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Biomedical subjects

M Rambausek

Publications and source records attributed to M Rambausek.

At least 37 records · Page 2Linked to original sources

Regulation of myocardial isomyosin V1 in uraemic rats.

Cardiac hypertrophy of various aetiologies is consistently associated with increased expression of V3 isomyosin. Uraemia is associated with cardiac hypertrophy. In the present study, we examined regulation of isomyosin in uraemic rats, using gel electrophoresis. Cardiac hypertrophy in uraemic animals was associated with a relative increase in V1 isomyosin. An increased proportion of V1 isomyosin was demonstrable 3 days after subtotal nephrectomy (NX 63.0 +/- 8.8%; control 43.6 +/- 7.2%; P less than 0.01) and persisted during uraemia of 80 days duration. Elevation of V1 isomyosin, relative to pair-fed controls, was observed in uraemic animals of various age. The proportion of V1 isomyosin changed in the same direction as controls when several manouevers were used which changed the isomyosin pattern, but the difference between uraemic animals and controls persisted. We studied the effect of carbohydrate loading or deprivation, starvation or administration of energetically inadequate diets, castration or administration of androgens and sodium depletion. With each of the above interventions, a difference between subtotally nephrectomized animals and sham-operated pair-fed control animals was statistically significant (P less than 0.05). Elevation of V1 isomyosin persisted during combined alpha and beta blockade and was still found when blood pressure was normalized by ACE inhibition using Ramipril. It is concluded that cardiac hypertrophy of uraemia differs from all other forms of cardiac hypertrophy by the occurrence of increased proportion of V1 isomyosin. The proportion of V1 isomyosin responds adequately to regulatory signals but is set at an abnormally high level.

Androgens↗

Immunoglobulin constant heavy chain gene polymorphisms of Caucasoids of west European origin.

We have used restriction fragment length polymorphism (RFLP) analysis to investigate the immunoglobulin constant heavy chain (IgCH) loci and the associated locus Dl4Sl, of Caucasoids from South East England and South-West. West Germany, Haplotypes were determined using probes to the Ig heavy chain switch loci S mu and S alpha 1, the IgC gamma 3 and IgC gamma 2 loci as well as the Dl4Sl locus which is 3' of the IgCH loci. The 6.3:1.7 kilobase (kb) Bst EII C gamma 3-C gamma 2 haplotype was the most prevalent in the population from South-East England (frequency 0.364), whilst the 2.3:3.7 kb C gamma 3-C gamma 2 haplotype was the major haplotype in the German population (frequency 0.400). With one exception, the major haplotypes of these two populations differed from the ones previously published for a Caucasoid population from California. This suggests that there may be a major ancestral IgCH haplotype which has been maintained in the population, whilst other haplotypes tend to be specific for a particular group of Caucasoids.

California↗

Cardiac changes in uraemia and their possible relationship to cardiovascular instability on dialysis.

In the past, cardiac changes in renal failure have commonly been ascribed to hypertension and poorly specified toxic effects ('uraemic cardiomyopathy'). Our recent experimental and clinical studies suggest (a) that cardiac hypertrophy can be dissociated from hypertension and that blood pressures may have only a permissive role, (b) that experimental uraemia is associated with specific activation of pericytes and intermyocardiocytic fibrosis. Cardiac hypertrophy not correlated with elevated blood pressure, and intermyocardiocytic fibrosis not observed in similarly hypertensive non-uraemic patients, have recently been documented in dialysis patients. The implications of these findings may be (a) electrical instability and predisposition to a sudden cardiac death and (b) diastolic cardiac malfunction with impaired LV filling and predisposition to dialysis hypotension. Some evidence for the latter possibility is provided.

Cardiomegaly↗

Frequency of mesangial IgA deposits in a non-selected autopsy series.

The frequency of mesangial IgA deposition was examined in 250 consecutive autopsy cases without known renal disease. Diffuse granular mesangial deposits of IgA were detected in 12 of 250 cases (4.8%). In six patients IgA deposits were associated with liver cirrhosis. Six patients (2.4%) suffered from various other conditions including endocarditis, bronchial asthma, cardiovascular disease, and neoplasia. Two of these patients had completely negative urine analysis on repeated investigations, whereas three patients exhibited microscopic haematuria and/or mild proteinuria. IgA1 was the major constituent in all specimens. C3c deposits in glomeruli were detected in one kidney. Our findings indicate that clinically overt renal disease is present in only a limited proportion of individuals with mesangial IgA deposits. Apparently, it represents the tip of an iceberg.

Antibodies, Monoclonal↗

Hypertension in chronic idiopathic glomerulonephritis: analysis of 311 biopsied patients.

Prevalence of hypertension and relation of hypertension to renal function, type of glomerulonephritis or histological features were evaluated in 311 patients with idiopathic chronic glomerulonephritis. The overall prevalence of hypertension was 49.8%. At least in women, prevalence of hypertension was increased even at serum creatinine levels less than 1.1 mg dl-1 compared with the local general population. Prevalence of hypertension was 2.12 and 8.6 fold higher at serum creatinine 1.1-1.4 mg dl-1 in males and females respectively. In patients with untreated hypertension, a relation was found between mean blood pressure and subsequent decline of estimated GFR. Furthermore, in patients with arterial sclerosis, but not in patients without, a significant relation was found between blood pressure and subsequent increase in serum creatinine.

Adolescent↗

[Immunogenetics of mesangial IgA glomerulonephritis and Schönlein- Henoch purpura].

We have recently examined polymorphisms of immunoglobuline heavy chain genes at S mu and S alpha 1 switch region loci by RFLP technique and described differences of genotype frequencies between healthy controls and patients with IgA-nephritis and Henoch-Schönlein-Purpura respectively. In the present study we further characterized the heavy chain constant region of IgG2 and IgG3 and, in addition, a hypervariable region (D 14 S 1) of unknown function localized downstream. In the present larger patient cohort we confirmed a higher frequency of S alpha 1 7.4 kb homozygotes in patients with IgA-nephritis (but not SHP), i.e. 62.0% vs 38.8% in controls, p less than 0.001. Compared to controls RFLP-frequencies of the constant region of IgG2 were also different in patients with IgA-nephritis, but not RFLP frequencies of D 14 S 1 or of the constant region of IgG3. Patients with IgA-nephritis homozygote for 7.4 kb in S alpha 1 had more adverse renal outcome and hypertension and more severe histological lesions (i.e. interstitial fibrosis, p less than 0.005).

Gene Frequency↗

Reaction patterns of the myocardial interstitium in different models of cardiac hypertrophy--stereological investigations.

Several experimental models of cardiac hypertrophy were investigated in rats: 1. mild hypertrophy induced by physical exercise (18 weeks), 2. mild hypertrophy induced by renovascular hypertension (24 weeks), 3. moderate hypertrophy induced by renovascular hypertension in diabetic and non-diabetic animals (8 weeks), 4. moderate hypertrophy induced by renovascular hypertension in diabetic and non-diabetic animals (12 weeks), 5. moderate hypertrophy induced by thyroxin application (4 weeks), 6. mild hypertrophy in chronic uremia (5/6 nephrectomy, 3 weeks). It is concluded from quantitative stereological parameters of the left ventricular papillary muscles that 1. in hypertrophic hearts myocardial blood flow and oxygen consumption, respectively, rather than the size of muscle fibres determine the capillary supply of the myocardium, 2. interstitial fibrosis occurs in hypertrophy induced by chronic pressure overload and depends on degree and duration of hypertension, 3. the extent of interstitial fibrosis in hypertension is magnified by diabetes mellitus, and 4. the interstitial fibrosis which occurs in chronic uremia is not caused by hypertension.

Animals↗

Myocardial interstitial fibrosis in experimental uremia--implications for cardiac compliance.

Experimental uremia is known to cause cardiac hypertrophy. In the present study we examined the effect of uremia with or without concomitant treatment of hypertension by the converting enzyme Ramipril (125 micrograms/day) on micromorphometric indices of cardiac interstitium at the light microscopical and ultrastructural level. In male SD rats, 21 days of uremia caused an increase of total heart weight (1040 +/- 73 mg wet wt vs. 871 +/- 81 in controls, P less than 0.05) with an increase of both right and left ventricular weight. This was accompanied by reduction of capillary cross-sectional area despite unchanged capillary length. The volume density (cm3/cm3) of cardiomyocytes was unchanged (0.881 +/- 0.01 vs. 0.871 +/- 0.016 in controls), but volume density of interstitial tissue (excluding capillary lumen) was significantly increased (0.042 +/- 0.011 cm3 interstitial tissue/cm3 total heart tissue vs. 0.019 +/- 0.007 in controls). This was associated with signs of activation of interstitial cells, that is, increased volume of interstitial cell nuclei and interstitial cell cytoplasm. Concomitantly, a significant increase of volume density of non-cellular interstitial ground substance was found which was not normalized by antihypertensive treatment using Ramipril. After three months of uremia, electron microscopy showed collagen fiber deposition in the interstitium. Comparable interstitial fibrosis was not observed in hearts of rats with renovascular (one clip-two kidney) hypertension. It is concluded that uremia increases myocardial interstitial ground substance by mechanisms independent of hypertension. The data may be relevant for recent findings of diastolic heart malfunction secondary to impaired compliance in uremic patients.

Angiotensin-Converting Enzyme Inhibitors↗

Tamm Horsfall glycoprotein interferes with bacterial adherence to human kidney cells.

The effect of Tamm Horsfall protein (THP) of 18 healthy subjects and 14 diabetics on adherence of Escherichia coli (06:K13) 2699 strain to human kidney cells (HUK) was studied. Adhesion of bacteria (without additions: 100 bacteria per cell) was reduced dose-dependently by THP, half maximal inhibition occurring with 250 micrograms THP ml-1. Maximal inhibition (-84% at 1000 micrograms ml-1) exceeded inhibition by alpha-methyl-mannoside (36% at 50 mM), was specific (not reproduced by other glycoproteins, e.g. ovalbumin, mucin or thyroglobulin) and reversible (abolished by washing THP off HUK cells). Anti-adherence property of THP was not abolished by neuraminidase treatment. No significant difference of anti-adherence activity of THP was found between controls and diabetics, despite altered carbohydrate composition of THP in diabetes.

Adult↗