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Biomedical subjects

M Griffin

Publications and source records attributed to M Griffin.

At least 217 records · Page 12Linked to original sources

Long-term use of an injectable contraceptive: effect of depot-norethisterone oenanthate on carbohydrate metabolism.

In order to determine the metabolic effects of long-term use of the injectable contraceptive norethisterone oenanthate, plasma glucose and serum insulin concentrations were studied in two groups of women who had used the method continuously for at least five years. Group 1 comprised 24 subjects, from whom only fasting blood samples were taken. Despite similar plasma glucose concentrations to those of the controls, the subjects had significantly increased serum insulin concentrations (164.5 (39.9) v 120.3 (34.3) pmol/l, p less than 0.01). In addition the insulin:glucose ratios were also significantly increased (34.3 (8.5) v 24.6 (6.7), p less than 0.01), consistent with decreased insulin sensitivity. Group 2 comprised 13 of the original 24 subjects who also had an oral glucose tolerance test. Basal plasma glucose concentrations were similar in the subjects and their controls, whilst the significantly increased insulin:glucose ratios (35.0 (7.7) v 28.7 (5.6), p less than 0.05) were consistent with the results of the larger group. Following oral glucose challenge, plasma glucose concentrations, serum insulin concentrations and insulin:glucose ratios were similar in the subjects and their controls throughout the test. Thus, long-term use of norethisterone oenanthate injections is associated with a decrease in peripheral insulin sensitivity. However, these changes are not associated with any evidence of oral glucose intolerance.

Adult↗

Correlation of changes in transglutaminase activity and polyamine content of neoplastic tissue during the metastatic process.

Transglutaminase activity and the levels of the polyamines putrescine, spermidine and spermine were measured in two transplantable rat sarcomata: P8 which metastasises consistently to the lung, and P7 which metastasises infrequently. With the P7 sarcoma no metastases were detected following implantation; similarly, no significant changes occurred in the levels of transglutaminase activity, putrescine, spermidine or spermine during tumour growth. However, with the P8 sarcoma at approx. 30 days after implantation there was a marked decrease in transglutaminase activity, mirrored exactly by a 20-fold increase in the levels of acid-soluble putrescine. Measurement of covalently-bound polyamines in the P8 sarcoma indicated a significant and corresponding decrease in the levels of bound putrescine. The timing of these changes coincided with the time at which the P8 sarcoma was shown to have metastasised, and suggests that the changes observed may be related to this phenomenon.

Animals↗

The relationship of endocrine cells, dysplasia and carcinoembryonic antigen in Barrett's mucosa to adenocarcinoma of the oesophagus.

This study was undertaken to assess the prevalence and characteristic hormonal profile of endocrine cells in Barrett's mucosa and to determine to what extent this profile was shared by endocrine cells of adenocarcinomas arising therefrom. In addition, lower oesophageal carcinomas, not associated with columnar metaplasia, were examined to see if they exhibited a different hormonal profile. The patients studied comprised 43 who had had multiple oesophageal biopsies. 35 who had had oesophagogastric resection for adenocarcinoma arising in Barrett's mucosa and 26 in whom the resection showed no metaplastic epithelium adjacent to tumour. Argyrophil cells were present in 90% of biopsies and resections of Barrett's mucosa combined, irrespective of the histological type of metaplastic epithelium. By immunocytochemistry the most frequently identified substance in mucosal endocrine cells was serotonin (82%) followed by somatostatin (54%), secretin (22%) and pancreatic polypeptide (17%). Gastrin, bombesin, cholecystokinin, ACTH and substance P were not identified in metaplastic mucosa in any case. The difference in expression of serotonin by endocrine cells of tumours arising in Barrett's mucosa (31%) and those not (3.8%) was statistically significant (P less than 0.0186). Carcinoembryonic antigen (CEA) was demonstrated in 60% of oesophageal carcinomas, both endocrine positive and endocrine negative. Focal CEA expression was seen in 4.6% of biopsies and 14% of Barrett's mucosa adjacent to tumour. These results indicate a higher prevalence of endocrine cells in Barrett's mucosa than hitherto documented and suggest that serotonin may be a useful marker in distinguishing between primary oesophageal and putative gastric cancers at the gastro-oesophageal junction. The identification of CEA in oesophageal columnar epithelium is of little value in predicting the development of malignancy.

Adenocarcinoma↗

Modification of caecal lymphoid tissue and relationship to granuloma formation in sporadic ileocaecal tuberculosis.

The histopathology of eight cases of sporadic ileocaecal tuberculosis is described with particular reference to caecal lymphoid tissue. Adjacent to areas of ulceration in all cases there was an increase in lymphoglandular complexes (LGC) and proliferation of paravascular lymphoid aggregates deeper in the gut wall. Early and fully-developed granulomas were present in locations comparable to LGC and lymphoid aggregates. Immunocytochemical staining of paraffin sections with monoclonal antibodies UCHL1 (T-lymphocyte membrane antigen) and LN-1, LN-2 and LN-3 (B-lymphocyte and Ia antigens) showed that central cells in LGC and lymphoid aggregates stained like follicular centre B-lymphocytes. Both LGC and lymphoid aggregates had a distinct peripheral rim of cells staining as T-lymphocytes, but LN-2 and LN-3 also stained scattered peripheral cells, some of which were recognizable as interdigitating reticulum cells. Most lymphocytes within and around granulomas stained as T-lymphocytes. In lymph nodes, granulomas appeared to occur first at the periphery of, and later to efface, cortical follicles. Lymph node compartments showed the expected T- and B-zonation, and lymphocytes associated with granulomas stained as in caecal granulomas. Our observations suggest that LGC are sites of mycobacterial antigen sampling, of T-lymphocyte and macrophage activation, and of (potential) granuloma formation in ileocaecal tuberculosis. Lymphoid aggregates deeper in the gut wall probably subserve a similar function during extension of the lesion. The location of both LGC and lymphoid aggregates beside lymphatics is suited to the transfer of their cellular constituents throughout the gut and to regional lymph nodes.

Aged↗

Plastics and synthetic fibres from microorganisms: a dream or a potential reality?

Potential microbial routes to the production of plastics and synthetic fibres can be divided into three categories. These are: (i) the production of biopolymers possessing the properties of plastics, (ii) the use of microorganisms as biocatalysts to produce specialized chemical intermediates or monomers, and (iii) the release of usable chemicals from renewable carbon sources such as lignin.

Bacteria↗

The definition of ABO factors in transplantation: relation to other humoral antibody states.

The first examples of hyperacute rejection of renal hemografts were seen almost 25 years ago when kidneys were transplanted to ABO incompatible recipients whose plasma contained antigraft isoagglutinins. Hyperacute rejection caused in sensitized recipients by lymphocytotoxic antibodies is similar in that the immune reaction triggers an acute inflammatory reaction that leads to widespread thrombotic occlusion and devascularization of the graft. The events after xenotransplantation between certain species are essentially the same. Potential strategies to avoid the precipitating antigen antibody reaction or to mitigate the resulting effector cascade are described.

ABO Blood-Group System↗

Separation of guinea-pig pancreatic juice proteins by reversed-phase high-performance liquid chromatography.

Using a Protesil 300 octyl reversed-phase column with a multistage water-acetonitrile solvent gradient system, it was possible to obtain a well-resolved separation of the nine major proteins present in guinea-pig pancreatic juice. The protein present in each peak of the pancreatic juice chromatogram could only be identified by molecular weight analysis as the acetonitrile denaturated the enzymes and altered their isoelectric points. However, using sodium dodecyl sulphate gel electrophoresis the protein fractions obtained by high-performance liquid chromatography were characterised. Preliminary work has indicated that this system may be capable of separating other complex biological protein mixtures, i.e., saliva.

Animals↗

A role for transglutaminase in glucose-stimulated insulin release from the pancreatic beta-cell.

Preincubation of rat islets of Langerhans with the potent inhibitors of islet transglutaminase activity, monodansylcadaverine (30-100 microM) and N-(5-aminopentyl)-2-naphthalenesulphonamide (100-200 microM), led to significant inhibition of glucose-stimulated insulin release from islets. In contrast, the respective N'-dimethylated derivatives of these two compounds, which did not inhibit islet transglutaminase activity, were much less effective as inhibitors of glucose-stimulated insulin release. None of the compounds inhibited rat spleen protein kinase C activity at concentrations which gave rise to inhibition of glucose-stimulated insulin release. When tested for their effects on calmodulin-stimulated bovine heart phosphodiesterase activity, of the compounds that inhibited insulin release, only monodansylcadaverine did not act as an effective antagonist of calmodulin at concentrations (up to 50 microM) that gave rise to significant inhibition of glucose-stimulated insulin release. Furthermore, at 50 microM, monodansylcadaverine did not inhibit methylation of islet lipids. The inhibition of glucose-stimulated insulin release by monodansylcadaverine is therefore likely to be attributable to its interference with islet transglutaminase activity. The sensitivity of islet transglutaminase to activation by Ca2+ was investigated by using a modified assay incorporating dephosphorylated NN'-dimethylcasein as a substrate protein. The Km for Ca2+ obtained (approx. 3 microM) was an order of magnitude lower than previously reported for the islet enzyme [Bungay, Potter & Griffin (1984) Biochem. J. 219, 819-827]. Mg2+ (2 mM) was found to have little effect on the sensitivity of the enzyme to Ca2+. Investigation of the endogenous substrate proteins of islet transglutaminase by using the Ca2+-dependent incorporation of [14C]methylamine into proteins of islet homogenates demonstrated that most of the incorporated radiolabel was present in cross-linked polymeric aggregates which did not traverse 3% (w/v) acrylamide gels. The radiolabelled polymeric aggregates were present in 71 000 g-sedimented material of homogenates, and their formation was transglutaminase-mediated. These findings provide new evidence for the involvement of islet transglutaminase in the membrane-mediated events necessary for glucose-stimulated insulin release.

Animals↗