Search Results
You are looking at 1 - 9 of 9 items for
- Author: R. N. SMITH x
- Refine by access: All content x
Search for other papers by R. N. SMITH in
Google Scholar
PubMed
SUMMARY
The innervation of the ferret's pituitary gland has been studied by means of a modification of Ranson's pyridine-silver technique.
Non-myelinated nerve fibres of characteristic appearance are present in the pars distalis. The number of these fibres is small, but their paucity may be accounted for by the varying depth of impregnation achieved. Structures resembling end-organs within the pars distalis are also described.
Search for other papers by L.A. SALAKO in
Google Scholar
PubMed
Search for other papers by A. J. SMITH in
Google Scholar
PubMed
Search for other papers by R. N. SMITH in
Google Scholar
PubMed
SUMMARY
Extracts of porcine thyroid containing calcitonin produced increases in urinary flow and urinary electrolyte content when infused or injected into anaesthetized rabbits. This response occurred more rapidly after intraaortic than after intravenous injection and was accompanied by an increase in glomerular filtration rate (inulin clearance) and renal plasma flow (paraaminohippuric acid clearance).
Preparations of calcitonin failed to affect the short-circuit current in isolated frog skin.
Although an effect of calcitonin on renal tubular transport mechanisms cannot be excluded it seems likely that one mechanism responsible for the diuretic effect of this compound in the rabbit is an increase in renal blood flow.
Search for other papers by H. C. K. LALJEE in
Google Scholar
PubMed
Search for other papers by R. N. SMITH in
Google Scholar
PubMed
Search for other papers by K. J. DORRINGTON in
Google Scholar
PubMed
SUMMARY
A mouse assay for thyrocalcitonin using either intravenous or intraperitoneal injections is described. Responses to porcine thyroid extracts were similar to those in rats. Extracts of human thyroid glands obtained at autopsy or surgical operation caused hypocalcaemia in the mouse. The rat was less sensitive to human thyrocalcitonin. Studies on autopsy tissue showed that human thyrocalcitonin could only be detected if thyroids were removed within 12 hr. after death. Crude extracts of human thyroids were assayed in mice by intraperitoneal injection and the thyrocalcitonin content was determined in tissue obtained from patients with thyrotoxicosis or non-toxic goitre.
Search for other papers by N. Watanabe in
Google Scholar
PubMed
Search for other papers by R. G. Rosenfeld in
Google Scholar
PubMed
Search for other papers by R. L. Hintz in
Google Scholar
PubMed
Search for other papers by L. A. Dollar in
Google Scholar
PubMed
Search for other papers by R. L. Smith in
Google Scholar
PubMed
ABSTRACT
In order to obtain a phenotypically stable cell population of chondrocytes, high density primary monolayer cultures of bovine articular chondrocytes were established. Using these cultures, a specific insulin-like growth factor-I/somatomedin-C (IGF-I/SM-C) receptor was demonstrated and characterized. At 15 °C steady-state binding was attained by 5 h, and averaged 25% per 2·2 × 106 cells. Fifty per cent displacement of 125I-labelled IGF-I/SM-C by unlabelled IGF-I/SM-C occurred at concentrations of only 2·3 ng/ml, whereas IGF-II and porcine insulin were approximately 15-and 1000-fold less potent respectively. Scatchard analysis gave a linear plot, with a calculated association constant of 2·26 × 109 l/mol and a receptor number of 15 400 sites per cell.
Preincubation of chondrocyte monolayers with either IGF-I/SM-C or porcine insulin at 37 °C for 20 h resulted in reduction of 125I-labelled IGF-I/SM-C binding in a dose-dependent manner, although higher concentrations were required with insulin. More than 40% down-regulation of the receptor occurred with IGF-I/SM-C at concentrations of 10 nmol/l and nearly 70% reduction at 50 nmol/l. Interestingly, after preincubation with either human (h) or bovine (b)GH, 40% down-regulation of 125I-labelled IGF-I/SM-C binding was observed at concentrations of 10 μmol/l. Local production of IGF-I/SM-C by chondrocytes in response to GH stimulation may have occurred, but, because only 120 pmol IGF-I/SM-C and < 30 pmol IGF-I/SM-C per litre were recovered from serum-free conditioned media preincubated with bGH and hGH respectively, this was not established.
These studies demonstrate that cultured bovine articular chondrocytes possess a highly specific IGF-I/SM-C receptor, and that this receptor population is regulated not only by IGF-I/SM-C and insulin but also by high concentrations of either hGH or bGH. These results are consistent with the growth-promoting action of IGF-I/SM-C on skeletal tissues, and suggest the possibility that GH itself may play its own role to modulate IGF-I/SM-C receptors on chondrocytes.
J. Endocr. (1985) 107, 275–283
Search for other papers by R N Kulkarni in
Google Scholar
PubMed
Search for other papers by D M Smith in
Google Scholar
PubMed
Search for other papers by M A Ghatei in
Google Scholar
PubMed
Search for other papers by P M Jones in
Google Scholar
PubMed
Search for other papers by S R Bloom in
Google Scholar
PubMed
Abstract
We have investigated the effects of antisense oligodeoxynucleotides (oligos) to islet amyloid polypeptide (IAPP) mRNA on the expression and secretion of IAPP and insulin, in the clonal β-cell line HIT-T15. Phosphorothioate-modified oligos were cytotoxic compared with phosphodiester (D)-oligos. Of the nine oligos tested using a lipofection reagent, 03, a 30-mer D-oligo complementary to a sequence downstream of the IAPP initiation codon, showed a significant dose-dependent suppression of IAPP mRNA, with a 42% decrease at 7·5 μm, compared with a scrambled (MS03) control oligo (n=3, P<0·01). A subsequent 89% suppression of IAPP release was observed in the 4-h period following antisense treatment (1·78 ± 0·13 (MS03) vs 0·19 ± 0·14 (03) pmol/106 cells per 240 min, n=7, P<0·01). A significant increase in insulin mRNA (100 ± 10% (MS03) vs 124 ± 8% (03), n=3, P<0·05) and insulin content (13·0 ± 0·9 (MS03) vs 17·4 ± 1·4 (03) pmol/106 cells, n=7, P=0·028) was observed following treatment with 03 at 7·5 μm. 08, a 20-mer D-oligo directed to a region of IAPP mRNA further downstream than 03, also showed a decrease in IAPP mRNA and peptide release and an increase in insulin content. No significant changes were observed in the expression and release of the unrelated β-cell peptide, neuropeptide Y. We thus show a suppression of synthesis and release of IAPP in HIT-T15 cells using antisense oligos. The associated increase in insulin mRNA and content in these cells after treatment with IAPP antisense oligos is in accord with an inhibitor action of IAPP on insulin availability.
Journal of Endocrinology (1996) 151, 341–348
Search for other papers by R N Kulkarni in
Google Scholar
PubMed
Search for other papers by D M Smith in
Google Scholar
PubMed
Search for other papers by M A Ghatei in
Google Scholar
PubMed
Search for other papers by S R Bloom in
Google Scholar
PubMed
Abstract
Insulin secretion is regulated by neural and neurohormonal factors. The report of nerves releasing pituitary adenylate cyclase-activating polypeptide (PACAP) – a 38 amino acid peptide – in the endocrine pancreas, suggests it may be important in modulating insulin release. We therefore carried out receptor-binding studies on membranes prepared from the glucose-responsive clonal β-cell line HIT-T15, and also examined the effects of PACAP38, PACAP27 – a C-terminal truncated form of the peptide – and vasoactive intestinal peptide (VIP) on insulin and islet amyloid polypeptide (IAPP) release. We showed by chemical cross-linking that PACAP and VIP stimulate secretion from the clonal cells by binding to a receptor with a molecular weight of 67 kDa (n=4). Binding was saturable when membranes were incubated with 125I-PACAP27 (K d 1·2±0·2 nm; Bmax 415·7±35·3 fmol/mg; n=4) or 125I-VIP (K d 1·3±0·3 nm; Bmax 354·8 ± 42·8 fmol/mg; n=4). We also demonstrated an increase in glucose-stimulated insulin (PACAP27, 366·6 ±25·8% PACAP38, 389·9 ±13·4%; VIP, 342·6± 16·1% of control; all at 1 μm, P<0·01 vs control) and IAPP release (PACAP27, 236·9 ±26·2%; PACAP38, 226·5 ± 10·9%; VIP, 242·9 ± 15·8% of control; all at 1 μm, P<0·01 vs control). Incubation of the cells with these peptides, for a duration of 12 h, in the presence of 5·5 mm glucose, did not alter the expression of insulin or IAPP. These findings suggest that PACAP and VIP stimulate secretion of insulin and IAPP by binding to a 67 kDa protein on clonal β-cells and do not alter the transcription of insulin and IAPP under the conditions tested.
Journal of Endocrinology (1995) 147, 121–130
Search for other papers by E. M. Wintour in
Google Scholar
PubMed
Search for other papers by M. B. Smith in
Google Scholar
PubMed
Search for other papers by R. J. Bell in
Google Scholar
PubMed
Search for other papers by J. G. McDougall in
Google Scholar
PubMed
Search for other papers by M. N. Cauchi in
Google Scholar
PubMed
ABSTRACT
The switch from γ (fetal) to β (adult) globin production was studied by the analysis of globin synthesis in chronically cannulated ovine fetuses and newborn lambs. The γ/α globin synthesis ratio decreased from 0·98 ± 0·11 (s.d.) (n = 4 samples) at 100–120 days of gestation to 0·15± 0·07 (n = 4) in lambs of 150–156 days post-conception, and the β/α synthesis ratio increased from 0·04 ± 0·06 (n = 4) to 1·13 ± 0·21 (n = 4) over the same period. In bilaterally adrenalectomized fetuses, which survived in utero until 151–156 days, the γ/α and β/α synthesis ratios were 0·64 ± 0·14 (n = 3) and 0·25 ± 0·07 (n = 3) respectively in the 150- to 156-day period. Bilateral adrenalectomy did not affect the time of onset of β globin synthesis, but significantly decreased the rate. In one bilaterally adrenalectomized fetus the infusion of increasing concentrations of cortisol restored the rate of β globin synthesis to normal. Treatment of three intact fetuses with 100 μg cortisol/h for 3 weeks, from 100 to 121 days, did not affect the timing or rate of switch from γ to β globin synthesis. Thus fetal adrenal secretions, probably cortisol, affected the rate of change of γ to β globin synthesis but other factors must have been involved in the initiation of the switch.
J. Endocr. (1985) 104, 165–170
Search for other papers by R. J. KEYNES in
Google Scholar
PubMed
Search for other papers by G. W. SMITH in
Google Scholar
PubMed
Search for other papers by J. D. H. SLATER in
Google Scholar
PubMed
Search for other papers by M. M. BROWN in
Google Scholar
PubMed
Search for other papers by S. E. BROWN in
Google Scholar
PubMed
Search for other papers by N. N. PAYNE in
Google Scholar
PubMed
Search for other papers by T. P. JOWETT in
Google Scholar
PubMed
Search for other papers by C. C. MONGE in
Google Scholar
PubMed
Measurements have been made of hormonal changes relevant to salt and water balance during prolonged exposure to hypoxia to improve our understanding of the syndrome of acute mountain sickness. We have attempted to delineate the detailed inter-relationships between the renin–aldosterone and the vasopressin systems by a metabolically controlled study, involving an orthostatic stress (45° head-up tilt) and an injection of a standard dose of ACTH to test adrenal responsiveness. Three Caucasian medical students underwent a 7-day equilibration at 150 m (Lima, Peru), followed by a 6-day sojourn at 4350 m (Cerro de Pasco, Peru) and a final 7 days at 150 m. Measurements were made of sodium and potassium balance, body weight and the 24-h renal excretion of vasopressin, cortisol and aldosterone 18-glucuronide. These variables showed little change, except for that of aldosterone 18-glucuronide, which fell sharply at altitude and rebounded even more sharply on return to sea level. At altitude, basal plasma levels of renin activity and aldosterone fell, and the response to orthostasis was attenuated, but the fall of plasma renin activity, as compared to plasma aldosterone, was delayed; on return to sea level this dissociation was exacerbated with the return of normal renin responsiveness lagging behind that of aldosterone. We suggest that unknown factors which dissociate the orthodox renin–aldosterone relationship, other than the activity of the angiotensin I-converting enzyme, are operative on exposure to hypoxia.
Search for other papers by C. L. van Papendorp in
Google Scholar
PubMed
Search for other papers by I. T. Cameron in
Google Scholar
PubMed
Search for other papers by A. P. Davenport in
Google Scholar
PubMed
Search for other papers by A. King in
Google Scholar
PubMed
Search for other papers by P. J. Barker in
Google Scholar
PubMed
Search for other papers by N. S. Huskisson in
Google Scholar
PubMed
Search for other papers by R. S. Gilmour in
Google Scholar
PubMed
Search for other papers by M. J. Brown in
Google Scholar
PubMed
Search for other papers by S. K. Smith in
Google Scholar
PubMed
ABSTRACT
The aim of this study was to investigate the localization of endothelin-like immunoreactivity (ET-IR) in human placenta, chorion and amnion and to compare the endogenous concentration of immunoreactive endothelin (ET) in these tissues before and after the onset of labour. ET-IR was detected in the endothelium of stem vessels in placental villi, as well as in decidual stromal cells in the basal maternal plate, by immunocytochemistry using a primary polyclonal rabbit antibody. A specific radioimmunoassay was used to detect endogenous concentration of ET in homogenized placental tissues. The endogenous concentration of ET-IR was significantly greater in amnion than in chorion and placenta (amnion 249 ±13 fmol/g; chorion 190 ±11 fmol/g; placenta 169±14 fmol/g; means ± s.e.m.; n = 12; P < 0·01). No significant difference was seen before or after the onset of labour. The detection of ET-IR in placenta, chorion and amnion suggests that the ETs may play a role in the paracrine control of human uterine function.
Journal of Endocrinology (1991) 131, 507–511
