[The NMR tomographic findings in von Recklinghausen's disease with extensive neurofibromas].
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Adult↗
Biomedical subjects
R Kaiser
Publications and source records attributed to R Kaiser.
Chronopharmacokinetics and cardiovascular effects of nifedipine.
Circadian phase dependency in pharmacokinetics and hemodynamic effects on blood pressure and heart rate of different galenic formulations of nifedipine (immediate-release, sustained-release, and i.v. solution) were studied in healthy subjects or in hypertensive patients. Pharmacokinetics of immediate-release but not sustained-release and i.v. nifedipine were dependent on time of day: immediate-release nifedipine had higher Cmax (peak concentration) and shorter tmax (time-to-peak concentration) after morning than evening application, and bioavailability in the evening was reduced by about 40%. Circadian rhythm in estimated hepatic blood flow as determined by indocyanine green kinetics may contribute to these chronokinetics. A circadian time dependency was also found in nifedipine-induced effects on blood pressure and heart rate as monitored by 24-h ambulatory blood pressure measurements. In conclusion, the dose response relationship of oral nifedipine is influenced by the circadian organization of the cardiovascular system as well as by the galenic drug formulation.
Administration, Oral↗
[The place of diagnostic imaging in xanthogranulomatous pyelonephritis].
The urographic, angiographic, sonographic and computed tomographic findings in 4 cases of xanthogranulomatous pyelonephritis are presented along with correlation with the pathological specimens. The parenchyma of the kidney was replaced by multiple, rounded, low-density respectively hypoechogenic areas on CT and sonography that corresponded to dilated calices and/or inflammatory tissue. For diagnosing the characteristic extrarenal extension of the disease sonography was not as accurate as CT.
Adult↗
Comparison of three classes of human liver alcohol dehydrogenase. Emphasis on different substrate binding pockets.
Conformational models of the three characterized classes of mammalian liver alcohol dehydrogenase were constructed using computer graphics based on the known three-dimensional structure of the E subunit of the horse enzyme (class I) and the primary structures of the three human enzyme classes. This correlates the substrate-binding pockets of the class I subunits (alpha, beta and gamma in the human enzyme) with those of the class II and III subunits (pi and chi, respectively) for three enzymes that differ in substrate specificity, inhibition pattern and many other properties. The substrate-binding sites exhibit pronounced differences in both shape and properties. Comparing human class I subunits with those of class II and III subunits there are no less than 8 and 10 replacements, respectively, out of 11 residues in the substrate pocket, while in the human class I isozyme variants, only 1-3 of these 11 positions differ. A single residue, Val294, is conserved throughout. The liver alcohol dehydrogenases, with different substrate-specificity pockets, resemble the patterns of other enzyme families such as the pancreatic serine proteases. The inner part of the substrate cleft in the class II and III enzymes is smaller than in the horse class I enzyme, because both Ser48 and Phe93 are replaced by larger residues, Thr and Tyr, respectively. In class II, the residues in the substrate pocket are larger in about half of the positions. It is rich in aromatic residues, four Phe and one Tyr, making the substrate site distinctly smaller than in the class I subunits. In class III, the inner part of the substrate cleft is narrow but the outer part considerably wider and more polar than in the class I and II enzymes. In addition, Ser (or Thr) and Tyr in class II and III instead of His51 may influence proton abstraction/donation at the active site.
Alcohol Dehydrogenase↗
Avian alcohol dehydrogenase. Characterization of the quail enzyme, functional interpretations, and relationships to the different classes of mammalian alcohol dehydrogenase.
The primary structure of the major quail liver alcohol dehydrogenase was determined. It is a long-chain, zinc-containing alcohol dehydrogenase of the type occurring also in mammals and hence allows judgement of the gene duplications giving rise to the classes of the human alcohol dehydrogenase system. The avian form is most closely related to the class I mammalian enzyme (72-75% residue identity), least related to class II (60% identity), and intermediately related to class III (64-65% identity). This pattern distinguishes the mammalian enzyme classes and separates classes I and II in particular. In addition to the generally larger similarities with class I, the avian enzyme exhibits certain residue patterns otherwise typical of the other classes, including an extra Trp residue, present in both class II and III but not in class I, with a corresponding increase in the UV absorbance. The avian enzyme further shows that a Gly residue at position 260 previously considered strictly conserved in alcohol dehydrogenases can be exchanged with Lys. However, zinc-binding residues, coenzyme-binding residues, and to a large extent substrate-binding residues are unchanged in the avian enzyme, suggesting its functional properties to be related to those of the class I mammalian alcohol dehydrogenases. In contrast, the areas of subunit interactions in the dimers differ substantially. These results show that (a) the vertebrate enzyme classes are of distant origin, (b) the submammalian enzyme exhibits partly mixed properties in relation to the classes, and (c) the three mammalian enzyme classes are not as equidistantly related as initially apparent but suggest origins from two sublevels.
Alcohol Dehydrogenase↗
Fast atom bombardment mass spectrometry and chemical analysis in determinations of acyl-blocked protein structures.
Peptide generation and fast atom bombardment mass spectrometry in combination with conventional chemical analysis was used to identify the blocking group and establish the N-terminal structure of six different proteins at the nanomole level. In this manner, the first terminal structures of three non-mammalian alcohol dehydrogenases were determined, demonstrating the presence of N-terminal acetylation in these piscine, amphibian, and avian enzymes. Similarly, two different yeast glucose-6-phosphate dehydrogenases and a minor variant of a human alcohol dehydrogenase were found to be acetylated. The exact end location of C-terminal structures was also established. Together, the analyses permit the definition of terminal regions and blocking groups, thus facilitating the delineation of remaining structures.
Acetylation↗
Microdissection and microcloning of human chromosome 7q22-32 region.
Genetic information contributing to cystic fibrosis in addition to the CF gene is suggested to reside on the long arm of the human chromosome 7. In our attempt to analyze this genomic region in detail, we generated a region-specific DNA probe library by microdissection and microcloning of the midpiece of the chromosome 7q arm. Microdissection was performed in unstained metaphase spreads from a human x mouse hybrid cell line containing chromosome 7 as the only human chromosome. We obtained 593 clones from 75 dissected chromosomal fragments. At least 88% of the microclones were true recombinants; 40% of the clones contained repetitive sequences as determined by plaque hybridization with genomic DNA as probe. The overall mean fragment size of insert fragments was 3.2 kb, the median size was 3.5 kb. Regional mapping of 30 DNA fragments was performed by the aid of hybrid cell lines containing different segments of human chromosome 7; 50% of the microcloned inserts were found to map to 7q22-32.
Animals↗
The frequency of the CF delta F508 deletion in CF chromosomes of different ethnic origin.
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Argentina↗
Aminopyridazine derivatives and TXA2-PGI2 balance.
Experiments carried out under the conditions adopted showed the strong affinity of aminopyridazine derivatives for the eicosanoids TXA2 and PGI2. But this affinity depended on the chemical structure of the molecule: a small change in the radical grafted onto the pyridazine ring could completely modify the pharmacological activity of the molecule. Consequently it should be possible to control the properties of pyridazine derivatives according to pharmacological needs. Thus: --pyridazin-3-one derivatives were mainly active on TXA2 biosynthesis: 2-aminoalkyl 5-arylidene 6-methyl (4H) pyridazin-3-ones inhibited the TXA2-synthesizing activity of cardiac tissue whereas 3-amino 4,6-diaryl pyridazin-3-ones were specific inhibitors of the TXA2 synthetase in vitro, but these effects were weak. --pyridazine derivatives were devoid of any effect on the TXA2-synthesizing activity of cardiac tissue: they acted on either TXA2 synthetase or PGI2 synthetase according to the radicals grafted onto the pyridazine ring. --none of the compounds under study was active on the PGI2-synthesizing activity of cardiac tissue.
Animals↗
Comparative effects of some 3-amino 4,6-diarylpyridazines on the biosynthesis in vitro of TXA2 and PGI2- and on the TXA2- and PGI2-synthesizing activities of cardiac tissue.
Some 3-amino 4,6-diarylpyridazine derivatives were tested for their effects on TXA2 and PGI2 biosyntheses in vitro and on the TXA2- and PGI2-synthesizing activities of cardiac tissue. Horse platelet and aorta microsomes were used as sources of thromboxane and prostacyclin synthetases respectively. The TXA2- and PGI2-synthesizing activities of cardiac tissue were studied on isolated perfused rabbit hearts (the heart microsomes being used both as TXA2 synthetase and PGI2 synthetase sources). TXB2 and 6-keto PGF1 alpha were determined by RIA. Among the compounds under study, 3-morpholino 4,6-diphenylpyridazine (III) was shown to inhibit specifically the TXA2 synthetase. Substitution of the morpholino group by a dimethylamino one (I) reinforced the inhibiting effects on TXA2 synthetase but it also revealed a slight anti-prostacyclin synthetase action of the molecule. Replacement of 3-morpholino moieties by either a 3-hydrazino (IV), or a 2-dimethylaminoethylamino (V), or a 2-morpholinoethylamino group (VI) abolished completely the effects of the molecule on TXA2 and PGI2 synthetases. Likewise the addition of chlorine on the para-position on the phenyl ring of I neutralized all its inhibitory effects both on TXA2 and PGI2 synthetases in vitro. None of the 3-amino 4,6-diarylpyridazine derivatives was active on either the TXA2- or PGI2-synthesizing activities of cardiac tissue.
Animals↗
Alcohol dehydrogenases.
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Alcohol Oxidoreductases↗
Automated DNA diagnostics using an ELISA-based oligonucleotide ligation assay.
DNA diagnostics, the detection of specific DNA sequences, will play an increasingly important role in medicine as the molecular basis of human disease is defined. Here, we demonstrate an automated, nonisotopic strategy for DNA diagnostics using amplification of target DNA segments by the polymerase chain reaction (PCR) and the discrimination of allelic sequence variants by a colorimetric oligonucleotide ligation assay (OLA). We have applied the automated PCR/OLA procedure to diagnosis of common genetic diseases, such as sickle cell anemia and cystic fibrosis (delta F508 mutation), and to genetic linkage mapping of gene segments in the human T-cell receptor beta-chain locus. The automated PCR/OLA strategy provides a rapid system for diagnosis of genetic, malignant, and infectious diseases as well as a powerful approach to genetic linkage mapping of chromosomes and forensic DNA typing.
Base Sequence↗
Rotavirus from children of an urban settlement of Papua New Guinea.
Rotavirus is a leading cause of severe dehydrating diarrhoea among children admitted to hospitals in Papua New Guinea. A community-based study in an urban settlement of Port Moresby, the capital of Papua New Guinea, revealed that rotavirus was a major cause of diarrhoea, especially of the severe type, in this community. Two serotypes of rotavirus were observed and were explained on the basis of a 'shift and drift' phenomenon, or an introduction of a new strain from outside. Implications for such observations are far reaching in developing countries and it is recommended that intervention strategies other than vaccine development be explored.
Acute Disease↗
Serologic evidence of human immunodeficiency virus infection of the central nervous system in African patients with acquired immunodeficiency syndrome.
The intrathecal synthesis of antibodies to human immunodeficiency virus (HIV) was determined by 3 different immunoassays in 15 African patients with pre-acquired immunodeficiency syndrome (AIDS) and AIDS. Isoelectric focusing together with affinity-mediated immunoblot were found to be superior to enzyme-linked immunosorbent assay and Western blot in providing information not only about the antigen specificity of locally produced antibodies but also about their clonal distribution. In 9 of the subjects, HIV-specific oligoclonal bands were demonstrable with higher frequency or intensity in the cerebrospinal fluid than in the autologous serum, indicating autochthonous synthesis of HIV-related antibodies.
Acquired Immunodeficiency Syndrome↗
Characteristics of mammalian class III alcohol dehydrogenases, an enzyme less variable than the traditional liver enzyme of class I.
Class III alcohol dehydrogenase, whose activity toward ethanol is negligible, has defined, specific properties and is not just a "variant" of the class I protein, the traditional liver enzyme. The primary structure of the horse class III protein has now been determined, and this allows the comparison of alcohol dehydrogenases from human, horse, and rat for both classes III and I, providing identical triads for both these enzyme types. Many consistent differences between the classes separate the two forms as distinct enzymes with characteristic properties. The mammalian class III enzymes are much less variable in structure than the corresponding typical liver enzymes of class I: there are 35 versus 84 positional differences in these identical three-species sets. The class III and class I subunits contain four versus two tryptophan residues, respectively. This makes the differences in absorbance at 280 nm a characteristic property. There are also 4-6 fewer positive charges in the class III enzymes accounting for their electrophoretic differences. The substrate binding site of class III differs from that of class I by replacements at positions that form the hydrophobic barrel typical for this site. In class III, two to four of these positions contain residues with polar or even charged side chains (positions 57 and 93 in all species, plus positions 116 in the horse and 140 in the human and the horse), while corresponding intraclass variation is small. All these structural features correlate with functional characteristics and suggest that the enzyme classes serve different roles. In addition, the replacements between these triad sets illustrate further general properties of the two mammalian alcohol dehydrogenase classes.(ABSTRACT TRUNCATED AT 250 WORDS)
Alcohol Oxidoreductases↗
Analysis of oligoclonal antibody bands against individual HIV structural proteins in the CSF of patients infected with HIV.
Intrathecal antibody responses to HIV were investigated by a highly sensitive immunoblot assay. Serum and CSF specimens were tested for reactivity with the recombinant HIV gag proteins p15, p17 and p24 and with the recombinant transmembrane protein p41. Autochthonous production of virus-specific IgG to one or more HIV structural proteins was seen in 8 of 10 asymptomatic seropositive subjects, in 3 of 4 men with AIDS-related complex, and in 9 of 13 patients with AIDS. These results were consonant with an elevated CSF/serum antibody ratio to total HIV antigen. The high frequency of local HIV-specific antibody synthesis in seropositive individuals without related clinical symptoms indicates an early involvement of the CNS in HIV infections.
Acquired Immunodeficiency Syndrome↗
Intrathecal synthesis of virus-specific oligoclonal antibodies in patients with enterovirus infection of the central nervous system.
Cerebrospinal fluid (CSF) and serum samples from six patients with enterovirus infections were investigated by isoelectric focusing (IEF) and affinity-mediated immunoblot AMI) for the clonal distribution of entervirus-specific antibodies. In two patients with either acute meningitis or encephalitis and in one patient with a relapse of multiple sclerosis, oligoclonal IgG bands specific for enteroviruses were found predominantly in the CSF, revealing intrathecal synthesis of these antibodies. In three other patients with neurological symptoms probably unrelated to a current enterovirus infection, IEF and AMI disclosed nearly identical patterns of coxsackievirus-B-specific oligoclonal bands in the CSF and serum, indicating diffusion of these antibodies from the serum into the CSF. Although the number of patients in this study is small, the results suggest that intrathecally synthesized enterovirus-specific antibodies may be used as a means of identifying an enterovirus infection of the CNS.
Adult↗