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Biomedical subjects

C Müller

Publications and source records attributed to C Müller.

At least 235 records · Page 13Linked to original sources
PubMed1998

Beta-galactoside-binding protein secreted by activated T cells inhibits antigen-induced proliferation of T cells.

We have used mRNA differential display PCR to search for genes induced in activated T cells and have found the LGALS1 (lectin, galactoside-binding, soluble) gene to be strongly up-regulated in effector T cells. The protein coded by the LGALS1 gene is a beta-galactoside-binding protein (betaGBP), which is released by cells as a monomeric negative growth factor but which can also associate into homodimers (galectin-1) with lectin properties. Northern blot analysis revealed that ex vivo isolated CD8+ effector T cells induced by a viral infection expressed high amounts of LGALS1 mRNA, whereas LGALS1 expression was almost absent in resting CD8+ T cells. LGALS1 expression could be induced in CD4+ and CD8+ T cells upon activation with the cognate peptide antigen and high levels of LGALS1 expression were found in concanavalin A-activated T cells but not in lipopolysaccharide-activated B cells. Gel filtration and Western blot analysis revealed that only monomeric betaGBP was released by activated CD8+ T cells and in vitro experiments further showed that recombinant betaGBP was able to inhibit antigen-induced proliferation of naive and antigen-experienced CD8+ T cells. Thus, these data indicate a role of betaGBP as an autocrine negative growth factor for CD8+ T cells.

Animals↗
PubMed1998

[Treatment of advanced pleural empyema].

Despite the widespread availability of antibiotics and a declining incidence, pleural empyema still represents a serious intrathoracic disease often requiring surgical treatment for successful therapy. 104 patients with complicated pleural empyema were treated at our hospital between June 1991 and June 1997. In this retrospective study the main causes for pleural empyema were pneumonia in 41.3% and direct inoculation of the pleural space by major and minor thoracic surgery in 30.8%. Further diseases leading to an empyma of the pleural space were oesophageal perforation (11.5%), ARDS (8.7%) and hematogenous infection (7.7%). Eighty-four patients (80.8%) underwent surgery, of whom 17 patients required multiple operations. Conservative therapy with chest tube drainage and systemic application of tested antibiotics was performed in 20 patients. The overall mortality of our patients was 19.2%, but depending on the underlying disease differed considerably between 8.3% and 44.4%. Multiple operations caused by persisting empyema had a significantly higher mortality rate (58.8%) than single operations (10.5%).

Adolescent↗
PubMed1998

[Virtual and three-dimensional bronchoscopy with spiral and electron beam computed tomography].

PURPOSE: To compare spiral computed tomography (CT) and electron-beam CT (EBT) for 3D and virtual CT-bronchoscopy. MATERIALS AND METHODS: 17 patients with various disorders of the tracheobronchial system were examined using fiberoptic bronchoscopy, spiral CT and EBT. 3D images were reconstructed from CT data sets using automated segmentation based on volume-growing methods. Surface-rendered, volume-rendered, and hybrid reconstructions were visualized in real time using a data helmet. RESULTS: All data sets could be processed to high-quality three-dimensional (3D) and virtual reconstructions. The reduction of motion artifacts due to shorter scan times made EBT data sets better suited for automated segmentation and less susceptible to motion artifacts. 3D and virtual reconstructions did not increase the diagnostic sensitivity of CT compared to axial reconstructions alone. CONCLUSIONS: Shorter scan times of CT imaging yield higher-quality 3D and virtual reconstructions. Modern reconstruction techniques are valuable visualization tools for select indications and are the prerequisite for future developments in computer-aided medicine.

Bronchial Neoplasms↗
PubMed1998

Prevalence and course of psychiatric disorders among nursing home admissions.

Several studies have shown that psychiatric disorders are common in nursing homes, but information on the course of psychiatric morbidity shortly after admission is still lacking. Therefore, we interviewed 262 residents of Austrian nursing homes within 2 weeks following admission, and a second time after 6 months. Using the Clinical Interview Schedule and its case criteria, prevalence was 76.3% at admission, and 69.9% 6 months later. In the intervening period, the mortality rate was markedly higher among psychiatric cases, and the incidence of new psychiatric cases (5.9%) was slightly lower than the rate of remission (8.6%). At both assessments, organic mental illness was the most frequent diagnosis. Nursing home residents suffering from psychiatric disorders were treated predominantly by general practitioners applying a psychotropic drug regimen.

Aged↗
PubMed1998

Tumour-specific MHC-class-II-restricted responses after in vitro sensitization to synthetic peptides corresponding to gp100 and Annexin II eluted from melanoma cells.

In a search for potentially tumour-specific MHC-class-II-restricted antigens, the immunogenicity of endogenous peptides that had been eluted from HLA-DR molecules of the human melanoma cell line FM3 (HLA-DRB1*02x, DRB1*0401) was tested in vitro. Two 16-mers representing gp100 positions 44-59, and annexin II positions 208-223 bound well to isolated DRB1*0401 molecules and are discussed here. HLA-DR-matched normal donors' T cells were cultured with peptide-pulsed artificial antigen-presenting cells (CHO cells cotransfected with genes for HLA-DRB1*0401 and CD80 and coexpressing high levels of both human molecules). Specific sensitization was achieved against both peptides, as measured in assays of autocrine proliferation and interleukin-2 secretion. Moreover, responses to native autologous melanoma cells but not to autologous B cells were also observed. In view of the expression of fas by the activated T cells and of fas ligand by the melanoma cells, blockade of potential fas/ fas-ligand interactions was undertaken using monoclonal antibodies (mAb). The antagonistic fas-specific mAb M3, but not the fas agonist M33, caused a markedly enhanced T cell response to FM3 cells. These results demonstrate that synthetic peptide antigens are able to sensitize T cells in vitro for effective MHC-class-II-restricted recognition of melanoma cells.

Animals↗
PubMed1998

A DNA probe for the detection of Dicrocoelium dendriticum in ants of Formica spp. and Lasius spp.

Repetitive DNA sequences present in the genome of Dicrocoelium dendriticum were identified by hybridization of genomic DNA that had been digested with different restriction enzymes with 32P-labeled genomic D. dendriticum DNA. DNA fragments containing repetitive sequences were isolated from PstI-digested D. dendriticum DNA and were subcloned into a plasmid vector. Plasmids containing repetitive sequences were identified by colony hybridization. One of these plasmids, designated Ddr-IV, was isolated and used as a probe in further studies. Ddr-IV is specific for D. dendriticum since it does not hybridize to DNA isolated from other trematodes. In addition, Ddr-IV was capable of detecting D. dendriticum metacercariae in ants (Formica cunicularia, F. rufibarbis, and Lasius sp.), which act as second intermediate hosts in the parasite's life cycle. Since metacercariae constitute the infectious stage of the parasite for grazing animals, Ddr-IV will provide a useful tool for epidemiology studies of dicrocoeliosis.

Animals↗
PubMed1998

The transposable elements resident on the plasmids of Pseudomonas putida strain H, Tn5501 and Tn5502, are cryptic transposons of the Tn3 family.

Genes for (methyl)phenol degradation in Pseudomonas putida strain H (phl genes) are located on the plasmid pPGH1. Adjacent to the phl catabolic operon we identified a cryptic transposon, Tn5501, of the Tn3 family (class II transposons). The genes encoding the resolvase and the transposase are transcribed in the same direction, as is common for the Tn501 subfamily. The enzymes encoded by Tn5501, however, show only the overall homology characteristic for resolvases/integrases and transposases of Tn3-type transposons. Therefore it is likely that Tn5501 is not a member of one of the previously defined subfamilies. Inactivation of the conditional lethal sacB gene was used to detect transposition of Tn5501. While screening for transposition events we found another transposon integrated into sacB in one of the sucrose-resistant survivors. This element, Tn5502, is a composite transposon consisting of Tn5501 and an additional DNA fragment. It is flanked by inverted repeats identical to those of Tn5501 and the additional fragment is separated from the Tn5501 portion by an internal repeat (identical to the left terminal repeat). Transposition of phenol degradation genes could not be detected. Analysis of sequence data revealed that the phl genes are not located on a Tn5501-like transposon.

Base Sequence↗
PubMed1998

Material and functional properties of articular cartilage and patellofemoral contact mechanics in an experimental model of osteoarthritis.

The purposes of this study were to determine the in situ functional and material properties of articular cartilage in an experimental model of joint injury, and to quantify the corresponding in situ joint contact mechanics. Experiments were performed in the anterior cruciate ligament (ACL) transected knee of the cat and the corresponding, intact contralateral knee, 16 weeks following intervention. Cartilage thickness, stiffness, effective Young's modulus, and permeability were measured and derived from six locations of the knee. The total contact area and peak pressures in the patellofemoral joint were obtained in situ using Fuji Pressensor film, and comparisons between experimental and contralateral joint were made for corresponding loading conditions. Total joint contact area and peak pressure were increased and decreased significantly (alpha=0.01), respectively, in the experimental compared to the contralateral joint. Articular cartilage thickness and stiffness were increased and decreased significantly (alpha=0.01), respectively, in the experimental compared to the contralateral joint in the four femoral and patellar test locations. Articular cartilage material properties (effective Young's modulus and permeability) were the same in the ACL-transected and intact joints. These results demonstrate for the first time the effect of changes in articular cartilage properties on the load transmission across a joint. They further demonstrate a substantial change in the joint contact mechanics within 16 weeks of ACL transection. The results were corroborated by theoretical analysis of the contact mechanics in the intact and ACL-transected knee using biphasic contact analysis and direct input of cartilage properties and joint surface geometry from the experimental animals. We conclude that the joint contact mechanics in the ACL-transected cat change within 16 weeks of experimental intervention.

Animals↗
PubMed1998

CD95 expression and CD95-mediated apoptosis of T cells in multiple sclerosis. No differences from normal individuals and no relation to HLA-DR2.

CD95-mediated apoptosis is a potent endogenous pathway of T cell elimination that has been suggested to be altered in multiple sclerosis (MS). MS is associated with the HLA-DR2, Dw2, DQ6 HLA class II haplotype. We have previously reported that T cell lines from HLA-DR2-positive individuals show enhanced production of tumor necrosis factor (TNF), a cytokine homologous to CD95 ligand, in response to specific antigen. Here we have studied CD95 expression and susceptibility to CD95-mediated apoptosis in peripheral blood mononuclear cells (PBMC) and activated T cells of 20 healthy individuals and 20 MS patients, half of whom were HLA-DR2-positive. MS patients did not differ from healthy individuals in either parameter. There was also no difference in CD95 expression or CD95-mediated apoptosis when MS patients and healthy individuals were grouped and compared according to HLA-DR status. These data reveal no differential regulation of PBMC/T cell apoptosis induced by CD95 receptor ligation in MS and show no impact of HLA-DR2 status on PBMC/T cell susceptibility to the same apoptotic stimulus. However, to assess the contribution of T cell apoptosis to the pathogenesis of MS further studies on other details of the complex system leading to T cell apoptosis are required.

Apoptosis↗
PubMed1998

Does dobutamine stress echocardiography induce damage during viability diagnosis of patients with chronic regional dysfunction after myocardial infarction?

Experimental hibernating-model investigations of animals have shown that myocardial necrosis can be induced by longer-term intracoronary dobutamine infusion. This study was designed to determine whether myocardial infarction could be ascertained in patients with chronic regional wall motion abnormalities and greater than 75% stenosis in the supplying coronary artery through dobutamine stress echocardiography. Twenty patients with coronary artery disease and regional resting wall motion abnormalities were examined with a standard dobutamine protocol (5 to 50 microg/kg/min). Exclusion criteria were an acute coronary syndrome, severe heart failure, and severe hypertension. Creatine kinase (CK, CKMB), myoglobin, and troponine-I were measured before and at each of the first 7 hours after beginning of infusion. Fourteen of these 20 patients exhibited viable myocardium. The serum markers CK, CKMB, myoglobin, and troponin-I demonstrated no increase beyond the reference range, suggesting that with this protocol, no myocardial necrosis was induced.

Blood Pressure↗
PubMed1998

Pre-operative sequential chemo- and radiochemotherapy in locally advanced carcinomas of the lower oesophagus and gastro-oesophageal junction.

The purpose of this trial was to examine the feasibility of intensive, sequential chemo- and radiochemotherapy followed by surgery in patients with locally advanced carcinomas of the lower oesophagus and the gastro-oesophageal junction (GO junction). The chemotherapy consisted of two courses of 6 weekly administrations of 5-fluorouracil (5-FU) (2.0 g/m2, 24 h infusion) and folinic acid (FA) (500 mg/m2, 2 h infusion) combined with twice weekly cisplatin (50 mg/m2, 1 h infusion). Irradiation of 30 Gy was given concurrently with one course of cisplatin and etoposide. 25 patients with locally advanced (T3-T4 NX M0) squamous cell or adenocarcinoma of the lower oesophagus and GO junction were included and evaluated. Toxicity was usually mild to moderate (WHO grade 1 and 2) with mucositis as the most important side-effect of the pre-operative treatment. Of the patients, 94 and 88% completed the chemo- and radiochemotherapy according to the protocol, respectively. A major response (= partial remission with subjective improvement) to chemotherapy was achieved in 6/10 patients with squamous cell carcinoma and 10/15 with adenocarcinoma. 19 patients had subsequent surgery and complete resection was achieved in 16 (3 patients had intra-abdominal metastases observed at laparotomy). The operative mortality rate was 16% (3/19). 10 of the 16 patients with tumour resection had a pathological complete response. 15 patients (43%) remain alive at a median follow-up of 20 months and the median survival exceeds 16+ months. Our data suggest that this intensive pre-operative chemoradiotherapy programme is feasible and remarkably effective in patients with locally advanced carcinomas of the lower oesophagus or GO junction.

Adenocarcinoma↗
PubMed1998

Phase I study of a weekly 1 h infusion of paclitaxel in patients with unresectable hepatocellular carcinoma.

The majority of patients with hepatocellular carcinoma will develop either unresectable or metastatic disease and, therefore, are candidates for systemic chemotherapy. Only a few chemotherapeutic agents have shown documented activity in the treatment of advanced hepatocellular carcinoma and there is clearly a need for the evaluation of new active drugs. Therefore, we performed a phase I trial with a weekly schedule of paclitaxel in patients with advanced hepatocellular carcinoma. 16 patients with documented progression of unresectable hepatocellular carcinoma were included. After premedication, paclitaxel was given as a 1 h infusion on days 1, 8, 15, 22, 29 and 36 representing one treatment cycle. The cycle was repeated every 50 days. The starting dose was 70 mg/m2 and the doses were escalated in steps of 10 mg/m2/week. A minimum of 3 patients were treated at each dose level. All treatment was given on an out-patient basis. Dose-limiting toxicity was reached at a dose of 100 mg/m2/week with 2 of 6 patients treated at that dose level having WHO grade 4 neutropenia. Other toxic side-effects were only mild. 1 partial response and 9 cases with disease stabilisation were observed in 16 patients with initially progressive disease. We, therefore, conclude that the recommended dose for a further phase II trial in patients with hepatocellular carcinoma is 90 mg/m2/week. These data indicate that paclitaxel given at this dose and schedule might have activity in hepatocellular carcinoma and further investigation in phase II trials is warranted.

Adult↗
PubMed1998

Benefits of growth hormone treatment on bone metabolism, bone density and bone strength in growth hormone deficiency and osteoporosis.

Bone mass is reduced in patients with GH deficiency (GHD) leading to an increased vertebral fracture rate and clinically significant osteoporosis. Patients with GHD of juvenile onset have reduced skeletal mineralization. When substituting GH in patients with GHD, bone turnover is increased and bone mineral density initially decreases during the first year due to the increase in remodelling space. From the experience in patients with acromegaly, cortical bone mass is increased and trabecular bone mass is normal in eugonadal or decreased in the hypogonadal patients. However, bone mineral content and bone area are increased leading to a higher biomechanical competence of bone as shown in rats. In patients with GHD of juvenile onset, mineralization and bone maturation are achieved during treatment with GH in adult life after having reached final body height leading to an increase in bone mass. The GH/ IGF-I system is dysregulated in patients with post-menopausal osteoporosis. This is shown by reduced systemic IGF and IGFBP-3-levels in osteoporosis suggesting a decrease of endogenous GH-secretion or a dysregulation of the GH receptor system which is beyond the normal ageing process of the GH/IGF system, the "somatopause". A premature somatopause may be responsible for the dysregulation in some patients with osteoporosis. However, 24-h GH profiles do not differ between patients suffering from osteoporosis or osteoarthritis. Treatment of osteoporosis with GH might be beneficial due to the increased bone metabolism and improved bone geometry which occurs with GH. The substantial increase of bone remodelling achieved with GH may be helpful during late post-menopause with decreased bone turnover and impaired osteoblastic function. Using GH to prevent physiological bone loss that occurs with age seems possible, but has to be discussed on an ethical and economic basis.

Acromegaly↗
PubMed1998

Effect of the H1 blocker d-chlorpheniramine on cerebral blood flow in the conscious dog during normocapnic hypoxia.

The mechanism causing cerebral vasodilatation during hypoxia remains unclear. A role for histamine is suspected because H2 receptor-blocking drugs blunt the hypoxia-induced increase in cerebral blood flow (CBF). Moreover, in vitro blockade of H1 receptors by chlorpheniramine decreases the vasodilatation of cerebral arteries that is induced by histamine. The present study tested the hypothesis that an H1 receptor blocker (d-chlorpheniramine) would have a similar effect in vivo during hypoxia. Isocapnic hypoxia (inspired oxygen fraction, FIO2 = 0.10; inspired carbon dioxide fraction, FICO2 = 0.035) was induced in 16 conscious dogs randomly divided into two groups: eight dogs received saline intravenously (controls) at time 0 (normoxia) and after 2 h and 4 h hypoxia, and the other eight dogs received d-chlorpheniramine intravenously (0.5 mg kg-1) to block the H1 receptors. Regional CBF was measured by the radioactive microspheres technique 15 min after each injection of d-chlorpheniramine or saline. In the control group, CBF increased during hypoxia in all regions of the brain. In the d-chlorpheniramine group, total CBF increased similarly after 2 h of hypoxia. After 4 h of hypoxia, the increase was limited, especially in the pons, cerebral peduncles, hippocampus, hypothalamus, thalamus, and occipital lobes (six out of 12 studied regions). It is concluded that the H1 blocker d-chlorpheniramine did not strongly inhibit the increase in CBF during hypoxia. After cumulative doses, however, as in the fourth hour of hypoxia, the increase in total CBF was limited.

Animals↗