Biomedical subjects

H Koike

Publications and source records attributed to H Koike.

At least 19 recordsLinked to original sources

PubMed1992

Thermoluminescence and flash-induced oxygen yield in herbicide resistant mutants of the D1 protein in Synechococcus PCC7942.

Several strains of Synechococcus PCC7942 carrying point mutations in the gene psbA were studied by thermoluminescence and polarographic measurement of flash-induced oxygen yield. The following results were obtained: (a) Replacement of Ser-264 in D1 by Ala (mutant Di1) or Gly (mutant G264) resulting in DCMU and atrazine resistance leads to a downshift of the thermoluminescence (TL) B-band peak temperature from 40 degrees C in wild-type thylakoids to about 30 degrees C. In dark adapted samples of both mutants the TL and oxygen yield pattern induced by a train of single turnover flashes were strongly damped indicative of a high miss factor. (b) In contrast to Ser-264 mutants, replacement of Phe-255 in D1 by Tyr (mutant Tyr5) induced strong resistance to atrazine but not to DCMU and did not affect the peak termperature of the B-band and the flash-induced TL and oxygen yield patterns. In this respect mutant Tyr5 resembles the wild type. (c) No significant differences have been found between strains with single site mutations in psbAI and normal psbAII/psbAIII genes, and strains with same mutations in psbAI but additional deletion of psbAII and psbAIII. Obviously in strains were psbAI is present, PS II complexes containing gene products of psbAII and psbAIII are not assembled in detectable amounts. (d) Strains with double mutations at positions 264 and 255 display a downshift of the B-band peak temperature. Their oscillatory patterns of B-band intensity and oxygen yield are highly damped. This behaviour is similar to strains D1 and G264 which are modified at position 264 only. We extend reports on additivity of mutation effects on herbicide binding to binding of QB. (e) Mutations at the QB site not only influence the binding of QB and herbicides but also change the thermoluminescence quantum yield and the lifetimes of the redox states S2 and S3 of the water oxidase. This finding might indicate long ranging effects on Photosystem II exerted by structural modifications of the QB site. From these data we conclude that Ser-264 is essential for binding of atrazine, DCMU and QB, whereas Phe-255 is involved in atrazine binding and its substitution by Tyr does not markedly affect QB or DCMU binding in Synechococcus PCC7942.

Atrazine↗

PubMed1992

Tissue selectivity of pravastatin sodium, lovastatin and simvastatin. The relationship between inhibition of de novo sterol synthesis and active drug concentrations in the liver, spleen and testis in rat.

Tissue selectivity of pravastatin sodium (pravastatin), lovastatin and simvastatin, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors was examined by measuring inhibition of de novo sterol synthesis and active drug concentrations in the liver, spleen and testis in rats after a single oral administration (25 mg/kg) of these drugs. Regarding tissue drug concentrations, all three drugs were liver selective: concentrations of drugs in the liver were about ten-times higher than those in the spleen and testis. On the other hand, pravastatin was far more liver selective in inhibiting sterol synthesis than two other inhibitors: pravastatin inhibited de novo sterol synthesis in the liver but minimally in the spleen and testis, whereas lovastatin and simvastatin inhibited in all three tissues. Microautoradiographic and in vitro cellular-uptake studies demonstrated that pravastatin remained in the extracellular space in the spleen, whereas the other drugs entered the cell. We conclude that pravastatin exhibits a liver-selective inhibition of sterol synthesis because the agent permeates the cell membrane in the liver, but not in non-hepatic tissues.

Animals↗

PubMed1992

Constitutive transcription of the gene for metallothionein in a cadmium-resistant yeast.

A cadmium-resistant strain of Saccharomyces cerevisiae produces a cadmium metallothionein encoded by the CUP1 gene as does a copper-resistant strain. The mechanism of expression of the gene is inducible by copper ions in the copper-resistant strain. However, assays of CUP1-specific mRNA revealed that the transcription of the CUP1 gene in the cadmium-resistant strain is constitutive and the rate of transcription is further increased by exposure to cadmium or copper ions. This result was confirmed by the appearance of constitutive-expression segregants from diploid crosses between the cadmium-resistant strain and a strain with a reporter gene having the promoter of CUP1.

Cadmium↗

PubMed1992

Synthesis and biological action of the aminotetrahydroisoquinocarbazoles and related compounds: a new class of compounds with antiarrhythmic activity.

A series of 12-aminotetrahydroisoquinocarbazoles and related compounds were synthesized using an intramolecular Diels-Alder reaction and screened for antiarrhythmic activity in chloroform-induced ventricular arrhythmias in mice. Several compounds showed more potent activity than disopyramide. There was some correlation between substituents on aromatic ring and angular position, and antiarrhythmic activity. An amino group or some functional groups containing an amino group on C-12 seemed to be essential to exhibit the activity. Ring size also influenced the activity. The compound (+)-10 (RS-2135) had the most favorable combination of antiarrhythmic activity and toxicity and was selected for further evaluation.

Action Potentials↗

PubMed1992

Detection and serotyping of rotaviruses in stool specimens by using reverse transcription and polymerase chain reaction amplification.

Direct rotavirus serotyping (VP7, G type) in stool specimens was carried out by reverse transcription and polymerase chain reaction amplification (RT-PCR) and compared to serotyping by enzyme immunoassay with monoclonal antibodies (EIA-MAb). The methods used for double-stranded (ds) RNA extraction, RT-PCR amplification, and the primers used were modified from previous reports [Gouvea et al.: Journal of Clinical Microbiology 29:519-523, 1990; Gentsch et al.: Journal of Clinical Microbiology, 1992]. For samples that were positive by both methods, the serotypes obtained were identical, however RT-PCR typing was found to be considerably more sensitive (70.4% samples serotyped) than EIA-MAb (35.6% of samples serotyped). The overall sensitivities for detection of rotavirus in stool samples by latex agglutination, enzyme immunoassay, electron microscopy, polyacrylamide gel electrophoresis, and RT-PCR were essentially the same. The results confirm that RT-PCR typing (genotyping) is extremely valuable for G typing of samples which cannot be typed by EIA-MAb. We also developed a PCR confirmation technique for serotypes 1, 2, and 4.

Acute Disease↗

PubMed1992

Eicosanoids production in endometriosis.

In order to investigate the production of eicosanoids in human endometrium, myometrium, leiomyoma, adenomyosis, normal ovary, non-endometrial cyst and endometrial cyst, slices of each tissue were incubated. 6-Keto-prostaglandin (PG) F1 alpha, thromboxane (TX) B2, PGF2 alpha and PGE2 concentrations in the incubation medium were measured by direct RIA. 6-Keto-PGF1 alpha production of adenomyosis was significantly higher than that of endometrium, myometrium and leiomyoma, especially in the menstrual phase. The production of eicosanoids in endometrial cyst was significantly higher than that of non-endometrial cyst and normal ovary. These results suggest that endometriosis is associated with increased eicosanoid production in vivo.

6-Ketoprostaglandin F1 alpha↗

PubMed1992

Correlation between dysmenorrheic severity and prostaglandin production in women with endometriosis.

The role of prostaglandins (PGs) in dysmenorrhea of endometriosis is poorly understood. The relationship between dysmenorrheic severity and prostaglandin production was investigated in endometriosis. Slices of normal myometrium, adenomyosis, normal ovary and endometrial cyst were incubated. 6-Keto-PGF1 alpha (a metabolite of PGI2), TXB2 (a metabolite of TXA2), PGF2 alpha, and PGE2 concentrations of the incubation medium were measured by RIA. The results showed that 6-keto-PGF1 alpha production in adenomyosis and endometrial cyst were significantly higher than those in normal myometrium and ovary. A direct relationship between the degree of dysmenorrheic severity and PGs production in tissue in endometriosis was observed.

6-Ketoprostaglandin F1 alpha↗

PubMed1992

Electrophysiologic effects of RS-2135, a new antiarrhythmic compound, on canine Purkinje fibers.

RS-2135 is the (+) isomer of a novel, fused carbazol derivative. The agent, when administered orally, shows long-lasting antiarrhythmic effects in several models of arrhythmia. We used standard microelectrode techniques to characterize the electrophysiological effects of the agent on canine Purkinje fibers. RS-2135 reduced the maximum upstroke velocity of the action potential (Vmax) and shortened the action potential duration (APD) in a concentration-related manner (0.3-3 microM). RS-2135 decreased Vmax at lower concentrations than disopyramide, flecainide, and mexiletine. RS-2135 shortened the effective refractory period (ERP), but significantly increased the ratio of ERP to APD90. Additionally, the effects of the (-) optical isomer of RS-2135 were compared with those of RS-2135, the (+) enantiomer. The (-) isomer was much less potent than RS-2135 in decreasing Vmax. These data suggest that RS-2135 belongs to the class I or "local anesthetic" type of antiarrhythmic agent and that the stereochemistry of the drug molecule is an important determinant of Na channel blocking activity.

Action Potentials↗

PubMed1992

Are free radicals involved in Ca(2+)-induced membrane damage of mitochondria?

Ca(2+)-Induced membrane damage of energized mitochondria has been proposed to be due to lipid peroxidation induced by Ca2+. To examine this possibility, we studied the effects of the radical scavenger, 3,5-di-tert-butyl-4-hydroxytoluene (BHT), and its derivative, 3,5-di-tert-butyl-4-methoxytoluene (MeO-BHT), on membrane damage of respiring mitochondria induced by Ca2+ in the presence of inorganic phosphate. Both compounds inhibited Ca(2+)-induced damage almost completely at 20 microM, and their effects were identical, although MeO-BHT had no radical scavenging ability. These results indicate that the protective effects of BHT and MeO-BHT are not due to their radical scavenging ability. Thus, free radicals are concluded not to be involved in Ca(2+)-induced membrane damage of mitochondria.

Animals↗

PubMed1992

Synthesis and antihypertensive activity of 3-acetoxy-2,3-dihydro-5-[2- (dimethylamino)ethyl]-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one (diltiazem) derivatives having substituents at the 8 position.

In order to improve the potency and duration of biological actions of diltiazem, a number of 1,5-benzothiazepine derivatives having the substituents at the 8 position were prepared and evaluated for their antihypertensive activity in spontaneously hypertensive rats. The introduction of methyl, ethyl, isopropyl, benzyl, methoxy, ethoxy, phenoxy, and methylthio groups increased the antihypertensive activity and prolonged duration of action, whereas cyclohexyl, cyclopentoxy, tolyloxy, p-methoxyphenoxy and phenylthio derivatives were less active than diltiazem. Among them, the 8-benzyl and phenoxy derivatives showed the most potent and long-lasting antihypertensive action.

Animals↗

PubMed1992

[Occlusion-reperfusion model of cerebral ischemia in Fischer 344 rats].

The effect of transient cerebral ischemia (from 15 to 180 min) by bilateral carotid arterial occlusion on postischemic mortality rate and the signs of nervous disorder in Fischer 344 rat was studied. Total mortality rate was 40 to 60% during 72 hr of reperfusion following 2 hr ischemia. Postischemic mortality rate did not vary distinctly with 10, 20 and 40 weeks-old.

Animals↗

PubMed1992

[A case of scrotal bladder hernia containing bladder cancer].

A 70-year-old man had a history of total laryngectomy for laryngeal cancer and bilateral inguinal hernia repair 5 years previously. The patient had suffered from difficulty with urination since then and had been treated for prostatic hypertrophy at our department. He developed microscopic hematuria from June 1991, and was admitted because a bladder tumor was detected by cystoscopy. Cystography showed a scrotal bladder hernia with filling defects in the bladder per se and the bladder hernia as well. Cystoscopy revealed tumors in the hernia and in the vicinity of the ureteral orifice. Biopsy indicated transitional cell carcinoma. Voiding cystourethrography showed normal urination and no residual urine. Excision of the tumor-containing hernia, partial cystectomy with right ureteral orifice, and reconstruction of the right inguinal canal were performed on October 25, 1991. The postoperative course was favorable and he was discharged on the 40th postoperative day. The tumors were respectively stage as TCC, G1, and pT1a, and TCC, G1 greater than G2, and pT1b. Thirty five cases of bladder hernia that have been reported in Japan. Eight cases of accompanied by cancer have been reported in Japanese (3 cases) and foreign (5 cases) literatures. These are reviewed and discussed.

Aged↗

PubMed1992

[A case of chronic toluene intoxication with atrophy of cerebrum, cerebellum and brainstem on CT and MRI].

A 28-year-old man developed neurological disorders consisting of cerebellar symptoms and dementia over a period of 8 years of inhalation of toluene. He also developed bilateral optic atrophy. CT scan and MRI revealed atrophy of cerebrum, cerebellum and brainstem. The severity of neurological symptoms corresponded with the findings of CT and MRI. Furthermore, MRI (T2) showed reduced signal intensity in bilateral thalamus. This patient was also admitted to another hospital 2.5 years ago. Compared with the previous findings, present examinations showed significant progress of the atrophy of cerebrum and brainstem. It was suggested from the results of ABR that the disturbance of the brainstem was aggravated through this period.

Adult↗

PubMed1992

[Effect of halothane on the mechanical properties of rabbit right ventricular papillary muscle in the presence of either alpha or beta stimulant positive inotropic agent].

The effects of halothane (1-3 MAC) on the isometric twitch tension, the contracture tension induced by 1 mM barium (Ba2+) in the rabbit right ventricular papillary muscles, and the transient tension response to step length change during barium contracture, were analyzed in the presence of either alpha (3 x 10(-5) M phenylephrine+10(-6) M bupranolol) or beta (10(-7) M isoproterenol) stimulants. The isometric twitch tension was significantly decreased with the administration of halothane dose dependently, in the presence of both alpha or beta stimulants. Both the time to peak (TP) and the time to half relaxation (THR) were remarkably shortened with the administration of halothane in the presence of both alpha or beta stimulants. The Ba2+ contracture tension was also decreased with the administration of halothane dose dependently in the presence of both alpha or beta stimulants. The tension transient became faster with the administration of halothane in the presence of the alpha stimulant, but not in the presence of the beta stimulant. These results suggest that halothane decreases the number of active crossbridges regardless of the inotropic states induced by the two different stimulants. Also on increase the rate of crossbridge kinetics occurs in the presence of the alpha stimulant but not in response to the beta stimulant.

Animals↗

PubMed1992

[The pharmacokinetics of intraperitoneal (IP) carboplatin (CBDCA) and dose-up study of intravenous (IV) cyclophosphamide (CPM) in combination with IP CBCDA for advanced ovarian cancer patients].

The pharmacokinetics of IP CBDCA was compared with IV CBDCA and a dose-up study of IV CPM was performed in combination with 400 mg/m2 IP CBDCA for advanced ovarian cancer patients. The maximum concentration of free platinum (F-Pt) in serum following IP CBDCA administration was approximately 1/3 that of F-Pt following IV CBDCA. F-Pt in serum remained more than 90% of total platinum following IP CBDCA until 12 hours after administration. The t1/2 of F-Pt in serum after IP CBDCA administration was two times longer when compared with t1/2 following IV CBDCA, showing the slow peritoneal clearance of CBDCA. The area under curve (AUC) following IP CBDCA was approximately 67% of AUC following IV CBDCA. Cumulative urinary secretion (CUS) of platinum following IP CBDCA was 37% of CUS after IV CBDCA. The maximum tolerable dose of IV CPM in combination with 400 mg/m2 IP CBDCA was 550-600 mg/m2. The dose limiting factor of this combination therapy was leukocytopenia. Thrombocytopenia was mild in this study. Combination of 400 mg/m2 IP CBDCA and 550-600 mg/m2 seemed to be a tolerable and repeatable therapy for most patients with advanced ovarian carcinoma. Since thrombocytopenia was mild and the pharmacokinetics showed the smaller AUC of free platinum in serum following IP CBDCA, a dose-up study for IP CBDCA should be considered.

Adenocarcinoma↗

PubMed1992

Pharmacological profile of a novel 1,5-benzothiazepine calcium antagonist.

The in vitro cardiovascular effects of a new 1,5-benzothiazepine derivative, RS-5773 ((2S,3S)-3-acetoxy-8-benzyl-2,3-dihydro-5-[2-(dimethylamino)ethyl]-2-(4- methoxy-phenyl)-1,5-benzothiazepine-4-(5H)-one hydrochloride, CAS 129173-57-5), were examined in isolated rat aorta and isolated guinea pig heart preparations. Like diltiazem or nifedipine, RS-5773 preferentially relaxed K(+)-contracted aorta rather than phenylephrine-contracted aorta, suggesting that the agent interfered with calcium channels. Vasorelaxant effects of RS-5773 on K(+)-contracted aorta was about 5 times more potent than those of diltiazem. The vasorelaxation with RS-5773 developed very slowly and was resistant to washout. The negative effects of the agent on contractile force of guinea pig papillary muscles and beating rate of guinea pig atria were not much different from those of diltiazem, although the actions of RS-5773 developed more slowly than those of diltiazem. These results indicate that RS-5773 is a diltiazem congener with vascular preference and long-lasting actions. In this respect, RS-5773 resembled clentiazem. But vascular and cardiac effects of RS-5773 developed more slowly than those of clentiazem and they were more resistant to washout.

Animals↗

PubMed1991

Phylogenetic affiliation of ancient and contemporary humans inferred from mitochondrial DNA.

Nucleotide sequence analysis of the major non-coding region of human mitochondrial DNA (mtDNA) from three major races was extended with data from 27 contemporary Mongoloids (20 from southeast Asia, seven from America) and 11 Ancient Japanese bones (five from Jomon Age; 3000-6000 years BP, six from the early modern Ainu; 200-300 years BP). In both cases, the sequence was determined directly from the polymerase chain reaction products. Based on a comparison of the 482 base pair sequences from a total of 128 contemporary humans, the nucleotide diversity is estimated to be 1.46%, which is three times higher than the corresponding value estimated from restriction-enzyme analysis of the whole mtDNA genome. The phylogenetic tree revealed that all lineages are classified into at least five clusters designated as C1-C5. C1 consists exclusively of Africans, and most Asians and Europeans formed C2, C3, C5 and C4, respectively. Phylogenetic analysis also indicated that part of the Asians, including the Japanese, subsequently diverged from the majority of Africans, and that Asians can therefore be separated into two distinct groups. Native Americans, however, appeared only in C3 and C5, suggesting that the size of the founder population was not so large during the peopling of American. Nucleotide sequences derived from ancient bones in a highly polymorphic region were also compared with those of contemporary humans. The nucleotide diversity among the 139 sequences in the region was estimated to be 2.26%. A group of ancient Japanese, including both Jomon peoples and the Ainu, showed a close phylogenetic affiliation with one group of contemporary Japanese and southeast Asians.(ABSTRACT TRUNCATED AT 250 WORDS)

Asian People↗

PubMed1991

Why is inorganic phosphate necessary for uncoupling of oxidative phosphorylation by Cd2+ in rat liver mitochondria?

The phosphate (Pi)-dependent uncoupling action of Cd2+ in oxidative phosphorylation in rat liver mitochondria was studied mainly in terms of Pi transport. Cd2+ at 2 microM caused full uncoupling in the presence of 10 mM Pi, but no uncoupling in the absence of Pi. Cd2+ released state 4 respiration after a certain lag-time, and then the respiration increased progressively with time. After its addition, Cd2+ was taken up by mitochondria in a similar period to the lag time before respiratory release. KIH-201, a potent and specific inhibitor of Pi transport via the Pi/H+ symporter, abolished the uncoupling completely. Cd2+ caused dissipation of the electric transmembrane potential (delta psi) and swelling of mitochondria in a Pi-dependent manner. Uncoupling by Cd2+ was found to take place in parallel with the uptake of Pi into mitochondria via the Pi/H+ symporter, suggesting that the uncoupling was due to acceleration of H+ influx through the Pi/H+ symporter activated by Cd2+.

Animals↗