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Biomedical subjects

W Martin

Publications and source records attributed to W Martin.

At least 271 records · Page 15Linked to original sources

Differential calcium dependence of contractile responses and 86Rb efflux from the rabbit aorta induced by vasoactive stimuli.

86Rb was used to monitor potassium movements in strips of rabbit aorta simultaneously with measurements of tension. Histamine, noradrenaline, the prostaglandin endoperoxide analogue U46619, angiotensin II, and 144 mM K+ each induced an increase in 86Rb efflux concomitantly with contraction. For the first four agonists there was a rank-order correlation between the contractile response and 86Rb efflux, but 144 mM K+ induced a massive increase in 86Rb efflux although it was the weakest contractile stimulus. Contraction and increase in 86Rb efflux-induced K+ were both reduced by verapamil, which blocks voltage-sensitive calcium channels, implying that both effects of K+ were mediated mainly by a depolarisation-induced influx of calcium. Noradrenaline increased both tension and 86Rb efflux through an action on alpha-adrenoceptors, but its effect on efflux, unlike its effect on tension, was apparently totally dependent on the presence of extracellular calcium. Experiments performed in the presence of lanthanum, which blocks calcium influx, showed that the intracellular store of calcium released by noradrenaline apparently played no role in inducing 86Rb efflux, although it could trigger contraction. Lanthanum also blocked contraction induced by K+ but had less effect on the increase in 86Rb efflux induced by K+. Thus, agonist-induced vascular contraction and 86Rb efflux can be dissociated, but under normal conditions all the contractile stimuli tested induced 86Rb efflux.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Spontaneous and agonist-induced 86Rb efflux from rabbit aortic smooth muscle cells in culture: a comparison with fresh tissue.

Potassium efflux was measured in rabbit aortic strips and smooth muscle cells cultured from them by monitoring the release of isotope from preparations preloaded with 86Rb. The basal rate of 86Rb efflux from rabbit subcultured aortic smooth muscle cells was eightfold higher than from freshly isolated strips, but calculations of reuptake of isotope in the tissue indicated that the measured rate constant for efflux from aortic strips underestimated the true rate by about fourfold. The rate constant for efflux from freshly dispersed cells was less than half that of subcultured cells and remained unchanged for 5 days in culture. It then rose and by around day 10 had reached the value for subcultured cells. The increase in efflux coincided with the onset of cell division. The increased rate of efflux was accompanied by an increased rate of uptake so that the internal potassium content of the cells remained constant. Heparin decreased the efflux of 86Rb from subcultured cells to that of freshly isolated cells concomitant with a reduction in the rate of proliferation. The onset of cell division and increased basal efflux of potassium was associated with a loss of responsiveness to noradrenaline and histamine as assessed by monitoring 86Rb efflux, although depolarising solutions of potassium chloride were still able to elicit a response. Responsiveness to noradrenaline and histamine could be restored by the addition of heparin. These results suggest that the lack of responsiveness of subcultured cells is not due to irreversible dedifferentiation but to a reversible loss in proliferating cells of receptors for vasoactive agents or of a coupling mechanism between receptor occupation and ion gating.

Animals↗

Assessment of skeletal uptake of 99mTc-diphosphonate over a five day period.

A new method for the sequential monitoring of skeletal uptake of 99mTc-diphosphonate over a 5-day period, utilising both a gamma camera and whole-body monitor, is presented. It has been found that diphosphonate continues to be removed from bone over this period. Normal subjects appear to lose skeletal activity initially at a more rapid rate than those with altered skeletal metabolism and it is suggested that differences in binding characteristics may exist.

Bone Neoplasms↗

The beriberi analogy to myocardial infarction.

Two pandemics of heart attack deaths have plagued the world's population during the past 130 years. The first pandemic, induced by beriberi, was caused by the industrial revolution altering the nutritional composition of rice. By 1892 a simple working knowledge, then at hand, could have terminated the beriberi plague; however, orthodox medicine being then enchanted with the false concept that all disease was caused by germs, permitted millions of Asians to die needlessly of beriberi by refusing to tell them to eat rice bran or to drink rice bran tea. A second pandemic of heart attack deaths, called myocardial infarction (MI), struck the developed nations of the Western World in full force after 1930. As a hypothesis, it is suggested that this MI pandemic, still raging today, was caused by a change in food processing that occurred after 1920, when the new oil seed industry introduced into our food three greatly harmful lipid substances. The unnatural trans-trans isomer of linoleic acid, which had never been in human food prior to 1920 and which entered our food in margarines and refined oils, blocked the conversion of natural cis-cis linoleic acid to prostaglandin E1, which tends to prevent MI, both by acting as a vasodilator and by minimizing platelet aggregation. Harmful lactones were also introduced into our food, increasing the risk of MI by decreasing the fibrinolytic activity of our blood. The oil seed industry also introduced into our diet free radical lipid peroxides that make the myocardium more vulnerable to infarction. It is suggested that except for the one in 500 of us who is afflicted by familial hypercholesterolemia, the cholesterol concept of MI is as false today as was the concept in 1900 that germs caused beriberi. It is further suggested that a working knowledge is at hand today that can make death from MI just as rare as death is now from a beriberi-induced heart attack.

Animals↗

Endothelium-dependent relaxation of the pig aorta: relationship to stimulation of 86Rb efflux from isolated endothelial cells.

Bradykinin, adenosine triphosphate (ATP) and acetylcholine each relaxed histamine-contracted strips of pig aorta in a dose-dependent manner. These relaxations were abolished when the endothelium was removed. Relaxation induced by ATP was mimicked by adenosine diphosphate (ADP) but adenosine monophosphate (AMP) and adenosine were about 120 times less potent. Relaxation induced by acetylcholine was antagonized by atropine in a competitive manner, and carbachol induced the same degree of relaxation as acetylcholine, but was about 10 times less potent. The calcium ionophore, A23187, also induced a dose-dependent relaxation of pig aortic strips provided the endothelium was present, suggesting that a rise in the level of ionized calcium within the endothelial cells is one means by which vascular smooth muscle relaxation can be triggered. Bradykinin, ATP, ADP, AMP, adenosine and A23187 each induced a dose-dependent increase in 86Rb efflux from preloaded pig aortic endothelial cells. The dose-response curves for stimulation of 86Rb efflux and for endothelium-dependent relaxation were similar for each individual compound. ADP was equipotent with ATP, but AMP and adenosine were about 120 times less potent. Neither acetylcholine nor carbachol, in concentrations that induce endothelium-dependent relaxation, had any effect on 86Rb efflux from isolated aortic endothelial cells. Lanthanum, which blocks calcium influx, abolished the increases in 86Rb efflux induced by bradykinin and ATP, and the calcium ionophore A23187 was the most effective stimulant of 86Rb efflux, suggesting that the potassium transport induced by these agents is calcium-activated. It is concluded that endothelial responses to bradykinin and ATP can be assessed by monitoring 86Rb efflux, which probably reflects a calcium-activated efflux of potassium associated with the endothelium-dependent vascular relaxation induced by these agents. This pathway is apparently not involved in endothelial responses to acetylcholine.

Acetylcholine↗

Loss of receptor-mediated 86Rb efflux from pig aortic endothelial cells in culture.

The responsiveness of freshly-isolated and subcultured pig aortic endothelial cells to adenosine triphosphate (ATP), bradykinin and ionophore A23187 was compared by monitoring agonist-induced 86Rb efflux. ATP, bradykinin and ionophore A23187 stimulated 86Rb efflux from freshly-isolated cells. ATP and bradykinin, which act via specific receptors, were less effective at inducing 86Rb efflux from subcultured cells but ionophore A23187 was as effective on subcultured as on freshly-isolated cells. These results suggest that pig aortic endothelial cells, when subcultured, lose receptors for ATP and bradykinin and/or develop an abnormality in the coupling-mechanism between receptor-occupation and calcium-mobilization.

Adenosine Triphosphate↗

Stimulation of endothelial prostacyclin production plays no role in endothelium-dependent relaxation of the pig aorta.

Stimulation of prostacyclin production by pig aortic endothelial cells adhering to microcarrier beads superfused in columns, or 3H release from cells prelabelled with [3H]-arachidonate, was studied in response to a range of agents that induce endothelium-dependent vascular relaxation. Bradykinin, adenosine triphosphate (ATP) and ionophore A23187 each stimulated release of prostacyclin from unlabelled cells and of 3H from prelabelled cells but acetylcholine did not. Bradykinin induced a parallel, dose-dependent increase in 3H release and 86Rb efflux, measured simultaneously from columns of aortic endothelial cells preloaded with 86Rb and [3H]-arachidonate. The rank-order of effectiveness at inducing both 3H and 86Rb release, measured simultaneously from columns of aortic endothelial cells prelabelled with 86Rb and [3H]-arachidonate and challenged with maximal doses of each agonist, was: A23187 greater than bradykinin greater than ATP. The similarity between agonist-induced 3H release (from cells prelabelled with [3H]-arachidonate) and 86Rb efflux indicates that a common mechanism may be responsible, and the effectiveness of ionophore A23187 suggests that a rise in the intracellular level of calcium may be involved. The lack of effect of acetylcholine on release of prostacyclin from unlabelled cells or of 3H from cells prelabelled with [3H]-arachidonate provides further evidence that acetylcholine acts on endothelial cells by a mechanism that does not involve calcium mobilisation. Although bradykinin, ATP and ionophore A23187 each induced release of prostacyclin from aortic endothelial cells, prostacyclin did not relax the pig aorta. Furthermore, endothelium-dependent relaxation was unaffected by pretreating aortic strips with aspirin. It therefore appears that neither prostacyclin nor any other cyclo-oxygenase product mediates endothelium-dependent relaxation of the pig aorta.

Acetylcholine↗

Giant-cell reparative granuloma of the hands and feet.

Giant-cell reparative granuloma occurring outside the jaw is unusual, being seen predominantly in the tubular bones of the hands and feet. It produces a lucent, expansile lesion in the metacarpals, metatarsals, or phalanges. The authors describe the radiographic and pathological features of 5 cases and review the literature.

Adolescent↗

A field trial, of preshipment vaccination, with intranasal infectious bovine rhinotracheitis-parainfluenza-3 vaccines.

A total of 849 calves, 278 controls, 335 vaccinated intranasally with IBR-PI3/TS and 236 vaccinated intranasally with IBR-PI3/PTC were studied in a field trial of preimmunization. All calves were vaccinated in Saskatchewan at least three weeks prior to shipment to feedlots. Four hundred and twenty six calves were not sold within eight weeks of vaccination; however, seven of these died within four weeks of vaccination. Treatment rates varied from 1.0% to 5.2%. There was no significant effect of vaccination on treatment rates. Similarly, there was no significant effect of vaccination in the 74 calves sold to feedlots in Saskatchewan. Three hundred and forty nine calves were sold to feedlots in Ontario. Two of these died from fibrinous pneumonia. Treatment rates varied from 1.7% to 33.3% in different feedlots, but there was no significant effect of vaccination on treatment rates. Therefore, preimmunization is unlikely to significantly reduce the overall treatment rate in calves entering feedlots.

Animals↗

Relative distribution of diphosphonate between bone and soft tissue at 4 and 24 hours: concise communication.

Digital bone scintigrams were obtained in 19 patients using Tc-99m hydroxyethylidene diphosphonate (HEDP). These were quantitated for skeletal, soft-tissue and renal uptake of tracer using a contrast-enhancement technique to define the regions of interest. Twenty-four hr whole-body retention (WBR) of HEDP was also measured. It was found that approximately 70% of retained diphosphonate was localized in the skeleton at 24 hr, with 26% in soft tissue and 4% in kidneys. However, we have shown that over a wide spectrum of whole-body retention measurements (18 to 70%) the 24-hr soft-tissue component, as a percentage of administered dose, remained relatively constant whereas skeletal tracer accumulation mirrored WBR (r = 0.98, p less than 0.001). The present study indicates that, despite a significant but essentially stable soft-tissue component, measurement of 24-hr WBR of HEDP accurately reflects skeletal metabolism.

Bone and Bones↗

Evaluation of digitalis in cardiac failure.

Ten patients in sinus rhythm with symptomatic cardiac failure participated in a study investigating the value of digitalis at rest and during dynamic exercise. A haemodynamic profile and left ventricular ejection fraction were measured before treatment, after intravenous ouabain, and after six weeks of maintenance treatment with digoxin. There was no significant change in the haemodynamic profile or in the left ventricular ejection fraction at rest after either glycoside. During exercise there was a significant reduction in left ventricular filling pressure from 39 +/- 3 mm Hg to 34 +/- 3 mm Hg (p less than 0.05) after ouabain and to 33 +/- 3 mm Hg (p less than 0.02) after digoxin. Cardiac index improved from 33 +/- 0.3 1/min/m2 to 4.0 +/- 0.4 l/min/m2 (p less than 0.01) after ouabain and to 3.8 +/- 0.4 l/min/m2 (p less than 0.01) after digoxin. During exercise stroke volume index and stroke work index also improved significantly with both glycosides. This was accompanied by an increase in left ventricular ejection fraction from 29 +/- 2% to 36 +/- 3% (p less than 0.05) after ouabain and digoxin. In this study both intravenous ouabain and maintenance treatment with oral digoxin exerted a modest positive inotropic effect in patients with cardiac failure in sinus rhythm. The haemodynamic benefit, however, was manifest only during exertion.

Adult↗

[Introduction of a Standardized "Paternity Index" for the Statistical Evaluation of Blood Group Findings in Paternity Testing (author's transl)].

The introduction of a standardized paternity in index (PI) for the statistical evaluation of blood group findings in cases of disputed paternity is proposed and explained. Using the PI X/Y as a parameter, it is not necessary to give the probability of paternity in percent. The PI includes the full information of the blood group findings. In addition to that, using the suggested standardization based on the probabilities of error according to Schulte Mönting and Walter, the test volume is also taken into account. The interpretation of the mathematical result is given by verbal predicates, the limitations of which are dependent on the verbal predicates for the probabilities of error according to Schulte Mönting and Walter, published by us previously. Besides the essential fact that the test volume is taken into account, the most important advantage of this procedure is that the mathematical result is involved in the court decision only by the PI (which is free of any valuation) and its verbal predicate and not by sometimes relatively high percentages, which may be misunderstood by laymen.

Blood Group Antigens↗

Case report 213.

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Diagnosis, Differential↗