PubMed Health⌕ Search

Biomedical subjects

R Waldherr

Publications and source records attributed to R Waldherr.

At least 73 records · Page 4Linked to original sources
PubMed1995

Tumor induction and prophylaxis following different forms of intestinal urinary diversion in a rat model.

Eighty Wistar rats were randomized into two groups. In group 1 vesicosigmoidostomy with proximal colostomy was performed, in group 2, vesicosigmoidostomy. The total tumor incidence did not significantly (group 1 10/40, 25%; group 2 13/40, 32.5%). The tumor spectrum differed, with more adenocarcinomas in group 2 (11/40, 27.5% vs 4/40, 10%; P = 0.047) and urothelial carcinomas only in group 1 (5/40, 2.5%). One hundred and ten other Wistar rats were randomized into three groups. Animals in group A received vesicoileosigmoidostomy, group B, two-step vesicosigmoidostomy with initial separation of urine and the urocolonic anastomosis, group C, vesicosigmoidostomy. Significantly fewer adenocarcinomas were observed in group A (2/40, 5%) than in group B (16/40, 40%; P < 0.002) and group C (9/30, 30%; P < 0.007). These results indicate a similar cancer risk in all continent forms of urinary diversion, at least via colon. Ileal interposition seems to be an effective carcinoma prophylaxis following ureterosigmoidostomy. The proliferative instability at the urointestinal anastomosis is crucial for the pathogenesis and prophylaxis of this form of carcinogenesis, whereas urine seems to play only a minor role.

Adenocarcinoma↗
PubMed1995

Effect of ursodeoxycholic acid on biochemical parameters, hepatocyte proliferation and liver histology in galactosamine hepatitis in the rat.

The effect of oral administration of ursodeoxycholic acid (UDCA) on biochemical parameters, liver histology and liver cell proliferation was investigated in rats with galactosamine hepatitis. Treatment with UDCA led to a decrease of aminotransferases, but did not show any significant changes in liver histology or liver cell proliferation. The improvement of liver enzymes without change of histology in this animal model of hepatitis following treatment with UDCA is in agreement with results obtained from clinical trials with UDCA in patients with chronic viral hepatitis.

Alanine Transaminase↗
PubMed1995

Hepatocyte proliferation in primary biliary cirrhosis as assessed by proliferating cell nuclear antigen and Ki-67 antigen labelling.

Expression of the proliferating cell nuclear antigen and Ki-67 antigen by hepatocytes was investigated in liver tissue specimens of 29 patients with primary biliary cirrhosis (stage I 13, stage II 6, stage III 5 and stage IV 5 patients) prior to treatment with ursodeoxycholic acid and of five control subjects using immunocytochemical methods. Proliferating cell nuclear antigen and Ki-67 expression were reevaluated in seven patients after 3 years of treatment with ursodeoxycholic acid. Proliferating cell nuclear antigen labelling indices were significantly higher in primary biliary cirrhosis (stage I, 6.4% to 32.4%, median, 10.9%; stage II, 9.6% to 21.6%, median 11.4%; stage III, 5.2% to 12.5%, median, 7.6%; stage IV, 3.8% to 8.9%, median, 5.6%) than in controls (0% to 0.5%, median, 0.1%; p < 0.005). Ki-67 antigen labelling counts were lower than proliferating cell nuclear antigen indices but elevated in all stages of primary biliary cirrhosis (stage I, 0.5% to 3.5%, median 2.0%; stage II, 1.8% to 3.6%, median 2.6%; stage III, 1.3% to 2.5%, median 1.9%; stage IV, 0.4% to 1.7%, median 1.0%) compared with controls (0% to 0.5%, median 0.3%; p < 0.005). After ursodeoxycholic acid treatment, mean proliferating cell nuclear antigen and Ki-67 labelling indices decreased from a median of 9.0% (range, 3.8% to 32.4%) to a median of 7.8% (range, 4.5% to 17.2%; p = 0.045) for proliferating cell nuclear antigen and from a median of 2.5% (range, 0.8% to 3.6%) to a median of 2.1% (range, 0.9% to 3.1%; p = 0.031) for Ki-67 antigen. It is concluded that hepatocyte proliferation is markedly increased in primary biliary cirrhosis, particularly in the early stages of the disease, and that ursodeoxycholic acid treatment reduces proliferative activity in primary biliary cirrhosis.

Cell Division↗
PubMed1995

Hemolytic uremic syndrome complicating postinfectious glomerulonephritis in the adult.

Hemolytic uremic syndrome/thrombotic thrombocytopenic purpura is known to occur as a secondary complication of primary renal diseases, specifically of lupus nephritis, membranous glomerulonephritis, and focal segmental glomerulosclerosis. In a patient without a family history of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura we observed biopsy-confirmed postinfectious glomerulonephritis with humps, with simultaneous subendothelial hyaline deposits and fibrinoid thrombi in arterioles. The patient had a history of febrile pharyngitis with diarrhea 10 days prior to renal biopsy. He presented with transient elevation of serum creatinine, a nephritic sediment, and hypertension not exceeding 160/100 mm Hg. The patient also had purpura, transient thrombocytopenia, and signs of intravascular hemolysis. Results of verocytotoxin serology were negative. With the exception of isolated microhematuria, all findings reverted to normal within 8 weeks without any specific treatment. This case illustrates that hemolytic uremic syndrome/thrombotic thrombocytopenic purpura may complicate primary postinfectious glomerulonephritis in adults.

Adult↗
PubMed1995

Functional rescue of the glomerulosclerosis phenotype in Mpv17 mice by transgenesis with the human Mpv17 homologue.

The germ line insertion of a defective retrovirus into the Mpv17 gene of mice is associated with a recessive phenotype. Mice homozygous for the integration develop glomerulosclerosis at a young age. The phenotype resembles human glomerulosclerosis in its physiological parameters as well as in histology. A human homologue of the Mpv17 gene has been identified, isolated and analyzed. We here show that this gene, which has a role in the production of reactive oxygen species, can rescue the phenotype of Mpv17 deficient mice when introduced by transgenesis. This provides formal proof for the hypothesis that the phenotype is caused by the loss of function of the Mpv17 gene. It also provides evidence for the functional conservation of the Mpv17 gene in mammals and points to a potential role of this gene in human kidney disease.

Animals↗
PubMed1995

Gender-dependent disease severity in autosomal polycystic kidney disease of rats.

The impact of gender on the course of chronic renal failure in polycystic kidney disease (PKD) has been under discussion for years. Recently an animal model of autosomal dominant PKD in the rat became available allowing this topic to be studied. The aim of this study was to evaluate disease severity according to gender, and the occurrence of anticipation and/or genetic imprinting. Male and female affected PKD rats were crossed with respective Wistar-Ottawa-Karlsburg (WOK) rats. From this P generation 26 affected F1 hybrids were obtained, which were then backcrossed with WOK rats, resulting in 275 backcrosses (BC generation). In BC rats the affected males had a significantly higher kidney weight, worse histology and poorer renal function than the females. In the male, but not the female rats of the BC generation, transmission from an affected F1 mother resulted in significantly higher kidney weight, worse histology and poorer renal function than when the gene was inherited through an affected father. Since at the same time body and kidney weight were higher in the respective unaffected males, the previous effect in the affected rats might be due to a growth factor transferred by the mother's milk. The sex of the P generation had no such impact on these parameters. Thus our data provide no evidence for disease anticipation and genetic imprinting (in the classical sense) in the PKD rats, and the assumption of a gender-dependent disease expressivity is favored.

Animals↗
PubMed1995

PDGF and TGF-beta contribute to the natural course of human IgA glomerulonephritis.

PDGF and TGF-beta are known mediators of mesangial cell proliferation and matrix expansion. The presence of these regulatory factors was examined in 30 renal biopsies from patients with IgA glomerulonephritis (IgA-GN) at the mRNA and protein level. Normal renal tissue served as control. The mRNA expression of PDGF A/B chains, PDGF-beta R and TGF-beta 1 was evaluated by means of RT/PCR with subsequent Southern blot hybridization and/or non-radioactive in situ hybridization. In addition, PDGF-AB/BB, PDGF-beta R, TGF-beta isoforms (beta 1, beta 1 + 2, beta 2 + 3), the small TGF-beta 1 latency associated peptide (TGF-beta 1 LAP) and the extracellular matrix proteins tenascin and decorin were analyzed by immunocytochemistry. The expression of growth factors was correlated with light microscopic and clinical features. Compared to normal control kidneys, an increased expression of PDGF-BB/PDGF-beta R mRNAs and the corresponding proteins was observed in all biopsies with IgA-GN. Up-regulation was related to the degree of glomerular proliferation and the extent of fibrosing interstitial lesions. In contrast, there was a discordance between TGF-beta 1 mRNA and protein expression (evaluated by immunocytochemistry). In all biopsies, irrespective of the stage of the disease, abundant TGF-beta 1 transcripts were detected, whereas TGF-beta 1 immunoreactivity was expressed to a lesser degree and disclosed a more variable staining pattern. In patients with significant proliferative glomerular lesions and minor tubulointerstitial alterations, TGF-beta 1 positivity was confined to areas of glomerular proliferation, whereas in cases with more severe histology including sclerosing lesions TGF-beta 1 immunoreactivity was less prominent. The distribution and the intensity of TGF-beta 1 LAP staining commonly exceeded the positivity noted for TGF-beta 1, indicating only limited TGF-beta 1 activation. A decreased reactivity for tenascin accompanied the morphological features of glomerular sclerosis. The staining patterns and the fact that only very few inflammatory cells, particularly CD68 positive monocytes/macrophages, were detected in glomeruli confirm that predominantly resident glomerular cells (mesangial and endothelial cells) are the major source of up-regulated growth factor production in IgA-GN. Since the expression of PDGF-AB/BB paralleled the severity of proliferative glomerular changes, PDGF seems to represent a potential indicator of activity in this condition. It is suggested that an imbalance between PDGF and TGF-beta (by restricted translation and/or activation) production contribute to the progressive nature of IgA-GN.

Adult↗
PubMed1995

Prevalence of Helicobacter pylori infection and gastritis among young adults in China.

To investigate the prevalence of gastritis and H. pylori infection among young Chinese in Henan Province, a high incidence area for oesophageal cancer in China, the gastric mucosa was examined in 194 asymptomatic subjects, aged 15-26 years, in the course of an epidemiological study of precursor lesions of oesophageal cancer. Histopathological grading of gastritis and determination of H. pylori infection were performed on haematoxylineosin and Warthin-Starry stained section. An enzyme-linked immunosorbent assay was used to detect the presence of serum IgG antibodies to H. pylori. A very high prevalence of gastritis (93.8%) was found: 71 subjects (36.6%) presented with superficial gastritis (14 active), 94 (48.5%) with diffuse gastritis (92 active) and in 17 cases (8.8%) diffuse gastritis (16 active) was accompanied by focal atrophy. Silver staining detected H. pylori in 166 (85.6%) of the study participants. However, serological techniques identified H. pylori in only 109 (56.2%). H. pylori was seen in all the 119 cases showing histological signs of active gastritis, in 41 of the 63 cases (65%) without activity, and also in 50% (6/12) of histologically normal subjects. H. pylori infection was found to be associated with a 2.5-fold higher prevalence of chronic atrophic gastritis compared with non-atrophic gastritis. A family history of stomach cancer, consumption of pickled vegetables more than twice a month, and a high monthly salt consumption (> 500 g/month) also showed a positive association.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Serum hepatocyte growth factor levels in primary biliary cirrhosis.

BACKGROUND: Recent studies have shown that serum levels of hepatocyte growth factor, a potent mitogen for hepatocytes, are increased in patients with fulminant liver failure and with advanced stages of liver cirrhosis. DESIGN: Retrospective study. METHODS: Serum levels of hepatocyte growth factor (HGF) were determined in 26 patients with advanced stages of liver cirrhosis by means of an enzyme-linked immunosorbent assay. In 23 of these patients, liver biopsies were obtained before treatment with ursodeoxycholic acid and investigated for hepatocyte expression of the proliferating cell nuclear antigen (PCNA) and the Ki-67 antigen by immunocytochemical methods. RESULTS: In 25 of the 26 patients, serum HGF levels did not differ from those of patients with histologically normal livers. Levels did not vary between the different stages of primary biliary cirrhosis but increased moderately when re-evaluated after a period of 24 +/- 4.9 months or 54 +/- 10.7 months. An abnormally increased serum HGF level was observed in only one patient, who had end-stage liver cirrhosis before liver transplantation. Both PCNA and Ki-67 antigen labelling indices were significantly higher at all stages of primary biliary cirrhosis than in normal liver, indicating increased hepatocyte proliferation, but the labelling indices did not correlate with the HGF concentrations in serum. CONCLUSION: Serum HGF levels in almost all patients with primary biliary cirrhosis were within normal limits despite increased hepatocyte proliferation. The results support the hypothesis that HGF serum levels may reflect liver dysfunction rather than active hepatocyte proliferation.

Adult↗
PubMed1995

Congenital erythropoietic porphyria associated with nephrotic syndrome and renal siderosis.

A 9-year-old boy with typical features of congenital erythropoietic porphyria who had received more than 50 blood transfusions developed the steroid-resistant nephrotic syndrome in the presence of normal glomerular function and glucosuria. Renal biopsy showed focal segmental glomerulosclerosis and widespread iron deposits. Magnetic resonance scanning revealed advanced siderosis of liver and kidneys. During a 4 year treatment by desferrioxamine the serum ferritin level was reduced, proteinuria dropped and serum proteins increased whilst glomerular filtration decreased slowly. It is suggested that the nephrotic syndrome may be a consequence of renal siderosis amenable to iron-chelating therapy.

Anti-Inflammatory Agents↗
PubMed1995

Circulating enzyme activities of collagen turnover and undulin in patients with various degrees of schistosomiasis and alcoholic liver cirrhosis.

In contrast to alcoholic liver disease, schistosomiasis leads to presinusoidal hepatic fibrosis, which determines the prognosis of the disease. Since conventional liver function tests and liver biopsy provide little information about the dynamics of the fibrotic process, we measured the activities of two circulating enzymes of collagen turnover, namely serum galactosylhydroxylysyl-glucosyl-transferase and plasma prolidase activity, together with undulin, a novel extracellular matrix glycoprotein. The study encompassed 15 healthy control subjects. 69 patients with various stages of Schistosoma mansoni/hematobium infection [28 with early active infection and no organ involvement, 27 with hepatosplenic involvement, and 14 with complications of portal hypertension] and 16 patients with alcoholic liver cirrhosis. Liver biopsies were obtained from 30 schistosomal patients for histopathological grading. Serum galactosylhydroxylysyl-glucosyl-transferase was significantly increased in all clinical stages of schistosomiasis (p < 0.05), but normal in alcoholic cirrhosis. In contrast, plasma prolidase activity showed a significant increase only in early schistosomiasis (p < 0.01), but dropped to subnormal levels in advanced stages (p < 0.001). Undulin was highly elevated both in alcoholic patients and in all schistosomal groups (p < 0.001), and was capable of distinguishing between early and advanced schistosomal stages. We conclude that serum undulin may be a valuable non-invasive parameter for monitoring the course of schistosomal and alcoholic liver disease.

Adult↗
PubMed1995

C3, C4, factor B and HLA-DR alpha mRNA expression in renal biopsy specimens from patients with IgA nephropathy.

The deposition of complement in the kidney mesangium is a constant finding associated with renal injury in IgA nephropathy, even though IgA does not bind complement. We have previously reported that complement gene expression in the kidney increases concurrently with the progression of immune complex disease in murine lupus nephritis. We have now studied the expression of C3, C4, factor B and HLA-DR alpha mRNA by in situ hybridization in renal biopsy specimens of patients with IgA nephropathy and compared these findings to those in patients with other immune-mediated diseases of the kidney, hereditary nephritis and normal kidney. In IgA nephropathy, C3 and factor B mRNA were expressed in the renal tubular epithelial cells, while no expression of either C3 or factor B mRNA was apparent in the glomerulus. Specimens from patients with other immune-mediated forms of chronic glomerulonephritis also showed a similar pattern of expression of C3 and factor B mRNA only in the tubules, but not in the glomerules. However, C3 and factor B mRNA were not found in normal kidney tissue or biopsy specimens from patients with hereditary nephritis. C4 mRNA was expressed in the tubular epithelial cells in all specimens examined, indicating that C4 mRNA is constitutively expressed in the human kidney. In IgA nephropathy HLA-DR alpha mRNA was observed in the interstitium, but not the tubules or glomerular cells. In contrast, HLA-DR alpha mRNA was present in the glomerulus and scattered in the interstitium in other immune-mediated kidney diseases. There was no expression of HLA-DR alpha mRNA in hereditary nephritis or normal kidney. Our findings, which reflect the immunopathogenic events in vivo, provide new insights as to the interpretation of the molecular immunology of this immune complex disease.

Adolescent↗
PubMed1995

Tissue factor expression in an animal model of hydronephrosis.

BACKGROUND: Hydronephrosis is associated with interstitial fibrosis and occlusion of renal capillaries by fibrin. However, the mechanisms leading to fibrin formation is unknown. METHODS AND RESULTS: Twenty days after unilateral ligation of the ureter, interstitial fibrosis occurred in the ligated kidney. Fibrosis was preceded by infiltration of inflammatory cells (macrophages, B and T lymphocytes). Staining with an antibody against von Willebrand factor demonstrated newly formed capillaries in the fibrosing tissue as well as prominent fibrin deposition. Fibrin staining was found around vessels, in the interstitium, the glomeruli, and tubuli. Fibrin deposition was less prominent in the non-ligated kidney and almost absent in sham-operated animals. The expression of tissue factor, the central initiator of coagulation, was induced within 5 days after ligation in the operated kidney but not in the sham-operated animals. Tissue factor positivity was observed by immunohistochemistry in vascular endothelial cells, the vessel wall, tubular epithelial cells, glomerular capsular cells, Bowman's space and in the interstitium. Tissue factor induction was due to increased transcription, since in-situ hybridization showed increased levels of mRNA in the ligated kidney compared to sham-operated rats. The tissue factor gene is under control of the transcription factors activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappa B). When extracts of operated organs were compared with kidneys of sham-operated rats or contralateral kidneys in electrophoretic mobility shift assays, an increase in AP-1 and NF-kappa B binding activity to their respective binding sites in the tissue factor gene was observed in the operated, but not in the contralateral kidney or kidneys of sham-operated animals. CONCLUSION: Ureteral ligation leads to infiltration of inflammatory cells, increased AP-1 and NF-kappa B expression in the kidney, resulting in increased tissue factor transcription and translation, and ultimately in increased fibrin deposition.

Animals↗