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Biomedical subjects

R Huber

Publications and source records attributed to R Huber.

At least 613 records · Page 34Linked to original sources
PubMed1983

The suitability of the human lymphocyte micronucleus assay system for biological dosimetry.

Human whole blood was irradiated with 220 keV X-rays at doses of 0-4.0 Gy. After incubation periods of 48, 60, 72, 84 and 96 h, lymphocytes were prepared without colcemid pretreatment according to 2 different methods, and micronuclei were scored. The crucial point of lymphocyte preparation was found to be the osmotic pressure of the hypotonic solution. Only a method that preserves the cytoplasm of lymphoblasts is suitable for a correct association of micronuclei with the main nucleus. Similar as for structural chromosome changes, now their intercellular distribution can be analysed. This is necessary for the derivation of appropriate statistical weights which have to be used for more reliable regression analyses. For 48 h, the data can be described by the linear model, for 84 and 96 h, by the linear-quadratic model. For 60 and 72 h no such definite conclusions can be drawn. For calibration purposes a standardized culture time cannot be recommended. Because the background frequency is high, the lymphocyte micronucleus assay system is not sensitive enough to detect a significant increase in the incidence of micronuclei after exposure to low doses (less than 0.3 Gy).

Cell Nucleus↗
PubMed1982

A simple high-performance liquid chromatographic pre-column technique for investigation of drug metabolism in biological fluids.

A simple reversed-phase high-performance liquid chromatographic pre-column technique for investigation of drug metabolism is described. This rapid method circumvents the "classical" sample purification via extraction by direct purification and enrichment of the sample on the pre-column. Almost 100% recovery of a drug (aminopyrine) and its metabolites from biological fluids is achieved. This is in strong contrast to "classical" sample preparation which allows a recovery of 30-100% depending on the polarity of the investigated compound. The procedure described has been successfully applied to the investigation of the metabolic pattern of aminopyrine in rat plasma and cell incubation media.

Aminopyrine↗
PubMed1982

Effect of food on antacid neutralizing capacity in man.

In order to estimate their in-vivo reactivity two antacids of equal theoretical neutralizing capacity (approximately 3.9 mol/l at pH 3.5) but of different chemical composition were employed as intragastric titrant (pH 3.5) following a liquid protein meal (oxo) in two groups of five volunteers each. The two antacids chosen (alucol and Camalox) contain different amounts of aluminium hydroxide, magnesium hydroxide and Camalox in addition contains calcium carbonate. The intragastric consumption of these two antacids was much higher than their respective theoretically available neutralizing capacity (Alucol 3.9 times, Camalox 2.4 times). In-vitro studies demonstrated that interaction with oxo reduced the neutralizing capacity of the two antacids at pH 3.5 from 3.9 mol/l to 1.7 mol/l (Alucol) and 2.5 mol/l (Camalox). This potency loss was related to the aluminium hydroxide content of the two antacids. This study indicates that the neutralizing capacity of antacids is not predictable from their reactivity in aqueous solution and is markedly reduced by protein-containing foods.

Adult↗
PubMed1982

Interaction of human alpha 1-proteinase inhibitor with chymotrypsinogen A and crystallization of a proteolytically modified alpha 1-proteinase inhibitor.

Human alpha 1-proteinase inhibitor (alpha 1-PI) can form very stable complexes with chymotrypsinogen A or chymotrypsin if limited proteolysis by a contaminant proteinase is prevented with diisopropyl fluorophosphate. The contaminant proteinase cleaves the alpha 1-PI component in the alpha 1-PI-chymotrypsinogen A complex close to its N-terminus, between threonine-11 and aspartate-12 and the chymotrypsinogen A part between tyrosine-146 and threonine-147. By this modification the complex becomes unstable and dissociates into modified alpha 1-PI and neo-chymotrypsinogen A. A tritium labelling experiment shows that the contaminant proteinase is present in a 0.5-1.0% (w/w) ratio in the inhibitor preparation. These experiments indicate that alpha 1-PI is not a temporary inhibitor for these enzymes, as assumed by other authors. Isolated modified alpha 1-PI can be crystallized as tetragonal bipyramides from 2.6M sodium potassium phosphate pH 8.0. The crystals are suitable for three dimensional X-ray structure analysis. In spite of the cleavage of the susceptible peptide bond by chymotrypsinogen A, the C-terminal 3.6 kDa cleavage peptide remains tightly bound to the inhibitor by means of non-covalent interactions. In accordance with the result of the known complete amino-acid sequence of the inhibitor this finding offers an alternative explanation to the suggestion of alpha 1-PI being a double headed inhibitor. Isolated neo-chymotrypsinogen A can be activated to active chymotrypsin and can form a very labile 1 : 1 complex with alpha 1-PI, which dissociates rapidly into inactive inhibitor and neo-chymotrypsinogen.

Amino Acid Sequence↗
PubMed1982

[Concentrically layered microconcrements in the renal medulla of nephrolithiasis patients. A contribution to the renal stone pathogenesis (author's transl)].

The electron microscopic investigation of the renal medulla in calcium oxalate stone patients has shown the frequent occurrence of globoid microconcrements in the basal laminae of the collecting ducts and of the thin limbs in Henle's loop. They have a concentrically layered structure, the diameter is usually below 1.5 microns, rarely more than 3 microns. Some of these objects were also seen in the interstitial connective tissue. Tissue of stone-free patients exhibited either no or only few such microconcrements which were usually located in the interstitial space. Histochemical tests and energy dispersive microprobe analysis suggest that calcium phosphate and acid mucopolysaccharides are principal components of the microconcrements. There are indications that some microconcrements might be expelled from the basal laminae into the urinary space and may form agglomerations. They might then furnish nuclei for heterogeneous crystallization especially in cases without hypercalciuria or hyperoxaluria.

Calcium Oxalate↗
PubMed1981

Fluorescence labelling in trace analysis of biological samples: simultaneous determination of free fatty acids and related carboxylic compounds.

Free fatty acids in serum, together with representatives of a new class of oxirane carboxylic acids having blood-glucose-lowering activity, were determined simultaneously by fluorescence labelling with 4-bromomethyl-7-methoxycoumarin (Br-Mmc) followed by separation by high performance liquid chromatography. Esterification kinetics of selected compounds were studied, and separation conditions for analysis of oxirane carboxylic acids, related compounds, and a series of saturated and unsaturated fatty acids as their Mmc estes were established. Three compounds (3, 6 and 7) were determined from serum quantitatively by extraction, derivatization, and analysis by high-performance liquid chromatography. Detection limits from serum (1ml) were 50 ng/ml. Two hours after intravenous bolus injection of 10 mg/kg of compound 6 in dog, a serum level of 1.1 mg/1 of administered compound was determined.

Animals↗
PubMed1980

Spatial structure of immunoglobulin molecules.

Immunoglobulin molecules of the class G (antibody molecules) consist of two heavy chains (50,000 dalton molecular weight) and two light chains (25,000 dalton). The overall shape is a Y with the arms formed by the light chains and the N-terminal half of the heavy chains in tight association. The stem is formed by the C-terminal halves of the heavy chains. The heavy and the light chains fold into globular domains of molecular weights of 12,000 dalton. There are four domains of the heavy chain and two of the light chain. All these domains show a similar fold, consisting of two B-sheets but display considerable differences in detail. The N-terminal variable domains of heavy and light chains and specifically the hypervariable polypeptide segments of the domains, located at the tips of the Y, constitute the antigen and hapten binding site. The nature of the amino acid residues of the hypervariable loops determines the shape and the specificity of the antibody. All domains pair tightly laterally, except the CH2 domains of the heavy chain. This domain has carbohydrate bound which prevents lateral association. Longitudinal interaction between the domains is loose and allows flexibility in the arrangement. Flexibility is probably of significance for antibody function. Arm (Fab) and stem (Fc) parts are linked by the hinge peptide which contains a segment with a unique conformation of two parallel poly-proline helices. Antigen binding triggers effector functions of antibodies. Antigen binding is at the tips of the Y-shaped antibody, but effector functions are displayed by the stem part. It is an open question whether conformational changes of the antibody molecule play a significant role in the trigger mechanism.

Amino Acids↗
PubMed1980

Nicotinic acid metabolism enzymic preparation and absolute configuration of the substrate for 2,3-dimethylmalate lyase.

1) A convenient method for the enzymatic preparation of a chemically and optically pure isomer of 2,3-dimethylmalic acid in g-amounts is described. Propionate, pyruvate and partially purified 2,3-dimethylmalate lyase (from Clostridium barkeri) were applied. 2) The enzymically formed product, m.p. 99--100 degrees C, [alpha]D20 = -16.4 (water), is related to the known stereochemistry of the Senecio alkaloid jacobine and to a laevorotatory 2,3-dimethylmalic acid derived from jaconecic acid, a degradation product of the alkaloid. From this relationship it appears likely that the substrate of the lyase is a component of the threo racemate and is of (2R,3S) configuration. 3) A three-dimensional X-ray structure analysis was performed and the structure refined to an R value of 0.049. The asymmetric unit contains three independent threo dimethylmalic acid molecules. The anomalous dispersion effects of carbon and oxygen were used to determine the absolute configuration. These measurements yielded a (2R,3S) configuration. 4) We conclude from these results that (2R,3S)-2,3-dimethylmalate is the substrate of the lyase. The results also establish that previously isolated racemic 2,3-dimethylmalic acids, m.p. 143 degrees C and m.p. 104--106 degrees C, represent the erythro and threo pair, respectively.

Chemical Phenomena↗
PubMed1980

Crystal structure analysis and molecular model of human C3a anaphylatoxin.

Human anaphylatoxin C3a, derived from complement component C3 has been crystallized and its crystal structure determined at 3.2 A resolution based on multiple isomorphous replacement. The electron density map was interpretable in terms of the known chemical sequence and molecular model constructed. The molecule has dimensions of 42 X 22 X 16 A. It resembles a drumstick. It is constructed from two helical segments Tyr15 to Met27 and Gly46 to Ser71 connected by a loop. Residues 1 to 14 are flexible. The C-terminal residues are in irregular conformation. The crystal structure analysis establishes the disulphide linkages as Cys22-Cys49, Cys23-Cys56, Cys36-Cys57.

Amino Acids↗
PubMed1980

[Pain reduction in peripheral arteriographies of the upper and lower extremities in a double blind test. Lidocain/ioglicinate versus metrizamide (author's transl)].

36 aortofemoral and 18 brachial angiographies effected under standardized conditions in a double blind test in approximately two equal parts with Lidocain/Ioglicinate and Metrizamide, respectively, were evaluated with regard to vascular pain and sensation of heat during the examination. With the femoralis angiograms reduction of vascular pain was on the average somewhat greater, although this could not be established statistically when using Metrizamide. In the case of the angiogram of the arm, pain was on the average equally low in both cases. Of the 14 patients who had received injections of both contrast media in varying succession at intervals of 20 minutes, 6 patients considered the Metrizamide injection to be more agreeable, whereas 2 preferred the Lidocain/Ioglicinate injection and 6 patients did not notice any significant difference. The average sensation of heat during contrast medium visualisation of the legs and arms was equal with both substances. Lidocain/Ioglicinate and Metrizamide are approximately equally well suited for peripheral angiography of arms and legs, rendering narcosis and strapping down of the extremities unneccessary in normal cases.

Anesthesia, Local↗