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Biomedical subjects

S R Bloom

Publications and source records attributed to S R Bloom.

At least 865 records · Page 48Linked to original sources

The value of S-100 immunostaining as a diagnostic tool in human malignant melanomas. A comparative study using S-100 and neuron-specific enolase antibodies.

The brain proteins S-100 and neuron-specific enolase have been reported by separate groups to be present in human malignant melanomas. There is no systematic study comparing the occurrence of these proteins in the same tumour specimens. We have examined 33 primary malignant melanomas, including 5 which were amelanotic, and 25 metastatic melanomas using immunohistochemical methods with specific, non-cross-reacting antibodies to S-100 and NSE. We found S-100 immunoreactivity to be present in all cases but one, whereas NSE immunoreaction was very weak and patchy, and present in only 6 cases. S-100 immunoreactivity was not demonstrated in 40 control tumours, either primary or metastatic in skin, including basal- and squamous-cell carcinomas, spindle-cell sarcomas, lymphomas and Merkel cell tumours. All intradermal (n = 4) and compound (n = 1) naevi were positive for S-100, 2 blue naevi showing much less reaction. NSE immunoreactivity was detected in Merkel cell tumours (n = 8), undifferentiated (n = 2) and small cell (n = 1) carcinomas, and all melanocytic naevi. It is suggested therefore that antibody to S-100 is the reagent of choice for demonstration of melanocytic tumours, and may be especially valuable in the diagnosis of amelanotic melanoma or metastatic tumours of doubtful origin where melanoma is suspected.

Fluorescent Antibody Technique↗

Radioimmunoassay and intramural distribution of PHI-IR in human intestine.

The objective of this study was to develop a radioimmunoassay for PHI and use this to assess its intramural distribution in the human intestine. The antibody was harvested following immunization with porcine PHI conjugated to bovine serum albumin by glutaraldehyde, and the iodinated PHI tracer was prepared by the Iodo-gen method. The assay system showed no cross-reaction with other members of the glucagon-secretin family of peptides and was sensitive to changes of PHI of 2 fmol/tube (95% confidence). High concentrations of immunoreactive PHI were found in the human intestine, exclusively localized in the nonendocrine gut layers, suggesting a possible neuroendocrinological or neurotransmitter role for PHI.

Chromatography↗

Peptide histidine isoleucine (PHI). A secretagogue in porcine intestine.

PHI (peptide histidine isoleucine) is a recently identified porcine peptide, present in large quantities in the intestine, which has sequence homologies with VIP, an established intestinal secretagogue, and with secretin, glucagon, and GIP. The effects of PHI on jejunal, ileal, and colonic fluid and electrolyte transport were studied in the pig. PHI appears to be an intestinal secretagogue inducing a reversible net secretion of fluid and electrolytes in jejunum and ileum and less marked effects in the colon.

Animals↗

Cell proliferation, plasma enteroglucagon and plasma gastrin levels in starved and refed rats.

The effects of starvation and refeeding on intestinal cell proliferation at several sites of the rat gastrointestinal tract were studied and used as a model of altered cell proliferation in order to investigate the relationship between the rate of cell production and plasma gastrin and enteroglucagon. There was a marked fall in crypt cell production rate after four days starvation, with the proximal sites of the gut being most affected. The response to refeeding varied with site, suggesting that there was more than one mechanism for the control of intestinal cell proliferation. Plasma gastrin and enteroglucagon both fell to one fifth of their control level after starvation. Plasma gastrin increased slowly after refeeding, whilst plasma enteroglucagon increased rapidly to values significantly above control. Plasma gastrin was only correlated with crypt cell production in the duodenum, while plasma enteroglucagon was correlated with crypt cell production rate at several sites, indicating that enteroglucagon may be involved in the control of intestinal cell production.

Animals↗

Increase in SP-like immunoreactivity in nerve fibres of rabbit iris and ciliary body one to four months following sympathetic denervation.

Substance P (SP) levels in rabbit iris-ciliary body preparations were found to be significantly elevated 30 days after removal of the superior cervical ganglion when compared with the contralateral unoperated side. These elevated levels were still apparent after two and three months. Immunohistochemical studies, using a monoclonal antibody to SP, revealed an increase in the density of SP-immunoreactive nerve fibres in the region of the iris dilator muscle and in the ciliary processes one to four months after sympathectomy, although the density of these fibres in other regions of the iris was not altered.

Animals↗

24-hour variation in content and release of hypothalamic neuropeptides in the rat.

The tissue content of up to eight neuropeptides, viz bombesin (BOM), cholecystokinin (CCK-8), neurotensin (NT), neuropeptide Y (NPY), peptide histidine isoleucine amide (PHI), somatostatin (SRIF), substance P (SP) and vasoactive intestinal polypeptide (VIP), in rat hypothalami removed at various times of the day, was measured using specific radioimmunoassays. There was significant variation in the content of BOM, CCK-8, NT, PHI, SP and VIP across a 24-h period. The levels of BOM, CCK-8 and NT were lowest around the onset of darkness (1900 h) and rose throughout the night to reach a peak around the time of lights on. Hypothalamic content of all eight peptides fell between 0700 h and 1300 h by an average of 45 +/- 4%. Basal release of these peptides, as well as that in the presence of 48 mM potassium (K+), was measured from hypothalami removed between 0700 and 1900 h and incubated in vitro in a CSF-like medium. Basal secretion of NT significantly increased, whilst that of CCK-8 significantly decreased over the same period. There was no significant change in the basal release of the other neuropeptides. The release in the presence of 48 mM K+ of SP decreased significantly during the day, whilst that of VIP significantly increased. There was also a significant change in the stimulated release of BOM, levels falling during the morning and rising again at 1900 h. 48 mM K+ caused a significant increase in the release of SRIF and SP at all times tested. Whilst 48 mM K+ induced a significantly higher release of CCK-8 and NT in the morning, this stimulus was ineffective in the evening. The contrary was true in the case of BOM, NPY and VIP, where a significant stimulation was induced only at 1900 h. The possible implications of these findings are discussed.

Animals↗

Dose-response comparisons of canine plasma gastroenteropancreatic hormone responses to bombesin and the porcine gastrin-releasing peptide (GRP).

This study compares the potencies of the porcine gastrin-releasing peptide (pGRP) and bombesin, in causing elevations of canine plasma gastroenteropancreatic (GEP) levels. In the dose range 0-600 pmol . kg-1 . h-1, infusion of both peptides resulted in obvious dose-related elevations of plasma levels of gastrin, pancreatic polypeptide, enteroglucagon, immunoreactive pancreatic glucagon, and insulin. In this dose range, no significant difference in potency between the two peptides in elevating plasma levels of the above hormones was observed. The results of this study, demonstrating equimolar potency of pGRP and bombesin, are in contrast to previous studies reporting that pGRP was less potent than bombesin in causing certain bioactivities in the rat following intracranial administration of the two peptides.

Animals↗

Neuropeptide Y (NPY) reduces myocardial perfusion and inhibits the force of contraction of the isolated perfused rabbit heart.

Isolated rabbit hearts, perfused under constant pressure (Langendorff technique) were used to study the effect of neuropeptide Y (NPY) on heart rate, force of heart contraction and rate of myocardial perfusion. No significant net change in heart rate was noted. A dose-dependent negative inotropic effect was consistently demonstrated which was characterised by slow onset and was often preceded by a transient positive inotropic response. Addition of small doses of NPY resulted in a prompt reduction in flow of the perfusate through the coronary vasculature. Since NPY is present locally in cardiac nerves, these effects may have physiological importance.

Acetylcholine↗

Peptidergic innervation of the human male genital tract.

Four peptides--vasoactive intestinal polypeptide, substance P, somatostatin and a peptide-like avian pancreatic polypeptide--have been found in nerves of the human male genitalia using highly sensitive and specific methods of immunocytochemistry and radioimmunoassay. Five other peptides (met-enkephalin, leu-enkephalin, neurotensin, bombesin and cholecystokinin-8) were absent. Vasoactive intestinal polypeptide was the most abundant peptide, its highest concentration being in the proximal corpus cavernosum. Immunoelectron microscopy localized this peptide to large (97 +/- 20 nm), round, electron-dense granules of p-type nerve terminals. Vasoactive intestinal polypeptide-immunoreactive neuronal cell bodies were found in the prostate gland and the root of the corpus cavernosum. Substance P immunoreactive material was present in smaller concentration and was mainly localized in nerves around the corpuscular receptors of the glans penis. Somatostatin immunoreactive nerves were associated mainly with the smooth muscle of the seminal vesicle and the vas deferens. When antiserum to avian pancreatic polypeptide was applied, certain nerves were stained, particularly in the vas deferens, the prostate gland and the seminal vesicle. However, chromatography detected no pure avian pancreatic polypeptide suggesting the presence of a structurally related substance, possibly neuropeptide Y, which cross-reacts with the avian pancreatic polypeptide antiserum. Similar distributions between vasoactive intestinal polypeptide-immunoreactive and acetylcholinesterase-positive nerves and between avian pancreatic polypeptide-immunoreactive and adrenergic nerves were observed. A general neuronal marker, neuron-specific enolase, was used to investigate the general pattern of the organ's innervation. The abundance and distribution patterns of these peptide-immunoreactive nerves indicate that they may play important roles in the male sexual physiology.

Adult↗

The effect of the mammalian neuropeptide, gastrin-releasing peptide (GRP), on gastrointestinal and pancreatic hormone secretion in man.

Gastrin-releasing peptide, a newly isolated mammalian peptide similar in its structure and actions to the amphibian peptide, bombesin, has recently been localized to nerves in the brain, gut and pancreas. The present study investigates its effects on gut and pancreatic peptides in man. Intravenous infusion of 0.7 and 2.9 pmol min-1 kg-1 produced significant elevation of plasma gastrin, cholecystokinin-like immunoreactivity and neurotensin. It was found also to potentiate glucose-dependent insulin secretion. Its specific location in nerve fibres in the proximal gut and pancreas and its selective effect on gastroenteropancreatic peptides may favour its role as a physiological regulatory neuropeptide.

Adult↗

Increased plasma pancreatic polypeptide in chronic alcohol abuse.

Post-prandial plasma gastrointestinal hormone profiles were measured in nine chronic alcoholics, one and fourteen days after complete alcohol withdrawal. Basal plasma pancreatic polypeptide concentration (PP--mean +/- SE mean) was significantly greater in alcoholics (control, 28 +/- 5 pmol/l; alcoholics, post-withdrawal day 1, 62 +/- 14 pmol/l, P less than 0.05; and post-withdrawal day 14, 89 +/- 17 pmol/1, P less than 0.005). The total integrated (TIR) PP response following a test breakfast was similarly elevated (control, 442 +/- 63 units; alcoholics, day 1, 1310 +/- 231 units, P less than 0.005; day 14,1066 +/- 66, P less than 0.005). Basal and TIR values for gastrin, gastric inhibitory peptide, insulin and glucagon were similar in alcoholics and controls. As PP has been shown to inhibit pancreatic exocrine enzyme secretion, these findings may help explain the abnormal pancreatic function seen frequently in alcoholics.

Adult↗

Enteroglucagon and GIP after oral glucose in patients with prolactinoma and acromegaly.

We have performed oral glucose tolerance tests (OGTT) in nine patients with prolactinomas, eight patients with active acromegaly, five patients with acromegaly in remission and nine normal controls, and measured blood glucose, plasma insulin, pancreatic glucagon, enteroglucagon, gastric inhibitory polypeptide (GIP) and GH during the test. Patients with prolactinomas and with active acromegaly were hyperinsulinaemic and five of the nine patients with prolactinomas had impaired glucose tolerance, with blood glucose levels that were significantly higher than the normal controls. Prolactinoma patients had higher GIP levels than those with active acromegaly and both showed a failure of suppression of pancreatic glucagon. Of particular interest was the finding that enteroglucagon, a putative gut growth factor, was low in active acromegaly when compared with acromegaly in remission, but similar to normal in the rest of the patients.

Acromegaly↗

The effects of an opiate agonist and antagonist on the human upper gastrointestinal tract.

Endogenous opiates may play a role in regulating intestinal function and we have investigated this possibility in the human upper gastrointestinal tract using loperamide as a locally-acting opiate agonist and naloxone as antagonist. Loperamide (4 mg) had no effect on the fasting pattern of motor activity in the antrum, duodenum and proximal jejunum. However, naloxone (40 micrograms kg-1 h-1, i.v.) abolished interdigestive motor activity in five of ten subjects and reduced antroduodenal motility index per cycle in all subjects (antrum: 1230 +/- 120 to 130 +/- 140 mm2; duodenum: 1120 +/- 150 to 225 +/- 160 mm2; P less than 0.005). These effects were not significantly affected by loperamide. Plasma motilin exhibited cyclic variation with significantly higher concentrations during antroduodenal phase 3 than during phases 1 and 2 of the interdigestive cycle. Plasma motilin was not altered by naloxone or loperamide, and neither drug had any effect on basal gastric acid secretion, duodenal output of amylase and bile salt or duodenogastric reflux. The results suggest that endogenous opiates regulate fasting motor activity in the human gastrointestinal tract but do not influence basal secretory function of the stomach, pancreas or biliary tree.

Adult↗