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Biomedical subjects

M Barth

Publications and source records attributed to M Barth.

At least 55 records · Page 3Linked to original sources
PubMed1993

Complex transcriptional control of the sigma s-dependent stationary-phase-induced and osmotically regulated osmY (csi-5) gene suggests novel roles for Lrp, cyclic AMP (cAMP) receptor protein-cAMP complex, and integration host factor in the stationary-phase response of Escherichia coli.

osmY (csi-5) is a representative of a large group of sigma s-dependent genes in Escherichia coli that exhibit both stationary-phase induction and osmotic regulation. A chromosomal transcriptional lacZ fusion (csi-5::lacZ) was used to study the regulation of osmY. We show here that in addition to sigma s, the global regulators Lrp, cyclic AMP (cAMP) receptor protein-cAMP complex (cAMP-CRP), and integration host factor (IHF) are involved in the control of osmY. All three regulators negatively modulate the expression of osmY, and they act independently from sigma s. Stationary-phase induction of osmY in minimal medium can be explained by stimulation by sigma s combined with a relief of Lrp repression. Stationary-phase induction of osmY in rich medium is mediated by the combined action of sigma s, Lrp, cAMP-CRP, and IHF, with the latter three proteins acting as transition state regulators. The transcriptional start site of osmY was determined and revealed an mRNA with an unusual long nontranslated leader of 244 nucleotides. The regulatory region is characterized by a sigma 70-like -10 promoter region and contains potential binding sites for Lrp, CRP, and IHF. Whereas sigma s, Lrp, CRP, and IHF are clearly involved in stationary-phase induction, none of these regulators is essential for osmotic regulation of osmY.

Amino Acid Sequence↗
PubMed1992

Characterization and crystal structure of zinc azurin, a by-product of heterologous expression in Escherichia coli of Pseudomonas aeruginosa copper azurin.

Azurin*, a by-product of heterologous expression of the gene encoding the blue copper protein azurin from Pseudomonas aeruginosa in Escherichia coli, was characterized by chemical analysis and electrospray ionization mass spectrometry, and its structure determined by X-ray crystallography. It was shown that azurin* is native azurin with its copper atom replaced by zinc in the metal binding site. Zinc is probably incorporated in the apo-protein after its expression and transport into the periplasm. Holo-azurin can be reconstituted from azurin* by prolonged exposure of the protein to high copper ion concentrations or unfolding of the protein and refolding in the presence of copper ions. An X-ray crystallographic analysis of azurin* at 0.21-nm resolution revealed that the overall structure of azurin is not perturbed by the metal exchange. However, the geometry of the co-ordination sphere changes from trigonal bipyramidal in the case of copper azurin to distorted tetrahedral for the zinc protein. The copper ligand Met121 is no longer co-ordinated to zinc which adopts a position close to the carbonyl oxygen atom from residue Gly45. The polypeptide structure surrounding the metal site undergoes moderate reorganization upon zinc binding. The largest displacement observed is for the carbonyl oxygen from residue Gly45, which is involved in copper and zinc binding. It moves by 0.03 nm towards the zinc, thereby reducing its distance to the metal from 0.29 nm in the copper protein to 0.23 nm in the derivative.

Azurin↗
PubMed1992

Nervous and immune systems as targets for developmental effects of benzodiazepines. A review of recent studies.

Prenatal exposure to benzodiazepines (BDZ) can cause behavioral dysfunctions both in humans and in experimental animals. In addition, prolonged impairment of cellular immune functions is found in rats after low dose BDZ exposure (e.g., diazepam 1.25 mg/kg/day) during part of fetal life [gestational days (GD) 14-20]. Analysis of diazepam and its metabolites in maternal and fetal tissues revealed that in this rat model the drug is no longer present at birth, which excludes direct effects of diazepam during the postnatal period. The main target of BDZ in brain, the GABAA receptor complex, is structurally and functionally heterogeneous. Besides alpha- and beta-subunits, gamma 2- or gamma 3-subunit should be coexpressed for a fully functional BDZ response. Signals of mRNAs encoding for alpha 1, beta 2 and gamma 2 are detected in fetal rat spinal cord and lower brainstem by GD 14 and reach telencephalic regions in later fetal life, reminiscent of BDZ receptor ontogeny. Regional subunit distribution differs from the adult brain, one interesting feature being a preponderance of gamma 2 mRNA throughout fetal life. Since subunit composition influences the sensitivity to BDZ, these data suggest that prenatal effects of BDZ depend upon regional subunit compositions present at different developmental stages. The delayed depression of cellular immune responses in prenatally BDZ-exposed rat offspring during the first 2 postnatal months is accompanied by various changes in immune cell biology. Binding characteristics of the peripheral (omega 3) type BDZ receptor are altered until adulthood (8 weeks). Membranes of spleen cell preparations containing mainly lymphocytes exhibit a decrease of affinity for the peripheral ligand [3H]PK11195, splenic macrophage preparations a decrease of maximal binding capacity. Various defects in cytokine production by macrophages and T lymphocytes were observed: Mitogen-stimulated release of macrophage-derived tumor necrosis factor-alpha (TNF-alpha) and of the T cell-derived interleukin-2 (IL-2) was drastically reduced at 2 and 4 weeks of life and recovered in young adulthood, exhibiting the same time course of depression as lymphocyte proliferation in response to immune stimuli. Interleukin-6 (IL-6) release remained diminished until adulthood. In female offspring, additional alterations were found in splenic noradrenaline turnover after immune stimulation. The mechanisms underlying the breakdown of the cytokine network in prenatally diazepam-exposed offspring, and the long-term consequences are as yet unknown.

Animals↗
PubMed1991

[Help, I can work again. Analysis of the rehabilitation process into work life of a chronically ill patient after survival of myocardial infarct].

The prime objective of the pension insurances' rehabilitation measures is to successfully reintegrate clients into their working environment. The high number of early retired clients indicates that Germany's health system cannot reach this objective satisfactorily. Empirical studies as to the various causes and factors leading to illness and--as a consequence--to early retirement provided only a few results. The client's personal and psycho-social situation in particular, as well as her/his biographical data and the available scope of action are hardly ever considered appropriately. With this in mind, we set out to reconstruct the rehabilitation process from a client's view using the method of structural hermeneutics. Against the background of biographical development, we describe the origin of illness, rehabilitation results and the opinion of social medicine experts preceding reintegration. The hermeneutic analysis shows that--in spite of the intentions of the persons concerned--an unconscious agreement arises between the client and the therapeutic system manifesting itself in the application of rehabilitation measures reproducing premorbid behaviour. On the basis of the reconstructed client-related situation a critical aspect of the general structure of Germany's health system becomes apparent: the fragmentation of the client into responsibilities of experts giving the opinion and those responsible for treatment.

Adaptation, Psychological↗
PubMed1990

Supercontracted state of vertebrate smooth muscle cell fragments reveals myofilament lengths.

Isolated cell preparations from chicken gizzard smooth muscle typically contain a mixture of cell fragments and whole cells. Both species are spontaneously permeable and may be preloaded with externally applied phalloidin and antibodies and then induced to contract with Mg ATP. Labeling with antibodies revealed that the cell fragments specifically lacked certain cytoskeletal proteins (vinculin, filamin) and were depleted to various degrees in others (desmin, alpha-actinin). The cell fragments showed a unique mode of supercontraction that involved the protrusion of actin filaments through the cell surface during the terminal phase of shortening. In the presence of dextran, to minimize protein loss, the supercontracted products were star-like in form, comprising long actin bundles radiating in all directions from a central core containing myosin, desmin, and alpha-actinin. It is concluded that supercontraction is facilitated by an effective uncoupling of the contractile apparatus from the cytoskeleton, due to partial degradation of the latter, which allows unhindered sliding of actin over myosin. Homogenization of the cell fragments before or after supercontraction produced linear bipolar dimer structures composed of two oppositely polarized bundles of actin flanking a central bundle of myosin filaments. Actin filaments were shown to extend the whole length of the bundles and their length averaged integral to 4.5 microns. Myosin filaments in the supercontracted dimers averaged 1.6 microns in length. The results, showing for the first time the high actin to myosin filament length ratio in smooth muscle are readily consistent with the slow speed of shortening of this tissue. Other implications of the results are also discussed.

Actin Cytoskeleton↗
PubMed1988

Estimation of missing cone data in three-dimensional electron microscopy.

The range of tilt angles for which projected images of two-dimensionally periodic specimens can be obtained in electron microscopy is limited both by technical aspects, such as goniometer design, and by the more fundamental limitation of object thickness. The lack of a full set of projections causes a missing cone in the reciprocal space data for the object, which will give an anisotropic resolution in a three-dimensional reconstruction and may cause the quality to be impaired by spurious features. The problem is governed by a linear operator which maps the three-dimensional object onto the set of projections. The eigenvalue spectrum of this operator is determined by the range of tilt angles and the spatial extent of the object. If the object is spatially restricted, the eigenvalues are all positive, and it is in principle possible to retrieve experimentally unavailable structure data from those that are measured. However, with restricted angle data, some of the eigenvalues are extremely small, so the problem is 'ill-conditioned' or sensitive to small perturbations in the data, such as noise, and it is necessary to regularize the solution. We applied two methods of band-limited extrapolation and inference on electron microscope data. Alternating projections onto convex sets regularized by a regularization parameter and a least squares estimation regularized by the Shannon entropy functional yield similar results if a close object extent constraint is available. The criterion of maximum entropy, however, allows a relaxation of this constraint.

Bacteria↗
PubMed1986

Three-dimensional structure of the regular surface layer (HPI layer) of Deinococcus radiodurans.

The low-resolution structure of the regular surface layer of Deinococcus radiodurans has been determined from negatively stained specimens by three-dimensional electron microscopy. The layer has P6 symmetry, a lattice constant of 18 nm and a thickness of 6.5 nm. Three-dimensional reconstruction was performed by a hybrid real space/Fourier space approach that incorporates partial compensation of lattice distortions: The model obtained is discussed in the light of independent information about the surface structure of this layer, derived from metal shadowing and surface relief reconstruction. While agreement is quite satisfactory for the apparently more rigid inner surface, the outer surface shows severe flattening effects. The structure of the HPI layer is compared with other bacterial surface layers using a classification scheme that is outlined in the Appendix.

Bacteria↗
PubMed1985

Decoration and shadowing of freeze-etched catalase crystals.

Aqueous suspensions of catalase crystals were freeze-cleaved, deep-etched and either shadowed with Ta/W at 45 degrees or decorated with 0.1-0.9 nm thick deposits of Au and Pt at normal incidence. The electron micrographs of the decorated specimens were processed by correlation averaging and compared with a relief reconstruction obtained from shadowed specimens. Pronounced decoration was observed on the catalase crystals at temperatures between 130 and 180 K. Disregarding the difficulties in interpretation, the averages of 0.1-0.2 nm thick Au and Pt films reveal more structural detail than the relief reconstruction. Perfect shadowing provides information on surface topography and is relatively easy to comprehend; decoration renders variations in physico-chemical affinity visible. Problems of the interference of decoration and shadowing effects in the intuitive interpretation of freeze-etch replicas and in relief reconstruction are discussed as well as the disturbing effects of a non-ideal carbon backing. The perspectives of using decoration intentionally as a positive staining technique for the investigation of frozen-hydrated surfaces are evaluated and quality criteria are defined.

Animals↗
PubMed1984

[Bezafibrate-induced myolysis and myoglobinuria in patients with impaired renal function].

A muscular syndrome has been described in patients on clofibrate and fenofibrate therapy. The present paper describes four patients with impaired renal function in whom symptoms and signs of skeletal muscle damage developed during treatment with another clofibrinic acid derivative, bezafibrate. The syndrome was characterized by variable degrees of muscular cramps and paresis, excessive elevation of muscle enzymes in serum, myoglobinemia and myoglobinuria. Transient deterioration of renal function was also common. All patients had been overdosed with bezafibrate with regard to their renal function. It is concluded that bezafibrate like other lipid lowering agents of the clofibrate type may induce muscle damage, at least if doses are not adjusted to renal function. Extreme caution is warranted when treating patients with renal impairment with bezafibrate and strict dose adjustment to kidney function is necessary to avoid muscle damage.

Aged↗
PubMed1983

[Importance of impulse cytophotometry in the diagnosis and prognosis of prostate cancer].

In 102 cases with hypertrophy and 73 patients with carcinoma of the prostate, all histologically proven, fine-needle biopsies were done and the obtained material investigated by conventional cytology as well as by flow-through cytophotometric determination of DNA content of the nuclei. In prostatic cancer the DNA determinations showed less diagnostic precision than conventional cytology. However as an additional diagnostic procedure the flow-through cytophotometry was able to improve the results of cytologic diagnostic for 10% in all cases with histologically proven cancer of all grades. In hypertrophy of prostate, the exclusion of carcinoma could be done by DNA determination with higher security than by conventional cytology. Flow-through cytophotometry is therefore considered a useful additional test in primary diagnostic and grading of prostatic cancer. In addition it is a method to evaluate the efficacy of drug therapy.

Flow Cytometry↗
PubMed1982

Conditioned aversion to a taste perceived while grooming.

Four experiments were conducted to determine how the characteristics of conditioned taste aversion (CTA), as described from studies conducted in the drinking and feeding contexts, applied in the grooming context. In Experiment 1, sodium saccharin was mixed with a "neutral-tasting" jelly and applied to the fur of male Sprague-Dawley rats. Rats injected with LiCl after the applications strongly avoided saccharin solutions in subsequent 1-hr, 2-choice (Saccharin solution vs water) drinking tests, whereas rats injected with NaCl or given plain jelly on the fur showed only an initial neophobic response to the saccharin solution. Thus, the taste of saccharin was perceived while grooming and the CTA formed in the grooming context generalized to drinking. In experiments 2-4, we obtained evidence that: (a) rats discriminated between one intensity of saccharin applied to the fur and another used in the test solution; and (b) rats differentiated between qualities of the two tastants applied to the fur in that saccharin overshadowed NaCl; and (c) taste qualities were more important than toxic properties when two stimuli (Saccharin, LiCl) were used (saccharin overshadowed NaCl in subsequent drinking tests). We speculate that taste, while grooming might play a role in social communication in some vertebrates. Further, CTA and grooming might have uses in rodent control (e.g., in agricultural situations) not previously considered such as in delivering a non-attractive, low-salience toxin so that the taste of the crop overshadows that of the bait, and induces crop aversion.

Animals↗
PubMed1981

[Admission to a psychiatric day clinic - demarcation of indications].

The results of a study of 547 day-time patients of the Medical Academy of Dresden who had been taken care of at the day-and-night type therapeutic department from 1974 to 1977 are presented. In this connection, problems of the availability of the day-time clinic, diagnostic structure, age structure, professional and social status of the patient group, results of dwelling time and occupational rehabilitation in dependence upon the mode of admission to this semi-clinical care system orientated on early rehabilitation are discussed. Finally, the respective conclusions with respect to the problems discussed are drawn.

Adult↗
PubMed1978

[Gastroduodenal complications after the ingestion of hydrochloric acid. One case (author's transl)].

The ingestion of a caustic acid resulted in retractile fibrosis of 2/3 of the stomach with a secondary duodenal fistula. The antro-pyloro-duodenal circuit was re-established at around the 3rd after ingestion. However, the duodenal fistula caused the formation of encysted pelvic abscesses which were difficult to drain and satisfactorily treat. The clinical course stretched over a period of 4 years.

Abscess↗