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Biomedical subjects

K Hatake

Publications and source records attributed to K Hatake.

At least 37 records · Page 2Linked to original sources
PubMed2000

Essential thrombocythemia transformed to acute myelogenous leukemia with t(3;17)(p24; q12), del(5)(q13q34) after treatment with carboquone and hydroxyurea.

In 1991, a 52-year-old woman was diagnosed as having essential thrombocythemia (ET). She was doing well with continuous medication with carboquone (CQ) and subsequently hydroxyurea (HU). However, substantial leukocytosis with leukemic blast cells, anemia and thrombocytopenia developed in 1996. Analysis of peripheral blood showed 4.4 x 10(3)/microl white blood cells with 82% of leukemic blast cells. These blasts showed negative staining with myeloperoxidase by immunostaining, but the myeloperoxidase was positive by electron microscopic analysis. Cytogenetic analysis of bone marrow cells revealed a t(3;17)(p24; q12), del(5)(q13q34). On the basis of these findings, the leukemic blast cells were classified as acute myelogenous leukemia (AML:M0) in the FAB classification. The causative agent, CQ and HU in secondary leukemia from ET and chromosomal abnormality related to ET blastic crisis (BC) are discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Sialyl-Tn- and neuron-specific enolase-positive minimally differentiated erythroleukemia.

Flow cytometric, immunochemical and molecular studies were performed on leukemic blasts from a patient with minimally differentiated erythroleukemia (AML-M6v). The blasts expressed CD36 and CD71 but not lymphoid antigens, myeloid antigens, CD41 or glycophorin A. Analysis of carbohydrate antigens showed that the blasts expressed the sialyl-Tn antigen. Immunochemistry revealed that the blasts had neuron-specific enolase (NSE). Serum sialyl-Tn and NSE levels were markedly increased. Finally, an erythroid lineage was confirmed in the presence of alpha-globin messages in the blasts. Sialyl-Tn and NSE expression in leukemic blasts may be useful to identify AML-M6v.

Antigens, CD↗
PubMed2000

Autologous peripheral blood stem cell transplantation for adults with B-lineage acute lymphoblastic leukemia: a pilot study.

We conducted a pilot study on autologous peripheral blood stem cell transplantation (PBSCT) for 11 adults with B-lineage acute lymphoblastic leukemia (ALL) in first complete remission (CR) or even in those with more advanced stages. All patients achieved CR by induction therapy, of whom 10 were treated with anthracycline, vincristine and prednisolone-based regimens. After consolidation therapy, all patients except one received high-dose cytarabine followed by granulocyte colony-stimulating factor (G-CSF) administration to collect PBSCs. Ten patients received busulfan 4 mg/kg for 4 days, etoposide 20 mg/kg for 3 days and ranimustine 200 mg/m2 for 2 days as a conditioning regimen. One received a regimen consisting of etoposide, cyclophosphamide and total body irradiation. From day 1, G-CSF was given intravenously, and no additional chemotherapy was administered. At the median follow-up time of 30.8 months, four of six patients with standard-risk B-lineage ALL survived within the range of 19.7 to 85.4 months without relapse. In contrast, only one of five with high-risk B-lineage ALL survived for 36.3 months without relapse. Autologous PBSCT as post-remission therapy may prolong CR in adults with standard-risk B-lineage ALL.

Adolescent↗
PubMed2000

[Low-dose prednisolone therapy for idiopathic thrombocytopenic purpura].

Prednisolone (PSL) is widely used for the treatment of idiopathic thrombocytopenic purpura (ITP). We compared the effects of a relatively low dose (0.5 mg/kg/day, LD group) of PSL and the conventional dose (1.0 mg/kg/day, CD group) on 59 ITP patients. Twenty-six patients were treated with low-dose PSL, and 23 patients with the conventional dose. No statistically significant difference was observed in the complete remission rates for the LD group (35%) and the CD group (39%). However, the mean duration of hospitalization was significantly (p < 0.001) shorter for LD group patients than for patients in the CD group (20 days versus 50 days, respectively). In conclusion, low-dose PSL may be as effective as the conventional dose and capable of reducing the cost of hospitalization, thus, improving the quality of life for patients with ITP.

Anti-Inflammatory Agents↗
PubMed2000

[Two cases of acute myelogenous leukemia complicated with fatal gastrointestinal tract bleeding after treatment with idarubicin and cytarabine].

We describe herein two newly diagnosed patients with acute myelogenous leukemia (AML), who were treated twice with an idarubicin hydrochloride (IDR)-containing regimen as a response-orientated induction therapy. Both patients had severe gastrointestinal tract hemorrhage complications at their nadir. The two patients were as follows: a 35-year-old male, FAB-M4, and a 47-year-old female, FAB-M0. They received the same induction chemotherapy (IDR 12 mg/m2 for four days and cytarabine 100 mg/m2 for ten days). No response (NR) was obtained in either, so they underwent the same regimen again. During the period of myelosuppression, they developed severe gastrointestinal hemorrhage. One died of sepsis, and the other of acute respiratory distress syndrome without a recovery in bone marrow. The fetal gastrointestinal tract complications may have been due to severe myelosuppression and mucosal damage in these patients. Careful observation will be needed to prevent such severe complications after the treatment with IDR.

Adult↗
PubMed2000

Ethanol suppresses L-arginine-induced relaxation response of rat aorta stimulated with bacterial lipopolysaccharide.

Using isolated rat aortic strips without endothelium, we investigated the effect of ethanol on L-arginine-induced relaxation. L-Arginine (10(-5)-10(-3) M) produced a relaxation response in vascular strips incubated for 6 hr with bacterial lipopolysaccharide (1 microgram/ml). The relaxation was either abolished by cycloheximide (10(-5) M) and actinomycin D (10(-5) M) or diminished by polymyxin B (10 micrograms/ml), dexamethasone (10(-5) M) and nitro-L-arginine (10(-4) M) under conditions in which these inhibitors were coincubated with lipopolysaccharide. Also, L-arginine-induced relaxation was significantly inhibited when ethanol (200, 400 mM) was present together with lipopolysaccharide during the 6-hr incubation. However, when ethanol was added to the organ bath after 6-hr incubation with lipopolysaccharide, it did not inhibit the relaxation. These results suggest that the relaxation response to L-arginine is mediated by an inducible type of nitric oxide synthase, which can be induced by lipopolysaccharide, and that ethanol may attenuate this nitric oxide-mediated relaxation by inhibiting expression of inducible nitric oxide synthase.

Animals↗
PubMed2000

Oxidative stress as a necessary factor in room temperature-induced apoptosis of HL-60 cells.

HL-60 cells undergo apoptosis when placed at room temperature (RT) [Shimura et al. (1997) FEBS Lett. 417, 379-384]. We report that superoxide anion radical, one of the reactive oxygen species (ROS), was produced after RT treatment. Affinity blot analysis with a biotinylated YVAD-CHO detected the generation of processed peptides with molecular masses of 15-25 kDa. Activation of such an ICE-like protease was completely abolished by N-acetylcysteine and exogenously expressed Bcl-2, known as antioxidants. We concluded that oxidative stress was a critical factor in the signal cascade of the apoptosis. Western blot analysis and experiments using tetrapeptide inhibitors suggested that caspases-1, -3, -4, -6, and -9 did not have an essential role in the apoptotic cascade. It is interesting that cyclosporin A (CsA) blocked RT-induced apoptosis with an inhibition of cytochrome c release from mitochondria. CsA, however, generated a significant amount of ROS with considerable reduction of mitochondrial membrane potential, implying that oxidative stress was one necessary factor for RT-induced apoptosis. It is also likely that mitochondrial membrane potential and the release of apoptotic factors from cytoplasm are differently regulated. Taken together with the reports that some Burkitt lymphoma cells showed apoptosis when exposed at low temperature followed by rewarming, and that hepatocytes or liver endothelial cells are susceptible to cold-induced apoptosis through the ROS function, we propose that studying the mechanism of RT-induced apoptosis of HL-60 cells may provide a therapeutic strategy for pathological conditions involving ROS, such as neurodegenerative diseases and ischemia.

Amino Acid Chloromethyl Ketones↗
PubMed2000

[Effect of etoposide added to individualized induction therapy of adult acute myeloid leukemia--the JALSG-AML-92 Study. Japan Adult Leukemia Study Group].

A multicenter prospective randomized study was undertaken to assess the efficacy of etoposide added to the standard remission induction therapy for acute myeloid leukemia (AML). Consecutively registered newly diagnosed adult AML patients were randomized to receive either daunorubicin (40 mg/m2/day x 4 or more), behenoyl cytarabine (200 mg/m2/day x 10 or more) and 6-mercaptopurine (70 mg/m2/day x 10 or more) (BH-AC-DM), or the same three drugs plus etoposide (100 mg/m2/day x 5) (BH-AC-EDM) for response-oriented individualized induction therapy. The patients achieving complete remission (CR) received the same 3 courses of consolidation therapy followed by 6 courses of maintenance/intensification therapy. M3 was excluded and M0 was included. Of 667 patients registered, 655 were evaluable. The median age was 49 years (range, 15 to 85). CR rates were 77% in the BH-AC-DM group and 75% in the BH-AC-EDM group. In M4 patients, CR rates were 86% and 69% (p = 0.009), and, in M5, 80% and 77% (p = 0.810) in the BH-AC-DM and BH-AC-EDM groups, respectively. The predicted 6-year overall survival rates were 30% and 38% for BH-AC-DM and BH-AC-EDM groups, and the disease-free survival (DFS) rates of CR patients were 25% and 35% (p = 0.925), respectively. In conclusion, the present study failed to show any advantage of the addition of etoposide to the standard individualized induction therapy in adult AML, even among M4 and M5. These above data have already been published in the Int J Hematol (70: 87-104, 1999).

Adolescent↗
PubMed2000

Successful treatment of multiple myeloma--associated amyloidosis by interferon-alpha, dimethyl sulfoxide, and VAD (vincristine, adriamycin, and dexamethasone).

A 45-year-old Japanese man was admitted to our hospital because of a mass in the submandibular region, abnormal hematologic findings, and proteinuria. A diagnosis of multiple myeloma was made based on the results of bone marrow analysis and M-protein in hematologic tests, and a diagnosis of amyloidosis was made on the basis of deposition of amyloid in the rectal submucosal and lip tissues and the mass in the submandibular region. Combination therapy of interferon (IFN)-alpha at 1-day intervals and daily oral dimethyl sulfoxide (DMSO) and vincristine, adriamycin, and dexamethasone (VAD) resulted in a marked decrease in the size of the mass and hypertrophy of the back, as well as a decrease in the levels of plasma cells in bone marrow and of M-protein and immunoglobulin G in serum. The results of this case indicate that long-term administration of IFN-alpha and DMSO with VAD is effective in treating amyloidosis with multiple myeloma.

Amyloidosis↗
PubMed1999

NH2-terminal pentapeptide of endothelial interleukin 8 is responsible for the induction of apoptosis in leukemic cells and has an antitumor effect in vivo.

We have reported that endothelial interleukin 8 (IL-8) induces apoptosis in leukemic cells in vitro and in vivo, and that interaction between endothelial cells and leukemic cells causes induction of apoptosis through the release of endothelial IL-8 (Y. Terui et al., Biochem. Biophys. Res. Commun., 243: 407-411, 1998; Y. Terui et al., Blood, 92: 2672-2680, 1998). Here, we examined whether a pentapeptide corresponding to the NH2-terminal region of endothelial IL-8 can induce apoptosis in leukemic cells. The NH2-terminal pentapeptide Ala-Val-Leu-Pro-Arg (AVLPR) was found to significantly induce apoptosis in the leukemic cell lines K562, HL-60, Jurkat, and Daudi, as compared with the COOH-terminal pentapeptide Arg-Glu-Ala-Asn-Ser (REANS). Moreover, the NH2-terminal pentapeptide AVLPR significantly inhibited growth of i.p. and s.c. tumor masses of K562 cells and induced apoptosis in these cells in vivo. The active site of endothelial IL-8 is the NH2-terminal pentapeptide AVLPR, and this may serve as a new therapy for hematological malignancies.

Animals↗
PubMed1999

Beta(2)-microglobulin identified as an apoptosis-inducing factor and its characterization.

Major histocompatibility complex (MHC) molecules play an important role in antigen presentation for induction of tumor as well as cellular and humoral immunities. Recent studies using anti-MHC antibodies demonstrated that antibodies specific for HLA class I molecules induced cellular activation and a type of apoptosis that may be distinct from Fas-dependent or TNFR (tumor necrosis factor-alpha receptor)-dependent processes. We purified a previously untested apoptosis-inducing factor from HL-60 human leukemic cell-conditioned media to homogeneity and sequenced it. It was identified as beta(2)-microglobulin (beta(2)m), which has been previously known as thymotaxin and is a part of the HLA class I antigen complex. beta(2)m acts on both T-leukemic cells and myeloid leukemic cells to induce apoptosis, which then activates caspase 1 and 3. Cross-linking studies showed that biotinilated beta(2)m recognized an epitope distinct from those recognized by the anti-HLA class I antibody, as reported previously. We demonstrated that beta(2)m plays a previously unrecognized and important role in regulating the elimination of tumor cells, which occurs as a result of the action of beta(2)m as an apoptosis-inducing factor.

Amino Acid Chloromethyl Ketones↗
PubMed1999

Inhibition of Vpr-induced cell cycle abnormality by quercetin: a novel strategy for searching compounds targeting Vpr.

Vpr, an accessory gene product of HIV-1 which induces cell cycle abnormality leading to the increased HIV replication, is supposed to be a possible target for anti-AIDS drugs. We recently established a cell line (MIT-23) in which Vpr-induced cell cycle perturbation could be manipulated by a tetracycline promoter. Here, we screened anti-Vpr activity in 27 kinds of herb drugs using MIT-23 cells. One of the extracts prepared from Houttuyniae herba showed an inhibitory activity. Quercetin (QCT), a compound of this crude drug, efficiently inhibited Vpr function without affecting its expression. Furthermore, data suggested that Vpr-induced transcription from HIV-LTR was considerably abrogated by QCT. These data indicate that QCT, a flavonoid previously reported to inhibit HIV replication, also targets Vpr, implicating that MIT-23 cell provides a novel strategy for screening compounds possessing anti-Vpr activity which would be in turn utilized for clarifying the mechanism of Vpr function.

Anti-HIV Agents↗
PubMed1999

Micronuclei formation with chromosome breaks and gene amplification caused by Vpr, an accessory gene of human immunodeficiency virus.

Vpr, an accessory gene of human immunodeficiency virus, induces cell cycle abnormality by accumulating cells at the G2-M phase. We reported recently that Vpr caused both micronuclei formation and aneuploidy. Here, we show that Vpr also induced chromosome breaks and gene amplification. Expression of Vpr induced more than 10-fold increase of colonies resistant to N-(phosphonacetyl)-L-aspartate, an inhibitor of pyrimidine de novo synthesis. Fluorescence in situ hybridization analysis detected that 4 of 10 N-(phosphonacetyl)-L-aspartate resistant clones studied had intrachromosomal amplification of carbamyl-phosphate synthetase/aspartate transcarbamoylase/dihydroorotase gene. Another single clone had dicentrics. Data suggested that the Vpr-induced chromosome breaks leading to gene amplification, followed by bridge-breakage-fusion cycle, were one of the possible mechanisms of Vpr-induced genomic instability.

Aneuploidy↗
PubMed1999

In vivo stimulatory effect of macrophage colony-stimulating factor on the number of stroma-initiating cells.

The in vivo effect of human macrophage colony-stimulating factor (M-CSF) on the number of cells that formed stromal colonies in an in vitro culture system (stroma-initiating cells; SICs) was investigated. We found that the number of SICs in the femurs of C57BL/6 mice was significantly increased by the treatment with M-CSF. We also found that the SICs were resistant to at least three different chemotherapeutic reagents, 5-fluorouracil (5-FU), cytarabine, and cyclophosphamide, because the femoral cells of mice treated with these reagents contained higher numbers of SICs than those of untreated mice. M-CSF treatment also increased the number of SICs of the reagent-pretreated mice. The SICs detected in our culture system were present only in Mac-1(-)CD45(-) cells, and the M-CSF treatment of 5-FU-pretreated mice actually increased the number of Mac-1(-)CD45(-) SICs. The Mac-1(-)CD45(-) SICs collected from mice that were pretreated with 5-FU and then treated with M-CSF formed stromal colonies under in vitro culture conditions that did not contain M-CSF but did contain a high concentration of fetal calf serum. This result suggested that SICs collected following the treatment procedure did not necessarily require the presence of M-CSF for their in vitro proliferation. Our study indicated that M-CSF has the ability to increase the number of progenitor or precursor cells for bone marrow stromal cells in vivo system.

Animals↗
PubMed1999

High serum levels of M-CSF and G-CSF in Kawasaki disease.

To examine any role of macrophage colony-stimulating factor (M-CSF), in the immune responses in Kawasaki disease (KD), we serially assayed M-CSF and several related cytokines using ELISA. In 10 paediatric patients with KD the level of M-CSF was significantly higher in the acute phase than in the convalescent phase (1476.1 +/- 443.6 v 805.0 +/- 184.7 U/ml). Higher levels of serum granulocyte colony-stimulating factor (G-CSF) and interleukin-6 were also found in the acute phase. These results suggest that M-CSF, G-CSF and interleukin-6, derived from monocytes as monokines or derived from vascular endothelial cells, might play an important role in the acute phase of KD.

Child↗
PubMed1999

Micronuclei formation and aneuploidy induced by Vpr, an accessory gene of human immunodeficiency virus type 1.

Vpr, an accessory gene of HIV-1, induces cell cycle abnormality with accumulation at G2/M phase and increased ploidy. Since abnormality of mitotic checkpoint control provides a molecular basis of genomic instability, we studied the effects of Vpr on genetic integrity using a stable clone, named MIT-23, in which Vpr expression is controlled by the tetracycline-responsive promoter. Treatment of MIT-23 cells with doxycycline (DOX) induced Vpr expression with a giant multinuclear cell formation. Increased micronuclei (MIN) formation was also detected in these cells. Abolishment of Vpr expression by DOX removal induced numerous asynchronous cytokinesis in the multinuclear cells with leaving MIN in cytoplasm, suggesting that the transient Vpr expression could cause genetic unbalance. Consistent with this expectation, MIT-23 cells, originally pseudodiploid cells, became aneuploid after repeated expression of Vpr. Experiments using deletion mutants of Vpr revealed that the domain inducing MIN formation as well as multinucleation was located in the carboxy-terminal region of Vpr protein. These results suggest that Vpr induces genomic instability, implicating the possible role in the development of AIDS-related malignancies.

Acquired Immunodeficiency Syndrome↗