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Biomedical subjects

Y Higashi

Publications and source records attributed to Y Higashi.

At least 307 records · Page 17Linked to original sources
PubMed1987

Gene structure of cytochrome P-450(M-1) specifically expressed in male rat liver.

Cytochrome P-450(M-1) [P-450(M-1)] is specifically expressed in adult male rat liver [Yoshioka, H., Morohashi, K., Sogawa, K., Miyata, T., Kawajiri, K., Hirose, T., Inayama, S., Fujii-Kuriyama, Y., & Omura, T. (1987) J. Biol. Chem. 262, 1706-1711]. Isolation and analysis of the gene for P-450(M-1) revealed that the coding region of the gene is interrupted by eight introns and is dispersed over a 35-kilobase pair region of chromosomal DNA. Intron insertion sites of the P-450(M-1) gene are located at equivalent positions to those of cytochrome P-450b and P-450e, which are phenobarbital-inducible. Sequence analysis of the 5'-upstream region of the P-450(M-1) gene shows that there is a homologous sequence to glucocorticoid regulatory elements (GRE) identified in glucocorticoid-responsive genes.

Amino Acid Sequence↗
PubMed1987

Enhancement of the rectal absorption of sodium ampicillin by N-acylamino acids in rats.

The promoting efficacies of N-acyl derivatives of amino acids on the rectal absorption of sodium ampicillin were investigated using the rat rectal loop technique. N-Acyl derivatives with longer carbon chains in the acyl moiety showed a greater promoting potency. The promoting potencies of N-acyl derivatives of phenylglycine and phenylalanine were greater than those of glycine and alanine derivatives when compared at the same length of carbon chain in their acyl moieties. The promoting action of N-acylamino acids was not influenced by the presence of N-ethylmaleimide or ouabain. The promoting potencies of N-acylamino acids were depressed in the presence of calcium chloride in the rectal loop. The contribution of the calcium ion sequestration capacity of N-acylamino acids to their promoting efficacies is discussed.

Amino Acids↗
PubMed1987

Clinical and EEG studies of zotepine, a thiepine neuroleptic, on schizophrenic patients.

The overall effect of zotepine was a "slightly improved" or better response in 20 patients (64.5%), "unchanged" in 10 (32.3%) and "worsened" in 1 (3.2%). Zotepine exhibited some degree of improvement in 54.5% of patients unresponsive to prior drugs. The onset of effect of zotepine was within one month in 19 patients. The improvement rate in the hebephrenic type (66.7%) was almost the same as in the paranoid type. The improvement rate classified by psychopathology was highest for hypobulia, followed by restlessness-excitement and hallucination, depressive mood, hypochondria and delusion. The side-effects were subjective complaints, such as general fatigue, dryness of mouth, sleepiness or fainting in a small number of cases. There was a slight increase in S-GPT in one patient and a slightly increased blood platelet count, also in one patient. Serial EEG changes associated with zotepine studied in another 17 chronic schizophrenics could be classified into three groups: those with increased slow waves, those with enhanced alpha waves and those with unchanged EEGs. There was a positive correlation between the incidence of slow waves and higher plasma levels of zotepine.

Antipsychotic Agents↗
PubMed1987

Inhibition by rifamycin AF/013 of thyroid hormone binding to the nuclear receptor.

Rifamycin AF/013, a potent inhibitor of nucleic acid polymerizing enzymes and of some hormone receptors, strongly inhibited thyroid hormone-binding to the isolated nuclear receptor. Fifty percent inhibition was obtained at AF/013 concentration of as low as 8 micrograms/ml. AF/013, however, only weakly promoted dissociation of the bound hormone from the receptor. The inhibitory action of AF/013 was competitive with respect to and reduced the receptor's affinity for the hormone.

Animals↗
PubMed1987

Small, bilateral, calcified intrarenal aneurysms--a case report.

With increased use of renal angiography and ultrasonography, intrarenal aneurysms and arteriovenous malformations have been easily diagnosed. The authors report a case of small, bilateral intrarenal aneurysms with calcifications that were associated with a visible pulsatile wall motion recorded by M-mode ultrasonography. The finding of selective renal angiography was consistent with bilateral intrarenal aneurysms. Accelerated atherosclerosis and long-term history of hypertension were thought to have caused them.

Aged↗
PubMed1987

Ketoconazole as a possible universal inhibitor of cytochrome P-450 dependent enzymes: its mode of inhibition.

Modes of inhibition and binding of ketoconazole, an orally antimycotic agent, to NADPH-cytochrome P-450 dependent enzymes were investigated using subcellular fractions of human and rat testes, human adrenocortical adenoma tissue and rat adrenals and livers. Ketoconazole competitively inhibited the activities of steroid 17 alpha-hydroxylase and C17-20 lyase in rat and human testes, 16 alpha-hydroxylase in human testes and 21-hydroxylase in rat adrenal glands. Ki values were in the order of 10(-8)M for human testicular enzymes, while the order was 10(-7)-10(-6) M for rat adrenal and testicular enzymes. Kinetic studies indicated that ketoconazole bound to cytochrome P-450 and not to other components of monooxygenase systems. Spectrophotometric studies also revealed direct binding of ketoconazole to cytochrome P-450 component by inducing type II difference spectra in all tissue preparations examined, indicating that ketoconazole is possibly a universal inhibitor of NADPH-cytochrome P-450 dependent monooxygenases which are involved in metabolism of many substances including steroids, toxins, carcinogens and others.

Adenoma↗
PubMed1987

[Fever attack in percutaneous nephrolithotomy and transurethral ureterolithotripsy].

We studied the fever attacks and their factors in the cases of percutaneous nephrolithotomy (PNL) and transurethral ureterolithotripsy (TUL). In PNL, fevers were significantly higher and more frequent in the cases with infected urinary stones than those with sterile stones, but prophylactic administration of antibiotics did not lower the fever or its frequency of attack. There was no significant difference between the cases of single procedure and those of multiple procedures although multiple procedures were likely to increase the frequency of fever attacks. In TUL, single J-catheter indwelling decreased fever attacks, but infection and administration of antibiotics did not affect the fever significantly. However, careful control of urinary tract infections before and after operation and of intrarenal pressure during operation are thought to be most important for prevention of fever attacks and urosepsis.

Adolescent↗
PubMed1987

[Morphological changes in the contralateral testis in patients with testicular tumor].

Biopsy of contralateral testis of 20 patients with an unilateral testicular tumor was carried out to evaluate the morphological changes of the contralateral testis caused by the tumor. Serum beta-chorionic gonadotropin (beta-hCG), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and alpha-fetoprotein (AFP) levels before orchiectomy were examined as a function influencing morphological changes of the contralateral testis. Typical carcinoma in situ was found in a case of ipsilateral testis. The presence of a few atypical germ cells, however, was the only finding of the contralateral testis of three patients. Five of 20 patients revealed hypospermatogenesis in the contralateral intact testis. Most of the other patients also showed sloughing of germinal epithelium suggesting disorder of spermatogenesis. Johnsen's mean score count and tubular wall thickening were related to neither clinical stages, ESR, serum beta-hCG, AFP, LH nor FSH levels. Tubular wall thickening was observed in 8 of 10 patients with a tumor weighting over 150 g, but was found in only 1 of 10 patients with a lighter tumor (p less than 0.01).

Adult↗
PubMed1987

Role of acidic phospholipids in tissue distribution of quinidine in rats.

The mechanism of interorgan variation in tissue distribution of quinidine was investigated from a viewpoint of binding characteristics to phospholipids and the composition of phospholipids in various tissues. The order of binding of quinidine to an individual standard phospholipid, expressed as a product of the association constant (K) and the number of binding sites (n), was: phosphatidyl ethanolamine (PhE) less than dipalmitoyl phosphatidyl choline (saturated PhC) less than or equal to phosphatidyl choline (unsaturated PhC) less than phosphatidyl inositol (PhI) less than phosphatidyl glycerol (PhG) less than phosphatidic acid (PhA) less than phosphatidyl serine (PhS). Thus, quinidine was found to bind preferentially to acid phospholipids such as PhS, PhA, PhG, and PhI. The greatest binding was obtained in PhS among the various phospholipids and was more than 300-fold that of neutral phospholipids such as PhC and PhE. The concentration of individual components of phospholipids in the lung, kidney, liver and heart was determined using a two dimensional thin-layer chromatography. The concentration of PhS, highly responsible for the quinidine binding to phospholipids in each tissue, was ranked in the following order: heart less than liver less kidney less than lung. The contribution of PhS to quinidine binding was more than 86% in all tissues. A good correlation between the concentration of PhS in each tissue and the Ct/Cp ratio in vivo was obtained (r = 0.984). Thus, it was concluded that the tissue distribution of quinidine in vivo depended on the composition of phospholipids in tissues and that a determinant of interorgan variation in the tissue distribution of quinidine was the concentration of PhS in the tissues.

Animals↗
PubMed1986

Complete nucleotide sequence of two steroid 21-hydroxylase genes tandemly arranged in human chromosome: a pseudogene and a genuine gene.

Two 21-hydroxylase [P-450(C21)] genes have been isolated from a human genomic library using a bovine P-450(C21) cDNA. The insert DNAs containing the P-450(C21) genes were also hybridized with the sequences of the 5' or 3' end regions of human C4 cDNA, indicating a close linkage of the P-450(C21) gene to the C4 gene. Sequence analysis has revealed that the two P-450(C21) genes are both approximately equal to 3.4 kilobases long and split into 10 exons. Comparing the two sequences, we found that the two genes are highly homologous including their introns and flanking sequences, but that three mutations render one of the two P-450(C21) genes nonfunctional--1 base insertion, an 8-base deletion, and a transition mutation--all of which may cause premature termination of the translation. Tandem arrangement of the highly homologous pseudo- and genuine genes in close proximity could account for the high incidence of P-450(C21) gene deficiency by homologous gene recombination.

Base Sequence↗
PubMed1986

Presence of a unique set of nuclear proteins at the sites sensitive to RNase A as well as DNase I.

A unique and simple set of proteins (S1 proteins) has been detected in the cell nuclei of various tissues of the rat (Inoue et al. (1983) Eur. J. Biochem. 135, 61-68). They were liberated from the nuclei by digestion with DNA-hydrolyzing enzymes under the conditions where transcriptionally active chromatin is preferentially digested and released into the reaction supernatant. S1 proteins account for 20% of the total supernatant proteins (Higashi et al. (1984) Biochem. Int. 9, 697-704). The present study demonstrates that S1 proteins occur at the sites sensitive to RNase A as well as DNase I, and are rapidly liberated from the nuclei by digestion with either enzyme.

Animals↗
PubMed1986

Enhanced small intestinal absorption of beta-lactam antibiotics in rats in the presence of monodesmosides isolated from pericarps of Sapindus mukurossi (Enmei-hi).

Monodesmoside, saponin A, B and C, isolated from pericarps of Sapindus mukurossi (Enmei-hi) have been shown to promote absorption of poorly absorbed beta-lactam antibiotics by the small intestine using an in situ loop method. Monodesmosides were solubilized with ginseng crude saponin extract, a mixture of bisdesmosides, saponin X, Y1 and Y2 which were isolated also from Sapindus mukurossi. These solubilizing agents were demonstrated not to influence the absorption promoting effect of monodesmosides. Among the monodesmosides, saponin B showed the greatest effect. No influence of osmolarity of the administered solution on the absorption promoting action was observed. The promoting functions of the three monodesmosides for the small intestinal absorption of antibiotics were suppressed by Ca2+ ion coexisting in the administered solution.

Animals↗
PubMed1986

Hepato-biliary transport of amaranth by single pass liver perfusion in normal and carbon tetrachloride or alpha-naphthylisothiocyanate treated rats.

Hepato-biliary transport of amaranth (AM) in normal and carbon tetrachloride (CCl4) or alpha-naphthylisothiocyanate (ANIT) treated rats was studied using single pass liver perfusion. CCl4-intoxicated rats were prepared by two different methods. One was a subcutaneous injection (CCl4s.c.) and the other was an oral administration (CCl4p.o.). Though AM had been recognized to be non-metabolized in the liver, AM has been reported to be metabolized via azo-reduction by intestinal microflora and/or in the liver to yield naphthionic acid (1-amino-4-naphthalene sulfonic acid) (NSA) after oral administration. In the present investigation, AM was metabolized also in the perfused rat liver to yield NSA, which was not excreted in the bile, but effluxed into the effluent. The hepatic clearance of AM was significantly decreased in all intoxicated livers compared with the untreated livers. The concentration of NSA effluxed in the effluent was decreased in CCl4s.c.-intoxicated livers. However, in other intoxicated livers, there was no significant difference from the untreated livers in the concentration of NSA in the effluent. The amount of AM excreted in the bile was significantly decreased in CCl4s.c.- or CCL4p.o.-intoxicated livers. In ANIT-intoxicated livers, no bile excretion was observed because of the biliary stagniation. From the results of pharmacokinetic analysis using a five-compartment model, the metabolism was not altered by all treatments investigated in the present study. Subcutaneous administration of CCl4, which caused a mild intoxication, affected only the permeability of the plasma membrane of the liver to AM, but oral administration of CCl4, which caused a severe intoxication, decreased the biliary excretion of AM as well as increased the permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Naphthylisothiocyanate↗
PubMed1986

A possible contribution of phospholipids in tissue distribution of quinidine in rats.

The tissue distribution of quinidine was investigated at three different steady-state plasma concentrations of quinidine in rats. The tissue distribution of quinidine (tissue-to-plasma concentration ratio, Ct/Cp) was studied in the liver, lung, kidney and heart and the highest distribution was found in the lung. Tissue binding characteristics of quinidine was determined in normal tissue homogenates and lipid-depleted tissue homogenates in vitro. No correlation was observed between the tissue bindings (product of association constant (K1) and number of binding sites (n), nK1) estimated in each normal tissue homogenate and the values of Ct/Cp in vivo. However, a marked decrease in the tissue binding of quinidine was observed in all lipid-depleted tissue homogenates, and the largest decrease was observed in the lung tissue. This result suggested that lipid may have an important role in the tissue binding of quinidine. However, no good relationship was observed between the values of Ct/Cp and the phospholipid contents in each tissue. In order to investigate the role of lipid in the tissue binding of quinidine, phospholipids extracted from each tissue were used for binding study. The phospholipids binding of quinidine (nK2) increased in the following order; heart less than liver less than kidney less than lung, and the plots of the values of Ct/Cp obtained in vivo against the binding ability of phospholipids (product of nK2 and the content of phospholipid in each tissue) gave a good linear relationship. Based on these observations, it was concluded that some species of phospholipids had an important and determining role in the tissue distribution of quinidine in vivo.

Animals↗