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Biomedical subjects

J S Price

Publications and source records attributed to J S Price.

At least 19 recordsLinked to original sources
PubMed1991

Neuropeptide Y (NPY) metabolism by endopeptidase-2 hinders characterization of NPY receptors in rat kidney.

1. Despite the observation of pharmacological responses to neuropeptide Y (NPY) in mammalian kidneys, there are species differences in the ease with which specific NPY binding sites can be demonstrated; we have investigated whether this can be explained by differential metabolism of NPY by a membrane-bound peptidase. 2. NPY receptors were identified on cell membranes isolated from the rabbit kidney (KD = 97 +/- 16 pM, Bmax = 290 +/- 30 fmol mg-1 protein), and this preparation did not degrade [125I]-NPY. However, a similar preparation of cell membranes from the rat kidney exhibited a much lower apparent receptor affinity (IC50 approximately 30 nM); these membranes rapidly degraded [125I]-NPY to fragments which did not bind NPY receptors in either tissue. 3. [125I]-NPY binding sites were revealed in the rat kidney when degradation was inhibited by insulin B chain. Chelating agents also inhibited degradation, but interfered with receptor binding. Binding sites could not be demonstrated in sections of rat kidney, even in the presence of insulin B chain. 4. The difference in degradative activity between rat and rabbit renal cell membranes, inhibition of degradation by chelating agents and insulin B chain, and insensitivity to phosphoramidon suggest that the enzyme responsible was endopeptidase-2, and this was confirmed by comparing the hydrolysis of [125I]-NPY by purified enzyme with rat renal tissue. Activity of this enzyme explains the difficulties encountered demonstrating receptors in the rat kidney. 5. Renal cell membranes from the mouse digested [125I]-NPY in a similar manner and this may be due to the closely related enzyme, meprin. NPY degradation has not previously been reported. The results suggest that NPY should be added to the list of peptides sensitive to these enzymes.

Animals↗
PubMed1991

Change or homeostasis? A systems theory approach to depression.

Looking at the onset of depressive states in linear terms, there is often a problem of distinguishing cause and effect: did the adverse life-events cause the depression, or did the depression cause the adverse life-events? If we abandon linear thinking and look at depression in systemic terms, the problem of cause and effect disappears, but it is replaced by another problem: is the patient/environment system characterized by homeostasis or change? Some depressed patients seem to be spiralling down towards disaster. Others seem to be stuck in a rut. In systems terms, can depression be at the same time an agent of change and an agent of stasis (or even homeostasis)? The paradox can be resolved if we postulate that the function of depression is to reconcile the individual to an involuntarily subordinate social role; depression which reconciles to a pre-existing subordinate position has static properties; depression which mediates a switch to a subordinate position from a previously dominant position has properties of systemic change.

Depressive Disorder↗
PubMed1990

125I-neuropeptide Y binding activity of pig spleen cell membranes: effect of solubilisation.

Crude preparations of pig spleen cell membranes were obtained by differential centrifugation. 125I-NPY bound specifically to these membranes with a KD of 56 +/- 13 pM and Bmax of 44 +/- 4.0 fmols/mg protein. After treatment with 1% CHAPS* and 10 mM 2-mercaptoethanol in the presence of 2 microM leupeptin, 2 microM pepstatin A, 10 microM phosphoramidon, 200 microM PMSF and 0.1% bacitracin, followed by centrifugation at 100,000 g a soluble preparation was obtained that contained a single population of specific 125I-NPY binding sites. The KD of the soluble receptor was significantly higher at 1.38 +/- 0.2 nM (P less than 0.01) but the Bmax of 59.6 +/- 6.6 fmols/mg protein was similar (N.S.). This is the first description of a method for obtaining NPY receptors in soluble form and should enable their purification and characterisation, though the low affinity of the soluble receptor may reflect disruption of the ligand binding site upon removal of the receptor from the membrane.

Animals↗
PubMed1989

PCR origins.

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DNA-Directed DNA Polymerase↗
PubMed1989

Self-rating.

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Depressive Disorder↗
PubMed1987

Adrenaline causes potassium influx in skeletal muscle and potassium efflux in cardiac muscle in rats: the role of Na/K ATPase.

Previous in vitro evidence suggests that adrenaline causes K influx in skeletal muscle by stimulating a ouabain sensitive Na/K ATPase membrane pump. However in rabbits, adrenaline induced hypokalaemia was not significantly altered by pretreatment with digoxin (50 micrograms/kg). Rats were infused with adrenaline or saline after being given a tracer dose of 42KCl. Adrenaline caused a highly significant uptake of 42K in skeletal muscle and a decrease in 42K uptake in ventricle. Rats were also studied after receiving a high dose of digoxin (1.4 mg/kg) which by itself produced a significant increase in plasma K, a decrease in plasma Na and a decreased uptake of 42K in ventricle and lung. These results suggest that adequate widespread Na/K ATPase inhibition had been achieved by this dose of digoxin but despite this, adrenaline still caused hypokalaemia and also still caused significant 42K tissue uptake by skeletal muscle. These results suggest that adrenaline causes K influx by skeletal muscle and K efflux by cardiac tissue. Furthermore, the former mechanism was not inhibited by pretreatment with digoxin.

Animals↗
PubMed1978

Mechanism of the antipsychotic effect in the treatment of acute schizophrenia.

In a double-blind trial in which 45 patients with acute schizophrenia took part the alpha-isomer of flupenthixol (which blocks the dopamine receptor) was found to be significantly more effective than both beta-flupenthixol (which does not) and placebo. The drug effect was confined to the "positive" symptoms--delusions, hallucinations, and though disorder--and appeared only in the 3rd and 4th weeks of the trial. It was as great in patients with evidence of deterioration (Feighner-positive patients) as in patients without deterioration and was less in patients who had affective disturbance in addition to schizophrenia symptoms. The findings are consistent with the hypothesis that dopamine-receptor blockade is the only requirement for antipsychotic activity and suggest that the antipsychotic effect occurs in patients with typically schizophrenic illnesses but may be limited to positive symptoms.

Acute Disease↗
PubMed1976

Control of scrotal colour in the vervet monkey.

The vervet monkey has a vivid blue scrotum which pales when the animal falls in social rank. Histology and electron microscopy showed dopa-positive melanocytes in the dermis each packed with fully melanised melanosomes. By transmitted light the scrotal skin was brown on a red background: by reflected light the colour was blue. Thus the blue colour is due to Tyndall scattering over a layer of melanin. Variation of scrotal colour was not due to changes in melanocyte number or dispersion of melanosomes. Pallor was induced by injecting fluid, and blueness could be restored by removing fluid. It is concluded that the blue-to-white colour variation is modulated by the degree of dermal hydration.

Animals↗
PubMed1975

Production, purification, and characterization of an extracellular chitosanase from Streptomyces.

The synthesis by Streptomyces sp. no. 6 of an extracellular chitosanase was induced by glucosamine. The enzyme was purified to homogeneity by Sephadex G-100, carboxymethyl-cellulose, and diethylaminoethyl-cellulose chromatography. The purified enzyme hydrolyzed chitosan (the beta-1,4-linked polymer of glucosamine) but not chitin nor carboxymethyl-cellulose. The only products of the hydrolysis detectable by paper chromatography were di- and triglucosamine. Sephadex G-100 chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the molecular weight of the enzyme was between 29,000 and 26,000. Acid hydrolysates of the enzyme contained no cysteic acid or glucosamine or other carbohydrate. At 25 C, maximum activity was obtained between pH 4.5 and 6.5. The enzymatic hydrolysis of chitosan occurred over a wide range of temperatures and was maximal at 60 C. The rate of the reaction was inhibited by concentrations of soluble chitosan higher than 0.5 g/liter. The apparent Km calculated from a Lineweaver-Burke plot was 0.688 g/liter at pH 5.5. The enzyme prevented spore germination and caused a significant decrease in the turbidity of germinated spore suspensions of the Mucor strains tested. Such a decrease was the result of a partial lysis of the cell wall.

Amino Sugars↗