Biomedical subjects

Y Okubo

Publications and source records attributed to Y Okubo.

At least 55 records · Page 3Linked to original sources

PubMed2001

Alcohol consumption and blood pressure change: 5-year follow-up study of the association in normotensive workers.

This study endeavours to clarify the effect of alcohol consumption on changes in the blood pressure of Japanese men. The subjects, who were followed from 1990 to 1995, were 2189 male normotensive steelworkers aged from 40 to 54 years in 1990. Drinking habits were represented by two variables: average daily baseline alcohol consumption, and change in alcohol consumption during the observation period, both derived from self-report questionnaires and interviews. Nine other items were analysed as covariates: systolic and diastolic blood pressure, age, body mass index (BMI), salt intake, physical activity, and levels of gamma glutamyl transpeptidase (GTP), uric acid and plasma glucose in 1990. The association between drinking habits and blood pressure was evaluated using ANCOVA. Subjects who had initiated antihypertensive therapy by 1995 were excluded from this dataset. The results of analysis disclosed that both daily alcohol consumption and its change were significantly associated with changes in systolic and diastolic blood pressure during the observation period. J-shaped associations of daily alcohol consumption with adjusted changes in systolic and diastolic blood pressure were found. Positive associations were observed between changes in alcohol consumption and adjusted changes in systolic and diastolic blood pressure. In conclusion, daily alcohol consumption was associated non-linearly with changes in blood pressure and with a threshold effect at 18 ml of ethanol per day in these middle-aged Japanese workers. In addition, increasing alcohol consumption was associated with blood pressure elevation, and decreasing consumption was associated with suppression of blood pressure elevation.

Adult↗

PubMed2001

Evidence for association of the myo-inositol monophosphatase 2 (IMPA2) gene with schizophrenia in Japanese samples.

In our search for candidate genes for affective disorder on the short arm of chromosome 18, we cloned IMPA2, a previously unreported myo-inositol monophosphatase gene, that maps to 18p11.2. We determined its genomic structure and detected three new single nucleotide polymorphisms (SNPs). In the present study, we screened the gene further to search for additional polymorphisms in Japanese samples and identified seven other SNPs, including a novel missense mutation. These polymorphisms clustered into three regions of the gene. Three relatively informative SNPs, 58G>A, IVS1--15G>A and 800C>T from clusters 1, 2 and 3, respectively, were selected for association tests using a case-control design. The Japanese cohort included 302 schizophrenics, 205 patients with affective disorder and 308 controls. Genotyping was done either by melting curve analysis on the LightCycler or by sequencing. All three SNPs showed significant genotypic association (nominal P = 0.031--0.0001) with schizophrenia, but not with affective disorder. These findings increase the relevance of 18p11.2 to schizophrenia susceptibility because GNAL, which has been shown previously to be implicated in schizophrenia in an independent study, is in close physical proximity to IMPA2. Our findings suggest that IMPA2 or a gene nearby may contribute to the overall genetic risk for schizophrenia among Japanese.

Adult↗

PubMed2001

Ten year progressive ventricular enlargement in schizophrenia: an MRI morphometrical study.

Recent studies of the brain using magnetic resonance imaging (MRI) have suggested progressive structural changes in schizophrenics. However, those studies were conducted over periods of less than 5 years and thus lacked sufficient capacity to determine the course and nature of this process. In this study, MRI scans were obtained in 15 schizophrenics and 12 controls at baseline and after 4- and 10-year follow ups. Volumes of the lateral ventricles were measured. Patients were assessed by the Brief Psychiatric Rating Scale (BPRS) at the same two time points: at baseline and at 10-year follow up. After 10 years, a significant lateral ventricular enlargement was found in patients (mean percentage change: +22.9%) but not in controls (5.1%). Although our results are not in disagreement with the neurodevelopmental hypothesis, they do provide strong evidence that in schizophrenia progressive brain reduction occurs even in its chronic stage.

Adult↗

PubMed2001

Absence of sleep spindles in human medial and basal temporal lobes.

All-night recordings from subdural electrocorticographic (ECoG) electrodes on the human medial and basal temporal lobes were analysed to examine spindling activities during sleep. Subjects were three males and three females who were candidates for neurosurgical treatments of partial epilepsy. Subdural electrodes were attached to the medial and basal temporal lobe cortices, allowing ECoG and electroencephalogram from the scalp vertex (Cz EEG) to be recorded simultaneously during all night sleep. In one case, subdural electrodes were attached also on the parietal lobe. Fast Fourier transformation (FFT) analyses were performed on the ECoG and Cz EEG signals. No organized sleep spindles or sigma band (12-16 Hz) peaks in FFT power spectra were observed from the medial or basal temporal lobes of the non-epileptogenic hemispheres during non-rapid eye movement (NREM) sleep. In a case with parietal electrodes, organized spindle bursts were observed in parietal signals synchronized with Cz spindles. Although delta band (0.3-3 Hz) power from both the medial and basal temporal lobes fluctuated across each night as expected, sigma activity changed little. However, 14 Hz oscillatory bursts were observed in the medial basal temporal lobe of epileptogenic hemisphere in two cases and bilaterally in one case during not only NREM sleep but rapid eye movement (REM) sleep and wakefulness. From the present study we conclude that sleep spindle activities are absent in the medial and basal temporal lobes. Fourteen Hz oscillatory bursts observed from the medial or basal temporal lobe in some cases were not considered to be sleep spindles since they also appeared during REM sleep and wakefulness. These waveforms could have originated due to epileptic pathology, since they frequently appeared in epileptic regions.

Adult↗

PubMed2001

Effect of hyperbaric oxygenation on bone induced by recombinant human bone morphogenetic protein-2.

We examined the effect of hyperbaric oxygen (HBO) therapy on the osteoinductive activity of recombinant human bone morphogenetic protein-2 (rhBMP-2), 5mg of which was implanted into the calf muscle of rats using atelopeptide type I collagen as a carrier. Thirty Wistar rats were divided equally to be given HBO or act as controls. New bone formation was measured radiographically, biochemically, and histol ogically 3, 7, and 21 days after implantation. In both groups, new bone formation was found on day 21. However, there was significantly more new bone in the HBO group. In the HBO group, cartilage was present at the outer edge of the implanted material on day 7. On days 7 and 21, the local tissue alkaline phosphatase activity and calcium content in the HBO group were significantly greater than in the control group. These results suggest that HBO accelerated the activity and rate of osteoinduction by rhBM P-2.

Alkaline Phosphatase↗

PubMed2001

Application of path analysis to urinary findings of cadmium-induced renal dysfunction.

In order to identify some causal relations among various urinary indices of cadmium-induced renal dysfunction, such as glucose, total protein, amino nitrogen, beta 2-microglobulin (beta 2-m), metallothionein (MT), and cadmium (Cd), we applied path analysis method to previous epidemiological studies targeting the residents of the Cd-polluted Kakehashi River basin of Ishikawa Prefecture, Japan. We obtained a diagram-termed path model, representing some causal relations among the above urinary indices. It shows that urinary Cd is located at the beginning point in the diagram, and Cd-induced renal dysfunction develops in the following order: Cd exposure-->increase of beta 2-m and/or MT excretion-->increase of amino-N and/or total protein excretion-->increase of glucose excretion. It was proved mathematically, that in the case of both males and females, increased excretions of beta 2-m and/or MT were the most sensitive urinary indices of the early stage of chronic Cd-induced renal dysfunction.

Aged↗

PubMed2001

KT3-671, an angiotensin AT1 receptor antagonist, attenuates vascular but not cardiac responses to sympathetic nerve stimulation in pithed rats.

Effects of KT3-671 on vascular and cardiac sympathetic neurotransmission were investigated in pithed rats. The pressor response to spinal stimulation (5 Hz) of the pithed rat without the adrenals was approximately 75% of that with the adrenals. Guanethidine (8 mg/kg, i.v.) decreased by about 76% the pressor response to sympathetic stimulation in the pithed rat with intact adrenals and the guanethidine-resistant response was almost completely abolished by bilateral adrenalectomy. Therefore, the following experiments were done using the pithed rat without the adrenals. KT3-671 (1-10 mg/kg, i.v.) as well as losartan (1-10 mg/kg, i.v.) inhibited dose-dependently the pressor response to sympathetic stimulation. KT3-671 was approximately four times more potent than losartan in inhibiting the pressor response. The two angiotensin II subtype 1 receptor antagonists (10 mg/kg, i.v.) did not affect the pressor response to exogenously administered norepinephrine. Neither KT3-671 nor losartan influenced the tachycardia induced by spinal stimulation and isoprenaline. Intravenous infusion of angiotensin II (100 ng/kg/min) did not affect both pressor and tachycardic responses to sympathetic stimulation. In conclusion, KT3-671 as well as losartan inhibits vascular but not cardiac sympathetic neurotransmission of the pithed rats, which may contribute to its overall antihypertensive efficacy.

Adrenalectomy↗

PubMed2001

Lipid analysis of peripheral blood monocytes in psoriatic patients using Fourier-transform infrared microspectroscopy.

In psoriasis vulgaris, there are immunological abnormalities of T cells and monocytes. We previously demonstrated that monocytes in the peripheral blood of patients with psoriasis vulgaris are activated and produce an excess of inflammatory cytokines. It has long been suggested that fat metabolism is impaired in patients with this illness. In addition, it has been reported that macrophages activated by engulfing low density lipoprotein (LDL) immune complexes release large quantities of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta. Hence we hypothesized that the monocytes of psoriatic patients are activated by engulfing lipids and overproduce inflammatory cytokines. Therefore we measured both the serum and monocyte levels of lipids in the peripheral blood of psoriatic patients. At the same time, we calculated the psoriasis area and severity index (PASI) scores and analyzed their correlation with the lipid kinetics. The results showed that the serum cholesterol ester level and the cholesterol ester level in monocytes of psoriatic patients were significantly higher than those in healthy individuals. However, the cholesterol ester level in monocytes of patients with hyperlipidemia was also high, and there was no correlation between cholesterol ester level in monocytes of psoriatics and PASI scores. The cholesterol ester level in the monocytes of psoriatic patients was high, but this does not seem to play an important role in the pathogenesis of psoriasis.

Adolescent↗

PubMed2001

Contribution of CD54 to human eosinophil and neutrophil superoxide production.

We have reported that CD54 on eosinophils is involved in eosinophil degranulation. However, the role of CD54 in eosinophil and neutrophil superoxide production is still uncertain. We assessed the effect of CD54 on eosinophils and neutrophils in recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF)- or phorbol myristate acetate (PMA)-induced superoxide production through CD18. Anti-CD54 monoclonal antibody attenuated leukocyte aggregation and superoxide production of rGM-CSF- or PMA-stimulated neutrophils and PMA-stimulated eosinophils. Anti-CD18 monoclonal antibody or theophylline attenuated superoxide production of eosinophils and neutrophils stimulated by either stimuli. Flow cytometric analysis demonstrated CD54 expression on freshly isolated neutrophils but not on freshly isolated eosinophils. CD54 newly expressed on eosinophils reached its peak expression 30 min after PMA stimulation. The increase in CD18 and CD54 expression on neutrophils caused by rGM-CSF stimulation was partially inhibited by theophylline. These data demonstrated that CD54 and CD18 interaction of eosinophils or neutrophils is involved in superoxide production and that the inhibition of superoxide production by theophylline may be at least partly due to the inhibition of CD54 and CD18.

Analysis of Variance↗

PubMed2001

Interleukin-4 is needed for the infection of monocytes by human cytomegalovirus.

OBJECTIVE: We studied the ability of human cytomegalovirus (HCMV) to infect peripheral blood mononuclear cells (PBMC) pretreated with or without Th2-cytokine interleukin-4 (IL-4) in vitro. METHODS: Adherent cells and nonadherent cells were obtained from PBMC. We inoculated these cells with HCMV at concentrations ranging from 0 to 10 ng/ml of IL-4. Immediate-early antigen-1 (IE-1) and glycoprotein H (gH) mRNAs were detected using the reverse-transcription polymerase chain reaction. RESULTS: IE-1 and gH mRNAs could be detected in monocytes pretreated with IL-4. In contrast, no IE-1 mRNA was detected in monocytes pretreated without IL-4. We tested whether higher infectious titers could result in the infection of monocytes whether or not they were pretreated with IL-4. However, no IE-1 mRNA was detected in the monocytes not pretreated with IL-4. To elucidate how HCMV-infected monocytes affect lung tissue, human embryonic lung fibroblasts MRC-5 were cocultured with HCMV-infected monocytes. The cytopathic effects of HCMV were observed microscopically and was confirmed by direct immunoperoxidase staining with a human monoclonal antibody against the HCMV IE-1. CONCLUSION: Our data strongly suggest that the ability of HCMV to infect monocytes may correlate with the presence of IL-4.

Cytomegalovirus↗

PubMed2001

Concurrent left-sided spontaneous pneumothorax in Japanese monogerminal twins.

Monogerminal twin brothers aged 17 were admitted because of concurrent left-sided spontaneous pneumothorax. A familial background of this common disease in association with the human leukocyte antigen (HLA) has been suggested; however, the actual mode of inheritance in association with HLA typing is still uncertain. HLA analysis in this family revealed the HLA-A24, B61 (40), Cw3, DR4, DR53, and DQ3 haplotype in the twins and their father, who also had a medical history of spontaneous pneumothorax. We report these cases as an extremely rare example of familial occurrence of spontaneous pneumothorax.

Adolescent↗

PubMed2001

Theophylline inhibits TNF-alpha-induced CD4 expression on human eosinophils and CD4+ eosinophil migration.

BACKGROUND: Increasing evidence regarding asthma suggests that CD4+ cells are preferentially recruited to sites of bronchial inflammation. Interleukin (IL)-16 has been reported as playing an important role in the accumulation of CD4+ cells. We have shown that the CD4 molecule is expressed on normal human eosinophils by tumor necrosis factor (TNF)-alpha stimulation. METHODS: We evaluated the effects of theophylline, KF19514 [a selective phosphodiesterase (PDE) IV inhibitor] and dexamethasone on CD4 expression on eosinophils and eosinophil migration in response to IL-16, a natural soluble ligand of the CD4 molecule. RESULTS: The maximum eosinophil migration was observed when eosinophils were cultured with TNF-alpha at 10 ng/ml for 18 h and the concentration of IL-16 was 10 pg/ml. CD4+ eosinophil migration in response to IL-16 was mostly, if not fully, chemokinetic and this migration was significantly inhibited by Fab of anti-CD4 monoclonal antibody. Theophylline (10(-4)-10(-3) M), KF19514 (10(-7)-10(-6) M) and dexamethasone (10(-8)- 10(-6) M) significantly inhibited CD4 expression on eosinophils induced by TNF-alpha. Theophylline (10(-3) M) and KF19514 (10(-6) M) inhibited CD4+ eosinophil migratory responses induced by IL-16, but 10(-6) M dexamethasone did not. Theophylline and KF19514 augmented the intracellular adenosine-3',5'-cyclic monophosphate (cAMP) concentration in eosinophils, suggesting modulation by cAMP of CD4 expression and eosinophil migration. CONCLUSIONS: These data suggest that TNF-alpha-induced CD4+ eosinophils may contribute to eosinophil migratory responses induced by IL-16. Theophylline and selective PDE IV inhibitor may prevent airway inflammation by downregulating CD4 expression on eosinophils and inhibiting eosinophil migration through CD4 and IL-16 interaction.

CD4 Antigens↗

PubMed2001

Chemotaxis of human CD4+ eosinophils.

We reviewed the biological functions of CD4+ eosinophils, which are observed in peripheral blood, sputum and bronchoalveolar lavage fluid of various diseases. We have shown that CD4 molecules on human eosinophils are induced by tumor necrosis factor-alpha (TNF-alpha) stimulation. Interleukin-16 (IL-16) has been reported to bind a natural soluble ligand for the CD4 molecule. We reported that TNF-alpha-stimulated eosinophils migrate in a time- and dose-dependent manner against IL-16. Theophylline and dexamethasone significantly inhibited CD4 expression. Theophylline inhibited CD4+ eosinophil chemotaxis, but dexamethasone did not. Theophylline may prevent airway inflammation by downregulating the expression of CD4 molecule and CD4+ eosinophil migration. However, dexamethasone may inhibit airway inflammation through the downregulation of CD4 expression.

Asthma↗

PubMed2001

2-Arachidonoylglycerol and anandamide oppositely modulate norepinephrine release from the rat heart sympathetic nerves.

Anandamide (10(-7) and 10(-6) M) as well as a synthetic cannabinoid HU210 (10(-8) to 10(-6) M) suppressed the norepinephrine release evoked by perivascular nerve stimulation (PNS) of the rat heart Langendorff's preparation. The effects of HU210 and the lower dose of anandamide were completely blocked by the cannabinoid CB1-receptor antagonist AM251, while that of anandamide at 10(-6) M was partly mediated by arachidonate-derived metabolites. 2-Arachidonoylglycerol (2-AG), at 10(-6) M in the presence of DFP and indomethacin, increased PNS-evoked norepinephrine release, which was completely blocked by AM251. The present results suggest that the two endocannabinoids may oppositely participate in the CB1-receptor-mediated modulation of sympathetic norepinephrine release.

Animals↗

PubMed2001

In vitro transmission of HCMV between fibroblasts and peripheral blood leukocytes in the presence of IL-4.

We demonstrated transmission of human cytomegalovirus (HCMV) from the human lung fibroblast MRC-5 to peripheral blood leukocytes (PBLs). mRNA of the HCMV immediately-early (IE) antigen was detected in PBLs cultured with IL-2 or IL-2 + IL-4 that made direct contact with HCMV-infected MRC-5, whereas it was not detected in PBLs prevented from making cell-to-cell contact. However, mRNA of HCMV IE was not detected in PBLs cultured with IL-2 and IFN-gamma that made direct contact with HCMV-infected MRC-5. Transmission of the pp65 antigen was increased in culture medium containing IL-4. At a higher viral infection titer, cell-free HCMV infected adherent PBLs cells. The subset, which did not adhere, did not infect cell-free viruses even at a very high multiplicity of infection. Moreover, the adhered subset of PBLs infected with HCMV was able to transmit HCMV to non-infected fibroblasts. Our results suggest that cell-to-cell contact (when PBLs make direct contact with HCMV-infected cells) is important in the mechanism of HCMV transmission and that the adherent cells of PBLs are one of the most important vehicles for HCMV infection. Moreover, we suggest that type 2 cytokines such as IL-4 enhance the transmission of HCMV to PBLs.

Antigens, Viral↗

PubMed2001

[Analysis of clinical costs for inpatients with the urologic diseases in 1997].

OBJECTIVES: Because of recent increases in health care costs, reformation care cost system similar to the disease related group/prospective payment system (DRG/PPS) was attracted attention in Japan. We analyzed the costs for inpatients with urologic diseases in our institution and compared them with the costs reported in Japanese trials of DRG/PPS. MATERIALS & METHODS: Subject consisted of 363 consecutive urologic diseases inpatients treated in our hospital in the period between April 1 1997 and March 31 1998. Of these 107 had bladder tumor, 79 BPH (benign prostatic hyperplasia), 34 prostate tumor, 32 renal tumor, 17 in urinary stone (excluding cases with bladder stones) and 94 cases in others. The total hospital charge for each case was calculated, and the averages and standard deviations for each disease were analyzed. We analyzed the relationship between hospital charges for each disease, and complications, the degree of disease, age and length of stay (LOS). Health care costs are assessed in unit, each of which is the equivalent of 10 yen. RESULTS: The average of total hospital charges was 108,841.6 points for bladder tumor, 61,692.2 points for BPH, 96,825.3 points for prostate tumor, 188,459.0 points for renal tumor, and 66,052.2 points for urinary stones. The standard deviation was 99,611.3 points for bladder tumors, 16,712.9 points for BPH, 65,419.3 points for prostate tumor, 204,389.6 points for renal tumor and 30,081.7 points for urinary stone. There was a positive correlation between hospital charge and LOS in most diseases. The average hospital charges for each disease were much higher than the reimbursement charges of the trial Japanese DRG/PPS. DISCUSSION: Shortening of LOS using established clinical pathways reduces health care costs. However, in Japan, the wide range of preliminary results suggests that it may be too early to introduce the DRG/PPS system for health care cost. Furthermore nationwide investigations are needed before the introduction of the DRG/PPS system into Japanese health care reimbursement system.

Adolescent↗

PubMed2001

In vitro and in vivo studies of a bone morphogenetic protein-2 expressing adenoviral vector.

BACKGROUND: Bone morphogenetic proteins (BMPs) play important roles in the migration of osteoblast progenitor cells, the proliferation of mesenchymal cells, and their differentiation into chondrogenic and osteogenic cells. However, the optimum procedure to deliver BMPs remains unknown. To examine the effectiveness of a gene transfer procedure for the delivery of BMP-2, we constructed a human BMP-2-expressing replication-deficient adenoviral vector, AxCAOBMP-2, and evaluated its osteoinductive activity in vitro and in vivo. METHODS: C2C12 myoblasts were infected in vitro with this viral vector or an Escherichia coli LacZ gene-expressing control adenovirus vector (AxCALacZ). Twenty-four hours after the infection, indirect immunofluorescence was performed. On day 5 after the infection, alkaline phosphatase (ALP) in the cells and osteocalcin in the culture medium were measured. Furthermore, to examine the effectiveness of gene transfer of BMP-2 in vivo, we evaluated osteoinduction by AxCAOBMP-2, under transient immunosuppression with cyclophosphamide, given at a dose of 125 mg/kg intraperitoneally the day before injection of the adenoviral vector. Twenty-five microliters of AxCAOBMP-2 (8.75 x 10(8) plaque-forming units [pfu], Group I) and AxCALacZ (1.75 x 10(8) pfu, control group) and 5 microl of AxCAOBMP-2 (1.75 x 10(8) pfu, Group II) were injected into a right calf muscle of Wistar rats. On day 21, bone formation in each group was investigated radiologically and histologically. RESULTS: Abundant BMP-2 expression in C2C12 cells infected with this viral vector was confirmed by immunofluorescence. C2C12 cells transferred with the BMP-2 gene by this vector produced ALP in the cells and also produced and secreted osteocalcin in the culture medium. Osteoinduction was found only in the AxCAOBMP-2 treated groups with immunosuppression. Osteoinduction activity was higher in Group I than in Group II. CONCLUSION: This study demonstrated the osteoinductive activity in vitro and in vivo by an adenoviral vector carrying the BMP-2 gene. CLINICAL RELEVANCE: Gene therapy with AxCAOBMP-2 under transient immunosuppression may be useful for bone reconstruction.

Adenoviridae↗

PubMed2001

[Receptor occupancy and antipsychotic drug action measured by PET and SPECT].

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) studies have demonstrated consistent findings of high dopamine D2 receptor occupancy (> 65-70%) in patients treated with antipsychotic drugs. Further, the risk of extrapyramidal side effects has been shown high in patients with occupancy above 80%. On the basis of these findings, an optimal interval for D2 receptor occupancy between 70% and 80% has been suggested. It has also been shown that several atypical antipsychotics induce marked occupancy of central 5-HT2 and D2 receptors in vivo. However, a low D2 occupancy has been observed in patients with clinical dose of clozapine or quetiapine. The antipsychotic effect of these atypical drugs with a low D2 receptor occupancy has been widely discussed with respect to actions on other receptor systems, limbic selectivity of antipsychotic action and episodic transient occupancy. The recent advances in PET/SPECT and developments of new radioligands have made it possible to evaluate antipsychotic drug actions directly in humans. The empirical data from occupancy measurements will enable us to open future directions of investigation of antipsychotic action and improvement of antipsychotic treatment.

Animals↗