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Biomedical subjects

F Hofmann

Publications and source records attributed to F Hofmann.

At least 271 records · Page 15Linked to original sources
PubMed1991

High voltage activated calcium channels: molecular composition and function.

Voltage-activated calcium channels comprise a group of similar yet distinct proteins or protein complexes that differ in electrophysiological properties, modulation by phosphorylation and GTP-binding proteins and in their relative sensitivity to organic calcium channel blockers. Cloning of the cDNA of L-type calcium channels from skeletal muscle, heart and smooth muscle opens the way to understanding the molecular basis of channel function and regulation and provides means of studying calcium channels in other tissues.

Animals↗
PubMed1991

Beta-adrenergic receptor stimulates L-type calcium current in adult smooth muscle cells.

The hormonal regulation of L-type calcium current was investigated in freshly isolated tracheal smooth muscle cells using the whole-cell configuration of the patch-clamp technique. Isoproterenol stimulated the L-type calcium current 2.6-fold through beta-adrenoceptors. Dialysis of these cells with cyclic AMP, cyclic AMP analogues or the catalytic subunit of cyclic AMP kinase had no effect on basal or isoproterenol-stimulated calcium current. The calcium current was stimulated and inhibited by dialysis of the cells with GTP gamma S and GDP beta S, respectively. Evidently, in some smooth muscle cells the beta-adrenoceptor couples directly to L-type calcium channels via a G protein.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

[Effects of porcelain fused to metal on the accuracy of fit of various alloys].

One high gold and five low gold porcelain bonding alloys were examined for dimensional changes after fusion of the porcelain. With the same processing techniques applied, the individual firings resulted in varying changes in the accuracy of fit of the tested alloys. Averaging at -0.09 mm Bond-on 4 showed the greatest marginal discrepancies and this was the only alloy that displayed a statistically significant difference to Degudent U.

Dental Bonding↗
PubMed1991

[Role of the school in preventive vaccination and infection control].

628 pupils from both the northern and southern parts of West Germany (Baden-Württemberg, Bavaria, Lower Saxony, Schleswig-Holstein) were interviewed via an "infectious diseases" questionnaire: 44 questions dealt with vaccination (vaccination history, opinions of efficiency of different vaccines), 38 with problems concerning AIDS/HIV. The results indicated significant lack in the acceptance of most of the common immunisations. Improvement of AIDS/HIV-information, especially on HIV-transmission and psychosocial, economical and political consequences seems to be necessary. Possibilities of future health education for pupils are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Effects of cyclic GMP on the secondary structure of cyclic GMP dependent protein kinase and analysis of the enzyme's amino-terminal domain by far-ultraviolet circular dichroism.

Far-UV circular dichroism spectra of bovine lung cyclic GMP dependent protein kinase (G-kinase) show that the enzyme contains alpha-helical and beta-pleated sheet elements. Binding of cyclic GMP changes the spectra in a way consistent with the induction of beta-sheet from random coil. Examination of the amino-terminal sequence of G-kinase indicates the presence of a strongly alpha-helical segment with several features in common with the leucine zipper motif. We propose that this sequence may be the important part of the dimerization domain of the enzyme. A synthetic peptide corresponding to amino acids 1-39 of G-kinase has a strongly alpha-helical CD spectrum, supporting the predicted secondary structure of this amino-terminal sequence. In contrast to the native enzyme, a structure reduced in alpha-helix was found when a constitutively active form of G-kinase, which lacks amino acids 1-77, was studied.

Allosteric Site↗
PubMed1990

Studies on the structural requirements for the activity of the skeletal muscle dihydropyridine receptor/slow Ca2+ channel. Allosteric regulation of dihydropyridine binding in the absence of alpha 2 and beta components of the purified protein complex.

A rabbit skeletal muscle dihydropyridine (DHP) receptor can be purified as an alpha 1-alpha 2-delta-beta-gamma complex, of which alpha 2 and delta are disulfide bonded. This complex has Ca2+ channel activity when incorporated into lipid bilayers. We reported recently that expression of alpha 1 in murine L cells (LCa cells) leads to appearance of both DHP binding and Ca2+ currents, and that we failed to detect alpha 2 by immunoblotting. LCa cell Ca2+ channel currents resembled those in rabbit skeletal muscle in their sensitivity to both voltage and the DHP agonist Bay K 8644, but differed in that they responded to depolarization much more slowly. We now report details of the molecular cloning of the cDNA encoding the 1857-amino acid long alpha 1 transfected into the L cells and results from studies on expression of beta, as well as, on allosteric regulation of DHP binding to these cells. The alpha 1 cDNA was cloned by a combination of cDNA library screening (5355 base pairs) and chemical synthesis (508 base pairs). Using rabbit labeled beta cDNA, which cross-reacts with murine beta mRNA, we failed to observe cross-hybridizing beta mRNA in LCa cells. Using a labeled single stranded 200-base long rabbit alpha 2 cDNA that cross-reacts with mouse alpha 2 mRNA, we likewise failed to observe cross-hybridizing alpha 2 mRNA in LCa cells and hence confirmed the absence of an endogenous murine alpha 2 in these cells. Using LCa cell membranes as DHP receptor source we found the binding of the DHP antagonist (+)-[3H]PN200-110 to be regulated by both verapamil and diltiazem as it is in rabbit skeletal muscle membranes. However, we noted a difference; at concentrations above 10(-6) M, verapamil inhibited residual DHP binding in LCa but not in skeletal muscle membranes. We conclude that neither alpha 2 nor beta are essential for expression of alpha 1 on the cell surface, or for its functioning as a voltage-gated Ca2+ channel, or for its allosteric regulation of DHP binding by Ca2+ channel antagonists. The studies neither exclude roles for gamma and delta, nor for alpha 2 or beta in determining more subtle properties of this channel.

Allosteric Regulation↗
PubMed1990

Sites phosphorylated in bovine cardiac troponin T and I. Characterization by 31P-NMR spectroscopy and phosphorylation by protein kinases.

Bovine cardiac troponin isolated in a highly phosphorylated form shows four 31P-NMR signals [Beier, N., Jaquet, K., Schnackerz, K. & Heilmeyer, L.M.G. Jr (1988) Eur. J. Biochem. 176, 327-334]. Troponin I, which contains phosphate covalently linked to serine-23 and/or -24 [Swiderek, K., Jaquet, K., Meyer, H. E. & Heilmeyer, L. M. G. Jr (1988) Eur. J. Biochem. 176, 335-342], shows three resonances. Mg2(+)-saturation of holotroponin shifts these troponin I resonances to higher fields. Direct binding of Mg2+ to the phosphate groups can be excluded. Both these serine residues of troponin I, 23 and 24, are substrates for cAMP- and cGMP-dependent protein kinases as well as for protein kinase C. Isolated bovine cardiac troponin T contains 1.5 mol phosphoserine/mol protein, indicating that minimally two serine residues are phosphorylated. One phosphoserine residue is located at the N-terminus. An additional phosphoserine is located in the C-terminal cyanogen bromide fragment, CN4, which contains covalently bound phosphate. Protein kinase C phosphorylates serine-194, thus demonstrating exposure of this residue on the surface of holotoponin.

Amino Acid Sequence↗
PubMed1990

Role of omega-conotoxin-sensitive calcium channels in inositolphosphate production and noradrenaline release due to potassium depolarization or stimulation with carbachol.

omega-Conotoxin GVIA (CTX) has been used to assess the role of voltage-sensitive Ca2+ channels involved in inositolphosphate (InsP) production and in noradrenaline (NA) release from washed brain homogenates. Stimulation was performed by depolarization with high [K+] and by the M-cholinergic agonist carbachol. In chicken brain CTX (1 mumol/l and less) nearly completely inhibited both InsP production and NA release due to high [K+]. The peptide depressed InsP production moderately but NA release largely when evoked with carbachol. In rat brain inhibition by CTX of InsP production or NA release was weak or even absent independent of the mode of stimulation. Independent of species or test system, the dihydropyridine derivative nitrendipine (1 mumol/l and above) was inactive. Because of its preferential CTX sensitivity chicken brain is particularly suitable to study the role of voltage-sensitive Ca2+ channels in presynaptic events. Here InsP production, like NA release, depends on entry of extracellular Ca2+ nearly completely when evoked by depolarization. When evoked by way of cholinergic M-receptor stimulation, InsP production is triggered by a second pathway in addition to the CTX-sensitive Ca2+ entry.

Animals↗
PubMed1990

[Risk of tuberculosis in employees of the public health service].

The risk of tuberculosis in the medical professions was assessed in the course of three studies: The distribution of positive tuberculin reactions (PTR) was determined in 3583 members of the University Hospital in Freiburg, FRG. The results obtained with persons older than 30 years were almost the same in the medical and non-medical professions. Younger persons professionally occupied in the medical sector had a higher PTR rate than their colleagues in the non-medical sector. In the course of a second (case control) study (1979-1988) it was shown that the incidence of tuberculosis in the University Hospital of Freiburg was the same as reported for the normal population of West Germany (0.25%). A third (longitudinal) study (1987-1989) was carried out to assess the future tuberculosis risk by determination of the annual TR conversion rate. The incidence of conversion was identical (2.2%) in the medical and non-medical professions. Determination of conversion rates in different departments showed that the highest rate (and, therefore, the highest tuberculosis risk) was observed in pathology, pulmology and lung surgery.

Adult↗
PubMed1990

[Statistical analysis of the in-vitro action of combination antiviral agents].

Similar to the chemotherapy of bacterial infections, with the advanced development of virostatics a combination of antiviral agents is supposed to be introduced into the causal treatment of viral illness. The present studies explain a method for in vitro testing of virostatic combinations in cell cultures. The principle of the method is based on the checkerboard-technique used to test antibiotic combinations. As example the combination of trisodium phosphonoformate with bromovinyl-2'-deoxyuridine, acyclovir or 2-hexadecylglycero-3-phosphocholine was tested against herpes simplex virus, type 1. For evaluation of the test results the so-called reduction dose 50 (RD50) was introduced. The RD50 corresponds to this substance concentration, which reduces alone or in combination with a second virostatic the virus concentration used in the test system to its TCID50. With analogy to the calculation of infectious doses the computation of the RD50 was performed by using the method of Spearman and Kaerber. The calculated values allow the comparability of the antiviral activity of substances and their combinations. Corresponding to testing of antibiotics the further analysis of combinations was carried out by calculation of fractional inhibitory concentration (FIC), synergy factors (SF), and the construction of isobolograms. In this way, indifferent, synergistic and antagonistic effects of substance combination should be determined.

Anti-Bacterial Agents↗
PubMed1990

The dihydropyridine-sensitive calcium channel of the skeletal muscle: biochemistry and structure.

The dihydropyridine-sensitive calcium channel of the rabbit skeletal muscle is the first voltage-gated calcium channel which has been purified and biochemically characterized. The alpha 1-subunit, a 165 kDa protein, of the purified dihydropyridine receptor contains all regulatory sites of a L-type calcium channel and the calcium conducting unit. The purpose of this review is to summarize and discuss recent findings on the structure and possible function of the skeletal muscle calcium channel subunits.

Animals↗
PubMed1990

[The determination of cortisol in plasma with a direct luminescence enzyme immunoassay].

The assay is based on the luminescent measurement of horseradish peroxidase. The IgG fraction of a cortisol antiserum is coated on suitable polystyrene tubes (in use for the measurement of luminescence). The enzyme activity of bound label was determined using a p-iodophenol enhanced chemiluminescent reaction. The assay was sensitive and precise for a wide cortisol concentration range and showed a good agreement with conventional ELISA-technique. There was no extraction necessary for cortisol from plasma. The diluted sample was heated to 60 degrees C or 8-aniline-1-naphthalene sulfonic acid was added in order to release cortisol from protein binding in plasma.

Buffers↗