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Biomedical subjects

S R Bloom

Publications and source records attributed to S R Bloom.

At least 361 records · Page 20Linked to original sources
PubMed1990

Secretion of epidermal growth factor in parotid saliva in diabetic patients: role of autonomic innervation.

Parotid saliva was collected over a 12-min period from 24 insulin dependent diabetic patients with varying degrees of autonomic neuropathy and 12 age and sex matched non-diabetic controls. Epidermal growth factor (EGF) concentrations in saliva were measured by radio-immunoassay. The EGF concentrations in diabetics with no autonomic neuropathy or with combined autonomic neuropathy were equivalent but secretion of EGF was significantly elevated at the 6- and 12-min periods of collection in diabetic patients with early or established autonomic neuropathy. It is postulated that when parasympathetic autonomic neuropathy is present a relative "over-activity" of the sympathetic innervation promotes release of salivary EGF. This sympathetic predominance may maintain salivary EGF concentration despite the elevated salivary flow and volume which is associated with parasympathetic autonomic neuropathy.

Autoimmune Diseases↗
PubMed1990

The effect of changes in adrenal blood flow on adrenal cortical responses to adrenocorticotrophin in conscious calves.

1. The effect of varying adrenal blood flow on the rate at which it was estimated that adrenocorticotrophin (ACTH) was presented to the adrenal gland was related to right adrenal cortisol output in conscious calves fitted with 'adrenal clamps'. 2. Intra-aortic infusions of endothelin at either 15.0 or 7.5 pmol min-1 kg-1 produced a substantial fall in right adrenal blood flow which was dose-related over this range. There was an associated fall in right adrenal cortisol output and cortisol output was linearly related to estimated ACTH presentation to the gland over the whole range investigated. The changes in adrenal cortisol output were reflected by changes in the concentration of cortisol in the peripheral plasma, which could be attributed entirely to the fluctuations in adrenal cortisol output. 3. It is concluded that delivery of ACTH to the adrenal gland is flow dependent over the physiological range in these animals and that changes in adrenal cortical blood flow can therefore be expected to result in changes in adrenal output due to variations in the presentation rate of ACTH.

Adrenal Cortex↗
PubMed1990

Regional hemodynamic effects of neuromedin U in conscious rats.

In conscious unrestrained Long-Evans rats, chronically instrumented with miniaturized pulsed Doppler flow probes, intravenous administration of porcine neuromedin U-8 by bolus (0.1 and 1.0 nmol) or infusion (1 and 10 nmol/h) exerted potent constrictor effects on the superior mesenteric vascular bed. With the choice of an appropriate dose, the reduction in superior mesenteric blood flow was not accompanied by any changes in systemic arterial blood pressure, heart rate, and renal or hindquarters blood flows. Porcine neuromedin U-25 had similar effects to neuromedin U-8, but was generally more potent. In Brattleboro rats the pattern of response to neuromedin U-25 was similar to that seen in Long-Evans rats, indicating that mesenteric vasoconstriction was not dependent on release of endogenous vasopressin. In Long-Evans rats the regional hemodynamic actions of rat neuromedin U were comparable with those of porcine neuromedin U-25. The latter peptide at a dose of 1.0 nmol caused a rise in total peripheral resistance and a reduction in cardiac output, with an inconsistent change in heart rate. The results raise the possibility that the high concentration of neuromedin U in the rat intestine is associated with the control of local blood flow.

Animals↗
PubMed1990

Magnetic bead separation of anterior pituitary cells.

The use of magnetic beads coated with anti-IgG antibodies should allow simultaneous purification and depletion of differing anterior pituitary cell types labelled with anti-hormone antibodies. This technique would be expected to give very similar results to fluorescence-activated cell sorting (FACS). Magnetic bead separation of dispersed, labelled anterior pituitary cells is cheap, easy and quick to perform (time from the end of anti-hormone antibody labelling to completion of purification is approximately 30 min) and the resulting cells are viable for at least 24 hours after purification. While the cell recovery for beads and FACS, 94% (SEM +/- 4.4) vs. 89% (SEM +/- 3.9) and purity of 88% (SEM +/- 2.2) vs. 96.7% (SEM +/- 1.7) for lactotrophs and purity of 87% (SEM +/- 1.9) vs. 98% (SEM +/- 1) for somatotrophs are similar, the results for depletion by the magnetic bead separation method are disappointing, only 30-40% of the labelled lactotrophs or somatotrophs cells bind to the beads and thus only a sub-population of cells may be purified by this method. These results are explicable on the basis of the sensitivity of the two techniques. Pituitary cells co-incubated with two specific anti-prolactin antibodies (one raised in rabbit and one in sheep) demonstrate that removal by Dynal magnetic beads (coated with rabbit IgG antibody) of those prolactin molecules bound to the rabbit anti-prolactin antibody also removed those prolactin molecules bound to a sheep anti-prolactin antibody. In contrast, co-incubating cells with the rabbit anti-prolactin antibody and a sheep anti-growth hormone antibody did not remove growth hormone labelling when the prolactin bound to the beads was removed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Sandostatin and the Hammersmith experience.

Ten patients with various metastatic pancreatic tumours have received Sandostatin (octreotide) for up to 5 years, initially 50 micrograms t.i.d. subcutaneously but increased over 6-12 months to 500 micrograms t.i.d. Three patients showed no biochemical or clinical response to Sandostatin. In the remaining patients, treatment was extremely effective: tumour secretions fell by nearly 60% and clinical symptoms improved or resolved in all. At 5-6 months, all patients showed worsening symptoms and rising hormonal concentrations. Although relapses were initially responsive to Sandostatin (at 500 micrograms t.i.d.), patients eventually became unresponsive to all therapies, and all died within 6 months of the development of this resistive phase. Side effects were minimal and long-term therapy was well tolerated. Steatorrhoea and the development of gallstones were not observed.

Gastrins↗
PubMed1990

Is peptide YY trophic to the intestinal epithelium of parenterally fed rats?

Four groups of intravenously maintained rats were infused with 0, 5, 20 or 80 micrograms/rat/day of peptide tyrosine tyrosine (PYY) for 3 days. After 3 days the rats were injected with 1 mg/kg of vincristine in order to arrest cells entering metaphase and were killed 2 h later. The gastrointestinal tract was removed, weighed and fixed. Samples of small intestine and colon were stained, microdissected and the mean number of metaphases per crypt determined. No significant effect on intestinal tissue mass or the 2-hour collection of metaphases was observed. It is concluded that PYY is not trophic to the gastrointestinal tract.

Animals↗
PubMed1990

Effect of ACTH on VIP and galanin release from the pituitary.

The effect of adrenocorticotropin (ACTH) on the release of four regulatory peptides from the anterior pituitary of male rats has been studied using an in vitro perfusion system. Quartered anterior pituitaries from male adult Wistar rats were perfused with buffer containing different concentrations of ACTH and, subsequently, 56 mM KCl. Fractions of 1.5 ml were collected at 3 min intervals and analyzed for vasoactive intestinal peptide (VIP), galanin, 7B2, and substance P, using specific radioimmunoassays. Concentrations of 0.02, 0.1, 0.2, and 0.4 microM ACTH produced increases of 117 +/- 50%, 155 +/- 90%, 163 +/- 14%, and 161 +/- 3% (mean + SE), respectively, of basal release of VIP (P less than 0.001). However, concentrations of 1 microM and 2 microM ACTH suppressed VIP release to 74 +/- 6% and 47 +/- 4%, respectively, compared to basal release (P less than 0.001). Results for galanin release were similar: concentrations of 0.02, 0.1, 0.2, and 0.4 microM ACTH increased galanin release to 129 +/- 4%, 136 +/- 8%, 143 +/- 9%, and 133 +/- 9% of basal release (P less than 0.001) and 1 and 2 microM ACTH provoked a suppression of 52 +/- 7% and 50 +/- 13%, respectively, compared with basal release (P less than 0.001). Doses of ACTH that altered the secretion of VIP and galanin had no effect on 7B2 and substance P release. These results demonstrate that ACTH causes a release of pituitary VIP and galanin in vitro and, moreover, that this is a biphasic phenomenon.

Adrenocorticotropic Hormone↗
PubMed1990

The influence of thyroid hormone status on the hypothalamo-hypophyseal growth hormone axis.

Growth hormone (GH) synthesis is known to be impaired by either abnormally high or low levels of thyroid hormone. To determine the effects of these conditions on the central regulation of GH secretion, we have examined their effects on the hypothalamic regulatory peptides GH-releasing hormone (GH-RH) and somatostatin (SRIF). In thyroidectomized rat hypothalamus, a dramatic increase in GH-RH mRNA occurred in parallel with a decrease in peptide content. The significance of this phenomenon is uncertain and might possibly reflect some posttranscriptional derangement of GH-RH synthesis or an increased rate of GH-RH synthesis and release. In the hyperthyroid group, GH-RH showed significant decreases in both peptide and mRNA levels that might possibly reflect a decrease in GH-RH synthesis and secretion. No change was observed in SRIF peptide or mRNA levels in either thyroidectomized or T4-treated animals. As expected, GH mRNA levels in the anterior pituitary were dramatically decreased by thyroidectomy and unaffected by T4 treatment. In addition, in thyroidectomized pituitaries, the mature GH mRNA was observed to alter its structure, increasing in size by approximately 100 nucleotides. This increase in size was found to result from an increase in poly(A) tail length, the significance of which is as yet unclear.

Animals↗
PubMed1990

Release of substance P from rat hypothalamus and pituitary by endothelin.

Endothelin-1 is a 21 amino acid peptide originally isolated from porcine aortic endothelium and has recently been localized within the central nervous system. We have administered endothelin-1 in a dynamic perfusion system in order to study its possible effects on the rat hypothalamus and anterior pituitary. Tissue (hypothalami or quartered pituitaries) was placed into plastic chambers and was perfused with oxygenated Krebs-bicarbonate solution. After an interval to establish stable basal peptide release, endothelin-1 was administered at two doses (0.1 and 1 microM) and the release of substance P, vasoactive intestinal peptide, 7B2, and somatostatin was measured, the last being detectable only in hypothalamic perfusates. Both concentrations of endothelin-1 led to a significant increase (P less than 0.01) in the release of substance P from the hypothalamus and pituitary, but not of vasoactive intestinal peptide, 7B2, or somatostatin. Thus after the 0.1 microM and 1 microM endothelin-1 perfusion substance P release from the hypothalamus increased by 125 +/- 5% and 215 +/- 15% (mean +/- SEM) of basal and from the pituitary by 168 +/- 8% and 276 +/- 15% (mean +/- SEM). No change occurred in the output of ACTH or other pituitary hormones. The release of substance P from hypothalamus or pituitary after stimulation with endothelin-1 was not blocked when a calcium free medium was used. Endothelin-1 binding sites were identified on rat pituitary cell membranes. These findings suggest the possibility that endothelin may act as a paracrine substance, neurotransmitter, or neuromodulator in the hypothalamo-pituitary axis.

Animals↗
PubMed1990

Effect of endocrine manipulation on anterior pituitary galanin in the rat.

Galanin is widely distributed throughout the rat neural and endocrine system. The highest concentrations are found in the anterior pituitary, and it can influence classical pituitary hormone secretion. The effects of endocrine manipulation on pituitary galanin content, mRNA, and immunostaining have been investigated in the rat. In females, medical (39 +/- 4 fmol/gland), surgical (33 +/- 2), or combined (28 +/- 6) castration resulted in a highly significant decrease in galanin content (control, 223 +/- 14; P less than 0.0001). Estrogen in physiological and pharmacological doses produced a significant increase in galanin content (368 +/- 14 and 373 +/- 13, respectively; P less than 0.01) associated with an increase in galanin mRNA content. In the male, high dose dexamethasone and thyroidectomy caused a fall in galanin content, while galanin mRNA levels showed a rise and fall, respectively. Adrenalectomy caused a rise in galanin content, while adrenalectomy and castration produced a dramatic decrease in tissue galanin content. No change in galanin mRNA was observed in these groups. Galanin immunostaining paralleled the results of tissue content in all groups examined, except in the medically castrated group, in which there was some intragroup variation in staining patterns. In normal and high-dose estrogen-treated females, galanin expression was seen mainly in lactotrophs, with a small number of somatotrophs and thyrotrophs staining. In the male, galanin expression was confined to somatotrophs and thyrotrophs. Galanin mRNA was localized at the cellular level by in situ hybridization. In the normal pituitary only scattered lactotrophs contained message, while in high-dose estrogen-treated animals the number of positive cells, mostly lactotrophs, was vastly increased. Thus, the cellular localization of galanin immunostaining varies between the sexes. Galanin peptide and mRNA levels in the pituitary are powerfully influenced by endocrine status.

Adrenalectomy↗
PubMed1990

The regulation of neuropeptide expression in rat anterior pituitary following chronic manipulation of estrogen status: a comparison between substance P, neuropeptide Y, neurotensin, and vasoactive intestinal peptide.

The neuropeptides substance P, neuropeptide Y, neurotensin, and vasoactive intestinal peptide are present in normal rat anterior pituitary gland and hypothalamus and can influence the secretion of classical pituitary hormones. We investigated the effects of estrogen manipulation on pituitary and hypothalamic expression of these four peptides by specific RIAs and cDNA probe analysis. Surgical ovariectomy produced a significant rise in the pituitary content of substance P immunoreactivity (IR) (130.2 +/- 4.8 fmol/gland vs. control 29.1 +/- 2.2, P less than 0.001), neuropeptide Y IR (34.9 +/- 3.9 vs. 19.6 +/- 2.0, P less than 0.05) and neurotensin IR (85.1 +/- 8.2 vs. 62.4 +/- 7.2, P less than 0.05), while vasoactive intestinal peptide IR showed a fall (201.2 +/- 18.8 vs. 285.4 +/- 25.9, P less than 0.05). These patterns were reversed with estrogen replacement or high dose estrogen treatment. Changes in peptide content were accompanied by parallel changes in the mRNA for each peptide. Treatment with an antiestrogen (tamoxifen) resulted in no change in substance P, neuropeptide Y, and neurotensin expression, while vasoactive intestinal peptide IR content decreased to below the assay detection limit. Hypothalamic expression of these peptides did not change with any of the treatments. These results indicate that: 1) the control of the pituitary expression of the four peptides under the influence of estrogen occurs predominantly at the level of gene transcription and 2) normalization of the castration induced changes by exogenous estrogen replacement suggests the changes to be mediated by the absence of this steroid. The regulation of the pituitary expression of these peptides by estrogen support the possibility of their having an autocrine or paracrine role.

Animals↗
PubMed1990

Localization of immunoreactivity for calcitonin gene-related peptide in the rat anterior pituitary during ontogeny and gonadal steroid manipulations and detection of its messenger ribonucleic acid.

Localization of calcitonin gene-related peptide (CGRP) expression in the rat anterior pituitary and its changes during ontogeny and after gonadal steroid manipulations were studied by immunocytochemistry, RIA, and in situ hybridization. Colocalization studies and the combined use of immunocytochemistry and in situ hybridization revealed that CGRP immunoreactivity is localized mainly in gonadotropes and alpha- and beta-CGRP messenger RNAs were detected in CGRP-immunoreactive cells. Immunoreactivity for CGRP also was detected in nerve fibers and colocalized with substance P immunoreactivity. Cells immunoreactive to CGRP antiserum were first detected in fetal rats at gestational day 18, and the incidence considerably increased between postnatal days 5 and 14. CGRP immunoreactivity was low in control adults of both sexes and in pregnant and ovariectomized females but increased in lactating, estrogen-supplemented ovariectomized and high-dose estrogen-treated females, and in high-dose estrogen-treated and castrated males. Testosterone supplement suppressed the effect of castration on CGRP immunoreactivity in males. Quantities of extractable immunoreactive CGRP under conditions of estrogen manipulation corresponded well to the immunocytochemical findings (females: controls, 96.4 +/- 13.1 fmol/gland; ovariectomized, 107.6 +/- 19.2; high-dose estrogen-treated, 212 +/- 23.0; estrogen-supplemented ovariectomized, 680 +/- 42.1). The present study suggests that pituitary CGRP is synthesized and stored in gonadotropes, is modulated by gonadal steroids, and may have a functional link with gonadotropins.

Aging↗
PubMed1990

Endothelin-like immunoreactivity in human breast cyst fluid.

Immunoreactive endothelin has been detected in 21 of 43 samples of breast cyst fluid (21 cases; 3.5 +/- 0.6 pmol/l, mean +/- SEM. Other 22 cases; not detectable, less than 0.5 pmol/l). Fast protein liquid chromatographic analysis of the immunoreactive endothelin of pooled breast cyst fluid showed two immunoreactive peaks; one in the void volume and the other in the position of endothelin-1. It is probable that endothelin-1 is produced by the epithelial cells lining breast cysts, but significance of the presence of endothelin-1 in breast cyst fluid remains to be elucidated.

Chromatography, High Pressure Liquid↗
PubMed1990

Acrolein depletes the neuropeptides CGRP and substance P in sensory nerves in rat respiratory tract.

The mammalian respiratory tract is densely innervated by autonomic and sensory nerves around airways and blood vessels. Subsets of these nerves contain a number of putative neurotransmitter peptides, such as substance P and calcitonin gene-related peptide (CGRP) in sensory nerves and vasoactive intestinal polypeptide (VIP), possibly serving autonomic functions. CGRP is also found in endocrine cells in rat airway epithelium. These peptides are all pharmacologically potent effectors of bronchial and vascular smooth muscle and bronchial secretion. Their functions in vivo are less well established. We have therefore examined the effects of inhaled acrolein, a sensory irritant, on three pulmonary neuropeptides: CGRP, substance P, and VIP. Groups of rats (n = 3 each) were exposed for 10 min to acrolein in air (Ct = 510, 1858, and 5693 mg.min/m3) or to air alone. Fifteen minutes later they were killed (pentabarbitone IP) and their respiratory tracts were dissected and fixed in 0.4% p-benzoquinone solution. Cryostat sections were stained by indirect immunofluorescence for a general nerve marker (PGP 9.5) and neuropeptides. The acrolein-treated animals had a dose-related decrease in tracheal substance P- and CGRP-immunoreactive nerve fibers compared with controls. No change was seen in total nerve fiber distribution and number (PGP 9.5) or VIP immunoreactivity, nor in CGRP-immunoreactive epithelial endocrine cells. It is concluded that the rat tracheal peptidergic nerves are a sensitive indicator of inhaled irritant substances. Their reduced immunoreactivity may be because of a release of sensory neuropeptides that could play a role in the physiological response to irritant or toxic compounds.

Acrolein↗
PubMed1990

Amylin and amylin-amide lack an acute effect on blood glucose and insulin.

Amylin-amide has been implicated in the pathogenesis of type II diabetes due to its proposed inhibitory effect on insulin release from beta cells of the pancreatic islets, and on glucose uptake by the skeletal muscle. In experiments with rats and rabbits we failed to demonstrate these anti-insulin actions of amylin and amylin-amide. A single bolus dose of the two peptides (500 pmol) administered i.v. failed to suppress plasma insulin levels or to elevate blood glucose levels. The continuous infusion of amylin-amide into rabbits also failed to suppress the release of insulin in response to hyperglycaemia produced by an i.v. bolus injection of glucose. These in vivo observations imply that the amylin peptides may not have a primary physiological role in carbohydrate metabolism, but in view of our previous findings, we speculate that the peptide has a more prominent role in calcium homeostasis.

Amyloid↗
PubMed1990

Glucagon-like peptide-1 (7-36)-NH2: a physiological inhibitor of gastric acid secretion in man.

Glucagon-like peptide (GLP)-1 (7-36)-NH2 is a peptide found in the mucosal endocrine cells of the intestine, and plasma levels of GLP-1 (7-36)-NH2 immunoreactivity show a rise after the ingestion of a fat or mixed-component meal. We investigated the effects of physiological infusion of GLP-1 (7-36)-NH2 on a submaximal gastric acid secretion in healthy volunteers at a rate known to mimic the observed postprandial rise in plasma concentrations. Corrected gastric acid output decreased to less than 50% and volume output to 33% of stimulated values. After the infusion, the secretion of gastric acid recovered immediately to preinhibition values. These results suggest a novel role for GLP-1 (7-36)-NH2 as a physiological inhibitor of gastric acid secretion in man.

Adult↗