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Biomedical subjects

M Schwarz

Publications and source records attributed to M Schwarz.

At least 55 records · Page 3Linked to original sources
PubMed2002

IFNgamma induces functional chemokine receptor expression in human mesangial cells.

Infiltration of leucocyte populations into sites of inflammation is a common feature in renal diseases. Glomerular mesangial cells are potent producers of a variety of chemokines, leading to specific attraction of distinct types of inflammatory leucocytes into the glomerulus, but so far there is limited knowledge about the responsiveness of mesangial cells to chemokines. We investigated the expression of chemokine receptors and the responsiveness of primary human mesangial cells (HMC) to the chemokines which they produce, namely monocyte chemoattractant protein-1 (MCP-1) and interleukin (IL)-8. We found that mRNAs of the chemokine receptors CCR1, which has been shown before, CCR2 and CXCR2 were induced by T-helper cytokine interferon-gamma (IFNgamma). In IFNgamma-stimulated cells, CCR2 and CXCR2 were detectable by flow cytometry. Following treatment with IFNgamma, HMC responded to MCP-1 and IL-8 with an increase of IL-6 mRNA and protein expression, which was in part blocked by pertussis toxin. Moreover, chemokine stimulation of transfected HMC led to an activation of the immunoregulatory transcription factors NFkappaB and AP-1. Additionally, we found that MCP-1 enhanced the expression of its own mRNA in cells activated to express CCR2, suggesting autocrine feedback mechanisms in MCP-1 regulation. Finally, IFNgamma-activated cells migrated towards an MCP-1 gradient in a chemotaxis assay. These results strengthen the assumption that chemokines are not only involved in the recruitment of immune cells to inflamed tissues, but also seem to play a central role in the autocrine regulation of local tissue cells, leading to proceeding inflammation and possibly contributing to healing by mediating cell growth and migration.

Autocrine Communication↗
PubMed2002

Use of ADCON-L to prevent peridural fibrosis following re-operation for recurrent lumbar radiculopathy: clinical results.

OBJECTIVE: To present the results of a small retrospective study in patients after they have undergone lumbar scar resection and ADCON-L application to prevent recurrent formation of peridural fibrosis. PATIENTS AND METHODS: Between May 1996 and December 1999 nineteen patients underwent surgery for peridural fibrosis. Sixteen patients were eligible for statistical analysis. The mean age was 46.2 years (range 29 to 69 years) and the mean follow-up period was 9.7 months with a range of 3 to 38 months. In 10 patients scar formation was the main factor for nerve root compression. Three out of these patients showed concomitant recurrent disc herniation. Six patients presented with peridural fibrosis but concomitant recurrent disc herniation as the main factor for clinical deterioration. After scar resection and decompression of the nerve roots ADCON-L was applied intraoperatively. RESULTS: Excellent or good results (Prolo score 8 - 10) were achieved in 5 of 16 patients, fair results (Prolo score 6 - 7) in 5 and poor results (Prolo score 2 - 5) in 6 patients. CONCLUSION: ADCON-L may improve the chances of a satisfactory outcome in a small subgroup of patients following scar resection in the postoperative course of lumbar discectomy. Further investigations are necessary to identify clinical and radiographic factors predicting outcome.

Adult↗
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↗
PubMed2002

[Improvement of osseointegration of bio-inert ceramics by modification of the surface--results of an animal experiment].

The aim of this experimental study was to screen different surface structures of alumina and zirconia ceramic implants for their osteointegration properties. Alumina and zirconia ceramic test implants having different surface structures (smooth, macro-structured, corundum-blasted, porous) were implanted in the femora of mini-pigs, and left in situ for 12 weeks. After removal, the implants were evaluated macroradiographically and histologically. The smooth and macro-structured ceramic surfaces showed virtually no bony ingrowth, neither in the cortical nor the cancellous bone areas. In contrast, a rough surface finish or a porous surface structure allowed extensive bony ingrowth. The osteointegration rates varied between 20.5% and 41.7% (cancellous bone), and between 26.0% and 52.8% (cortical bone). With regard to the development of ceramic implants for clinical use, for example in the field of total hip replacement, these data provide a basis for further, more comprehensive studies.

Aluminum Oxide↗
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↗