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Hideki Ito

Publications and source records attributed to Hideki Ito.

At least 19 recordsLinked to original sources
PubMed2006

Effect of the moisture content in aerosol on the spray performance of Stmerin D HFA preparations.

Stmerin D, a pressurized metered dose inhaler (MDI) for treatment of asthma, contains CFCs (chlorofluorocarbons) as a propellant. For the CFC replacement study, two formulations were prepared using hydrofluoroalkanes (HFA-134a and HFA-227) and the effect of storage on the spray performance was investigated under accelerated stress conditions. Drug stability, moisture content and spray performances such as the emitted dose uniformity and aerodynamic particle size distribution were evaluated. Drug content did not change after 3 months storage at 40 degrees C/75% RH. However, the emitted dose uniformity varied and the respirable fraction (RF) was reduced remarkably. While stored at 40 degrees C/ambient for 3 months, no change was observed in either drug content or spray performances. This study clarified that the moisture content in the canister played an important role on the spray performance, and it changed not only the emitted dose uniformity but also the particle size distribution. Consequently, in order to improve the stability of the spray performance of aerosol prepared with HFAs, moisture permeation into the canister must be controlled.

Aerosols↗
PubMed2006

[Japanese Elderly Diabetes Intervention Trial (J-EDIT)].

Treatment goals of medical care for the elderly patients with diabetes mellitus are maintaining high quality of life and elongating healthy longevity. In order to clarify how the elderly patients with diabetes mellitus should be treated for those purposes, a randomized controlled intervention study using 1,173 Japanese elderly patients with diabetes mellitus is now performing. All subjects have moderate or severe glucose intolerance. Subjects have been divided into two groups, ordinary treatment group and treatment group treated as same as adult patients with diabetes mellitus. The study has not been finished. Therefore, intermediate results were demonstrated and expectation for the study were discussed.

Aged↗
PubMed2006

Genetic strain differences in platelet aggregation of laboratory mice.

To investigate the physiological role of novel genes and proteins in platelet activation, various knockout mice have been produced. A number of standard inbred mouse strains each possessing genetically unique characters such as high tumor generation, hyperglycemia or hyperlipidemia, have been bred. In breeding knockout mice for investigation of specific physiological functions, appropriate selection of parental or backcross strains is necessary. Thus, examination of strain-specific platelet characteristics is important. In the present study, platelet aggregation responses of 13 laboratory mouse strains, 129/Sv, A, AKR, BALB/c, C3H/He, C57BL/6J, CBA, DBA/1, DBA/2, ddY, FVB, ICR, and NZW, and the diabetic strain C57BL/KsJ db/db, were compared. Marked strain differences were observed in ADP- and collagen-induced platelet aggregation. The highest responses with both were seen in AKR/J and NZW/N, whereas the lowest were seen in DBA/2 and DBA/1. There was a 5-fold difference in the platelet aggregation threshold index (PATI) for ADP-induced PRP aggregation between AKR/J (0.6 microM) and DBA/2 (3.0 microM). With whole blood aggregation, the highest response was seen in AKR, whereas the lowest was seen in DBA/2 and DBA/1. The present study demonstrated that there is considerable strain difference in platelet aggregation among laboratory mice, which should be taken into account in backcrossing knockout strains.

Animals↗
PubMed2005

Analysis of varicella zoster virus attenuation by evaluation of chimeric parent Oka/vaccine Oka recombinant viruses in skin xenografts in the SCIDhu mouse model.

Varicella-zoster virus (VZV) is the only human herpes virus for which a vaccine has been licensed. A clinical VZV isolate, designated the parent Oka (pOka) strain was passed in human and non-human fibroblasts to produce vaccine Oka (vOka). The pOka and vOka viruses exhibit similar infectivity in cultured cells but healthy susceptible individuals given vaccines derived from vOka rarely develop the cutaneous vesicular lesions characteristic of varicella. Inoculation of skin xenografts in the SCIDhu mouse model of VZV pathogenesis demonstrated that vOka had a reduced capacity to replicate in differentiated human epidermal cells in vivo (Moffat, J.F., Zerboni, L., Kinchington, P.R., Grose, C., Kaneshima, H., Arvin A.M., 1998a. Attenuation of the vaccine Oka strain of varicella-zoster virus and role of glycoprotein C in alphaherpesvirus virulence demonstrated in the SCID-hu mouse. J Virol. 72:965-74). In order to investigate the attenuation of vOka in skin, we made chimeric pOka and vOka recombinant viruses from VZV cosmids. Six chimeric pOka/vOka viruses were generated using cosmid sets that incorporate linear overlapping fragments of VZV DNA from cells infected with pOka or vOka. The cosmid sets consist of pOka and vOka DNA segments that have identical restriction sites. As expected, the growth kinetics and plaque morphologies of the six chimeric pOka/vOka viruses were indistinguishable in vitro. However, the chimeric viruses exhibited varying capacities to replicate when evaluated in skin xenografts in vivo. The presence of ORFs 30-55 from the pOka genome was sufficient to maintain wild-type infectivity in skin. Chimeric viruses containing different vOka components retained the attenuation phenotype, suggesting that vOka attenuation is multi-factorial and can be produced by genes from different regions of the vOka genome.

Animals↗
PubMed2005

Association of plasma homocysteine with serum interleukin-6 and C-peptide levels in patients with type 2 diabetes.

Hyperhomocysteinemia is an independent risk factor for atherosclerotic disease. Because serum markers of inflammation and the metabolic syndrome are also associated with atherosclerotic disease and insulin resistance, we investigated whether plasma homocysteine (Hcy) levels were associated with serum markers of inflammation and factors of metabolic syndrome in 223 elderly patients with type 2 diabetes mellitus. The levels of plasma Hcy and serum interleukin-6 (IL-6), high-sensitivity C-reactive protein, and C-peptide were measured. The C677T mutation of methylenetetrahydrofolate reductase (MTHFR) gene was detected using the polymerase chain reaction-restriction fragment length polymorphism method. The number of abnormal metabolic factors (presence of diabetes, blood pressure > or =130/85 mm Hg, triglycerides > or =150 mg/dL, high-density lipoprotein cholesterol <35 mg/dL (men) or <39 mg/dL (women), or body mass index >25 kg/m 2 ) was assessed. Elevated plasma Hcy levels correlated significantly with serum IL-6 ( r = 0.25, P < .001), C-peptide ( r = 0.22, P < .01), and the number of abnormal metabolic factors ( r = 0.20, P < .01), but not with C-reactive protein. Multiple linear regression analysis revealed that log-transformed IL-6, serum C-peptide, vitamin B12 , and creatinine were significant determinants of plasma Hcy levels. The correlation between Hcy and IL-6 levels was strongest in those with TT genotype of C677T MTHFR among 3 genotypes. The association between plasma Hcy and serum IL-6 levels supports the hypothesis that the activation of innate immunity is involved in the pathogenesis of arteriosclerosis in patients with diabetes mellitus who are homozygous for the TT genotype of C677T MTHFR.

Aged↗
PubMed2005

Role of the varicella-zoster virus gene product encoded by open reading frame 35 in viral replication in vitro and in differentiated human skin and T cells in vivo.

Although genes related to varicella-zoster virus (VZV) open reading frame 35 (ORF35) are conserved in the herpesviruses, information about their contributions to viral replication and pathogenesis is limited. Using a VZV cosmid system, we deleted ORF35 to produce two null mutants, designated rOkaDelta35(#1) and rOkaDelta35(#2), and replaced ORF35 at a nonnative site, generating two rOkaDelta35/35@Avr mutants. ORF35 Flag-tagged recombinants were made by inserting ORF35-Flag at the nonnative Avr site as the only copy of ORF35, yielding rOkaDelta35/35Flag@Avr, or as a second copy, yielding rOka35Flag@Avr. Replication of rOkaDelta35 viruses was diminished in melanoma and Vero cells in a 6-day analysis of growth kinetics. Plaque sizes of rOkaDelta35 mutants were significantly smaller than those of rOka in melanoma cells. Infection of melanoma cells with rOkaDelta35 mutants was associated with disrupted cell fusion and polykaryocyte formation. The small plaque phenotype was not corrected by growth of rOkaDelta35 mutants in melanoma cells expressing the major VZV glycoprotein E, gE. The rOkaDelta35/35@Avr viruses displayed growth kinetics and plaque morphologies that were indistinguishable from those of rOka. Analysis with ORF35-Flag recombinants showed that the ORF35 gene product localized predominantly to the nuclei of infected cells. Evaluations in the SCIDhu mouse model demonstrated that ORF35 was required for efficient VZV infection of skin and T-cell xenografts, although the decrease in infectivity was most significant in skin. These mutagenesis experiments indicated that ORF35 was dispensable for VZV replication, but deleting ORF35 diminished growth in cultured cells and was associated with attenuated VZV infection of differentiated human skin and T cells in vivo.

Base Sequence↗
PubMed2005

Is the diagnosis of metabolic syndrome useful for predicting cardiovascular disease in asian diabetic patients? Analysis from the Japan Diabetes Complications Study.

OBJECTIVE: The metabolic syndrome (MetS) is believed to be associated with an increased risk of cardiovascular disease (CVD). Although its prevalence is extremely high among diabetic patients, its prevalence in those with no history of CVD has not been determined. Moreover, prospective studies published on the association between MetS and cardiovascular events in diabetic populations have used only the World Health Organization (WHO) definition of MetS and included only white European subjects. The aim of this study was to determine the prevalence of MetS, as defined by both the WHO and the National Cholesterol Education Program (NCEP), and its predictive value for CVD in Asian diabetic patients in a long-term, prospective setting. RESEARCH DESIGN AND METHODS: The baseline characteristics and incidence/hazard ratio of cardiovascular events (coronary heart disease and stroke) were determined in 1,424 Japanese type 2 diabetic patients with and without MetS, as defined by WHO (WHO-MetS) or the NCEP. RESULTS: A high prevalence (38-53%, depending on sex and definition) of MetS was found among diabetic patients, even those with no history of CVD. During the 8-year study period, only WHO-MetS was a predictor for CVD in female patients. In male patients, although both definitions of MetS were significant predictors for CVD, individual components of MetS, such as hyperlipidemia or hypertension, were equivalent or better predictors. CONCLUSIONS: We found that MetS is relatively common in diabetic patients with no history of CVD. We suggest that the commonly used definitions of MetS, at least in their present forms, have limited clinical usefulness for Asian diabetic patients and may need some ethnic group-specific modifications for global use.

Adult↗
PubMed2004

Varicella-zoster virus transfer to skin by T Cells and modulation of viral replication by epidermal cell interferon-alpha.

Primary infection with varicella-zoster virus (VZV) causes the characteristic syndrome of varicella, or chickenpox. Experiments in severe combined immunodeficiency mice with human skin grafts (SCIDhu mice) indicate that VZV infection of T cells can mediate transfer of infectious virus to skin. VZV-infected T cells reached epithelial sites of replication within 24 h after entering the circulation. Memory CD4+ T cells were the predominant population recovered from skin in SCIDhu mice given uninfected or infected mononuclear cells, suggesting that immune surveillance by memory T cells may facilitate VZV transfer. The increased susceptibility of memory T cells to VZV infection may further enhance their role in VZV pathogenesis. During VZV skin infection, viral gene products down-regulated interferon-alpha to permit focal replication, whereas adjacent epidermal cells mounted a potent interferon-alpha response against cell-cell spread. Interleukin-1alpha, although activated in VZV-infected cells, did not trigger expression of endothelial adhesion molecules, thereby avoiding early recruitment of inflammatory cells. The prolonged varicella incubation period appears to represent the time required for VZV to overcome antiviral responses of epidermal cells and generate vesicles at the skin surface. Modulation of VZV replication by cutaneous innate immunity may avoid an incapacitating infection of the host that would limit opportunities for VZV transmission.

Animals↗
PubMed2004

Impaired gamma carboxylation of osteocalcin in elderly women with type II diabetes mellitus: relationship between increase in undercarboxylated osteocalcin levels and low bone mineral density.

We conducted a cross-sectional examination of the role of serum vitamin K levels as they relate to bone metabolism in elderly women with type II diabetes mellitus (DM). Eighty-five elderly women with type II DM were enrolled. Three fractions of vitamin K, phylloquinone (PK), menaquinone 4 (menatetrenone; MK 4), and menaquinone 7 (MK 7), along with undercarboxylated osteocalcin (UcOC), intact osteocalcin (IOC), urinary deoxypyridinoline (udpd), urinary type I collagen N-telopeptide (NTx), and intact parathyroid hormone (IPTH) were measured. Bone mineral density was measured in the lumbar spine (LSBMD) by dual-energy X-ray absorptiometry (DXA), and T scores or Z scores were calculated. The patients were divided into two groups by T score, under -2.5 (osteoporotic group) and over -2.5 (non-osteoporotic group). UcOC levels in osteoporotics patients were significantly higher than those in the non-osteoporotic group (3.09 +/- 3.94 vs 1.82 +/- 1.76 ng/ml, P = 0.02). The correlation between Z score and logarithmic UcOC/IOC levels in type II DM showed a negative trend ( P = 0.07) and a significantly and negatively association with logarithmic NTx ( r = -0.38; P = 0.001). In osteoporotic DM, the UcOC/IOC ratio was significantly correlated with the Z score ( r = -0.61; P << 0.05). Furthermore, logarithmic UcOC/IOC showed a negative correlation with logarithmic MK 7 ( r = -0.50; P = 0.001). In conclusion, the reduction in LSBMD in elderly women with type II DM may be associated, in part, with a defect in Gamma-glutamylcarboxylation by vitamin K.

Aged↗
PubMed2004

Cilostazol inhibits platelet-leukocyte interaction by suppression of platelet activation.

The influence of three anti-platelet drugs, cilostazol, aspirin, and tirofiban, was investigated on platelet-leukocyte interaction by flow cytometry. When platelets and leukocytes were pre-incubated with anti-platelet drugs and stimulated by thrombin or collagen, cilostazol was found to inhibit platelet adhesion to monocytes and polymorphonuclear cells (PMNs). Similar effects were observed with anti-CD62P antibody, while aspirin and tirofiban did not appear to interfere with interaction between platelets and leukocytes. In the platelets pre-incubated with anti-platelet drugs, cilostazol significantly reduced CD62P expression and GPIIb/IIIa activation on platelet surface stimulated by thrombin or collagen. Aspirin inhibited CD62P expression and GPIIb/IIIa activation induced by collagen, but not thrombin. Tirofiban significantly blocked GPIIb/IIIa activation induced with both, and weakly inhibited CD62P expression induced by collagen. When added after stimulation of platelets, cilostazol again significantly inhibited CD62P expression and GPIIb/IIIa activation, although to a lesser extent than in the pre-incubation study. Aspirin hardly inhibited CD62P expression or GPIIb/IIIa activation, while tirofiban strongly blocked GPIIb/IIIa activation induced by thrombin or collagen, but had little effects on CD62P expression. In conclusion, our results suggest that cilostazol inhibits platelet-leukocyte interaction by reducing CD62P expression on the platelet surface.

Antibodies, Monoclonal↗
PubMed2004

Low well-being is an independent predictor for stroke in elderly patients with diabetes mellitus.

OBJECTIVES: To examine whether psychological factors are risk factors for the development of stroke in elderly diabetic patients. DESIGN: Prospective cohort study. SETTING: Outpatient clinic. PARTICIPANTS: Three hundred seventy-six diabetic outpatients free of stroke; mean age 75. METHODS: Well-being and diabetes-specific burden were assessed at baseline using the Philadelphia Geriatric Center morale scale and the Elderly Diabetes Burden Scale (EDBS), respectively. Symptomatic stroke was defined as a focal neurological deficit with rapid onset that persists for more than 24 hours, supported by brain computed tomography or magnetic resonance imaging. RESULTS: During the 3-year follow-up period, 25 symptomatic strokes (24 ischemic strokes and 1 cerebral hemorrhage) occurred. Low scores on the morale scale (</=7) were significant predictors for stroke after adjustment for age; sex; body mass index; hemoglobin A1c level; systolic blood pressure; serum levels of total cholesterol, triglycerides, and high-density lipoprotein cholesterol; smoking; and previous ischemic heart disease (IHD) (hazard ratio (HR)=3.0, 95% confidence interval (CI)=1.2-7.3, P=.017). The relationship between low morale scores and future stroke remained significant after adjusting for socioeconomic factors and microalbuminuria. Increased symptom burden and social burden, but not dietary restrictions, worry about diabetes mellitus (DM), treatment satisfaction, and burden by tablets or insulin of EDBS, were also significant predictors for stroke after adjustment for age, sex, duration of DM, previous IHD, and microalbuminuria (HR=2.6, 95% CI=1.1-6.5, P=.039). CONCLUSION: Low well-being and symptom burden were predictors of stroke in elderly patients with diabetes mellitus (DM), although the causal relationship remains unknown.

Aged↗
PubMed2004

The immediate-early 63 protein of Varicella-Zoster virus: analysis of functional domains required for replication in vitro and for T-cell and skin tropism in the SCIDhu model in vivo.

The immediate-early 63-kDa (IE63) protein of varicella-zoster virus (VZV) is a phosphoprotein encoded by open reading frame (ORF) ORF63/ORF70. To identify functional domains, 22 ORF63 mutations were evaluated for effects on IE63 binding to the major VZV transactivator, IE62, and on IE63 phosphorylation and nuclear localization in transient transfections, and after insertion into the viral genome with VZV cosmids. The IE62 binding site was mapped to IE63 amino acids 55 to 67, with R59/L60 being critical residues. Alanine substitutions within the IE63 center region showed that S165, S173, and S185 were phosphorylated by cellular kinases. Four mutations that changed two putative nuclear localization signal (NLS) sequences altered IE63 distribution to a cytoplasmic/nuclear pattern. Only three of 22 mutations in ORF63 were compatible with recovery of infectious VZV from our cosmids, but infectivity was restored by inserting intact ORF63 into each mutated cosmid. The viable IE63 mutants had a single alanine substitution, altering T171, S181, or S185. These mutants, rOKA/ORF63rev[T171], rOKA/ORF63rev[S181], and rOKA/ORF63rev[S185], produced less infectious virus and had a decreased plaque phenotype in vitro. ORF47 kinase protein and glycoprotein E (gE) synthesis was reduced, indicating that IE63 contributed to optimal expression of early and late gene products. The three IE63 mutants replicated in skin xenografts in the SCIDhu mouse model, but virulence was markedly attenuated. In contrast, infectivity in T-cell xenografts was not altered. Comparative analysis suggested that IE63 resembled the herpes simplex virus type 1 U(S)1.5 protein, which is expressed colinearly with ICP22 (U(S)1). In summary, most mutations of ORF63 made with our VZV cosmid system were lethal for infectivity. The few IE63 changes that were tolerated resulted in VZV mutants with an impaired capacity to replicate in vitro. However, the IE63 mutants were attenuated in skin but not T cells in vivo, indicating that the contribution of the IE63 tegument/regulatory protein to VZV pathogenesis depends upon the differentiated human cell type which is targeted for infection within the intact tissue microenvironment.

Animals↗