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J R Oliver

Publications and source records attributed to J R Oliver.

At least 55 records · Page 3Linked to original sources

Distribution of tyrosine hydroxylase and neuropeptide Y-like immunoreactive neurons in rabbit medulla oblongata, with attention to colocalization studies, presumptive adrenaline-synthesizing perikarya, and vagal preganglionic cells.

We studied the distribution, within the rabbit medulla oblongata, of neuronal cell bodies containing either tyrosine hydroxylase or neuropeptide Y-like immunoreactivity. Both avidin-biotin and immunofluorescence procedures were used. Because the two primary antibodies were raised in different species it was possible to perform simultaneous colocalization studies with the immunofluorescence procedure. Tyrosine hydroxylase-containing neurons in the rostral medulla were demonstrated to contain a catecholamine by the colchicine-enhanced FAGLU (formaldehyde-glutaraldehyde) fluorescence histochemical procedure. These neurons are presumably adrenergic, corresponding to the C1 and C2 groups described in the rat. No C3 group was found in the rabbit. The distribution of tyrosine hydroxylase-containing neurons in the caudal medulla was in accordance with previous descriptions of the A1 and A2 groups based on the unenhanced FAGLU procedure. Neuropeptide Y-like immunoreactivity was observed in cell groups corresponding to those already described in the rat, but additional groups were discovered in the rabbit. Some neurons containing neuropeptide Y-like immunoreactivity were observed in nucleus raphe pallidus and these also contained serotonin (5-HT). In the nearby nucleus reticularis gigantocellularis there were occasional neurons that contained neuropeptide Y-like immunoreactivity without any colocalized 5-HT. Neuropeptide Y-like immunoreactivity was also observed in the dorsal motor nucleus of the vagus, rostral to the obex, and these neurons were demonstrated to be true vagal preganglionic cells by colocalization of neuropeptide Y-like immunoreactivity and Fast Blue retrogradely transported from the cervical vagus. We found that neuropeptide Y-like immunoreactivity was colocalized in approximately 75% of the tyrosine hydroxylase-containing neurons in the rostral medulla (C1 and C2 cells). A smaller proportion of the A1 cells also contained this peptide but it was absent from both the most caudal A1 cells and from the A2 cells. Some tyrosine hydroxylase-containing neurons occur in direct apposition to vagal preganglionic cells in both the dorsal motor nucleus of the vagus and the nucleus ambiguous. However, colocalization studies revealed that none of these neurons contained Fast Blue when this dye was retrogradely transported from the cervical vagus. Medullary catecholamine-synthesizing neurons apparently do not contribute axons to the vagus nerve. This finding is consistent with our own studies in the rat but is in contrast to studies in this species published by other workers.

Animals↗

Time-course of changes in plasma lipids in diabetic rats fed diets high in fish or safflower oils.

Adult male rats were maintained for 10 days on a standard chow diet or that diet supplemented with either safflower or marine fish oils, and then rendered diabetic with streptozotocin (40 mg/kg of body weight) and circulating metabolites determined over the next 3 days. Pre-diabetic concentrations of glucose and insulin did not differ between groups, and the severity of hyperglycaemia and lowering of insulin in streptozotocin-treated animals were also similar. Pre-diabetic concentrations of plasma free fatty acids and triacylglycerols were lower, and blood ketone bodies were higher in non-diabetic rats fed fish oil than in both other groups. However, following streptozotocin treatment, plasma free fatty acids rose significantly more in both groups of oil-fed animals than in chow-fed ones. Plasma triacylglycerols were unaltered from pre-treatment levels in rats fed chow, but rose considerably in both groups fed oil-supplemented diets. In a subsequent experiment it was shown that the increase in triacylglycerols persisted for up to 11 days after streptozotocin and the hypertriglyceridaemia was greatest in the fish oil group. The rise would seem to result from defective clearance of lipoproteins of dietary origin. It appears that fish oil-supplemented diets should be avoided in diabetics until the possibility of increased hypertriglyceridaemia has been excluded by controlled studies.

Animals↗

Neurochemically similar myenteric and submucous neurons directly traced to the mucosa of the small intestine.

Antisera to neuropeptide Y (NPY) gave an intense immunohistochemical reaction of certain nerve cells in the myenteric and submucous plexuses of the guinea-pig small intestine. Each nerve cell had up to 20 branching, tapering processes that were less than approximately 50 micron long and a long process that could be followed for a considerable distance. This morphology corresponds to that of the type-III cells of Dogiel. The long process of each myenteric cell ran through the circular muscle to the submucosa, and in most cases the process could be traced to the mucosa. The submucous nerve cell bodies also had processes that extended to the mucosa. These cell bodies, in both plexuses, also stained with antisera raised against calcitonin gene-related peptide (CGRP), cholecystokinin (CCK), choline acetyltransferase (ChAT) and somatostatin (SOM), but did not stain with antibodies against enkephalin, substance P or vasoactive intestinal peptide. Thus, it has been possible for the first time to trace the processes of chemically specified neurons through the layers of the intestinal wall and to show by a direct method that CGRP/CCK/ChAT/NPY/SOM myenteric and submucous nerves cells provide terminals in the mucosa.

Animals↗

Plasma lipids and insulin in gall stone disease: a case-control study.

Fasting plasma lipid and insulin concentrations were measured in 173 patients with gall stones and 284 hospital controls to investigate their relationship to this disease. Multivariate methods of analysis were used to estimate the net associations between individual plasma variables and the risk of developing gall stones. In both sexes increased plasma insulin values were associated with an increased risk of gall stones independently of plasma triglyceride values; increased plasma triglyceride concentrations were associated with an increased risk of gall stones in young subjects only; increased plasma total cholesterol concentrations were associated with a decreased risk of gall stones only after controlling for plasma insulin and triglyceride concentrations; while increased plasma high density lipoprotein cholesterol concentrations were associated with a decreased risk of gall stones, but were confounded by plasma insulin and triglyceride values. These associations were independent of obesity and dietary intake.

Analysis of Variance↗

Growth hormone releasing factor immunoreactivity in rat hypothalamus.

Neurones immunoreactive to antibodies against human pancreatic growth hormone releasing factor1-40 (hpGRF) were identified in the hypothalamus of the rat after pretreatment with colchicine. Reactive perikarya were concentrated in the arcuate nucleus and were also present around the anterior commissure. hpGRF immunoreactive fibres were observed in the median eminence and preoptic area where they tended to complement the distribution of somatostatin immunoreactive fibres. The distribution of GRF-immunoreactive perikarya in the rat hypothalamus is similar to that reported in monkey, and is consistent with other studies which suggest that neural mechanisms stimulatory for growth hormone secretion in the rat are situated in the medial basal hypothalamus.

Animals↗

Evidence that the regulation of growth hormone secretion is mediated predominantly by a growth hormone releasing factor.

Spontaneous pulsatile growth hormone (GH) secretion and stress-induced suppression of GH was examined in chronically cannulated male rats with electrolytic lesions of the periventricular preoptic anterior hypothalamic area (PO/AHA) where somatostatin neurons innervating the median eminence are known to be located. Median eminence somatostatin was depleted in lesioned animals by 85%. Bursts of GH secretion occurred more frequently than in sham-lesioned animals (1.9 +/- 0.2 vs. 2.6 +/- 0.2 h, respectively, p less than 0.025), however, average concentrations of GH were reduced by lesions (118.4 +/- 11.6 vs 192.3 +/- 28.4 ng/ml, p less than 0.025). Suppression of GH by stress was unaffected by PO/AHA lesions. It is concluded that somatostatin plays only minor roles in the generation of GH troughs during rhythmic GH secretion, and in the suppression of GH during stress. Inhibition of GH releasing factor secretion, therefore, is presumed to be the likely method by which GH suppression is achieved in these physiological situations.

Animals↗

Pulsatility of immunoreactive somatomedin-C in chronically cannulated rats.

Pituitary GH secretion is pulsatile in man and the rat, but evidence of pulsatility in the GH-dependent somatomedins (insulin-like growth factors) has not been described. In this study serum immunoreactive somatomedin-C periodicity was examined in 10 chronically cannulated unstressed rats. Blood samples were taken at 15-min intervals over 6 h, and serum rat GH and somatomedin-C measured by RIA. For somatomedin-C assay samples were first extracted into acid-ethanol to dissociate protein-bound peptide. Serum GH levels indicated episodic secretion, with a frequency of 2.85 +/- 0.24 h; some secretory episodes were polyphasic. The mean frequency of all GH spikes reaching 400 ng/ml or greater was 1.99 +/- 0.87 h. Somatomedin-C levels showed fluctuations over an average 2-fold concentration range, 0.60 +/- 0.20 to 1.21 +/- 0.29 U/ml (mean, 0.86 +/- 0.18 U/ml), with peaks occurring 1-1.5 h after most GH secretory peaks. The somatomedin-C peak frequency was 1.93 +/- 0.47 h. Summed GH values from 0-5 h were significantly correlated with summed somatomedin-C values from 1-6 h (r = 0.861, P = 0.0007), suggesting a 1-h lag between GH pulses and the following rise in somatomedin-C. Somatomedin-binding protein showed no regular fluctuations. This study indicates that serum somatomedin-C levels in unstressed rats show periodicity which may be directly related to pulsatile GH secretion.

Animals↗

Stimulatory role for medial preoptic/anterior hypothalamic area neurones in growth hormone and prolactin secretion. A kainic acid study.

The role of preoptic/anterior hypothalamic area (PO/AHA) neurones in the regulation of basal patterns of growth hormone (GH) and prolactin (Prl) secretion was investigated in unanesthetized male rats prepared with chronic indwelling venous cannulae. PO/AHA injections of the neurotoxin kainic acid (KA) substantially reduced both GH and Prl secretion. Histological examination of tissue sections indicated that KA treatment had produced extensive neuronal loss and gliosis in the medial (m) but not the periventricular (p) PO/AHA. These findings suggest that m-PO/AHA neurones are facilitatory to the basal secretion of both GH and Prl. It is proposed that GH-facilitatory m-PO/AHA neurones provide an inhibitory input to the GH release-inhibiting factor neurones which are known to reside in the p-PO/AHA. Prl-facilitatory m-PO/AHA neurones may secrete, or stimulate the secretion of a Prl releasing factor.

Animals↗

Somatostatin is contained in and released from cholinergic nerves in the heart of the toad Bufo marinus.

The heart of the toad Bufo marinus contained a substance with somatostatin-like immunoreactivity which eluted with somatostatin on reverse phase high pressure liquid chromatography. Immunoreactivity to somatostatin was localised histochemically to nerve fibers in muscle bundles of the sinus venosus, atria and ventricles and to nerve cell bodies in the sinus venosus and inter-atrial septum. Nerve cell bodies were localised both by interference contrast microscopy and immunohistochemistry; all detectable intracardiac neurons were immunoreactive. Synthetic somatostatin inhibited the rate and force of beat of atrial preparations, but did not affect the driven ventricle. Vagal stimulation caused inhibition of all cardiac chambers. After muscarinic blockade with hyoscine, vagal stimulation with 3 Hz or more still caused inhibition of the pacemaker and atrium, but not of the ventricle. The hyoscine-resistant vagal effects were diminished by about 60% after induction of tachyphylaxis to somatostatin. When when the vagus nerves were stimulated intermittently for 1 h at 10 Hz, in the presence or absence of hyoscine, the effect of somatostatin was reduced by about 60%. It is concluded that the cholinergic postganglionic neurons of the cardiac vagus contain somatostatin. When the vagus is stimulated at 3 Hz or more, the neurons release sufficient somatostatin to inhibit the pacemaker and atrial muscle.

Animals↗

The surface concentration of H-2 antigens on mouse pancreatic beta-cells and islet cell transplantation.

Measurement of the concentration of H-2 complex antigens in the surface membrane of mouse pancreatic beta-cells by a quantitative immunoferritin-labeling technique revealed that the antigens were present in very small amounts on the beta-cells of five strains. A comparison of the labeling densities in the five strains suggested that beta-cells from C57BL/10Sn congenic strains have about half the H-2 antigen density of BALB/c and C3H/HeJ cells. In C57BL/10Sn mice the antigen density on beta-cells was slightly greater than that on erythrocytes, about 20% of that on thymocytes, and about 2.5% of that present on peritoneal macrophages. Intraperitoneal allografts of c57BL/10Sn islets were uniformly rejected by B10.BR/SgSn diabetic recipients only when the islets were accompanied by 10(7) peritoneal lymphoid cells. When transplanted without peritoneal cells, C57BL/10Sn islets were only marginally rejectable. In a group of nine such allografts, three diabetic recipients were permanently cured and three others showed rejection times of about 30 days. Sensitization of the three mice showing permanent cures, using 10(7) allogeneic peritoneal cells at about 40 days after the transplant, did not cause rejection of the allografts. Isogeneic transplantation of cell suspensions from dissociated islets of Langerhans was markedly less effective in controlling diabetes than intact islets, and dissociation did not obviously improve the rate of allograft survival. However, 5/19 diabetic mice receiving allografts of dissociated islet cells showed long-term reversals of diabetes that were unaffected by administration of 10(7) peritoneal cells at about 100 days after the transplant. Recipient mice whose diabetes was reversed by islet allografts and unaffected by specific sensitization had pancreatic insulin concentrations characteristic of diabetic mice. Our reversals of diabetes with untreated islet allografts may be due to the cleanliness of islet preparations obtained with a modified isolation technique, and to the very low density of H-2 complex antigens on C57BL/10Sn beta-cells.

Animals↗

Detection and characterisation of neurotransmitters, particularly peptides, in the gastrointestinal tract.

There are now about twelve substances, many of them peptides, that are thought to act as neurotransmitters in the enteric nervous system. Most of the studies of peptides have relied on immunochemical methods for their detection. However, difficulties arise in these studies because of the close similarities between peptides. Related peptides can be grouped in several ways according to similarities of origin, function, effects in bioassays and amino acid sequences. Peptides with the same function in different species, and only slight differences in amino acid sequence, have been called isopeptides. Peptide families that have sequences of amino acids in common, but do not necessarily have similar functions are described. In the guinea-pig small intestine, used as a model, the concentrations of fourteen nerve-related peptides and amines are compared. The actual chemical natures of the peptides are discussed. It is concluded that nerves containing authentic leu- and met-enkephelin, somatostatin and substance P are present. VIP in guinea-pig enteric nerves is different from the porcine standard. Peptides similar to authentic CCK8 and amphibian skin bombesin are present. Angiotensin and neurotensin-like peptides shown immunohistochemically are not the authentic peptides. In the longitudinal muscle plus myenteric plexus, most neuropeptide concentrations are in the range of 10-500 pmole/g. The exception is met-enkephalin (1,300 pmole/g). The amine transmitters have considerably higher concentrations, noradrenaline having a concentration of about 3,500 pmole/g and acetylcholine 1-2 x 10(5) pmole/g.

Angiotensins↗

The effect of somatostatin on the activation of adenosine 3',5'-monophosphate-dependent protein kinase in isolated rat islets of Langerhans.

Somatostatin has been reported to inhibit the increases in cAMP levels induced by glucagon in isolated islets of Langerhans. The present study was undertaken to test whether the reported effects of somatostatin on islet cAMP levels were also reflected in changes in the cAMP-dependent protein kinase activity. Isolated islets were found to contain both isoenzymes of the cAMP-dependent protein kinase. In the presence of theophylline (2 mM), glucagon (2.9 X 10(-6) M) increased the islet protein kinase activity ratio from 0.24 +/- 0.02 to 0.55 +/- 0.02. Somatostatin (6.6 X 10(-7) M) fully inhibited both the glucagon (2.9 X 10(-7) M)- and theophylline (2 mM)-induced increases in the protein kinase activity ratio. Omission of Ca2+ from the islet incubation media did not alter the inhibitory effect of somatostatin on the glucagon-dependent activation of the cAMP-dependent protein kinase. The present study has demonstrated that in the islets of Langerhans, glucagon-dependent activation of the cAMP-dependent protein kinase can be modulated by somatostatin.

Animals↗

Effects of human growth hormone on the secretion of rat growth hormone.

Human growth hormone (hGH) was administered to chronically cannulated male rats and its effect upon the physiological secretory patterns of rat growth hormone (rGH) and prolactin were observed. In comparison with injected control animals, a reduction in the size of spontaneous secretory bursts of rGH was apparent when hormone concentrations were compared 3-6 h after administration of hGH (136.27 +/- 27.31 (S.E.M.) v. 76.22 +/- 20.98 ng/ml respectively). However, the mean frequency of secretory episodes of rGH was unaltered. It is therefore postulated that endogenous rGH may modulate the amplitude but not the rhythmicity of secretory episodes of rGH.

Animals↗