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Biomedical subjects

H Furukawa

Publications and source records attributed to H Furukawa.

At least 19 recordsLinked to original sources
PubMed2006

Genetic characterisation of spontaneous ankylosing arthropathy with unique inheritance from Fas-deficient strains of mice.

BACKGROUND: The spontaneous onset of macroscopic arthropathy in the ankle of the particular F1 mice descended from two Fas-deficient strains of mice; a mutant substrain of MRL/Mp.Fas(lpr) (MRL/rpl) and C3H/He.Fas(lpr) (C3H/lpr) was recently observed. AIM: To histopathologically characterise and genetically interpret the unique inheritance mode of disease in this arthropathy model. METHODS: MRL/rpl, C3H/lpr, (MRL/rpl x C3H/lpr; MC) F1, (C3H/lpr x MRL/rpl; CM) F1 and MCF2 mice were bred under specific pathogen-free conditions. Histopathological grade of arthropathy was determined at 6 months by examination under a light microscope. To search for a linkage locus to the arthropathy, the whole genome of selected 48 male MCF2 mice with 71 polymorphic microsatellite markers was scanned, followed by quantitative trait locus analysis. RESULTS: The incidence of microscopically defined arthropathy in the male and female MCF1 groups was 100% and 19.4%, respectively. No incidence was observed in the parental strains, MRL/rpl and C3H/lpr, and in CMF1 mice. In the MCF1 mice, the arthropathy mainly affected the ankle joints and was histopathologically characterised by marked entheseal proliferation with chondrocytic differentiation and ossification in the ankle joints, the manifestations similar to ankylosing enthesitis reported previously. An MRL/rpl-derived autosomal dominant susceptibility locus was mapped in the distal of D7Mit68 (60 cM) to the ankylosis onset. CONCLUSION: The MCF1 mice stably develop spontaneous ankylosing disorders in the ankle, with a male predominance. The unique inheritance mode of ankylosis is possibly interpreted by the genetic interaction between the autosomal dominant locus and a Y-linked locus.

Animals↗
PubMed2006

Moderate increase of mean daily temperature adversely affects fruit set of Lycopersicon esculentum by disrupting specific physiological processes in male reproductive development.

BACKGROUND AND AIMS: Global warming is gaining significance as a threat to natural and managed ecosystems since temperature is one of the major environmental factors affecting plant productivity. Hence, the effects of moderate temperature increase on the growth and development of the tomato plant (Lycopersicon esculentum) were investigated. METHODS: Plants were grown at 32/26 degrees C as a moderately elevated temperature stress (METS) treatment or at 28/22 degrees C (day/night temperatures) as a control with natural light conditions. Vegetative growth and reproductive development as well as sugar content and metabolism, proline content and translocation in the androecium were investigated. KEY RESULTS: METS did not cause a significant change in biomass, the number of flowers, or the number of pollen grains produced, but there was a significant decrease in the number of fruit set, pollen viability and the number of pollen grains released. Glucose and fructose contents in the androecium (i.e. all stamens from one flower) were generally higher in the control than METS, but sucrose was higher in METS. Coincidently, the mRNA transcript abundance of acid invertase in the androecium was decreased by METS. Proline contents in the androecium were almost the same in the control and METS, while the mRNA transcript level of proline transporter 1, which expresses specifically at the surface of microspores, was significantly decreased by METS. CONCLUSIONS: The research indicated that failure of tomato fruit set under a moderately increased temperature above optimal is due to the disruption of sugar metabolism and proline translocation during the narrow window of male reproductive development.

Amino Acid Transport Systems, Neutral↗
PubMed2006

Five-year results of a randomized, single-center study of tacrolimus vs microemulsion cyclosporine in heart transplant patients.

BACKGROUND: Previous multicenter, randomized trials, lacking standardized post-transplant protocols, have compared tacrolimus (Tac) and cyclosporine (CyA, Sandimmune) and demonstrated similar outcomes with some different adverse effects. The microemulsion form of CyA (mCyA, Neoral) has replaced Sandimmune CyA as the more widely utilized CyA formulation. This is the first 5-year follow-up study of a large, single-center trial (n = 67) under a standardized post-transplant protocol comparing Tac and mCyA. METHODS: Sixty-seven heart transplant patients were randomized to Tac (n = 33) or mCyA (n = 34), both in combination with corticosteroids and azathioprine without cytolytic induction. Five-year end-points included survival, Grade > or = 3A or treated rejection, angiographic cardiac allograft vasculopathy (CAV; any lesion > or = 30% stenosis), renal dysfunction (creatinine > or = 2.0 mg/dl), use of two or more anti-hypertensive medications, percent diabetic and lipid levels. RESULTS: Five-year survival, freedom from Grade > or = 3A or any treated rejection and angiographic CAV, mean cholesterol level and percent diabetic were similar between the two groups. The Tac group had a significantly lower 5-year mean triglyceride level (Tac 97 +/- 34 vs mCyA 175 +/- 103 mg/dl, p = 0.011) and average serum creatinine level (Tac 1.2 +/- 0.5 mg/dl vs mCyA 1.5 +/- 0.4 mg/dl, p = 0.044). There was a trend toward fewer patients requiring two or more anti-hypertensive drugs in the Tac group (Tac 33% vs mCyA 59%, p = 0.065). CONCLUSIONS: Tac and mCyA appear to be comparable with regard to 5-year survival, freedom from rejection and CAV. However, compared with mCyA, Tac appears to reduce the adverse effect profile for hypertriglyceridemia and renal dysfunction and the need for hypertensive medications.

Adult↗
PubMed2006

Effects of hepatic CYP3A4 activity on disposition of micafungin in liver transplant recipients with markedly small-for-size grafts.

Micafungin, the first candin antifungal drug developed in Japan, has a significant therapeutic effect against deep-seated mycoses caused by Candida or Aspergillus. Little is known, however, about the optimal dosage or disposition of micafungin in patients with severe hepatic impairment. Nine liver transplant recipients (5 males and 4 females) were enrolled in this study. In 1 recipient with a markedly small-for-size graft (ratio of graft volume to standard liver volume at the time of transplantation: 25.9%), the areas under the plasma concentration-time curves up to 12 hours postdose (AUC(0-12 h)) at doses of 50 and 100 mg/d were 79.38 and 601.17 mug.h/mL, respectively. The corresponding elimination half-life (T(1/2)) values were 16.01 and 75.75 hours, and saturated elimination was observed only at the dose of 100 mg/d. The mean urinary ratio of 6beta-hydroxycortisol to cortisol (6beta-OHF/F) in the small-for-size graft recipient was significantly (P < .05) lower than that in the other recipients. In conclusion, graft size was an important factor affecting disposition of micafungin. For liver transplant recipients with markedly small-for-size grafts, the optimal dosage of micafungin to reach and maintain therapeutic plasma levels is estimated to be 50 mg/d.

Antifungal Agents↗
PubMed2006

NK026680, a novel compound suppressive of dendritic cell function, ameliorates mortality in acute lethal graft-versus-host reaction in mice.

A role for dendritic cells (DCs) has been emphasized in the onset of acute graft-versus-host disease (GVHD). We have made efforts to develop a new strategy for suppression of DC functions with a chemical compound in the treatment of acute GVHD. We here describe the immunological characterization of the new chemical compound NK026680. It was found that NK026680 significantly suppressed (1) expression of CD83, CD86, and major histocompatibility complex (MHC) class I and II antigens on human monocyte-derived DCs, (2) excretion of interleukin-12p40 on activation of monocyte-derived DCs, (3) allogeneic responses of human and mouse T cells and (4) mortality in mice with acute GVHD evoked across MHC class I or II. The beneficial effect of NK026680 administered orally was without any recognizable adverse effects. Early intervention in acute GVHD was required for this effect, indicating that an early event in acute GVHD is a critical target of NK026680. We propose the use of NK026680 as a prophylactic for acute GVHD.

Administration, Oral↗
PubMed2006

Variation of microvascular blood flow augmentation--supercharge in esophageal and pharyngeal reconstruction.

AIM OF THE STUDY: A gastric tube is commonly used in thoracic esophageal reconstruction. When a gastric tube is not available, pedicled jejunum transfer and colonic interposition are alternative methods. Oral end of the reconstructed esophagus occasionally has poor blood flow and may result in partial necrosis of the oral segment. We performed additional microvascular blood flow augmentation, the "supercharge" technique, to improve a blood flow circulation in the oral segment of the reconstructed esophagus. METHODS: A series of 86 esophageal reconstructions with microvascular blood flow augmentation using the "supercharge" technique were performed. Reconstructive methods included a gastric tube in five patients, a gastric tube combined with a free jejunual graft in one, an elongated gastric tube in eight, a pedicled colonic interposition in 22, and a pedicled jejunum in 50. Recipient vessels were used in neck or chest region. RESULTS: The color and blood flow of the transferred intestine appeared greatly improved after microvascular blood flow augmentation. Thrombosis was noticed in three patients during the surgery, and all thrombosies were salvaged by re-anastomosis. There were only three patients with partial graft necrosis of oral segment, two patients with anastomotic leakage, one anastomotic stricture. CONCLUSIONS: Augmentation of microvascular blood flow by this "supercharge" technique can be expected to reduce the risk of leakage and partial necrosis of the transferred intestine. This technique contributes to the successful reconstruction of esophageal defect.

Adult↗
PubMed2006

[Surgical technique of aortic valve replacement for small aortic annulus in elderly patients].

Recent reports have shown that aortic valve replacement in elderly patients over 65 years with atherosclerotic aortic stenosis and a small aortic annulus is possible by using a small sized bioprosthesis (Carpentier-Edwards pericardial valve). Here we present out surgical technique. Firstly, the native calcified aortic valve was removed completely to gain total exposure of the surrounding aortic root and sinus of Valsalva like Bentall procedure. Secondly, a small sized bioprosthesis was implanted with intermittent noneverting mattress 2-0 sutures with spaghetti and small polytetrafluoroethylene (PTFE) felt. Aortic annulus is the dilated by inserting Hegar dilator sizing from 25 to 27 mm. Therefore, aortic valve replacement for small aortic annulus in intra- or supra-annular position should be easily accomplished. Good surgical results and hemodynamic state were achieved in 25 consecutive cases using this technique.

Aged↗
PubMed2005

Positron emission tomography scanning is not superior to whole body multidetector helical computed tomography in the preoperative staging of colorectal cancer.

BACKGROUND: The role of positron emission tomography with the glucose analogue [18F] fluoro-2-deoxy-D-glucose (FDG-PET) in the initial staging of disease in patients with primary colorectal cancer (CRC) has not been adequately assessed. AIMS: To evaluate the additional value of FDG-PET as a staging modality, complementary to routine multidetector row computed tomography (MDCT) in patients with CRC. METHODS: Forty four patients with CRC underwent preoperative MDCT and FDG-PET. The accuracy of intraoperative macroscopic staging was also investigated compared with histopathological diagnosis. All FDG-PET images were evaluated with respect to detectability of the primary tumour, lymph node involvement, and distant metastases. Both MDCT and FDG-PET diagnoses and treatment plan were compared with surgical and histopathological results. RESULTS: Thirty seven patients underwent surgery. Tumour detection rate was 95% (42/44) for MDCT, 100% (44/44) for FDG-PET, and 100% (37/37) for intraoperative macroscopic diagnosis. Pathological diagnosis of T factor was T1 in five, T2 in four, T3 in 24, and T4 in four cases. Concordance rate with pathological findings of T factor was 57% (21/37) for MDCT and 62% (23/37) for macroscopic diagnosis. Lymph node involvement was pathologically positive in 19 cases. Regarding N factor, overall accuracy was 62% (23/37) for MDCT, 59% (22/37) for FDG-PET, and 70% (26/37) for macroscopic diagnosis. For all 44 patients, FDG-PET findings resulted in treatment changes in only one (2%) patient. CONCLUSION: FDG-PET is not superior to routine MDCT in the initial staging of primary CRC.

Adult↗
PubMed2005

Induction of apoptosis by carbazole alkaloids isolated from Murraya koenigii.

In the current study, we isolated 10 carbazole alkaloids from the plant species Murraya koenigii (Rutaceae), and examined their effects on the growth of the human leukemia cell line HL-60. Three carbazole alkaloids, mahanine (6), pyrayafoline-D (7) and murrafoline-I (9), showed significant cytotoxicity against HL-60 cells. Fluorescence microscopy with Hoechst 33342 staining revealed that the percentage of apoptotic cells with fragmented nuclei and condensed chromatin was increased in a time-dependent manner after treatment with each alkaloid. Interestingly, each carbazole alkaloid induced the loss of mitochondrial membrane potential. In addition, both caspase-9 and caspase-3 were also time-dependently activated upon treatment with the alkaloids. Caspase-9 and caspase-3 inhibitors suppressed apoptosis induced by these alkaloids. The results suggest that these three alkaloids induced apoptosis in HL-60 cells through activation of the caspase-9/caspase-3 pathway, through mitochondrial dysfunction.

Apoptosis↗
PubMed2005

An epistatic effect of the female specific loci on the development of autoimmune vasculitis and antinuclear autoantibody in murine lupus.

OBJECTIVE: To identify the genetic loci regulating the incidence and severity of renal autoimmune vasculitis developed in murine lupus. METHODS: Vasculitis of renal arteries was histopathologically evaluated in MRL/Mp-Fas(lpr) (MRL/lpr), C57BL/6-Fas(lpr) (B6/lpr), (MRL/lpr x B6/lpr) F1, and MRL/lpr x (MRL/lpr x B6/lpr) F1 backcross mice. Using genomic DNA samples of the backcross mice, genome-wide scans, association studies, and linkage analyses were carried out based on genotypes of polymorphic microsatellite markers. Correlations of vasculitis grade and levels of various autoantibodies were also evaluated. RESULTS: Two recessive susceptibility loci of the MRL allele were identified on chromosomes 4 and 1, which had previously been defined as the autoimmune related loci termed Arvm1 and Sle-1/Nba2, respectively. The former was epistatic to the latter in a female specific manner. The titre of antinuclear autoantibody (ANA) in IgG class, but not ANA in IgM class or anti-dsDNA in either IgG or IgM class, correlated significantly with vasculitis grade. CONCLUSIONS: The present loci have been reported in previous studies using a different set of murine strains, suggesting that they are of importance in the development of autoimmune vasculitis in murine models. The concomitance of autoimmune vasculitis and IgG ANA suggests a shared genetic factor regulating these traits.

Animals↗
PubMed2005

CUL1, a component of E3 ubiquitin ligase, alters lymphocyte signal transduction with possible effect on rheumatoid arthritis.

Ubiquitination affects various immune processes and E3 ubiquitin ligases (E3) play an important role in determining substrate specificity. We identified 11 human E3 ligase genes of potential importance in pathogenesis of autoimmune diseases by search of public databases and screened them for candidacy of biological investigation with case-control linkage disequilibrium tests on multiple SNPs in the genes using rheumatoid arthritis (RA) as a model of autoimmune diseases. Significant association with RA was observed in an SNP in intron 3 of Cullin 1 (CUL1) that affected transcriptional efficiency of the promoter activity in lymphocytic cell lines. Quantitative expression analysis revealed that CUL1 mRNA was highly detected in lymphoid tissues including spleen and tonsil, and was specifically expressed in T and B lymphocytes in fractionated peripheral leukocytes. Histological evaluation of tonsils indicated that CUL1 protein expression was relatively specific for maturing germinal centers. Suppression of CUL1 expression had influence on the phenotype of T-cell line, that is, it inhibited IL-8 induction, which is known to play an important role in the migration of inflammatory cells into the affected area seen in RA. Our data suggest that the regulation of CUL1 expression in immunological tissues may affect the susceptibility of RA via altering lymphocyte signal transduction.

Arthritis, Rheumatoid↗
PubMed2004

Evolution of immunosuppression in liver transplantation: contribution of cyclosporine.

Liver transplantation has become the standard therapy for patients with end-stage liver disease or acute liver failure, with excellent outcomes in terms of quality of life and length of survival. The use of immunosuppressive agents, without any doubt, has played a crucial role in the establishment of this technique and improved short- and long-term survival rates. Eventually, mortality from acute or chronic rejection may be entirely eliminated. Minimizing the adverse effects of immunosuppressive agents is essential to improve long-term survival and quality of life. In this chapter, we review the history of immunosuppressive agents for liver transplantation with consideration of the pre- and the postcyclosporine eras. We also review the development and contributions of cyclosporine, the excellent outcomes from C2 monitoring, comparisons between the cyclosporine microemulsion and the oil-based formula, as well as between cyclosporine microemulsion versus tacrolimus. In addition, details are provided on the newer immunosuppressive agents: mycophenolate mofetil, sirolimus, and the IL-2 receptor antagonists, as well as agents in development: CAMPATH 1-H, thymoglobulin, everolimus, FT720, and FK778.

Cyclosporine↗
PubMed2004

Characterization of the 5' regulatory region of the mouse angiopoietin-like protein 4.

The 5' regulatory region of the mouse angiopoietin-like protein 4 (mANGPTL4), a remarkably versatile secreted protein responsible for hyperlipidaemia and angiogenesis, was cloned and functionally characterized. Three potential transcriptional start sites were determined by 5'-RACE and found to be at -129, -126 and -118, relative to the translation initiation codon. The activities of the putative promoters were confirmed using a firefly luciferase reporter gene assay system, following transient transfection into COS-1 cells. The PPAR alpha-regulated region and the minimal region required for basal activity of the mANGPTL4 promoter were determined by generating a series of deletion constructs, and were found to be encoded by a sequence between -2761 to -383 and -50 to -30, relative to the transcription start site. Putative recognition sequences for the transcription factor AP2 were identified in the minimal promoter sequences. These results are the first molecular characterization of the regulatory region of this important gene.

Angiopoietin-Like Protein 4↗
PubMed2003

Affinity selection of target cells from cell surface displayed libraries: a novel procedure using thermo-responsive magnetic nanoparticles.

Biotinylated thermo-responsive magnetic nanoparticles for use in affinity selection from yeast cell surface display libraries were prepared by coating magnetite nanoparticles with a thermo-responsive polymer consisting of N-isopropyl acrylamide and a biotin derivative. These particles showed a reversible transition between flocculation and dispersion at around the lower critical solution temperature of 30 degrees C, above which the flocculated particles--which absorbed a large amount of avidin due to their large surface area--were quickly separable by magnet. The model library was constructed by mixing control yeast cells with target yeast cells co-displaying IgG binding protein (ZZ) and enhanced green fluorescence protein. Biotinylated IgG and avidin were subsequently added to the model library, and target cells were efficiently enriched with the biotinylated magnetic nanoparticles by avidin-biotin sandwich and ZZ-IgG interaction. The few target cells (0.001%) in the model library were enriched by up to 100% in only 5 days by an affinity selection procedure repeated four times. This novel method based on magnetic nanoparticles and a yeast cell surface display system could fulfill a wide range of applications in the analysis of protein-protein interactions and rapid isolation of novel biomolecules.

Avidin↗
PubMed2003

Effect of AD-5423 on animal models of schizophrenia: phencyclidine-induced behavioral changes in mice.

The antipsychotic efficacy of AD-5423, which has the properties of both a serotonin 5-HT(2) and a dopamine D(2) receptor antagonist, was evaluated using animal models of schizophrenia. Sensitization to phencyclidine (PCP)-induced hyperlocomotion is considered a model of the positive symptoms of schizophrenia, and was significantly antagonized by AD-5423 and haloperidol. The PCP-induced enhancement of immobility induced by the forced swimming test, a model of the negative symptoms of schizophrenia, was attenuated by AD-5423 but not by haloperidol. Since this attenuated effect of AD-5423 was antagonized by DOI, a serotonin 5-HT(2) receptor agonist, it is postulated to be mediated by serotonin 5-HT(2) receptors. These findings suggest that AD-5423 would be clinically effective against both the positive and negative symptoms of schizophrenia.

Animals↗
PubMed2003

Influence of continuous venovenous haemodiafiltration on the pharmacokinetics of tacrolimus in liver transplant recipients with small-for-size grafts.

In adult-to-adult living donor liver transplantation (LDLT), the graft volume is inevitably much smaller than the ideal liver mass (standard liver volume) for the recipient's metabolic demand. Patients with small-for-size grafts are treated with continuous venovenous haemodiafiltration (CVVHD) for the artificial liver support. However, little is known about the influence of CVVHD on the elimination of tacrolimus. The objective of this study was to elucidate the effect of CVVHD on the pharmacokinetics of tacrolimus in recipients of LDLT with small-for-size grafts. Three liver transplant recipients (one male and two females) and donors (two males and one female) were enrolled in this study. Blood samples from inflow port and outflow port were obtained on the first day at the start of CVVHD. Whole-blood concentrations of tacrolimus were measured immediately using the microparticle enzyme immunoassay (MEIA; Abbott Laboratories). There was no significant difference between concentrations of tacrolimus in blood sampled at inflow port and outflow port sites and t(1/2)-values of tacrolimus in the three recipients were 29.9, 63.6 and 28.8 h. CVVHD did not cause a decrease in the blood tacrolimus concentration. Adjustment to the dose or dosing interval is not required for patients treated with tacrolimus during CVVHD.

Adult↗