PubMed Health⌕ Search

Biomedical subjects

Matthias Ebert

Publications and source records attributed to Matthias Ebert.

4 recordsLinked to original sources

Expression of G1 phase cyclins in human gastric cancer and gastric mucosa of first-degree relatives.

The aim of this study was to investigate the expression of D-type cyclins and cyclin E in gastric cancer patients (N = 34), in healthy first-degree relatives of gastric cancer patients (N = 29), and in control subjects (N = 18). Expression of cyclins D1, D2, D3, and E was determined by RT-PCR. Localization of cyclin expression was determined by immunohistochemistry. Expression of cyclins D2, D3, and E was more frequently detected in tumor tissue compared with tumor-free gastric mucosa (P < 0.05) and was associated with the presence of intestinal metaplasia. In contrast, cyclin D1 was frequently expressed in both tumor- and tumor-free tissue. Cyclin D3 expression was more frequently detected in the antrum mucosa of first-degree relatives compared to controls (P < 0.01) and was associated with the presence of Helicobacter pylori. Our data suggest that deregulation of G1 phase cyclins may play a role in gastric carcinogenesis, and may point to the presence of molecular alterations in individuals at an increased risk for gastric cancer.

Aged↗

Transgenic overexpression of amphiregulin induces a mitogenic response selectively in pancreatic duct cells.

BACKGROUND & AIMS: The epidermal growth factor (EGF) receptor family and the corresponding ligands are frequently overexpressed in pancreatic cancer. To compare the biological effects of transforming growth factor (TGF)-alpha and amphiregulin (AR) on growth and differentiation of the exocrine pancreas, we have generated transgenic mice overexpressing AR under control of the elastase promoter. METHODS: Two independently generated transgenic mouse lines overexpress 50-, 43-, 28-, 26-, and 16-kilodalton AR forms in the pancreas. RESULTS: Morphologic and immunohistochemical examinations suggest that small intralobular duct and centro-acinar cells proliferate in response to AR in these mice. AR transgenic mice display increased Ras, Erk1/2, cyclin D/CDK4, and cyclin E/CDK2 activity and G1/S progression in pancreatic duct cells. In contrast to TGF-alpha transgenic mice, AR neither induced tubular complex formation nor elicited a strong fibrogenic response. AR induced a slight induction of ErbB2 on duct cells, whereas TGF-alpha resulted in overexpression of the EGF receptor in cells within tubular complexes. Furthermore, AR and TGF-alpha displayed different effects on differentiation of isolated acini in vitro comparable to the situation in vivo. CONCLUSIONS: These data suggest that AR induces a mitogenic response selectively in small duct cells through activation of Ras, CDK2, and CDK4, respectively. The closely related EGF receptor ligands, AR and TGF-alpha, display different biological effects when overexpressed in the exocrine pancreas in vivo.

Amphiregulin↗

Soluble thrombomodulin plasma levels are an early indication of a lethal course in human acute pancreatitis.

BACKGROUND: The potential to predict severe disease and lethality by using plasma soluble thrombomodulin (sTM) and C-reactive protein (CRP) levels in 73 patients with acute pancreatitis was analyzed in a prospective 5-year investigation performed at a single institution. METHODS: According to the Atlanta criteria, pancreatitis was classified as mild in 23 patients and as severe in 50 patients. Blood was collected on days 1, 3, 5, 7, 10, 14, 21, and 28 after the onset of pain and analyzed for sTM and CRP. RESULTS: During the period between days 3 and 10 of acute pancreatitis when most of the admissions occurred, sTM levels at a cutoff of 75 ng/mL on day 3 (sensitivity, 100%; specificity, 77%; positive predictive value, 38%; negative predictive value, 100%) and 71 ng/mL on day 10 (sensitivity, 100%; specificity, 77%; positive predictive value, 41%; negative predictive value, 100%) were predictive of a lethal outcome. With sTM levels, it was not possible to differentiate patients with mild pancreatitis from those with severe pancreatitis (Atlanta classification). In contrast, CRP levels at a cutoff of 113 mg/L on day 3 differentiated severe from mild courses with a diagnostic sensitivity of 84%, a specificity of 60%, a positive predictive value of 78%, and a negative predictive value of 69%. CRP levels at a cutoff of 122 mg/L on day 10 differentiated mild from severe courses (nonsurvivors) with a diagnostic sensitivity of 72%, a specificity of 72%, a positive predictive value of 86%, and a negative predictive value of 53%. In contrast, differentiation of mild forms of acute pancreatitis from severe pancreatitis (survivors) on day 10 was not possible. CONCLUSIONS: CRP is a valuable marker of disease severity in acute pancreatitis especially in the first period of pancreatitis, whereas sTM identifies early those patients with the most severe courses and a high risk of dying (negative predictive value, 100%). Determination of sTM in addition to CRP offers the opportunity of identifying early those patients who require intensive care most urgently. Of course, further investigations of sTM in acute pancreatitis are indicated to confirm our results.

Acute Disease↗

Parker weights revisited.

The short-scan case in fan-beam computed tomography requires the introduction of a weighting function to handle redundant data. Parker introduced such a weighting function for a scan over pi plus the opening angle of the fan. In this article we derive a general class of weighting functions for arbitrary scan angles between pi plus fan angle and 2pi (over-scan). These weighting functions lead to mathematically exact reconstructions in the continuous case. Parker weights are a special case of a weighting function that belongs to this class. It will be shown that Parker weights are not generally the best choice in terms of noise reduction, especially when there is considerable over-scan. We derive a new weighting function that has a value of 0.5 for most of the redundant data and is smooth at the boundaries.

Algorithms↗