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Biomedical subjects

S R Bloom

Publications and source records attributed to S R Bloom.

At least 667 records · Page 37Linked to original sources
PubMed1985

Medullary carcinoma of the thyroid. An immunocytochemical and histochemical study of 25 cases using eight separate markers.

The current study was undertaken on 25 cases of thyroid medullary carcinoma to compare the diagnostic value of calcitonin with other peptides including PDN-21, the C-terminal flanking peptide of human calcitonin within the calcitonin precursor, and calcitonin gene-related peptide, CGRP. Antiserum raised to chromogranin, an acidic protein of 68,000 daltons, was also used to compare its diagnostic value as a general marker for neuroendocrine neoplasia with neuron-specific enolase (NSE) and Grimelius' argyrophil silver staining. Immunocytochemistry was performed using the peroxidase-antiperoxidase method at the light microscopic level and the immunogold staining procedure at the ultrastructural level. All tumors were reactive to calcitonin and CGRP antisera, whereas PDN-21 was present in 23 cases. It was also found that these peptides were colocalized in the majority of C-cells. The intensity and specificity of CGRP and PDN-21 immunoreaction was comparable to and in some cases even better than that obtained with calcitonin antiserum. In the majority of tumors, somatostatin and bombesin immunoreactivity was either absent, weak, or variable in intensity and distribution. The current study thus demonstrates that together with calcitonin, PDN and, in particular, CGRP antisera may be applied to corroborate immunocytochemical diagnosis in medullary carcinoma of the thyroid. With regard to general neuroendocrine markers, Grimelius' and chromogranin provided the most consistent results. NSE isoenzyme immunoreactivity, on the other hand, was more variable, probably reflecting the metabolic state of the tumor cells.

Bombesin↗
PubMed1985

Colocalization of neuropeptide Y immunoreactivity in brainstem catecholaminergic neurons that project to the paraventricular nucleus of the hypothalamus.

Immunohistochemical methods were used in the rat to plot the distribution of neuropeptide Y (NPY) immunoreactivity in the paraventricular (PVH) and supraoptic (SO) nuclei of the hypothalamus, and a combined retrograde transport-double immunohistochemical labeling technique was used to determine the extent to which NPY immunoreactivity is coexpressed in brainstem cell groups that stain with antisera to phenylethanolamine-N-methyltransferase (PNMT; a marker for adrenergic neurons) or dopamine-beta-hydroxylase (DBH; a marker for adrenergic and noradrenergic neurons) and also project to the PVH. The results confirm the existence of a major NPY-immunoreactive pathway that is in a position to influence each major class of output neurons in the PVH. Thus, most parts of the parvicellular division receive a dense input that is similar to, though somewhat more extensive than, the one stained by DBH antisera. However, in the magnocellular division catecholaminergic inputs are preferentially associated with vasopressinergic neurons, while NPY-stained fibers tend to be more evenly distributed in regions containing both oxytocinergic and vasopressingergic neurons, and their density appear to be lower than that of DBH-stained fibers. In the SO, only a moderate NPY-stained input was apparent, while, as described previously, DBH-immunoreactive fibers are rather dense and are preferentially distributed in vasopressinergic regions of the nucleus. The results of combined retrograde transport-double immunohistochemical labeling experiments may be summarized as follows: the vast majority of cells in the medulla that were retrogradely labeled after discrete implants of the fluorescent tracer true blue into the PVH, and were PNMT-immunoreactive, also stained for NPY. However, less extensive co-localization was detected in noradrenergic cell groups of the caudal medulla. About 60% of the retrogradely labeled-DBH positive cells in the A1 cell group were also NPY-positive, while those in the caudal part of the nucleus of the solitary tract (the A2 cell group) usually failed to stain with anti-NPY. Similarly, in the locus coeruleus (the A6 cell group) where virtually all retrogradely labeled neurons were DBH-positive, only rarely were triply labeled cells detected. These results suggest that NPY immunoreactivity is extensively co-contained within adrenergic neurons of the C1, C2, and C3 groups that project to the PVH, while the correspondence in noradrenergic cell groups is less complete, and generally limited to a subset of neurons in the A1 cell group.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic Fibers↗
PubMed1985

Distribution and chromatographic characterization of neuromedin B-like immunoreactivity in the human spinal cord.

The quantitative regional distribution of neuromedin B-like immunoreactivity in normal postmortem human spinal cord was studied by a specific radioimmunoassay. Neuromedin B-like immunoreactivity was found in highest concentration in the dorsal part of the sacral cord. Chromatographic analyses by gel permeation and reverse-phase high-pressure liquid chromatography revealed two major peaks of neuromedin B-like immunoreactivity and the prevalent molecular form, approx. 90% of the total immunoreactivity, was chromatographically identical to synthetic porcine neuromedin B.

Aged↗
PubMed1985

Chromatographic characterisation of neurotensin-like immunoreactivity in plasma and tissue extracts from hepatoma patients.

To determine the nature of the neurotensin-like immunoreactivity produced by some cases of primary liver carcinoma, plasma and tumour neurotensin-like immunoreactivities were characterised in patients with neurotensin-producing hepatoma by chromatographic analysis in conjunction with radioimmunoassay with C- and N-terminally directed antisera. Gel filtration revealed that the majority of neurotensin-like immunoreactivity extracted from the tumour was co-eluted with synthetic neurotensin, whereas a substantial amount of the plasma immunoreactive neurotensin emerged at the void volume. Tumour neurotensin-like immunoreactivity showed a degree of heterogeneity on gel filtration and high pressure liquid chromatography that contrasted with neurotensin-like immunoreactivity extracted from ileal mucosa, suggesting a different post-translational processing of neurotensin within tumour tissue. The ratio of neurotensin 1-8 to neurotensin 1-13 in the patients' plasma suggested that neurotensin was metabolised in a manner similar to that in healthy subjects. The clinical and biological significance of the ectopic production of neurotensin in some hepatomas remains unclear.

Carcinoma, Hepatocellular↗
PubMed1985

Dissociation of neuropeptide Y and somatostatin in Parkinson's disease.

The concentration of neuropeptide Y has been determined in the cortex and hippocampus of subjects with Parkinson's disease and compared to changes of activity of dopamine beta-hydroxylase and concentration of somatostatin. Despite a marked reduction in the concentration of somatostatin in the severely demented subject, in both cortex and hippocampus, no significant change in concentration of NPY was found in either region. This finding therefore suggests that the majority of NPY within the cortex is independent of somatostatin. This study provides some further evidence of neurochemical similarities between the dementia of Parkinson's disease and Alzheimer's disease.

Brain Chemistry↗
PubMed1985

Effect of long acting somatostatin-analogue, SMS 201 995, on gut hormone secretion in normal subjects.

SMS 201 995 is a new long acting analogue of somatostatin. We have investigated its effect on basal and meal stimulated secretion of gut hormones and have shown that after a single s.c. injection of 50 micrograms it lowers significantly the basal plasma levels of pancreatic polypeptide, secretin, motilin, pancreatic glucagon and insulin, it also effectively suppresses the postprandial release of pancreatic polypeptide, gastrin, secretin, gastric inhibitory peptide, pancreatic glucagon and insulin. Except for the usual brief discomfort of an injection, no symptoms or untoward effects were observed.

Adult↗
PubMed1985

Neuropeptide Y innervation of the rodent pineal gland and cerebral blood vessels.

Neuropeptide Y (NPY)-immunoreactivity has been shown to be present in sympathetic nerve fibres in the rat pineal gland and a dense network of NPY-containing nerve fibres demonstrated to innervate the rat circle of Willis. The NPY content of the major rabbit intracranial arteries was determined by radioimmunoassay and maximal levels found in the anterior cerebral arteries. After bilateral superior cervical ganglion (SCG) removal, no NPY was detectable in the rat pineal gland; however, significant NPY-immunoreactive nerve fibres remained throughout the rat vertebrobasilar arteries, and 47% of the assayable NPY was still present. Neither intraventricular 6-hydroxydopamine (6-OHDA) nor the combination of 6-OHDA treatment and SCG removal resulted in any further loss of NPY. In conclusion, the NPY innervation of the pineal gland originates exclusively from the peripheral sympathetic nervous system. In contrast the caudal portion of the rat circle of Willis contains NPY fibres which are resistant to sympathectomy.

Animals↗
PubMed1985

Cytochemical relationships in the paracervical ganglion (Frankenhäuser) of rat studied by immunocytochemistry.

Vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) immunoreactivities have been demonstrated in the paracervical ganglion of the rat using immunocytochemistry. Dopamine beta-hydroxylase (D beta H) and neurofilament protein triplet immunoreactivities have also been demonstrated in this region. The VIP, NPY, D beta H and neurofilament immunoreactivities were located in ganglion cells and nerve fibres, while CGRP immunoreactivity was localized only in nerve fibres. Many cells immunoreactive with D beta H antiserum were also immunoreactive with NPY antiserum. A small number of cells immunoreactive with VIP antiserum were also immunoreactive with NPY antiserum. CGRP-immunoreactive nerve fibres were distributed in certain regions of the ganglion only.

Animals↗
PubMed1985

Regional distribution of a novel pituitary protein (7B2) in the rat spinal cord: effect of neonatal capsaicin treatment and thoracic cord transection.

Using a specific radioimmunoassay, a novel pituitary protein (7B2) was shown to be distributed throughout the rat spinal cord. The concentration of 7B2-like immunoreactivity (7B2-IR) was significantly higher in dorsal lumbar than in whole lumbar cord, and the highest level was found in the sacral region. On both gel and high-performance liquid chromatography, 7B2-IR in rat spinal cord eluted in the same position as 7B2-IR extracted from porcine pituitary gland. Neonatal capsaicin treatment did not change dorsal lumbar spinal cord 7B2-IR concentrations, suggesting that it is not predominantly present in unmyelinated primary afferent fibres. Thoracic cord transection, however, resulted in significant increases of 7B2-IR in lumbar and especially sacral regions, providing evidence of a 7B2-containing ascending pathway originating in the lumbosacral spinal cord.

Animals↗
PubMed1985

Somatostatin and the dumping syndrome.

Infusion of somatostatin reduced the symptoms of the early dumping syndrome after oral glucose was given and also reduced the associated tachycardia and rise in packed cell volume. It inhibited the secretion of enteroglucagon, neurotensin, and vasoactive intestinal polypeptide, which are raised in patients with the dumping syndrome and may have an aetiological role. It also prevented the reactive hypoglycaemia of late dumping by inhibiting the release of gastric inhibitory polypeptide and insulin. Somatostatin, possibly through its inhibitory effects on hormonal secretion, may have a role in the management of patients with the early and late dumping syndrome.

Blood Glucose↗
PubMed1985

Distribution and origin of calcitonin gene-related peptide (CGRP) immunoreactivity in the sensory innervation of the mammalian eye.

The occurrence, distribution, and origin of immunoreactive calcitonin gene-related peptide (CGRP) in nerves of rat, guinea pig, cat, and monkey eyes were investigated by immunocytochemistry, radioimmunoassay, and chromatography. A rich network of CGRP-immunoreactive nerve fibres was noted in the anterior uvea, which was widely distributed in both dilator and constrictor pupillae muscles and extended to the ciliary body and uveal blood vessels. Numerous CGRP-immunoreactive neuronal cells were present in the trigeminal ganglion. The extractable CGRP was 8.6 +/- 1.8 pmoles/gm of tissue in the iris and 44.0 +/- 8.1 pmoles/gm in the trigeminal ganglion. Following damage to the Gasserian ganglion a marked decrease of CGRP immunoreactivity was observed in the anterior uvea (control 11.3 +/- 1.6 pmoles/gm; operated 1.4 +/- 0.1 pmoles/gm) confirming the origin of the immunoreactive fibres from trigeminal primary sensory neurons. The sensory nature of the CGRP-immunoreactive fibres was substantiated by the depletion of CGRP immunoreactivity observed after treatment with capsaicin, which is known to cause selective degeneration of sensory neurons. Comparative studies on the distribution and colocalisation of CGRP and the putative sensory neurotransmitter substance P revealed a closely parallel distribution of the two peptides in certain regions of the uvea and their coexistence in a subpopulation of trigeminal primary sensory neurons. This study suggests that the sensory nervous system in the eye is more heterogeneous in terms of its putative neurotransmitters than previously indicated.

Animals↗
PubMed1985

Regulation of neuroendocrine gene expression by alternative RNA processing. Colocalization of calcitonin and calcitonin gene-related peptide in thyroid C-cells.

The generation of two discrete mRNAs encoding different polypeptide products in expression of the rat calcitonin, CGRP gene provides an example of developmentally determined alternative RNA processing events in the neuroendocrine system. Both mature mRNA transcripts and their peptide products, encoding either calcitonin or calcitonin gene-related peptide (CGRP) are co-produced in identical thyroid C-cells, in a ratio of 95:1, respectively. These data suggest that the generation of the two mRNAs reflect the actions of a factor(s) dictating alternative RNA processing events.

Animals↗
PubMed1985

Bombesin-like immunoreactivity in female rat genito-urinary tract.

The quantitative distribution and localization of bombesin-like immunoreactivity (BLI), by antiserum which cross-reacted fully with gastrin-releasing peptide (GRP), was determined by radioimmunoassay and immunocytochemistry in various regions of female rat urogenital tract. The highest concentration of BLI was found in the vagina, with lower but significant concentrations in the uterus and bladder. Bombesin-like immunoreactive nerve fibres were localized by immunocytochemistry in the smooth muscle layer, around blood vessels and in the submucosa of the vagina and bladder. BLI was separable into two immunoreactive peaks on both gel permeation chromatography and reverse phase HPLC. The major peak emerged exactly in the position of neuromedin C (C-terminal decapeptide of GRP) in both chromatographic systems, while the remaining immunoreactivity emerged close to the position of porcine GRP on gel permeation chromatography, but was easily distinguishable from this on HPLC. This suggests a significant species difference between rat and porcine GRP. Amphibian bombesin and mammalian neuromedin C have previously been shown to have potent biological actions in the rat urogenital tract. The presence of mammalian bombesin-like peptides in nerve fibres of the urogenital tract suggests that they may have a regulatory role in these organs.

Animals↗
PubMed1985

Isolation and characterization of neuropeptide Y from porcine intestine.

The isolation and primary structure of intestinal neuropeptide Y (NPY) is described. The peptide was purified from porcine intestinal extracts using a chemical assay and radioimmunoassay for NPY. The amino acid sequence of this peptide is: Tyr-Pro-Ser-Lys-Pro-Asp-Asn-Pro-Gly-Glu-Asp-Ala-Pro-Ala-Glu-Asp-Leu-Ala- Arg-Tyr-Tyr- Ser-Ala-Leu-Arg-His-Tyr-Ile-Asn-Leu-Ile-Thr-Arg-Gln-Arg-Tyr-NH2. This the structure of intestinal NPY is identical to the NPY of brain origin.

Amino Acid Sequence↗
PubMed1985

Neuropeptides in neurological tumours.

Concentrations of seven neuropeptides have been determined in 69 human neurological tumours. The majority of tumours were intrinsic to the central nervous system, being astrocytomas. In general, within the the better differentiated tumours (Grade I/II astrocytomas) higher concentrations of five neuropeptides (neuropeptide Y, somatostatin, substance P, vasoactive intestinal peptide and cholecystokinin) were measured in comparison to the poorly differentiated tumours. Of the metastatic tumours, five were derived from oat cell carcinoma of the bronchus. Very high concentrations of bombesin were identified in these metastases.

Astrocytoma↗
PubMed1985

Neuropeptide Y (NPY)-like immunoreactive amacrine cells in retinas of frog and goldfish.

The distribution of neuropeptide Y (NPY)-like immunoreactivity in rat, rabbit, chick, frog and goldfish retinas was investigated by immunohistochemistry. Positive results were observed only in the frog and goldfish retinas. NPY immunoreactivity was associated with a small population of amacrine cell bodies in the inner nuclear layer and cell processes in the inner plexiform layer of both retinas. In the frog retina, three distinct layers containing immunoreactivity were observed in the inner plexiform layer. In contrast, the immunoreactivity in the same area of the goldfish retina was more or less separated into two layers. Convincing evidence could not be found for the co-existence of NPY-like material with other putative transmitter-like substances in the two retinas. Radioimmunoassay revealed the presence of small amounts of NPY-like immunoreactivity in the rabbit retina; the goldfish and frog retinas contained significantly more immunoreactive material. High performance liquid chromatography of the immunoreactive material in frog and goldfish retinas showed each retina containing different molecular forms of NPY-like proteins, neither of which resembled porcine NPY or PYY. The endogenous NPY-like material of the frog retina can be released by potassium depolarisation in a calcium-dependent way. In view of all these data an NPY-like protein must now be considered a potential retinal transmitter.

Animals↗