DOCSLIB.ORG

Review Article

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Review Article J Clin Pathol: first published as 10.1136/jcp.36.7.723 on 1 July 1983. Downloaded from J Clin Pathol 1983;36:723-733 Review article Granulomatous inflammation- a review GERAINT T WILLIAMS, W JONES WILLIAMS From the Department ofPathology, Welsh National School ofMedicine, Cardiff SUMMARY The granulomatous inflammatory response is a special type of chronic inflammation characterised by often focal collections of macrophages, epithelioid cells and multinucleated giant cells. In this review the characteristics of these cells of the mononuclear phagocyte series are considered, with particular reference to the properties of epithelioid cells and the formation of multinucleated giant cells. The initiation and development of granulomatous inflammation is discussed, stressing the importance of persistence of the inciting agent and the complex role of the immune system, not only in the perpetuation of the granulomatous response but also in the development of necrosis and fibrosis. The granulomatous inflammatory response is Macrophages and the mononuclear phagocyte ubiquitous in pathology, being a manifestation of system many infective, toxic, allergic, autoimmune and neoplastic diseases and also conditions of unknown The name "mononuclear phagocyte system" was aetiology. Schistosomiasis, tuberculosis and leprosy, proposed in 1969 to describe the group of highly all infective granulomatous diseases, together affect phagocytic mononuclear cells and their precursors more than 200 million people worldwide, and which are widely distributed in the body, related by http://jcp.bmj.com/ granulomatous reactions to other irritants are a morphology and function, and which originate from regular occurrence in everyday clinical the bone marrow.' Macrophages, monocytes, pro- histopathology. A knowledge of the basic monocytes and their precursor monoblasts are pathophysiology of this distinctive tissue reaction is included, as are Kupffer cells and microglia. Label- therefore of fundamental importance in the under- ling studies with tritiated thymidine have shown that standing of many disease processes. granuloma cells, including both epithelioid cells and Granulomatous inflammation is best defined as a multinucleated giant cells, are also of the same special variety of chronic inflammation in which cells lineage2-5 and it is claimed that monocytes in tissue on October 1, 2021 by guest. Protected copyright. of the mononuclear phagocyte system are pre- culture may develop into epithelioid cells and giant dominant and take the form of macrophages, cells.6 epithelioid cells and multinucleated giant cells. In The origin of tissue macrophages (histiocytes) most instances these cells are aggregated into well from bone marrow precursors via circulating mono- demarcated focal lesions called granulomas, cytes is now well established,7 the maturation pro- although a looser, more diffuse arrangement may be cess being accompanied by progressive morphologi- found. In addition there is usually an admixture of cal and functional changes which continue even other cells, especially lymphocytes, plasma cells and when macrophages enter the tissues.8 The produc- fibroblasts. tion of monocytes is under positive and negative Before considering the pathogenesis of feedback control, with peripheral macrophages and granulomatous inflammation it is essential to review lymphocytes secreting factors that are both our knowledge of the three fundamental cells stimulatory and inhibitory to stem cell proliferation involved, namely the macrophage, the epithelioid in the marrow.9 Recruitment and localisation of cell and the multinucleated giant cell. monocytes into inflammatory lesions is aided by two groups of substances. The emigration of monocytes from the circulation is promoted by chemotactic Accepted for publication 14 March 1983 agents including microbial products, complement 723 J Clin Pathol: first published as 10.1136/jcp.36.7.723 on 1 July 1983. Downloaded from 724 Williams, Williams components, fibrin degradation products and antibodies, similar to those presently available for lymphokines while the immobilisation of lymphocyte subsets'9 is the most hopeful approach. macrophages within a lesion is aided by other The ability to ingest a wide variety of substances lymphokines including migration inhibition and into membrane bound vacuoles (endocytosis) is a macrophage adhesion factors.'0 " Although distinctive but not unique property of mononuclear immigration from the circulation seems to be by far phagocytes. Two mechanisms are involved, the most important source of macrophages in the pinocytosis and phagocytosis. Macrophages take up inflammatory reaction, local macrophage mitosis fluids and soluble proteins, immune complexes, does occur.'2 However, perhaps due to hormones, lectins and other macromolecules by chromosomal instability, this seems to be limited to pinocytosis20 21 whereas larger particles are engulfed very few divisions."3 by phagocytosis. The process is initiated by interac- Light microscopy of routine haematoxylin and tion between a particle and a surface receptor which eosin stained sections does not allow macrophages then triggers intracytoplasmic contractile proteins, to be distinguished from other mononuclear cells in including actin and myosin, to create membrane an inflammatory infiltrate unless they contain movement and pseudopodial ingestion.20 22-24 recognisable ingested material. Macrophages may Macrophage surface receptors are of many types be round, oval or spindle shaped in outline with a and specificity. Particles opsonised by cytoplasm which varies from eosinophilic and finely immunoglobulin G and E interact with Fc granular to clear and vesicular. The nucleus has a receptors25 26 while those attached to the third com- smooth or sometimes indented membrane with ponent of complement bind to C3b receptors.27 marginated heterochromatin and usually a single Both Fc and C3b receptors may also react with nucleolus. On ultrastructural examination the cell immune complexes while non-immunological membrane is irregular, being thrown into folds and receptors exist for lectins,28 alternative pathway processes. Cytoplasmic organelles vary greatly complement activators29 and other particles. according to the functional activity of the cell8 and Particulate ingestion is followed by phagosome- include endoplasmic reticulum (rough and smooth), lysosome fusion allowing intracellular degradation mitochondria, Golgi complexes, microtubules, and microbial killing. Digestion of particulate mater- microfilaments and membrane bound vesicles, the ial and dead organisms is accomplished by lysosomal latter including primary and secondary lysosomes enzymes'3 but killing of micro-organisms depends and residual bodies. However, in the absence of on other methods, in particular the production of obviously phagocytosed material there is no ultra- superoxides, hydrogen peroxide and hydroxyl radi- structural feature that is absolutely diagnostic for cals30 and other microbicidal substances. The pro- http://jcp.bmj.com/ the macrophage. cess is aided by the presence of antibody, IgG for Enzyme histochemistry is more valuable in the bacteria, IgE for metazoa." tissue identification of cells of the mononuclear Intracellular killing of micro-organisms is greatly phagocyte series, but suffers from the disadvantage enhanced by the phenomenon of macrophage of requiring specially prepared material. activation,32 a change which is accompanied by Macrophages typically contain non-specific ester- morphological8 and many other functional altera- ases diffusely in the cytoplasm, and the presence of tions including the secretion of a range of different on October 1, 2021 by guest. Protected copyright. membrane bound lysosomal enzymes, especially substances, enhanced phagocytic capacity, and an acid phosphatase and lysozyme is also useful in their ability to recognise and kill tumour cells."' Activa- recognition. Furthermore, variations in the tion can be accomplished by immunoglobulins, cytoplasmic distribution of peroxidase correspond to immune complexes, activated complement compo- different stages in macrophage differentiation.'4 nents, lymphokines, and by non-immunological 5-nucleotidase, leucine aminopeptidase and alkaline agents such as bacterial endotoxin." phosphodiesterase I are cell membrane-associated Extracellular secretion by activated macrophages macrophage enzymes which have also been used as is now recognised as a most important function34 35 macrophage markers.'5 Intracellular localisation of and some idea of the myriad of secretory products macrophage products, notably alpha-i -antitrypsin,'6 can be obtained from the Table. It can be seen that also has a role in cell identification. However, it is among the factors produced are those with essen- the development of monoclonal antibodies to tially opposing effects, for example collagenase and specific cell types that holds the most promise for the fibrogenic substances, suggesting that there are very identification of mononuclear phagocyte cells.7 18 If subtle controls over secretion which at present are the various stages of functional differentiation of almost a complete mystery. Nevertheless it is known these cells are to be recognised morphologically that activation is not an "all or none" phenomenon, then immunohistology with specific monoclonal and that the function of activated macrophages can J Clin Pathol: first published as 10.1136/jcp.36.7.723 on 1 July 1983. Downloaded from Granulomatous inflammation-a
Load more

Recommended publications
  • Thrombokinetics in Giant Cell Arteritis, with Special Reference to Corticosteroid Therapy
    Ann Rheum Dis: first published as 10.1136/ard.38.3.244 on 1 June 1979. Downloaded from Annals of the Rheumatic Diseases, 38, 1979, 244-247 Thrombokinetics in giant cell arteritis, with special reference to corticosteroid therapy ANNA-LISA BERGSTROM, BENGT-AKE BENGTSSON, LARS-BERTIL OLSSON, BO-ERIC MALMVALL, AND JACK KUTTI From the Departments of Internal Medicine and Infectious Diseases, Eastern Hospital, University of Gothenburg, S-416 85 Gothenburg, Sweden SUMMARY Duplicate platelet survival studies were carried out on 8 patients with giant cell arteritis (GCA), once before the institution of any therapy, and the second time when they were in a com- pletely asymptomatic phase after having received corticosteroid treatment. The time interval be- tween the studies ranged between 5 and 14 months. In the first study the mean peripheral platelet count was 486 ±25 x 109/1 and in the second 326 ±25 x 109/1. The difference between the means was highly significant (P<0 001). The mean life-span of the platelets was normal in the duplicate experiments (6 * 7 ±0 * 3 and 7 *3 ±0 *4 days, respectively). Platelet production rate was significantly (P<0 001) raised in the first experiment but became normal in response to corticosteroid therapy. It is concluded that the thrombocytosis seen in GCA is reactive to the inflammation present in this disease, and it seems reasonable to assume that the reduction in the peripheral platelet count which occurs in response to corticosteroid therapy accurately reflects the clinical improvement of the patient. Thrombocytosis is frequently present in patients Table 1 Eight patients with GCA in whom duplicate platelet sutrvival studies were carried out with untreated giant cell arteritis (GCA) (Olhagen, http://ard.bmj.com/ 1963; Hamrin, 1972; Malmvall and Bengtsson, Patients Age Sex Time interval Maintenance.
    [Show full text]
  • Pigmentation Associated Histopathological Variations in Sympathetic Ophthalmia
    Br J Ophthalmol: first published as 10.1136/bjo.64.3.220 on 1 March 1980. Downloaded from British Jolarnal of Ophthalmology, 1980, 64, 220-222 Pigmentation associated histopathological variations in sympathetic ophthalmia GEORGE E. MARAK, JR., AND HIROSHI IKUI From the Department of Ophthalmology, Georgetown University, Washington, DC, USA, and the Department of Ophthalmology, Kyishia University, Fukiioka, Japani SUMMARY The severity of inflammation in sympathetic ophthalmia is related to the degree of pigmentation, and the granulomatous response seems to be related to pigmentation. Eosinophilia is also associated with pigmentation, but this association appears to be fortuitous and is a result of the association of eosinophilia with severity of the inflammation. Elsching presented his most confusing pearl to the reasonably be considered intermediate in pigmen- ophthalmological community when he proposed tation between North American black and white that sympathetic ophthalmia represented an autoim- populations. mune response to uveal pigment.12 Recent obser- The magnitude of choroidal thickening by the vations have raised considerable doubts about the inflammatory infiltrate, the intensity of tissue role of uveal pigment as the offending antigenin eosinophilia, and the proportion of the epithelioid sympathetic ophthalmia.34 The function of the uveal cell response in the choroid compared to the melanocytes in sympathetic ophthalmia is not well lymphocytic infiltration were rated by a single understood, but pigmentary disturbances occur
    [Show full text]
  • Fine Structure and Histochemistry of Epithelioid Cells in Sarcoidosis
    Thorax: first published as 10.1136/thx.29.1.115 on 1 January 1974. Downloaded from Thorax (1974), 29, 115. Fine structure and histochemistry of epithelioid cells in sarcoidosis E. M. VALERIE JAMES and W. JONES WILLIAMS Pathology Department, Welsh National School of Medicine, The Heath, Cardiff James, E. M. Valerie and Jones Williams, W. (1974). Thorax, 29, 115-120. Fine structure and histochemistry of epithelioid cells in sarcoidosis. In this fine structure study of epithelioid cells in the granulomata of sarcoidosis we confirm our previous findings that they appear to be synthesizing rather than phagocytosing cells. The numerous characteristic intracyto- plasmic vesicles, 0 5 ,u in size, are shown to contain mucoglycoprotein and only rarely acid phosphatase activity. Epithelioid cells show varying quantities of extravesicular acid phos- phatase activity which is sometimes on the outer surface of the protein-containing vesicles. The possible role of secretory products of epithelioid cells in the formation and persistence ofgranulomata is discussed. It is suggested that epithelioid cells may be forming lymphokines. We have previously demonstrated that the fine that of Ericsson and Trump (1965) using the lead structure of granulomata in sarcoidosis and tuber- nitrate Gomori technique. Substrate-free and sodium culosis (Jones Williams, Erasmus, James, and fluoride control blocks were also prepared. After being Davies, 1970), in the Kveim test lesion (Jones washed in acetate buffer solutions the tissues were post-fixed in Millonig's osmium tetroxide, dehydrated, Williams, 1972), and in chronic beryllium disease and embedded in Araldite. Sections were cut on an (Jones Williams, Fry, and James, 1972a) are LKB ultramicrotome and 0.5 ,u sections were stained http://thorax.bmj.com/ similar.
    [Show full text]
  • Biomaterials and the Foreign Body Reaction: Surface Chemistry Dependent Macrophage Adhesion, Fusion, Apoptosis, and Cytokine Production
    BIOMATERIALS AND THE FOREIGN BODY REACTION: SURFACE CHEMISTRY DEPENDENT MACROPHAGE ADHESION, FUSION, APOPTOSIS, AND CYTOKINE PRODUCTION by JACQUELINE ANN JONES Submitted in partial fulfillment of the requirements For the degree of Doctor of Philosophy Dissertation Advisor: James Morley Anderson, M.D., Ph.D. Department of Biomedical Engineering CASE WESTERN RESERVE UNIVERSITY May, 2007 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the dissertation of ______________________________________________________ candidate for the Ph.D. degree *. (signed)_______________________________________________ (chair of the committee) ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ (date) _______________________ *We also certify that written approval has been obtained for any proprietary material contained therein. Copyright © 2007 by Jacqueline Ann Jones All rights reserved iii Dedication This work is dedicated to… My ever loving and ever supportive parents: My mother, Iris Quiñones Jones, who gave me the freedom to be and to dream, inspires me with her passion and courage, and taught me the true meaning of friendship. My father, Glen Michael Jones, a natural-born teacher who taught me to be an inquisitive student of life, inspires me with his strength and perseverance, and gave me his kind, earnest heart that loves deeply and always
    [Show full text]
  • 2016 Essentials of Dermatopathology Slide Library Handout Book
    2016 Essentials of Dermatopathology Slide Library Handout Book April 8-10, 2016 JW Marriott Houston Downtown Houston, TX USA CASE #01 -- SLIDE #01 Diagnosis: Nodular fasciitis Case Summary: 12 year old male with a rapidly growing temple mass. Present for 4 weeks. Nodular fasciitis is a self-limited pseudosarcomatous proliferation that may cause clinical alarm due to its rapid growth. It is most common in young adults but occurs across a wide age range. This lesion is typically 3-5 cm and composed of bland fibroblasts and myofibroblasts without significant cytologic atypia arranged in a loose storiform pattern with areas of extravasated red blood cells. Mitoses may be numerous, but atypical mitotic figures are absent. Nodular fasciitis is a benign process, and recurrence is very rare (1%). Recent work has shown that the MYH9-USP6 gene fusion is present in approximately 90% of cases, and molecular techniques to show USP6 gene rearrangement may be a helpful ancillary tool in difficult cases or on small biopsy samples. Weiss SW, Goldblum JR. Enzinger and Weiss’s Soft Tissue Tumors, 5th edition. Mosby Elsevier. 2008. Erickson-Johnson MR, Chou MM, Evers BR, Roth CW, Seys AR, Jin L, Ye Y, Lau AW, Wang X, Oliveira AM. Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion. Lab Invest. 2011 Oct;91(10):1427-33. Amary MF, Ye H, Berisha F, Tirabosco R, Presneau N, Flanagan AM. Detection of USP6 gene rearrangement in nodular fasciitis: an important diagnostic tool. Virchows Arch. 2013 Jul;463(1):97-8. CONTRIBUTED BY KAREN FRITCHIE, MD 1 CASE #02 -- SLIDE #02 Diagnosis: Cellular fibrous histiocytoma Case Summary: 12 year old female with wrist mass.
    [Show full text]
  • Perivascular Epithelioid Cell Tumor of Gastrointestinal Tract Case Report and Review of the Literature
    Perivascular Epithelioid Cell Tumor of Gastrointestinal Tract Case Report and Review of the Literature Biyan Lu, MD, PhD, Chenliang Wang, MD, Junxiao Zhang, MD, Roland P. Kuiper, PhD, Minmin Song, MD, Xiaoli Zhang, MD, Shunxin Song, MD, Ad Geurts van Kessel, PhD, Aikichi Iwamoto, MD, PhD, Jianping Wang, MD, PhD, and Huanliang Liu, MD, PhD Perivascular epithelioid cell tumors of gastrointestinal tract (GI PECo- markers. Molecular pathological assays confirmed a PSF-TFE3 gene mas) are exceedingly rare, with only a limited number of published fusion in one of our cases. Furthermore, in this case microphthalmia- reports worldwide. Given the scarcity of GI PEComas and their associated transcription factor and its downstream genes were found to relatively short follow-up periods, our current knowledge of their exhibit elevated transcript levels. biologic behavior, molecular genetic alterations, diagnostic criteria, Knowledge about the molecular genetic alterations in GI PEComas and prognostic factors continues to be very limited. is still limited and warrants further study. We present 2 cases of GI PEComas, one of which showed an (Medicine 94(3):e393) aggressive histologic behavior that underwent multiple combined che- motherapies. We also review the available English-language medical Abbreviations: AML = angiomyolipoma, CCMMT = clear cell literature on GI PEComas-not otherwise specified (PEComas-NOS) and myomelanocytic tumor of the falciform ligament/ligamentum teres, discuss their clinicopathological and molecular genetic features. CCST = clear cell ‘‘sugar’’ tumor of the lung, CDK2 = cyclin- Pathologic analyses including histomorphologic, immunohisto- dependent kinase 2, C-MET = met proto-oncogene, CRP = C- chemical, and ultrastructural studies were performed to evaluate the reactive protein, CT = computed tomography, DCT = dopachrome clinicopathological features of GI PEComas, their diagnosis, and differ- tautomerase, GAPDH = glyceraldehyde-phosphate dehydrogenase, ential diagnosis.
    [Show full text]
  • Malignant Tenosynovial Giant Cell Tumor: the True €Œsynovial Sarcoma?€• a Clinicopathologic, Immunohistochemical
    Modern Pathology (2019) 32:242–251 https://doi.org/10.1038/s41379-018-0129-0 ARTICLE Malignant Tenosynovial Giant Cell Tumor: The True “Synovial Sarcoma?” A Clinicopathologic, Immunohistochemical, and Molecular Cytogenetic Study of 10 Cases, Supporting Origin from Synoviocytes 1 2 1 1 1 3 Alyaa Al-Ibraheemi ● William Albert Ahrens ● Karen Fritchie ● Jie Dong ● Andre M. Oliveira ● Bonnie Balzer ● Andrew L. Folpe1 Received: 5 July 2018 / Revised: 31 July 2018 / Accepted: 1 August 2018 / Published online: 11 September 2018 © United States & Canadian Academy of Pathology 2018 Abstract We present our experience with ten well-characterized malignant tenosynovial giant cell tumors, including detailed immunohistochemical analysis of all cases and molecular cytogenetic study for CSF1 rearrangement in a subset. Cases occurred in 7 M and 3 F (mean age: 52 years; range: 26–72 years), and involved the ankle/foot (n = 1), finger/toe (n = 3), wrist (n = 1), pelvic region (n = 3), leg (n = 1), and thigh (n = 1). There were eight primary and two secondary malignant 1234567890();,: 1234567890();,: tenosynovial giant cell tumors. Histologically, all cases showed definite areas of typical tenosynovial giant cell tumor. The malignant areas varied in appearance. In some cases, isolated malignant-appearing large mononuclear cells with high nuclear grade and mitotic activity were identified within otherwise-typical tenosynovial giant cell tumor, as well as forming larger masses of similar-appearing malignant cells. Occasionally, these nodules of malignant large mononuclear cells showed transition to pleomorphic spindle cell sarcoma, with varying degrees of collagenization and myxoid change. One malignant tenosynovial giant cell tumor was composed of sheets of monotonous large mononuclear cells with high nuclear grade, growing in a hyalinized, osteoid-like matrix, with areas of heterologous osteocartilaginous differentiation.
    [Show full text]
  • Avian Blood. the Transformed Cells Occurred in Incubated Blood
    THE FORMATION OF MACROPHAGES, EPITHEIID CELLS AND GIANT CELLS FROM LEUCOCYTES IN INCUBATED BLOOD * MAGARET REED LEWIS (From th Carxge Laboratory of Embryology, Johns Hopkixs edical Scho) While tissue cultures would seem to afford an appropriate technic for the study of the part taken by the white blood-cells in various conditions, this method has seldom been employed. In 1914 Awro- row and Tlmofejewskij studied the white blood-cells of leukemic blood in plasma cultures, Loeb (i92o) followed the amebocytes of the king crab in dotted blood, and Carrel (192I) observed the growth of the buffy coat of the centrifuged blood of the adult chicken in plasma cultures. The method by which the observations incor- porated in this paper were made is simpler than that of any of the above investigators, consisting merely of the incubation of hanging drops of blood taken, by means of a paraffined pipette, either from the heart or from the peripheral circulation. The transformation and growth of the leucocytes into macro- phages, epithelioid cells, and giant cells were observed in the blood of the chick embryo, young chicken, adult hen, mouse, guinea-pig and dog, and i human blood. In every kind of blood emined there developed first a large wandering cell, several times larger than any of the normal leucocytes, which was phagocytic for red blood- cells, melanin granules, carbon partides, dead granulocytes, and tuberde bacili Somewhat later there appeared a cell more like a prmitive mesenchyme cell, and still later the epithelioid cell was formed. This cell was sometimes binudeate and in some instances a :ypical multinudeated giant cell (Lahans giant cell) was formed.
    [Show full text]
  • The Pathogenesis of Giant Cell Arteritis: Morphological Aspects
    The morphology of GCA / C. Nordborg et al. The pathogenesis of giant cell arteritis: Morphological aspects C. Nordborg1, E. Nordborg2, V. Petursdottir1 1Department of Pathology, 2Department of ABSTRACT in GCA. When studying V-beta families Rheumatology, Sahlgrenska University The light-microscopic, electron-micro- of the T-cell infiltrate with flow cyto- Hospital, Göteborg, Sweden. scopic and immunocytochemical charac- metry, Schaufelberger et al. found that These studies were supported by grants teristics of giant cell arteritis (GCA) the infiltrating lymphocytes are polyclo- from the Göteborg Medical Society, the have been investigated in a number of nal (3). On the other hand, Weyand et Swedish Heart-Lung Foundation, the studies on temporal arteries. Arterial al. (4) demonstrated the identical clonal Swedish Rheumatism Association, Rune atrophy and calcification of the internal expansion of a small proportion of the och Ulla Amlöfs Stiftelse and Syskonen elastic membrane appear to be prere- T-lymphocytes in separate segments of Holmströms Donationsfond. quisites for the evolution of the inflam- the same artery, which indicates antigen Please address correspondence and reprint matory process. Foreign body giant cells stimulation. A correlation between va- requests to: Claes Nordborg, Department form close to calcifications, apparently rious infections and the onset of GCA of Pathology, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden. without connection with other inflam- has been reported; it has been speculated E-mail: [email protected] matory cells and probably by the fusion that infectious disorders might trigger the of modified vascular smooth muscle inflammatory process (5). Zoster-vari- Clin Exp Rheumatol 2000: 18 (Suppl. 20): cells.
    [Show full text]
  • In Vivo Studies of the Foreign Body Reaction to Biomedical
    IN VIVO STUDIES OF THE FOREIGN BODY REACTION TO BIOMEDICAL POLYMERS by Junghoon Yang Submitted in partial fulfillment of the requirements For the degree of Master of Science Thesis Adviser: Dr. James M. Anderson Department of Biomedical Engineering CASE WESTERN RESERVE UNIVERSITY May, 2013 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of Junghoon Yang candidate for the Master of Science in Biomedical Engineering. Chair of the Committee Dr. James M. Anderson Members of the Committee Dr. Horst von Recum Dr. Roger Marchant Date of Defense: March 7th, 2013 Table of Contents List of Tables………………………………………………………………………..ii List of Figures……………………………………………………………………….iv Abstract……………………………………………………………………………..vii Chapter I: Introduction………………………………………………………………1 Chapter II: Quantitative Versus Qualitative Assessment of the Extent of Foreign Body Reaction (Percent Fusion, Cell Density, and Nuclei Density)……...7 Materials and Methods……………………………………………………….11 Results………………………………………………………………………...31 Discussion……………………………………………………………………..65 References…………………………………………………………………….70 Chapter III: Controlling Fibrous Capsule Formation through Long-Term Down-Regulation of Collagen Type 1 (COL1A1) Expression by Nanofiber- Mediated siRNA Gene Silencing……………………………………………………….73 Materials and Methods…………………………………………………………75 Results…………………………………………………………………………..79 Discussion……………………………………………………………………….84 i List of Tables Chapter II Table 1. Animal Phenotype Table Indicating Strain, General Information, Specific Traits, and References………………………………………………………….9 Table 2. Quantitative Percent Fusion for PEU with Timepoints 14, 21, and 28 Days…..37 Table 3. Average Cell Density for PEU with Timepoints 14, 21, and 28 Days…………39 Table 4. Average Nuclei Density for PEU with Timepoints 14, 21, and 28 Days………41 Table 5. Qualitative Normalized Average Grading for PEU with Timepoints 14, 21, and 28 Days…………………………………………………………43 Table 6. Quantitative Percent Fusion for PET with Timepoints 14, 21, 28 Days ………45 Table 7.
    [Show full text]
  • Giant Cell Arteritis
    GIANT CELL ARTERITIS What is giant cell arteritis (GCA)? Giant cell arteritis (GCA) is a form of vasculitis—a family of rare disorders characterized by inflammation of the blood vessels, which can restrict blood flow and damage vital organs and tissues. Also called temporal arteritis, GCA typically affects the arteries in the neck and scalp, especially the temples. It can also affect the aorta and its large branches to the head, arms and legs. GCA is the most common form of vasculitis in adults over the age of 50. The most common symptoms of GCA include persistent, throbbing headaches, tenderness of the temples and scalp, jaw pain, fever, joint pain, and vision problems. Early treatment is vital to prevent serious complications such as blindness or stroke. GCA is typically treated with high doses of corticosteroids such as prednisone, sometimes in combination with other medications that suppress the immune system. Prompt treatment usually relieves symptoms, however GCA is a chronic condition with periods of relapse and remission, so ongoing medical care is usually necessary. Patients with GCA may also have symptoms of polymyalgia rheumatica (PMR), a closely related inflammatory disorder. Causes The cause of GCA is not yet fully understood by researchers. Vasculitis is classified as an autoimmune disorder—a disease which occurs when the body’s natural defense system mistakenly attacks healthy tissues. Researchers believe a combination of factors may trigger the inflammatory process. Studies have linked genetic factors, infectious agents, and a prior history of cardiovascular disease to the development of GCA. Who gets GCA? GCA is the most common form of vasculitis in older adults, affecting people over 50 years of age, with an average onset of 74 years of age.
    [Show full text]
  • Differentiation of Macrophages from Normal Human Bone Marrow in Liquid Culture
    Differentiation of macrophages from normal human bone marrow in liquid culture. Electron microscopy and cytochemistry. D R Bainton, D W Golde J Clin Invest. 1978;61(6):1555-1569. https://doi.org/10.1172/JCI109076. Research Article To study the various stages of human mononuclear phagocyte maturation, we cultivated bone marrow in an in vitro diffusion chamber with the cells growing in suspension and upon a dialysis membrane. At 2, 7, and 14 days, the cultured cells were examined by electron microscopy and cytochemical techniques for peroxidase and for more limited analysis of acid phosphatase and arylsulfatase. Peroxidase was being synthesized in promonocytes of 2- and 7-day cultures, as evidenced by reaction product in the rough-surfaced endoplasmic reticulum, Golgi complex, and storage granules. Peroxidase synthesis had ceased in monocytes and the enzyme appeared only in some granules. By 7 days, large macrophages predominated, containing numerous peroxidase-positive storage granules, and heterophagy of dying cells was evident. By 14 days, the most prevalent cell type was the large peroxidase-negative macrophage. Thus, peroxidase is present in high concentrations in immature cells but absent at later stages, presumably a result of degranulation of peroxidase-positive storage granules. Clusters of peroxidase-negative macrophages with indistinct borders (epithelioid cells), as well as obvious multinucleated giant cells, were noted. Frequently, the interdigitating plasma membranes of neighboring macrophages showed a modification resembling a septate junction--to our knowledge, representing the first documentation of this specialized cell contact between normal macrophages. We suggest that such junctions may serve as zones of adhesion between epithelioid cells.
    [Show full text]