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Biomedical subjects

A Tannapfel

Publications and source records attributed to A Tannapfel.

At least 109 records · Page 6Linked to original sources

Apoptosis and the expression of Fas and Fas ligand (FasL) antigen in rejection and reinfection in liver allograft specimens.

BACKGROUND AND METHODS: To investigate the frequency of apoptosis and the expression of Fas/Fas ligand (FasL) in liver allografts, we examined 97 biopsy specimens from 62 patients after orthotopic liver transplantation. The results of the biopsies were as follows: acute allograft rejection (n=32); hepatitis C virus (HCV) reinfection (n=18); cytomegalovirus infection (n=5); acute rejection plus HCV reinfection (n=3); and stable graft function (n=30); and after treatment of acute rejection (n=9). RESULTS: Apoptotic cells were found in all cases examined, and their frequency increased significantly during acute rejection (0.17 vs. 9.0; P<0.05). The immunoreactivity of Fas and FasL antigen was higher in specimens with acute rejection than in those with stable graft function. Increased apoptosis, Fas, and FasL expression, however, were also seen in HCV reinfection. CONCLUSION: We conclude that apoptosis plays an important role in the hepatocellular damage observed in acute rejection and also in HCV reinfection. However, these parameters are, taken by themselves, not useful as indicators of acute rejection or HCV reinfection.

Apoptosis↗

Apoptosis and proliferation in relation to histopathological variables and prognosis in hepatocellular carcinoma.

The prognosis of patients with resectable hepatocellular carcinoma depends mainly on the anatomical extent of the tumour and on the general condition of the patient. Given the growing evidence that proliferation indices may be of prognostic significance in hepatocellular carcinomas and that parameters of cell loss (usually, but not exclusively, due to programmed cell death) are biologically relevant, the identification and quantitation of proliferative capacity and apoptosis may be of prognostic importance. In this study four different methods have been used to assess proliferation in a series of 193 curatively (R0) resected hepatocellular carcinomas: mitotic count, immunohistochemical assessment of MIB-1 (Ki-67), proliferating cell nuclear antigen (PCNA), and silver-stained nucleolar organizer regions (AgNORs). Apoptosis was assessed using the in situ-end labelling (ISEL) technique in combination with morphological criteria. Patients who received liver transplantation were excluded. The results obtained were compared with histopathological stage (according to UICC), Edmondson grade, several other histopathological factors, and survival rate. Significant statistical correlations were seen between the mitotic index, the rate of nuclear positivity for MIB-1 and PCNA, and the number of AgNOR dots. In univariate survival analysis, tumour stage and Edmondson grade, mitotic index, MIB-1 and PCNA index, and mean AgNOR number were significant factors influencing patients' survival. On multivariate Cox survival analysis, mitotix index, concomitant cirrhosis, Edmondson grade, and patient age were the only significant independent prognostic factors. Apoptosis was not related to prognosis or to other parameters examined. These results indicated that mitotic index is an additional prognostic parameter which could provide auxiliary information for patients' outcome. MIB-1 and PCNA immunostaining and AgNORs showed a good correlation among themselves. Apoptosis did not predict prognosis in hepatocellular carcinoma.

Apoptosis↗

Expression of p73, a novel protein related to the p53 tumour suppressor p53, and apoptosis in cholangiocellular carcinoma of the liver.

p73, the first homologue of the tumour suppressor protein p53, was recently discovered on chromosome 1p36 and has been shown to induce apoptosis in a p53-like manner. The present study was performed with the aim of investigating the expression of p53, its new homologue p73 and the occurrence of apoptosis in cholangiocellular carcinoma. Protein levels of p73 were examined in 41 patients with curatively (R0-) resected cholangiocellular carcinomas with an antiserum, raised against a peptide in the N-terminal domain of p73. The incidence of mutations in the p53 gene was analysed by direct sequencing and also immunohistochemically. Apoptotic cell death was assessed using in-situ end-labelling (ISEL) technique in combination with morphological criteria. The results obtained were correlated with patient survival. Immunostaining of p73 protein was detected in 17/41 carcinomas examined (41%). The immunoreactivity was confined to the cell nucleus. In 15/41 patients (37%), mutations of the p53 gene were observed. Eleven out of these 15 patients stained also positive for p73. In contrast, out of 26 patients without any detectable p53 mutation, only six exhibited p73 immunostaining. We failed to observe a correlation between p73 expression or p53 and apoptosis within a given tumour. Survival analysis including the parameters stage and grade of disease, p73 and p53, and also apoptosis, showed that tumour stage and grade as well as p53 and p73 were significantly related to prognosis. In Cox regression survival analysis, however, only extent of primary tumour and lymph node status had an independent prognostic impact. Our results with a high prevalence of p73 within tumours harbouring mutated p53 gene suggest that p73 could compensate for p53 function. We failed to establish p73 or p53 as independent prognostic factors in cholangiocellular carcinoma of the liver.

Apoptosis↗

The pancreatitis-associated protein in hereditary and chronic alcoholic pancreatitis.

The pancreatitis-associated protein (PAP) was investigated in patients with hereditary and chronic alcoholic pancreatitis. Blood levels of pancreatic enzymes and PAP were measured in nine families with hereditary pancreatitis; in three of them, the mutation N21I, and in six, the R117H variant of the cationic trypsinogen were present. In all family members, similar to controls, only normal values of the PAP were found. There was no evidence for polymorphism of the PAP gene in patients with hereditary or alcoholic pancreatitis. Immunohistochemically PAP was detected in the apical parts of the acinar cells but not in ducts, interstitial tissue, islets, or blood vessels. Intensity of PAP labeling was directly related to the deterioration of the acinar units, and its concentration was inversely related to chymotrypsinogen immunoreactivity in the same tissue. Similar immunohistochemical findings were present in chronic alcoholic and hereditary pancreatitis. We conclude that there is a lack of PAP polymorphism in hereditary and alcoholic pancreatitis and that expression of the PAP in both groups of patients is related to the degree of cellular damage of the pancreas.

Acute-Phase Proteins↗

Comparison of different double immunostaining protocols for paraffin embedded liver tissue.

Most of the double immunostaining protocols that have been introduced so far have been developed for application on fresh frozen material or based on different species antibodies. In liver tissue, general problems of double immunostaining techniques are further complicated by tissue-specific difficulties, such as necrosis or high intracellular protein content. To assess a reliable double immunostaining protocol for archived, paraffin embedded liver tissue, different protocols based on the use of same species primary antibodies were evaluated in terms of sensitivity, specificity and non-specific background staining in pathological liver specimens. We compared peroxidase-anti-peroxidase, alkaline phosphatase-anti-alkaline phosphatase (PAP/APAP), labelled-avidin-biotin (LAB/LAB) and digoxigenin-anti-digoxigenin (dig-a-dig/PAP) techniques using different cytokeratin antibodies and an antibody against PCNA. Comparison of the double immunostaining techniques revealed a high sensitivity and specificity in all procedures. Sections, which were stained employing PAP/APAP-technique, displayed a higher background staining compared to sections which were treated with the LAB/LAB or dig-a-dig/PAP protocol. In contrast to the dig-a-dig/PAP protocol, the LAB/LAB technique provides a better time/cost relationship. Therefore, we would like to recommend a modified LAB/LAB protocol for simultaneous detection of different antigens in archived liver tissue.

Animals↗

Investigation of microvessel density after irradiation.

It is believed that malignant cell populations need the development of microvessels to grow and metastasize. The aim of our investigation was to find out whether gamma irradiation can affect proliferation of endothelial cells and thus can affect microvessel density in vivo. We used fertilized chicken eggs. The vascularized part of the yolk sac membrane (area vasculosa) of the eggs received single doses of 2 to 10 Gy. Forty-eight hours after irradiation, the area vasculosa was photographed in vivo, and prints of known magnification were evaluated to determine the density of the blood vessels. Microvessel count is the well-established marker used to determine vascular density. In addition, the proliferative activity of endothelial cells in the yolk sac membrane was determined by estimating the expression of proliferating cell nuclear antigen (PCNA). PCNA immunostaining was assessed immunohistochemically. After a single dose of 10 Gy, a statistically significant increase in vascular density was found compared to values determined at 0, 2, 4 and 8 Gy (P < 0.05). Twenty-four hours after 10 Gy irradiation, 44.8% (mean) of the endothelial cells were PCNA-positive. This was significantly higher (P < 0.05) compared to the results 24 h after 4.0 Gy (22.7%) and compared to control (19.4%). Twenty-four hours later, i.e. 48 h after irradiation with 10 Gy, the endothelial cells also showed a significantly (P < 0.05) higher PCNA positivity with a mean of 34.1% compared to the nonirradiated area vasculosa (18.1%) and compared to the results after 4.0 Gy irradiation (12.0%). The prerequisite for blood vessel formation is the proliferation of endothelial cells. Thus a single-dose irradiation with 10 Gy induces endothelial cell proliferation and subsequent neovascularization in the area vasculosa of the fertilized egg.

Animals↗

Relative versus absolute carbohydrate-deficient transferrin as a marker of alcohol consumption in patients with acute alcoholic hepatitis.

BACKGROUND: Carbohydrate-deficient transferrin has been described as a sensitive and specific marker for alcohol consumption. This study investigated the usefulness of carbohydrate-deficient transferrin as a marker of alcohol consumption in acute alcoholic hepatitis. METHODS: Absolute concentrations (U/I) and relative values (%) of carbohydrate-deficient transferrin determined in serum with commercial assays, as well as conventional markers for alcohol consumption, were compared with the alcohol consumption (as estimated by a questionnaire) in patients with acute alcoholic hepatitis (n = 19), alcoholic liver cirrhosis (n = 37), and nonalcoholic liver diseases (n = 16). RESULTS: The concentration of carbohydrate-deficient transferrin was increased (p < 0.001) in nonabstaining patients (median intake 80 g alcohol/day) with alcoholic liver cirrhosis (45.7 +/- 30 U/l), but not in patients with acute alcoholic hepatitis (20.0 +/- 7.8 U/l) despite higher alcohol consumption (median 130 g/d), nor in abstainers with alcoholic liver cirrhosis (19.4 +/- 6.0 U/l) or nonalcoholic liver disease (18.5 +/- 6.7 U/l). However, the relative values of carbohydrate-deficient transferrin were increased both in acute alcoholic hepatitis (7.9 +/- 2.1%) and nonabstainers with alcoholic liver cirrhosis (7.4 +/- 2.8%), but not in abstainers with alcoholic liver cirrhosis (4.6 +/- 3.5%) or nonalcoholic liver disease (3.8 +/- 0.9%) (p < 0.001). In acute alcoholic hepatitis, the sensitivity and specificity were only 32% and 87% for absolute concentrations, respectively, but 79% and 97% for relative values of carbohydrate-deficient transferrin. The concentrations of carbohydrate-deficient and total transferrin in serum were strongly correlated (r = 0.60; p = 0.008). CONCLUSIONS: The relative value (% of total), but not the absolute concentration, of carbohydrate-deficient transferrin in serum is a useful marker of alcohol consumption in acute alcoholic hepatitis.

Adult↗

Apoptosis, proliferation, bax, bcl-2 and p53 status prior to and after preoperative radiochemotherapy for locally advanced rectal cancer.

PURPOSE: To investigate the relationship between apoptotic cell death, proliferative activity, and the expression of apoptosis regulating proteins in rectal cancer prior to and after radiochemotherapy. MATERIALS AND METHODS: In 32 patients dispositioned to receive preoperative radiochemotherapy for locally advanced rectal carcinoma, pretherapy biopsies and the final resected specimen after radiochemotherapy were available for analyses. Apoptotic cells were identified and quantified using in situ end labeling (ISEL) technique. The expression of the bax protein was assessed immunohistochemically. Additionally, double immunostaining was performed for apoptotic cells and bax expression. The proliferative activity was determined by immunohistochemical assessment of the Ki67 (MIB-1) and the proliferating cell nuclear antigen (PCNA). p53- and bcl-2 expression was analyzed immunohistochemically. A clinical-to-pathologic downstaging after radiochemotherapy was achieved in 25 of 32 patients (78%). During follow-up, tumor recurrence was observed in six cases. In one case, no residual tumor was detected after radiochemotherapy. RESULTS: After radiochemotherapy, the apoptotic index increased significantly in almost every case examined. In contrast, the proliferative activity was significantly decreased in resected specimens as compared to biopsies. Bax immunostaining was detected in 12/31 (39%) biopsies and in 26/31 (84%) resected specimens. In the resected specimen, significantly more apoptotic cells that were bax-positive were found than in biopsies. Bcl-2 immunostaining occurred in 15/31 biopsies and 12/31 resected specimens, respectively. Tumors that were immunohistochemically negative for p53 (20/31 [65%]) generally exhibited a higher apoptotic index and a high expression level of bax than p53-positive tumors (11/31 [35%]). However, we did not find any correlation between the (pre- and post-therapeutic) rate of apoptosis or the level of bax expression and the degree of clinical-to-pathologic downstaging or the frequency of tumor recurrence. CONCLUSION: Our results indicate that radiochemotherapy is associated with an increase in bax expression and also in apoptotic cell death. The observation of higher rates of apoptosis and bax in p53-negative tumors suggests that p53 might be a possible regulating factor of apoptosis in rectal cancer.

Adult↗

[Proliferation and apoptosis before and after preoperative simultaneous radiochemotherapy of rectal carcinomas].

PURPOSE: To investigate the relationship between apoptotic cell death, proliferative activity, and the status of the tumor suppressor gene p53 in rectal cancer before and after radiochemotherapy. MATERIALS AND METHODS: Thirty-two patients dispositioned to receive preoperative radiochemotherapy for locally advanced rectal carcinoma prior to radical surgical tumor resection were analysed. In all cases, pretherapy biopsies and the final resected specimens after radiochemotherapy were available for analyses. Apoptotic cells were identified and quantified using in situ end labeling (ISEL) technique. The proliferative activity was determined by immunohistochemical assessment of the Ki67 (MIB-1) antigen. p53 expression was analysed immunohistochemically as well. A clinical-to-pathologic downstaging after radiochemotherapy was achieved in 25/32 patients (78%). In one case, no residual tumor was detected after radiochemotherapy. RESULTS: After radiochemotherapy, the apoptotic index increased significantly in almost every case examined. In contrast, the proliferative activity was significantly decreased when comparing biopsies and resected specimens. Tumors that were immunohistochemically negative for p53 generally exhibited a higher apoptotic index than p53 positive tumors. However, we did not find any correlation between the (pre- and post-therapeutic) rate of apoptosis and the degree of clinical-to-pathologic downstaging. CONCLUSION: Our results indicate, that radiochemotherapy induces an increase in apoptotic cell death. The observation of higher rates of apoptosis in p53 negative tumors suggests that p53 might be a regular of apoptosis in rectal cancer.

Adenocarcinoma↗

Distribution and pharmacokinetics of Photofrin in human bile duct cancer.

Prognosis of patients with bile duct tumors is mostly poor due to late diagnosis and a lack of adequate curative and palliative treatment modalities. To evaluate the potential of photodynamic therapy (PDT) as a novel and alternative treatment approach, we have investigated the uptake and tumor-specific localization of the photosensitizer Photofrin in human biliary tract neoplasms. We have quantified the distribution and the pharmacokinetics of Photofrin in normal and tumor tissue biopsies of the human bile duct by quantitative fluorescence microscopy and digital image analysis of cryosections. Fluorescence intensities (expressed as a percentage of a standard) are 19.0 +/- 11.4% and 25.2 +/- 12.7% for tumors and 10.9 +/- 2.9% and 13.2 +/- 9.1% (mean +/- SD) for normal bile duct tissue at 24 h (n = 5) and 48 h (n = 8) after Photofrin administration (2 mg kg-1 i.v.), respectively, and decrease afterwards in normal bile duct tissue over the period of investigation (4-35 days). The ratios of fluorescence in tumor versus normal tissue are found to be 1.7 +/- 0.7 and 2.3 +/- 1.2 (mean +/- SD) at days one and two after Photofrin administration, respectively. Thus, Photofrin preferentially accumulates in bile duct neoplasms, reaching peak values during the first two days. These data suggest that laser irradiation should be performed within this period after Photofrin injection to achieve tumor selectivity of PDT for effective treatment of bile duct carcinoma.

Adenocarcinoma↗

Primary amyloidosis of the mesentery and the retroperitoneum presenting with lymphedema.

We report the case of a 57-yr-old woman presenting with moderate weight loss, abdominal distension, and lymphedema of the legs and vulva. Computed tomography of the abdomen revealed massive thickening of the rectal wall, mesentery, and retroperitoneum. Primary amyloidosis was diagnosed by immunohistochemistry from the rectum and duodenum. To our knowledge, lymphedema due to primary amyloidosis has not yet been reported. The diagnosis should be presumed in the case of retroperitoneal thickening and lymphedema and can be established by immunohistochemistry.

Amyloidosis↗

[Cronkhite-Canada syndrome. Epidemiology, symptoms, morphology and therapy based on a case report and literature review].

Juvenile polyposis was first described by Cronkhite and Canada in 1955. This disease is characterized by juvenile intestinal polyps and ectodermal abnormalities. The etiology of Cronkhite-Canada syndrome (CCS), however, is still not well understood. Interestingly among patients with CCS a significant correlation (16.5%) with intestinal carcinomas has been observed. Thus, malignant transformation and/or genetic predisposition may be involved in the initiation of the disease. In the following, epidemiology, symptoms, morphology and therapy of CCS are discussed. Our examinations are based on studies reported in the literature and on a case report of a female patient who developed a colon carcinoma 2 years after initial diagnosis of CCS.

Adenocarcinoma↗

Multiple simultaneous gastric carcinomas.

A total of 1664 patients with gastric cancer were examined to evaluate the rate of multiple synchronous primary tumours. In cases of multiple synchronous cancer (MSC), the tumours were analysed immunohistochemically for their expression pattern of p53, c-erbB2, ras, E-cadherin and proliferative activity. Multiple synchronous gastric carcinomas (MSCs) were observed in 61 out of 1664 patients (3.7%), with a total of 134 carcinomas. In our series, early carcinoma was observed more frequently in MSC than in solitary cancers. The comparison of tumour stage in MSC and solitary tumours revealed that multiple early gastric cancers were significantly more often of type I (protruded type) and IIa (superficial elevated type) than solitary early cancer. Multiple advanced carcinomas were more often of a lower pT category than solitary advanced gastric cancer. Performing immunohistochemistry for p53, c-erbB2 and ras in 134 tumours with MSCs, we observed positivity rates of 33%, 59% and 87% respectively. In 43 patients, the multiple tumours in each individual patient demonstrated an identical status of p53 and c-erbB2, and in 42 patients a similar pattern of E-cadherin expression was observed. The proliferative index, determined by proliferating cell nuclear antigen (PCNA) immunolabelling, did not differ significantly between the MSC in each patient. Ras immunostaining was detected in 53 out of 61 patients, but also in metaplasia and regenerative hyperplasia in the specimens. In survival analysis, no difference was observed between patients with solitary or multiple early or advanced carcinomas. Our results suggest that in at least a high proportion of patients with gastric cancer multiple primary tumours arise from precancerous conditions leading to similar genetic alterations.

Aged↗

Systemic infection with Mycobacterium genavense following immunosuppressive therapy in a patient who was seronegative for human immunodeficiency virus.

We describe, to our knowledge, the first case of disseminated Mycobacterium genavense infection in a patient who was seronegative for human immunodeficiency virus. The patient, a 47-year-old woman, had been previously treated with immunosuppressive drugs for 9 months to control an unclassified immunologic disorder characterized by intermittent fever and inflammatory pulmonary, hepatic, and dermal infiltrates. Antemortem and postmortem examinations revealed the presence of numerous mycobacteria in the bone marrow, spleen, kidneys, and lungs; these organisms failed to grow in vitro and were identified as M. genavense by 16S rRNA gene sequencing. This case illustrates that systemic M. genavense infections are not restricted to patients with AIDS but can also occur in otherwise immunocompromised patients.

Female↗