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Biomedical subjects

J Ehrmann

Publications and source records attributed to J Ehrmann.

At least 19 recordsLinked to original sources

[Special aspects of diagnosis and therapy of diabetes in liver diseases].

The core of this review are questions dealing with links between diabetes mellitus and liver diseases. Based on the literature and on their own observations the authors conclude that a liver disease may induce and/or worsen the development of type-2 diabetes mellitus (so called hepatogenic diabetes) and vice versa, a diabetes may result in a liver damage, e.g. simple steatosis or even non-alcoholic-steatohepatitis. The diagnosis of diabetes in hepatopathy is defined according to the same criteria as in patients without any hepatic involvement. The treatment is based on adequate food intake without alcohol and on restricted physical activity. Complementary insulin treatment is recommended whenever the BG-concentrations in a daily profile exceed 10.0 mmol/l. Oral antidiabetic drugs should be used only if they result in a marked improvement of diabetes control and no signs of liver damage appear.

Diabetes Mellitus, Type 2↗

Apoptosis of malignant cells in Hodgkin's disease is related to expression of the cdk inhibitor p27KIP1.

Previous results from B-cell chronic lymphocytic leukaemia suggest that expression of p27KIP1 might be important in protection from apoptosis. Given the relevance of apoptosis to the pathogenesis of Hodgkin's disease (HD), it was decided to examine the expression of p27KIP1 in relation to apoptosis in these lesions. Paraffin-wax sections from a total of 65 histologically confirmed HD tumours were used to derive apoptotic index (AI) and DNA fragmentation index (DFI) scores, which were compared with the expression of various cell-cycle-regulating proteins, including p27KIP1 (p27), p21WAF1/CIP1 (p21) and cyclin D1, and with Epstein-Barr virus (EBV) status. The DFI was measured by TdT-mediated dUTP-FITC nick end-labelling (TUNEL), and the AI by conventional morphology. Cells showing the typical morphology of apoptosis, together with those resembling so-called 'mummified' Hodgkin/Reed-Sternberg (HRS) cells, were included in AI measurements. Increasing numbers of p27-positive HRS cells were associated with lower levels of apoptosis in these cells, as indicated by significantly lower AI and DFI scores. There was a trend towards poorer survival in those patients with the highest numbers of p27-positive HRS cells and with lower AI and DFI scores, but these differences were not statistically significant. p21-positive HRS cells were significantly more frequent in those cases with lower AI scores. A similar trend was observed for p21 and DFI, although this relationship was not statistically significant. There was also a trend towards higher levels of cyclin D1 protein in HD cases with high AI and DFI values. A tendency for increasing numbers of p27-positive and p21-positive HRS cells in EBV-positive cases was noted, but this relationship was not statistically significant. EBV status did not correlate with either AI or DFI scores. The results of this study suggest that p27, and possibly also p21, may be involved in protection from apoptosis in HD.

Apoptosis↗

Apoptosis-related proteins, BCL-2, BAX, FAS, FAS-L and PCNA in liver biopsies of patients with chronic hepatitis B virus infection.

While the elimination of hepatitis B virus (HBV) is a common phenomenon at the end of the acute phase of disease, the persistence of HBV is characteristic for chronic hepatitis (CHB). Recent evidence indicates that the elimination of HBV is achieved by FAS/FAS-L induced apoptosis of infected hepatocytes. The aim of this study was to test the hypothesis that HBV persistence in the hepatocytes of CHB patients is due to the delayed onset of apoptosis caused by altered FAS/FAS-L interactions between lymphocytes and hepatocytes. The expression of FAS, FAS-L, BAX, BCL-2, ICE and PCNA in the liver biopsies of 55 patients (14 HBsAg positive, 20 patients with alcoholic hepatopathy, 21 patients with other hepatopathies) was tested by immunohistochemistry. Apoptosis of hepatocytes was evaluated by morphological as well as by TUNEL method. The results were correlated with a grading/staging score and analysed statistically using a one way analysis of variance and the Duncan test. Significantly highernumbers of BAX positive hepatocytes were observed in HBsAg positive patients when compared to control groups. Similarly, both BAX and FAS positive lymphocytes were more frequent in HBsAg positive patients. FAS-L positive lymphocytes and hepatocytes were numerous in all patient groups. Increased numbers of BAX positive hepatocytes in CHB may reflect the increased readiness of these cells to undergo apoptosis. However, the increased numbers of both BAX and FAS positive lymphocytes in CHB suggest that these cells may be particularly sensitive to FAS-L mediated apoptosis potentially resulting in lowered viability of these lymphocytes. This may explain, at least in part, the defective removal of virus-infected cells in chronic hepatitis. However, we cannot rule out the possibility that survival of hepatocytes during CHB may be due to other mechanisms such as defects in apoptosis activation triggered by CD40, defects involving DNase and/or other caspases downstream in the apoptotic cascade within these cells, or to defects in CTL function.

Apoptosis↗

The expression of apoptosis-related proteins and the apoptotic rate in glial tumors of the brain.

Modern molecular biology methods allow a more precise analysis of the biological characteristics of tumors and, consequently, a more precise treatment plan. The determination of apoptotic rate and expression of apoptosis-related proteins belong among the important prognostic/diagnostic markers in many tumors. The validity of these factors had not yet been sufficiently analyzed in astroglial tumors. The aim of this work was therefore to study mutual relationships between apoptotic rate, expression of apoptosis-regulating proteins and some clinical and histopathological data. The TUNEL method was used for the determination of apoptosis in 44 astroglial tumor specimens. The percentage of TUNEL positive cells was expressed by the TUNEL index (TI). The TI data was compared with the immunohistochemically detected expression of proteins involved in apoptosis (BCL-2, FAS, FAS-L, and caspase 1), with grading, age, proliferative activity (assessed by PCNA expression analysis) and overall survival of patients. The statistical evaluation of results was done by two-way sample analysis of variance. We have demonstrated significantly higher values of both TI and expression of FAS-L and caspase 1 in low grade tumors, which were characterized by a longer survival, lower average age and a lower expression of PCNA. FAS-L expression correlated significantly with the expression of the caspase 1. No significant difference was found between the expression of BCL-2 and FAS. These results suggest that the determination of TI in astroglial tumors may be an important prognostic marker. The expression of FAS-L and caspase 1 in low grade astroglial tumors could indicate the increased readiness to apoptosis via the FAS/FAS-L cascade.

Adolescent↗

[Can we foresee the end of the alphabet in viral hepatitis?].

There is a number of viruses which may cause acute or chronic liver damage. Only some of them belong into the group of hepatotropic viruses and only the latter are the cause of acute or chronic viral hepatitis. So far we know seven hepatotropic viruses. The virus of hepatitis A (HAV), virus of hepatitis B (HBV), virus of hepatitis C (HCV), virus of hepatitis D (HDV), virus of hepatitis E (HEV), virus of hepatitis G (HGV) and Transfusion-Transmitted-Virus (TTV). For HAV and HEV orofaecal transmission is typical, the others are transmitted by the parenteral route. All cause acute hepatitis. Only HAV and HEV infections develop into the chronic stage. The decisive finding for the dynamic development of the problem of viral hepatitis was the discovery of the Australian antigen (Au antigen) by B. Blumberg in 1965. The discovery made it possible to recognize viral hepatitis B and by the application of new biotechnologies the genes of other viruses were detected. Some of them were not visualized so far. A great advance was alpha interferon and lamivudine treatment in patients with chronic hepatitis B and alpha interferon treatment along with ribavirine in chronic hepatitis C.

Hepatitis, Viral, Human↗

[Characteristics of still unknown hepatotropic viruses and a clinical picture of the disease].

So far seven hepatotropic viruses were identified. They are described by letters A,B,C,D,E, G and TTV. The virus of hepatitis F is so far speculative. Virus of hepatitis A and E are transmitted by the orofaecal route and cause only acute hepatitis. The remaining hepatotropic viruses are transmitted by the parenteral route and have a longer incubation period than viruses A and E. The infection with the virus of hepatitis B develops into the chronic stage in about 10% and that of virus C in 50-90%. At least one third of chronic carriers of the virus of hepatitis B or C develop within 10-20 years liver cirrhosis or hepatocellular carcinoma. The objective of therapeutic regimes is eradication of the viruses or at least arrest or retarding of the activity of the disease. Corticoids are not used. The basis of therapeutic regimes is interferon alpha or lamivudine in hepatitis B and interferon alpha with ribavirine in hepatitis C. There is a permanent therapeutic response only in cca 40-50%. Active immunisation is possible against virus of hepatitis A and B. The virus of hepatitis D is a false virus, i.e. a so-called virold, and the cause is a super- or co-infection with the virus of hepatitis B. In this country it is practically not encountered, similarly as the virus of hepatitis E. The assembled findings on virus of hepatitis G are not applied so far very much in practice.

Hepatitis Viruses↗

Immunohistochemical analysis of the functional status of estrogen receptor cascade in breast cancer.

Hormone receptor expression in human breast cancer cells does not always reflect tumor response to therapy. Thus, relations between hormone receptor status and other parameters need further examination. The aim of this study was to test the ability of estrogen receptors (ER) to induce progesterone receptor (PR) synthesis as well as to test their role in the regulation of cell proliferation. Measurement of the relation between expressions of ER and the estrogen receptor related protein p29 (ERRP) was a further goal. The results show that some hormone receptor phenotypes are closely related to tumor proliferative activity: in the ER-group, especially ER-PR-phenotype, proliferative activity shows no obvious relationship to phenotype status, suggesting that proliferation in this group probably is not under estrogen control, while in the ER+ group, PR expression was related to reduced proliferation. There was no clear association between ERRP and nuclear ER but the highest ERRP expression was most closely related to ER negative (ER-) or slightly positive (ER +/-) hormone receptor statuses. Tumors with these phenotypes are known to have a poorer prognosis. The conclusion drawn is that simultaneous estimation of proliferative activity, ERRP p29 expression and a comparison with ER/PR hormone receptor phenotype, could provide pathologist with a valuable tool for predicting hormone response and prognosis in breast cancer patients.

Adult↗

[Surgical treatment of a complication of Crohn's disease of the duodenum].

In 1995-1997 at the First Surgical Clinic, Medical Faculty, Palacký University and Faculty Hospital Olomouc three patients were treated on account of obstruction of the pyloroduodenal region caused by Crohn's disease. The condition was treated by anastomosis, possibly with vagotomy, depending on the site of stenosis. Clinical, laboratory and endoscopic control examinations after a 6-month to 3-year interval revealed good results of this approach.

Adolescent↗

Immunohistochemical analysis of Bcl-2, Bcl-X, Mcl-1, and Bax in tumors of central and peripheral nervous system origin.

The expression of Bcl-2, Bcl-X, Mcl-1, and Bax was examined by immunohistochemical methods in 93 tumors of nervous system origin, including 49 gliomas (30 astrocytomas and 19 glioblastoma multiforme (GMs)), 16 medulloblastomas (MBs), 19 neuroblastomas (NBs; 9 undifferentiated and 10 differentiated), and 9 miscellaneous neuroectodermal neoplasms. Among the 49 gliomas, immunopositivity (defined as > or = 10%) was observed for Bcl-2 in 45 (92%), Bcl-X in 48 (98%), Mcl-1 in 49 (100%), and Bax in 48 (98%) of 49 specimens. In 11 (37%) of 30 astrocytomas (WHO grades I to III), the tumor specimens were composed predominantly of malignant cells with strong-intensity Bcl-2 immunostaining, whereas none of the 19 GMs (WHO grade IV) exhibited strong-intensity Bcl-2 immunoreactivity (P = 0.001). Similarly, Mcl-1 immunointensity was strong in 15 (50%) of 30 astrocytomas, compared with only 2 (11%) of 19 GMs (P = 0.005). The percentage of Mcl-1-immunopositive tumor cells was also higher in astrocytomas than GMs (P < 0.002). Thus, contrary to a priori expectations, the expression of the anti-apoptotic proteins Bcl-2 and Mcl-1 was significantly higher in astrocytomas than in GMs. Of the 16 MBs, immunopositivity was found for Bcl-2 in 4 (25%), Bcl-X in 9 (56%), Mcl-1 in 8 (50%), and Bax in 16 (100%) of the cases. The intensity of immunostaining was strong for Bcl-2 in only 1 (6%) specimen, for Bcl-X in 3 (19%), and for Mcl-1 in 2 (12.5%), in contrast to Bax immunostaining, which was strong in 12 (75%) tumors. Significantly higher percentages of Bax-immunopositive tumor cells were also found in MBs, compared with Bcl-2, Bcl-X, and Mcl-1 (P < 0.0001). All 19 NBs were immunopositive for Bcl-2, Bcl-X, Mcl-1, and Bax. Higher percentages of Bcl-X- and Mcl-1-immunopositive tumor cells were observed in well differentiated tumors (P = 0.04 and 0.004, respectively). The intensity of Mcl-1 immunostaining was also generally higher in differentiated than undifferentiated NBs (strong immunointensity in 7 of 10 versus 0 of 9; P = 0.002). Conversely, strong-intensity Bax immunostaining was associated with undifferentiated histology (5 of 9 (56%) versus 1 of 10 (10%); P = 0.03). Taken together, these findings begin to delineate trends in the regulation of the relative levels of the Bcl-2 family proteins, Bcl-2, Bcl-X, Mcl-1, and Bax in gliomas, MBs, NBs, and some of their histological subtypes. The suggestion that expression of some of these Bcl-2 family genes may be differentially regulated in association with tumor progression and differentiation provides insights into the diverse biology and clinical behavior of these tumors of nervous system origin.

Central Nervous System Neoplasms↗

Prognostic factors in astrocytomas: relationship of p53, MDM-2, BCL-2 and PCNA immunohistochemical expression to tumor grade and overall patient survival.

The immunohistochemically detected expression of p53, BCL-2, MDM-2 and PCNA proteins in samples of tumor tissues of 42 patients with astrocytomas or glioblastoma multiforme was statistically compared to degree of malignancy and overall survival. We found relation between p53 protein expression and survival in the high grade astrocytomas group (more cases of p53 immunonegative tumors with longer survival), and significantly higher BCL-2 protein expression as well as significantly higher MDM-2 protein expression in the group of low grade astrocytomas. PCNA protein expression showed any relation to tumor grade or survival. Despite the rather small number of samples these results support the hypothesis that MDM-2 protein may be a potent regulator of functional p53, expressed in low grade astrocytoma only.

Adult↗

[Familial occurrence of Crohn's disease].

The authors give an account of the occurrence of Crohn's disease in first grade relatives. Within a short time interval on account of Crohn's disease daughter, son and mother were operated.

Adult↗

The level of neopterin in blood serum as one of the possible prognostic markers of Crohn's disease activity.

Neopterine is considered to be one of the markers of immunity system activity. An increased level of this pteridine derivate is determined in blood or urine in infections, transplant rejections, and in other conditions accompanied by changes in the immunity system. Monitoring its level in various body liquids can be important when assessing the immunity system condition, nevertheless, its non-specificity causes difficulties when interpreting the results. Up to now, very few papers have been published dealing with the determination of neopterine levels in patients with IBD. We studied a group of 25 patients who are monitored in a longterm manner at our clinic suffering from Crohn's disease. During 1993 and 1994, we were determining their levels of neopterine in blood together with other parameters. It was a group of patients chosen at random in different stages of disease, and we were interested in the correlation of the height of neopterine level with the activity of Crohn's disease. We proved statistically unimportant correlation between the height of neopterine level in blood serum and Crohn's disease activity. The question is discussed whether the examination of this marker be useful when monitoring Crohn's disease activities.

Biomarkers↗

C-ANCA and p-ANCA in patients with Crohn's disease.

In 32 patients suffering from various stages of activity of Crohn's disease, c-ANCA and p-ANCA in serum were examined. Altogether, 54 blood samples were examined. In 21 patients of 32, i.e. 65.6%, at least in one examination of c-ANCA in serum the value was higher than 9 units (positive finding). In 10 patients of 32, i.e. 32.2%, at least in one examination of p-ANCA in serum the value was higher than 9 units (positive finding). In the case of high activity of Crohn's disease, c-ANCA in serum were higher than 9 units (positive finding) in 69.6% examinations, in case of low activity, values of c-ANCA in serum were higher than 9 units (positive finding) only in 9.5% examinations. p-ANCA in serum were, when the activity was high, positive in 46.1% examinations, while when the activity of Crohn's disease was low, p-ANCA were positive in 9.5%. The question of specificity of findings is discussed.

Adolescent↗

Fulminant hepatitis caused by a hepatitis B virus infection in the patients with haematologic malignancies. Report of 5 cases.

We describe 5 cases of fulminant hepatitis caused by the HBV infection in patients with haematological diseases, mostly malignancies (ALL, lymphoma, aplastic anemia, AML) following intensive chemotherapy. Infection was confirmed by serological examination (HBsAg positivity) and by electron microscopy (viral particles). After termination of chemotherapy fulminant hepatitis developed with hepatic failure and very high levels of AST and ALT. Autopsy revealed massive necrosis without signs of regeneration. We suggest that immunosuppressive therapy increases the risk of severe infection of hepatocytes with HBV and subsequent withdrawal of chemotherapy causes "immunological rebound" leading to massive necrosis.

Anemia, Aplastic↗

Immunohistochemical study of the expression of BCL-2, PCNA and P53 proteins in the patients with hepatitis B. The pilot study.

In HBV related hepatitis it is generally accepted that the liver injury is mediated by an immune response to the virus, since HBV is not directly cytopathic. The first step in cytotoxic T lymphocyte mediated immune reaction in HBV infected mice is the induction of apoptosis. The role of BCL-2, p53 and PCNA (as the main regulators of cell cycle homeostasis) in this process has not been studied. The aim of this pilot study is to estimate immunohistochemically the expression of the BCL-2, p53 and PCNA in a group of HBV infected patients at various stages of the disease. Formalin fixed, paraffin embedded liver biopsies from 5 patients with HBsAG positivity in their serum were used for immunohistochemical study of the expression of BCL-2, PCNA (PC10) and P53 (DO1clone). As the chromogen we used both the DAB and AEC. The results were co-related with the 3 liver biopsies as controls. In the hepatocytes of the all cases (including controls) we did not found any positivity of BCL-2, p53 and PCNA. However the majority of the lymphocytes present in the liver of some cases of HBV infected patients were strongly BCL-2 positive. This preliminary results of very small group of patients could indicate that hepatocytes in the HBV infection are in the quiescent stage as in the controls and that the cell cycle regulation during infection could be controlled by other genes such as bax, bcl-Xs, FAS etc., but further studies are required.

Animals↗

[Anti-HCV positivity in blood donors].

At the blood transfusion department of the Faculty Hospital in Olomouc in 1992 and 1993 18,293 blood donors were examined and in 70, i.e. 0.38% anti-HCV positivity was found. All positive subjects were subjected to clinical, laboratory and sonographic examination and are checked regularly at the Second Medical Clinic. In none of the patients liver biopsy was performed so far. The clinical, laboratory and sonographic findings provide evidence of liver damage in 15, i.e. 21.4%. In two of them, i.e. in 2.8%, the findings support the diagnosis of chronic active hepatitis; this will be verified by biopsy. The authors consider dispensarization of anti-HCV positive subjects useful. In all examination of RNA HCV however must be made.

Adult↗