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Biomedical subjects

S R Bloom

Publications and source records attributed to S R Bloom.

At least 451 records · Page 25Linked to original sources
PubMed1989

Production of endothelin 1 by cultured bovine retinal endothelial cells and presence of endothelin receptors on associated pericytes.

Endothelinlike immunoreactivity was detected by radioimmunoassay in medium conditioned by cultured endothelial cells obtained from bovine retinal microvessels (9.2 +/- 6.5 pM, n = 4). Sephadex G-25 column chromatography and fast-protein liquid chromatography revealed that most of the endothelinlike immunoreactivity was eluted in an identical position to synthetic endothelin 1. Retinal capillary pericyte-conditioned medium contained 2.9 pM endothelinlike immunoreactivity. In contrast to endothelial cells, retinal pericytes were found to bind endothelin. The dissociation constant and binding capacity were 0.14 nM and 1.5 x 10(5) sites/cell (n = 3), respectively. These findings suggest that endothelin produced by the retinal endothelial cells binds to the pericytes, adding support to the suggestion that pericytes in the retina may have a musclelike function.

Animals↗
PubMed1989

Gut hormone release by intraduodenal stimulation in duodenal ulcer patients.

After an overnight fast, plasma levels of gut peptide hormones were determined before and after intraduodenal stimulation (IDS) with glucose and citric acid in 8 patients with a recent endoscopically proved duodenal ulcer (DU) attack and in 8 healthy volunteers. The DU patients had a hyperacidic mean BAO of 6.6 and an average PAO of 41.8 mEq/h. In DU, basal secretin levels were similar to those in controls, and after IDS secretin release was not impaired. There was no defect of VIP liberation or of the neurotensin response (basal 21 +/- 7 vs 16 +/- 3, after IDS 68 +/- 28 vs 35 +/- 5 pmol/l) which could account for gastric acid hypersecretion. Although fasting GIP levels were significantly lower than in controls (16 +/- 2.5 vs 25 +/- 1.4 pmol/l), they did not correlate negatively with BAO. In contrast to former studies with oral test meals, integrated GIP release was rather reduced after IDS. Basal plasma levels of gastrin were significantly lower in DU (4.0 +/- 0.4 vs 12 +/- 2 pmol/l) and were inversely related to BAO (r = -0.82, p less than 0.02). From the present data, there is insufficient evidence for abnormal plasma levels of gut hormones as major etiologic factors for basal hyperchlorhydria in ordinary DU disease.

Adult↗
PubMed1989

Coeliac sprue: abnormalities of the hormone profile of gastroduodenal mucosa.

To further characterize coeliac sprue, the hormonal content of routine endoscopic biopsies of gastroduodenal mucosa was estimated in 5 coeliac sprue patients and in 8 volunteers without upper gastrointestinal disease. Levels of cholecystokinin-like immunoreactivity tended to be lower in duodenal mucosa of coeliac sprue patients, while the mucosal map of GIP and somatostatin exhibited no peculiar profile. Gastrin was markedly elevated in the antral mucosa of coeliac sprue patients (3013 +/- 760 versus 1048 +/- 392 pmol/g), while basal plasma gastrin was normal. The mucosal VIP content of the descending duodenum was significantly higher in coeliacs than in controls (409 +/- 161 versus 81 +/- 16 pmol/g) and tended to be increased also in the remaining upper small intestine. This rise may be a reaction to mucosal irritation and a reason for enhanced fluid secretion. Even in antral mucosa of coeliac sprue patients, VIP levels were elevated when compared to controls (82 +/- 14 versus 40 +/- 8 pmol/g) and may have some impact, e.g. on local mucosal blood flow or mucus secretion. The mucosal concentration of another putative neurotransmitter, substance P, also showed a tendency to be raised in the mucosa of upper small intestine of coeliac sprue patients.

Biopsy↗
PubMed1989

Endocrine tumors of the pancreas.

We have described the clinical presentation of the commonest syndromes associated with hormone production by functioning pancreatic tumors. The role of the radiologist in tumor localization, staging, and treatment is discussed and the various imaging methods employed are examined individually. The problems of reviewing the world literature on such rare lesions are discussed and a tentative diagnostic algorithm is suggested.

Adenoma, Islet Cell↗
PubMed1988

Isolation and characterisation of GLP-1 7-36 amide from rat intestine. Elevated levels in diabetic rats.

Glucagon-like peptide-1 (GLP-1) was purified to homogeneity by HPLC and anion-exchange chromatography. A molecular mass of 3297.4 Da was obtained by FAB mass spectrometry which corresponded exactly to GLP-1 7-36 NH2, providing evidence that amidation occurs at an arginine residue during the post-translational processing of GLP-1. The distribution of GLP-1 7-36 NH2-like immunoreactivity (GLP-1 7-36 NH2 IR) was determined in the rat gastrointestinal tract. Highest concentrations were found in terminal ileum and colon. Streptozocin-induced diabetic rats, who showed a significant increase in food intake, had a significant increase of GLP-1 7-36 NH2 IR in the colon.

Animals↗
PubMed1988

Identification and characterization of glucagon-like peptide-1 7-36 amide-binding sites in the rat brain and lung.

High-affinity binding sites for glucagon-like peptide-1 7-36 amide (GLP-1 7-36 NH2) were identified in rat brain and lung membranes. Binding of [125I]GLP-1 7-36 NH2 was rapid, reversible, specific, saturable and pH dependent. Specific binding in the central nervous system was particularly high in the hypothalamus and the brain stem. Oxyntomodulin, glucagon-like peptide-1, glucagon-like peptide-2 and glucagon were 100-1000-fold less potent than GLP-1 7-36 NH2 in competition for this binding site.

Animals↗
PubMed1988

Lithium dramatically potentiates neurotensin/neuromedin N gene expression.

Lithium perturbs intracellular signal transduction pathways used by neurotransmitters, suggesting that changes in receptor signalling may underlie its actions in the treatment of manic depressive illness. Little attention, however, has been directed toward possible additional actions at the level of specific gene expression, particularly of genes encoding neurotransmitters or neuromodulators. In PC12 pheochromocytoma cells, lithium dramatically potentiates increases in intracellular levels of the neuropeptide neurotensin and the mRNA encoding it, caused by combinations of nerve growth factor, dexamethasone, and the adenylate cyclase activator, forskolin. This result demonstrates that lithium can profoundly influence the expression of a specific neuropeptide gene in a previously unanticipated manner and suggests that changes in gene expression might be involved in its therapeutic activity.

Adrenal Gland Neoplasms↗
PubMed1988

Peptide YY in diabetics treated chronically with an intestinal glucosidase inhibitor.

Peptide YY (PYY) is a recently discovered peptide found in the distal ileum and colon. It circulates in plasma and concentrations rise in malabsorptive conditions. The potential of PYY as an indicator of impaired carbohydrate digestion was studied in a pharmacological model of intestinal glucosidase inhibition. Thirteen type-2 diabetics on long-term treatment with the alpha-glucosidase inhibitor acarbose (3 x 100 mg per day) had test meals with and without acarbose 100 mg before and after the treatment period (mean 46 weeks), a test meal with acarbose after 20 weeks of continuous treatment and a final test meal without acarbose 6 weeks after cessation of treatment. Without acarbose mean plasma PYY concentrations rose from a mean basal value of 11.5 +/- 2.9 pmol/l to 19.5 +/- 3.9 pmol/l 120 min postprandially (P less than 0.01). Acarbose treatment did not effect basal plasma PYY concentrations but significantly enhanced food stimulated PYY concentrations acutely, at 20 weeks and at the final treatment test meal. Mean incremental integrated plasma responses (area under curve) rose by 183%, 184% and 169%, respectively (P less than 0.05). After cessation of treatment postprandial responses returned to pretreatment values within 6 weeks. Conversely, the integrated incremetal postprandial plasma responses of glucose and insulin were reversibly reduced by acarbose to 58% +/- 9% and 60% +/- 10% of controls, respectively. Self-assesed side effects of flatulence and more frequent bowel action showed no regular relationship to the PYY response. PYY seems to act as an indicator of the increased carbohydrate load to the distal intestine even in the absence of clinical symptoms. It may contribute to the hypoglycaemic effect of alpha-glucosidase inhibitors by slowing down intestinal transit.

Acarbose↗
PubMed1988

Symptomatic secondary hormone syndromes in patients with established malignant pancreatic endocrine tumors.

Over a five-year period, we measured concentrations of gut hormones in plasma samples from 353 patients in whom diagnoses of pancreatic endocrine tumors were subsequently confirmed. A median of 19 months (range, 7 to 120) after the initial diagnosis, 24 of these patients (6.8 percent) had elevated concentrations of other hormones in association with new clinical symptoms. In 13 of these patients (8 with glucagonomas, 3 with tumors secreting vasoactive intestinal polypeptide, and 2 with insulinomas), hypergastrinemia developed along with the clinical features of a gastrinoma; 5 patients died of gastrointestinal perforation or bleeding, apparently caused by this second tumor. We conclude that patients with pancreatic endocrine tumors, regardless of their initial clinical picture, require continued surveillance for new elevations of hormones.

Adenoma, Islet Cell↗
PubMed1988

The presence and molecular forms of cardiodilatin immunoreactivity in the human and rat right atrium.

A sensitive and specific radioimmunoassay has been developed for cardiodilatin, the N-terminal peptide sequence of the atrial natriuretic peptide (ANP) prohormone. Cardiodilatin-immunoreactivity (-IR) concentrations in the human right atrial appendage were found to correlate with ANP-IR concentrations, determined by an established radioimmunoassay, (cardiodilatin-IR = 13.2 +/- 1.2 nmol/g, ANP-IR = 19.8 +/- 2.0 nmol/g, r = 0.80, p less than 0.001). Characterisation of the cardiodilatin-IR in the human and rat right atrium by gel permeation and fast protein liquid chromatography revealed only two cardiodilatin-IR molecular forms. The larger more hydrophobic form, the majority of the cardiodilatin-IR, contained in addition ANP-IR and therefore represents the prohormone. The smaller, less hydrophobic form, lacked ANP-IR and thus represents the cleaved N-terminal peptide sequence of the prohormone. These findings indicate that the prohormone is the major molecular form in the human and rat atrium. Furthermore, they demonstrate that a single large N-terminal peptide, cardiodilatin, derived from the prohormone, may exist as a distinct molecular form in the atrium of these species.

Animals↗
PubMed1988

Isolation of human pancreastatin fragment containing the active sequence from a glucagonoma.

The primary structure of a human pancreastatin-like peptide was determined from a pancreatic glucagonoma. The 28-amino acid peptide was identified using a specific antibody raised against porcine pancreastatin 1-49 and showed a 75% sequence homology with porcine pancreastatin 22-49 and bovine chromogranin A 267-294. Several forms of pancreastatin-like immunoreactivity were found in human endocrine tumors of which the purified peptide was the smallest and contained the active sequence of pancreastatin.

Adenoma, Islet Cell↗
PubMed1988

Ventricular and atrial myocytes of newborn rats synthesise and secrete atrial natriuretic peptide in culture: light- and electron-microscopical localisation and chromatographic examination of stored and secreted molecular forms.

We have demonstrated that atrial natriuretic peptide-like immunoreactivity is stored and secreted by ventricular and atrial myocytes in dissociated cell culture preparations from the heart of newborn rat. Culture preparations were maintained in either foetal calf serum-supplemented medium 199 or in hormone-supplemented, serum-free medium 199. The presence of atrial natriuretic peptide-like immunoreactivity in the cultured myocytes was demonstrated at both light- and electron-microscopical levels. Release of atrial natriuretic peptide-like immunoreactivity into the culture medium was measured by radioimmunoassay; molecular forms of the stored and secreted peptide were determined by gel column chromatography. The atrial natriuretic peptide-like immunoreactivity of cultured atrial and ventricular myocytes was concentrated in the perinuclear cytoplasm and was localised to electron-dense secretory granules. The number of immunoreactive ventricular myocytes and the intensity of their immunofluorescence changed with time in culture and was higher in cultures in foetal calf serum-supplemented medium than in serum-free medium. Gamma-atrial natriuretic peptide was stored and released by cultured atrial and ventricular myocytes, but was broken down to alpha-atrial natriuretic peptide in the growth medium. This process was foetal calf serum-independent, since it occurred in both the media used, indicating that cardiac myocytes in culture may release a factor that cleaves gamma-atrial natriuretic peptide to form alpha-atrial natriuretic peptide.

Animals↗
PubMed1988

Combined use of in situ hybridisation and immunocytochemistry for the investigation of prolactin gene expression in immature, pubertal, pregnant, lactating and ovariectomised rats.

We have investigated the use of in situ hybridisation together with immunocytochemistry for the study of endocrine cell function, using as an example the expression of prolactin messenger RNA (mRNA) in pituitaries of rats under various endocrinological conditions. In situ hybridisation using a 32P-labelled cRNA probe for rat prolactin was carried out on sections of 4% paraformaldehyde-fixed pituitaries from prepubertal, pubertal, pregnant, lactating and ovariectomised rats and adjacent sections were immunostained for prolactin. Northern gel analysis was performed on total RNA extracts of pregnant, lactating and control pituitaries. While in ovariectomised rat pituitaries both prolactin immunoreactivity and prolactin mRNA were decreased, no differences in prolactin immunostaining were seen between prepubertal, pubertal, pregnant or lactating rats and controls, even when the supra-optimal dilution technique was used. However, using in situ hybridisation, prolactin mRNA signal was increased in prepubertal rats, and with hybridisation and northern gel analysis the signal was reduced in pregnant rats and markedly increased in lactating rats. The combined use of in situ hybridisation and immunocytochemistry provides morphological information concerning endocrine gene expression and protein synthesis in the pituitary gland.

Animals↗
PubMed1988

Distribution of a novel pituitary protein (7B2) in mammalian gastrointestinal tract and pancreas.

The distribution of a novel pituitary protein (7B2) was determined in the gastrointestinal tract and pancreas of four mammalian species (man, pig, guinea pig, and rat) by a specific radioimmunoassay. The highest concentrations of cross-reacting immunoreactive 7B2 (IR-7B2) were observed in the pancreas and the proximal gut (antrum or duodenum). While the intestinal concentrations varied widely among species, pancreatic IR-7B2 concentrations appeared to be similar in all four species. In the rat, pancreatic islets were found to contain high concentrations of IR-7B2 (5.73 +/- 0.14 fmol/islet, mean +/- SEM). Neonatal capsaicin treatment and enteric nerve section did not affect the concentrations of IR-7B2 in the rat intestine. Layer separation of human gut showed that IR-7B2 is mainly (71 +/- 8%) present in the epithelial fraction. Chromatographic analysis of intestinal and pancreatic extracts from the four species on Sephadex G-100 showed the presence of two immunoreactive peaks at Kav 0.3 and 0.6, but there were both inter- and intraspecies variations in the proportions of the larger and smaller molecular forms.

Animals↗
PubMed1988

Elevated 7B2 levels during normal human pregnancy.

In a cross-sectional study the plasma concentrations of immunoreactive 7B2, a novel protein originally isolated from the pituitary gland, was measured in 60 healthy pregnant and postpartum women. The mean circulating concentration of 7B2 immunoreactive equivalents was found to be significantly increased throughout pregnancy (10 to 12 weeks, 52.2 +/- 13.1 pmol/L; 20 to 22 weeks, 74.4 +/- 20.1 pmol/L; 30 to 32 weeks, 56.0 +/- 12.9 pmol/L; and 36 to 40 weeks, 85.7 +/- 13.6 pmol/L) when compared with a group of 32 age-matched nonpregnant controls (19.7 +/- 5.0 pmol/L); (p less than 0.01). The highest 7B2 plasma concentrations were found shortly before delivery (36 to 40 weeks) and fell sharply after birth, returning to normal within 4 to 6 weeks. Fetal plasma from both umbilical artery and vein was found to have particularly high concentrations of 7B2-like immunoreactivity (396 +/- 19 and 361 +/- 24 pmol/L, respectively), and 7B2 was extractable from the placenta. Chromatographic analysis of plasma and tissue extracts showed the main peak of immunoreactivity to coincide with that originally described in the pituitary gland. Although the function of 7B2 is at present unknown, our data suggest that 7B2 immunoreactivity in fetal blood originates from the fetus and may play an important role in pregnancy.

Adolescent↗
PubMed1988

Temporal relationships of cholecystokinin release, pancreatobiliary secretion, and gastric emptying of a mixed meal.

The influence of gastric emptying of nutrients on plasma cholecystokinin and pancreatobiliary functions is poorly understood. We therefore temporally related the emptying of fat, protein, and glucose of a mixed meal to release of the gut hormones cholecystokinin, pancreatic polypeptide, and peptide YY and outputs of trypsin, lipase, bilirubin, and bile salts. Five healthy volunteers with a multilumen duodenal tube ingested a mixed meal with phase-specific markers for the aqueous phase, liquid fat, solid fat, and solid protein phases. Duodenal passage was determined by intraduodenal infusion of a second set of phase-specific nonabsorbable markers. Plasma cholecystokinin levels and pancreatobiliary secretions rose to a maximum at 30-60 min and then gradually declined (p less than 0.01) despite continued entry of protein and fat into the duodenum throughout the whole 4-h experimental period. High levels of both pancreatic polypeptide and peptide YY were observed in the last 2 h of the experiment. Release of factors capable of inhibiting cholecystokinin release and subsequently pancreatobiliary secretion may be responsible for the observed time-course.

Adult↗