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Biomedical subjects

M Rambausek

Publications and source records attributed to M Rambausek.

At least 55 records · Page 3Linked to original sources

Tamm Horsfall glycoprotein in diabetes mellitus: abnormal chemical composition and colloid stability.

Tamm Horsfall glycoprotein (THP) was isolated, using sodium chloride precipitation technique, from 24-h urine of 19 non-proteinuric insulin-dependent diabetics and 19 matched controls. Tamm Horsfall glycoprotein was pure, as judged by PAGE electrophoresis, by Ouchterlony double diffusion against anti-THP or anti-albumin antibodies, and by isoelectric focusing. Content of carbohydrates (gas-chromatography), amino acids or amino sugars (AA-analyser), N-acetylneuraminic acid (thiobarbituric acid method) and lysyl-bound glucose (furosine method) were determined and showed the following abnormalities: THP of diabetics had significantly higher glucose content (d: 2.55 +/- 0.66 g 100 g-1 THP; CO: 0.99 +/- 0.23; P less than 0.05) and increased lysyl-bound glucose, but diminished N-acetyl-neuraminic acid content (3.54 +/- 0.25 vs. 4.96 +/- 0.15; P less than 0.01) with no significant differences of amino acids or amino sugars. Low N-acetyl-neuraminic acid content was paralleled by reduced surface charge density of THP, as revealed by polyelectrolyte titration. No abnormality of the protein core was revealed by amino acid analysis and by probing reactivity to seven different monoclonal antibodies to human THP. Altered colloid stability, i.e. greater precipitation of THP of diabetic patients, was demonstrated by laser nephelometry. The data are consistent with abnormal post-translational modification of THP in diabetes.

Adult↗

Relation of mesangial IgA glomerulonephritis to polymorphism of immunoglobulin heavy chain switch region.

We have investigated the switch regions of Ig heavy chain genes of patients with IgA glomerulonephritis (IgA-GN) using restriction fragment length polymorphism (RFLP) analysis. Genomic DNA from patients and controls was digested with the restriction endonuclease Sst I and transferred to nylon membranes using the Southern blot procedure and hybridized with a probe homologous to the switch region of the Ig C mu gene (S mu) which detects RFLPs in both S mu and the switch region of the Ig C alpha 1 gene (S alpha 1). A significant decrease in the frequency of the 2.6;2.1 kb heterozygous S mu phenotype was found in patients with IgA-GN (P = 0.003). With respect to the S alpha 1 region, there was a significant increase in the frequency of the 7.4 kb S alpha 1 phenotype (P = 0.002). In addition, a significant increase in the frequency of the 7.4 kb S alpha 1 allele was found (P = 0.0002). These results suggest that gene(s) within the Ig heavy chain loci may be important in the pathogenesis of IgA-GN.

Genes, Regulator↗

HBV DNA and other hepatitis B virus markers in sera from long-term hemodialysis and kidney transplant patients.

Sera from 191 long-term hemodialysis patients and from 115 renal transplant patients were studied for the presence of HBsAg and other HBV markers. In 19.1% of the hemodialysis patients and 28.7% of the transplant patients, the sera were positive for HBeAg.HBV DNA in sera was detected by molecular hybridization. HBV DNA was present in the sera of 15 out of 16 hemodialysis patients positive for HBeAg, and in one hemodialysis patient positive for anti-HBe. All renal transplant patients positive for HBeAg were also positive for HBV DNA. Twelve transplant patients were positive for HBV DNA, but negative for both HBeAg and anti-HBe. Determination of HBV DNA was the most sensitive marker of infectivity in patients with end-stage renal disease, and in renal transplant patients.

Adult↗

Familial glomerulonephritis.

Between 1970 and 1984, the diagnosis of glomerulonephritis was made in 860 patients on the basis of a nephritic sediment and/or renal biopsy; of these patients, 86 (10%) had at least one first-degree relative with glomerulonephritis. These patients originated from 45 families and 1674 family members were screened; 172 had glomerulonephritis, of whom 101 could be classified. The diagnostic breakdown of the 101 patients showed that 50.5% had classical Alport's syndrome; 21.8% had atypical forms; 17.8% had familial IgA glomerulonephritis; 1.9% had focal segmental glomerulosclerosis with Wolff-Parkinson-White syndrome; and 7.9% had benign familial haematuria. The proportion of patients with glomerulonephritis who had familial disease was higher than expected. The family history is an important point to consider in the examination of patients with glomerulonephritis.

Adolescent↗

Mesangial IgA nephropathy and idiopathic nephrotic syndrome.

A 17-year-old male presented with nephrotic syndrome associated with microscopic hematuria. Renal biopsy showed only minor glomerular abnormalities (light microscopy). Immunohistology demonstrated strong mesangial deposition of IgA. Electronmicroscopy disclosed widespread effacement of foot processes in combination with isolated osmiophilic mesangial deposits. The patient responded to standard corticosteroid therapy with complete disappearance of proteinuria. Microscopic hematuria, however, persisted. Five months after steroid therapy was stopped, the nephrotic syndrome relapsed. It was again steroid-responsive with persisting microhematuria. From clinical and morphological data we conclude that the patient has concomitant idiopathic nephrotic syndrome (minimal change glomerulonephritis) and mesangial IgA glomerulonephritis. The simultaneous presence of these two diseases may give some hint as to their pathogenesis. In both, abnormalities in T cell regulation have been found. If these were indeed involved in the pathogenesis of the two glomerular diseases, a higher than expected probability for the two entities to coexist in the same patient is to be expected.

Adolescent↗

Genetic polymorphism of C3 and Bf in IgA nephropathy.

C3 and Bf alleles were examined in the general population, in 67 patients with biopsy-confirmed mesangial IgA nephropathy and 81 patients with other types of glomerulonephritis, from the Heidelberg and Leiden renal programmes respectively. In both populations, a significant excess of homozygous phenotype C3FF (3.4% in controls; 10.4% in IgA nephropathy) and a deficit of C3FS heterozygous phenotype (35.8% in controls; 19.4% in IgA nephropathy) were observed in patients with IgA nephropathy, but not in other types of glomerulonephritis. No difference of C3 gene frequencies was found. C3FF was associated with an adverse clinical outcome (a higher prevalence of renal failure and hypertension). A significant excess of Bf-F gene frequency was noted (0.20 in controls; 0.33 in IgA nephropathy). In addition, an excess of phenotype BfFF was found (none in controls; 10.4% in IgA nephropathy). BfFF homozygotes also carried a higher risk of an adverse outcome (renal failure and hypertension). The data suggest a role for genetically coded (presumably) immunological factors in the genesis and course of IgA nephropathy.

Adult↗

Abnormal radiofurosemide binding by Tamm Horsfall glycoprotein of diabetic patients.

In the present study, 8 Type 1 diabetic patients with normal creatinine clearance and 8 matched controls were examined. Tamm Horsfall glycoprotein was isolated with the NaCl precipitation procedure. Its purity was checked by gel-electrophoresis, immunodiffusion and isoelectric focussing. Tamm Horsfall glycoprotein of diabetic patients had higher glucose (p less than 0.05) and lower N-acetylneuraminic acid content (p less than 0.01) than controls. 14C-furosemide binding by Tamm Horsfall glycoprotein was examined using an Amicon ultrafiltration system at 0 degree C. In nominally sodium-free medium, furosemide binding by Tamm Horsfall glycoprotein was significantly (p less than 0.01) higher in diabetic patients than in matched controls. The increment of binding capacity with sodium was similar in controls and diabetic patients so that maximal binding capacity in a NaCl system was 1.7 +/- 0.3 in controls and 3.64 +/- 0.5 in diabetic patients (p less than 0.025). Half maximal furosemide binding by Tamm Horsfall glycoprotein occurred at 1.4 +/- 0.2 mmol Na/l in controls and 0.52 +/- 0.12 in diabetic patients (p less than 0.01). Abnormal radiofurosemide binding of Tamm Horsfall glycoprotein of diabetic patients may be the consequence of abnormal postribosomal modification of the glycoprotein which is synthesized in an insulin- and glucose-sensitive nephron segment.

Adult↗

Myocardial hypertrophy in rats with renal insufficiency.

Increased defatted dry wt of the heart and increased heart calcium content were observed in subtotally nephrectomized male Sprague-Dawley rats compared with sham-operated pairfed controls. Increased heart wt contrasted with no change of the weight of viscera (liver, spleen) and markedly decreased weight of striated muscle. Heart wt was unchanged after 5 days of renal insufficiency, but significantly increased after 14 or 21 days. Increased heart wt persisted despite effective beta adrenoreceptor blockade (2 X 10 mg metroprolol/kg/day i.p.) or effective alpha-1-adrenoreceptor blockade (2 X 2 mg prazosin/kg/day i.p.). Increased heart wt was also demonstrable despite normalization of basal blood pressure (intraarterial blood pressure measurement in conscious animals): blood pressure was lowered in one series with hydralazine/nadolol in drinking water (calculated to deliver 20 and 2 mg/kg/day, respectively) and in another series with furosemide in drinking water (15 mg/kg/day) combined with metoprolol (2 X 10 mg/kg/day i.p.). Increased heart wt was also noted despite correction of anemia by blood transfusion (Hct greater than 40%) and after parathyroidectomy in animals kept eucalcemic with high dietary calcium. Micromorphometry of left ventricular myocardium in perfusion-fixed tissue showed no significant change of the relative proportion of connective tissue and myocardial fibers. Myocardial isomyosin pattern was changed with an increase of fast-migrating V1 isomyosin in animals with renal insufficiency compared to sham-operated pairfed controls.

Adenosine Triphosphatases↗

Digitalis in chronic renal insufficiency.

Cardiac dysfunction is common in patients with terminal renal failure. However, no consensus has been reached with respect to the indications for digitalis therapy. Depression of myocardial contractility may occur as a result of circulating toxic factors, parathyroid hormone, and altered catecholaminergic responsiveness. On the other hand, paradoxical positive inotropic effects have been observed possibly as a result of a circulating natriuretic factor (an endogenous digitalis analogue) which inhibits Na,K-ATP'ase. Pharmacokinetics and pharmacodynamics of digitalis steroids are altered in uremia. Elimination half-lives of strophanthin and digoxin are prolonged, whereas the elimination half-life of digitoxin is unchanged. Altered protein binding and volume of distribution have been noted. Despite its long elimination half-life, most nephrologists favor administration of digitoxin because of its insensitivity to changes in renal function.

Animals↗

Vaccination against hepatitis B in patients with renal insufficiency.

To define the degree of renal insufficiency at which the immune response to vaccination against hepatitis B is impaired, anti-HB concentrations after vaccination with 20 micrograms HB-Vax at 0, 1 and 6 months were examined in 76 dialysis patients, 24 patients with incipient renal failure (S-creatinine 1.4-3.5mg/dl) and in 43 controls. Compared with controls, seroconversion rate and anti-HB concentrations were significantly (p less than 0.02) lower in patients with incipient renal failure. The time course of anti-HBs in dialysis patients with successful vaccination, either with three doses (0, 1, 6 months) or with five doses (0, 1, 2, 4, 6 months) of HB-Vax was compared with healthy controls. The proportion of patients losing anti-HBs and the decrease of antibody concentration was significantly greater in dialysis patients immunised with three doses of the vaccine. In dialysis patients vaccinated with five doses, the percentage losing HB antibodies was slightly higher than in controls, but final titres after 24 months were comparable.

Adult↗