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Biomedical subjects

K Hirashima

Publications and source records attributed to K Hirashima.

At least 73 records · Page 4Linked to original sources
PubMed1994

[Effects of subcutaneous administration of erythropoietin on autologous blood predonation in open heart surgery: Japanese multicenter double-blinded dose-study].

The effects of subcutaneous administration of recombinant human erythropoietin (EPO) on harvesting autologous blood predonation (ABP) and decreasing homologous blood transfusion (HBT) in open-heart surgery were examined prospectively in 132 patients treated in a 32-institute multicenter study. Single doses of 6000, 12,000, 18,000 and 24,000 unit (IU) of EPO with intravenous iron (40 mg) were administered once a week for 3 weeks with ABP (400 ml/week) before surgery. ABP volume (ml), change of blood hemoglobin level (C-Hb), preoperative net blood hemoglobin increase (delta Hb [g/dl] including ABP, perioperative blood loss (ml), and HBT rate, were as follows; [table: see text] Preoperative reduction of Hb (C-Hb) was less in administration dose of 18,000 IU and 24,000 IU than 6000 IU (p < 0.05). The increase of delta Hb was highest in 18,000 IU and HBT rate was lowest in administration dose of 24,000 IU, however, there was no statistical difference. In conclusion, both 18,000 IU and 24,000 IU of EPO treatment is effective to minimize the progression of anemia according to ABP for open heart surgery.

Blood Transfusion, Autologous↗
PubMed1993

Differentiation-dependent expression of sialyl stage-specific embryonic antigen-1 and I-antigens on human lymphoid cells and its implications for carbohydrate-mediated adhesion to vascular endothelium.

Expression of two developmentally regulated carbohydrate antigens, the sialyl stage-specific embryonic antigen-1 (SSEA-1) and I-antigens, in human lymphocytes and lymphocytic leukemia cells was investigated using specific monoclonal antibodies. Sialyl SSEA-1 was expressed only on natural killer (NK) cells, and was essentially absent on resting mature T and B cells among normal peripheral lymphocytes. On the other hand, the I-antigen was strongly expressed on virtually all mature B cells, moderately expressed on most mature T cells, but not expressed on NK cells in normal donors. Expression of the two antigens on normal T and B cells was reversible; in vitro stimulation of normal lymphocytes with concanavalin A (Con A) resulted in the loss of I-antigen and appearance of sialyl SSEA-1 on CD3+ T blasts, whereas stimulation with pokeweed mitogen led to loss of I-antigen expression and appearance of sialyl SSEA-1 antigen on CD19+ B blasts. Among lymphocytic leukemia cells, sialyl SSEA-1 was detected primarily on leukemia cells having immature properties such as most common acute lymphocytic leukemia (cALL) blasts, while the I-antigen was frequently expressed on malignant cells having relatively mature properties, such as those found in adult T-cell leukemia or chronic lymphocytic leukemia, and only occasionally on cALL blasts. Among normal peripheral lymphocytes, the sialyl SSEA-1+I-antigen- NK cells selectively underwent E-selectin (ELAM-1, endothelial-leukocyte adhesion molecule-1)-dependent adhesion to endothelial cells, while the I-antigen+sialyl SSEA-1- mature T and B cells did not, in line with the recent finding that sialyl SSEA-1 serves as a specific ligand for E-selectin. Con A blasts, which are sialyl SSEA-1+I-antigen-, also exhibited significant E-selectin-dependent adhesion to endothelial cells. These results indicate that expression of the sialyl SSEA-1 and I-antigens varies alternately depending on the differentiation/activation status of the lymphocytes, and that this at least partly regulates the behavior of lymphocytes at the vessel wall.

Antibodies, Monoclonal↗
PubMed1993

Detection of monoclonal hematopoiesis using restriction fragment length polymorphism (RFLP) of phosphoglycerokinase (PGK) gene in a patient with hypoplastic myelodysplastic syndrome (MDS).

A clonal analysis of hematopoiesis in a hypoplastic MDS patient was performed. Monoclonal utilization of PGK gene on her two X chromosomes was detected by Southern blot analysis of the bone marrow cells using a PGK probe after methylation-sensitive restriction enzyme treatment. This is compatible with monoclonal construction of her hematopoiesis, confirming MDS nature with a progression of her morphological dysplasia in bone marrow cells. RFLP of PGK gene on X chromosome is thus useful to detect a monoclonality in hematopoietic diseases.

Adolescent↗
PubMed1993

A clonal study of hematopoiesis using the M27 beta probe: aberrant band patterns caused by incomplete digestion of a methyl-sensitive enzyme in the the inactive X-chromosome.

The M27 beta probe has been used to determine the clonality of human tumors, based upon X-chromosome inactivation. However, it occasionally gives rise to aberrant results. In this study, the M27 beta probe was used for clonal analysis in Japanese women with clonal stem cell disorders and in those with normal hematopoiesis. Restriction digestion with PstI indicated heterozygosity for the DXS255 locus in 41 out of 50 individuals (82%). Further digestion with HpaII in heterozygous women led to four distinct band patterns: I, both fragments were partially digested; II, either one of the two fragments was completely digested; III, a three-band pattern; and IV, neither fragment was digested. Of 21 hematologically normal females, 17 (81%) and four (19%) had patterns I and III, respectively. In some subjects with pattern I, imbalanced HpaII digestion in the two alleles was seen. Fifteen (65%) of the 23 patients with clonal stem cell disorders had pattern II, while the remainder (35%) had pattern IV. The normal tissues of three acute myeloid leukemia patients with pattern IV all revealed pattern I. It is possible that the aberrant band patterns could be caused by incomplete HpaII digestion in inactive X-chromosomes. In this study, we propose a hypothesis whereby, in normal tissues, aberrant cells, the DXS255 locus of which is not digested with HpaII despite their inactive status, would be mixed with cells demonstrating the usual methylation pattern. In normal tissues, complex of proportion of aberrant cells and skewed Lyonization could produce a variety of band patterns. If a cell with the usual methylation pattern proliferated monoclonally, pattern II would be seen: whereas if an aberrant cell proliferated, pattern IV would be demonstrated.

Blotting, Southern↗
PubMed1993

Clinical and cytogenetic findings of myelodysplastic syndromes showing hypocellular bone marrow or minimal dysplasia, in comparison with typical myelodysplastic syndromes.

Hematologic and cytogenetic data were collected on 401 myelodysplastic syndromes (MDS) patients in Japan and their clinical relevance was analyzed. More than 50% of the MDS patients with hypocellular bone marrow had > 5% marrow blasts at the time of MDS diagnosis and frequently had complex aberrations (chromosome changes at three or more regions). They showed peripheral blood findings resembling those of aplastic anemia, but progression into leukemic phase and the prognosis tended to mimic typical MDS. In MDS patients with minimal dysplasia, hematologic parameters were different from those of aplastic anemia. However, the low incidence of leukemic transformation and the favorable prognosis was similar to that of aplastic anemia. More than 90% of the patients in this group had refractory anemia and had normal karyotypes. Thus differential diagnosis from a low grade aplastic anemia is important, since this type of MDS might have a clonal nature as well. In conclusion, although some hematologic and clinical deviations are noticed in MDS with hypocellular marrow or minimal dysplasia, these MDS subtypes might constitute marginal forms of MDS.

Adult↗
PubMed1993

[Clinical evaluation of combination therapy with sulbactam/cefoperazone and amikacin sulfate for infections associated with hematological disorders].

We evaluated the efficacy and safety of combination therapy with sulbactam/cefoperazone (SBT/CPZ) and amikacin sulfate (AMK) in severe infections associated with hematological disorders. The clinical efficacy rate in 82 evaluable patients was 70.7%. The efficacy rate in sepsis from which causative organisms were isolated was high, 75% (3/4). No significant difference was found between those cases for which no previous antibiotic therapies were made and those for which antibiotic therapies were done and changed to the combination during the course of the therapies. No side effects nor substantial abnormal laboratory test results attributable to the test drugs were observed. From these observations, we have concluded that the combination therapy with SBT/CPZ plus AMK is a very useful empiric therapy for severe infections associated with hematological disorders.

Adolescent↗
PubMed1993

Clinical implications of chromosomal abnormalities in 401 patients with myelodysplastic syndromes: a multicentric study in Japan.

It is well known that cytogenetic analysis in patients with myelodysplastic syndrome (MDS) provides information useful in determining their prognosis. Based on the chromosomal results obtained from 401 MDS patients by a multicentric study in Japan, we studied correlations between chromosomal findings and prognosis or leukemic transformation in MDS patients. Patients with complex aberrations (cytogenetic abnormalities at more than three chromosomes), of any subtype, had a poor prognosis; for example, > 60% of patients with refractory anemia (RA) showing complex aberrations died within one year, but only 11% of them developed leukemia. In patients with RA with ringed sideroblasts (RARS), > 70% of those with complex aberrations evolved into the leukemic phase and survived for less than one year, suggesting a biologic heterogeneity in RARS patients. By contrast, about 5% of patients with RA or RARS exhibiting chromosomal findings other than -7/7q-, +8, two aberrations, and complex aberrations, developed leukemia and had a favorable prognosis. Therefore, the presence of chromosome abnormalities alone in patients with RA or RARS is not a factor in predicting leukemic transformation or poor prognosis. In patients with refractory anemia with an excess of blasts (RAEB), the presence of chromosome aberrations at MDS diagnosis affected the occurrence of leukemic transformation (24% versus 43%), however, no particular difference was noted in patients with RAEB in transformation with regard to whether they had chromosome changes or not, and about 60% of them evolved into leukemia. The poor prognosis related to complex aberrations was consistently noted in all MDS subtypes or age-matched groups, indicating that this cytogenetic anomaly is an independent risk factor for a poor prognosis in MDS patients. The duration between MDS diagnosis and development of the leukemic phase and that between the latter and death were significantly shorter in patients with complex aberrations than those without this change. Although the clinical significance of certain chromosomal abnormalities differs among subtypes of MDS, a new scoring system for predicting prognosis by cytogenetic changes, in combination with hematologic parameters, was proposed.

Adolescent↗
PubMed1992

A hematological remission by clonal hematopoiesis after treatment with recombinant human granulocyte-macrophage colony-stimulating factor and erythropoietin in a patient with therapy-related myelodysplastic syndrome.

We treated a patient with therapy-related myelodysplastic syndrome (MDS) with human recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (Epo). The patient achieved a hematological remission which continued for more than 16 months despite discontinuation of the treatment. Before the treatment with GM-CSF and Epo the patient had severe pancytopenia, required frequent red cell transfusions, and experienced episodes of severe infection, but after the therapy he no longer needed transfusion and no longer had the infection. While the patient remained in hematological remission, bone marrow examination revealed trilineage dysplasia, and cytogenetic analysis showed an abnormal karyotype [48, XY, +8, +der(1q5p)] in 100% of the metaphases examined. These findings suggest that the hematological remission of this patient may not result from the recovery of the non-clonal hematopoiesis of a normal clone, but result from the monoclonal hematopoiesis of a neoplastic clone.

Blood Cell Count↗
PubMed1992

Treatment of hairy cell leukemia with deoxycoformycin (YK-176). The Deoxycoformycin (YK-176) Study Group.

Eleven patients with hairy cell leukemia (HCL) were treated with YK-176 (2'-deoxycoformycin) at a dose of 5 mg/m2 by intravenous injection every week or every other week. Patients received a median of eight (range 4-19) injections of YK-176. Five patients had previously been untreated, four of whom had massive splenomegaly. Six patients had previously been treated, four with interferon-alpha (IFN-alpha) or IFN-alpha and chemotherapy and two with prednisolone. Two patients had had splenectomies. Five patients achieved complete remission (CR) and six, partial remission (PR) according to WHO criteria (remission rate 100%, 95% confidence interval (CI) 74-100%). All six neutropenic patients recovered > 1,500/microliters neutrophils, six of seven anemic patients recovered > 12.0 g/dl hemoglobin and five of nine thrombocytopenic patients recovered > 100,000/microliters platelets following the treatment. According to the response criteria for HLC, five patients achieved CR, two PR and four minor response. The overall remission (CR + PR) rate was 64% (95% CI 35-85%). The CR and PR have lasted from > 30 to > 718 days (median, > 281 days) so far with no relapses. Of four patients previously treated with IFN-alpha, two achieved CR and one, PR. All patients were alive with a median survival time of > 290 days from treatment (range > 50- > 763 days). The treatment was generally well tolerated. Mild to moderate nausea, vomiting, appetite loss and general fatigue were experienced in two patients, skin rash in one and a transient fever in three. YK-176 was a highly active agent in the treatment of HCL.

Adult↗
PubMed1992

[Splenic lymphoma of Ki-1 positive B-cell type treated with CHOP].

A 75-year old man was admitted to our hospital by complaining of his left supraclavicular lymphadenopathy. Physical examination also revealed splenomegaly and cervical lymphadenopathy. An abdominal CT scan showed paraaortic lymphadenopathy and splenomegaly with multiple low density area. A pathological diagnosis of Ki-1 lymphoma was made by the biopsied supraclavicular lymph node because the node consists of large cells with clear cytoplasms and conspicuous nucleoli and large cells were positive for IgM, lambda, CD20 and CD30 (Ki-1). The primary lesion of lymphoma was suspected to be spleen because of the radiological finding of the spleen. The patient responded to systemic chemotherapy (CHOP) with complete remission. Pathological and clinical characteristics of this B-cell Ki-1 lymphoma were discussed.

Aged↗
PubMed1992

Interleukin-3 and granulocyte colony-stimulating factor as survival factors in murine hemopoietic stem cells in vitro.

We examined the role of various hemopoietic factors in the survival of hemopoietic stem cells in methylcellulose culture. Bone marrow cells from 5-fluorouracil (5-FU)-treated mice were cultured without hemopoietic factors. Several days later, a mixture of colony-stimulating factors (CSF interleukin-3 (IL-3), interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), and erythropoietin (Ep)) was added to the culture (delayed addition of CSF) to induce the maximal colony growth in surviving progenitors. In this system few colonies grew, suggesting that some hemopoietic factors are required for the survival of hemopoietic stem cells in vitro. In a further series of experiments, similar cultures were initiated with single known hemopoietic factors or with a mixture of CSF, followed by the addition of CSF 7 days later. Although IL-3 and G-CSF, as single factors, supported colony growth, the other factors did not. In this experiment, while the total number of colonies in cultures initiated with IL-3 or G-CSF was less than that observed in cultures initiated with a mixture of CSF, the number of multipotential GEMM (granulocyte-erythrocyte-macrophage-megakaryocyte) colonies remained constant. We concluded that IL-3 and G-CSF played important roles as single factors in the survival of murine dormant hemopoietic stem cells in vitro.

Animals↗
PubMed1992

Effect of human recombinant erythropoietin on reduction of homologous blood transfusion in open-heart surgery. A Japanese Multicenter study.

BACKGROUND: Recombinant human erythropoietin (EPOCH) has been shown to increase erythropoiesis; therefore, EPOCH has been used in conjunction with autologous blood predonation (ABP) before surgery. However, the administration methods of EPOCH to obtain an adequate volume of ABP before open-heart surgery have not been determined. METHODS AND RESULTS: The effects of EPOCH on harvesting ABP and decreasing homologous blood transfusion (HBT) in open-heart surgery were examined prospectively in 205 patients treated in a 29-institute multicenter study. Single dose of 3,000, 6,000, or 9,000 IU of EPOCH were administered for 2 weeks (two or three times per week) without ABP (group 1, n = 69) or for 3 weeks (two or three times per week) with ABP (group 2, n = 97) and compared with control subjects (n = 39). Preoperative blood hemoglobin increase (delta Hb[g/dl]) was < 1.0 g/dl in group 1. When EPOCH was given three times a week, the delta Hb in each subgroup of group 2 was 0.6 +/- 1.1 (control), 2.1 +/- 1.3 (3,000 IU), 2.4 +/- 1.4 (6,000 IU), and 2.8 +/- 1.5 (9,000 IU), which was significantly higher than the control (p < 0.05) and was dose dependent. The HBT rates in patients with a moderate perioperative blood loss of between 15 and 50 ml/kg were 75.0% (control), 35.7% (3,000 IU), 52.9% (6,000 IU), and 66.7% (9,000 IU) in group 1, and respective volumes in group 2 were 40.0% (control), 20.0% (3,000 IU), 26.9% (6,000 IU), and 12.5% (9,000 IU). The overall HBT rate of EPOCH-treated patients with a moderate blood loss was 50% (20 of 40) in group 1 and 21% (13 of 62) in group 2. The HBT rate was significantly reduced by combination of preoperative EPOCH treatment (three times per week) and ABP (p < 0.0001). CONCLUSIONS: Dose-dependent increase of blood hemoglobin level was observed by EPOCH treatment with ABP; combination of EPOCH treatment and ABP can reduce HBT during open-heart surgery.

Blood Transfusion↗
PubMed1992

[Regulation of proliferation and differentiation of hematopoietic cells by cytokines].

Recent studies on the hematopoietic system have revealed that both constitutive and inducible hematopoiesis are regulated by complicated networks composed of various kinds of cytokines and that there are some general rules for hematopoietic cytokine biology. Further accumulation of knowledge about the regulation of proliferation and differentiation of hematopoietic cells by cytokines will serve to clarify the pathophysiology of hematological diseases, resulting in the development of therapeutic strategy for these diseases.

Cell Differentiation↗
PubMed1991

Enhancement by transforming growth factor-beta 1 (TGF-beta 1) of the proliferation of leukemic blast progenitors stimulated with IL-3.

We studied the effect of transforming growth factor-beta 1 (TGF-beta 1) on colony formation of leukemic blast progenitors from ten acute myeloblastic leukemia (AML) patients stimulated with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), interleukin-6 (IL-6), or interleukin-1 beta (IL-1 beta). These CSFs and interleukins by themselves stimulated the proliferation of leukemic blast progenitors without adding TGF-beta 1. G-CSF, GM-CSF, and IL-3 stimulated blast colony formation in nine patients, IL-6 stimulated it in five, and IL-1 beta stimulated in four. TGF-beta 1 significantly reduced blast colony formation stimulated by G-CSF, GM-CSF, or IL-6 in all patients. In contrast, TGF-beta 1 enhanced the stimulatory effect of IL-3 on blast progenitors from three cases, while in the other seven patients TGF-beta 1 reduced blast colony formation in the presence of IL-3. To study the mechanism by which TGF-beta 1 enhanced the stimulatory effect of IL-3 on blast progenitors, we carried out the following experiments in the three patients in which it occurred. First, the media conditioned by leukemic cells in the presence of TGF-beta 1 stimulated the growth of leukemic blast progenitors, but such effect was completely abolished by anti-IL-1 beta antibody. Second, the addition of IL-1 beta in the culture significantly enhanced the growth of blast progenitors stimulated with IL-3. Third, leukemic cells of the two patients studied were revealed to secrete IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) constitutively; the production by leukemic cells of IL-1 beta and TNF-alpha was significantly promoted by TGF-beta 1. Furthermore, the growth enhancing effect of TGF-beta 1 in the presence of IL-3 was fully neutralized by anti-IL-1 beta antibody. These findings suggest that TGF-beta 1 stimulated the growth of blast progenitors through the production and secretion of IL-1 beta by leukemic cells.

Aged↗