[What is your diagnosis? Answer: splenic hamartoma].
Explore the source record for details and available documents.
Diagnosis, Differential↗
Biomedical subjects
J Ehrmann
Publications and source records attributed to J Ehrmann.
[The role of STAT proteins in the regulation of the response to the interferone alpha therapy in chronic hepatitis C].
The currently used standard treatment for chronic hepatitis C using a dual combination of IFNalpha/RBV is only successful in 50% cases. With the exception of some clinical and biochemical factors, degree of inflammation (grading) and degree of fibrosis (staging), there are no other known markers which may serve as valid predictors of response to therapy. Interference of hepatitis C virus (HCV) with signaling pathways modulated by JAK-STAT, ERK 1/2, NFkappaB and MAP proteins is one mechanism which may influence the interaction between HCV and IFNalpha. These proteins regulate different cell processes such as activation of cytokines, activation of apoptosis, regulation of cell proliferation etc. Therefore, it is possible that impaired signaling or inhibition/dysregulation of some of these proteins by HCV infection may cause resistance to IFNalpha treatment. This review is completed by results of preliminary study the aim of which was immunohistochemical assessment and analysis of expression of STAT 2, 3 proteins, their inhibitors SOCS 2, 3 and PIAS 3 and proteins JAK 1 and ERK 1/2 in liver biopsies of 26 patients with chronic hepatitis C treated by dual combination IFNalpha/RBV and subsequent correlation of the results of immunohistochemical analysis (histoscore) with histological picture and clinical response to treatment. The results shows increased expression of STAT 3, STAT 2 and ERK 1 proteins and decreased expression of SOCS 3 and SOCS 2 in hepatocytes of patients with more marked inflammation and fibrosis. In patients with sustained virological response there was increased expression of SOCS 3 and JAK 1 and decreased expression of SOCS 2. Relapse was associated with increased expression of SOCS 3 and PIAS 3. However, owing to the small sample size, the results only approximated statistical significance, but we suggest that proteins of STAT family and their inhibitors SOCS and PIAS probably play an important regulatory role during response to treatment for chronic hepatitis C.
Antiviral Agents↗
[The subacute angiohypertrophic myelomalacia Foix-Alajouanine--a rare disease?].
The subacute angiohypertrophic myelomalacia Foix-Alajouanine was first described by French authors in 1926 and belongs to the wider category of CNS vascular malformations. Both individual casuistics and larger sets of patients with this disease can be found in literature scarcely. We are presenting three necroptic cases of subacute angiohypertrophic myelomalacia (Foix-Alajouanine) that were mistakenly diagnosed clinically, once as metastatic lesion of spinal canal, once as amyotrophic lateral sclerosis, and once as inflammatory lesion of spinal cord. The histologic finding is dominated by myelomalacia of varying extent with varicosely dilated, constricted or even occluded arterialized both extra- and intramedullary veins, sporadically coupled with secondary thrombi. Clinical diagnostics is difficult and requires spinal angiography. According to literature data, it is presumable that this disease is not as rare as it may seem at first sign.
Aged↗
Nestin as a diagnostic and prognostic marker: immunohistochemical analysis of its expression in different tumours.
The designation NESTIN refers to a member of the family of intermediate filaments and comes from the fact that this protein is expressed mainly in neuroepithelial stem cells. However, nestin is not expressed in mature elements and terminal cell differentiation is associated with loss of immunoreactivity to this protein. Therefore, immunohistochemical assessment of nestin expression might be useful to differentiate between mature and immature elements. The aim of this study was to analyse nestin expression in various tumours of neuroectodermal and vascular origin and to determine whether its detection has practical relevance. The results indicate that the immunohistochemical detection of nestin expression could be useful in astrocytomas and malignant melanomas, where it could be used as an auxiliary indicator of dedifferentiation and progression. Because of the weak and heterogeneous expression of nestin in neurinomas, phaeochromocytomas, and carcinoids, nestin detection in these lesions is of little practical use.
Adolescent↗
Peroxisome proliferator-activated receptors (PPAR) agonists affect cell viability, apoptosis and expression of cell cycle related proteins in cell lines of glial brain tumors.
The nuclear receptors PPARs (peroxisome proliferator-activated receptors) are transcription factors activated by specific ligands. PPARs play an important role in carcinogenesis, inflammation, atherosclerosis, lipid metabolism and diabetes. There is evidence that activation of PPARs by specific ligands is able to suppress the growth of different types of human cancer by mechanisms including the growth arrest, apoptosis and induction of differentiation, although the detailed signalling pathways have not been completely elucidated to date. The aim of our study was to determine whether synthetic ligands of PPARalpha and PPARgamma could affect the viability, proliferation, differentiation, apoptosis and expression of some cell cycle related proteins in glial tumor cell lines. The study was performed on human glioblastoma cell lines U-87 MG, T98G, A172 and U-118 MG. Cell lines were treated by ligands of PPARalpha (bezafibrate, gemfibrozil) and PPARgamma (ciglitazone). MTT, flow cytometry, TUNEL assay and immunoblotting were used for detection of changes in cell viability, proliferation, differentiation and apoptosis. Bezafibrate, ciglitazone and gemfibrozil inhibited viability of glioblastoma cell lines. The synthetic ligands significantly reduced or induced the expression of cyclins, p27Kip1, p21Waf1/Cip1, MDM-2, Bcl-2, Bax, PARP, Caspase 3, androgen receptors, etc. and did not affect the expression of the differentiation marker GFAP. Flow cytometry confirmed arrest of the cell cycle although the detection of apoptosis was controversial. Apart from hypolipidemic and hypoglycaemic effects, PPAR ligands may also have significant cytostatic effects of potential use in anticancer treatment.
Apoptosis↗
[Immunohistochemical study of the apoptotic and proliferative mechanisms in the intestinal mucosa during coeliac disease].
Mechanisms leading to morphological changes of the small intestine during coeliac disease are not yet completely recognized, however, two main processes have been suggested recently: remodelling of mucosa by matrix metalloproteinases, and mucosal atrophy by apoptosis. The aim of this study was to analyze the expression of proteins regulating apoptosis and some markers of proliferation in the mucosa of the small intestine of children with active (ACD) and latent form (LCD) of coeliac disease (CD). Intestinal biopsies of 43 children with ACD and LCD were analyzed by standard indirect immunohistochemical technique for Fas, Fas ligand (Fas-L), tissue transglutaminase (tTG), Bcl-2, Bid, glutathione S-transferase (GST), CAS 3, CAS 8, PARP, Ki-67, Topoisomerase IIa, PCNA expression. We found significantly lower numbers of Fas-expressing enterocytes in ACD patients than in LCD patients and controls. The number of Fas-positive mucosal lymphocytes was decreased in ACD when compared with LCD. Fas-L expression in enterocytes and mucosal lymphocytes was higher in ACD and LCD compared to controls. We found significantly more Bcl-2 negative lymphocytes in ACD than in LCD and controls. Bid expression in enterocytes was higher in LCD compared to ACD and controls. In intraepithelial lymphocytes, there was higher Bid expression in LCD than in ACD and controls compared to expression in mucosal lymphocytes, where was found higher number of positive cells in controls than in ACD and LCD. Expression of CAS 8 in mucosal lymphocytes was significantly higher in ACD compared to LCD. The expression of tTG in extracellular matrix and basal lamina was significantly higher in LCD and ACD when compared to controls. Expression of tTG was higher in the group of ACD and LCD in the enterocytes and in the lymphocytes. Our findings showed that Fas/Fas-L, Bcl-2, and CAS 8 may be involved in modulation of apoptosis during CD. Increased apoptotic elimination of IEL in LCD can partially explain preservation of the normal villous architecture. Increased tTG expression may be an early sign of increased apoptosis or may be related to its role in CD pathogenesis.
Apoptosis↗
Nestin expression by newly formed human blood vessels.
Nestin is a type VI intermediate filament protein originally described in neural stem cells. Here we report that immature endothelial cells generated in the course of angiogenesis express nestin. Endothelial cells of embryonic capillaries destined to vascularize growing organs also express this intermediate filament protein. Whereas nestin was sporadically expressed in mature adult human endothelial cells sporadically express nestin, this protein was consistently expressed in adult angiogenic vasculature. Nestin expression was also detected in capillaries of the corpus luteum, which replenishes itself by angiogenesis. Nestin-immunoreactive vessels were also observed in the infarcted hearts where transient ischemia triggered regeneration accompanied with neovascularization of the myocardium. Nestinpositive endothelial cells lined vessels nourishing solid growing tumors, including melanoblastomas and glioblastomas. Our data provide definitive evidence that endothelial precursors express the neural stem cell marker nestin and that this protein participates in formation of the cytoskeleton of newly formed endothelial cells. Because nestin expression was recognized under all conditions of vascular development, nestin represents a novel and reliable marker of neovascularization.
Blood Vessels↗
Solitary intracranial metastasis of follicular carcinoma of the thyroid gland clinically mimicking a meningioma.
We describe a rare case of solitary metastasis of follicular carcinoma of the thyroid gland into the petroclival region in a 58-year-old woman. The metastasis was the first and only manifestation of the disease. The histology of the tumor, differential diagnosis and clinical course are discussed. In a few similar cases described so far the tumor was always a well or moderately differentiated follicular carcinoma located in the petroclival region. As in this presentation, these cases also clinically mimic a meningioma. The differential diagnosis includes adenoma of the thyroid gland and thyroid gland dystopia. We demonstrated the primary focus of carcinoma within the thyroid after its detailed examination initiated by our finding. The clinical outcome of such rare cases is usually excellent, much better than in metastases of papillary carcinoma into the brain.
Adenocarcinoma, Follicular↗
[Initial experience in the treatment of chronic hepatitis C in an HIV-positive patient].
Explore the source record for details and available documents.
Bibliometrics↗
[Etiopathogenesis of diarrhea and basic principles of diagnosis and therapy].
Acute diarrhoea is worldwide the second most frequent disease after acute inflammations of the airways. Chronic diarrhoea is a less frequent disease, nevertheless the GP, specialist in internal medicine or gastroenterologist encounters it very frequently. For correct understanding of basic diagnostic and therapeutic principles of diarrhoea knowledge of its etiopathogenesis is necessary. In the submitted review the author mentions the functions of the small and large intestine and their part in the development of diarrhoea. He gives also the definition and classification of diarrhoea. The author presents the basic characteristics of osmotic, secretory, inflammatory, motor diarrhoea and diarrhoea associated with increased intestinal filtration. The basic diagnostic and therapeutic principles are in the last part of the review which has an educational character.
Diarrhea↗
Apoptosis, analysed by means of lamin B detection, correlates with grade of astroglial tumours but not with p27Kip1/retinoblastoma protein expression.
The aim of our study was to correlate apoptosis, assessed by means of lamin B degradation, with grade of tumour and immunohistochemical expression of p27Kip1 and retinoblastoma protein (pRB) in a series of 32 low-grade astrocytomas (LGA) and 43 high-grade astrocytomas (HGA). Determination and analysis of lamin B expression was achieved stereologically with the use of computerised interactive image analysis. The average stereological surface density of the lamin-positive nuclear surface of cells showing evidence of lamin degradation cells was 13.80 mm2/mm3 in LGA and 21.02 mm2/mm3 in HGA. The average range of immunopositivity of p27 and pRB expression was 2.85 and 2.10, respectively, in LGA and 1.80 and 0.88, respectively, in HGA. The rate of apoptosis indirectly correlated with the expression of both p27 and pRB but was not fully significant (P < or = 0.09). Our findings suggest that there may be a loss of function of main cell-cycle regulators and increased uncontrolled cell death in addition to increased cell proliferation in high-grade astrocytomas. Moreover, we believe that the detection of lamin B degradation in astroglial tumours can be an alternative, precise and convenient assay for the detection of a defined set of apoptotic cells. However, before being applied more generally, comparative research should be done on different methods of quantifying apoptosis, with the intent of finding the difference between biologically different methods. Such studies would also be able to find the method associated with the strongest prognostic power.
Apoptosis↗
Expression of ob gene coding the production of the hormone leptin in hepatocytes of liver with steatosis.
Leptin is a circulating pleiotropic hormone that play an important role in appetite control, fat metabolism, regulation of body weight, fetus growth, growth and aging of adults and hematopoiesis. It is expressed abundantly and specifically in the adipose tissue. A liver cell with developed steatosis represents a cell metabolism similar to metabolism of cells of adipose tissue. Analyses of serum leptin and free leptin receptor in the serum of patients with steatosis showed significant variations from reference limits of normal values. However in liver tissue with verified steatosis detection of mRNA gene for leptin was not proven. Such expression of ob gene for leptin was not found even in the liver tissue without steatosis. With respect to the absence of ob gene expression, the direct effect of ob gene expression on other parameters of leptin metabolism could not be evaluated. The RT-PCR method with verified specificity and satisfying sensitivity was developed. The results obtained from analysis of serum leptin and free leptin receptor in the serum are presented and evaluated. The used methods were verified and reference limits for Czech population were defined in dependence on age and other clinical parameters.
Fatty Liver↗
[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 H/RS cells in relation to expression of cell cycle proteins and EBV infection in patients with malignant lymphogranuloma].
Explore the source record for details and available documents.
Apoptosis↗
[Long-term follow-up of patients with extensive ulcerous colitis with emphasis on the occurrence of dysplastic changes and colorectal carcinoma].
The chronic course of idiopathic intestinal inflammations is characterized also by a relatively high incidence of complications, local ones affecting the entire large intestine, as well as extraintestinal ones in remote organs. In the submitted paper the authors present the results of a six-year follow-up focused on the incidence of dysplastic changes of the intestinal mucosa and colorectal carcinoma in 46 patients from a group of 220 patients followed up on a long-term basis at the Second Medical Clinic of the Faculty Hospital and Medical Faculty Olomouc because of the extensive type of ulcerative colitis. The incidence of these complications is not high in our group and is only slightly higher than in the general population. As it is however a very serious disease and so far an optimal algorithm for its follow up has not been elaborated, we feel it is useful to investigate this high risk group of patients after 6-24-month intervals according to the confirmed grade of dysplasia of the intestinal mucosa.
Adult↗
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↗