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Biomedical subjects

J Brod

Publications and source records attributed to J Brod.

At least 19 recordsLinked to original sources
PubMed1991

Acylceramides and lanosterol-lipid markers of terminal differentiation in cultured human keratinocytes: modulating effect of retinoic acid.

Epidermal differentiation is accompanied by profound changes in the synthesis of a variety of intracellular proteins and intercellular lipids. In conventional, submerged culture keratinocytes have been shown to lose the ability to synthesize the protein markers of differentiation. They re-express them, however, when they are cultured in medium supplemented with delipidized [retinoic acid (RA)-depleted] serum or in air-exposed cultures using de-epidermized dermis (DED) as a substrate. Recent studies have revealed that acylceramides (AC) and lanosterol (LAN), which are present only in trace amounts in cultures of keratinocytes grown under submerged conditions on DED in medium supplemented with normal serum, become expressed in significant amounts when the culture is lifted to the air-liquid interface. Inasmuch as culture conditions may markedly affect the extent of keratinocyte differentiation, the present study aimed to investigate the effect of normal (RA-containing) or delipidized (RA-depleted) serum and of RA administration on lipid composition (especially of the AC and LAN contents) in cells cultured under submerged and air-exposed conditions. To test a possible effect of dermal substrate (used in the air-exposed model), the lipid composition of keratinocytes grown under submerged conditions on a plastic and on a dermal substrate (de-epidermized dermis, DED) has also been compared. The results revealed that under all culture conditions, RA deprivation of fetal bovine serum resulted in a marked increase of total ceramide content. Even under submerged conditions, the presence of both AC and LAN could be detected. In air-exposed culture, the content of these lipids was markedly increased. Addition of RA at 1 microM concentration to cultures grown in RA-depleted medium induced marked changes in lipid composition under all culture conditions tested. In cells grown under submerged conditions (both on plastic and on DED) AC and LAN were no longer present in detectable amounts. Also in air-exposed culture, a marked decrease in the content of these lipids was observed. These results suggest that liposoluble serum components, like RA, control the synthesis of lipids that are present in later stages of epidermal differentiation.

Biomarkers↗
PubMed1985

Volume homeostasis, renal function and hypertension.

A generalised vasoconstriction, for almost a century believed to be the basis of all types of human hypertension, was disproved by recent haemodynamic studies. In our investigation of hypertension in chronic parenchymatous non-uraemic, non-anaemic renal disease, we have established that the earliest haemodynamic abnormality in subjects, of whom over 90% later develop high blood pressure, has actually started while their blood pressure is still normal. This consists of hypervolaemia and a high cardiac output (hyperkinesis) with tissue hyperperfusion. Hypervolaemia is due to a failure of these still normotensive patients to excrete isotonic saline as readily as subjects with completely normal kidneys.The chronic hypervolaemia in these subjects leads to a release of the natriuretic factor which depresses the Na(+)-K(+)-ATPase in the cell membranes and which is responsible for an increase in sodium (and calcium) content of the vascular smooth muscle cells, diminishing their compliance and thus raising the vascular resistance together with the thickening of the vascular wall of the originally hyperperfused vessels. With the disappearance of the vascular adjustment to the increased cardiac output, the blood pressure rises and the 'pressure diuresis' restores the circulating blood volume (and the renal homeostatic efficiency) to normal. With a further rise of the peripheral vascular resistance the cardiac output falls. At this late stage of renal hypertension renin may play a contributory role.Thus, the primary abnormality in the chain of events leading eventually to hypertension is a renal inability to maintain a proper balance between sodium intake and output. This suggested pathophysiological mechanism is probably valid in every kind of human hypertension where a reason for such a disturbance is present.

Blood Volume↗
PubMed1984

Investigations on the Na+, K+-pump in erythrocytes of patients with renal hypertension.

The ouabain-sensitive 42K+ flux from an artificial medium into erythrocytes was measured in 29 control subjects, 66 patients with chronic parenchymatous renal disease and in 32 subjects with primary hypertension. The ouabain-sensitive 42K+ influx was reduced in subjects with chronic renal disease by about 20%, even when they were normotensive. The reduction in these patients was greater than that in patients with essential hypertension. The changes in 42K+ influx and Na+ content with a decrease in the 42K+ influx/Na+ content ratio suggest an inhibition of the Na+ pump in the patients with chronic renal disease. The inhibition of the Na+ pump may be secondary to the hypervolaemia which we suggest is the initial event leading to renal hypertension.

Adult↗
PubMed1980

Effect of the angiotensin antagonist saralasin on hemodynamics in hypertensive non-uraemic chronic renal disease.

The effect of an intravenous infusion of saralasin in a rising dosage on blood pressure, central haemodynamics, forearm blood flow and venous distensibility was tested in 11 subjects with chronic non-uraemic renal disease. Only 1 subject had an elevated resting plasma renin activity, and in him saralasin produced a drop in systolic and diastolic blood pressures due to a decrease of the total peripheral vascular resistance whereas the plasma renin activity markedly rose. Among the remaining 10 subjects, whose plasma renin activity was within the normotensive range, blood pressure rose transiently in 3, with the lowest dose of aralasin, due to an increase in the total peripheral vascular resistance. Both these parameters returned to the control level when continuing the infusion and increasing its dosage. Excluding this initial period from the analysis, no relevant change, even with a more than tenfold increase in the saralasin dosage and a duration of the infusion of 1 h, was found in the following: blood pressure, cardiac and stroke index, heart rate, total peripheral vascular resistance, central and peripheral venous pressures, forearm blood flow and vascular resistance, forearm blood volume and venous distensibility. The haemodynamic response to the Valsalva manoeuvre remained unaffected by saralasin. It is concluded that angiotensin plays an active role in changing the haemodynamics and in elevating the blood pressure in subjects with chronic non-uraemic renal disease only in those cases where plasma renin activity is raised.

Adult↗
PubMed1979

Effect of an alpha- and beta-adrenoceptor-blocking agent (labetalol) on haemodynamics in hypertension.

1 The effect of an intravenous bolus of labetalol (0.6--1.6 mg/kg body weight) on central and peripheral haemodynamics was studied in nine subjects with essential hypertension and in eleven subjects with chronic renal disease and hypertension. 2 The BP reduction amounting to 20/13 mmHg was entirely due to the lowering of the total peripheral vascular resistance. This also included the vascular resistance in the muscles. 3 This peripheral vasodilatation was not counteracted by a reflex increase of the cardiac output. 4 The reflex tachycardia and overshoot of BP in Valsalva's manoeuvre were largely abolished. 5 Central and peripheral venous BPs, vascular volume of the forearm and venous distensibility did not show any significant change after treatment with labetalol. 6 In spite of the lowering of the vascular resistance of the forearm by labetalol, forearm blood flow was not significantly affected due to the parallel decrease in the perfusion pressure. 7 Plasma renin activity fell after labetalol in all instances.

Adult↗
PubMed1978

Effect of diazoxide on capacitance vessels.

Haemodynamic changes after an i.v. bolus of diazoxide 300 mg were studied in 11 hypertensive subjects. A hypotensive effect due to a fall in total peripheral vascular resistance was found in all of them, but changes in the peripheral circulation were less regular. A uniform change in forearm blood volume, blood flow, vascular resistance and venous distensibility was not found after diazoxide. This is interpreted as being due to a reflex increase in sympathetic activity, which counteracts the direct vasodilator action of the drug.

Adult↗