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Biomedical subjects

K Kodama

Publications and source records attributed to K Kodama.

At least 19 recordsLinked to original sources
PubMed2006

Increased expression of CCAAT/enhancer binding protein-beta and -delta and monocyte chemoattractant protein-1 genes in aortas from hyperinsulinaemic rats.

AIMS/HYPOTHESIS: We evaluated whether hyperinsulinaemia stimulates the expression of transcription factor CCAAT/enhancer binding protein (C/EBP)-beta and C/EBP-delta and leads to the induction of the chemokine (C-C motif) ligand 2 gene (Ccl2, also known as MCP-1) expression in aortas. METHODS: Hyperinsulinaemia was induced by feeding rats a high-fructose diet. CCL2 production was analysed by ELISA. The expression of Ccl2, Cebpb and Cebpd mRNAs was investigated by quantitative RT-PCR. The binding of C/EBP-beta to Ccl2 was assessed by chromatin immunoprecipitation (ChIP) assay. RESULTS: Insulin at a concentration of 10 nmol/l significantly stimulated the expression of Cebpb, Cebpd and Ccl2 mRNAs, depending on activation of phosphatidylinositol 3-kinase (PI3K) in cultured vascular smooth muscle cells. The knock-down of C/EBP-beta with siRNA abolished the insulin-induced Ccl2 mRNA expression. In the aortas from fructose-fed rats, the levels of phosphorylation of Akt/protein kinase B, a downstream effector of PI3K, were also increased. The expression of Cebpb, Cebpd and Ccl2 mRNAs in the aortas from fructose-fed rats were significantly elevated, by 330, 300 and 300%, respectively, compared with those of control-fed rats. The induction Ccl2 mRNA expression in the aortas was significantly correlated with the expression of Cebpb and Cebpd mRNAs in the aortas. Furthermore, the ChIP assay showed elevated binding of C/EBP-beta to the 5' upstream region of Ccl2 in the aortas from fructose-fed rats. CONCLUSIONS/INTERPRETATION: These findings clearly indicate the role of C/EBPs in the mechanism of upregulation of CCL2, an inflammation-related protein, observed in the hyperinsulinaemic state, which may initiate the process of atherosclerosis.

Animals↗
PubMed2006

Randomised study of adjuvant chemotherapy for completely resected p-stage I-IIIA non-small cell lung cancer.

We evaluated the therapeutic usefulness of adjuvant chemotherapy in patients with completely resected non-small cell lung cancer (NSCLC). We also examined the relation between DNA ploidy pattern and the response to chemotherapy. A total of 267 patients with NSCLC (pathologically documented stage I, II, or IIIA) underwent complete resection, and DNA ploidy pattern was analysed. Patients with stage I disease (n=172) were randomly assigned to receive surgery alone (group A) or surgery followed by adjuvant chemotherapy (UFT (oral anti-cancer drug, a combination of Uracil and Tegaful) 400 mg day-1 for 1 year after surgery; group B). Stage II or IIIA disease patients (n=95) were randomly assigned to surgery alone (group C) or surgery followed by chemotherapy (two 28-day courses of cisplatin 80 mg m-2 on day 1 plus vindesine 3 mg m-2 on days 1 and 8, followed by UFT 400 mg day-1 for at least 1 year; group D). Eight-year overall survival rate in patients with stage I disease was 74.2% (95% confidence interval (CI): 64.4-84.0%) in group B and 57.6% (95% CI: 46.4-68.8%) in group A (P=0.045 by log-rank test). In patients with stage II and IIIA disease, no difference was found between groups C and D. Analysis according to DNA ploidy pattern revealed no difference between the groups. Postoperative chemotherapy with UFT was suggested to be useful in patients with completely resected stage I NSCLC. No difference was seen in relation to DNA pattern in any treatment group.

Age Factors↗
PubMed2006

Suppression of tumorigenicity, but not anchorage independence, of human cancer cells by new candidate tumor suppressor gene CapG.

Previously, we isolated a series of cell lines from a human diploid fibroblast lineage as a model for multistep tumorigenesis in humans. After passaging a single LT-transfected fibroblast clone, differently progressed cell lines were obtained, including immortalized, anchorage-independent and tumorigenic cell lines. In the present paper, we analysed the gene expression profiles of these model cell lines, and observed that expression of the CapG protein was lost in the tumorigenic cell line. To examine the possibility that loss of CapG protein expression was required for tumorigenic progression, we transfected CapG cDNA into the tumorigenic cell line and tested for tumor-forming ability in nude mice. Results showed that ectopic expression of CapG suppressed tumorigenicity, but not growth in soft agar or liquid medium. We also found that certain cancer cell lines including stomach cancer, lung cancer and melanoma had also lost CapG expression. One such cancer cell line AZ521 also became non-tumorigenic after the introduction of CapG cDNA. Moreover, we showed that CapG expression was repressed in small-cell lung cancer tissues. Together, our findings indicated that CapG is a new tumor suppressor gene involved in the tumorigenic progression of certain cancers.

Animals↗
PubMed2005

Dietary-fat-induced obesity in mice results in beta cell hyperplasia but not increased insulin release: evidence for specificity of impaired beta cell adaptation.

AIMS/HYPOTHESIS: Increased dietary fat intake is associated with obesity and insulin resistance, but studies have shown that the subsequent increase in insulin release is not appropriate for this obesity-induced insulin resistance. We therefore sought to determine whether the impaired beta cell adaptation is due to inadequate expansion of the beta cell population or to a lack of an adaptive increase in insulin release. METHODS: Male mice were fed diets containing increasing amounts of fat (15, 30 or 45% of energy intake) for 1 year, after which islet morphology and secretory function were assessed. RESULTS: Increased dietary fat intake was associated with a progressive increase in body weight (p<0.001). Fractional beta cell area (total beta cell area/section area) was increased with increasing dietary fat (1.36+/-0.39, 2.46+/-0.40 and 4.93+/-1.05%, p<0.001), due to beta cell hyperplasia, and was positively and highly correlated with body weight (r2=0.68, p<0.005). In contrast, insulin release following i.p. glucose did not increase with increasing dietary fat (118+/-32, 108+/-47 and 488+/-200 pmol/l per mmol/l, p=0.07) and did not correlate with body weight (r2=0.11). When this response was examined relative to fractional beta cell area (insulin release/fractional beta cell area), it did not increase but rather tended to decrease with increasing dietary fat (157+/-55, 43+/-13 and 97+/-53 [pmol/l per mmol/l]/%, p=0.06) and did not correlate with body weight (r2=0.02). CONCLUSIONS/INTERPRETATION: Long-term fat feeding is associated with an increase in the beta cell population but an inadequate functional adaptation. Thus, a functional rather than a morphological abnormality appears to underlie dietary-fat-induced beta cell dysfunction.

Animals↗
PubMed2005

Serial changes in plasma brain natriuretic peptide concentration at the infarct and non-infarct sites in patients with left ventricular remodelling after myocardial infarction.

OBJECTIVES: To clarify the role of infarct and non-infarct sites on left ventricular (LV) remodelling after myocardial infarction by measuring brain natriuretic peptide (BNP) from each site. METHODS AND RESULTS: BNP from the aorta and the anterior interventricular vein (AIV) was measured in 45 patients with first anterior myocardial infarction at one, six, and 18 months. The LV was significantly dilated (> 10 ml/m(2) of end diastolic volume from one to 18 months) in 20 patients (remodelling (R) group) but not in 25 others (non-remodelling (NR) group). Patient characteristics and LV functions did not differ significantly at one month but plasma BNP concentration was higher in group R than in group NR (336 (288) v 116 (106) pg/ml, p < 0.01), predicting the degree of LV dilatation. The difference in BNP concentration between the aortic root and AIV (DeltaBNP), reflecting BNP secreted from the infarct site, did not differ at one month. In both groups BNP and DeltaBNP significantly decreased from one to six months (p < 0.05) and decreased from six months to 18 months, but the change was not significant. BNP and DeltaBNP were significantly higher in group R than in group NR after six months, when LV dilatation was not evident in both groups. CONCLUSION: Enhanced BNP secretion at one month in the non-infarct and infarct ventricular sites predicts subsequent LV dilatation (that is, remodelling). The slower process of LV remodelling decreased BNP secretion at both sites. Thus, BNP concentration should be useful for monitoring ventricular remodelling after infarction.

Cardiomyopathy, Dilated↗
PubMed2005

First experience with direct, selective factor Xa inhibition in patients with non-ST-elevation acute coronary syndromes: results of the XaNADU-ACS Trial.

BACKGROUND: Unfractionated heparin is widely used in patients with non-ST-elevation acute coronary syndromes but has important limitations. Anticoagulants with predictable kinetics and anticoagulant effects, better efficacy, and greater safety are needed. OBJECTIVE: To investigate the efficacy and safety of a direct, selective factor Xa inhibitor, DX-9065a (Daiichi Pharmaceuticals LTD, Inc.) compared with heparin, in patients with non-ST-elevation acute coronary syndromes. PATIENTS AND METHODS: Patients (n = 402) from the USA, Canada, and Japan were randomized to blinded, weight-adjusted heparin, low-dose DX-9065a, or high-dose DX-9065a. RESULTS: The primary efficacy endpoint of death, myocardial infarction, urgent revascularization, or ischemia on continuous ST-segment monitoring occurred in 33.6%, 34.3%, and 31.3% of patients assigned to heparin, low-dose DX-9065a, and high-dose DX-9065a (P = 0.91 for heparin vs. combined DX-9065a). The composite of death, myocardial infarction, or urgent revascularization occurred in 19.5%, 19.3%, and 11.9% (P = 0.125 for heparin vs. high-dose DX-9065a) of patients; major or minor bleeding occurred in 7.7%, 4.2%, and 7.0% of patients; and major bleeding in 3.3%, 0.8%, and 0.9% of patients. Higher concentrations of DX-9065a were associated with a lower likelihood of ischemic events (P = 0.03) and a non-significant tendency toward a higher likelihood of major bleeding (P = 0.32). CONCLUSIONS: In this small phase II trial, there was a non-significant tendency toward a reduction in ischemic events and bleeding with DX-9065a compared with heparin in patients with acute coronary syndromes. The absence of an effect on ST-monitor ischemia warrants further investigation. These data provide the rationale for adequately powered studies of DX-9065a in acute coronary syndromes or percutaneous intervention.

Acute Disease↗
PubMed2003

Vegetable and fruit intake and stroke mortality in the Hiroshima/Nagasaki Life Span Study.

BACKGROUND AND PURPOSE: Fruits and vegetables are known for their beneficial effects on chronic diseases. The purpose of the present study was to investigate the protective effect of a diet rich in fruits and vegetables on total stroke mortality and its 2 main subtypes in men and women separately. METHODS: A prospective cohort study of 40 349 Japanese men and women was initiated in 1980-1981 and followed until 1998. Fruit and vegetable intake was assessed at baseline on the basis of the response to a food frequency questionnaire. During the 18-year follow-up period, deaths from stroke were registered. RESULTS: A total of 1926 stroke deaths were identified during the follow-up period. An increasing frequency of intake of green-yellow vegetables and fruit was associated with a reduced risk of death from intracerebral hemorrhage and cerebral infarction. Daily intake of green-yellow vegetables was associated with a significant 26% reduction in the risk of death from total stroke in men and women compared with an intake of once or less per week. The protective effect associated with daily fruit and vegetable intake was observed for both cerebral infarction and intracerebral hemorrhage mortality but was slightly stronger and clearer for infarction than for hemorrhage, with a 32% reduction in men and a 30% reduction in women. Daily fruit intake was associated with a significant 35% reduction in risk of total stroke in men and a 25% reduction in women and was equally strong for both intracerebral hemorrhage and cerebral infarction. CONCLUSIONS: Daily consumption of green-yellow vegetables and fruits is associated with a lower risk of total stroke, intracerebral hemorrhage, and cerebral infarction mortality. The protective effects are similar in both men and women.

Adult↗
PubMed2003

Secretory phospholipase A2 activity in the normal and kainate injected rat brain, and inhibition by a peptide derived from python serum.

The present study aimed to elucidate sPLA(2) activity in the normal and kainate-lesioned hippocampus using selective inhibitors of sPLA(2). In normal rats the highest levels of sPLA(2) were observed in the hippocampus, pons, and medulla, followed by the cerebral neocortex and caudate nucleus. After intracerebroventricular kainate injections an increase in total PLA(2) activity was observed in the rat hippocampus. Using a selective sPLA(2) inhibitor 12-epi-scalaradial, sPLA(2) activity was found to be significantly increased by 2.5-fold on the side of the intracerebroventricular injection compared to the contralateral side. A peptide P-NT.II, derived from the amino acid sequence of "PLA(2)-inhibitory protein," discovered in the serum of the reticulated python, also showed potent sPLA(2) inhibitory activity in homogenates from the kainate-injected hippocampus. These results show that there is a high level of sPLA(2) activity in the normal hippocampus, pons, and medulla oblongata, and that the level increases further in the hippocampus after kainate-induced excitotoxic injury. The increased PLA(2) activity was inhibited by P-NT.II, indicating a potential use of this peptide as a PLA(2) inhibitory agent in the brain.

Amino Acid Sequence↗
PubMed2003

Anxiety induced by repetitive transcranial magnetic stimulation is suppressed by chronic treatment of paroxetine in rats.

Repetitive transcranial magnetic stimulation (rTMS) has been shown to have a therapeutic effect on affective disorder and anxiety disorders. However, some reports have linked rTMS to a significant increase in anxiety in normal volunteers. This study investigates the effect of rTMS on anxiety and the use of acute and chronic paroxetine treatment on this animal model of anxiety. In normal rats, rTMS for 10 days induced anxiety, as shown by elevated plus maze, black and white box, and conditioned fear tests. This anxiety was suppressed by chronic, but not acute, paroxetine. These results suggest that rats receiving chronic rTMS treatment can be used as a model of anxiety and that the anxiety induced by rTMS might involve the serotonergic system.

Acute Disease↗
PubMed2003

Radiation dose-dependent increases in inflammatory response markers in A-bomb survivors.

PURPOSE: The well-documented increases in malignant tumours in the A-bomb survivors have recently been supplemented by reports that non-cancer diseases, including cardiovascular disease, may also have increased in incidence with increasing radiation dose. Given that low-level inflammatory responses are widely accepted as a significant risk factor for such diseases, we undertook a detailed investigation of the long-term effects of ionizing radiation on the levels of the inflammatory markers C-reactive protein (CRP) and interleukin 6 (IL-6) in A-bomb survivors. MATERIALS AND METHODS: Blood samples were taken from 453 participants in a long-term epidemiological cohort of A-bomb survivors. Plasma levels of CRP and IL-6 were measured using standard antibody-mediated procedures. Relationships between CRP or IL-6 levels and radiation dose were then investigated by multivariate regression analysis. Blood lymphocytes from each individual were used for immunophenotyping by flow cytometry with murine monoclonal antibodies to CD3, CD4 and CD8. RESULTS: CRP levels were significantly increased by about 31% Gy(-1) of estimated A-bomb radiation (p=0.0001). Higher CRP levels also correlated with age, male gender, body mass index and a history of myocardial infarction. After adjustments for these factors, CRP levels still appeared to have increased significantly with increasing radiation dose (about 28% increase at 1Gy, p=0.0002). IL-6 levels also appeared to have increased with radiation dose by 9.3% at 1Gy (p=0.0003) and after multiple adjustments by 9.8% at 1Gy (p=0.0007). The elevated CRP and IL-6 levels were associated with decreases in the percentages of CD4(+) helper T-cells in peripheral blood lymphocyte populations. CONCLUSIONS: Our results appear to indicate that exposure to A-bomb radiation has caused significant increases in inflammatory activity that are still demonstrable in the blood of A-bomb survivors and which may lead to increased risks of cardiovascular disease and other non-cancer diseases.

Aged↗
PubMed2002

Escherichia coli cells penetrated by chrysotile fibers are transformed to antibiotic resistance by incorporation of exogenous plasmid DNA.

A suspension of recipient Escherichia coli cells in stationary phase, chrysotile asbestos, and pUC18 donor DNA spread over the surface of a Luria-Bertani agar plate using a streak bar several times, resulted in intracellular uptake of the plasmid DNA by the E. coli cells. The transformation efficiency was highest with a duration of cell exposure to chrysotile of more than 60 s and an agar concentration of 2%. To improve chrysotile-mediated transformation efficiency, we systematically optimized various conditions and parameters. In comparison to chrysotile exposure without cations, exposure with cations produced up to 100-fold more transformants. Optimized conditions resulted in 10(6) transformants/ micro g pUC18 DNA. The drastic physical change due to 'quick drying on the surface of the agar plate' when cells were exposed to chrysotile, was essential for chrysotile-mediated transformation. We suggest that DNA uptake mediated by chrysotile asbestos is the result of a mechanical physical transformation of E. coli, since the E. coli cells are not chemically competent. Electron microscopy of cells exposed to chrysotile suggested penetration of the E. coli membrane by chrysotile fibers. It is suggested that E. coli transformation by the plasmid DNA was the result of penetration by chrysotile fibers to which plasmid DNA is bound or adsorbed.

Agar↗
PubMed2002

Magnetic superstructure in the two-dimensional quantum antiferromagnet SrCu2(BO3)2.

We report the observation of magnetic superstructure in a magnetization plateau state of SrCu2(BO3)2, a frustrated quasi-two-dimensional quantum spin system. The Cu and B nuclear magnetic resonance (NMR) spectra at 35 millikelvin indicate an apparently discontinuous phase transition from uniform magnetization to a modulated superstructure near 27 tesla, above which a magnetization plateau at 1/8 of the full saturation has been observed. Comparison of the Cu NMR spectrum and the theoretical analysis of a Heisenberg spin model demonstrates the crystallization of itinerant triplets in the plateau phase within a large rhomboid unit cell (16 spins per layer) showing oscillations of the spin polarization. Thus, we are now in possession of an interesting model system to study a localization transition of strongly interacting quantum particles.

Journal Article↗
PubMed2002

Superconductivity and magnetic fluctuations in Cd(2))Re(2)O(7) via Cd nuclear magnetic resonance and re nuclear quadrupole resonance.

We report Cd nuclear magnetic resonance (NMR) and Re nuclear quadrupole resonance (NQR) studies on Cd(2)Re(2)O(7), the first superconductor among pyrochlore oxides (T(c) approximately 1 K). The Re NQR spectrum at zero magnetic field below 100 K rules out any magnetic or charge order. The spin-lattice relaxation rate below T(c) exhibits a pronounced coherence peak and follows the weak-coupling BCS theory with nearly isotropic energy gap. The results of Cd NMR point to a moderate ferromagnetic enhancement at high temperatures followed by a rapid decrease of the density of states below the structural transition temperature of 200 K.

Journal Article↗
PubMed2002

A case of apolipoprotein C-II deficiency with coronary artery disease.

A 56-year-old male with apolipoprotein C-II deficiency experienced a myocardial infarction without pancreatitis. A coronary angiogram showed complete occlusions of both the right and circumflex coronary arteries. His serum lipid levels were as follows: fasting total cholesterol 3.15 mmol/l; postprandial total cholesterol 3.62 mmol/l; fasting triglycerides 1.46 mmol/A; postprandial triglycerides 6.14 mmol/l; fasting high-density lipoprotein-cholesterol 0.47 mmol/l; and postprandial high-density lipoprotein cholesterol 0.36 mmol/l. His fasting level of plasma apolipoprotein C-II was 0.005 g/l, but his plasma levels of other apolipoproteins were within normal ranges. A DNA sequence analysis of the apolipoprotein C-II gene showed no mutations in exon 1, 2, 3, or 4, where most gene mutations related to apolipoprotein C-II deficiency occur. We report this patient's very rare heterozygous apolipoprotein C-II deficiency with coronary artery disease. Although this patient had some risk factors for coronary artery disease, coronary atherosclerosis in this patient might have occurred as a result of lipoprotein abnormalities caused by at least one mutation in the apolipoprotein C-II gene.

Apolipoprotein C-II↗
PubMed2002

Comparative biochemical studies of carotenoids in catfishes.

The carotenoids of 12 species of Siluriformes fishes (eight families) were investigated from a comparative biochemical point of view. The patterns of carotenoids in catfishes belonging to the family Siluridae were quite different from those of the other seven families of catfishes (Bagridae, Amblycipitidae, Clariidae, Plotosidae, Ictaluridae, Callichthyidae and Malapteruridae). 7, 8-Dihydro-beta-carotene; 7, 8, 7', 8'- and 7, 8, 9, 10-tetrahydro-beta-carotene; (3R)-7', 8'-dihydro-beta-cryptoxanthin; 7, 8-dihydrolutein A; 7, 8-dihydrolutein B; parasiloxanthin; 7', 8'-dihydroparasiloxanthin; and 4 or 4'-hydroxyparasiloxanthin were characteristic carotenoids found in only one family, Siluridae, and these carotenoids accounted for 24-60% of total carotenoids. In catfishes belonging to the other seven families except Siluridae, the carotenoid patterns were very similar and the most predominant carotenoid was zeaxanthins (23-56%).

Animals↗
PubMed2002

Pros and cons of chest wall reconstruction using prosthetic meshes in a two-layer fashion.

A 46-year-old woman with giant chondrosarcoma of the sternum underwent wide full-thickness resection of the anterior chest wall, which included the pericardium and lung. The free rectus abdominus musculocutaneous flap was transplanted onto prosthetic meshes placed in two layers. While stability and esthetic effect were both good, the subsequent infection in the space between the two meshes prolonged for one month. As a result, the space was closed with an omentum flap. As a consequence, we recommend one-stage omentopexy to prevent the space problem between the two meshes.

Bone Neoplasms↗