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Biomedical subjects

K Shimada

Publications and source records attributed to K Shimada.

At least 37 records · Page 2Linked to original sources

Relation between aortic stiffness and coronary flow reserve in patients with coronary artery disease.

OBJECTIVES: To investigate the relation between aortic stiffness and coronary flow reserve (CFR) in patients with coronary artery disease (CAD). DESIGN: Observational study. SETTING: Coronary care unit of a primary care hospital. PATIENTS: 192 consecutive patients who underwent coronary angiography. MAIN OUTCOME MEASURE: Brachial-ankle pulse wave velocity (ba-PWV), CFR, and severity of CAD. RESULTS: According to the angiographic findings, patients were divided into four subgroups: patients without significant stenosis (normal coronary artery (NCA) group, n = 28) and those with one vessel disease (1VD group, n = 92), two vessel disease (2VD group, n = 50), or three vessel disease (3VD group, n = 22). ba-PWV increased with the number of diseased vessels and was significantly correlated with the number of diseased vessels (NCA group v 1VD group v 2VD group v 3VD group: 1481 (252) v 1505 (278) v 1577 (266) v 1727 (347) cm/s, p < 0.001). CFR had a significant negative correlation with ba-PWV (r = -0.45, p < 0.0001). The diastolic to systolic velocity ratio obtained in 45 patients also was significantly correlated with ba-PWV (r = -0.35, p < 0.05). Multiple regression analysis showed that ba-PWV was an independent determinant of CFR (p < 0.01). CONCLUSIONS: Coronary flow is altered with aortic stiffening in patients with CAD. These results suggest one possible mechanism for recent reports that aortic stiffness is a key cardiovascular risk factor.

Ankle↗

Aberrant expression of RAB1A in human tongue cancer.

This study was designed to identify specific gene expression changes in tongue squamous cell carcinomas (TSCCs) compared with normal tissues using in-house cDNA microarray that comprised of 2304 full-length cDNAs from a cDNA library prepared from normal oral tissues, primary oral cancers, and oral cancer cell lines. The genes identified by our microarray system were further analysed at the mRNA or protein expression level in a series of clinical samples by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis and imuunohositochemistry. The microarray analysis identified a total of 16 genes that were significantly upregulated in common among four TSCC specimens. Consistent with the results of the microarray, increased mRNA levels of selected genes with known molecular functions were found in the four TSCCs. Among genes identified, Rab1a, a member of the Ras oncogene family, was further analysed for its protein expression in 54 TSCCs and 13 premalignant lesions. We found a high prevalence of Rab1A-overexpression not only in TSCCs (98%) but also in premalignant lesions (93%). Thus, our results suggest that rapid characterisation of the target gene(s) for TSCCs can be accomplished using our in-house cDNA microarray analysis combined with the qRT-PCR and immunohistochemistry, and that the Rab1A is a potential biomarker of tongue carcinogenesis.

Aged↗

Synergistic effects on the inhibition of human CD8+ cytotoxic T lymphocytes-mediated killing against xenograft cells by coexpression of membrane-bound Human FasL and decoy Fas antigen.

The principal barrier to the use of pigs as donors to humans is hyperacute rejection mediated by the interaction of alpha-gal abundantly expressed on pig cells and the natural anti-Gal antibody, abundantly produced in humans. This antibody-mediated hyperacute rejection may be overcome by an alpha1, 3 galactosyltransferase gene-knockout pig. However, xenograft cells could be rejected by T cells, especially CD8+ cytotoxic T lymphocytes (CTL)-mediated response, because these elements show great cytotoxicity against xenografted cells. We previously demonstrated that the Fas/FasL pathway is a major contributor to CD8+ CTL function. Furthermore, we sought to prevent this cytotoxicity by overexpression of membrane-bound FasL carrying the deletion at the metalloproteinase cleavage site or by decoy Fas antigen that does not contain the death domain in its cytoplasmic region. To investigate the effects of coexpression of these molecules, we cotransfected both genes into swine endothelial cells (SEC). The double-overexpression effectively prevented CD8+ CTL-mediated killing. Although cotransfectants and single transfectants of either membrane-bound FasL or decoy Fas gene showed similar inhibition of cytotoxicity, the expression levels of decoy Fas in SEC cotransfectants were much lower than those of decoy Fas single transfectants. These data suggest that beneficial effects for prevention of CTL-mediated xenocytotoxicity may be produced by the double expression of these molecules. The overexpression of both molecules on xenografted cells may decrease the innate cellular response to xenografts creating a window of opportunity to facilitate xenograft survival.

Acute Disease↗

Solid tumors after hematopoietic stem cell transplantation in Japan: incidence, risk factors and prognosis.

To evaluate the incidence, risk factors and prognosis for solid tumors after hematopoietic stem cell transplantation (HSCT) in Japan, 809 patients who had received HSCT between 1981 and 2000 were retrospectively analyzed. In all, 19 newly diagnosed secondary cancers were observed. The risk for cancer development was 2.8 times as high as that for expected cases. The cumulative incidence ratios at 5 and 10 years were 1.9 and 4.2%, respectively. The risk was significantly elevated for buccal cavity cancer (standard incidental ratio (SIR), 44.42: 95% confidence interval (CI) 17.86-91.51), esophageal cancer (SIR, 22.36: 95% CI 6.09-57.25), and cervical cancer (SIR, 8.58: 95% CI 1.04-31.01). Of 15 patients who developed solid cancers following allografting, 12 had chronic graft-versus-host disease (GVHD), and all 10 patients with squamous cell carcinoma of the buccal cavity or esophagus had chronic GVHD. On multivariate analysis, extensive chronic GVHD and age over 45 years at the time of transplantation were associated with a higher risk for solid cancers. In all, 17 patients received therapy for secondary cancers, nine of whom are still alive and the 5-year probability of survival from the diagnosis is 42.8%. Our data suggest that early detection of secondary cancers is very important in prolonging overall survival.

Adult↗

Kink in the dispersion of layered strontium ruthenates.

We present detailed energy dispersions near the Fermi level along the high symmetry line GammaX on the monolayer and bilayer strontium ruthenates Sr2RuO4 and Sr3Ru2O7, determined by high-resolution angle-resolved photoemission spectroscopy. A kink in the dispersion is clearly shown for the both ruthenates. The energy position of the kink and the slope in the low-energy part near the Fermi level are almost identical between them, whereas the dispersion in the high-energy part varies, like the behavior of the kink for the cuprate superconductors.

Journal Article↗

Vascular supply of the subcutaneous pedicle of Nagata's method in microtia reconstruction.

Nagata's method is a two-stage method for total ear reconstruction in patients with microtia. In the first stage of this procedure, mastoid flap and posterior lobule flap are elevated with a subcutaneous pedicle. However, contribution to the vascular supply by this pedicle has been controversial. We investigated the presence or absence of apparent vessels in the subcutaneous pedicle in 14 primary cases of microtia in the first stage operation. In all cases some vessels were included in the pedicle. In lobular and small concha type microtia, the vessels originated from the parotid fascia or aponeurotic tissue behind the remnant cartilage. In concha type microtia, apparent vessels could be preserved by including the perichondrium of the conchal cartilage. These findings suggest that the mastoid and posterior lobule flaps or W-shaped flap in Nagata's first stage operation are actually the perforator-based flaps. The source vessel of the perforators seemed to be the posterior auricular artery because of its location although further dissection was not performed in order not to damage the vascular supply. The presence of the vessels can augment the blood supply of not only W-shaped flaps but also the skin flap cephalad to them. By confirming the preservation of the perforators in the subcutaneous pedicle the surgeon may be able to trim the covering skin more safely.

Blood Vessel Prosthesis Implantation↗

Adeno-associated virus vector-mediated interleukin-10 gene transfer inhibits atherosclerosis in apolipoprotein E-deficient mice.

Inflammation is a major contributor to atherosclerosis by its effects on arterial wall biology and lipoprotein metabolism. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that may modulate the atherosclerotic disease process. We investigated the effects of adeno-associated virus (AAV) vector-mediated gene transfer of IL-10 on atherogenesis in apolipoprotein E (ApoE)-deficient mice. A murine myoblast cell line, C2C12, transduced with AAV encoding murine IL-10 (AAV2-mIL10) secreted substantial amounts of IL-10 into conditioned medium. The production of monocyte chemoattractant protein-1 (MCP-1) by the murine macrophage cell line, J774, was significantly inhibited by conditioned medium from AAV2-mIL10-transduced C2C12 cells. ApoE-deficient mice were injected with AAV5-mIL10 into their anterior tibial muscle at 8 weeks of age. The expression of MCP-1 in the vascular wall of the ascending aorta and serum MCP-1 concentration were decreased in AAV5-mIL10-transduced mice compared with AAV5-LacZ-transduced mice. Oil red-O staining of the ascending aorta revealed that IL-10 gene transfer resulted in a 31% reduction in plaque surface area. Serum cholesterol concentrations were also significantly reduced in AAV5-mIL10-transduced mice. To understand the cholesterol-lowering mechanism of IL-10, we measured the cellular cholesterol level in HepG2 cells, resulting in its significant decrease by the addition of IL-10 in a dose-dependent manner. Furthermore, IL-10 suppressed HMG-CoA reductase expression in the HepG2 cells. These observations suggest that intramuscular injection of AAV5-mIL10 into ApoE-deficient mice inhibits atherogenesis through anti-inflammatory and cholesterol-lowering effects.

Adenoviridae↗

Clonal structure and flowering traits of a bamboo [Phyllostachys pubescens (Mazel) Ohwi] stand grown from a simultaneous flowering as revealed by AFLP analysis.

Abstract Although many bamboo species are characterized by simultaneous flowering at long intervals of up to 120 years, few studies have revealed the length of the flowering interval for very-long-lived bamboo species by observing the whole life cycle of a single clone. The flowering interval of Phyllostachys pubescens had been determined to be 67 years by means of observation through the entire life cycle from 1912 to 1979. We observed and analysed the clonal structure and flowering traits of a P. pubescens community which had regenerated from seed in 1930 and began to flower in 1997. Although this interval was again 67 years, flowering and nonflowering culms were mixed, and the flowering event lasted three years in the community. AFLP analysis of DNA samples showed distinct genets that originated from the previous flowering event and that each genet had its own flowering time. This is the first report to show that (i) different genets are mixed in a community of a large bamboo species with a leptomorphic rhizome system, and (ii) a community that originated from a single flowering event can have a range of flowering years.

Computer Simulation↗

Implications of plasma concentrations of adiponectin in patients with coronary artery disease.

OBJECTIVE: To investigate whether concentrations of plasma adiponectin constitute a significant coronary risk factor, with particular focus on the relation between plasma concentrations of adiponectin and the development of acute coronary syndrome (ACS). SUBJECTS AND METHODS: Plasma concentrations of adiponectin were measured in 123 patients with coronary artery disease (CAD) and in 17 control participants. Patients were divided into three groups according to condition type: acute myocardial infarction (AMI) group (n = 59), unstable angina pectoris (UAP) group (n = 28), and stable angina pectoris (SAP) group (n = 36). RESULTS: Plasma concentrations of adiponectin correlated negatively with body mass index (r = -0.18, p < 0.05), serum triglyceride (r = -0.25, p < 0.01), and fasting glucose concentrations (r = -0.21, p < 0.05), but correlated positively with age (r = 0.26, p < 0.01), high density lipoprotein cholesterol concentrations (r = 0.35, p < 0.01), and low density lipoprotein particle size (r = 0.37, p < 0.01). Plasma concentrations of adiponectin in patients with ACS, in both the AMI and UAP groups, were significantly lower than those in patients with SAP and in the control group (ACS, 6.5 (3.0) microg/ml; SAP, 11.3 (5.9) micro g/ml; control 12.8 (4.3) microg/ml; p < 0.01). Additionally, plasma concentrations of adiponectin in patients with CAD (7.9 (4.6) microg/ml, p < 0.01) were significantly lower than in the control group. There were, however, no significant differences between patients with SAP and the control group (p = 0.36). Multiple logistic regression analysis showed that smoking, fasting glucose concentration, and low log adiponectin concentration correlated independently with the development of an ACS. CONCLUSIONS: The findings suggest that measurement of plasma concentrations of adiponectin may be of use for assessing the risk of CAD and may be related to the development of ACS.

Adiponectin↗

Effect of dietary sodium intake on the expression of endothelin-converting enzyme in the renal medulla.

BACKGROUND/AIM: Endothelin-converting enzyme (ECE) catalyzes the generation of endothelin-1 (ET-1) from its inactive precursor big-ET-1. Previous studies suggested that the ET-1 system is involved in the regulation of sodium excretion by the kidney. In particular, ET-1 via the ET(B) receptor-mediated signaling has been shown to increase renal medullary blood flow and decrease sodium transport in the collecting duct, both acting to promote renal sodium excretion. The present study was designed to evaluate the possibility that alterations in dietary salt intake may regulate the ECE-1. METHODS: Wistar rats were fed for 3 days either with a diet containing low salt (0.01% NaCl), normal salt (0.5% NaCl), or high salt intake, either by high salt diet (4% NaCl) or normal salt diet plus 0.9% saline drinking. The expression of and immunoreactive protein levels of ECE-1 in the renal medulla was studied by RT-PCR, Northern blotting and Western blotting techniques. RESULTS: The expression of ECE-1 mRNA (by RT-PCR and Northern blotting), as well as the immunoreactive levels of ECE-1, were significantly higher in the renal medulla of rats exposed to high salt intake than in rats on normal salt diet. CONCLUSION: The findings suggest that upregulation of ECE-1, leading to increased generation of ET-1 in the renal medulla, may be a compensatory mechanism promoting enhanced sodium excretion by the kidney in response to high salt intake.

Animals↗

Changes in expression of the mouse homologues of KIAA genes after subchronic methamphetamine treatment.

Amphetamine abuse may be associated with adaptive changes in gene expression in the brain. In the present study, a newly developed cDNA array system comprising mouse KIAA (mKIAA) cDNA clones was used to examine the gene expression affected by chronic methamphetamine treatment. Approximately 800 mKIAA clones were blotted onto a nylon membrane and hybridized with 33P-labeled cDNA derived from mRNAs isolated from the whole brains of mice that had been treated daily with saline or methamphetamine (2 mg/kg, i.p.) for 2 weeks. The arrays displayed robust hybridization for almost all transcripts. The results obtained from five experiments were averaged, each performed with triplicate samples. Several clones were chosen as positive candidates for methamphetamine-induced changes; however, only Per2 and mKIAA0099 genes showed a significantly increased expression (P < .05). Subsequently, with the focus on the period-related proteins, the expression of these proteins in various parts of the rat brain were assessed by immunoblot analysis. Chronic administration of methamphetamine (8 mg/kg, i.p., for 10 days) caused increased Per2 protein expression in the hippocampus. Interestingly, chronic methamphetamine treatment at a lower dose (4 mg/kg, i.p., for 10 days) induced an increase in SCN circadian oscillatory protein (SCOP) expression, also in the hippocampus. These data suggest that long-lasting alterations of the period-related gene expressions in the hippocampus might play an important role in methamphetamine addiction.

Animals↗

Histopathology, pathogenesis and molecular genetics in primary central nervous system lymphomas.

Recent increases in the incidence of primary central nervous system lymphoma (PCNSL), a rare non-Hodgkin's lymphoma arising in the brain, have been noted in both immunodeficient and immunocompetent patients. Compared with lymphomas originating outside the central nervous system, the biology of PCNSL at the molecular or cytogenetic level has not been well characterized, yet it is important to thoroughly understand the etiology of this rare malignant lymphoma if effective therapies are to be developed. This review will focus on the epidemiology, clinical aspects, histopathology, pathogenesis, and molecular genetics of this aggressive, extranodal lymphoma in immunocompetent patients.

Animals↗

Environmental impacts of the Japanese beef-fattening system with different feeding lengths as evaluated by a life-cycle assessment method.

The objectives of this study were to evaluate the environmental impacts of a beef-fattening system using the life-cycle assessment (LCA) method and to investigate the effects of feeding length on the LCA results. The functional unit was defined as one animal, and the stages associated with the beef-fattening life cycle, such as feed (concentrate and rough-age) production, feed transport, animal management, animal body (i.e., biological activity of cattle), and the treatment of cattle wastes, were included in the system boundary. Our results suggest that enteric or gut CH4 emissions of cattle were the major source in the impact category of global warming (2,851 kg of CO2 equivalents), whereas NH3 emissions from cattle waste were the major source in the impact categories of acidification (35.1 kg of SO2 equivalents) and eutrophication (6.16 kg of PO4 equivalents). Feed production also contributed a great deal to all categories. A shorter feeding length resulted in lower environmental impacts in all the environmental impact categories examined in the current study, such as global warming and acidification, although there was a difference in effect of reducing environmental impacts among the categories.

Ammonia↗

[New surgical technique of pulmonary segmentectomy by ultrasonic scalpel and absorbable sealing materials].

We developed new surgical technique of pulmonary segmentectomy by ultrasonic scalpel to sever intersegmental pulmonary tissue and absorbable sealing materials to cover the cut surface of lung. This method is expected to preserve more anatomical lung volume than the segmentectomy with surgical stapler. Two cases of post surgical recurrent lung cancer, 3 cases of pulmonary metastasis and 4 cases of primary lung cancer were applied this technique to preserve function. Among 3 materials examined, best result was obtained with polyglycolic acid felt (PGAF:Neoveil). PGAF is a very soft and thin (0.15 mm depth) new absorbable material that is able to closely adhere to irregular sections of the lung with fibrin glue and effectively seals air leakage. Mean chest drainage period after surgery in 6 cases with PGAF was 3.3 days. Excellent lung expansion was obtained immediately after the surgery and PGAF was disappeared completely on chest CT within 1 year. Although the possible superiority of this method is suggested in the present study, further comparative study is necessary to clarify the advantage of this new technique.

Absorbable Implants↗