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Biomedical subjects

S Okubo

Publications and source records attributed to S Okubo.

At least 19 recordsLinked to original sources
PubMed2006

Effect of vitamin C on common cold: randomized controlled trial.

OBJECTIVE: To investigate the relationship between the common cold and vitamin C supplementation. DESIGN: A double-blind, 5-year randomized controlled trial. SETTING: A village in Akita prefecture, one of the regions in Japan with the highest mortality from gastric cancer. SUBJECTS: Participants in annual screening programs for circulatory diseases conducted under the National Health and Welfare Services Law for the Aged, and diagnosed as having atrophic gastritis. Of the 439 eligible subjects, 144 and 161 were assigned to receive 50 or 500 mg of vitamin C, respectively, after protocol amendment. During the supplementation phase, 61 dropped out, and 244 completed the trial. INTERVENTION: Daily vitamin C supplementation of 50 mg (low-dose group) or 500 mg (high-dose group). RESULTS: Total number of common colds (per 1000 person-months) was 21.3 and 17.1 for the low- and high-dose groups, respectively. After adjustment for several factors, the relative risks (95% confidence interval (CI)) of suffering from a common cold three or more times during the survey period was 0.34 (0.12-0.97) for the high-dose group. No apparent reduction was seen for the severity and duration of the common cold. CONCLUSION: A randomized, controlled 5-year trial suggests that vitamin C supplementation significantly reduces the frequency of the common cold but had no apparent effect on the duration or severity of the common cold. However, considering several limitations due to protocol amendment, the findings should be interpreted with caution.

Adult↗
PubMed2005

Energy structure of a finite Haldane chain in Y2BaNi0.96Mg0.04O5 studied by high field electron spin resonance.

This Letter presents the fine structure of energy levels for the edge states of a Haldane chain. In order to investigate the edge states, we have performed high field and multifrequency electron spin resonance (ESR) measurements of finite length S=1 antiferromagnetic chains in Y2BaNi0.96Mg0.04O5. Owing to the high spectral resolution by high fields and high frequencies, observed ESR signals can be separated into the contributions of the finite chains with various chain lengths. Our results clearly show that the edge spins actually interact with each other through the quantum spin chain and the interaction depends on the chain length N. This N dependence has been obtained experimentally for the first time, and shows that the correlation length xi in the real system is somewhat larger than that calculated by a simple Heisenberg model.

Journal Article↗
PubMed2004

Additive antitumour effect of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (Iressa, ZD1839) and the antioestrogen fulvestrant (Faslodex, ICI 182,780) in breast cancer cells.

A high expression level of epidermal growth factor receptor (EGFR)/HER1 has been suggested to lead to a shorter survival time and resistance to endocrine therapy in patients with breast cancer. To test the hypothesis that inhibition of the EGFR signalling pathway affects the antitumour effect of endocrine therapy, an EGFR tyrosine kinase inhibitor (EGFR-TKI), gefitinib, and an oestrogen receptor (ER) antagonist, fulvestrant, were administered to human breast cancer cells. A total of five human breast cancer cell lines were used. The effects of single or combined treatments with gefitinib and/or fulvestrant on cell growth, cell cycle progression and apoptosis were analysed. Changes in the expression levels of cyclin-dependent kinase inhibitors, p21 and p27, an antiapoptotic factor, Bcl-2, and a proapoptotic factor, Bax, were also investigated. All cell lines tested were sensitive to gefitinib (50% growth inhibitory concentration, 10-28.5 microM). Breast cancer cell lines with a high expression level of HER1 or HER2 were more sensitive to gefitinib than the others. Gefitinib induced a significant G1-S blockade in ER-positive KPL-3C cells. Gefitinib induced significant apoptosis in HER1-overexpressing MDA-MB-231 cells. Gefitinib additively increased the antitumour effect of fulvestrant in all three ER-positive cell lines in a medium supplemented with 17beta-oestradiol. The combined treatment promoted cell cycle retardation in KPL-3C cells, which is associated with an upregulation of p21 by fulvestrant and gefitinib, respectively. Apoptosis was associated with downregulation of Bcl-2 by gefitinib in MDA-MB-231 cells. These results suggest an additive interaction between the EGFR-TKI gefitinib and the antioestrogen fulvestrant in ER-positive breast cancer cells.

Antineoplastic Agents↗
PubMed2003

Squamous cell carcinoma developing in a 12-year-old boy with nonHallopeau-Siemens recessive dystrophic epidermolysis bullosa.

We report a 12-year-old boy with nonHallopeau-Siemens recessive dystrophic epidermolysis bullosa (nHS-RDEB) who developed two skin lesions of squamous cell carcinoma (SCC) on the left foot. The incidence of SCC in nHS-RDEB is much lower than in the HS-RDEB subtype. Furthermore, this boy is the youngest among 92 previously described patients with DEB to develop SCC. This study emphasizes the importance of vigilance in monitoring the possible development of SCC in DEB patients regardless of age or clinical severity.

Age of Onset↗
PubMed2003

A case of micrographia after subcortical infarction: possible involvement of frontal lobe function.

Most reports of micrographia associated with focal brain lesions have related this finding to damage in the left basal ganglia. Here we describe the case of a 68-year-old man presenting with reversible micrographia accompanied by hypophonia in the absence of extrapyramidal signs after cerebral infarction in the left subcortical region. At the time of the patient's admission, diffusion-weighted magnetic resonance imaging sequence showed the lesion to principally involve the corona radiata, with some involvement of the putamen. Neurologically, mild right-sided brachiofacial hemiparesis and grasp reflexes - a frontal lobe sign - were observed. As his micrographia and hypophonia improved, the patient's grasp reflexes improved in parallel. In addition, recovery of regional cerebral blood flow in the left frontal lobe was confirmed by single photon emission computed tomography (technetium-99 m HMPAO). The present case suggests the possibility that the function of frontal-subcortical circuit might also be involved in the production and improvement of micrographia and that micrographia and hypophonia may share a common pathophysiology.

Aged↗
PubMed2002

Residuals of beta-hexachlorocyclohexane, dichlorodiphenyltrichloroethane, and hexachlorobenzene in serum, and relations with consumption of dietary components in rural residents in Japan.

To estimate levels of organochlorine residuals in the Japanese population and the contribution of dietary factors to these levels, we determined serum levels of beta-hexachlorocyclohexane (beta-HCH), hexachlorobenzene (HCB), p,p'-dichlorodiphenyldichloroethane (p,p'-DDD), 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (p,p'-DDE) and p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) in 41 volunteers (14 men and 27 women) in a rural area of Northern Japan. These organochlorine levels were measured using gas-chromatography mass-spectrometry. By a self-administered dietary history questionnaire, the usual dietary intake was estimated. Their median levels (range) were as follows: beta-HCH, 0.50 (0.05-1.50); HCB, 0.20 (0.02-0.70); and total DDT (p,p'-DDE + p,p'-DDT), 5.0 (0.9-31.0) ng/ml serum. Levels of p,p'-DDD were detected in only seven subjects (0.05-0.6 ng/ml serum). The beta-HCH levels were increased with rice and milk intakes, but the least squares means were not simply increased according to the quartile of the intakes. Concerning HCB, fish intake showed a borderline significant correlation (0.20, P = 0.052). In terms of total DDT, intakes of meat, fish, vegetable and milk showed a positive relationship, although none of them provided statistically significant results. No other statistically significant relation between any organochlorines and any food intakes examined was observed in this study. The present study suggests that organochlorine compounds are transported into the human body via foods in the Japanese population. Their effects on health should thus be investigated and monitored.

Aged↗
PubMed2001

Gene transfer of heat-shock protein 70 reduces infarct size in vivo after ischemia/reperfusion in the rabbit heart.

BACKGROUND: Heat-shock protein 70 (HSP 70) plays a role in myocardial protection. No studies are available, however, to show that direct gene transfer of HSP 70 reduces myocardial infarction in vivo. METHODS AND RESULTS: Rabbit hearts were injected with vehicle or Ad.HSP70 at 3 sites (1.5x10(9) pfu, 50 microL/site) in the left ventricle (LV). Four days later, hearts were removed, and expression of inducible (HSP 70) and constitutive (HSC 70) proteins was measured in the LV and right ventricle (RV). Subsets of 5 to 7 animals in the vehicle-, Ad.lacZ-, and Ad.HSP70-treated groups were subjected to 30 minutes of ischemia and 3 hours of reperfusion. Infarct size was measured by tetrazolium staining. Increased expression of HSP 70 was observed in LV injected with Ad.HSP70 compared with vehicle-treated hearts. HSP 70 was undetectable in RV, the noninjected region of the heart. The expression of HSC 70 remained unchanged in hearts treated with vehicle or Ad.HSP70. Infarct size (% risk area) decreased to 24.5+/-2.8 in Ad.HSP70-injected hearts compared with 41.9+/-2.8 and 42.7+/-2.5 in the vehicle- and Ad.LacZ-treated hearts (P<0.01). The infarct size was not different between the vehicle- and Ad.LacZ-treated hearts (P>0.05). The risk areas (% of LV) were not different among the 3 groups, ie, 50.1+/-5.2, 47.7+/-3.5, and 53.3+/-2.9 in vehicle-, Ad.lacZ-, and Ad.HSP70-treated groups (P>0.05). CONCLUSIONS: Direct gene delivery of HSP 70 in vivo reduces the severity of ischemic injury in the heart.

Adenoviridae↗
PubMed2001

Prognosis of acute poststreptococcal glomerulonephritis (APSGN) is excellent in children, when adequately diagnosed.

BACKGROUND: Recently, the prognosis of acute poststreptococcal glomerulonephritis (APSGN) has been reported as improved, compared with the results of previous studies. In an attempt to clarify this, we analyzed the clinical course of patients with APSGN. METHODS: A total of 220 children with acute nephritic syndrome were treated in the affiliated hospitals of our department, between January 1988 and December 1997. Among them, 138 children who were diagnosed with APSGN according to the presence of hematuria, transient hypocomplementemia and evidence of group A beta-hemolytic streptococcal infection, were studied. RESULTS: Serum creatinine and blood urea nitrogen levels at onset were 0.5 +/- 0.2 mg/dL and 20 +/-12 mg/dL, respectively. There were no patients with renal dysfunction (serum creatinine level > or = 1.5 mg/dL), but one patient with nephrotic syndrome. Blood pressure was well controlled in all patients and there were no patients with persistent hypertension. Serum complement levels were normalized within 12 weeks (100%), hematuria disappeared within 4 years (100%) and proteinuria disappeared within 3 years (100%) from the onset. CONCLUSIONS: These data indicate that the prognosis of APSGN during childhood is excellent, when adequately diagnosed and treated.

Acute Disease↗
PubMed2001

Morphological differences between glomerular epithelial cells (GEC) excreted during chemotherapy with antineoplastic drugs and GEC excreted in renal diseases.

BACKGROUND: To better understand the mechanisms of glomerular epithelial cell (GEC) injuries in various diseases, we compared GEC excreted during chemotherapy (antineoplastic drugs) and GEC excreted in renal diseases. METHODS: For 19 patients undergoing chemotherapy (85 courses), 69 patients with IgA nephropathy and 16 patients with Henoch-Schölein purpura nephritis, the number of excreted GEC and GEC casts were counted by an immunofluorescent study. The morphological features of GEC were also studied in an immunofluorescent study combined with Hoechst stain. RESULTS: Glomerular epithelial cells were detected in 78% of the chemotherapy courses and in 94% of the patients with renal diseases. The GEC casts were observed in 2% of chemotherapy courses, while in renal diseases GEC casts were observed in 60% of the patients. Proteinuria (>30 mg/dL) and hematuria were not identified in any of the chemotherapy courses. The morphology and size of GEC were more variable than that in patients with nephropathy. Furthermore, GEC in patients undergoing chemotherapy often showed small nuclei and fragmented nuclei, which were rarely observed in patients with nephropathy. CONCLUSIONS: These results showed that the detachment of podocytes was not directly associated with proteinuria or hematuria. The findings also suggest that GEC are damaged via an apoptotic process by chemotherapy. On the contrary, GEC may be detached through a non-apoptotic process in renal diseases.

Adolescent↗
PubMed2001

Mechanism of synergy between epigallocatechin gallate and beta-lactams against methicillin-resistant Staphylococcus aureus.

Compared to MICs (more than 800 microg/ml) of (-)-epigallocatechin gallate (EGCg) against Escherchia coli, MICs of EGCg against methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA) were 100 microg/ml or less. Furthermore, less than 25 microg EGCg per ml obviously reversed the high level resistance of MRSA to all types of tested beta-lactams, including benzylpenicillin, oxacillin, methicillin, ampicillin, and cephalexin. EGCg also induced a supersusceptibility to beta-lactams in MSSA which does not express mecA, encoding penicillin-binding protein 2' (PBP2'). The fractional inhibitory concentration (FIC) indices of the tested beta-lactams against 25 isolates of MRSA were from 0.126 to 0.625 in combination with 6.25, 12.5 or 25 microg of EGCg per ml. However, no synergism was observed between EGCg and ampicillin against E. coli. EGCg largely reduced the tolerance of MRSA and MSSA to high ionic strength and low osmotic pressure in their external atmosphere, indicating damage of the cell wall. Unlike dextran and lipopolysaccharide, peptidoglycan from S. aureus blocked both the antibacterial activity of EGCg and the synergism between EGCg and oxacillin, suggesting a direct binding of EGCg with peptidoglycan on the cell wall. EGCg showed a synergistic effect with DL-cycloserine (an inhibitor of cell wall synthesis unrelated to PBP2') but additive or indifferent effect with inhibitors of protein and nuclear acid synthesis. EGCg did not suppress either PBP2' mRNA expression or PBP2' production, as confirmed by reverse transcription-PCR and a semiquantitative PBP2' latex agglutination assay, indicating an irrelevance between the synergy and PBP2' production. In summary, both EGCg and beta-lactams directly or indirectly attack the same site, peptidoglycan on the cell wall. EGCg synergizes the activity of beta-lactams against MRSA owing to interference with the integrity of the cell wall through direct binding to peptidoglycan.

Anti-Bacterial Agents↗
PubMed2001

Biochemical alterations during medication withdrawal in Parkinson's disease with and without neuroleptic malignant-like syndrome.

The object was to assess alterations in CSF concentrations of monoamine metabolites during withdrawal of medication in patients with Parkinson's disease in relation to the presence or absence of episodes resembling neuroleptic malignant syndrome (NMS). This syndrome is a fatal condition developing after neuroleptic therapy, and a neuroleptic malignant-like syndrome (NMLS) may also occur after withdrawal of antiparkinsonian drugs in patients with Parkinson's disease. Previous biochemical assays showed that the CSF concentration of the dopamine metabolite homovanillic acid (HVA) is an independent prognostic factor for development of NMLS in patients with Parkinson's disease. In the present study, CSF concentrations of HVA, the noradrenaline (norepinephrine) metabolite 3-methoxy-4-hydroxyphenylethylene glycol, and the serotonin metabolite 5-hydroxyindole acetic acid were assayed using high performance liquid chromatography with electrochemical detection. The study population consisted of nine patients with Parkinson's disease with NMLS and 12 without NMLS, in whom metabolites were assayed during both withdrawal and remedicated periods. Concentrations of HVA in the CSF were significantly lower during the withdrawal period than the medicated period regardless of whether patients developed NMLS, and HVA concentrations were comparably increased after remedication in both groups. However, HVA concentrations were significantly lower in patients with NMLS than in those without NMLS during both withdrawal and medicated periods. Other metabolites showed no significant differences. The present data provide further biochemical evidence for extremely suppressed central dopaminergic activity during NMLS, which may indicate a narrow safety margin for medication withdrawal in patients with Parkinson's disease.

Aged↗
PubMed2000

Stereospecific analysis of lorazepam in plasma by chiral column chromatography with a circular dichroism-based detector.

The chiral separation of lorazepam was achieved on a chiral column with UV and circular dichroism (CD) detection. The good resolution of lorazepam enantiomers was obtained on the column of beta-cyclodextrin derivative immobilized silica gel under reversed-phase conditions. The enantiomeric separation and identification of lorazepam were succeeded by CD detector. The method described allows the quantitation of the stereoisomers of lorazepam in human plasma following the administration of a therapeutic dose of the racemic drug. Chiroptical detection is useful for the pharmacokinetic study of chiral drugs.

Anti-Anxiety Agents↗
PubMed2000

Enantiomeric determination of L- and D-lactic acid in human cerebrospinal fluid by chiral ligand exchange high-performance liquid chromatography.

Enantiomeric determination of L- and D-lactate in human cerebrospinal fluid (CSF) was achieved by HPLC on a chiral stationary phase with UV detection. Samples were submitted to a solid-phase extraction procedure using Oasis HLB Plus Extraction Cartridge and L- and D-lactate in the extract were separated by Shodex ORpac CRX-453 B column, a ligand exchange column for chiral separation, using a mobile phase containing copper (II) ion. L- and D-lactate were determined in 25 min. Intra-assay precision in CSF was 4.98% (mean 1.85 mmol/L) for L-lactate and 10.1% (mean 4.96 micromol/L) for D-lactate (n = 5). Detection limits were between 1.0 (L-lactate) and 1.5 (D-lactate) pmol. The mean values (n = 3) of analytical recovery for L- and D-lactate were 95% and 107%, respectively. The mean +/- SD of concentrations of L- and D-lactate in CSF (n = 20) were 1.52 +/- 0.54 mmol/L and 10.98 +/- 5.15 micromol/L, respectively.

Calibration↗
PubMed2000

Neurological and neuroradiological progression in hereditary spastic paraplegia with a thin corpus callosum.

We followed-up a Japanese man suffering from hereditary spastic paraplegia with a thin corpus callosum (HSP-TCC) by single photon emission computed tomography (SPECT) using 123IN-isopropyl-piodoamphetamine (123I-IMP) over 4 years (25 to 29 years old). Besides the initial symptoms of lower limb spasticity, mental deterioration slightly progressed and upper limb spasticity and slight cerebellar ataxia were developed, during the period. Cranial magnetic resonance imaging (MRI) revealed an extremely thin corpus callosum and medial frontal atrophy, which remained essentially unchanged during the period. 123I-IMP SPECT demonstrated that cerebral blood flow was decreased in the thalamus and the medial frontal, temporal and parietal cortices at the first examination, and that the thalamus showed further reduction but the other involved regions presented essentially no progression during the follow-up period. This is the first report referring to the longitudinal clinical and neuroradiological changes in HSP-TCC.

Adult↗
PubMed2000

Effects of three-month oral supplementation of beta-carotene and vitamin C on serum concentrations of carotenoids and vitamins in middle-aged subjects: a pilot study for a randomized controlled trial to prevent gastric cancer in high-risk Japanese population.

Prior to a randomized controlled trial to prevent gastric cancer by oral supplementation of beta-carotene and vitamin C in a high-risk Japanese population, we examined the serum response to three-month oral supplementation of beta-carotene (0, 3, 30 mg / day) and vitamin C (0, 50, 1000 mg / day) by a three-by-three factorial design using 54 subjects (age range = 40 - 69 years). Serum concentrations of carotenoids, alpha-tocopherol, and ascorbic acid were examined at baseline, and one, two, and three-month points. Both serum beta-carotene and ascorbic acid were significantly higher in high-dose groups than in each placebo group during the supplementation. The serum beta-carotene increased gradually (597 - 830% increase) during the study, whereas the serum ascorbic acid reached nearly a steady-state at the one-month point and remained stable thereafter (88 - 95% increase). No statistically significant interaction between beta-carotene and vitamin C supplementations was observed either for serum beta-carotene or for serum ascorbic acid. Among carotenoids and alpha-tocopherol examined, serum lycopene in the high-dose beta-carotene group was significantly higher than in the placebo group at all points. No unfavorable change in carotenoids and alpha-tocopherol was observed in any group.

Administration, Oral↗
PubMed2000

Tyrosine kinase signaling in action potential shortening and expression of HSP72 in late preconditioning.

We investigated the role of tyrosine kinase (TK) signaling in the opening of the ATP-sensitive K(+) (K(ATP)) channel and 72-kDa heat shock protein (HSP72) expression during late preconditioning. Rabbits were subjected to surgical operation (sham) or were preconditioned (PC) with four cycles of 5 min of ischemia and 10 min of reperfusion. Twenty-four hours later, animals were subjected to 30 min of ischemia and 180 min of reperfusion. Genistein (1 mg/kg ip) was used to block the receptor TK. Six groups were studied: control, sham, genistein-sham, PC, genistein-PC, and vehicle-PC group (1% dimethyl sulfoxide). Genistein or vehicle was given 30 min before the surgical procedure. Genistein pretreatment decreased the expression of HSP72 in PC hearts and suppressed action potential duration shortening during ischemia in sham and PC groups. Infarct size (%risk area) was reduced in the PC (11.6 +/- 1.0%) and vehicle-PC (19.3 +/- 2.0%) compared with the control (40.0 +/- 3.8%) or sham (46.0 +/- 2.0%) groups (P < 0.05). Genistein pretreatment increased infarct size to 46.4 +/- 4.1% in the PC hearts. We conclude that TK signaling is involved in K(ATP) channel opening and HSP72 expression during late PC.

Action Potentials↗