Home About us Contact
|
Home About us Contact | ||
|
|
||
Histologic Severity (histologic + severity)
Selected AbstractsPharmacodynamics of Mycophenolate Mofetil after Heart Transplantation: New Mechanisms of Action and Correlations with Histologic Severity of Graft RejectionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2002Markus J. Barten The primary mechanism of action in vivo of mycophenolate mofetil (MMF) is believed to be inhibition of lymphocyte proliferation. We used novel assays of lymphocyte functions (pharmacodynamics, PD) in whole blood collected from rat heart allograft recipients treated with MMF to investigate the mechanisms of action of the active metabolite of MMF, mycophenolate acid (MPA) in vivo. Allograft recipients were treated orally once daily with 3 different doses of MMF. Seven days after transplantation, blood was collected 24 h after the penultimate dose and several timepoints after the last dose, after which grafts were removed for microscopic grading of rejection. Lymphocytes in whole blood samples were mitogen stimulated through calcium-dependent and -independent signaling pathways. Inhibition of PD was measured by lymphocyte proliferation and expression of several surface antigens on T cells, and was calculated as area under the time-inhibition of immune function effect curve (AUE0,24 h). We found that inhibition of lymphocyte proliferation and antigen expression by MPA correlated highly with MMF-dose, MPA level and with the histologic severities of graft rejection (p <,0.05). In summary, MPA suppressed lymphocyte proliferation and expression of T-cell surface antigens in whole blood collected from MMF-treated allograft recipients, thus demonstrating the multiple mechanisms of suppression of rejection on peripheral blood T cells after MMF treatment. [source] Oro-facial granulomatosis: Crohn's disease or a new inflammatory bowel disease?INFLAMMATORY BOWEL DISEASES, Issue 9 2005FRCP, Jeremy Sanderson MD Abstract Background: Oro-facial granulomatosis (OFG) is a rare chronic inflammatory disorder presenting characteristically with lip swelling but also affecting gingivae, buccal mucosa, floor of mouth, and a number of other sites in the oral cavity. Histologically, OFG resembles Crohn's disease (CD), and a number of patients with CD have oral involvement identical to OFG. However, the exact relationship between OFG and CD remains unknown. Methods: Thirty-five patients with OFG and no gut symptoms were identified from a combined oral medicine/gastroenterology clinic. All underwent a standardized assessment of the oral cavity and oral mucosal biopsy to characterize the number of sites affected and the type of inflammation involved. Hematological and biochemical parameters were also recorded. All 35 patients underwent ileocolonoscopy and biopsy to assess the presence of coexistent intestinal inflammation. Results: Ileal or colonic abnormalities were detected in 19/35 (54%) cases. From gut biopsies, granulomas were present in 13/19 cases (64%). An intestinal abnormality was significantly more likely if the age of OFG onset was less than 30 years (P = 0.01). Those with more severe oral inflammation were also more likely to have intestinal inflammation (P = 0.025), and there was also a correlation between the histologic severity of oral inflammation and the histologic severity of gut inflammation (P = 0.047). No relationship was found between any blood parameter and intestinal involvement. Conclusions: Endoscopic and histologic intestinal abnormalities are common in patients with OFG with no gastrointestinal symptoms. Younger patients with OFG are more likely to have concomitant intestinal involvement. In these patients, granulomas are more frequent in endoscopic biopsies than reported in patients with documented CD. OFG with associated intestinal inflammation may represent a separate entity in which granulomatous inflammation occurs throughout the gastrointestinal tract in response to an unknown antigen or antigens. [source] Quantitative Analysis of Inflammatory and Immune Responses in Dogs with Gastritis and Their Relationship to Helicobacter spp.JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2005Infection The present study sought to quantitatively examine mucosal inflammatory and immune responses in dogs with gastritis and the relationship of these responses to infection with Helicobacter. Gastric biopsies from 30 dogs were evaluated for B- and T-lymphocytes, neutrophils, eosinophils, macrophages, and mast cells. Mucosal atrophy, fibrosis, cellularity, and severity of gastritis were graded qualitatively. Messenger-RNA (mRNA) for actin, interleukin-1, (IL-1,), IL-4, IL-8, and IL-10, transforming growth factor beta (TGF-,), and interferon gamma (IFN-,) was quantified by polymerase chain reaction (PCR). The presence of Helicobacter spp. was determined by urease activity, histology, PCR, and enzyme-linked immunosorbent assay. mRNA for IL-1,, IL-8, IL-10, TGF-,, and IFN-, was detected in most dogs. IL-4 mRNA was detected in only 1 dog. Correlations were observed for IL-1, versus IL-8 and IL-10; IL-8 versus IL-10, IFN-,, and TGF-,; and IL-10 versus IFN-,. Mucosal pathology was related to cytokine mRNA expression (neutrophils to IL-8 and IFN-,, macrophages and lymphocytes to IFN-,, and fibrosis to IL-1,). Gastritis was categorized as lymphoplasmacytic in all dogs, and its histologic severity correlated with atrophy, infiltration with lymphocytes and macrophages, and expression of IL-10 and IFN-,. Of the dogs examined, 76.7% were infected with Helicobacter spp. Infection was associated with increased expression of TGF-, and fibrosis. Circulating anti- Helicobacter immunoglobulin G titers were higher in uninfected than infected dogs. We conclude that lymphoplasmacytic gastritis in dogs is characterized by concurrent activation of proinflammatory and immunomodulatory cytokines, with increased mRNA expression related to mucosal pathology. No significant associations between Helicobacter infection and proinflammatory cytokine expression, severity of gastritis, or differences in the pathogenicity of different Helicobacter spp. were found. [source] Glucocorticoid-induced leucine zipper is an endogenous antiinflammatory mediator in arthritisARTHRITIS & RHEUMATISM, Issue 9 2010Elaine Beaulieu Objective Glucocorticoid-induced leucine zipper (GILZ) is a glucocorticoid-induced protein, the reported molecular interactions of which suggest that it functions to inhibit inflammation. However, the role of endogenous GILZ in the regulation of inflammation in vivo has not been established. This study was undertaken to examine the expression and function of GILZ in vivo in collagen-induced arthritis (CIA), a murine model of rheumatoid arthritis (RA), and in RA synoviocytes. Methods GILZ expression was detected in mouse and human synovium by immunohistochemistry and in cultured cells by real-time polymerase chain reaction and permeabilization flow cytometry. GILZ function was assessed in vivo by small interfering RNA (siRNA) silencing using cationic liposome,encapsulated GILZ or control nontargeting siRNA and was assessed in vitro using transient overexpression. Results GILZ was readily detectable in the synovium of mice with CIA and was up-regulated by therapeutic doses of glucocorticoids. Depleting GILZ expression in vivo increased the clinical and histologic severity of CIA and increased synovial expression of tumor necrosis factor and interleukin-1 (IL-1), without affecting the levels of circulating cytokines or anticollagen antibodies. GILZ was highly expressed in the synovium of patients with active RA and in cultured RA synovial fibroblasts, and GILZ overexpression in synovial fibroblasts inhibited IL-6 and IL-8 release. Conclusion Our findings indicate that GILZ functions as an endogenous inhibitor of chronic inflammation via effects on cytokine expression and suggest that local modulation of GILZ expression could be a beneficial therapeutic strategy. [source] | ||||||||||