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Biomedical subjects

R Ohno

Publications and source records attributed to R Ohno.

At least 91 records · Page 5Linked to original sources
PubMed2000

A study of orientation in a zero gravity environment by means of virtual reality simulation.

When the International Space Station (ISS) is completed and starts its operation, crew members will be stationed for three months or more in orbit aboard the ISS. As they stay longer in the space environment, "habitability" for them will become most important in the design of the interior space. One of the problems about habitability in a zero gravity (0 G) environment is disorientation. Crew members have difficulty in discriminating between "up" and "down" and more serious disorientations may cause space motion sickness. Crew members rely on visual perception to orient themselves because they can't use their sense of equilibrium in a 0 G environment. Although color and the direction of equipment of Space Shuttles or modules has been considered, no systematic study has been conducted on interior space. This study intended to clarify how people acquire visual information and recognize their orientation in a 0 G environment by an experiment in which a subject wears a head-mounted display (HMD) and enters a virtual weightless state represented by computer graphics (CG). Visual information of a room and the degree-of-freedom of motion were varied to examine the influence of the conditions on such a simple task as movement through several connected modules, and the performance and the behavior of each subject were investigated.

Humans↗
PubMed1999

Increased cytosolic Ca(2+) concentration in endothelial cells by calmodulin antagonists.

Many functions of endothelial cells are Ca(2+)/calmodulin dependent, whereas the role of calmodulin in the regulation of cytosolic Ca(2+) ([Ca(2+)](i)) remains largely unexplained. In the present study, effects of various calmodulin antagonists on [Ca(2+)](i) were investigated in cultured aortic endothelial cells loaded with the Ca(2+)-sensitive dye fura-2/AM, and were compared with those of calmodulin-dependent protein kinase II (CaM kinase II) inhibitors. The calmodulin antagonists W-7, calmidazolium and fendiline provoked dose-dependent increases in [Ca(2+)](i). However, the CaM kinase II inhibitors KN-93 and lavendustin C had no effect on [Ca(2+)](i). In the absence of extracellular Ca(2+), pretreatment of cells with bradykinin (BK) and thapsigargin completely prevented W-7-stimulated increase in [Ca(2+)](i). Alternatively, pretreatment with W-7 also completely blocked BK- and thapsigargin-stimulated increases in [Ca(2+)](i). The time course of the Ca(2+)-response in W-7 treated cells was identical to that in thapsigargin-treated cells, but not that in BK-stimulated cells, suggesting that calmodulin antagonists could share a common signaling pathway with thapsigargin to increase [Ca(2+)](i) in endothelial cells. These findings indicate that calmodulin is involved in the regulation of [Ca(2+)](i), and may play an important role in the uptake of Ca(2+) to intracellular stores.

Animals↗
PubMed1999

Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia.

Internal tandem duplication of the FLT3 gene and point mutations of the N-RAS gene are the most frequent somatic mutations causing aberrant signal-transduction in acute myeloid leukemia (AML). However, their prognostic importance is unclear. In this study, their prognostic significance was analyzed in 201 newly diagnosed patients with de novo AML except acute promyelocytic leukemia. Three patients had mutations in both genes, 43 had only the FLT3 gene mutation, 25 had only the N-RAS gene mutation, and 130 had neither. These mutations seemed to occur independently. Both mutations were related to high peripheral white blood cell counts, and the FLT3 gene mutation was infrequently observed in the French-American-British (FAB)-M2 type. AML cases with wild FLT3/mutant N-RAS had a lower complete remission (CR) rate than those with wild FLT3/wild N-RAS, whereas the presence of mutant FLT3 did not affect the CR rate. Univariate analysis showed that unfavorable prognostic factors for overall survival were age 60 years or older (P =.0002), cytogenetic data (P =.002), FAB types other than M2 (P =.002), leukocytosis over 100 +/- 10(9)/L (P =.003), and the FLT3 gene mutation (P =.004). However, the N-RAS gene mutation was only a marginal prognostic factor (P =.06). For the subjects under 60 years old, multivariate analysis showed that the FLT3 gene mutation was the strongest prognostic factor (P =.008) for overall survival. The FLT3 gene mutation, whose presence is detectable only by genomic polymerase chain reaction amplification and gel electrophoresis, might serve as an important molecular marker to predict the prognosis of patients with AML.

Acute Disease↗
PubMed1999

Multidrug resistance P-glycoprotein function of bone marrow hematopoietic cells and the reversal agent effect.

The multidrug resistance P-glycoprotein (P-gp) expression and function in hematopoietic stem/progenitor cells were studied to investigate whether the inhibition of hematopoietic cell P-gp function by multidrug resistance reversal agent increases the cytotoxicity of chemotherapy drugs on the hematopoietic cells. The expression of P-gp on the surface of CD34+ cells from healthy human marrow was examined by flow cytometry. The multidrug resistance reversal agent MS-209 was used to measure the effects of MS-209 on the Rhodamin-123 uptaking of CD34+ hematopoietic cells. By using methylcellulose semi-solid culture, normal human granulocyte-macrophage clonal formation unit (CFU-GM) was cultured. The changes in CFU-GM inhibitory rate caused by daunorubicin were determined in the presence or absence of MS-209. The results showed that the P-gp expression rate of bone marrow CD34+ cells was 13.3%. MS-209 obviously increased the Rhodamin-123 uptake of CD34+ positive cells. The mean inhibitory rate of daunorubicin for CFU-GM was 29.6%, but it was increased to 43.3% in the presence of MS-209 with the difference being significant (P < 0.05). It was concluded that hematopoietic cells expressed P-gp protein and possessed active function. MS-209 could inhibit the membrane efflux pump and increase the cytotoxicity of chemotherapy drugs to the clonal growth of hematopoetic stem cells, suggesting the side effects of these drugs on the hematopoietic system should be taken into consideration in the clinical use.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1999

Involvement of myosin light-chain kinase in chloride-sensitive Ca2+ influx in porcine aortic endothelial cells.

OBJECTIVES: This study was designed to investigate the involvement of myosin light-chain kinase (MLCK) in bradykinin- and thapsigargin-induced changes in intracellular Cl- and Ca2+ concentrations ([Cl-]i; [Ca2+]i) in porcine aortic endothelial cells. METHODS: Using the fluorescent probes N-ethoxycarbonylmethyl-6-methoxyquinolinium bromide (MQAE) and fura-2/AM, the effects of different MLCK inhibitors on bradykinin- and thapsigargin-induced changes in [Cl-]i and [Ca2+]i were assessed. RESULTS: Bradykinin and thapsigargin significantly decreased the MQAE fluorescence intensity, which indicates increased [Cl-]i; these changes were reversed by removal of extracellular chloride (Cl-o) and were significantly inhibited by Cl(-)-channel inhibitor N-phenylanthranilic acid but not by Na(+)-K(+)-Cl- cotransport inhibitor furosemide. Pretreatment with ML-9 and wortmannin, two different selective inhibitors of MLCK, significantly reduced these changes in a dose-dependent manner. The inhibitory effects of ML-9 and wortmannin on the Cl- responses were not significantly different and were not additive. Bradykinin and thapsigargin provoked large increases in [Ca2+]i, which were significantly diminished by removal of Cl-o and by pretreatment with the Cl(-)-channel inhibitor N-phenylanthranilic acid. CONCLUSIONS: The study shows that an increase in [Cl-]i may be involved in the Ca2+ influx in response to bradykinin and thapsigargin and that MLCK might be involved in the Cl- response. We suggest that MLCK might be involved in the Cl(-)-sensitive endothelial Ca2+ responses to bradykinin and thapsigargin.

Androstadienes↗
PubMed1999

Simple and reliably sensitive diagnosis and monitoring of Philadelphia chromosome-positive cells in chronic myeloid leukemia by interphase fluorescence in situ hybridization of peripheral blood cells.

Philadelphia (Ph) chromosome or the bcr/abl fusion gene is the hallmark of chronic myeloid leukemia (CML) and serves as a prognostic marker during its treatment. Its detection has been primarily done by karyotype analysis of bone marrow cells. The major limitation of the karyotypic technique is an absolute need for metaphases, often difficult to obtain in an appropriate number in patients under therapy. Fluorescence in situ hybridization (FISH) is a sensitive and quantitative method to detect the bcr/abl fusion gene in cells in both metaphase and interphase. Using M-bcr and abl probes, we performed the interphase FISH in the peripheral blood of 30 healthy volunteers and in 20 hematologically normal bone marrow samples. False-positive cells were detected in 2.7 +/- 0.7% (mean +/- standard deviation) and 2.3 +/- 0.7% among 500 cells, respectively. Then we tested 31 patients with CML at various stages of disease on 50 occasions. Although there was a good correlation between the percentage of FISH-positive cells in the peripheral blood and that in the bone marrow (r = 0.977), between the percentage of FISH-positive cells in the peripheral blood and that of Ph chromosome in the bone marrow (r = 0.841), and between the percentage of FISH-positive cells and that of Ph chromosome in the bone marrow (r = 0.933), the limits of agreement in each group were not small, and thus the peripheral blood FISH test can not be interpreted as the same method with conventional karyotyping. Additionally, we could easily rule out CML in 15 individuals with leukocytosis without performing bone marrow aspiration. The present study indicates that FISH analysis in the peripheral blood is a simple and reliably sensitive test for the detection and quantitative monitoring of the M-bcr/abl fusion gene in CML in routine clinical practice, although this can not entirely replace karyotype analysis of bone marrow cells.

Adult↗
PubMed1999

Extensive cytogenetic studies of clonality following interferon-alpha therapy in chronic myeloid leukemia occurring in monosomic cells in a patient with Turner syndrome mosaic.

In a 27-year-old female with Turner syndrome mosaic, Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) occurred only in the monosomic cells (45, Xc). Extensive cytogenetic studies, including triple-color fluorescence in situ hybridization (FISH), revealed that Ph-positive monosomic cells (45, Xc), Ph-negative monosomic cells and normal diploid cells (46, XX) were present in her bone marrow at diagnosis. After successful interferon therapy, the non-leukemia cells expanded and reconstituted normal hematopoiesis resulting in complete cytogenetic response, following the selective suppression of the monosomic Ph-positive leukemia clone. The ratio of Xc to XX cells in bone marrow cells was significantly increased to that in skin fibroblasts. Moreover, the ratio of Ph-positive cells to Ph-negative cells was found to be significantly different between karyotyping and FISH. Studies of this quite unique case not only confirmed the clonality of CML, effectiveness of interferon-alpha and X chromosome imbalance among different tissues, but also demonstrated a discrepant increase of the BCR/ABL-positive clone in CML. The latter supports the hypothesis that reduced programmed cell death may be the primary mechanism responsible for the expansion of the leukemia clone in CML. Our study verifies the importance of extensive analysis of a neoplastic disease in patients with a constitutional chromosomal abnormality.

Adult↗
PubMed1999

Molecular evolution of acute myeloid leukaemia in relapse: unstable N-ras and FLT3 genes compared with p53 gene.

Relapse is a major cause of treatment failure in acute myeloid leukaemia (AML), and is usually accompanied by resistance to chemotherapy. To study whether relapse is accompanied by genetic alterations, we compared N-ras, p53 and FLT3 gene mutations in paired samples obtained at initial diagnosis and first relapse. 28 patients with relapsed AML were studied, and their duration of complete remission ranged from 133 to 989 d (mean 318 d). Karyotype changes were observed at relapse in 11 patients. Point mutations of the N-ras gene were positive at both stages (+/+) in three patients, positive at initial diagnosis and negative at relapse (+/-) in three patients, and negative at initial diagnosis and positive at relapse (-/+) in two patients. Internal tandem duplications of the FLT3 gene (FLT3/ITD) were +/+ in five patients, +/- in one patient, and -/+ in six patients. The p53 gene mutations were +/+ in two patients, +/- in one patient, and -/- in 25 patients. FLT3/ITD and mutant p53 at relapse were associated with short survival after relapse. These results indicate that relapse is frequently accompanied by molecular alterations that include the loss and/or acquisition of mutations. Thus relapse can be understood as clonal shift or collateral succession rather than clonal progression.

Acute Disease↗
PubMed1999

Serum thrombopoietin levels in patients with chronic hepatitis and liver cirrhosis.

OBJECTIVE: Thrombocytopenia is a common manifestation of cirrhosis. The aim of this study was to examine the relationship between serum thrombopoietin concentrations, circulating platelet levels, and the stage of hepatic fibrosis in patients with chronic viral hepatitis. METHODS: The study included 48 patients with chronic viral hepatitis (14 with stage 1 fibrosis; five with stage 2 fibrosis; three with stage 3 fibrosis; 26 with cirrhosis) and 30 healthy volunteers. Serum thrombopoietin levels were measured using an enzyme-linked immunosorbent assay. Spleen size, platelet counts, and prothrombin time were measured. RESULTS: Thrombopoietin levels of patients with fibrosis stage 1 (2.50 +/- 1.60 fmol/ml) or stage 2 (1.89 +/- 0.65) were significantly higher than those in patients with cirrhosis (1.21 +/- 0.55) or healthy volunteers (1.26 +/- 0.74). Mean platelet counts of patients with cirrhosis (8.0 +/- 4.6 x 10(4)/microl) were significantly lower than those with fibrosis stage 1 (18.6 +/- 3.9) or stage 2 (16.0 +/- 5.8), or healthy volunteers (24.5 +/- 7.3). Patients with cirrhosis had larger spleens (30.9 +/- 18.4 cm2) than those with fibrosis stage 1 (18.2 +/- 6.4). Platelet counts showed a significant inverse relationship to spleen size (p = -0.51, p < 0.0005) and a significant positive relationship with thrombopoietin levels (p = 0.34, p < 0.02). Thrombopoietin levels were significantly correlated to prothrombin time (p = 0.45, p < 0.005). CONCLUSIONS: Serum thrombopoietin levels are elevated in patients with an early stage of chronic viral hepatitis. As the disease progresses from mild fibrosis to cirrhosis, decreased production of thrombopoietin may contribute to the further development of thrombocytopenia in cirrhosis.

Adult↗
PubMed1999

Growth hormone advances spermatogenesis in premature rats treated with gonadotropin-releasing hormone agonist.

To clarify the effect of GH on the development of seminiferous tubules in premature male rats, we investigated whether GH accelerates spermatogenesis under the condition of gonadotropin deprivation. Male Wistar rats aged three weeks were divided into three groups and subjected to administration of either long-acting GnRH agonist (GnRHa) or a combination of GnRHa and rat GH, with normal saline solution as control. After the 4-week treatment, sperm density and motility in the right epididymis were measured and seminiferous tubules of right testes were histologically examined. Sperm density and motility were significantly higher in GnRHa+GH-treated rats than in GnRHa-treated rats. In histological examination, the numbers of germ cells in various stages were increased in GnRHa+GH-treated rats compared with GnRHa-treated rats, with the number of mature spermatid being noticeably higher in GnRHa+GH-treated rats. These results suggest that administration of GH decreases loss of germ cells at various stages of spermatogenesis under the condition of gonadotropin withdrawal.

Analysis of Variance↗
PubMed1999

[Phase I clinical study of SH L573 (fludarabine phosphate) in patients with chronic lymphocytic leukemia and adult T-cell leukemia/lymphoma].

We have conducted a phase I clinical study of fludarabine phosphate, a new purine nucleoside derivative, in patients with chronic lymphocytic leukemia and adult T-cell leukemia/lymphoma. The patients were given intravenous administration at a dose of 15 mg/m2/day followed by 20 mg/m2/day and 25 mg/m2/day, each dose given consecutively for 5 days. The dose limiting factors were thrombocytopenia and neutropenia. The thrombocyte count and neutrocyte count dropped to their lowest value in week 1 to 2 after administration, but the changes were reversible, and these counts recovered in most patients. The maximum tolerated dose of the study drug was 25 mg/m2/day, and it was decided to administer 20 mg/m2/day as the recommended dose for the subsequent phase II clinical study.

Adult↗
PubMed1999

[Clinical and bacteriological evaluation of ceftriaxone (CTRX) dosed once daily in children with community-acquired pneumonia].

Clinical and bacteriological evaluation was performed as follows on ceftriaxone (CTRX) at a dose of 50 mg/kg once daily to pediatric patients with community-acquired pneumonia. Of 48 subject patients, CTRX was markedly effective in 36 (75.0%), effective in 9 (18.7%), slightly effective in 2 (4.2%), and failure in 1 (2.1%), indicating the overall effective rate of 93.7%. In 47 (97.9%) patients with the exception of 1, it was observed during the period of administration that fever was resolved and clinical symptoms as well as radiographically abnormal shadows were found relieved or improved. Patients infected by an isolated strain accounted for 34 (70.8%), while those by multiple strains 14 (29.2%), indicating that either Streptococcus pneumoniae or Haemophilus influenzae, or both were detected in almost all patients (45 cases). Of the 48 patients, bacteriological effect was eliminated in 44 (91.7%), and replacement of the bacteria in the remaining 4 (8.3%). MIC90 of CTRX against detected bacteria was 0.2 microgram/ml with H. influenzae, < or = 0.025 microgram/ml with PSSP, 0.1 microgram/ml with PISP, and 0.39 microgram/ml with PRSP. Blood concentration of CTRX at 50 mg/kg upon completion of 1-hour drip intravenous infusion was 89.7 +/- 25.2 micrograms/ml, and 6.6 +/- 0.9 micrograms/ml at 24 hours after the completion, indicating that the concentrations had been well above the levels of MIC90 throughout the 24 hours. Abnormal symptoms, which were most likely adverse drug reactions, were not observed in any patients, and no abnormal changes were noted in patients, whose clinical lab values were taken before or after the administration. Situations may differ by region in Japan, however, infants under 3 are generally exempted from medical payment regardless of inpatients or outpatients. When hospitalized, psychological burden upon pediatric patients without guardians attended must be enormous. If they are over 3, there is a difference in medical costs between inpatients and outpatients, with greater economic burden on inpatients. Thus, it was considered worth attempting the outpatient treatment as one of new therapies for community-acquired pneumonia, though the outpatient treatment should not be encouraged without due consideration. Based on these results, CTRX dosed once daily to pediatric patients with community-acquired pneumonia is clinically and bacteriologically superior in usefulness. Further review may be necessary, however, it is considered that outpatient treatment can also serve as one of the options, if safety of once-a-day administration of CTRX can be established.

Ceftriaxone↗
PubMed1999

[Clinical effect of idarubicin on malignant lymphoma].

The anti-tumor efficacy and safety of idarubicin (IDR) were investigated among patients in whom the standard therapy for malignant lymphoma had failed or who had suffered a recurrence. IDR was administered at a dose of 12 mg/m2 or 15 mg/m2 by a single i.v. bolus, and this dosage regimen was repeated every 3 weeks. Among total of 21 evaluable patients, there were 3 CRs and 1 PR, for an overall response rate of 19.0% (4/21). All patients who attained CR were cases which had recurred after receiving combination chemotherapy including doxorubicin. Adverse reactions were bone marrow suppression, including leucopenia (90.5%), neutropenia (95.2%), and thrombocytopenia (47.6%); gastrointestinal symptoms such as nausea/vomiting (42.9%) and stomatitis (9.5%); alopecia (23.8%) and fever (19.0%). These results indicate that IDR is effective against refractory malignant lymphoma.

Adult↗