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M Harada

Publications and source records attributed to M Harada.

At least 469 records · Page 26Linked to original sources
PubMed1997

[A nonparametric estimation of survival curve with interval censored data].

Although survival analysis dealing with right-censored data has enjoyed wide use, analysis of data with left-censored and interval censored cases is available only to a very limited number of clinical researchers because of the difficulty in understanding the concepts and performing the calculations. This paper applies Turnbull's self-consistency algorithm, which he applied in his paper on survival data with only left-censored cases, for nonparametric estimation of survival curve including both left and interval censored data. A difference in the estimates of survival rate among different modes of calculation was demonstrated using the data from the Hematopoietic Cell Transplantation Registry of the Japan Society for Hematopoietic Cell Transplantation, which illustrated the necessity of a correct analysis.

Algorithms↗
PubMed1997

Mobilization of peripheral blood progenitor cells for allogeneic transplantation.

Allogeneic transplantation of peripheral blood stem/progenitor cells (PBSC/PBPC) has been increasingly used as an alternative to allogeneic bone marrow transplantation. To mobilize and collect a sufficient number of PBSC/PBPC for engraftment after allotransplantation, granulocyte colony-stimulating factor (G-CSF) has been preferentially used. The mobilization protocol, however, has not been fully established. In this review, dose and schedule of G-CSF administration, characteristics of G-CSF-mobilized PBPC products, cytokines other than G-CSF for PBSC/PBPC mobilization, and safety of the PBSC/PBPC donors are discussed for clinical application of allogeneic PBSC/PBPC transplantation.

Antigens, CD34↗
PubMed1997

[Transfusion associated acute lung injury].

Transfusion associated acute lung injury (TRALI) is an infrequent but hazardous complication of transfusion. This syndrome is characterized by symptoms of acute respiratory distress and clinically evident noncardiogenic pulmonary edema. The occurrence of this entity is linked to the circulating leukoagglutinins. However many reports showed the incidence of this syndrome around 0.01% per unit transfusion, only three cases whose diagnosis were considered as TRALI were reported in Japan. It is because this syndrome was often misdiagnosed as other diseases, including cardiogenenic pulmonary edema or pneumonia. Some reports showed that the implicated donors were multiparous females. In an effort to prevent this syndrome, blood collection centers should limit component usage from multiparous donors to washed red cells.

Acute Disease↗
PubMed1997

Quantification of area at risk in acute myocardial infarction by tomographic imaging.

UNLABELLED: The purpose of this study was twofold: to validate, in a phantom heart model, a simple threshold technique for the quantification of defect size using 123I-15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid (BMIPP) imaging and to compare, in patients with acute myocardial infarction, defect size as shown by BMIPP imaging, with the extent of severe hypokinesis shown by left ventriculography. METHODS: In a phantom study, defect size was calculated using a standard geometric formula. In a clinical study, BMIPP imaging was performed in 20 patients 10 +/- 5 days after the onset of their infarction. Using the centerline method, the area at risk was defined by contrast ventriculography as the percentage of chords with wall motion >2 s.d. below normal. RESULTS: In the phantom study, a threshold value of 60% yielded the best agreement between true and measured defect size. In the clinical study, the defect size shown by BMIPP imaging was greater in anterior than in inferior infarcts (p < 0.001) and correlated well with the risk area revealed by contrast ventriculography (r = 0.80, p < 0.0001) CONCLUSION: The above preliminary data, admittedly from a small group of patients, suggest that tomographic BMIPP imaging provides an accurate quantification of defect size by means of a simple threshold technique and, in the subacute phase, permits determination of the amount of myocardium at risk after acute myocardial infarction.

Coronary Angiography↗
PubMed1997

Role of cardiac nonmyocytes in cyclic mechanical stretch-induced myocyte hypertrophy.

In cardiac hypertrophy or ventricular remodeling, not only the enlargement of myocytes but also interstitial or perivascular fibrosis are observed simultaneously, which suggests an interaction between cardiac myocytes and fibroblasts. In this study, we examined the mechanism of cyclic mechanical stretch-induced myocyte hypertrophy, highlighting the interaction between myocytes and cardiac nonmyocytes, mostly fibroblasts. Ventricular myocytes (MC) and cardiac nonmyocytes (NMC) were separately extracted from neonatal rat ventricles by the discontinuous Percoll gradient method and primary cultures of cardiac cells were prepared. Cyclic mechanical stretch was applied to the cultures with a Flexercell Stress Unit. In addition to cell size, we examined atrial natriuretic peptide/brain natriuretic peptide (ANP/BNP) production as the most sensitive biological markers for MC hypertrophy. Cyclic stretch did not induce hypertrophic responses in MC when they were cultured without NMC. In contrast, when MC were co-cultured with NMC, cyclic stretch induced further increase in ANP/BNP production (2.2-fold and 2.1-fold increases versus non-stretch group, after 48-h incubation). This increase in ANP/BNP production in the co-culture was significantly suppressed by CV-11974, an angiotensin II type 1 receptor antagonist. Moreover, ANP/BNP production in the co-culture was significantly suppressed by BQ-123, an endothelin A receptor antagonist, whether cyclic stretch was applied or not. This study raised the possibility that NMC mediate the hypertrophic effect of mechanical stress on MC by increasing endothelin production. It was also suggested that, in this process, angiotensin II is involved in the crosstalk between MC and NMC.

Angiotensin Receptor Antagonists↗
PubMed1996

The soluble form of Fas molecule is elevated in parkinsonian brain tissues.

Fas is an apoptosis-signaling receptor molecule on the surface of a number of cell types. The soluble form of Fas (sFas) was measured for the first time in brain (caudate nucleus, putamen and cerebral cortex), ventricular cerebrospinal fluid (VCSF), and lumbar CSF (LCSF) from control and parkinsonian patients by a highly sensitive two-site sandwich enzyme-linked immunosorbent assay (ELISA). The concentrations of sFas in nigro-striatal dopaminergic regions were significantly higher in parkinsonian patients than those in controls, whereas this product in cerebral cortex showed no significant difference between parkinsonian and control subjects. Neither VCSF nor LCSF contained the sFas molecule in the detectable amounts (< 16 pg/ml). These results suggest that the presence of sFas possibly leads to cell death/neurodegeneration in parkinsonian brain.

Aged↗
PubMed1996

Molecular cloning and expression of rat liver aminopeptidase B.

We isolated, by immunological screening of a Uni-ZAP XR cDNA library constructed from rat liver mRNAs, a cDNA clone with 2212 base pairs encoding aminopeptidase B (EC 3.4.11.6). The open reading frame encodes a 649-amino acid protein with a theoretical molecular mass of 72,545 Da and bears the consensus sequence of the zinc metalloexopeptidases, indicating that the enzyme belongs to this family, which includes aminopeptidase A, aminopeptidase N, and leukotriene-A4 hydrolase. Escherichia coli SOLR cells infected with the pBluescript phagemid excised from the Uni-ZAP XR vector containing the aminopeptidase B cDNA had a high L-arginyl-beta-naphthylamidase activity. The recombinant protein was purified to homogeneity from the recombinant E. coli extracts. The enzyme had Cl--dependent aminopeptidase activity specifically restricted to the Arg and Lys derivatives and contained 1 mol of zinc per mol of the enzyme.

Amino Acid Sequence↗
PubMed1996

Defect of thymocyte emigration in a T cell deficiency strain (CTS) of the mouse.

As bone marrow progenitors migrate to the thymus, differentiate into immunologically competent T cells, then leave the thymus and home to the peripheral lymphoid organs, each migration or homing is an essentially critical process for T cell differentiation. Homing of thymocytes into peripheral lymphoid organs has been extensively analyzed. On the contrary, little is known about the mechanism whereby mature thymocytes emigrate from the thymus to peripheral lymphoid organs. In this work, we show that the mutant T cell deficiency strain (CTS) of mouse, previously described as a peripheral T cell deficiency strain, has a novel defect of mature thymocyte emigration process. Flow-cytometric analysis demonstrated a marked decrease in T lymphocytes in peripheral lymphoid organs and an accumulation of mature thymocytes in the thymus. Histologic study revealed the high concentration of thymocytes within the giant perivascular space at thymic corticomedullary junction. These accumulating cells closely resemble normal peripheral T lymphocytes in terms of cell surface phenotype and responsiveness to mitogens or allogeneic cells. They were found to express the Mel-14 Ag, the homing receptor to lymph nodes, and had a high capability of homing to peripheral lymphoid organs when explanted thymocytes were injected i.v. The intrathymic labeling methods detected hardly any emigrating CTS thymocytes from the thymus. These results indicate that emigration defect lies in the thymus of CTS mice, and suggest that this mutation is due to abnormal releasing mechanisms occurring between the thymus and the bloodstream. Complete delineation of the precise mechanisms of this defect, however, requires further studies.

Animals↗
PubMed1996

In vitro expansion of hematopoietic progenitor cells induces functional expression of Fas antigen (CD95).

Fas antigen (Fas Ag; CD95) is a cell surface molecule that can mediate apoptosis. Bcl-2 is a cytoplasmic molecule that prolongs cellular survival by inhibiting apoptosis. To investigate the role of both molecules in hematopoiesis, we evaluated the expression of Fas Ag and Bcl-2 on CD34+ hematopoietic progenitor cells expanded in vitro. CD34+ cells isolated from bone marrow were cultured in iscove's modified Dulbecco's medium supplemented with 10% fetal calf serum, 1% bovine serum albumin, 50 ng/mL stem cell factor, 50 ng/mL interleukin-3 (IL-3), 50 ng/mL IL-6, 100 ng/mL granulocyte colony-stimulating factor, and 3 U/mL erythropoietin for 7 days. Colony-forming unit of granulocytes/macrophages (CFU-GM) and burst-forming unit of erythroids (BFU-E) were expanded 6.9-fold and 8.8-fold in number at day 5 of culture, respectively. Freshly isolated CD34+ cells did not express Fas Ag, whereas approximately half of them expressed Bcl-2. CD34+ cells cultured with hematopoietic growth factors gradually became positive for Fas Ag and rapidly lost Bcl-2 expression. Furthermore, apoptosis was induced in the cultured CD34+ population when anti-Fan antibody (IgM; 1 microgram/mL) was added, as shown by significant decrease in the number of viable cells, morphologic changes, induction of DNA fragmentation, and significant decrease in the number of clonogenic progenitor cells including CFU. GM and BFU-E. These results indicate that functional expression of Fas Ag is induced on CD34+ cells expanded in vitro in the presence of hematopoietic growth factors. Induction of Fas Ag and downregulation of Bcl-2 may be expressed as part of the differentiation program of hematopoietic cells and may be involved in the regulation of hematopoiesis.

Adult↗
PubMed1996

bcl-2 protein is increased in the brain from parkinsonian patients.

The proto-oncogene bcl-2 is involved in the regulation of cell death and may be able to block apoptosis in neurons through reduced generation of reactive oxygen species (ROS). The bcl-2 product was measured for the first time in brain (caudate nucleus, putamen and cerebral cortex), ventricular cerebrospinal fluid (VCSF), and lumber CSF (LCSF) from control and parkinsonian patients by highly sensitive two-site sandwich enzyme-linked immunosorbent assay (ELISA). The concentrations of bcl-2 in the nigrostriatal dopaminergic regions were significantly higher in parkinsonian patients than those in controls, whereas this product in cerebral cortex showed no significant difference between parkinsonian and control subjects. Neither VCSF nor LCSF from control or parkinsonian subjects contained the bcl-2 product in the detectable amount (< 5 U/ml). Since oxidative stress may be involved in neurogenerative disorders, accumulation of bcl-2 may reflect a mechanism for counterbalancing ROS-mediated damage, or it might represent the impairment of bcl-2-dependent protection from ROS in parkinsonian brain.

Aged↗
PubMed1996

Selective removal of human serum amyloid P component from rat blood by use of an immunoaffinity membrane in an extracorporeal circulation system.

We examined the suitability of an immunoaffinity membrane (IAM) bearing specific antibody as a ligand for removing human serum amyloid P component (hSAP) from blood passed through a simple extracorporeal circulation system established in rats. The specific antibody was the most effective of the various ligands tested for removing hSAP from human blood. To determine the value of the hSAP in human or rat plasma, we also developed a simple ELISA. In the rat extracorporeal circulation system, the hSAP level in the inlet blood to the IAM module decreased to 49% of the initial concentration within 60 min. In contrast, the hSAP remained at the initial concentration throughout the study in the module without the IAM. The use of this extracorporeal circulation system in this case allows preclinical evaluation of the ex vivo removal of a human plasma component in an animal model. Biocompatibility of the IAM was also examined. No change in blood cell counts or activation of the coagulation system occurred after contact with the IAM. Non-specific adsorption was not observed, since there was no statistically significant difference in IgG, complement C3, or albumin level between the pre- and post-treatment with this module. The immunological effects of the IAM were also examined using this system. Four weeks after the termination of the extracorporeal circulation, the rats examined showed no detectable antibody titer to the ligand.

Adsorption↗
PubMed1996

Interleukin (IL)-1 beta, IL-2, IL-4, IL-6 and transforming growth factor-alpha levels are elevated in ventricular cerebrospinal fluid in juvenile parkinsonism and Parkinson's disease.

Interleukin (IL)-1 beta , IL-2, IL-4, IL-6, epidermal growth factor (EGF), and transforming growth factor (TGF)-alpha were measured for the first time in ventricular cerebrospinal fluid (VCSF) from control non-parkinsonian patients, patients with juvenile parkinsonism (JP) and patients with Parkinson's disease (PD) by highly sensitive sandwich enzyme immunoassays. All cytokines were detectable in VCSF from control and parkinsonian patients, and the concentrations were much higher than those in lumbar CFS. The concentrations of IL-1 beta, IL-2, IL-4 and TGF-alpha in VCSF were higher in JP than those in controls (P < 0.05). In contrast, the concentrations of IL-2 and IL-6 in VCSF from patients with PD were higher than those from control patients (P < 0.05). These results agree with our previous reports, in which the cytokine levels were elevated in the striatal dopaminergic region of the brain from patients with PD. Since VCSF is produced in the ventricles, the alteration of cytokines in VCSF may reflect the changes of cytokines in the brain. Because cytokines play an important role as mitogens and neurotrophic factors in the brain, the increases in cytokines as a compensatory response may occur in the brain of patients of JP or PD during the progress of neurodegeneration. Increase in cytokines may contribute not only as a compensatory response but as a primary initiating trigger for the neurodegeneration.

Adolescent↗
PubMed1996

Persistence of multipotent progenitors expressing AML1/ETO transcripts in long-term remission patients with t(8;21) acute myelogenous leukemia.

The leukemia-specific AML1/ETO fusion gene has been shown to be detected by reverse transcriptase polymerase chain reaction (RT-PCR) analysis in patients with t(8;21) acute myelogenous leukemia (AML) in long-term remission. In the present study, the AML1/ETO mRNA could be detected by RT-PCR in bone marrow (BM) and/or peripheral blood (PB) samples from all 18 patients who had been maintaining complete remission for 12 to 150 months (median, 45 months) following chemotherapy or PB stem cell transplantation (PBSCT), whereas it could not be detected in four patients who had been maintaining remission for more than 30 months following allogeneic BM transplantation (BMT). We surveyed the expression of AML1/ETO mRNA in clonogenic progenitors from BM in these cases. Notably, 51 of 2,469 colonies from clonogenic progenitors (2.1%) expressed the AML1/ETO mRNA in 18 cases who were RT-PCR+ in BM and/or PB samples. Expression was observed in various clonogenic progenitors, including granulocyte-macrophage colonies, mixed colonies, erythroid colonies, and megakaryocyte colonies. Furthermore, we analyzed the clonality of these progenitors by X-chromosome inactivation patterns of the phosphoglycerate kinase (PGK) gene in four female patients. The AML1/ETO mRNA+ progenitors showed the PGK allele identical to that detected in the leukemic blasts from the time of initial diagnosis. Normal constitutive hematopoiesis was sustained by polyclonal BM reconstitution in these patients. Accordingly, these committed progenitor cells that express AML1/ETO mRNA during remission likely have arisen from common t(8;21)+ pluripotent progenitor cells with at least trilineage differentiation potential. These data strongly suggest that the origin of the clonogenic leukemic progenitors of t(8;21) AML may be multipotent hematopoietic progenitors that acquired the t(8;21) chromosomal abnormality.

Adult↗