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Biomedical subjects

A Kribben

Publications and source records attributed to A Kribben.

At least 55 records · Page 3Linked to original sources
PubMed1995

[Type I cryoglobulinemia].

HISTORY AND CLINICAL FINDINGS: For 2 years a 52-year-old man had repeated bouts of purpura, arthralgia and fever. He was known to have abnormal monoclonal gammaglobulins, type IgG-lambda and vasculitis when he had another bout with acute renal failure and necrotizing ulcers in the legs. TESTS: Several laboratory tests were abnormal: erythrocyte sedimentation rate (122 mm), haemoglobin level (9.1 g/dl), white cell count (32,000/microliters), platelet count (562,000/microliters), creatinine level (4.1 mg/dl) and liver enzyme activities. He also had proteinuria (4.5 g daily) and nephritic urinary sediments. The immunoglobulin was subtype IgG3, and a cryoglobulinaemia was also present. Total complement level (CH 50) was not measurable. Bone marrow aspirate revealed plasmocytoma infiltration, and renal biopsy demonstrated necrotizing arteritis, as well as granular subendothelial deposits of IgG and complement. TREATMENT AND COURSE: After three plasma separations and initiation of the first treatment cycle with a four-day infusion of vincristine, doxorubicin and dexamethasone the creatinine concentration fell to within the normal range and the necroses healed slowly. No cryoglobulin activity has been demonstrable over the past 24 months.

Acute Kidney Injury↗
PubMed1995

Induced alterations in calcium uptake rate in normoxic rate proximal tubules.

This study is well-oxygenated, freshly isolated rat proximal tubules (RPT), examined the effects of several drugs that alter the transmembrane K+ and Na+ gradients across cell membranes, including valinomycin (VAL), amphotericin B (AMPHO), and ouabain (OUAB). The effects of high extracellular potassium chloride (KCl) concentrations (45 mM) and low extracellular sodium concentration (100mM) were also studied. After 10 min of drug exposure Ca2+ uptake rate (nmol/mg/min) increased from 2.7 to 3.8 with VAL (p < .02), from 2.9 to 3.7 with AMPHO (p < .05), from 3.6 to 4.1 with OUAB (p < .05), and from 3.2 to 4.8 with 45 mM KCl (p < .001). Ca2+ uptake rate was sustained at these high levels at 20 min in all treated RPT except those exposed to OUAB. LDH release averaged less than 15% in control tubules and did not increase significantly except in RPT treated with VAL, where LDH release at 10 min was 48% and at 20 min was 57% (both p < .001). Of importance, only in VAL-treated RPT did ATP decrease to low levels (6.7 nmol/mg in control to 2.0 +/- 0.3 nmol/mg in VAL, p < .001). Treatment with verapamil reduced Ca2+ uptake rates at 10 min in VAL-treated RPT (from 3.8 to 3.1, p < .02, in AMPHO-treated RPT (from 3.8 to 3.1 p < .001), in OUAB-treated tubules (from 4.0 to 3.4, p < .01), and in KCl-treated RPT (from 3.7 to 3.2, p < .01). These results indicate that acute changes in the transmembrane ion gradient in RPT are accompanied by increased Ca2+ uptake rates. Ca2+ uptake rates are also increased during O2 deprivation in RPT, a situation in which the transmembrane ion gradient is likewise altered. The increased Ca2+ uptake rate observed in the present study and during hypoxia may have a common basis, that is, altered transmembrane ion gradients or some function thereof.

Adenosine Triphosphate↗
PubMed1994

Vascular smooth muscle cells grown on Matrigel. A model of the contractile phenotype with decreased activation of mitogen-activated protein kinase.

Vascular smooth muscle cells have been shown to exist in two phenotypic states which have been designated proliferative and contractile. The properties of rat aortic vascular smooth muscle cells grown on Matrigel were compared with cells grown on untreated plastic culture dishes. Cells grown on Matrigel manifested at least four important properties characteristic of the contractile phenotype as compared with cells grown on plastic. The cells grown on Matrigel had altered morphology similar to in vivo studies of contractile vascular smooth muscle. The cells had a low proliferative index, showed enhanced levels of the smooth muscle isoform of alpha-actin, and had an enhanced contractile response to the vasoconstrictor arginine vasopressin. All of these changes were maintained through at least five passages and could be reversed by replating cells grown on Matrigel back to uncoated plastic dishes. Changes in post-receptor signaling pathways which could account for the altered physiologic responses of the cells were investigated. Cells grown on Matrigel showed no alterations in agonist-induced mobilization of intracellular Ca2+ or agonist-stimulated cAMP levels. However, stimulation of mitogen-activated protein kinase (MAP kinase) by both vasoconstrictors and growth factors was inhibited by 50% in cells grown on Matrigel as compared with plastic. This decrease in agonist-induced MAP kinase was associated with a decrease in the levels of both p42 and p44 MAP kinase protein and a decrease in tyrosine phosphorylation of both isoforms in cells grown on Matrigel. Alterations in MAP kinase activation can account at least in part for the observed physiologic responses of contractile vascular smooth muscle. Growth of vascular smooth muscle cells on Matrigel represents a useful model to examine phenotypic-dependent alterations in post-receptor signaling.

Actins↗
PubMed1994

Inhibition of vasopressin action in vascular smooth muscle by the V1 antagonist OPC-21268.

In vascular smooth muscle cells arginine vasopressin acting through the V1 receptor increases intracellular Ca2+, leading to vasoconstriction. Recent studies have also shown that vasopressin activates mitogen-activated protein kinase (MAP kinase), which may contribute to vasopressin-induced hypertrophy of vascular smooth muscle cells. We examined the ability of an orally active, nonpeptide selective V1 antagonist (OPC-21268) to block vasopressin binding and postreceptor signaling in these cells. [3H]Vasopressin binding at 2 x 10(-9) mol/L was half-maximally blocked at 10(-9) mol/L OPC-21268. To compare effects of OPC-21268 on binding and postreceptor signaling, we stimulated cells with 10(-8) mol/L vasopressin. At this vasopressin concentration, half-maximal inhibition of binding occurred at 5 x 10(-9) mol/L OPC-21268. Half-maximal inhibition of Ca2+ efflux or increases in intracellular free Ca2+ required higher concentrations of antagonist (10(-7) mol/L), and half-maximal inhibition of vasopressin-stimulated MAP kinase was observed only at 10(-6) mol/L OPC-21268. These results indicate that this agent selectively blocks both vasopressin binding and postreceptor signaling in vascular smooth muscle cells. The requirement of higher concentrations of OPC-21268 for blocking increases in intracellular Ca2+ and activation of MAP kinase suggests that binding to a fraction of V1 receptors generates maximal levels of second messengers or the existence of subtypes of the V1 receptor with differential affinity for this antagonist. These data have implications for the clinical use of this compound.

Animals↗
PubMed1994

Evidence for role of cytosolic free calcium in hypoxia-induced proximal tubule injury.

The role of cytosolic free Ca2+ ([Ca2+]i) in hypoxic injury was investigated in rat proximal tubules. [Ca2+]i was measured using fura-2 and cell injury was estimated with propidium iodide (PI) in individual tubules using video imaging fluorescence microscopy. [Ca2+]i increased from approximately 170 to approximately 390 nM during 5 min of hypoxia. This increase preceded detectable cell injury as assessed by PI and was reversible with reoxygenation. 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA; 100 microM) reduced [Ca2+]i under basal conditions (approximately 80 nM) and during hypoxia (approximately 120 nM) and significantly attenuated hypoxic injury. When [Ca2+]i and hypoxic cell injury were studied concurrently in the same individual tubules, the 10 min [Ca2+]i rise correlated significantly with subsequent cell damage observed at 20 min. 2 mM glycine did not block the rise in [Ca2+]i, yet protected the tubules from hypoxic injury. These results indicate that in rat proximal tubules, hypoxia induces an increase of [Ca2+]i which occurs before cell damage. The protective effect of BAPTA supports a role for [Ca2+]i in the initiation of hypoxic proximal tubule injury. The glycine results, however, implicate calcium-independent mechanisms of injury and/or blockade of calcium-mediated processes of injury such as activation of phospholipases or proteases.

Adenosine Triphosphate↗
PubMed1993

AVP-induced activation of MAP kinase in vascular smooth muscle cells is mediated through protein kinase C.

Arginine vasopressin (AVP) has been shown to stimulate tyrosine phosphorylation and activation of p42 mitogen-activated protein (MAP) kinase (p42MAPK) in vascular smooth muscle cells (VSMC). In VSMC, AVP increases free intracellular Ca2+ concentration ([Ca2+]i) and activates protein kinase C (PKC) through activation of phospholipase C. The contribution of PKC and [Ca2+]i in p42MAPK regulation was therefore determined. Activation of PKC by phorbol 12-myristate 13-acetate (PMA) stimulated tyrosine phosphorylation and activation of p42MAPK to the same extent as AVP. Inhibition of PKC by staurosporine or downregulation of PKC by PMA pretreatment abolished AVP-induced stimulation of p42MAPK. When [Ca2+]i was elevated to the same level as with AVP, using either ionomycin (0.1 microM) or thapsigargin (0.1 microM), MAP kinase was only partially activated. Elevation of [Ca2+]i to supraphysiological levels by 1 microM ionomycin stimulated MAP kinase activity to the same extent as AVP. This effect was blocked by downregulation of PKC. The intracellular Ca2+ chelator BAPTA [1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid] blocked AVP-induced [Ca2+]i increase but did not affect AVP stimulation of p42MAPK. Thus AVP-induced activation of p42MAPK requires only the activation of PKC but not an increase in [Ca2+]i.

Animals↗
PubMed1993

Calcium modulation and cell injury in isolated rat proximal tubules.

The possible role of an increased calcium influx in mediating hypoxia-induced injury in isolated rat proximal tubules was examined. Reduction of extracellular calcium delayed the development of proximal tubule cell injury as reflected by the release of lactate dehydrogenase (LDH). This protection, as assessed by LDH release, was not associated with improvements of cell ATP or potassium concentrations. The calcium channel blocker verapamil also delayed the development of cell injury due to hypoxia. This protective effect was evident in the presence of normal or low extracellular calcium. Specifically, hypoxic tubules incubated in low calcium medium were further protected by the addition of verapamil. The protection with verapamil was evident not only by diminished LDH release, but also by improvements in cell ATP and potassium concentration. Further experiments demonstrated that verapamil also increased cell potassium levels in control oxygenated tubules incubated in normal calcium medium. Thus, the results demonstrate that low calcium medium delays the onset of cell membrane injury during hypoxia as assessed by LDH release. The protective effects of verapamil can be demonstrated in the presence of normal or low calcium media, and involve not only diminished LDH release but also increased cell ATP and potassium concentrations. Therefore, in addition to any effect on calcium influx, the effect of verapamil appears to involve a protective effect at cell membrane or mitochondria sites.

Adenosine Triphosphate↗
PubMed1992

[Self measurement of blood pressure: automation and management problems].

In the Federal Republic of Germany, the introduction of clinical testing of devices designed for the self-measurement of blood pressure resulted in an improvement of quality of these devices during the last ten years. Further progress seems to be possible by more restrictive administrative prescriptions. Now, electronic devices have the same accuracy as stethoscope devices. They facilitate self-measurement especially in handicapped persons. Devices working by the oscillometric method do not measure blood pressure more accurately than Korotkow devices, but they are a bit less sensitive for wrong placing of the bladder. In most devices automation of the prescribed deflation rate (2 to 3 mmHg/s) was successful.

Blood Pressure Determination↗
PubMed1990

Dietary sodium restriction: adverse effect on plasma lipids.

In order to examine the effect of dietary sodium intake on plasma lipids, 15 healthy male volunteers were given a low-salt diet (20 mmol/day) for 3 weeks, adding either placebo, sodium chloride (200 mmol/day), or a non-chloride sodium salt (sodium citrate, 200 mmol Na/day) for one week each, in a single-blind randomized crossover study. Plasma levels of total cholesterol and LDL cholesterol were significantly higher at the end of the placebo period than with either sodium chloride (by 8.7 and 11.9%, respectively) (P less than 0.005) or sodium citrate (by 11.3% and 16.8%, respectively) (P less than 0.005). Thus this effect was dependent on sodium but not on chloride intake. Triglyceride and HDL-cholesterol levels were not affected by the dietary regimens. We conclude that short-term dietary sodium restriction may lead to a rise in plasma total and LDL cholesterol, thereby possibly increasing the risk of atherosclerotic vascular disease. Our findings render it possible that diuretic-induced lipid disturbances may also be caused by sodium depletion.

Adult↗
PubMed1990

Salt sensitivity in humans is associated with abnormal acid-base regulation.

Metabolic acidosis has recently been observed in rat models of salt-sensitive genetic hypertension. To test the hypothesis that salt sensitivity in humans may be associated with abnormal acid-base homeostasis, we performed arterial blood gas analyses in young (20-31 years old) normotensive subjects (n = 40) who were placed on a low salt diet (20 mmol NaCl/day) for 2 weeks with either 200 mmol sodium chloride or placebo added to the low salt diet for 1 week each in a randomized, single-blind crossover order. Furthermore, a subset of the subjects (seven salt-sensitive and eight salt-resistant) received 200 mmol sodium/day as the citrate salt as a supplement to the low salt diet for a third week. During each regimen, blood pressure as well as arterial pH and bicarbonate levels were measured. Salt sensitivity was defined as a significant drop in mean arterial pressure greater than 3 mm Hg (mean of 30 readings taken during each diet, p less than 0.05) while the subject was on the low salt diet. According to this definition, 16 subjects were salt-sensitive and 24 salt-resistant. During the high sodium chloride regimen, arterial pH and bicarbonate levels were significantly lower in the salt-sensitive than in the salt-resistant group (p less than 0.0001). The increase in blood pressure caused by sodium chloride correlated inversely to the arterial pH (r = -0.57, p = 0.0002) and bicarbonate levels (r = -0.52, p = 0.0007) during the high salt diet. Sodium chloride increased mean arterial blood pressure in the salt-sensitive subjects; sodium citrate did not. Sodium citrate led to an increase in pH and bicarbonate levels in both groups. Our finding that a sodium chloride-induced rise in blood pressure is associated with lower arterial plasma pH and bicarbonate levels points to an abnormality in renal acid-base regulation in salt-sensitive subjects.

Acid-Base Equilibrium↗
PubMed1989

Reliability of salt-sensitivity testing in normotensive subjects.

We examined the reliability of dietary salt-sensitivity testing by repeatedly studying the effects of a high (220 mmol/day) and low (20 mmol/day) salt diet in 15 normotensive subjects. Reliability of classification of salt-sensitivity as described by the kappa statistic was 0.87 implying an almost perfect strength of agreement between the two parts of the study. Whereas only 20% of the subjects with negative familial histories of hypertension were salt-sensitive, this was the case with 68% of the subjects with positive familial histories. Our results show that salt-sensitivity can be reliably tested in normotensive subjects and that it is related to a familial history of hypertension.

Adult↗
PubMed1989

Alpha 2- and beta 2-adrenoceptor downregulation in marathon runners.

The regulation of platelet alpha 2- and lymphocyte beta 2-adrenoceptor densities by alterations in endogenous catecholamines was examined. In order to activate the sympathetic nervous system eight trained male normotensive subjects carried out a marathon run. Adrenoceptor densities and plasma catecholamine concentrations were measured before and immediately after the run. Platelet alpha 2-adrenoceptor density and lymphocyte beta-adrenoceptor density decreased after the run (P less than 0.05), whereas both plasma noradrenaline and adrenaline concentrations increased (P less than 0.01). Mean arterial pressure decreased (P less than 0.05), and the heart rate increased (P less than 0.001). The data suggest that increases in endogenous catecholamine concentrations cause downregulation of both alpha- and beta-adrenoceptor densities on human blood cells.

Adult↗
PubMed1989

The contribution of the sympathetic nervous system to hypertension in diabetes mellitus.

Hyperactivity of the sympathetic nervous system has repeatedly been assumed to play a role in the pathogenesis of essential hypertension. Particularly in young hypertensive patients, sympathetic nervous activity seems to be slightly elevated. On the other hand an increased pressor effect of noradrenaline has also been reported in some patients with essential hypertension. While neither the slightly elevated sympathetic tone nor the inconstant increased reactivity to noradrenaline could alone be responsible for the blood pressure elevation, both factors together appear to form an important determinant of the level of arterial blood pressure. There is no uniform evidence that sympathetic nervous activity is changed in uncomplicated diabetes. A diminished sympathetic nervous activity in patients with secondary complications is so far not proved. A slight increase in circulatory reactivity to noradrenaline is described independent of the height of blood pressure, however, data in moderate and accelerated hypertensive diabetic patients are not available.

Diabetes Complications↗
PubMed1988

Different effects of furosemide on alpha-adrenoceptors and on platelet aggregation in man.

The effect of a long-term administration of furosemide (2 x 30 mg/day for 3 weeks) on platelet alpha 2-adrenoceptor density and the fraction of high-affinity binding sites, as well as on platelet aggregation induced by adrenaline and ADP, was studied ex vivo in 8 normotensive volunteers. For comparison the in vitro effect of furosemide on platelet aggregation was also evaluated. Furosemide decreased alpha 2-adrenoceptor-density (P less than 0.01) and the fraction of high-affinity binding sites (P less than 0.05). Adrenaline-induced platelet aggregation was not altered ex vivo and in vitro. Furosemide inhibited ADP-induced platelet aggregation ex vivo (P less than 0.05) and in parallel in vitro (P less than 0.01) in a dose-dependent manner. The reduction of the density of alpha 2-adrenoceptors in the high affinity state may be of functional importance for the hemodynamic effects of furosemide. The inhibitory effect of furosemide on ADP-induced platelet aggregation ex vivo and in vitro, which is not related to the effects on adrenoceptors, seems to involve direct effects of furosemide on platelet function. It remains to be seen whether the latter effect is of clinical importance.

Adult↗