PubMed Health⌕ Search

Biomedical subjects

U Pfeifer

Publications and source records attributed to U Pfeifer.

At least 55 records · Page 3Linked to original sources
PubMed1996

Histopathologic findings in chronic hepatitis C.

Evaluation of liver biopsies in hepatitis C is aimed at confirming the clinical and serologic diagnosis, grading of necroinflammatory activity, staging of consecutive fibrosis, ruling out or confirming liver diseases of different etiology, and assessment of therapeutic effects. Usually, the course of chronic hepatitis C virus (HCV) infection is slow, with mild inflammatory changes. Nevertheless, even in mild asymptomatic chronic hepatitis C episodes of higher inflammatory activity associated with extensive piecemeal necrosis and porto-central bridging, necrosis can accelerate the course of the disease. For this reason, the traditional, morphologically based classification of chronic hepatitis and the term "chronic persistent hepatitis" have lost their predictive usefulness, especially in hepatitis C. Chronic hepatitis should be characterized by etiologic designation as well as grade and stage of the disease. Portal lymphoid aggregates, some inflammatory bile duct damage and mild steatosis are the most characteristic features by which hepatitis C can be differentiated from other progressive inflammatory liver diseases. Antibodies directed against HCV antigens allow identification of viral proteins by immunohistochemistry. Immunostaining for hepatitis B antigens, for alpha-1-antitrypsin and copper staining are helpful in detecting hepatitis B and congenital liver diseases (Wilson's disease, alpha-1-antitrypsin deficiency) as possible causes of chronic progressive inflammatory liver disease. Centrilobular Mallory's hyalin, identified by immunostaining for ubiquitin in combination with perivenular fibrosis, is helpful in diagnosing concomitant alcoholic liver disease. In our own biopsy material (n = 100) and autopsy material (n = 58), HIV/HCV-coinfected patients have a significantly higher rate of fibrosis and cirrhosis than HIV patients without HCV infection. Hepatitis C can apparently aggravate the course of HIV infection. Our morphologic findings support the clinical observation that chronic HCV infection seems to be the main cause of liver failure, especially in the risk group of HCV/HIV-coinfected hemophiliacs.

Chronic Disease↗
PubMed1995

Progressive liver failure in a patient with adult Niemann-Pick disease associated with generalized AL amyloidosis.

We report a case in which an adult form of Niemann-Pick disease (type B of NPD) was associated with a rapidly progressive generalized AL amyloidosis of kappa type. Both diagnosis were made by biopsy, the NPD by bone marrow biopsy and fibroblast culture, the amyloidosis by liver biopsy. Malignant non-Hodgkin lymphoma was not found. The patient, a 67-year-old woman, died from hepatic coma subsequent to a progressive liver failure. We discuss possible relations between the lysosomal storage disease and the development and rapid progression of amyloidosis.

Aged↗
PubMed1995

Hyperproliferative state of liver acini and pancreatic islets after intraportal transplantation of a small mass of islets of Langerhans in streptozotocininduced diabetic rats.

After the portal-embolic transplantation of a low number of isologous islets of Langerhans into streptozotocin-diabetic rats altered liver acini emerge down-stream to the islet grafts. The hepatocytes of these altered liver acini store high amounts of glycogen and/or fat. The proliferation of the hepatocytes of such altered acini and simultaneously their apoptotic elimination were increased strongly, compared with the surrounding unaltered liver acini. After transplantation of a high number of islets, altered liver acini were not observed. The reason for these focal phenomena was supposed to be the persistent systemic hyperglycemic diabetic state which stimulates the beta cells to produce insulin and to secrete it in maximal amounts. This hypothesis has been supported by electron-microscopical examination of the transplanted islets in a former publication, but the proliferative activity of the transplanted islet epithelial cells has not so far been examined. Furthermore, the period of observation has been only three weeks, and it seemed of interest to determine whether the locally increased hepatocytic proliferation and the stimulation of the beta-cells would persist for a longer time. 450-500 (group I, n = 14) or 1500-2000 (group II, n = 8) isologous pancreatic islets were transplanted to adult male Lewis-rats made diabetic by streptozotocin. Group I animals stayed hyperglycemic after transplantation, group II animals became normoglycemic. 5-bromo-2'-desoxyuridine (BrdU) was applied by osmotic minipumps for 6 days before death (6, 13, 21 and 67-77 days after islet transplantation). In group I animals the mitotic index (number of mitotic figures per 1000 hepatocytic nuclei), the apoptotic index (number of apoptotic bodies per 1000 hepatocytic nuclei) and the immunohistochemical-labeling index for BrdU (BrdU-labeled hepatocytic nuclei per 100 hepatocytic nuclei) of these altered acini (A) were compared with the adjacent non-altered acini (NA). The mitotic index in A was 40-fold to 100-fold increased compared with NA (for the whole period of observation). The apoptotic index in A was 6-fold to 20-fold increased compared with NA. The BrdU-LI in A was 20-fold to 80-fold increased compared with NA. In group II animals altered liver acini did not emerge. Furthermore, BrdU-LI of epithelial cells of group I islets were significantly higher compared with group II islets (28.4 vs. 6.3 at day 6, 28.8 vs. 4.2 at day 13, 23.2 vs. 2.9 at day 21, 15.3 vs. 0.1 at days 67 to 77, respectively). It is supposed that two different types of proliferative stimuli were active in this model of low number islet transplantation: 1) The chronic hyperglycemia induces endocrine epithelial cell proliferation in the grafts. 2) The local chronic hyperinsulinism induces glycogen and fat storage, proliferation and apoptotic elimination of the hepatocytes in the liver acini down-stream to the stimulated islets.

Animals↗
PubMed1995

[Hepatitis and posthepatic cirrhosis in AIDS].

Liver biopsy (n = 35) and autopsy (n = 71) specimens from HIV infected HCV-positive and HCV-negative haemophiliacs and non-haemophiliacs and liver biopsies (n = 33) from HIV-negative HCV-infected haemophiliacs and non-haemophiliacs were studied by histo- and immunohistochemistry to investigate the influence of HIV-coinfection on chronic C hepatitis (> 10 years duration). Almost all HIV-infected patients had a CD4 cell counts < 200/microns3. In biopsies and autopsies HCV-infection lead to stronger portal, periportal and lobular inflammatory changes independent from HIV-infection and haemophilia. However, HIV-infected patients with HCV-coinfection showed much more granulocytic infiltrates, particularly in the small bile ducts. In biopsies and autopsies HCV infection was associated with a stronger (centrilobular) fibrosis, particularly in HIV-positive haemophiliacs, and significantly stronger compared to HCV-negative patients. In the autopsy group half of the HIV-infected and HCV-positive haemophiliacs (n = 20) had developed posthepatitic liver cirrhosis due to C hepatitis, contrasted by two liver cirrhosis in HCV-infected non-haemophiliacs (n = 6) due to chronic B and C hepatitis and chronic alcohol abuse; no liver cirrhosis was observed in HIV-positive HCV-negative non-haemophiliacs (n = 45). Cholestasis and mild granulocytic cholangiolitis was a predominant feature in HIV/HCV-coinfection and similar distributed in haemophiliacs and non-haemophiliacs. The findings are suggestive that HIV-coinfection aggravates the course of a preceding hepatitis C virus infection, by a more granulocytic inflammatory infiltrate, stronger (centrilobular) fibrosis followed by a high incidence of posthepatitic cirrhosis--particularly in multitransfused haemophiliacs--and by cholestatic hepatopathy.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Hyperproliferative liver acini after intraportal islet transplantation in streptozotocin-induced diabetic rats.

BACKGROUND: Since insulin is known to have growth-promoting effects, it seemed of interest to study whether a local hyperinsulinemia after intraportal islet transplantation would induce a focal proliferation of the hepatocytes. EXPERIMENTAL DESIGN: Four, 11, and 21 days after isologous intraportal transplantation of 450 to 1000 islets of Langerhans in streptocotocin-induced diabetic adult male Lewis-rats (n = 12) the animals were perfused with 3% glutaraldehyde, and the livers were cut into sections of 0.5-mm thickness. Stereomicroscopically the islets and the accompanying acini could be identified. These areas were prepared for histologic examination (1-micron-thick sections, staining by Richardson). The islets of Langerhans in the portal triads had induced remarkable changes (accumulation of fat and glycogen) of the hepatocytes in the respective acini. Therefore, it was possible to identify them for the examination of local cell proliferation. The mitotic index (number of mitotic figures per 1000 hepatocytic nuclei) and the apoptotic index (number of apoptotic bodies per 1000 hepatocytic nuclei) of these altered acini (A) were compared with the adjacent nonaltered acini (NA). In a further nine islet-transplanted diabetic animals 5-bromo-2'-desoxyuridine (BrdU) was applicated by osmotic minipumps for 6 days before death (6, 13, and 21, days after islet transplantation). The immunohistochemical labeling indices for BrdU (BrdU-labeled hepatocytic nuclei per 100 hepatocytic nuclei) of A and NA were compared. RESULTS: The mitotic indices in A and NA were 1.2 and 0.06 at day 4, 2.5 and 0.09 at day 11, and 6.4 and 0.25 at day 21, respectively. The apoptotic indices in A and NA were 2.9 and 0.63 at day 4, 4.1 and 0.54 at day 11, and 8.0 and 0.5 at day 21, respectively. The BrdU labeling indices in A and NA were 28.0 and 1.3 at day 6, 37.0 and 1.9 at day 13, and 17.5 and 0.9 at day 21. CONCLUSIONS: These data show that after intraportal islet transplantation the proliferative activity and at the same time the apoptotic elimination of hepatocytes are significantly increased focally in the long-term hyperinsulinemic liver acini.

Animals↗
PubMed1993

[Primary hyperreninemia. An unusual cause of secondary arterial hypertension].

In 1975, scintigraphy revealed a 6.5 x 5 cm tumour in the region of the left adrenal in a 36-year-old man with known hypertension for 5 years (systolic pressure up to 250 mm Hg, diastolic up to 130 mm Hg). A laparotomy was performed for a suspected phaeochromocytoma. A tumour was located in the upper pole of the kidney and removed together with the kidney. The blood pressure quickly returned to normal after the operation: it remained stable for the following 17 years (between 130/80 to 150/90 mm Hg). Originally the tumour could not be clearly classified either clinically or histologically. But recently the paraffin-imbedded tumour specimen was re-examined by immunohistochemistry and in-situ hybridization. This identified a renin-producing tumour so that primary reninism was the cause of the arterial hypertension.

Adult↗
PubMed1993

Expression of HBs- and HBc-antigen in neoductular epithelium in chronic active hepatitis B. A further support for hepato-ductular metaplasia.

Biopsy specimens (n = 61) from patients with chronic active hepatitis B and progressive fibrosis (n = 61) were studied immunohistochemically to obtain information about the histogenesis of neoductules. All the biopsies contained clusters of oval-shaped cells often arranged in the form of neoductular aggregates. These expressed cytokeratins 7 and 19 which in the normal liver are found only in bile duct and ductular epithelium but not in hepatocytes. Using monoclonal and polyclonal antibodies both hepatocytes and these oval neoductular cells were found to express HBs- and HBc-antigen in 15% and 20% of the biopsies, respectively. Taking into consideration the strong hepatocytotropism of the hepatitis B virus, the expression of HBV-antigens in neoductular cells suggest their development from HBV-infected hepatocytes. Using proliferating cell nuclear antigen (PCNA) as a marker of cell proliferation positive staining was detected only in hepatocytes but not in neoductular cells. Taken together findings further support the concept of hepatoductular metaplasia in the histogenesis of so-called "proliferating" ductules. In general the data show that hepatitis B virus infection does not prevent hepatocytes from undergoing ductular metaplasia.

Bile Ducts, Intrahepatic↗
PubMed1993

Role of fat-storing cells in schistosomal hepatic fibrosis of mice.

The involvement of fat-storing cells (FSC) in hepatic schistosomal granuloma was investigated in mice infected with Schistosoma mansoni cercariae. After infection, 24 animals were treated with s.c. injections of vitamin A in a total dose of 210,000 IU given twice a week for 3 weeks. Two other groups of 24 animals each were: a) non-infected vitamin A-treated animals and (b) untreated infected controls. Animals from all groups were killed at weekly intervals from the 5th through the 10th week following infection. Pieces of liver were examined by light microscopy and transmission electron microscopy. In all vitamin A-treated animals, FSC disclosed prominent cytoplasmic fat droplets, which permitted their prompt identification in the light and in the electron microscope. They were found in large numbers as a constituent of periovular granulomas. In infected controls, FSC were not identified in granulomas, possibly because lipid droplets disappeared during differentiation to the fibroblastic phenotype. FSC also appeared within areas of septal fibrosis. These data suggest that FSC play an important part in focal portohepatic fibrosis during granuloma formation around S. mansoni eggs in the liver of mice.

Adipocytes↗
PubMed1993

Induction of immediate-early genes by angiotensin II and endothelin-1 in adult rat cardiomyocytes.

OBJECTIVE: Few molecular signals for induction of myocardial hypertrophy have been identified. This study was carried out to investigate the action of angiotensin II and endothelin on the growth- and differentiation-related genes Egr-1 (early growth response gene 1) and c-fos in isolated adult rat cardiomyocytes. METHODS: Cardiac myocytes from male Wistar-Kyoto rats were isolated and incubated with angiotensin II and endothelin-1 in Dulbecco's modified Eagle's medium. RNA was isolated and blotted, and densitometric analysis was performed. All experiments were repeated at least three times. RESULTS: Endothelin-1 (10(-7) mmol/l) induced a 20-25-fold rise in Egr-1 messenger RNA within 15 min. This effect was dose-dependent. c-fos was induced 10-20-fold within 15 min with similar dose-response characteristics. Angiotensin II also induced Egr-1 and c-fos with kinetics similar to endothelin but a cofactor from fetal calf serum was needed for full c-fos expression. The protein kinase C activator phorbol 12-myristate 13-acetate also induced Egr-1. CONCLUSIONS: The results identify Egr-1 and c-fos as target genes for the action of endothelin and angiotensin II in the adult myocardium suggesting that induction of the genes may be part of the signal transduction pathway for angiotensin II and endothelin in the myocardium.

Angiotensin II↗
PubMed1993

[Morphological classification and comparison of the different types of stromal nodules in benign prostatic hyperplasia].

The expression of immunohistochemical markers for cytoskeletal differentiation and that of neuroendocrine- and immunological cells showed in general the same tendency in the 4 types of prostatic stromal nodules: missing or low expression in immature-mesenchymal-, distinct augmentation in fibroblastic-, a maximum in fibro-muscular- and a slight decline in smooth-muscular nodules. These results are in agreement with developmental sequences, revealed by immunohistochemical investigations of fetal prostates, and seem to confirm the hypothesis that the four types of stromal nodules represent successive degrees of maturation, recapitulating ontogenetic processes.

Biomarkers↗
PubMed1992

Fatal bleeding from duodenal varices as a late complication of neonatal thrombosis of the inferior vena cava.

A 21-year-old man was hospitalized with repeated bleeding from the gastrointestinal tract, the cause of which could not be detected by gastroscopy, colonoscopy or arteriography. After the third surgical intervention he died of uncontrollable bleeding. At autopsy, marked and partly ulcerated duodenal varices were found to be the cause of the bleeding. They were part of a collateral circulation that had developed from chronic obstruction of the inferior vena cava, where thrombosis had arisen in association with neonatal renal vein thrombosis. There was consecutive renal infarction which had required a left nephrectomy on the 2nd day after birth.

Adult↗
PubMed1992

Inhibition of cellular autophagy in proximal tubular cells of the kidney in streptozotocin-diabetic and uninephrectomized rats.

To examine the significance of anti-catabolism in renal hypertrophy, cellular autophagy was investigated by electron microscopic morphometry in proximal tubular cells (PTCs) of the outer cortex of the rat kidney after the induction of diabetes mellitus by streptozotocin (STZ) and after unilateral nephrectomy. Adult male Sprague-Dawley rats were divided into three groups and killed by retrograde perfusion fixation, 1, 2 and 3 days after the induction of diabetes (group D; n = 24), after unilateral nephrectomy (group N; n = 24) and after combined treatment (group DN; n = 24). Untreated, age-matched litter mates served as controls (group C; n = 24). By comparison with these controls, the left kidney to initial body weight ratio was increased by 8, 23, and 15% in group D animals, by 8, 23, and 24% in group N animals, and by 10, 21, and 25% in group DN animals at the first, second and third day, respectively. Quantitative evaluation of large test areas showed that the volume and numerical densities of autophagic vacuoles (AVs) in PTCs were significantly lower in these hypertrophed kidneys than in the controls. The average reduction in AV volume density was about 65% in group D animals, about 50% in group N animals and about 75% in group DN animals. These data show that autophagic degradation of cytoplasmic components in PTCs is inhibited in renal hypertrophy independently of the growth stimulus, i.e. uninephrectomy or diabetes. Since insulin per se inhibits cellular autophagy in PTCs, the expected effect of insulin dificiency seems to be counteracted by as yet undefined stimuli that may be related to metabolic work load.

Animals↗
PubMed1992

Cellular autophagy in proximal tubules of early diabetic rats following insulin treatment and islet transplantation.

The influence of insulin treatment (group 1) and allogenic islet transplantation (group 2) on renal cellular autophagy were evaluated in adult Lewis rats in the early phase of streptozotocin-induced diabetes mellitus--a condition in which autophagy is inhibited and renal mass is increased. Three days after insulin treatment or islet transplantation (IT), the right kidney was resected and cortical tubular tissue was examined by quantitative electron microscopy. In group 1, the volume and numerical densities of autophagic vacuoles (AVs) increased by 70% and 80% respectively in the proximal tubular cells compared with saline-injected controls. The additive effect of unilateral nephrectomy (Ux) on cellular autophagy was investigated 1 or 2 days after Ux. Compared with the resected right kidney, the volume and numerical densities of AVs in the remnant left kidney decreased by 49% and 43% in the insulin-treated rats, and by 43% and 39% in the saline-injected diabetic animals. In group 2, the volume and numerical densities of AVs increased by 45% and 44% in parenchyma regressing from diabetic hypertrophy after IT, compared with sham-operated controls. After Ux, the volume and numerical densities of AVs decreased by 49% and 43% in IT rats, and by 41% and 53% in the still diabetic sham-operated animals. The data show that inhibition of cellular autophagy in the proximal tubules of the early diabetic kidney can be reversed by insulin replacement, despite the fact that insulin per se inhibits cellular autophagy in the nondiabetic kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Glutathione homeostasis and turnover in the totally hepatectomized rat: evidence for a high glutathione export capacity of extrahepatic tissues.

Glutathione (GSH) homeostasis and turnover were investigated in totally hepatectomized (HX) rats. A technique is described to remove the liver totally, with preservation of the hepatic portal and vena caval vasculature. Euglycemia could be maintained with hourly infusions of 50 mg 100 g-1 b.m. of glucose after bolus i.v. injection of glucose at the same dose. The efficiency of the animal model was demonstrated by examination of paraclinical blood parameters: progressive increases in total plasma bilirubin and alkaline phosphatase activity were noted after HX; the other parameters tested were predominantly in the normal range during the observation period of 6 hours. Histological examination revealed an acute but reversible impairment of intestine and kidneys. These results indicate that the surgical procedure and postoperative care were able to secure sufficient physiological conditions for the experiments over a longer period. 3 to 6 hours after HX we observed a decreased but stable plasma GSH level in anhepatic rats (about 50% of the control value). The GSH levels of brain and kidney were not changed. With increasing time period after HX the heart and lung GSH levels were depressed. A small depression of muscle GSH concentration was observed 4 and 6 hours after HX. A progressive increase in the concentration of oxidized glutathione was seen in brain and kidney. Our observations could be indicative for a high GSH export capacity of extrahepatic tissues contributing about 50% of the total GSH influx into circulation. Probably, the skeletal musculature is an important GSH origin for plasma.

Animals↗
PubMed1991

[Cardiac involvement in non-Hodgkin's lymphoma].

In a 47-year-old man with non-Hodgkin's lymphoma which had been treated by polychemotherapy and radiation, cardiac involvement was suspected on computed tomography (CT) two years after diagnosis. The ECG demonstrated atrial flutter and a slow ventricular rate. After a further cycle of chemotherapy the patients declined further treatment. Two years later he was admitted urgently because of cardiac failure, atrial fibrillation with a slow ventricular rate, and clear signs of abnormal repolarization. CT of the thorax again provided signs of cardiac involvement with lymphoma. In addition there were extensive tumour infiltrates in the liver and paraaortic lymph-node. Despite intensive medical treatment he died shortly after admission from cardiac failure. At necropsy all four cardiac chambers and the coronary arteries were surrounded completely by tumour tissue. The membranous interventricular septum, the area of the Hiss bundle and the tricuspid and mitral valves had also been infiltrated. Histologically the infiltrates consisted of lymphoid cells of centrocytic type. Increasing tumour cell involvement went together with complete disintegration of myocardial fibres.

Arrhythmias, Cardiac↗
PubMed1991

Generalized amyloidosis from beta 2-microglobulin, with caecal perforation after long-term haemodialysis.

A 73-year-old man with chronic renal failure of undetermined aetiology had received haemodialysis for 12 years when he died of acute purulent peritonitis due to caecal perforation. Amyloid deposits detected in a cystic bone lesion in the left hip had caused a pathological fracture 17 days before death. At autopsy, extensive amyloid deposits were found in the osteoarticular system, in the cartilaginous surface and the capsular tissue of joints, ligaments, vertebral discs and bone. In addition, vascular amyloid deposits were diagnosed in the heart, kidneys, testes, lungs, skin and in the gastrointestinal tract. A special feature of this case were interstitial amyloid deposits forming a fine-meshed structure in the myocardium and plate-like deposits in the gastrointestinal tract. Immunohistochemically, all these deposits reacted strongly with antibody to human beta 2-microglobulin but showed no reaction with antibodies to AA, A-lambda, A-kappa and AF. The present case demonstrates that extra-osteoarticular manifestations of AB-amyloidosis can cause serious complications.

Aged↗
PubMed1991

[Epidemiological and pathomorphological autopsy findings in AIDS].

The autopsy findings in 41 AIDS patients (1982-1991), including a rather large group of 8 patients without one of the classical risk factors for HIV, showed a much higher rate of opportunistic infections, especially CMV and fungal infections, as well as Kaposi's sarcoma in homosexuals than in the others. There was no decline in the incidence of Kaposi's sarcoma over the last few years. The bone marrow findings, which presented a remarkable high cellularity in these patients, well correlated with the so-called HIV-myelopathy, which is highly suggestive to represent a direct HIV-related damage of the bone marrow.

Acquired Immunodeficiency Syndrome↗