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Biomedical subjects

C Müller

Publications and source records attributed to C Müller.

At least 451 records · Page 25Linked to original sources

[Applied psychoacoustics in space flight].

Simulation free field hearing by head phones by means of digital filter technics was used to investigate directional hearing and audiocinetic vection in microgravity. Our data showed basic informations for the understanding of the reciprocal influence of vestibular and auditory inputs for dynamic orientation. The technical equipment of free field hearing simulation by headphones and the performed experiments are described in detail. Furthermore the new established technology is discussed in terms of the value in psychoacoustic research as well as in clinical practice.

Auditory Perception↗

[Extended resections in bronchial cancer: complications and late results].

From 1982 through April 1992, 192 patients underwent extended resection for non-small cell carcinoma of the lung (NSCLC) invading the chest wall (n = 52) or the mediastinum (n = 140). Complete resection of the tumor was possible in 81 (58%) patients with invasion of mediastinum and in 34 (65%) patients with invasion of the chest wall. The operative mortality was 9%, respiratory complications causing most of the postoperative morbidity and mortality. Incomplete resection was associated with poor prognosis. The mean survival of these patients was 10 month. The 5 year actuarial survival rate of patients having curative resection was 20%. In these patients the presence of lymphatic metastases significantly reduced survival, with a 3 year actuarial survival rate of 40% of patients with No disease, and 30% or 5% for those with N1 or N2 disease, respectively. In conclusion, extended resection for advanced NSCLC offers a significant chance for long-term survival in the absence of N2 lymphatic metastases. In the presence of N2 metastases and poor overall prognosis however, reasonable palliation is the primary goal of surgical management.

Carcinoma, Bronchogenic↗

[Expandable metal mesh stents for treatment of tracheal stenoses and tracheomalacia].

The treatment of tracheo-bronchial stenosis or tracheomalacia is mainly carried out by means of resection or tracheoplastic operative strategies. Since the introduction of metal-mesh stents, a definitive endoluminal therapy has to be considered under new aspects. Six patients with malignant stenosis or tracheomalacia due to compression were treated by implantation of Palmaz- or Wallstents. Immediately after the implantation, patients were relieved from dyspnoea, the forced inspiratory volume-1 (FIV1) was normalized. All implanted stents were well tolerated, even in the long-time follow-up (19 months). Bronchoscopic control showed overgrowth of the metal meshes by respiratory epithelium. The implantation of metal-mesh stents is an adequate alternative in the treatment of malignant stenosis and tracheomalacia.

Aged↗

In situ hybridization of virulent canine distemper virus in brain tissue, using digoxigenin-labeled probes.

Only a few hybridization experiments have been performed for detection of canine distemper virus (CDV) nucleic acid sequences in tissue cultures and in various tissues. Those published studies used probes derived from tissue culture-adapted CDV, and hybridization signals were not obtained in the CNS tissue, although infective CDV and viral antigen were detectable in this tissue. We developed probes complementary to virulent CDV and were able to detect viral RNA not only in primary brain cell cultures, but also in brain tissues, by use of in situ hybridization. Sensitivity of the test at least equaled that of immunohistochemistry. We applied digoxigenin-labeled, strand-specific RNA probes complementary to the nucleoprotein-coding viral nucleic acid sequence. Our results indicate that to detect CDV nucleic acid sequences in brain tissues, it is essential to use probes derived from the virulent virus.

Animals↗

Dopamine D2 receptor imaging and measurement with SPECT.

Only recently it has become possible to label and visualize dopamine D2 receptors in the living human brain using an [123I]labeled ligand and the SPECT technique. Iodobenzamide (S(-)IBZM) is a substance with high affinity and high specificity for D2 receptors and was used in controls and in patients with different extrapyramidal disorders. After the i.v. administration of 5mCi (185 MBq) of [123I] labeled S(-)IBZM data collection was performed with a rotating double head scintillation camera between 60 and 110 minutes. In a semiquantitative approach a ratio was calculated between mean counts/pixel in the striatum and a region in the lateral frontal cortex, which gives an index of receptor density. In a group of 21 controls this ratio is 1.73 +/- 0.09. A highly significant age-related decline is found in controls and in 57 patients with PD. PD patients without L-DOPA or dopamine agonist treatment do not differ from controls (1.72 +/- 0.09; n = 18), whereas patients under dopaminergic therapy show a significantly lower binding ratio (1.65 +/- 0.13; n = 39; p = 0.017) suggesting receptor downregulation. Comparing the striatum ipsi- and contralateral to clinical symptoms in 18 hemiparkinsonian patients shows slightly but significantly higher values on the contralateral side, indicating receptor supersensitivity (1.71 +/- 0.11 vs. 1.66 +/- 0.09; p = 0.0014). No correlation between D2 receptor binding and clinical stage, duration of disease or duration of dopaminergic therapy exists. Markedly reduced ratios are measured in 7 patients with progressive supranuclear palsy and multiple system atrophies and in 18 patients with Huntington's disease (1.40 +/- 0.09 and 1.37 +/- 0.12 respectively; p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Vocational promotion of psychiatrically handicapped patients in a Frankfurt am Main vocational training center].

In 1988, the Frankfort on Main Vocational Retraining Centre had decided in favour of increased, on-going admission of psychiatrically disabled adults, offering opportunities for their vocational education. The centre's objective is to enable psychiatrically disabled rehabilitees to successfully complete formal occupational training in as "normal" a setting as possible. This means: the Centre is a vocational rehabilitation facility, and is not directed at therapy or care. Psychiatrically disabled rehabilitees are accepted for up to 10 percent of available places in the various programme types. The overall objective is formal occupational qualification. A "training centre" open to all training orientations has been established for individualized service provision in the event of crisis situations during programme participation. Special attention is focussed on intensive, continuous further education of staff, inter alia by group supervision.

Combined Modality Therapy↗

Effects of nocloprost (9 beta-chloro-16,16-dimethyl PG E2) on absorption and disposition of antipyrine and sulfamethazine in healthy volunteers.

Prostaglandins are known to interfere with drug metabolizing processes. Nocloprost (9 beta-chloro-16,16-dimethyl PG E2) is a promising new cytoprotective prostaglandin in clinical evaluation for the treatment of ulcer disease and prophylaxis of gastric lesions caused by NSAID. Pharmacokinetic interactions of 400 micrograms nocloprost with 15 mg/kg antipyrine and 500 mg sulfamethazine (all given p.o.) were studied with a controlled, single-blind crossover trial in 16 healthy male volunteers (age 22-25 years, body weight 63-94 kg, body height 175-187 cm) in order to measure potential interferences with oxidative and conjugative drug metabolism. All individuals were extensive metabolizers of debrisoquine, 9 were slow and 7 rapid acetylators of sulfamethazine. Antipyrine and its major metabolites were measured in serum respectively, urine with the HPLC-method, sulfamethazine and its acetylated metabolite with a colorimetric technique. Nocloprost premedication (30 min prior to the test drugs) did neither interfere significantly with the oxidative processes involved in the disposition of antipyrine nor with the N-acetylation of sulfamethazine. Higher metabolic and renal clearance values of sulfamethazine in slow acetylators were most likely the result of the affected drug absorption. Nocloprost significantly reduced absorption rates of antipyrine and sulfamethazine in the group of slow but not of rapid acetylators. The extent of bioavailability remained unchanged. This phenomenon was certainly caused by the effects of the cytoprotective prostaglandin on those gastrointestinal functions which are determinants of drug absorption.

Acetylation↗

Perforin and its role in T lymphocyte-mediated cytolysis.

The killing mediated by cytotoxic T lymphocytes (CTL) represents an important mechanism in the immune defence against tumors and virus infections. The lytic mechanism has been proposed to consist of a polarized secretion of granule-stored molecules, occurring on effector-target cell contact. By electron microscopy, membrane deposited, pore-like lesions are detected on the target cell membrane during cytolysis by CTL. These structures resembled strikingly pores formed during complement attack. Granules of CTL isolated by nitrogen cavitation and Percoll gradient centrifugation were shown to retain cytotoxic activity. Further purification of proteins stored in these granules led to the discovery of a membranolytic protein named perforin which was capable of polymerizing into pore-like structures. In addition to this cytolytic protein, a set of serine esterases was found as well as lysosomal enzymes and proteoglycans, whose function are not yet clearly defined. The role of perforin in the cytotoxic process is currently being explored by ablating the active gene in mice.

Animals↗

Engagement of the T-cell receptor during positive selection in the thymus down-regulates RAG-1 expression.

We have examined the expression of the recombination activating gene RAG-1 by in situ hybridization to thymi from mice bearing transgenes for the T-cell receptor (TCR) alpha chain, TCR beta chain, or both TCR alpha and beta chains. RAG-1 transcription was found in the thymic cortex of transgenic mice carrying a single TCR alpha- or TCR beta-chain transgene, comparable to normal mice. However, RAG-1 transcription was strikingly reduced in the thymic cortex from transgenic mice carrying both TCR alpha- and beta-chain genes and expressing major histocompatibility complex (MHC) class I (H-2b) molecules necessary for positive selection of the transgenic TCR. In contrast, thymi of transgenic mice also carrying both TCR alpha- and beta-chain genes but expressing MHC molecules (H-2d) that did not positively select the transgenic TCR displayed high levels of RAG-1 transcription. The low thymic RAG-1 expression coincided with high transgenic TCR alpha-chain surface expression and with inhibition of endogenous TCR alpha-chain rearrangement. Our findings suggest that binding of the TCR to self MHC molecules during positive selection down-regulates RAG-1 transcription in cortical thymocytes and thereby prevents further TCR alpha-chain rearrangements.

Animals↗

Constitutive monocyte-restricted activity of NF-M, a nuclear factor that binds to a C/EBP motif.

In a search for monocyte-specific nuclear factors, we analyzed in human cells the promoter of the chicken myelomonocytic growth factor, a gene that, in the chicken, is expressed in myeloid and myelomonocytic cells. Reporter gene constructs were active in monocytic Mono Mac 6 cells and in monoblastic THP-1 cells but not in the hematopoietic stem cell line K562. When a region with homology to the sequence recognized by CAAT enhancer-binding proteins (C/EBP) was inactivated by site-directed mutagenesis, the reporter activity was reduced by a factor of 10. Multimers of this region, termed F, in front of a heterologous promoter were active in Mono Mac 6 and THP-1 cells but not in K562 cells, WIL2 B cells, BT20 mammary carcinoma cells, MelJuso melanoma cells, or SK-Hep-1 hepatoma cells. Gel shift analysis with the F oligonucleotide identified DNA-binding activity in monocytic Mono Mac 6, monoblastic THP-1, and myelomonocytic HL60 cells. No binding was detected in myelomonocytic RC2A cells, in myeloid KG-1 cells, or in the hematopoietic stem cell line K562. Furthermore, a panel of solid tumor cell lines, representing various tissues, were also negative. Stimulation by PMA could not induce this binding factor in any of the negative cell lines. Analysis of primary cells (granulocytes, T cells, monocytes, and alveolar macrophages) revealed binding activity only in monocytes and macrophages. This DNA-binding factor, termed NF-M, was found to consist of two molecules, of 50 and 72 kDa, as determined by affinity cross-linking. Binding of NF-M was competed by the region F oligonucleotide and by the C/EBP motif from the albumin enhancer but not by an AP-2 motif. These data suggest that NF-M is a member of the C/EBP family of nuclear factors. The monocyte-restricted activity of NF-M suggests that this nuclear factor may be involved in regulation of monocyte-specific genes.

Base Sequence↗

Monitoring of ajmaline in plasma with high-performance liquid chromatography.

A rapid, reliable and sensitive assay for routine determination of ajmaline in plasma by high-performance liquid chromatography with fluorimetric detection is presented. A low limit of detection in plasma (less than 1 ng/ml ajmaline) could be achieved by the extraction of plasma samples and the use of fluorimetric detection. Deproteinization of the plasma sample instead of extraction, or the use of an ultraviolet detector, yielded a higher limit of detection (less than 50 ng/ml). Two different eluents were studied. Eluent 1 allowed clear separation of ajmaline from isoajmaline and sandwicine, but did not separate isoajamaline from sandwicine. With eluent 2, separation of isoajmaline and sandwicine was achieved, but separation of ajmaline from sandwicine was less optimal than with eluent 1. Therefore, eluent 1 was used for further clinical studies. No interference was observed from therapeutic doses of other commonly co-administered drugs, such as acetylsalicylic acid, digoxin, digitoxin, ranitidine, dopamine, dobutamine, furosemide, captopril or glycerol trinitrate. In addition, the chemical stability of ajmaline and a possible rearrangement of ajmaline to its stereoisomers isoajmaline and sandwicine was studied in vivo and in vitro. Ajmaline proved to be unusually stable under both in vivo and in vitro conditions.

Ajmaline↗

Liver function in acute viral hepatitis as determined by a hepatocyte-specific ligand: 99mTc-galactosyl-neoglycoalbumin.

Twelve patients with recently diagnosed acute viral hepatitis underwent serial 99mTc-galactosyl neoglycoalbumin scanning of the liver (for up to 8 mo). Injection of 99mTc-galactosyl neoglycoalbumin (150 mBq) at a rate of 3.5 mg (50 nmol; 1 ml) revealed that the liver is the exclusive site of tracer uptake. Simulation of 99mTc-galactosyl neoglycoalbumin kinetics allowed quantification of galactosyl neoglycoalbumin binding to human hepatic binding protein. Return of liver function test scores to normal values was associated in two patients with hepatitis A, in four patients with hepatitis B and in two patients with non-A, non-B hepatitis virus infection, with increases in hepatic binding protein concentration (up to three times the initial concentration), binding rate constant and hepatic blood flow. In the other four patients (three patients with hepatitis B and one patient with cytomegalovirus infection) a prolonged course of disease was monitored. In the mean, hepatic binding protein increased from 0.41 +/- 0.11 mumol/L after onset of acute hepatitis (n = 12) to 0.78 +/- 0.21 mumol/L after 6 mo of follow-up (n = 10) (p less than 0.001). During this period, binding rate constant (72.4 +/- 12.6 vs. 82 +/- 11.5 mumol/L/sec; p less than 0.05) and hepatic blood flow (0.027 +/- 0.0051 vs. 0.031 +/- 0.0083 L/sec; p less than 0.05) increased. Hepatic binding protein concentration correlated highly with actual laboratory test results for liver function (r = 0.98; p = 0.0001). We conclude that scintigraphic evaluation of functional liver cell mass using the new receptor-tracer 99mTc-galactosyl neoglycoalbumin could provide an in vivo diagnostic means of quantifying liver function and assessing liver morphology. In addition, our findings suggest that changes in hepatic binding protein-receptor concentration are likely to occur in vivo.

Acute Disease↗