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Biomedical subjects

J Goto

Publications and source records attributed to J Goto.

At least 127 records · Page 7Linked to original sources
PubMed1993

Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a degenerative disorder of motor neurons in the cortex, brainstem and spinal cord. Its cause is unknown and it is uniformly fatal, typically within five years. About 10% of cases are inherited as an autosomal dominant trait, with high penetrance after the sixth decade. In most instances, sporadic and autosomal dominant familial ALS (FALS) are clinically similar. We have previously shown that in some but not all FALS pedigrees the disease is linked to a genetic defect on chromosome 21q (refs 8, 9). Here we report tight genetic linkage between FALS and a gene that encodes a cytosolic, Cu/Zn-binding superoxide dismutase (SOD1), a homodimeric metalloenzyme that catalyzes the dismutation of the toxic superoxide anion O2.- to O2 and H2O2 (ref. 10). Given this linkage and the potential role of free radical toxicity in other neurodenegerative disorders, we investigated SOD1 as a candidate gene in FALS. We identified 11 different SOD1 missense mutations in 13 different FALS families.

Amino Acid Sequence↗
PubMed1993

Organization and expression of mouse Hox3 cluster genes.

We determined the physical linkage of six mouse Hox3 homeobox sequences, including a new homeobox sequence (Hox3.5), by analysis of overlapping genomic clones. Additionally, we defined the locations of Hox1.7 and Hox1.8 in the Hox1 cluster. Analysis of the expression patterns of Hox3.6 and Hox3.5 during embryogenesis revealed that the relationship between relative position in the Hox3 cluster and expression domain along antero-posterior axis appears similar to that seen for members of the other Hox clusters.

Amino Acid Sequence↗
PubMed1993

Potential bile acid metabolites. 20. A new synthetic route to stereoisomeric 3,6-dihydroxy- and 6-hydroxy-5 alpha-cholanoic acids.

An improved procedure for the syntheses of stereoisomeric 3,6-dihydroxy- and 6-hydroxy-5 alpha-cholanoic acids (and their methyl esters) is described. The principal reactions employed are those reported in the preceding paper of this series, with the commercially available hyodeoxycholic acid as starting material. The final step in the procedure is the reduction of the key 5 alpha C-6 ketones with either the stereoselective equatorial reagent, Li/NH3/MeOH, or the axial reagent, Zn(BH4)2. The results of analysis of the prepared 6-monohydroxylated and 3,6-dihydroxylated stereoisomers by thin-layer chromatographic, high performance liquid chromatographic and gas-liquid chromatographic mobilities, and 1H and 13C nuclear magnetic resonance spectra are discussed along with the data for the corresponding compounds in the 5 beta-series.

Bile Acids and Salts↗
PubMed1993

Potential bile acid metabolites. 19. The epimeric 3 alpha,6,7 beta-trihydroxy- and 3 alpha,6,7 beta,12 alpha-tetrahydroxy-5 alpha-cholanoic acids.

Syntheses by a new procedure of the known 3 alpha,6 alpha,7 beta- and 3 alpha,6 beta,7 beta-trihydroxy-5 alpha-cholanoic acids, and of the once-reported analog 3 alpha,6 alpha,7 beta,12 alpha-, as well as the new 3 alpha,6 beta,7 beta,12 alpha-tetrahydroxy-5 alpha-cholanoic acids, are described. Key intermediates of the syntheses are the 6-oxo-7 beta-ols of the respective 5 alpha-cholanoic acids (and their methyl esters) prepared by allomerization at C-5 of appropriate 6-bromo-7-oxo derivatives of the corresponding 5 beta-acids. Successful reduction of the 6,7-ketols to the desired products depended on the proper choice of reagents, either Zn(BH4)2 or Li/NH3/MeOH.

Ammonia↗
PubMed1993

Enzyme immunoassay for 4-hydroxy-2-(4-methylphenyl)benzothiazole.

A specific enzyme immunoassay (EIA) has been developed for 4-hydroxy-2-(4-methylphenyl)benzothiazole (KB-2714) (1), an active metabolite of 4-acetoxy-2-(4-methylphenyl)benzothiazole (KB-2683) (2) which is a promising anti-rheumatic agent. The EIA was based upon antiserum elicited against 5-(2-carboxyphenylazo)-4-hydroxy-2-(4-methylphenyl)benzothiazole (3)-bovine serum albumin conjugate and beta-galactosidase-labelled 5-amino-4-hydroxy-2-(4-methylphenyl)benzothiazole (5). The sensitivity of the EIA was significantly improved by the utilization of a bridge heterologous combination system. An appropriate dose-response curve of EIA for 4-hydroxy-2-(4-methylphenyl)benzothiazole was obtained in the range of 10 pg tube-1-20 ng tube-1. The specificity of EIA proved to be satisfactory in terms of cross-reactivities to 14 benzothiazole-related compounds including glucuronic acid and sulphuric acid conjugates. The proposed method was evaluated to be useful for the determination of 1 in urine and plasma with acceptable recovery and inter- and intra-assay precision.

Antigens↗
PubMed1993

The glycinamide ribonucleotide transformylase (GART) gene is not responsible for familial amyotrophic lateral sclerosis.

Though the nature of the underlying metabolic defect which leads to amyotrophic lateral sclerosis (ALS) remains obscure, certain biochemical anomalies have been found, such as, reduced RNA content in ALS motor neurons. Recently, a gene causing the familial form of ALS (FALS) has been assigned to an interval of approximately 10 cM including the locus D21S58 on chromosome 21q22.1. This region includes the GART gene which encodes an enzyme catalyzing three steps in the de novo biosynthesis of purine nucleotides which are precursors for RNA. A defect of this gene might result in reduced RNA production and predispose to premature death of motor neurons. In order to test GART as a candidate we developed two highly informative DNA markers in this region and carried out linkage analyses for FALS. GART is excluded as a candidate for FALS.

Acyltransferases↗
PubMed1992

Studies on steroids. CCLIV. Gas chromatographic-mass spectrometric determination of 4- and 6-hydroxylated bile acids in human urine with negative ion chemical ionization detection.

A method for the determination of 4- and 6-hydroxylated bile acids with a vicinal glycol moiety in human urine by gas chromatography-mass spectrometry with negative ion chemical ionization detection is described. The 4 beta-hydroxylated bile acids labelled with 18O and 2H were prepared as internal standards by the exchange reaction of the carbonyl group on the steroid nucleus with H2(18)O, followed by metal deuteride reduction. Bile acids in urine were extracted with a Sep-Pak C18 cartridge and, after solvolysis and hydrolysis of the conjugated forms, transformed into pentafluorobenzyl ester diethylhydrogensilyl ether diethylsilylene derivatives. Subsequent resolution into individual 4- and 6-hydroxylated bile acids was carried out on a cross-linked fused-silica capillary column; a characteristic carboxylate anion, [M-PFB]-, was used to monitor each bile acid in the negative ion mode. The newly developed method was applied to the separation and determination of 4- and 6-hydroxylated bile acids in a urine specimen from a newborn infant.

Bile Acids and Salts↗
PubMed1992

Synthesis of N-acetylglucosaminides of unconjugated and conjugated bile acids.

3-N-Acetylglucosaminides of unconjugated, glycine- and taurine-conjugated bile acids have been synthesized. Bile acids appropriately protected were condensed with acetochloroglucosamine through the 3 alpha-hydroxyl group by means of the Koenigs-Knorr reaction using cadmium carbonate as a catalyst. Subsequent borohydride reduction and/or alkaline hydrolysis provided desired 3-N-acetylglucosaminides of unconjugated bile acids. Glycine-conjugates were obtained from N-acetylglucosaminides of unconjugated bile acids and ethyl glycinate by the carbodiimide method. The preparation of N-acetylglucosaminides of taurine-conjugates was attained by the Koenigs-Knorr reaction of bile acid p-nitrophenyl esters followed by condensation with taurine. 7-N-Acetylglucosaminides of ursodeoxycholates were prepared in a similar fashion. The convenient synthesis of 3-N-acetylglucosaminides of unconjugated bile acids is also described.

Acetylglucosamine↗
PubMed1992

Aerobic and anaerobic bacterial interactions in the development of anaerobic bacterial pneumonia.

The interactions between aerobic and anaerobic bacteria in the development of anaerobic bacterial pneumonia were studied by introducing Bacteroides fragilis and Escherichia coli alone or in combination into guinea pigs by tracheal infusion. The lung lesions induced by B. fragilis were mainly located near the pleura, unlike those induced by E. coli, and were accompanied by pneumonia, lung abscess, and pleuritis. The lung lesions produced by mixed infection with B. fragilis (10(9) cfu) and E. coli (10(7) cfu) were significantly more severe than those induced by either microbe alone, and the redox potentials at the foci of inflammation were markedly reduced (max: -330 mV). Analysis of lung lesions after treatment with aztreonam and clindamycin and neutrophil phagocytic activity suggested that E. coli was primarily responsible for the lung lesions and that B. fragilis promoted the accompanying inflammation, resulting in increased pathogenicity of the mixed infections.

Animals↗
PubMed1992

Enzyme labeling in steroid enzyme immunoassays. The p-nitrophenyl ester method for alkaline phosphatase and glucose oxidase labelings.

The p-nitrophenyl ester method was assessed as an enzyme labeling technique. The active ester of a carboxylated testosterone derivative was treated with alkaline phosphatase and glucose oxidase to give labeled antigens, using various molar ratios of steroid to enzyme. Satisfactory immunoreactivities with an anti-testosterone antibody in an enzyme immunoassay system were obtained with the labeled antigens prepared at pH 8.5 by the use of molar ratios higher than 30 and 10, respectively, in the alkaline phosphatase and glucose oxidase labelings.

Alkaline Phosphatase↗
PubMed1992

Use of the thermostable glucose-6-phosphate dehydrogenase as a label enzyme in steroid enzyme immunoassays.

A thermostable glucose-6-phosphate dehydrogenase was assessed as a label enzyme in a testosterone enzyme immunoassay system. Enzyme labeling of a steroid with the enzyme was carried out by the N-succinimidyl ester method. A dose-response curve with a satisfactory sensitivity could be obtained by the use of the enzyme-labeled antigen. This enzyme should be useful in hapten enzyme immunoassays because of its relatively high stability.

Glucosephosphate Dehydrogenase↗
PubMed1992

Inhibition by HS-142-1, a novel nonpeptide atrial natriuretic peptide antagonist of microbial origin, of atrial natriuretic peptide-induced relaxation of isolated rabbit aorta through the blockade of guanylyl cyclase-linked receptors.

HS-142-1, a specific nonpeptide antagonist for the atrial natriuretic peptide (ANP) receptor, equally blocked rat ANP (rANP)-, porcine brain natriuretic peptide-, or porcine C-type natriuretic peptide-stimulated GMP production in cultured bovine aortic smooth muscle (BASM) and bovine aortic endothelial (BAE) cells in a concentration-dependent fashion, at concentrations of 1-300 micrograms/ml. But, even at 300 micrograms/ml, HS-142-1 only weakly inhibited the specific binding of 125I-rANP to the BASM and BAE cells, where only a small portion of the binding sites are linked to guanylyl cyclase. Further, with BAE cell membranes, HS-142-1 recognized only the 135-kDa ANP receptor, which is thought from 125I-rANP affinity cross-linking studies to be the guanylyl cyclase-linked receptor. HS-142-1 also, if anything, inhibited the labeling of 135-kDa ANP receptors in the affinity cross-linking studies with BASM membranes, suggesting that a major portion of the 135-kDa ANP receptors are HS-142-1 insensitive and only a small portion of the 135-kDa ANP receptors are responsible for the blockade by HS-142-1 of GMP production in BASM cells. At a concentration of 100 micrograms/ml, HS-142-1 reversibly prevented ANP-induced relaxation of the isolated rabbit thoracic aorta induced to contract with 3 x 10(-7) M phenylephrine, but not the relaxation induced by sodium nitroprusside, isoproterenol, or papaverine. These results suggest that HS-142-1 specifically inhibits natriuretic peptide-induced vasorelaxation through the blockade of guanylyl cyclase-linked natriuretic peptide receptors. HS-142-1 thus will be a powerful tool for understanding the physiological roles, in vasculature, of natriuretic peptides, which contribute to the homeostasis of blood pressure and intravascular volume.

Animals↗
PubMed1991

Studies on steroids. CCLIII. Capillary gas chromatographic behaviour of diethylhydrogensilyl-diethylsilylene derivatives of stereoisomeric bile acids.

The capillary gas chromatographic behaviour of diethylhydrogensilyl (DEHS) ethers and/or diethylsilylene (DES) derivatives of fifty bile acids including 4- and 6-hydroxylated compounds is described. The methylene unit (MU) values of methyl and pentafluorobenzyl esters of bile acids were determined as their trimethylsilyl (TMS), dimethylethylsilyl (DMES) ethers and DEHS-DES derivatives. The differences in methylene unit values between the corresponding TMS ethers and DMES ethers or DEHS-DES derivatives were used for estimating the number and stereochemistry of hydroxyl groups on the steroid nucleus. On treatment with the silylating agent N,O-bis (diethylhydrogensilyl)trifluoroacetamide, bile acids possessing isolated hydroxyl in addition to diaxial trans-glycol groups were easily converted into the DEHS ehters, whereas those having a vicinal glycol group except for the diaxial group were converted into cyclic DES derivatives. The mass spectrometric properties obtained with negative-ion chemical ionization detection are discussed.

Bile Acids and Salts↗