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Biomedical subjects

J Mason

Publications and source records attributed to J Mason.

At least 217 records · Page 12Linked to original sources
PubMed1987

The uptake and intracellular distribution of [35S]trithiomolybdate in bovine liver in vivo.

[35S] trithiomolybdate was administered intravenously to a group of four steer at two dose rates, 1 and 26 mg Mo per animal. Radioactivity appeared rapidly in the liver and was distributed in all the subcellular fractions examined. Examination by Sephadex G-100 gel-filtration of the cytosol fraction showed that distinct 35S-binding protein peaks were present. The protein-bound radioactivity was displaceable and was identified as [35S]thiomolybdates. No radioactivity eluted with metallothionein, but 35S was associated with the high molecular weight copper fraction, eluted in the void volume of the column, which increased transiently after the administration of the higher dose. It was suggested that the presence of protein-bound thiomolybdates in the liver gave rise to new ligands, which altered the equilibrium of copper between the different metal-binding proteins. This might be similar to the alteration in the copper-binding of albumin produced by the presence of thiomolybdates.

Animals↗
PubMed1987

Spectral and kinetic studies on the binding of trithiomolybdate to bovine and canine serum albumin in vitro: the interaction with copper.

Spectral studies showed that copper and trithiomolybdate participated in a three-way interaction with bovine and canine serum albumin. The interaction with the proteins was affected by increased pH and ionic strength. Kinetic studies of binding equilibria indicated that [35S] trithiomolybdate bound to both albumins at a single site. The affinity of the site, but not the capacity of the protein, was increased by copper. It was concluded that the site was distinct from the N-terminal copper (and nickel) binding site, which is present on BSA but absent from CSA. Whether or not the N-terminal site has a role in copper transport is discussed. Reversible thiomolybdate-copper-protein interactions of this type may play a fundamental role in the pathogenesis of Mo-induced syndromes, since as the normal binding patterns are perturbed the interprotein equilibria are altered and the copper distribution patterns are modified.

Animals↗
PubMed1987

The contribution of vascular obstruction to the functional defect that follows renal ischemia.

Experiments were performed on rats subjected to renal ischemia and various treatment procedures to determine the origin and functional consequences of vascular obstruction. To this end, its occurrence and severity was assessed qualitatively and quantitatively in the outer medulla, where it is particularly prominent. The incidence of medullary hyperemia was not influenced by inhibiting thrombocyte aggregation with 5 or 70 mg/kg of acetyl salicylic acid or preventing fibrin deposition with 100 IE/kg of heparin before ischemia, and these substances produced no improvement renal function. The incidence and degree of hyperemia, however, could be substantially reduced or completely eliminated by acutely raising blood pressure after ischemia or by decreasing the number of circulating erythrocytes before ischemia. These procedures were effective in raising filtration rate and tubular reabsorption from 20% to 60% of normal, in restoring renal blood flow and vascular resistance to completely normal, and in diminishing epithelial damage both three and 18 hours after ischemia. The following conclusions are drawn: first, vascular obstruction, which is not lessened by inhibiting thrombus formation but is easily reversed or prevented by raising perfusion pressure or decreasing hematocrit, is probably caused by erythrocyte aggregation during ischemia. Second, vascular obstruction, which appears to raise renal vascular resistance and lower blood flow and filtration rate, cannot be limited to the medulla but must also be present in the cortex. Finally, reversing or preventing vascular obstruction can fully restore renal perfusion, partially restore glomerular and tubular function, greatly reduce tubular necrosis and thus prevent renal failure.

Animals↗
PubMed1987

Dietary molybdenum as a putative copper antagonist in the horse.

Four horses were stabled and fed a diet of hay ad libitum, and 2 kg oats per animal per day, for a month. The basic diet was then supplemented with molybdenum, at a rate of 20 mg/kg dry matter for 4.5 months. For one month of this period the diet was supplemented also with sulphur at a rate of 1.2 g/kg dry matter. Analyses of jugular blood samples, obtained at intervals varying between two and 20 days, showed no evidence of a decline in total plasma copper or of an increased proportion of trichloroacetic acid (TCA) insoluble copper in plasma over this period. In separate studies, two other horses were given 99molybdenum (molybdate, 20 to 28 mg Mo, 4 mCi per animal) per os, initially while being fed the basic diet and later while maintained on the molybdenum supplemented diet. 99Molybdenum appeared rapidly in plasma, but the radioactivity was then quickly cleared (half-life 7 to 10 h). The 99molybdenum present was identified as (99Mo)-molybdate. There was no evidence of the persistent, protein-bound (99Mo)thiomolybdates which appear in ruminants. These studies indicate that increased dietary molybdenum is unlikely to interfere with copper metabolism in horses.

Administration, Oral↗
PubMed1987

Sulphate/molybdate interactions: in vivo and in vitro studies on the group VI oxyanion transport system in ovine renal tubule epithelial cells.

The study was undertaken to investigate the mechanism by which increased dietary sulphur compounds accelerate the excretion of molybdate in ruminants. Clearance studies show that [99Mo]molybdate and [35S]sulphate have similar behaviours in sheep; at plasma molybdate concentrations equal to or below the apparent t max the injection of sulphate accelerates the excretion of molybdate and vice-versa. The uptake of [35S]sulphate into brush-border membrane vesicles isolated from ovine kidney cortex by a Ca++ precipitation method was investigated by a rapid filtration technique. Transport of [35S]sulphate into the vesicles was stimulated in the presence of Na+ but not by K+. A typical "overshoot" phenomenon was observed in the presence of the Na+ gradient (initially 100 mM Na+ outside/zero mM Na+ inside). Both the rate and extent of accumulation was reduced by the presence of other group VI oxyanions, molybdate, selenate and tungstate and by an analogue thiosulphate, but not by other divalent anions such as phosphate or by pyruvate. Uptake was inhibited by HgCl2, N-ethyl-maleimide (NEM) and ouabain. The experiments indicate the presence of an electroneutral Na+/SO4- or group VI oxyanion co-transport system in ovine proximal tubule brush border membranes similar to that described in the rat. Sulphate/molybdate competition for sites in tubular reabsorption is another factor to be considered in the complex interactions of S and Mo compounds with copper in animal nutrition.

Animals↗
PubMed1986

Thiomolybdates: mediators of molybdenum toxicity and enzyme inhibitors.

The evidence for a role for thiomolybdates in the important ruminant disease syndromes of molybdenosis and Mo-induced hypocuprosis is outlined and present knowledge of their chemistry and metabolism in vivo is reviewed in an attempt to provide a less empirical basis for their toxicology. The compounds are novel enzyme inhibitors in vitro and have also been used therapeutically, apparently successfully, in the treatment of Wilson's disease. While the changes which occur in vivo are complex they can be best understood in terms of an alteration in the affinities for copper of some of the competing ligands, including albumin, which leads to a change in the distribution of copper between the different systemic pools and an overall depletion.

Animals↗
PubMed1986

Reversible inhibition of ovine ceruloplasmin by thiomolybdates.

The synthesis and purification of the sodium salts of di (MoO2S2(2-)), tri (MoOS3(2-)) and tetra (MoOS4(2-)) thiomolybdate is reported. All three compounds were reversible inhibitors of the ovine ceruloplasmin (Cp) catalysed oxidation of O-dianisidine. Na2MoO2S2 inhibited via a non-competitive mechanism whereas Na2MoOS3 showed mixed non competitive and Na2MoS4 competitive mechanisms. All showed upward curving slope replots. Molybdenum trisulfide (MoS3) was synthesized and displayed mixed type inhibition kinetics but with a linear slope replot. Preliminary evidence suggested that both MoOS3(2-) and MoS4(2-) may also be substrates for ovine Cp.

Animals↗
PubMed1986

The inhibition of bovine ceruloplasmin oxidase activity by thiomolybdates in vivo and in vitro: a reversible interaction.

The administration of pharmacological doses (greater than 100 mg Mo) of trithiomolybdate or tretrathiomolydbate to ruminants causes a transient apparent decrease in the ceruloplasmin oxidase activity of plasma and a more persistent increase in copper bound to plasma albumin. Sephadex gel-filtration and/or dilution of "inhibited" samples taken from an infused animal or of plasma treated with thiomolybdate in vitro restores activity back to pretreatment levels. The increase in albumin bound copper does not appear to be related to ceruloplasmin breakdown. It is concluded that, contrary to a recent report, the inhibition of ceruloplasmin oxidase activity is reversible and thus unlikely to be of pathological relevance, since circulatory thiomolybdate concentrations in molybdenotic animals are likely to be very low. It is recommended that thiomolybdate preparations used for in vitro and in vivo studies should be carefully purified by Sephadex chromatography.

Animals↗
PubMed1986

Psychological distress, depression and prolactin response in stressed persons.

We examined the relationship of psychological distress to serum prolactin response in 54 persons who had lost a spouse or were threatened with a loss. We found that our two measures of psychological distress, both separation anxiety and depression, were directly correlated with prolactin response during a stressful interview (p less than .05). When we stratified the sample first by depression score and then by separation anxiety, we found a positive correlation between separation anxiety and prolactin response only in the highly depressed half of the sample (r = .32) and a positive correlation between depression and prolactin response only in the highest quartile of intensity for separation anxiety (r = .49, p less than .05). This suggested that both depression and separation anxiety, each in conjunction with high levels of the other but not independently, rendered the individual under stress more physiologically sensitive to distressing challenges such as a stressful interview. Alternatively, it was global distress above a certain threshold that was associated with degree of physiological response.

Anxiety, Separation↗
PubMed1986

Tubuloglomerular feedback control of distal fluid delivery: effect of extracellular volume.

A closed-feedback loop micropuncture method was used to examine tubuloglomerular feedback (TGF) and the regulation of distal fluid delivery in hydropenic rats (CON), moderately hemorrhaged rats (HEM), and rats given desoxycorticosterone (DOC) and 0.6% saline to drink. Distal delivery and TGF response curves were measured with four samples per nephron: a spontaneous early distal collection, two distal collections during moderate (7.5 nl/min) and saturating (30 nl/min) perturbations in nephron fluid load, and a proximal collection to measure single-nephron glomerular filtration rate (SNGFR) during TGF inhibition. Arterial pressure, predistal volume reabsorption, SNGFR, and early distal flow were significantly higher in DOC than in HEM; the CON group exhibited intermediate values. Except for a greater maximum TGF response in HEM, the normalized TGF responses were similar in all three groups, as was the regulation of distal fluid delivery. However, the TGF onset threshold and the TGF operating point, defined by the spontaneous rates of early distal flow and SNGFR, were reset such that distal fluid delivery and SNGFR were higher in DOC than in HEM, as was renal sodium excretion. The results show that the level around which TGF stabilizes distal fluid delivery is reset when extracellular fluid volume is altered.

Analysis of Variance↗
PubMed1986

Accumulation of copper on albumin in bovine plasma in vivo after intravenous trithiomolybdate administration.

The initial disappearance of intravenously administered copper (10 to 20 mg) from bovine plasma in vivo was delayed by the intravenous injection of trithiomolybdate (20 to 75 mg molybdenum per 400 to 445 kg steer); however, the most characteristic effect was the retention of up to about 0.5 mg copper per litre plasma for up to 24 hours after injection. Sephadex G-100 gel filtration of plasma samples showed that this retained copper was associated with the albumin fraction. The effect of trithiomolybdate was very dependent upon the interval between the injections of trithiomolybdate and copper. It is suggested that this variability was due to thiomolybdate metabolism. The infusion of trithiomolybdate (12 to 75 mg molybdenum) over 24 hours also caused the accumulation of albumin-bound copper. The amount bound did not exceed approximately 0.5 mg copper per litre plasma even when the diet of the steers was supplemented with copper sulphate or when copper sulphate (2 X 15 mg copper) was injected directly during the infusion. It is suggested that the longer term effects of trithiomolybdate are not merely a consequence of a simple copper-thiomolybdate reaction but result from three-way interactions between trithiomolybdate, albumin and copper, and that slow infusion of trithiomolybdate provides a model for the study of the systemic effects of dietary molybdenum in cattle.

Animals↗
PubMed1985

Rheumatology training at internal medicine and family practice residency programs.

The Medical Research Education Subcommittee of the American Rheumatism Association surveyed a random selection of large and small programs in internal medicine and family practice residency programs in order to evaluate their rheumatology training. Formal rheumatology training is offered in 90% of these residency programs, but many available positions are not being filled. A full-time staff rheumatologist was present at 69% of large internal medicine programs, 32% of small internal medicine programs, and 11% of family practice programs. The methods of rheumatology training are similar in most programs, although small internal medicine programs and family practice programs more often utilize physicians' offices or outside medical centers for the rheumatology elective training. A majority of the directors of these residency programs thought that many basic skills and techniques were not taught adequately and that the training of their rheumatology residents was not equal to that of residents in cardiology or gastroenterology.

Evaluation Studies as Topic↗
PubMed1985

Some studies on the metabolism of labelled molybdenum compounds in cattle.

An initial experiment showed that [99Mo]di- and trithiomolybdates could be detected in bovine plasma after the introduction of [99Mo]molybdate into the rumen. It was felt that this justified the use of [99Mo]trithiomolybdate for the subsequent studies made of plasma thiomolybdate metabolism in vivo in cattle. Rapid intravenous injection of [99Mo]trithiomolybdate into cattle showed that doses of 50 mg Mo were subject to extensive hydrolysis over the first few minutes postinjection, but at lower dose rates this was reduced so that tracer doses (less than 1.5 mg Mo) were relatively stable. The plasma metabolism was unaffected by copper status within the limits of the experiments (that is, liver copper levels down to 9 mg/kg d.m.) The disappearance of [99Mo] and [35S]trithiomolybdate (1 mg Mo) from plasma was delayed for up to 10 hr by the immediate preinjection of copper, although no chemical modification of the thiomolybdate appeared to occur.

Animals↗