DOCSLIB.ORG

(12) Patent Application Publication (10) Pub. No.: US 2011/0185439 A1 Gaitanaris Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

US 2011 0185439A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/0185439 A1 Gaitanaris et al. (43) Pub. Date: Jul. 28, 2011 (54) GPROTEIN COUPLED RECEPTORS AND Publication Classification USES THEREOF (51) Int. Cl. (75) Inventors: George A. Gaitanaris, Seattle, WA GOIN 33/48 (2006.01) (US); John E. Bergmann, Mercer AOIK 67/027 (2006.01) Island, WA (US); Alexander CI2N 15/87 (2006.01) Gragerov, Seattle, WA (US); John CI2N 5/10 (2006.01) Hohmann, Seattle, WA (US); C07K I4/47 (2006.01) Fusheng Li, Seattle, WA (US); C7H 2L/04 (2006.01) Linda Madisen, Seattle, WA (US); A63L/7088 (2006.01) Kellie L. McIlwain, Washington, A6IP 25/00 (2006.01) DC (US); Maria N. Pavlova, A6IP3/00 (2006.01) Seattle, WA (US); Demetri CI2O I/68 (2006.01) Vassilatis, Seattle, WA (US); A6IP 9/00 (2006.01) Hongkui Zeng, Shoreline, WA A6IP 700 (2006.01) (US) GOIN 33/53 (2006.01) (52) U.S. Cl. ..................... 800/3; 800/18: 800/8: 800/21: (73) Assignee: OMEROS CORPORATION, 435/325; 530/350,536/23.5; 514/44 R; 435/6.11; Seattle, WA (US) 435/6.13:435/7.1 (21) Appl. No.: 12/970,094 (57) ABSTRACT (22) Filed: Dec. 16, 2010 The present invention provides GPCR polypeptides and poly nucleotides, recombinant materials, and transgenic mice, as Related U.S. Application Data well as methods for their production. The polypeptides and polynucleotides are useful, for example, in methods of diag (63) Continuation of application No. 12/243,731, filed on nosis and treatment of diseases and disorders. The invention Oct. 1, 2008, now abandoned, which is a continuation also provides methods for identifying compounds (e.g., ago of application No. 10/527,265, filed on Jan. 26, 2006, nists or antagonists) using the GPCR polypeptides and poly now abandoned, filed as application No. PCT/US03/ nucleotides of the invention, and for treating conditions asso 28226 on Sep. 9, 2003. ciated with GPCR dysfunction with the GPCR polypeptides, (60) Provisional application No. 60/409,303, filed on Sep. polynucleotides, or identified compounds. The invention also 9, 2002, provisional application No. 60/461.329, filed provides diagnostic assays for detecting diseases or disorders on Apr. 9, 2003. associated with inappropriate GPCR activity or levels. Patent Application Publication Jul. 28, 2011 Sheet 1 of 31 US 2011/O185439 A1 O e Seqeed ysselo Patent Application Publication Jul. 28, 2011 Sheet 2 of 31 US 2011/O185439 A1 s Patent Application Publication Jul. 28, 2011 Sheet 3 of 31 US 2011/0185439 A1 £SSBIO Vsselo Patent Application Publication Jul. 28, 2011 Sheet 4 of 31 US 2011/0185439 A1 W W W W W W N |N M M W W W W W W N W Patent Application Publication Jul. 28, 2011 Sheet 5 of 31 US 2011/0185439 A1 Patent Application Publication Jul. 28, 2011 Sheet 6 of 31 US 2011/O185439 A1 „HI'50|| Patent Application Publication Jul. 28, 2011 Sheet 7 of 31 US 2011/0185439 A1 |N W W W W W W YN W W’H H Patent Application Publication Jul. 28, 2011 Sheet 8 of 31 US 2011/0185439 A1 SSSSSSSSSS 8 Patent Application Publication Jul. 28, 2011 Sheet 9 of 31 US 2011/0185439 A1 II'50|| Patent Application Publication Jul. 28, 2011 Sheet 10 of 31 US 2011/0185439 A1 Patent Application Publication Jul. 28, 2011 Sheet 11 of 31 US 2011/0185439 A1 Patent Application Publication Jul. 28, 2011 Sheet 12 of 31 US 2011/0185439 A1 Patent Application Publication Jul. 28, 2011 Sheet 13 of 31 US 2011/O185439 A1 s s Patent Application Publication Jul. 28, 2011 Sheet 14 of 31 US 2011/O185439 A1 Patent Application Publication Jul. 28, 2011 Sheet 15 of 31 US 2011/0185439 A1 SSEEIGN ?Ndrioffiueqd?G Patent Application Publication Jul. 28, 2011 Sheet 16 of 31 US 2011/0185439 A1 FIC, 1P Patent Application Publication Jul. 28, 2011 Sheet 17 of 31 US 2011/0185439 A1 Peptide æuouujoHDI Patent Application Publication Jul. 28, 2011 Sheet 18 of 31 US 2011/0185439 A1 Patent Application Publication US 2011/0185439 A1 ueudio§B?HS |eºupy[Jo,d?oou Patent Application Publication Jul. 28, 2011 Sheet 20 of 31 US 2011/0185439 A1 HowD Joideoou?una Patent Application Publication Jul. 28, 2011 Sheet 21 of 31 US 2011/0185439 A1 Neurotransmitter Peptide : - - - - - - - - in n Patent Application Publication Jul. 28, 2011 Sheet 22 of 31 US 2011/0185439 A1 plouesoola? Patent Application Publication Jul. 28, 2011 Sheet 23 of 31 US 2011/0185439 A1 Peptide £8ue?duo Z?ue?duO H_id #:: *.No.??ae» }}}}-----------FLU ±&********************************************* z***************w****** ********************************&&~~ ? ESS’e|O +--~~~~--~~~~*…*…***************************************************************** Patent Application Publication Jul. 28, 2011 Sheet 24 of 31 US 2011/0185439 A1 g-ºgÝ5)t######\*** **?¢) ?}+\######********************************************···---···---··· ??UITEEosselo Patent Application Publication Jul. 28, 2011 Sheet 25 of 31 US 2011/0185439 A1 FIG. 2I Patent Application Publication Jul. 28, 2011 Sheet 26 of 31 US 2011/O185439 A1 Genes : i Hypothalamus Amygdala i Brain Stem Cerebellum Cortex Frontal Cortex Hippocampus Adrenal Colon intestine Kidney Liver Lung is . Muscle Ovary PBL Prostate Skin Spleen Stornach Testis Thymus Thyroid Uterus Patent Application Publication Jul. 28, 2011 Sheet 27 of 31 US 2011/O185439 A1 8 i : : i polkul snukul SESL upeLoS ueeds US eyesold 19d AJeNO eSW 5un Keup'sJe. eugseu U000 eupy Sueye Line S Srdueodd H X900 euo Keio) uneqe.80 LeSueelepbuy Shujeelodh Patent Application Publication Jul. 28, 2011 Sheet 28 of 31 US 2011/0185439 A1 Patent Application Publication Jul. 28, 2011 Sheet 29 of 31 US 2011/0185439 A1 Patent Application Publication Jul. 28, 2011 Sheet 30 of 31 US 2011/0185439 A1 Patent Application Publication Jul. 28, 2011 Sheet 31 of 31 US 2011/O185439 A1 US 2011/O 185439 A1 Jul. 28, 2011 GPROTEIN COUPLED RECEPTORS AND and modulating compounds for use in the treatment and diag USES THEREOF nosis of a wide variety of disorders and diseases. SUMMARY OF THE INVENTION CROSS-REFERENCES TO RELATED APPLICATIONS 0007. The present invention provides GPCR polypeptides and polynucleotides, recombinant materials, and transgenic 0001. This application is a continuation of U.S. patent mice, as well as methods for their production. The polypep application Ser. No. 12/243,731, filed Oct. 1, 2008, now tides and polynucleotides are useful, for example, in methods pending, which is a continuation of U.S. patent application of diagnosis and treatment of diseases and disorders. The Ser. No. 10/527,265, filed Jan. 26, 2006, now abandoned, invention also provides methods for identifying compounds which is a U.S. national stage application of PCT Patent (e.g., agonists or antagonists) using the GPCR polypeptides and polynucleotides of the invention, and for treating condi Application No. PCT/US03/28226, filed Sep. 9, 2003, which tions associated with GPCR dysfunction with the GPCR claims the benefit under 35 U.S.C. S 119(e) of U.S. Provi polypeptides, polynucleotides, or identified compounds. The sional Patent Application No. 60/409,303, filed Sep. 9, 2002, invention also provides diagnostic assays for detecting dis and U.S. Provisional Patent Application No. 60/461,329, filed eases or disorders associated with inappropriate GPCR activ Apr. 9, 2003, where all of the above applications are incor ity or levels. porated herein by reference in their entireties. 0008. In one aspect, the invention features a variety of substantially pure GPCR polypeptides. Such polypeptides STATEMENT REGARDING SEQUENCE include: (a) polypeptides including a polypeptide sequence LISTING having at least 90%, 95%, 97%, 98%, or 99% identity to a polypeptide listed in Table 2; (b) polypeptides that include a 0002 The Sequence Listing associated with this applica polypeptide listed in Table 2; (c) polypeptides having at least tion is provided in text format in lieu of a paper copy, and is 90%.95%,97%.98%, or 99% sequence identity to a polypep hereby incorporated by reference into the specification. The tide listed in Table 2; and (d) polypeptides listed in Table 2. name of the text file containing the Sequence Listing is 0009 Polypeptides of the present invention also include variants of the aforementioned polypeptides, including all NG 1 0058 US3 SEQUENCELISTING..txt. The text file allelic forms and splice variants. Such polypeptides vary from is 4.87 MB, was created on Dec. 13, 2010, and is being the reference polypeptide by insertions, deletions, and sub submitted electronically via EFS-Web, concurrent with the stitutions that may be conservative or non-conservative, or filing of the specification. any combination thereof. Particularly desirable variants are those in which several, for instance from 50 to 30, from 30 to BACKGROUND OF THE INVENTION 20, from 20 to 10, from 10 to 5, from 5 to 3, from 3 to 2, or from 2 to 1 amino acids are inserted. Substituted, or deleted, in 0003. The invention relates to the fields of medicine and any combination. drug discovery. 0010 Polypeptides of the present invention also include 0004 Mammalian G protein coupled receptors (GPCRs) polypeptides that include an amino acid sequence having at least 30, 50, or 100 contiguous amino acids from any of the constitute a superfamily of diverse proteins with thousands of polypeptides listed in Table 2. Polypeptides of the invention members. GPCRs act as receptors for a multitude of different are desirably biologically active or are antigenic or immuno signals. Chemosensory GPCRs (csGPCR) are receptors for genic in an animal, especially in a human. sensory signals of external origin that are sensed as odors, 0011. The polypeptides of the present invention may be in pheromones, or tastes. Most other GPCRs respond to endog the form of the “mature' polypeptide, or may be a part of a enous signals, such as peptides, lipids, neurotransmitters, or larger polypeptide Such as a precursor or a fusion protein.
Recommended publications
  • General Pathomorpholog.Pdf

    General Pathomorpholog.Pdf

    Ukrаiniаn Medicаl Stomаtologicаl Аcаdemy THE DEPАRTАMENT OF PАTHOLOGICАL АNАTOMY WITH SECTIONSL COURSE MАNUАL for the foreign students GENERАL PАTHOMORPHOLOGY Poltаvа-2020 УДК:616-091(075.8) ББК:52.5я73 COMPILERS: PROFESSOR I. STАRCHENKO ASSOCIATIVE PROFESSOR O. PRYLUTSKYI АSSISTАNT A. ZADVORNOVA ASSISTANT D. NIKOLENKO Рекомендовано Вченою радою Української медичної стоматологічної академії як навчальний посібник для іноземних студентів – здобувачів вищої освіти ступеня магістра, які навчаються за спеціальністю 221 «Стоматологія» у закладах вищої освіти МОЗ України (протокол №8 від 11.03.2020р) Reviewers Romanuk A. - MD, Professor, Head of the Department of Pathological Anatomy, Sumy State University. Sitnikova V. - MD, Professor of Department of Normal and Pathological Clinical Anatomy Odessa National Medical University. Yeroshenko G. - MD, Professor, Department of Histology, Cytology and Embryology Ukrainian Medical Dental Academy. A teaching manual in English, developed at the Department of Pathological Anatomy with a section course UMSA by Professor Starchenko II, Associative Professor Prylutsky OK, Assistant Zadvornova AP, Assistant Nikolenko DE. The manual presents the content and basic questions of the topic, practical skills in sufficient volume for each class to be mastered by students, algorithms for describing macro- and micropreparations, situational tasks. The formulation of tests, their number and variable level of difficulty, sufficient volume for each topic allows to recommend them as preparation for students to take the licensed integrated exam "STEP-1". 2 Contents p. 1 Introduction to pathomorphology. Subject matter and tasks of 5 pathomorphology. Main stages of development of pathomorphology. Methods of pathanatomical diagnostics. Methods of pathomorphological research. 2 Morphological changes of cells as response to stressor and toxic damage 8 (parenchimatouse / intracellular dystrophies).
  • Stesura Seveso

    Stesura Seveso

    DOI: 10.4081/aiua.2020.2.158 ORIGINAL PAPER Evaluation of the influence of subinguinal varicocelectomy procedure on seminal parameters, reproductive hormones and testosterone/estradiol ratio Ünal Öztekin, Mehmet Canikliog˘lu, Sercan Sarı, Volkan Selmi, Abdullah Gürel, Mehmet S¸akir Tas¸pınar, Levent Is¸ıkay Bozok Unıversıty Faculty of Medicine, Department of Urology, Yozgat, Turkey. Summary Objective: Varicocele is the most commonly ly identified (1). There is also limited evidence of how surgically curable cause of male infertility. Leyding cells and testosterone production are affected However, the mechanisms related to the effect of reducing fer- after varicocelectomy and how much it changes testos- tility potential have not been clearly identified. The aim of this terone production (5). study was to investigate the effects of varicocelectomy on semen parameters, reproductive hormones and testosterone / In the literature, it is generally indicated that Leydig cell estradiol ratio. function is negatively affected in varicocele patients with Matherial and methods: Fifty seven patients outcomes were decreased testosterone production and that also hor- evaluated before and 6 months after subinguinal microsurgical mone level is improved by varicocelectomy (4, 6, 7). varicocelectomy. Semen parameters, reproductice hormones Studies on rats have shown pathological changes such as and testosteron/estradiol ratio results of patients were com- increased apoptosis of Leydig and Sertoli cells causing pared retrospectively. decreased viability and testosterone synthesis due to Results: The mean age was 26.8 years. Fifty four (94.7%) varicocele (8, 9). However, there are studies advocating patients had grade 3 and 3 (5.3%) patients had grade 2 varic- that varicocelectomy has no effect on serum testosterone ocele.
  • Classification of Thyroid Tumors Benign Tumors - Adenoma 1

    Classification of Thyroid Tumors Benign Tumors - Adenoma 1

    DERMATOPATHOLOGY PATHOLOGY OF ENDOCRINE SYSTEM Thyroid carcinoma, Hashimoto thyroiditis, Graves‘ disease, neuroendocrine tumor, Institute of Pathological Anatomy melanoma, pigmented naevus, psoriasis, eczema FM CU BA DERMATOPATHOLOGY • 10-year-old boy with a pigmented lesion on his shoulder, sharply demarcated from the surrounding skin, with a diameter of 2.3 cm, dark brown in color, without noticeable changes. CASE NO. 1 ➢Suggested examinations? ➢Your diagnosis? ➢Describe the microscopic finding. Pigmented nevus of the skin Congenital pigmented nevus of the skin PIGMENTED NEVUS • benign skin formation arising as a result of melanocyte accumulation • the most common skin lesion of the white race • most nevi form in childhood and adolescence Classification of nevi according to the position of growth in the skin • Junctional nevus - nests of melanocytes are found at the dermo-epidermal junction • Mixed nevus - nests of melanocytes are found at the junction but also in the dermis • Intradermal nevus - clusters of melanocytes are found in the upper part of the dermis WITHOUT connection with the epidermis Histological variants of pigmented nevus • Congenital nevus • Blue nevus • Halo nevus • Familial dysplastic nevus Mixed pigmented nevus Junctional pigmented nevus Intradermal pigmented nevus • 73-year-old patient was admitted to hospital for progressive weakness, shortness of breath. You notice that both the skin and the sclera are icteric. • laboratory hyperbilirubinemia, hypoalbuminemia and mineral imbalance, positive oncomarkers (S100) • abdominal ultrasound with spherical structures found in the liver parenchyma • personal medical history - malignant melanoma of the eye CASE NO. 2 30 years ago, CLL 3 years ago, now in remission ➢Suggested examinations? ➢Your diagnosis? ➢Complications? ➢Describe the microscopic finding.
  • Spontaneous Regression of Divided Nevus of the Eyelid Evaluated by Dermoscopy Leaving a Hypopigmented Lesion

    Spontaneous Regression of Divided Nevus of the Eyelid Evaluated by Dermoscopy Leaving a Hypopigmented Lesion

    Case Report Spontaneous regression of divided nevus of the eyelid evaluated by dermoscopy leaving a hypopigmented lesion Danang Tri Wahyudi1, Izzah Aulia2, Aida S.D. Hoemardani1, Agassi Suseno Sutarjo1 1. Department of Dermatology and Venereology, Dharmais National Cancer Hospital, Jakarta, Indonesia 2. Department of Dermatology and Venereology Faculty of Medicine Universitas Indonesia/ Dr. Cipto Mangunkusumo National Central General Hospital Jakarta, Indonesia Email: [email protected] Abstract Background: Divided nevus, also known as “kissing nevus,” is a rare form of congenital melanocytic nevus that occurs on opposing margins of upper and lower eyelids. A paucity of literature on this rare anomaly exists, with most being case reports and series. Moreover, regression of this lesion was rarely reported. Case Illustration: We present a rare case of congenital divided nevus of the eyelid that regressed after eight years, confirmed with dermoscopy. A siX-year-old boy presented to the Dharmais National Cancer Hospital with two pigmented macules on the upper and lower right eyelid since birth. A year ago, the lesions started gradually disappearing and were replaced by a hypopigmented area. We evaluated the clinical and dermoscopic findings for two consecutive years. The dermoscopy showed pseudopigment networks, surrounded by a hypopigmented area resembling a halo. The pigmented lesions cleared with no residual lesions. Discussion: The dermoscopic findings of the patient resemble a solar lentigo characterized by pseudopigment networks, a feature caused by the relatively flattened rete ridge on the face. The hypopigmented area reflects a regression process, like the halo nevus, and is accompanied by leukotrichia of the eyelashes, a feature usually found in patients with vitiligo.
  • Clinical Dermatology Notice

    Clinical Dermatology Notice

    This page intentionally left blank Clinical Dermatology Notice Medicine is an ever-changing science. As new research and clinical experience broaden our knowledge, changes in treatment and drug therapy are required. The editors and the publisher of this work have checked with sources believed to be reliable in their efforts to provide information that is complete and generally in accord with the standards accepted at the time of publication. However, in view of the possibility of human error or changes in medical sciences, neither the editors nor the publisher nor any other party who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect accurate or complete, and they disclaim all responsibility for any errors or omissions or for the results obtained from use of such information contained in this work. Readers are encouraged to confirm the information contained herein with other sources. For example and in particular, readers are advised to check the product information sheet included in the package of each drug they plan to administer to be certain that the information contained in this work is accurate and that changes have not been made in the recommended dose or in the contraindications for administration. This recommendation is of particular importance in connection with new or infrequently used drugs. a LANGE medical book Clinical Dermatology Carol Soutor, MD Clinical Professor Department of Dermatology University of Minnesota Medical School Minneapolis, Minnesota Maria K. Hordinsky, MD Chair and Professor Department of Dermatology University of Minnesota Medical School Minneapolis, Minnesota New York Chicago San Francisco Lisbon London Madrid Mexico City Milan New Delhi San Juan Seoul Singapore Sydney Toronto Copyright © 2013 by McGraw-Hill Education, LLC.
  • Identification of Hypothalamic Sites That Control Puberty Onset and Sexual Maturation

    Identification of Hypothalamic Sites That Control Puberty Onset and Sexual Maturation

    Identification of hypothalamic sites that control puberty onset and sexual maturation by Megan Louise Greenwald-Yarnell A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Neuroscience) in the University of Michigan 2013 Doctoral Committee: Professor Martin G. Myers, Jr., Chair Professor Robert Denver Professor Michael Lehman, University of Mississippi Medical Center Professor Sue Moenter Assistant Professor David Olson Professor Audrey Seasholtz Basic research is what I'm doing when I don't know what I'm doing. - Wernher von Braun © Megan Louise Greenwald-Yarnell 2013 Dedication Dedicated to my amazing husband, James. I am eternally grateful for your never-ending love, understanding and encouragement. ii Acknowledgements I’d like to acknowledge the support of my mentor, Martin Myers, and the entire Myers lab- past and present. The culture of cooperation and teamwork that Martin expects in his lab has made my time there truly enjoyable. I am so thankful that he welcomed me into the lab and allowed me to pursue my research interests, despite the fact that at times they were so very different from what the rest of the lab was working on. I’d like to thank Dr. Christa Patterson who has been so instrumental in my success in lab and also in maintaining my sanity over the years. Thank you to Meg Allison and Amy Sutton for the evenings of pizza and drinks in lab and for always being available to talk- whether the topic is science or personal. Without the guidance of former lab members Drs. Rebecca Leshan, Gwen Louis, Scott Robertson, Eneida Villanueva and Darren Opland early on, none of this would have been possible.
  • Bulletin of of Medicine Testicular

    Bulletin of of Medicine Testicular

    BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE JUNE 1948 TESTICULAR DYSFUNCTION* E. PERRY MCCULLAGH Cleveland Clinic, Cleveland, Ohio HEtestis is composed of two main parts and has two main functions. The tubule creates the male gamete, the sper- matozoon, and nourishes it till it passes to the epididymis where it is stored and matures from a state of relative immotidity to motility. The interstitial cells lie in compact groups between the tubules. They produce the male hormone which has many important effects, spermatogenic, masculinizing, and meta- bolic. In the immature testes the tubular cells are crowded, undifferen- tiated and the tubule not laminated. Leydig cells are poorly developed and simulate the fibroblasts from which they develop. The adult Leydig or interstitial cells lie in discrete masses in the intertubular spaces. These cells vary greatly in size, and have large granular nuclei. The smaller cells are elongated, the larger ones ovoid or polyhedral and are 20 or more microns in diameter. The larger cells have pale areas in their cytoplasm which appear to grow with the aging of the cell and form vacuoles. In their cytoplasm lie rod-shaped crystalloids and granules which react chemically as neutral fats and steroids. In the adult the tubule is composed of a thin basement membrane through which all nutriments must pass to the intertubular cells. Within the tubule are * Given October 16, 1947 at the 20th Graduate Fortnight of rhe New York Academy of Medicine. 3 4 2 342 THETE BULLETIN Figure 1. Normal testis of a boy 8 years and 10 months of age.
  • Determinants of Plasma Androgen and Estrogen Levels In

    Determinants of Plasma Androgen and Estrogen Levels In

    Determinants of Plasma Androgen and Estrogen Levels in Men The work presented in this thesis was conducted at the department of Internal Medicine of the Erasmus Medical Center Rotterdam and at the department of Endocrinology of the VU Medical Center Amsterdam Cover: spotted hyena by Bas Scheffers Financial support for the publication of this thesis was provided by: Ipsen Farmaceutica B.V., Goodlife Healthcare, Novartis Oncology, Organon NVO, Procter and Gamble Pharmaceuticals, Schering Nederland B.V., Eli Lilly Nederland B.V. en Novo Nordisk. Determinants of Plasma Androgen and Estrogen Levels in Men Determinanten van plasma androgeen en oestrogeenspiegels bij de man Proefschrift ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam op gezag van de rector magnificus Prof.dr. S.W.J. Lamberts en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op woensdag 20 september 2006 om 15:45 uur door Willem de Ronde geboren te Delft Promotiecommissie Promotoren: Prof.dr. F.H. de Jong Prof.dr. H.A.P. Pols Overige leden: Prof.dr. L.J. Gooren Prof.dr. A.J. van der Lely Prof.dr. D.E. Grobbee Contents Aim of the thesis 9 Chapter 1 The importance of oestrogens in males 13 Based on: de Ronde W, PolsHA, van Leeuwen JP, de Jong FH 2003 Clin Endocrinol (Oxf) 58:529-542 Chapter2 Associations of sex hormone binding globulin with non-SHBG bound 43 levels of testosterone and estradiol in independently living men de Ronde W, van der Schouw YT, Muller M, Grobbee DE, Gooren LJ, PolsHA, de Jong FH 2005
  • Photo Diagnosis

    Photo Diagnosis

    Photo Diagnosis Illustrated quizzes on problems seen in everyday practice Case 1 An 11-year-old boy presents with pain over the left clavicle after falling from an eight-foot high ladder and landing on a outstretched left hand. Questions 1. What is the diagnosis? 2. What is the significance? Answers 1. Fractured left clavicle. 2. The majority of clavicular fractures heal spontaneously through callus formation. Immobilization of the affected arm for pain control can be easily and effectively accomplished by an arm sling. A figure-of-eight splint offers no advantage over the sling and can be uncomfortable for some children. Inappropriate use of the splint may occasionally even lead to edema of the ipsilateral upper limb, compression of axillary vessels and brachial plexopathy. Provided by Dr. Alexander K.C. Leung; and Dr. Justine H.S. Fong, Calgary, Alberta. Share your photos and diagnoses with us! Do you have a photo diagnosis? Send us your photo and a brief text explaining the presentation of the illness, your diagnosis and treatment, and receive $25 per item if it is published. The Canadian Journal of Diagnosis 955, boul. St. Jean, suite 306, Pointe-Claire (Quebec) H9R 5K3 E-mail: [email protected] Fax: (514) 695-8554 The Canadian Journal of Diagnosis / January 2005 47 Photo Diagnosis Case 2 A 32-year-old former soccer player presents with recurrent attacks of excruciating pain in the right first metatarsophalangeal joint. The attacks have been occurring for the past six months. Questions 1. What is the diagnosis? 2. What is the significance? 3. What is the treatment? Answers 1.
  • High Frequency of Association of Rheumatic/Autoimmune Diseases

    High Frequency of Association of Rheumatic/Autoimmune Diseases

    Available online http://arthritis-research.com/content/3/6/362 Research article High frequency of association of rheumatic/autoimmune diseases and untreated male hypogonadism with severe testicular dysfunction F Javier Jiménez-Balderas*, Rosario Tápia-Serrano†, M Eugenia Fonseca‡, Jorge Arellano§, Arturo Beltrán*, Patricia Yáñez*, Adolfo Camargo-Coronel* and Antonio Fraga* *Departmento de Reumatología, Hospital de Especialidades, Centro Médico Nacional SXXI IMSS México, DF, México †Sección de Andrología, Hospital de Especialidades, Centro Médico Nacional SXXI IMSS México, DF, México ‡Laboratorio de Hormonas, Hospital de Especialidades, Centro Médico Nacional SXXI IMSS México, DF, México §Unidad de Investigación Médica en Inmunología, Hospital de Pediatría, Centro Médico Nacional SXXI IMSS México, DF, México Correspondence: F Javier Jiménez-Balderas MD, Pregonero #161, Col Fraccionamiento Colina del Sur, CP 01430, México, DF, México. Tel: +52 5 627 69 00, ext 13-15; fax: +52 5 584 00 89; e-mail: [email protected] Received: 10 January 2001 Arthritis Res 2001, 3:362-367 Revisions requested: 16 March 2001 This article may contain supplementary data which can only be found Revisions received: 25 July 2001 online at http://arthritis-research.com/content/3/6/362 Accepted: 7 August 2001 © 2001 Balderas et al, licensee BioMed Central Ltd Published: 12 September 2001 (Print ISSN 1465-9905; Online ISSN 1465-9913) Abstract Our goal in the present work was to determine whether male patients with untreated hypogonadism have an increased risk of developing rheumatic/autoimmune disease (RAD), and, if so, whether there is a relation to the type of hypogonadism. We carried out neuroendocrine, genetic, and rheumatologic investigations in 13 such patients and 10 healthy male 46,XY normogonadic control subjects.
  • United States Patent (10) Patent No.: US 7,657,310 B2 Buras (45) Date of Patent: Feb

    United States Patent (10) Patent No.: US 7,657,310 B2 Buras (45) Date of Patent: Feb

    USOO765731 OB2 (12) United States Patent (10) Patent No.: US 7,657,310 B2 Buras (45) Date of Patent: Feb. 2, 2010 (54) TREATMENT OF REPRODUCTIVE 4,867,164 A 9, 1989 Zabara ENDOCRINE DISORDERS BY VAGUS NERVE 4.909,263 A 3/1990 Norris ......................... 6O7/39 STMULATION 4,920,979 A 5, 1990 Bullara 5,025,807 A 6, 1991 Zabara (75) Inventor: William R. Buras, Friendswood, TX 5,074,868 A 12/1991 Kuzmak (US) 5,154,172 A 10/1992 Terry, Jr. et al. 5,179,950 A 1/1993 Stanislaw (73) Assignee: Cyberonics, Inc., Houston, TX (US) 5, 186,170 A 2f1993 Varrichio et al. (*) Notice: Subject to any disclaimer, the term of this 5,188,104 A 2f1993 Wernicke et al. patent is extended or adjusted under 35 U.S.C. 154(b) by 17 days. (21) Appl. No.: 11/340,309 (Continued) (22) Filed FOREIGN PATENT DOCUMENTS 22) Filed: Jan. 26, 2006 9 EP 1145736 10, 2001 (65) Prior Publication Data US 2007/O173891 A1 Jul. 26, 2007 (51) Int. Cl (Continued) A61N L/00 (2006.01) OTHER PUBLICATIONS (52) U.S. Cl. .......................................................... 6O7/2 (58) Field of Classification Search ..................... o, PCT US2007.000342 search Report (Aug. 30, 2007). 607/3, 45, 116, 118, 39, 46 (Continued) See application file for complete search history. Primaryy Examiner—George9. Manuel (56) References Cited (74) Attorney, Agent, or Firm—Williams, Morgan & U.S. PATENT DOCUMENTS Amerson P.C.; Timothy L. Scott 3,796,221 A 3/1974 Hagfors (57) ABSTRACT 4,305.402 A 12/1981 Katims 4.338,945 A 7, 1982 Kosugi et al.
  • Dermoscopy Patterns of Halo Nevi

    Dermoscopy Patterns of Halo Nevi

    OBSERVATION Dermoscopy Patterns of Halo Nevi Isabel Kolm, MD; Alessandro Di Stefani, MD; Rainer Hofmann-Wellenhof, MD; Regina Fink-Puches, MD; Ingrid H. Wolf, MD; Erika Richtig, MD; Josef Smolle, MD; Helmut Kerl, MD; H. Peter Soyer, MD; Iris Zalaudek, MD Background: Halo nevi (HN) are benign melanocytic globular and/or homogeneous patterns in more than 80% nevi surrounded by a depigmented area (halo). This study of HN. Follow-up of 33 HN revealed considerable size aims to evaluate the dermoscopic features of HN and their reduction of the nevus component, but this was not as- changes during digital dermoscopic follow-up and to in- sociated with significant structural changes. Of a total of vestigate the frequency of the halo phenomenon in a se- 475 melanomas, only 2 revealed an encircling halo, but ries of melanomas. both displayed clear-cut melanoma-specific patterns ac- cording to dermoscopy. Observations: In a retrospective study, digital dermo- scopic images of HN from patients who attended the Pig- Conclusions: Halo nevi exhibit the characteristic der- mented Skin Lesions Clinic of the Department of Der- moscopic features of benign melanocytic nevi, repre- matology, Medical University of Graz, between October sented by globular and/or homogeneous patterns that are 1, 1997, and March 31, 2004, were reviewed and classi- typically observed in children and young adults. Halo nevi fied by dermoscopic morphologic criteria. For HN that reveal considerable changes of area over time during digi- were followed up with digital dermoscopy, the percent- tal dermoscopic follow-up, albeit their structural pat- ages of changes in the size of the nevus and halo com- terns remain unchanged.