Polycystic liver disease: immunohistochemical characterization of cyst epithelia and extracellular matrix.
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Biomedical subjects
Publications and source records attributed to A Zimmermann.
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112 patients with idiopathic childhood nephrotic syndrome have been referred from 1970 through 1989 at the Department of Pediatrics, University of Berne. One patient remitted spontaneously without medication. Ninety-eight patients responded to prednisone: 15 had a single bout of nephrosis, 47 developed a tendency towards relapses and 36 steroid dependence. In 28 patients with tendency towards relapses cure took place on either prednisone alone or prednisone plus cyclophosphamide. In 18 patients with steroid dependency cure took place on prednisone alone or prednisone plus cyclophosphamide. Thirteen patients failed to respond to steroids. The course of the disease was more benign in 68 patients with minimal change disease as compared with 14 patients with focal and segmental glomerular sclerosis. Immunofluorescence studies demonstrated mesangial IgM deposits in 14 out of 54 patients, but this finding was not a marker for poor steroid response or progression to renal failure. The course of the disease was especially unfavourable in patients with persisting nephrosis on completion of the initial course of steroid therapy. In conclusion it appears appropriate to define the disease in terms of steroid responsiveness as steroid resistant patients sometimes show normal glomeruli, steroid responsive sometimes have focal and segmental glomerular sclerosis or mesangial IgM deposits, and decisions depend more on the steroid responsiveness than on the histological features.
Effects of x-irradiation on the urinary bladder of male New Zealand rabbits were studied by means of light microscopy 100 weeks after exposure. The absorbed dose was 33, 36 or 39 Gy given in 5 daily fractions administered to the whole, the cranial or the caudal part of the bladder. The changes in the epithelium and in the muscular tissue were dose-dependent while the changes in the submucosa and in the extramuscular layer were not. The transitional epithelium was generally either atrophic or hyperplastic. If dysplastic or neoplastic changes were seen, the involved areas were mostly surrounded by an apparently normally differentiated epithelium and the highly specialized superficial cells lining the bladder cavity were always present. The submucosal and muscular tissues showed fibrosis and changes in blood vessels and, sometimes also in lymph vessels.
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Forty-five extrahepatic bile duct carcinomas (i.e., tumors of the region proximal to the duct junction, including Klatskin tumors, tumors of the lower mid-region, and tumors of the ampulla of Vater) and 11 gallbladder carcinomas were immunohistochemically examined for p53 protein expression, using the DO-7 monoclonal (mAb) and the CM-1 polyvalent (pAb) antibodies and an antigen retrieval method. Because the DO-7 mAb was found to be significantly more reliable than the CM-1 pAb in detecting p53 immunoreactivity, the immunohistochemical results obtained with the former antibody were used for comparing p53 protein immunoreactivity with tumor site, tumor grade, and survival of patients. Approximately one third (3 of 10) of the proximal tumors were found to express weak p53 immunopositivity, whereas moderate immunopositivity and higher rate (18 of 29) was observed in tumors of the lower mid-region. Finally, moderate and marked p53 immunopositivity was observed in tumors of the ampulla (5 of 6) and gallbladder (8 of 11). In tumors of the lower mid-region of the ampulla and the gallbladder, a significantly higher p53 positivity was noted in high-grade compared with low-grade neoplasms. For the cases in which complete follow-up was available (11 tumors of the low mid-region), median survival of patients with p53-negative tumors was 25.7 months, whereas survival of those with p53-positive tumors was 5.2 months.(ABSTRACT TRUNCATED AT 250 WORDS)
The aim of this study was to investigate the long-term consequences of non-rearterialization of the graft in rat liver transplantation. Liver transplantation with (AOLT) and without graft rearterialization (NOLT) was performed in anesthetized male Lewis rats. Quantitative morphometry and semiquantitative histopathology of the liver were performed at various times after operation. Volume fractions of tissue components were determined. The number of arteries and bile ducts per portal tract were measured in histological sections from both groups. Hepatic blood flow was measured using the radioactive microsphere technique in rats after NOLT (6 months). AOLT livers had a preserved lobular architecture at all time points and unaltered volume fractions. In addition, AOLT livers maintained approximately one artery and one bile duct per portal tract after transplantation. NOLT livers showed bile duct damage at 3 days, cellular infiltration and ductular proliferation at 1 week, increased ductular proliferation at 4 weeks, and fibrosis at 6 months. The volume fractions for nonhepatocyte parenchyma (3 days, 19.14 +/- 1.29; 1 week, 20.44 +/- 1.76; 4 weeks, 15.46 +/- 3.14), bile ducts/ductules (1 week, 4.88 +/- 1.07; 4 weeks, 7.20 +/- 2.42), and connective tissue (4 weeks, 4.02 +/- 1.66; 6 months, 14.94 +/- 0.63) were significantly increased. Hepatocyte volume fraction was significantly decreased at all time points. A total of 1.58 +/- 0.08 arteries/portal tract were found in NOLT livers after 4 weeks, rising to 2.44 +/- 0.10 arteries/portal tract after 6 months. At 6 months, hepatic arterial blood flow (0.69 mL/min/g) was significantly higher (P < .02) than control (0.25 mL/min/g).(ABSTRACT TRUNCATED AT 250 WORDS)
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Iron overload to the liver induces hepatic injury, eventually ending up with liver fibrosis or cirrhosis. Pathogenic mechanisms involved in liver damage are only partially known, but there is evidence for an important role of iron-induced reactive oxygen species. We have, therefore, analyzed the immunohistochemical reactivity for two major free radical scavengers, copper/zinc and manganese superoxide dismutase (Cu/Zn- and Mn-SOD's) in three situations of hepatic iron overload, and compared enzyme patterns with grades of iron deposition, grades of fibrosis, and levels of microphotometrically measured type IV collagen immunoreactivity. Cu/Zn- and Mn-SOD reactivity was detectable in hepatocytes with a heavy and a low iron burden, but Cu/Zn-SOD staining was more intense than that of Mn-SOD in the three groups analysed. There was trend for microphotometrically measured type IV collagen levels to increase with the amount of iron, and increased collagen IV was correlated with higher grades of Cu/Zn-SOD, but not of Mn-SOD, reactivity. The findings suggest that the two SOD's may be differentially expressed in states of hepatic iron overload, and that low expression of the inducible radical scavenger, Mn-SOD, may play a role in chronic iron toxicity.
Early fulminant liver allograft failure is a post-transplant syndrome presenting as massive haemorrhagic necrosis of the graft. A single organ Shwartzman reaction has previously been suggested as a cause. We report on a patient who lost her liver graft due to fulminant graft failure ten days after orthotopic liver transplantation (OLT), the liver showing massive haemorrhagic necrosis. Fresh thrombosis was noted in the portal and hepatic veins. As a Shwartzman reaction could be expected to lead to complement deposition in vessel walls, tissue was analyzed for the presence of complement components. However, even though protein-rich and fibrinogen-containing deposits were detected within the vessel walls, these deposits were not immunoreactive for complement (C3 and Clq). These findings suggest that pathogenesis of fulminant liver allograft failure differs from that of a complement-mediated Shwartzman reaction, or of a hyperacute rejection, where IgM and Clq had previously been detected in hepatic veins and arteries.
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NGF receptor bearing peripheral glial cells, purified from chicken embryo dorsal root ganglia, were found to secrete neurite growth promoting activity (NGPA) but no NGF (detection limit 1 pM). If, however, minute concentrations of NGF (2 pM) were added to the glial cultures, an autocrine response was observed. Levels of NGF-like activity in the medium rose up to 50-fold. Induction of this autocrine response occured within a narrow range of NGF concentrations. NGPA production was not affected by addition of NGF. Coculture with neurons influenced the neurotrophic factor production. The data suggest that glial cells can "sense" traces of NGF and regulate its availability during neural development.
The nucleotide sequence of a highly variant of the encephalomyocarditis virus, PV21, was determined. Discounting the poly(A) tail the viral genome is 7.861 kb in length, including a poly(C) region of 157 or 158 nucleotides. The sequence differs in 38 positions from another virulent EMCV variant, EMCV-R (1). However, the PV21 sequence shows only 85% identity with two nonlethal variants isolated in this laboratory (2). A cDNA clone covering the complete virus sequence including a poly(C) region of approximately 150 nucleotides was constructed. The recombinant virus was shown to be infectious in NMRI mice.
We analysed p53 protein immunoreactivity in hepatocellular carcinomas (HCCs) and in liver cell dysplasia (LCD) of patients from an area in Northern China, using five anti-p53 protein antibodies recognizing different epitopes of the protein. In HCCs, the overall prevalence of p53 protein immunoreactivity was 78.3%. However, prevalence was strongly influenced by the type of antibody used, ranging from 67.5% for antibody PAb-1801 to only 10.8% for antibodies PAb-421 and DO-7. p53 protein immunoreactivity was not related to type or grade of HCC. In contrast to former reports, p53 protein staining was restricted to nuclei only when using the CM-1 antibody, whereas two other antibodies yielded both, nuclear and cytoplasmic or membrane staining, and no nuclear staining was observed with antibodies PAb-421 and DO-7, the latter two, however, demonstrating cytoplasmic and membrane staining. For LCD, three subtypes were morphologically and karyometrically defined. Nuclei of some LCD cells were p53 immunoreactive, but positivity was restricted to the small cell variant of LCD. Positivity was different for cirrhosis with or without associated HCC, amounting to 18.9% in the former and 39.4% in the latter. Interestingly, p53 protein immunoreactivity also occurred in a set of small hepatocytes not showing the typical feature of LCD and therefore classified as simple regenerating liver cells.
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Secondary biliary cirrhosis in the rat can be induced by bile duct ligation; the aim of the present study was to investigate whether susceptibility to this injury depends on development. Rats aged 4, 7, 14 and 22 weeks were bile-duct ligated or sham operated. Four weeks later, stereologic analysis of the liver was performed and the volume fraction of parenchyma, bile ducts and connective tissue was determined. Microsomal function was assessed in vivo by the aminopyrine breath test and in vitro by determining the microsomal cytochrome P450 content and microsomal lipid composition. In addition, portal pressure was measured. The volume fraction of parenchyma decreased in an age-dependent fashion in bile-duct ligated rats from 64.0 +/- 11.2% in the youngest to 46.4 +/- 8.4% in the oldest age group. This decrease was compensated by an age-dependent increase in both ductular proliferation and fibrosis. Microsomal function both in vivo and in vitro showed an age-dependent deterioration. Microsomal cholesterol and some individual phospholipids showed age-dependent changes. Portal hypertension developed in all bile-duct ligated groups, but portal pressure was significantly lower in the oldest bile-duct ligated groups (16.0 +/- 2.6 cmH2O) compared with other bile-duct ligated groups (around 21 cmH2O). We conclude that susceptibility to the sequelae of chronic cholestasis depends on the stage of development in rats. In experiments using this model, the age of the rats should be explicitly stated.
To investigate the potential role of lysosomes in cirrhosis, the activity of lysosomal enzymes was analyzed in rats with cirrhosis induced by bile-duct ligation. Twenty-eight days after surgery, the activity of lysosomal enzymes was markedly increased in the homogenate of cirrhotic livers (e.g. arylsulfatase 7 +/- SD 1 vs 17 +/- 3 nmol.min-1.mg-1 in controls and cirrhotics, respectively; p < 0.001). The corresponding plasma levels were also increased (arylsulfatase: 10 +/- 1 vs 25 +/- 9 pmol.min-1.mg-1; p < 0.01). In contrast, the activities of these enzymes in lysosomal fractions did not differ, suggesting an increase in number of lysosomes. The increased lysosomal activity correlated with severity of cirrhosis as assessed by the aminopyrine breath test and with cholestatic parameters but less with transaminases. Since macrophages, cells which are rich in lysosomes, could contribute to the increase in lysosomal enzyme content, these cells were estimated stereologically after being marked immunohistochemically with a monoclonal antibody against the rat macrophage membrane antigen ED2. ED2 positive cells were increased 2.7-fold in cirrhotic livers. This increase cannot account for the observed increase in hepatic lysosomal enzyme content. Furthermore, 1 week after bile-duct ligation, when there was cholestasis but not yet cirrhosis, lysosomal enzyme activities were already increased. These data support the idea that the increased hepatic lysosomal activity in biliary cirrhosis is of hepatocyte rather than of macrophage origin, and is presumably related to cholestasis.
A proto-oncogene, bcl-2, encodes a protein that inhibits programmed cell death (apoptosis) and may play a role in cell and tissue differentiation. As bcl-2 appears to be involved in the turn-over of stem or precursor cells, it is thought to be operational in carcinogenesis pathways. However, apart from certain lymphomas, only limited data are available on the frequency of its expression in solid tumors. Immunohistochemical analysis with an antibody specific for bcl-2 protein was used to detect the protein in hepatocellular carcinomas and in one of the putative precursor lesions, liver cell dysplasia. We detected bcl-2 protein in 5 of 37 hepatocellular carcinomas. Immunoreactivity was not related to type, grade, or extent of PCNA staining of the tumours. No bcl-2 protein staining was observed in three types of liver cell dysplasia. Thus, bcl-2 is abnormally expressed in some hepatocellular carcinomas but not in potential tumour precursor cells.
The aim of this study was to evaluate the predictability of guided tissue regeneration (GTR), using ePTFE-membranes (Gore-Tex) in the treatment of advanced periodontal disease. The study presents long-term results for 88 teeth in 23 patients at least 9 months after membrane surgery. The periodontal lesions included severe horizontal and/or vertical bone loss. The bone level (BL and BL') and the tissue level (TL), a new parameter between cemento-enamel junction and coronal margin of the tissue in the defect, were recorded during surgery: immediately before application of the membrane (BL), after membrane removal (TL) and during a re-entry procedure (BL') 9 to 12 months later. The average tissue gain in the periodontal defect (BL-Tl) at membrane removal was 65.7% (p < 0.001) and the average gain in mineralized tissue at re-entry (BL-BL'), 30.4%, meaning more than 46% of the gained tissue at removal was mineralized at re-entry. The decreased amount of mineralized tissue at re-entry in relation to the tissue gain at membrane removal might be due to formation of a so-called long connective tissue attachment or to mineralization-induced shrinkage of the new tissue and some surgical difficulties in coverage of the newly formed tissue. Nevertheless, an absolute gain of 31% mineralized tissue after GTR can provide a marked improvement in the prognosis of a periodontally severely damaged tooth.