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Biomedical subjects

C Kaiser

Publications and source records attributed to C Kaiser.

At least 109 records · Page 6Linked to original sources
PubMed1985

Myofibrillar degeneration--a common type of myocardial lesion and its selective identification by a modified luxol fast blue stain.

Myofibrillar degeneration is a very common form of myocardial damage. It occurs as a disseminated lesion after various forms of injury (e.g. association with cardiovascular surgery, raised intracranial pressure). As a localized alteration it surrounds the coagulation necrosis of infarcts. The present study introduces a modification of the Luxol Fast Blue (LFB) stain as a specific marker of myofibrillar degeneration. In formalin-fixed and paraffin-embedded myocardium of human autopsies and biopsies two LFB-reaction types are demonstrable: A) irregular blue transverse bands and B) a diffuse blue staining of the entire myocyte. The first type corresponds to the cross band lesion typical of myofibrillar degeneration. By electron microscopy it consists of dense aggregations of disorganized myofilaments. The second form exhibits diffusely LFB-coloured cells and ultrastructurally an irregular felt-like splitting of myofibrils. The latter represents another, until now unrecognized type of myofibrillar degeneration which is not clearly detectable when using other staining methods. Since a coagulation necrosis is only faintly LFB-positive, this method is not suitable for the detection of early stages of infarcts. The obvious advantages of the LFB-method are: detection of type, amount and distribution pattern of myofibrillar degeneration in low-power-views, even if myocytes are cut transversely, high sensitivity, easy handling and reliability. The affinity of damaged cells for the LFB-stain seems to be related to the pathogenesis of myofibrillar degeneration, in which abundant Ca++-influx plays a primary role.

Autopsy↗
PubMed1985

Dopamine receptor agonist activity of some 5-(2-aminoethyl)carbostyril derivatives.

The potency of beta-adrenoreceptor agonists, e.g., isoproterenol, is strikingly increased by substitution of the meta catecholic hydroxyl group with the NH group of a carbostyril system. To explore the possibility that comparable potency enhancement might occur upon similar modification of the catechol ring of dopamine, a series of 5-(2-aminoethyl)carbostyril derivatives was prepared and examined for D-1 and D-2 dopamine receptor-stimulating activity. Only the parent compound, 5-(2-aminoethyl)-8-hydroxycarbostyril (2), produced measurable activation of dopamine-sensitive adenylate cyclase (29% at a concentration of 10 microM). Some of the compounds, however, did produce significant activity in tests, namely displacement of [3H]spiroperidol binding from bovine pituitary homogenate and an isolated perfused rabbit ear artery preparation, that measure interaction with D-2 receptors. Potency of the carbostyrils was enhanced by 8-hydroxylation and by appropriate substitution of the amino group of the ethylamine side chain. The most potent member of the series was 8-hydroxy-5-[2-[[2-(4-hydroxyphenyl)ethyl]-n-propylamino]ethyl] carbostyril (16b). This compound was about 3 times more effective than dopamine in the D-2 receptor tests. Clearly, the results of this study indicate that potency of dopamine receptor agonists is not increased by carbostyril replacement of the m-hydroxyl as is noted with the beta-adrenergic receptor agonists.

Adenylyl Cyclases↗
PubMed1985

Orally active and potent inhibitors of gamma-aminobutyric acid uptake.

3-Pyrrolidineacetic acid (1a), certain piperidinecarboxylic acids--i.e., 3-piperidinecarboxylic acid (2a), 1,2,5,6-tetrahydro-3-pyridinecarboxylic acid (3a), and cis-4-hydroxy-3-piperidinecarboxylic acid (4a)--cis-3-aminocyclohexanecarboxylic acid (5a, cis-3-ACHC), and gamma-aminobutyric acid (6a, GABA) itself are among the most potent inhibitors of [3H]GABA uptake by neurons and glia in vitro. These hydrophilic amino acids, however, do not readily enter the central nervous system in pharmacologically significant amounts following peripheral administration. We now report that N-(4,4-diphenyl-3-butenyl)-3-piperidinecarboxylic acid (2b) is a specific GABA-uptake inhibitor that is more potent, more lipophilic and, in limited testing, as selective as 2a. Similar results were obtained with the N-(4,4-diphenyl-3-butenyl) derivatives of 1a, 3a, and 4a. By contrast, N-(4,4-diphenyl-3-butenyl) derivatives of 5a and 6a were not more potent than the parent amino acids and appear to inhibit GABA uptake, at least in part, by a nonselective mechanism of action. The N-(4,4-diphenyl-3-butenyl)amino acids 1b-4b exhibit anticonvulsant activity in rodents following oral or intraperitoneal administration [Yunger, L.M.; et al. J. Pharmacol. Exp. Ther. 1984, 228, 109].

4-Aminobutyrate Transaminase↗
PubMed1985

NADPH-cytochrome P-450 reductase (pig liver). Studies on the sequence of the cyanogen bromide peptides from the catalytic domain and on the reactivity of the thiol groups.

The reactivity of the cysteine residues in the non-denatured catalytic domain of the NADPH-cytochrome P-450 reductase (pig liver) was studied using the -SH reagent monobromobimane. Prerequisite was the characterization of the cysteine residues by their surrounding amino-acid sequences. In pursuit of these aims the CNBr fragments obtained from the catalytic domain were sequenced. The cysteine residues are distributed on six CNBr fragments of the catalytic domain [Vogel and Lumper (1984) Hoppe-Seyler's Z. Physiol. Chem. 365, 1074]. Only the 11-kDa CNBr peptides with the N-terminal sequences Val-Gly-Pro-Thr- and Ala-Ser-Ser-Ser-, respectively, contain two cysteine residues each. The cysteine residues of the catalytic domain accessible to monobromobimane were localized on three CNBr peptides with the N-terminal sequences Val-Gly-Pro-Thr-, Ala-Ser-Ser-Ser- and Ala-Arg-Asp-Val-, respectively. Inactivation of the trypsin-solubilized enzyme by -SH-directed reagents is caused by the modification of the accessible cysteine residue (which can be protected by NADPH) in the 11-kDa CNBr fragment (N-terminal sequence: Val-Gly-Pro-Thr-). The cosubstrate NADPH protected a second cysteine residue localized in the 11-kDa CNBr peptide with the N-terminal sequence Ala-Ser-Ser-Ser-, which is however modified at a distinctly slower rate than the critical cysteine residue characterized by the sequence -Gly-Glu-Thr-Leu-Leu-Tyr-Tyr-Gly-Cys-Arg-Arg. Five non-reacting thiol groups were localized on CNBr fragments with the N-terminal sequences Val-Gly-Pro-Thr-, Ala-Ser-Ser-Ser-, Ser-Leu-Asn-Asn-, Gly-Lys-Tyr-Val-Asp- and Ala-Ala-Asp-Pro-.

Amino Acid Sequence↗
PubMed1985

Antigenic characterization of influenza A (H1N1) viruses recently isolated from pigs and turkeys in France.

The spread of influenza A viruses from one animal reservoir to another forms an important part of the epidemiological study of influenza. The precise characterization of viral antigens by monoclonal antibodies makes possible an interesting immunological approach to the transfer of strains from one reservoir to another.This work has shown that the recent porcine strains in France, Belgium, and Spain are closely related antigenically, and distinct from the A/sw/NJ/8/76 strain. Their prototype is strain A/sw/Fin/2899/82.An avian strain, A/ty/Brit/46/83, which has caused limited epidemics of reduced egg-laying among turkeys, has a haemagglutinin identical with that of strain A/sw/2899/82.This immunological finding, combined with epidemiological information (geographical location and absence of any influenza antibody in turkey farms in previous years), suggests that the transfer of influenza viruses has taken place in the direction from pig to turkey.

Animals↗
PubMed1985

[Immunovirologic markers of the risk of influenza A H3N2 among swine].

A seroepidemiological survey using the radial haemolysis test has been performed on a representative sampling of the pig herds in Brittany. Since 1978, Influenza A H3N2 strains spread in that reservoir giving subclinical infections. We detected antibodies directed against the Influenza prototypes isolated during the human outbreaks from 1973 to 1977. Only one H3N2 virus was isolated in 1980: its antigenic structure was in agreement with the previous serological data. In 1984 outbreaks of swine Influenza A H3N2 occurred. The isolated viruses carried an hemagglutinin antigenically identical to the one of the 1980's strain but the neuraminidase looked clearly different. When studying the specific immune response of the young animals to the influenza infection, it appeared that the hemagglutinin of the 1984's viruses antigenically varied from the 1980's ones in about 2/3 of all the animals. With monoclonal antibodies anti N3 and N2 of the human prototypes we confirmed the data obtained in using the post infection ferret antisera. Monoclonal antibodies directed against the swine H3N2 1984 viruses are in preparation. We have no precise information so far on the mechanism of the antigenic variations.

Animals↗
PubMed1984

The location of a second in vivo phosphorylation site in the A alpha-chain of human fibrinogen.

By quantitative phosphorus determination on the single chains of human fibrinogen it is demonstrated that the covalently bound phosphorus of adult and fetal fibrinogen is exclusively located in the A alpha chain. The A alpha-chain of fetal fibrinogen contains about twice as much phosphorus as the adult A alpha-chain in the well known position of Ser 3 of fibrino-peptide A as well as in a hitherto unknown second position on the A alpha-chain. By consecutive cleavage of the A alpha-chains of fetal and adult fibrinogen with cyanogen bromide, trypsin, and chymotrypsin, separation of the resulting peptide mixtures and analysis for phosphorylated amino acids, this second phosphorylation site could be traced to Ser 345 of the A alpha-chain. There is only one sequence homology between the two now known in vivo phosphorylation sites of human fibrinogen, namely that the second amino acid to the carboxyl side of the phosphorylated Ser is Glu. The sequence specificity of the up to now unidentified protein kinase phosphorylating fibrinogen allows it to be classified as a member of the group of type-2 casein kinases or casein kinases TS.

Amino Acid Sequence↗
PubMed1984

Synthesis, resolution, absolute stereochemistry, and enantioselectivity of 3',4'-dihydroxynomifensine.

3',4'-Dihydroxynomifensine, 8-amino-1,2,3,4-tetrahydro-4-(3,4-dihydroxyphenyl)-2-methylisoquinoli ne (1a), is an agonist of dopamine receptors in central and peripheral systems. Since this dopamine receptor agonist bears an asymmetric center at position 4, its synthesis and resolution were undertaken as part of a study directed toward determining the mode of interaction of these agents with the receptor(s). The enantiomers of 3',4'-dihydroxynomifensine are of particular interest, as they provide additional probes of present conceptual models of the dopamine receptor(s). Initial attempts to prepare 1a were inefficient or unsuccessful; instead, an isomeric compound, 1,2,4,5-tetra-hydro-2-(3,4-dihydroxyphenyl)-4- methyl-3H-1,4-benzodiazepine (9), was obtained. For this reason, a new route to 3',4'-dihydroxynomifensine was employed. The racemic dimethoxy intermediate 1d, thus obtained, was resolved. Methoxyl cleavage of the isomers of 1d afforded the enantiomers of 1a. Enantiomeric excess of these antipodes or appropriate derivatives was examined by NMR, CD, and HPLC methods. CD analysis suggests an enantiomeric excess greater than 99%. Determination of the absolute configuration of the enantiomers of 1a was determined by single-crystal X-ray diffractometric analysis. Examination of the isomers in several pharmacological test systems revealed a high degree of enantioselectivity. D-1 dopaminergic activity resides almost exclusively in the S enantiomer. The findings of the study have been employed to suggest an accessory binding site on the dopamine receptor(s) that differs from that advanced earlier. This accessory binding site may be specific for the D-1 subpopulation of dopamine receptors.

Adenylyl Cyclases↗
PubMed1983

Synthesis of rat-liver lactate dehydrogenase and characterization of its mRNA.

Rat liver lactate dehydrogenase (LDH) has been synthesized in hepatocytes and in a cell-free translation system. The subunit synthesized in both systems displayed the same electrophoretic mobility upon sodium dodecyl sulfate/polyacrylamide slab gel electrophoresis. Sequence analysis of the subunits translated in vitro and synthesized in vivo indicated N-acetyl-alanyl-alanine for both N termini. Thus, the newly synthesized subunit does not exhibit an amino-terminal extension. The mRNA for the lactate dehydrogenase subunit was exclusively found in free polysomes. A size of 2120 +/- 240 nucleotides was estimated for the mRNA. Only about 50% of these nucleotides are needed to code for the polypeptide chain of the enzyme.

Amino Acid Sequence↗
PubMed1983

N-terminal amino acid sequences of precursor and mature forms of alpha-1-antitrypsin.

alpha-1-Antitrypsin is found in hepatocytes as a high-mannose glycoprotein (Mr 49 000), extracellularly as a complex-type glycoprotein (Mr 54 000). Deglycosylation of both forms with peptide: N-glycosidase led to proteins of identical app. Mr (41 000). The sequence of 26 N-terminal amino acids of rat alpha 1-antitrypsin was determined. A high content of polar amino acids was found. The partially characterized presequence of in vitro synthesized alpha 1-antitrypsin showed a cluster of hydrophobic amino acids. A pre-peptide of 24 amino acids is proposed. There is no evidence for the existence of a propeptide.

Amino Acid Sequence↗
PubMed1983

Potential usefulness of renal vasodilators in hypertension and renal disease: SK&F 82526.

SK&F 82526 and its enantiomers have been shown to increase renal blood flow and decrease renal vascular resistance in the anesthetized dog. The effect of the racemate on lowering systemic blood pressure in the anesthetized dog and the spontaneously hypertensive rat has been shown to be caused by the R-enantiomer with the S-enantiomer being devoid of significant activity on blood pressure. The mechanism by which the R-enantiomer decreases blood pressure is not systemic vasodilatation or prejunctional inhibition of norepinephrine release but appears to result from a unique stimulation of the postjunctional dopamine receptor. Racemic SK&F 82526 also has been shown to increase renal blood flow in an ischemic model of acute renal failure.

Animals↗
PubMed1983

Laboratory diagnosis of viral infections.

When a suspected viral agent requires laboratory confirmation, specimens must be properly collected and stored, and appropriately transported to a virology laboratory. Viruses can be isolated from a variety of specimens in tissue cultures, and characteristic cell changes may be seen in Papanicolaou smears and scrapings of vesicles. Serologic, immunofluorescent and immunoradiologic techniques are useful in identifying both antigens and antibodies.

Antigen-Antibody Reactions↗
PubMed1983

[Experimental swine influenza. Comparison of the pathogenicity of swine-type wild influenza viruses and strains of human type H3 N2 whose reservoir is swine].

Intra-nasal inoculation of 10-day-old piglets, free of specific pathogenic flora, with swine influenza virus A/H1 N1 and A/H3 N2 produces lesions of viral pneumonia without detectable clinical signs. Following indirect contamination all the strains studied were able to multiply in the respiratory tract; in those cases where no macroscopic lesion was seen, microscopic examination revealed variable modification of the pulmonary tissue depending on the virus causing infection. Influenza virus type H3 N2 are naturally found in many groups of pigs and can therefore play an important role in the respiratory pathology of the hog. Experimental results when compared to findings in the field indicate that the severity of the disease is linked to associated etiological factors as well as to the virulence of the viral strains themselves.

Animals↗
PubMed1983

[Epizootic swine influenza on animal farms in Brittany].

Since 1976, seroepidemiological surveys using radial haemolysis and isolation trials from samples collected from pigs at the abattoir showed that Brittany was an important reservoir of swine subclinical infections due to the human Influenza A viruses H3N2. Influenza A H1Sw N1Sw subclinical infections sporadically occurred from 1979 to 1981. In January 1982 an epizootic started in Finistère which spread from west to east. The H1Sw and N1Sw antigens of 28 stains isolated from 1979 to 1982 were studied with ferret and rabbit anti sera and appeared to be variants of the previous strains (1976-1967-1961-1930). A reinforced serological survey in pigs demonstrated that both Influenza A viruses H1Sw N1Sw and H3N2 simultaneously spread in herds. There is no actual prove of recent human infections by A H1Sw N1Sw virus.

Adolescent↗