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Biomedical subjects

T Higuchi

Publications and source records attributed to T Higuchi.

At least 451 records · Page 25Linked to original sources

Circadian variation in R-THBP-induced enhancement of the ambulation-increasing effect of methamphetamine on mice.

6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-THBP), a co-factor for tyrosine hydroxylase and tryptophan hydroxylase, induces the enhancement of ambulation-increasing effect of methamphetamine on mice. In this study, we investigated the circadian variation in the interaction between R-THBP and methamphetamine by changing the time-of-day of both methamphetamine administration and pretreatment with R-THBP. The mouse's ambulatory activity was measured by a tilting-type activity cage for 4 hr. In the daytime, but not in the nighttime, the ambulation-increasing effect of methamphetamine (1 and 2 mg/kg, s.c.) was significantly enhanced by the pretreatment with R-THBP (100 mg/kg, s.c., 2 or 6 hr before). These data indicate the possibility that peripherally administered R-THBP increases the biosynthesis of catecholamine especially in the daytime.

Analysis of Variance↗

Abolition of prolactin surge induced by ovarian steroid hormones in the lactating rat.

There are data indicating that stress-induced prolactin (PRL) release is blunted in the lactating rat like the release of other stress-associated hormones. In this experiment, the PRL release evoked by administration of estrogen, which is another principal stimulus for PRL release, was examined in ovariectomized lactating rats 8-15 days after delivery. Estradiol benzoate (EB, 20 micrograms) injections into ovariectomized nonlactating rats induced a PRL surge starting between 13:00 and 15:00 h with a peak at 17:00 h 2 days after the treatment, whereas the EB-induced PRL surge was absent in ovariectomized lactating rats separated from their pups at 09:00 h on the day or in mothers without separation from their pups. Injection of either thyrotropin-releasing hormone (TRH; 10 micrograms/kg) or pimozide (0.5 mg/kg) elevated serum PRL concentrations similarly in lactating and nonlactating rats when examined just before the beginning of the expected estrogen-induced PRL surge. Thus, the main cause for the reduced PRL response to estrogen in lactating rats seems not to be in the pituitary gland but in the brain. Progesterone, which is known to induce a PRL surge in ovariectomized estrogen-primed rats by acting on the mediobasal hypothalamus, also failed to evoke a PRL surge in lactating rats. Recovery from the inhibitory influence of suckling on PRL response to EB followed a time course similar to that observed in response to immobilization stress or to morphine injection; estrogen-induced PRL surge started to recover at 6 days and was almost fully recovered 8 days after weaning.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Influence of prostaglandin E1 on slight proteinuria in non-azotaemic diabetics.

In an investigation into the effect of prostaglandin E1 on proteinuria in nephrotic diabetic nephropathy, five patients were treated with 40 micrograms prostaglandin E1 administered intravenously over 2 h twice daily for 4 weeks. The following parameters were compared before and after treatment: protein excretion in urine; total serum protein concentration; serum albumin concentration; creatinine clearance; blood urea nitrogen; and serum creatinine content. A further five patients with nephropathy resulting from non-insulin-dependent diabetes mellitus were selected as controls. Analysis of the results using Student's t-test showed no significant change in any of the parameters before and after treatment.

Adult↗

Enhancing effect of sodium chloride on in vitro adsorption of paraquat onto activated carbon.

The enhancing effect of sodium chloride addition on the adsorption of paraquat onto activated carbon was discussed from the standpoints of equilibrium amount adsorbed and adsorption rate in vitro. The amount of paraquat adsorbed was increased by the addition of sodium chloride. The amount adsorbed with 0.1% addition was about five times greater than that in sodium chloride-free solution at an equilibrium concentration of 1 mg/L. The adsorption rate of paraquat onto activated carbon was also accelerated by sodium chloride addition. Kinetic constants in 0.1% and 0.9% sodium chloride solution were about 1.4 and 2.0 times greater, respectively, than that in sodium chloride-free solution. It was confirmed that paraquat removal by activated carbon was enhanced by sodium chloride addition. The reason was assumed to be the interrupted dissociation of paraquat in solution caused by sodium chloride addition.

Adsorption↗

An evaluation of analyzed data of hemoglobin derivatives by CO-Oximeter in medico-legal autopsy.

We examined blood samples of autopsy cases by a CO-Oximeter and evaluated the data for investigation of death including asphyxia. When sampling methods were examined, oxyhemoglobin (O2-Hb) concentrations increased, and reduced hemoglobin (R-Hb) concentrations decreased, by the contact of the blood with the air, while carboxyhemoglobin (CO-Hb) and methemoglobin (Met-Hb) concentrations appeared to be unchanged. The CO-Hb concentrations in the left heart blood were higher than those of the right. In the cases of death due to cold exposure, O2-Hb concentrations of the left heart blood were prominently higher than those of the right. In the cases of death in house fires and the asphyxiated, O2-Hb concentrations were extremely low (below 10%) in both of the left and right heart blood.

Asphyxia↗

[Structures of isomers of ursodeoxycholic acid: 3 beta,7 alpha- and 3 beta,7 beta-dihydroxy-5 beta-cholan-24-oic acids].

Isomers of ursodeoxycholic acid, 3 beta,7 alpha- and 3 beta,7 beta-dihydroxy-5 beta-cholan-24-oic acids (3 beta 7 alpha U and 3 beta 7 beta U) crystallize in the orthorhombic space group P2(1)2(1)2(1) containing one molecule and in the monoclinic group P2(1) containing two independent molecules in an asymmetric unit. The cell dimensions are a = 28.032(17), b = 9.973(5), c = 8.049(6) A for 3 beta 7 alpha U, and a = 11.771(8), b = 27.999(12), c = 6.637(2) A, beta = 90.78(6) degrees for 3 beta 7 beta U, respectively. Both structures were solved by the direct method and refined to the residual values of 0.065 (3 beta 7 alpha U) and 0.059 (3 beta 7 beta U). The conformations of the D rings of each molecule are different from each other: 3 beta 7 alpha U intermediate, 3 beta 7 beta U (A and B) half-chair form. In the crystal, 3 beta 7 alpha U molecules are connected by a hydrogen bond extended nearly parallel to the bc plane and 3 beta 7 beta U molecules are connected by the helical hydrogen bond system or by the zigzag one parallel to the ac plane.

Molecular Conformation↗

[Studies on the glucose tolerance and the endocrine function of the pancreas in primary sclerosing cholangitis].

The responses of serum IRI, serum IRG, and blood sugar levels to 75 g oral glucose and serum IRI to glucagon injection were investigated in 26 chronic hepatitis, 20 liver cirrhosis, 5 primary sclerosing cholangitis (PSC) and 8 healthy volunteers served as controls. The results obtained herein were as follow: 1) The frequency of the glucose intolerance in PSC was higher than the other liver diseases. The mean values of the insulinogenic index (delta IRI/delta BS 30 min) in PSC was lower than control subjects. No suppression of IRG by glucose was observed in PSC. 2) The maximum IRI value (max delta IRI) in PSC during glucagon test was lower than that in control subjects. 3) In one case of 5 PSC ICSA was founded to be positive. These data suggest that we should pay much attention to suffering from diabetes mellitus in natural history of PSC.

Aged↗

Factors affecting acetohexamide reductase activities in microsomes and cytosol from the kidney of male rats: age and castration.

Acetohexamide reductase activity in microsomes from the kidney of male rats increased markedly at puberty to approach the maximum level at 8 weeks of age; it was not detected until 4 weeks of age. Furthermore, castration suppressed effectively the activity in kidney microsomes at 8 weeks of age. These findings clearly indicate that the activity in kidney microsomes can be regulated by androgens. On the other hand, in cytosol from the kidney of male rats, a higher acetohexamide reductase activity was observed at all weeks of age tested. Castration had no significant effect on the activity in kidney cytosol.

Aging↗

Three stages of copper accumulation in hepatocellular lysosomes: X-ray microanalysis of copper-loaded golden hamsters.

Male golden hamsters were loaded with copper by supplying them for up to 12 weeks with drinking water containing 0.5% cupric acetate. The copper feeding increased hepatic copper to widely varying levels. Energy dispersive X-ray microanalysis could always identify a copper-sulphur complex in the hepatocyte lysosomes of copper-loaded hamsters and the X-ray intensity of copper was found to be a reliable parameter to measure in-situ copper accumulation. Combining this parameter with the copper binding ratio expressed by delta Cu/delta S enabled us to discern two stages of sub-histochemical copper accumulation. The first stage was marked by low levels of both lysosomal copper and binding ratio, which suggested that this initial copper transfer was mediated by unsaturated cuproproteins. The second stage was characterized by median amounts of lysosomal copper and a binding ratio of more than 0.50. At the third stage, histochemically detectable copper appeared in animals whose lysosomal copper was extraordinarily high in later experimental periods. With the copper binding ratio being in the same range of 0.50-0.83, it seemed that saturated cuproproteins were the main mediator of copper transport in the later two stages.

Animals↗

Site-directed mutagenesis of Escherichia coli aspartate aminotransferase: role of Tyr70 in the catalytic processes.

Site-directed mutagenesis of Tyr70 in the active site of Escherichia coli aspartate aminotransferase (AspAT) followed by kinetic studies has elucidated the roles of the hydroxyl group and benzene ring of Tyr70. X-ray crystallographic analysis showed that replacement of Tyr70 by Phe did not alter the active-site conformation of the enzyme. Comparison of the kinetic parameters of the four half-transamination reactions (the pyridoxal 5'-phosphate form of the enzyme with L-aspartate or L-glutamate and the pyridoxamine 5'-phosphate form with oxalacetate or 2-oxoglutarate) between the wild-type and [Tyr70----Phe]AspATs showed that the mutation increases the energy level of the transition state by 2 kcal.mol-1 for all the four substrates, suggesting some contribution of the hydroxyl group of Tyr70 to the transition state. When Phe70 was further replaced by Ser, the energy level of the transition state for L-glutamate or 2-oxoglutarate, but not for L-aspartate or oxalacetate, was further increased by 2-3 kcal.mol-1, suggesting that the presence of a benzene ring at position 70 is essential for recognizing the L-glutamate-2-oxoglutarate pair as substrates.

Amino Acid Sequence↗

Enhancement by retinoic acid and dibutyryl cyclic adenosine 3':5'-monophosphate of the differentiation and gene expression of human neuroblastoma cells induced by interferon.

Human neuroblastoma cell lines are induced to differentiate and display neuronal phenotypes when treated with interferon (IFN)-alpha 2, retinoic acid (RA), or dibutyryl cyclic AMP (dbcAMP). We investigated the effects of combinations of these agents in induction-differentiation in the neuroblastoma cell line, NUB-6. The inductive effect of IFN-alpha 2 was markedly enhanced when used in combination with RA or dbcAMP. In parallel, RA or dbcAMP also enhanced the level of 2'-5'-oligoadenylate (2-5A) synthetase, and enzyme induced by IFNs and implicated in their biological action. The levels of another IFN-inducible enzyme, p68 kinase, were not enhanced by the combination treatments. The enhancement effects appeared to be exerted largely at the posttranscriptional level as both RA and dbcAMP stabilized IFN-induced 2-5A synthetase mRNA, resulting in increased enzyme activity. Thus, the 2-5A synthetase system is likely involved in mediating the IFN-alpha 2-induced differentiation of neuroblastoma cells and may also mediate the enhancement effects of RA and dbcAMP on IFN activity in these cells. These results also provide a rational basis for establishing a combination therapeutic approach for the treatment of neuroblastoma.

2',5'-Oligoadenylate Synthetase↗

Thermostable aspartate aminotransferase from a thermophilic Bacillus species. Gene cloning, sequence determination, and preliminary x-ray characterization.

The gene encoding aspartate aminotransferase of a thermophilic Bacillus species, YM-2, has been cloned and expressed efficiently in Escherichia coli. The primary structure of the enzyme was deduced from nucleotide sequences of the gene and confirmed mostly by amino acid sequences of tryptic peptides. The gene consists of 1,176 base pairs encoding a protein of 392 amino acid residues; the molecular mass of the enzyme subunit is estimated to be 42,661 daltons. The active site lysyl residue that binds the coenzyme, pyridoxal phosphate, was identified as Lys-239. Comparison of the amino acid sequence with those of aspartate aminotransferases from other organisms revealed very low overall similarities (13-14%) except for the sequence of the extremely thermostable enzyme from Sulfolobus solfataricus (34%). Several amino acid residues conserved in all the compared sequences include those that have been reported to participate in binding of the coenzyme in three-dimensional structures of the vertebrate and E. coli enzymes. However, the strictly conserved arginyl residue that is essential for binding of the distal carboxyl group of substrates is not found in the corresponding region of the sequences of the thermostable enzymes from the Bacillus species and S. solfataricus. The Bacillus aspartate aminotransferase has been purified from the E. coli clone cell extracts on a large scale and crystallized in the buffered ammonium sulfate solution by the hanging drop method. The crystals are monoclinic with unit cell dimensions a = 121.2 A, b = 110.5 A, c = 81.8 A, and beta = 97.6 degrees, belonging to space group C2, and contain two molecules in the asymmetric unit. The crystals of the enzyme-alpha-methylaspartate complex are isomorphous with those without the substrate analog.

Amino Acid Sequence↗

Tracheo-bronchitis as a complication of Crohn's disease--a case report.

A case of Crohn's enterocolitis associated with diffuse tracheo-bronchitis is presented herein. Although respiratory tract involvement in Crohn's disease is extremely rare, our review of the world literature revealed several common clinical pathologic features. These features include a productive cough with chest X-ray films which are normal except for some peripheral involvement. Bronchoscopy, however, shows diffuse inflammation of the trachea and bronchi with widely scattered whitish lesions while biopsy reveals a granulomatous infiltration of inflammatory cells. This tracheobronchitis typically responds well to treatment with prednisone.

Adult↗

Multi-center study of seasonal affective disorders in Japan. A preliminary report.

A multi-center study on seasonal affective disorder (SAD) was conducted from the autumn of 1988 to the spring of 1989 with the cooperation of 16 facilities in Japan. Forty-six SAD patients were identified among 1104 respondents to our advertisements in mass media, or patients seen at the outpatient clinics. Essentially similar findings to other previous reports were obtained in terms of onset age of the first episode, duration of episode, high proportion of depression in first-degree relatives and atypical vegetative symptoms. However, a nearly equal sex ratio, together with a high proportion of unipolar depression, is characteristic of the present study. Increased appetite and carbohydrate craving were predominant only in female patients, whereas hypersomnia was prominent in both sexes. Effective response to light therapy was found in 17 SAD patients. However, a controlled study on a large number of patients is required to allow final conclusions on the efficacy of light therapy in Japanese SAD patients.

Adolescent↗

Tyr225 in aspartate aminotransferase: contribution of the hydrogen bond between Tyr225 and coenzyme to the catalytic reaction.

Tyr225 in the active site of Escherichia coli aspartate aminotransferase (AspAT) was replaced by phenylalanine or arginine by site-directed mutagenesis. X-ray crystallographic analysis of Y225F AspAT showed that the benzene ring of Phe225 was situated at the same position as the phenol ring of Tyr225 in wild-type AspAT. The mutations resulted in a great decrease in the rate of the transamination reaction, suggesting that Tyr225 is important for efficient catalysis. The kinetic analysis of half-transamination reactions of Y225F AspAT with four substrates (aspartate, glutamate, oxalacetate, and 2-oxoglutarate) and some analogues (2-methylaspartate, succinate, and glutarate) revealed a considerable increase in the affinities for all these compounds. In contrast, affinity for the amino acid substrates was decreased by mutation to arginine, but affinities for the keto acid substrates and the two dicarboxylates (succinate and glutarate) were increased. The electrostatic interaction between O(3') of the coenzyme [pyridoxal 5'-phosphate (PLP)] and the residue at position 225 affected the pKa value of the Schiff base, which is formed between the epsilon-amino group of Lys258 and the aldehyde group of PLP; based on the spectrophotometric titration the pKa values were determined to be 6.8 for wild-type AspAT, 8.5 for Y225F AspAT, and 6.1 for Y225R AspAT in the absence of substrate. The absorption spectra of the three AspATs were almost identical in the acidic pH region, but the spectrum of Y225F AspAT differed from that of wild-type or Y225R AspAT in the alkaline pH region.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Relation between body size and bone mineral density with special reference to sex hormones and calcium regulating hormones in elderly females.

We studied the relation between body size and bone mineral density in elderly females. The study included a total of 93 ambulatory females aged over 60 years. They were divided into 3 groups according to their body mass index (BMI; kg/m2): slender group with BMI less than 20 (n = 28), normal group with BMI of 20 to 24.9 (n = 43) and obese group with BMI greater than or equal to 25 (n = 22). Fracture incidence, bone mineral density, calcium regulating hormones and steroid hormones were studied in an intergroup comparative manner. The incidence of vertebral fracture was found to be negatively correlated with BMI (the incidences of vertebral fracture in slender, normal and obese were 78.6, 48.8 and 22.7%, respectively) and bone mineral density was also BMI-related (0.390 +/- 0.016, 0.456 +/- 0.015 and 0.493 +/- 0.018 g/cm2, respectively: p less than 0.01 in ANOVA; mean +/- SE). The number of years after menopause was shorter in patients with a higher BMI. There was no intergroup difference in serum levels of PTH, vitamin D and estrogens. On the other hand, serum levels of calcitonin, DHEA, DHEAS, delta-4 androstenedione and testosterone were found to be higher in subjects with a higher BMI. From the present results, it seems that bone mineral density is supported not only by weight-bearing stress upon bone, but also by serum levels of calcitonin and androgens in obese females.

Age Factors↗