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J Spencer

Publications and source records attributed to J Spencer.

At least 271 records · Page 15Linked to original sources

Histamine, histamine formation capacity and gastrin in cysteamine-induced peptic ulcer.

We attempted to induce chronic peptic ulcer in the rat by injection of consecutive doses of cysteamine. We investigated the incidence of peptic ulceration and measured gastric mucosal histamine, histamine formation capacity (HFC), plasma gastrin and tissue (oesophagus, duodenum, liver and lung) histamine in rats 1, 7, 14, 21, and 28 days after injection of cysteamine-HCl (300 mg/kg s.c. and 100 mg/kg 8 h later). Saline injections were used in control rats. After 24 h all rats given cysteamine had duodenal ulcers and the ulcer incidences after 7 and 14 days were 60 and 40%, respectively. After Day 21 no ulcers were found. Microscopy revealed ulcer healing seen as epithelialized scars from Day 14 onwards. A rising incidence of gastric metaplasia of the duodenal mucosa was noted from Day 7 after cysteamine treatment, which may have pathophysiological significance. Gastric mucosal histamine was higher and plasma gastrin was lower after 24 h compared with controls and values obtained later in the study. Rats with duodenal ulceration had significantly higher gastric mucosal histamine than those without lesions and control rats. A direct relationship was found between plasma gastrin and HFC in rats given cysteamine. A small but significant increase in histamine content of the liver was also observed after 24 h. No significant changes were found in other tissue specimens. Thus, a rise in gastric histamine is associated with duodenal ulcers in this model.

Animals↗

Surgery for achalasia cardiae: the Dor operation.

This review describes our use of the Dor operation in the management of 22 patients with achalasia of the cardia over the period 1970 to 1989. There was a male to female ratio of 1.8:1. All presented with dysphagia of varying degree, with regurgitation (86%), weight loss (73%), pain (59%) and chest infections (14%) being associated symptoms. Two patients had undergone previous balloon dilatation, with temporary benefit. The morbidity was low and follow-up results were good in 94% of cases. None of the patients had symptoms of gastro-oesophageal reflux in the postoperative period. In our experience, the Dor modification of the Heller operation has yielded gratifying results.

Adolescent↗

Expression of disulfide-linked and non-disulfide-linked forms of the T cell receptor gamma/delta heterodimer in human intestinal intraepithelial lymphocytes.

Immunohistochemistry has been used to investigate disulfide- and non-disulfide-linked forms of the T cell receptor gamma/delta heterodimer (TcR gamma/delta) in blood and intestinal epithelium of normal human small intestine, intestine of patients with untreated coeliac disease (in whom T cells expressing TcR gamma/delta are disproportionately raised), intestine of patients with tropical malabsorption, and in the human fetus. In blood from adult volunteers, 90% of T cells expressing TcR gamma/delta use the disulfide-linked form. In contrast in the epithelium in normal small intestine, coeliac disease and tropical malabsorption, most of the T cells expressing TcR gamma/delta use the non-disulfide-linked form. This is especially prominent in untreated coeliac disease where the increase in TcR gamma/delta T cells is mainly restricted to those using the non-disulfide-linked form. In human fetal small intestinal epithelium, however, only cells using the disulfide-linked form are present. These variations in expression of different forms of TcR gamma/delta in the gut epithelium in different conditions suggests that antigen, or some as yet undefined factor may determine the frequency of each subpopulation.

Antibodies, Monoclonal↗

Isolated central nervous system granulomatosis resembling sarcoidosis.

Isolated central nervous system (CNS) granulomatosis resembling sarcoidosis occurred in a 30-year-old woman who had amenorrhea, ataxia, and obstructive hydrocephalus, and a 9-year course of progressive neurological deterioration with recurrent bouts of diabetes insipidus. Lamellar and nodular meningeal hyalinosis resembling amyloid was noted on an initial brain biopsy. At autopsy, the brain had a non-necrotizing granulomatous meningitis and ventriculitis, most prominent at the base of the brain, including the third ventricle and the hypothalamus, but there were no systemic granulomas.

Adult↗

Gastric histamine in a chronic duodenal ulcer model induced by partial thoracic irradiation.

In a new model, chronic duodenal ulcers are generated by irradiating the lower mediastinum of mice with single doses of X-rays. Histamine, a potent secretagogue, may have a role in the aetiology. Seven days after irradiation, the lag period for ulcerogenesis, mice were given a gastric perfusion test. In mice given irradiation to the lower mediastinum tissue histamine in the oxyntic region of the stomach assayed after perfusion was significantly lower than that of controls. Acid and peptic activity were not different from controls. Histamine release may mediate the abscopal ulcer without increasing acid and peptic activity.

Animals↗

Immunoproliferative small-intestinal disease. An immunohistochemical study.

We performed a detailed histological and immunohistological study on both fresh-frozen and paraffin-embedded tissue from full-thickness jejunal biopsy specimens taken from three patients with immunoproliferative small-intestinal disease (IPSID). In all three patients, the mucosal infiltrate consisted of "centrocyte-like" (CCL) cells forming lymphoepithelial lesions and plasma cells. In one patient, the mucosal infiltrate was strikingly follicular. Immunohistochemistry showed alpha 1 heavy chain, but no light chain, in the perinuclear space and cytoplasm of the CCL cells and in the plasma cells. In two patients, the plasma cells (but not the CCL cells) also contained alpha 2 heavy chain. In the case showing a follicular pattern, the extrafollicular CCL cells and most of the cells within the mucosal follicles expressed alpha 1 heavy chain, but a minor and variable population of cells expressed polytypic IgM. The dendritic reticulum cells stained for alpha 1 (but not alpha 2) heavy chain, mu chain, and both light chains. In all cases, the CCL cells did not stain for common acute lymphoblastic leukaemia antigen (CALLA); in the follicles, CALLA negative cells displaced a residual CALLA-positive population to the periphery and merged with the CALLA negative cells outside the follicles. These findings confirm the homology between IPSID and low-grade B-cell "Western" lymphomas arising in mucosa-associated lymphoid tissue; they suggest that the follicular pattern sometimes seen in these lymphomas is caused by selective colonization of reactive follicles by CCL tumor cells.

Adolescent↗

Heterogeneity in intraepithelial lymphocyte subpopulations in fetal and postnatal human small intestine.

Intraepithelial lymphocytes (IEL) are present in fetal human small intestine from 14 weeks' gestation independent of exogenous dietary or microbial antigens. We have now studied the heterogeneity of IEL in 18-22-week-old human fetal intestine and in postnatal small intestine by single and sequential immunoenzyme histochemistry. In normal children and adults, there were 6-27 CD3+ IEL per 100 epithelial cells, whereas in fetal gut there were 3-5 CD3+ IEL per 100 epithelial cells. Postnatal intestine contained a population of CD3-,7+, non-T cell IEL (7-25% of total CD7+). These cells were absent from fetal IEL but were occasionally seen in the fetal lamina propria. About 6% of CD3+ postnatal IEL were CD4-,8-. In contrast in the fetus, 35-70% of CD3+ IEL were subset negative. Since CD3 and CD7 are always co-expressed on fetal IEL, 28-58% of fetal IEL were also CD7+,4-,8-. Only about 20% of the CD3+ IEL expressed the gamma delta chains of the T cell antigen receptor. We conclude from these studies that CD3+,4-,8- T cells migrate to the epithelium in the absence of exogenous antigen and that there is a population of CD3-,7+ non-T cells in postnatal gut which is absent in fetal gut.

Biopsy↗

Histamine and duodenal ulceration in renal transplant recipients.

Six of 25 renal transplant recipients had a duodenal ulcer at endoscopy. Histamine concentration and the activity of histamine methyltransferase, the degrading enzyme of histamine, were measured in gastric mucosal biopsies obtained at endoscopy and compared with patients with duodenal ulcer but not undergoing transplant and with patients with an apparently normal stomach and duodenum. Histamine concentrations in the corpus (no ulcer, median: 151 nmol/g; DU, median: 122 nmol/g) and in the antrum (no ulcer, median: 118 nmol/g; with DU, median: 113 nmol/g) of renal transplant patients, irrespective of ulcer diagnosis, and in patients with a chronic duodenal ulcer (median corpus histamine: 137 nmol/g and median antral histamine: 126 nmol/g) were not different from one another but significantly lower than the corresponding values in normal subjects (median corpus histamine: 241 nmol/g, p less than 0.01, and median antral histamine: 178 nmol/g, p less than 0.05). Histamine concentration in the corpus was significantly higher than in the antrum in all three groups of patients (p less than 0.05). There were no significant differences in histamine methyltransferase activity in any of the groups studied. Mucosal histamine and histamine methyltransferase activity were significantly correlated in the corpus (p less than 0.05) and antrum (p less than 0.02). Plasma concentration of histamine after transplant was higher in the patients who subsequently were discovered to have a duodenal ulcer (p less than 0.05). The occurrence of ulcer after transplantation was not related to the serum creatinine level. The uniform depletion of gastric histamine and increase in circulatory histamine after renal transplantation may be a factor in the pathogenesis of duodenal ulcer disease in this clinical situation.

Adult↗

Changes in intraepithelial lymphocyte subpopulations in coeliac disease and enteropathy associated T cell lymphoma (malignant histiocytosis of the intestine).

Studies of the morphologic and phenotypic diversity of intraepithelial T cells in human small intestine have shown them to be heterogeneous, yet distinct from most extra intestinal T cells. In this study sequential immunoenzymatic staining was used to define new intraepithelial lymphocyte subpopulations in man. In normal human jejunum approximately 6% of the intraepithelial T cells expressing CD3 (an antigen associated with the T cell receptor) do not express the T cell subset antigens CD4 or CD8. Approximately 20% of CD7+ cells (T cells and null cells) do not express CD4 or CD8 and 14% of the CD7+ cells do not express CD3 and are therefore not T cells. The CD7+, CD3+/-, CD4-, CD8- population is concentrated in the tips of the villi. In coeliac disease, the ratios of the subsets change significantly. The percentage of CD3+, 4-, 8- cells increases to 28%, the proportion of CD7+, 4-, 8- cells remains unchanged and the CD7+, CD3- (non-T cell) population is reduced to 1.4% of the CD7+ cells. In contrast, in patients with villous atrophy of uncertain aetiology, all CD4-, CD8- lymphocyte subsets are decreased compared with normal biopsies. Finally, in enteropathy associated T cell lymphoma (malignant histiocytosis of the intestine) in which the 'uninvolved mucosa' is histologically similar to untreated coeliac disease, the changes in the intraepithelial T cell sub-sets are indistinguishable from those in coeliac disease, suggesting that the lymphoma is a complication of coeliac disease.

Adult↗

Primary B cell gastric lymphoma. A genotypic analysis.

A series of cases of gastric lymphoproliferative disease exhibiting the features of pseudolymphoma, frank lymphoma, or both was investigated immunohistochemically and genotypically for evidence of B cell clonality. Immunoperoxidase studies on frozen and paraffin sections showed that all cases clearly exhibited immunoglobulin light chain restriction (eight cases kappa, six cases lambda). Southern blotting using JH, Ck, and Cl probes to detect clonally rearranged gene fragments confirmed monoclonality in each case, and the immunohistochemical and genotypic data were in agreement in all cases except one (1 light chain restriction/k gene rearrangement). The study confirmed that light chain restriction in gastric lymphoid infiltrates is synonymous with monoclonality ant there is a histologic continuum between low grade B cell gastric lymphoma with features of pseudolymphoma and high grade B cell lymphoma. The authors believe that histologic and immunohistochemical features such as light chain restriction clearly discriminate reactive and neoplastic gastric lymphoid infiltration. Therefore, light chain-restricted lymphoid proliferation, previously termed pseudolymphoma is, in fact, an early stage of frank lymphoma, which obviates the need to use the term pseudolymphoma.

B-Lymphocytes↗

CO and suicide.

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Adult↗

Evidence that activated mucosal T cells play a role in the pathogenesis of enteropathy in human small intestine.

T cells in explants of human fetal small intestine in organ culture were stimulated in situ with PWM or anti-CD3 antibody to test the hypothesis that activated T cells produce enteropathy in human small intestine. T cell activation was measured by the appearance of CD25+ cells in the lamina propria of the explants and IL-2 production into the organ culture supernatant. We have previously shown that the number of T cells in human fetal gut increased between 14 and 22 wk gestation. Accordingly, after the addition of PWM to cultured explants of fetal intestine the number of CD25+ cells in the lamina propria and the amounts of IL-2 secreted into the organ culture supernatant increased with the age of the explanted tissue. The addition of PWM also produced an age-related enteropathy, most noticeably crypt epithelial cell hyperplasia and villous atrophy, with relatively minor changes in 14-17-wk-old intestine but severe tissue damage in 18-22-wk-old fetal intestine. These enteropathic effects were also produced when mucosal T cells were activated with anti-CD3 mAb. Cyclosporin A completely inhibited the PWM-induced development of CD25+ cells and related tissue damage. These experiments show that activated T cells in human small intestine produce enteropathy. The model provides a new system with which to dissect the mechanisms of T cell-mediated intestinal damage.

Antibodies, Monoclonal↗