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S Matern

Publications and source records attributed to S Matern.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed2001

[Heterophile antibodies, lack of communication and the diagnostic dilemma].

BACKGROUND: Heterophilic antibodies represent a great danger to clinical care by producing false-positive values for certain markers. Too large confidence in specificity of laboratory markers together with lack of communication between clinicians and clinical chemists may lead to unnecessary interventional diagnostic and therapeutic procedures. The prevalence of heterophilic antibodies is probably much higher than assumed up till now and several markers can be affected. AIM: In this review for clinicians, we explain formation of heterophilic antibodies, mechanisms of interference and present clinical data about affected markers and "side effects" from the literature. Furthermore we discuss possible alternatives and measures against this phenomenon. We consider broad awareness of this problem among clinicians the most important action to avoid further harm to patients.

Antibodies, Heterophile↗
PubMed2001

Molecular cloning and expression of human bile acid beta-glucosidase.

A novel microsomal beta-glucosidase was recently purified and characterized from human liver that catalyzes the hydrolysis of bile acid 3-O-glucosides as endogenous compounds. The primary structure of this bile acid beta-glucosidase was deduced by cDNA cloning on the basis of the amino acid sequences of peptides obtained from the purified enzyme by proteinase digestion. The isolated cDNA comprises 3639 base pairs containing 524 nucleotides of 5'-untranslated and 334 nucleotides of 3'-untranslated sequences including the poly(A) tail. The open reading frame predicts a 927-amino acid protein with a calculated M(r) of 104,648 containing one putative transmembrane domain. Data base searches revealed no homology with any known glycosyl hydrolase or other functionally identified protein. The cDNA sequence was found with significant identity in the human chromosome 9 clone RP11-112J3 of the human genome project. The recombinant enzyme was expressed in a tagged form in COS-7 cells where it displayed bile acid beta-glucosidase activity. Northern blot analysis of various human tissues revealed high levels of expression of the bile acid beta-glucosidase mRNA (3.6-kilobase message) in brain, heart, skeletal muscle, kidney, and placenta and lower levels of expression in the liver and other organs.

Amino Acid Sequence↗
PubMed2001

[Benign metastasizing leiomyoma of the lung--a rare differential diagnosis of pulmonary space-occupying lesions].

HISTORY AND ADMISSION FINDINGS: A 45-year-old woman was refferred for diagnosis of an accidentally found symptomless space-occupying lesions in the central part of the right lung. She had undergone a hysterectomy 4 years before and reported smoking 15 cigarettes daily since the age of 17 years. Physical examination was normal. INVESTIGATIONS: As primary bronchial carcinoma or metastasis to the lung was suspected she underwent a series of diagnostic tests: sonography, computed tomography (CT), gastroscopy, coloscopy, bronchoscopy, skeletal scintigraphy, gynaecological examination and various laboratory tests, none of which indicated a primary extrapulmonary tumour. CT-guided fine-needle biopsy then suggested benign metastasizing pulmonary leiomyoma (BMPL). TREATMENT AND COURSE: The largest of the tumours were surgically removed, confirming BMPL. Hormone receptors (for oestrogen, progesterone) having been demonstrated, progesterone treatment was initiated as prophylaxis against recurrences. CT 6 months later revealed new intrapulmonary foci. Administration of luteinizing hormone-releasing hormone analog to stop completely any oestrogen effect, and CT of the thorax 6 months later showed that both tumour numbers and their size had been reduced. The patient remained asymptomatic and the findings had not changed in the subsequent 12 months. CONCLUSION: BMPL is a rare cause of a space-occupying pulmonary lesion, predominantly affecting middle-aged women after hysterectomy for uterine myoma. The pathogenesis remains unclear, hormone-dependent tumour growth being discussed as a possible mechanism. Anti-oestrogen administration is the treatment of choice to achieve remission and effective prevention of recurrences.

Biopsy↗
PubMed2001

Metabolism and effects on cholestasis of isoursodeoxycholic and ursodeoxycholic acids in bile duct ligated rats.

Isoursodeoxycholic acid (isoUDCA), the 3 beta-epimer of ursodeoxycholic acid (UDCA), may have pharmaceutical potential because of its similar hydrophilicity and in vitro cytoprotection as compared with UDCA. We compared metabolism and effects on cholestasis of UDCA and isoUDCA in experimental cholestasis in rats. Cholestasis was induced by bile duct ligation. For bile flow and biliary bile acid analysis, UDCA or isoUDCA were infused intraduodenally. For the study of chronic effects, chow was supplemented with 2.5 g/kg UDCA or isoUDCA for 3 weeks. Sham-operated animals served as controls. IsoUDCA became completely converted to UDCA in the liver. Choleresis and biliary bile acids were the same after the intraduodenal administration of either compound. Oral administration of UDCA or isoUDCA significantly improved liver biochemistry but not clinical and histological parameters in chronic cholestasis. The decrease of serum cholic acid in control animals was more pronounced after isoUDCA (-93%) than after UDCA (-76%). Only after UDCA, this decrease was compensated by increases of UDCA, beta-muricholic acid (MCA), and Delta(22)-beta-MCA. Our results show that isoUDCA has the same effect on choleresis and liver biochemistry as UDCA. IsoUDCA features pro-drug characteristics of UDCA and causes compared to the latter lower serum bile acid concentrations in non-cholestatic animals.

Animals↗
PubMed2001

[Solitary fibrous thoracic wall tumor. Progression with percutaneous radiotherapy].

HISTORY AND CLINICAL FINDINGS: A 81-year-old patient free of pain was referred to the university hospital for further evaluation and therapy of tumour masses in the right thorax. Clinical examination revealed dullness to percussion and reduced breathing in the right lower lung. INVESTIGATIONS: Computed tomography showed an enlarged solid tumour mass attached to the thoracic cavity and pleural effusion on the right side. Quantification of pulmonary perfusion presented significant defects in the right upper and middle lobe. DIAGNOSIS, TREATMENT AND COURSE: The pulmonary masses were biopsied under CT-guidance. Biopsy and immunohistochemical findings proved a malignant solitary fibrous tumour of the chest wall, a mesenchymal tumour of its own entity. Because of pain in the right arm and because of missing other reliable therapeutic options a palliative irradiation was performed. The tumour did increase in size due to radiotherapy and a severe right ventricular heart failure occurred. The patient died 5 months after diagnosis has been made. Autopsy revealed a transition of tumour cells to sarcomatic growth. CONCLUSION: In our case we conclude an accelerated progression of the solitary fibrous chest wall tumour in the course of irradiation. Whether the development of sarcomatic growth occurred as a result of radiotherapy remains speculative.

Aged↗