Biomedical subjects

Z Schaff

Publications and source records attributed to Z Schaff.

At least 37 records · Page 2Linked to original sources

PubMed1998

[Histo-pathological evaluation of response to 6 and 12 months of interferon alpha therapy].

BACKGROUND AND AIMS: Interferon-alfa (IFN-alfa) has recently been introduced for chronic C hepatitis treatment; however, the response rate is merely 25-50%. The aims of this follow-up study were to compare the efficacy of 6 and 12-month IFN-alfa treatment via liver biopsy scores and to evaluate the correlation with the biochemical response. PATIENTS AND METHODS: 20 chronic C hepatitis patients were studied. 10 patients received IFN-alfa therapy for 6 months, and 10 for 12 months (3 million units three times a week). Liver biopsy material was taken before and after therapy. RESULTS: There was a significant serum alanine aminotransferase (ALT) level improvement in both groups, but a significant histological improvement in necroinflammatory activity (grade) occurred only in the 12-month group. The Chevallier stage scores demonstrated a significant progression in both groups. CONCLUSIONS: 12-month IFN-alfa treatment affords a better response in the liver histology grade and serum ALT level, but not the stage; a normal ALT does not guarantee hepatitis inactivity. Liver biopsies appear indispensable for monitoring the fibrotic changes in chronic C hepatitis.

Adult↗

PubMed1998

P53 expression in stage I squamous cell lung cancer.

P53 expression was studied using immunohistochemistry in patients (n=94) with pathologic stage I squamous cell lung cancer treated surgically between 1991-1992. The overall p53 positivity ratio was 48/94. 83 of the cases proved to be suitable for follow-up analysis carried out in November, 1995. 46/83 were p53 positive, and 25/46 patients were alive at the time of analysis. The patients who died (21/46) had a mean survival time of 17.5 months. In p53 negative cases (37/83), however, 29/37 patients were still alive at the time of follow-up, and 8/37 had died with a mean survival time of 23.1 months. A significant correlation could be found between p53 immunopositivity and reduced survival time (p=0.0125). Interestingly, out of 83 cases analyzed histologic evidence of tuberculous scar tissue was present in 9 tumors with a p53 positivity ratio of only 1/9. When flow cytometry was used to examine tumor samples from all subgroups mentioned above (n=32), no correlation was found between the p53 immunopositivity or the prognosis and the DNA content of tumor tissues. Our results suggest that in the early stage of squamous cell lung cancer the p53 positivity may be an indicator of a more aggressive tumor behavior and a shortened survival time.

Adult↗

PubMed1998

Experimental and human liver fibrogenesis.

In this work, we provide an overview of our results obtained by studying the role of transforming growth factor beta1 and proteoglycans in liver fibrogenesis. It has been found that transforming growth factor beta1 is one of the most important stimulators of extracellular matrix synthesis in the liver. In chronic liver injury, desmin-positive non-parenchymal liver cells expressed transforming growth factor beta1. The extracellular localization of the growth factor correlated well with types I, III and IV procollagen-alpha, which were detected in the fibrous septa of chronically injured livers. A similar distribution pattern was observed in human specimens. To identify the role of transforming growth factor beta1 in liver extracellular matrix protein synthesis, transforming growth factor beta1-positive transgenic mice were generated. Animals expressing the growth factor in their liver showed spontaneous liver fibrosis. Proteoglycans also participate in fibrogenesis. The majority of liver-specific heparan sulfate proteoglycans, such as syndecan-1 and fibroglycan, are produced by hepatocytes. The extracellular matrix proteoglycans decorin and perlecan are synthesized by non-parenchymal liver cells. The amount of the latter is very low in normal liver, but increases dramatically in liver fibrosis. The effect of regulatory factors on liver proteoglycans seems to be cell type-specific. In contrast to previous observations, elevated amounts of decorin did not inhibit the action of transforming growth factor beta1 in the liver.

Animals↗

PubMed1998

Human and experimental hepatocarcinogenesis.

Human liver cancer is increasing worldwide, including in Hungary. The detection of liver tumors in premalignant or early malignant states is essential for successful treatment. MC-29 virus-induced chicken hepatoma and rodent, fish and monkey models for chemical hepatocarcinogenesis were studied and compared to humans. Changes in phenotypic enzyme alterations and in the expression of certain oncogens and growth factors characterize the experimentally induced hepatomas, and might also be characteristic of human premalignant and malignant focal liver lesions. Fish hepatocarcinogenesis is useful for studying compounds in environmental pollution. Increased expression of transforming growth factor á can be observed both in experimental and human liver tumors. Increased tumor incidence was detected in transgene mice containing both transforming growth factor alpha and c-myc genes. Animal models of hepatocarcinogenesis help to understand the development of liver tumors. Methods applied in studies using those models are useful in the study of premalignant and malignant human liver lesions.

Animals↗

PubMed1998

Histological evaluation of the response to interferon-alpha therapy in chronic hepatitis C.

BACKGROUND AND AIMS: The response rate of interferon-alpha (IFN-alpha), recently introduced in the treatment of chronic hepatitis C, is merely 25-50%. The aims of this follow-up study were to compare the efficacy of 6 and 12-month IFN-alpha treatment via liver biopsy scores and to evaluate the correlation with the biochemical response. PATIENTS AND METHODS: Twenty chronic hepatitis C patients were studied; 10 received IFN-alpha therapy for 6 months and 10 for 12 months. Liver biopsy material was taken before and after therapy. RESULTS: There was a significant serum alanine aminotransferase (ALT) level improvement in both groups, but a significant histological improvement in necroinflammatory activity (grade) only in the 12-month group. The Chevallier stage scores demonstrated a significant progression in both groups. CONCLUSIONS: Twelve-month IFN-alpha treatment affords a better response in the liver histology grade and serum ALT level, but does not influence the staging; a normal ALT does not guarantee hepatitis inactivity. Liver biopsies appear indispensable for monitoring.

Adult↗

PubMed1998

The pathomorphology of a human xenotransplanted basaloid squamous cell carcinoma.

To elucidate some factors related to the malignant phenotype of an oral tumor with mixed cell population the question has been raised whether the biological behavior of the basaloid or the squamous cells show any difference in an immunosuppressed host organism. Basaloid squamous cell carcinoma (BSCC) surgically removed from sublingual location was xenotransplanted either subcutaneously or in the oral submucosa and the histology, ultrastructures, LDH isoenzyme pattern were investigated. The epithelial origin of the established tumor line (HTB-1) could be recognized according to the characteristic epithelial ultrastructures, while the type of the LDH isoenzymes proved its human origin. The squamous cell population dominating the parent surgical specimen of BSCC regressed during xenotransplantation in the subcutan location, on the contrary the basaloid cells grew and maintained the tumor. Interestingly the basaloid cells transplanted from the subcutis to the oral submucosa generated a squamous cell population with an infiltrative growth pattern. The xenografted BSCC offer a promising model to investigate the contribution of each cell populations in the malignant phenotype. The presented data indicate that the basaloid cells are responsible for maintaining the tumor cell population, but certain malignant features (i.e. infiltrative growth) is associated to the squamous cells which are generated from the basaloid cells only under specific circumstances. Thus this particular model system showed that different malignant features could be associated to the basaloid and to the squamous cell component.

Animals↗

PubMed1997

[Pathology and pathogenesis of viral hepatitis].

Several factors viral genotype, mutations, vírus-host interaction, expression of viral proteins and host immune-reaction are very important in the pathogenesis of hepatotrop viral infections. Activation of Fas/Fas ligand system occurs during hepatitis which is responsible for the apoptosis of vírus infected hepatocytes. The histological features in chronic hepatitis can be classified based on the activity of near inflammatory alterations ("grade"). Stage of chronic hepatitis describes the degree of fibrosis and architectural alterations.

Apoptosis↗

PubMed1997

Hepatitis C virus core protein shows a cytoplasmic localization and associates to cellular lipid storage droplets.

There is now abundant evidence to substantiate an important role of hepatitis C virus (HCV) core protein in cellular gene expression as well as in the viral cycle. Thus the subcellular localization of this protein has important implications. However, several studies have shown controversial results: the HCV core has been, indeed, described as cytoplasmic or nuclear depending on the size of the protein or on the genotype analyzed. We have studied the localization of the HCV core protein in two different cell lines, one nonhepatic (CHO) and the other hepatic (HepG2). Double immunofluorescence staining using a nuclear membrane marker and confocal analysis showed the core protein pattern to be cytoplasmic and globular. This pattern is not cell cycle-regulated. Electron microscopy analysis revealed the nature of the globular staining observed in immunofluorescence. The HCV core protein accumulated at the surface of lipid droplets that were also the unique morphological feature of nonhepatic core transfected cells. The lipid droplets were isolated by sequential ultracentrifugation on the basis of their density; biochemical analysis revealed a prevalence of triglycerides. In addition the core protein colocalized with apolipoprotein AII at the surface of the lipid droplets as revealed by confocal microscopy. Moreover analysis of liver biopsies from chronically HCV-infected chimpanzees revealed that HCV core is cytoplasmic and localized on the endoplasmic reticulum and on lipid droplets. These results clearly define the subcellular localization of the HCV core protein and suggest a relationship between the expression of the HCV core protein and cellular lipid metabolism.

Animals↗

PubMed1996

[Immunohistochemical study of hepatitis B and D virus antigens (HBsAg, HBcAg, HDAg) in chronic liver diseases].

Authors have investigated the hepatitis B and D virus antigens in the liver tissue of 30 HBsAg and/or anti-HD seropositive patients (23 males, 7 females, age: 20-65, mean: 44 years) by immunohistochemical method. The immunohistochemical identification of HBsAg, HBcAg and HDAg in 42 liver sample (36 obtained by percutaneous biopsy, 6 from dissection) of 30 patients was performed with Dako and Sorin Biomedica kits. The detailed virus serologic examinations were carried out with Biomedica and Abbott kits by radioimmunoassay and ELISA methods. Examining 36 liver tissue samples of 27 HBsAg seropositive patients, HBsAg could be demonstrated in 31 cases. Each patient suffering of active HBV and/or HDV replication was HBsAg positive by immunohistochemistry, while the tissue samples of patients in integrational phase of HBV infection were positive in only 9 cases of 14. There was no HBsAg tissue positivity in HBsAg seronegative cases. 7 of 16 tissue samples of 12 patients classified to active HBV replication state were HBcAg positive by immunohistochemistry. HBcAg could be detected in the liver tissue of each HBe seropositive patient, while in only 3 of 8 cases with only IgM anti-HBc seropositivity (indicating low level of HBV replication). Tissue HBcAg positivity, indicating active virus replication, was verified in 2 of 11 patients classified to HBV integration state by serology. Authors detected HDAg tissue positivity only in cases with serologically active HDV replication (IgM anti-HD seropositive) and HDAg could also be identified from liver tissue in each IgM anti-HD seropositive case. No HBsAg, HBcAg and HDAg tissue positivity was observed in HBsAg negative cases. Authors emphasise mainly the importance of immunohistochemical detection of HBcAg and HDAg completing the serologic diagnosis of chronic HBV and HDV infections, helping the verification or exclusion of active virus replication being essential for selecting adequate therapy.

Adult↗

PubMed1996

Ultrasound guided spleen biopsy in chimpanzees (pan troglodytes).

To the best of our knowledge, this is the first published investigation of the size and position of chimpanzee spleens as measured by ultrasound, and that a fine-needle biopsy of the chimpanzee spleen, guided by ultrasound, has been performed. In general, the chimpanzee spleen is smaller than the human spleen (mean length of 8.9 cm, SD 1.17 cm; mean thickness 2.4 cm, SD 0.35 cm; n = 14) and its position may be different due to different numbers of thoracic vertebrae. Fine-needle biopsy is a safe and simple method to obtain lymphoid tissue sufficient for PCR testing of HIV-1.

Animals↗

PubMed1996

Monocytes of individual human subjects display heterogeneous bacterial uptake and antilisterial activity.

Peripheral blood monocytes (Mo) of normal human donors simultaneously exhibit two subsets differing in their functional activity towards the facultative intracellular bacterium Listeria monocytogenes. One subset (on average, 25% of total Mo) was characteristically able to ingest a large number of L. monocytogenes bacteria and permitted intracellular growth of these bacteria. The other Mo subpopulation (on average, 75% of total Mo) was far less active in phagocytosing L. monocytogenes and restricted intracellular L. monocytogenes growth. Electron microscopy revealed that the Listeria-permissive Mo subset allowed the bacteria to escape to the cytosol, a mechanism by which these bacteria evade the lethal attack of phagocytes. The Listeria-restrictive Mo subset, on the other hand, confined the bacteria to the phagolysosomes, where they were exposed to the killing mechanisms of the Mo. Permissiveness for L. monocytogenes growth was further associated with differences in the capacity of the Mo subsets to synthesize tumor necrosis factor alpha TNF-alpha), an important mediator in the defense against intracellular bacteria. Following challenge with L. monocytogenes, the Listeria-restrictive Mo subset secreted two to six times more TNF-alpha than did the Listeria-permissive Mo subset. Enhanced TNF-alpha secretion was paralleled by increased accumulation of TNF-alpha mRNA as assessed by quantitative PCR. Despite these functional differences, the two Mo subsets were indistinguishable with respect to expression of cell surface markers known to be involved in adherence and phagocytosis of microbes. A speculative physiological role of the two Mo subsets may lie in the dual function of Mo as microbicidal effector cells and accessory cells for antigen-specific immune reactions.

Base Sequence↗

PubMed1995

p53 in malignant and benign liver lesions.

p53 expression was studied by immunohistochemical methods in benign and malignant human epithelial liver lesions in 46 patients from Hungary. Positive immunostaining for p53 protein, indicating the overexpression or prolonged half-life of p53 protein, was detected in the nuclei of tumour cells of seven of the 16 hepatocellular carcinomas (HCC) (44%), including three HCC patients with hepatitis B virus infection. Immunostaining of p53 was seen in one of the seven hepatoblastomas, none of the 17 focal nodular hyperplasias, and none of the six hepatocellular adenomas. The detection of p53 in a relatively high percentage of the HCC cases in Hungary, a country in which aflatoxin contamination of the diet is rare, suggests that factors other than aflatoxin led to the accumulation or overexpression of p53 in these patients.

Adenoma, Liver Cell↗

PubMed1994

Overexpression of transforming growth factor-alpha in hepatocellular carcinoma and focal nodular hyperplasia from European patients.

The expression of transforming growth factor-alpha (TGF-alpha) was studied in 33 surgically excised human hepatocellular carcinomas (HCCs), focal nodular hyperplasias (FNHs), and the surrounding liver tissue from patients who were life-long residents of Hungary. Monoclonal antibodies were used to localize TGF-alpha and hepatitis B surface antigen (HBsAg) using an avidin-biotin-peroxidase immunohistochemical method on paraffin-embedded sections. Transforming growth factor-alpha was detected in the tumor tissue in 13 of 16 patients with HCC (81%) and in 12 of 17 patients with FNH (71%). Three patients with HCC were actively infected with hepatitis B virus, indicated by the detection of HBsAg in the serum and in adjacent nontumorous liver. Transforming growth factor-alpha was detected in the same nontumorous hepatocytes as HBsAg, often in areas of the hepatocyte cytoplasm, with a "ground glass" appearance. Bile duct cells were stained for TGF-alpha in the surrounding nontumorous liver tissue and a more intensive immunostaining was observed in the proliferating bile ducts in the FNH cases, which suggests that TGF-alpha may participate in the growth regulation of bile ducts.

Adolescent↗

PubMed1993

[Ursodeoxycholic acid therapy in biliary cirrhosis].

Six female patients (mean age 48.5 years) suffering from primary biliary cirrhosis were evaluated during ursodeoxycholic acid (UDCA, Ursofalk, 10 mg/kg/day) therapy. The following examinations were performed: liver function tests, immunological studies [electrophoresis, immunoglobulin determination, T-B lymphocyte rate, antibody dependent cellularly cytotoxicity (ADCC), natural killer (NK) activity, blast transformation]. The patients showed a definite clinical improvement. Short term therapy (1 month) resulted in a decrease of gamma-GT, SGPT (ALT), SGOT (AST), bilirubin, alkaline phosphatase, cholesterol, triglyceride. The longer period of therapy (9 month) was associated with decrement in transaminase and gamma-GT levels. The statistically significant decrease of the IgG level, NK activity and spontaneous blast transformation during therapy suggest a potential immunosuppressive effect of the UDCA treatment. The authors believe that the use of UDCA could be effective in the treatment of primary biliary cirrhosis.

Adult↗

PubMed1993

[Flow-cytometric study of the DNA content in adrenal cortex tumors].

Flow cytometric deoxyribonucleic acid measurements were performed on 26 adrenocortical tumours and 9 non-tumours adrenals. All but one tumours were classified both histologically and clinically as benign, however, two thirds of them had abnormal deoxyribonucleic acid stemlines. Proliferative indices of adenomatous tissues were significantly higher than those of non-tumorous adrenals (p < 0.01). When compared to tumors smaller than 5 cm in size, tumours larger than 5 cm displayed significantly higher proliferative indices (p < 0.01). Thus, flow cytometry appears to have only a limited value in distinguishing between benign and malignant adrenocortical tumours, but it may provide additional information about the prognosis of these tumours.

Adenoma↗

PubMed1993

[Long-term follow up study of children with celiac disease].

27 long term monitored coeliac children were assessed. The average length of follow-up was 6.4 years, the average age of the children was 11.5 years (ranging 6.3 to 20.1 years). Of the 11 boys and 16 girls 4 adolescents consume a normal diet, while another 2 are on semistrict diet, all 6 of them without any enteral symptoms. Out of the 15 children aged younger than 13 years 9 are on a strict diet. Semistrict diet has an impact on gliadin antibody levels respectively. Serum ferritin levels of those on a normal diet are significantly lower than those of the control group. Out of the 25 lactose breath tests 7 showed abnormal results, irrelevant both to the strictness of the diet and to gliadin antibody levels. In the view of weight and length percentiles there is no difference at present between those eating normal food and diet. Nevertheless, with regards to the risk of malignancy in coeliac disease the necessity of a strict diet must be stressed. In long term follow-up the levels of gliadin antibodies and of serum ferritin are of pathognostic importance.

Adolescent↗

PubMed1993

Diagnosis and treatment of bronchial carcinoid tumors: clinical and pathological review of 120 operated patients.

Clinical and pathological review is presented of 120 patients operated on for bronchial carcinoid tumors between 1976 and 1986. The usual oncologic features were analyzed. The Grimelius reaction, immunohistochemical staining for neuron specific enolase (NSE), serotonin and chromogranin, and DNA-analysis by flow cytometry were performed in these tumors and in small cell lung cancers (SCLC). In our experience the usual oncologic criteria--atypia, tumor-size, localization, history and regional lymph node metastasis--fail to give clear information for the prognosis. The Grimelius reaction has no significant differential diagnostic importance. Immunostaining for NSE can aid in distinguishing between neuroendocrine and non-neuroendocrine pulmonary tumors. The carcinoids and SCLCs could be differentiated by immunostaining for chromogranin and by flow cytometry but none of these methods are suitable for differential diagnosis within the carcinoid group. Resection by thoracotomy is the only treatment of choice: it can provide an excellent result (the 5-year survival rate is above 90%) with a low hospital mortality (0.8%). Parenchyma-sparing resections are to be encouraged.

Adolescent↗

PubMed1993

Potential markers (enzymes, proteoglycans) for human liver tumors.

In the present work the activities of GGT and G-6-Pase and the content of Cyt P-450 were determined in surgically removed liver specimens (16 hepatocellular carcinomas, 8 focal nodular hyperplasias and 4 adenomas). The activities were compared to the surrounding seemingly normal liver tissue. In the adenomas neither of the enzymes studied showed alterations, characteristic for hepatocarcinogenesis. Four out of 8 FNHs had the enzyme pattern that was found in experimental liver carcinogenesis. Liver carcinoma specimens proved to be heterogenous. Neither elevated GGT nor reduced G-6-Pase activity was consistent in these samples although the average of G-6-Pase activity decreased to 50 percent. Cytochrome P-450 was significantly reduced in the majority of cases, showing the best agreement with the tendency observed in experimental models. As an other approach, the qualitative and quantitative alterations of proteoglycans (PG) were analized in the same tumor samples. The amount of sugar components of PGs the glycosaminoglycans (GAG) increased by many times in liver tumors. Carcinoma samples were characterized by about twentyfold increase in chondroitin sulfate content, compared to normal liver. The enhancement of GAGs is partly the consequence of a selective alteration in PG expression. The amount of perlecan and decorin was found to be increased, while syndecan disappeared from liver carcinomas. These data suggest that malignant transformation in liver is accompanied by specific alteration in the content, composition and structure of PGs. Presumably, these changes have significance in tumor progression and have also the potential to be used as markers for liver tumors.

Adenoma↗