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Biomedical subjects

Y Sakai

Publications and source records attributed to Y Sakai.

At least 19 recordsLinked to original sources

Combined therapy of transcatheter hepatic arterial embolization with intratumoral dendritic cell infusion for hepatocellular carcinoma: clinical safety.

The curative treatments for hepatocellular carcinoma (HCC), including surgical resection and radiofrequency ablation (RFA), do not prevent tumour recurrence effectively. Dendritic cell (DC)-based immunotherapies are believed to contribute to the eradication of the residual and recurrent tumour cells. The current study was designed to assess the safety and bioactivity of DC infusion into tumour tissues following transcatheter hepatic arterial embolization (TAE) for patients with cirrhosis and HCC. Peripheral blood mononuclear cells (PBMCs) were differentiated into phenotypically confirmed DCs. Ten patients were administered autologous DCs through an arterial catheter during TAE treatment. Shortly thereafter, some HCC nodules were treated additionally to achieve the curative local therapeutic effects. There was no clinical or serological evidence of adverse events, including hepatic failure or autoimmune responses in any patients, in addition to those due to TAE. Following the infusion of (111)Indium-labelled DCs, DCs were detectable inside and around the HCC nodules for up to 17 days, and were associated with lymphocyte and monocyte infiltration. Interestingly, T lymphocyte responses were induced against peptides derived from the tumour antigens, Her-2/neu, MRP3, hTERT and AFP, 4 weeks after the infusion in some patients. The cumulative survival rates were not significantly changed by this strategy. These results demonstrate that transcatheter arterial DC infusion into tumour tissues following TAE treatment is feasible and safe for patients with cirrhosis and HCC. Furthermore, the antigen-non-specific, immature DC infusion may induce immune responses to unprimed tumour antigens, providing a plausible strategy to enhance tumour immunity.

Aged↗

Observation of B+ --> Lambda c+ Lambda c- K+ and B0 --> Lambda c+ Lambda c- K0 decays.

We report the first measurements of the doubly charmed baryonic B decays B --> Lambda c+ Lambda c- K. The B+ --> Lambda c+ Lambda c- K+ decay is observed with a branching fraction of (6.5(-0.9)(+1.0)+/-1.1+/-3.4)x10(-4) and a statistical significance of 15.4sigma. The B0 --> Lambda c+ Lambda c- K0 decay is observed with a branching fraction of (7.9(-2.3)(+2.9)+/-1.2+/-4.1)x10(-4) and a statistical significance of 6.6sigma. The branching fraction errors are statistical, systematic, and the error resulting from the uncertainty of the Lambda c+ --> pK- pi+ decay branching fraction. The analysis is based on 357 fb(-1) of data accumulated at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+ e- collider.

Journal Article↗

Observation of a near-threshold D(0)D[over](0)pi(0) enhancement in B-->D(0)D[over](0)pi(0)Kappa decay.

We report the first observation of a near-threshold enhancement in the D(0)D[over](0)pi(0) system from B-->D(0)D[over](0)pi(0)Kappa decays using a 414 fb(-1) data sample collected at the Upsilon(4S) resonance. The enhancement peaks at a mass M=3875.2+/-0.7(+0.3)/(-1.6) +/-0.8 MeV/c2 and the branching fraction for events in the peak is B(B-->D(0)D[over](0)pi(0)Kappa)=(1.22+/-0.31(+0.23)/(-0.30))x10(-4). The data were collected with the Belle detector at the KEKB energy-asymmetric e+ e- collider.

Journal Article↗

Cortical trapping of alpha-[(11)C]methyl-l-tryptophan, an index of serotonin synthesis, is lower in females than males.

One neural system that may exhibit gender differences is serotonin (5-HT), a neurotransmitter implicated in the regulation of mood, cognitive processes, and impulse-control. However, most of the available evidence of gender-related differences in this system has been indirect and at times contradictory. The objective of the present study was to follow up on preliminary evidence that there are gender differences in brain regional 5-HT synthesis, as measured by trapping of alpha-[(11)C]methyl-l-tryptophan (alpha-[(11)C]MTrp). Sixty-minute dynamic scans were performed in healthy volunteers, 28 women and 31 men. Functional images of the brain trapping constant, used as a proxy for 5-HT synthesis, which correlate in the rat brain with tryptophan's conversion into 5-HT, were transferred to the standardized 3D space. The voxel based comparison was performed by Statistical Parametric Mapping with proportional normalization. There was lower normalized alpha-[(11)C]MTrp trapping in females than males throughout much of the cerebral cortex, including the left middle frontal gyrus, the bilateral inferior frontal gyrus, the bilateral precentral gyrus, the left supramarginal gyrus, the bilateral inferior parietal lobule, the left superior temporal gyrus, the bilateral posterior cingulate gyrus, and the bilateral precuneus. There were no regions in which the normalized trapping was significantly higher in females than in males. Gender differences in sub-cortical sites were not found. Women, compared to men, may have lower rates of this tracer trapping, used as a proxy for 5-HT synthesis, throughout much of the cerebral cortex which is likely related to differences in 5-HT synthesis because relative differences in the normalized trapping should be the same as those in 5-HT synthesis. These differences may be related, at least in part, to previously suggested gender differences in affect, cognitive processes, and susceptibility to 5-HT-related neuropsychiatric and neurological disorders.

Adult↗

Significance of nerve growth factor overexpression and its autocrine loop in oesophageal squamous cell carcinoma.

Nerve growth factor (NGF) is overexpressed not only in nervous system, but also in several types of cancers. However, the role of NGF in oesophageal squamous cell carcinoma (OESCC) remains unclear. Here, we show the first evidence of NGF-TrkA autocrine loop and clinical significance of NGF overexpression in OESCC. Immunohistochemical study of 109 OESCC specimens revealed that NGF overexpression, found in 63 out of 109 patients (57.8%), was associated with lymph node metastasis, distant metastasis, higher TNM stage, poorer tumour differentiation, and poorer survival. NGF overexpression was also associated with strong expression of TrkA and negative expression of low-affinity neurotrophin receptor (p75NTR). Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) of 19 surgical specimens showed upregulation of NGF mRNA in 17 out of 19 (89%) patients. All five OESCC cell lines tested in vitro secreted detectable NGF in enzyme-linked immunosorbent assay, and expressed TrkA and p75NTR on RT-PCR and Western blot. The motility of HSA/c, one of the OESCC cell lines overexpressing NGF, was significantly decreased by either neutralising anti-NGF antibody, an inhibitor of TrkA, or NGF-small interfering RNA in transwell migration assay. Our findings suggest that NGF is of potential interest not only as a prognostic factor, but also as a novel therapeutic target in OESCC.

Adult↗

Observation of a chi(c2)' candidate in gamma gamma --> DD production at belle.

We report on a search for new resonant states in the process gamma gamma --> DD. A candidate C-even charmonium state is observed in the vicinity of 3.93 GeV/c2. The production rate and the angular distribution in the gamma gamma center-of-mass frame suggest that this state is the previously unobserved chi(c2)', the 2(3)P2 charmonium state.

Journal Article↗

Monocyte chemoattractant protein-1 gene delivery enhances antitumor effects of herpes simplex virus thymidine kinase/ganciclovir system in a model of colon cancer.

Suicide gene therapy using the herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system is a well-characterized tool for cancer gene therapy; however, it does not yet exhibit sufficient efficacy to cure patients of malignancies. We have reported that adenovirally delivered monocyte chemoattractant protein (MCP)-1 augmented the antitumor effects of the HSV-tk/GCV system in an athymic nude mouse model. The current study, which uses an immunocompetent mouse model of colon cancer, was designed to evaluate the antitumor effects of MCP-1 gene delivery in conjunction with this suicide gene therapy system. Subcutaneous tumor foci were directly transduced with both recombinant adenoviruses (rAds) expressing an HSV-tk gene and either of the MCP-1, CD80 and LacZ genes, followed by GCV administration. The growth of tumors was markedly suppressed by codelivery of HSV-tk and MCP-1 genes, which was exclusively associated with the recruitment of monocytes/macrophages, T helper 1 (Th1) cytokine gene expression and cytotoxic activity of the splenocytes. Furthermore, the antitumor effects were more efficient than that obtained by the combination of HSV-tk and CD80 genes. These results suggest an immunomodulatory effect of MCP-1 in the context of suicide gene therapy of colon cancer via orchestration of innate and acquired immune responses.

Adenoviridae↗

An unusual renal vascular anomaly: common origin of arteries to the lower poles demonstrated by a computed tomography angiography using 16-slice multidetector computed tomography.

Arterial connection between the left and right kidneys is extremely rare. Only eight cases of such anomalous conditions have been reported in the world literature and all were confirmed by invasive angiography or dissection. We report a patient with this vascular anomaly clearly demonstrated by 16-slice multidetector computed tomography.

Angiography↗

Cell preparation of Enterococcus faecalis strain EC-12 prevents vancomycin-resistant enterococci colonization in the cecum of newly hatched chicks.

The use of antimicrobials in broilers is considered to be a cause of the appearance of vancomycin-resistant enterococci (VRE). Once VRE penetration occurs, whatever its origin, it is difficult to expel the enterococci from the intestine because of their multiple resistance, whether natural or acquired. In this study, we evaluated the prevention of VRE colonization by the dietary supplementation of a cell-wall preparation of Enterococcus faecalis strain EC-12 (EC-12) in newly hatched broilers that were challenged by experimental infection with VRE. The chicks were fed a basal diet supplemented with 0.05% (wt/wt) EC-12 powder for 15 d. The control group and that administered Lactobacillus sp. were fed the basal diet. The VRE challenge was administered orally when the chicks were 2 d old (d 0). Dietary EC-12 reduced VRE colonization in the intestine from d 3 to 14. Total IgA in the cecal digesta and total IgG in the serum were higher on d 14 in the EC-12 treatment group. However, VRE-specific and EC-12-specific antibodies were not affected in serum. Hence, it appeared that dietary EC-12 stimulated the gut immune system and reinforced the immune reaction against the VRE challenge to accelerate its defecation from the chick intestine.

Animals↗

Osteogenic potential of cells in vitro derived from haemarthrosis of the knee induced by injury to the anterior cruciate ligament.

We have investigated whether cells derived from haemarthrosis caused by injury to the anterior cruciate ligament could differentiate into the osteoblast lineage in vitro. Haemarthroses associated with anterior cruciate ligament injuries were aspirated and cultured. After treatment with beta-glycerophosphate, ascorbic acid and dexamethasone or 1,25 (OH)(2)D(3), a significant increase in the activity of alkaline phosphatase was observed. Matrix mineralisation was demonstrated after 28 days and mRNA levels in osteoblast-related genes were enhanced. Our results suggest that the haemarthrosis induced by injury to the anterior cruciate ligament contains osteoprogenitor cells and is a potential alternative source for cell-based treatment in such injury.

Adolescent↗

Persistent diffusion abnormalities in the brain stem of three children with mitochondrial diseases.

We report 2 children (patients 1 and 2) with Kearns-Sayre syndrome and 1 (patient 3) with Leigh syndrome, who underwent serial diffusion-weighted MR imaging (DWI) studies for 2.8 (patient 1), 4.2 (patient 2), and 1.0 years (patient 3). The DWI revealed the persistent hyperintense signals in the pontine and mesencephalic tegmenta. The apparent diffusion coefficient in the affected regions remained constantly low, suggesting that cytotoxic edema and spongiform degenerations may compose these brain stem lesions.

Basal Ganglia↗

Temperament and job stress in Japanese company employees.

BACKGROUND: This study aims to demonstrate the relevance of temperament to job stress. METHOD: The subjects were 848 male and 366 female Japanese company employees. Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire version (TEMPS-A) and Munich Personality Test (MPT) were administered to assess temperaments, and the NIOSH Generic Job Stress Questionnaire (GJSQ) to assess job stress. We used hierarchical multiple linear regression analysis in order to demonstrate whether temperament variables added any unique variance after controlling the effects of other predictors such as gender, age and job rank. RESULTS: In all subscales of the GJSQ, temperament predicted a large share of the variance in job stress. Remarkably, for interpersonal relationship stressors, the temperament variables added greater variance than that predicted by gender, age and job rank. Summary of the hierarchical linear regression analysis showed that the irritable temperament was associated with the most prominent vulnerability, followed by cyclothymic and anxious temperaments. The schizoid temperament had difficulty in the area of social support. On the other hand, the hyperthymic temperament displayed significant robustness in facing most job stressors; the melancholic type showed a similar pattern to a lesser degree. LIMITATION: The findings may be different in a clinical Japanese sample, or a cohort of healthy employees from a different cultural background. CONCLUSIONS: Temperament influences job stress significantly-indeed, it impacts on such stress with greater magnitude than age, gender and job rank in most areas examined. Temperament influences interpersonal relationship stressors more than workload-related stressors. Interestingly, in line with previous clinical and theoretical formulations, the hyperthymic and melancholic types actually appear to be "hyper-adapted" to the workplace.

Adult↗

Flow-cytometric analysis on cytotoxic effect of thimerosal, a preservative in vaccines, on lymphocytes dissociated from rat thymic glands.

There is a concern on the part of public health community that adverse health consequence by thimerosal, a preservative in vaccines for infants, may occur among infants during immunization schedule. Therefore, the cytotoxic action of thimerosal was examined on lymphocytes dissociated from thymic glands of young rats using a flow cytometer and respective fluorescent probes for monitoring changes in intracellular Ca2+ concentration ([Ca2+]i) and membrane potential, and for discriminating intact living cells, apoptotic living cells and dead cells. Incubation with thimerosal at 3 microM or more (up to 30 microM) for 60 min depolarized the membranes, associated with increasing the [Ca2+]i. Thimerosal at 30 microM induced an apoptotic change in membranes of almost all living cells. Furthermore, the prolonged incubation with 30 microM thimerosal induced a loss of membrane integrity, leading to cell death. Since the blood concentration of thimerosal after receiving vaccines is theoretically submicromolar, it may be unlikely that thimerosal affects lymphocytes of infants.

Animals↗

Highly efficient transfection of human marrow stromal cells by nucleofection.

Human marrow stromal cells (hMSCs) are an attractive source for autologous cell and gene therapies. In this study, we developed a highly efficient transfection method for hMSCs. Although they tend to show efficient gene delivery, nonviral vectors offer several advantages over viral vectors for gene therapies. They are inexpensive to produce and suitable to adopt particularly with respect to little or no specific immune responses; they are simple to use; they entail easier large-scale production; and they have a high degree quality control. hMSCs and rat marrow stromal cells were transfected with the plasmid pEGFP-N1 that encoded a green fluorescent protein component by using two nonviral methods: nucleofection and electroporation. Nucleofection provided a much better rate of transfer than electroporation particularly in hMSCs.

Animals↗

Favourable association of leg fat with cardiovascular risk factors.

OBJECTIVES: To assess the association of trunk and leg fat mass (FM) and leg lean tissue mass (LTM) with conventional cardiovascular risk factors. DESIGN: Cross-sectional study. SETTING AND SUBJECTS: We studied 1249 men and 3007 women (age 20-79 years) who attended a research institute for a health checkup between October 1995 and February 2004. MAIN OUTCOME MEASURES: Body mass index, waist circumference (WC), hip circumference (HC), systolic and diastolic blood pressure, total cholesterol, HDL cholesterol, triglycerides, glucose and haemoglobin A(1C) were measured. Trunk FM, leg FM and leg LTM were obtained by dual-energy X-ray absorptiometry. We evaluated the associations between the indices for regional body composition and cardiovascular risk factors, which included hypertension, hypercholesterolaemia, hypo-HDL cholesterolaemia, hypertriglyceridaemia, dyslipidaemia and diabetes mellitus. RESULTS: Increase in WC and HC respectively showed increase and decrease in odds ratios of cardiovascular risk factors. Increase in trunk FM by 1 kg significantly increased the risk of the cardiovascular risk factors with the odds ratios ranging between 1.11 and 1.45. Increase in leg FM by 1 kg significantly decreased the risk with the odds ratios ranging between 0.52 and 0.90, except for the nonsignificant results for hypercholesterolaemia and hypo-HDL cholesterolaemia in men. Odds ratios of 1 kg increase in leg LTM were only significant for dyslipidaemia in men and hypercholesterolaemia in women (both 0.93). CONCLUSIONS: WC and HC showed opposite and independent associations with cardiovascular risk factors. The favourable association of HC was mainly attributable to that of leg FM.

Adipose Tissue↗

Gallbladder aspiration for acute cholecystitis in average-surgical-risk patients.

We conducted a retrospective case note review to assess whether or not gallbladder aspiration can be applied as a temporary measure for the treatment of acute cholecystitis in average-surgical-risk patients. Gallbladder aspiration was performed in 79 consecutive average-surgical-risk patients with acute cholecystitis, who had no indications of emergent surgery and who complained of severe colicky pain. Elective surgery became possible in 92% of patients by gallbladder aspiration. The percentage reached 97 when percutaneous cholecystostomy was added (four patients). Emergent surgery was needed in one patient suffering bile leakage following gallbladder aspiration. Colicky pain was controlled soon after the procedure in most cases. Neither major complications nor mortalities were observed in the following surgical therapies. It is suggested that gallbladder aspiration might be applied as a temporary measure for acute cholecystitis in average-surgical-risk patients, although early surgery should remain the primary choice of therapy in such patients.

Aged↗

Contralateral pharyngeal paralysis caused by medial medullary infarction.

A patient with unilateral upper medial medullary infarction presented with contralateral paralysis of the pharyngeal constrictor muscle in association with lemniscal sensory loss, pyramidal insufficiency, and central facial palsy on the same side. Individual differences in supranuclear control of the pharyngeal muscles may explain this rare occurrence. The combination of these signs is described as a syndrome of upper medial medullary lesion.

Brain Stem Infarctions↗

Elution and adsorptive concentration of Japanese cedar (Cryptomeria japonica) pollen allergen in environmental water.

Elution of Japanese cedar pollen allergens (Cry j I and others) from pollen grains and its adsorptive concentration onto hydrophobic and hydrophilic surfaces were investigated using the surface plasmon resonance technique. Results showed that the allergen elution was obviously enhanced when the ion concentration was higher than that within the human body, indicating that the pollen tend to release its allergen in environmental water having a high ion concentration. However, higher adsorption capacity was observed on hydrophobic surface than hydrophilic surface. These results indicate that water puddles on roadsides beside heavy traffic including large amounts of ion compounds and hydrophobic diesel exhaust particles (DEPs) are a pollen allergen-DEP complex generator. DEPs are easily absorbed into the living body; therefore these mechanisms may be responsible for causing the highest incidence of pollinosis among residents living alongside roads with heavy automobile traffic.

Adsorption↗