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Biomedical subjects

G Metz

Publications and source records attributed to G Metz.

At least 19 recordsLinked to original sources
PubMed1992

Asp85 is the only internal aspartic acid that gets protonated in the M intermediate and the purple-to-blue transition of bacteriorhodopsin. A solid-state 13C CP-MAS NMR investigation.

High-resolution solid-state 13C NMR spectra of the ground state and M intermediate of the bacteriorhodopsin mutant D96N with the isotope label at [4-13C]Asp and [11-13C]Trp were recorded. The NMR spectra show that Asp85 is protonated in the M intermediate. The environment of Asp85 is quite hydrophobic. On the other hand, Asp212 remains deprotonated and a slight shift to lower field indicates a more hydrophilic environment. Asp85 also protonates in the purple-to-blue transition of bacteriorhodopsin in the deionized membrane, where it experiences a similar environment to M. The shift of Trp resonances in M reflect a conformational change of the protein in forming the M intermediate.

Aspartic Acid↗
PubMed1992

High-resolution solid state 13C NMR of bacteriorhodopsin: characterization of [4-13C]Asp resonances.

Solid state 13C nuclear magnetic resonance measurements of bacteriorhodopsin labeled with [4-13C]Asp show that resonances of single amino acids can be resolved. In order to assign and characterize the resonances of specific Asp residues, three different approaches were used. (1) Determination of the chemical shift anisotropy from side-band intensities provides information about the protonation state of Asp residues. (2) Relaxation studies and T1 filtering allow one to discriminate between resonances with different mobility. (3) A comparison of the spectra of light- and dark-adapted bacteriorhodopsin provides evidence for resonances from aspartic acid residues in close neighborhood of the chromophore. In agreement with other investigations, four resonances are assigned to internal residues. Two of them are protonated in the ground state up to pH 10 (Asp96 and Asp115). All other detected resonances, including Asp85 and Asp212, are due to deprotonated aspartic acid. Two lines due to the two internal deprotonated groups change upon dark and light adaptation, whereas the protonated Asp residues are unaffected.

Amino Acid Sequence↗
PubMed1990

High resolution 13C-solid state NMR of bacteriorhodopsin: assignment of specific aspartic acids and structural implications of single site mutations.

Three mutant strains of Halobacterium sp. GRB with the site of mutation in the bacterioopsin gene (PM 326: Asp96----Asn; PM 374: Asp96----Gly; PM 384: Asp85----Glu) were grown in a synthetic medium containing (4-13C)-Asp. The mutant bacteriorhodopsins labeled with (4-13C)-Asp (37%-45%), and owing to the metabolism of Halobacteria also with (11-13C)-Trp (50%-100%), were isolated as purple membranes and 13C Solid State Magic Angle Sample Spinning (MASS) Nuclear Magnetic Resonance (NMR) spectra of the samples were taken. The Asp96 mutants lacked the signal at 171.3 ppm which was previously assigned to a protonated internal Asp (Engelhard et al. 1989a). This observation supports the conclusion that Asp96 is protonated in the ground state. PM 384 (Asp85----Glu) has an absorption maximum at 610 nm. It can be converted into a purple form (lambda max = 540 nm) by treatment with a detergent (CHAPSO). The NMR-spectra of these two species differ from each other and from the wild type. The intensity of the resonance at 173 ppm in the wild type spectrum is reduced in both forms of the mutant protein. It is probable that this signal is caused by Asp85. The amino acid changes result not only in a perturbation of their direct environment but also effects on Trp residues and the chromophore protein interaction can be observed.

Aspartic Acid↗
PubMed1990

[Emergency intubation and ventilation therapy in severe bronchial asthma].

37 patients were treated with emergency intubation because of severe asthma bronchiale. In 30 patients the usual bronchospasmolytic therapy was ineffective, 12 patients were under permanent treatment. Halothane produced immediate and unequivocal improvement of respiratory global insufficiency and resolution of bronchospasm in 8 out of 13 patients, ketamine in 6 of 18 and a combination of both drugs in 4 of 9 patients. Both drugs are an efficient complement to conventional emergency treatment. A step-by-step schema for anaesthesia in severe asthma bronchiale requiring intubation is presented.

Aged↗
PubMed1989

Magic angle sample spinning 13C nuclear magnetic resonance of isotopically labeled bacteriorhodopsin.

Bacteriorhodopsin (bR), the light-driven proton pump protein from Halobacterium halobium, was biosynthetically labeled with [4-13C]Asp. The incorporation yield was 48%. The magic angle sample spinning (MASS) 13C nuclear magnetic resonance (NMR) spectrum of this sample revealed six different peaks superimposed on a broad band of naturally abundant peptide-bond 13C. Two of the six carbonyl signals can be attributed to internal-protonated Asp carboxyl groups, one of which might be Asp115. An additional resonance at 110 ppm can be associated with the C-11 carbon of Trp, indicating an unusual biosynthetic pathway of this amino acid in Halobacterium halobium. Similar measurements performed on papain-treated purple membrane which lacks the C-terminal tail display two new intense signals at 178 and 178.9 ppm. If the same spectrum is taken without cross-polarization, these signals do not decrease or disappear. On the basis of their intensities and their chemical shifts, one can assign in addition to the C-terminal Asp four Asp residues facing the cytoplasmic phase. In native bR, at least two of these form a salt-bridge-like bond which also might include the C-terminal tail. These experiments not only provide data about the chemical environment of the Asp residues within the hydrophobic core of bacteriorhodopsin but also yield information about the interactions between surface components.

Amino Acid Sequence↗
PubMed1987

Calmodulin antagonism: a pharmacological approach for the inhibition of mediator release from mast cells.

Several Ca2+ antagonists with either Ca2+-entry blocking or calmodulin (CaM) antagonistic properties and antiallergic drugs were investigated for their effects on mediator release from mast cells induced by different secretagogues (compound 48/80, concanavalin A, antigen-IgE and Ca2+ ionophore A23187) and for their ability to inhibit the function of CaM or phospholipid/Ca2+-dependent protein kinase (C-kinase). The effects of the different agents--with the only exception of cromolyn sodium--on histamine release elicited by compound 48/80 correlated well with their actions on two CaM-dependent enzymes whereas the activity of C-kinase was far less altered, or not altered at all. CaM antagonism of cloxacepride, picumast, oxatomide, fendiline and bepridil correlated not only with the inhibition of exocytosis evoked by compound 48/80 but also with that induced by A23187, concanavalin A and antigen-IgE. This indicates an action of these substances distal to the generation of the Ca2+ signal since the various secretagogues elevate the intracellular Ca2+ concentration by different mechanisms. However, prenylamine and thioridazine inhibited concanavalin A- and antigen-IgE-induced mediator release more potently and more effectively than that elicited by compound 48/80 or A23187. Therefore inhibition of allergic histamine release by these drugs may in part be dependent on an impairment of the Ca2+ signal. Since for each of two agents inhibition of histamine release (evoked by different releasers) parallels that of serotonin release it may be concluded that these mediators are secreted via the same mechanism. The results obtained with agents exhibiting different pharmacological properties but which share one common property, namely antagonism of CaM, strengthen the view that CaM is involved in exocytosis of mediators from mast cells.

Animals↗
PubMed1986

Failure of ibuprofen in treatment of herpes genitalis.

Motrin (ibuprofen), a potent inhibitor of prostaglandin synthetase, was tested in women and men for treatment of recurrences of genital herpes. In a double-blind trial, no statistically significant differences were observed between treated and placebo groups in any of the measured parameters.

Adult↗
PubMed1986

Effect of etofylline clofibrate on experimental thrombus formation and prostacyclin activation.

1-(7-Theophyllinyl)-2-ethyl-[2-(p-chlorophenoxy)-isobutyrate] (etofylline clofibrate, theofibrate, Duolip) was shown to possess substantial thrombus disaggregating activity in the microcirculation of the hamster cheek pouch following minor vascular damage by electrical stimulation. At 12 mg/kg p.o. the moderate effect of a single dose (12% reduction in disaggregation time) increased to a maximum reduction of 31 and 43% following 5 and 7 consecutive daily applications, respectively. Etofylline clofibrate was more active than other drugs already tested in this test system, but less than the prostaglandins PGE1 and PGI2. The antithrombotic efficacy found in both in vivo tests, thrombus formation and disaggregation, suggests as mode of action of etofylline clofibrate an agonistic interaction with intimal PGI2. This could be by enhancement of its production or by a synergistic interaction with this prostanoid, rather than inhibition of thromboxane A2 synthetase.

Animals↗
PubMed1985

Blood transfusion requirements in coronary artery surgery with and without the activated clotting time (ACT) technique.

Control of anticoagulation during cardiopulmonary bypass (CPB) with the automated activated whole blood clotting time (ACT) and reversal of heparin after CPB using a computerized ACT dose-response curve method resulted in significant reductions of blood transfusion requirements, surgical time, and protamine doses in 150 patients undergoing coronary artery bypass grafting procedures (ACT group) as compared to 200 patients for whom a standard fixed dose protocol for heparin and protamine was used (control patients). Mean transfusion requirements were 1,938 +/- 60 SEM ml whole blood and 853 +/- 48.3 SEM ml red blood cells for control patients and 1,397 +/- 59 SEM ml whole blood (P less than 0.001) and 695 +/- 34 SEM ml red blood cells (P less than 0.01) in the ACT group. ACT group patients also required less protamine with 26.2 +/- 0.60 SEM ml Protamine 1,000 (Roche) as compared to 33.9 +/- 0.49 SEM ml for control patients (P less than 0.001) but more heparin with 31,440 +/- 783 SEM I.U. versus 26,760 +/- 263 SEM I.U. (P less than 0.001). Surgical time decreased from 321 +/- 5.5 SEM min for control patients to 289 +/- 5.4 SEM min for ACT group patients (P less than 0.001).

Blood Coagulation Tests↗
PubMed1979

[Naevus spongiosus albus mucosae. Review and personal observations].

White sponge nevus of the mucosa is a rare, mostly verifiable hereditary ectodermal dysplasia of the mucous membranes. Because associated symptoms of the skin are missing, it is classified as a distinctive disease among the congenital leukokeratoses. In the most cases the symptomless mucosal lesions are detected by dentological examination though they are present at birth or appear in the first years of life. On the basis of three own observations clinical appearance, histopathology, electronmicroscopy and differential diagnosis are discussed.

Child↗
PubMed1978

[Relative bioavailability of a vincamine retard formulation. Pharmacokinetic study in normal subjects (author's transl)].

The study was carried out in 6 healthy volunteers in cross-over design. The pharmacokinetic parameters were calculated after application of 60 mg vincamine base in comparison to a sustained release formulation (vincamine ratio-pharm 30 mg) on the basis of a GC method. Summarizing it can be stated that the sustained release formulation has a flatter profile and is therefore more adapted to clinical application. The extent of absorption expressed as AUC of the serum concentration-time curve, has three times the extent of the curve with the pure substance.

Biological Availability↗
PubMed1978

[Juvenile dermatofibrosarcoma protuberans].

Dermatofibrosarcoma protuberans is observed in younger or middle-aged patients after the transformation from the initial stage of a chronic fibrous plaque into a rapidly growing, sometimes painful or bleeding tumor. First manifestation in early childhood is considered in about 10 per cent of the reported patients. In the case that we observed the neoplasma was present at birth and increased to a multinodular tumor between three and four years of age. Repeated local recurrences in the scar were observed after the surgical removal. The clinical behavior of the tumor in childhood is comparable to those of adults. Because of its malignant potential extended early excision should be undertaken despite of the risk of widespread scarring.

Child↗
PubMed1978

[Nevoid hair bundles in man].

Between the different forms of multiple hairs the circumscribed occurence of compound hairs is a rare nevoid hair-abnormality. It is caused by merging of several follicles in the middle or upper corium. The deep parts and the papillae are independent units. The pathogenesis, clinical relevance and therapy of compound hairs are discussed on the basis of an own observation.

Adult↗