PubMed Health⌕ Search

Biomedical subjects

Y Ikeda

Publications and source records attributed to Y Ikeda.

At least 19 recordsLinked to original sources
PubMed2007

Total body irradiation and granulocyte colony-stimulating factor-combined high-dose cytarabine as a conditioning regimen in allogeneic hematopoietic stem cell transplantation for advanced myelodysplastic syndrome: a single-institute experience.

In this study, we retrospectively evaluated the efficacy and safety of total body irradiation (TBI) and granulocyte colony-stimulating factor (G-CSF)-combined high-dose cytarabine as a conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in patients with advanced myelodysplastic syndrome (MDS). We evaluated 22 patients with advanced MDS, including refractory anemia with excess blasts (RAEB; n=10), RAEB in transformation (n=2), acute myelogenous leukemia transformed from MDS (n=6) and chronic myelomonocytic leukemia (n=4). The conditioning regimen consisted of 12 Gy of TBI and high-dose cytarabine (3 g/m(2)) every 12 h for 4 days, and the cytarabine was combined with continuous administration of G-CSF. The stem cell sources were bone marrow or peripheral blood stem cells from human leukocyte antigen (HLA)-identical siblings (n=12) and bone marrow from HLA serologically matched unrelated donors (n=10). Three patients experienced disease relapse, two of whom died of disease progression. Of 22 patients, 16 are currently alive and disease-free. The 5-year estimated overall survival, disease-free survival, relapse and non-relapse mortality rates are 76.7, 72.2, 16.6 and 14.1%, respectively. These results suggest that G-CSF-combined high-dose cytarabine could be a promising component of the conditioning regimen of allogeneic HSCT for advanced MDS, providing a low incidence of both relapse and treatment-related mortality.

Adolescent↗
PubMed2007

Planar polarity of root hair positioning in Arabidopsis.

The co-ordinated polarity of cells within the plane of a single tissue layer (planar polarity) is intensively studied in animal epithelia but has only recently been systematically analysed in plants. The polar positioning of hairs in the root epidermis of Arabidopsis thaliana provides an easily accessible system for the functional dissection of a plant-specific planar polarity. Recently, mutants originally isolated in genetic screens for defects in root hair morphogenesis and changes in the sensitivity to or the production of the plant hormones auxin and ethylene have identified players that contribute to polar root hair placement. Here, we summarize and discuss recent progress in research on polar root hair positioning from studies in Arabidopsis.

Animals↗
PubMed2006

Origin of spontaneous activity in neonatal and adult rat bladders and its enhancement by stretch and muscarinic agonists.

This study examined the origin of spontaneous activity in neonatal and adult rat bladders and the effect of stretch and muscarinic agonists and antagonists on spontaneous activity. Rats were anesthetized and their bladders were excised, cannulated, and loaded with voltage- and Ca(2+)-sensitive dyes. Intracellular Ca(2+) and membrane potential transients were mapped using photodiode arrays in whole bladders, bladder sheets, or cross-section preparations at 37 degrees C. Intravesical pressure was recorded from whole bladders. In neonatal bladders and sheets, spontaneous Ca(2+) and electrical signals arose at a site near the dome and spread in a coordinated manner throughout the bladder with different dome-to-neck conduction velocities (Ca(2+): 3.7 +/- 0.4 mm/s; membrane potential: 46.2 +/- 3.1 mm/s). In whole bladders, optical signals were associated with spontaneous contractions (10-20 cmH(2)O). By contrast, in adult bladders spontaneous Ca(2+) and electrical activity was uncoordinated, originating at multiple sites and was associated with smaller (2-5 cmH(2)O) contractions. Spontaneous contractions and optical signals were insensitive to tetrodotoxin (2 muM) but were blocked by nifedipine (10 muM). Stretch or low carbachol concentrations (50 nM) applied to neonatal whole bladders enhanced the amplitude (to 20-35 cmH(2)O) of spontaneous activity, which was blocked by atropine. Bladder cross sections revealed that Ca(2+) and membrane potential transients produced by stretch or carbachol began near the urothelial-suburothelial interface and then spread to the detrusor. In conclusion, spontaneous activity in neonatal bladders, unlike activity in adult bladders, is highly organized, originating in the urothelium-suburothelium near the dome. Activity is enhanced by stretch or carbachol and this enhancement is blocked by atropine. It is hypothesized that acetylcholine is released from the urothelium during bladder filling to enhance spontaneous activity.

Animals↗
PubMed2006

Inhibition of HIV-1 replication by simian restriction factors, TRIM5alpha and APOBEC3G.

Old World monkey TRIM5alpha targets incoming human immunodeficiency virus type 1 (HIV-1) viral capsid, whereas the apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like (APOBEC)3 family hypermutate/degrade viral sequences. Here, we show the potentials of simian TRIM5alpha and APOBEC3G as therapeutic sequences for AIDS gene therapy. Both rhesus and African green monkey (agm) TRIM5alpha efficiently restrict HIV-1 vectors with divergent Gag from different HIV-1 subtypes. Human T cells genetically engineered to express agm-TRIM5alpha block or delay HIV-1 replication. Although agm-APOBEC3G expression alone only transiently suppresses HIV-1 replication, co-expression of agm-APOBEC3G and agm-TRIM5alpha successfully block the virus replication for more than 5 weeks.

Animals↗
PubMed2006

Establishment of a new human acute monocytic leukemia cell line TZ-1 with t(1;11)(p32;q23) and fusion gene MLL-EPS15.

Human leukemia cell lines are of great value in investigating basic and applied aspects of cell biology and clinical medicine. There have been 37 leukemia cell lines carrying 11q23 translocation and MLL rearrangements; however, cell lines harboring with t(1;11)(p32;q23) have not been established. We report here for the first time a new acute monocytic leukemia (AMoL) cell line with t(1;11)(p32;q23), designated TZ-1, and herein describe its biological characteristics. Mononuclear cells isolated from the ascites from a patient with AMoL (French-American-British classification; acute myeloid leukemia M5a) were isolated and passaged by liquid culture medium for a year. TZ-1 cells revealed typical monocytic features in morphology and had a t(1;11)(p32;q23) translocation. The immunoprofiling as determined by flow cytometry showed that TZ-1 cells are positive for myeloid and monocytic markers with lymphoid-associated markers. Fluorescence in situ hybridization and reverse transcription-polymerase chain reaction analyses revealed MLL-EPS15 fusion transcript and protein. Taken together, these results suggest that TZ-1 is a new monocytic leukemia cell line with t(1;11) translocation and fusion gene MLL-EPS15. The established cell line, TZ-1, could provide a valuable model in the analysis of the pathogenesis of MLL-EPS15-positive leukemia and in the development of new agents for this type of leukemia.

Aged↗
PubMed2006

Biochemical markers of bone turnover predict bone loss in perimenopausal women but not in postmenopausal women-the Japanese Population-based Osteoporosis (JPOS) Cohort Study.

INTRODUCTION: The predictive value of biochemical markers of bone turnover for subsequent change in bone density in a population sample of healthy women with a wide range of ages has not been fully established. METHODS: We followed 1,283 women aged 15-79 years at baseline selected randomly from the inhabitants of three areas in Japan for 6 years, and examined 1,130 subjects with no disease or administration of drugs affecting bone metabolism. The annual change in bone density at the spine, total hip, and distal one third of the radius was determined during the follow-up period by dual x-ray absorptiometry and was compared among the groups using different levels of biochemical markers at baseline, including serum osteocalcin (OC) and bone-specific alkaline phosphatase (bone ALP), free and total (tDPD) forms of immunoreactive deoxypyridinoline, and type I collagen crosslinked C-terminal telopeptide (CTX) in urine. RESULTS: Premenopausal women aged 45 years or older with elevated levels of OC, bone ALP, CTX, or tDPD showed significantly greater bone loss at most skeletal sites during the follow-up period than those with lower levels, after adjustment for the effects of age, height, weight, dietary calcium intake, regular exercise, and current smoking. The greatest coefficient of determination of the model was observed in the association between CTX and bone loss at the hip during the first 3 years of follow-up (42.8%). These subjects were pooled with perimenopausal women at baseline, and those who still menstruated at follow-up in this pooled group showed significant but more modest associations, whereas those who entered menopause during the follow-up period showed clear associations. However, early postmenopausal women with less than 5 or 10 years since menopause showed an association that was limited mostly to the distal radius, and other postmenopausal groups had virtually no association. CONCLUSION: Biochemical markers of bone turnover may predict bone loss in women undergoing menopausal transition but may not predict bone loss in postmenopausal women.

Adolescent↗
PubMed2006

Two types of autoantibody-mediated thrombocytopenia in patients with systemic lupus erythematosus.

OBJECTIVES: To determine whether autoantibodies to two platelet-specific antigens, glycoprotein IIb/IIIa (GPIIb/IIIa) and thrombopoietin receptor (TPOR), contribute to thrombocytopenia in patients with systemic lupus erythematosus (SLE). METHODS: Circulating B cells producing anti-GPIIb/IIIa antibodies and serum anti-TPOR antibodies were measured in 32 SLE patients with thrombocytopenia, 30 SLE patients without thrombocytopenia, 92 patients with idiopathic thrombocytopenia and 60 healthy controls. The megakaryocyte density in bone-marrow smears from all the patients with thrombocytopenia was evaluated. RESULTS: Anti-GPIIb/IIIa and anti-TPOR antibody responses were more frequent in SLE patients with thrombocytopenia than in those without thrombocytopenia (88 vs 17%, P<0.0001; and 22% vs 0%, P=0.01, respectively). The frequencies of these platelet-related antibodies were comparable between SLE patients with thrombocytopenia and patients with idiopathic thrombocytopenia. Twenty-nine (91%) SLE patients with thrombocytopenia had either anti-GPIIb/IIIa or anti-TPOR antibody, and six had both. In SLE patients with thrombocytopenia, the anti-TPOR-positive patients had significantly higher frequencies of megakaryocytic hypoplasia and poorer therapeutic responses to corticosteroids and intravenous immunoglobulin than did the anti-TPOR-negative patients, most of whom had the anti-GPIIb/IIIa antibody alone. CONCLUSIONS: Anti-GPIIb/IIIa and anti-TPOR antibodies are major factors contributing to SLE-associated thrombocytopenia, but the clinical presentations associated with these autoantibodies are different.

Adult↗
PubMed2006

Pharmacological brain cooling with indomethacin in acute hemorrhagic stroke: antiinflammatory cytokines and antioxidative effects.

We evaluated the effects of a novel pharmacological brain cooling (PBC) method with indomethacin (IND), a nonselective cyclooxygenase inhibitor, without the use of cooling blankets in patients with hemorrhagic stroke. Forty-six patients with hemorrhagic stroke (subarachnoid hemorrhage; n = 35, intracerebral hemorrhage; n = 11) were enrolled in this study. Brain temperature was measured directly with a temperature sensor. Patients were cooled by administering transrectal IND (100 mg) and a modified nasopharyngeal cooling method (positive selective brain cooling) initially. Brain temperature was controlled with IND 6 mg/kg/day for 14 days. Cerebrospinal fluid concentrations of interleukin-1beta (CSF IL-1beta) and serum bilirubin levels were measured at 1, 2, 4, and 7 days. The incidence of complicating symptomatic vasospasm after subarachnoid hemorrhage was lower than in non-PBC patients. CSF IL-1beta and serum bilirubin levels were suppressed in treated patients. IND has several beneficial effects on damaged brain tissues (anticytokine, free radical scavenger, antiprostaglandin effects, etc.) and prevents initial and secondary brain damage. PBC treatment for hemorrhagic stroke in patients appears to yield favorable results by acting as an antiinflammatory cytokine and reducing oxidative stress.

Acute Disease↗
PubMed2006

A novel neuroprotective compound FR901459 with dual inhibition of calcineurin and cyclophilins.

Brain ischemia leads to severe damage in the form of delayed neuronal cell death. In our study, we show that the marked neuroprotection of the new immunosuppressant FR901495 in forebrain ischemia is due not only to inhibition of calcineurin, but also to protection against mitochondrial damage caused by mitochondrial permeability transition pore formation through cyclophilin D, one of the prolyl cis/trans isomerase family members. These findings shed light on the clinical application and development of new drugs for the treatment of ischemic damage in the brain as well as in the heart and liver.

Animals↗
PubMed2006

Search for novel gene markers of traumatic brain injury by time differential microarray analysis.

Neuronal and glial cell death caused by axonal injury sometimes contributes to whole brain pathology after traumatic brain injury (TBI). We show that neuroprotection by 2 types of immunosuppressants, cyclosporin A (CsA) and tacrolimus (FK506), in a cryogenic brain injury model results from inhibition of calcineurin and protection from mitochondrial damage caused by formation of a mitochondrial permeability transition pore induced by cyclophilin D (CyPD), one of the prolyl cis/trans isomerase family members. We evaluated why CsA is neuroprotective by microarray analysis of gene expression in the cryogenic brain injury rat model. Analyses of expression patterns demonstrated that expression of over 14,000 genes changed between the groups with and without CsA treatment, and about 350 genes among them were extracted showing a significant difference. We learned that the differential expression of several gene targets showed specific patterns in a time-dependent manner. These results may help elucidate the mechanisms of neuronal cell death after TBI and the neuroprotective effects of CsA after TBI.

Animals↗
PubMed2006

Prolonged thrombocytopenia after allogeneic hematopoietic stem cell transplantation: associations with impaired platelet production and increased platelet turnover.

To evaluate the mechanisms underlying prolonged thrombocytopenia after allogeneic hematopoietic stem cell transplantation (SCT), an index for plasma glycocalicin normalized for the individual platelet count (GCI), plasma thrombopoietin (TPO), and circulating B cells producing anti-GPIIb-IIIa antibodies were measured in 50 SCT recipients with or without prolonged thrombocytopenia, 42 patients with idiopathic thrombocytopenic purpura, nine patients with aplastic anemia, and 22 healthy individuals. All three indices were significantly higher in the SCT recipients with thrombocytopenia than in those without (P < 0.01 for all comparisons), and were significantly correlated with the platelet count in SCT recipients. Stepwise multiple regression analysis of the samples from the SCT recipients revealed that GCI and TPO independently pointed to specific mechanisms of thrombocytopenia. The GCI and TPO status in SCT recipients with thrombocytopenia had a pattern similar to that seen in aplastic anemia, suggesting a major role for impaired thrombopoiesis. An antiplatelet antibody response was frequently detected in SCT recipients, but the development of thrombocytopenia is likely to depend on additional factors, such as reticuloendothelial function. In summary, post transplant prolonged thrombocytopenia is associated with complex mechanisms, including impaired thrombopoiesis and increased platelet turnover.

Adult↗
PubMed2006

Induction of cell death in human papillomavirus 18-positive cervical cancer cells by E6 siRNA.

Human cervical cancer is caused by high-risk types of human papillomavirus (HPV) such as HPV16 and HPV18, which possess the E6 and E7 oncogenes, whose concurrent expression is a prerequisite for cancer development and maintaining malignant phenotypes. Silencing these oncogenes is considered to be applicable in molecular therapies of human cervical cancer. However, it remains to be determined whether E6, E7, or both should be silenced to obtain most efficient antitumor activity by an HPV small-interfering RNA (siRNA). Herein, we report two types of siRNAs targeting HPV18 E6, that exerted a negative growth effect on HPV18-positive cervical cancer cells (HeLa and SW756), in part, inducing cell death. One siRNA (Ex-18E6), designed to target both E6-E7 mRNA and its splicing variant, E6*I-E7 mRNA, efficiently knocked down both E6 and E7 expression. The other (Sp-18E6), designed to specifically target E6-E7 mRNA but not E6*I-E7 mRNA, suppressed E6 to a similar level as Ex-18E6; however, it less efficiently inhibited E7 as compared to Ex-18E6. Although both siRNAs induced cell death, Sp-18E6 siRNA induced more prominent cell death than Ex-18E6. Our results suggest that E6-specific suppression may induce more potent anticancer activity than simultaneous E6 and E7 suppression, and that E6-specific targeting is a promising strategy for siRNA-based therapy for HPV-positive cervical cancer.

Animals↗
PubMed2006

Preliminary laboratory based diagnostic criteria for immune thrombocytopenic purpura: evaluation by multi-center prospective study.

BACKGROUND: We proposed diagnostic criteria for immune thrombocytopenic purpura (ITP) by modifying the existing guidelines for diagnosis of ITP and by incorporating laboratory tests found useful for predicting its diagnosis, for example erythrocyte count, leukocyte count, anti-GPIIb/IIIa antibody-producing B cells, platelet-associated anti-GPIIb/IIIa antibodies, percentage of reticulated platelets, and plasma thrombopoietin. OBJECTIVE AND METHODS: To validate our criteria, we conducted a multi-center prospective study involving 112 patients with thrombocytopenia and a morphologically normal peripheral blood film at the first visit. Each patient underwent a physical examination, routine laboratory tests, and specialized tests for the anti-GPIIb/IIIa antibody response and platelet turnover. RESULTS: Ninety-one patients (81%) satisfied the proposed criteria at first visit. Clinical diagnosis was made by skilled hematologists > 6 months after the first visit; ITP was diagnosed in 88 patients and non-ITP disorders in 24. The proposed criteria had 98% sensitivity, 79% specificity, a 95% positive predictive value, and a 90% negative predictive value. A relatively low specificity appears to be attributed to a few patients who had both ITP and aplastic anemia or myelodysplastic syndrome. CONCLUSIONS: Our preliminary diagnostic criteria based on ITP-associated laboratory findings were useful for the differential diagnosis of ITP, but additional evaluations and modifications will be necessary to develop criteria that can be used routinely.

Adolescent↗
PubMed2006

The expression of IGF-I and myostatin mRNAs in skeletal muscle of hypophysectomized and underfed rats during postnatal growth.

AIM: To determine the roles of myostatin and insulin-like growth factor-I (IGF-I) during postnatal growth, we examined IGF-I and myostatin mRNA expression in the skeletal muscles of hypophysectomized and underfed rats during postnatal growth. METHODS: Five-week-old rats were divided into four groups: freely fed control, moderately underfed, severely underfed and hypophysectomized. Four weeks later, blood and muscle samples were gathered to determine serum IGF-I, myosin heavy chain (MHC) isoforms, IGF-I Ea, IGF-I Eb and myostatin mRNA. RESULTS: The weights of soleus, plantaris and masseter muscles were decreased in underfed and hypophysectomized rats. Hypophysectomy resulted in significant increases of type I MHC at the expense of type IIx in plantaris muscle and of neonatal MHC at the expense of types IIx and IIb in masseter muscle. Serum IGF-I was decreased by underfeeding and hypophysectomy. Plantaris muscle IGF-I Ea mRNA in underfed and hypophysectomized rats was significantly lower than in normal controls. Plantaris muscle IGF-I Eb mRNA in underfed rats was significantly lower than in normal controls. Masseter muscle IGF-I Eb mRNA in severely underfed rats was significantly lower than in normal control and hypophysectomized rats. Soleus muscle myostatin mRNA in hypophysectomized rats was significantly higher than in normal and significantly underfed rats. No significant differences in plantaris and masseter muscle myostatin mRNA were observed between groups. CONCLUSION: Suppressed muscle growth caused by hypophysectomy and underfeeding may be attributed mainly to reduced circulating IGF-I and partially to reduced IGF-I mRNA, rather than to a change in myostatin.

Animals↗
PubMed2006

MR findings of granulocytic sarcoma of the breasts.

We report a case of isolated extramedullary relapse of acute myeloid leukaemia (AML) that presented as granulocytic sarcoma of both breasts, with no other signs of relapse even in the bone marrow. The T2 weighted coronal images on MR showed both multiple ill-defined heterogeneous hyperintense masses relative to breast parenchyma; these masses were seen also with a visual washout enhancement. Pathohistological study showed infiltration by myeloblasts, which were relatively uniform in appearance, featuring round or oval nuclei and a small cytoplasm. After chemotherapy and radiotherapy, both breast masses disappeared on MR images. Although the MR findings of granulocytic sarcoma were indistinguishable from those of multicentric carcinoma and malignant lymphoma, the MR images were useful for evaluating and monitoring responses to the treatments, as well as for detecting non-palpable relapsed tumours.

Breast Neoplasms↗
PubMed2006

[Mid-term results of overlapping cardiac volume reduction for ischemic cardiomyopathy].

BACKGROUND: Left ventricular restoration (LVR) is thought to be effective for ischemic cardiomyopathy (ICM). We assessed the early and mid-term results of overlapping cardiac volume reduction (OLCVR) as an operation for LVR on patients with ICM. METHODS: From February to June 2004, 4 patients with ICM underwent OLCVR in our department. RESULTS: There was no death. Significant decreases in the left ventricular end diastolic volume index and in the left ventricular end systolic volume index were observed in the early postoperative period in all the 4 patients. These effects were still evident 1 year later, with improved New York Heart Association (NYHA) functional class and a smaller left ventricular diastolic diameter. One patient required implantation of a cardioverter defibrillator 16 months postoperatively. CONCLUSION: The favorable early and mid-term results of the OLCVR indicate that it is an effective procedure for patients with ICM.

Aged↗