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Biomedical subjects

T Maruyama

Publications and source records attributed to T Maruyama.

At least 37 records · Page 2Linked to original sources
PubMed2005

Combined therapy of deoxyspergualin and plasmapheresis: a useful treatment for antibody-mediated acute rejection after kidney transplantation.

Antibody-mediated acute rejection (AbAR) is one of the primary causes of graft impairment in kidney transplant recipients. Deoxyspergualin (DSG), which displays an antiproliferative action against antigen-stimulated B cells inhibiting antibody production, may be effective to rescue AbAR in combination with plasmapheresis by suppressing antibody production and elimination. In the present study, we report our experience with DSG/plasmapheresis therapy for the treatment of AbAR. Five kidney transplant patients experienced a steroid-resistant acute rejection requiring dialysis followed by an AbAR that was confirmed by biopsy and flow cytometry crossmatch (FCXM) results. DSG was administration at 3 mg/kg per day for 10 days with plasmapheresis reduce antidonor antibody. Treatment outcome, effectiveness, and adverse events were examined; in two cases sequential FCXM examinations were performed to evaluate antibody status. All five patients received DSG/plasmapheresis therapy. The number of plasmapheresis treatments ranged from 1 to 9 according to treatment outcomes. Four patients recovered graft function following treatment; whereas one showed no response to the treatment, and the graft was lost. No serious side effects or infections were observed during or after treatment. Monitoring of sequential FCXM correlated with the clinical course. AbAR shows a worse prognosis than cellular rejection. It is refractory to conventional antirejection therapy. In the present study, DSG/plasmapheresis therapy was effective in four of five patients (80%) with AbAR. It may be considered the first choice of treatment for cases of acute humoral rejection.

Acute Disease↗
PubMed2005

Malignant progression of benign brain tumors after gamma knife radiosurgery: is it really caused by irradiation?

Malignant transformation of benign neoplasm after radiosurgery is usually diagnosed based on the initial presence of benign tumor, its exposure to ionizing radiation, elapsed time from radiation exposure to malignant progression, and different histological characteristics or growth rate of the regrowing tumor comparing with those originally treated. Three presented cases fulfilled these diagnostic criteria; however, it seems that progression of the tumors (schwannoma, meningioma, chordoma) resulted from the natural course of the disease, rather than represented side effects of gamma knife radiosurgery. Evaluation of the proliferative potential of the benign neoplasm before radiosurgical treatment either directly, if tumor sampling is available, or indirectly, by calculation of the tumor growth rate and/or analysis of the data of the metabolic imaging (PET, MRS) is important for identification of "aggressive" subtypes, precise prediction of prognosis, and confirmation of the radiation-induced malignant transformation in cases of tumor regrowth.

Adult↗
PubMed2005

Elevated macrophage migration inhibitory factor (MIF) levels in the urine of patients with focal glomerular sclerosis.

The pathogenesis of focal glomerular sclerosis (FGS) is poorly understood. Macrophage migration inhibitory factor (MIF) is a potent pro-inflammatory cytokine released from T cells and macrophages, and is a key molecule in inflammation. To examine further the possible role of MIF in FGS, we measured MIF levels in the urine. The purpose of the present study was to evaluate the involvement of MIF in FGS. Urine samples were obtained from 20 FGS patients. The disease controls included 40 patients with minimal-change nephrotic syndrome (MCNS) and membranous nephropathy (MN). A group of healthy subjects also served as controls. Biopsies were performed in all patients prior to entry to the study. The samples were assayed for MIF protein by a sandwich enzyme-linked immunosorbent assay (ELISA). The levels of MIF in the urine of FGS patients were significantly higher than those of the normal controls and patients with MCNS and MN. In contrast, the levels of urinary MIF (uMIF) in patients with MCNS and MN did not differ significantly from normal values. In the present study, attention also focused on the relationship between uMIF levels and pathological features. Among the patients with FGS, uMIF levels were significantly correlated with the grade of mesangial matrix increase and that of interstitial fibrosis. There was also a significant correlation between uMIF levels and the number of both intraglomerular and interstitial macrophages. Although the underlying mechanisms remain to be determined, our study presents evidence that urinary excretion of MIF is increased in FGS patients with active renal lesions.

Adult↗
PubMed2004

Evidence for an oscillatory signature in atmospheric neutrino oscillations.

Muon neutrino disappearance probability as a function of neutrino flight length L over neutrino energy E was studied. A dip in the L/E distribution was observed in the data, as predicted from the sinusoidal flavor transition probability of neutrino oscillation. The observed L/E distribution constrained nu(micro)<-->nu(tau) neutrino oscillation parameters; 1.9x10(-3) 0.90 at 90% confidence level.

Journal Article↗
PubMed2004

Search for electron neutrino appearance in a 250 km long-baseline experiment.

We present a search for electron neutrino appearance from accelerator-produced muon neutrinos in the K2K long-baseline neutrino experiment. One candidate event is found in the data corresponding to an exposure of 4.8 x 10(19) protons on target. The expected background in the absence of neutrino oscillations is estimated to be 2.4+/-0.6 events and is dominated by misidentification of events from neutral current pi(0) production. We exclude the nu(micro) to nu(e) oscillations at 90% C.L. for the effective mixing angle in the 2-flavor approximation of sin((2)2theta(microe)( approximately 1/2sin((2)2theta(13))>0.15 at Deltam(2)(microe)=2.8 x 10(-3) eV(2), the best-fit value of the nu(micro) disappearance analysis in K2K. The most stringent limit of sin((2)2theta(microe)<0.09 is obtained at Deltam(2)(microe)=6 x 10(-3) eV(2).

Journal Article↗
PubMed2004

Limits on the neutrino magnetic moment using 1496 days of Super-Kamiokande-I solar neutrino data.

A search for a nonzero neutrino magnetic moment has been conducted using 1496 live days of solar neutrino data from Super-Kamiokande-I. Specifically, we searched for distortions to the energy spectrum of recoil electrons arising from magnetic scattering due to a nonzero neutrino magnetic moment. In the absence of a clear signal, we found micro(nu)</=(3.6x10(-10))micro(B) at 90% C.L. by fitting to the Super-Kamiokande day-night spectra. The fitting took into account the effect of neutrino oscillation on the shapes of energy spectra. With additional information from other solar neutrino and KamLAND experiments constraining the oscillation region, a limit of micro(nu)</=(1.1x10(-10))micro(B) at 90% C.L. was obtained.

Journal Article↗
PubMed2004

Role of genetic factors (CETP gene Taq I B polymorphism and Apo A-I gene Msp I polymorphism) in serum HDL-C levels in women.

BACKGROUND AND AIM: Plasma high density lipoprotein cholesterol (HDL-C) levels are determined by a variety of environmental and genetic factors. The cholesteryl ester transfer protein (CETP) and apolipoprotein A-I (Apo A-I) are considered to be associated with HDL-C metabolism. The aim of this study was to investigate the relationship between the CETP gene Taq I B and Apo A-I gene Msp I polymorphisms and plasma lipid levels taking into account environmental factors, and to determine the combined effects of these polymorphisms on HDL-C levels in Japanese women. METHODS AND RESULTS: The study involved 270 Japanese women aged 30-69 years. We found a significant association between the CETP genotypes and HDL-C levels (p=0.0020), which were also associated with the Apo A-I gene (M1) polymorphism. Stepwise multiple regression analysis revealed that both the CETP Taq I B and Apo A-I gene (M1) genotypes were independent predictive variables. The strength of the association between the Apo A-I (M1) subgroup and HDL-C levels was reduced in the subjects with a high Body Mass Index (BMI). The combination of genotypes provided more detailed information about HDL-C levels. The "high risk" combination of the M1+ (M1+/+) and B1B1 genotypes was associated with the lowest HDL-C level (1.52+/-0.36 mmol/L), and the "low risk" combination of the M1- (M1+/- or M1-/-) and B2B2 genotypes was associated with the highest HDL-C levels (2.06+/-0.34 mmol/L). CONCLUSIONS: Our results suggest that the combination of the two polymorphisms influences HDL-C levels in women, and that the association between genetic factors and HDL-C levels is altered by environmental factors. They may also help to detect individuals with low HDL-C levels at high risk for coronary artery syndrome.

Adult↗
PubMed2004

Excess accumulation of body fat is related to dyslipidemia in normal-weight subjects.

OBJECTIVE: To assess the relationship of fat mass (FM) and its distribution to hypertension and dyslipidemia in normal-weight Japanese individuals. DESIGN: Cross-sectional study. SUBJECTS: Apparently healthy Japanese subjects with a body mass index (BMI) between 20 and 23.5 kg/m(2) (265 males and 741 females, age 21-69 y). MEASUREMENTS: BMI, waist circumference (WC), waist-hip ratio (WHR), systolic and diastolic blood pressure, serum levels of total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C) and triglyceride (TG) were measured. Low-density lipoprotein-cholesterol (LDL-C) was calculated by the Friedewald formula. Percentage fat mass (%FM) and trunk fat mass-leg fat mass ratio (FM(trunk)/FM(legs)) were obtained by dual-energy X-ray absorptiometry. RESULTS: WC, WHR, %FM and FM(trunk)/FM(legs) were significantly correlated with TC, LDL-C, HDL-C and TG with the tendency of FM(trunk)/FM(legs) to show the strongest correlations. For %FM and FM(trunk)/FM(legs) in both sexes, odds ratios (ORs) of the third tertiles with respect to the first tertiles increased for LDL-C elevation, TG elevation and dyslipidemia. In males, ORs of the third tertiles of WC were significantly high for LDL-C elevation and dyslipidemia whereas those of WHR were high for TG elevation and dyslipidemia. ORs of the third tertiles of WC and WHR were significantly high for TG elevation in females. BMI was not associated with the risk of abnormal lipid levels. ORs for hypertension showed significant increases in none of the variables of obesity. CONCLUSIONS: Excess accumulation of FM, especially to the upper body, was related to dyslipidemia in normal-weight subjects. Simple anthropometric variables, WC and WHR, may be useful for screening and management of dyslipidemia in these subjects.

Absorptiometry, Photon↗
PubMed2004

Paraoxonase 1 Gln/Arg polymorphism is associated with the risk of microangiopathy in Type 2 diabetes mellitus.

AIMS: To investigate possible associations between diabetic microangiopathy and genetic polymorphisms in factors relevant to arterial thrombosis. METHODS: We conducted a case-control study on a total of 280 patients with Type 2 diabetes, comparing those without retinopathy or nephropathy (n = 92) and those with microangiopathies (n = 188), for the association of polymorphisms in four candidate genes, paraoxonase 1 (PON1), plasminogen activator inhibitor-1, fibrinogen, and platelet glycoprotein Ibalpha. RESULTS: There were no differences between the two study groups in gender distribution, age at diagnosis of diabetes (47.9 +/- 8.4 and 49.0 +/- 11.4 years, respectively), or duration of diabetes (14.9 +/- 4.5 and 14.5 +/- 8.4 years, respectively). Among the gene polymorphisms tested, the 192Gln/Arg polymorphism of PON1 was associated with the prevalence of retinopathy [odds ratio (OR) = 3.13, 95% confidence interval (CI) = 1.42-6.89, P = 0.0046, Gln/Gln vs. Gln/Arg and Arg/Arg]. This polymorphism was also associated with nephropathy (OR = 3.01, 95% CI = 1.30-6.98, P = 0.0103). There were no differences between the three PON1 genotypes (Gln/Gln, Gln/Arg, and Arg/Arg) with regard to the present disease status. Logistic regression analysis for the adjustment of other risk factors revealed that genotypes with PON1 192Arg were an independent predictor of retinopathy. No associations were found between microangiopathies and the other polymorphisms evaluated (plasminogen activator inhibitor-1, fibrinogen, and platelet glycoprotein Ibalpha). CONCLUSIONS: This study suggests that the presence of the 192Arg-allele in the PON1 gene is a genetic risk factor for microangiopathy in Type 2 diabetes mellitus.

Aryldialkylphosphatase↗
PubMed2004

Downregulation of prostaglandin E receptor subtype EP3 during colon cancer development.

BACKGROUND AND AIMS: Involvement of prostaglandin E(2) (PGE(2)) receptors EP(1), EP(2), and EP(4) in the formation of aberrant crypt foci (ACF) and/or intestinal polyps has been suggested. In contrast, EP(3) appears to have no influence on the early stages of colon carcinogenesis. In the present study, we examined expression of PGE(2) receptor subtypes EP(1), EP(2), EP(3), and EP(4) in normal colon mucosa and colon cancers, and assessed the contribution of EP(3) to colon cancer development. METHODS: mRNA expression of PGE(2) receptor subtypes EP(1), EP(2), EP(3), and EP(4) in normal colon mucosa and colon cancers in azoxymethane (AOM) treated mice and rats, and in humans, were examined by reverse transcription-polymerase chain reaction (RT-PCR), quantitative real time RT-PCR, and immunohistochemical analyses. Evaluation of the role of EP(3) was performed by intraperitoneal injection of AOM, using EP(3) receptor knockout mice. Effects of EP(3) receptor activation on cell growth of human colon cancer cell lines were examined using ONO-AE-248, an EP(3) selective agonist. Moreover, EP(3) expression in colon cancer cell lines was analysed with or without 5-aza-2'-deoxycytidine (5-aza-dC) treatment. RESULTS: Expression levels of EP(1) and EP(2) mRNA were increased in cancer tissues. EP(4) mRNA was constantly expressed in normal mucosa and cancers. In contrast, expression of EP(3) mRNA was markedly decreased in colon cancer tissues, being 5% in mice, 9% in rats, and 28% in humans compared with normal colon mucosa, analysed by quantitative real time RT-PCR. Immunohistochemical staining demonstrated the rat EP(3) receptor protein to be expressed in epithelial cells of normal mucosa and some parts of small carcinomas but hardly detectable in large carcinomas of the colon. Colon cancer development induced by AOM in EP(3) receptor knockout mice was enhanced compared with wild-type mice, with a higher incidence of colon tumours (78% v 57%) and mean number of tumours per mouse (2.17 (0.51) v 0.75 (0.15); p<0.05). Expression of EP(3) mRNA was detected in only one of 11 human colon cancer cell lines tested. Treatment with 5 microM of an EP(3) selective agonist, ONO-AE-248, resulted in a 30% decrease in viable cell numbers in the HCA-7 human colon cancer cell line in which EP(3) was expressed. Treatment with 5-aza-dC restored EP(3) expression in CACO-2, CW-2, and DLD-1 cells but not in WiDr cells, suggesting involvement of hypermethylation in the downregulation of EP(3) to some extent. CONCLUSION: The PGE(2) receptor subtype EP(3) plays an important role in suppression of cell growth and its downregulation enhances colon carcinogenesis at a later stage. Hypermethylation of the EP(3) receptor gene could occur and may contribute towards downregulating EP(3) expression to some extent in colon cancers.

Animals↗
PubMed2003

Expression of foreign proteins in Escherichia coli by fusing with an archaeal FK506 binding protein.

Improper protein-folding often results in inclusion-body formation in a protein expression system using Escherichia coli. To express such proteins in the soluble fraction of E. coli cytoplasm, we developed an expression system by fusing the target protein with an archaeal FK506 binding protein (FKBP). It has been reported that an archaeal FKBP from a hyperthermophilic archaeon, Thermococcus sp. KS-1 (TcFKBP18), possesses not only peptidyl-prolyl cis-trans isomerase activity, but also chaperone-like activity to enhance the refolding yield of an unfolded protein by suppressing irreversible protein aggregation. To study the effect of this fusion strategy with FKBP on the expression of foreign protein in E. coli, a putative rhodanese (thiosulfate sulfurtransferase) from a hyperthermophilic archaeon and two mouse antibody fragments were used as model target proteins. When they were expressed alone in E. coli, they formed insoluble aggregates. Their genes were designed to be expressed as a fusion protein by connecting them to the C-terminal end of TcFKBP18 with an oligopeptide containing a thrombin cleavage site. By fusing TcFKBP18, the expression of the target protein in the soluble fraction was significantly increased. The percentage of the soluble form in the expressed protein reached 10-28% of the host soluble proteins. After purification and protease digestion of the expressed antibody fragment-TcFKBP18 fusion protein, the cleaved antibody fragment (single-chain Fv) showed specific binding to the antigen in ELISA. This indicated that the expressed antibody fragment properly folded to the active form.

Archaeal Proteins↗
PubMed2003

Search for nu(e) from the sun at Super-Kamiokande-I.

We present the results of a search for low energy nu(e) from the Sun using 1496 days of data from Super-Kamiokande-I. We observe no significant excess of events and set an upper limit for the conversion probability to nu(e) of the 8B solar neutrino. This conversion limit is 0.8% (90% C.L.) of the standard solar model's neutrino flux for total energy=8-20 MeV. We also set a flux limit for monochromatic nu(e) for E(nu(e))=10-17 MeV.

Journal Article↗
PubMed2003

Improved direct measurement of the parity-violation parameter Ab using a mass tag and momentum-weighted track charge.

We present an improved direct measurement of the parity-violation parameter A(b) in the Z boson-b-quark coupling using a self-calibrating track-charge technique applied to a sample enriched in Z-->bb events via the topological reconstruction of the B hadron mass. Manipulation of the Stanford Linear Collider electron-beam polarization permits the measurement of A(b) to be made independently of other Z-pole coupling parameters. From the 1996-1998 sample of 400,000 hadronic Z decays, produced with an average beam polarization of 73.4%, we find A(b)=0.906+/-0.022(stat)+/-0.023(syst).

Journal Article↗
PubMed2003

Search for supernova relic neutrinos at Super-Kamiokande.

A search for the relic neutrinos from all past core-collapse supernovae was conducted using 1496 days of data from the Super-Kamiokande detector. This analysis looked for electron-type antineutrinos that had produced a positron with an energy greater than 18 MeV. In the absence of a signal, 90% C.L. upper limits on the total flux were set for several theoretical models; these limits ranged from 20 to 130 macro nu(e) cm(-2) s(-1). Additionally, an upper bound of 1.2 macro nu(e) cm(-2) s(-1) was set for the supernova relic neutrino flux in the energy region E(nu)>19.3 MeV.

Journal Article↗
PubMed2003

Indications of neutrino oscillation in a 250 km long-baseline experiment.

The K2K experiment observes indications of neutrino oscillation: a reduction of nu(mu) flux together with a distortion of the energy spectrum. Fifty-six beam neutrino events are observed in Super-Kamiokande (SK), 250 km from the neutrino production point, with an expectation of 80.1(+6.2)(-5.4). Twenty-nine one ring mu-like events are used to reconstruct the neutrino energy spectrum, which is better matched to the expected spectrum with neutrino oscillation than without. The probability that the observed flux at SK is explained by statistical fluctuation without neutrino oscillation is less than 1%.

Journal Article↗
PubMed2003

Dynamics of microcystin-degrading bacteria in mucilage of Microcystis.

To reveal the process of degradation of hepatotoxic microcystin produced in Microcystis cells during the Microcystis bloom period, we used fluorescence in situ hybridization (FISH) to analyze the population dynamics of microcystin-degrading bacteria in Microcystis mucilage. We designed and applied an oligonucleotide probe targeted to the 16S rRNA sequence of strain Y2 of a microcystin-degrading bacterium (MCD-bacterium), which was isolated from Lake Suwa, Japan. In both the 1998 and 1999 tests, FISH clearly showed that MCD-bacteria existed in the mucilage and that, when a high concentration of cell-bound microcystin was detected, MCD-bacteria exceeded 10% of the sum of bacteria hybridized with group-specific probes. The concentration of MCD-bacteria was highest in summer 1998, when a toxic species, M. viridis, was dominant. There was a high correlation between the number of MCD-bacteria in the mucilage and the concentration of cell-bound microcystin in the lake. Our results suggest that MCD-bacteria responded to changes in the concentration of microcystin and degraded the microcystin when it was released from Microcystis cells. We also analyzed changes in the bacterial community structure associated with the Microcystis colonies by using domain- and group-specific oligonucleotide probes. Changes in the concentrations of the Cytophaga/Flavobacterium group and delta-Proteobacteria, which can degrade macromolecules derived from Microcystis cells, were synchronized with changes in the concentration of Microcystis. The results not only suggest the significant role of MCD-bacteria in detoxification, but also demonstrate a possible sequence of degradation from Microcystis cells to microcystin maintained in the cell, which is then carried out by bacterial consortia in the mucilage.

Adhesives↗
PubMed2003

Simultaneous stimulation of EP2 and EP4 is essential to the effect of prostaglandin E2 in chondrocyte differentiation.

OBJECTIVE: Prostaglandin E(2)(PGE(2)) has been reported to stimulate chondrocyte differentiation. However, the precise actions and signal transduction pathways of PGE(2)in cartilage are largely unknown. Our purpose is to identify which of the four PGE(2)receptor subtype(s), EP1-4, mediates the action of PGE(2)on chondrocyte differentiation. DESIGN: We used primary chondrocytes derived from the resting zone of rat rib cartilage. The effects on chondrocyte differentiation were assessed by measuring the Alcian blue-stainable proteoglycan content and the expression levels of type II collagen mRNA by Northern blot analysis. The expression of the four PGE(2)receptor subtypes in rat primary chondrocytes was examined by reverse transcription-polymerase chain reaction. RESULTS: PGE(2)stimulated the accumulation of proteoglycan and up-regulated the expression of type II collagen mRNA in primary chondrocytes. Dibutyryl cAMP, a cell-permeable analog of cAMP, an important intracellular mediator of PGE(2)signaling, also enhanced the expression of type II collagen mRNA and proteoglycan accumulation in chondrocytes. No EP agonist alone induced the expression of type II collagen mRNA. However, simultaneous administration of EP2 and EP4 agonists at high concentrations cooperatively induced the expression of type II collagen mRNA, mimicking the PGE(2)effect. The simultaneous stimulation of EP2 and EP4 also cooperatively enhanced proteoglycan accumulation and intracellular cAMP production. Moreover, an EP4 antagonist partially blocked the stimulatory actions of PGE(2)on the expression of type II collagen mRNA. CONCLUSION: These results suggest that simultaneous stimulation of EP2 and EP4 is necessary and sufficient to elicit the effect of PGE(2)on rat primary chondrocyte differentiation.

Animals↗