting, as a Foreign Guest, Professor Hu Developmental Neuroscience Shu-Tsu of the Hypoxia Laboratory at the Chinese ThisSpecial InterestGroup has nowbeen reconvened. Academy of Sciences, Shanghai. Professor Hu is the Three Communications were presented covering pre-eminent respiratory physiologist in China and is astroglial responses to GABA in rat optic nerve, the an authority on acclimatisation to altitude and on the morphology of astroglial relationships with nodes of central mechanisms responsible for the inhibitory Ranvier in mouse optic nerve and ion channels in component of the ventilatory response to hypoxia. cultured cochlear hair cells in neonatal mice. Two PiersNye posters described the entrainments of responses in dorsal roots and the expression of c-fos in isolated rat AT THE SOUTHAMPTON MEETING spinal cord. The final poster presented the derivation A of amathematical model for the growth and decay of human retinoblasts which differentiate into Cellular Neurophysiology photoreceptors. Retinoblasts may also give rise to There have now been two Cellular Neurophysiology retinoblastoma and the derived curves closely fit data Designated Sessions, one at UCL in July and one at on the incidence of retinoblastoma obtained from Southampton in September. An encouraging interest cancer registries. was shown by the number of abstracts submitted At the Group's Business Meeting it was decided that both as Oral Communications and as poster asymposiumonDevelopmentalNeuroscienceshould presentations and I would like to thank those that be organised at the Cambridge Meeting of the Society presented and those that attended to discuss in July 1994, which is being held in conjunction with presentations forcontributing to some very interesting the Anatomical Society. Iwould welcome suggestions and lively sessions. Data presented ranged from single for this symposium. channel and whole cell currents, through miniature synaptic events, Ca- measurement and cell Simon Miller morphology to the outcome of pathological changes Comparative Physiology and Comparative in neuronal circuits and included species from & Invertebrate Neuroscience molluscs to mammals. The Comparative Physiology (CP) and Comparative After the second session, there was a brief Business & Invertebrate Neuroscience (CI) Special Interest Meeting at which the future format of these Sessions Groups held a very successful joint meeting at was discussed. In general, the format had been Southampton. The highlight of the meeting was the successfulanditwasfeltthatourDesignatedSessions Designated Lecture given by Professor Allen should continue to concentrate on Communications Selverston from San and Posters. However, if the membership wishes to Diego,USA on "The have plenary lectures or specialised symposia in Invertebrate Central future, these can be arranged; please raise these points Pattern Generator at the with me or at future Business Meetings. Indeed, let Interface of Molecular me have any of your thoughts, ideas or criticisms and Systems Neuro­ about the Group and contact either me or the Society biology". He described office in Oxford if you wish to be added to our list. the elegant experimen­ There is no rigid structure laid down beyond the tation which has Domestic Rules of the Society and this is, after all, uncovered the flexible your Group, so please help me to make the Sessions patterns of interaction as useful and as enjoyable for you as I can. We can between the constituent propose as many or as few Sessions as we wish. A neurones in the number of those present in Southampton expressed stomatogastric ganglion an interest in having a Session at the forthcoming controlling the lobster Bristol Meeting. Iwould also suggest that, in addition stomach, enabling it to to the session at Bristol, we have Designated Sessions swallow, chew, filter and digest food. This work is Allen Selverston at the Cambridge Meeting in July and the Birmingham uncovering fundamental principles governing the deliveringhis Meeting in December, to spread them evenly through behaviour of neural networks. lectnre the year, but if you have alternative suggestions, The potential for comparative studies to enhance our again, let me know and check the Magazine and understanding of general biological principles was Programmes for future announcements. emphasised by the theme of our research symposium Please remember to mark your abstracts "Cellular on "Comparative Studies on Control Mechanisms". Neurophysiology". The Meetings Secretary cannot The symposium was chaired by Ted Taylor, convenor be expected to be clairvoyant and to assign your of the Comparative Physiology Group, who presentation to a Session you have not expressed an emphasised the increasing interest in comparative interest in. studies within the Society and illustrated their utility Alex Thomson by describing work on cardiorespiratory interactions Email: [email protected] in fish which led to work on the generation of respiratory sinus arrhythmia in human neonates. Bob Boutilier then described the integrative roles of circulating catecholamines in the control of oxygen uptake and supply during hypoxia in fish; Neil Hazen described the role of the renin-angiotensin system in therein) is asked to contact me for inclusion on the thecontrol ofionand waterbalancein eelsacclimatised mailing list. Suggestions are requested for an invited to freshwater and seawater, with the study of gill speaker for the Birmingham Meeting. ionoregulation extending to in situ hybridisation and David Potts dot blots allowing quantitative estimates of the expression of mRNA for the subunits of Na'/K' SPECIAL INTEREST GROUP NEWS ATPase. Paul Benjamin then discussed the very sophisticated collaborative studies of the neural Sensorimotor Control control of cardiac function in snails, enabling genes We had an excellent and lively meeting at UCL, for the cardioactive peptide FMRF to be sequenced London. There were 14Communications, with a wide and cloned, revealing that separate axons encode for range ofresearch areas. Only three of them concerned different forms of the peptide which physiological work in animal preparations. A short Business Meeting studiesrevealedhaddifferentpostsynapticeffectson was held. It was agreed to hold the next Session in cardiac neurones. Claudio Agnisola described the Bristol. detailed morphology ofthe myocardium and coronary The Group hosted a special Motor Control party at the circulation in fish and cephalopod hearts and then IJPS Congress in Glasgow. This was a great success gave an insight into how in vitro and in situ studies and provided a delightful social gathering in the haveincreasedourunderstandingoftheirfunctioning. Institute of Physiology for all those interested in Finally, John Simmers returned to the theme of the sensorimotor control. Over 180 people attended, clear neural networks controlling the lobster stomach, evidence of the strong interest in this field. The success describing how inputs from single interneurones of the party was due entirely to the brilliant reorganised networks into changed configurations to organisation and hard work of Bill Ferrell and his control the separate functions of this complex organ. team. Thanks are also due to several symposium This joint meeting also included 16 Communications organisers who contributed financially. and 22 Posters on themes as diverse as the effects of Professor Sten Grillner (Karolinska Institute, anaesthetics on snail neurones, regulation of KCI Stockholm) has agreed to be our Plenary Speaker at transport in horse red blood cells and the effect of red the start of the day. This will make an excellent start to hot chili peppers (capsaicin) on heart rate and what promises to be a very good Session on ventilation in decerebrate dogfish. Sensorimotor Control. Ted Taylor Roger Lemon Renal Physiology The Group met at TRENDS IN CELLULAR AND Southampton. Professor MOLECULAR PHYSIOLOGY: Raynald Laprade from UNDERGRADUATE SYMPOSIUM Montreal University gaetheal ninvedle A symposium for BSc Honours students will be held on "Coupling betwen on Wednesday 8 December 1993 in the apicalandbasolateralion Cohen Lecture Theatre, Duncan Building, University of Liverpool, transport in the kidney commencing with coffee at 10.30 am and concluding proximal tubule: role of with a wine reception from 4.50 pm onwards. cellular calcium, pH, Speakers will include: ATP and volume". There 0 Ole Petersen: spatial dynamics of theintracellular were 11 Communi- messengers IP3 and Ca 2* cations, seven Posters * Bob Burgoyne: regulated exocytosis and a short Business Meeting. In an 0 Trevor Lamb: signalling in G-protein cascades: the photoreceptor as an example Raynald Laprade experimental change of (left) relaxing protocol at the Poster approval session, one author 0 Annette Dolphin: why neurones need calcium with Jon Beck for each Poster gave a brief (one minute) summary of channels after his lecture the main points of the Poster, prior to discussion and 0 David Eisner: control of contraction in cardiac vote. This seemed to be an improved way of muscle proceeding with the approval of Posters (although 0 Graham Dockray: temporal dynamics of peptide somemembersof theGroupwould abandonapproval hormone production . altogether). For further information and registration details, The main business consisted of discussion of plans contact Mrs Hazel Dickinson, Physiological for future Meetings. In view of the European meeting Laboratory, University of Liverpool, at Erlangen-Nurnburg on 23-27 April, it was decided P0 Box 147, Liverpool L69 3BX, tel (051)7945325, fax 5315 to accept the invitation of E Johns and colleagues to (051) 794 hold the next Renal Physiology Session at Birmingham in December 1994. Anyone who wishes to be a member of the Group and who for some reason is not in the Grey Book (or not identified as a renal physiologist No notice is carriedfor more than three 4th International Meeting on 2 A candidate must have published at least successive editions. Notices are starredso that HIGH PRESSURE BIOLOGY one full research paper on a physiological readers can see at a glance whether this is the 10-13 September 1994 subject in a reputable journal. This paper first (one star) or final (three stars) appearanceof Aberdeen, Scotland, UK will form part of the documentation the notice. Notices for the February(Bristol) Further details from: Dr A Macdonald, Dept considered by the Committee, so that in the edition should reach the Editor or the of Biomedical Sciences, University of case of a paper that has more than one Administration Office by 30 November 1993. Aberdeen, Aberdeen AB9 1AS, Scotland, UK, author details of the contribution made by tel (0224) 273005, fax (0224) 273019 * the candidate must be provided. 9th Annual Symposium on Wellcome Centre for Medical Science 3 The candidate must obtain the signatures Biotechnology One day Open Meetings of SIX Members of the Society who will sign THE NEW BIOLOGY OF a statement declaring that the candidate is CARBOHYDRATES The Wellcome Centre for Medical Science, in well known to them, is practising in 16-17 December 1993 collaboration with the CIBA Foundation, is physiology or a cognate subject and is likely UCL Medical School, London organising one day Open Meetings to follow to remain so, fulfils the criteria for Further details from Mrs B Cavilla, Institute a selection of CIBA Symposia. The calendar Membership and is likely to benefit from of Biology, 20 Queensberry Place, London for 1994 is as follows: Membership of the Society and take part in SW7 2DZ *** its activies. 1 January: Antimicrobial peptides New York Academy of Sciences 18 March: Vaccines againstvirally induced There are currently two classes of BRAIN CORTICOSTEROID cancers Membership for which individuals can be RECEPTORS 29 April: Calcium waves, gradientsand considered. Candidates for Ordinary 2-5 March 1994 oscillations Membership will reside in the British Isles or Arlington, Virginia 20 May Cell adhesion and human disease have worked for a substantial period in the Studies on the mechanism, function and 15 July: Molecular biology of somatostatinand British Isles or have served the Society in neurotoxicity of corticosteroid action. Further its receptors some significant way. Candidates for Foreign information from: Conference Dept, New 2 September. Non-reproductive action of sex Membership will normally reside outside the York Academy of Sciences, 2 East 63rd steroids British Isles. Street, New York, NY 10021, USA, tel (010 1) 212 838 0230, fax (010 1) 212 838 6540 * The meetings will be held in the Wellcome Full details and forms are available from the Trust Building at 183 Euston Road, London Administrator (Membership), The International Federation of Automatic NW1 2BE. The registration fee is £10 (£5 for Physiological Society, Administration and Control Symposium graduate students) in advance for each Publications Office, PO Box 506, Oxford OXI 798092. MODELING & CONTROL IN meeting, including refreshments, lunch and 3XE, tel (0865) 798498, fax (0865) BIOMEDICAL SYSTEMS documentation. Further information from: Contributors 27-30 March 1901 Sheila Pusinelli, tel (071) 636 9456 * Galveston, Texas, USA Corticospinal Function and Voluntary Contributors to this issue of the Magazine, Deadline for extended abstracts and advance Movement other than those whose current addresses are registration: 1January 1994. Further details Monographs of The Physiological included in the Society's membership from: IFAC Biomedical Symposium, Texas Society, No 45 handbook known as the Grey Book (1993 ed), Galveston,University TXMedical 77555-5176, Branch, USA, Box 55176,tel (010 1) £60/$95 hardback, ISBN 0-19-857745-1, OUP arasflo:are as follows: 409 770 6628, fax (010 1) 409 770 6825 ** This 40 ax(0070 62, ) 0977 625Robert newPorter, Monograph, gives an by account Roger ofLemon the and Nicola Boland, Dept of Physiology, anatomical and functional organisation of University of Edinburgh, Medical School, PEDIATRIC3rd International PAIN Symposium on thetoc brain an which providesunctiona fororgthe the Teviot Place, Edinburgh EH8 9AG 6-9 June 1994 performance of skilled voluntary Philade USA movements, especially the accurate and Ian Brown, Dept of Physiology & Philadelphia,precise control of the use of the fingers and Pharmacology, University of Southampton, Further details from: The Conference Center, the hand by monkeys and humans. For Bassett Crescent East, Southampton S09 3TU 12407 Kemp Mill Road, Silver Spring, ordering details, see the tear-out Special Maryland 20902, USA, tel (010 1) 301 622 Christmas Offers to Members from OUP, Roger Gosden, Dept of Physiology, 7795, fax (010 1) 301 622 4978 ** included in this issue of the Magazine. * University of Edinburgh, Medical School, Teviot Place, Edinburgh EH8 9AG Myc Rl r, inormi Officer L'Association Francalse de Nutrition Directory of UK Biological Societies, Le Symposium Lavoisier 1993-94 Myc Riggulsford, Information Officer, METABOLIC FUEL SELECTION A new edition has been published, giving Research for Health Charities Group, PO Box 13-16 July 1994 details of societies' secretaries, activities, 1417, Shepton Mallet, Somerset BA4 4YZ Paris, France publications and subscriptions. Members and Deadline for receipt of abstracts: 1 April Affiliates may obtain copies at special rates Rick Skilton, Biological Research Facility, St 1994. Further details from Pr J-F Desjeux, via The Physiological Society; please contact George's Hospital Medical School, Cranmer INSERM U 290, Hopital St-Lazare, 107 Fg St- the Administration Office. Terrace, Tooting, London SW17 ORE Denis, 75010 Paris, France, tel (010 33) 1 45 23 24 07, fax (010 33) 1 47 70 28 35 * Membership of The Physiological 9th nteratinal onfeencSocetyWorsley Georgina MedicalWatson, &Biomedical Dental Building, Services, 9th International Conference Society University of Leeds, Leeds LS2 9NQ BIOCHEMISTRY OF EXERCISE The minimum criteria for consideration by Dic (R G) Williams, Dept of Physiology & 21-26 July 1994 the Committee for inclusion on the Pharmacology, University of Southampton, Aberdeen, Scotland, UK Membership ballot (as Ordinary or Foreign Bassett Crescent East, Southampton S09 3TU Deadline for registration and submission of Members) are: poster abstracts: 31 January 1994. Further details from: Dr R J Maughan, University 1 A candidate must have given at least one Medical School, Foresterhill, Aberdeen AB9 Communication or Demonstration in person 2ZD, Scotland, tel (0224) 681818 Ext 52482, to the Society. fax (0224) 662990 TITLE AUTHOR PAGE 2* GABAB receptor modulation of Ca currents in rat sensory CAMPBELL, Veronica, BERROW, Nick & DOLPIN, Annette C 1 neurones by the G protein G.: antisense oligonucleotide studies

Human sodium channel myotonia; slowed channel inactivation LERCHE, H, HEINE, R, PIKA, U, GEORGE, A L Jr, MITROVic, N, 13 due to substitutions for a glycine within the IIl-IV linker BROWAT7KI, M, WEISS, T, RIVET-BASTIDE, M, FRANKE, C, LOMONACO, M, RICKER, K & LEIIMANN-HORN, F

Calcium currents and calcium-dependent potassium currents RICHtTER, D W, CIiAMPAGNAT, J, JACQUIN, T & BENACKA, R 23 in mammalian medullary respiratory neurones

Membrane potential modulates inositol 1,4,5-trisphosphate- GANITKEVICH, Vladimir Ya & ISENBERG, Gerrit 35 mediated Ca2 ' transients in guinea-pig coronary myocytes

A dendritic gain control mechanism in axonless neurons of the LAURENT, Gilles 45 locust, Schistocercaamericana

ATP modulation of calcium channels in chromaffin cells GANDiA, L, GARCIA, A G, & MORAD, M 55 2 Two phosphatase sites on the Ca channel affecting different ONO, Katsushige & FOZZARD, Harry A 73 kinetic functions

Respiratory sensations, cardiovascular control, kinaesthesia and GANDEVIA, S C, KILLIAN, K, MCKENZIE, D K, CRAWFORD, M, 85 transcranial stimulation during paralysis in humans ALLEN, G M GORMAN, R B & HALES, J P

The effects of low calcium on the voltage-dependent conductances ART, J J, FETI'PLACE, R & Wu, Y-C 109 involved in tuning of turtle hair cells

The frequency content of common synaptic inputs to FARMER, S F, BREMNER, F D, HALLIDAY, D M, ROSENBERG, JR & 127 motoneurones studied during voluntray isometric contraction STEPHENS, J A in man

Power production and working capacity of rabbit tibialis anterior JARVIS, Jonathan C 157 muscles after chronic electrical stimulation at 10 Hz

Characteristics of multiple voltage-activated K- currents in acutely WISGIRDA, Mary E & DRYER, Stuart E 171 dissociated chick ciliary ganglion neurones

Thyroliberin-induced changes in the fluorescence of a membrane SHORTE, S L, STAFFORD, S J V, BAMFORD, M, COLLETT, V J & 191 probe in individual bovine anterior pituitary cells SCHOFIELD, J G

Characterization of the outward rectifying potassium channel in a MOLLEMAN, Areles, THUNEBERG, Lars & HUIZINGA, Jan D 211 novel mouse intestinal smooth muscle cell preparation

The influence of thermoregulatory mechanisms on post-exercise FRANKLIN, P J, GREEN, D J & CABLE, N T 231 hypotension in humans

Uniform olivocerebellar conduction time underlies Purkinje cell SUGIHARA, I, LANG, E J & LLINA S,R 243 complex spike synchronicity in the rat cerebellum

Electrophysiological properties of cat reticular thalamic neurones CONTRERAS, Diego, CURRO Dossi, Roberto & STERIADE, Mircea 273 in vivo 2 Voltage-dependent block by internal Ca , ions of inwardly MATSUDA, Hiroko & CRUZ, Jader dos Santos 295 rectifying K* channels in guinea-pig ventricular cells

A voltage-dependent proton current in cultured human skeletal BERNHEIM, L, KRAUSE, R M, BAROFEIO, A, HAMANN, M, KAELIN, A 313 muscle myotubes & BADER, C-R 2 Effects of ryanodine on the properties of Ca release from the OYAMADA, H, INo, M & ENDO, M 335 sarcoplasmic reticulum in skinned muscle fibres of the frog

Expression of subunit-omitted mouse nicotinic acetylcholine Liu, Yuan & BREHM, Paul 349 receptors in Xenopus laevis oocytes

Modification of the transient outward current of rat atrial PIKE, G K, BRET.AG, A H & ROBERTS, M L 365 myocytes by metabolic inhibition and oxidant stress

Direct comparison of corticospinal volleys in human subjects to BURKE, David, HICKS, Richard, GANDEVIA, S C, STEPHEN, John, 383 transcranial magnetic and electrical stimulation WOODFORTH, Ian & CRAWFORD, Matthew

Inward current activated by carbachol in rat intestinal smooth ITO, Shigeo, OHTA, Toshio & NAKAZATO, Yoshikazu 395 muscle cells

Calcium and potassium currents in ventricular myocytes isolated JOURDON, Philippe & FEUVRAY, Danielle 411 from diabetic rats TITLE AUTHOR PAGE

Axonal projections and synaptic connections of C5 segment DoUsE, Mark A & DUFFIN, James 431 expiratory interneurones in the cat

Electrical coupling of circular muscle to longitudinal muscle and Liu, Louis W C & HUIZINGA, Jan D 445 intersitial cells of cajal in canine colon

The role of vasopressin in the regional vascular responses evoked LouWERSE, Anne-Marie M & MARSHALL, Janice M 463 in the spontaneously breathing rat by systemic hypoxia

The influence of vasopressin on the arterioles and venules of MARS[HALL, Janice M, LIOYD, Julia & MIAN, Rubina 473 skeletal muscle of the rat during systemic hypoxia Differential expression of sodium channels in acutely isolated CHIu, S Y 485 myelinating and non-myelinating Schwann cells of rabbits

Mitogenic factors regulate ion channels in Schwann cells cultured WILSON, G F &CHiu, S Y 501 from newborn rat sciatic nerve

Role of GTP-protein and endothelium in contraction induced by KUROIWA, Mari, AOKI, Hiroki, KOBAYASIII, Sei, NISItIMURA, 521 ethanol in pig coronary artery Junji & KANAIDE, Hideo

Mechanism of popioid receptor-mediated presynaptic inhibition CAPOGNA, Marco, GAHWILER, Beat H & THOMIsoN, Scott, M 539 in the rat hippocampus in vitro

A comparison of effect of temperature on phosphorus metabolites, MARJANOVIC, M, GREGORY, C, GiHosu, P, WILIs, JS 559 2 pH and Mg ' in human and ground squirrel red cells & DAWSON, M J Calcium-mediated modulation of N-methyl-D-aspartate (NMDA) VYKLICKY, Ladilslav Jr 575 responses in cultured rat hippocampal neurones

Long-term modulation of the exercise ventilatory response MARTIN, Patricia A & MITCHELL, Gordon S 601 in goats

Somatostatin-mediated inhibitory postsynaptic potential in SHEN, K-Z &SURPRENANT, Annmarie 619 sympathetically denervated guinea-pig submucosal neurones

Evidence for active maternal-fetal transport of Na' across the STULC, Jan, STULCOVA, Barbora & SIBLEY, Colin P 637 placenta of the anaesthetized rat

Transport into retina measured by short vascular perfusion in GRATTON, J A, LIGHTMAN, S L & BRADBURY M W 651 the rat

Electrophysiological effects of tachykinins and capsaicin on MYERS, Allen C & UNDEM, Bradley J 665 guinea-pig bronchial parasympathetic ganglion neurones

The effect of epidural anaesthesia with 1% lidocaine on the pressor FRIEDMAN, D B,BRENNUM, J, SZTUK, F, HANSEN, 0 B,CLIFFORD, P S, 681 response to dynamic exercise in man BACH, F, ARENDT-NIELSEN, L, MITCHELL, J H & SECHER, N H

Neural control of cardiovascular responses and of ventilation STRANGE, S, SECHER, N H, PAWELCZYK, J A, KARPAKKA, J, 693 during dynamic exercise in man C1 RISTENSEN, N J, MITCHELL, J H & SALTIN B

Rundown of N-methyl-D-aspartate channels during whole-cell ROSENMUND, Christian & WESTBROOK, Gary L 705 recording in rat hippocampal neurons: role of Ca 2' and ATP 2 Cytoplasmic Ca oscillation in rat megakaryocytes evoked by a UNEYAMA, Chikako, UNEYAMA, Hisayuki & AKAIKE, Norio 731 novel type of purinoceptor

Lateral hypothalamic lesions alter baroreceptor-evoked inhibition NISSEN, Ralph, CUNNINGHAM, J Thomas & RENAUD, Leo P 751 of rat supraoptic vasopressin neurones T eJunlo Ph soo yNoe m e 193Vo67

TITLE AUTHOR PAGE

Calcium channel currents recorded from isolated myocytes of rat LANGTON, P D I basilar artery are stretch sensitive

Simultaneous oscillations in the membrane potential of pig VON DER WELD, Pierre-Yves & BINY, Jean-Louis 13 coronary artery endothelial and smooth muscle cells

Evidence that distinct neural pathways mediate parasympathetic CANNING, Brendan J & UNDEM, Bradley J 25 contractions and relaxations of guinea-pig trachealis

M, muscarinic receptors increase calcium current and GALLO, Maria Pia, ALLOATTi, Giuseppe, EVA, Carola, 41 phosphoinositide turnover in guinea-pig ventricular cardiocytes OBERTO, Alessandra & LEVI, Renzo Cesare

Cholinergic neuromusclar transmission in the longitudinal CousINS, Helen M, EDWARDS, F R, HIRST, G D S & WENDT, I R 61 muscle of the guinea-pig ileum 2 Evidence for multiple open states of the Ca ' channels in smooth NAKAYAMA, S & BRADING, Alison F 87 muscle cells isolated from the guinea-pig detrusor 2 Inactivation of the voltage-dependent Ca ' channel current in NAKAYAMA, S & BRADING, Alison F 107 smooth muscle cells isolated from the guinea-pig detrusor

Space and time characteristics of transmitter release at the GIROD, Romain, CORRtGES, Philippe, JACQUET, Jean 129 nerve-electroplaque junction of Torpedo & DUNANT, Yves

Role of 5-HT3 receptors in peristaltic reflex elicited by stroking NEYA, Toshiaki, MIZUTANI, Masatoshi & YAMASATO, Teruhiro 159 the mucosa in the canine jejunum

The electrophysiological effects of endogenous GABA in the STAPELFELDT, W H, PARKMAN, H P & SZURSZEWSKI, J H 175 guinea-pig inferior mesenteric ganglion

Enteric GABA-containing nerves projecting to the guinea-pig PARKMAN, H P, STAPELFELDT, W H, WILLIAMS, C L, LENNON, V A 191 inferior mesenteric ganglion modulate acetylcholine release & SZURSZEWSKI, J H

Hypothalamic modulation of splenic natural killer cell activity KATAFUCHI, Toshihiko, IcHiJo, Tomoyasu, TAKE, Sachiko & 209 in rats HORI, Tetsuro

Task-related changes in the effect of magnetic brain stimulation NIELSEN, J, PETERSEN, N, DEUSHCL, G & BALLEGAARD, M 223 on spinal neurones in man

Phorbol esters enhance synaptic transmission by a presynaptic, PARFITr, Karen D & MADISON, Daniel V 245 calcium-dependent mechanism in rat hippocampus 2 Modulation of basal L-type Ca ' current by adenosine in ferret Qu, Yusheng, CAMPBELL, Donald L, WHORTON, A Richard & 269 isolated right ventricular myocytes STRAUSS, Harold C 2 Modulation of L-type Ca ' current by extracellular ATP in ferret Qu, Yusheng, CAMPBELL, Donald L & STRAUSS, Harold C 295 isolated right ventricular myocytes

Ultra-deep blockade of Na' channels by a quaternary ammonium GINGRICH, K J, BEARDSLEY, D & YUE, D T 319 ion: catalysis by a transition-intermediate state?

Buffering of calcium influx by sarcoplasmic reticulum during the JANCZEWSKI, Andrzej M & LAKATrA, Edward G 343 action potential in guinea-pig ventricular myocytes

Renal sympathetic responses to conflicting baroreceptor inputs: HALLIWELL, John R, MINISI, Anthony, J, SMITH, Michael L 365 rapid ventricular pacing in dogs & ECKBERG, Dwain L

Detection of weak synaptic interactions between single Ia afferent CONWAY, Bernard A, HALLIDAY, David M & ROSENBERG, Jay R 379 and motor-unit spike trains in the decerebrate cat

Motoneuronal output and gradation of effort in attempts to GANDEVIA, S C, MACEFIELD, V G, BIGLAND-RITCHIE, B, 411 contract acutely paralysed leg muscles in man GORMAN, R B & BURKE, David

The firing rates of human motoneurones voluntarily activated in MACEFIELD, V G, GANDEVIA, S C, BIGLAND-RITCHIE, B, 429 the absence of muscle afferent feedback GORMAN, R B & BURKE, David

Recruitment of motor units in response to transcranial magnetic BAWA, Parveen & LEMON, Roger N 445 stimulation in man

Pacemaker potentials in lymphatic smooth muscle of the VAN HELDEN, Dirk F 465 guinea-pig mesentery

Evidence for all-or-none regulation of neurotransmitter release: PERKEL, David J & NICOLL, Roger A 481 implications for long-term potentiation TITLE AUTHOR PAGE

Corticocortical inhibition in human motor cortex KUJIRAI, T, CARAMIA, M D, ROTHWELL, J C, DAY, B L, THOMPSON, 501 P D, FERBERT, A, WROE, S, ASSELMAN, P & MARSDEN, C D

Changes in global cerebral blood flow in humans: effect on RAMSAY, S C, MURPHY, K, SHEA, S A, FRISTON, K J, 521 regional cerebral blood flow during a neural activation task LAMMERTSMA, A A, CLARK, J C, ADAMS, L, Guz, A & FRACKOWIAK, R S J

Mechanisms underlying enhanced responses of J receptors of ANAND, Ashima, PAINTAL, A S & WHITTERIDGE, D 535 cats to excitants in pulmonary oedema

Regulation of fluid secretion and intracellular messengers in ASHTON, N, EVANS, R L, ELLIOT, A C, GREEN, R & ARGENT, BE 549 isolated rat pancreatic ducts by acetylcholine 2 Effect of isoprenaline on Ca channel current in single smooth MURAKI, K, BOLTON, T B,IMAIZUMI, Y & WATANABE, M 563 muscle cells isolated from taenia of the guinea-pig caecum

The modulatory effects of endothelin-1, carbachol and Wu, Mei-Lin & TSENG, Yung-Zu 583 isoprenaline upon Na'-H' exchange in dog cardiac Purkinje fibres

Theophylline affects three different potassium currents in MUNAKATA, Mitsutoshi & AKAIKE, Norio 599 dissociated rat cortical neurones

The anion transport inhibitor DIDS increases rat hepatocyte K' WEHNER, Frank, ROSIN-STEINER, Sigrid, BEETZ, Gabriela & 617 conductance via uptake through the bilirubin pathway SAUER, Heinrich

Interstitial glucose and lactate balance in human skeletal muscle ROSDAHL, H, UNGERSTEDT, U, JORFELDT, L & HENRIKSSON, J 637 and adipose tissue studied by microdialysis

Activation and inactivation of the bursting potassium channel EDRY-SCHILLER, Jackie & RAHAMIMOFF, Rami 659 from fused Torpedo synaptosomes

Selective brain cooling in goats: effects of exercise and BAKER, M A & NIJLAND, M J M 679 dehydration

Analysis of co-ordination between breathing and exercise rhythms BERNASCONI, Paolo & KOHL, Jana 693 in man

Effects of sympathetic nerve stimulation on the sino-atrial node of CHOATE, J K, EDWARDS, F R, HIRST, G D S & O'SHEA, J E 707 the guinea-pig

Synaptic- and agonist-induced chloride currents in neonatal rat KRUPP, J & FELTZ, P 729 sympathetic preganglionic neurones in vitro

Stable co-expression of calcium channel a, 3 and a2, subunits WELLING, Andrea, BOSSE, Eva, CAVALIt, Adolfo, 749 in a somatic cell line BOTTLENDER, Ronald, LUDWIG, Andreas, NASTAINCZYK, Wolfgang, FLOCKERZI, Veit & HOFMANN, FRANZ

Adenosine-activated potassium current in smooth muscle cells DART, C &STANDEN, N B 767 isolated from the pig coronary artery

Behaviour of short and long latency reflexes in fatigued human DUCHATEAU, J & HAINAUT, K 787 muscles

Effects of axotomy or target atrophy on membrane properties of SANCHEZ-VIVES, Maria V & GALLEGO, Roberto 801 rat sympathetic ganglion cells

Photocurrents in retinal rods of pigeons (Colurnba livia): kinetics PALACIOS, A G & GOLDSMITH, T H 817 and spectral sensitivity TITLE AUTHOR PAGE Review Article Osteoclast function and its control ZAIDI, Mone, PAZIANAS, Michael, SliANKAR, Vijai S, BAX, 721 Bridget E, BAX, Christopher M R, BEVIS, Peter J R, STEVENS, Clifford, HUANG, Christopher L-H, BLAKE, David R, MOONGA, Baljit S & ALAM, A S M Towhidul Full Length Papers

Degree of breast emptying explains changes in the fat content, but DALY, Steven E J, Di Rosso, Annalisa, OWENS, Robyn A & 741 not fatty acid composition, of human milk HARTMANN, Peter E

The neuropeptide Phe-Met-Arg-Phe-NH 2 (FMRFamide) increases FALCONER, S W P, CARTER, A N, DOWNES, C P & COTTRELL, G A 757 levels of inositol 1,4,5-trisphosphate in the tentacle retractor muscle of Helix aspersa

The effect of the putative AT2 agonist, p-aminophenylalanine, COONEY, A S & FITZSIMONS JT 767 angiotensin II, on thirst and sodium appetite in rats

Thermoregulatory responses to /-adrenergic agonists at low CARLISLE, Harry J & STOCK, Michael J 775 ambient temperatures in the rat

Carbon dioxide-sensitive superior laryngeal nerve afferents in the BRADFORD, A, NOLAN, P, O'REGAN, R G & MCKEOGIH, D 787 anaesthetized cat

Spread of the dorsal root reflex in an isolated preparation of BAGUST, J,CIHEN, Y & KERKUT, G A 799 hamster spinal cord

Correlation between spontaneous bursts of activity recorded CHEN, Y, BAGUST, J,KERKUT, G A & TYLER, A W 811 from the dorsal roots in an isolated hamster spinal cord preparation

Heart rate and blood pressure variability in subjects exposed to McKENZIE, I 825 simulated increases in gravity Rapid Communications Activity of inspiratory neurones of the ambiguus complex during DAWID-MILNER, M S, LARA, J P, MILAN, A & GONZALEZ-BARON, S 835 cough in the spontaneously breathing decerebrate cat

Acute systemic hypoxia and the surface ultrastructure and MIAN, Rubina, WESTWOOD, D, STANLEY, P, MARSHALL, Janice M & 839 morphological characteristics of rat leucocytes COOTE, J H

Stimulation of taurine efflux from human placental tissue by a SIIENNAN, D B, McNELL1E, S A & CURRAN, D E 843 hyposmotic challenge

Heat stress increases ammonia accumulation during exercise SNOW, Rodney J,FEBBRAIO, Mark A, CAREY, Michael F & 847 in humans HARGREAVES, Mark

Evidence for an age-dependent decrease in the immunoreactive SIAUD, Philippe, BARBANEL, Gerard, GIVALoIs, Laurent, REYMOND, 851 prolactin-containing terminals of the median eminence of Marianne J,BALMEFREZOL, Monique & ASSENMACHER, Ivan male rats THE BEST PHYSIOLOGY TITLES FROM OXFORD Special Christmas Offer to members of the Physiological Society 25% discount on the titles below Order your copies on the following order form (This offer is not available through bookshops)

The Central Nervous System A PRACTICAL APPROACH TO PHYSIOLOGY Structure and Function Biomechanics - Materials: A Practical Approach Per Brodal Edited by Julian F. V. Vincent A superb, illustrated textbook of neuroanatomy, ideal for medical students. The mechanical testing of biological materials presents many difficulties. It provides beautifully clear descriptions of brain structures and This book provides protocols that successfully cross the barriers between incorporates modern neuroscience in the discussion of their functions. biologist and engineer and encourage effective interdisciplinary 0-19-505518-7, 478 pp., numerous line figures and table (OUP USA), communication. An iinvaluable experimental resource for researchers February 1993 £27.50 SPECIAL PRICE -£20.63 interested in these areas. Human Baroreflexes in Health and Disease Practical Approach Series No. 105 Dwain L. 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A rapidly expanding area which has resulted in 0-19-857693-5,588 pp., halftones, line illustrations, Clarendon Press, significant advances in the fields of zoology, physiology, and biomedical March 1992 £65.00 SPECIAL PRICE - £48.75 engineering, this book emphasizes the ways in which an animal's body responds to mechanical stress. Textbook of Endocrine Physiology Practical Approach Series No. 94 Second Edition 0-19-963268-5, 310pp., halftones, line drawings, tables,spiral bound (IRL Press), Edited by James E. Griffin, and Sergio R. Ojeda July 1992 £42.50 SPECIAL PRICE. £31.88 Athorough, well-balanced textbook for medical students, this book 0-19-963267-7,paperback £25.00 SPECIAL PRICE - £18.75 provides a broad, richly illustrated perspective of endocrine physiology. Ranging from molecular mechanisms of hormone action to clinical Monitoring Neuronal Activity: A Practical Approach assessment of endocrine function, the book draws on clinical examples to Edited by J. A. 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Steven Vogel Practical Approach Series No. 116 'It is difficult to find fault with this eccentric and lively account of 0-19-963348-7, 316 pp., halftones,line drawings, tables, spiral bound (IRL Press), the circulation... Istrongly recommend this book to anybody who February 1993 £32.50 SPECIAL PRICE - £24.3f teaches the physiology of the circulatory system, and to cardiolog- 0-19-963347-9, paperback £22.50 SPECIAL PRICE - £16.8S ists and all those who live in fear of them.' Nature For details of other Practical Approach titles send for our leaflet - contact Sharon Webster tel. +44-(0)865-56767; 0-19-508269-9,326 pp., line figures, graphs, paperback (OUP USA), fax +44-(o)865-267782 July 1993 £9.95 SPECIAL PRICE - £7.47 0-19-507155-7, hardback £19.95 SPECIAL PRICE - £14.96 \_ ---..... _ OXFORD UNIVERSITY PRESS Orern you Oxor Unvrst Prs books­

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Russell, IJ, Prof, BSc,MSc,PhD,FRS Rutishauser, S C B, BSc,PhD School of Biological Sciences, Biology Building, University of Dept of Physiological Sciences, University of Manchester. Sussex, Falmer, BRIGHTON, Sussex, BNI 9QG UK Stopford Building, Oxford Road, MANCHESTER, M 13 9PT 1990; Associate 1973; CI UK Tel (0273) 606755/678397 Fax(0273) 678433 1976; 15/18/23 AF Tel (061) 275 5466 Fax(061) 275 5572

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Russell, N J W, BSc,PhD Ryder, Kathryn Olivia, MB,BS,DPhil Biotechnology Dept, ICI Pharmaceuticals Division, Mereside, Dept of Cardiovascular Medicine, John Radcliffe Hospital, Alderley Park, MACCLESFIELD, SK1O 4TG UK Headington, OXFORD, OX3 9DU UK 1982; 07/23/26 AF 1993; 07/04/08 HCICMC Tel (0625) 512720 Fax(0625) 514463 Tel (0865) 220136 Fax(0865) 68844

Russell, W J, MB,BS,FFARCS,DIC Sacco, P, BSc/MSc,PhD Dept of Anaesthesia & Intensive Care, Royal Adelaide Hospital, Dept of Physiology, University College London, Gower Street, North Terrace, ADELAIDE, SA 5000 AUSTRALIA LONDON, WCIE 6BT UK 1975; 01/05/26 1993; 12/22/23 HP,MC,SC Tel (010 61) 8 224 5446 Fax(010 61) 8 232 6938 Tel (071) 387 7050 Ext 3218 Fax(071) 383 7005

Rutherford, 0 M (Olga), BA,MSc,PhD Sage, S 0, MA,PhD Dept of Physiology & Biophysics, St Mary's Hospital Medical Physiological Laboratory, Cambridge University, Downing School, Imperial College, Norfolk Place, LONDON, W2 IPG Street, CAMBRIDGE, CB2 3EG UK UK 1991; 03/04/08 SM Email [email protected] 1992; 22/21/11 CC Tel (0223) 333870 Fax(0223) 333840 Tel (071) 723 1252 Ext 5908 Fax(071) 723 7185

110 The PhysiologicalSociety

GRANTS AND FUNDING SCHEMES

TITLE PURPOSE ELIGIBILITY AWARDS APPLICATIONS

AFFILIATE To enable Affiliates to Affiliates in the British Isles Up to £600 Applications are TRAVEL GRANT attend meetings and who have not already considered at the end of SCHEME symposia overseas received a grant under this January, March, May, scheme July, September and (Eligibility continues for a November year after election to Membership of the Society)

BENEVOLENT To assist persons who have Physiologists, their staff and Depend on Applications are FUND contributed to the dependants circumstances reviewed immediately on advancement of Physiology receipt and are in necessitous circumstances

BURSARIES To support graduates Science graduates of Up to £2,000 Applications are undertaking MSc courses in institutions in the British considered at the end of physiological disciplines Isles May and November who cannot obtain funds from other sources

DALE FUND To promote new Physiologists working in the Up to £500 for travel Applications are physiological research in the British Isles grants for considered throughout British Isles collaborative the year research, learning new techniques, attending practical workshops and training courses. Up to £300 for travel to conferences and symposia

EASTERN To support centres of Centres of physiological Up to £10,000 per Applications are EUROPEAN AND scientific excellence where research in Eastern European annum, for up to considered at the end of THIRD'WORLD high quality physiological and Third World countries three years January, March, May, SUPPORT research is threatened by demonstrating scientific July, September and SCHEME lack of resources excellence and financial need November

EASTERN To allow physiological Physiologists in Eastern Up to £1,500 Applications must be EUROPEAN AND workers in Eastern European and Third World made by the host in the THIRD WORLD European and Third World countries seeking to British Isles, and are VISITOR FUND countries to visit undertake collaborative considered at the end of laboratories in the British research in the British Isles January, March, May, Isles July, September and November

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RUSHTON FUND To promote new Young physiologists working Up to £500 for travel Applications are physiological research in the in the British Isles who are grants for considered throughout British Isles not yet Members of the collaborative the year Society research, learning new techniques, attending practical workshops and training courses. For office uConfidential A IR ILAPPLICATION FORM FOR AFFILIATION TO THE PHYSIOLOGICAL SOCIETY

Name (INCAPrrAlS) ...... Date of Birth ......

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Members of The PhysiologicalSociety proposingCandidates should read the Guidelinesoverleaf and sign the following statement.

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On completion, please return this form to: The Physiological Society (Affiliation), PO Box 506, OXFORD OX1 3XE, (UK). w% GUIDELINES TO MEMBERS OF THE PHYSIOLOGICAL SOCIETY PROPOSING CANDIDATES FOR AFFILIATION

This form of association with the Society is intended for physiologists still in the early stages of their careers working in laboratories in the UK, Eire or abroad. It is open to postgraduate students registered for a higher degree in Physiology or a cognate subject and to postdoctoral workers who are not yet Members of the Society. It is expected that postdoctoral workers proposed as Affiliates will normally be (a) within the first five years of attaining a first professional qualification (PhD or medical degree) or (b) awaiting the outcome of their proposal for nomination for election to Membership of the Society. The Committee has authorised the Committee Secretary to consider and accept or reject proposals for Affiliation to the Society as they are received throughout the year, so that these can be processed quickly. The Committee Secretary regards himself as free to withdraw a proposal and return the papers to the Proposer. Affiliation is for a term of five years in the first instance. Affiliation must be renewed by payment of the appropriate fee at the start of each year (which for this purpose is the academic year, ie October to September). For administrative convenience, Affiliates registered after October will have to pay for the full year. The fees are determined from time to time by the Treasurer; they are currently:- UK & Eire Europe Non-Europe With Abstracts £10 £30 £35 Without Abstracts £ 5 £15 £20 All Affiliates receive copies of programmes, notices and the Society's Magazine. Affiliates can attend Meetings in theirown rightbut mustbe introduced bya Memberof theSociety when giving a Communication or Demonstration. Affiliates are not Members of the Society and do not have the right to vote at its General Meetings.

Field of Interest:

01 Anaesthesia 16 General Physiology 02 Anatomy &Embryology 17 Immunology 03 Biochemistry 18 Liver &Bile 04 Biophysics 19 Lipids &Steroids 05 Biomedical Engineering 20 Microbiology 06 Blood 21 Minerals, Bone &Teeth 07 Cardiovascular 22 Muscle & Exercise 08 Cellular &Tissue 23 Neuroscience 09 Comparative Physiology 24 Nutrition &Food 10 Electrolyte &Water Balance 25 Pathology 11 Endocrines 26 Pharmacology 12 Energy Metabolism & 27 Radiation Temperature Regulation 28 Renal 13 Environmental 29 Reproduction 14 Enzymes 30 Respiration 15 Gastrointestinal You may specify up to threefields of interest.

Special Interest Groups Current Codes AF Autonomic Function HS Higher Sensory Functions BB Blood-Brain Barrier IC Ionic Channels CC Cardiovascular Control ME Microvascular &Endothelial Physiology CI Comparative &Invertebrate Neuroscience MC Muscle Contraction CN Cellular Neurophysiology NE Neuroendocrinology CP Comparative Physiology PP Placental &Perinatal Physiology DP Developmental Physiology RP Renal Physiology EM Epithelia &Membrane Transport RE Respiratory Physiology GI Gastrointestinal Tract SC Sensorimotor Control HC Heart/Cardiac Muscle SM Smooth Muscle HI History of Physiology SP Somatosensory Physiology HP Human Physiology

06/93 iiAo;

D Yu Budko and L L Moroz from the Byelorussian State University with their E M Sedgwick and V S Weerasinghewith their Demonstrationof functionalbrain audio monitorfor physiologicaland neurobiologicalstudiesand a simple instrument imaging from scalp recordedpotentialsat the Southampton Meeting. for electricalclearingof inicroelectrodesat the Southampton Meeting.

A quiet moment at one of the Society stands at the Glasgow The Congress Congress. The Society's T-shirts soon sold out, but anyone Book: The Logic ted by interested in obtainingone of the small number of Congress of Life, available C . Boyd and D. N umbrellas remainingshould contactthe Adninistration from Oxford Office in Oxford. UniversityPress.

23 pThe Physiological 2 sm, S*1s*alsociety's Meetings stand at THE:CALLENGE OF]INTEGRATIVE PHYSIOGY If the Congress.

Back cover Imaging of drug concentrationsinsideand outsidea single cell. The frames are from a sequence of confocal microscope images of a single cell. The sequence beginsat top left, continuing horizontally along the top rowe and then in middle and lower rows. The images arefalse-colour representationsof fluorescenceintensity with red being high fluorescence and blue low fluorescence.the first images show the cell autofluorescence.In frame 9 the fluorescentanticancerdrugdoxorubicin was added to the externalmedium. The drugaccumulates in the cell membrane and in organellesin the cytoplasm to a level higher than that in the external solution. This work will be demonstratedat the King's CollegeMeeting ("Measurement of doxorubicintransportin single cells using confocal microscopy" by A Sardiniand PA McNaughton). II

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