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Biomedical subjects

I Saito

Publications and source records attributed to I Saito.

At least 91 records · Page 5Linked to original sources
PubMed2001

[The validity of revised death certificates (ICD-10) for ischemic heart disease in Oita City, Japan].

PURPOSE: Mortality statistics have recorded an increased number of deaths from ischemic heart disease (IHD) since death certificates were revised to reflect the International Classification of Diseases, tenth revision (ICD-10) in Japan, in 1995. However, it remains unclear whether the validity of IHD diagnosis improved after this revision. METHODS: We conducted the Oita Cardiac Death Survey to validate IHD certified deaths that occurred among residents aged 25-74 in Oita City, Japan (mean population = 273,000). Of the eligible 342 fatalities, 328 cases (95.0%) were examined by a review of the medical records and/or interviews with physicians. The MONICA criteria were applied and provided a reference standard against which to assess the validity of certified fatal IHD. Sensitivity (Se), positive predictive value (PPV), specificity (Sp) and negative predictive value (NPV) for IHD as the cause of death were analyzed, assuming that all validated IHD deaths were true. Multivariate logistic models were used to determine associations of false positive and false negative cases with sex, age at time of death and place of death. RESULTS: Vital statistics revealed 273 fatalities to be due to cardiac disease, including 143 from acute myocardial infarctions (AMI), 27 from other IHD, 52 from heart failure and 51 from other heart diseases. After validation, 25 'definite fatal AMI' and 71 'possible fatal AMI or IHD death' were identified among all subjects according to the MONICA criteria. In all, Se, PPV, Sp and NPV for IHD certified as the cause of death were 86.5% (95% Cl: 77.6-92.3), 50.3% (42.5-58.1), 64.7% (58.1-70.7), and 92.0% (86.5-95.5), respectively. PPV among persons aged 25-54 years was remarkably decreased. PPV and Sp among out-of-hospital deaths were significantly lower than for in-hospital deaths. Multivariate logistic models revealed out-of-hospital deaths and being aged 25-54 years to be significant predictors of false positive cases (odds ratio (OR) = 2.03, P < 0.001 versus in-hospital deaths and OR = 2.79, P < 0.05 versus ages of 65-74 years, respectively). CONCLUSIONS: Because false positive cases increased among certified IHD deaths after the revision, PPV and Sp percentages decreased. Out-of-hospital deaths and being aged 25-54 years were associated with increased possibility of false positive. Given our findings, IHD deaths in vital statistics may increase due to the tendency of physicians to certify IHD as the cause of death in cases without clear sign suggestive of other causes.

Adult↗
PubMed2000

Cell cycle arrest and apoptosis induced by Notch1 in B cells.

Notch receptors play various roles for cell fate decisions in developing organs, although their functions at the cell level are poorly understood. Recently, we found that Notch1 and its ligand are each expressed in juxtaposed cell compartments in the follicles of the bursa of Fabricius, the central organ for chicken B cell development. To examine the function of Notch1 in B cells, a constitutively active form of chicken Notch1 was expressed in a chicken B cell line, DT40, by a Cre/loxP-mediated inducible expression system. Remarkably, the active Notch1 caused growth suppression of the cells, accompanied by a cell cycle inhibition at the G(1) phase and apoptosis. The expression of Hairy1, a gene product up-regulated by the Notch1 signaling, also induced the apoptosis, but no cell cycle inhibition. Thus, Notch1 signaling induces apoptosis of the B cells through Hairy1, and the G(1) cell cycle arrest through other pathways. This novel function of Notch1 may account for the recent observations indicating the selective inhibition of early B cell development in mice by Notch1.

Animals↗
PubMed2000

Amplification of pepleomycin-mediated DNA cleavage and apoptosis by unfused aromatic cations.

An important approach to improve chemotherapy of members of the bleomycin (BLM) family of antibiotics is to find compounds (amplifiers) that enhance the activity of BLM-mediated DNA cleavage and apoptosis. Using a DNA-sequencing technique and pulsed field gel electrophoresis, we have investigated whether BLM-mediated cleavage of isolated and cellular DNA is amplifed by three compounds (RW-12, LS-20, 1S-5Me) which have a conformationally flexible, unfused polyaromatic system and cationic side chain in the molecules. RW-12 enhanced most effectively both pepleomycin (PEM)-induced cytotoxicity and apoptosis. The order of the maximum enhancing effect of amplifiers on PEM-mediated DNA damage is RW-12 > LS-20 > 1S-5Me. RW-12 amplified PEM-mediated DNA cleavage most effectively not only in vitro but also in cultured cells. We have reported that the order of the DNA binding constants of these compounds is RW-12 > LS-20 > 1S-5Me. In this study, we found a good correlation between PEM-mediated cleavage of isolated DNA and cellular DNA. These results suggest that BLM amplifiers bind to DNA and by doing so enhance drug-mediated DNA degradation, ultimately leading to apoptosis. The present study on amplifiers of anticancer agents shows a novel approach to the potentially effective anticancer therapy.

Apoptosis↗
PubMed2000

Autoantigen-specific CD4+CD28low T cell subset prevents autoimmune exocrinopathy in murine Sjögren's syndrome.

Organ-specific autoimmune exocrinopathy resembling Sjögren's syndrome (SS) that spontaneously develops in NFS/sld mutant mice thymectomized 3 day after birth is dependent on Th1-type CD4+ T cells. We previously reported that a cleavage product of 120-kDa alpha-fodrin may be an important autoantigen in the pathogenesis of SS in both an animal model and the patients. We demonstrate that in an animal model of SS with overt exocrinopathy, a unique CD4+ T cell subset expressing CD28low is dramatically increased in spleen cells before the disease onset, but that the CD4+ T cells of diseased mice were virtually all CD28high. We found that the spleen cells in these mice before the disease onset showed a significant increase in autoantigen-specific T cell proliferation. Analysis of in vitro cytokine production by spleen cells indicated, before the disease onset, severely impaired production of IL-2 and IFN-gamma in the animal model, whereas high levels of IL-4 were observed. Expression of cytokine genes, including IL-4, IL-10, and TGF-beta, was detected in FACS-sorted CD4+CD28low T cells by RT-PCR analysis. Transfer of CD4+CD28low T cells into the animal model actually prevented the development of autoimmune lesions including autoantibody production. These results suggest that a CD4+CD28low T cell subset that is continuously activated by an organ-specific autoantigen may play a regulatory role in the development of organ-specific autoimmune disease in an animal model of SS.

Adoptive Transfer↗
PubMed2000

Nontraditional risk factors for coronary heart disease incidence among persons with diabetes: the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Major risk factors explain much of the excess risk for coronary heart disease produced by diabetes, but nontraditional factors may also relate to incident coronary heart disease. OBJECTIVE: To examine the association of traditional and nontraditional risk factors with incidence of coronary heart disease in adults with diabetes. DESIGN: Prospective cohort study. SETTING: The Atherosclerosis Risk in Communities (ARIC) Study. PARTICIPANTS: 1676 middle-aged persons who had diabetes but no history of prevalent coronary heart disease. MEASUREMENTS: Multiple risk factors were recorded at baseline. Follow-up was from 1987 through 1995. RESULTS: 186 participants developed incident coronary heart disease events during follow-up. As expected, the incidence of coronary heart disease in participants with diabetes was associated positively with traditional risk factors (hypertension, smoking, total cholesterol level, and low high-density lipoprotein [HDL] cholesterol level). After adjustment for sex, age, ethnicity, and ARIC field center, incident coronary heart disease was also significantly associated with waist-to-hip ratio; levels of HDL3 cholesterol, apolipoproteins A-I and B, albumin, fibrinogen, and von Willebrand factor factor VIII activity; and leukocyte count. However, after adjustment for traditional risk factors for coronary heart disease, only levels of albumin, fibrinogen, and von Willebrand factor; factor VIII activity; and leukocyte count remained independently associated with coronary heart disease (P < 0.03). The relative risks associated with the highest compared with lowest groupings of albumin, fibrinogen, factor VIII, and von Willebrand factor values and leukocyte count were 0.64 (95% CI, 0.44 to 0.92), 1.75 (CI, 1.12 to 2.73), 1.58 (CI, 1.02 to 2.42), 1.71 (CI, 1.11 to 2.63), and 1.90 (CI, 1.16 to 3.13), respectively. Adjustment for diabetes treatment status attenuated these associations somewhat. CONCLUSIONS: Levels of albumin, fibrinogen, and von Willebrand factor; factor VIII activity; and leukocyte count were predictors of coronary heart disease among persons with diabetes. These associations may reflect 1) the underlying inflammatory reaction or microvascular injury related to atherosclerosis and a tendency toward thrombosis or 2) common antecedents for both diabetes and coronary heart disease.

Apolipoproteins↗
PubMed2000

Cloning and characterization of a human brain Na(+)-independent transporter for small neutral amino acids that transports D-serine with high affinity.

We isolated a cDNA for the human homologue of system asc transporter Asc-1 from human brain. The encoded protein designated as hAsc-1 (human Asc-1) exhibited 91 % sequence identity to mouse Asc-1. Consistent with mouse Asc-1, hAsc-1 required 4F2 heavy chain for its functional expression in Xenopus oocytes. hAsc-1 exhibited the properties of amino acid transport system asc which transports small neutral amino acids in a Na(+)-independent manner. hAsc-1 transported D-serine at high affinity with a K(m) value of 22.8 microM. In brain, 2.0 kb mRNA was highly expressed. hAsc-1 gene was mapped to human chromosome 19, region q12-q13.1. Because of the high-affinity transport with the K(m) value close to the physiological concentration of D-serine, together with the high levels of expression in brain, hAsc-1 is proposed to play significant roles in the D-serine mobilization in brain.

Amino Acid Transport System y+↗
PubMed2000

Comparison of biotin production by recombinant Sphingomonas sp. under various agitation conditions.

Biotin production by fermentation of recombinant Sphingomonas sp./pSP304 was investigated. A complex medium containing 60g/l of glycerol and 30g/l of yeast extract was suitable for biotin production. Biotin was produced in the late logarithmic or stationary phase after glycerol starvation. The optimum pH value for biotin production was 7.0. When the dissolved oxygen concentration (DO) was controlled at a constant level, the biotin concentration produced after 120h was significantly lower than that obtained in a test tube culture. Therefore, a batchwise jar-fermentor culture with a constant agitation speed and without DO control was conducted for investigating the effect of agitation conditions on biotin production. Six types of impeller were tested: turbine-blade type, turbo-lift type, rotating mesh type (EGSTAR((R))), screw with draft tube type, Maxblend((R))type, and anchor type. With some impellers, agitation speed was also changed. Both the maximum cell concentration and biotin production varied depending on agitation conditions. Relatively high cell concentrations were attained with four of the impeller types, turbine-blade type, rotating mesh type, Maxblend((R)) type, and anchor type. Among these impellers, the turbine-blade impeller with sintered sparger was suitable for biotin production. After 120h, the cell concentration reached an OD(660) of 43 and a biotin concentration of 66mg/l was obtained, which was comparable with the results from the test tube culture. Morphological variation was also observed depending on the agitation conditions: oval-shaped, rod-shaped, and elongated-shaped cells. Biotin production was relatively high in slightly long rod-shape cells but low in elongated cells. The difference in morphology appeared to depend on the shear stress. It was found that biotin production was strongly correlated with cell length and the oxygen transfer coefficient (k(L)a); cell lengths in the range 4-7µm and k(L)a values in the range 1.5-2.0/min were found to be suitable for biotin production in jar-fermentor culture.

Journal Article↗
PubMed2000

Possible role of cytotoxic T cells in acute liver injury in hepatitis C virus cDNA transgenic mice mediated by Cre/loxP system.

A line of hepatitis C virus (HCV) transgenic mice was established previously that was mediated by Cre/loxP system using HCV cDNA, including core, E1, E2 and NS2 genes. Intravenous infection of a recombinant adenovirus that expresses Cre DNA recombinase (AxCANCre) induced HCV structural protein expression in the liver of transgenic mice. HCV core protein production and transgene recombination in the mouse liver were serially evaluated after AxCANCre infusion. Core proteins were expressed efficiently and transgene was almost completely recombined in the liver of mice after 3 days and then the levels of both core protein production and transgene recombination decreased continuously for 28 days. However, 30.6% of the transgene recombination remained at 28 days and only 2.7% of core production remained at 28 days after infection. Compared with nontransgenic controls, the serum alanine aminotransferase levels in transgenic mice were significantly higher 10, 14, and 21 days after adenovirus infection. Histological scoring also indicated severe pathological changes in the liver of transgenic mice after adenovirus infection. AxCANCre infusion increased CD8+ lymphocyte infiltration into the liver of transgenic mice compared with that of non-transgenic controls. Furthermore, cytotoxic T lymphocytes (CTLs) isolated from transgenic mice during liver injury were specific for the HCV proteins. These results suggest that HCV structural proteins expressed in the liver of transgenic mice enhanced liver injury. HCV-specific CTLs may be to enhance hepatitis. Thus, the present HCV transgenic mouse model provides a useful model of liver injury due to HCV, and the host immune response may play a pivotal role(s) in the pathogenesis of HCV.

Adenoviridae↗
PubMed2000

Severe destructive autoimmune lesions with aging in murine Sjögren's syndrome through Fas-mediated apoptosis.

When we evaluated the age-associated changes in autoimmune exocrinopathy in a NFS/sld murine model for primary Sjögren's syndrome (SS), severe destructive autoimmune lesions developed in the salivary and lacrimal glands in the aged mice, compared with those observed in the younger model. We detected a decreased secretion of saliva and tear flow in the aged group. A significant increase of TUNEL(+)-apoptotic epithelial duct cells in the salivary glands was detected in the aged SS animal model. A higher proportion of mouse salivary gland cells bearing Fas was found in the aged group, whereas no significant changes were seen on tissue-infiltrating CD4(+) T cells bearing FasL in the salivary glands from young and aged mice. We detected an increased cleavage product of organ-specific autoantigen, 120-kd alpha-fodrin, in the aged salivary gland tissues on immunoblotting, and an increase in serum autoantibody production against 120-kd alpha-fodrin by enzyme-linked immunosorbent assay. An increase in the proliferative response of splenic T cells against organ-specific autoantigen was observed, whereas nonspecific concanavalin A responsiveness was decreased in the aged mice. In addition, a decrease in Fas expression was found on splenic CD4(+) T cells in the aged mice, and anti-Fas mAb-stimulated apoptosis was down-regulated on CD4(+) T cells. These results indicate that age-associated dysregulation of CD4(+) T cells may play a crucial role on acceleration of organ-specific autoimmune lesions in a murine model for primary SS through Fas-mediated apoptosis.

Aging↗
PubMed2000

CTLA4IgG gene delivery prevents autoantibody production and lupus nephritis in MRL/lpr mice.

MRL/MP-lpr/lpr (MRL/lpr) mice spontaneously develop an autoimmune syndrome closely resembling systemic lupus erythematosus (SLE) in humans, characterized by hypergammaglobulinemia, various autoantibody production, and the development of fatal glomerulonephritis. We have previously demonstrated that systemic administration of soluble form of CTLA4IgG prevented autoantibody-related diseases in MRL/lpr mice. To test the potential protective effects of CTLA4IgG gene delivery on the development of lupus nephritis, we injected MRL/lpr mice with a recombinant adenovirus vector containing CTLA4IgG gene, Adex1CACTLA4IgG (AdCTLA4IgG). It was demonstrated that a single administration of intravenous injection of AdCTLA4IgG into MRL/lpr mice resulted in almost complete amelioration of lupus nephritis.

Abatacept↗
PubMed2000

Presence of sonographically detectable parathyroid glands can predict resistance to oral pulsed-dose calcitriol treatment of secondary hyperparathyroidism.

Oral pulsed-dose calcitriol administration has been shown to be effective therapy for patients with secondary hyperparathyroidism. However, this effect is not consistently observed in the clinical setting. This study was undertaken to examine whether enlarged parathyroid glands can serve as a clinical marker that predicts the suppressive effect of calcitriol. Thirty-five patients undergoing chronic hemodialysis (HD) were examined (age, 51.9 +/- 14.9 years; duration of HD, 72.0 +/- 56.0 months). Based on the volume of parathyroid glands measured using an ultrasonographic scanner, patients were divided into two groups: 15 patients with undetectable parathyroid glands (ND group) and 20 patients with detectable parathyroid glands (D group; mean volume of parathyroid glands, 261. 9 +/- 347.5 mm(3)). No significant differences were found in serum ionized calcium (Ca(++)) or parathyroid hormone (PTH) levels before calcitriol administration between the two groups. For each patient, 8 microg of calcitriol was administered orally at the end of the HD session, and the changes in serum PTH levels were determined 44 hours after dosing. No significant differences were found between the two groups in serum Ca(++) levels. However, a significant decrease in serum PTH levels was observed in the ND group, whereas no significant changes were found in the D group. The results of the study show that the suppressive effect on PTH through calcitriol therapy was reduced in patients with detectable enlarged parathyroid glands. This may indicate that the size of parathyroid glands is one factor determining the therapeutic potential of pulsed-dose calcitriol administration for secondary hyperparathyroidism.

Administration, Oral↗
PubMed2000

Angiotensin II antagonists for hypertension: are there differences in efficacy?

We compared the antihypertensive efficacy of available drugs in the new angiotensin-II-antagonist (AIIA) class. The antihypertensive efficacy of losartan, valsartan, irbesartan, and candesartan was evaluated from randomized controlled trials (RCT) by performing a metaanalysis of 43 published RCT. These trials involved AIIA compared with placebo, other antihypertensive classes, and direct comparisons between AIIA. A weighted-average for diastolic and systolic blood pressure reduction with AIIA monotherapy, dose titration, and with addition of low-dose hydrochlorothiazide (HCTZ) were calculated. Weighted-average responder rates were also determined. The metaanalysis assessed a total of 11,281 patients. The absolute weighted-average reductions in diastolic (8.2 to 8.9 mm Hg) and systolic (10.4 to 11.8 mm Hg) blood pressure reductions (not placebo-corrected) for AIIA monotherapy were comparable for all AIIA. Responder rates for AIIA monotherapy were 48% to 55%. Dose titration resulted in slightly greater blood pressure reduction and an increase in responder rates to 53% to 63%. AIIA/hydrochlorothiazide combinations produced substantially greater reduction in systolic (16.1 to 20.6 mm Hg) and diastolic (9.9 to 13.6 mm Hg) blood pressure reductions than AIIA monotherapy and responder rates for AIIA/HCTZ combinations were 56% to 70%. This comprehensive analysis shows comparable antihypertensive efficacy within the AIIA class, a near-flat AIIA-dose response when titrating from starting to maximum recommended dose, and substantial potentiation of the antihypertensive effect with addition of HCTZ.

Angiotensin II↗
PubMed2000

Treatment with anti-CD86 costimulatory molecule prevents the autoimmune lesions in murine Sjögren's syndrome (SS) through up-regulated Th2 response.

Intraperitoneal administration with anti-CD86 (B7.2) MoAb into the murine model for primary SS in NFS/sld mutant mice resulted in dramatically inhibitory effects on the development of autoimmune lesions, while no significant effects were observed when the mice were administered with anti-CD80 (B7.1) MoAb. We found that spleen cells in the murine SS model treated with anti-CD86 MoAb showed a significant impairment of autoantigen-specific T cell proliferation. T cell activation markers (CD44high, CD45RBlow, Mel-14low) were significantly down-regulated in the spleen cells gated on CD4 in anti-CD86-treated mice. We detected a higher level of cytokine production of IL-4 from splenic T cells in anti-CD86-treated mice, but not of IL-2, and interferon-gamma (IFN-gamma), compared with those in the anti-CD80- and PBS-treated SS model. Moreover, serum autoantibody production against alpha-fodrin autoantigen was almost entirely suppressed in anti-CD86-treated mice. These data provide strong evidence that in autoimmune exocrinopathy resembling SS in NFS/sld mutant mice, the CD86 costimulatory molecule plays a crucial role in the initiation and subsequent progression of Th1-mediated autoimmunity in the salivary and lacrimal glands.

Animals↗
PubMed2000

Mechanisms of neonatal tolerance induced in an animal model for primary Sjögren's syndrome by intravenous administration of autoantigen.

Neonatal exposure to autoantigen is believed to induce effective antigen-specific T-cell tolerance in experimental models of autoimmunity. We have identified 120 kDa alpha-fodrin autoantigen in an animal model for primary Sjögren's syndrome (SS), that has been determined as a candidate autoantigen in both an animal model and the patients with primary SS. We demonstrate here that neonatal injection of autoantigen induce relevant tolerance when treated with intravenous (i.v.) administration within 24 h after birth, but not with i.v. injection after the thymectomy or with intraperitoneal injection. Autoantigen-specific T-cell response was significantly reduced in mice induced neonatal tolerance, and the activation markers of splenic CD4+ T cells were down-regulated in mice treated with neonatal administration. Because we detected that neonatal i.v. injection of autoantigen prevented Th1 response, it is possible that the autoantigen administration within 24 h after birth induce regulatory T cells that had a protective effect against Th1-mediated autoimmune diseases. These results indicate that the prevention of the spontaneous anti-120 kDa alpha-fodrin response in vivo, by tolerization of the autoantigen-reactive T cells, blocked the development of autoimmune lesions in an animal model for primary SS.

Animals↗
PubMed2000

Analysis of hemodynamic response with 1/R control on biventricular bypass goat.

A conductance and arterial pressure based method (1/R control) to determine the cardiac output (CO) of a total artificial heart (TAH) was developed to provide a central nervous system with control over the output of TAH. In order to clarify the deference in hemodynamic response between natural heart and 1/R control, biventricular bypass was introduced in the goat. After 2 pneumatically driven sac-type blood pumps were connected to the natural heart, the pulmonary artery was totally clamped to acquire 100% right heart bypass, and the ascending aorta was stenosed to acquire about 60 to 90% left heart bypass; 1/R control was performed substituting the output of the right artificial heart for the CO. The results demonstrated that stable control could be achieved. A discrepancy was often seen between the pulse rate (PR) of the artificial heart and the heart rate (HR) in absolute value. However, the relative changes of PR were quite similar to that of HR for the most part, indicating that the responses of 1/R control were the duplication of natural cardiac responses in normal daily activity.

Animals↗
PubMed2000

Development of a miniature undulation pump for the distributed artificial heart.

Research of the distributed artificial heart is important not only to acquire the means of individual organ perfusion but also to clarify the characteristics of the organ and the mechanism of blood distribution. To investigate the distributed artificial heart, the miniature undulation pump was developed. The outer diameter and the thickness of the developed pump were 38 mm and 11 mm, respectively. The priming volume of the pump was 3.2 ml. The total size including the motor unit was 38 mm in diameter and 32 mm in length. The total weight was 67.5 g. The total volume was 27.5 ml. The pump was driven with pulse width modulation by using a 1 chip motor controller. More than 5 L/min of continuous output could be obtained. The results showed that the developed miniature undulation pump system had enough performance for individual organ perfusion.

Biomechanical Phenomena↗