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Biomedical subjects

H Oh

Publications and source records attributed to H Oh.

At least 73 records · Page 4Linked to original sources
PubMed1999

No beneficial effect from addition of etoposide to daunorubicin, cytarabine, and 6-mercaptopurine in individualized induction therapy of adult acute myeloid leukemia: the JALSG-AML92 study. Japan Adult Leukemia Study Group.

To assess the efficacy of etoposide added to the standard remission induction therapy for acute myeloid leukemia (AML), newly diagnosed adult AML patients were randomized to receive either daunorubicin (40 mg/m2/day x 4 or more), behenoyl cytarabine (200 mg/m2/day x 10 or more), and 6-mercaptopurine (70 mg/m2/day x 10 or more) (BHAC-DM), or the same three drugs plus etoposide (100 mg/m2/day x 5) (BHAC-EDM) for response-oriented individualized induction therapy. The patients achieving complete remission (CR) received the same 3 courses of consolidation therapy followed by 6 courses of maintenance/intensification therapy. M3 patients were excluded because all-trans retinoic acid was used. Of 667 patients registered, 655 were evaluable. The median age was 49 (range 15 to 85). CR rates were 77% in the BHAC-DM group and 75% in the BHAC-EDM group. In 173 M4 patients, CR rates were 86% and 69% (P = 0.009), and in 32 M5 patients, 80% and 77% (P = 0.810) in the BHAC-DM and the BHAC-EDM groups, respectively. The predicted 6-year overall survival rates were 30% and 38% (P = 0.925) for the BHAC-DM and BHAC-EDM groups, and the disease-free survival rates of CR patients were 25% and 35% (P = 0.352), respectively. Nonhematological toxicities after the first course of induction therapy were almost equal among the two groups, with the exception of a greater loss of hair (P = 0.024) and more frequent diarrhea (P = 0.013) in the BHAC-EDM group. We concluded that in the present study, the addition of etoposide to the standard individualized induction therapy showed no advantage in adult AML, even among M4 and M5 patients.

Acute Disease↗
PubMed1999

[Relationship between diabetes mellitus-associated obstructive sleep apnea syndrome and hyperinsulinemia].

The purpose of this study was to examine the prevalence of sleep disordered breathing and background factors, especially hyperinsulinemia, in diabetic patients. The subjects were 70 patients randomly selected from 143 noninsulin-dependent diabetic patients hospitalized for educational purposes. Obstructive sleep apnea syndrome (OSAS) was diagnosed in 13 subjects, equivalent to a prevalence of 18.6%. The mean +/- S.D. immunoreactive insulin (IRI) values for 11 of the 13 OSAS patients (excluding insulin-treated patients) and for 49 non-OSAS patients were 10.7 +/- 6.8 microU/ml and 5.8 +/- 3.5 microU/ml, respectively. The value for the OSAS group was higher than that for the non-OSAS group (p = 0.04). However, a positive correlation between body mass index (BMI) and IRI was observed in both the OSAS (Y = 1.148 X - 20.006, r = 0.834, p = 0.001) and non-OSAS (Y = 0.466 X - 5.820, r = 0.524, p = 0.0001) groups. Multivariate analysis demonstrated that the presence of OSAS had a statistically significant influence on IRI (p = 0.001), but not on BMI (p = 0.391). These findings suggest that hyperinsulinemia may be exacerbated in diabetic patients with OSAS regardless of BMI.

Body Mass Index↗
PubMed1998

Angiotensin II interferes with leukemia inhibitory factor-induced STAT3 activation in cardiac myocytes.

Recently, we reported that leukemia inhibitory factor (LIF), a member of the interleukin (IL)-6 cytokine family, transduced hypertrophic and cytoprotective signals via Januas Kinase-signal transducer and activator of transcription (JAK-STAT) pathway in cardiac myocytes. Angiotensin II (AII) is also known to activate STATs and reported to induced apoptosis in adult rat ventricular myocytes. In the present study, we investigated potential interactions between gp130 dependent and AII signaling pathways, by examining AII regulation of LIF-induced anti-apoptotic effect and STAT3 activation in cardiac myocytes. Although LIF attenuated the DNA fragmentation induced by serum depletion, AII augmented the DNA fragmentation in cultured neonatal rat cardiac myocytes. Furthermore, LIF-mediated cytoprotective effect was inhibited by AII pretreatment. LIF rapidly and transiently tyrosine phosphorylated STAT3 in cardiac myocytes which was not observed by AII. AII pretreatment inhibited LIF-induced phosphorylation of STAT3 in a dose dependent manner. This inhibitory effect of AII on STAT3 activation was blocked by the AII type I (AT1) receptor antagonist CV11974. These results demonstrate that negative crosstalk between gp130 and AT1 receptor dependent signaling exists in cardiac myocytes. This crosstalk may contribute to the modulation of pathophysiological process in myocardial disease.

Angiotensin II↗
PubMed1998

Activation of phosphatidylinositol 3-kinase through glycoprotein 130 induces protein kinase B and p70 S6 kinase phosphorylation in cardiac myocytes.

Phosphatidylinositol (PI) 3-kinase is known to be activated by cytokine stimulation through different types of receptors to transduce intracellular responses. We have previously reported that leukemia inhibitory factor (LIF) induces the activation of Janus kinase signal transducer and activator of transcription (JAK-STAT) and mitogen-activated protein (MAP) kinase pathways through glycoprotein (gp) 130 in cardiac myocytes. However, whether PI 3-kinase is involved in regulation of gp130 signaling and the activation mechanisms by which it associates with other tyrosine-phosphorylated proteins remain unknown. We found that LIF induced the activation of PI 3-kinase in cardiac myocytes. Moreover, JAK1 binds to PI 3-kinase, and LIF stimulation increases the PI 3-kinase activity in JAK1 immunoprecipitates. Activation of MAP kinase and protein kinase B by LIF was attenuated by wortmannin. LIF-induced p70 S6 kinase activation, protein synthesis, and c-fos mRNA expression were inhibited by wortmannin and rapamycin. Both inhibitors failed to appreciably affect the phosphorylation of STAT3. In conclusion, PI 3-kinase is activated with LIF in cardiac myocytes, and JAK1 is found to associate with this enzyme. PI 3-kinase provides a crucial link between gp130, MAP kinase, protein kinase B, and p70 S6 kinase in cardiac myocytes.

Androstadienes↗
PubMed1998

Response-oriented individualized induction therapy with six drugs followed by four courses of intensive consolidation, 1 year maintenance and intensification therapy: the ALL90 study of the Japan Adult Leukemia Study Group.

Adult patients with acute lymphoblastic leukemia (ALL) were treated according to the ALL90 study, the second prospective study for ALL of the Japan Adult Leukemia Study Group (JALSG). Its characteristics included response-oriented individualized induction therapy with six drugs (doxorubicin, mitoxantrone, vincristine, prednisolone, [corrected] cyclophosphamide and L-asparaginase), and a prospective comparison between allogeneic bone marrow transplantation (allo-BMT) and chemotherapy alone in patients below 45 years of age. The protocol consisted of one or two courses of induction, four courses of consolidation, and three courses of intensification including 12 month maintenance and six times of central nervous system (CNS) prophylaxis. Of 180 evaluable patients (median age, 43), 125 (69%) achieved complete remission (CR). Predicted overall survival (OAS), event-free survival and disease-free survival (DFS) were 15, 10 and 14%, respectively at the median follow-up period of 62 months. No specific toxicities were observed. Leukocytes < 30,000/microliter, normal karyotype, and blasts < 10% in bone marrow at day 15 of induction therapy were significantly favorable prognostic factors for the achievement of CR, DFS and OAS by univariate analysis. Multivariate analysis showed leukocytes < 30,000/microliter and blasts < 10% on day 15 was a significant factor for the achievement of CR, DFS and OAS. Ph-chromosome was found in 28% (36/130) of patients examined and was one of the worst prognostic factors. All Ph positive patients were predicted to die within 600 days. Allo-BMT was not significantly superior to chemotherapy with respect to DFS (P = 0.226). The overall results were inferior to those of the former ALL87 protocol. As reasons, the older median age of 43 years old (vs. 38 years old) and lower dose intensity, especially of l-asparaginase, etc. were suggested. However, patients with good prognostic factors (leukocyte < 30,000/microliter and age < 30 years old) showed better survival than others (P < 0.0001), and the result was similar to that of older children, the high risk group of childhood ALL, suggesting that ALL could be a disease of single entity, showing higher resistance to chemotherapy as patients become older.

Adult↗
PubMed1998

Arenarins A-C: new cytotoxic fungal metabolites from the sclerotia of aspergillus arenarius

Three new terphenyl-type metabolites, arenarins A-C (1-3), have been isolated from the sclerotia of Aspergillus arenarius (NRRL 5012). The structures of these compounds were elucidated by analysis of 1-D and 2-D NMR data. Arenarins A-C exhibited mild activity in feeding assays against the dried-fruit beetle Carpophilus hemipterus and cytotoxicity against human tumor cell lines.

Journal Article↗
PubMed1998

Chemotherapy vs HLA-identical sibling bone marrow transplants for adults with acute lymphoblastic leukemia in first remission.

There is controversy about whether chemotherapy or an HLA-identical sibling bone marrow transplant is better treatment for adults with acute lymphoblastic leukemia (ALL) in first remission. A previous study of patients treated in 1980-1987 showed similar leukemia-free survivals with these approaches. We re-examined this issue in more recently treated patients receiving different chemotherapy. Chemotherapy subjects (n = 76) participated in trial ALL-87 of the Japan Adult Leukemia Study Group (JALSG). Transplant subjects (n = 214) were reported to the International Bone Marrow Transplant Registry (IBMTR). Treatment-related mortality, relapse and leukemia-free survival were compared after adjusting for differences in subject- and disease-related variables and time-to-treatment. Outcomes differed in persons < or = and >30 years of age. Five-year treatment-related mortality in persons < or =30 years was 3% (95% confidence interval, 0-12%) with chemotherapy vs 32% (23-41%; P < 0.0001) with transplants. The difference was greater among persons >30 years, 13% (2-31%) with chemotherapy vs 57% (43-69%; P < 0.0001) with transplants. Five-year relapse probability in persons < or =30 years was 69% (50-84%) with chemotherapy vs 22% (14-32%; P < 0.0001) with transplants. Among persons >30 years, 5-year relapse was 70% (53-85%) with chemotherapy vs 32% (20-45%; P < 0.0001) with transplants. Leukemia-free survival at 5 years was significantly worse with chemotherapy than with transplants in persons < or =30 years (30% (15-48%) vs 53% (44-63%; P = 0.02)) but not in persons >30 years (26% (13-41%) vs 30% (20-41%; P = 0.70)). We concluded that transplants result in more treatment-related deaths but fewer relapses than chemotherapy. Leukemia-free survival is better with transplants than chemotherapy in persons < or =30 years of age but comparable in older persons.

Adolescent↗
PubMed1998

Plasma thrombopoietin levels in marrow transplant patients with veno-occlusive disease of the liver.

Platelet transfusion requirements are higher among patients with veno-occlusive disease (VOD), compared to patients without VOD. One possible explanation is inadequate production of thrombopoietin (TPO), a protein synthesized in the liver. We prospectively studied 28 patients to test the hypothesis that plasma TPO levels were decreased in patients who developed VOD. Plasma TPO levels to day +30 were measured by ELISA (normal, 0.36+/-0.15 fmol/ml). VOD developed in 18/28 patients. Platelet transfusion requirements were significantly different in patients with and without VOD (97+/-46.1 units vs 51+/-33.2 units, P = 0.008). Plasma TPO levels were elevated at baseline (10.8+/-13.0 fmol/ml) and increased after transplant, with peak values of 32.3+/-10.3 fmol/ml at day +7. TPO levels were significantly higher at days +7 and +17 among patients with VOD than among those without VOD (P < 0.01). Regression analysis of TPO levels vs platelet counts showed a significant inverse relationship. We conclude that TPO levels were higher in patients with VOD and were inversely correlated with platelet counts, suggesting that regulation of TPO levels was related to platelet mass. Thrombocytopenia in patients with VOD cannot be explained by inadequate hepatic synthesis of TPO.

Adult↗
PubMed1998

Analysis of prognostic factors in newly diagnosed acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Japan Adult Leukemia Study Group.

PURPOSE: We conducted a multicenter study of differentiation therapy with all-trans retinoic acid (ATRA) followed by intensive chemotherapy in patients with newly diagnosed acute promyelocytic leukemia (APL) and analyzed the prognostic factors for predicting complete remission (CR), event-free survival (EFS), and disease-free survival (DFS). PATIENTS AND METHODS: All patients received ATRA until CR. If patients had an initial leukocyte count greater than 3.0 x 10(9)/L, they received daunorubicin (DNR) and behenoyl cytarabine (BHAC). During therapy, if patients showed blast and promyelocyte counts greater than 1.0 x 10(9)/L, they received additional DNR and BHAC. After achieving CR, patients received three courses of consolidation and six courses of maintenance/intensification chemotherapy. RESULTS: Of 198 registered, 196 were assessable (age range, 15 to 86 years; median, 46) and 173 (88%) achieved CR. Multivariate analysis showed that no or minor purpura at diagnosis (P = .0046) and age less than 30 years (P = .0076) were favorable factors for achievement of CR. Predicted 4-year overall survival and EFS rates were 74% and 54%, respectively, and the 4-year predicted DFS rate for 173 CR patients was 62%. Multivariate analysis showed that age less than 30 years (P = .0003) and initial leukocyte count less than 10 x 10(9)/L (P = .0296) were prognostic factors for longer EFS, and initial leukocyte count less than 10.0 x 10(9)/L was a sole significant prognostic factor for longer DFS (P = .0001). CONCLUSION: Our results show that age, hemorrhagic diathesis, and initial leukocyte count are prognostic factors for APL treated with ATRA followed by intensive chemotherapy.

Adolescent↗
PubMed1998

[Transformation of myelofibrosis into acute myelogenous leukemia (M0) with multiple tumor emboli].

A 60-year-old woman was admitted in August 1995 complaining of abdominal pain. A diagnosis of essential thrombocythemia had been made in 1987, and myelofibrosis developed in the patient thereafter. Physical examination revealed massive hepatosplenomegaly, and the peripheral blood showed leukoerythroblastosis with chromosomal abnormalities in peripheral blood cells. In May, 1996, blastic transformation occurred. Based on the findings of surface marker analysis, the blasts met the diagnostic criteria for acete myelogenous leukemia because they were negative for peroxidase and positive for CD13. In June, the patient died of multiple organ failure. Postmortem examination revealed multiple tumor emboli.

Cell Transformation, Neoplastic↗
PubMed1998

[Prevalence and a drug use development model for the study of adolescent drug use in Japan].

The purposes of this study were to estimate the prevalence of drug use, to examine the correlation between drug use and drinking/smoking in Japan, and to test a developmental model of adolescents' drug use based on three basic theories of deviance: Strain, Social control, and Differential association. The survey was conducted from April to May, 1996, in 14 public high schools in Tokyo, using anonymous self-reporting. A total of 4,171 (99.45%) students responded to our questionnaire. It included central concept items in the three deviant theories, beliefs about the ill effects of drugs, sex, grades, etc. The following findings were obtained: 1) Among the subjects, 255 students (6.1%) reported drug use within the past year. Of these drug users, 73.3% used drugs soon after being "tempted" by friends. Responding to "When was it.", as a first year junior high school was the most common first experience, and the next most common was during the sixth year of elementary school. 2) Drinking and smoking appeared to be gateway drugs for adolescents in Japan as has been shown in the United States. 3) Multiple regression and logistic multiple regression analyses suggested that differential association variables were far more powerful predictors of adolescent drinking, smoking and drug use than either the control or strain variables. Results provided modest support for the Differential Association Theory as an explanation of drug use. 4) LISREL's goodness-of-fit statistic indicated a much better fit between the model and the data. (CN: 282, GFI: 0.967, AGFI: 0.941). These findings show two processes by which adolescents become involved in drug use. Strain and Social Control do not directly affect drug use. However, Social Control is important because it works indirectly, through Differential Association resulting in drug use. Second, though weaker, Differential Association appears to lead to dangerous beliefs in drug use followed by actual drug use.

Adolescent↗
PubMed1997

Retinoblastoma protein expressed in human non-Hodgkin's lymphoma cells generates resistance against radiation-induced apoptosis.

Inactivation of the retinoblastoma susceptibility (Rb) gene has been observed in various cancers. Nevertheless, in several cancer cases, including non-Hodgkin's lymphoma, previous investigations showed that the Rb gene product (pRb) was abundantly expressed with varying degree. Here we report the THS-SP1.1 cell line isolated from non-Hodgkin's lymphoma. The THS-SP1.1 cells abundantly expressed pRb and showed resistance against radiation-induced apoptosis. Culture with the antisense phosphorothioate oligonucleotide complementary to the Rb gene augmented the apoptosis of THS-SP1.1 cells after radiation, whereas the control oligonucleotides did not. These data showed that pRb abundantly expressed in the lymphoma cells inhibited radiation-induced apoptosis.

Apoptosis↗
PubMed1997

Magnetic resonance imaging of reticulo-endothelial system in patients with idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura (ITP) is characterized by accelerated platelet destruction in the reticulo-endothelial system (RES). We performed magnetic resonance imaging (MRI) to estimate the degree of activated RES. MRI was performed with a Gyroscan S-15 (1.5 tesla) in 7 healthy volunteers and 22 patients with ITP. The 22 patients included 19 who were at initial diagnosis or were nonresponders to the therapy (non-DX group), and 3 who were responders. For the non-DX group, the T1 relaxation time of the spleen was initially significantly shorter than for healthy volunteers, but normalized after responding to the therapy. The initially shorter T1 values of the spleen for ITP patients correlated with a low platelet count (P < 0.05). This condition may indicate foam cells or fatty components due to platelet destruction. There was no significant relationship between the sequestration in (111)In-scan and T1 values of the liver or spleen. However, MRI is a noninvasive method, and it may be a clinically useful tool in the evaluation of RES in patients with ITP.

Adolescent↗
PubMed1997

[Treatment of acute lymphoblastic leukemia of young adults (15-22 years of age): results of co-operative study with internal medicine and pediatrics].

Ten young adults (15-22 years of age) with acute lymphoblastic leukemia were treated with the protocol of internal medicine and pediatrics co-operative study group since 1989. All patients had complete remission within 5 weeks. Four of 6 patients of low risk group (less than 30,000/microliter of WBC count at diagnosis) and 1 of 4 patients of high risk group have continued the complete remission. Three patients relapsed in bone marrow (BM), and 2 patients in both BM and central nervous system (CNS). All patients could be treated without serious complications except for infection. We obtained the good results of treatment for the low risk group, but did not for the high risk group in this study. Little is known about acute lymphoblastic leukemia in young adults because these individuals are at the borderline age between internal medicine and pediatrics. Taken together with the psychologically distinct age of these patients, it is necessary to establish a closer relationship between internal medicine and pediatrics.

Adolescent↗
PubMed1996

Temporal changes in regional end-diastolic wall thickness early after reperfusion in acute anterior myocardial infarction: relation to myocardial viability and vascular damage.

We investigated early temporal changes in end-diastolic wall thickness (EDWT) of the infarcted myocardium in 46 patients with reperfused anterior acute myocardial infarction in relation to myocardial viability. Two-dimensional echocardiography was performed on days 1 and 2 of acute myocardial infarction, and the EDWT of the anterior segment was measured in the short-axis view. Patients were divided into three groups on the basis of day 1 to day 2 ratio of EDWT: the ratio < or = 0.85 as group A (n = 13), >0.85 but < or = 1.15 as group B (n = 23), and >1.15 as group C (n = 1 0). Left ventricular functional improvement was significantly better in group B than in groups A and C. Substantial size of "no reflow" phenomenon was observed only in groups A (n = 9, 69%) and C (n = 6, 60%). The frequency of transient ST re-elevation after reperfusion was the highest in group C (70%), and left ventricular expansion was observed at day 2 only in group A. We conclude that changes in the EDWT of the infarct segment early after reperfusion, either decreases or increases, are related to irreversibly damaged myocardium. A decrease in EDWT and concomitant ventricular expansion may be related to impaired myocardial perfusion. An increase in EDWT after reperfusion may be caused by accelerated myocardial and microvascular damage after reperfusion.

Adult↗