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Biomedical subjects

H Kuroda

Publications and source records attributed to H Kuroda.

At least 19 recordsLinked to original sources
PubMed2006

Allogeneic stem cell transplantation in children with acute lymphoblastic leukemia after isolated central nervous system relapse: our experiences and review of the literature.

The prognosis of patients with acute lymphoblastic leukemia (ALL) and central nervous system (CNS) relapse has historically been very poor. Although chemo-radiotherapy has improved outcomes, some patients still have a poor prognosis after CNS relapse. Therefore, allogeneic hematopoietic stem cell transplantation (allo-SCT) has recently become an option for treatment of CNS leukemia; however, information, particularly on the long-term outcome of transplant recipients, is limited. We performed allo-SCT in eight pediatric patients with ALL (n=7) or T-cell type non-Hodgkin's lymphoma (n=1), who had isolated CNS relapse. All patients survived for a median of 70.5 (range, 13-153) months after SCT. Sequelae developed late in some patients: mental retardation (IQ=47) in one patient, severe alopecia in two patients, limited chronic graft-versus-host-disease in three patients, and amenorrhea and/or hypothyroidism in three patients. Except for a pre-school child with post transplant CNS relapse, six out of seven patients show normal school/social performance. Our results clearly indicate a high cure rate of isolated CNS relapse by allo-SCT in pediatric lymphoid malignancies; however, there needs to be further studies to determine which are the appropriate candidates for transplantation and what is the best transplant regimen to achieve high cure rate and maintain good quality of life.

Adolescent↗
PubMed2005

Characterization of lipoxygenase-1 null mutants in barley.

This study describes the discovery and characterization of lipoxygenase-1 (LOX-1) null mutants in barley. Six lines did not exhibit any significant LOX activity in the silenced seed extract. Immunological analysis showed that these lines lacked the authentic LOX-1 protein. Genetic analysis of the F2 population revealed that this trait was governed by a single recessive gene located at the LoxA locus on chromosome 4H. The six LOX-1 null mutants shared similar features and the same unique polymorphism in a structural gene region, implying that these mutants might be derived from the same ancestral origin.

Blotting, Southern↗
PubMed2005

Eradication of hepatocellular carcinoma xenografts by radiolabelled, lipiodol-inducible gene therapy.

The promoter region of the early-growth response-1(Egr-1) gene has been shown to be activated by external radiation, thus making a selective tumoricidal effect possible. A previous experiment showed that the Egr-1 promoter can be activated by internal radiation using radioisotopes as well as external radiation. Internal radiation using I-131 lipiodol (I-131-Lip) has been established as one of the most useful therapeutic strategies against hepatoma. We herein linked the Egr-1 promoter to the herpes simplex virus-thymidine kinase (HSV-TK) gene, and investigated its efficacy in hepatoma gene therapy in combination with I-131-Lip. A luciferase assay showed the Egr-1-promoter activity to be markedly increased in hepatoma tissue specimens in an I-131-dose-dependent manner, whereas a less than two-fold increase in this activity was observed in other organs. In addition, the radioactivity derived from I-131 was selectively accumulated in the tumor tissue specimens. To examine the efficacy of EgrTK/ganciclovir (GCV) gene therapy in vivo, subcutaneous hepatoma xenografts in nude mice were transfected using a hemagglutinating virus of Japan (HVJ)-liposome vector. Complete tumor regression was observed in all the EgrTK-transfected tumors following combination treatment with I-131-Lip and GCV 42 days after treatment without any side effects (n=8). In contrast, the tumors continued to grow in all control mice (n=10). Furthermore, the serum alpha-fetoprotein levels decreased in the combination therapy group, while they increased in the controls. In conclusion, these data indicate that Egr-1 promoter-based gene therapy combined with internal radiation has a selective effect on hepatoma tumors while also showing an improved in vivo efficacy. This combination therapy might, therefore, be an effective human hepatoma gene therapy, even in advanced multiple cases.

Animals↗
PubMed2005

Involvement of transforming growth factor-beta and thrombopoietin in the pathogenesis of myelodysplastic syndrome with myelofibrosis.

We investigated the cause of myelofibrosis and proliferation of megakaryocytes in myelodysplastic syndrome with myelofibrosis (MDS-MF (+)). Plasma-transforming growth factor-beta1 (PTGF-beta1) concentrations closely correlated with myelofibrosis grade in MDS-MF (+) and were higher than those in idiopathic myelofibrosis (IMF), essential thrombocythemia (ET), idiopathic thrombocytopenic purpura (ITP), MDS-without MF (MDS-MF (-)) or healthy volunteers (HV). Peripheral blood mononuclear cells from MDS-MF (+) patients expressed more TGF-beta1 mRNA than those from IMF, MDS-MF (-) or HV. When we immunostained bone marrow specimens of MDS-MF (+) for TGF-beta, the intensity of blasts was apparently higher than that of megakaryocytes, while in MDS-MF (-), megakaryocytes were immunostained with a similar intensity as that in MDS-MF (+), but blasts were negative for staining. In IMF, megakaryocytes, monocytes and small mononuclear cells representing CD34+ cells were all similarly stained with a much lower intensity than that of blasts in MDS-MF (+). The number of bone marrow megakaryocytes were increased the most in MDS-MF (+), followed by ET, ITP, MDS-MF (-) and NHL and correlated with plasma thrombopoietin (TPO) levels or with plasma TGF-beta1 levels, respectively, in each disease. Thus, in MDS-MF (+), both myelofibrosis and the increased megakaryocytes were ascribed to overproduction of TGF-beta1 from blasts.

Adult↗
PubMed2004

[Double valve replacement for infective endocarditis following osteomyelitis; report of two cases].

Infective endocarditis(IE) is relatively common but it is lethal complication of osteomyelitis. We report the case of 2 patients who had been diagnosed as IE during their conservative therapy of osteomyelitis. Both of the patients had been admitted because of severe back pain. Then IE was revealed from congestive heart failure and/or persistent fever. As several times of echocardiogram showed the progression of valvular lesion despite their antibiotic therapies, they underwent the operation of aortic and mitral valve replacements. On bacteremia-related disease like osteomyelitis, high index of suspicion and early diagnosis of IE are essential to its successful treatment.

Aged↗
PubMed2003

Nitrogen removal from water containing high nitrate nitrogen in a paddy field (wetland).

Nowadays, it has become very common to find in Japan that nitrate nitrogen concentrations are very high in spring water and in well water where the land use of a watershed is agricultural. We have often observed around 50 mg/L of nitrate nitrogen in the spring water where we live. Crops produced in those fields are mainly vegetables such as celery, cabbage, lettuce, carrots, and so on. Green tea is also popular in Japan. In order to produce good quality green tea, farmers apply a great amount of nitrogen fertilizer. This amount can reach up to 1,000 kg/ha in some areas, although the average application amounts to 628 kg/ha in Japan. As a result, ground water that is rich in nitrate flows into the river, which results in a high nitrogen concentration in river water and ground water. Further, this causes a low pH in river water in some tributary rivers in Japan, though this kind of case is very rare. We knew from field tests that if water contained a high nitrogen concentration and was introduced into paddy fields, high nitrogen removal would be performed. This paper presents the outline and results of a system on how to remove nitrogen using paddy fields (wetlands). Further, this paper presents the evaluated results of the removal quantity at the watershed level.

Agriculture↗
PubMed2002

Measurements of blue shifts due to collisionless absorption in harmonic generation from subpicosecond laser-produced plasmas.

Harmonic generation from solid surface plasmas is studied using a subpicosecond Nd:glass laser system. For a 45 degrees angle of incidence, the speculars up to the fifth harmonics are blue shifted when the laser intensity exceeds 2 x 10(16) W cm(-2). The second harmonic is blueshifted by approximately 16 A, and the fifth harmonic is blue shifted by approximately 51 A for p polarization at the intensity of 1 x 10(17) W cm(-2). We observed the blue shift of the fifth harmonics and found that the magnitude of blue shift is higher compared with that for the second harmonics. The blue shift is interpreted as a collisionless absorption due to the anomalous skin effect. It is also found that the divergence of harmonics preserves a smaller divergence when using a shorter pulse length for the driving laser.

Journal Article↗
PubMed2001

Total synthesis of cyclic ADP-carbocyclic-ribose, a stable mimic of Ca2+-mobilizing second messenger cyclic ADP-ribose.

The synthesis of cyclic ADP-carbocyclic-ribose (cADPcR, 4) designed as a stable mimic of cyclic ADP-ribose (cADPR, 1), a Ca2+-mobilizing second messenger, was achieved using as the key step a condensation reaction with the phenylthiophosphate-type substrate 14 to form an intramolecular pyrophosphate linkage. The N-1-carbocyclic-ribosyladenosine derivative 16 was prepared via the condensation between the imidazole nucleoside derivative 17, prepared from AICA-riboside (19), and the readily available optically active carbocyclic amine 18. Compound 16 was then converted to the corresponding 5' '-phosphoryl-5'-phenylthiophosphate derivatives 14. Treatment of 14 with AgNO3 in the presence of molecular sieves (3 A) in pyridine at room temperature gave the desired cyclization product 32 in 93% yield, and subsequent acidic treatment provided the target cADPcR (4). This represents a general method for synthesizing biologically important cyclic nucleotides of this type. 1H NMR analysis of cADPcR suggested that its conformation in aqueous medium is similar to that of cADPR. cADPcR, unlike cADPR, was stable under neutral and acidic conditions, where under basic conditions, it formed the Dimroth-rearranged N6-cyclized product 34. cADPcR was also stable in rat brain membrane homogenate which has cADPR degradation activity. Furthermore, cADPcR was resistant to the hydrolysis by CD38 cADPR hydrolase, while cADPR was rapidly hydrolyzed under the same conditions. When cADPcR was injected into sea urchin eggs, it caused a significant release of Ca2+ in the cells, an effect considerably stronger than that of cADPR. Thus, cADPcR was identified as a stable mimic of cADPR.

ADP-ribosyl Cyclase↗
PubMed2001

Validity and safety of sputum induction by inhaled uridine 5'-triphosphate.

UNLABELLED: Inhalation of hypertonic saline during sputum induction causes bronchoconstriction. We studied the validity and safety of sputum induction by uridine 5'-triphosphate (UTP). Sputum was induced by a 5-min inhalation of hypertonic saline (3%) on Day 1 and UTP (5 mg/ml in 0.9% saline) on Days 8 and 15 in 16 healthy subjects and 16 patients with mild-to-moderate asthma. Inhaled UTP produced twofold greater amounts of sputum than did hypertonic saline. There were significant differences in oxygen desaturation and bronchoconstriction during the procedure between the two methods: the maximal fall in Sa(O(2)), the AUC of the Sa(O(2))-time response, and the fall in PEF were less in the subjects who received UTP than in those who received hypertonic saline. Sputum total cell and differential cell counts, with a high proportion of eosinophils in asthmatics, were similar between specimens obtained by hypertonic saline and UTP. When we compared two consecutive measurements on the UTP-induced sputum samples, the reproducibility calculated by the intraclass correlation coefficient was high for the proportion of eosinophils, neutrophils, and macrophages. Therefore, inhalation of UTP aerosols may provide an effective, relatively noninvasive, valid, and reproducible method of sputum induction for the assessment of airway inflammation in asthma. KEYWORDS: uridine triphosphate; induced sputum; airway inflammation; bronchoconstriction; asthma

Administration, Inhalation↗
PubMed2001

Complementarity of the 16S rRNA penultimate stem with sequences downstream of the AUG destabilizes the plastid mRNAs.

Escherichia coli mRNA translation is facilitated by sequences upstream and downstream of the initiation codon, called Shine-Dalgarno (SD) and downstream box (DB) sequences, respectively. In E.coli enhancing the complementarity between the DB sequences and the 16S rRNA penultimate stem resulted in increased protein accumulation without a significant affect on mRNA stability. The objective of this study was to test whether enhancing the complementarity of plastid mRNAs downstream of the AUG (downstream sequence or DS) with the 16S rRNA penultimate stem (anti-DS or ADS region) enhances protein accumulation. The test system was the tobacco plastid rRNA operon promoter fused with the E.coli phage T7 gene 10 (T7g10) 5'-untranslated region (5'-UTR) and DB region. Translation efficiency was tested by measuring neomycin phosphotransferase (NPTII) accumulation in tobacco chloroplasts. We report here that the phage T7g10 5'-UTR and DB region promotes accumulation of NPTII up to approximately 16% of total soluble leaf protein (TSP). Enhanced mRNA stability and an improved NPTII yield ( approximately 23% of TSP) was obtained from a construct in which the T7g10 5'-UTR was linked with the NPTII coding region via a NheI site. However, replacing the T7g10 DB region with the plastid DS sequence reduced NPTII and mRNA levels to 0.16 and 28%, respectively. Reduced NPTII accumulation is in part due to accelerated mRNA turnover.

Bacteriophage T7↗
PubMed2001

Prevention of lethal acute graft-versus-host disease in mice by oral administration of T helper 1 inhibitor, TAK-603.

Acute graft-versus-host diseases (GVHD) is a major cause of morbidity and mortality in patients undergoing allogeneic bone marrow transplantation (BMT). T helper 1 (Th1)-type cytokines such as interferon-gamma or tumor necrosis factor-alpha have been implicated in the pathogenesis of acute GVHD. TAK-603 is a new quinoline derivative, which is now in clinical trials for use as a disease-modifying antirheumatic drug. In preclinical studies, it inhibited delayed-type hypersensitivity, but not Arthus-type reaction, in mice, and selectively suppressed Th1 cytokine production. Thus, the present study was designed to investigate whether the Th1 inhibitor (TAK-603) ameliorates lethal acute GVHD in a mouse model. Administration of TAK-603 into BALB/c mice given 10 Gy total body irradiation followed by transplantation of bone marrow and spleen cells from C57BL/6 mice markedly reduced the mortality in association with minimal signs of GVHD pathology in the liver, intestine, and skin. TAK-603 reduced not only the production of Th1-type cytokines, but also the proportion of Th1 cells in CD4(+) helper T cells in this GVHD mouse model. These results suggest that TAK-603 could be a potent therapeutic agent for acute lethal GVHD.

Acute Disease↗
PubMed2001

Human ovarian surface epithelial (OSE) cells express LH/hCG receptors, and hCG inhibits apoptosis of OSE cells via up-regulation of insulin-like growth factor-1.

Gonadotropins including luteinizing hormone (LH) or human chorionic gonadotropin (hCG) have been implicated as playing an important role in the development of epithelial ovarian carcinomas, most of which are believed to originate from the ovarian surface epithelium (OSE). To address this issue, we examined the expression of LH/hCG receptors and the influence of hCG on cell proliferation and on the apoptosis of cultured human OSE cells. RT-PCR and binding assay revealed that OSE cells express the LH/hCG receptor mRNA and have specific binding activity for hCG. Treatment with hCG stimulated the proliferation of OSE cells in a dose-dependent manner. In addition, hCG treatment inhibited the apoptosis of OSE cells induced by serum deprivation. Among the apoptosis-related genes, hCG treatment did not change the mRNA levels of bcl-2, bax and IGF-1 receptor but significantly increased that of IGF-1. Treatment with IGF-1 alone also suppressed the apoptosis of OSE cells, and treatment by hCG along with neutralization antibody against IGF-1 receptor reversed the anti-apoptotic effect of hCG. Accordingly, LH/hCG signaling followed by up-regulation of IGF-1 is involved in the inhibition of apoptosis of OSE cells, the possible histogenetic origin of epithelial ovarian carcinomas.

Apoptosis↗
PubMed2001

Signaling pathway of ciliary neurotrophic factor in neuroblastoma cell lines.

BACKGROUND: Ciliary neurotrophic factor (CNTF) is a member of the interleukin-6 (IL-6) cytokine family and affects the survival and differentiation of several classes of neurons. For signal transduction, CNTF requires a receptor complex, composed of the IL-6 signal transducing molecule gp130, leukemia inhibitory factor receptor (LIFR)-beta, and CNTFR-alpha. There are two major independent pathways (Jak-STAT and Ras-MAPK) in cell signaling, and some recent reports show interaction between these pathways. The signal of the IL-6 family is mainly transduced to the Jak-STAT pathway through gp130. However, it has not been examined in neuroblastoma in detail. PROCEDURE AND RESULTS: Here we examine the signaling pathway of CNTF in 11 neuroblastoma cell lines. Northern blot analysis revealed that 3 of the 11 cell lines expressed c-fos mRNA after CNTF stimulation. Cell lysates were immunoprecipitated with agarose-conjugated antiphosphotyrosine antibody and blotted with anti-gp130, anti-Jak1, or anti-STAT3 antibody. Tyrosine phosphorylation of gp130, Jak1, and STAT3 was observed after CNTF stimulation in these three cell lines. Furthermore, tyrosine phosphorylation of ERK1 (one of the MAPKs) was also observed in all of them. CONCLUSIONS: These results demonstrate that CNTF signaling is conserved in some of the neuroblastoma cell lines and suggest that not only a Jak-STAT pathway but a MAPK pathway is activated by CNTF through gp130 in neuroblastoma cell lines.

Antigens, CD↗