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Biomedical subjects

A Distler

Publications and source records attributed to A Distler.

At least 109 records · Page 6Linked to original sources
PubMed1994

The specific antibacterial proliferation of reactive arthritis synovial T cells is not due to their higher proportion of CD45RO+ cells compared to peripheral blood.

OBJECTIVE: To determine the role of synovial fluid (SF) compared to peripheral blood (PB) CD45RO+ T cells in patients with reactive arthritis (ReA) and undifferentiated oligoarthritis. METHODS: We examined SF and PB of 8 patients with a specific lymphocyte proliferation to Yersinia enterocolitica (n = 5) and Chlamydia trachomatis (n = 3). After depletion of the CD45RA+ T cell subset by dynabeads, the remaining T cells (> 95% CD45RO+) from PB and SF of these patients were again stimulated with these bacterial antigens. RESULTS: The mean stimulation index (SI) of these 8 patients with ReA (n = 5) and undifferentiated oligoarthritis (n = 3) was 30.3 +/- 21.86 in SF compared to 1.36 +/- 0.75 in PB. The enrichment of CD45RO+ cells influenced the antigen specific proliferative response of T cells neither in PB (SI = 1.75 +/- 1.35) nor in SF (26.1 +/- 24.05); the initial difference remained unchanged. CONCLUSION: Our findings suggest that the antigen specific lymphocyte proliferation obtained with SF cells is not due to abundance of nonspecific CD45RO+ T cells but can rather be taken as an indication of specific recognition of local bacterial antigens in ReA.

Adult↗
PubMed1994

Angiotensin II infusions elevated blood pressure independently of platelet cytosolic calcium concentrations in humans.

A remarkably close correlation between platelet cytosolic calcium ([Ca2+i]) and arterial blood pressure has been identified in patients with essential hypertension. We tested the notion that a pharmacologically relevant infusion of angiotensin (Ang) II is associated with an increase in cytosolic calcium [Ca+2i]. Five normal volunteers received Ang II (5 ng/kg/min) for three hours or vehicle intravenously in random sequence respectively. The investigations were conducted at least 14 days apart. Plasma renin activity and blood pressure were measured every 20 minutes. [Ca+2i] was measured with the fluorescent indicator fura-2 before and at the end of the last hour of Ang II infusion. Mean arterial blood pressure increased by 10 mmHg during Ang II infusion (P < 0.05). Plasma renin activity decreased from 2.21 +/- 0.28 to 1.31 +/- 0.22 ng/ml/hour during the Ang II infusion (P < 0.05). On the other hand, [Ca+2i] was 131 +/- 13 nmol/l before and 129 +/- 13 nmol/l after the infusion (P = NS). The data suggest that agonists may increase blood pressure without an increase in platelet [Ca+2i]. Furthermore, Ang II may increase blood pressure independently of [Ca+2i].

Adolescent↗
PubMed1994

Acid-base abnormalities in hypertension.

Recent evidence from both salt-sensitive humans and several rat models of hypertension indicates an association between metabolic acidosis and genetic hypertension. Preliminary findings of increased renal acid excretion suggest that the perturbation of acid-base status may be the result of increased metabolic acid production. This would be compatible with the previous findings of enhanced Na+/H(+)-antiporter activity, reduced intracellular pH levels, and abnormalities of carbohydrate and lipid metabolism present in both patients with essential hypertension and rat models of genetic hypertension. Further investigation of the factors controlling acid-base metabolism in animal models of hypertension and in salt-sensitive humans may disclose underlying metabolic abnormalities that could account for both the alterations in blood pressure and acid-base status associated with genetic hypertension.

Acid-Base Imbalance↗
PubMed1994

The evolutionarily conserved ribosomal protein L23 and the cationic urease beta-subunit of Yersinia enterocolitica O:3 belong to the immunodominant antigens in Yersinia-triggered reactive arthritis: implications for autoimmunity.

BACKGROUND: Reactive arthritis (ReA) is a T cell mediated inflammatory process. The immune response is primarily directed against a triggering organism, although autoimmunity has been invoked in long-lasting, antibiotic-resistant disease. Although a variety of different species are known to trigger Reactive arthritis, the clinical manifestations are strikingly similar as well as closely associated to the HLA-B27 (70%). MATERIALS AND METHODS: Various antigenic fractions and single antigens of Yersinia enterocolitica were prepared, and their immunological activity was assessed by proliferation of synovial fluid mononuclear cells from 10 Reactive arthritis patients. The gene encoding one hitherto unknown antigen has been sequenced. Nonapeptides deduced from sequences of the target antigens were tested in an assembly assay. RESULTS: Two immunodominant proteins of Yersinia enterocolitica were found, one being the urease beta-subunit and the other the 50 S ribosomal protein L23. The latter has been sequenced and belongs to the evolutionarily conserved ribosomal proteins with homology to procaryotes and eucaryotes. One nonapeptide derived from the urease beta-subunit was identified as a possible epitope for HLA-B27-restricted cytotoxic T cells by its high affinity. This epitope is also highly conserved. CONCLUSION: Sharing of conserved immunodominant proteins between different disease triggering microorganisms could provide an explanation of the shared clinical picture in Reactive arthritis. Moreover, autoimmunity in Reactive arthritis might be mediated by antigen mimicry between evolutionarily conserved epitopes of ribosomal proteins and their host analogs.

Adolescent↗
PubMed1993

Widespread vasculopathy with hemolytic uremic syndrome, perimyocarditis and cystic pancreatitis in a young woman with mixed connective tissue disease. Case report and review of the literature.

A 15-year-old girl had severe Raynaud's phenomenon and arthralgias. A high ANA-IF titer was found and undifferentiated connective tissue disease was diagnosed. After 7 years of moderately flaring disease the patient deteriorated and presented with congestive heart failure, pleuropericardial effusion, hemolytic uremic syndrome, proteinuria and moderate hypertension. Autoantibodies against DNA, Sm-protein, and very high titers against U1RNP were detected. Therapy with high steroid doses, a cyclophosphamide pulse and 4 weeks of plasmaphresis with plasma exchange improved the heart, but not the renal condition. Symptomatic pancreatitis became the dominant problem of a progressively consuming process that resulted in the death of the patient. Post-mortem examination revealed widespread vasculopathy with intima proliferation and only minimal fibrosis involving the kidneys, heart and other main organs, including the pancreas. Taken together, the clinical picture was of an overlap between scleroderma and systemic lupus erythemathosus; the serologic and histopathologic findings suggest a diagnosis of a severe form of mixed connective tissue disease (MCTD).

Adolescent↗
PubMed1993

Effects of sodium salts on plasma renin activity and norepinephrine response to orthostasis in salt-sensitive normotensive subjects.

The blood pressure-raising effect of sodium chloride in salt-sensitive individuals depends on the administration of both sodium and chloride. While sodium chloride is well known to suppress the activity of the renin-angiotensin-aldosterone and the sympathetic nervous system, the effects of nonchloride sodium salts on the response of these systems to physiological stimuli have not been previously studied. We therefore examined the effect of dietary intake of sodium chloride or sodium citrate on the activity of the renin-angiotensin-aldosterone and the sympathetic nervous system during rest and following stimulation by active orthostasis in normotensive salt-sensitive (n = 7) and salt-resistant (n = 8) subjects. The subjects were given a low-salt diet (20 mmol/day) for 3 weeks, to which a supplement of 200 mmol sodium per day, provided as either sodium chloride or sodium citrate, or a placebo, was added for 1 week each. We found that sodium chloride raised blood pressure in the salt-sensitive subjects (P < .005), while sodium citrate did not. Both salts, however, led to a similar suppression of the plasma levels of renin activity, angiotensin II, aldosterone, and norepinephrine (P < .01). Both sodium salts attenuated the renin response to orthostasis in salt-sensitive and salt-resistant individuals (P < .01), but the orthostasis-induced rise in renin activity was significantly smaller in the salt-sensitive than in the salt-resistant group under both sodium salts (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effect of dietary salt restriction on urinary serotonin and 5-hydroxyindoleacetic acid excretion in man.

OBJECTIVE: To determine the effect of dietary salt restriction on urinary excretion of serotonin and its principal metabolite 5-hydroxyindoleacetic acid (5-HIAA) in man. DESIGN: We studied 16 healthy male volunteers (age range 20-28 years) who ate a standard diet containing 20 mmol/day NaCl, to which either 220 mmol/day NaCl or placebo was added as a supplement for 1 week each, according to a randomized, single-blind crossover design. METHODS: Urinary excretion of serotonin, 5-HIAA, noradrenaline and vanillylmandelic acid (VMA) were measured during the low- and high-salt periods using reverse-phase high-performance liquid chromatography. RESULTS: During the low-salt diet, 24-h urinary excretion of serotonin increased by 42%, accompanied by a 52% rise in the excretion of 5-HIAA. Salt restriction also increased noradrenaline excretion by 77% and VMA excretion by 40%. Regression analysis revealed a strong positive relationship between the excretion of serotonin and of noradrenaline (r = 0.84, P < 0.001) and between that of 5-HIAA and of VMA (r = 0.74, P < 0.001). CONCLUSIONS: Salt restriction stimulates the serotonergic system in man. Stimulation of this system, in conjunction with the sympathetic nervous system, may contribute to renal sodium conservation during dietary salt restriction in man.

Adult↗
PubMed1993

T cells bind to the endothelial adhesion molecule GMP-140 (P-selectin).

A crucial step in an effective immune response is the adhesion of circulating lymphocytes. Lymphocytes must attach to endothelial cells before they can migrate into the graft. It has been shown that T cells bind to ICAM-1 and VCAM-1. Additionally, certain T cell subsets bind to ELAM-1. We now report that resting CD4+ and CD8+ T cells as well as individual CD4+ T cell clones and CD8+ T cell lines bind to GMP-140 in an adhesion assay using protein chimeras consisting of the extracellular domain of GMP-140 linked to the hinge domain of human IgG1. Whereas resting T cells bound similarly to ELAM-1 IgG and GMP-140 IgG, activated T cells represented by CD4+ T cell clones and CD8+ T cell lines bound to GMP-140 IgG, but not to ELAM-1 IgG. Neither the binding to immobilized GMP-140 IgG, nor to immobilized ELAM-1 IgG could provide T cells with costimulatory signals for proliferation in the presence of submitogenic concentrations of anti-CD3 antibodies. The binding of T cells to the endothelial adhesion receptor GMP-140 might be important during the initial adhesion process of lymphocytes in rejecting grafts.

Cell Adhesion↗
PubMed1993

Insulin resistance in young salt-sensitive normotensive subjects.

Insulin resistance has been demonstrated in patients with essential hypertension, and insulin-mediated sodium retention is believed to contribute to hypertension in these individuals. Recently, a hyperinsulinemic response to an oral glucose load has been found in salt-sensitive normotensive subjects, suggesting that insulin resistance may be present in these hypertension-prone individuals before the development of hypertension. In the present study, we examined the relation between insulin sensitivity and blood pressure response to salt intake in young, lean normotensive subjects on a high and a low salt diet. Insulin sensitivity was estimated by the "insulin suppression test," i.e., by measuring the plasma glucose and insulin concentrations achieved during a 180-minute infusion of somatostatin, insulin, and glucose in 18 healthy male volunteers (age, 21-28 years) given a standardized low salt diet (20 mmol/day) for 2 weeks, supplemented by either 220 mmol of NaCl per day or placebo in a single-blind randomized order for 1 week each. We defined salt sensitivity as a significant decrease in mean arterial blood pressure (> 3 mm Hg [p < 0.05]) measured for 60 minutes at 1-minute intervals on the low salt diet. By this definition, seven of the 18 subjects were salt sensitive. Although insulin infusion resulted in similar plasma insulin levels (approximately 50 milliunits/L) in both groups, concomitant glucose infusion resulted in plasma glucose levels that were more than 50% higher in the salt-sensitive than in the salt-resistant group (p < 0.005 by two-way analysis of variance).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Renal acid-base excretion in normotensive salt-sensitive humans.

Reduced extracellular pH and bicarbonate levels recently have been reported in normotensive salt-sensitive subjects. To assess the possible role of altered renal acid-base handling in the perturbation of acid-base status in these individuals, we measured the renal acid-base excretion after an acute oral administration of either an alkali or acid load in normotensive salt-sensitive and salt-resistant men. Twenty-four young (22 to 29 years old), healthy male volunteers were placed on a low-salt diet (20 mmol NaCl per day) for 2 weeks with either 220 mmol NaCl or placebo added to the low-salt diet for 1 week each in a randomized single-blind crossover order. Salt sensitivity was defined as a significant drop in mean arterial pressure (> 3 mm Hg, mean of 60 readings taken on the seventh day of each diet, P < .05) during the low-salt diet. On the fifth and seventh days of each week, subjects were given an oral load of either sodium citrate (0.7 mmol/kg) or ammonium chloride (2.2 mmol/kg), respectively, in a randomized order, and arterial and urinary acid-base status was assessed at baseline and followed for 8 hours thereafter. According to the above definition, 13 subjects were considered salt sensitive. During the high-salt diet, mean arterial pressure was higher in the salt-sensitive than in the salt-resistant group (P < .01). Cumulative urinary bicarbonate excretion after the administration of sodium citrate was lower in the salt-sensitive than in the salt-resistant subjects during both the low-salt (46%, P < .001) and high-salt (32%, P < .01) diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗
PubMed1993

Flashlamp exited pulsed dye laser and electrohydraulic lithotripsy: in vitro study on tissue effects.

Intracorporal lithotripsy has gathered momentum in the management of gallstone disease due to the increasing sophistication of technical equipment for the percutaneous, as well as the retrograde-endoscopic route. Laser-induced shock wave lithotripsy (LISL) and electrohydraulic lithotripsy (EHL) have proved feasible by allowing reliable fragmentation of biliary calculi. Evaluation of therapeutic risks, e.g., effects of accidental irradiation of the gallbladder wall, has been performed in small sample sizes only. We investigated the effects of LISL and EHL on multiple sets of human and porcine gallbladders under in vitro conditions. Gallbladders were freshly harvested, mounted, and immersed in different mediums (normal saline, blood, bile). They were swiftly exposed to LISL (Pulsolith¿) and EHL (Lithotron EL 23¿) under differing experimental conditions (energy setting, pulse mode, exposition time, medium, probe pressure) and subjected to standard procedures for morphometric evaluation (Bioquant¿). Tissue effects were described by the depth (d) and width (w) of the cratered lesions, as well as the extension of the damage in the surrounding tissue(s). Serial cuts of the exposed areas yielded 894 section for morphometric analysis. Multivariate analysis of variance (MANOVA) revealed a significant effect of laser energy (p[d] less than 0.002, p[w] < 0.05, p[s] < 0.05), medium (p[d] less than 0.03, p[w] < 0.001, p[s] < 0.04, and exposition time (p[d] less than 0.001, p[s] < 0.001) on the degree of tissue lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1992

Development of ulcerative colitis under the immunosuppressive effect of cyclosporine.

In recent studies, cyclosporine has been used for the treatment of both ulcerative colitis and Crohn's disease. The results of these studies were variable. We report on a patient who was treated for 6 years with cyclosporine after kidney transplantation. He developed chronic distal colitis with all the features of ulcerative colitis. An infectious etiology of the colitis was carefully excluded. High-dose treatment with methylprednisolone was required to induce remission. This report shows that immunosuppressive therapy with cyclosporine did not prevent the development of ulcerative colitis in this patient.

Colitis, Ulcerative↗
PubMed1992

Protein phosphorylation and intracellular free calcium in platelets of patients with essential hypertension.

Platelet intracellular free calcium concentration [Ca2+]i from patients with essential hypertension has been found to be elevated, but the intracellular effects of this increase are still unclear. As protein phosphorylation is an important regulatory step in cell activation and increased protein phosphorylation has been demonstrated in platelets from hypertensive animals, we investigated protein phosphorylation and [Ca2+]i in platelets from patients with essential hypertension and age-matched normotensives. We measured the 32P incorporation into a 20 kDa protein and a 47 kDa protein in 17 hypertensive patients and 20 normotensive, age-matched subjects. The [Ca2+]i was measured with the fluorescent dye fura-2. Protein phosphorylation and [Ca2+]i were assessed in unstimulated platelets and after exposure of the cells to 0.1 and 0.25 U/mL thrombin at 20, 60, and 300 sec. In addition we assessed the activity of protein kinase C by incubating the platelets with phorbol-ester TPA at 20, 60, and 300 sec. Basal phosphorylation of the two proteins was not different between the two groups. After exposure of the platelets to thrombin 32P, incorporation into the 20 kDa protein and the 47 kDa protein was significantly increased in platelets from hypertensive patients at all times. Furthermore, the specific stimulation of protein kinase C with TPA resulted in a significantly higher phosphorylation of the 47 kDa protein, whereas the 20 kDa protein was not phosphorylated after incubation with TPA for 1 min. Basal [Ca2+]i was higher in platelets from hypertensive patients (124 +/- 7 nmol/L v 104 +/- 5 nmol/L, P less than .05), although there was a wide overlap between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗
PubMed1992

Hyperreninemia and secondary hyperaldosteronism in a patient with pheochromocytoma and von Hippel-Lindau disease.

In a 21-year-old Caucasian women with von Hippel-Lindau disease, norepinephrine-producing adrenal pheochromocytoma was identified as the underlying cause of severe hypertension. She was found to have extremely elevated levels of circulating renin and aldosterone, and she was markedly hypokalemic. Administration of captopril further enhanced renin secretion, while her blood pressure improved. The patient became normokalemic following tumor removal, and her blood pressure decreased to normal levels with reestablishment of normal circadian blood pressure rhythm. This case demonstrates that, in the absence of renovascular or malignant hypertension, pheochromocytoma can be the underlying cause for the clinical syndrome of hypertension associated with severe hypokalemia and hyperreninemic hyperaldosteronism.

Adrenal Gland Neoplasms↗
PubMed1992

Effects of sodium salts on pressor reactivity in salt-sensitive men.

Blood pressure in patients with essential hypertension is raised by sodium chloride but not by nonchloride sodium salts. Although a high sodium chloride diet is known to augment the pressor response to norepinephrine and angiotensin II, the effect of nonchloride sodium salts on pressor responsiveness has not been studied so far. To examine whether sodium chloride and nonchloride sodium salts evoke different pressor responses to these agonists, we performed graded norepinephrine and angiotensin II infusions in salt-sensitive (n = 7) and salt-resistant (n = 8) normotensive subjects. The subjects were given a low salt diet (20 mmol/day) for 3 weeks, to which a supplement of 200 mmol sodium per day, provided as either sodium chloride or sodium citrate, or a placebo was added for 1 week each. We found that, although sodium chloride raised mean arterial blood pressure in the salt-sensitive subjects (p less than 0.005), sodium citrate did not. However, under both sodium salts pressor response to norepinephrine and angiotensin II was significantly greater than under placebo (p less than 0.02). Furthermore, with both sodium salts, pressor response in the salt-sensitive subjects was greater than in the salt-resistant subjects (p less than 0.01). This study thus demonstrates that, although blood pressure in salt-sensitive individuals is raised by sodium chloride only, both sodium chloride and sodium citrate evoke similar increases in pressor response to norepinephrine and angiotensin II. Since pressor response increased with both sodium salts but resting blood pressure increased only with sodium chloride, enhanced pressor responsiveness alone cannot account for the sodium chloride-induced rise in resting blood pressure.

Adult↗
PubMed1992

[Value of 24-hour blood pressure measurement in patients with arterial hypertension, left heart enlargement and increased cardiac risk].

Non-invasive 24-h blood pressure and a 24-h electrocardiogram were recorded in 45 normotensive and 97 matched, untreated, hypertensive subjects, with and without echocardiographic signs of left-ventricular hypertrophy and without signs of coronary artery disease. Forearm vascular resistance was calculated from mean blood pressure and postischemic blood flow, which was measured by venous plethysmography. Systolic ambulant 24-h blood pressure exhibited the closest correlation with left-ventricular mass index in hypertensives (r = 0.48; p less than 0.001). No relation could be found between blood-pressure fall overnight and left-ventricular hypertrophy. Blood-pressure variability was significantly higher in hypertensive subjects. Furthermore, systolic 24-h blood pressure significantly correlated with the rate of ventricular arrhythmias in hypertensives. Casual blood pressure exhibited no comparable correlations. A significant close correlation between 24-h blood pressure and vascular resistance was identified in hypertensives. Furthermore, left-ventricular mass index and vascular resistance were correlated (in hypertensives: r = 0.32; p less than 0.01). This finding speaks for a parallel development of total peripheral resistance and left-ventricular hypertrophy in essential hypertension. The close relationships between ambulatory 24-h blood pressure, left-ventricular hypertrophy, ventricular arrhythmias, and vascular resistance demonstrates the high diagnostic and, possibly, the prognostic value of long-term blood-pressure measurement.

Adult↗
PubMed1992

Pathogenetic role of Chlamydia, Yersinia and Borrelia in undifferentiated oligoarthritis.

We studied the cellular and humoral immune response to Chlamydia trachomatis, Yersinia enterocolitica and Borrelia burgdorferi in paired samples of peripheral blood and synovial fluid (SF) in undifferentiated oligoarthritis, reactive arthritis (ReA) and rheumatoid arthritis. Antigen specific lymphocyte proliferation was found in SF of 43% of patients with ReA and 34% of patients with undifferentiated oligoarthritis. C. trachomatis was the most frequent single agent. HLA-B27 was positive in 83% of patients with ReA and in 62% of patients with undifferentiated oligoarthritis with antigen specific lymphocyte proliferation. Antigen specific lymphocyte proliferation correlated poorly with the specific antibody response. Only chlamydial antigen was detected in SF cells using monoclonal antibodies. We conclude that some patients with undifferentiated oligoarthritis may have a forme fruste of ReA. This finding is important in view of recent evidence supporting the efficacy of antibiotic therapy in ReA.

Adult↗