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Biomedical subjects

B Müller

Publications and source records attributed to B Müller.

At least 253 records · Page 14Linked to original sources

Lung surfactant components in bronchoalveolar lavage after inhalation of NO2 as markers of altered surfactant metabolism.

To study the effects of nitrogen dioxide (NO2) inhalation on lung lavage surfactant components as markers of an altered surfactant metabolism in type II pneumocytes, rats were exposed to atmospheres with increasing NO2 concentrations (0.8, 5.0, and 10.0 ppm) over 1 and 3 days. After exposure lung lavage was performed and surfactant components as well as lavageable cells analyzed. An increased number of total lavage cells was found with increasing concentration and duration of NO2 exposure. Cell distribution showed an elevation in the number of granulocytes and lymphocytes whereas the number of macrophages was diminished. The amount of total lavage protein revealed an increase related to NO2 concentration and duration. Also the content of lavage phospholipid was increased, with a decreased portion of phosphatidylcholine (PC). Further analyses of PC showed a diminished composition of saturated fatty acids but an elevated content of the unsaturated portion. Functional studies on surfactant phospholipid extracts exhibited comparable values for the surface tension at equilibrium, as well as for the maximal and minimal surface tension of animals exposed to 0.8 ppm NO2 and controls. Higher NO2 concentrations (5 and 10 ppm) resulted in increased values for surface tension compared to controls. This was also observed with purified surfactant that was obtained from controls and from NO2-exposed rats. These experiments show that in vitro exposure of purified surfactant to NO2 atmospheres was more effective than exposure in vivo. When the structure of the surfactant proteins A was studied it was found not to be altered by the NO2. The data clearly demonstrate that NO2 inhalation impaired function of surfactant components that may be used as markers of altered surfactant metabolism.

Animals↗

Atraumatic needle reduces the incidence of post-lumbar puncture syndrome.

We investigated the occurrence of the post-lumbar syndrome (PPS) in relation to the puncture technique used, in a prospective randomised double-blind study comprising 100 patients. A new atraumatic 22-gauge cannula was compared with a 20-gauge cannula with a Quincke bevel. The atraumatic cannula is a needle with a tip shaped like a closed circular cone with a lateral opening, usually used with an outer cannula (introducer). The study showed that both the frequency of PPS and of acute complaints during lumbar puncture can be dramatically reduced with the atraumatic puncture technique. A marked PPS occurred after lumbar puncture with the 20-gauge cannula in 31% of patients, whereas only 5% of patients reported marked post-puncture symptoms after lumbar puncture with the atraumatic cannula.

Adult↗

Assessment of proliferative activity in type II pneumocytes after inhalation of NO2 by AgNOR-analysis.

Adult male Sprague Dawley rats were exposed to 0.8, 5 and 10 ppm NO, alternatively for 1 or 3 days. After exposure the proliferative activity of the airway epithelium was assessed by means of BrdU incorporation and AgNOR-analysis at three different airway levels--in the bronchial, the bronchiolar epithelium and in Type 2 cells. The BrdU-labeling index (BrdU-LI), and AgNOR-number (AgNOR-N) were used to quantify the epithelial proliferation. Cytologic specimens of Type II cells showed a significant increase of the AgNOR-number and BrdU-LI after exposure to 5 ppm NO2 for 3 days and 10 ppm for 1 and 3 days. In the bronchiolar epithelium both, the AgNOR-number and BrdU-LI were significantly elevated in all the exposure groups. In the bronchial epithelium a significant response of the AgNOR-number was found after exposure to 10 ppm for 3 days. The correlation between AgNOR-number and BrdU-LI was 0.78 (p < 0.005).

Administration, Inhalation↗

beta-Adrenergic priming of rats in vivo modulates the effect of beta-agonist in vitro on surfactant phospholipid metabolism of isolated lungs.

To evaluate the effects of multiple beta-adrenergic stimulations on pulmonary surfactant phospholipids, perfused lungs from beta-adrenergic primed and non-primed rats were challenged with the beta-agonist terbutaline in vitro. Cell-free lung lavage, lavagable alveolar cells and lung tissue were analysed for phospholipid content and incorporation of precursors. In lung lavage, terbutaline in vitro doubled the incorporation of 14C-choline and 3H-palmitate into total phosphatidylcholine (PC) and of 3H-palmitate into phosphatidylglycerol (PG). beta-adrenergic priming in vivo prior to terbutaline in vitro lowered the increase of precursor incorporation. For lavagable cells, terbutaline in vitro increased the incorporation of 3H-palmitate into PC. Priming in vivo reduced this effect and diminished the specific 3H-choline incorporation into lavagable cell PC below control level. For lung tissue, priming increased the amounts of PC and disaturated PC (DSPC) whereas terbutaline in vitro decreased DSPC in both primed and non-primed lungs. Terbutaline in vitro slightly increased the incorporation of 14C-choline and 3H-palmitate into PC and DSPC in non-primed but not in primed lungs. beta-adrenergic blockade by ICI 118.551 prevented all effects but generally increased 3H-palmitate incorporation into the phospholipids and, in lavagable cells, the amount of PC. We conclude that long-term beta-adrenergic treatment may alter the metabolism of pulmonary surfactant phospholipids by increasing tissue PC and DSPC and by decreasing the secretion of newly-synthesized PC.

Adrenergic beta-Antagonists↗

On the origin of deletions and point mutations in Duchenne muscular dystrophy: most deletions arise in oogenesis and most point mutations result from events in spermatogenesis.

We present the results of a study of the rate and origin of mutations in Duchenne muscular dystrophy (DMD). Depending on the type of mutation (deletion/duplication or point mutation) present in the patient, there are widely varying ratios of male to female mutation rates. In deletions, the male mutation rate is only 30% of the female one. In non-deletional/non-duplicational mutations (presumably containing a high proportion of point mutations) the male mutation rate is at least 2.2 as high as the female one and probably much higher. Allowing for the presence of autosomal recessive phenocopies we find that k in non-deletional/non-duplicational mutations is 40.3. These findings mean that the vast majority of deletions arise in oogenesis, while most point mutations stem from spermatogenesis. Previous investigations have shown that in other diseases and genes, most notably haemophilia B and A, but also the ZFY and ZFX genes, the male mutation rate for point mutations tends to be higher than the female one. Our results can be seen as a confirmation of this for the special case of DMD. The influence on risk figures is considerable. As an example, the risk of the mother of an isolated case of DMD without an apparent structural anomaly of the gene of being a carrier increases from 67% to at least 76%. Given the estimate of 40.3 for k, allowing for the presence of autosomal recessive phenocopies mentioned above, it increases even further to 98%. However, as confidence intervals are still large, more data are needed to improve the estimates. Germinal mosaicism in this context is discussed.

Fathers↗

Molecular evidence for non-penetrance in Best's disease.

The present study provides evidence for a possible case of non-penetrance in Best's disease. We have analysed the at risk members of a three generation family with an established history of Best's disease by ophthalmoscopic examination, electrophysiological tests, and genetic analysis. The clinical examination identified 10 affected and five unaffected persons in this family. Genetic linkage analysis strongly supports linkage of the disease locus to DNA microsatellite markers from proximal 11q. The genotyping data were used to construct the familial haplotype associated with Best's disease. One person was identified who has inherited the Best's disease haplotype from his affected mother. Fundus examination and electrophysiological tests have repeatedly been performed in this patient but failed to show any signs of the disease. Based on these findings we have jointly estimated the most likely order of the Best's disease locus relative to the closet flanking markers at various penetrance values. A maximum likelihood estimate for the heterozygote penetrance was reached for the locus order D11S903-Best's disease-PYGM at a penetrance value of 0.96.

Adult↗

pH-dependent LAK cell cytotoxicity.

In the microenvironment of many solid tumors the pH is considerably lower (mean pH between 6.6 to 7.2) than the pH in normal tissue (pH 7.0-7.5). Therefore, the influence of acidic pH on the cytotoxic activity of lymphokine-activated killer cells (LAK cells) after different culture periods was tested. K-562 human erythroleukemia cells were selected as target cells. Cell killing was measured using a two-color flow cytometric method. At physiological pH of 7.4, LAK cell-mediated cytotoxicity ranged from 15 to 48% (E:T ratio = 50:1). The specific lysis of target cells was considerably reduced (up to 70% inhibition of specific lysis) under acidic conditions (pH 6.8, 6.3, 5.8). This effect was independent of donors, duration of the culture period, and the E:T ratio in the cytotoxic assay. As pH gradients surrounding tumor cells may reach values below pH 6.0 at the cell surface, the pH-dependence of LAK cell cytotoxicity could at least partially explain the inhibition of the natural immune response in solid tumors. Therapeutic immunological strategies concerning the enhancement of the natural immune response like LAK cell and IL-2 immunotherapy including IL-2 gene therapy may only be successful if a simultaneous inhibition of the acidification process and an elevation of tumor pH is achieved.

Cell Line↗

Increased angiotensin-I converting enzyme gene expression in the failing human heart. Quantification by competitive RNA polymerase chain reaction.

Local activation of the components of the renin angiotensin system in the heart is regarded as an important modulator of cardiac phenotype and function; however, little is known about their presence, regulation, and potential activation in the human heart. To investigate the gene expression of major angiotensin-II-forming enzymes in left ventricles of normal (n = 9) and failing human hearts (n = 20), we established a competitive RNA-polymerase chain reaction (PCR) for mRNA quantification of angiotensin-I converting enzyme (ACE) and human heart chymase. For each gene, competitor RNA targets with small internal deletions were used as internal standards to quantify the original number of transcripts and to control reverse transcription and PCR. In PCR, each target and the corresponding competitor were amplified by competing for the same primer oligonucleotides. The variability of ACE RNA-PCR was 11% indicating a high reproducibility of this method. In addition, ACE mRNA levels obtained by competitive RNA-PCR correlated favorably with traditional slot blot hybridization (r = 0.69, n = 10; P < 0.05). Compared with nonfailing hearts, the number of ACE transcripts referred to 100 ng of total RNA was increased threefold in patients with chronic heart failure (4.2 +/- 2.5 vs. 12.8 +/- 6 x 10(5); P < 0.0005). In contrast, no significant difference was found in chymase gene expression between normal and failing hearts. Thus, the expression of the cardiac ACE but not of human heart chymase is upregulated in failing human heart indicating an activation of the cardiac renin-angiotensin system in patients with advanced heart failure.

Adult↗

[Discrete dynamic systems: the effect of perceptual structuring on composition and transfer of knowledge about operating sequences].

This paper reports two experiments in which we explored the impact of perceptual grouping of elements on the organization and use of knowledge about how to operate a device. Experiment 1 explored the effects of different perceptual display regions on the creation of chunks when sequences of inputs had to be reproduced. The effects of regions were not homogeneous, but rather their influence depended on interactions between different modalities and learning conditions. Experiment 2 investigated the influence of grouping-induced composition of knowledge elements on the transfer of sequential knowledge. Two different learning criteria were used in the acquisition phase to manipulate the degree of composition of knowledge elements. In the transfer phase, subjects could transfer (1) the whole sequence of one region, (2) two partial sequences of adjacent regions, or (3) single components. It was found that regional invariance and immediate succession of components were both important for transfer performance. These results suggests that the temporal order of regions is important for the organization and use of sequential knowledge, and not the grouping of elements by itself.

Adult↗

[Availability of technical examination equipment. Results of a survey of 347 clinics].

In spring 1993 a survey was carried out in order to establish the availability of technical equipment in neurology departments throughout Germany. Ninety-seven percent of the questionnaires were returned completed. The results showed that extracranial and transcranial ultrasound, EEG, EMG, ENG, VEP, AEP, SEP are the basic technical investigations generally used in almost every neurology department. Long-term EEG and duplex ultrasound, although less commonly used, are usually performed within the hospital's neurology department. Our study showed that most university hospitals have a specialized neuroradiology department, whereas in general hospitals neuroradiologic examinations are conducted by general radiologists. Myelography is often done by neurologists. In contrast to CT scans, MRI is not yet widely available in many hospitals, but is usually in private practices. Patients have to be referred to these practices. In the former East Germany patients have to travel considerable distances. Only a very few highly specialized centers offer PET and SPECT facilities. As expected, there are still significant differences between the former East and West Germany concerning the structure f neurology health care. In West Germany a higher degree of specialization with many institutions for rehabilitation prevails whereas in East Germany almost half of all neurology beds are within neuropsychiatry departments, and specialized clinics are scarce.

Diagnostic Imaging↗

Laboratory diagnostics in light of massive changes in official health policies.

Virtually 100% of the German population has health insurance. Of this 100%, approximately 90% are members of the Statutory Health Insurance plan. This insurance plan assumes responsibility for practically all of the costs of treatment; self-participation by the patient in the costs is minimal. To counteract the financial deficits of the Statutory Health Insurance funds, the Health Care Reform Act was introduced in 1993, bringing with it massive economy measures for everyone involved in the health sector. For the practitioner sector, this new legislation provides for, among other things, revision of the structure and the reimbursement of laboratories. In this context, the originally agreed-upon introduction of lump-sum payments as reimbursement for laboratory tests was abandoned, in the face of vigorous resistance by the medical profession. Instead, the system of reimbursement for each individual test continues to apply. However, the number of tests is to be limited for each specific group of doctors. In addition, the laboratory fee in the practitioner sector is being reduced by 20%.

Clinical Laboratory Techniques↗

[A separate special consultation for relatives].

Relatives of mental ill have their own problems. This paper resumes first experiences with a special offer for relatives. The adviser must not be involved in the therapy with the sick member of the family.

Adaptation, Psychological↗

Rapid solution assays for retroviral integration reactions and their use in kinetic analyses of wild-type and mutant Rous sarcoma virus integrases.

A rapid method for quantitating products of the oligodeoxynucleotide processing reaction in vitro has been developed to facilitate enzymatic studies of the retroviral integrases. Unlike earlier procedures, this assay does not depend on polyacrylamide gel electrphoresis but separates products by batch adsorption to PEI-cellulose. A joining assay has also been modified, to facilitate measurement of the two distinct steps in the integration reaction under parallel conditions. Since these methods allow quantitation of numerous samples in a short period of time, they are especially useful for investigation of kinetic parameters and to measure the effects of possible inhibitors of integrase. These assay systems were used to examine the enzymatic activity of wild-type Rous sarcoma virus integrase and selected mutant proteins with substitutions of single conserved amino acids. In contrast to previous studies, reactions were performed under conditions of substrate excess, and rates, rather than yields of product generated after a given period of incubation, were determined. The results showed that substitutions of several highly conserved residues in what is most likely an evolutionarily conserved catalytic domain of the integrases resulted in a 4- to 10-fold decrease in the apparent rate of processing relative to wild type, under optimized standard conditions. Changing an invariant acidic residue reduced the rate by approximately 60-fold. When joining activity was determined, the relative effects of the substitutions tested generally paralleled the results with processing. However, with both wild-type and mutant integrase proteins, the linear phase of the joining reaction was preceded by what appears to be an exponential "burst" phase.

Amino Acid Sequence↗