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Biomedical subjects

M A Ghatei

Publications and source records attributed to M A Ghatei.

At least 343 records · Page 19Linked to original sources
PubMed1983

Tissue localization and relative distribution of regulatory peptides in separated layers from the human bowel.

The localization and distribution of regulatory peptides was studied in separated epithelium, lamina propria, submucosa, and external muscular layer from 16 specimens of human bowel. Immunoreactive enteroglucagon, gastric inhibitory polypeptide, and neurotensin were almost confined to the epithelial fraction (97.5 +/- 2.2%, 97.5 +/- 4.2%, and 99.3 +/- 1.1% of their respective total content, mean +/- SEM) and were only localized in endocrine cells. Vasoactive intestinal polypeptide-, substance P-, and bombesinlike peptides were virtually restricted to the nonepithelial layers (99.6 +/- 0.2%, 99.6 +/- 0.2%, and 100%) and were demonstrated exclusively in nerves. A particularly rich vasoactive intestinal polypeptide- and substance P-immunoreactive nerve supply was seen in the nonepithelial mucosa, which contained the highest concentrations of these peptides, while bombesin was mainly recovered from the external muscle (87.7 +/- 2.7%). Somatostatin, measured with an antiserum highly specific for somatostatin-14, was found throughout the wall, mainly in the epithelium (39.9 +/- 5.2%) and lamina propria (29.5 +/- 5.9%), but could be immunostained only in endocrine cells.

Aged↗
PubMed1983

Evidence for a humoral mechanism after small intestinal resection. Exclusion of gastrin but not enteroglucagon.

It is generally agreed that the adaptive response in the residual bowel after major intestinal resection is dependent on luminal nutrition and pancreaticobiliary secretions. Recent evidence, however, suggests that humoral mechanisms, e.g., gastrin or enteroglucagon, may also play a part in this process. A 75% proximal small bowel exclusion was performed in 16 male Wistar rats and the excluded bowel was fashioned into a Thiry-Vella fistula. Half of the animals were allowed food ad libitum, while the rest were fed intravenously. The animals were killed at 12 days, and plasma, gastrin, and enteroglucagon were measured, while cell proliferation was determined by measuring the crypt cell production rate employing a stathmokinetic method using vincristine and crypt microdissection. In addition to these animals, 16 rats had a jejunal transection only, with half of these animals nourished intravenously, while the remainder were allowed food ad libitum. In the Thiry-Vella rats, plasma enteroglucagon was greater with oral feeding (566 +/- 59 pmol/L) than with intravenous feeding (120 +/- 452 pmol/L) (p less than 0.01), but gastrin levels did not differ in the two groups. In the ileum in continuity, crypt cell production rate per hour was greater in the orally fed animals (52 +/- 8) compared with the intravenously fed group (18 +/- 5) (p less than 0.001). In the excluded fistula, crypt cell production rate per hour was reduced by 23.8 +/- 2 in orally fed rats, but this was greater than in the intravenously fed group (16 +/- 1.5) (p less than 0.01). Both orally and intravenously fed transected rats had significantly lower plasma hormone levels, and reduced crypt cell production rate compared with the respective Thiry-Vella groups. This study suggests a distinct role for a humoral agent responsible for the proliferative changes seen after small bowel resection, and in this respect enteroglucagon appears more relevant than gastrin.

Adaptation, Physiological↗
PubMed1982

Decreased plasma motilin concentrations in pregnancy.

Plasma motilin concentrations were measured in 37 women during the second and third trimester of pregnancy and one week after delivery. The mean plasma motilin concentrations, both fasting and after a glucose load and a mixed meal, were significantly (p less than 0.001) reduced during pregnancy, returning to the normal range one week post partum. Pregnancy appears to have a profound inhibitory effect on plasma motilin, and this may in part be responsible for the gastrointestinal hypomotility associated with pregnancy.

Female↗
PubMed1982

Developmental changes in bombesin, substance P, somatostatin and vasoactive intestinal polypeptide in the rat brain.

The regional distribution of the 4 neuropeptides, bombesin, substance P, somatostatin and vasoactive intestinal polypeptide (VIP) were investigated in the developing rat brain. Specific radioimmunoassay and immunocytochemistry were employed. VIP and bombesin were undetectable in the foetal brain whereas substance P and somatostatin were shown to be present in all regions as early as 14 days postcoitus. There was a dramatic postnatal increase in all 4 peptides in most regions. These results are discussed and compared with results of previous investigations of the ontogeny of the classic neurotransmitters.

Aging↗
PubMed1982

The effect of altered luminal nutrition on cellular proliferation and plasma concentrations of enteroglucagon and gastrin after small bowel resection in the rat.

Luminal nutrition is known to have a trophic effect on small bowel mucosa after intestinal resection. Humoral agents, however, may also contribute to this process. Two of the proposed humoral agents, enteroglucagon and gastrin, were therefore investigated after intestinal resection and transection in the rat, and changes in their concentration in the plasma were related to cellular proliferation. Forty-eight male Wistar rats had either 75 per cent proximal small bowel resection or jejunal transection. The animals were further divided into three groups, each with a different nutritional intake. The first group were allowed food ad libitum. The second group were kept under hypothermic conditions which resulted in hyperphagia, while the last group were nourished intravenously. A further 8 animals had a laparotomy only (sham operation). All animals were killed 12 days after operation, plasma enteroglucagon and gastrin were measured, while determination of the crypt cell production rate (CCPR) was used to denote cellular proliferation. In each group resected rats had significantly higher crypt cell production rates and greater enteroglucagon levels compared with transected animals. However, only in the normally fed group was plasma gastrin increased in resected animals, there being no significant difference in the plasma concentration of this peptide in transected compared with resected rats, in both the intravenously fed and hyperphagic groups. In the models studied enteroglucagon appears to be a more likely candidate for a humoral trophic agent than gastrin in intestinal adaptation.

Adaptation, Physiological↗
PubMed1982

Pancreatic glucagon in human foetal stomach.

A combination of immunocytochemistry at light and electron microscopic levels, direct radioimmunoassay and measurement after gel chromatography have been used to identify and characterise a glucagon-like peptide detected in human foetal stomach. Immunocytochemistry, with region specific antisera, demonstrated that the glucagon-containing cells were indistinguishable from pancreatic A cells. Radioimmunoassay of tissue extracts confirmed the presence of significant quantities of glucagon, mean 21 pmol/g wet weight (range 14-29) in 16-26 week old foetuses, increasing to 41 pmol/g wet weight (range 31-52) in 33-30 week old foetuses and after gel chromatography the peptide was found to elute at the same position as standard porcine glucagon. It is apparent, therefore, that the human foetal fundus contains significant quantities of true pancreatic-type glucagon.

Female↗
PubMed1982

Bombesin production by human small cell carcinoma of the lung.

A series of continuous cell lines of human small cell carcinoma of the lung (SCCL) have been evaluated for the production of bombesin (BN). In early established cultures BN was detected in the medium of 9 out of 11 cell lines and in 6 out of 7 cell homogenates examined. Levels in the medium were frequently higher in cultures of later passages compared to earlier passages of the same line and low levels developed in the two previously negative cell lines. Plasma concentrations were greater than 80 pmol/l in 2 out of 27 (7%) randomly selected patients with SCCL. A culture (DMS 406) established from the tumor of a patient with the highest plasma level (1240 pmol/l) was the highest producer in vitro. The results indicate that BN, which has been demonstrated immunocytochemically to be present in normal bronchial mucosal cells, is frequently produced by SCCL in vitro but elevated plasma levels are infrequently found in patients with this neoplasm.

Bombesin↗
PubMed1982

Bombesin: action on gut hormones and calcium in man.

Bombesin, a peptide with widespread biological actions, has been demonstrated in human tissues by immunological methods. To investigate its effect in man, synthetic bombesin was infused at low doses in six male volunteers. Bombesin at 2.4 pmol kg-1 min-1 produced significant rises in plasma insulin, glucagon, pancreatic polypeptide, gastrin, cholecystokinin, motilin, glucose-dependent insulinotropic polypeptide, neurotensin, enteroglucagon, vasoactive intestinal polypeptide, and serum calcium. In contrast, bombesin caused a profound fall in parathyroid hormone levels and reduced plasma glucose concentrations. A late rise in plasma calcitonin was also observed. Bombesin had no significant effect on the pituitary hormones, TSH, GH, PRL, or cortisol. No hormonal changes or alterations in calcium were noted during saline infusions. Bombesin has a marked stimulatory effect on gastrointestinal hormones, which is unique and opposite to the effect of somatostatin, a potent inhibitor of gut hormone release. Bombesin also influences calcium-regulating hormones, either directly or through its action on gut hormones. The bombesin concentrations achieved with the dosages used were low enough to indicate a possible physiological role for the endogenous peptide.

Adult↗
PubMed1982

Development of intestinal regulatory peptides in the human fetus.

The time of first appearance and subsequent development of eight regulatory peptides in the small and large intestine of human fetuses has been investigated. Gastrin, secretin, motilin, gastric inhibitory peptide, vasoactive intestinal peptide, enteroglucagon, and somatostatin were first detected as early as 8 wk of age, while neurotensin was only demonstrated at 12 wk. Adult patterns of distribution were established by 20 wk of age. Of the peptides examined only vasoactive intestinal peptide was localized to nerve fibers and these were seen clearly in the myenteric plexus at the 12-wk fetal stage and in the later fetuses in both the enteric plexuses. The concentrations of regulatory peptides increased steadily until term when they were close to adult levels. Secretin and vasoactive intestinal peptide showed only a single molecular size species by gel permeation chromatography but the other peptides showed multiple peaks, the ratios tending to change through the gestational period in favor of the smaller molecular sized moieties. Thus the regulatory peptide system of the gut is present in th early fetus and its role in the process of maturation requires investigation.

Chromatography, Gel↗
PubMed1981

Release of vasoactive intestinal peptide in the dumping syndrome.

To determine the effect of gastric surgery on the plasma vasoactive intestinal peptide (VIP) concentration, 13 patients with gastrectomy and seven controls were given an oral hypertonic load (200 ml 50% glucose solution). Blood was taken at intervals during the test for measurement of VIP and blood glucose concentrations and packed cell volume. At the same time observations were made on the occurrence of dumping symptoms and a record kept of the pulse rate. VIP values in the patients with gastrectomy were significantly increased by glucose ingestion, while these did not alter in controls (p less than 0.001). There was a highly significant correlation between the rate of rise in plasma VIP concentration and the rates of rise in packed cell volume (r = 0.85; p less than 0.001) and blood glucose concentration (r = 0.76; p less than 0.01) in patients with gastrectomy. Changes in packed cell volume and blood glucose values and the occurrence of dumping symptoms during the test were significantly different when postoperative patients were compared with controls (p less than 0.001, p less than 0.005, and p less than 0.001 respectively). Furthermore, when the patients with gastrectomy were divided into those without symptoms and those with dumping after meals the latter group showed a significantly greater rise of VIP (p less than 0.05). Despite the increased plasma VIP concentrations observed during dumping, VIP cannot be taken as the sole factor in the pathogenesis of the dumping syndrome.

Aged↗
PubMed1981

The influence of an intact pylorus on postprandial enteroglucagon and neurotensin release after upper gastric surgery.

Upper partial gastrectomy for carcinoma of the gastric cardia or fundus is unavoidably accompanied by truncal vagotomy, so it is orthodox practice to carry out pyloroplasty with this procedure. In order to assess the effect of leaving an intact pylorus in this operation, 21 patients were investigated with an oral hypertonic load (200 ml 50 per cent glucose solution), and blood was taken at intervals during the test, for the ileal gut hormones, enteroglucagon and neurotensin, as well as for measurements of haematocrit and blood glucose. Clinical features of dumping during the test were sought. There were 7 patients with upper partial gastrectomy, truncal vagotomy and an intact pylorus, 7 patients without a pylorus (total or near total gastrectomy) and 7 patients not subjected to gastric surgery. No significant difference was found in any of the measurements between gastrectomy patients with an intact pylorus and those draining through an enterostomy. However, both these groups differed significantly from normal controls in having greater rates of rise and higher peak values of enteroglucagon, neurotensin, haematocrit and blood glucose, together with a more frequent occurrence of dumping symptoms during the test. As the above measurements probably reflect transit of glucose into the small intestine, the findings in this study suggest that leaving an intact unstenosed pylorus is unlikely to lead to gastric stasis following upper partial gastrectomy.

Aged↗
PubMed1981

A qualitative comparison of canine plasma gastroenteropancreatic hormone response to bombesin and the porcine gastrin-releasing peptide (GRP).

The effect on plasma gastroenteropancreatic hormone levels on infusing the porcine gastrin-releasing peptide and bombesin into dogs demonstrated no qualitative difference in the spectrum of activity of the two peptides. Sustained elevation in plasma immunoreactive gastrin, pancreatic polypeptide, enteroglucagon, gastric inhibitory polypeptide, pancreatic glucagon and transient elevations in plasma insulin were seen during infusions of both peptides. The similar spectrum of activities and the structural homology between the two peptides suggests that the porcine gastrin releasing peptide is the porcine counterpart of the amphibian peptide bombesin.

Animals↗
PubMed1981

Effect of a long-acting octapeptide analogue of somatostatin on growth hormone and pancreatic and gastrointestinal hormones in man.

1. The biochemical specificity and duration of action of a single 5 mg subcutaneous dose of des-AA1,2,4,5,12,13-D-Trp8-somatostatin were evaluated in eight patients with symptomatic pancreatic endocrine tumours. 2. There was a reduction by more than 50% for at least 10 h in plasma concentrations of growth hormone, glucagon, gastrin and motilin and for 4--5 h in plasma insulin, pancreatic polypeptide, gastric inhibitory polypeptide and enteroglucagon. 3. This study shows that this octapeptide analogue of somatostatin, like somatostatin itself, lacks specificity in the hormones it suppresses. However, its prolonged duration of action against several hormones when given subcutaneously suggests that it may be of therapeutic use in a number of disease states where excessive plasma concentrations of one or more of these hormones occur.

Gastrointestinal Hormones↗
PubMed1981

Bombesin, somatostatin and neurotensin-like immunoreactivity in bronchial carcinoma.

Bombesin, a regulatory peptide found in adult lung and in higher concentration during development in the foetal lung, has potent biological actions which include the ability to stimulate the release of a number of hormones. Radioimmunoassay of extracts of tumour, lung and plasma from patients with bronchial carcinoma revealed very high tissue bombesin concentrations in two oat cell carcinomas, with lower levels in two out of six adenocarcinomas exceeding the concentrations found in normal lung. The oat cell carcinomas also contained significant amounts of somatostatin and in one case neurotensin. Neurotensin was further detected in two out of seven squamous tumours and three adenocarcinomas. Secretion of regulatory peptides by bronchial carcinomas may account for some of their ill-understood non-metastatic clinical manifestations.

Adenocarcinoma↗
PubMed1981

Molecular forms of motilin in the mammalian and human gut and human plasma.

Regional specific antibodies and gel permeation chromatography were used to analyze the molecular forms of motilin in the human gut and plasma and in the porcine gut. The same antibodies were also used for immunocytochemical localization of the cell of origin of motilin. Two main molecular forms of motilin were identified, peak I eluting at a volume suggesting a larger molecular weight substance (Kav = 0.16) and peak II coeluting with the porcine motilin standard (Kav = 0.67). Peak I accounted for over 50% of the total motilin immunoreactivity in the human gut, whereas in the porcine intestine it represented less than 5%. Peak I thus appeared to have a greater N-terminal sequence similarity with the porcine motilin standard. Chromatographic analysis of human plasma showed the presence of both immunoreactive peaks in approximately equal amounts which were both suppressed following infusion of somatostatin. Infusion of porcine motilin resulted in the expected rise of plasma immunoreactivity in the peak II position, whereas peak I was significantly depressed, suggesting the possibility of a negative feedback. Immunocytochemistry revealed that both antibodies immunostained equally the non argentaffin cell, which contained small round, electron-dense granules. In addition some argentaffin enterochromaffin cells were stained predominantly with the N-terminal specific antibody.

Adult↗
PubMed1980

Elevation of plasma neurotensin in the dumping syndrome.

1. The pathophysiology of the dumping syndrome is poorly understood. Plasma levels of four small intestinal hormones have been measured after an oral glucose provocation test in 19 patients with dumping symptoms and in matched controls. 2. Plasma levels of neurotensin, a newly discovered highly potent, hypotensive ileal peptide, were significantly increased in symptomatic patients compared with those of controls [20 min rise of 43 +/- 6.0 (mean +/- SEM) pmol/l in 19 symptomatic patients, 8.0 +/- 5.5 pmol/l in 20 postoperative symptom-free patients, and 4.1 +/- 3.5 pmol/l in 20 pre-operative patients with duodenal ulcer, P < 0.01]. 3. The rise in enteroglucagon was greater than normal but of similar magnitude to that seen in several other gastrointestinal conditions not associated with dumping symptoms. 4. The release of both gastric inhibitory peptide and motilin did not differ significantly from that of controls.

Blood Glucose↗