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Biomedical subjects

K Okazaki

Publications and source records attributed to K Okazaki.

At least 55 records · Page 3Linked to original sources
PubMed2001

Analysis of cytokines in the early development of gastric secondary lymphoid follicles in Helicobacter pylori-infected BALB/c mice with neonatal thymectomy.

Immunological interaction between the host and Helicobacter pylori seems to play a critical role in follicular formation in gastric mucosa. We reported H. pylori-induced follicular gastritis model using neonatally thymectomized mice. In this study, we investigated the involvement of various cytokines in this model. BALB/c mice were thymectomized on the third day after birth (nTx). At 6 weeks old, these mice were orally infected with H. pylori. Histological studies showed that follicular formation occurred from 8 weeks after the infection and that most of the infiltrating lymphocytes were CD4(+) and B cells. Neutrophils increased transiently at 1 week after the infection. Gamma interferon, interleukin-7 (IL-7), and IL-7 receptor were expressed in the stomach of the nTx mice irrespective of the infection. In contrast, expressions of the tumor necrosis factor alpha, IL-4 and lymphotoxin-alpha genes were remarkably upregulated by the infection. Our findings suggest that follicular formation may require cooperative involvement of a Th2-type immune response, tumor necrosis factor alpha and lymphotoxin-alpha in addition to the Th1-type immune response in H. pylori-induced gastritis in nTx mice.

Animals↗
PubMed2001

Activation of TRAF5 and TRAF6 signal cascades negatively regulates the latent replication origin of Epstein-Barr virus through p38 mitogen-activated protein kinase.

Latent Epstein-Barr virus (EBV) is maintained by the virus replication origin oriP that initiates DNA replication with the viral oriP-binding factor EBNA1. However, it is not known whether oriP's replicator activity is regulated by virus proteins or extracellular signals. By using a transient replication assay, we found that a low level of expression of viral signal transduction activator latent membrane protein 1 (LMP1) suppressed oriP activity. The binding site of the tumor necrosis factor receptor-associated factor (TRAF) of LMP1 was essential for this suppressive effect. Activation of the TRAF signal cascade by overexpression of TRAF5 and/or TRAF6 also suppressed oriP activity. Conversely, blocking of TRAF signaling with dominant negative mutants of TRAF5 and TRAF6, as well as inhibition of a downstream signal mediator p38 MAPK, released the LMP1-induced oriP suppression. Furthermore, activation of TRAF6 signal cascade by lipopolysaccharides (LPS) resulted in loss of EBV from Burkitt's lymphoma cell line Akata, and inhibition of p38 MAPK abolished the suppressive effect of LPS. These results suggested that the level of oriP activity is regulated by LMP1 and extracellular signals through TRAF5- and TRAF6-mediated signal cascades.

Binding Sites↗
PubMed2001

Infectivity-enhancing antibodies to Ebola virus glycoprotein.

Ebola virus causes severe hemorrhagic fever in primates, resulting in mortality rates of up to 100%, yet there are no satisfactory biologic explanations for this extreme virulence. Here we show that antisera produced by DNA immunization with a plasmid encoding the surface glycoprotein (GP) of the Zaire strain of Ebola virus enhances the infectivity of vesicular stomatitis virus pseudotyped with the GP. Substantially weaker enhancement was observed with antiserum to the GP of the Reston strain, which is much less pathogenic in humans than the Ebola Zaire and Sudan viruses. The enhancing activity was abolished by heat but was increased in the presence of complement system inhibitors, suggesting that heat-labile factors other than the complement system are required for this effect. We also generated an anti-Zaire GP monoclonal antibody that enhanced viral infectivity and another that neutralized it, indicating the presence of distinct epitopes for these properties. Our findings suggest that antibody-dependent enhancement of infectivity may account for the extreme virulence of the virus. They also raise issues about the development of Ebola virus vaccines and the use of passive prophylaxis or therapy with Ebola virus GP antibodies.

Animals↗
PubMed2001

Cytoplasmic microtubular system implicated in de novo formation of a Rabl-like orientation of chromosomes in fission yeast.

Chromosomes are not packed randomly in the nucleus. The Rabl orientation is an example of the non-random arrangement of chromosomes, centromeres are grouped in a limited area near the nuclear periphery and telomeres are located apart from centromeres. This orientation is established during mitosis and maintained through subsequent interphase in a range of species. We report that a Rabl-like configuration can be formed de novo without a preceding mitosis during the transition from the sexual phase to the vegetative phase of the life cycle in fission yeast. In this process, each of the dispersed centromeres is often associated with a novel Sad1-containing body that is contacting a cytoplasmic microtubule laterally (Sad1 is a component of the spindle pole body (SPB)). The Sad1-containing body was colocalized with other known SPB components, Kms1 and Spo15 but not with Cut12, indicating that it represents a novel SPB-related complex. The existence of the triplex structure (centromere-microtubule-Sad1 body) suggests that the clustering of centromeres is controlled by a cytoplasmic microtubular system. Accordingly, when microtubules are destabilized, clustering is markedly reduced.

Centromere↗
PubMed2001

Cloning and nucleotide sequence of the mycodextranase gene from Streptomyces sp. J-13-3.

Mycodextranase (EC 3.2.1.61) is an alpha-glucanase that cleaves alpha-1,4-bonds of alternating alpha-1,3- and alpha-1,4-linked D-glucan (nigeran). The gene encoding mycodextranase from Streptomyces sp. J-13-3 was cloned by hybridization with a degenerate oligonucleotide probe from the amino-terminal amino acid sequence of the enzyme and its nucleotide structure was analyzed. The open reading frame consisted of 1,803 base pairs encoding a signal peptide of 60 amino acids and a mature protein of 540 amino acids with a calculated molecular weight of 56,078. The deduced amino acid sequence showed weak similality to a chitinase homolog from Streptomyces lividans and a chitinase from Xanthomonas sp.

Amino Acid Sequence↗
PubMed2001

Production of monoclonal antibody against Scrippsiella trochoidea cysts and its application to analysis during cyst formation and enzyme-linked immunosorbent assay.

A monoclonal antibody was produced by the fusion of mouse myeloma cells with spleen cells from a mouse immunized with the cysts of Scrippsiella trochoidea, marine phytoplankton. Immunofluorescence microscopic observation showed that the antibody reacted with the spines on the cyst but not with the vegetative cells and cyst walls. An enzyme-linked immunosorbent assay could be used to measure the cysts in muddy bottom sediments using the purified antibody conjugated with horseradish peroxidase.

Animals↗
PubMed2001

Clinical usefulness of the common carotid artery blood flow velocity ratio as measured by an ultrasonic quantitative flow measurement system: evaluation with respect to prevalence of ischemic heart disease.

The present study evaluated the clinical usefulness of the measurement of common carotid artery blood flow velocity by an ultrasonic quantitative flow measurement system (QFM), and its correlation with the prevalence of ischemic heart disease (IHD). The subjects in this study included 287 patients (149 men and 138 women; mean age, 67.6+/-11.0 years) being treated as outpatients. Bilateral common carotid artery blood flow velocity was measured using a QFM-1100 (Hayashi Denki Co., Ltd.). The "high to low velocity ratio" (H/L ratio) was calculated by dividing the higher value by the lower value of the velocity of the common carotid artery. In 43 of 287 patients, we used an SSA-270 ACE (Toshiba Co., Ltd) to determine the presence of plaque and measure intimal-medial thickness (IMT) in the common carotid arteries. The mean H/L ratio was 1.45, with a median value of 1.25. The patients were stratified into subgroups based on H/L ratios from 1.0 and above in 0.1 increments in order to compare the prevalence rates of IHD. The prevalence rates in groups with H/L ratios of 1.3 and greater were significantly higher than those in the group with H/L ratios less than 1.3. In logistic regression analysis, the unadjusted H/L ratio was an independent risk factor for IHD at ratios from greater than 1.1 to greater than 1.6. The age-adjusted H/L ratio was an independent risk factor for IHD at ratios from greater than 1.1 to greater than 1.4. IMT was significantly higher in patients with a H/L ratio of 1.4 or greater versus patients with a ratio less than 1.4 (1.154+/-0.417 mm vs. 0.421+/-0.425 mm; p<0.05). The prevalence of carotid artery plaque was also significantly higher in patients with a H/L ratio of 1.4 or greater versus patients with a ratio of less than 1.4 (76.5% vs. 38.5%; p<0.03). Therefore, determination of the carotid artery H/L ratio by means of QFM may be clinically useful in screening patients for coronary artery lesions.

Aged↗
PubMed2001

Clinical usefulness of measuring pulse wave velocity in predicting cerebrovascular disease: evaluation from a cross-Sectional and longitudinal follow-up study.

The present study was designed both as a cross-sectional and longitudinal follow-up study to evaluate the association between pulse wave velocity (PWV) and cardiovascular disease. The subjects in this study included a total 260 patients (134 men and 126 women) ranging from 25 to 91 years (mean, 67.6+/-11.0 years). Carotid to femoral PWV was measured in all patients. The subsequent development of a cerebrovascular or coronary event was defined as a cardiovascular event. The longitudinal follow-up study was conducted with the occurrence of a cardiovascular event as the endpoint. The patients were classified into two groups: an L group with a PWV of less than 10 m/sec and an H group with a PWV of 10 m/sec or higher. Cross-sectional study at baseline: The H group patients were significantly older than the L group patients. The prevalence of hypertension, cardiovascular disease, ischemic heart disease, and cerebrovascular disease were significantly higher in the H group. Systolic blood pressure and serum uric acid were significantly higher in the H group than in the L group. However, there were no significant differences between the two groups with respect to other risk factors. Multivariate analysis using the prevalence of cardiovascular disease as the dependent variable showed "age" and "H group" to be independent variables. When the prevalence of ischemic heart disease or cerebrovascular disease was used as dependent variable, only "age" was an independent variable. Longitudinal follow-up study: The prevalence of cardiovascular event and cerebrovascular event were significantly higher in the H group than in the L group. The prevalence of coronary event in the H group tended to be higher than in the L group, but the difference was not statistically significant. Multivariate analysis using the cardiovascular event rate or coronary event rate as the dependent variable showed only "age" to be an independent variable. When the cerebrovascular event rate was used as the dependent variable, "uric acid" and "H group" were independent variables. The results of this study suggest a higher rate of cerebrovascular disease in patients with high PWV.

Adult↗
PubMed2001

Ileus after administration of cold remedy in an elderly diabetic patient treated with acarbose.

A 69-year-old type 2 diabetic man was admitted due to diabetic gangrane. He had a history of subtotal gastrectomy. During hospitalization, he was treated with regular insulin and 300 mg/day of acarbose. He developed a low grade fever, cough and nasal discharge, and was given a compound "cold" remedy with anticholenergic properties. The next day, he suffered from a paralytic ileus. Oral intake and acarbose were withheld and the ileus spontaneously resolved after 2 days. These finding indicate the possibility that the ileus was triggered by drugs with anticholinergic properties in this elderly diabetic patient treated with alpha-glucosidase inhibitors.

Acarbose↗
PubMed2001

Comparison of ticlopidine and cilostazol for the prevention of restenosis after percutaneous transluminal coronary angioplasty.

Prevention of restenosis after percutaneous transluminal coronary angioplasty (PTCA) continues to be a significant problem. Recent controlled studies have demonstrated that cilostazol suppresses restenosis after PTCA. The effects of ticlopidine, another antiplatelet agent, were compared in terms of outcomes of patients randomized for treatment with the two drugs after PTCA. A total of 35 patients (47 lesions) were assigned prospectively and randomly to ticlopidine (17 patients, 24 lesions) and cilostazol (18 patients, 23 lesions) groups. Minimal luminal diameter (MLD) and percentage of stenosis to reference diameter were estimated before PTCA, just after the procedure and after 4 months follow-up. All patients underwent 4 months angiographic follow-up, at the end of which MLD was 2.03+/-0.71 mm in the ticlopidine group and 2.05+/-0.68 mm in the cilostazol group (p = 0.95), and the percentage of stenosis to reference diameter was 31.4+/-16.7% and 30.0+/-17.0%, respectively (p = 0.78). The restenosis rate was 12.5% in the ticlopidine group and 17.4% in the cilostazol group (p = 0.69), relatively low as compared to the 20% to 30% reported in previous studies. Adverse drug reactions during the follow-up period were observed in two of the ticlopidine group and none of the cilostazol group. We conclude that both ticlopidine and cilostazol are effective for the prevention of restenosis after PTCA, however the former may be associated with slight side effects.

Aged↗
PubMed2001

Evaluation of radioinduced damage and repair capacity in blood lymphocytes of breast cancer patients.

Genetic damage caused by ionizing radiation and repair capacity of blood lymphocytes from 3 breast cancer patients and 3 healthy donors were investigated using the comet assay. The comets were analyzed by two parameters: comet tail length and visual classification. Blood samples from the donors were irradiated in vitro with a 60Co source at a dose rate of 0.722 Gy/min, with a dose range of 0.2 to 4.0 Gy and analyzed immediately after the procedure and 3 and 24 h later. The basal level of damage and the radioinduced damage were higher in lymphocytes from breast cancer patients than in lymphocytes from healthy donors. The radioinduced damage showed that the two groups had a similar response when analyzed immediately after the irradiations. Therefore, while the healthy donors presented a considerable reduction of damage after 3 h, the patients had a higher residual damage even 24 h after exposure. The repair capacity of blood lymphocytes from the patients was slower than that of lymphocytes from healthy donors. The possible influence of age, disease stage and mutations in the BRCA1 and BRCA2 genes are discussed. Both parameters adopted proved to be sensitive and reproducible: the dose-response curves for DNA migration can be used not only for the analysis of cellular response but also for monitoring therapeutic interventions. Lymphocytes from the breast cancer patients presented an initial radiosensitivity similar to that of healthy subjects but a deficient repair mechanism made them more vulnerable to the genotoxic action of ionizing radiation. However, since lymphocytes from only 3 patients and 3 normal subjects were analyzed in the present paper, additional donors will be necessary for a more accurate evaluation.

Adult↗
PubMed2001

[A four-year prospective study on the influence of serum elevated lipoprotein (a) concentration on ischemic heart disease and cerebral infarction in elderly patients with type 2 diabetes].

To clarify the influence of elevated serum lipoprotein (a) (Lp(a)) concentration on ischemic heart disease (IHD) and the perforating artery occlusion type of cerebral infarction (CI) in elderly patients with type 2 diabetes, we measured the serum levels of Lp(a) of type 2 diabetic patients (n = 158, 81 men and 77 women). The group was followed up prospectively for 4 years and the incidence of IHD or CI was monitored. The diagnosis of CI was confirmed by computed tomography and that of IHD, which includes myocardial infarction and angina pectoris, was diagnosed by electrocardiogram and blood chemistry examination, Lp(a) concentrations of 20 mg/dl or more were identified as elevated Lp(a) levels and Lp(a) concentrations of less than 20 mg/dl were identified as normal Lp(a) levels. A Kaplan-Meier survival analysis (log-rank test) assessed the time to event rate stratified by an Lp(a) cutoff point of 20 mg/dl. The predictive value for CI or IHD events was assessed by multiple logistic regression analysis. The probability of IHD events was significantly higher in the elevated Lp(a) group than in the normal Lp(a) group without a history of IHD but was similar in the two groups for those patients with a history of IHD. There was no significant difference between the elevated Lp(a) group and the normal Lp(a) group with regard to CI events in patients without a history of CI and with a history of CI. On multiple logistic regression analysis, Lp(a), hyperlipidemia and a history of IHD were significant predictors of IHD and hypertension, hyperlipidemia and a history of CI were significant predictors of CI. These results show that elevated serum Lp(a) concentrations is an independent risk factor for IHD, but not for the perforating artery occlusion type of CI in type 2 elderly diabetic patients.

Aged↗
PubMed2001

Mucosal vaccination against influenza: protection of pigs immunized with inactivated virus and ether-split vaccine.

Effective vaccinations against swine influenza reduce the economic loss of pig industries, and also may minimize the possibility of emergence of new pandemic viruses, since pigs are intermediate hosts to generate reassortant viruses among avian and mammalian influenza viruses. In this study, we showed that intranasal immunization of pigs with formalin-inactivated or ether-split influenza vaccine (A/Aichi/2/68) induced virus-specific IgG, IgM, and IgA antibodies in their nasal secretions and sera, resulting in complete protection from virus challenge. Antibody response to the challenge virus was not observed in the immunized pigs, suggesting that the replication of the virus in the primary targets, respiratory epithelial cells, was inhibited. The present results indicate that intranasal immunization of pigs with inactivated vaccines is effective to control swine influenza, and also provide a good model, as well as a mouse model, to evaluate an intranasal application of influenza vaccine for humans.

Administration, Intranasal↗
PubMed2001

An oral drug delivery system targeting immune-regulating cells ameliorates mucosal injury in trinitrobenzene sulfonic acid-induced colitis.

Control of immune-regulating cells in the colonic mucosa is important in the treatment of patients with inflammatory bowel disease (IBD). The aim of study was to examine the therapeutic effect of dexamethasone (DX) microspheres on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats, a model for human Crohn's disease. DX microspheres and DX alone were administered orally to rats with TNBS-induced colitis. The macroscopic score, histological score, myeloperoxidase (MPO) activity, nitric oxide (NO) production, and gene expressions of proinflammatory cytokines, cyclooxygenase (COX)-1, and COX-2 in the colonic tissue were determined. Proliferating cell nuclear antigen (PCNA) staining and expression of nuclear transcription factor (NF)-kappaB in colonic tissues were also investigated. Macroscopic score, histological score, MPO activity, and NO production in rats treated with DX microspheres were significantly lower than in those treated with DX alone. The gene expression of proinflammatory cytokines and COX-2 in rats treated with DX microspheres was down-regulated, compared with that in rats treated with DX alone. The number of PCNA-positive cells in the DX microsphere group was larger than in the group treated with DX alone. DX microspheres suppressed NF-kappaB activation in TNBS-induced colitis more strongly than DX alone. Oral administration of DX microspheres appears to ameliorate mucosal injury in TNBS-induced colitis. This drug delivery system could be an ideal therapy for human IBD.

Administration, Oral↗
PubMed2001

[Problems regarding palliative home care for end-stage cancer patients after the enforcement of the care insurance system].

Since in a home care nurse station the arrangement of personnel is planned to carry out patient's home care in accordance with the individual patient's Care Plan, to provide palliative home care to end-stage cancer patients who frequently require extraordinary visits, it is necessary to employ full-time nurses. On the other hand, to make ends meet there must be at least two full-time nurses for every seven end-stage cancer patients in a home care nurse station monthly. However, a home care nurse station taking care of seven end-stage cancer home patients monthly is very rare. According to these circumstances only several special home care nurse stations are able to provide palliative home care to end-stage cancer patient; thus, palliative home care for such patients is generally provided by hospital or doctor's office staff members. Therefore, if the authorities concerned intend to accelerate to care the end-stage cancer patient at home, several additional charges which are able to be claimed in ordinary home care nurse station must be able to be claimed in hospital or doctor's office in the same way.

Home Care Services, Hospital-Based↗