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Biomedical subjects

K Sakurada

Publications and source records attributed to K Sakurada.

At least 55 records · Page 3Linked to original sources
PubMed1997

[A case of infantile anaplastic astrocytoma treated with surgery and chemotherapy].

A 5-month-old girl presented with enlargement of the head circumference. Neurological examination revealed right hemiparesis and bulging of the anterior fontanel. T1-weighted magnetic resonance imaging with gadolinium DTPA showed a well-enhanced, huge tumor extending from the left frontal lobe to the parietal lobe. Cerebral angiography showed the main feeding arteries were the central sulcus artery and the posterior parietal artery. The tumor was totally removed using a sulcotomy and temporary clipping of these feeding arteries to control bleeding. The histological diagnosis was anaplastic astrocytoma. Postoperative radiation therapy was avoided so as to prevent the side effect of radiation therapy such as mental retardation and growth impairment. Chemotherapy using VP-16 and CDDP was given every six months as adjunct therapy. No tumor recurrence has been recognized for over a period of 2 years and 5 months after surgery and growth and mental development have been satisfactory. Total removal using great care not to damage neurological function followed by postoperative chemotherapy is the treatment of preference to obtain good prognosis and quality of survival in infant with such tumors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Reversal effect of itraconazole on adriamycin and etoposide resistance in human leukemia cells.

Itraconazole is a triazole antifungal agent that inhibits cell membrane serol biosynthesis. Currently, itraconazole is a potent candidate for in vivo use to revert multidrug resistance in acute leukemias, with the added benefit of its antifungal effect. As previously reported, itraconazole, as well as verapamil, reversed adriamycin-resistant K562 cells (K562/ADR) and HL60 cells (HL60/ADR) in dosages compatible to the plasma levels achieved by the therapeutic dosages used for the treatment of fungal infections. By RT-PCR analysis of mdr1, mdr3, and mrp mRNA, these adriamycin-resistant cells showed a higher expression of the transcript of these genes than those of the parent cells. By FACS analysis, both the adriamycin-resistant cells showed a higher expression of P-glycoprotein on their cell surfaces. These results suggested the involvement of itraconazole in the mdr gene and/or mrp gene product-associated resistance. Furthermore, itraconazole partially reversed etoposide resistance in both the K562 and K562/ADR cells. The present study suggests that itraconazole may reverse multidrug resistance, at least in part, via a classical MDR-associated mechanism.

Antibiotics, Antineoplastic↗
PubMed1996

Myosin light chain diphosphorylation is enhanced by growth promotion of cultured smooth muscle cells.

The characteristics of actively growing smooth muscle cells (a variant, SM-3) were compared with those of growth-arrested cells with regard to response of myosin light chain (MLC) phosphorylation. Augmented MLC phosphorylation, in particular diphosphorylation, was observed in actively growing cells when stimulated with 30 microM prostaglandin F2alpha (PGF2alpha). The maximum level of diphosphorylation in growing cells was significantly higher than that in growth-arrested cells. The MLC diphosphorylation was sensitive to protein kinase C down-regulation by phorbol dibutylate and pretreatment by the protein kinase inhibitors, staurosporine (30 nM) and isoquinoline sulphonamide HA1077 (20 microM). The actively growing cells contained larger amounts of protein kinase C than growth-arrested cells. The phosphorylation sites of mono- and diphospho-MLC were determined to be MLC kinase-dependent sites (Thr18, Ser19). The PGF2alpha concentration/response curves of MLC diphosphorylation were shifted to the left and upwards in the presence of the protein phosphatase inhibitor calyculin A. These results suggest that PGF2alpha stimulation of actively growing SM-3 cells augments MLC kinase-dependent MLC diphosphorylation. Protein kinase C is involved indirectly in this reaction, possibly through MLC phosphatase-sensitive regulatory mechanisms.

Animals↗
PubMed1996

Phorbol ester, but not endotoxin, desensitizes mannan-induced glycogenolysis in the perfused rat liver.

Mannan, a ligand for the mannose/N-acetylglucosamine (GlcNAc) receptor, induces suppression of oxygen consumption and increases glucose production in the perfused rat liver, and repeated infusion of mannan causes desensitization of the responses. In this study, we examined whether activation of Kupffer cells by endotoxin and phorbol ester alters the glycogenolytic responses to mannan. Infusion of lipopolysaccharide (LPS, 10 micrograms/ ml) in the perfusate failed to inhibit the responses to mannan. Intravenous administration of LPS (1 mg/kg) 6 and 24 h before perfusion did not desensitize the responses to mannan, suggesting that the responses through mannose/GlcNAc receptors in the liver are retained even after activation of Kupffer cells by LPS. In contrast, prior infusion of phorbol 12-myristate 13-acetate (PMA, 100 nM) in vitro abolished the glycogenolytic responses to subsequently infused mannan, but not that to norepinephrine (100 nM), while prior infusions of 4-alpha-phorbol 12,13-didecanoate (100 nM), A23187 (50 nM), or forskolin (1 microM) had no effect on the mannan-induced responses. H-7, an inhibitor of protein kinase C, reduced the glycogenolytic responses to mannan, while it failed to restore the desensitization. These results suggest that protein kinase C may be involved in the process of glycogenolysis by mannan, but is unlikely to be involved in the homologous desensitization of the responses.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1996

Acetylpolyamine amidohydrolase from Mycoplana ramosa: gene cloning and characterization of the metal-substituted enzyme.

We have cloned a gene (aphA) encoding acetylpolyamine amidohydrolase from Mycoplana ramosa ATCC 49678, (previously named Mycoplana bullata). A genomic library of M. ramosa was screened with an oligonucleotide probe designed from a N-terminal amino acid sequence of the enzyme purified from M. ramosa. Nucleotide sequence analysis revealed an open reading frame of 1,023 bp which encodes a polypeptide with a molecular mass of 36,337 Da. This is the first report of the structure of acetylpolyamine amidohydrolase. The aphA gene was subcloned under the control of the trc promoter and was expressed in Escherichia coli MM294. The recombinant enzyme was purified, and the enzymatic properties were characterized. Substrate specificities, Km values, and Vmax values were identical to those of the native enzyme purified from M. ramosa. In the analysis of the metal-substituted enzymes, we found that the acid limb of pH rate profiles shifts from 7.2 for the original zinc enzyme to 6.6 for the cobalt enzyme. This change suggests that the zinc atom is essential for the catalytic activity of the enzyme similarly to the zinc atom in carboxypeptidase A.

Actinomycetales↗
PubMed1996

Cytogenetic effects of advanced maternal age and delayed fertilization on first-cleavage mouse embryos.

It has been shown that both advanced maternal age and delayed fertilization may induce chromosomal anomalies. We therefore examined the combined effects of these two factors on chromosomal anomalies in first-cleavage mouse embryos. We set up normal and (6-h) delayed subgroups in two different age groups (young, 3-4 mo; aged, 9-11 mo) and compared the incidence of chromosomal anomalies. In first-cleavage embryos, egg-derived chromosomes can be distinguished from sperm-derived chromosomes. The incidence of maternally derived aneuploidy was highest in the aged-delayed fertilization subgroup. We therefore conclude that advanced maternal age affects the production of aneuploidy more severely when combined with the effect of delayed fertilization.

Aneuploidy↗
PubMed1996

[Sport-anemia: studies on hematological status in high school boy athletes].

High prevalence of anemia and iron deficiency state are found among athletes. To determine the influence of sports activities on the hematological state, we have performed hematological tests and examined the iron metabolism, in addition to some serum enzyme activities and some characters of red blood cells before and after exercise in high school boy athletes. The red blood cell count, hemoglobin level, and hematocrit value were significantly lower than those in the non-athletes boy students. The serum ferritin level in the athletes was significantly lower than that in the control group and healthy adults. Iron deficiency anemia was found in 12% of the athletes. The serum haptoglobin level in the athletes was significantly lower than that in the control group and the level before exercise, suggesting intravascular hemolysis, but the serum hemopexin level showed no difference before and after exercise, suggesting that the hemolysis was not so severe. The serum CPK and myoglobin levels showed a significant increase after exercise, but those levels were quite lower than that of muscle diseases. These findings suggest that daily exercise is closely associated with the increased risk of iron deficiency state, particularly in the high school boy athletes. The mechanism of hemolysis in athletes may partly depend on the increased fragility of iron deficiency red blood cells on mechanical strength.

Adolescent↗
PubMed1995

Selectivity of action of staurosporine on Ca2+ movements and contractions in vascular smooth muscles.

We examined the effects of staurosporine, a protein kinase inhibitor, on Ca2+ movements and contractions due to KCl and 12-deoxyphorbol 13-isobutyrate (DPB), which are thought to activate myosin light chain kinase and protein kinase C, respectively. In rabbit aortae, staurosporine inhibited contractions due to KCl (65.4 mM) and DPB (1 mu M) with IC50 values of 140.5 +/- 1.3 nM and 13.3 +/- 1.3 nM, respectively. Calphostin C, a putative inhibitor of protein kinase C, inhibited DPB-induced contraction with much less effect on the KCl-induced one. On the other hand, wortmannin, an inhibitor of myosin light chain kinase, was 4 times more potent on KCl-induced contraction than the DPB-induced one. Staurosporine at 100 nM decreased the rise in cytosolic Ca2+ due to KCl, whereas wortmannin did not affect it. In rabbit cerebral arteries permeabilized with beta-escin, staurosporine at 100 nM, but not 30 nM, inhibited Ca2+ -induced contraction in the presence of 1 mM ATP. The results indicate that staurosporine preferentially inhibits a contraction dependent on protein kinase C than that dependent on myosin light chain kinase in vascular smooth muscles. Its ability to inhibit KCl-induced contraction involves inhibition of voltage-dependent Ca2+ channels.

Alkaloids↗
PubMed1995

Soluble c-kit levels in acute GVHD after allogeneic bone marrow transplantation.

Serum soluble c-kit concentrations were measured in 11 patients with or without acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation. The serum soluble c-kit levels in the patients with moderate to severe acute GVHD (grade II-IV) were significantly lower than those in the patients with no or mild acute GVHD (grade 0-I) following the onset. The data from this study indicate that measurement of serum soluble c-kit concentration is a useful indicator of severe acute GVHD.

Adolescent↗
PubMed1995

Cytokine gene expression after allogeneic bone marrow transplantation.

Cytokines produced by T lymphocytes, monocytes/macrophages, and fibroblasts play a central role in the immune response and in the development of graft-versus-host disease (GVHD). Also, it has been reported that dysregulated production of cytokines maybe the primary mediator of clinical manifestation of acute GVHD. Regarding cytokine gene expression after human allogeneic bone marrow transplantation (allo BMT), we have demonstrated increased IL-1 beta, IL-6, and TNF-alpha mRNA expression in peripheral blood mononuclear cells during the development of acute and chronic GVHD and that the degree of the increase was dependent on the severity of the disease. Furthermore, overexpression of these cytokine mRNAs could be detected before the clinical manifestations of GVHD developed. In contrast, IL-2 mRNA expression was not detected in peripheral blood mononuclear cells in GVHD patients. On the other hand, we have reported that increased mRNA expression and protein product of IL-2 and IFN-gamma were evident in the mixed lymphocyte culture of the cases who developed severe lethal transplantation-related complications. Therefore, the detection of increased IL-2 and IFN-gamma gene expression in MLC appeared to be useful for predicting transplantation-related complications in BMT patients. Furthermore, we found increased IL-2 receptor alpha subunit mRNA expression in the peripheral blood mononuclear cells during GVHD. These findings may indicate the important role of inflammatory cytokines such as IL-1 beta, IL-6 and TNF-alpha in the development of the clinical manifestation of GVHD and also may be indicative of the important role of IL-2 and the IL-2 receptor in allo response perhaps mainly as an autocrine effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Transplantation↗
PubMed1995

Transplantation-related complications predicted by cytokine gene expression in the mixed lymphocyte culture in allogeneic bone marrow transplants.

In this study, we have investigated cytokine (IL-1 beta, IL-2, IL-5, IL-6, IFN-gamma, TNF-alpha) and T cell surface molecule (IL-2 receptor, CD28, CTLA-4) gene expression in two way mixed lymphocyte cultures (MLC) enhanced by concanavalin A (ConA) to assess whether this is a useful predictive method for severe graft-versus-host disease (GVHD) and graft failure in allogeneic bone marrow transplantation (allo BMT) patients. Our present study revealed increased mRNA expression of IL-2, IL-5 and IFN-gamma using this assay in patients with delayed engraftment followed by graft failure and patients who developed grade III acute GVHD. Elevated IL-2 and IFN-gamma levels in MLC medium were also observed in these patients. Concerning T cell surface molecule gene expression in our modified MLC, IL-2 receptor gene expression was not altered so much in allo BMT patients, however, CD28 and CTLA-4 gene expression were elevated in patients with graft failure and severe acute GVHD. The elevated expression of cytokines (IL-2, IL-5 and IFN-gamma) and T cell surface molecules (CD28 and CTLA-4) mRNA in our modified MLC, in patients who developed severe lethal transplantation-related complications may suggest an important role for these molecules in inducing a strong alloresponse. Therefore, the detection of increased gene expression of those molecules, in our modified MLC system, appeared to be useful for predicting transplantation-related complications in allo BMT patients. In addition, this modified MLC assay may also be useful for the selection of the most compatible related and unrelated donors.

Antigens, CD↗
PubMed1995

Cytokine receptor gene expression in peripheral blood mononuclear cells during graft-versus-host disease after allogeneic bone marrow transplantation.

Interleukin-1 receptor type 1 (IL-1R), IL-2 receptor alpha subunit (IL-2R) and IL-6 receptor alpha subunit (IL-6R) mRNA expression in peripheral blood mononuclear cells (PBMC) in 17 patients who underwent allogeneic bone marrow transplantation (allo BMT) and 2 patients who underwent autologous transplantation were analyzed using a semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR). There were several exceptions in some cases and IL-1R expression was found to vary in a rather wide range, however, the expression of IL-2R and IL-6R mRNA tended to increase during the development of graft-versus-host disease (GVHD). In particular, IL-2R mRNA expression was increased in four patients with GVHD and graft failure. In contrast, IL-2R and IL-6R mRNA expression was not increased in autologous (auto) BMT and auto peripheral blood stem cell transplantation (PBSCT) patients. These findings suggest that IL-2R and maybe IL-6R mRNA expression in PBMC play an important role in the development of an allo response and GVHD. Therefore, the analysis of cytokine receptor mRNA expression in PBMC after allo BMT may provide important information concerning the immune response and the cytokine network system in marrow transplants.

Acute Disease↗