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Biomedical subjects

M Schwarz

Publications and source records attributed to M Schwarz.

At least 19 recordsLinked to original sources
PubMed2002

Interaction of fibronectin and aggregation substance promotes adherence of Enterococcus faecalis to human colon.

This in vitro study investigates the interaction between aggregation substance (AS), a virulence factor of Enterococcus faecalis, and colonic mucosal fibronectin in normal colon and colon from patients with Crohn's disease. Fibronectin was found to be overexpressed in Crohn's disease compared to normal colon. Compared to E. faecalis OG1X:pAM944 (AS-negative), E. faecalis OG1X:pAM721 (expressing AS) showed a significantly enhanced adhesion to human colonic mucosa in normal colon and in colon from patients with Crohn's disease. Double-staining of fibronectin and AS-positive enterococci showed that colocalization of bacteria and fibronectin was significantly more frequent in Crohn's disease than in normal colon. Preincubation of bacteria with soluble fibronectin caused a significant reduction in the adherence to fibronectin. In conclusion, the interaction between AS and fibronectin plays is an important factor that mediates adhesion of Enterococcus faecalis to colonic mucosa. This might be one of the mechanisms responsible for bacterial translocation of Enterococcus faecalis.

Bacterial Adhesion↗
PubMed2002

Craniofacial and brain abnormalities in Laron syndrome (primary growth hormone insensitivity).

OBJECTIVE: To investigate abnormalities in the craniofacial structures and in the brain in patients with Laron syndrome. DESIGN: Eleven patients with classical Laron syndrome, nine untreated adults aged 36-68 years and two children aged 4 and 9 years (the latter treated by IGF-I), were studied. METHODS: Magnetic resonance images of the brain were obtained in all the patients. One patient also underwent computed tomography. The maximal diameter of the maxillary and frontal sinuses was measured and compared with reference values, the size of the sphenoid sinus was evaluated in relation to the sella, and the mastoids were evaluated qualitatively (small or normal). The brain was evaluated for congenital anomalies and parenchymal lesions. RESULTS: In the adult untreated patients, the paranasal sinuses and mastoids were small; in six patients, the bone marrow in the base of the skull was not mature. The diploe of the calvaria was thin. On computed tomography in one adult patient, the sutures were still open. A minimal or mild degree of diffuse brain parenchymal loss was seen in ten patients. One patient demonstrated a lacunar infarct and another periventricular high signals on T2-weighted images. Two patients had cerebellar atrophy. CONCLUSIONS: The present study has demonstrated the important role IGF-I plays in the development of the brain and bony structures of the cranium.

Adult↗
PubMed2001

Selective pressure during tumor promotion by phenobarbital leads to clonal outgrowth of beta-catenin-mutated mouse liver tumors.

Tumor promoters are non-mutagenic chemicals which increase the probability of cancer by accelerating the clonal expansion of cells transformed during tumor initiation. Phenobarbital (PB) is an antiepileptic drug which promotes hepatocarcinogenesis in rodents when administered subsequent to an initiating carcinogen like diethylnitrosamine (DEN). Here we have investigated the prevalence and patterns of mutations in two genes, Ha-ras and beta-catenin, both known mutational targets in mouse hepatocarcinogenesis. Liver tumors were generated by a single administration of DEN to 6 week old mice followed by feeding of PB (0.05%) containing or control diet for 39 weeks. Mutations at Ha-ras codon 61 were screened by allele-specific oligonucleotide hybridization; beta-catenin mutations were detected by direct sequencing of PCR products spanning exon 2. In tumors from mice treated with DEN alone, the prevalence of Ha-ras mutations was approximately 30% (6/20), while no beta-catenin mutations (0/13) were detectable in tumors of this treatment group. By contrast, Ha-ras mutations were undetectable in tumors from mice treated with DEN/PB (0/32), while approximately 80% (37/46) of tumors from this group showed beta-catenin mutations. These results demonstrate that PB strongly affects the prevalence of mutations in the two cancer-related genes, presumably by positive and negative selection for cells harboring the respective mutation.

Animals↗
PubMed2001

Efficacy of oral ofloxacin for single-dose perioperative prophylaxis in general surgery--a controlled randomized clinical study.

BACKGROUND: Perioperative antibiotic prophylaxis surely reduces surgical infection rate. Pharmacokinetic data of oral ofloxacin in combination with its antibacterial spectrum suggest effective protection against perioperative infection. In addition, costs, adverse effects, and induction of microbial resistance are low. Therefore we performed a controlled randomized study comparing oral and intravenous single dose prophylaxis. METHODS: A total of 61 patients undergoing colonic or pancreatic resection randomly received either a single dose standard intravenous prophylaxis or ofloxacin 400 mg and metronidazole 500 mg orally 2 h before surgery. Postoperative infections were recorded for 3 weeks. RESULTS: Groups were very well comparable regarding age, overweight, concomitant disease, type and duration of surgery, blood loss, and volume support. Infectious complications occurred in 14.8% after parenteral and 3.3% after enteral antibiotic prophylaxis. There was no difference in post-operative hospital stay. CONCLUSION: The data demonstrate that single-dose oral ofloxacin is at least as effective as a standard intravenous prophylaxis in patients with colonic or pancreatic resection. It offers significant advantages regarding costs and ease of administration.

Administration, Oral↗
PubMed2001

Positional cloning of heart and soul reveals multiple roles for PKC lambda in zebrafish organogenesis.

BACKGROUND: The Par-3/Par-6/aPKC complex is a key regulator of cell polarity in a number of systems. In Drosophila, this complex acts at the zonula adherens (adherens junctions) to establish epithelial polarity and helps to orient the mitotic spindle during asymmetric neuroblast divisions. In MDCKII cells, this complex localizes to the zonula occludens (tight junctions) and appears to regulate epithelial polarity. However, the in vivo role of this complex during vertebrate embryogenesis is not known, due to the lack of relevant mutations. RESULTS: We have positionally cloned the zebrafish heart and soul (has) mutation, which affects the morphogenesis of several embryonic tissues, and show that it encodes atypical protein kinase C lambda (aPKC lambda). We find that loss of aPKC lambda affects the formation and maintenance of the zonula adherens in the polarized epithelia of the retina, neural tube, and digestive tract, leading to novel phenotypes, such as the formation of multiple lumens in the developing intestine. In addition, has mutants display defects in gut looping and endodermal organ morphogenesis that appear to be independent of the defects in epithelial polarity. Finally, we show that loss of aPKC lambda leads to defects in spindle orientation during progenitor cell divisions in the neural retina. CONCLUSIONS: Our results show that aPKC lambda is required for the formation and maintenance of the zonula adherens during early epithelial development in vertebrates and demonstrate a previously undescribed yet critical role for this protein in organ morphogenesis. Furthermore, our studies identify the first genetic locus regulating the orientation of cell division in vertebrates.

Adherens Junctions↗
PubMed2001

Intrinsic activating properties of GP IIb/IIIa blockers.

Potential intrinsic activating properties are probably the most controversially discussed issues with respect to GP IIb/IIIa blockers, especially since clinical trials with oral GP IIb/IIIa blockers revealed disappointing results. Based on the finding that currently clinically used GP IIb/IIIa blockers are ligand mimetics, experimental data are discussed, demonstrating an intrinsic activating effect of ligand mimetic GP IIb/IIIa blockers that potentially results in fibrinogen binding to alpha(IIb)beta(3) and in platelet aggregation. Furthermore, the inhibitory effect of aspirin on GP IIb/IIIa blocker-induced platelet aggregation is discussed as a clinically relevant finding. Finally, the potential association of GP IIb/IIIa blocker-induced thrombocytopenia with platelet activation is described.

Antibodies, Monoclonal↗
PubMed2001

Evaluation of different tubing geometries for high-speed counter-current chromatography.

Different tubing geometries were evaluated for use in high-speed counter-current chromatography. Standard round tubing was compared to rectangular and twisted rectangular tubing. The number of theoretical plates for a standard anthocyanin mixture from black currant was determined for each experiment. The results of twisted rectangular tubing were superior to a standard setup.

Anthocyanins↗
PubMed2001

Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor constitutively activates NF-kappa B and induces proinflammatory cytokine and chemokine production via a C-terminal signaling determinant.

Kaposi's sarcoma-associated herpesvirus (KSHV) is believed to be the causative agent of Kaposi's sarcoma (KS), a multicentric growth factor-dependent tumor common in AIDS patients characterized histopathologically by spindle cell proliferation, angiogenesis, and leukocyte infiltration. Recently, open reading frame 74 of KSHV has been implicated as a major viral determinant of KS. Open reading frame 74 encodes KSHV G protein-coupled receptor (GPCR), a constitutively active chemokine receptor that directly transforms NIH 3T3 cells in vitro and induces multifocal KS-like lesions in KSHV-GPCR-transgenic mice. Interestingly, receptor-positive cells are very rare in lesions from these mice, implicating an indirect mechanism of tumorigenesis. In this regard, here we report that expression of KSHV-GPCR in transfected epithelial, monocytic, and T cell lines induced constitutive activation of the immunoregulatory transcription factors AP-1 and NF-kappaB. This was associated with constitutive induction of the proinflammatory NF-kappaB-dependent cytokines IL-1beta, IL-6, and TNF-alpha, and chemokines monocyte chemoattractant protein-1 and IL-8, as well as the AP-1-dependent basic fibroblast growth factor. In addition, IL-2 and IL-4 production was induced in transfected Jurkat T cells. Truncation of the final five amino acids in the cytoplasmic tail of KSHV-GPCR caused complete loss of its transforming and NF-kappaB-inducing activities, without affecting receptor expression or ligand binding. These data suggest that KS results in part from KSHV-GPCR induction of proinflammatory cytokine and growth factor gene expression, mediated by a signaling determinant within the last five amino acids of the C terminus, a domain that is also critical for direct cell transformation.

3T3 Cells↗
PubMed2001

Down-regulation of intestinal scavenger receptor class B, type I (SR-BI) expression in rodents under conditions of deficient bile delivery to the intestine.

Scavenger receptor class B, type I (SR-BI) is expressed in the intestines of rodents and has been suggested to be involved in the absorption of dietary cholesterol. The aim of this study was to determine whether intestinal SR-BI expression is affected in animal models with altered bile delivery to the intestine and impaired cholesterol absorption. SR-BI protein and mRNA levels were determined in proximal and distal small intestine from control, bile-duct-ligated and bile-diverted rats and from control and bile-duct-ligated mice. Two genetically altered mouse models were studied: multidrug resistance-2 P-glycoprotein-deficient [Mdr2((-/-))] mice that produce phospholipid/cholesterol-free bile, and cholesterol 7alpha-hydroxylase-deficient [Cyp7a((-/-))] mice, which exhibit qualitative and quantitative changes in the bile-salt pool. Cholesterol-absorption efficiency was quantified using a dual-isotope ratio method. SR-BI was present at the apical membrane of enterocytes in control rats and mice and was more abundant in proximal than in distal segments of the intestine. In bile-duct-ligated animals, levels of SR-BI protein were virtually absent and mRNA levels were decreased by approximately 50%. Bile-diverted rats, Mdr2((-/-)) mice and Cyp7a((-/-)) mice showed decreased levels of intestinal SR-BI protein while mRNA levels were unaffected. Cholesterol absorption was reduced by >90% in bile-duct-ligated and bile-diverted animals and in Cyp7a((-/-)) mice, whereas Mdr2((-/-)) mice showed an approximately 50% reduction. This study shows that SR-BI is expressed at the apical membrane of enterocytes of rats and mice, mainly in the upper intestine where cholesterol absorption is greatest, and indicates that bile components play a role in post-transcriptional regulation of SR-BI expression. Factors associated with cholestasis appear to be involved in transcriptional control of intestinal SR-BI expression. The role of SR-BI in the cholesterol-absorption process remains to be defined.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2001

Rolipram reduces excitotoxic neuronal damage.

Proinflammatory cytokines are supposed to be involved in the pathophysiology of neuronal damage following excitotoxic lesions. We examined the effect of rolipram, a TNF-alpha-inhibitor, on excitotoxic neuronal damage. Quinolinic acid (240 nmol in 1 microl) was injected stereotactically into the striatum of male Wistar rats. Four groups of QA rats were treated i.p. with solvent, MK-801 (4 mg/kg) or rolipram (0.3 mg/kg) which was started either 6 or 24 h after QA injection and continued with daily applications for 14 days. QA injection induced neuronal damage which affected 93% of the striatal area. MK-801 reduced this damage to 12% of the striatal area. Treatment with rolipram when started at 6 h after QA injection resulted in neuronal damage amounting to 60%; the result after starting at 24 h was not different from solvent (91%). The present results demonstrate that rolipram reduces neuronal damage induced by intrastriatal QA application.

Animals↗
PubMed2001

Masseter reflex and blink reflex abnormalities in Chiari II malformation.

Masseter reflex and blink reflex were evaluated in 64 patients with a myelomeningocele and Chiari II malformation. In 46 patients, no brainstem signs or symptoms were present. Brainstem dysfunction related to Chiari II malformation occurred in 18 patients. The masseter reflex was more frequently abnormal in the symptomatic than asymptomatic patients (P = 0.02). Although the blink reflex was similarly affected in the two groups of patients (P > 0.1), it was very sensitive, being abnormal in 83% of symptomatic and 65% of asymptomatic patients. Concomitant abnormality of masseter reflex and the late contralateral blink reflex component (R2c) was almost exclusively found in symptomatic patients and reached the highest significance in separating the two groups (P = 0.002).

Adolescent↗
PubMed2001

Cerebral spinal fluid flow, venous drainage and spinal cord compression in achondroplastic children: impact of magnetic resonance findings for decompressive surgery at the cranio-cervical junction.

UNLABELLED: In order to investigate the diagnostic properties of MRI of the brain and spine in achondroplastic children with regard to decompressive surgery, 25 patients were examined by conventional morphological and by "functional" imaging of CSF flow and magnetic resonance angiography (MRA) of the veins and sinuses at the cranial base following a special protocol. The results were compared to those from age-matched controls and were correlated with each other and retrospectively with the neurological findings. Measurements of distances and angulations at the cranio-cervical junction (CCJ) from MR scans showed similar values to those from conventional radiographs and CTs and thus can be used without correction for spatial distorsion. Signs of cervical medullary compression, myelomalacia and intramedullary cyst formation were found in six, seven and three children respectively. These alterations correlated significantly with each other (P < 0.05). Semiquantitative evaluation of CSF flow demonstrated interruption of CSF pathways at the CCJ, which correlated with CCJ narrowing (P < 0.05). MRA showed a significant narrowing of the jugular foramina with a variable compensatory enlargement of the emissary veins and a significant reduction of the total outflow area (P < 0.01). There were no significant correlations between these MR changes and neurological deficits. CONCLUSION: Due to this unexpectedly poor correlation between magnetic resonance and clinical findings in achondroplastic children, the present role of magnetic resonance in the clinical setting is limited to the demonstration of spinal cord compression in individual cases. In three of our patients with prominent neurological abnormalities, the severe changes demonstrated by magnetic resonance imaging strongly supported the indication for surgical decompression.

Achondroplasia↗
PubMed2001

Bovine pericardium for duraplasty: clinical results in 32 patients.

Bovine pericardium has been widely used for grafts in cardiac surgery and seems to have suitable properties for use as a dural graft. We report on the use of solvent-preserved, gamma-sterilized Tutoplast bovine pericardium for dural grafts in 32 patients undergoing cranial and spinal operations with the objective of clinically assessing this material and technique by a retrospective analysis. All available records were reviewed and information regarding the indication for grafting, complications, and outcome were collected and analyzed for all patients. Indications for grafting included tethered cord myelolysis, closure of lumbosacral myeloceles, Chiari decompression, posterior fossa craniotomy, supratentorial craniotomy, and trauma. Outcomes were excellent in 31 patients; the one poor outcome was unrelated to surgical closure. The dural graft was not intended for outcome in any patient. Bovine pericardium was found to be a flexible and easily suturable, safe and cost-effective material for duraplasty. These results confirm the excellent suitability of Tutoplast bovine pericardium for dural substitution.

Adolescent↗
PubMed2001

A novel long-QT 5 gene mutation in the C-terminus (V109I) is associated with a mild phenotype.

Mutations in the human minK gene KCNE1 have been linked to autosomal dominant and autosomal recessive long-QT (LQT) syndrome, a cardiac condition predisposing to ventricular arrhythmias. minK and KvLQT1, the LQT1 gene product, form a native cardiac K+ channel that regulates the slowly delayed rectifier potassium current I(Ks). We used single-strand conformation polymorphism and sequencing techniques to identify novel KCNE1 mutations in patients with a congenital LQT syndrome of unknown genetic origin. In 150 unrelated index patients a missense mutation (V109I) was identified that significantly reduced the wild-type I(Ks) current amplitude (by 36%) when coexpressed with KvLQT1 in Xenopus oocytes. Other biophysical properties of the I(Ks) channel were not altered. Since we observed incomplete penetrance (only one of two mutation carriers could be diagnosed by clinical criteria), and the family's history was unremarkable for sudden cardiac death, the 109I allele most likely causes a mild phenotype. This finding may have implications for the occurrence of "acquired" conditions for ventricular arrhythmias and thereby the potential cardiac risk for asymptomatic mutation carriers still remains to be determined.

Alleles↗
PubMed2001

Clinical aspects and prognosis of ependymoma in infants and children. A single institution experience.

Thirty-two patients (22 boys and 10 girls) with a histologically confirmed diagnosis of ependymoma were treated between 1972 and 1999. A total macroscopic resection was achieved in 16 of these patients, whereas 15 resections were classified by the surgeon as subtotal. In 1 patient a ventriculostomy was created as part of a palliative strategy. All children over 3 years old were treated with postoperative radiotherapy. Chemotherapy consisted of procarbazine, ifosfamide, etoposide, methotrexate, cisplatin and cytosine arabinoside. There was 1 perioperative death. Twenty children developed a relapse of disease within 2 months to 13 years and 1 month after the initial therapy. A maximal number of five recurrences were seen in 1 patient. The value of adjuvant chemotherapy on the prognosis of children with ependymoma seems to be limited. With regard to the poor outcome, the advisability of further treatment after multiple recurrences is debatable.

Adolescent↗
PubMed2001

Pharmacokinetic basis for oral perioperative prophylaxis with ofloxacin in general surgery.

BACKGROUND: Perioperative prophylaxis is recommended to be administered intravenously which, compared to oral prophylaxis, is more expensive. However, pharmacokinetic data on oral perioperative prophylaxis in patients with preoperative surgical and anesthesiological preparation are not available. PATIENTS AND METHODS: 40 patients with open hernial repair or cholecystectomy (low-risk group), colonic or pancreatic resection (high-risk group) received a standard single-dose perioperative prophylaxis with 4.5 g mezlocillin and 0.5 g metronidazole intravenously in addition to 400 mg ofloxacin orally 2 h prior to surgery. Antibiotic concentrations were measured perioperatively and pharmacokinetic data calculated. RESULTS: Serum and tissue concentrations of ofloxacin were above the MIC90 of the potential bacterial spectrum for surgical infection throughout the entire operation. Pharmacokinetic data were not influenced by preoperative surgical or anesthesiological preparation. CONCLUSION: Tissue and serum concentrations and the antibacterial spectrum of orally administered ofloxacin suggest effective protection against perioperative infection. Pharmacokinetic data confirm that oral ofloxacin may be used effectively as single-dose perioperative antibiotic prophylaxis. Since there are no clinical data comparing oral and intravenous singLe-dose prophylaxis, a prospective randomized clinical trial should be performed.

Administration, Oral↗
PubMed2001

Is a preoperative multidiagnostic approach to predict surgical resectability of periampullary tumors still effective?

BACKGROUND: Multimodality staging is recommended in patients with periampullary tumors to optimize preoperative determination of resectability. We investigated the potency of currently used diagnostic procedures in order to determine resectability. METHODS: Ninety-five consecutive patients with periampullary tumors prehospitally staged resectable underwent preoperative diagnostic tests: helical-computed tomography (CT) with maximum intensity projection of arterial vessels (MIP), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreaticography (MRCP), endoscopic ultrasonography (EUS), endoscopic retrograde cholangiopancreaticography (ERCP), digital subtraction angiography (DSA), and positron emission tomography (PET). Diagnoses were verified by surgery and histopathology. RESULTS: In 45 patients with benign and 50 patients with malignant periampullary tumors sensitivity for tumor diagnosis was 89% to 96% in CT, MRI, EUS, and PET. Small tumors were best diagnosed by EUS (100%). Diagnosis of malignancy was made with 85% (EUS), 83% (CT), 82% (PET), and 72% (MRI) accuracy. Arterial vessel infiltration was best predicted by CT/MIP with an accuracy of 85%. For venous vessel infiltration MRI reached 85% accuracy. Accuracy rates for local nonresectability were 93% (EUS), 92% (MRI), and 90% (CT). Two and 4 of 8 patients with distant metastases were identified by CT and PET, respectively. The correct diagnosis of malignancy and determination of resectability was made by CT in 71% and by MRI in 70%. Biliary stenting reduced accuracy of CT diagnosis of malignancy from 88% to 73%. CONCLUSIONS: CT obtained before stenting was the single most useful test, providing correct diagnosis in 88% and resectability in 71% of patients. If no tumor is depicted in CT, EUS should be added. Uncertain venous vessel infiltration can be verified by MRI or EUS. Angiography should no longer be a routine diagnostic procedure. Equivocal tumors or possible metastasis may be further examined with PET.

Ampulla of Vater↗