Biomedical subjects

S R Bloom

Publications and source records attributed to S R Bloom.

At least 775 records · Page 43Linked to original sources

PubMed1984

Human and porcine immunoreactive gastric inhibitory polypeptides (IR-GIP) are not identical.

Immunoreactive gastric inhibitory polypeptide (IR-GIP) from human and porcine intestine was quantified by radioimmunoassay and the molecular forms characterised by gel permeation and reverse-phase high pressure liquid chromatography (HPLC). Gel filtration revealed two major immunoreactive peaks corresponding to the previously described 5-kDa and 8-kDa molecular forms, which appeared similar in both species. Isocratic reverse-phase HPLC revealed that the major immunoreactive GIP peak (5-kDa) in the human tissue eluted earlier than the corresponding porcine molecular form, indicating the latter to be less hydrophobic. These findings suggest significant species differences between human and porcine GIP.

Animals↗

PubMed1984

Neurotensin secretion by fibrolamellar carcinoma of the liver.

Serum neurotensin concentrations were supranormal in 5 out of 20 patients with carcinoma of the liver. Liver specimens from 4 of these 5 patients demonstrated features typical of fibrolamellar carcinoma. Neurotensin may be suitable as a tumour marker for fibrolamellar carcinoma and may be useful for the detection of recurrences after treatment.

Carcinoma, Hepatocellular↗

PubMed1984

Regional distribution of bombesin and seven other regulatory peptides in the human brain.

In order to compare within the same brains the quantitative distributions of a range of neuropeptides, bombesin, N- and C-terminal glucagon, cholecystokinin, neurotensin, somatostatin, substance P and vasoactive intestinal polypeptide immunoreactivities were determined by radioimmunoassay in 24 regions of 5 normal adult human brains. Each peptide showed a different distribution pattern. Of the peptides not previously mapped in detail in the human brain, bombesin-like immunoreactivity was present in all regions with the highest concentrations in particular areas of the hypothalamus, septal nuclei, nucleus accumbens, globus pallidus, amygdala, periaqueductal grey and substantia nigra. C- and N-terminal glucagon immunoreactivities were detected only in the ventromedial hypothalamus. The concentrations of the remaining 5 peptide immunoreactivities, and their molecular forms, were in good general agreement with those reported individually by others in both human brains and those of experimental animals. The quantitative mapping of the regulatory peptides in the human brain provides an essential base for further comparative study in diseased postmortem brains.

Adult↗

PubMed1984

Neuron specific enolase: a marker for the early development of nerves and endocrine cells in the human lung.

Neuron specific enolase (NSE), an isoenzyme of the glycolytic enzyme enolase, has been established by immunocytochemical means as a marker of morphological and functional maturation in central neurons and appears late in development. However, little is known about the presence of NSE in developing peripheral neurons and endocrine cells and its relationship to the development of classical neurotransmitters and peptides. We therefore investigated the appearance of NSE immunoreactivity in nerves and mucosal endocrine cells of the human respiratory tract in foetal, neonatal and adult life. NSE was found to be present in neuroblasts, nerve fibres and endocrine cells from the earliest period of gestation examined (8 weeks), before the appearance of acetylcholinesterase activity (10-12 weeks), dopamine-beta-hydroxylase (20 weeks), vasoactive intestinal polypeptide (20 weeks) or calcitonin (20 weeks). Bombesin-like immunoreactivity was found in a small proportion of mucosal endocrine cells as early as eight weeks in the foetal respiratory tract. These findings indicate that unlike central neurons and their processes, peripheral neurons of the lung contain NSE immunoreactivity well before full maturation and establishment of synaptic contact with end organs.

Endocrine Glands↗

PubMed1984

VIP and asthma.

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Asthma↗

PubMed1984

The effect of previous endocrine therapy on responses to a single dose of an LHRH analogue.

Serum concentrations of gonadotropins, testosterone and dehydrotestosterone were determined in patients receiving conventional endocrine therapy for advanced metastatic adenocarcinoma of prostate. The effect over 4 h of a single dose of a long acting analogue of LHRH was determined in these patients and compared to the response in patients receiving the analogues as first choice of treatment. Oestrogen therapy was found to suppress basal and stimulated gonadotropins and testicular androgens. Cyproterone therapy only partially reduced basal hormone concentrations and the response to the LHRH analogue was delayed. Orchidectomy resulted in elevated gonadotropins and an exaggerated response to the analogue. As patients who relapse while failing conventional therapy, may subsequently be treated by further endocrine manipulation, precise determination of their endocrine status should predict any expected benefit. Patients previously treated with stilboestrol are unlikely to respond to orchidectomy or LHRH analogue.

Adenocarcinoma↗

PubMed1984

How glucagon-like is glucagon-like peptide-1?

Although glucagon-like peptide-1 has the appearance of a glucagon-homologue that may be co-secreted with glucagon, synthetic glucagon-like peptide-1-(1-37) does not significantly affect plasma glucose and insulin concentrations when administered at high doses (100 and 400 micrograms) to cortisone-pretreated rabbits. This synthetic preparation thus lacks the primary metabolic effect of glucagon at the doses tested. An intra- or extra-pancreatic role of glucagon-like peptide-1 has yet to be discovered.

Amino Acid Sequence↗

PubMed1984

Impaired growth hormone response to human pancreatic growth hormone releasing factor [GRF(1-44)] in type 2 (non-insulin-dependent) diabetes.

Human pancreatic growth hormone releasing factor [GRF(1-44)] is the largest molecule of several peptides recently isolated from pancreatic tumours associated with acromegaly. It has been shown to stimulate the release of growth hormone in normal subjects and provides a safe and reliable tool for examining growth hormone release. A study was conducted to examine the release of growth hormone in patients with Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes. GRF(1-44) stimulated the release of growth hormone in normal subjects and produced no side effects. A response of similar magnitude occurred in Type 1 diabetic patients despite their concomitant hyperglycaemia. In contrast, the response in Type 2 diabetes was significantly impaired compared with normal volunteers (p less than 0.05) and Type 1 diabetic patients (p less than 0.02). These findings may well indicate that there is a defect in central hormonal control in Type 2 diabetes.

Adolescent↗

PubMed1984

Visualisation of messenger RNA directing peptide synthesis by in situ hybridisation using a novel single-stranded cDNA probe. Potential for the investigation of gene expression and endocrine cell activity.

The neuropeptide tyrosine precursor (pre-pro-NPY) messenger RNA (mRNA) has been localised in formaldehyde-fixed human phaeochromocytoma tissue using a sensitive in situ hybridisation procedure and a novel single-stranded cDNA probe. The reaction product was revealed by avidin-biotin-peroxidase complex and streptavidin-gold complex with silver enhancement. This technique may be applied for the determination of biosynthetic activity of endocrine and neuronal cell bodies. This is largely due to its rapidity by comparison with conventional autoradiographic procedures, to the permanence of the reaction product and to the sensitivity of the visualisation steps.

Adrenal Gland Neoplasms↗

PubMed1984

The nerves of the juxtaglomerular apparatus of man and other mammals contain the potent peptide NPY.

The juxtaglomerular apparatus, a neuroendocrine unit located in the vascular pole of the glomerulus and influencing blood pressure by the secretion of renin, is known to have a rich supply of monoaminergic nerve fibres. Neuropeptide Tyrosine (NPY), a newly discovered, potent, vasoconstrictor peptide of 36 amino acids, has been found by immunocytochemistry to be present in a dense plexus of fibres around the juxtaglomerular apparatus of man, monkey, mouse, hamster, rat and guinea pig. NPY-immunoreactivity was markedly depleted after chemical sympathectomy by 6-hydroxydopamine. The concentration of NPY within the whole mouse kidney was 29.6 +/- 6.8 pmol/g and fractionation of the extracts demonstrated that the NPY-like immunoreactivity co-eluted from the column in the same position as the porcine NPY standard. The role of this peptide in renal physiology and pathology now needs urgent investigation.

Animals↗

PubMed1984

Peptide YY (PYY) immunoreactivity is co-stored with glucagon-related immunoreactants in endocrine cells of the gut and pancreas.

In this study we report the localisation of PYY immunoreactivity in intestinal mucosa endocrine (EG) cells containing glucagon-related peptides and also in foetal pancreatic A cells of rat and man. Radioimmunoassay of human foetal pancreatic extracts revealed the presence of PYY immunoreactivity, the concentration of which declined with age (from 65.42 pmol/g at week 20 to 17.0 pmol at week 40; correlation coefficient = -0.893), in contrast to the amount of glucagon which remained statistically constant throughout the same foetal period. The identity of this PYY immunoreactive material with the original 36 amino acid porcine peptide has been shown by high pressure liquid chromatography (HPLC).

Adult↗

PubMed1984

Peptide-immunoreactive nerves in the mammalian female genital tract.

Vasoactive intestinal polypeptide, substance P, neuropeptide Y and peptide histidine isoleucine immunoreactivities have been demonstrated in the female genitalia of rat, cat, mouse and guinea-pig using immunocytochemistry and radioimmunoassay. They were localized to nerves. Each type of immunoreactive nerve showed a distinct pattern of distribution, though all were associated to some degree with blood vessels and smooth muscle. Vasoactive intestinal polypeptide-immunoreactive and neuropeptide Y-immunoreactive nerves were the most abundant. Higher concentrations of peptides were detected in the female genitalia of the mouse than those of the other species studied. Vasoactive intestinal polypeptide-immunoreactive nerves were particularly concentrated in the cervix (89.1 +/- 17.2 pmol/g, mean +/- S.E.M.) and the uterus (57.4 +/- 14.8 pmol/g) of the mouse, while neuropeptide Y immunoreactivity was more abundant in the Fallopian tube of the mouse (31.6 +/- 11.8 pmol/g) and the vagina of the rat (38.6 +/- 4.8 pmol/g) than in other regions. Separate populations of ganglion cells in the paracervical ganglia were found to contain vasoactive intestinal polypeptide and neuropeptide Y immunoreactivities. Peptide histidine isoleucine-immunoreactive and vasoactive intestinal polypeptide-immunoreactive nerves were similarly distributed, but the former were much less frequent. Substance P-immunoreactive nerves were seen mainly beneath the epithelium of the vagina and were, in general, more numerous in the guinea-pig than in other species. The significance of these peptide-immunoreactive nerves in the female genital organ remains to be determined.

Animals↗

PubMed1984

Plasma enteroglucagon and CCK levels and cell proliferation in defunctioned small bowel in the rat.

Luminal nutrients exert a powerful trophic effect on small bowel mucosa. Recent evidence suggests that a circulating factor, possibly enteroglucagon, is also growth-promoting. In order to study the isolated effect of nonluminal influences on bowel mucosa, Thiry-Vella fistulae (TVF) were constructed in rats. Circulating enteric hormone concentrations were manipulated by resecting different lengths of remaining gut. Thirty-two male Wistar rats had either 25%, 50%, 75%, or 90% proximal small bowel resection. In each animal the first 25% of resected bowel was exteriorized as a Thiry-Vella fistula. Seven control rats underwent jejunal transection. Twelve days postoperatively the fasted animals were killed, and circulating and tissue concentrations of enteroglucagon and CCK were estimated by radioimmunoassay. Crypt-cell production rate was used as an index of cellular proliferation in the Thiry-Vella fistulae. Proximal small bowel defunctioned in the Thirty-Vella fistulae had a significantly lower crypt-cell production rate and enteroglucagon and CCK content than the equivalent segment in transected rats. Further small bowel resection produced a subsequent increase in circulating enteroglucagon and CCK concentrations, an increase in the Thiry-Vella fistula content of these hormones, and a doubling of the crypt-cell production rate in the Thiry-Vella fistulae. These results show that circulating enteroglucagon and CCK concentrations match closely with enterocyte production even when luminal influences are excluded. It is suggested that circulating factors may play a major role in postresectional ileal hyperplasia. This hyperplasia apparently affects endocrine cells as well as enterocytes.

Animals↗

PubMed1984

Effects of VIIth (facial) nerve degeneration on vasoactive intestinal polypeptide and substance P levels in ocular and orbital tissues of the rabbit.

Levels of vasoactive intestinal polypeptide (VIP)- and substance P (SP)-like immunoreactivity were measured in ocular and orbital tissues of albino rabbits. Substantial amounts of VIP were detected in the choroid (22.6 +/- 3.6 pmol g-1), and in the lacrimal (13.6 +/- 4.4 pmol g-1) and Harderian glands (20.2 +/- 4.9 pmol g-1). Somewhat less was found in the anterior uvea (3.6 +/- 1.1 pmol g-1), retina (5.4 +/- 1.3 pmol g-1) and optic nerve head (4.1 +/- 1.1 pmol g-1). Other tissues, including conjunctiva and extraocular muscle showed very little VIP-like immunoreactivity. Seven days after diathermic damage to the region of the pterygopalatine ganglion VIP was virtually eliminated from all these tissues. SP levels were also reduced, notably in the anterior uvea, probably due to concurrent destruction of sensory fibres. Electron microscopy revealed extensive degeneration of unmyelinated axons in the short ciliary nerves and in the choroid. No changes in ocular VIP levels were detected after sympathetic denervation, although a significant rise in SP was observed in the anterior uvea. The decrease in retinal VIP, believed to be confined to the amacrine cells, is considered to be a result of post-operative lid closure, rather than of VIIth nerve degeneration. Nevertheless, with this exception, VIP in ocular and orbital tissues of the rabbit appears to be contained exclusively within parasympathetic fibres of facial nerve origin.

Animals↗

PubMed1984

Elevation of neuropeptide Y (NPY) in substantia innominata in Alzheimer's type dementia.

Concentrations of neuropeptide Y (NPY) have been determined in 12 areas of control brains and compared to those found in brains from patients with Alzheimer's type dementia (ATD). The distribution of NPY in the control brains was compared with those reported previously. Highest concentrations were identified in the subcortical structures, in particular, nucleus accumbens (203 +/- 21.7 pmol/g), amygdala (136.7 +/- 15.8 pmol/g), and substantia innominata (109.0 +/- 12.6 pmol/g). A significant elevation in NPY concentrations was identified in the region of the substantia innominata of Alzheimer brains (controls: 109.0 +/- 12.6 pmol/g, ATD: 206 +/- 28.2 pmol/g, P less than 0.001). This change in NPY concentration was similar to the increase in somatostatin concentration in this region of ATD brain. In contrast, although cortical concentrations of somatostatin were reduced in ATD, no change was found in the concentrations of NPY in the 4 regions of cerebral cortex and the remaining subcortical areas examined.

Aged↗

PubMed1984

The effects of ileal transposition and jejunoileal bypass on food intake and GI hormone levels in rats.

Male Wistar rats received three different types of small intestinal surgery. Two groups of rats had either 10 or 20 cm of lower ileum transposed to mid-duodenum. A third comparison group of rats had 85% jejunoileal bypass. All three experimental groups showed a sustained post-operative reduction in food intake and a change in body weight gain. Measurements made 36 days after surgery showed that all experimental groups had a large increase in basal and meal-stimulated enteroglucagon. The total-integrated plasma levels of gastrin, GIP, insulin and blood glucose were significantly reduced. At sacrifice, there were large increases in the wet weight of the small intestine and pancreas. These changes were probably due to the chronic stimulation of the lower ileum with nutrient-rich chyme and may be due to the release of ileal hormones.

Animals↗

PubMed1984

Peptide-containing nerves in human urinary bladder.

Nerves containing immunoreactive vasoactive intestinal polypeptide (VIP), substance P and two newly discovered peptides, neuropeptide tyrosine (NPY) and PHI (peptide having N-terminal histidine and C-terminal isoleucine), have been found in the human urinary bladder by immunocytochemistry and radioimmunoassay. Somatostatin immunoreactivity was detected by radioimmunoassay. The VIP-immunoreactive nerves were widely distributed in all regions, but were particularly dense beneath the epithelium and in the muscle layer. Scattered intramural ganglia were found to be reactive to VIP antiserum. Higher concentrations of extractable VIP were detected in the trigone than in the dome. VIP- and PHI-immunoreactive nerves were similarly distributed, the latter being less numerous. NPY-immunoreactive nerves were seen mainly in the muscle layer, particularly in the trigonal area. The distribution patterns of VIP- and NPY-immunoreactive nerves resembled those of the previously reported cholinergic and adrenergic nerves, respectively. Many blood vessels were found to be innervated by both types of immunoreactive nerves. Scattered substance P-immunoreactive fibers were occasionally seen, being present in the submucosa and around the detrusor muscles. The significance of these nerves remains to be elucidated.

Fluorescent Antibody Technique↗

PubMed1984

Radioimmunoassay of neuropeptide Y.

The development of a radioimmunoassay to the newly isolated peptide, neuropeptide Y is described. Four separate antisera have been developed using different immunisation schedules. Two of these antisera (YNI and YNIO) are directed to the C-terminal region of the peptide and cross-react with the related peptide PYY, whereas YN7 is specific being directed to the N-terminal region of NPY, YN6 is similarly specific for NPY, but is unable to bind the available fragments. These four antisera provide similar results for determination of NPY immunoreactivity within porcine brain extracts, however YN6 consistently undervalues all extracts from the other species examined (human, rat, guinea pig, cat and mouse). Chromatographic analysis by means of reverse phase high pressure liquid chromatography (HPLC) shows that NPY immunoreactivity of human extracts elutes in an earlier position than the porcine standard. It seems likely therefore that human and porcine NPY differ in their amino acid sequences.

Animals↗