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Biomedical subjects

H S el-Gabalawy

Publications and source records attributed to H S el-Gabalawy.

5 recordsLinked to original sources

Anti-inflammatory therapy.

The inflammatory response involves a complex set of stereotyped biochemical and cellular reactions that aim to eliminate pathogens. Systemic inflammatory disorders, such as rheumatoid arthritis and systemic lupus erythematosus, feature a persistent, uncontrolled inflammatory response that typically culminates in tissue damage. The control of this inflammatory response is of paramount importance in preventing irreversible tissue damage, as well as in controlling symptoms. NSAIDs and corticosteroids are the most effective agents currently available to control the clinical manifestations of inflammation, although they usually need to be used in conjunction with other "disease modifying" strategies in order to achieve optimum control of chronic inflammatory disorders. As with all pharmacologic therapy, the risk to benefit ratio of each agent needs to be considered carefully before embarking on extended courses of therapy. Strategies to minimize the long-term risks of NSAIDs and corticosteroids are continuing to evolve and hold the promise of greater safety without loss of efficacy.

Anti-Inflammatory Agents↗

The differential expression of a novel intestinal epithelial glycoprotein in various forms of inflammatory bowel disease.

A13D8 is a monoclonal IgM antibody that identifies an as yet unknown antigen that is expressed intensely and ubiquitously in enterocytes. Immunohistochemically, it was shown that A13D8 has a granular supranuclear staining pattern in columnar epithelial cells of normal small intestine and the colon. In ulcerative colitis, this staining pattern was retained. However, during active inflammation, staining also was evident in goblet cells. To test whether this feature of goblet cell staining was unique to ulcerative colitis, tissue sections from a variety of colitides were examined. Crohn's disease, infectious colitis, and ischemic colitis had similar staining patterns to that seen with ulcerative colitis. There was significantly more inflammation in the biopsies from patients with ulcerative colitis and Crohn's disease with positive goblet cell staining than in the biopsies from those patients with negative goblet cell staining. Almost all positive goblet cell staining in ulcerative colitis and Crohn's disease occurred in biopsies that were actively inflamed, whereas there was rare staining in biopsies that were noninflamed (regardless of whether or not there was active inflammation elsewhere in the colon). Ileal goblet cells stained positively with A13D8 only in cases of active ileitis. In cases of collagenous colitis, with comparable degrees of inflammation to that seen in ulcerative colitis and Crohn's disease, there was rarely goblet cell staining and in graft-versus-host disease goblet cell staining of A13D8 was not observed. The binding of A13D8 to tissue sections was completely inhibited by N-acetyl-D-galactosamine. These results, in conjunction with immunochemical studies, suggest that the antibody recognizes an N-acetyl-D galactosamine-containing epitope on a glycoprotein(s). In conclusion, these data suggest that A13D8 recognizes a glycoprotein expressed by intestinal columnar epithelial cells and during specific inflammatory states, particularly those associated with a neutrophilic infiltrate, becomes evident in goblet cells. Further work is required to establish the exact nature of this molecule and whether it is a pro- or anti-inflammatory factor.

Antibodies, Monoclonal↗

Immunohistologic study of T-cell receptor delta-chain expression in rheumatoid synovial membranes.

Lymphocytes expressing gamma delta T-cell receptors (TCRs) have been shown to be reactive to mycobacterial antigens as well as the so-called stress proteins. The detection of increased numbers of gamma delta cells in the synovial fluid and peripheral blood of some patients with rheumatoid arthritis has suggested a potential role for these lymphocytes in the pathogenesis of this disorder. Twenty-three rheumatoid synovial membranes were studied using immunohistology and monoclonal antibodies in an attempt to define the patterns of distribution of gamma delta T cells in rheumatoid synovitis. Consecutive sections were stained for T1(CD5), T4(CD4), T8(CD8), TAC(CD25), the delta-chain markers delta TCR1 and delta TCS1, and the beta-chain marker beta F1. Our results show some regional differences in the distribution of CD4 and CD8 cells, the former being prominent in the lymphocytic aggregates and the latter most prominent in diffuse infiltrates immediately adjacent to the synovial lining layer. All tissues showed extensive staining for beta F1; an estimated average of more than 90% of T cells expressed alpha beta TCR. The majority of samples showed limited staining for both delta-chain antibodies, with 20 of the 23 tissues appearing to have less than 1% of T lymphocytes expressing these markers. Three tissues stained extensively for both delta TCR1 and delta TCS1 in particular areas of the section. In these areas, small perivascular lymphocytic aggregates appeared to be composed mainly of gamma delta cells. TAC staining was virtually absent in all areas and tissues. It was concluded that the majority of T lymphocytes infiltrating rheumatoid synovial membranes express alpha beta TCR.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Rheumatoid↗

The histopathology of early synovitis.

Early diagnosis and therapeutic intervention are needed to prevent the morbidity related to erosive arthropathies such as rheumatoid arthritis (RA), yet it is difficult to distinguish various forms of synovitis early in the disease course. The availability of synovial tissue biopsy techniques has facilitated the analysis of synovial tissue from patients with early disease. Comparison of the histopathologic features of synovial tissue in early RA, established RA, and in non-RA synovitis has shown subtle, but potentially important differences in histologic features, cytokine and protease expression patterns, and apoptosis. Ultimately, it remains to be shown definitively that analysis of the histopathological features of synovial tissue early in disease is of independent value in identifying patients destined to have persistent synovitis or erosive disease, and in turn, in allocating patients to specific therapeutic strategies.

Adult↗