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Biomedical subjects

H Yoshimura

Publications and source records attributed to H Yoshimura.

At least 91 records · Page 5Linked to original sources
PubMed1996

Hamster liver cytochrome P450 (CYP2A8) as a 4-hydroxylase for 2,5,2',5'-tetrachlorobiphenyl.

Metabolism of 2,5,2',5'-tetrachlorobiphenyl (TCB) was studied using liver microsomes of hamsters and two hamster P450 isoforms, CYP1A2 and 2A8. CYP2A8 catalyzed selectively 4-hydroxylation of 2,5,2',5-TCB at a rate of 21.7 pmol/min/nmol P450. In contrast, CYP1A2 showed no activity for hydroxylation of 2,5,2',5'-TCB. Immunological study revealed that rabbit antiserum against CYP2A8 almost completely inhibited the microsomal 4-hydroxylation but that against CYP1A2 did not. It was also shown that the induction pattern of CYP2A8 protein by P450 inducer was similar to that of the 4-hydroxylase activity in hamster liver microsomes. These results suggest that CYP2A8 plays a major role in the 4-hydroxylation of 2,5,2',5'-TCB in hamster liver.

Animals↗
PubMed1996

Ciliary neurotrophic factor attenuates spatial cognition impairment, cortical infarction and thalamic degeneration in spontaneously hypertensive rats with focal cerebral ischemia.

Ciliary neurotrophic factor (CNTF) has been shown to exhibit potent neurotrophic activity on peripheral and central neurons in vitro and in vivo. However, it remains to be determined whether or not CNTF rescues neuronal loss due to focal cerebral ischemia and prevents ischemia-induced disability of space navigation in rats. In the present in vivo study, we infused CNTF continuously for 4 weeks into the lateral ventricle, starting just after permanent occlusion of the left middle cerebral artery (MCA) of stroke-prone spontaneous hypertensive rats. CNTF infusion prevented the occurrence of ischemia-induced learning disability in a dose-dependent manner in rats subjected to the Morris water maze task. Subsequent histological examinations showed that cortical infarction and retrograde degeneration of the ipsilateral thalamic neurons in ischemic rats infused with CNTF were significantly less severe than those in ischemic rats infused with vehicle alone. These findings suggest that postischemic CNTF treatment prevents the occurrence of spatial learning disability in rats with permanent MCA occlusion, possibly by reducing neuronal damage within the cerebral cortex and secondary retrograde degeneration of the thalamus.

Analysis of Variance↗
PubMed1996

Interleukin-6 prevents ischemia-induced learning disability and neuronal and synaptic loss in gerbils.

Interleukin-6 (IL-6) has been shown to have potent neurotrophic activity on peripheral and central neurons in vitro. However, it remains to be determined whether or not IL-6 rescues hippocampal CA1 neurons from lethal ischemia and prevents ischemia-induced learning disability. In the present in vivo study, we infused IL-6 continuously for 7 days into the lateral ventricle of gerbil starting 2 h before 3-min forebrain ischemia. IL-6 infusion prevented the occurrence of ischemia-induced learning disability in a dose-dependent manner as revealed by a step-down passive avoidance task. Subsequent light and electron microscopic examinations showed that pyramidal neurons in the CA1 region of the hippocampus as well as synapses within the strata moleculare, radiatum and oriens of the region were significantly more numerous in gerbils infused with IL-6 than in those receiving vehicle infusion. These findings suggest that IL-6 has a trophic effect on ischemic hippocampal neurons.

Animals↗
PubMed1996

Purification of a phenobarbital-inducible UDP-glucuronosyltransferase isoform from dog liver which catalyzes morphine and testosterone glucuronidation.

A morphine UDP-glucuronosyltransferase (UGT) which could belong to the UGT2B subfamily was isolated from liver microsomes of a male beagle dog treated with phenobarbital. Glucuronidation toward morphine in the dog liver microsomes was increased threefold by the treatment. The microsomes were solubilized with Emulgen 911 and applied on a column of hemisuccinate derivative of Sepharose 4B column which has been developed in our laboratory. An isoform of UGT in the eluate was purified further by chromatofocusing and UDP-hexanolamine-affinity chromatography. A purified enzyme, UGTDOG-PB, was homogeneous on sodium dodecyl sulfate polyacrylamide gel electrophoresis and two-dimensional electrophoresis and exhibited a subunit molecular weight of 50 kDa. This isoform showed activities toward the 3-hydroxyl group of morphine, 4-hydroxybiphenyl, 4-nitrophenol, 4-methylumbelliferone, and testosterone, but not toward chloramphenicol and the 6-hydroxyl group of morphine. The substrate specificity of UGTDOG-PB is similar to that of stably expressed UGT2B1 which is considered a phenobarbital-inducible morphine UGT in the rat except that UGTDOG-PB is capable of glucuronidating 4-nitrophenol but not chloramphenicol. The NH2-terminus until the 30th residue of UGTDOG-PB is highly homologous to UGT2B subfamily, and the NH2-terminal 15 residues of UGTDOG-PB are completely identical to those of UGT2B1, UGT2B8, and UGT2B15. This is the first report describing the UGT isoform of dog and the purification of morphine UGT which may belong to UGT2B subfamily.

Amino Acid Sequence↗
PubMed1996

Simultaneous early gastric cancer in identical twins: report of a case.

We report the unusual case of identical male twins developing early gastric cancers that were found almost simultaneously. A 39-year-old man underwent a barium-swallow examination to investigate the cause of right hypochondrial discomfort; the examination revealed evidence of gastric cancer in the upper body of the stomach. A diagnosis of adenocarcinoma was confirmed by endoscopic biopsy, and a total gastrectomy was performed. Subsequent screening of the patient's asymptomatic identical twin revealed gastric cancer in the lower body of the stomach, for which distal gastrectomy with Billroth I reconstruction was performed. The histopathological types of the two cancers were similar and both had infiltrated the submucosa. The relevant etiological factors contributing to the development of gastric adenocarcinoma in these identical twins is discussed, following the case report.

Adenocarcinoma↗
PubMed1996

Simplified physiological pacing after cardiac surgery.

Temporary pacing wires are routinely placed at the end of cardiac surgery. These pacing wires are helpful in maintaining patients with postoperative bradycardias, and physiological pacing is also more desirable in critically ill patients. We herein report our simplified procedure for atrial pacing. This technique uses commercially available intravenous pacing catheters. The catheter is passed through the skin, and its tip is placed at the pericardial oblique sinus just between the right and left pulmonary veins. Atrial pacing is then initiated with a temporary pulse generator. This procedure is simple and effective for patients undergoing cardiac surgery. We also report two clinical cases that satisfactorily underwent atrial pacing using this procedure.

Adult↗
PubMed1996

Phyllodes tumor in epileptics: a report of two cases.

Phyllodes tumor is an uncommon breast neoplasm characterized by a proliferation of both stromal and epithelial elements. In 1989, two young patients with phyllodes tumors were referred to our surgical department because of the detection of breast lumps. Interestingly, both patients also had epilepsy and had been taking anticonvulsants. An analytical case control study revealed that no significant difference between the control group and phyllodes group was found for various categories. In addition, no anticonvulsant medication had been prescribed in either the control group or the phyllodes group except for these two cases. We herein report two cases of phyllodes tumors occurring in two young epileptic patients.

Adolescent↗
PubMed1996

Ginseng root prevents learning disability and neuronal loss in gerbils with 5-minute forebrain ischemia.

The present study was designed to investigate the possible neuroprotective activity of ginseng roots in 5-min ischemic gerbils using a step-down passive avoidance task and subsequent neuron and synapse counts in the hippocampal CA1 region. The following drugs were administered for 7 days before the induced ischemia: red ginseng powder (RGP), crude ginseng saponin (CGS), crude ginseng non-saponin (CGNS), and pure ginsenosides Rb1, Rg1 and Ro. Oral administration of RGP significantly prevented the ischemia-induced decrease in response latency, as determined by the passive avoidance test, and rescued a significant number of ischemic hippocampal CA1 pyramidal neurons in a dose-dependent manner. Intraperitoneal injections of CGS exhibited a similar neuroprotective effect. CGNS had a significant but less potent protective effect against impaired passive avoidance task and degeneration of hippocampal CA1 neurons. Ginsenoside Rb1 significantly prolonged the response latency of ischemic gerbils and rescued a significant number of ischemic CA1 pyramidal neurons, whereas ginsenosides Rg1 and Ro were ineffective. Postischemic treatment with RGP, CGS or ginsenoside Rb1 was ineffective. The neuroprotective activities of RGP, CGS and ginsenoside Rb1 were confirmed by electron microscopy counts of synapses in individual strata of the CA1 field of ischemic gerbils pretreated with the drugs. These findings suggest that RGP and CGS are effective in the prevention of delayed neuronal death, and that ginsenoside Rb1 is one of the neuroprotective molecules within ginseng root.

Animals↗
PubMed1996

Anterior pulmonary translocation without conduit for the repair of truncus arteriosus.

A technique with autologous tissue for the correction of type III truncus arteriosus is described. The truncal root was excised as a cylinder that incorporated pulmonary arteries and that was translocated anterior to the ascending aorta. The proximal section of the cylinder was closed and the pulmonary tract was reconstructed with anastomosis of a widely opened distal section to the right ventricle. Autologous pericardium was sutured to the entire surface of the pulmonary tract.

Anastomosis, Surgical↗
PubMed1996

Correction of truncus arteriosus with autologous arterial flap in neonates and small infants.

BACKGROUND: This study describes the results of techniques using the autologous truncal wall and part of the pulmonary artery for correction in anticipation of the growth of the pulmonary tract in patients with truncus arteriosus. METHODS: Seven consecutive patients with truncus arteriosus were reviewed. The posterior wall of the pulmonary tract was obtained by anastomosing the lower edge of the truncal arteriotomy to the upper corner of the ventriculotomy from the truncus in types I and II. Anterior translocation of the pulmonary artery was performed in a type III. A pericardial patch with or without a monocusp was placed to complete the right ventricular outflow tract. RESULTS: There were two hospital deaths, one of which was unrelated to a cardiac problem. Postoperative right-to-left ventricular peak pressure ratio was less than 0.55. There was one left pulmonary stenosis due to monocusp adherence in the late postoperative period. The sizes of the pulmonary tract at anastomosis were between 107% and 166% of the normal value between 7 months and 3.8 years of follow-up. CONCLUSIONS: The use of autologous arterial wall instead of a conduit is recommended for the repair of truncus arteriosus to expect growth of the pulmonary tract.

Follow-Up Studies↗
PubMed1996

Involvement of cytochrome b5 in the metabolism of tetrachlorobiphenyls catalyzed by CYP2B1 and CYP1A1.

The role of cytochrome b5 in the cytochrome P450 (CYP)-dependent hydroxylation of tetrachlorobiphenyl (TCB) isomers was examined using a reconstituted mixed function oxygenase (MFO) system containing purified CYP2B1 or 1A1, and rat liver microsomes. Hydroxylations of 2,2',5,5'- and 3,3',4,4'-TCBs were catalyzed mainly by CYP2B1 and 1A1, respectively, in the reconstituted MFO system and those of 2,3',4',5- and 2,3',4,4'-TCBs were mediated by both cytochrome P450 systems. The activity toward 2,2',5,5'- and 2,3',4',5-TCB was significantly increased 6.5- and 5.5-fold, respectively, by addition of cytochrome b5 in the reconstituted MFO system containing of CYP2B1. Either hydroxylation activity toward 2,3',4,4'-TCB with the CYP2B1 system was very low or decreased by addition of cytochrome b5. These results suggest that the involvement of cytochrome b5 to the hydroxylation of TCBs is dependent on the TCB congener being metabolized, and the cytochrome P450 isoform involved in its metabolism.

Animals↗
PubMed1996

Analysis of micronucleus induction of pyrimethamine in in vitro CHL cells and in in vivo mouse bone marrow cells.

In vivo and in vitro mutagenicity of pyrimethamine were examined in the micronucleus test. Pyrimethamine strongly induced micronuclei in a dose-dependent manner in the in vitro micronucleus test using the Chinese hamster lung (CHL) cell line, when treated at 0.2-1.6 micrograms/ml for 48 h. The in vivo micronucleus test was carried out in mice after the first, second, third and fourth administration of doses up to 40 mg/kg p.o. The results showed no increased frequency of micronuclei after any treatment, though pyrimethamine was shown to persist at levels > 2 micrograms/ml in plasma after a single oral administration of 50 mg/kg.

Animals↗
PubMed1996

Microsomal aldehyde oxygenase (MALDO): purification and characterization of a cytochrome P450 isozyme responsible for oxidation of 9-anthraldehyde to 9-anthracenecarboxylic acid in monkey liver.

Oxidative activity of 9-anthraldehyde (9-AA) to 9-anthracenecarboxylic acid in monkey liver was mainly located in microsomes. The reaction required NADPH as an essential cofactor and was significantly inhibited by SKF 525-A, metyrapone, disulfiram, and CO, potent inhibitors of microsomal aldehyde oxygenase (MALDO). Two cytochrome P450 isozymes, named P450JM-A and P450JM-C, which mediate the oxidative biotransformation of 9-AA were purified from hepatic microsomes of untreated male and female Japanese monkeys, respectively. These isozymes each showed a single band of molecular mass 51,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The NH2-terminal amino acid sequences of P450JM-A and P450JM-C are highly homologous with those of several P450s belonging to the CYP2A and CYP2B subfamilies, respectively. The anti-P450JM-C antibody significantly suppressed 9-AA MALDO activity in monkey liver, but anti-P450JM-A antibody did not. The antibody against CYP2C11, which is a major isozyme responsible for 9-AA MALDO in male rat liver, also inhibited the activity. These results indicate that P450JM-C and isozyme(s) immunologically related to CYP2C11 predominantly possess MALDO activity toward 9-AA.

Amino Acid Sequence↗
PubMed1996

Prognostic significance of proliferating cell nuclear antigen (PCNA) in squamous cell carcinoma of the esophagus.

Proliferating cell nuclear antigen (PCNA) has been shown to be of prognostic significance in some gastrointestinal tumors. Immunohistochemical analysis was performed to determine whether PCNA is useful for predicting the outcome of patients with squamous cell carcinoma of the esophagus. Using a mouse monoclonal antibody, PC 10, the expression of PCNA was studied in resected squamous cell carcinomas of the esophagus from 59 patients who had undergone curative esophagectomy. None had received any preceding therapy. The proliferation rate was assessed in terms of the percentage of the PCNA-positive nuclear area relative to the total area of cancer nuclei using a cell analysis system (CAS). Clinicopathological variables including PCNA staining were assessed in relation to prognosis. Survival rate was obtained by the Kaplan-Meier method. The PCNA indices (percentage of the positive nuclear area) of the tumors varied from 4.4% to 96.2%. Among the clinicopathological variables, only tumor size (5 cm) and depth of invasion were correlated significantly with PCNA index (P<0.05). Microscopically, PCNA was stained in non-keratinized cells but not in keratinized cells. However the histological grade was not correlated with PCNA index. The survival rate was significantly worse in patients with high PCNA indices (> or = 40%) than in those with low indices (<40%) (P<0.05). However, multivariate analysis revealed that PCNA index was not an independent prognostic factor.

Aged↗
PubMed1996

Acute changes in left atrial and left ventricular diameters after physiological pacing.

The present study examined alterations in left atrial diameter (LAD) and diastolic left ventricular diameter (LVDd) in 37 patients (72.2 +/- 9.8 years old) who received physiological pacemakers; 22 with atrioventricular (AV) block and 15 with sick sinus syndrome (SSS). After pacemaker implantation, LAD and LVDd were serially measured using echocardiography, and their diameters were expressed per body surface area (LADI and LVDdI; mm/m2). Pulmonary capillary wedge pressure (PCWP) and cardiac output (CO) were measured in ten patients with SSS and ten with AV block during both right ventricular and AV sequential pacing. After AV sequential pacing, CO increased in 19 of 20 patients (3.2 +/- 0.9 L/min to 3.9 +/- 1.0 L/min; P < 0.001). LADI decreased from 24.9 +/- 4.2 mm/m2 to 21.8 +/- 4.4 mm/m2 (P < 0.001) in 22 patients with AV block and from 24.1 +/- 3.4 mm/m2 to 20.4 +/- 3.8 mm/m2 (P < 0.001) in 15 SSS patients. However, LVDdI did not change significantly in either group of patients. The changes in LAD after the implantation of a physiological pacemaker occurred rapidly, i.e., LAD began to decrease within 1 minute after the procedure, and then reached a plateau. This plateau phase continued for at least 7 days during physiological pacing. There was a positive correlation between the changes in LADI after pacemaker implantation and those in PCWP observed during the AV sequential pacing performed prior to the implantation (r = 0.86; P < 0.001). The reduction in LAD following pacemaker implantation was rapid and seemed to be accompanied by improvement of cardiac function. Thus, it is suggested that the serial measurement of LADI is useful to predict the efficacy of physiological pacemaker implantation.

Aged↗
PubMed1996

Inhibition of anandamide amidase activity in mouse brain microsomes by cannabinoids.

Mouse brain microsomes contain an amidase that catalyzes the hydrolysis of N-arachidonylethanolamide to arachidonic acid and ethanolamine. The enzymatic activity is dependent on the protein concentration of the microsomes and observed over a wide range of pH, 7.4 to 9.5. Kinetic analysis indicated that K(m) (microM) and Vmax (nmol/min/mg protein) were 17.7 +/- 4.1 and 1.81 +/- 0.32, respectively. Cannabidiol (CBD), cannabinol (CBN) and delta 9-tetrahydrocannabinol (delta 9-THC) significantly inhibited the hydrolysis of the amide by mouse brain microsomes. At a concentration of 160 microM, the inhibitory potency decreased in the following order, CBD (66%) > CBN (46%) > delta 9-THC (31%).

Amidohydrolases↗