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S R Bloom

Publications and source records attributed to S R Bloom.

At least 235 records · Page 13Linked to original sources
PubMed1994

Distribution and developmental pattern of neuromedin U expression in the rat gastrointestinal tract.

This study has quantified, for the first time, the relative levels of neuromedin U (NmU) mRNA in the rat gastrointestinal tract using Northern blot analysis. NmU message was detected in all regions of the gastrointestinal tract from the oesophagus to the rectum. The greatest levels were found in the duodenum and jejunum, the principal sites for absorption, which were 2.5- and 3-fold respectively above ileal levels. Quantification of NmU mRNA and peptide contents in the duodenum, jejunum and ileum during postnatal development of the rat showed message and peptide levels to be greater in the maturing rat than in neonates. Message levels in the duodenum, jejunum and ileum showed 14-, 7- and 4-fold increases respectively between 1 and 56 days after birth, whilst the corresponding peptide levels in the duodenum, jejunum and ileum showed 33-, 14- and 25-fold increases respectively. Food deprivation caused a small, but significant, decrease in message levels in the jejunum and colon, but there was no change in the duodenum or ileum. This shows that the presence of food has little effect on NmU mRNA levels in the gut.

Age Factors↗
PubMed1994

Differential response of neuropeptide Y, substance P and vasoactive intestinal polypeptide in the rat anterior pituitary gland to alterations in thyroid hormone status.

We have compared the effects of thyroidectomy with those of thyroxine (T4) replacement and excess T4 treatment on neuropeptide Y (NPY) in the rat anterior pituitary, and compared these with the effects on substance P (SP) and vasoactive intestinal peptide (VIP). Thyroidectomy produced large increases in the peptide content of NPY (335 +/- 58 fmol/gland vs 15 +/- 4 fmol/gland in controls), SP (581 +/- 90 vs 199 +/- 32 fmol/gland) and VIP (1386 +/- 395 vs 417 +/- 77 fmol/gland) together with large increases in the respective prohormone encoding mRNAs, NPY 21,760% +/- 1290%, preprotachykinin-A (PPT-A; which encodes the substance P precursor) 1744% +/- 190% and VIP 680% +/- 129%. Thyroidectomy together with T4 replacement produced an increase in both NPY peptide (426 +/- 72 vs 15 +/- 4 fmol/gland) and mRNA content (970% +/- 156% of controls). The peptide contents of SP and VIP were not significantly different from controls. PPT-A and VIP mRNA levels were decreased relative to controls (31% +/- 8% and 23% +/- 10% respectively). In intact animals treated with excess T4 (hyperthyroid animals), SP and VIP peptide contents were significantly reduced (55 +/- 13 vs 199 +/- 32 fmol/gland and 226 +/- 24 vs 417 +/- 77 fmol/gland respectively) and the SP and VIP encoding mRNAs were also decreased (8% +/- 3% and 11% +/- 4% respectively). In this group there was no detectable alteration in either the peptide or mRNA content of NPY.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Gut neuroendocrine tumors.

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Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Localization of metastatic gastroenteropancreatic tumours by somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]-octreotide.

Most gastroenteropancreatic tumours express somatostatin receptors, allowing imaging using radiolabelled somatostatin analogues. Octreotide can be modified by coupling a DTPA moiety to the N-terminal D-phenylalanine to allow labelling with In111. We studied the comparative effectiveness of this radiopharmaceutical in identifying tumour extent. Twenty-two patients with metastatic gastroenteropancreatic tumours were scanned using [111In-DTPA-D-Phe1]-octreotide. In 11 patients with the carcinoid syndrome, one of six primary lesions was identified by CT scanning and by [111In-DTPA-D-Phe1]-octreotide scanning. Hepatic metastases were present in all patients, 9 of whom had positive scintigraphy. Two other sites of intra-abdominal uptake and four distant sites, not previously identified, were demonstrated. Five other distant sites were confirmed to be carcinoid metastases. All 11 patients with other gastroenteropancreatic tumours had positive scans, demonstrating 7/9 primary lesions, 12 intra-abdominal lesions, including hepatic metastases in all cases, and one distant lesion, all previously identified. Thus [111In-DTPA-D-Phe1]-octreotide imaging effectively identified the extent of metastatic disease from gastroenteropancreatic tumours, and confirmed lesions whose significance was uncertain following previous imaging procedures.

Adult↗
PubMed1993

The effect of central blockade of kappa-opioid receptors on neuropeptide Y-induced feeding in the rat.

Neuropeptide Y (NPY) and the endogenous kappa-opioid receptor ligand, dynorphin (dyn), stimulate feeding when injected centrally in the rat. Norbinaltorphimine (norBNI, 25 nmol) reduced the feeding response to NPY (2.4 nmol) by 67% (P < 0.02). An additive effect of dynorphin and NPY was seen on food intake (saline 0.8 +/- 0.1, dyn 1.9 +/- 0.4, NPY 6.1 +/- 1.4, dyn and NPY 9.7 +/- 2.2). A component of NPY-induced feeding may be mediated by kappa-opioid neuronal systems.

Animals↗
PubMed1993

The lung contents of endothelin are altered by thyroid hormone status in rat.

Endothelin-1 (ET-1) is a 21-residue peptide isolated from the conditioned medium of cultured porcine endothelial cells and is widely distributed throughout the body, with relatively high levels in the kidney and lung. Animal studies have revealed that the lung appears to have the largest capacity for ET-1 removal from the blood stream. In this study we have examined the possible influence of thyroid status on immunoreactive endothelin (IR-ET) levels in the plasma and lung of the male rats. 3 weeks after the surgical removal of the thyroid gland from male rats, the IR-ET levels in the lung were reduced by 39%. Similarly, IR-ET levels were decreased 46% in the lung of rats rendered hypothyroid by treatment with 0.1% (w/w) PTU in the drinking water for 30 days, and replacement with daily L-thyroxine (T4) injections (5 micrograms/100 g) prevented this decrease. However, thyrotoxicosis induced by daily L-T4 injections (10 micrograms/100 g) also caused a decrease of the lung IR-ET levels by 49%. Nevertheless, the plasma IR-ET levels are similar in each group. Fast protein liquid chromatography study verified the presence of ET-1 immunoreactivity in both rat plasma and lung tissue extracts. This study demonstrates that euthyroid status is required for the maintenance of physiological concentrations of IR-ET in the lung of male rats.

Animals↗
PubMed1993

Galanin regulates basal and oestrogen-stimulated lactotroph function.

Oestrogen, an essential physiological regulator of reproductive function, controls lactotroph proliferation and prolactin release. The neuropeptide galanin co-localizes to the lactotroph, but its physiological function is largely unknown. Pituitary galanin expression is extremely sensitive to the oestrogen status of the animal. A marked elevation occurs during pregnancy and lactation, and exogenous 17 beta-oestradiol can cause a 4,000-fold increase in messenger RNA levels. Here we report that galanin is secreted by a minority of lactotrophs and is essential for the regulation of basal and vasoactive-intestinal-polypeptide-stimulated prolactin release. Hyperoestrogenization increases the number of galanin-secreting cells and the resulting increase in basal prolactin release is completely abolished by treatment with galanin antiserum. Galanin is a potent lactotroph growth factor and galanin-immunoneutralization completely inhibits the previously reported mitogenic effects of oestrogen on the lactotroph. These findings represent direct evidence for paracrine regulation of lactotroph function and demonstrate that the effect of oestrogen on lactotroph proliferation and prolactin release are mediated by locally secreted galanin.

Analysis of Variance↗
PubMed1993

Characterization of a high-affinity galanin receptor in the rat anterior pituitary: absence of biological effect and reduced membrane binding of the antagonist M15 differentiate it from the brain/gut receptor.

Structure-activity studies demonstrate that galanin fragments 1-15 and 2-29 are fully active, whereas fragment 3-29 has been reported to be inactive, in a number of different in vivo models. M15, a chimeric peptide comprising galanin 1-13 and substance P5-11, has recently been found to be a potent galanin antagonist. Direct effects of galanin at the level of the pituitary have been defined, yet, paradoxically, a number of studies have been unable to demonstrate galanin binding to an anterior pituitary receptor. Porcine galanin stimulated prolactin release from dispersed rat anterior pituitary cells up to 180% +/- 12% (mean +/- SEM) of control secretion. The addition of a specific galanin antiserum caused a profound inhibition of basal prolactin release, maximal inhibition being 12% +/- 0.5% of control secretion. Addition of M15 produced no effect on basal or galanin-stimulated prolactin release. Galanin fragment 3-29 was fully active when compared to galanin 1-29. Fragments 5-29 and 8-29 stimulated prolactin release to a lesser extent and galanin 1-15, 10-29, and 20-29 had no significant prolactin-releasing activity. Using [mono(125I)iodo-Tyr26]galanin or porcine 125I-labeled Bolton-Hunter [mono(125I)iodo-Lys25]galanin, no anterior pituitary membrane binding was observed. In contrast, 125I-labeled Bolton-Hunter N-terminally labeled galanin allowed characterization of a single high-affinity anterior pituitary galanin receptor with a Kd of 4.4 +/- 0.34 nM and a Bmax of 79 +/- 8.3 fmol/mg of protein. The IC50 for porcine galanin was 0.51 +/- 0.04 nM but for M15 was in excess of 10 microM. Galanin 3-29 fully displaced the label with an IC50 of 0.96 +/- 0.7 nM. The IC50 for galanin 5-29 was 200 nM, whereas 8-29 and 1-15 were > 1 microM. Galanin 10-29 and 20-29 failed to displace the label. These data suggest the presence of a high-affinity pituitary galanin receptor, designated GAL-R2, in which region 3-10 and amino acid 25 are crucial for membrane binding and biological activity, in contrast to the known gut/brain galanin receptor (designated GAL-R1). A number of tissues known to bind or respond to galanin were screened. GAL-R2 would appear to be expressed only in the anterior pituitary and hypothalamus.

Animals↗
PubMed1993

The differential release of amino acids and neuropeptides from purified subpopulations of mammalian GABAergic and cholinergic cerebrocortical synaptosomes.

GABAergic and cholinergic synaptosome populations were isolated by immunomagnetophoresis. Analysis of 8 amino acids showed that the GABAergic population was enriched in GABA (3 fold). The cholinergic population was enriched in citrulline (5 fold). CCK was found in both populations, but was enriched in the GABAergic. No monoamines were found in either subpopulation. Stimulated release (veratridine 50 microns), measured using a superfusion system, showed that glutamate was only released from the cholinergic subpopulation, as was VIP. In the GABAergic population, stimulated SRIF release was slow and prolonged, and the CCK release was delayed and rapid. GABA release was rapid, only occurring during application of the stimulus and only from the GABAergic synaptosomes. The GABAergic release could be modified by GABAA and GABAB targeted drugs. The cholinergic subpopulation exhibited late release of both VIP and CCK, each showing the same time pattern of release. All release was calcium and tetrodotoxin dependent.

Acetylcholine↗
PubMed1993

Assessment of neurological injury due to circulatory arrest during profound hypothermia. An experimental study in vertebrates.

To investigate brain changes in induced deep core hypothermia (15 degrees C) with circulatory arrest, five groups of neonatal pigs were subjected to cardiopulmonary bypass (CPB), with circulatory arrest (CA) periods varying from 70-120 min. The parameters analysed were: 1. Histology and electron microscopy of the brain six hours post-CPB, 2. Creatinophosphokinase (CPK) from cerebrospinal fluid (CSF), 3. Vasointestinal neuropeptide (VIP) and 7B2 specific neuropeptide both in plasma and brain tissue. The earliest morphological changes were seen after 90 min CA and were highly significant after 120 min arrest. These changes involved mainly the Purkinje cells of the interior half of the cerebellum with vacuolation in their cytoplasm. A rise in CPK in CSF occurred in all piglet-groups. The differences among the various groups were highly significant at 2 and 5 h post-CPB. (P < 0.05). Statistically significant differences were not exhibited among the various groups both in serum and brain tissue total mean values of VIP and 7B2 neuropeptides. We suggest that 1. The cerebellar region is the most sensitive where ischemic lesions attain their maximal severity and extent; the frequency and pattern of selective vulnerability of the cerebellum may be related primarily to its pattern of blood supply 2. The maximum time of CA without histopathological sequelae should not exceed 70 min.

Anesthesia, General↗
PubMed1993

Amino acid infusion blocks renal tubular uptake of an indium-labelled somatostatin analogue.

The Indium-labelled somatostatin analogue pentetreotide has been successfully developed for imaging of somatostatin receptor positive tumours. However there is significant renal tubular uptake of the radiolabelled peptide, which can obscure upper abdominal tumours and would preclude its use for targeted radiotherapy. The aim of this study was to determine whether amino acid infusion, which has been shown to block renal tubular peptide reabsorption, diminishes renal parenchymal uptake of this radiolabelled analogue. Eight patients being scanned with the 111In-labelled somatostatin analogue, pentetreotide, for localisation of gastroenteropancreatic tumours received an infusion of synthetic amino acids. The ratio of isotope uptake in kidney to that in spleen was assessed, and compared to the ratio for matched control patients, to determine if amino acid infusion reduced renal parenchymal uptake of the radiopharmaceutical. The amount of isotope in the urine was determined to ensure that any effect of the amino acid infusion was unrelated to changes in clearance. Infusion of amino acids significantly reduced renal parenchymal uptake of isotope at 4 h. There was a non-significant increase in urinary clearance of isotope over the 4 h, consistent with reduced reuptake and a lack of effect on glomerular filtration rate. This technique, by preventing renal damage, may allow the use of this somatostatin analogue for local radiotherapy, and could be of wider value in blocking tubular re-uptake of potentially nephrotoxic agents, such as radiolabelled Fab fragments.

Adult↗
PubMed1993

Comparison of plasma pancreastatin and GAWK concentrations, presumed processing products of chromogranin A and B, in plasma of patients with pancreatic islet cell tumors.

Plasma pancreastatin (PST) and GAWK, peptides processed from chromogranin A and B, were elevated in patients with various neuroendocrine tumors. In the present study, we measured plasma PST- and GAWK-like immunoreactivity (LI) concentrations in 12 patients with pancreatic islet cell tumors and evaluated them as a marker for these tumors. We also performed the gel filtration of the plasma from a gastrinoma patient and investigated the processing of PST and GAWK in plasma. Elevation of plasma PST-LI was found in 4 of 12 patients (33%) and elevation of plasma GAWK-LI was found in 6 of 12 patients (50%). A significant correlation was not found between plasma PST- and GAWK-LI concentrations of the patients. In the gel permeation chromatography of the plasma from a gastrinoma patient, PST-LI composed of a single peak but GAWK-LI composed of several components with wide range molecular weights.

Adenoma, Islet Cell↗
PubMed1993

Molecular form of islet amyloid polypeptide (amylin) released from isolated rat islets of Langerhans.

Islet amyloid polypeptide (IAPP) is a 37-amino acid residue polypeptide, originally isolated from the pancreatic amyloid deposits of patients with type II diabetes mellitus. Subsequently, IAPP was found to be colocalised with insulin in beta-cell secretory granules of the normal mammalian pancreas. Recently, IAPP has been reported to inhibit glucose-stimulated insulin release from isolated rat islets and to be released in response to glucose and arginine. To investigate further the regulation of IAPP release from the islet, we used a previously developed specific radioimmunoassay for IAPP and measured IAPP secretion from isolated rat islets of Langerhans. Release of IAPP-like immunoreactivity (-LI) was stimulated by glucose: 3.3 +/- 0.3, 3.9 +/- 0.3, and 11.1 +/- 1.5 (n = 5, mean +/- SEM) fmol/islet/60 min at 2, 7, and 20 mM, respectively. Carbachol (0.1 mM) increased the release of IAPP-LI at the lower glucose concentrations: 8.1 +/- 0.9, 8.7 +/- 0.6, and 11.7 +/- 1.8 fmol/islet/60 m in at 2, 7, and 20 mM glucose. Somatostatin (1 microM) suppressed glucose-stimulated IAPP-LI release (17.5 +/- 1.5 vs. 5.1 +/- 0.5 fmol/islet/60 min). Chromatographic characterisation of the IAPP-LI released into the incubation medium revealed two immunoreactive forms: The major peak (74% of the total IAPP-LI) corresponded to synthetic IAPP-37, while a smaller form, comprising 26% IAPP-LI, eluted later. In acid extracts of islets, all (> 95%) immunoreactivity co-eluted with the synthetic IAPP.

Amyloid↗
PubMed1993

Insulin and intestinal epithelial cell proliferation.

The effects of modification of the levels of endogenous plasma insulin on intestinal epithelial cell proliferation were investigated in rats maintained by total parenteral nutrition (TPN) using either a TPN diet that was high in glucose, or a low glucose (hypocaloric) TPN diet and in orally fed rats (normal and sham operated). The rats were put on their respective treatments for 7 days and were then injected with vincristine sulphate to arrest cells as they entered metaphase. Intestinal tissue was fixed for the determination of crypt cell production rate (CCPR) and blood plasma was taken for hormone radioimmunoassay. Sham operation had no effect on either plasma hormone levels or on CCPR. The standard TPN diet was associated with significantly reduced levels of gastrin, peptide YY and enteroglucagon. Gastrin and PYY were further reduced by the hypocaloric diet. However, plasma insulin was much increased in the TPN but not in the hypocaloric group. Small intestinal CCPR was reduced in the TPN groups, but no difference was observed between the standard and the low calorie TPN diets. The lack of difference in CCPR between the two TPN diets despite the massive elevation of plasma insulin strongly suggests that insulin does not have a substantial role in the control of gastrointestinal epithelial cell renewal.

Administration, Oral↗
PubMed1993

Evaluation of a proposed technique to assess unscheduled DNA synthesis and genotoxicity.

Results from a recent, new assay suggest that omeprazole, a potent inhibitor of gastric acid secretion, is genotoxic. The principle of this assay is that the non-proliferating zone of surface gastric epithelial cells can be selectively removed by controlled digestion so that any incorporation of tritiated thymidine into these cells represents unscheduled DNA synthesis. Parietal cells (which are located below the uppermost proliferating cells) and proliferating cells in semiconservative, regular DNA synthesis could always be shown in the digested fraction, and as regular DNA synthesis takes up a thousand fold more thymidine than unscheduled DNA synthesis, any signal from unscheduled synthesis would therefore be swamped. The digestion process was also uneven, as histological analysis showed denuded patches of mucosa, and gland like structures were seen in the digest. Quantification of the number of silver grains over the nuclei showed no increase in low level labelling after omeprazole administration, indicating that there was no unscheduled DNA synthesis. The labelling index of undigested gastric tissue from omeprazole treated rats was not significantly different from that of the control group, despite an increase in the plasma gastrin value.

Animals↗