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Biomedical subjects

S Matern

Publications and source records attributed to S Matern.

At least 19 recordsLinked to original sources
PubMed2006

[Severe refractory pulmonary hypertension after liver transplantation for hepatitis C liver cirrhosis].

BACKGROUND: We report the case of a 43-year-old male with liver cirrhosis based on a chronically active hepatitis C. CASE REPORT: Before liver transplantation right-ventricular pressure values of 36 mmHg (+ central venous pressure) were measured whereas, after transplantation, he developed severe pulmonary hypertension with pressure values up to 90 mmHg. These elevated pressure values correlated inversely with graft function. Given the diagnosis of portopulmonary hypertension, we initiated treatment with intravenous epoprostenol and inhalative iloprost but both treatments were not tolerated because of systemic side effects. A combined heart-lung transplantation was considered but the patient died from insufficient cardiac function. CONCLUSIONS: The case report discusses the present diagnostic and therapeutic state of the art in portopulmonary hypertension and reveals basic problems of the present screening strategy.

Adult↗
PubMed2005

Eosinophilic gastroenteritis with severe protein-losing enteropathy: successful treatment with budesonide.

We report the clinical, laboratory, endoscopic and histopathological findings in a 40-year-old woman with watery diarrhoea and hypoproteinaemia. Elevated alpha(1)-antitrypsin clearance confirmed massive protein-losing enteropathy. Gastroscopic and colonoscopic biopsies showed abundant infiltration of the small bowel wall with eosinophils in proximal duodenum and terminal ileum, respectively. These findings established the diagnosis of eosinophilic gastroenteritis. Both the inflammatory alterations and the severe intestinal protein loss were successfully treated with budesonide, a topically active corticosteroid preparation with controlled small bowel release. The case report illustrates that remission of protein-losing enteropathy secondary to eosinophilic gastroenteritis can be achieved with budesonide, thus supporting its use for this uncommon disease characterised by inflammatory intestinal lesions.

Adult↗
PubMed2005

[Extrahepatic manifestations of chronic liver diseases].

Chronic liver diseases are commonly associated with extrahepatic disease manifestations. Liver cirrhosis, the end stage of chronic liver diseases of different etiologies, can result in severe neurological, renal and pulmonary complications. Hepatic encephalopathy plays an important socio-economic role, since it affects daily functioning and fitness to drive. During the clinical course of chronic viral hepatitis, many patients develop extrahepatic disease manifestations, which lead to significant morbidity and mortality. In particular, mixed cryoglobulinemia, membranoproliferative glomerulonephritis and polyarteriitis nodosa are strongly associated with chronic viral hepatitis. Most extrahepatic manifestations are due to immunological and lymphoproliferative pathomechanisms. Knowledge of extrahepatic disease manifestations is important for adequate medical care and risk assessment of patients with chronic liver diseases by insurance companies.

Chronic Disease↗
PubMed2005

Cutaneous mucinosis and skin necrosis complicates interferon alfacon-1 (consensus interferon) treatment of chronic hepatitis C.

A 59-year-old Caucasian suffering from chronic hepatitis C started daily subcutaneous self-injections of interferon alfacon-1 (consensus interferon) according to the protocol of a randomised multicentre study. At week 10, he developed painful erythematous lesions at two injection sites. Consensus interferon dosage was reduced, and eventually, the lesions healed with small areas of scarring due to central necrosis. At week 51, again large areas of erythematous thickened skin arose at two other injection sites followed by substantial ulceration and central necrosis. Skin biopsy revealed excessive dermal mucin deposition so that cutaneous mucinosis was diagnosed. After 3-6 months, the lesions healed with central scarring. Due to a persistently negative HCV-PCR from serum (from week 12 onwards), consensus interferon treatment was not stopped but continued until week 60 according to the study protocol. - Cutaneous mucinosis has not been previously reported to complicate treatment with consensus interferon in patients with chronic hepatitis C and should therefore be added to the list of dermatological side-effects associated with interferon alfacon-1 therapy.

Antiviral Agents↗
PubMed2005

Identification of fibrosis-relevant proteins using DIGE (difference in gel electrophoresis) in different models of hepatic fibrosis.

Proteomics became a more and more important technique for the large-scale analysis of proteins during the last years. Two-dimensional (2D) electrophoresis as a major tool of proteomics is a powerful method to compare two different biological stages (e. g. healthy and diseased tissue) and to find differences in their protein pattern. One major problem in proteomics is the gel to gel variation of two-dimensional gel electrophoresis, which could cause artefacts in the detection of expression differences. The "difference in gel electrophoresis" (DIGE) technique allows the separation of two proteomes in the same gel. The protein pools were labelled with different fluorescent dyes and equal amounts of protein were separated in the same gel. Another advantage of DIGE is the possibility to separate an internal standard labelled with a third dye in the same gel to allow quantitative expression analysis. We compared proteomes of three different fibrosis models with the appropriate control (tissue inhibitor of metalloproteinases-1 (TIMP-1) overexpressing HepG2 cells in comparison to a HepG2 control, freshly isolated HSC in comparison to activated HSC and healthy mouse liver in comparison to fibrotic mouse liver). Among the differentially expressed proteins several were already found to be relevant for fibrosis but we also detected some proteins like the selenium binding protein 2 which might be relevant for hepatic fibrosis.

Animals↗
PubMed2004

[Extracellular matrix -- from basic research to clinical significance. An overview with special consideration of matrix metalloproteinases].

Matrix metalloproteinases (MMPs) hydrolyze most components of the extracellular matrix (ECM). These proteinases play a central role in many biological processes such as normal tissue remodeling, embryogenesis, wound healing and angiogenesis. Currently about 26 MMP genes have been identified, and most are multidomain zinc endopeptidases. Knowledge of their tertiary structure is crucial for the understanding of the functional properties of MMPs. In healthy tissue a strict regulation of MMPs is critical in order to maintain proper ECM homeostasis. Among other levels of regulation, MMPs are precisely regulated by their main endogenous protein inhibitors (TIMPs). Disruption of this balance results in serious diseases such as fibrosis, arthritis, and tumour growth. Several studies have documented the importance of MMP-mediated ECM destruction for tumour initiation, growth, migration, angiogenesis, invasion and metastasis. Certain MMPs such as gelatinases (MMP-2, MMP-9) have special mechanisms to localize at leading edges in tumour tissue. MMPs can no longer be thought of solely as ECM destructionists, but as part of an elegant communication system through which epithelial and tumor cells interact with the stroma.

Animals↗
PubMed2004

[Gastrointestinal stromal tumors: a broad clinical spectrum from incidental -discovery to acute gastrointestinal bleeding].

Three cases of gastrointestinal stromal tumors (GIST) are reported as typical examples of the broad clinical spectrum in which these rare tumors can be detected. The first case describes an 82-year-old patient with a hemorrhagic shock due to upper gastrointestinal bleeding from a GIST of the stomach. GIST most frequently present with either gastrointestinal bleeding, abdominal pain or a detectable mass on physical examination or by ultrasound imaging. Clinically asymptomatic tumor growth also occurs as demonstrated by the second case of a 44-year-old -woman with an incidental finding of GIST during surgery of the esophagus. The cases are used to discuss the consequences for therapy and prognosis resulting from the heterogeneity of this tumor entity; the relevant immunohistochemical markers used to distinguish between various tumor subtypes of gastrointestinal mesenchymal tumors (GIMT) are listed. Since gastrointestinal stromal tumors (GIST) represent the most common subgroup of GIMT, we focus on the clinicopathological prognostic factors of GIST. The third case of a 40-year-old patient with a malignant GIST recurrence after surgery and exhibiting secondary resistance after one year of successful therapy with the receptor tyrosine kinase inhibitor imatinib (Gleevec), antagonizing pathogenetically relevant constitutive c-KIT activation, illustrates the potential and limitations of the only effective drug treatment for advanced GIST.

Abdominal Pain↗
PubMed2004

Impedance characteristics of esophageal motor function in achalasia.

Detailed data on patterns of esophageal bolus transport in patients with achalasia are still lacking. To study these we applied the novel technique of multichannel intraluminal impedance measurements. Ten patients with achalasia were studied using a 16 channel system. Liquid and semisolid boluses of 10 mL were applied with the patients in a supine position. Patterns of bolus transport were determined and analyzed as compared to results obtained from 20 healthy subjects. The healthy subjects featured a unique typical primary peristalsis pattern independent of bolus viscosity. In contrast, achalasia patients demonstrated different impedance characteristics, including: (i) significantly lower baseline esophageal impedance during the resting state as compared with healthy volunteers (999 omega +/- 108 versus 2749 omega +/- 113); (ii) failed bolus transport through the esophagus in all cases; (iii) impedance evidence of luminal content regurgitation in 35% of the swallows (iv) impedance evidence of pathological air movement within the proximal esophagus during deglutition in 38% of the swallows, so called air trapping. Thus, impedance characteristics of achalasia have been defined and can be attributed to known symptoms of achalasia. They can be used as basic findings for further classification of pathological bolus transports in other esophageal motility disorders.

Adult↗
PubMed2004

Influence of biliary cirrhosis on the detoxification and elimination of a food derived carcinogen.

BACKGROUND AND AIMS: The liver is the central organ for the detoxification of numerous xenobiotics, including carcinogens. We studied the influence of cholestasis and biliary cirrhosis on the detoxification, elimination, and tissue distribution of a model compound and food derived carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). METHODS: Wistar rats were injected with (14)C-PhIP into the portal vein one or six weeks after common bile duct ligation (CBDL). Bile flow was reconstituted, bile and urine were collected over 120 minutes, and metabolites were analysed using high performance liquid chromatograpy. Total tissue radioactivity levels in several organs as well as tissue bound (ethanol insoluble tissue fraction) radioactivity levels were determined. RESULTS: Significant downregulation of the transport proteins multidrug resistance associated protein 2 and breast cancer resistance protein was observed in biliary cirrhosis. Biliary excretion of radioactivity was significantly reduced in cholestasis and biliary cirrhosis compared with controls (15 (2.9)% and 3.2 (1)% of the dose v 36.5 (2)%, respectively). Phase II metabolism was severely reduced in cirrhotic rats, resulting in a twofold increase in tissue radioactivity levels in the liver, kidney, and colon. Biliary cirrhosis increased tissue binding of reactive metabolites, as expressed in cpm/100 mg tissue in the liver and the colon (3267 (1218) v 1191 (429) in the liver, 3044 (1913) v 453 (253) in the colon). CONCLUSIONS: Biliary cirrhosis induced by CBDL causes impaired metabolism and elimination of PhIP, and leads to higher tissue levels of potentially genotoxic metabolites in the liver and colon of rats. These data may explain the increased incidence of hepatic and extrahepatic cancers in cholestasis and liver cirrhosis.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2003

[Confocal laser scanning microscopy: a deep look into the cell].

Confocal laser scanning microscopy (CLSM) is a powerful technology for assaying biomolecular distribution and dynamics in cells and tissues. Innovations in CLSM-techniques, coupled with the development of new dyes and genetically encoded indicators, have increased both in vitro and in vivo imaging approaches. CLSM has had wide application in basic science, but little impact so far on medical investigations. As a "cutting edge" technology CLSM has proved to be a valuable tool in some areas within medical applications including pathology, dermatology, ophthalmology and research in various other fields of medicine. This paper gives an overview about the wide range of CLSM-applications and shows the enormous potential of this technology in medical research and development.

Animals↗
PubMed2003

Constitutive rat multidrug-resistance protein 2 gene transcription is down-regulated by Y-box protein 1.

BACKGROUND/AIMS: Molecular mechanisms underlying transcriptional rat multidrug-resistance protein 2 (Mrp2, Abcc2) gene regulation are mostly unclear. Given the presence of putative binding sites for the Y-box binding protein YB-1 in the regulatory sequence, its trans-regulatory influence was analyzed. METHODS: Reporter assays in HepG2 cells with various Mrp2 deletion constructs in the absence and presence of co-transfected YB-1 were performed. DNA binding studies with recombinant YB-1 protein and nuclear extracts obtained from HepG2 cells and rat liver tissue were carried out. RESULTS: The minimal promoter sequence was confined to the proximal 186 bp. A YB-1 responsive element, Mrp2 YRE-1, was mapped at -186/-157, which exhibits specific YB-1 binding. YB-1 acts as a potent repressor of Mrp2 promoter activity in vitro. CONCLUSIONS: Constitutive Mrp2 gene expression is conferred through the proximal -186 bp. YB-1 acts as a repressor in vitro by specific binding to a defined element in the proximal promoter sequence.

ATP-Binding Cassette Transporters↗
PubMed2003

Mouse models for genetic dissection of polygenic gastrointestinal diseases.

Many diseases with a major public health impact are the result of complex interactions between environmental factors and multiple genes. In the past decade, methods for genome analysis, in particular quantitative trait locus (QTL) analysis in animal models, were developed to identify and localize the genes responsible for multifactorial (polygenic) diseases; QTL analysis is based on experimental crosses between inbred strains with high and low genetic susceptibility. Recently the genes underlying several QTLs could be cloned successfully. Here we describe the impact of these genomic approaches in mice on our understanding of the multifactorial genetics of three gastrointestinal diseases related to metabolism (cholesterol cholelithiasis), development (gastroschisis), and colorectal cancer. The examples demonstrate how mouse models continue to be an invaluable tool in unravelling complex pathomechanisms and unlocking our understanding of human diseases.

Animals↗
PubMed2003

Effect of glutathione depletion and hydrophilic bile acids on hepatic acute phase reaction in rats with extrahepatic cholestasis.

BACKGROUND: Extrahepatic cholestasis by biliary obstruction induces an acute phase reaction in the liver. It is a complex process involving cytokines, hormones and growth factors. To determine whether the regulation of acute phase proteins (APP) in cholestasis depends on glutathione (GSH), the effect of buthionine sulfoximine-induced (BSO-induced) GSH depletion on the expression of various APP was studied. In addition, we determined the influence of hepatoprotective bile acids on hepatic APP and underlying cytokine events. METHODS: Liver samples of bile-duct-ligated or sham-operated rats were examined. mRNA expression was quantified by densitometric analysis of Northern blots. RESULTS: Expression of APP increased 2-5-fold in bile-duct-ligated rats as compared to sham-operated controls. This acute phase reaction remained similar independently of whether cholestasis occurred for 5 days or 3 weeks. In contrast to alpha2-macroglobulin and tissue inhibitor of metalloproteinases-1 (TIMP-1), mRNA levels of both beta-fibrinogen and haptoglobin were significantly up-regulated after GSH depletion by BSO in cholestasis. Feeding of ursodeoxycholic and iso-ursodeoxycholic acid markedly down-regulated alpha2-macroglobulin and TIMP-1 expression in cholestasis but did not affect overexpression of beta-fibrinogen and haptoglobin. Cholestasis leads to an increased APP expression accompanied by an increased expression of inflammatory cytokines (IL-6, TNF-alpha). After feeding of hydrophilic bile acids, increases in inflammatory cytokines were abrogated. CONCLUSIONS: We show that GSH is involved in the acute phase reaction during obstructive cholestasis. In addition, bile acids might selectively ameliorate the acute phase response by reducing expression of the APP not affected by GSH depletion (alpha2-macroglobulin and TIMP-1).

Acute-Phase Proteins↗
PubMed2003

Pituitary deficiency following aneurysmal subarachnoid haemorrhage.

OBJECTIVE: To investigate the incidence and severity of pituitary insufficiency after aneurysmal subarachnoid haemorrhage. METHODS: Pituitary function was tested in a series of patients more than 12 months but less than 60 months after aneurysmal subarachnoid haemorrhage using a combined TRH-LHRH-arginine test and the insulin tolerance test, to elucidate possible deficits in the gonadotrophic, somatotrophic, thyreotrophic, and corticotrophic hormonal axes. RESULTS: Of 21 patients screened, nine (43%) showed deficiencies of at least one pituitary hormone axis. Four patients had corticotrophin deficiency, one had partial growth hormone deficiency, two had severe growth hormone deficiency, and two had severe growth hormone deficiency plus corticotrophin deficiency. CONCLUSIONS: Persistent pituitary dysfunction may be more common after aneurysmal subarachnoid haemorrhage than has so far been recognised and warrants further investigation, given the possibility that some health and neurobehavioural problems in these patients could result from hormone deficiency.

Adrenocorticotropic Hormone↗
PubMed2002

[Molecular genetics of cholesterol cholelithiasis: identification of human and murine gallstone genes].

Cholesterol cholelithiasis is one of the most common gastroenterological diseases in Western countries. It is a polygenic disease resulting from disturbed biliary cholesterol homeostasis. Association studies identified six human gallstone candidate genes. Polymorphisms in the genes encoding the apolipoproteins B and E, phospholipid flippase ( ABCB4), cholesterol ester transfer protein ( CETP), cholesterol-7alpha-hydroxylase ( CYP7A1) and ileal bile acid transporter ( SLC10A2) are correlated with gallstone prevalence. Quantitative Trait Locus (QTL) analysis localises additional unknown gallstone genes in inbred mice. Based on the natural variation of cholesterol gallstone susceptibility among different inbred strains, 5 lithogenic ( Lith) loci have been identified. Hepatobiliary transporters (e. g. bile salt export pump Abcb11) and key proteins of the lipoprotein metabolism (e. g. hepatic lipase Lipc) could be established as creedal candidate genes for Lith loci. The rapid progress of mouse and human genome projects provides the basis for the analysis of orthologous human LITH genes in gallstone patients, which might offer new prospects for individual risk assessment and molecular targets for stone prevention.

Animals↗
PubMed2001

Activity and cellular origin of gelatinases in patients with colon and rectal carcinoma differential activity of matrix metalloproteinase-9.

BACKGROUND: Expression and enzymatic activity of gelatinases were examined in biopsy specimens from patients with colon and rectal neoplasms. The objective of this study was to determine whether the activity of these enzymes is altered between tumor areas compared with areas of noninvolved, normal mucosa and between colon and rectal carcinoma. METHODS: Matrix metalloproteinase (MMP) production was analyzed by Western immunoblot analysis and gelatin zymography. mRNA was determined by quantitative, real-time polymerase chain reaction analysis. RESULTS: Patients with colon carcinoma (n = 20 patients) showed a significant increase in levels of MMP-9 (92 kDa and 88 kDa) and MMP-2 (72 kDa and 62 kDa) in tumor areas compared with noninvolved regions. In contrast, patients with rectal carcinoma (n = 10 patients) had revealed the same high activity of MMP-9 in tumor regions and corresponding healthy tissue. Confirming activity measurements, in colon tumors, but not in rectal tumors, there was significant up-regulation of MMP-9 transcription compared with healthy tissue in the same patients. There were no significant changes in the tissue inhibitor of metalloproteinase-1 protein when colon and rectal tumor tissues were compared with the corresponding noninvolved regions. Cell culture experiments revealed fibroblasts as the cellular origin of MMPs. The findings showed that the secretion and activation of gelatinases depend on soluble factors secreted by tumor cells and are influenced by extracellular matrix components. CONCLUSIONS: This is the first report showing differences in MMP-9 activity between rectal carcinoma and colon carcinoma. Previous results indicating an active involvement of stromal cells in the generation of MMPs during tumor invasion are extended. Because the abundance of gelatinases increases in colorectal carcinoma, inhibitors of these proteases may be of therapeutic value.

Blotting, Western↗