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Biomedical subjects

A G Bean

Publications and source records attributed to A G Bean.

10 recordsLinked to original sources

A role for BP-3/BST-1 antigen in early T cell development.

In the mouse thymus, pre-T cells are defined by their CD3(-)CD4(-)CD8(-) triple-negative, CD44lo/- CD25+ phenotype. We made a rat mAb IF-7, that, among all T cell subsets analyzed, reacted exclusively with pre-T cells. Molecular cloning revealed that the antigen recognized by IF-7 was identical to BP-3/BST-1, a glycosyl-phosphatidylinositol-linked, CD38-related molecule previously described as a possible co-activation molecule of pre-B cells. We found that IF-7 cross-linking enhances the proliferative response of sorted pre-T cells to anti-CD3 stimulation. In addition, IF-7 enhances and accelerates the development of fetal thymic organ culture (FTOC), although the gamma delta lineage is unaffected by the treatment. In addition, sorted IF-7+ pre-T cells give preferentially rise to alpha beta TCR+ thymocytes in FTOC. Our observations strongly suggest that BP-3/BST-1 is implicated in both early B and T cell growth and development, and is an early marker for the alpha beta lineage.

ADP-ribosyl Cyclase

Inflammatory bowel disease in C.B-17 scid mice reconstituted with the CD45RBhigh subset of CD4+ T cells.

Chronic inflammation developed spontaneously in the large intestine of C.B-17 scid mice restored with the CD45RBhigh subset of CD4+ T cells obtained from normal BALB/c mice. The inflammation, which extended diffusely from the cecum to the rectum, was localized to the lamina propria of mildly affected mice but became transmural in severely affected mice. Immunohistochemical and flow cytometric analyses showed that the inflammatory infiltrate contained numerous macrophages accompanied by moderate numbers of activated CD4+ lymphocytes. Some mice also had scattered multinucleated giant cells. Mucin depletion and epithelial hyperplasia resulting in glandular elongation and mucosal thickening were also consistently seen. Less frequent findings included ulceration with fibrosis, crypt abscesses, crypt loss, and granulomatous inflammation. Immunofluorescent analysis of inflamed large intestinal sections demonstrated increased epithelial expression of major histocompatibility class II antigens. The changes in the large intestine of these mice are similar to those seen in patients with idiopathic inflammatory bowel disease (Crohn's disease and ulcerative colitis). This murine model may be useful for studying mucosal immunoregulation as it relates to the pathogenesis and treatment of chronic inflammatory bowel diseases in the large intestine of human patients.

Animals

CD38 expression on mouse T cells: CD38 defines functionally distinct subsets of alpha beta TCR+CD4-CD8- thymocytes.

We have examined CD38 expression on mouse lymphocytes using the rat mAb NIM-R5 and demonstrate that CD38 expression is restricted to approximately 8% of thymocytes. Although CD38 is absent from the majority of CD4+CD8- and CD4-CD8+ T cells, we detected a strong correlation between CD38 expression and alpha beta+CD4-CD8- T cells in the thymus, with nearly 80% of alpha beta TCR+CD4-CD8- thymocytes being CD38+. Using heat stable antigen (HSA) and CD38, we divided alpha beta+CD4-CD8- thymocytes into four subsets: HSA+CD38-, HSA-CD38hi, HSA-CD38low and HSA-CD38-. Two established characteristics of alpha beta TCR+CD4-CD8- cells, bias towards V beta 8.2 TCR expression and high levels of IL-4 production, were used to establish a possible relationship between the above thymocyte subsets. Our present data show that the HSA+CD38- subset is not biased towards V beta 8.2 TCR expression whereas the HSA-CD38- subset does show this bias (approximately 47%). Neither of these subsets make IL-4 upon CD3 mediated stimulation. In contrast, the CD38+ subsets are heavily biased toward V beta 8.2 expression and produce large amounts of IL-4 upon stimulation, particularly the CD38low cells. Taken together, these data suggest that these four subsets represent various stages of a possible differentiation pathway for alpha beta TCR+CD4-CD8- cells, with the HSA+CD38- subset being the most immature while the HSA-CD38low subset is the most functionally mature. These characteristics support the view that alpha beta TCR+CD4-CD8- T cells represent an independent lineage with a distinct, but as yet obscure, role in immunity.

ADP-ribosyl Cyclase

Repeated resection for malignant liver tumours.

Fifteen repeat hepatic resections were performed on 12 patients with either recurrent or residual malignant tumours of the liver. Of these, one patient underwent three repeat resections and another underwent two. Five had primary liver liver tumours and seven had liver metastases. Planned, 'staged', repeat resections were performed on three patients because of multiple deposits of tumour, cirrhosis or extensive disease at initial presentation. There was no operative mortality. The period of follow-up from the time of repeat sections ranged between 4 months and 36 months during which two patients died from recurrent disease. The mean survival after the repeat resection was 16.8 months (range 4-36 months). Although technically demanding, repeat hepatectomy is feasible and provide similar benefits.

Aged

Interleukin 10 protects mice against staphylococcal enterotoxin B-induced lethal shock.

We investigated the ability of interleukin 10 (IL-10) to protect mice against lethal shock induced by staphylococcal enterotoxin B (SEB). Treatment of mice with IL-10 prevented the death of mice injected with SEB in a dose-dependent manner. IL-10-mediated protection was apparent when administered either prior to or concurrent with SEB but was less effective when administered following SEB injection. This observation indicates that IL-10 is capable of regulating T-cell activation in vivo.

Animals

Phenotypic characterization of chicken thymic stromal elements.

Phenotypic profiles of the thymic stromal components provide an excellent approach to elucidating the nature of the microenvironment of this organ. To address this issue in chickens, we have produced an extensive panel of 18 mAb to the thymic stroma. These mAb have been extensively characterized with respect to their phenotypic specificities and reveal that the stromal cells are equally as complex as the T cells whose maturation they direct. They further demonstrate that, in comparison to the mammalian thymus, there is a remarkable degree of conservation in thymic architecture between phylogenetically diverse species. Eleven mAb reacted with thymic epithelial cells: MUI-73 was panepithelium, MUI-54 stained all cortical and medullary epithelium but only a minority of the subcapsule, MUI-52 was specific for isolated stellate cortical epithelial cells, MUI-62, -69, and -71 were specific for the medulla (including Hassall's corpuscle-like structures), MUI-51, -53, -70, and -75 reacted only with the type-1 epithelium, or discrete regions therein, lining the subcapsular and perivascular regions and MUI-58 demonstrated the antigenic similarity between the subcapsule and the medulla. Seven other mAb identified distinct isolated stromal cells throughout the cortex and medulla. Large thymocyte-rich regions, which often spanned from the outer cortex to medulla, lacked epithelial cells. These mAb should prove invaluable for determining the functional significance of thymic stromal-cell subsets to thymopoiesis.

Animals

Item-domain relationships in the Adaptive Behavior Scale (ABS).

The internal consistency reliability of the domains on the Adaptive Behavior Scale was examined using ratings provided by client care-staff on 265 institutionalized, mentally retarded persons. Nine of the 10 Part I domains and 6 of the 14 Part II domains had coefficient alpha reliabilities of .80 or greater. An item analysis was obtained by correlating each ABS item with each domain score. About 62% of Part I items and 61% of Part II items were judged as satisfactory by item analytic criteria. The implications of these results for users of the ABS were discussed.

Adolescent