C-reactive protein and metabolic syndrome.
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C-Reactive Protein↗
Biomedical subjects
E Oda
Publications and source records attributed to E Oda.
The free-radical scavenger, edaravone, augments NO release from vascular cells and platelets after laser-induced, acute endothelial injury in vivo.
In vitro and in vivo experimental models have demonstrated that vascular endothelial function is significantly impaired as a result of oxidative stress, mediated by the generation of oxygen-derived free radicals in response to chronic or acute inflammation. In particular, super-oxide () at specific concentrations leads to the impairment of nitric oxide (NO) bioactivity, and it is known that NO plays a fundamental role in the maintenance of vascular homeostasis. The relationship between reactive oxygen species (ROS) and NO release in thrombosis-related endothelial damage in the peripheral microvasculature remains unclear, however. The purpose of the present study was to investigate the effect of the free-radical scavenger, edaravone, on NO synthesis and thrombotic potential in arterioles after exposure to laser irradiation. Highly sensitive electrochemical NO microsensors were positioned in femoral arterioles of mice, and the kinetics of NO release were recorded in response to standardized laser irradiation in vivo. In addition, images of NO release from damaged vascular cells were investigated in a similar rat model using the NO-sensitive dye 4,5-diaminofluorescein diacetate (DAF-2DA). Thrombogenesis was assessed in carotid arterioles by continuous video microscopy using image analysis software. Laser irradiation led to NO release from perturbed endothelial cells and from platelet-rich thrombi. Edaravone had no significant effect on NO release in non-laser treated, intact endothelium compared with placebo. In contrast, edaravone demonstrated a dose-dependent effect on NO release and thrombogenicity. At a concentration of 10.5 mg/kg per h, edaravone promoted a 5-fold increase in NO and a reduction in platelet-rich thrombus volume to 58% of the placebo values. Our data provide direct evidence to confirm that acute endothelial damage in peripheral microvessels initially induces NO release and that the free-radical scavenger, edaravone, augments NO synthesis leading to suppression of platelet thrombus formation.
Animals↗
Cut points of waist circumference for Japanese people.
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Adult↗
Varying the ratio of dietary n-6/n-3 polyunsaturated fatty acid alters the tendency to thrombosis and progress of atherosclerosis in apoE-/- LDLR-/- double knockout mouse.
We have investigated the influence of dietary n-6/n-3 (ù-6/ù-3) polyunsaturated fatty acid-balance on the tendency to arterial thrombosis and the progress of atherosclerosis in apoE-/- LDLR-/- double knockout mouse. Homozygous apoE-/- LDLR-/- double knockout mouse (DKO mice, 129XC57BL/6J background) and male C57BL/6 mice aged 6 weeks were divided into four groups. Each group was fed a diet containing a different n-6/n-3 ratio (Group l: 0.29; Group 2: 1.43; Group 3: 5.00; Group 4: 8), prepared with high linolenic (LNA) flaxseed oil (n-3 rich) and high linoleic (LA) safflower oil (n-6 rich). There were no statistical differences in the gain in body weight between the four groups. After 16 weeks, plasma triglyceride and LDL levels in Group 1 were significantly lower than in the other groups. Conversely, HDL was the highest. After 8 and 16 weeks, the tendency to arterial thrombosis was assessed using a He-Ne laser-induced thrombosis model. The degree of atherosclerosis was measured using the entire aorta method employing image analysis software. The n-6/n-3 ratio had a dose-dependent antithrombotic effect (thrombus volume decreased 23%, Group 1 vs. Group 4), In addition, the extent of atherosclerosis was less in the animals fed a low n-6/n-3 ratio compared with the high n-6/n-3 ratio group (atherosclerotic area decreased 40%, Group 1 vs. Group 4). The lowest n-6/n-3 ratio tested (0.29) was the most effective in suppressing the thrombotic and atherosclerotic parameters in these DKO mice.
Animals↗
Reprimo, a new candidate mediator of the p53-mediated cell cycle arrest at the G2 phase.
A novel gene, Reprimo, in which induction in cells exposed to X-irradiation is dependent on p53 expression, has been isolated. Ectopic p53 expression results in the induction of its mRNA. Reprimo is a highly glycosylated protein and, when ectopically expressed, it is localized in the cytoplasm and induces G(2) arrest of the cell cycle. In the arrested cells, both Cdc2 activity and nuclear translocation of cyclin B1 are inhibited, suggesting the involvement of Reprimo in the Cdc2.cyclin B1 regulation pathway. Thus, Reprimo may be a new member involved in the regulation of p53-dependent G(2) arrest of the cell cycle.
Amino Acid Sequence↗
Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis.
A critical function of tumor suppressor p53 is the induction of apoptosis in cells exposed to noxious stresses. We report a previously unidentified pro-apoptotic gene, Noxa. Expression of Noxa induction in primary mouse cells exposed to x-ray irradiation was dependent on p53. Noxa encodes a Bcl-2 homology 3 (BH3)-only member of the Bcl-2 family of proteins; this member contains the BH3 region but not other BH domains. When ectopically expressed, Noxa underwent BH3 motif-dependent localization to mitochondria and interacted with anti-apoptotic Bcl-2 family members, resulting in the activation of caspase-9. We also demonstrate that blocking the endogenous Noxa induction results in the suppression of apoptosis. Noxa may thus represent a mediator of p53-dependent apoptosis.
Amino Acid Motifs↗
Loss of transcription factor IRF-1 affects tumor susceptibility in mice carrying the Ha-ras transgene or nullizygosity for p53.
The transcription factor IRF-1 has been implicated in tumor suppression: IRF-1 suppresses cell transformation and mediates apoptosis in vitro. Here we show that the loss of IRF-1 alleles per se has no effect on spontaneous tumor development in the mouse but dramatically exacerbates previous tumor predispositions caused by the c-Ha-ras transgene or by nullizygosity for p53. Grossly altered tumor spectrum, as compared to p53-null mice, was also observed in mice lacking both IRF-1 and p53, and cells from these mice show significantly higher mutation rate. Our results suggest that IRF-1 is a new member of the tumor susceptibility genes.
Animals↗
[The critical appraisal of QOL questionnaire for prostate cancer patients].
BACKGROUND: Prostate cancer is a common malignancy that affects Japanese elderly men. Its incidence is increasing, recently, and its treatments are various. The measurement of quality of life (QOL) has become important for the evaluation of and selection of treatments. In Japan, however, there is no standard way of measuring QOL for prostate cancer patients, except the Japanese version of the EORTC QOL questionnaire for prostate cancer patients. We examined the validity and feasibility of this translated EORTC QOL questionnaire for prostate cancer patients. METHODS: Sixty-nine prostate cancer patients who were under treatment in 4 hospitals were selected for this study. We applied the content validity, the factorial validity which was analyzed by the oblique principal component cluster analysis, the internal consistency analyzed by the alpha coefficient of Cronbach, the convergent validity which was used GHQ, IPSS and PS as external measures, and the feasibility. RESULTS: This questionnaire showed good internal consistency, as the alpha coefficient was 0.61 to 0.90 in all domains, except for sex life, which was the lowest. This questionnaire was classified into 7 clusters by the oblique principal component cluster analysis. Consequently, the factorial validity was good, except for items regarding sex life. As domains correlate well with external measures except in sex life, the convergent validity was good. It was suggested that only two items were not acceptable in regard to the content validity and the feasibility, and that the translation into Japanese of 2 items was inadequate. CONCLUSIONS: Our study suggests that the Japanese version of the EORTC QOL questionnaire for prostate cancer patients demands improvement for the practical employment in clinical trials, as there is a problem of translation and feasibility.
Aged↗
Functionally inactivating point mutation in the tumor-suppressor IRF-1 gene identified in human gastric cancer.
Loss of heterozygosity (LOH) observed in human tumors strongly suggests the existence of (a) tumor-suppressor gene(s) at the concerned locus. A series of studies has revealed that LOH on the long arm of chromosome 5 (5q) frequently occurs in differentiated gastric adenocarcinomas. Furthermore, it has been shown that the interferon regulatory factor-1 (IRF-1) locus on chromosome 5q31.1 is one of the common minimal regions of LOH in these cancers. IRF-1 is a transcriptional activator that shows tumor-suppressor activity in the mouse. In the present study, we examined the sequence of the IRF-1 gene in 9 cases of histologically differentiated gastric adenocarcinomas, all of which exhibited LOH at the IRF-1 locus. We identified a mis-sense mutation in the residual allele in one case. This mutated form of IRF-1 showed markedly reduced transcriptional activity. In addition, overexpression of wild-type IRF-1 induced cell-cycle arrest, whereas such activity was attenuated in the mutant IRF-1. These results suggest that the loss of functional IRF-1 is critical for the development of human gastric cancers.
3T3 Cells↗
Involvement of the IRF family transcription factor IRF-3 in virus-induced activation of the IFN-beta gene.
The virus-induced activation of interferon alpha/beta (IFN-alpha/beta) gene transcription is essential for host defense. The IFN-beta promoter is controlled primarily by the virus-inducible enhancer elements, the IRF-Es. Here we show that IRF-3, an IRF family transcription factor, translocates to the nucleus from the cytoplasm upon virus infection in NIH/3T3 cells. The nuclear IRF-3 is phosphorylated, interacts with the co-activators CBP/p300, and binds specifically to the IFN-beta IRF-E. Furthermore, overexpression of IRF-3 causes a marked increase in virus-induced IFN-beta mRNA expression. Thus, IRF-3 is a candidate transcription factor mediating the activation of the IFN-beta gene.
3T3 Cells↗
Type I interferons are essential mediators of apoptotic death in virally infected cells.
BACKGROUND: The interferons (IFNs) have been extensively studied in the context of host defence against viral infection. In the established model of IFN action, virally infected cells secrete type I IFNs (IFN-alpha/beta) which induce an antiviral state in uninfected cells. However, it is not clear how IFNs function on the infected cells. It has been reported that cells infected by some viruses die by apoptosis. RESULTS: In the present study, we found that three types of viruses commonly induce apoptosis in primary cell cultures. Importantly, we observed that virus-induced apoptosis was inhibited by anti-IFN-alpha/beta antibodies, and in cells lacking either the type I IFN receptor 1 (IFNAR1) or its downstream mediator, Stat1 (Signal transducer and activator of transcription 1). IFN-alpha treatment by itself did not induce apoptosis unless it was combined with transfection by double-stranded RNA (dsRNA), which is normally generated during the course of viral infection. CONCLUSION: These results indicate a novel antiviral function of the type I IFNs, i.e. the selective induction of apoptosis in virally infected cells. In effect, these IFNs have a bifunctional role in limiting the spread of virus; eliciting an antiviral state in uninfected cells while promoting apoptosis in infected cells. Our results may help explain why IFNs are sometimes useful in the treatment of viral diseases and will provide further insight into the mechanisms of virus-induced pathogenesis.
Animals↗
Induction of Sp1 in differentiating human embryonal carcinoma cells triggers transcription of the fibronectin gene.
Cells of the human embryonal carcinoma line NEC14 proliferate as densely packed clusters consisting of small, polygonal stem cells and do not express a detectable level of fibronectin (FN). Upon induction of differentiation by treatment with N,N'-hexamethylene bisacetamide (HMBA), the level of FN mRNA increased steeply within 24 h and FN began to be accumulated, along with the organization of actin filaments in the cells. The FN promoter elements required for the activation were analyzed in reference to a cluster of GC boxes by using the chloramphenicol acetyltransferase (CAT) gene fused to 5' sequential-deletion derivatives of the promoter and promoters carrying base substitutions in the GC boxes. Among four GC boxes, GC boxes 2 and 3 had the greatest effect on promoter activation, and base substitutions in these GC boxes resulted in 80% reduction in promoter activity. The pattern of DNA-protein complex formation with these GC boxes changed drastically after induction of differentiation. The extract prepared from undifferentiated NEC14 cells formed fast-migrating complexes (UnD complexes), while the extract prepared from NEC14 cells treated with HMBA for 24 h formed slow-migrating complexes containing Sp1. Both complexes were formed predominantly with GC box 2. Base substitutions within the GC boxes completely abolished the formation of both UnD and Sp1 complexes. Consistent with these changes, the Sp1 level increased steeply within 24 h. Induction of Sp1 expression in NEC14 cells effectively stimulated the promoter activity of the transfected FN promoter-CAT constructs. These results indicate that activation of the FN promoter in differentiating NEC14 cells occurs by the steep induction of Sp1, which prevents an undifferentiated cell factor from binding to the Sp1 sites.
Base Sequence↗
Cloning and characterization of a GC-box binding protein, G10BP-1, responsible for repression of the rat fibronectin gene.
Fibronectin (FN) is an extracellular matrix protein that connects the extracellular matrix to intracellular cortical actin filaments through binding to its cell surface receptor, alpha5beta1, a member of the integrin superfamily. The expression level of FN is reduced in most tumor cells, facilitating their anchorage-independent growth by still unclarified mechanisms. The cDNA clone encoding G-rich sequence binding protein G10BP-1, which is responsible for repression of the rat FN gene, was isolated by using a yeast one-hybrid screen with the G10 stretch inserted upstream of the HIS3 and lacZ gene minimal promoters. G10BP-1 comprises 385 amino acids and contains two basic regions and a putative zipper structure. It has the same specificity of binding to three G-rich sequences in the FN promoter and the same size as the G10BP previously identified in adenovirus E1A- and E1B-transformed rat cells. Expression of G10BP-1 is cell cycle regulated; the level was almost undetectable in quiescent rat 3Y1 cells but increased steeply after growth stimulation by serum, reaching a maximum in late G1. Expression of FN mRNA is inversely correlated with G10BP-1 expression, and the level decreased steeply during G1-to-S progression. This down regulation was strictly dependent on the downstream GC box (GCd), and base substitutions within GCd abolished the sensitivity of the promoter to G10BP-1. In contrast, the level of Sp1, which competes with G10BP for binding to the G-rich sequences, was constant throughout the cell cycle, suggesting that the concentration of G10BP-1 relative to that of Sp1 determines the expression level of the FN gene. Preparation of glutathione S-transferase pulldowns of native proteins from the cell extracts containing exogenously or endogenously expressed G10BP-1, followed by Western blot analysis, showed that G10BP-1 forms homodimers through its basic-zipper structure.
Adenovirus E1A Proteins↗
[The physical, mental and social impacts of telling prostate cancer patients the true diagnosis].
BACKGROUND: Telling cancer patients the true diagnosis is inevitable to acquire informed consent especially in the Western world. In Japan, however, no such consensus has been established yet. We investigated the influence of telling the true diagnosis on QOL of prostate cancer patients. METHODS: We measured physical, mental and social aspect of prostate cancer outpatients by the General Health Questionnaire (GHQ) and the international Prostate Symptom Score (I-PSS). Using the general linear models we tried to explore which variables would attribute to "severe depression", "anxiety and insomnia" and "social dysfunction". RESULTS: No significant differences were found in any of the eight variables (age, performance status, clinical stage, I-PSS and Goldberg's four factors of GHQ) among the two groups that were informed the true diagnosis or not. The correlation structures of "severe depression", "somatic symptoms" and I-PSS are significantly different in the two groups. As a result of the analysis by the GLM, "somatic symptoms", I-PSS and clinical stages had main effect on "severe depression". Also, there was an interaction between the effect of telling the true diagnosis and "somatic symptoms". CONCLUSION: These results suggest that the mental condition of prostate cancer patients remain stable when they are in good physical condition regardless of being informed the true diagnosis or not. However, the patients who weren't told the true diagnosis have a tendency to get depression accompanying deterioration of physical condition. It is therefore considered that telling the true diagnosis makes the patients understand the changes of their physical conditions and help their mind to be stable.
Aged↗
[Reliability and factorial structure of a rating scale for persistent vegetative state].
We developed a new rating scale, Kohnan Vegetative Score, to measure severity and small clinical changes in vegetative state patients. It has 7 items corresponding to the conditions of vegetative state by Japanese Society of Neurosurgery: motor function, food ingestion, urination and defecation, eye movement, vocalization, communication, and facial expression. Each item is rated in 5 ordinal categories: slight (score = 1), mild(2), moderate(4), and extreme(5). The sum of the scores is used as the summary score, which ranges from 7 to 35, and high score means 'severe'. We examined the reliability and the factorial structure of the Kohnan Vegetative Score. The subjects were 10 patients who met the conditions of vegetative state. Four neurosurgeons rated the subjects, and then 2 of them repeated the rating after one week interval. As a measure of reliability, the (weighted) Kappa coefficient proposed Cohen (1960, 1968) was calculated for each item, and the intraclass correlation coefficient (ICC) was calculated for the summary score. To analyze the factorial structure, the factor analysis was carried out. The minimum and the maximum weighted Kappa values were 0.44 and 0.64 for intra-rater reliability, and 0.37 and 0.69 for inter-rater reliability, respectively. Concerning the factorial structure, the contribution of the first factor was 91.5% which indicated the unidimensionality of the scale. The ICC's estimate for the summary score were 0.90 (95% C.I.: 0.766-0.970). On the basis of these results, the Kohnan Vegetative Score has unidimensionality and high reliability enough for a practical use.
Aged↗
Isolation and characterization of the human inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP) gene (ITIHL1).
Inter-alpha-trypsin inhibitor (ITI) family heavy chain-related protein (IHRP) is a novel human glycoprotein that shows significant homology in amino acid sequence to proteins of the ITI family heavy chains from human plasma. Three overlapping clones that encode the human inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP) gene (ITIHL1) were isolated and characterized. The IHRP gene spans 15 kb and is composed of 24 exons from 27 to 207 bp in size with consensus splice sites. The gene codes for the precursor of IHRP, which is similar to inter-alpha-trypsin inhibitor (ITI) family heavy chains. Two major transcription initiation sites were identified in the 5'-flanking region. They contain putative promoter elements, but no typical TATA box. Some exons of this gene showed significant similarities to those of the ITI-H1 gene in nucleotide length and in intron phasing. The tissue-specific transcription of this gene may be due to the presence of binding sites for the hepatocyte nuclear factors LF-A1, HNF-5, NF-IL6, and C/EBP. This gene was found to be localized very close to another unknown gene related to EST (GenBank accession #: R54643, R50663, R50563, H27139, and R54913).
Base Sequence↗
[A clinical evaluation of fluconazole in deep seated fungal infections associated with hematological disorders].
The effectiveness of fluconazole on deep seated fungal infections associated with hematological disorders was evaluated in a multicenter clinical study. The underlying diseases included acute myeloblastic leukemia, acute lymphocytic leukemia, malignant lymphoma, adult T cell leukemia, multiple myeloma and others. Fluconazole (FLCZ) was administrated 100-400 mg/day intravenously or orally to 79 patients with systemic fungal infections complicated with hematological disorders and it was possible to evaluate clinical efficacies in 60 patients. 27 patients were diagnosed as having determinate systemic fungal infections and 33 patients suspected fungal infections. The clinical efficacies were 81.5% (22/27) in patients with diagnosed fungal infections and 57.6% (19/33) in patients with suspected fungal infections. The overall clinical efficacy was 68.3% (41/60). No side effects such as gastrointestinal symptoms, vascular pain and renal dysfunction were observed in this study. As for abnormal laboratory test, transient increases in GOT, GPT, Al-P, LDH, serum Na, Cl and decrease in serum K were observed in 9 patients (11.4%). These results indicated that FLCZ has a high therapeutic efficacy on deep seated fungal infections in patients with hematological disorders.
Aged↗
[Reliability and factorial structure of a rating scale for amyotrophic lateral sclerosis].
The Modified Norris Scale is a rating scale for amyotrophic lateral sclerosis (ALS), which consists of two parts, the Limb Norris Scale and the Norris Bulbar Scale. The Limb Scale has 21 items to evaluate extremity function and the Bulbar Scale has 13 items to evaluate bulbar function. Each item is rated in 4 ordinal categories. Considering the habitual difference, we translated the English scale into Japanese one with minor modification, and added more detailed explanations for all categories of each item. Then we examined reliability and factorial structure of the translated scale. The subjects were 23 patients with motor disturbance and each subject was rated twice by 2-4 neurologists. As a measure of reliability, the Kappa coefficient proposed by Cohen (1960) and Kraemer (1980) was calculated for each item and the intraclass correlation coefficient (ICC) was evaluated for total scores of each of two scales. To analyze the factorial structure, the factor analysis was carried out. The minimum and the maximum Kappa values were .70 and .97 for intra-rater reliability of the Limb Scale's items, .60 and .83 for inter-rater reliability of the Limb Scale's items, .41 and 1.00 for intra-rater reliability of the Bulbar Scale's items and .26 and .81 for inter-rater reliability of the Bulbar Scale's items, respectively. Concerning the factorial structure, the contribution of the first factor was 83.6% for the Limb Scale and that for the Bulbar Scale was 66.7%. This indicates unidimensionality of both Scales. The ICCs for the total scores were .97 (95%C.I. .95-.99) for the Limb Scale and .86 (.73-.93) for the Bulbar Scale, respectively. On the basis of these results, the Scale has unidimensionality and high reliability enough for practical use.
Adult↗