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Biomedical subjects

S Nakao

Publications and source records attributed to S Nakao.

At least 145 records · Page 8Linked to original sources
PubMed1997

Isolation of a T-cell clone showing HLA-DRB1*0405-restricted cytotoxicity for hematopoietic cells in a patient with aplastic anemia.

The existence of T cells capable of inhibiting in vitro hematopoiesis has been shown in aplastic anemia (AA), although whether such inhibition is mediated by a specific immune reaction involving an HLA allele remained unknown. We isolated a CD4+ Vbeta21+ T-cell clone that was most dominant among Vbeta21+ T cells in the bone marrow (BM) of an AA patient whose HLA-DRB1 alleles included 1501 and 0405. The T-cell clone named NT4.2 lysed an autologous Epstein-Barr virus-transformed lymphoblastoid cell line (LCL) and phytohemagglutinin-stimulated lymphocytes (PHA-blasts) as well as allogeneic LCLs sharing HLA-DRB1*0405. Cytotoxicity against LCL cells and PHA-blasts by NT4.2 was blocked by anti-HLA-DR monoclonal antibody (MoAb) or anti-CD3 MoAb. NT4.2 also lysed autologous BM mononuclear cells enriched with CD34+ cells that had been cultured for one week in the presence of colony-stimulating factors as well as allogeneic CD34+ cells of a normal individual carrying HLA-DRB1*0405, cultured in the same way. Moreover, NT4.2 strongly inhibited colony formation by hematopoietic progenitor cells derived from cultured CD34+ cells sharing HLA-DRB1*0405. These results indicate that the AA patient has T cells capable of killing hematopoietic cells in an HLA-DRB1*0405-restricted manner and that such cytotoxic T cells may contribute to the pathogenesis of AA.

Aged↗
PubMed1997

Pterin-6-aldehyde, an inhibitor of xanthine oxidase, has superoxide anion radical scavenging activity.

Superoxide anion radical (O2.-) scavenging activity of neopterin (NP) and its photodegraded products was studied. NP did not affect O2.- release in hypoxanthine/xanthine oxidase (HPX/XOD) reaction system, but pterin-6-aldehyde (P6A), one of photodegraded products of NP, suppressed it. The identification of P6A was successful by confirming inhibiting property of xanthine oxidase. In neutrophil/phorbol myristate acetate reaction system, NP did not affect the O2.- release but P6A suppressed it. The suppression by P6A was not associated with oxygen uptake, which indicated that P6A did not inhibit the generation of O2.- but directly scavenged it. These findings suggest that P6A has ameliorating effects on ischemic-reperfusion injury in which O2.-, which is generated both in HPX/XOD reaction and in activated neutrophil, is one of the major substances to damage the tissues.

Biopterins↗
PubMed1997

Enhanced mobilization of hematopoietic progenitor cells by mouse MIP-2 and granulocyte colony-stimulating factor in mice.

Human interleukin-8 (IL-8) induces a rapid mobilization of hematopoietic progenitor cells (HPCs) into peripheral blood in mice and primates. Because an exact homologue of human IL-8 does not exist in mice, a chemokine, macrophage inflammatory protein-2 (MIP-2), is supposed to substitute the function of IL-8 in mice. Hence, we investigated the capacity of mouse MIP-2 to induce HPC mobilization in mice. Mouse MIP-2 induced, in either untreated or splenectomized mice, a rapid HPC mobilization, as evidenced by increased numbers of colony-forming unit granulocyte-macrophage (CFU-GM) and lineage marker (Lin)-c-kit+Sca-1+ cells. Although release of elastase from activated neutrophils was proposed to be involved in IL-8-induced HPC mobilization, mouse MIP-2 induced similar levels of HPC mobilization in elastase-deficient beige mice at a similar level to normal ones. This HPC mobilization by MIP-2 was markedly enhanced by pretreatment with granulocyte-colony-stimulating factor (G-CSF). Moreover, the combination of G-CSF and MIP-2 apparently down-regulated L-selectin expression on Lin-Sca-1+ cells in peripheral blood as well as bone marrow. Thus, MIP-2 may down-modulate the interaction between HPCs and bone marrow stroma by reducing L-selectin expression on HPCs and cause rapid mobilization of HPCs into peripheral blood.

Animals↗
PubMed1997

Shell-size preference of hermit crabs depends on their growth rate

The hypothesis that hermit crabs modify their shell-size preference according to their prospective growth rate was examined in the hermit crab Pagurus middendorffiiA simple model predicts that individuals should select larger shells when (1) shell availability is limited, (2) they approach moulting and (3) they will have a large increase in size at the next moult. In experiments, selected shell size decreased with the duration of the moult, and increased with increasing growth, supporting predictions 2 and 3.

Journal Article↗
PubMed1997

Abnormal immunostaining for dystrophin in isoproterenol-induced acute myocardial injury in rats: evidence for change in dystrophin in the absence of genetic defect.

Abnormalities in the gene for Duchenne muscular dystrophy produce skeletal and myocardial changes, by impairing dystrophin production in patients with Duchenne and Becker muscular dystrophy. However, it is not known whether myocardial dystrophin may be altered in patients with other heart diseases. To investigate whether changes in myocardial dystrophin may be induced by acute myocardial injury, the immunostaining patterns of myocardial dystrophin were examined, together with those of myocardial actin, in rats with isoproterenol-induced myocardial damage. Hearts were excised at 6, 12, 24 and 48 h, and 1 and 4 weeks after the subcutaneous administration of 100 mg/kg of isoproterenol. Frozen serial sections were prepared for haematoxylin and eosin staining, and for immunostaining for dystrophin and actin. The immunostaining patterns of actin were used as an indicator of cell injury. The myocardial cells observed were classified into four types, according to staining pattern: normal for both actin and dystrophin (Type 1): normal for actin, but abnormal for dystrophin (Type 2); abnormal for actin, but normal for dystrophin (Type 3); and abnormal for both actin and dsytrophin (Type 4). The percentage of myocardial cells with abnormal staining (Types 2, 3 and 4) at 6, 12, 24 and 48 h after isoproterenol injection was 22.4, 12.6, 16.0 and 2.4%, respectively; most cells were Types 3 and 4. One week after injection or later, no Type 3 or 4 cells were detected, while the percentages of Type 2 cells were 2.7% for 1 week and 2.2% for 4 weeks, significantly higher than the corresponding value in the control group. In conclusion, changes in myocardial dystrophin may occur in isoproterenol-induced myocardial injury in rats.

Actins↗
PubMed1997

Transesophageal Doppler echocardiographic assessment of systolic and diastolic coronary blood flow velocities at baseline and during adenosine triphosphate-induced coronary vasodilation in chronic aortic regurgitation.

Few reports exist on the changes in systolic and diastolic coronary flow velocities (CFVs) at baseline and during coronary vasodilation in patients with chronic aortic regurgitation (AR). We examined the left anterior descending CFVs in 21 patients with AR (11 patients with mild AR and 10 patients with moderate to severe AR), 9 patients without AR (no AR group), and 6 patients who had undergone surgery for moderate to severe AR (postoperation group) with transesophageal Doppler echocardiography. Adenosine triphosphate (ATP) was infused into a peripheral right arm vein at four different doses (35, 70, 100, and 140 micrograms/kg/min). Coronary flow velocity response in systole and diastole was calculated as the ratio of systolic peak and mean and diastolic peak and mean CFVs during maximal ATP infusion to those at baseline. The systolic peak and mean CFVs and the diastolic peak and mean CFVs at baseline were significantly increased in the moderate to severe group compared with those in the other groups (p < 0.05, respectively). Systolic and diastolic CFVs were significantly increased during ATP infusions in the four groups. No significant differences of systolic and diastolic CFVs were observed among the four groups during maximal ATP infusion. The coronary flow velocity response calculated from the peak and mean diastolic CFVs were significantly decreased in the moderate to severe group (1.6 +/- 0.3 and 1.7 +/- 0.4) compared with those in the other three groups (3.6 +/- 0.7 and 3.2 +/- 1.1 in the no AR group, 2.6 +/- 0.6 and 2.5 +/- 0.4 in the mild group, and 2.5 +/- 0.7 and 2.4 +/- 0.6 in the postoperation group) (p < 0.05, respectively). In conclusion, the systolic and diastolic left CFVs at baseline appeared to be significantly increased in patients with moderate to severe chronic AR. However, the velocities during coronary vasodilation by ATP were equal to those in other groups, resulting in a decrease of coronary flow velocity response in systole and diastole.

Adenosine Triphosphate↗
PubMed1997

Use of the QRS scoring system in the early estimation of myocardial infarct size following reperfusion.

While the QRS scoring system has been established as a convenient tool for estimating infarct size in nonreperfused patients during the chronic stage of myocardial infarction, its applicability to reperfused patients in the acute stage has not been established. To investigate whether infarct size could be estimated by the QRS scoring system soon after reperfusion, we evaluated QRS scores obtained serially 6 hours to 1 month after reperfusion, total creatine kinase release, and left ventricular ejection fraction in 126 patients with acute myocardial infarction who underwent successful reperfusion therapy. A significant correlation was observed between the QRS score obtained after 6 hours and that obtained after 1 month (r = .89). The QRS scores obtained after 6 hours and 1 month were significantly correlated with total creatine kinase release (r = -.65 and r = -.75, respectively) and left ventricular ejection fraction (r = .62 and r = .76, respectively). Thus, the QRS scoring system can be used as a simple and economical method for estimation of infarct size soon after reperfusion.

Aged↗
PubMed1997

Induction of autocytotoxic T cells with cyclosporine and interferon-gamma for patients with non-Hodgkin's lymphoma after transplantation of peripheral blood stem cells.

BACKGROUND: Autologous graft-versus-host disease is inducible after autologous bone marrow transplantation by means of administration of cyclosporine. OBJECTIVE: This study was performed to investigate the inducibility of autologous graft-versus-host disease after transplantation of peripheral blood stem cells (PBSCs). METHODS: Two patients with non-Hodgkin's lymphoma in remission underwent PBSC transplantation followed by administration of cyclosporine and low-dose interferon-gamma. RESULTS: Although autologous graft-versus-host disease did not develop in either patient, T lymphocytes with cytotoxic activity against autologous lymphocytes appeared transiently in the early posttransplant period. Such autocytotoxic lymphocytes were not detectable in another patient who underwent PBSC transplantation who did not receive cyclosporine and interferon-gamma. When CD4+ and CD8+ cells were sorted from the peripheral blood mononuclear cells of one of the two patients and tested for cytotoxicity against autologous lymphocytes, only CD8+ cells exhibited cytotoxic activity. CONCLUSIONS: The results indicate that administration of cyclosporine and interferon-gamma after PBSC transplantation can induce autocytotoxic CD8+ T cells, even though it may not produce autologous graft-versus-host disease. It is unclear whether induction of such autocytotoxic T cells among patients with non-Hodgkin's lymphoma who undergo PBSC transplantation has any antilymphoma effect.

Adult↗
PubMed1997

Bradykinin regulates the histamine-induced Ca2+ mobilization via protein kinase C activation in human gingival fibroblasts.

We previously demonstrated that histamine and bradykinin evoke an increase in intracellular Ca2+ ([Ca2+]i) in human gingival fibroblasts by using a fluorescent Ca2+ indicator Fura-2. In this paper, we further demonstrate the regulation of the histamine-induced Ca2+ mobilization by bradykinin. In fibroblasts stimulated with bradykinin (1 microM), subsequent stimulation with histamine (100 microM) failed to mobilize Ca2+, whereas bradykinin induced an increase in [Ca2+]i in the cells pre-stimulated with histamine. The attenuation of the histamine response was dependent on the concentration of bradykinin for the first stimulation. Histamine also failed to induce the formation of inositol 1,4,5-trisphosphate in fibroblasts pretreated with bradykinin. In fibroblasts pretreated with bradykinin (1 microM) for 3 min and then washed with fresh medium, the effect of histamine on [Ca2+]i quickly returned to the control level. The activation of protein kinase C by phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (PMA) elicited a marked decrease in histamine-induced Ca2+ mobilization. When the protein kinase C activity was inhibited with H7, a protein kinase C inhibitor, or was down-regulated by pretreatment with PMA for 20 h, the inhibitory effect of PMA on the histamine response was relieved. In the fibroblasts pretreated with H7 or PMA for 20 h, histamine evoked Ca2+ mobilization even after bradykinin stimulation. These results suggest that the histamine response is regulated by bradykinin receptor activation via the activation of protein kinase C in human gingival fibroblasts.

Bradykinin↗
PubMed1997

Immune mechanism of aplastic anemia.

Immune-mediated suppression of hematopoiesis has been considered the most important mechanism in the development of idiopathic aplastic anemia (AA), mainly based on high rates of response to immunosuppressive therapy in patients with AA. However, the lack of an experimental animal model and the heterogeneity of the disease has hindered elucidation of immune mechanisms underlying AA. Recent studies on a subset of AA patients characterized by repetitive response to cyclosporine (CyA) therapy revealed a strong association of HLA-DRB1*1501 with susceptibility to such immune-mediated AA. Other studies of the T-cell clonotype in the bone marrow (BM) of the patients using the polymerase chain reaction (PCR)-single strand conformation polymorphism analysis and sequencing of T-cell receptor V beta cDNA showed dominant proliferation of a limited number of T-cells, indicating the presence of certain antigenic stimuli in the BM. More recently, we isolated a CD4+ T-cell clone that proliferated most dominantly among V beta 21+ T-cells in the BM of a CyA-dependent AA patient and was capable of killing autologous hematopoietic cells. Lysis of allogeneic hematopoietic cells by this T-cell clone required the presence of HLA-DR4 on the target cells. Further studies on such T-cell clones will help identify key molecules on hematopoietic cells that induce the development of AA.

Anemia, Aplastic↗
PubMed1997

Serum levels of cardiac troponin I and troponin T in estimating myocardial infarct size soon after reperfusion.

BACKGROUND: Cardiac troponin I (TnI) and troponin T (TnT) are highly specific myocardial markers. OBJECTIVE: To determine whether their serum levels can be used to estimate myocardial infarct size soon after reperfusion. METHODS: We measured the serum levels of TnI, TnT, and creatine kinase every 3 h, and the serum cardiac myosin light chain I (MLCI) every 24 h, in 42 patients with acute myocardial infarction in whom reperfusion therapy had successfully been performed. We calculated the severity of regional hypokinesis by analyzing the follow-up ventriculograms with the centerline method. RESULTS: The time from reperfusion to the peak level for TnI was 6.1 +/- 3.5 h, significantly shorter than those for creatine kinase (7.5 +/- 4.1 h) and MLCI (55 +/- 28 h). The time to peak level for TnT (6.8 +/- 4.0 h) differed significantly from that for MLCI but not from that for creatine kinase. There was a significant correlation between the peak levels of TnI and TnT (r = 0.86). The peak TnI and TnT levels were correlated well to the peak creatine kinase level (r = 0.67 and 0.69, respectively), total creatine kinase release (r = 0.66 and 0.66), and the peak MLCI level (r = 0.71 and 0.80). We observed excellent correlations between the peak levels of TnI and TnT, and regional hypokinesis (r = -0.84 and -0.85, respectively). These were comparable to the correlations between regional hypokinesis and the peak creatine kinase level (r = 0.75), total creatine kinase release (r = -0.72), and the peak MLCI level (r = -0.76). CONCLUSIONS: These results suggest that the peak serum levels of TnI and TnT in patients with successful reperfusion are accurate and early indices of infarct size.

Angioplasty, Balloon, Coronary↗
PubMed1997

Effects of isoflurane on in vivo release of acetylcholine in the rat cerebral cortex and striatum.

BACKGROUND: Acetylcholine (ACh) is one of the major excitatory neurotransmitters in the central nervous system, and changes in neural activity induced by anesthesia alter the release of ACh. However, the effects of isoflurane, one of the most widely used volatile anesthetics, on ACh release are not known. The present study attempts to clarify the dose-effect relationship of isoflurane on the in vivo release of ACh in rat brains. METHODS: Changes in the extracellular concentration of ACh and choline in the cerebral cortex and striatum induced by 0.5, 1.0, and 1.5 minimum alveolar concentration (MAC) of isoflurane were determined using a brain microdialysis technique. RESULTS: In the cortex, the ACh release decreased to 30.8+/-10.1 (mean+/-SEM), 10.2+/-4.1, and 8.1+/-2.9% of basal value by increasing doses of isoflurane, and in the striatum, to 73.3+/-4.4, 49.2+/-4.2, and 40.7+/-4.5%. The ACh release rapidly recovered control levels with the discontinuance of isoflurane. Choline concentration was not changed significantly by isoflurane except for a decrease to 74.8+/-4.6% in the striatum by 0.5 MAC. In both the cortex and striatum, the choline concentration decreased with the discontinuance of isoflurane to 70.3+/-13.3, and 68.2+/-5.4%, respectively. CONCLUSION: The fact that all classic anesthetics reported previously, as well as isoflurane, reduce ACh release supports the hypothesis that the suppression of cholinergic cells is, at least in part one of the mechanisms of anesthesia.

Acetylcholine↗
PubMed1997

A quantitative assessment of serum chylomicron by light scattering intensity: application to the intestinal fat absorption test.

A novel fat absorption test to clarify the malabsorption syndrome was developed using a micronephelometric technique and compared with the classic conventional technique using 131I-triolein. An integrity of time-sequential light scattered from chylomicron-related turbidity in serum was determined between 0 and 300 min after butter fat load, being expressed in terms of the light scattering intensity (LSI). A good correlation was obtained between LSI and the serum level of chylomicron-triglyceride determined by an ultracentrifugation technique (r = 0.819, P < 0.001). The maximal LSI was consistently observed at 180 min after administration of a test meal in the normal group (n = 39), whereas the malabsorption syndrome group (n = 35) was distinctly different and could be further classified according to four patterns of LSI changes. In addition, an inverse correlation was found between this fat absorption test and the 131I-triolein absorption test. It was concluded that the micronephelometric technique which does not use a radionuclide is advantageous in its simple and safe evaluation of fat malabsorption syndrome.

Adult↗
PubMed1997

Apheresis therapy for prolonged red cell aplasia after major ABO-mismatched bone marrow transplantation.

Two cases of leukemia were treated successfully with apheresis for delayed recovery of erythropoiesis due to antibody-mediated red cell aplasia after ABO-mismatched bone marrow transplantation (BMT). A 25-year-old female (ABO group O) underwent BMT from her brother (group A). Immunoadsorption using Biosynsorb A performed on day 146 after BMT followed by double filtration plasma pheresis (DFPP) reduced anti-A antibody titers from 1:32 to 1:2. Anemia improved dramatically within 2 weeks. A 49-year-old female (group O) underwent BMT from her mother (group A). She was treated with DFPP on day 131 after BMT. Anti-A antibody titers dropped from 1:16 to 1:1 and anemia improved gradually.

ABO Blood-Group System↗
PubMed1997

[Living related liver transplantation for patients with ornithine transcarbamylase deficiency].

Ornithine transcarbamylase deficiency (OTCD) is an inborn error of urea synthesis inherited as an X-linked trait, a clinical manifestation of which is a repeated episodes of hyperammonemic coma. Recently, liver transplantations have been performed in these patients in the USA and Europe. We experienced the anesthetic managements of liver transplantations in two OTCD patients, who had been suffering from several episodes of hyperammonemic decompensation despite a restricted protein diet with administration of sodium benzoate. Anesthesia was induced and maintained with a combination of fentanyl and midazolam in both cases. Their postoperative courses were good without any neurological damages, though one patient had hyperammonemic attack during the operation.

Amino Acid Metabolism, Inborn Errors↗
PubMed1997

[Sudden cardiac tamponade due to hemorrhagic myocarditis after preconditioning marrow transplantation with cyclophosphamide in a patient with aplastic anemia].

A 28-year-old male was diagnosed as aplastic anemia in 1983. He maintained on corticosterone with a large transfusion requirement for being resistant to other therapies, and combined with hemochromatosis at 20-year-old. In February 1994, he was admitted to the hospital for consideration of BMT. Echocardiogram was normal on admission. He was transplanted with bone marrow from his HLA-matched MLC negative sister following contained of TLI (7.5 Gy) and CY 50 mg/kg for four days on March 10 1994. Disturbance of consciousness appeared, an echocardiogram showed severe pericardial effusion on day 1 after BMT. He was diagnosed cardiac tamponade, pericardiocentesis was done immediately and 100 ml pericardial effusion was removed. Transiently he became alert, however, irreversible cardiac arrest occurred on day 2. Postmortem examination revealed thickened left ventricles with intramyocardial hemorrhage. It seems necessary to reduce CY, or substitute it with anti-thymocyte globulin (ATG) or TBI etc. for BMT in aplastic anemia accompanied by hemochromatosis.

Adult↗