Primary IgA nephropathy: from the first-described cases to the present.
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Biomedical subjects
Publications and source records attributed to J Berger.
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Treatment of adult rats of three age groups (8, 11 and 29 weeks) with haematotoxic doses of three different cytostatic agents (cyclophosphamide, 5-(2-dimethyl-aminoethoxy)-7-oxo-7H-benzo(c)fluorene, and lomustine) demonstrated a tendency to lower the sensitivity of elder animals to cytotoxic effects. The influence of age was especially distinct in changes of the reticulocyte or segmented neutrophil counts after all drugs tested. Changes in marrow nucleated erythroid cell counts were not significantly influenced by age. Reactions of other characteristics also depended on this factor but not following the administration of every drug.
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This is a study of the processing of procollagen to collagen in cultures of skin and tendon fibroblasts. Processing was markedly increased by growing cells for 2-4 days postconfluence and then adding ascorbate to the medium for 2 days prior to labeling with [3H] proline. With this system, more than two-thirds of the pro-alpha chains of type I procollagen in the culture medium, and more than 90% of those in the cell layer, were rapidly processed to pC-alpha, pN-alpha, or alpha chains. Purified, exogenous procollagen was also rapidly processed in cell-free culture medium. The results showed for the first time that exogenous procollagen can be processed in conditioned cell-free medium. The system was then used to compare the processing of procollagen in the medium of normal fibroblasts, cells from one bovine and four human variants of osteogenesis imperfecta, and those from eight human variants of the Ehlers-Danlos syndrome. The cells could be divided into three groups, based on their ability to process type I procollagen: normal, consistently slow, and very slow. The cause of the decreased processing was shown to be associated with either a mutation causing a shortening of an alpha chain or decreased activity of procollagen N-proteinase in cell-free culture medium. Decreased processing of procollagen to collagen occurred with cultured fibroblasts from patients with different forms of both osteogenesis imperfecta and Ehlers-Danlos syndrome. Both of these disease syndromes are associated with abnormalities in the structure or metabolism of procollagen in fibrous connective tissues, bones, and teeth. The results show that defects in the structure, synthesis, or processing of procollagen are readily demonstrated with cultured fibroblasts.
The effectiveness of a single, morning oral dose of 40 mg omeprazole or a twice daily oral dose of 150 mg ranitidine was compared in a randomized endoscopically controlled double-blind trial at 37 clinics in Austria, Germany and Switzerland. A total of 178 out-patients in stages I-IVa (after Savary and Miller) were entered into the trial: 78 in stage I, 60 in stage II, 27 in stage III, and in 13 in stage IVa. As early as at the end of the third treatment week there was a significantly higher rate of complete healing or reduction into a lower stage with omeprazole than ranitidine (85% vs 67%; P less than 0.02). After six treatment weeks, healing tendency after omeprazole compared with ranitidine was 85% vs 45% (P less than 0.04). Omeprazole also brought earlier improvement in symptoms. The difference was statistically significant for heartburn (pyrosis): P less than 0.01. Both drugs were equally well tolerated and there were no clinically significant side-effects. This is the first demonstration that the ATPase inhibitor omeprazole is superior to the H2-receptor antagonist ranitidine in the treatment of reflux oesophagitis.
Alkaline treatment of proteins leads to chemical changes which alter the proteins' digestibility. Severely alkali-treated casein (0.2N NaOH, 80 degrees C, 1 hour) in the diet reduces food intake and growth of young but not of adult Sprague Dawley rats. Gastrointestinal transit time is not reduced significantly in either young or adult rats. Food intake and growth rate are improved by amino acid supplementation. In this case, protein content and total leucine aminopeptidase activity are increased in the distal part of the small intestine whereas gamma-glutamyl-transpeptidase and maltase activities are increased in both the proximal and distal parts. Alkaline phosphatase activity remains unchanged. These intestinal adaptations differ from those observed in rats receiving a diet containing untreated casein and graded levels of a synthetic trypsin inhibitor. In the latter, protein digestibility remains high, gamma-glutamyltranspeptidase and also maltase activities are increased in the proximal and medial parts of the small intestine only. Intestinal adaptation in rats receiving alkali-treated casein does not result from a deficiency of pancreatic proteases activity. Ileal accumulation of undigested peptides from insufficient hydrolysis of alkali-treated casein may account for these mucosal adaptations.
Direct immunofluorescence studies of graft biopsies from 662 renal transplant recipients demonstrated linear IgG deposition along tubular basement membranes (TBM) in 18 cases. In ten of them, circulating anti-TBM antibodies, whose detectable levels varied from 1/4 to 1/100, were demonstrated by indirect immunofluorescence on normal human kidneys. These antibodies reacted with every human kidney tested and in two cases, it could be demonstrated that they recognized the TBM of the patient's own end-stage kidney. Hence, they reacted as autoantibodies. Circulating anti-TBM antibodies were detected within the first 6 months after transplantation, remained present for an average of 3 months, and never recurred once they had disappeared. Serial biopsies demonstrated the loss of IgG linear fixation on TBM. Neither tubular nor interstitial injury was significantly associated with the presence of anti-TBM antibodies, and the transplant survival was not different in these patients who developed anti-TBM antibodies compared to our entire population of transplant biopsies.
Purification, molecular weights, amino acid compositions, and partial sequencing of intestinal alkaline phosphatases (EC 3.1.3.1) from human adult, human fetal, and bovine sources is reported. Additional sequence information is presented for the bovine liver isozyme. Comparisons are made of the partial primary structures of intestinal alkaline phosphatases with those of the isozymes from liver and placenta. Homologies among these isozymes provide structural data to corroborate some concepts of the etiology of these isozymes and refute others.
The objective of this study was to determine the rate of bile-pancreatic secretion of zinc, protein and carboxypeptidase (CP) in response to three different dietary proteins, egg white (EW), soy protein isolate (SPI) and casein. The infusion of protein into the duodenum stimulated a significant increase in the secretion rate of zinc, protein and CP in bile-pancreatic juice. There was a high degree of correlation between the concentration of zinc and enzyme activity (CPA and CPB) in bile-pancreatic juice indicating that zinc in bile-pancreatic juice is associated with CP activity. The average secretion rate of zinc, protein and CP during the 1-h period after infusion of protein was significantly greater after SPI infusion than after casein. The bile-pancreatic secretion rate of protein, zinc and CPB in response to EW infusion was consistently intermediate between SPI and casein and did not differ statistically from either. Only CPA secretion rate was significantly greater after EW than after casein. Differences in protein digestibility appear to account for the greater pancreatic response to SPI, and this factor may be important in understanding the effect of protein source on zinc bioavailability.
A significant correlation between MCV and RBCC in intact rats was discovered (r = -0.868, p much less than 0.001, slope = -6.756). Anaemia was induced and the changes in this relationship were studied. Slopes of regression lines (from +1.813 to -118.398) depended on the time which elapsed after strong PHZ-induced haemolytic event: first they changed to positive values, subsequently (during deepest anaemia) to the normal state and to more negative values during the recovery from anaemia. Emergence of MCV values from the regression curve began after weak haemolytic stress from repeated loading of PHE but the values observed did not exceed the prediction interval for individual MCVs.
Fifty-nine unrelated Liberians have been studied for human leukocyte antigens (HLA). Twenty-three individuals were classified as localized and 24 as generalized onchocerciasis, and the remaining 12 subjects showed no signs of the infection. HLA-typing documented differences in phenotype frequencies for class I (A, B, C) and class II (DR) antigens between the 3 groups of tested subjects. The strongest differences were observed between the localized form and the group without infection with a predominance of HLA-B35 (52% vs. 25%), Cw4 (48% vs. 25%), DR3 (57% vs. 17%), DR5 (65% vs. 8%, DRw52 (96% vs. 33%), and a decrease of DR1 (4% vs. 42%). Differences could also be stated for distinct HLA antigen combinations comprising these relevant antigens. The findings in part hold also true for the comparison of the total group of onchocerciasis (localized plus generalized form) versus the group without infection, however, at a lower level of difference. This pilot study indicates that both forms of onchocerciasis represent different immunological types of host responsiveness.
Twelve of 767 renal allograft recipients developed linear fixation of IgG along the glomerular basement membrane (GBM) by direct immunofluorescence technique. This was associated with linear fixation along the tubular basement membrane in 7 of them. Circulating anti-GBM antibodies were not detected by indirect immunofluorescence or radioimmunoassay in any patient whereas anti-TBM antibodies were found in 2 of 4 with linear TBM fixation. Among the 12 patients with linear GBM fixation, 5 had Alport's syndrome; the 7 others had various renal diseases, excluding anti-GBM nephritis. Among the 767 patients, 34 had Alport's syndrome or variants (i.e., 4.5%). The incidence of linear GBM fixation is much higher in Alport's syndrome than in other renal diseases. Linear GBM fixation was not clearly related to anti-GBM antibodies and was not accompanied by significant deterioration of graft function. These findings may be relevant, however, to the missing GBM antigen in Alport's syndrome.
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Increased nuclear segmentation was experimentally induced in rat mature granulocytes. Some mature hypersegmented granulocytes were tetraploid, other hypersegmented granulocytes were diploid. The phenomenon of the formation of tetraploid mature granulocytes has not been observed till the present time. Our data suggest that the increase in nuclear segmentation of granulocytes can be stimulated by elevated DNA content, but the process of nuclear lobe formation is not dependent on cellular content of DNA.
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The effectiveness of omeprazole (20 mg orally each morning) or ranitidine (150 mg orally twice daily) in the treatment of gastric ulcer was compared in 184 out-patient in a randomized, endoscopically controlled multi-centre double-blind ("double dummy") trial. Healing rates with omeprazole after two, four and eight weeks were 43, 81 and 95%, respectively, those with ranitidine were 45, 80 and 90%, a statistically not significant difference. Independently of medication, small ulcers (less than 8 mm diameter) healed more quickly than larger ones. Ulcers in the body of the stomach responded poorest to both drugs. Smoking had no statistically significant effect on healing rate. Omeprazole and ranitidine had similarly favourable effects on symptoms. Neither side effects nor changes in biochemical parameters could be ascribed to omeprazole. Both drugs had equivalent effects on the healing of gastric ulcers in the stated dosages.