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Biomedical subjects

R Kaiser

Publications and source records attributed to R Kaiser.

At least 217 records · Page 12Linked to original sources
PubMed1987

Lysosomal sialidase deficiency: increased ganglioside content in autopsy tissues of a sialidosis patient.

Organs obtained at autopsy from a patient with sialidosis were analyzed for 'bound' sialic acid and their ganglioside and neutral glycolipid patterns determined. The water-soluble bound sialic acid was increased between 10- and 17-fold in visceral organs, but only about 2-fold in the brain, when compared to normal controls. Lipid-bound sialic acid was increased up to 8-fold in visceral organs due to elevated amounts of gangliosides GM3, GD3 and probably GM4 and LM1, whereas the brain showed no deviation from controls. An alteration of the neutral glycolipid pattern was also observed. The results indicate an impaired catabolism of gangliosides in sialidosis in addition to that of sialyloligosaccharides and sialoglycoproteins.

Adult↗
PubMed1986

cDNA and protein structure for the alpha subunit of human liver alcohol dehydrogenase.

Two cDNA clones for human liver alcohol dehydrogenase (ADH) were identified, together covering 1450 nucleotides that contain the cDNA sequence of the ADH1 locus and include a coding region of 1122 nucleotides for the alpha subunit of the enzyme. In parallel, direct peptide analyses of the carboxymethylated protein also established most of the amino acid sequence. Nucleotide and peptide data were in complete agreement and show exchanges at 24 positions in the alpha relative to the beta subunit. One of the cDNA clones had a 139-nucleotide internal deletion at a position of possible interest in relation to mRNA processing, ancestral connections, or DNA replication. The structure of the alpha subunit is homologous to that of the beta and gamma subunits but has many exchanges, also of functionally important residues, explaining the different enzymatic properties. In total, 35 of 374 amino acid residues differ between the class I isozymes, and the substitutions add an extra SH group in the alpha subunit. Only in the beta-pleated sheet region of the coenzyme-binding domain is almost complete lack of substitutions noted, illustrating the importance of this region. In contrast, the active site region is far less conserved. However, similar exchanges of functional significance have also been found in distantly related alcohol and polyol dehydrogenases.

Alcohol Dehydrogenase↗
PubMed1985

Mitochondrial aldehyde dehydrogenase from human liver. Primary structure, differences in relation to the cytosolic enzyme, and functional correlations.

The 500-residue amino acid sequence of the subunit of mitochondrial human liver aldehyde dehydrogenase is reported. It is the first structure determined for this enzyme type from any species, and is based on peptides from treatments with trypsin, CNBr, staphylococcal Glu-specific protease, and hydroxylamine. The chain is not blocked (in contrast to that of the acetylated cytosolic enzyme form), but shows N-terminal processing heterogeneity over the first seven positions. Otherwise, no evidence for subunit microheterogeneities was obtained. The structure displays 68% positional identity with that of the corresponding cytosolic enzyme, and comparisons allow functional interpretations for several segments. A region with segments suggested to participate in coenzyme binding is the most highly conserved long segment of the entire structure (positions 194-274). Cys-302, identified in the cytosolic enzyme in relation to the disulfiram reaction, is also present in the mitochondrial enzyme. A new model of the active site appears possible and involves a hydrophobic cleft. Near-total lack of conservation of the N-terminal segments may reflect a role of the N-terminal region in signaling the transport of the mitochondrial protein chains. Non-conservation of interior regions may reflect the differences between the two enzyme forms in subunit interactions, explaining the lack of heterotetrameric molecules. The presence of some internal repeat structures is also noted as well as apparently general features of differences between cytosolic and mitochondrial enzymes.

Aldehyde Dehydrogenase↗
PubMed1985

Structural relationships among class I isozymes of human liver alcohol dehydrogenase.

The alpha subunit of human liver alcohol dehydrogenase has been submitted to structural analysis. Together with earlier work on the beta and gamma subunits, the results allow conclusions on the relationship of all known forms of the class I type of the enzyme. Two segments of the alpha subunit were determined; one was also reinvestigated in the beta and gamma subunits. The results establish 11 residue replacements among class I subunits in the segments analyzed and show that the alpha, beta, and gamma protein chains each are structurally distinct in the active site regions, where replacements affect positions influencing coenzyme binding (position 47; Gly in alpha, Arg in beta and gamma) and substrate specificity (position 48; Thr in alpha and beta, Ser in gamma). Residue 128, previously not detected in beta and gamma subunits, corresponds to a position of another isozyme difference (Arg in beta and gamma, Ser in alpha). The many amino acid replacements in alcohol dehydrogenases even at their active sites illustrate that in judgements of enzyme functions absolute importance of single residues should not be overemphasized. Available data suggest that alpha and gamma are the more dissimilar forms within the family of the three class I subunits that have resulted from two gene duplications. The class distinction of alcohol dehydrogenases previously suggested from enzymatic, electrophoretic, and immunological properties therefore also holds true in relation to their structures.

Alcohol Dehydrogenase↗
PubMed1985

Transient blindness following transurethral resection of the prostate in an achondroplastic dwarf.

Neurological complications associated with transurethral resection of the prostate have been reported in the past. We report on an achondroplastic dwarf who suffered transient blindness following transurethral resection of the prostate. The blindness correlated with a markedly elevated serum glycine level of 13,734 mumol. per l. We discuss the possibility of glycine being responsible for this complication.

Achondroplasia↗
PubMed1984

Human liver alcohol dehydrogenase. 1. The primary structure of the beta 1 beta 1 isoenzyme.

Determination of the amino acid sequence of the beta 1 subunit from the class I (pyrazole-sensitive) human liver alcohol dehydrogenase isoenzyme beta 1 beta 1 revealed a 373-residue structure differing at 48 positions (including a gap) from that of the subunit of the well studied horse liver alcohol dehydrogenase EE isoenzyme. The structure deduced is compatible with known differences in composition, ultraviolet absorbance, electrophoretic mobility and catalytic properties between the horse and human enzymes. All zinc-liganding residues of the horse E subunit are strictly conserved in the human beta 1 subunit, despite an earlier report of a mutation involving Cys-46. This residue therefore remains conserved in all known alcohol dehydrogenase structures. However, the total cysteine content of the beta 1 structure is raised from 14 in the subunit of the horse enzyme to 15 by a Tyr----Cys exchange. Most exchanges are on the surface of the molecule and of a well conserved nature. Substitutions close to the catalytic centre are of interest to explain the altered substrate specificity and different catalytic activity of the beta 1 homodimer. Functionally, a Ser----Thr exchange at position 48 appears to be of special importance, since Thr-48 in beta 1 instead of Ser-48 in the horse enzyme can restrict available space. Four other substitutions also line the active-site pocket, and appear to constitute partly compensated exchanges.

Alcohol Dehydrogenase↗
PubMed1984

Human liver alcohol dehydrogenase. 2. The primary structure of the gamma 1 protein chain.

The primary structure of the gamma 1 subunit of human liver alcohol dehydrogenase isoenzyme gamma 1 gamma 1 was deduced by characterization of 36 tryptic and 2 CNBr peptides. The polypeptide chain is composed of 373 amino acid residues. gamma 1 differs from the beta 1 subunit of human liver alcohol dehydrogenase at 21 positions, and from the E subunit of horse liver alcohol dehydrogenase at 43 positions including a gap at position 128 as in the beta 1 subunit. All zinc-liganding residues from the E subunit of the horse protein and the beta 1 subunit of the human enzyme are conserved, but like beta 1, gamma 1 also has an additional cysteine residue at position 286 (in the positional numbering system of the horse enzyme) due to a Tyr----Cys exchange. Most amino acid exchanges preserve the properties of the residues affected and are largely located on the surface of the molecules, away from the active site and the coenzyme binding region. However, eight positions with charge differences in relation to the E subunit of the horse enzyme are noticed. These result in a net positive charge increase of one in gamma 1 versus E, explaining the electrophoretic mobilities on starch gels. Of functional significance is the conservation of Ser-48 in gamma 1 relative to E. The residue is close to the active site but different (Thr-48) in the beta 1 subunit of the human enzyme. Thus, the closer structural relationship between human gamma 1 and horse E enzyme subunit than between beta 1 and E is also reflected in functionally important residues, explaining a greater similarity between gamma 1 gamma 1 and EE than between beta 1 beta 1 and EE.

Alcohol Dehydrogenase↗
PubMed1984

A novel form of the polypeptide PHI isolated in high yield from bovine upper intestine. Relationships to other peptides of the glucagon-secretin family.

A novel form of the polypeptide termed PHI (peptide HI with N-terminal histidine and C-terminal isoleucine amide) has been isolated from bovine upper intestine. This bovine peptide was obtained in a 40 times higher yield than the corresponding polypeptide isolated from porcine intestine. Bovine PHI is, like porcine PHI, composed of 27 amino acid residues. The complete amino acid sequence of the bovine peptide is His-Ala-Asp-Gly-Val-Phe-Thr-Ser-Asp-Tyr-Ser-Arg-Leu-Leu-Gly-Gln-Leu-Ser- Ala- Lys-Lys-Tyr-Leu-Glu-Ser-Leu-Ile-NH2. This sequence differs from porcine PHI at position 10 and from human PHI at positions 10, 12 and 27. The amino acid residue exchange between porcine and bovine PHI makes the latter more similar to the vasoactive intestinal polypeptide (VIP), gastric inhibitory polypeptide (GIP), glucagon and the growth-hormone-releasing factor (GRF).

Amino Acid Sequence↗
PubMed1984

Human liver mitochondrial aldehyde dehydrogenase: a C-terminal segment positions and defines the structure corresponding to the one reported to differ in the Oriental enzyme variant.

A C-terminal segment of mitochondrial human liver aldehyde dehydrogenase was characterized. The results prove that a central part of this segment largely but not completely agrees with a structure of a tryptic peptide previously reported for the same isoenzyme. This part corresponds to a segment that contains the exchanged residue in the functionally deficient Oriental variant of mitochondrial aldehyde dehydrogenase [(1984) Proc. Natl. Acad. Sci. USA 81, 258-261]. The data suggest important functions for the C-terminal region of aldehyde dehydrogenase, clarify previously inconsistent results, and establish this structure in the typical enzyme, including the position corresponding to the mutation in the functional variant.

Aldehyde Dehydrogenase↗
PubMed1984

Duration of the climacteric syndrome in women treated by hormonal substitution and in controls.

This study investigates the duration of symptoms occurring in vegetative climacteric syndrome in women treated by hormonal substitution and in untreated controls. The average duration of the problem in 97 women who refused hormone treatment and served as the control group was 4.5 yr. A mean duration of 5.4 yr was seen in 85 women treated with oral oestrogens, of 6.4 yr in 20 women treated with a combination of oestradiol and prasterone , and of 12.9 yr in 28 women receiving a combination of oestradiol and testosterone. All of these groups were practically identical as regards initiation of therapy, age, and 17 other case-history, sociological and clinical criteria. Although hormonal treatment of the climacteric syndrome can lengthen the duration of the symptoms, this is not necessarily always the case. The type of medication and the dose undoubtedly play an important role in this connection. It has been shown that oestradiol-testosterone combinations can prolong the period during which the symptoms of the climacteric syndrome occur beyond the period that their occurrence may be regarded as physiological.

Administration, Oral↗
PubMed1984

Human alcohol dehydrogenase: structural differences between the beta and gamma subunits suggest parallel duplications in isoenzyme evolution and predominant expression of separate gene descendants in livers of different mammals.

Human alcohol dehydrogenase (ADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) occurs in multiple forms, which exhibit distinct electrophoretic mobilities and enzymatic properties. The homogeneous isoenzymes beta 1 beta 1 and gamma 1 gamma 1 were isolated from livers of Caucasians with "typical" ADH phenotype by double ternary complex affinity chromatography and ion exchange chromatography. The differences between the beta 1 and gamma 1 subunits were determined by structural analysis of all tryptic peptides from the carboxymethylated proteins. The human beta 1 and gamma 1 chains differ at 21 of the 373 positions (5.6%). Ten tryptic peptides account for the differences. All residue substitutions are compatible with one-base mutations and result in largely unaltered properties, but five lead to charge differences. Sixteen substitutions are at positions corresponding to the catalytic domain of the well-known horse enzyme; five correspond to the coenzyme-binding domain. Substitutions adjacent to important regions may correlate with differences in coenzyme binding, substrate specificities, and active-site relationships. The residue replacements between the beta 1 and gamma 1 subunits of human ADH are not identical to the known substitutions between ethanol-active (E) and steroid-active (S) subunits of horse ADH. Thus, the duplication leading to human beta 1 and gamma 1 subunits is separate and different from that leading to equine E and S subunits. Both duplications are likely to have occurred after the ancestral separation of human and equine ADH. Of the 21 residues that are different between beta 1/gamma 1, 13 in gamma 1 but only 6 in beta 1 are identical to those of the horse E chain. This suggests a closer relationship between gamma 1 and E, although beta 1 in man and E in the horse are the subunits recovered in highest yield from liver ADH preparations. Consequently, in these two mammalian species, relative activities of genes for an isoenzyme family appear to be different.

Alcohol Dehydrogenase↗
PubMed1983

[Effects of hormonal treatment on the duration of the climacteric syndrome].

The duration of symptoms occurring in vegetative climacteric syndrome in 97 women who refused hormone treatment and served as the control group was 4.5 years. A mean duration of 5.4 years was determined in 85 women treated with oral estrogens, 6.4 years in 20 women treated with a combination of estradiol and prasterone and 12.9 years in 28 women receiving a combination of estradiol and testosterone. All these groups were practically identical as to initiation of therapy and age, as well as to 17 further case history, sociological and clinical characteristics. Hormonal treatment of the climacteric syndrome can therefore lengthen symptomatic problems. This applies particularly to estradiol-testosterone combinations, in which the testosterone assumes decisive significance for the extent of the lengthening. Adjustment to the symptomatic timespan experienced by the control group depends largely on a relatively quick reduction of dosage.

Climacteric↗
PubMed1982

[Computer tomographic ventriculography (author's transl)].

A method for elucidating complex abnormalities of CSF circulation by using a positive contrast medium (metrizamide) and computer tomography is described. The technique for the method, the results and their clinical significance is demonstrated. The value of this method is compared with traditional ventriculography and with computer tomography without the use of contrast medium. It is shown that the technique represents an important extension of the scope of computer tomography.

Adolescent↗