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K Kuriyama

Publications and source records attributed to K Kuriyama.

At least 19 recordsLinked to original sources
PubMed2005

Checkpoint and physiological apoptosis in germ cells proceeds normally in spaceflown Caenorhabditis elegans.

It is important for human life in space to study the effects of environmental factors during spaceflight on a number of physiological phenomena. Apoptosis plays important roles in development and tissue homeostasis in metazoans. In this study, we have analyzed apoptotic activity in germ cells of the nematode C. elegans, following spaceflight. Comparison of the number of cell corpses in wild type or ced-1 mutants, grown under either ground or spaceflight conditions, showed that both pachytene-checkpoint apoptosis and physiological apoptosis in germ cells occurred normally under spaceflight conditions. In addition, the expression levels of the checkpoint and apoptosis related genes are comparable between spaceflight and ground conditions. This is the first report documenting the occurrence of checkpoint apoptosis in the space environment and suggests that metazoans, including humans, would be able to eliminate cells that have failed to repair DNA lesions introduced by cosmic radiation during spaceflight.

Animals↗
PubMed2004

Night-time restricted feeding normalises clock genes and Pai-1 gene expression in the db/db mouse liver.

AIMS/HYPOTHESIS: An increase in PAI-1 activity is thought to be a key factor underlying myocardial infarction. Mouse Pai-1 (mPai-1) activity shows a daily rhythm in vivo, and its transcription seems to be controlled not only by clock genes but also by humoral factors such as insulin and triglycerides. Thus, we investigated daily clock genes and mPai-1 mRNA expression in the liver of db/db mice exhibiting high levels of glucose, insulin and triglycerides. METHODS: Locomotor activity was measured using an infrared detection system. RT-PCR or in situ hybridisation methods were applied to measure gene expression. Humoral factors were measured using measurement kits. RESULTS: The db/ db mice showed attenuated locomotor activity rhythms. The rhythmic expression of mPer2 mRNA was severely diminished and the phase of mBmal1 oscillation was advanced in the db/db mouse liver, whereas mPai-1 mRNA was highly and constitutively expressed. Night-time restricted feeding led to a recovery not only from the diminished locomotor activity, but also from the diminished Per2 and advanced mBmal1 mRNA rhythms. Expression of mPai-1 mRNA in db/db mice was reduced to levels far below normal. Pioglitazone treatment slightly normalised glucose and insulin levels, with a slight reduction in mPai-1 gene expression. CONCLUSIONS/INTERPRETATION: We demonstrated that Type 2 diabetes impairs the oscillation of the peripheral oscillator. Night-time restricted feeding rather than pioglitazone injection led to a recovery from the diminished locomotor activity, and altered oscillation of the peripheral clock and mPai-1 mRNA rhythm. Thus, we conclude that scheduled restricted food intake may be a useful form of treatment for diabetes.

Animals↗
PubMed2003

Expression and distribution of transcripts for sonic hedgehog in the early phase of fracture repair.

Localization and expression of mRNAs for sonic hedgehog (Shh) at a fracture site in the early phase postfracture were investigated by in situ hybridization and reverse transcription and polymerase chain reaction (RT-PCR). A closed fracture was made in the midshaft of the right tibia of 5-week-old ICR mice, and fractured sites were harvested prefracture (day 0) and on days 2 and 12. In situ hybridization revealed that transcripts for Shh were not detected on day 0, but they were detected in proliferating callus-forming cells in the periosteum and the surrounding tissue, and in the medullary cavity prior to apparent new cartilage and bone formation. Gli 1 (a signaling mediator for Shh) and bone morphogenetic protein-4 transcripts were colocalized with those for Shh transcripts on day 2. The RT-PCR showed that Shh mRNA was detected in the PCR product from day 2, but not from days 0 and 12. These findings are the first description about the activation of Shh gene in the early postfracture reaction.

Animals↗
PubMed2003

Localization of bone morphogenetic protein-2 in human osteoarthritic cartilage and osteophyte.

OBJECTIVES: To examine the localization of bone morphogenetic protein (BMP)-2 mRNA and protein in human osteoarthritic (OA) articular cartilage and osteophyte. DESIGN: Five normal, four growing and 14 OA human cartilage samples, graded histomorphologically by Mankin Score, were studied by in situ hybridization and immunohistochemistry for the expression of BMP-2. RESULTS: BMP-2 mRNA was present in chondrocytes in neonatal growing articular cartilage, but was scarcely present in normal adult articular cartilage. In OA articular cartilage, BMP-2 mRNA and protein were detected in both clustering and individual chondrocytes in moderately or severely damaged OA cartilage. In moderately damaged OA cartilage, BMP-2 mRNA was localized in both upper and middle zone chondrocytes, but was not detected in deep layer chondrocytes. In severely damaged OA cartilage, cellular localization of BMP-2 mRNA was extended to the deep zone. In the area of osteophyte formation, BMP-2 mRNA was intensely localized in fibroblastic mesenchymal cells, fibrochondrocytes, chondrocytes and osteoblasts in newly formed osteophytic tissue. The pattern of BMP-2/4 immunolocalization was associated with that of mRNA localization. CONCLUSIONS: BMP-2 mRNA and BMP-2/4 were detected in cells appearing in OA tissues. BMP-2 was localized in cells of degenerating cartilage as well as osteophytic tissue. Given the negative localization of BMP-2 in normal adult articular cartilage, BMP-2 might be involved in the regenerating and anabolic activities of OA cells, which respond to cartilage damage occurring in osteoarthritis.

Aged↗
PubMed2003

The percentage of myeloperoxidase-positive blast cells is a strong independent prognostic factor in acute myeloid leukemia, even in the patients with normal karyotype.

To examine whether the percentage of myeloperoxidase (MPO)-positive blast cells is useful as a prognostic factor for acute myeloid leukemia (AML), cytochemical analysis of MPO was performed in 491 patients who were registered to the Japan Adult Leukemia Study Group-AML92 study. Patients were divided into two using the percentage of MPO-positive blast (high [>or=50%] and low (<50%)). Complete remission rates were 85.4% in the former and 64.1% in the latter (P=0.001). The overall survival (OS) and the disease-free survival (DFS) were significantly better in the high MPO group (48.3 vs 18.7% for OS, and 36.3 vs 20.1% for DFS, P<0.001, respectively). Multivariate analysis showed that both karyotype and the percentage of MPO-positive blast cells were equally important prognostic factors. The high MPO group still showed a better survival even when restricted to the intermediate chromosomal risk group or the patients with normal karyotype (P<0.001). The OS of patients with normal karyotype in the high MPO group was almost equal with that of the favorable chromosomal risk group. The percentage of MPO-positive blast cells is a simple and highly significant prognostic factor for AML patients, and especially useful to stratify patients with normal karyotype.

Acute Disease↗
PubMed2002

Epstein-Barr virus-associated T-lymphoproliferative disease with hemophagocytic syndrome, followed by fatal intestinal B lymphoma in a young adult female with WHIM syndrome. Warts, hypogammaglobulinemia, infections, and myelokathexis.

A rare association of Epstein-Barr virus-associated T- and B-lymphoproliferative disease (EBV(+) T- and EBV(+) B-LPD) in a patient with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome is reported. A 26-year-old Japanese female, who had been treated for WHIM syndrome since early childhood, developed hemophagocytic syndrome associated with EBV(+) T-LPD at the lymph nodes and spleen. The disease rapidly resolved in response to prednisolone therapy. However, 6 weeks later, fatal EBV(+) B lymphoma unresponsive to chemotherapy occurred in the intestine and other organs. Caution must be exercised that the patient with WHIM syndrome may be at risk for EBV-LPD.

Adult↗
PubMed2002

Vitamin E ointment at high dose levels suppresses contact dermatitis in rats by stabilizing keratinocytes.

OBJECTIVE: The pharmacological effect of vitamin E ointment at high dose levels was investigated in rats and mice during the development of contact dermatitis. MATERIALS AND METHODS: Allergic or irritant contact dermatitis was induced in sensitized or unsensitized animals by topical application of chemical agent(s). Cultured keratinocytes were prepared from dorsal skin of rats. RESULTS: The vitamin E ointment at 20-40% suppressed allergic and irritant contact dermatitis, exerting a comparable effect to that of 0.5% prednisolone ointment. Microscopic findings revealed that 20% vitamin E ointment reduced the keratinocyte damage, whereas 0.5% prednisolone was ineffective. The protective action of vitamin E on keratinocyte damage was also confirmed in a cell culture experiment. Furthermore, 20% vitamin E ointment blocked down-regulation of skin barrier function induced by contact dermatitis, although 0.5% prednisolone ointment was inactive. CONCLUSIONS: These results indicate that 20% vitamin E ointment suppresses contact dermatitis by stabilizing keratinocytes, concomitantly with novel, interesting properties.

Administration, Topical↗
PubMed2002

Prognostic significance of the null genotype of glutathione S-transferase-T1 in patients with acute myeloid leukemia: increased early death after chemotherapy.

We investigated the prognostic significance of genetic polymorphism in glutathione-S transferase mu 1 (GSTM1), glutathione-S transferase theta 1 (GSTT1), NAD(P)H:quinone oxidoreductase (NQO1) and myeloperoxidase (MPO), the products of which are associated with drug metabolism as well as with detoxication, in 193 patients with de novo acute myeloid leukemia (AML) other than M3. Of the patients, 64.2% were either homozygous or heterozygous for GSTT1 (GSTT1(+)), while 35.8% showed homozygous deletions of GSTT1 (GSTT1(-)). The GSTT1(-) group had a worse prognosis than the GSTT1(+) group (P = 0.04), whereas other genotypes did not affect the outcome. Multivariate analysis revealed that GSTT1(-) was an independent prognostic factor for overall survival (relative risk: 1.53; P = 0.026) but not for disease-free survival of 140 patients who achieved complete remission (CR). The rate of early death after the initiation of chemotherapy was higher in the GSTT1(-) group than the GSTT1(+) group (within 45 days after initial chemotherapy, P = 0.073; within 120 days, P = 0.028), whereas CR rates and relapse frequencies were similar. The null genotype of GSTT1 might be associated with increased toxicity after chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study.

In order to improve the disappointing prognosis of adult patients with acute lymphoblastic leukemia (ALL), we applied similar induction therapy as that used for acute myeloid leukemia (AML), ie frequent administration of doxorubicin (DOX). DOX 30 mg/m(2) was administered from days 1 to 3 and from days 8 to 10 together with vincristine, prednisolone, cyclophosphamide and L-asparaginase, followed by three courses of consolidation and four courses of intensification. From December 1993 to February 1997, 285 untreated adult patients with de novo ALL were entered. Of 263 evaluable patients (age 15 to 59; median 31), 205 (78%) obtained complete remission (CR). At a median follow-up period of 63 months, the predicted 6-year overall survival (OS) rate of all patients was 33%, and disease-free survival (DFS) rate of CR patients was 30%, respectively. By multivariate analysis, favorable prognostic factors for the achievement of CR were age <40 and WBC <50 000/microl; for longer OS were age <30 and WBC <30 000/microl; and for longer DFS of CR patients were FAB L1 and ALT <50 IU/l. Among 229 patients who had adequate cytogenetic data, 51 (22%) had Philadelphia (Ph) chromosome. Ph-negative chromosome was a common favorable prognostic factor for CR, longer OS and DFS. DFS was not different between early sequential intensification (n = 48) and intermittent intensification (n = 43) during the maintenance phase. Among CR patients under 40 years old, the 6-year survival was not different between the allocated related allo-BMT group (34 patients) and the allocated chemotherapy group (108 patients). However, among patients with Ph-positive ALL, the survival of patients who actually received allo-BMT was superior to that of patients who received chemotherapy (P = 0.046).

Antibiotics, Antineoplastic↗
PubMed2001

Developmental changes in PSD-95 and Narp mRNAs in the rat olfactory bulb.

Glutamate is the main neurotransmitter in the olfactory bulb. Recently, postsynaptic-density 95 (PSD-95) and neuronal activity-regulated pentraxin (Narp) have been reported to be pivotal for targeting and clustering of NMDA receptors and AMPA receptors, respectively. We thus investigated the expressions of PSD-95 and Narp mRNAs in the rat developing olfactory bulb. PSD-95 mRNA was already expressed in most neurons on the first postnatal day (P1). On the other hand, Narp mRNA expression was weakly seen only in mitral cells on P1. Thereafter, we found initial expression of Narp mRNA on P7 in periglomerular cells, and on P14 in granular cells, indicating that in the developing olfactory bulb PSD-95 mRNA expression precedes Narp mRNA expression, and that the expression pattern of Narp mRNA seems to be well correlated with the maturation of the neurons. These results indicate that PSD-95 and Narp play important roles in making efficient excitatory synapses in the developing rat olfactory bulb, and suggest that olfactory neurons might first express PSD-95 for making efficient NMDA receptors and thereafter express Narp for efficient AMPA receptors.

Animals↗
PubMed2001

Developmental changes in gephyrin and collybistin mRNA expressions in the rat olfactory bulb.

GABA and glycine are inhibitory neurotransmitters in the olfactory bulb. Recently, gephyrin, a receptor-associated peripheral membrane protein, and collybistin, a gephyrin-binding protein have been shown to be pivotal for the formation of postsynaptic glycine and GABA(A) receptor clusters. In this study, we, thus, examined expressions of gephyrin and collybistin mRNAs in the developing olfactory bulb using in situ hybridization. Although collybistin has two splice variants, we found only collybistin 1 isoform mRNA in the developing olfactory bulb. On the first postnatal day (P1), mitral cells abundantly expressed gephyrin and collybistin 1 mRNAs. However, their expressions were weak or not detected in the other regions. On P3, we first detected both transcripts in granule cells. It was on P7 when periglomerular cells first showed hybridization signals for gephyrin and collybistin mRNAs. The sequence of their expressions was well correlated with that of the maturation of individual neurons, suggesting that gephyrin and collybistin 1 mRNA expressions are induced when neurons arrive at their final destinations and ready for synaptogenesis, and that they are indispensable to make efficient inhibitory synapses in the developing rat olfactory bulb.

Animals↗
PubMed2001

Requirement for etoposide in the treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis.

PURPOSE: We sought to identify the clinical variables most critical to successful treatment of Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH). PATIENTS AND METHODS: Among the factors tested were age at diagnosis (< 2 years or > or = 2 years), time from diagnosis to initiation of treatment with or without etoposide-containing regimens, timing of cyclosporin A (CSA) administration during induction therapy, and the presence or absence of etoposide. RESULTS: By Kaplan-Meier analysis, the overall survival rate for the entire cohort of 47 patients, most of whom had moderately severe to severe disease, was 78.3% +/- 6.7% (SE) at 4 years. The probability of long-term survival was significantly higher when etoposide treatment was begun less than 4 weeks from diagnosis (90.2% +/- 6.9% v 56.5% +/- 12.6% for patients receiving this agent later or not at all; P <.01, log-rank test). Multivariate analysis with the Cox proportional hazards model demonstrated the independent prognostic significance of a short interval from EBV-HLH diagnosis to etoposide administration (relative risk of death for patients lacking this feature, 14.1; 95% confidence interval, 1.16 to 166.7; P =.04). None of the competing variables analyzed had significant predictive strength in the Cox model. However, concomitant use of CSA with etoposide in a subset of patients appears to have prevented serious complications from neutropenia during the first year of treatment. CONCLUSION: We conclude that early administration of etoposide, preferably with CSA, is the treatment of choice for patients with EBV-HLH.

Adolescent↗
PubMed2001

Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies.

Mutations of receptor tyrosine kinases are implicated in the constitutive activation and development of human malignancy. An internal tandem duplication (ITD) of the juxtamembrane (JM) domain-coding sequence of the FLT3 gene (FLT3/ITD) is found in 20% of patients with acute myeloid leukemia (AML) and is strongly associated with leukocytosis and a poor prognosis. On the other hand, mutations of the c-KIT gene, which have been found in mast cell leukemia and AML, are clustered in 2 distinct regions, the JM domain and D816 within the activation loop. This study was designed to analyze the mutation of D835 of FLT3, which corresponds to D816 of c-KIT, in a large series of human hematologic malignancies. Several kinds of missense mutations were found in 30 of the 429 (7.0%) AML cases, 1 of the 29 (3.4%) myelodysplastic syndrome (MDS) cases, and 1 of the 36 (2.8%) acute lymphocytic leukemia patients. The D835Y mutation was most frequently found (22 of the 32 D835 mutations), followed by the D835V (5), and D835H (1), D835E (1), and D835N (1) mutations. Of note is that D835 mutations occurred independently of FLT3/ITD. An analysis in the 201 patients newly diagnosed with AML (excluding M3) revealed that, in contrast to the FLT3/ITD mutation (n = 46), D835 mutations (n = 8) were not significantly related to the leukocytosis, but tended to worsen disease-free survival. All D835-mutant FLT3 were constitutively tyrosine-phosphorylated and transformed 32D cells, suggesting these mutations were constitutively active. These results demonstrate that the FLT3 gene is the target most frequently mutated to become constitutively active in AML.

Acute Disease↗
PubMed2001

Developmental changes in GABA transporter (GAT1 and GAT3) mRNA expressions in the rat olfactory bulb.

Developmental expressions of GABA transporters 1 and 3 (GAT1 and GAT3) were investigated in the rat olfactory bulb by using in situ hybridization histochemistry. We found that the expression of GAT1 and GAT3 mRNAs was dramatically changed in the granule cell layer (GCL), external plexiform layer (EPL) and glomerular layer (GL) during postnatal development. Among bulbar neurons, granule cells and periglomerular cells are GABAergic and they are localized in the GCL and GL, respectively. In the EPL, granule cells make GABAergic synapses with mitral cell dendrites. Thus, the changes seen in the GCL, EPL and GL seemed related to the development of the GABAergic system in the olfactory bulb. On the whole, our results demonstrated that expression patterns of GAT1 and GAT3 mRNAs have become similar to adult patterns on postnatal day 14 (P14), suggesting that GABA transporters may play a pivotal role in GABAergic neurotransmission after P14. However, expression patterns of GAT1 and GAT3 mRNAs in early postnatal days were quite distinct from those in adulthood. For example, in the GCL, immature granule cells already exhibited strong levels of GAT1 mRNA on P1 and the expression level was higher than that of granule cells in adulthood. GAT3 mRNA was strongly expressed in presumable radial glial cells surrounding the subependymal layer. In the EPL, few signals for the two transcripts were detected on P1 but they were markedly increased by P14. Our results indicate that GAT1 and GAT3 may play important roles in the development of the GABAergic system in the olfactory bulb.

Animals↗
PubMed2001

Morphological diagnoses of the Japan adult leukemia study group acute myeloid leukemia protocols: central review.

A morphological review system of the Japan Adult Leukemia Study Group has developed from the AML-87 through the AML-92 experience. We reviewed 1427 (90%) of 1592 cases enrolled in the AML-87, -89, or -92 protocols for morphology; 1408 (88%) were eligible. The rate of diagnostic concordance between each institute and the Committee on Morphological Diagnosis ranged from 76% to 80%. Acute myeloid leukemia (AML) subtypes were as follows: AML M0, 27 (2%); M1, 179 (13%); M2, 472 (34%); M3, 358 (25%); M4, 265 (19%); M5, 57 (4%); M6, 39 (3%); and M7, 11 (1%). The reason for the high number of patients with AML M3 is that many M3 patients were enrolled in the AML-92 protocol, which contained all-trans-retinoic acid. AML M0, M6 and M7 belonged to the poor prognostic groups. Auer bodies were found in 284 (53%) of 538 patients who survived significantly longer than those without Auer bodies in AML-87/-89. In AML-92 except for AML M3, 259 (43%) of 602 cases were Auer+ and also showed better survival rates. The survival of patients with >50% myeloperoxidase (MPO)-positive blast cells was better than those with < or =50% MPO+ blast cells in AML-87/-89. This trend was also seen in AML-92 excluding M3. AML with trilineage dysplasia (AML/TLD) is characterized as a subtype of de novo AML that shows morphological dysplasia of mature hematopoietic cells on a background of leukemic blast cells The number of patients with AML/TLD was 89 (16.5%) of 545 patients reviewed in AML-87/-89. AML-92, except for M3, showed a higher rate of patients with TLD (161 cases; 27.6%) because there were no patients with TLD in the AML M3 group. Survival rates for AML/TLD were worse than those for AML/non-TLD in both the AML-87/-89 and -92 protocols. Eighty percent of all cases (793/986) entered in AML-92 were analyzed cytogenetically. Fifty-one cases were not available for karyotyping because of a lack of mitoses or inappropriate preparations. The most frequent karyotype was normal, which accounted for 34.2%. The t(15;17), t(8;21), and inv(16) karyotypes, which are regarded as good risk factors, were 23.8%, 9.2%, and 1.6%, respectively. Abnormal chromosomes 5, 7, t(9;22), and t(6;9) were considered to be poor or intermediate risk factors As a new system of karyotyping begins in the ongoing AML protocol, useful chromosomal data will be obtained in the near future.

Acute Disease↗
PubMed2001

Risk factors for cytomegalovirus retinitis following bone marrow transplantation from unrelated donors in patients with severe aplastic anemia or myelodysplasia.

Two cases of cytomegalovirus (CMV) retinitis following bone marrow transplantation (BMT) from unrelated donors are reported. 1 patient had been treated for severe aplastic anemia (SAA) and the other for hypoplastic myelodysplastic syndrome (MDS). Because first line therapy with antithymocyte globulin (ATG) and cyclosporin A (CsA) had failed, BMT was performed following a conditioning regimen of ATG, cyclophosphamide, and total lymphoid irradiation. Treatment for CMV retinitis was successfully carried out with gancyclovir (systemic and intraocular injection), foscarnet, and photocoagulation (Case 1) and gancyclovir and foscarnet (Case 2). Both patients also developed Epstein-Barr virus-associated lymphoproliferative disease (EBV-LPD). We compared these 2 cases with 14 SAA patients who did not develop CMV retinitis after BMT using marrow from either HLA-identical siblings (n = 9) or from unrelated donors (n = 5). Unlike the retinitis patients, the latter 5 patients received ATG only once. The retinitis patients had significantly lower CD4+ T-cell levels in their peripheral blood than the 14 patients who did not develop CMV retinitis. We believe that repeated treatment with ATG and transplantation from unrelated donors may lead to immune dysfunction that could increase the likelihood of CMV retinitis, as well as LPD. For such BMT patients, regular ophthalmic examinations and careful testing for CMV antigenemia are recommended.

Adolescent↗
PubMed2001

Multicenter prospective study of interferon-alpha versus bone marrow transplantation for newly diagnosed patients with chronic myelogenous leukemia: a preliminary analysis.

Interferon-alpha (IFN-alpha) therapy was compared with bone marrow transplantation (BMT) in patients with chronic myelogenous leukemia (CML) in a multicenter, prospective study. Of 254 evaluable patients, 175 received IFN-alpha and 79 received allogeneic BMT, 50 of whom received transplants from human leukocyte antigen (HLA)-identical related donors and 29 from HLA-matched unrelated donors. Complete hematologic response was achieved by 148 patients (89%) in the IFN-alpha group and 53 (78%) in the BMT group. In the IFN-alpha group, a complete cytogenetic response was induced in 25 patients (15%), a partial cytogenetic response in 37 (23%), and a minor cytogenetic response in 41 (25%). At a median follow-up of 38 months, in the IFN-alpha group the predicted 5-year survival rate was 79%, and the predicted 5-year rate of remaining in chronic phase was 66%. In the BMT group the predicted 5-year survival rate was 72% for related-donor BMT and 67% for unrelated-donor BMT. Among low Sokal-risk patients, 5-year survival did not differ between IFN-alpha therapy and BMT, irrespective of age. In higher Sokal-risk patients, survival for related-donor BMT and unrelated-donor BMT tended to be better than that with IFN-alpha therapy in younger patients. On the other hand, in older patients, survival in the BMT group, especially for those receiving unrelated-donor BMT, appeared to be inferior to that in the IFN-alpha group. Unrelated-donor BMT can be recommended for high-risk younger patients. However, for older patients, it should be performed after careful consideration of prognostic factors such as age, Sokal score, and response to IFN-alpha.

Adolescent↗