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S Kuriya

Publications and source records attributed to S Kuriya.

At least 19 recordsLinked to original sources
PubMed1992

In vitro and in vivo effects of MDP-Lys(L18) on mouse megakaryocyte progenitor cells (CFU-Meg).

We investigated the in vitro and in vivo effects of MDP-Lys(L18), a derivative of muramyl dipeptide (MDP), on megakaryocyte progenitor cells (megakaryocyte colony-forming units, CFU-Meg) in the mouse bone marrow and spleen. When CFU-Meg culture was performed with a suboptimum concentration (2%) of pokeweed mitogen-stimulated mouse spleen-conditioned medium (PWM-SCM), addition of 0.1-20 micrograms/ml of MDP-Lys(L18) increased the number of megakaryocyte colonies. The size of the megakaryocyte colonies (the number of megakaryocytes per colony) was also significantly increased by the addition of MDP-Lys(L18) under the same culture conditions in comparison with cultures without MDP-Lys(L18). MDP-Lys(L18) itself did not stimulate megakaryocyte colony formation without PWM-SCM, and it failed to enhance megakaryocyte colony formation in cultures with an optimum PWM-SCM concentration (10%). Furthermore, no effect of MDP-Lys(L18) was observed in cultures of phagocytic cell-depleted bone marrow cells. However, MDP-Lys(L18) enhanced megakaryocyte colony formation in cultures of T-lymphocyte-depleted bone marrow cells. The culture supernatant from a macrophage cell line, J774.1, plus MDP-Lys(L18) enhanced in vitro megakaryocyte colony formation in cultures with a suboptimum PWM-SCM concentration. Although interleukin 1 (IL-1)beta in the culture supernatant of J774.1 plus MDP-Lys(L18) was increased in a dose-dependent manner in response to MDP-Lys(L18), the effect of the culture supernatant was not blocked by an anti-IL-1 antibody, and IL-1 beta failed to enhance megakaryocyte colony formation in the presence of suboptimum PWM-SCM levels. The enhancement of megakaryocyte colony formation by MDP-Lys(L18) could be neutralized, however, by an anti-interleukin 6 (IL-6) antibody. Intraperitoneal administration of MDP-Lys(L18) (100 micrograms daily for 3 days) significantly increased the number of bone marrow and spleen megakaryocyte colonies at 24 to 72 h after the final injection. These in vitro and in vivo observations strongly suggest that MDP-Lys(L18) indirectly enhances the proliferation and differentiation of mouse CFU-Meg via colony-stimulating factor(s) other than IL-1, probably as a result of the stimulation of macrophages to produce IL-6.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1991

Superoxide anion hyperproduction by neutrophils in a case of myelodysplastic syndrome. Association with Sweet's syndrome and interstitial pneumonia.

The complication of Sweet's syndrome and interstitial pneumonia occurred in a patient with myelodysplastic syndrome. Superoxide anion production by the patient's neutrophils was considerably higher than that by neutrophils obtained from normal controls after stimulation with opsonized zymosan, phorbol myristate acetate, or myristic acid. Prednisone, which a potent inhibitor of superoxide anion production by neutrophils, dramatically improved the skin and pulmonary lesions, suggesting that they were parts of the same clinical spectrum associated with the superoxide anion hyperproduction.

Dermatitis↗
PubMed1991

Transforming genes and chromosome aberrations in therapy-related leukemia and myelodysplastic syndrome.

The presence of activated transforming genes was investigated in four patients with therapy-related leukemia and in three with therapy-related myelodysplastic syndrome. DNA of bone marrow cells from six of the patients exhibited transforming activity in the tumorigenicity assay. Five of the six patients who were positive in the tumorigenicity assay contained activated N-ras oncogenes, and three contained activated K-ras oncogenes. Thus, concurrent activation of N-ras and K-ras oncogenes was observed in two patients. In vitro DNA amplification followed by oligonucleotide dot-blot analysis was used to investigate mutations in codons 12, 13, and 61 of the N-ras and K-ras oncogenes. Two patients exhibited an N-ras mutation, substituting aspartic acid (GAT) for glycine (GGT), and three patients exhibited an N-ras codon 13 mutation, substituting valine (GTT) for glycine. Two patients exhibited K-ras codon 12 mutations, substituting aspartic acid (GAT) or cysteine (TGT) for glycine (GGT), respectively, and one case exhibited a K-ras codon 61 mutation, substituting lysine (AAA) for glutamic acid (CAA). Cytogenetic analysis revealed that loss of chromosome 7 was frequent (four patients: 57%). Our data indicate that activation of N-ras and K-ras genes, as well as loss of heterozygosity for specific alleles on chromosome 7, plays a more important role in the leukemogenesis of both therapy-related leukemia and myelodysplastic syndrome.

Aged↗
PubMed1991

The relationship between the site of breakpoints within the bcr gene and thrombopoiesis of Philadelphia-positive chronic myelocytic leukemia.

We determined the position of the breakpoint within the bcr gene in 22 patients with Philadelphia-positive chronic myelocytic leukemia using conventional Southern-blots and analyzed its relationship to thrombopoiesis. After DNA digestion with restriction endonucleases (Hind III, Bam HI and Bgl II), we localized the breakpoint in bcr using two genomic probes. The location of the breakpoint within the bcr was assigned to one of five zones. Breakpoints in zones 1 and 2 were grouped as "5"', and those in zones 3, 4 and 5 as "3'". Thus we subdivided patients with bcr rearrangements into those with genomic breaks at either 5' or 3' of the Bam HI site, just upstream of exon 3. Nine patients had 5' breakpoints and 13 patients had 3' breakpoints. The platelet counts of 3' patients were significantly higher than those of 5' patients (1395 vs 274 x 10(9)/l; p less than 0.03). The megakaryocyte counts from bone marrow histological sections in 3' patients (n = 12) and 5' patients (n = 7) were 63.4/mm2 and 19.5/mm2, respectively, with a significant difference of p less than 0.006. The mean number of megakaryocyte progenitor cells assayed by in vitro cloning was 128.3/2 x 10(5) bone marrow cells for 3' patients (n = 7) compared with 46.3 for 5' patients (n = 4). These results suggest that Philadelphia-positive CML patients with 3' breakpoints have higher thrombopoietic activity than patients with 5' breakpoints.

Adult↗
PubMed1991

Decrease in the specific forms of cytochrome P-450 in liver microsomes of a mutant strain of rat with hyperbilirubinuria.

Eisai-hyperbilirubinuria rats (EHBR) is a mutant originated from Sprague Dawley rats. The activities of UDP-glucuronyltransferase and drug metabolizing enzymes in EHBR were compared with those in Sprague Dawley rats as the control. The activity of aniline hydroxylase was significantly increased in liver microsomes of EHBR whereas the activity of ethylmorphine N-demethylase was found to be significantly decreased in EHBR as compared to control rats. In addition, the activity of testosterone 7 alpha-hydroxylase was increased in EHBR whereas the activity of testosterone 6 beta-hydroxylase was significantly decreased in EHBR as compared to control rats. Western blot analysis of liver microsomes of EHBR with antibodies to P-450IA2, P-450IIB1, P-450IIC11 and P-450IIIA2 showed that the amounts of P-450IIB1 and P-450IIIA2 in liver microsomes were significantly lower in EHBR than in control rats. These results indicated the form-specific alteration in the amounts of cytochrome P-450 in liver microsomes of EHBR.

Aniline Hydroxylase↗
PubMed1990

Anti-thoracic duct lymphocyte globulin stimulates human megakaryocytopoiesis in vitro.

Anti-thoracic duct lymphocyte globulin (ALG) therapy is effective in patients with aplastic anemia. We examined the effect of ALG on human megakaryocyte progenitor cells (colony-forming unit-megakaryocyte, CFU-Meg) in vitro. Normal human bone marrow mononuclear cells (MNC) were cultured in plasma clots with varying concentrations of ALG or non-immunized horse IgG. After 12 days of culture, significant megakaryocyte colony formation was observed in cultures containing ALG but not in cultures containing non-immunized horse IgG. The peak stimulatory effect seemed to occur with 10-25 micrograms/ml of ALG. When marrow MNC, depleted of adherent and T cells, were cultured in plasma clots with ALG, its stimulatory effect on megakaryocytopoiesis decreased markedly. Finally, it was demonstrated that ALG stimulated marrow MNC to produce a factor stimulatory for CFU-Meg. The in vitro megakaryocytopoietic stimulatory effect of ALG may be related to its clinical efficacy in some patients with aplastic anemia.

Antilymphocyte Serum↗
PubMed1990

[Diverse hemostatic abnormalities in a patient with biclonal multiple myeloma].

A 58-year-old female was referred to us because of M-proteinemia and anemia. Bone marrow showed normal cellularity with 14.8% of atypical plasma cells. Serum electrophoresis on cellulose acetate membrane revealed a single M-peak (56.9%). Immunoelectrophoresis showed large M-bows against anti-IgA and anti-lambda, together with small M-bows against anti-IgG and anti-kappa of the same electrophoretic mobility. In the urine, lambda type Bence Jones protein was found. The skull X-ray showed multiple punched out lesions. APTT was 61 seconds, fibrinogen 118 mg/dl, factor VIII clotting activity 25% with normal factor VIII related antigen, and factor IX clotting activity 38%. Circulating anticoagulants were not detected. These hemostatic abnormalities were thought ascribable to the interference of clotting activities by paraproteins. On the 33rd hospital day, she suffered from intracerebral hemorrhage, which was possibly due to these hemostatic abnormalities.

Blood Coagulation Disorders↗
PubMed1990

Clinical usefulness of vinca alkaloid slow infusion in the treatment of chronic refractory idiopathic thrombocytopenic purpura: a multicenter cooperative study.

Thirty-eight patients with chronic refractory idiopathic thrombocytopenic purpura (ITP) were treated with weekly slow infusions of vincristine (0.02 to 0.04 mg/kg) or vinblastine (0.1 to 0.2 mg/kg). Twenty-two patients showed good to excellent responses after one to eight infusions. These responses were generally short, and lasted only in six patients after discontinuance of the therapy. The efficacy was comparable between vincristine and vinblastine. Neither the age, sex, duration of the disease, prior splenectomy nor combined use of adrenocortical steroids was likely to have influenced the therapeutic effect. Side effects such as peripheral neuropathy, alopecia, gastrointestinal symptoms and leukopenia occurred in 34 patients, and necessitated discontinuance of the therapy in eight patients. Slow infusions of vinca alkaloids can be an effective means of inducing platelet response in patients with chronic refractory ITP, but frequent side effects limit its clinical usefulness.

Adolescent↗
PubMed1990

Three stages of differentiation in mouse megakaryocyte progenitor cells (CFU-Meg).

Mouse megakaryocyte colonies developed in a fibrin clot culture system were morphologically classified into three types: immature homogeneous (IH), heterogeneous (H), and mature homogeneous (MH) colonies. The colony size (number of megakaryocytes per colony), the ploidy distribution of megakaryocytes in colonies, and the ratios of their progenitors (megakaryocyte colony-forming units, CFU-Meg) in the S-phase of the cell cycle were compared among the three types. Also, morphological changes in colonies were examined in time sequence. The mode of the number of megakaryocytes per colony on day 6 of culture was greater than 64, between 17 and 32, and between 4 and 8, in IH, H, and MH colonies, respectively. The mean DNA content of megakaryocytes was 3.1N, 4.2N, and 7.2N on day 6 of incubation, in IH, H, and MH colonies, respectively, these values being significantly different from each other (p less than 0.001). The mean proportion of CFU-Meg synthesizing DNA was 21.9%, 26.0%, and 48.6% for CFU-Meg forming IH, H, and MH colonies, respectively (p less than 0.01; IH- versus MH-CFU-Meg and H- versus MH-CFU-Meg). Successive observation of the colony morphology from days 5 to 11 of culture suggested a transformation of the colony types from IH colony to MH colony through H colony. These observations indicate that the three types of megakaryocyte colonies classified on the basis of their morphological features reflect various stages of differentiation of mouse CFU-Meg.

Animals↗
PubMed1989

Partial purification of human urinary megakaryocyte colony-stimulating factor.

Urinary extracts from patients with aplastic anemia are known to promote murine megakaryocytopoiesis. In this report, we show a simple method for the partial purification of megakaryocyte colony-stimulating factor from human urine. A four-step purification procedure, which included ethanol precipitation, CM Affi-Gel Blue chromatography, wheat germ agglutinin-Sepharose chromatography and high-resolution hydroxyapatite chromatography, resulted in an about 430- to 630-fold increase of specific activity. The final fractions were still contaminated with erythropoietin, but the contaminated content of erythropoietin was not enough to stimulate mouse megakaryocytopoiesis in our culture system. We also demonstrate that human urinary extracts stimulated human megakaryocyte colony formation.

Anemia, Aplastic↗
PubMed1989

[Effects of recombinant human alpha-2b and gamma interferons on bone marrow megakaryocyte progenitors (CFU-Meg) from patients with chronic myelocytic leukemia].

The effects of recombinant human interferon (IFN) alpha-2b and gamma on the bone marrow megakaryocyte progenitors (CFU-Meg) were compared between eight patients in the chronic phase of Ph1-positive chronic myelocytic leukemia (CML) and five hematologically normal patients. CFU-Meg was assayed in plasma clot culture added with phytohemagglutinin-stimulated leukocyte-conditioned medium as a source of colony stimulating activity. The average count of CFU-Meg colonies formed from the bone marrow of CML patients was 5.5 times that of normal controls. Spontaneous CFU-Meg colonies were grown in seven of eight CML patients, but in none of five controls. Colony formation by CFU-Meg in CML as well as normal bone marrow was suppressed by the two preparations of IFN in a dose dependent fashion. Their suppressive influence on colonies from CFU-Meg was comparable between CML and normal bone marrow at lower concentrations, but was less marked for CML than normal bone marrow at higher concentrations. The formation of CFU-Meg colonies from CML bone marrow was more severely suppressed by IFN-gamma than IFN-alpha-2b. Depletion of either T lymphocytes or adherent cells from the CML bone marrow cells diminished the suppressive effects of IFN-gamma, but had no influence on the effects of IFN-alpha-2b.

Adult↗
PubMed1989

[Philadelphia-positive acute mixed leukemia with monosomy 7].

A 26-year-old male was admitted to our hospital because of fever and leukocytosis. On admission, a white blood cell count was 28,300/microliters with 46.5% blast cells and 16.0% atypical monocytoid cells, a hemoglobin level 13.7 g/dl, and a platelet count 15.0 X 10(4)/microliters. Bone marrow contained 58.8% of peroxidase-negative blast cells. He was diagnosed as acute lymphoblastic leukemia (ALL L2) according to the FAB classification. Chromosome analysis revealed the marrow cells to contain 45, XY, -7, t(9; 22) (q34; q11). On surface marker analysis, the leukemic cells were positive for both lymphoid (CD10) and myeloid markers (CD13). Two color flow-cytometric analysis showed two distinct populations with CD10 and CD1 3, respectively. Rearrangements of both immunoglobulin heavy chain and T cell receptor beta-chain were observed. The "breakpoint cluster region" on chromosome 22 was not rearranged. On the basis of these findings, we thought this case being acute mixed leukemia. He was refractory to AdVP therapy and BHAC-DMP therapy. He is now under treatment with A-Triple-V therapy.

Adult↗
PubMed1989

Prognosis of chronic thrombocytopenic purpura.

A multicenter prospective study on the treatment of chronic idiopathic thrombocytopenic purpura (ITP), conducted by the Idiopathic Disorders of Hematopoietic Organ Research Committee, the Ministry of Health and Welfare of Japan, is currently in progress. In this study we analyzed the clinical records of 256 patients with chronic ITP in order to define the prognostic factors. As of November, 1988 after a median observation period of 34 months, 174 of the 256 patients (68%) were alive, 11 (4%) dead and 71 (28%) lost to follow-up. Bleeding was a direct cause of death in only one patient. Assessment of the status of patients based on platelet count at the final observation revealed that 48% of patients were in remission, 21% showed improvement, and 31% remained unchanged or worsened. Univariate analyses identified 4 parameters associated with favorable prognosis: presenting platelet count less than 2 x 10(4)/microliters, platelet count greater than 10 X 10(4)/microliters after one-year follow-up, maximal platelet count greater than 10 X 10(4)/microliters during administration of the initial dose of corticosteroids and splenectomy.

Adolescent↗
PubMed1989

A simple method for ultrastructural observation of in vitro hematopoietic and leukemic colonies formed in fibrin- and plasma-clots.

A simple method has been developed for the ultrastructural study of in vitro hematopoietic and leukemic colonies formed in fibrin- or plasma-clots. A technique for selective embedding of the target colony in situ into Epon without picking it up from the semi-solid culture medium was developed. Using this technique, not only the intracellular structure of the cells composing the colonies but also the ultrastructural details of the colonies can be examined without destroying their native structure in situ.

Animals↗
PubMed1989

[RAEB in transformation in continuing complete remission by small doses of cytarabin].

Two patients with refractory anemia with excess of blasts in transformation having entered remission and in continuing complete remission with the small-dose cytarabine therapy (SDCA) are reported. SDCA was the only chemotherapy used in these two patients. Cytarabine was injected subcutaneously every 12 hours at doses 15 mg and 10 mg, respectively, in cases 1 and 2. Case 1, a 60-year-old woman, achieved remission after a 14-day course of SDCA. Thereafter, she received SDCA for seven consecutive days every month or every other months in the first year and every two or three months in subsequent years. Her remission has been maintained for 57 months. Case 2, a 76-year-old man, attained a remission after three courses of SDCA, each consisting of 16, 11 and 14 days, respectively. SDCA was then repeated every month for 6 consecutive days. He is still in remission after 33 months. Whereas SDCA caused severe bone marrow suppression during induction, it was well tolerated when given in remission without necessitating any supportive measure.

Aged↗
PubMed1989

[Successful treatment of secondary erythroleukemia with androgen].

A case of secondary erythroleukemia treated with apparent success with androgen is reported. The patient is 63-year-old Japanese female. She had a history of multiple myeloma and had been treated with melphalan, vincristine and prednisolone. She developed erythroleukemia 88 months after the initiation of chemotherapy, while her myeloma was a complete remission. She was treated first with vitamin D3 with no beneficial effect and subsequently with 0.5 mg/kg of mepitiostane. A hematologic improvement began two months from the initiation of androgen therapy, and a complete remission of erythroleukemia was attained thereafter. A chromosomal abnormality of bone marrow cells, which was observed at the time of developing erythroleukemia, also disappeared after the treatment. She remained in good condition and hematologic remission under the androgen therapy at the latest follow-up, 1-year after the development of erythroleukemia. Androgen therapy may be considered as a useful treatment for secondary erythroleukemia.

Androstanols↗