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Biomedical subjects

B Müller

Publications and source records attributed to B Müller.

At least 307 records · Page 17Linked to original sources
PubMed1992

Structural and functional impairment of surfactant protein A after exposure to nitrogen dioxide in rats.

The major surfactant protein A (SP-A) determines the dynamics of surfactant metabolism and function. We now for the first time studied the in vivo exposure of the SP-A to nitrogen dioxide (NO2) and compared it to in vitro exposure effects. Several properties that are believed to possess physiological functions were investigated. Exposure of rat SP-A to NO2 showed 1) a higher alveolar pool size after in vivo exposure, 2) a slightly decreased mannose binding capacity for the in vivo exposed form but a highly decreased binding after in vitro exposure, 3) an affected protein-lipid aggregation that was impaired most by the in vitro exposed protein, 4) a low inhibition for the secretion of phosphatidylcholine in isolated type II pneumocytes, and 5) no difference in apparent molecular weight and immunological reactivity of the differently exposed SP-A. The NO2-induced alterations of the SP-A may contribute to the pulmonary toxicity of this oxidant. It is clear from this study that the extend of the effects from in vivo and in vitro exposure are different. Therefore both forms of exposure are necessary to assess the biological significance of NO2 exposure.

Animals↗
PubMed1992

Leber's hereditary optic neuroretinopathy and the X-chromosomal susceptibility factor: no linkage to DXs7.

Leber's hereditary optic neuroretinopathy (LHON) was the first human disease for which mitochondrial inheritance was demonstrated. Analysis of genealogies, however, suggests the existence of an interacting X-linked factor, and linkage to DXS7 was recently described. We tested this location in four LHON families, with DXS7 and two flanking markers, OTC and DXS426. We found recombinations with DXS7 in two families and with DXS426 in one. The two point lod scores to DXS7 were negative with all the allele frequencies for the X-linked factor tested (q = 0.5; 0.35; 0.05).

Female↗
PubMed1992

Parkinson's disease in twins.

Among nine monozygotic (MZ) and 12 dizygotic (DZ) twin pairs in which an index case had typical Parkinson's disease (PD) or PD with associated dementia, three MZ and three DZ pairs were concordant. Three of the six affected co-twins were first diagnosed during the study. Occurrence of PD in families of MZ and DZ index cases was more frequent than expected from population rates. The study underlines the need for personal examination using defined criteria in a cross-sectional twin study on PD. Although the study did not establish a major genetic impact in the etiology of PD, a genetic predisposition for the disease cannot be ruled out for some individuals.

Adult↗
PubMed1992

The autosomal dominant familial exudative vitreoretinopathy locus maps on 11q and is closely linked to D11S533.

Autosomal dominant familial exudative vitreoretinopathy (adFEVR) is a hereditary disorder characterized by the incomplete vascularization of the peripheral retina. The primary biochemical defect in adFEVR is unknown. The adFEVR locus has tentatively been assigned to 11q by linkage studies. We report the results of an extended multipoint linkage analysis of two families with adFEVR by using five markers (INT2, D11S533, D11S527, D11S35, and CD3D) from 11q13-q23. Pairwise linkage data obtained in the two families were rather similar and hence have not provided evidence for genetic heterogeneity. The highest complied two-point lod score (3.67, at a recombination fraction of .07) was obtained for the disease locus versus D11S533. Multipoint analyses showed that the adFEVR locus maps most likely, with a maximum location score of over 20, between D11S533/D11S527 and D11S35, at recombination rates of .147 and .104, respectively. Close linkage without recombination (maximum lod score 11.26) has been found between D11S533 and D11S527.

Chromosome Mapping↗
PubMed1992

Cough induced by ACE-inhibitors. A kinin related phenomenon?

Cough induced by ACE-inhibitors may be related to bronchial hyperreactivity and/or to an accumulation of kinins. In a placebo-controlled, double-blind randomized study in asthmatic and hypertensive patients lung function and bronchial reactivity to histamine and bradykinin remained unaltered although in hypertensive patients with cough, reactivity to histamine tended to be more pronounced and bronchial hyperreactivity to be more frequent than in those without cough. The findings do not support a major role of kinins in ACE inhibitor-induced cough.

Adult↗
PubMed1992

Airway responsiveness and cough induced by angiotensin converting enzyme inhibition.

Dry cough is one of the most common side-effects of angiotensin converting enzyme inhibitors. The mechanism of cough induced by ACE inhibitors is not completely understood and may be related to bronchial hyperreactivity and/or an accumulation of kinins. In a placebo-controlled, double-blind randomised study, the effect of captopril on lung function and bronchial reactivity to histamine and bradykinin was investigated in eight asthmatic and 12 hypertensive patients (six with and six without cough during previous ACE inhibition). Lung function did not change in any patient after a single (25 mg) or short-term (2 x 25 mg for two weeks) administration of captopril. Bronchial reactivity to histamine and bradykinin remained unaltered in all groups. In hypertensive patients with cough, reactivity to histamine tended to be more pronounced and bronchial hyperreactivity to be more frequent than in those without cough. In conclusion, the present results do not support a major role for kinins in cough induced by ACE inhibition. On the other hand, bronchial hyperreactivity may be important in some patients. Additionally, these results demonstrate that treatment with ACE inhibitors is safe in most patients with bronchial asthma.

Adult↗
PubMed1992

Proximal spinal muscular atrophy (SMA) types II and III in the same sibship are not caused by different alleles at the SMA locus on 5q.

Proximal spinal muscular atrophy (SMA) is a group of progressive muscular diseases recently mapped to chromosome 5q. SMA is usually classified into types I-III, and there are cases of two types of SMA in the same sibship. Becker and others later proposed that these sibships might be due to the existence of several alleles at the same locus predisposing to the different forms of the disease. In a sample of four sibships in which both SMA type II and SMA type III occur, this hypothesis was clearly rejected for the SMA locus on 5q, by using information on the segregation of linked markers (P less than .001). Thus the difference between SMA type II and SMA type III is not due to different alleles at the SMA locus on 5q. This finding is suggestive of an involvement of other factors, genetic or environmental, in the determination of disease severity in SMA.

Alleles↗
PubMed1991

The ability of cationic amphiphilic compounds to depress the transition temperature of dipalmitoylphosphatidic acid liposomes depends on the spatial arrangement of the lipophilic moiety.

The hypothesis was tested with the help of model compounds that the ability of cationic amphiphilic drugs to depress the phase-transition temperature Tt of dipalmitoylphosphatidic acid (DPPA) liposomes depends on the spatial arrangement of the lipophilic moiety. The main structure of the compounds with identical cationic side chain was 1-dimethylamino-3-phenylpropane (compound I). A further phenyl ring was introduced either at C3 of the propane chain (compound II) to broaden the lipophilic moiety, or in para-position of the phenyl ring (compound III) to elongate it. As shown by differential scanning calorimetry, the reduction of Tt (control 64 degrees) amounted for compound I to 29 degrees, for compound II to 28 degrees and for compound III to 53 degrees. In order to assess the binding affinity of the compounds to DPPA, their inhibitory effect on 45Ca(2+)-binding to DPPA films was measured. The IC50 values were 2100 microM for compound I, 40 microM for compound II, and 9 microM for compound III. Thus, binding affinity corresponded with the hydrophobicity of the compounds. In contrast, the depressing effect on the transition temperature was only augmented by the additional phenyl ring when substituted in the elongating position.

Calcium↗
PubMed1991

Factors contributing to the inhibition of HIV reverse transcriptase by chain-terminating nucleotides in vitro and in vivo.

Arguments are presented leading to the conclusion that two major factors contribute to the potency of inhibition of DNA-polymerase activity by chain-terminating nucleotides. The relative significance of these factors varies with the reaction conditions, particularly with the length of the template and the concentration ratio of enzyme (reverse transcriptase or other DNA polymerase) to primer. It is concluded that potent inhibition of HIV-reverse transcriptase activity under typical in vitro and in vivo conditions arises from different features of the interaction of chain terminators with the enzyme. A new method of testing for the parameter important under in vivo conditions is suggested.

HIV↗
PubMed1991

Action of RecBCD enzyme on Holliday structures made by RecA.

In vitro, Escherichia coli RecA protein acts upon gapped and partially homologous linear duplex DNA to generate recombination products linked by Holliday junctions. When strand exchange reactions are supplemented with purified RecBCD enzyme, we observe the formation of products that resemble "patch" recombinants. The formation of "splice" recombinant products was not observed. The individual subunits, RecB, RecC, or RecD, had no effect on RecA protein-mediated strand exchange nor on the Holliday junctions formed in the reaction. Analysis of the way in which patch products arise indicates exonucleolytic digestion of the linear arms of the recombination intermediates (alpha-structures) by RecBCD enzyme. We find no evidence for specific resolution events at the site of the Holliday junction by RecBCD enzyme using these DNA substrates.

Crossing Over, Genetic↗
PubMed1991

RecA-mediated annealing of single-stranded DNA and its relation to the mechanism of homologous recombination.

We demonstrate that RecA protein can mediate annealing of complementary DNA strands in vitro by at least two different mechanisms. The first annealing mechanism predominates under conditions where RecA protein causes coaggregation of single-stranded DNA (ssDNA) molecules and where RecA-free ssDNA stretches are present on both reaction partners. Under these conditions annealing can take place between locally concentrated protein-free complementary sequences. Other DNA aggregating agents like histone H1 or ethanol stimulate annealing by the same mechanism. The second mechanism of RecA-mediated annealing of complementary DNA strands is best manifested when preformed saturated RecA-ssDNA complexes interact with protein-free ssDNA. In this case, annealing can occur between the ssDNA strand resident in the complex and the ssDNA strand that interacts with the preformed RecA-ssDNA complex. Here, the action of RecA protein reflects its specific recombination promoting mechanism. This mechanism enables DNA molecules resident in the presynaptic RecA-DNA complexes to be exposed for hydrogen bond formation with DNA molecules contacting the presynaptic RecA-DNA filament.

Adenosine Triphosphate↗
PubMed1991

Expression of the heterodimeric form of human immunodeficiency virus type 2 reverse transcriptase in Escherichia coli and characterization of the enzyme.

A system for the expression of recombinant human immunodeficiency virus type 2 (HIV-2) reverse transcriptase (RT) in Escherichia coli has been developed, which allows purification of the heterodimeric form of the enzyme as well as the separate purification of the two subunits. It is shown that equilibrium formation between monomeric and homodimeric forms of the recombinant 66- and 51-kDa subunits is considerably more rapid than in the case of the corresponding homodimeric forms of HIV-1 RT. In accordance with our previously published studies on HIV-1 RT (Restle, T., Müller, B., and Goody, R.S. (1990) J. Biol. Chem. 265, 8986-8988) RNA-dependent DNA polymerase activity of the HIV-2 RT preparations can be exactly correlated to their dimer content. No significant heterodimer formation can be observed upon coexpression of the 66-kDa subunit of HIV-2 RT with the 51-kDa subunit of HIV-1 RT in the same cell, indicating differences in the dimerization domains of the two proteins. Recombinant HIV-2 RT is not recognized by a set of 23 monoclonal antibodies raised against HIV-1 RT, although it shows weak cross-reactivity with sera from HIV-1-infected patients.

Chromatography, Gel↗
PubMed1991

Zardaverine as a selective inhibitor of phosphodiesterase isozymes.

The pyridazinone derivative zardaverine has recently been introduced as a potent bronchodilator in vivo and in vitro. In addition, zardaverine exerts a positive inotropic action on heart muscle in vitro. The actions of zardaverine are thought to be mediated via inhibition of phosphodiesterase (PDE) activity. Recent data suggest that there are multiple forms of phosphodiesterases and at least five different isozyme families are now recognized. In the present study, the effects of zardaverine on the different PDE isozymes were investigated in several tissues. PDE isozymes were separated by chromatography on Q-sepharose. Zardaverine inhibited the cyclic GMP-inhibitable PDE III from human platelets and the rolipram-inhibitable PDE IV from canine trachea and human polymorphonuclear (PMN) cells with IC50-values of 0.58, 0.79 and 0.17 microM, respectively. The pyridazinone derivative affected the calmodulin-stimulated PDE I, the cyclic GMP-stimulated PDE II and the cyclic GMP-specific PDE V only marginally at concentrations up to 100 microM. Zardaverine inhibits the ADP-induced aggregation of human platelets with an IC50 of 1.6 microM. This inhibition was synergistically increased by activators of adenylate cyclase such as PGE1 and forskolin. In human PMN cells, zardaverine inhibited the zymosan-induced superoxide anion generation with an IC50 of 0.40 microM. Again, this effect was increased by activators of adenylate cyclase. These data clearly demonstrate that zardaverine is a selective inhibitor of PDE III and PDE IV isozymes.

Animals↗
PubMed1991

Morphology and distribution of catecholaminergic amacrine cells in the cone-dominated tree shrew retina.

The tree shrew (Tupaia belangeri) has a cone-dominated retina with a rod proportion of only 5%. This is in contrast to the usual mammalian pattern of rod-dominated retinae. Rod bipolar cells are present at relatively low densities in the tree shrew retina, suggesting that a reduced, but normal, rod pathway might be preserved. The present study investigated another common constituent of the rod pathway, the dopaminergic amacrine cells, and analysed their morphology and distribution by light and electron microscopy. Catecholaminergic (presumed dopaminergic) amacrine cells were labelled with an antibody against tyrosine hydroxylase (TH). Intense TH-immunoreactivity was found in perikarya and dendrites of a uniform amacrine cell population. TH-immunoreactive amacrine cell density varies across the retina from 10 cells/mm2 in the periphery to 40 cells/mm2 in more central regions (mean cell density about 25 cells/mm2). The relatively large cell bodies are located exclusively in the innermost part of the inner nuclear layer. The dendrites form a dense plexus at the border between the inner plexiform layer and the inner nuclear layer. The finer dendritic processes contain many varicosities and form characteristic dendritic "rings" like those seen in other mammals. TH-immunoreactive processes also run between cell bodies in the vitread inner nuclear layer; a few extend into the sclerad inner nuclear layer and occasionally reach the outer plexiform layer (possible interplexiform cells). A few TH-immunoreactive processes are seen in the middle of the inner plexiform layer. Electron microscopy of TH-immunoreactive processes revealed conventional synapses onto somata and processes of unlabelled amacrine cells.

Animals↗
PubMed1991

Interaction of fluorescently labeled dideoxynucleotides with HIV-1 reverse transcriptase.

Succinylfluorescein-labeled dideoxyTTP has been used as a substrate for reverse transcriptase from HIV-1. On addition to the 3'-end of a primer molecule, there is a reduction of fluorescence yield of a factor of ca. 4. Release of a fluorescent DNA/DNA primer/template duplex from its complex with reverse transcriptase results in a reduction of fluorescence by a further factor of 2. The fluorescent nucleotide is incorporated somewhat less efficiently than 3'-azidoTMP and TMP, which show similar incorporation kinetics. Fluorescent chain-terminated primers have been used to investigate the interaction of normal and chain-terminated primer/template complexes with reverse transcriptase. The dissociation constant of a 36/18-mer was 0.65 nM, whereas that of the same complex after the addition of the fluorescent chain-terminating nucleotide to the primer was 3 nM at 25 degrees C. The rate of dissociation of the latter complex from the enzyme was 0.04 s-1. This was decreased by a factor of ca. 10 at high concentrations (greater than 200 microM) of the nucleotide triphosphate complementary to the next position of the template. The results obtained suggest that potent inhibition of reverse transcriptase activity in in vitro assays results from formation of a slowly dissociating complex between the enzyme and chain-terminated primer/template complexes. However, arguments are presented that lead to the conclusion that this is not the mode of inhibition in cells invaded by HIV. At the prevailing relative concentrations in this situation, chain termination resulting in incomplete transcription is likely to be the major factor.

Binding, Competitive↗