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Biomedical subjects

J Spencer

Publications and source records attributed to J Spencer.

At least 325 records · Page 18Linked to original sources

Human Peyer's patches: an immunohistochemical study.

We have used immunoperoxidase techniques to characterise the Peyer's patches in human terminal ileum. The mantle zones of the B cell follicles in human Peyer's patches were surrounded by B cells which did not express surface IgD but which mostly expressed surface immunoglobulin of the IgM and/or IgA1 isotype. Few cells expressing surface IgG or IgA2 were detected. Cells with cytoplasmic immunoglobulin of all isotypes except IgD were present in the dome regions of the Peyer's patches as well as in the lamina propria. There was little evidence of traffic of immunoglobulin synthesising cells across the high endothelial venules. T cells were seen to surround the lymphoid follicles. They were most concentrated on the serosal aspect around the high endothelial venules. Cells with macrophage-like morphology were present in both the lamina propria and the dome region of the follicles; those in the lamina propria containing lysozyme and those in the dome region S100 protein. The results are discussed in relation to the generation and dissemination of antibody producing cells in human gut.

B-Lymphocytes↗

Histamine and duodenal ulcer: effect of omeprazole on gastric histamine in patients with duodenal ulcer.

Gastric mucosal concentrations of histamine and of its metabolic enzyme, histamine methyltransferase activity, were measured in patients with duodenal ulcer disease and patients with an apparently normal stomach and duodenum. Patients with duodenal ulcer had significantly less (p less than 0.05) mucosal histamine (median 204 nmol/g) than control subjects (median 252 nmol/g). There was no significant difference between the two groups in their histamine methyltransferase activity values. Omeprazole therapy did not significantly change mucosal histamine (+23%), histamine methyltransferase activity (+5%), histamine release before (+5%) or during (+7%) pentagastrin infusion. It significantly decreased acid secretion during pentagastrin stimulation (median -73%, p less than 0.001). Omeprazole, like cimetidine, does not stop histamine release during pentagastrin stimulation.

Anti-Ulcer Agents↗

Acid, pepsin, and mucus secretion in patients with gastric and duodenal ulcer before and after colloidal bismuth subcitrate (De-Nol).

Basal and pentagastrin stimulated gastric secretion was measured in seven patients with duodenal, and six with gastric ulcers before and after four weeks' treatment with colloidal bismuth subcitrate (as De-Nol), one tablet four times a day. Each duodenal and all but one of the gastric ulcers healed. After De-Nol there were no significant changes in basal, or pentagastrin stimulated volume, acid output, or primary parietal component. There were marked decreases in basal (duodenal ulcer -25%; gastric ulcer -16%) and pentagastrin stimulated total pepsin outputs, (duodenal ulcer -42%, gastric ulcer -36%). There were insignificant decreases in basal output of mucus, but postpentagastrin stimulated mucus output was significantly inhibited (p less than 0.05) in patients with duodenal (-16%) and with gastric ulcer (-27%). The drop in gastric proteolysis after De-Nol is unlikely to be because of the healing of the ulcers and is more likely to be because of the drug. The ulcer healing efficacy of De-Nol may be related to this decline in the proteolytic action of gastric juice, but is unlikely to be because of a quantitative change in mucus, or in acid secretion.

Adult↗

Maximization of biofeedback following cognitive stress preselection in generalized anxiety.

53 subjects, who scored high on an anxiety check list, were evaluated for their responsiveness to relaxation exercises and biofeedback. Each subject was cognitively stressed prior to the training phase by imagining anxiety-provoking situations. Analysis was done on pertaining/posttraining anxiety scores and physiological parameters (galvanic skin response, differences in finger temperature, and frontalis muscle activity). Subjects given feedback corresponding to that physiological parameter which changed the most when stressed, maximized that feedback more than subjects receiving nonrelevant or no feedback. All groups reported significant reductions in anxiety symptoms. Follow-up analysis 15 mo. later showed 76% of the subjects were still symptom-free for anxiety regardless of type of feedback received.

Adult↗

Surgical management of radiation enteritis.

Seventy patients (17 men and 53 women) were seen with radiation-injured gut between 1958 and 1984. The median age at treatment with radiotherapy was 54 years. External radiotherapy was used in all cases, combined with internal treatment for cervical cancer. Ninety-seven gastrointestinal lesions were produced. There were 63 strictures, 14 fistulas, 12 perforations, and eight bleeds. The period between radiotherapy and clinical manifestation of the lesion was approximately 2 years, being longest for strictures. The majority of the lesions were in the rectosigmoid or mid and distal small bowel. Sixty-one patients required one or more operations, and review of the operative results up to 1977 showed a high incidence of anastomotic leak and death after resection and primary anastomosis. However, we noticed that the ascending, transverse, and descending colon were relatively free of radiation-induced disease. Since then we have used a nonirradiated part of the colon for one end of the anastomosis. Thus terminal ileal resection has been followed by an ileotransverse anastomosis and rectosigmoid resection by mobilization of the splenic flexure to bring it down for anastomosis. With these techniques there has been one leak in 14 anastomoses and none of the 12 patients have died. These results are significantly better (p less than 0.02) than our previous figures when 14 of 27 anastomoses leaked, with 10 deaths. We conclude that use of nonirradiated bowel for at least one end of an anastomosis significantly improves the results of resection of irradiated bowel.

Adolescent↗

The development of gut associated lymphoid tissue in the terminal ileum of fetal human intestine.

Lymphoid tissue in formalin fixed and snap frozen human fetal ileum has been studied using immunohistochemistry. At 11 weeks gestation clusters of cells expressing CD4 (leu-3a positive) are present in fetal ileum but these do not express CD3 (UCHT1 negative) and are probably macrophages. Aggregates of lymphoid tissue are apparent from 14 weeks gestation which contain T cells of helper/inducer and suppressor/cytotoxic phenotype. Both B and T cells are present at 16 weeks but with no cellular zonation. By 19 weeks, distinct follicles of B cells are present surrounded by T cells of helper/inducer and suppressor/cytotoxic phenotype. Follicular dendritic cells are also present within the B cell areas. The B cells at this age express surface IgM and IgD, C3b- and C3d-receptors. They also express the antigen CD5 which has been shown by others to be present on some fetal B cells but which is almost exclusively associated with T cells in the adult. HLA-D region antigens are present on apparently all of the cells within the fetal lymphoid follicles. The antigen on activated B cells, CD23 (recognized by MHM6), was present on some cells scattered within the B cell follicle. This is indicative of antigen independent B cell proliferation.

B-Lymphocytes↗

T cell subclasses in fetal human ileum.

Lymphocytes within fetal human ileum were studied by immunocytochemistry to determine the appearance of T cells in human small intestine and the role of enteric antigen in the accumulation of cells of the suppressor/cytotoxic phenotype in the gut epithelium. In fetal human gut epithelium, cells bearing the pan T cell marker UCHT1 (CD3) were present in all of the specimens studied (11-19 weeks gestation). Of these, UCHT4+ (CD8, suppressor/cytotoxic phenotype) predominated over the leu3a+ (CD4, helper/inducer phenotype), although the differences were not as marked as in postnatal gut. UCHT1+ cells were also present in the lamina propria, frequently as small aggregates beneath the epithelium.

Child↗

Gastrointestinal histamine after thoracic irradiation in the mouse.

Thoracic irradiation induced duodenal lesions in mice as an indirect effect. We studied the influence of partial thoracic irradiation on endogenous histamine stores in the alimentary canal. Mice subjected to lower mediastinal irradiation had significantly higher (+19%) median gastric histamine, but lower (-44%) distal duodenal histamine than controls. They also had significantly lower proximal (-39%) and distal (-44%) duodenal histamine than mice who received upper mediastinal irradiation. Twenty-three percent of mice after lower mediastinal irradiation had duodenal lesions; these had significantly lower proximal (-30%) and distal (-44%) duodenal histamine than controls. Thus, irradiation to the lower mediastinum induced both duodenal lesions and significant changes in gastric and duodenal histamine stores. Histamine may be involved in the pathogenesis of these lesions.

Animals↗

Duodenal diversion with vagotomy and antrectomy for severe or recurrent reflux oesophagitis and stricture: an alternative to operation at the hiatus.

In cases of mild symptomatic gastro-oesophageal reflux, standard antireflux surgery, such as fundoplication or the Angelchik prosthesis, produces satisfactory results. Duodenal diversion is recommended for use only in patients with severe oesophageal damage. This situation commonly arises where the gastro-oesophageal junction cannot be reduced into the abdomen, or where previous surgery has made reoperation at the hiatus difficult and hazardous. Fifty-seven patients with severe reflux oesophagitis have been treated by Roux-en-Y duodenal diversion and antrectomy. Thirty three patients had vagotomy in addition. Median follow-up after operation is 6.1 years. In 35 patients (61%), the technique was used as primary surgical treatment. These included 22 patients in a randomized trial of the method. Thirteen (23%) had previously had unsuccessful antireflux surgery. Nine (16%) had undergone previous operations for peptic ulcer or achalasia. There was no operative mortality. No patient in the series required stricture resection. Good or excellent overall results were achieved in 86% of patients. Eighteen of twenty seven patients with severe strictures required an average of three dilatations after operation before dysphagia was completely relieved. Heartburn was dramatically relieved and oesophagitis settled within an average period of 6 months. Poor or unsatisfactory overall results were observed in 8 (14%) patients. These included one tight fibrous stricture which required endoscopic intubation despite resolution of oesophagitis, and four patients who developed a stomal ulcer. No patients suffered from the dumping syndrome. Malignancy must be carefully excluded by biopsy in all cases of stricture.

Adult↗

Radiation-induced gastrointestinal fistulae.

Seventy patients with radiation enteritis presented to a single surgical unit between 1958 and 1984. Of these 10 (14%) had 14 radiation-induced fistulae. The median latent period between radiotherapy and presentation of the fistula was 20 months. The fistulae were often multiple and/or associated with other radiation-induced lesions, patients presenting with fistulae being significantly more likely to have synchronous lesions compared with those who presented with strictures (P = 0.005). These patients are often unfit for major surgery. Wide resection and anastomosis, or exclusion operations are the surgical procedures of choice.

Enteritis↗

Malignant histiocytosis of the intestine: a T-cell lymphoma.

Malignant lymphoma complicating coeliac disease has been characterised on morphological and immunocytochemical grounds as malignant histiocytosis of the intestine (MHI). Fresh tissue from four cases of MHI was studied by means of a panel of monoclonal antibodies; in three cases tumour DNA was studied for immunoglobulin and T-cell receptor (TCR) gene rearrangement. Immunocytochemistry showed a T-cell phenotype in all four cases, confirmed by the demonstration of a rearranged TCR beta-chain gene in the three cases studied. Lymphoma complicating coeliac disease thus appears to be of T-cell, rather than histiocyte, origin.

Adult↗

The natural history of clinically established radiation enteritis.

70 patients presenting to a surgical unit with radiation enteritis were followed up. 11 of the 61 who underwent operations died of operation-related causes. The 51 patients who survived for more than 3 months were followed up for up to 12 years (median 12 months). 24 had no further symptoms related to their radiation enteritis. The other 27 patients had persistence of symptoms, post-operative complications, new radiation-related problems, or a combination of these. The twenty new radiation-related problems were stricture (8 patients), malabsorption (5), fistula (1), and miscellaneous (6). These developed in 12 of 36 patients presenting initially with stricture, compared with 8 of 9 patients presenting with a perforation or fistula (p = 0.007 Fisher's exact test) and none whose first symptom was bleeding (p = 0.001 vs perforation and fistula combined). 10 of the 27 patients with further problems required operations and 5 of them died. Radiation enteritis is thus a progressive disease, with further complications becoming apparent in about half of those surviving the initial lesion. Perforation or fistula formation indicates a poorer prognosis than does stricture or haemorrhage.

Enteritis↗

Homologous recombination between autonomously replicating plasmids in mammalian cells.

The ability of autonomously replicating plasmids to recombine in mammalian cells was investigated. Two deletion plasmids of the eukaryotic-prokaryotic shuttle vector pSV2neo were cotransfected into transformed monkey COS cells. Examination of the low molecular weight DNA isolated after 48 hr of incubation revealed that recombination between the plasmids had occurred. The DNA was also used to transform recA- E. coli. Yield of neoR colonies signified homologous recombination. Examination of the plasmid DNA from these colonies confirmed this view. Double-strand breaks in one or both of the input plasmids at the sites of deletion resulted in an enhancement of recombination frequency. The recombination process yielded monomeric and dimeric molecules. Examination of these molecules revealed that reciprocal recombination as well as gene conversion events were involved in the generation of plasmids bearing an intact neo gene. The COS cell system we describe is analogous to study of bacteriophage recombination and yeast random-spore analysis.

Animals↗