Biomedical subjects

S Harvey

Publications and source records attributed to S Harvey.

At least 145 records · Page 8Linked to original sources

PubMed1990

Exchange of spacer regions between rRNA operons in Escherichia coli.

The Escherichia coli rRNA operons each have one of two types of spacer separating the 16S and 23S coding regions. The spacers of four operons encode tRNA(Glu2) and the other three encode both tRNA(Ile) and tRNA(Ala1B). We have prepared a series of mutants in which the spacer region of a particular rrn operon has been replaced by the opposite type. Included among these were a mutant retaining only a single copy of the tRNA(Glu2) spacer (at rrnG) and another retaining only a single copy of the tRNA(Ile)-tRNA(Ala1B) spacer (at rrnA). While both mutants grew more slowly than controls, the mutant deficient in tRNA(Glu2) spacers was more severely affected. At a frequency of 6 X 10(-5), these mutants phenotypically reverted to faster growing types by increasing the copy number of the deficient spacer. In most of these phenotypic revertants, the deficient spacer type appeared in a rrn operon which previously contained the surplus type, bringing the ratio of spacer types closer to normal. In a few cases, these spacer changes were accompanied by an inversion of the chromosomal material between the donor and recipient rrn operons. Two examples of inversion of one-half of the E. coli chromosome between rrnG and rrnH were observed. The correlation of spacer change with inversion indicated that, in these particular cases, the change was due to an intrachromatid gene conversion event accompanied by a reciprocal crossover rather than reciprocal exchange between sister chromatids.

Base Sequence↗

PubMed1990

Comparison of ultrafiltration devices for assessing theophylline protein binding.

The ability of two commercially available ultrafiltration devices to assess the protein binding of theophylline was compared using human serum albumin in pH 7.4 buffer at 37 degrees C. The devices compared were the Millipore-MC filter units (Catalog number UFC3LGC00) and the Amicon Centrifree Micropartition System; both rely on centrifugal force to separate the unbound and bound molecules. The results from each device were essentially identical provided that the Millipore units were centrifuged using conditions that would not allow heat buildup to occur and thereby cause a decrease in the binding. This problem could be minimized if the Millipore units were available in a low-binding 30,000 dalton cutoff membrane instead of the 10,000 dalton membrane currently available. The use of the Millipore 30,000 dalton cutoff polysulfone membrane (UFC3TTK00) reduced the centrifugation time necessary to obtain a sufficient volume of ultrafiltrate for assay, thereby minimizing the possibility of heat generation. Furthermore, the binding of theophylline to this device was low and comparable to the binding to the Centrifree devices. Because this low degree of membrane binding may not hold for other drugs, we would suggest that a Millipore unit supplied with a low-binding, 30,000 dalton cutoff membrane could provide binding data with an efficacy comparable to that achieved with the Centrifree devices.

Humans↗

PubMed1990

Contrasting effects of nitrofurans on plasma corticosterone in chickens following administration as a bolus or diet additive.

Administration of furazolidone as a bolus dose (8-500 mg/kg), produced a decrease in plasma corticosterone in chickens. In contrast, addition of furazolidone or furaltadone to the diet (0.04% or above, 10 days), increased plasma corticosterone. Pre-treatment with a 200-mg/kg bolus of furazolidone or furaltadone did not affect pentobarbitone anaesthesia time in the birds. In chickens pre-treated with a nitrofuran in the diet, however, pentobarbitone anaesthesia time was significantly less than that in controls. Furaltadone in the diet, produced significant increases in the amount of cytochrome P-450 and the activity of aniline hydroxylase in the liver microsomes. It is suggested that nitrofurans given in the diet stimulated corticosterone biosynthesis in the adrenal glands and induced mixed-function oxidase activity in the liver. Nitrofurans given as a bolus did not produce these effects. Furazolidone (200 mg/kg) produced severe anorexia, which lasted 2 days in T-line birds. The anorexia seemed to be associated with tissue damage in the birds rather than the ensuing adrenal cortical insufficiency.

Administration, Oral↗

PubMed1990

Application of the guidelines for client-centred practice to paediatric occupational therapy.

This paper outlines the process of incorporating the "Guidelines For the Client-Centred Practice of Occupational Therapy" into the practice of occupational therapy in an out-patient rehabilitation facility serving young people with physical disabilities. Specifically, the areas of practice addressed are screening and assessment. The process started in 1987 with an identification of the need to find a holistic framework that meets the complex needs of clients with chronic physical disabilities. The conceptual model of occupational performance, as outlined in the Guidelines, provided such a framework. The process of incorporating the Guidelines into the screening and assessment practices of occupational therapists at Erinoak Serving Young People With Physical Disabilities is described, with examples of documents developed by the department. Suggestions are given to integrate the conceptual model of occupational performance into the practice of occupational therapists working with children and adolescents with physical disabilities.

Adolescent↗

PubMed1990

Parathyroid hormone messenger ribonucleic acid in the rat hypothalamus.

Polyadenylated RNA, extracted from rat hypothalami, cross-hybridized with a RNA probe complementary in sequence to rat PTH (rPTH) messenger RNA (mRNA). Amplification of complementary DNA (cDNA) by the polymerase chain reaction also demonstrated the presence of rPTH mRNA in the rat hypothalamus and parathyroid gland. rPTH mRNA was localized by in situ hybridization in the paraventricular and supraoptic nuclei of the rat hypothalamus. These results demonstrate the expression of the PTH gene in the central nervous system of the rat in areas which suggest roles for PTH in neuroendocrine function.

Animals↗

PubMed1990

Feedback-inhibition of growth hormone (GH) secretion in fowl: GH-induced down-regulation of thyrotrophin-releasing hormone binding to pituitary membranes.

Administration of ovine GH to immature domestic fowl blunted their subsequent GH response to thyrotrophin-releasing hormone (TRH), a GH secretagogue in birds. The in-vivo administration of GH also reduced the ability of radiolabelled TRH to bind to plasma membranes of the pituitary caudal lobe, in which GH cells predominate. These inhibitory effects of GH were mediated by extrapituitary actions, since GH had no direct inhibitory effects on TRH-induced GH release or on pituitary TRH binding in vitro. GH inhibition of GH secretion and TRH binding would not appear to be mediated by hypothalamic somatostatin (SRIF) or peripheral somatomedin (IGF-I), since SRIF and IGF-I had no direct effects in vitro.

Animals↗

PubMed1990

Growth hormone-binding sites in chicken hypothalamus.

Specific binding of 125I-labelled recombinant DNA-derived chicken GH (rcGH; 2.1 +/- 0.41 (S.E.M.) % of total counts) and of 125I-labelled bovine GH (1.80 +/- 0.27% of total counts) to crude plasma membranes of the chicken hypothalamus was demonstrated. Binding of 125I-labelled rcGH was related to the amount of tissue incubated and was significant over the range 250-950 micrograms membrane protein per tube. Binding of 125I-labelled rcGH was saturable over the range 0.14-0.40 pmol and was to a single class of high-affinity (33.5 pM) low-capacity (2.14 fmol/mg protein) binding site. Binding of 125I-labelled rcGH was displaced by ovine GH and by ovine prolactin. These results demonstrate, for the first time, central GH-binding sites in a vertebrate species.

Animals↗

PubMed1990

Thyroidal inhibition of growth hormone secretion in fowl: tri-iodothyronine-induced down-regulation of thyrotrophin-releasing hormone-binding sites on pituitary membranes.

The number, but not affinity, of binding sites for [3H]3-methyl-histidine2-TRH ([3H]Me-TRH) on chicken adenohypophysial plasma membranes was increased in chickens made hypothyroid by goitrogen (methimazole) treatment (50 mg/kg per day for 7 days), which also increased circulating GH concentrations. Daily i.p. injection of thyroxine (T4; 100 micrograms/kg for 7 days) had no effect on [3H]Me-TRH binding to pituitary membranes, although it suppressed endogenous GH secretion. Binding of [3H]Me-TRH to pituitary caudal lobe membranes was, however, suppressed by tri-iodothyronine (T3) injected chronically (100 micrograms/kg per day, i.p., for 7 days) or acutely (100 micrograms/kg, 2 h before being killed). The suppression of [3H]Me-TRH binding and inhibition of GH secretion following T3 administration was dose related. Binding of [3H]Me-TRH to caudal lobe membranes was also suppressed following the incubation of pituitary glands with T3 in vitro, and the response was both dose and time related. These results suggest that T3 inhibits GH secretion in fowl by a down-regulation of pituitary TRH receptors. However, other mechanisms are involved in thyroidal inhibition of GH release in birds, since T4 had no effects on [3H]Me-TRH binding yet suppressed GH secretion in vivo.

Animals↗

PubMed1990

Somatostatin binding to chicken adenohypophysial membranes.

[125I-Tyr1]-Somatostatin (SRIF)-binding sites were demonstrated on crude plasma membrane preparations from chicken pituitary glands. These binding sites were saturable and of high affinity (dissociation constant less than 1.0 nM) and low capacity (maximal binding capacity less than 200 fmol/mg protein) and were specific for SRIF moieties. The number and affinity of these binding sites in the caudal lobe of the pituitary, in which somatotrophs predominate, were similar to those in the cephalic lobe, in which lactotrophs and thyrotrophs are confined. Gonadotrophs are present in the caudal lobe, but whereas exogenous SRIF inhibited secretagogue-induced GH release from incubated pituitary glands, it had no effect on basal or secretagogue-induced LH release. The half-maximal binding of SRIF to the caudal lobe membranes (3 nM) was similar to that required for half-maximal suppression of TRH-induced GH release, suggesting a role for these binding sites in the regulation of GH secretion in birds.

Animals↗

PubMed1990

Desensitization of thyrotrophin-releasing hormone (TRH)-induced growth hormone secretion in chickens: coincident down-regulation of TRH binding to pituitary membranes.

Release of GH is stimulated by TRH in chickens. However, for 60 min following a priming injection of TRH, a second injection of TRH is unable to provoke further GH release. TRH binds to the plasma membranes of the pituitary caudal lobe, in which somatotrophs predominate, although the magnitude of [3H]3-methyl-histidine2-TRH ([3H]Me-TRH) binding was reduced (by 25-50%) 30 min after the i.v. administration of a dose of TRH (5 micrograms/kg) maximally effective in provoking GH release. A significant reduction in [3H]Me-TRH binding to caudal lobe membranes was also observed within 15 min of TRH administration and was maintained for at least 60 min. Control levels of [3H]Me-TRH binding were restored 2 h after TRH injection, coincident with the restoration of GH responsiveness to TRH challenge. The suppression of [3H]Me-TRH binding to pituitary membranes 30 min after in-vivo TRH administration was dose related, whereas the maximal (10 min) GH response to TRH was biphasic. The suppression of [3H]Me-TRH binding to chicken pituitary membranes was due to direct pituitary actions of TRH and could be induced by a 30-min exposure to 100 nM TRH in vitro. These results demonstrate that avian pituitary TRH-binding sites differ greatly from mammalian ones in the timing of the onset and duration of down-regulation. Pituitary TRH-binding sites in birds are rapidly and transiently down-regulated following TRH administration in vivo, coincident with the period of GH refractoriness to TRH challenge.

Animals↗

PubMed1990

Growth hormone receptors in hypothalamic and extra-hypothalamic tissues.

Central GH receptors (GHR) have been identified in hypothalamic and extra-hypothalamic tissues of rabbit and chicken brains. Plasma membranes of the rabbit brain demonstrated specific saturable high-affinity, low-capacity binding sites for 125I-labelled GH. RNA extracted from hypothalamic and extra-hypothalamic tissues of rabbit and chicken brains contained mRNA that hybridized with a cDNA probe for the rabbit liver GHR. This transcript was of a similar size to the major GHR mRNA moiety in rabbit liver. The expression of these moieties was age related, and higher in adult than in neonatal animals.

Age Factors↗

PubMed1990

Participation of tri-iodothyronine and metabolic clearance rate in the inhibition of growth hormone secretion in thyroxine-treated domestic fowl.

Surgical thyroidectomy increases basal and TRH-induced GH concentrations in the peripheral plasma of immature domestic fowl. Replacement therapy with thyroxine (T4; 100 micrograms/kg per day for 7 days, i.m.) suppressed the GH responses to thyroidectomy. Bolus administration of T4 (10 micrograms/kg, i.m.) to thyroidectomized birds promptly lowered the circulating GH concentrations, which remained suppressed for at least 4 h. Chronic (daily injections for 7 days) or acute (one injection) pretreatment of thyroidectomized birds with iopanoic acid (IOP; 40 mg/bird, i.m.) before the bolus administration of T4 attenuated, but did not prevent, inhibition of circulating GH levels by T4. Administration of IOP (40 mg/bird i.m.) 24 h and immediately before the administration of tri-iodothyronine (T3; 3 micrograms/kg, i.m.) or T4 (10 micrograms/kg, i.m.) also failed to suppress thyroidal inhibition of circulating GH concentrations in thyroidectomized birds. Administration of IOP alone had no effect on GH concentrations. Circulating T3 concentrations were not enhanced following the administration of T4 to IOP-treated birds, indicating its inhibition of hepatic monodeiodinase activity. The metabolic clearance rate (MCR) of 125I-labelled chicken GH in the plasma of thyroidectomized fowl was less than that in sham-thyroidectomized birds. Following pretreatment with T4 (100 micrograms/kg per day for 7 days) sham-thyroidectomized and thyroidectomized birds did not differ significantly in their MCR. The GH secretion rate in thyroidectomized birds was similar to that in sham-thyroidectomized birds and in both groups was markedly reduced following pretreatment with T4. These results demonstrate thyroidal inhibition of circulating GH concentrations in fowl.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Thyrotrophin-releasing hormone: a growth hormone-releasing factor.

The regulation of pituitary GH has traditionally been considered to be under dual hypothalamic control, by inhibitory and stimulatory releasing factors (SRIF and GRF respectively). The specificity of these factors is not absolute, however, and both SRIF and GRF have been implicated in the regulation of other pituitary hormones. Likewise, TRH not only regulates pituitary thyrotrophin but is also an acknowledged prolactin releasing factor. Since TRH also stimulates GH release throughout the vertebrates, it should also be considered as a GRF.

Acromegaly↗

PubMed1990

Feedback effects of growth hormone on anterior pituitary function in chickens.

Circulating GH concentrations were suppressed 24 h after intracerebroventricular (i.c.v.) injection of native or recombinant DNA-derived chicken GH (rcGH) (10 micrograms in 4 microliters vehicle) into the right lateral ventricles of conscious 6-week-old cockerels. Plasma concentrations of LH were suppressed within 1 h of i.c.v. administration of GH at doses of 1 or 10 micrograms, and remained suppressed for 24 h in birds injected with the highest concentration of GH. In contrast, concentrations of plasma prolactin were increased 24 h after i.c.v. administration of GH (10 micrograms). The i.v. administration of rcGH (at concentrations of 10 or 100 micrograms/kg) did not mimic the effects of i.c.v. injection of GH. These results demonstrate central effects of GH on pituitary function in the domestic fowl.

Animals↗

PubMed1990

Tri-iodothyronine inhibition of thyrotrophin-releasing hormone-induced growth hormone release from the chicken adenohypophysis in vitro.

Tri-iodothyronine (T3) had no effect on the basal level of GH release from chicken hemipituitary glands perifused in vitro. The GH response to TRH was, however, markedly suppressed following exposure to T3. Suppression of TRH-stimulated GH secretion was observed after a 2-h preincubation with T3, and was induced, in a dose-related way, by 0.01-10 mumol T3/l. Exposure to T3 also reduced the effectiveness of TRh, at concentrations of 0.001-10 micrograms/ml, to stimulate GH release. These results demonstrate that, in addition to a hypothalamic site of action, T3 is likely to suppress GH secretion in vivo by direct effects on pituitary GH release.

Animals↗

PubMed1990

Central action of thyrotrophin-releasing hormone on growth hormone secretion in domestic fowl.

Peripheral plasma concentrations of GH in adult chickens were increased, in a dose-related manner, between 5 and 30 min after the intracerebroventricular (i.c.v.) injection of 0.1 or 10 micrograms TRH. In contrast, i.v. administration of comparable doses of TRH had no significant effect on circulating GH concentrations. [3H]3-methyl-histidine2-TRH [( 3H]Me-TRH) was located in the pituitary gland and peripheral plasma within 5 min of its i.c.v. administration, although in amounts that were unlikely to affect directly pituitary function. [3H]Me-TRH rapidly accumulated in the hypothalamus following its i.c.v. administration (but not after i.v. injection), and the central effect of TRH on GH secretion in birds is therefore likely to be induced by effects at hypothalamic sites.

Animals↗

PubMed1990

Short-loop inhibition of thyrotrophin-releasing hormone-induced growth hormone secretion in fowl.

The i.c.v. administration of 0.1 or 10 micrograms ovine (o)GH to 12- to 16-week-old hypothyroid chickens of a sex-linked dwarf (SLD) strain suppressed the basal plasma GH concentrations, measured 24 h afterwards. The GH response of the oGH-injected SLDs to TRH was suppressed, in a dose-related way, in comparison with that induced by TRH in birds given control injections (10 micrograms) of bovine serum albumin (BSA). Basal circulating concentrations of GH in euthyroid K strain birds of the same age were even lower than in the SLDs following injection of 10 micrograms oGH, and were not further reduced by oGH administration. The GH response to TRH in the K strain birds injected i.c.v. with 0.1 or 10 micrograms oGH was, nevertheless, suppressed in comparison with the BSA-injected K strain controls. The i.c.v. administration of oGH also suppressed circulating concentrations of LH and the LH response to TRH in the K strain birds. Twenty-four hours after i.c.v. administration of oGH (10 micrograms), the somatostatin (SRIF) content in the medial basal hypothalamus of 8-week-old euthyroid cockerels was greater than that in BSA (10 micrograms)-injected controls. At the same time, the binding of [3H]3-methyl-histidine2-TRH to the pituitary caudal and cephalic lobes of GH-injected birds was less than that in the controls. These results suggest that GH regulation in avian species is partly mediated by an inhibitory short-loop mechanism (mediated by hypothalamic SRIF and a down-regulation of pituitary TRH-binding sites) that suppresses basal and secretagogue-induced GH release.

Animals↗

PubMed1990

Homologous and heterologous regulation of somatostatin-binding sites on chicken adenohypophysial membranes.

Binding of 125I-labelled [Tyr1]-somatostatin (125I-[Tyr1]-SRIF) to pituitary caudal lobe membranes was suppressed in immature chickens 1 and 2 h after i.v. administration of unlabelled SRIF at concentrations of 1-100 micrograms/kg. In-vitro preincubation of chicken pituitary glands for 0.5-4.0 h with 0.1 mumol SRIF/l similarly reduced the binding of 125I-[Tyr1]-SRIF to caudal lobe membrane preparations. After a 4-h incubation in 0.1 mmol SRIF/l, the withdrawal of SRIF from the incubation media was accompanied 4 h later by a partial recovery in the binding of 125I-[Tyr1]-SRIF to pituitary membranes. Passive immunoneutralization of endogenous SRIF resulted in a prompt (within 1 h) and sustained (for at least 24 h) suppression of 125I-[Tyr1]-SRIF binding to pituitary membranes. The i.m. administration of cysteamine (300 mg/kg) to 12-week-old birds depleted hypothalamic SRIF stores and decreased the density of 125I-[Tyr1]-SRIF-binding sites in the caudal and cephalic lobes of the chicken pituitary gland. The reduction in SRIF content and in SRIF-binding sites occurred within 1 h of cysteamine administration and was maintained for at least 24 h. In 6-week-old birds, cysteamine (300 mg/kg) administration suppressed pituitary binding of 125I-[Tyr1]-SRIF for at least 5 days. Circulating concentrations of GH were markedly decreased 1 and 4 h after cysteamine injection, but not after 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗