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Biomedical subjects

H Sakurai

Publications and source records attributed to H Sakurai.

At least 145 records · Page 8Linked to original sources

Cardiogenic shock triggered by verapamil and atenolol: a case report of therapeutic experience with intravenous calcium.

Cardiogenic shock developed in a 72-year-old Japanese woman during combination therapy with verapamil and atenolol for recurrent supraventricular arrhythmia. She had coronary atherosclerosis, liver cirrhosis and bradycardia-tachycardia syndrome. Despite of the high-dose catecholamines and counterpulsation, she progressively deteriorated. Bolus administration of intravenous calcium chloride (CaCl2) immediately resolved her hemodynamic collapse.

Adrenergic beta-Antagonists↗

Health effects of chronic exposure to polychlorinated dibenzo-P-dioxins (PCDD), dibenzofurans (PCDF) and coplanar PCB (Co-PCB) of municipal waste incinerator workers.

A national survey of polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF) in emission gases from the municipal waste incinerators in 1997 revealed that the Nose Bika Center was heavily contaminated by PCDF. Ninety-four workers underwent a physical examination, and blood biochemistry, lymphocyte marker, and NK activity studies were carried out, along with blood dioxin measurements. Information on working history, life-style, and dietary habits was obtained by questionnaire and interview. The blood dioxin levels were as follows. The median TEQ of dioxins was 39.7 pg I-TEQ/g lipid, and the range was 13.3 to 805.8. The median 2,3,7,8-TCDD concentration was 3.9 pg TEQ/g lipid, and the range was <1 pg TEQ/g lipid (one case) to 13.4 pg TEQ/g lipid. The median TEQ of coplanar PCB was 10.8 pg I-TEQ/g lipid, and the range was 3.1 to 54.2 pg TEQ/g lipid. The congener-specific distribution was quite similar to that in soil around incinerator and waste in the factory. The relationship between dioxin concentrations and work history in the factory showed that the fluidized incinerator and fly ash treatment areas were high-risk work areas. Correlation analyses between body burden, PCDD/PCDF TEQ, Co-PCB TEQ and various laboratory data showed significant positive correlations between dioxin levels and GGT, total protein, uric acid and calcium, and a negative correlation with Fe. However, these correlations disappeared as a result of multivariate analysis adjusted for age, smoking status, and alcohol drinking. Increased NK activity and lower response to PHA stimulation remained significant even after adjusting for age. History of hyperlipidemia and allergy had significantly increased odds ratios. A study on the risk to other workers in the same type of incinerators is under way. Health effects of chronic exposure mainly to PCDF will be clarified by follow-up.

Adolescent↗

Relationship between the blood coagulation-fibrinolysis system and the subclinical indicators of arteriosclerosis in a healthy male population.

A cross-sectional observation was performed to assess the relationship between the coagulation-fibrinolysis system and the subclinical indicators of arteriosclerosis in a healthy male population. Subjects were 445 workers (18.9-49.4, Av. 36.2 yrs) in viscose rayon manufacturing factories in Japan. Coagulation-fibrinolysis parameters determined were D-dimer(DD), thrombin antithrombin III complex (TAT), tissue plasminogen activator (TPA), and plasminogen activator inhibitor 1 (PAI1). The following indicators of arteriosclerosis were examined; systolic and diastolic blood pressure (SBP, DBP), stiffness parameter of the carotid artery using ultrasound (beta), pulse wave velocity of the aorta (PWV), and a number of lacunar infarctions from brain MRI. After age-stratification(-29, 30-39, 40+ yrs), the subjects were classified into quartiles by coagulation-fibrinolysis parameters. The mean values of SBP and DBP and beta and PWV, the prevalence of brain infarctions were compared across these quartiles by means of analysis of variance, chi-square test, respectively. Multivariate analysis was also employed to adjust other risk factors. In conclusion, SBP and DBP and beta, PWV were elevated by increase of PAI1, TAT, respectively, in the 40+ years group even after adjustment for other possible risk factors. DD had no relation to any of the indicators of arteriosclerosis. None of the coagulation-fibrinolysis parameters had any relation to brain infarctions.

Adolescent↗

Carcinogenicity and other health effects of acrylonitrile with reference to occupational exposure limit.

The occupational exposure limit for acrylonitrile (AN) has been set by many organizations on the basis of its carcinogenicity. However, recent epidemiological studies do not afford evidence supporting the hypothesis that AN is carcinogenic to humans. Review of the 18 published cohort studies revealed that, although there is not adequate evidence in humans for carcinogenicity of AN, the possibility of a causal association between high exposure to AN and lung cancer in humans cannot be excluded. It was pointed out that carcinogenic potential of AN may be weak, if any, to humans, and the current occupational exposure limit (OEL) for AN of 2 ppm was evaluated as appropriate in view of AN exposure levels reported by epidemiological studies. Based also on review of the literature on health effects other than carcinogenicity, it was concluded that the current OEL for AN is a reasonable value and there is no need for a revision at present.

Acrylonitrile↗

[Relation between hippocampal damage and cerebral cortical function in Alzheimer's disease].

We investigated the relation between hippocampal damage and cerebral cortical dysfunction in Alzheimer's disease (AD) using MRI and SPECT. Nineteen patients with AD and 10 control subjects were studied. Hippocampal damage (including hippocampal formation, entorhinal cortex, and parahippocampal white matter) was assessed to evaluate the severity of atrophy and the magnetization transfer ratio (MTR) and cerebral cortical dysfunction was evaluated by quantitative cerebral blood flow (CBF) measurements using SPECT with 99mTc-ECD. Compared with controls, patients with AD had significantly more atrophy of the medial temporal lobe and a decrease in MTRs of the hippocampus and parahippocampus. There were significant correlations between the severity of hippocampal damage and regional CBF in temporoparietal lobes. Mini-Mental State Examination scores significantly correlated with the severity of hippocampal damage and regional CBFs in temporoparietal lobes. These results suggest that the functional effect of hippocampal damage occurs in temporoparietal lobes in AD, probably due to neuronal disconnections between hippocampal areas (including the entorhinal cortex) and temporoparietal lobes.

Aged↗

Lysophosphatidylcholine enhances superoxide anions production via endothelial NADH/NADPH oxidase.

Reactive oxygen species (ROS) including superoxide anions (O2(-)) play a key role in atherogenesis, and endothelial cells have the ability to generate ROS. To investigate the enzymatic sources of ROS and the effects of lysophosphatidylcholine (LPC), an atherogenic lipid, we measured ROS production in cultured bovine aortic endothelial cells (BAECs) by the lucigenin-enhanced chemiluminescence (CL) method and electron spin resonance (ESR). BAEC homogenates had the enzymatic activity of NADH/NADPH oxidase. BAECs cultured on microcarrier beads generated O2(-) under basal conditions. The inhibition of NADH/ NADPH oxidase by diphenylene iodonium (DPI) significantly attenuated O2(-) production, whereas no inhibitors of other oxidases suppressed it. Although LPC enhanced O2(-) production approximately 3.1-fold, its action was suppressed by DPI. Tyrosine kinase inhibitors significantly attenuated LPC-induced O2(-) production. ESR with DMPO demonstrated that LPC increased the formation of the DMPO-hydroxyl adduct in dose- and time-dependent manners. These data suggest that the basal production of O2(-) in endothelial cells is mainly mediated by the NADH/NADPH oxidase system and that LPC activates this oxidase to enhance O2(-) production through a tyrosine kinase-dependent pathway. The enhancement of ROS production by LPC is probably involved in its atherogenic property.

Acridines↗

Microsurgical reconstruction of the thermally injured upper extremity.

The use of free flaps for coverage of the deeply burned hand has advantages that include the salvage of the exposed vessels, nerves, tendons, joints, and bone; a single operation to obtain wound closure, minimizing the risk of infection; and earlier physical therapy. This article focuses on the choice of suitable free flaps for the coverage of the deeply burned hand; and it also presents some case reports.

Adult↗

[Evaluation of cardiac autonomic nerves by iodine-123 metaiodobenzylguanidine scintigraphy and ambulatory electrocardiography in patients after arterial switch operations].

The autonomic cardiac nerves reach the heart after passing through the vicinity of the aortic root and the pulmonary trunk. The arterial switch operation (ASO) completely transects the ascending aorta and the pulmonary trunk. Therefore, this surgical procedure virtually denerves the heart. Cardiac sympathetic denervation and reinnervation were evaluated in patients after ASO using iodine-123 metaiodobenzylguanidine (MIBG) myocardial scintigraphy and parasympathetic denervation and reinnervation using ambulatory electrocardiography [Holter electrocardiogram (ECG)]. MIBG scintigraphy was performed in 14 patients who underwent ASO (ASO group) and 3 patients who underwent other open heart surgery (control group). All patients in the ASO group underwent the operation in the neonatal or infantile period. Planar and single photon emission computed tomography (SPECT) images of the myocardium were obtained. Defect score was determined by the SPECT images as a semi-quantitative index. The mean interval between ASO and MIBG scintigraphy was 25.6 +/- 14.6 months. Holter ECG was also performed in 14 patients in the ASO group and 19 age-matched normal children. The Holter ECGs were plotted on a Lorenz plot. The H index, which is related to vagal tone for the cardiovascular system, was calculated from the R-R intervals. The mean interval between the ASO and Holter ECG was 8.3 +/- 9.7 months. MIBG scintigraphy in the control group demonstrated an almost normal homogeneous tracer uptake, but showed extremely reduced tracer uptake and significantly higher defect score in the ASO group. The extent and degree of the reduction of MIBG uptake improved with time after the ASO. The heart-to-mediastinum MIBG count ratio tended to increase with time. The H index of the ASO group was lower than that of normal children (< 12 months: Control group 0.0280 +/- 0.0068 vs ASO group 0.0219 +/- 0.0083), and gradually increased with time (1-3 years: 0.0470 +/- 0.0157 vs 0.0314 +/- 0.0124). These results indicate that MIBG scintigraphy reflects the presence of sympathetic denervation and the possibility of reinnervation after ASO, and that H index reflects the presence of parasympathetic denervation and the possibility of reinnervation after ASO. These are simple and useful methods for assessing the extent and degree of autonomic denervation and reinnervation.

3-Iodobenzylguanidine↗

Successful treatment of IBL-like T-cell lymphoma with cyclosporin A: two case reports with special reference to serum cytokine levels.

The prognosis of immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma is grave, and its effective treatments have not been established. We applied oral cyclosporin A (CsA) treatment to two cases of IBL-like T-cell lymphoma, and succeeded in achieving complete remissions. CsA is known to have a suppressive effect on the immune system, most notably T-cells, but it also has a direct cytotoxic/apoptosis-inducing effect on lymphocytes. Its combined effects on neoplastic T-cells might have played an important role in achieving remission. In both cases, serum levels of interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF-alpha) were elevated and decreased or returned to normal after achieving remissions. Considering that both cytokines represent monokines, it seems that a macrophage system is also involved in the pathogenesis of this disorder. Our two cases indicate that administration of CsA may be an effective therapy for IBL-like T-cell lymphoma.

Administration, Oral↗

[Mid-term results of the arterial switch operation for transposition of the great arteries: effect of fresh autologous pericardial patch in preventing postoperative pulmonary stenosis].

To evaluate the differences in patch-materials used to reconstruct the pulmonary artery in arterial switch operation for transposition of the great arteries, we compared mid-term results in 50 consecutive survivors who underwent arterial switch operation. In 35 patients (XP-group), the pulmonary artery was reconstructed using a glutaraldehyde-treated heterologous pericardial patch, while in 15 patients (AP-group) it was reconstructed using a fresh autologous pericardial patch. A W-shaped patch was used in 14 patients of the XP-group. In 21 patients of the XP-group and all those of the AP-group, a square patch was used. The mean length of follow-up has been 94.1 +/- 38.1 months after surgery in XP-group, and 16.7 +/- 11.8 months in AP-group, respectively. Four patients in XP-group required balloon angioplasty for pulmonary stenosis and 5 patients in XP-group underwent reoperation, but no patients in AP-group required balloon angioplasty or reoperation for pulmonary stenosis. The risk factors influencing postoperative pulmonary stenosis (sex, age at surgery, preliminary pulmonary artery banding, patch shape and material) were analyzed by multiple regression analysis. The patch material (heterologous patch) was the only identifiable risk factor for pulmonary stenosis. These data suggest that pulmonary artery reconstruction with an autologous pericardial patch may be effective to prevent postoperative pulmonary stenosis, although the long-term prognosis remains unknown.

Female↗

[Modified Konno procedure for a child with left ventricular outflow tract obstruction after repair of atrioventricular septal defect: a transaortic transpulmonary approach].

A one-year-old infant underwent repair of atrioventricular septal defect with common orifice. About 2 years later, echocardiography revealed a left ventricular outflow tract obstruction for the first time. Because of progression of the obstructive lesion, a modified Konno procedure through a transaortic transpulmonary approach was later performed at 8 years old, and the postoperative course was uneventful. This is a useful procedure for left ventricular outflow tract obstruction with normal aortic valve and aortic annulus, because it can both preserve a native aortic valve and dose not necessitate right ventriculotomy in resection of hypertrophied muscle and patch enlargement of interventricular septum.

Aorta↗

Potentially lethal damage repair and its inhibitory effect of caffeine in two yolk sac tumor cell lines with different radiosensitivities.

PURPOSE: In order to investigate the role of potentially lethal damage repair (PLDR) in cellular radiosensitivity, PLDR and its inhibitory effect by caffeine was examined. In addition, cell cycle distribution was also examined. MATERIALS AND METHODS: Two rat yolk sac tumor cell lines, NMT-1 and NMT-1R, with different radiosensitivities in vitro were used. The capacity for PLDR was examined using confluent-phase cells, and evaluated by calculating the recovery ratio. Inhibitory effect of caffeine on PLDR was examined with doses of 1, 5 and 10 mM. RESULTS: The capacity of PLDR in two cell lines reflected radiosensitivity. The recovery ratio after irradiation of 5 Gy was 2.8 in the radiosensitive NMT-1 and 5.2 in the radioresistant NMT-1R, and recovery reached its peak level at 6 h in both cell lines. The degree of inhibition of PLDR was weaker in NMT-1R than that in NMT-1 at the same dose level, and was correlated with reduction of G2-arrested cells by caffeine. CONCLUSIONS: The results of this study suggest that the capacity of PLDR may be one of the determinant factors for radiosensitivity in the two cell lines used, and the inhibitory effect of caffeine on PLDR was in part attributable to the modification of the cell cycle progression.

Animals↗

Molecular cloning of rat ATX1 homologue protein.

An ATX1 homologue of 503 bp length was cloned from a rat cDNA library, and the deduced protein from the cDNA was found to contain 68 amino acids with a predicted molecular mass of 7.2 kDa. The rat ATX1 homologue protein (Rah1p), which shows 35%, 38%, and 89% identities with Atx1p, CUC-1, and HAH1, respectively, conserves both the MTCXXC copper-binding site in the N terminus and the KTGK lysine-rich region in the C terminus. In Northern blot analysis, rah1 mRNA was found to be expressed at high levels in the liver, small intestine, and testis. Expression of rah1 cDNA complemented a null atx1 mutant strain in yeast. Thus, Rah1p was concluded to be a functional copper chaperone.

Amino Acid Sequence↗

IkappaB kinases phosphorylate NF-kappaB p65 subunit on serine 536 in the transactivation domain.

Recent investigations have elucidated the cytokine-induced NF-kappaB activation pathway. IkappaB kinase (IKK) phosphorylates inhibitors of NF-kappaB (IkappaBs). The phosphorylation targets them for rapid degradation through a ubiquitin-proteasome pathway, allowing the nuclear translocation of NF-kappaB. We have examined the possibility that IKK can phosphorylate the p65 NF-kappaB subunit as well as IkappaB in the cytokine-induced NF-kappaB activation. In the cytoplasm of HeLa cells, the p65 subunit was rapidly phosphorylated in response to TNF-alpha in a time dependent manner similar to IkappaB phosphorylation. In vitro phosphorylation with GST-fused p65 showed that a p65 phosphorylating activity was present in the cytoplasmic fraction and the target residue was Ser-536 in the carboxyl-terminal transactivation domain. The endogenous IKK complex, overexpressed IKKs, and recombinant IKKbeta efficiently phosphorylated the same Ser residue of p65 in vitro. The major phosphorylation site in vivo was also Ser-536. Furthermore, activation of IKKs by NF-kappaB-inducing kinase induced phosphorylation of p65 in vivo. Our finding, together with previous observations, suggests dual roles for IKK complex in the regulation of NF-kappaB.IkappaB complex.

Amino Acid Sequence↗

Involvement of singlet oxygen in cytochrome P450-dependent substrate oxidations.

Cytochrome P450 (P450)-dependent p-hydroxylation of aniline and o-deethylation of 7-ethoxycoumarin were examined in rat liver microsomes in the presence of radical scavengers. The addition of beta-carotene, a quencher of singlet oxygen species ((1)O(2)), suppressed the aniline hydroxylation, while the addition of sodium azide (NaN(3)) ((1)O(2) quencher) enhanced the reaction. No other reactive oxygen scavengers or chelating agents such as superoxide dismutase, catalase, dimethylsulfoxide, or deferoxamine altered the reaction. In contrast, the microsomal o-deethylation of 7-ethoxycoumarin was suppressed by the addition of NaN(3). (1)O(2) was detectable during the reaction of microsomes and NADPH by ESR spin-trapping when 2,2,6,6-tetramethyl-4-piperidone (TMPD) was used as a spin trap, and the (1)O(2) was quenched by the additions of beta-carotene, NaN(3), aniline, and 7-ethoxycoumarin. The enhancement effect of NaN(3) in the hydroxylation of aniline appeared to be due to the conformational change of P450 protein, which in turn enhances the binding of aniline to P450 in terms of the spectral dissociation constant (K(s)). In contrast, (1)O(2) appeared to be active in the o-deethylation of 7-ethoxycoumarin. On the basis of the results, the involvement of (1)O(2) in P450-dependent substrate oxygenations is proposed.

7-Alkoxycoumarin O-Dealkylase↗

Electron transfer kinetics in purified reaction centers from the green sulfur bacterium Chlorobium tepidum studied by multiple-flash excitation.

Reaction center preparations from the green sulfur bacterium Chlorobium tepidum, which contain monoheme cytochrome c, were studied by flash-absorption spectroscopy in the near-UV, visible, and near-infrared regions. The decay kinetics of the photooxidized primary donor P840(+), together with the amount of photooxidized cytochrome c, were analyzed along a series of four flashes spaced by 1 ms: 95% of the P840(+) was reduced by cytochrome c with a t(1/2) of approximately 65 micros after the first flash, 80% with a t(1/2) of approximately 100 micros after the second flash, and 23% with a t(1/2) of approximately 100 micros after the third flash; after the fourth flash, almost no cytochrome c oxidation occurred. The observed rates, the establishment of redox equilibrium after each flash, and the total amount of photooxidizable cytochrome c are consistent with the presence of two equivalent cytochrome c molecules per photooxidizable P840. The data are well fitted assuming a standard free energy change DeltaG degrees of -53 meV for electron transfer from one cytochrome c to P840(+), DeltaG degrees being independent of the oxidation state of the other cytochrome c. These observations support a model with two monoheme cytochromes c which are symmetrically arranged around the reaction center core. From the ratio of menaquinone-7 to the bacteriochlorophyll pigment absorbing at 663 nm, it was estimated that our preparations contain 0.6-1.2 menaquinone-7 molecules per reaction center. However, no transient signal due to menaquinone could be observed between 360 and 450 nm in the time window from 10 ns to 4 micros. No recombination reaction between the primary partners P840(+) and A(0)(-) could be detected under normal conditions. Such a recombination was observed (t(1/2) approximately 19 ns) under highly reducing conditions or after accumulation of three electrons on the acceptor side during a series of flashes, showing that the secondary acceptors can stabilize three electrons. From our data, there is no evidence for involvement of menaquinone in charge separation in the reaction center of green sulfur bacteria.

Bacterial Proteins↗