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Biomedical subjects

T Matsui

Publications and source records attributed to T Matsui.

At least 235 records · Page 13Linked to original sources

[M-CSF levels during peripheral blood stem cell harvest and autologous stem cell transplantation].

Plasma macrophage colony-stimulating factor(M-CSF) levels were determined during peripheral blood stem cell harvest and autologous stem cell transplantation(PBSCT). Plasma of 10 patients were analyzed by using ELISA system. The average peak values during PBSCT were quite higher than those during harvest(20,092 vs 1,681 pg/ml). Peak values were observed mainly around leukocyte nadir(Phase II) during harvest. On the other hand, they were detected just after pretreatment(Phase I) during PBSCT courses. Moreover, samples showing extremely high M-CSF values(Phase I) were associated with increase in serum LDH levels. These data suggest that plasma M-CSF in Phase I are mainly derived from chemotherapy-induced cellular damage during PBSCT courses, and there might be different mechanisms to raise M-CSF around the nadir of leukocytes. It is necessary to elucidate the biological meanings of M-CSF.

Adult↗

[Retrospective study of acute myelogenous leukemia in 83 elderly patients: clinical and biological characteristics].

In order to characterize clinical and biological characteristics of elderly patients with acute myelogenous leukemia (AML), we retrospectively analysed 83 elderly patients aged 60 years or more and, as a control, 114 younger patients aged 15 to 59 years who were admitted to our hospital between August 1984 and January 1998. There was a significantly higher incidence of preceding myelodysplastic syndromes in the elderly patients. They also had a significantly higher incidence of unfavorable cytogenetic abnormalities (loss or partial deletion of chromosome 5 or 7) and a significantly lower incidence of favorable cytogenetic abnormalities, such as t(15:17), t(8:21), or inv(16). With regard to FAB subtypes in de novo AML, the incidence of M3 subtype was significantly lower in the elderly group. Myeloperoxidase positivity of AML cells in the elderly group was lower than that in the younger group. Laboratory data at presentation disclosed a lower peripheral leukemic cell count, a higher fibrinogen level, a lower serum protein level, and a higher serum creatinine level in the elderly group. They also had poorer performance status and more frequent concomitant diseases at presentation, including liver diseases, heart diseases, or documented infections. It was concluded that elderly AML patients 60 years or older had a higher incidence of poor prognostic factors compared to younger patients.

Adolescent↗

[Retrospective study of acute myelogenous leukemia in elderly patients: treatment and outcome of 83 consecutive patients].

We retrospectively analyzed treatments and outcomes for 83 acute myelogenous leukemia (AML) patients aged 60 years or more (median age 71) admitted to our hospital between August 1984 and January 1998. Complete remission was achieved in 36% of 78 patients who received anti-leukemic therapy, and median overall survival was 227 days. In addition to abnormal karyotypes involving chromosome 5 or 7, administration of less than 120 mg/m2/course of daunorubicin (DNR) during the initial treatment phase was an unfavorable prognostic factor for both CR and survival. Only 41% of all patients received 120 mg/m2/course of DNR or more, and had a significantly higher CR rate (56%) and longer survival, with a median of 389 days. It was suggested that intensive chemotherapy was effective for selected elderly AML patients who were relatively younger and had good performance status, although the number of such patients was limited in our study.

Age Factors↗

[A comparative study on the clinical utility of cefozopran and cefpirome against complicated urinary tract infections].

Aiming at evaluating the utility of cefozopran (CZOP) against complicated urinary tract infections with the velocity of eradication of causal bacteria in early treatment and clinical efficacy by new criteria of UTIs, a comparative study was conducted using cefpirome (CPR) as the control drug. CZOP and CPR were administered by intravenous drip infusion at a dose of 1 g twice daily. The duration of treatment was for 5 days. The study method involved randomized assignment of the subjects to either group CZOP or group CPR. The results were as follows: 1. Of a total of 80 cases treated, 65 (CZOP group--32 cases, CPR group--33 cases) were evaluated for efficacy. 2. The overall clinical efficacy evaluation according to the criteria proposed by Japanese UTI Committee rated the CZOP group as 90.6% (29/32), and the CPR group as 90.9% (30/33), with no significant difference between the 2 groups. Clinical efficacy evaluated by attending physicians rated the CZOP group as 93.8% (30/32) and the CPR group as 90.9% (30/33). There was no significant difference between the 2 groups. 3. The efficacy rates to pyuria on day 2 were 26.7% and 0% for the CZOP group and the CPR group, respectively, indicating a higher efficacy rate for the former (p < 0.05). Those on after treatment were 59.4% and 54.5% for the CZOP group and the CPR group, respectively, with no significant difference between the 2 groups. 4. Regarding the bacteriological effect, the eradication rates of both groups were over 90% on day 1 and after treatment. There was no significant difference between the 2 groups. 5. Side effects occurred in 1 case (2.6%) out of 39 in the CZOP group and in 1 case (2.4%) out of 41 in the CPR group. Laboratory test value fluctuation was noted in 8 (20.5%) of 39 cases in the CZOP group and 11 (26.8%) of 41 cases in the CPR group. There was no significant difference between the 2 groups. The results indicate that CZOP achieves an early efficacy to pyuria, and is as useful as CPR against complicated urinary tract infections.

Adult↗

[First documentation of transfusion-associated babesiosis in Japan].

A 40-year-old man received blood transfusion in December 1998 because of gastric bleeding from a peptic ulcer. One month later, he developed febrile hemolytic anemia. Administration of high doses of glucocorticoid significantly reduced the hemolysis, but did not cure the disease. To investigate the cause of the hemolysis, the patient was transferred to our hospital in May 1999. Giemsa-stained peripheral blood smears showed Babesia parasites in the red blood cells (RBC), and PCR analysis confirmed the presence of Babesia microti DNA. The parasitemia disappeared hematologically after 2 weeks of quinine and clindamycin therapy. However, parasite DNA was still detectable in the RBC. Although treatment with oral atovaquone was given for 2 weeks, parasitemia and febrile hemolysis recurred within a month after the last treatment. Fortunately, complete remission was obtained after a second 12-week course of therapy with quinine and clindamycin. PCR analysis revealed asymptomatic Babesia infection in one of eight samples from the original blood donor. The initial steroid therapy given to the patient without an accurate diagnosis seemed to have delayed augmentation of the specific antibodies (IgG) against Babesia microti, thus prolonging the parasitemia after the initial acute stage of babesiosis.

Adult↗

Instigation and control of treadmill locomotion in high decerebrate cats by stimulation of the hook bundle of Russell in the cerebellum.

In high decerebrate cats, pulse train microstimulation of a restricted region of the midline cerebellar white matter produced a generalized increase in postural muscle tone in the neck, trunk, and limb extensor muscles, and air-stepping of all four legs on a stationary surface. On the moving belt of a treadmill, such stimulation produced well coordinated, fore- and hindlimb locomotion as evoked by stimulating the mesencephalic locomotor region (MLR). Microinjection of a neural tracer into the cerebellar locomotion-inducing site resulted in a bilateral retrograde labeling of cells limited to the fastigial nuclei simultaneously with anterograde labeling of fibers projecting bilaterally to the medial pontomedullary reticular formation (mPMRF) the vestibular complex and upper cervical segments. These results have led to our proposition that the effective cerebellar locomotor region (CLR) corresponds to the midline region of the hook bundle of Russell. Passing through this structure are crossed fastigioreticular and fastigiovestibular fibers, together with fastigiospinal fibers. Subsequently, we showed that CLR stimulation resulted in simultaneous short-latency synaptic activation of long-descending reticulospinal and vestibulospinal cells with high synaptic security. Clearly, the fastigial nucleus possesses potential capability to recruit and regulate posture- and locomotor-related subprograms which are distributed within the brainstem and spinal cord by the in-parallel activation of fastigiospinal, fastigioreticular, and fastigiovestibular pathways.

Animals↗

Restoration of contractile function in isolated cardiomyocytes from failing human hearts by gene transfer of SERCA2a.

BACKGROUND: Failing human myocardium is characterized by abnormal relaxation, a deficient sarcoplasmic reticulum (SR) Ca(2+) uptake, and a negative frequency response, which have all been related to a deficiency in the SR Ca(2+) ATPase (SERCA2a) pump. METHODS AND RESULTS: To test the hypothesis that an increase in SERCA2a could improve contractile function in cardiomyocytes, we overexpressed SERCA2a in human ventricular myocytes from 10 patients with end-stage heart failure and examined intracellular Ca(2+) handling and contractile function. Overexpression of SERCA2a resulted in an increase in both protein expression and pump activity and induced a faster contraction velocity (26.7+/-6.7% versus 16.6+/-2.7% shortening per second, P<0.005) and enhanced relaxation velocity (32. 0+/-10.1% versus 15.1+/-2.4%, P<0.005). Diastolic Ca(2+) was decreased in failing cardiomyocytes overexpressing SERCA2a (270+/-26 versus 347+/-30 nmol/L, P<0.005), whereas systolic Ca(2+) was increased (601+/-38 versus 508+/-25 nmol/L, P<0.05). In addition, the frequency response was normalized in cardiomyocytes overexpressing SERCA2a. CONCLUSIONS: These results support the premise that gene-based therapies and targeting of specific pathways in human heart failure may offer a new modality for the treatment of this disease.

Calcium↗

Adenoviral gene transfer of activated phosphatidylinositol 3'-kinase and Akt inhibits apoptosis of hypoxic cardiomyocytes in vitro.

BACKGROUND: The intracellular signaling pathways that control cardiomyocyte apoptosis have not been fully defined. Because insulin-like growth factor-1 (IGF-1) prevents cardiomyocyte apoptosis, we examined the role of its downstream signaling molecules in an in vitro model of hypoxia-induced cardiomyocyte apoptosis. METHODS AND RESULTS: Treatment of rat neonatal cardiomyocytes with IGF-1 increased activity of both phosphatidylinositol 3' (PI 3)-kinase and its downstream target, Akt (also known as protein kinase B or PKB). Cardiomyocytes were subjected to hypoxia for 24 hours, and apoptosis was assessed by DNA laddering, TUNEL staining, and ELISA for histone-associated DNA fragments. IGF-1 treatment (100 nmol/L) reduced cardiomyocyte apoptosis, and this effect was inhibited by simultaneous treatment with a PI 3-kinase inhibitor. Cardiomyocytes were infected with either a control adenovirus (Ad.EGFP) or adenoviruses carrying constitutively active forms of PI 3-kinase (Ad.BD110) or Akt (Ad. myr-Akt-HA). Ad.BD110 significantly inhibited apoptosis of hypoxic cardiomyocytes compared with Ad.EGFP (61.0+/-4.6% less DNA fragmentation than in Ad.EGFP-infected cells, P<0.0001). Ad. myr-Akt-HA even more dramatically inhibited apoptosis of hypoxic cardiomyocytes (90.9+/-1.4% less DNA fragmentation than in controls, P<0.0001). CONCLUSIONS: IGF-1 activates PI 3-kinase and Akt in cardiomyocytes. Activated PI 3-kinase and Akt are each sufficient to protect hypoxic cardiomyocytes against apoptosis in vitro. Adenoviral gene transfer provides a useful tool for investigating the role of these signaling pathways in cardiomyocyte apoptosis.

Adenoviridae↗

Free-living nematodes Caenorhabditis elegans possess in their mitochondria an additional rhodoquinone, an essential component of the eukaryotic fumarate reductase system.

The respiratory chain of Caenorhabditis elegans was characterized in mitochondria isolated from aerobically grown nematodes. Nematode mitochondria contain ubiquinone-9 as a major component and rhodoquinone-9 as a minor component. The ratio of ubiquinone-9/rhodoquinone-9 is higher in C. elegans mitochondria than in mitochondria from second-stage larvae of Ascaris suum, the free-living stage of porcine gut-dwelling nematode. The individual oxidoreductase activities comprising succinate oxidase and the amount of substrate-reducible cytochromes are comparable to those of mitochondria from second-stage larvae of A. suum. The specific activity of fumarate reductase is lower in C. elegans mitochondria than in mitochondria from second-stage larvae of A. suum, but still higher than in mammalian mitochondria. These results indicate that the free-living nematode C. elegans is capable of synthesizing rhodoquinone, as distinguished from aerobic mammalian species, although its mitochondria appear more aerobic than A. suum larval mitochondria.

Aerobiosis↗

Segment-specific branching patterns of single vestibulospinal tract axons arising from the lateral vestibular nucleus in the cat: A PHA-L tracing study.

The purpose of the present study was to detail the spinal cord (SC) trajectories and arborization patterns of vestibulospinal axons descending from the lateral vestibular nucleus (LVN). An anterograde neural tracer, Phaseolus vulgaris-leucoagglutinin (PHA-L), was focally injected into the right-side LVN in 8 cats. Their subsequent survival times varied from 4 days to 12 weeks. The labeled axons were found mainly in the brainstem after 4-5 days and in successively more caudal spinal segments after longer survival times: i.e., in C1-T2 after 2-3 weeks, in C3-T11 after 6-7 weeks, and in T7-S1 after 10-12 weeks. The trajectories of 28 single, thick (diameter >/=2.4 microm) lateral vestibulospinal tract (LVST) axons were traced from serial transverse sections of the SC from C1-8 (n = 10), T1-9 (n = 11), and T11-L7 (n = 7). In the cervical segments, the LVST axons gave off collateral fibers, which terminated mainly in Rexed's laminae VII-VIII. The terminal-field patterns of these collaterals differed from one stem axon to another. In the thoracic segments, the terminal-field patterns from a given LVST axon were similar at each segmental level, i.e., a few main branches with or without short side branches. At the L3-5 midlumbar level, the collaterals usually arborized more extensively, such that their terminal fields occupied a much greater region of laminae VII-VIII. In contrast, at the L6-7 lower lumbar level, collaterals arising from thin axons (diameter <1.0 microm) tended to innervate, with even more extensive arborization, the medial part of the lamina VIII. These results revealed common and segment-specific collateral distribution patterns of LVST axons along the full extent of the spinal neuraxis.

Animals↗

Activation of ERM proteins in vivo by Rho involves phosphatidyl-inositol 4-phosphate 5-kinase and not ROCK kinases.

When activated, ERM (ezrin, radixin, moesin) proteins are recruited to the plasma membrane, with concomitant carboxy-terminal threonine phosphorylation, where they crosslink actin filaments to the plasma membrane to form microvilli (reviewed in [1] [2] [3] [4] [5]). Here, we report that, when NIH3T3 or HeLa cells were transfected with a constitutively active mutant of the small GTPase RhoA (V14RhoA), microvilli were induced and the level of carboxy-terminal threonine-phosphorylated ERM proteins (CPERM) [6] [7] increased approximately 30-fold. This increase was not observed following transfection of constitutively active forms of two other Rho-family GTPases, Rac1 and Cdc42, or of a direct effector of Rho, Rho-kinase (also known as ROKalpha or ROCK-II) [8] [9] [10]. The V14RhoA-induced phosphorylation of ERM proteins was not suppressed by Y-27632, a specific inhibitor of ROCK kinases including Rho-kinase [11]. Overexpression of another direct effector of Rho, phosphatidylinositol 4-phosphate 5-kinase (PI4P5K) type Ialpha [12] [13] [14], but not a kinase-inactive mutant [15], increased approximately sixfold the level of CPERM, and induced microvilli. Together with the previous finding that the PI4P5K product phosphatidylinositol 4,5-bisphosphate (PIP(2)) activates ERM proteins in vitro [16], our data suggest that PIP(2), and not ROCK kinases, is involved in the RhoA-dependent activation of ERM proteins in vivo. The active state of ERM proteins is maintained through threonine phosphorylation by as yet undetermined kinases, leading to microvillus formation.

3T3 Cells↗

ABO blood group antigens on human plasma von Willebrand factor after ABO-mismatched bone marrow transplantation.

von Willebrand factor (vWF) is synthesized exclusively by endothelial cells and megakaryocytes, and stored in the intracellular granules or constitutively secreted into plasma. ABO blood group antigens are covalently associated with asparagine-linked sugar chains of plasma vWF. The effect of ABO-mismatched bone marrow transplantation (BMT) or blood stem cell transplantation (BSCT) on the expression of ABO blood group antigens on the vWF was examined to obtain information on the origin of these antigens. In ABO-mismatched (HLA-matched) groups, 8 cases of BMT and 4 cases of BSCT were examined. In all cases, the ABO blood groups on red blood cells were gradually converted to the donor's type within 80 to 90 days after the transplantation. The blood group antigens on the vWF were consistent with the recipient's blood group for the period monitored by enzyme-linked immunosorbent assay (ELISA). When vWF was isolated from normal platelets and examined for the blood group antigens using ELISA or immunoblotting, it showed few antigens. However, vWF extracted from veins expressed blood group antigens. These findings indicate that platelet (megakaryocyte)-derived vWF does not contain blood group antigens and that these antigens may be specifically associated with vWF synthesized in endothelial cells and secreted into plasma. Furthermore, it is possible that the persistence of the recipient's blood group antigens on plasma glycoproteins such as vWF, independent of the donor-derived erythrocytes, after ABO-mismatched stem cell transplantation, may influence the immunological system in the production of anti-blood group antibodies resulting in the establishment of immunological tolerance in the recipient plasma.

ABO Blood-Group System↗

Cerebrospinal fluid levels of amyloid beta-peptide1-42, but not tau have positive correlation with brain glucose metabolism in humans.

To address the question of whether assay for cerebrospinal fluid (CSF) levels of amyloid beta-peptide 1-42 (A(beta)1-42) and tau allow us to monitor the neurodegenerative processes that lead to a progressive and massive death of neurons in Alzheimer's disease (AD) and non-AD patients, cerebral glucose metabolism using 2-[18F] fluoro-2-deoxy-glucose was quantified by positron emission tomography in fifteen AD patients and nine non-AD patients with defined levels of CSF-A(beta)1-42 and CSF-tau. The CSF-A(beta)1-42 levels, but not the CSF-tau levels, in both AD and non-AD patients consistently and significantly correlated with global and, in particular, temporal lobe glucose metabolism. Results from our study suggest that the CSF-A(beta)1-42 levels may reflect residual brain function and help monitoring progression of dementing disorders.

Aged↗

Induction of catecholamine synthesis in human neuroblastoma cells by replication inhibitors and sodium butyrate.

Various inhibitors of DNA synthesis induced neurite extension in human neuroblastoma cells. In order to clarify morphology-function relationship in differentiation of neuroblastoma cells, the effect of the replication inhibitors on inducibility of catecholamine synthesis was examined. The reagents alone did not affect production of dopamine and noradrenaline, but joint administration of each inhibitor and sodium butyrate considerably promoted the catecholamine synthesis, without additional change in neurite profile. Although inactive in neurite extension, sodium butyrate was moderately active in catecholamine production. The promoting effect of thymidine (or hydroxyurea) and sodium butyrate was repealed by alpha-amanitin, actinomycin D or cycloheximide.

Amanitins↗

Genomic analysis of a murine cell-surface sialomucin, MGC-24/CD164.

MGC-24 is a sialomucin originally found in human gastric carcinoma cells, and in human hematopoietic progenitor cells. In the human, soluble and transmembrane forms of MGC-24 are present, and the transmembrane form has been implicated in adhesion of hematopoietic progenitor cells to marrow stroma cells. In the mouse, we found that only the transmembrane form was expressed in many organs. Northern blotting and in situ hybridization analysis showed that MGC-24 mRNA was widely expressed in various adult and embryonic tissues. The mouse MGC-24 gene, which we isolated, spanned about 12 kb and was comprised of six exons. The transmembrane domain and the cytoplasmic domain were encoded by a single exon; the finding agrees with the absence of an alternatively spliced product of mouse MGC-24. The minimal promoter of mouse MGC-24 was embedded in GC-rich sequences, in which two Sp1 binding motifs were found, but it lacked TATA and CAAT boxes. That the promoter resembles that of house-keeping genes is consistent with the broad expression of mouse MGC-24 mRNA.

Animals↗