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Biomedical subjects

J Sugihara

Publications and source records attributed to J Sugihara.

68 records · Page 4Linked to original sources

A new electrophoretic variant of hemoglobin (Ogi) in which a leucine residue is replaced by an arginine residue at position 34 of the alpha-chain.

Hemoglobin Ogi, in which an arginine is substituted for a leucine residue at position 34 of the alpha-chain, was detected in a Japanese family. Although slightly increased oxygen affinity is associated with this amino acid substitution in the alpha 1 beta 1 contact, it is without obvious deleterious effect on the hematological parameters of the individuals heterozygous for this variant.

Amino Acid Sequence↗

Frequency and distribution of structural variants of hemoglobin and thalassemic states in Western Japan.

Hemolysates from 100,000 people who visited the Kyushu University Hospital and affiliated hospitals during the past 15 years were screened for hemoglobinopathies using electrophoresis on thin-layer starch gel; those exhibiting an abnormality were characterized further on clinical, biochemical, and genetic grounds. Of about 97,000 adult and 3,140 cord blood samples, 29 contained electrophoretically detectable abnormalities in the heterozygous condition. Another 17 samples had quantitative changes in the levels of the minor hemoglobin components. Of the thalassemic conditions, 12 involved beta-thalassemia, 3 alpha-thalassemia, 1 delta beta-thalassemia, and 1 delta-thalassemia. Among 45 carriers of beta-thalassemia from 12 families, 5 were noted to have thalassemia intermedia since they exhibited much more severe hemolytic syndromes than those with typical beta-thalassemia minor. The frequency with which we could detect a structural variant of Hb A in the adults by electrophoresis was one in 3,800 samples. About one in 8,000 carried a beta-thalassemia gene.

Adult↗

Metabolic fate of timepidium bromide (SA-504)--Unstable metabolities in the rats.

The colored substances excreted in bile or urine have bee investigated after adminstration of a high dose of SQ-504 to rats. A reddish-violet colored substance and a bluish-violet colored substance were dominant. Their chemical structures were not assigned because of their small quantity and instability. It was recognized that the colored substances were metabolites of SA-504 from the studies with 3H and 14C labelled SA-504 and the derivatives of SA-504.

Animals↗

[Biological fate of 3H-labeled penfluridol. (3) Correlation between concentration of 3H-penfluridol in the brain and its anti-methamphetamine activity].

The Penfluridol (PFL) is a potent and long-acting neuroleptic belonging to the diphenylbutyl piperidine series. The purpose of the present study is to investigate a correlation between the brain concentration of unchanged 3H-PFL and its neuroleptic activity in the methamphetamine-antagonism test. The experimental animal comprised adult male Wistar rats weighing about 200 g. All the rats were administered 3H-PFL orally and killed at appropriate times after administration. After killing blood samples were collected and the brain and liver were excised. The blood was extracted with 4 volumes of ethanol. The brain and the liver were homogenized in 9 volumes of ethanol. The amount of 3H-PFL in the ethanol extract was determined by thin-layer chromatography. The result showed that the drug level in the brain was relatively constant when the dose was the median effective dose (ED50) for the test at those time intervals after administration.

Animals↗

Enhanced production of leukotriene B4 by peripheral blood mononuclear cells in patients with fulminant hepatitis.

The production rate of leukotriene B4 (LTB4) was measured using peripheral blood mononuclear cells (PBMC) in patients with fulminant hepatitis (FH) or other liver diseases. LTB4 in the culture media of PBMC under stimulation with Ca-ionophore was fractionated by HPLC and measured by radioimmunoassay. The production rate of LTB4 was elevated in 16 of 17 FH patients (3.3 +/- 0.2 ng/10(6) cells for 5 min), while the production was below detectable level in patients with acute or chronic hepatitis and in healthy controls. In FH patients, the highest production rate of LTB4 was observed in the initial period of the disease. Enhanced LTB4 production may indicate the primed state of PBMC--the primed mononuclear cells are regarded as participating in the development of massive liver necrosis and of other organ failures in FH.

Hepatic Encephalopathy↗

An empty sella associated with hypopituitarism in a woman with rheumatoid arthritis.

A 66-year-old woman with rheumatoid arthritis experienced severe hyponatremia and hypoglycemia of repeated occurrence. Endocrinologic examinations revealed hypopituitarism and the metrizamide computerized tomographic scan showed a primary empty sella. No evidence of a pituitary or suprasellar tumor was obtained. During the 5-year follow-up, she remains well under replacement therapy and there are no signs of an intracranial tumor. The possibility of an autoimmune mechanism linked to the development of hypopituitarism is discussed.

Aged↗

Metabolism of ethyl 2-(4-chlorophenyl)-5-(2-furyl)-oxazole-4-acetate, a new hypolipidemic agent, in the rat, rabbit, and dog. Glucuronidation of carboxyl group and cleavage of furan ring.

Metabolism of ethyl 2-(4-chlorophenyl)-5-(2-furyl)-oxazole-4-acetate (TA-1801), a new hypolipidemic agent, was studied in the rat, rabbit, and dog. Animals were given a single oral dose of 50 mg/kg TA-1801 labeled with 14C. The first metabolic reaction for TA-1801 was hydrolysis of the ester linkage. The resulting metabolite M1 was found to undergo further biotransformations, i.e. glucuronidation at the carboxyl group and ring cleavage of the furan group. These metabolic pathways were observed in all the species examined, although species differences were seen in the amount of metabolites.

Animals↗

Mechanism of metabolic cleavage of a furan ring.

We studied the mechanism of metabolic cleavage of a furan ring, using a new hypolipidemic agent, ethyl 2-(4-chlorophenyl)-5-(2-furyl)oxazole-4-acetate (TA-1801), as a model compound. A TA-1801 analogue labeled with deuterium at the 5-position of its furan ring was administered orally to rats. The analysis of urinary metabolites by GC/MS revealed that the deuterium of the furan was retained in the ring-opened metabolite (M3). Metabolic cleavage of furan has been generally considered to proceed by hydroxylation of the 5-position followed by tautomerism and hydrolysis of the resulting 5-hydroxyfuran derivative. However, if the cleavage proceeded by this pathway, the deuterium of the 5-position would be eliminated during hydroxylation. Therefore, we propose that the ring was cleaved directly to form an unsaturated aldehyde, considering the mechanism of oxidation by cytochrome P-450. Although this "intermediate" was not detected in the biological specimens, a synthetic unsaturated aldehyde was transformed to the actual urinary metabolites M2 and M3 (major ring-opened metabolites) in the isolated rat liver.

Animals↗