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Biomedical subjects

J Spencer

Publications and source records attributed to J Spencer.

At least 289 records · Page 16Linked to original sources

Effect of gastric irradiation on gastric secretion and histamine in mice.

Gastric irradiation selectively inhibits acid secretion. Histamine may have a role in the inhibitory process. Seven days after gastric irradiation with 9 Gy X-rays, mice underwent a stomach perfusion and secretion test. Under pentagastrin stimulation (62.5 micrograms/kg), acid and histamine secretion was significantly lower than that of the unirradiated controls, while pepsin and potassium outputs were unchanged. Histamine concentration in the oxyntic region of the stomach assayed after the perfusion test was significantly lower than that of controls. It is postulated that the fall in the endogenous histamine store may contribute to the reduction in acid production.

Animals↗

Relative allergenic potential of four proteases used as contact lens cleaners.

The general use of enzymatic cleaners for soft contact lenses has led to reports of incidents of allergic reactions in previously sensitized patients. In light of this, experiments were performed to assess the relative allergenic potential of four such enzymes: papain, subtilisin A, subtilisin B, and pancreatin. Mice immunized intraperitoneally (i.p.) with either subtilisin A or papain exhibited little serum immunoglobulin E (IgE), even after tertiary doses of protein. Primates immunized intradermally (i.d.) with the four enzymes showed various levels of response to challenges: none to papain, mild to moderate to subtilisin A and pancreatin, and severe to subtilisin B. Finally, guinea pigs instilled ocularly with enzymes weekly for 15 weeks exhibited significant hyperemia and chemosis only to the positive control protein, ovalbumin, and not to any of the enzymes tested. We conclude that three of the four enzymes tested have low potential to sensitize human beings, and, further, that animal models may find increased use in screening products of biotechnology.

Allergens↗

HLA-DR expression in human fetal intestinal epithelium.

Villus epithelial cells in fetal human small intestine are HLA-DR- until 17 weeks gestation. At 18 weeks HLA-DR begins to be expressed in the epithelial cells, usually at the villus tips. Of 13 specimens examined between 18 and 22 weeks gestation, two were HLD-DR-, seven had HLA-DR expressed only at the villus tips and in four most of the villus epithelial cells were HLA-DR+. The epithelium overlying the Peyer's patches in fetal intestine was also HLA-DR+. T cells in explant cultures of fetal intestine were activated in situ using pokeweed mitogen. The local cell mediated immune reaction increased expression of HLA-DR on the villus and crypt epithelial cells. Organ culture supernatants from explants treated with pokeweed mitogen induced HLA-DR expression on the HT-29 epithelial cell line; an effect inhibited by antibody against human interferon gamma.

Epithelium↗

Paraventricular nucleus stimulation causes gastroduodenal mucosal necrosis in the rat.

The effects of stimulation in the paraventricular nucleus (PVN) of the hypothalamus on the development of gastrointestinal ulceration have been examined in urethan-anesthetized male Sprague-Dawley rats. Electrical stimulation (200 microA, 60 Hz, 100-microseconds pulse width) in the PVN was performed for 1 h, after which samples of the stomach and duodenum were fixed for subsequent histological assessment of damage. Such damage was scored, blindly, on a 0 (normal) to 3 (severe) scale. Stimulation in the PVN resulted in necrosis and hemorrhage in both the stomach (mean damage score of 1.8 +/- 0.3) and duodenum (1.7 +/- 0.4). In contrast, similar stimulation in regions immediately adjacent to the PVN was found to be without significant effect on the stomach (0.3 +/- 0.1) or duodenum (0.6 +/- 0.2). In a second series of studies PVN stimulation following bilateral vagotomy resulted in damage scores (stomach: 0.2 +/- 0.1; duodenum: 0.1 +/- 0.1) that were significantly reduced compared with the PVN-stimulated vagal-intact group (P less than 0.05) but were not significantly different from the group stimulated in regions outside the PVN (P greater than 0.1). These data suggest an important role for PVN efferents influencing medullary vagal preganglionic neurons in the development of acute gastroduodenal ulceration.

Animals↗

The bad old days.

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Efficiency↗

Enteropathy-associated T cell lymphoma (malignant histiocytosis of the intestine) is recognized by a monoclonal antibody (HML-1) that defines a membrane molecule on human mucosal lymphocytes.

Enteropathy-associated T cell lymphoma (EATCL; malignant histiocytosis of the intestine) arises in patients with enteropathy, which in some cases is known to be a result of gluten sensitivity. The lymphoma arises in the intestine, where it may remain localized, although eventual dissemination is the rule. Intraepithelial tumour cells often are seen at the mucosal tumor margin. These features suggest that EATCL may be a tumor of intraepithelial lymphocytes. A monoclonal antibody (HML-1) has been produced recently that recognizes the entire intraepithelial lymphocyte population and 50% of lamina propria T cells but very few cells outside the mucosa. Immunocytochemistry has shown that all cases of enteropathy-associated T cell lymphoma studied are HML-1 positive and all peripheral T cell lymphomas and mucosal B cell lymphomas are HML-1 negative. This suggests strongly that EATCL is a tumor of mucosal T cells, possibly the intraepithelial T cell component.

Antibodies, Monoclonal↗

Stimulation of mucosal T cells in situ with anti-CD3 antibody: location of the activated T cells and their distribution within the mucosal micro-environment.

Mucosal T cells in explants of human fetal small intestine (17-20 weeks gestation) in organ culture were activated in situ using monoclonal anti-CD3 antibody. Changes in the distribution of T cells within the mucosa, and their phenotype, were monitored by immunohistochemistry on frozen sections. Anti-CD3 stimulated T cells (as determined by expression of CD25) were predominantly in the lamina propria and were rarely seen in the epithelium. In control cultures, after 72 h, CD3+ IEL decreased to low numbers compared to day zero. However, in cultures treated with anti-CD3, IEL numbers were maintained and in some experiments significantly increased compared to day zero levels. At onset of culture 50-60% of CD3+ IEL were CD4-, 8-, and virtually all were HML-1+. The T cell infiltrate into the epithelium induced by activation of lamina propria T cells with anti-CD3 was also mostly CD3+, 4-, 8-, HML-1+. These experiments provide strong evidence that increases in IEL numbers can be a consequence of lamina propria T cell activation.

Antibodies↗

Esophageal dilation as an outpatient procedure.

This report describes a ten year experience with esophageal dilation done on an outpatient basis for a variety of esophageal strictures. An account is given of the two main types of dilators used, showing no particular advantage of one type compared with the other for long term results. All types of strictures have been found to be suitable for this form of therapy. The low morbidity rate and lack of general anesthesia make these interventions ideal for outpatient procedures. Attention is drawn to the possibility that malignant disease may supervene in benign strictures or be missed initially, and frequent biopsies are advocated.

Adolescent↗

Gastrointestinal haemorrhage from a second source in patients with colonic angiodysplasia.

Angiodysplasia of the colon is increasingly recognized as a cause of obscure gastrointestinal haemorrhage. On review of 71 patients with angiodysplasia, 40 came to surgery. Of these, nine (22.5 per cent) were also found to have small bowel lesions, either at the original laparotomy (7) or later when further investigations were performed for recurrent bleeding. Angiodysplasia can only be confidently diagnosed as the source of blood loss if seen to be actively bleeding. If a synchronous small bowel lesion is seen, we recommend that it should be removed at the same time as the colectomy.

Blood Vessels↗

Natural history and surgical management of radiation enteritis.

Radiation enteritis is an increasing problem. The effect of ionizing radiation is due to a direct effect on proliferating cells and due to a progressive obliterative vasculitis. Predisposing factors include the dose of radiation, combination with chemotherapy, previous operations and vascular disease. Management is related to the stage of disease at presentation, and tailored to the clinical problem. Surgical management must take into account the poor healing associated with irradiated intestine.

Enteritis↗

Selective biopsy of human Peyer's patches during ileal endoscopy.

During routine lower gastrointestinal endoscopy of children for suspected chronic inflammatory bowel disease, it is possible to visualize lymphoid follicles (Peyer's patches) in the last few centimeters of the terminal ileum. Biopsy specimens have been taken from these Peyer's patches and the lymphoid cells have been isolated by collagenase digestion. The mean cell yield of Peyer's patch cells was 1.7 x 10(8) lymphocytes/g tissue. Isolated Peyer's patch cells were 26%-54% CD3+ (pan T cells), 14%-34% CD4+ (helper/inducer T cells), and 9%-17% CD8+ (suppressor/cytotoxic T cells). Twenty six percent to 48% of the Peyer's patch cells were B cells; less than 1% contained cytoplasmic immunoglobulin A. When stimulated in vitro with phytohemagglutinin or pokeweed mitogen, cells from Peyer's patches proliferated. The successful isolation of functional cells from Peyer's patches will now allow studies to be done at the afferent limb of mucosal immunoregulation in humans.

Adolescent↗

Immunology of gastrointestinal lymphoma.

Experimental work showing that IgA plasma cell precursors activated in gut associated lymphoid tissue (GALT) of rats and sheep migrate to the lamina propria of the gut via the regional lymphatics, mesenteric lymph node and blood, has been supported by immunohistochemical studies. In rats, immunoblasts with cytoplasmic IgA are present in the Peyer's patches in association with the high endothelial venules which is probably an important, though not the only, site of extravasation into the gut, whereas cells with cytoplasmic IgA are rarely observed in the dome regions of Peyer's patches. Immunohistochemical studies of human Peyer's patches have revealed differences between the distribution of cells with cytoplasmic IgA in man compared to rats. In man, immunoblasts with cytoplasmic IgA are not concentrated in the zone of cells containing the high endothelial venules, whereas they are present in the dome regions of the Peyer's patches. The following questions arise: Do precursors of IgA plasma cells activated in human GALT migrate to the lamina propria via the blood, but extravasate predominantly via the capillary network, rather than the high endothelial venules? or do IgA plasma cell precursors 'mature' in situ in the Peyer's patches of man and subsequently migrate laterally to seed the lamina propria? Three lines of evidence from studies of primary B cell lymphomas of GALT support the latter hypothesis: 1) Primary B cell lymphomas of the gut remain localized to GALT for long periods of time; 2) Histological studies of the lymphoid tissue in these lymphomas have shown a gradation of cell types, from the muscularis mucosae towards the mucosal epithelium, which strongly suggests that plasma cells develop in situ in the gut from the adjacent layers of cells; 3) Preliminary studies of DNA extracted from the blood-borne cells from patients with GALT-derived B cell lymphoma have failed to demonstrate the presence of clonal gene rearrangements. Normal and malignant human GALT contains a perifollicular population of B cells with centrocyte-like morphology which lack surface IgD. No direct equivalent can be detected in rodent Peyer's patches. Their quiescent nature and distribution in malignant GALT suggests that they are follicle centre cell-derived and precursors of immunoblasts and plasma cells. As such they may be memory B cells. Their association with epithelium is a consistent feature of normal and malignant GALT which is of unknown but undoubted significance. The function of intraepithelial T cells is still unknown. Malignant T cells in MHI may be derived from intraepithelial T cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Digestive System↗