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Biomedical subjects

K Sakurada

Publications and source records attributed to K Sakurada.

At least 109 records · Page 6Linked to original sources
PubMed1991

Increased N-acetylglucosamine-1-phosphotransferase activity in sera from patients with leukemia.

In human cancer, lysosomal hydrolases contain increased amounts of phosphorylated sugar chains. Sugar chains of the hydrolases undergo post-translational processing which is catalyzed by N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase) at the first step. In the present study we estimated serum GlcNAc-phosphotransferase in 50 adults suffering from leukemia and myelodysplastic syndrome. The serum GlcNAc-phosphotransferase was increased to moderate or high levels in patients with acute nonlymphocytic leukemia (ANLL), acute lymphoblastic leukemia and chronic myelogenous leukemia, suggesting that the serum transferase is released from leukemic cells. In many cases of ANLL examined, activity of the transferase was decreased concomitantly with reduction of peripheral blastic cells by effective chemotherapy.

Acetyltransferases↗
PubMed1991

Establishment and characterization of a plasma cell leukaemia cell line dependent for growth on IL-6 and a bi-phenotypic subclone dependent upon both IL-3 and IL-6.

A human plasma cell leukaemia cell line (HSM-2) and a subclone (HSM-2.3) have been established from the bone marrow of a patient with bi-phenotypic leukaemia. Proliferation assays using a variety of cytokines demonstrated that HSM-2 proliferated in response to recombinant interleukin-6 (rIL-6), but did not respond to rIL-1, rIL-2, rIL-3, rIL-4, rIL-5, recombinant granulocyte-colony stimulating factor (rG-CSF), or recombinant granulocyte-macrophage-colony stimulating factor (rGM-CSF), and that HSM-2.3 responded to rIL-3 and rIL-6. HSM-2 expressed the CD38 (OKT10), PCA-1, cytoplasmic-IgM, and surface kappa light chain. HSM-2.3 expressed the CD14 (My4), CD33 (My9), CD38 (OKT10), CD19 (B4), CD24 (OKB2), CD10 (J5), PCA-1. HSM-2 and HSM-2.3 are useful tools for analysing the possible role of IL-3 and IL-6 in the oncogenesis of plasma cell leukaemia.

Aged↗
PubMed1991

[Torsade de pointes ventricular tachycardia in a patient with acute myelocytic leukemia].

The anti-leukemic antibiotics, anthracyclines, are most effective agents in the treatment of acute leukemia. However, they have severe cardiac toxicities, which ordinarily shows dose-dependency, but sometimes produce acute cardiomyopathy. We experienced Torsade-de-pointes arrhythmia during the treatment of acute myelocytic leukemia (AML); The patient was a 28 year old woman and had an AML-M1. After the short course administration of daunorubicin (total 90 mg/m2) and aclarubicin (total 219 mg/m2), she suffered from an attack of Torsade-de-pointes ventricular tachycardia and passed away, since any treatment against ventricular arrhythmia was not effective. Autopsy studies revealed degeneration and atrophy of cardiac muscle in the area around His's bundle, which suggested an anthracycline-induced cardiac toxicity.

Aclarubicin↗
PubMed1991

[Therapeutic effect of ranimustine(MCNU) on myeloproliferative disorder and chronic myelomonocytic leukemia].

Seventeen patients with myeloproliferative disorders and one patient with chronic myelomonocytic leukemia (CMMoL) were treated with ranimustine++ (MCNU), and the efficacy was evaluated. MCNU was given intravenously by drip infusion at an usual dose of 100 approximately 150 mg with intervals arranged according to the counts of peripheral blood cells. A complete remission was achieved in all 10 patients with chronic myelogenous leukemia (CML) in chronic phase. In three of patients with polycythemia vera (PV) the excellent effects were obtained, and the other 2 cases showed moderate effect. An excellent effect was obtained in both 2 patients with essential thrombocythemia (ET). A patient with CMMoL revealed partial remission. The overall efficacy rate was 100%. The cases with CML needed more long term and much more dose of the drug in order to get remission compared with PV and ET. After remission in both PV and ET, well controlled states were maintained for a relatively long period with no additional administration. In CMMoL, MCNU combined with 6-mercaptopurine also showed remarkable anti-tumor effects. It suggests that MCNU may be one of the useful drugs for the treatment of CMMoL. The side effects observed with MCNU were a slight degree of nausea and vomiting (28%), however they showed no trouble on carrying out the therapy.

Adult↗
PubMed1990

Mechanochemical coupling in actomyosin energy transduction studied by in vitro movement assay.

In order to study the mechanochemical coupling in actomyosin energy transduction, the sliding distance of an actin filament induced by one ATP hydrolysis cycle was obtained by using an in vitro movement assay that permitted quantitative and simultaneous measurements of (1) the movements of single fluorescently labeled actin filaments on myosin bound to coverslip surfaces and (2) the ATPase rates. The sliding distance was determined as (the working stroke time in one ATPase cycle, tws) x (the filament velocity, v). tws was obtained from the ATPase turnover rate of myosin during the sliding (kt), the ATP hydrolysis time (delta t) and the ON-rate at which myosin heads enter into the working stroke state when they encounter actin (kON); tws approximately 1/kt-delta t-1/kON. kt was estimated from the ATPase rates of the myosin-coated surface during the sliding of actin filaments. delta t has been determined as less than 1/100 per second, kON was estimated by analyzing the movements of very short (40 nm) filaments. The resulting sliding distance during one ATP hydrolysis cycle near zero load was greater than 100 nm, which is about ten times longer than that expected for a single attachment-detachment cycle between an actin and a myosin head. This leads to the conclusion that the coupling between the ATPase and attachment-detachment cycles is not determined rigidly in a one-to-one fashion.

Actins↗
PubMed1990

In vivo administration of cytokine in allogeneic bone marrow chimeras.

When we analyzed the in vivo efficacy of cytokine administration in murine allogeneic bone marrow chimeras, mitogen-induced responses to ConA, PHA, LPS, or PWM were increased by the in vivo administration of human recombinant granulocyte colony-stimulating factor (rG-CSF), human recombinant interleukin 2 (rIL-2), or WEHI-3B conditioned medium (CM). Furthermore, we found increased alloreactive mixed lymphocyte reactions (MLRs) against donor and/or host type alloantigens in spleen cells from (BALB/c----C3H/He) chimeras, although cytotoxic activity against BALB/c or C3H/He target cells was not detected in spleen cells from these chimeras. Since no significant increase of T cells or Ia positive cells was observed, some functional activation, rather than changes in the cell count, appeared to relate to increase immunoreactivity. An increased IL-2 production in spleen cells from chimeras injected with cytokine was observed shortly after the cessation of cytokine administration. Thereafter, an IL-2 production in these chimeras decreased around 45 days after bone marrow transplantation and then recovered nearly to the control level. An increased IL-2 responsiveness was also observed in spleen cells from these chimeras. These findings suggest that the in vivo administration of rG-CSF as well as rIL-2 or WEHI-3B CM (IL-3) can modulate the immunoreactivity in chimeras via the network of immune systems.

Animals↗
PubMed1990

Inhibitory effect of bestatin on the growth of human leukemic cells.

We examined the effect of bestatin (Ubenimex) on the growth of human leukemic cells (i.e, HL-60, K562, MT-1, MT-2, Molt-4, and Raji cells). The growth of each cell line was inhibited by the cocultivation with bestatin at higher concentrations than employed for clinical use in Japan. [3H]TdR incorporation was also inhibited in MT-1 and MT-2 cells by treatment with bestatin. Degenerated cell-to-cell adhesion was observed among the treated cells. These findings suggest that the inhibitory effect on some leukemic cells, especially on MT-1 cells, results from the inhibition of DNA synthesis.

Antibiotics, Antineoplastic↗
PubMed1990

[Anemia in the elderly].

We measured red blood cell counts, hemoglobin levels, hematocrit values, serum iron levels, total iron binding capacity, transferrin saturation, and serum ferritin levels in 364 elderly subjects in the eighth decade, who consisted of 283 subjects (171 males, 112 females) living in their own homes and 81 subjects (28 males, 53 females) living in an old-age home. The mean values of RBC, Hb, Ht, SI, s-Ft in both male and female subjects living in their own homes were 469 X 10(4)/microliters vs 439 X 10(4)/microliters, 14.6 g/dl vs 13.3 g/dl 44.3% vs 40.6%, 95.6 micrograms/dl vs 84.8 micrograms/dl, 50.2 ng/ml vs 42.6 ng/ml, respectively. On the other hand, the mean values of RBC, Hb, Ht, SI, s-Ft in both male and female subjects living in an old-age home were 421 X 10(4)/microliters vs 390 X 10(4)/microliters, 13.8 g/dl vs 12.6 g/dl, 39.9% vs 36.7%, 74.2 micrograms/dl vs 58.6 micrograms/dl, 98.8 ng/ml vs 69.1 ng/ml, respectively. All erythrocyte parameters were significantly lower in females than in males in both groups, and significantly lower in subjects living in an old-age home than in subjects living in their own homes. The erythrocyte parameters of subjects living in their own homes showed little difference compared with those of normal young adults. These results suggest that a sedentary lifestyle in the elderly people contribute to the tendency to have anemia and this is considered to relate to age-associated pathology such as inflammation. As anemia in elderly people often follows a underlying illness, we must always give attention to the factors which cause anemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

[Treatment of aplastic anemia with KRN8601 (rhG-CSF)].

Thirty-nine patients with severe or moderate aplastic anemia received treatment with recombinant human granulocyte colony-stimulating factor (rhG-CSF). The first group of eight patients received rhG-CSF in doses of 100 to 400 micrograms/m2/d by a daily 30-minute intravenous infusion for one or two weeks. Doses up to 400 micrograms/m2/d were well tolerated and resulted in increases of neutrophil counts in 5 out of 8 patients. We gave rhG-CSF (400 micrograms/m2/d) to the second group of 26 patients by a daily 30-minute intravenous infusion for two weeks. The treatment resulted in an increase of neutrophil counts in 15 out of 26 patients (3.1 to 29.5 fold). Further, higher doses (800 or 1,200 micrograms/m2/d) were administered in 5 patients who did not respond to the dose of 400 micrograms/m2/d. The treatment increased the neutrophil counts in 3 out of 5 patients. The third group of five patients received rhG-CSF subcutaneously in doses of 20 to 400 micrograms/m2/d. An increase of neutrophil counts was noted in all five patients. Differential counts of bone marrow aspirate revealed an increase of myeloid: erythroid ratios. However, the responses were transient and neutrophil counts returned to basal levels within 1 approximately 2 weeks after discontinuing treatment. No severe toxicity due to rhG-CSF was observed. These results suggest that rhG-CSF is effective on stimulating granulopoiesis in patients with aplastic anemia. This treatment will be particularly useful for the patient with aplastic anemia suffering from bacterial or fungal infections.

Adolescent↗
PubMed1989

Processing enzymes acting on carbohydrate moiety of lysosomal hydrolases in leukemic cells: elevated activity of N-acetylglucosamine-1-phosphotransferase.

We previously demonstrated that an acidic variant form of lysosomal arylsulfatase B accumulated in chronic myelogenous leukemia (CML) cells was highly phosphorylated at its carbohydrate moiety (Uehara Y, et al, Cancer Res 43:5618, 1983). Since lysosomal hydrolases including the sulfatase underwent the posttranslational phosphorylation processing at the carbohydrate moiety, we investigated two enzymes acting on the processing in peripheral leukocytes from leukemia patients. The activity level of the first enzyme in the processing, an N-acetylglucosamine-1-phosphotransferase to form phosphodiester at the carbohydrates, was significantly higher in CML cells than in normal control. The transferase level in CML cells was also higher compared with that in normal bone marrow cells, which include myeloid progenitor cells. However, the activity of the second processing enzyme, a phosphodiester glycosidase that converts a phosphodiester to a phosphomonoester, showed no consistent change in CML cells. Thus, increment of the sulfatase variant containing phosphomonoesters and diesters in CML cells is most probably associated with elevated activities of the phosphotransferase. In two cases of CML in blastic crisis and a case of acute myelogenous leukemia (AML), activity of the processing enzyme was considerably decreased concomitant with reduction of peripheral blastic cells by chemotherapy.

Adult↗
PubMed1989

bcr rearrangement and C-abl gene expression in Ph1-positive hybrid acute leukemia with simultaneous proliferation of lymphoid and myeloid blasts.

bcr gene rearrangement and c-abl gene expression were analyzed in a patient with Philadelphia chromosome (Ph1)-positive hybrid acute leukemia with simultaneous proliferation of lymphoid and myeloid blasts. These data were compared with those from a patient with chronic myelogenous leukemia (CML) in mixed crisis. The leukemic cells of both patients showed immuno-phenotypic profiles such as non-T, non-B common ALL with some MPO-positive leukemic cells and rearranged JH genes. On analysis of molecular events associated with the Ph1 chromosome, the leukemic cells of a patient with CML in mixed crisis showed bcr rearrangement and an 8.5-kb bcr-abl chimeric mRNA, but those of a patient with Ph1-positive hybrid acute leukemia showed no 8.5-kb bcr-abl mRNA, as previously reported in a number of Ph1-positive acute lymphoblastic leukemia (ALL) cases. These results revealed that the molecular event found in Ph1-positive ALL is not only restricted to lymphoid lineage but may play an important role in the proliferation of the myeloid lineage.

Adult↗
PubMed1989

[Allogeneic bone marrow transplantation after the treatment of alpha-IFN and high-dose SNMC in two cases of acute myeloblastic leukemia with post-transfusional non-A, non-B hepatitis].

Two patients of acute myeloblastic leukemia (M2) with post-transfusional hepatitis (non-A, non-B) were treated with alpha-IFN and high-dose SNMC before allogeneic bone marrow transplantation. Bone marrow transplantation from HLA identical and MLR negative sibling donor was carried out when their hepatic functions were almost normalized. In the early phase after bone marrow transplantation, the hepatic function in both two cases has been stable, thus indicating that this treatment should be tried for reducing hepatic dysfunction and for safety bone marrow transplantation.

Adult↗
PubMed1989

Fibrinogen Sapporo: dysfibrinogenemia characterized by the replacement of A alpha arginine-16 by histidine resulting in the delayed release of fibrinopeptide A by thrombin.

Congenital dysfibrinogenemia was found in a 60-year-old asymptomatic female and her daughter. Purified fibrinogen derived from the propositus, apparently a heterozygote for the abnormality, characteristically showed delayed but complete release of fibrinopeptide A upon digestion with thrombin but its defective release by Ancrod, a snake venom enzyme, from half of her fibrinogen molecules. This congenital dysfibrinogenemia with an A alpha arginine (Arg) to histidine (His) substitution was tentatively designated as fibrinogen Sapporo. Although this type of abnormal fibrinogen had been identified among Caucasians, no such cases have so far been reported in Japan.

Female↗
PubMed1989

[Polycythemia vera with an inhibitor against factor XII].

A case of polycythemia vera with an inhibitor against factor XII was reported. A 60-year-old female was admitted to Hokkaido University School Hospital because of erythrocytosis and hepatosplenomegaly. The hemoglobin was 22.5 g/dl and white cell count was 9,500/microliters without immature cells. The platelet count was 484,000/microliters. Bone marrow specimens showed marked hypercellularity. Philadelphia chromosome was not found on chromosome analysis. She was diagnosed as polycythemia vera according to the criteria of polycythemia Vera Study Group. Activity of factor XII was found to be decreased on the initial examination, but she had no personal and familial history of bleeding. In order to clarify the cause of decreased activity of factor XII, her plasma was mixed with normal plasma, and then examined PTT using factor XII deficient plasma. Her plasma mixed with equivalent normal plasma did not show the correction of prolonged PTT. It was suggested that an inhibitor of her plasma was included in the IgG fraction using gel chromatography. The patient was treated with phlebotomy and administration of N4-palmitoyl (1- -D-arabinofurasyl) cytosine (derivative of cytosine arabinoside; PLAC) 200 mg/day and Busulfan (1 mg/day). Factor XII was not corrected by phlebotomy, but corrected gradually by administration of PLAC and Busulfan.

Factor XII↗
PubMed1989

[Measurement of anti-HTLV-I antibody titer in cerebrospinal fluid].

Anti HTLV-I antibody was measured in 590 cerebrospinal fluids (CSFs) employing a gelatin particle agglutination (PA) method. Anti HTLV-I antibody was detected in the CSFs from 24 patients (4.1%). The serum from the 24 patients also showed positive results. Out of the 24 patients, 11 cases (45.8%) had HAMs. Of the remaining patients 3 had ATLs with meningeal infiltration. Only 11 cases out of 24 patients were positive for anti HTLV-I antibodies when an immunofluorescence (IF) method was employed. This discrepancy of the results obtained by two methods may be explained by the presence of the patients whose CSFs contain anti HTLV-I antibodies of low titer. It is concluded that PA method is both sensitive and specific for the detection of anti HTLV-I antibodies in CSFs. Further, PA method is more convenient than IF method. So, it will be a very useful tool in the diagnosis of HTLV-I related neurological disorders and asymptomatic carriers.

Adolescent↗