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Biomedical subjects

K Hirashima

Publications and source records attributed to K Hirashima.

At least 109 records · Page 6Linked to original sources
PubMed1990

Prophylactic and therapeutic effects of oral administration of amphotericin B in mycosis associated with hematologic diseases. Study Group of Mycosis in Hematologic Disease.

The prophylactic and therapeutic effects of the oral administration of amphotericin B (AMPH) to patients with deep mycosis associated with hematologic diseases were evaluated in an investigation including determination of serum concentrations of the antibiotic. Prophylactic effects were examined in 111 subjects, and the efficacy rates averaged 83.8% at daily doses from 1,200 to 4,800 mg. The efficacy was significantly higher at a dose of 2,400 mg/day than at a dose of 1,200 mg/day (P less than 0.05). The efficacy rate tended to be higher when the length of administration period was 1 month or more. The percentage of the number of days of fever by neutrophil count was significantly less at a daily dose of 2,400 mg than at 1,200 mg in patients with neutrophil count of 1,000 cells/mm3 or less (P less than 0.001). The safety was evaluated in 131 subjects, and adverse effects were found in only 2 cases of nausea for an incidence rate of 1.5%. Therapeutic effects were studied in 12 cases, and efficacy rates averaged 58.3% at daily doses from 2,400 to 7,200 mg. Adverse effects consisted of 1 case of diarrhea among 15 subjects who were evaluated for the safety for an incidence rate of 6.7%. The serum concentrations of the antibiotic were examined in 60 of the prophylactic and therapeutic subjects. Average concentrations of AMPH at 4 hours after the first daily dose of 1,200, 2,400 and 4,800 mg were 0.040, 0.053 and 0.078 micrograms/ml, respectively. Concentrations gradually increased thereafter and reached averages of 0.089, 0.090 and 0.132 micrograms/ml, respectively, for the 3 dose levels on the 7th day. These results indicated that there were no serious adverse effects and serum concentrations were above the Candida MIC values at daily prophylactic and therapeutic doses of 1,200 to 7,200 mg of AMPH. Based on these findings, this drug can be expected to show prophylactic and therapeutic effects with safety in cases of deep mycosis.

Administration, Oral↗
PubMed1990

[Aspergillosis of the maxillary sinus in a patient with Ph1 positive acute lymphoblastic leukemia: a case report].

A 46-year-old woman was admitted to our hospital because of leukocytosis. A diagnosis of acute lymphoblastic leukemia (FAB: L2 type) was made by reviewing peripheral blood smear and bone marrow aspirate. Chromosome analysis showed the presence of Philadelphia chromosome. A combination chemotherapy with L-asparaginase, doxorubicin, vincristine, and prednisolone was started, but complete remission was not achieved. During a neutropenic period after combination chemotherapy with doxorubicin, vincristine, vinblastine, and VP-16, high fever and tender swelling of the right cheek were noticed. A diagnosis of maxillary sinusitis was made with tomography and CT scan of the maxillary sinus. Since culture of the aspirate from the maxillary sinus grew aspergillus, a diagnosis of aspergillosis of the maxillary sinus was made. Immediately after the intravenous administration of amphotericin B and the lavage of the sinus with amphotericin B was started, high fever subsided and clinical improvement was observed. Several regimens of chemotherapy failed to obtain hematological remission, she died of sepsis of Enterobactor cloacae without evidence or relapse of dissemination of aspergillosis after initial successful treatment. While a few cases with aspergillus maxillary sinusitis were reported in leukemic patients, the possible occurrence of this complication must be kept in mind in a severe neutropenic period after intensive chemotherapy. The combination of intravenous administration and local lavage of amphotericin B appeared to be an effective treatment in the Aspergillus maxillary sinusitis.

Amphotericin B↗
PubMed1989

Prolonged survival of mice with myeloid leukemia by subcutaneous injection of recombinant human G-CSF.

We studied the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on leukemia development and survival of mice with leukemia by using a radiation-induced myeloid leukemia cell line (C2M) with A-type phosphoglycerate kinase (PGK) as marker isoenzyme. C3H/He mice with B-type PGK were inoculated with 2 x 10(6) C2M cells through the tail vein. From the next day, they received a daily subcutaneous injection of 1 microgram rhG-CSF or control solution. The survival of rhG-CSF-treated recipients of C2M was significantly longer than control-solution-treated recipients. In rhG-CSF-treated recipients, not only spleen weight but also the number of blasts in hemopoietic organs was less than those in control recipients. While there was a remarkable decrease in bone marrow content of CFU-GM in control recipients, the content in rhG-CSF-treated recipients was comparable to that in normal mice. A reduced bone marrow and spleen content of leukemic colony-forming cells (L-CFU) was observed in rhG-CSF-treated recipients in comparison with control recipients. The electrophoretic analysis of PGK phenotypes of hemopoietic organs indicated the delayed appearance of A-type PGK from C2M cells in rhG-CSF-treated recipients. From these findings, we concluded that the injection of rhG-CSF delayed the onset of leukemia and improved the survival and several hematological parameters by suppressing C2M cells in recipient mice.

Animals↗
PubMed1989

Effects of recombinant human granulocyte colony stimulating factor (rG-CSF) on murine myeloid leukemia: stimulation of proliferation of leukemic cells in vitro and inhibition of development of leukemia in vivo.

We have established an experimental murine myeloid leukemia model and investigated the effects of recombinant granulocyte colony stimulating factor (rG-CSF) on myeloid leukemia in vitro and in vivo. rG-CSF stimulated colony formation by the leukemic cells in semisolid agar medium, and exponential growth of the clonogenic cells in suspension medium. Thus, rG-CSF was able to stimulate both the differentiation and self-renewal processes of the leukemic stem cells in vitro. However, 14 consecutive daily injections of rG-CSF prolonged the mean survival time of the mice implanted with the leukemic cells. This effect of rG-CSF was accompanied by a delay in the emergence of the blast cells in peripheral blood and by a decreased blast population in the spleen, suggesting that development of leukemia was suppressed in the rG-CSF-treated-mice. The prolongation of the survival time by rG-CSF was more evident when rG-CSF was administered in therapeutic combination with cyclophosphamide. These results indicate that the effect of rG-CSF on the development of leukemia is not exactly predicted from in vitro experiments.

Animals↗
PubMed1989

Effects of recombinant human G-CSF and GM-CSF on primary human leukemic cells.

The effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on primary human leukemic cells were studied. Phagocyte-depleted mononuclear cells containing more than 88% blasts were obtained from peripheral blood of 11 AML and 2 ALL patients and from bone marrow aspirates from 2 ALL patients. The leukemic cells were incubated with these CSF in suspension cultures or in methylcellulose cultures. In suspension cultures, the spontaneous proliferation was observed in 1 M4 patient. RhG-CSF stimulated the leukemic cell proliferation in 5 AML, cases and rhGM-CSF that in 4 AML cases. In methylcellulose cultures, spontaneous colony formation occurred in 3 M4 patients. RhG-CSF and rhGM-CSF stimulated the leukemic colony formation in 8 AML cases. The CSFs had an additive effect in both cultures. Neither CSF induced O2- production or phagocytic activity. From these results, we concluded that both CSFs stimulated the proliferation of leukemic cells without inducing differentiation.

Acute Disease↗
PubMed1989

[Analysis of VH genes which encode the variable region of monoclonal antibodies directed to cancer-associated carbohydrate antigens].

Immune responses against cancer-associated, carbohydrate antigens are investigated by studying idiotypic determinants of specific antibodies with monoclonal anti-idiotypic antibodies, and by analyzing the structure of VH genes which encode the V region of the anti-carbohydrate antibodies. Four syngenic anti-idiotypic antibodies towards monoclonal antibodies which are specific to the sialyl Lewis A antigen and two kinds of SSEA-1 related antigens (sialyl SSEA-1 and fucosul SSEA-1) were obtained. Antibodies directed to carbohydrate antigens were mostly of IgM isotype, indicating these antigens are T-independent antigens, while anti-idiotypic monoclonal antibodies directed to those antibodies were mostly of IgG isotype, suggesting that T cells participate actively in the anti-idiotypic response. The Northern blotting analysis of VH genes of monoclonal antibodies directed to negatively-charged carbohydrate antigens such as gangliosides or sulfated glycolipids expressed the VH gene family J558 (group 1), followed by J606 (group 6) and Q52 (group 2) families. On the other hand, monoclonal antibodies directed to SSEA-1 related neutral carbohydrate antigens expressed VH genes of a minor family such as X24 (group 4), V31 (group 9), or 7183 (group 5). The same VH family as expressed in anti-SSEA-1 antibody (x24) was also expressed in the antibodies such as anti-i and anti-I antibodies, which are directed to the synthetic precursors of the SSEA-1 antigen. In either case, the antibodies directed to one particular carbohydrate antigen tended to express the VH gene of one particular family exclusively. This suggests idiotypic homogeneity of the anti-carbohydrate antibodies.

Animals↗
PubMed1989

Sialyl SSEA-1 antigen as a carbohydrate marker of human natural killer cells and immature lymphoid cells.

The distribution of a carbohydrate antigen, the sialyl SSEA-1 (sialyl Lex-i), in human lymphoid cells was investigated by flow cytometry with a specific monoclonal antibody, MoAb FH-6. We concluded that the lymphocytes positive for the sialyl SSEA-1 antigen present in normal peripheral blood (PB) are natural killer (NK) cells since the positive cells had an NK activity toward K562 cells, and most of the sialyl SSEA-1+ cells were simultaneously positive for Leu-11 (CD-16) and Leu-19. Essentially, no T and B cells, defined by Leu-4 (CD3) and Leu-16 (CD20), were positive for the sialyl SSEA-1 antigen in PB samples taken from healthy donors and patients with disorders unrelated to lymphoid malignancies. Among the malignant lymphoid cells, many sialylated SSEA-1+ cells were observed in large granular lymphocyte (LGL) leukemia cells and some acute lymphoblastic leukemia (ALL) blasts, but not in CLL cells or malignant lymphoma cells. Sialyl SSEA-1 was also positive in some cultured human lymphoid cell lines. We conclude that expression of the sialyl SSEA-1 antigen is strictly limited to a distinct population of NK cells among the mature lymphocytes in normal PB, but the antigen is present in a wide range of immature lymphoblasts of T- and B-cell lineages as well as the NK-cell lineage. The sialyl SSEA-1 antigen disappears from the surface of immature lymphocytes of T- and B-cell lineages during the course of maturation.

Antibodies, Monoclonal↗
PubMed1989

[1 alpha(OH) D3 (Alfarol) is effective for the treatment of chronic B cell leukemia: a case report].

We reported a case of chronic B-cell leukemia reacted to the administration of 1 alpha (OH)D3 (Alfarol-CHUGAI Pharm. Co.), The patient showed pancytopenia with IgM-kappa type monoclonal protein in the serum. The bone marrow aspiration was failed due to a dry tap, but the biopsied specimen showed a marked infiltration of small sized lymphoid cells with wide cytoplasm. The leukemic cells from peripheral blood showed a morphology of atypical hairy cells, Surface markers of the leukemic cells were IgM, D(kappa)+, CD 19+, CD 20+, CD 21- and HLADR+, The leukemic cells showed no L-tartrate resistant acid phosphatase sensitivity. This case was diagnosed as a chronic B-cell leukemia closely related to a hairy cell leukemia. The treatment with estrogen-chlorambucil compound (Bestrabucil-KUREHA Chem, Co.) or splenic irradiation was not effective. However, after two months' administration of Alfarol the regular blood transfusion was not needed because of increment of the Hb concentration. After eight months of its administration, the bone marrow aspirate showed a marked decrease in the number of the leukemic cells and a restoration of normal hematopoietic cells. This experience suggested that Alfarol in usefull for the treatment of chronic B cell leukemia including hairy cell leukemia and chronic lymphocytic leukemia.

Aged↗
PubMed1989

[Clinical application of cancer-associated carbohydrate antigens in the diagnosis and therapy of human cancers].

Cell surface carbohydrates are important cancer-associated antigens. The carbohydrate antigens which have been proved to be useful for the serum diagnosis of human cancers are classified from their biochemical primary structure into three categories; the type 1 chain antigens, type 2 chain antigens, and core structure-associated antigens. The SPan-1 antigen, the newly-introduced tumor marker for human pancreas cancers, seems to be a type 1 chain antigen, judging from its distribution pattern among human cancers and its good correlation with other type 1 chain antigens. Another newly-introduced tumor marker, the CA54/61 antigen, which is specific for ovarian cancers, seems to belong to the family of the core-structure-associated antigens, since both antibodies (MA54 and MA61) used for the detection of the CA54/61 antigen are shown to recognize the antigen molecule which is closely related to sialyl Tn antigen, the well-known carbohydrate core structure of mucins. There are two approaches for the therapy of human cancers employing carbohydrate antigens as target molecules. One is the direct application of the specific monoclonal antibodies (alone, or in the drug-conjugated forms) in cancer patients. In this case, special attention is paid to the use of murine antibodies in human patients. The other approach is to induce specifically an effective immune response against the cancer-associated carbohydrate antigens. For this approach, further methodological development is necessary to determine how to obtain an effective immune response to carbohydrate antigens, since they have long been known as very poor immunogens which are T-independent.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1988

Fucosylated type-2 chain polylactosamine antigens in human lung cancer.

Four specific monoclonal antibodies (MAbs) have been used to study distributions of fucosylated type-2 chain polylactosamine antigens, Lex, poly Lex, Ley and sialylated Lex-i antigens, in human lung cancer tissues and in the serum of patients with lung cancers. Radioimmunoassay frequently showed abnormally high antigen levels in the sera of 66 lung cancer patients tested. When histological typing was performed, high serum levels of the above 4 antigens were most frequently observed in patients with adenocarcinoma of the lung; i.e., after combining the results from the 4 antigens, 75% of the sera from patients with lung adenocarcinoma were positive (50% in the case of large-cell carcinoma, 30% in the case of squamous-cell carcinoma and 27% for small-cell carcinoma). Among the 4 antigens, the sialylated Lex-i antigen had the highest positive incidence, 58%, in the sera of patients with adenocarcinoma of the lung, compared to 33% for Ley, 29% for poly Lex, and 8% for Lex antigen. On the other hand, when the distributions of these antigens in the lung cancer tissues of 42 patients were studied by immunohistological techniques, the Ley antigen had the highest positive incidence, 100%, in lung adenocarcinoma tissues, poly Lex antigen had 86%, sialylated Lex-i antigen had 71%, and Lex antigen had 29%. In cancer tissues, the incidence of non-sialylated antigens, such as Ley, poly Lex and Lex antigens, often exceeds the positive incidence of the sialylated antigen, but the sialylated form of the antigen, such as sialylated Lex-i antigen, appears more often than the non-sialylated form in patients' sera.

Adenocarcinoma↗
PubMed1988

A new cell line of murine myeloid leukemia with A-type phosphoglycerate kinase as marker isoenzyme.

A new murine myeloid leukemia cell line (C2M) with A-type phosphoglycerate kinase (PGK) as marker isoenzyme was established from myeloid leukemia which arose in a female C3H/He strain mouse of the genotype Pgk-1a/Pgk-1b 1 yr after a whole body X-irradiation of 3 Gy. Cytochemical stainings indicated that C2M cells had myelomonocytic characteristics. Chromosomal analysis showed the partial deletion of No. 2 chromosome. Intravenous injection of C2M cells resulted in the development of myeloid leukemia in syngeneic mice owing to the growth of C2M cells. When C2M cells were transplanted to C3H/He mice with B-type PGK, PGK of spleen expressed two bands on electrophoresis; A-type PGK from transplanted C2M cells and B-type PGK from recipient mice, and the density of A-type PGK became prominent as the disease progressed. When granulocyte/macrophage progenitor cells of bone marrow cells from leukemic mice were cultured, two types of colonies were observed. By determining PGK types of the colonies, leukemic colonies could be differentiated from normal granulocyte/macrophage colonies. Since C2M cell line has an advantage of processing A-type PGK which can be readily distinguished by the electrophoresis from normal cells, it will serve as a useful tool to study the interaction between leukemic cells and normal hematopoietic cells.

Animals↗
PubMed1988

Heritable rare fragile sites in patients with leukemia and other hematologic disorders.

Fragile site studies were performed on a total of 126 patients with leukemia and other hematologic disorders including myelodysplastic syndrome (MDS) and polycythemia vera (PV). Compared with an incidence (6.0%) of heritable rare fragile sites in the healthy population, the frequency was not higher in the patient group (3.2%), as a whole. However, two cases of fra(17)(p12) in MDS appeared fourfold larger than expected for this group of patients. In one case, a homozygous carrier of fra(17)(p12) in PV was also very rarely expected from its population incidence. These findings suggested a possible role of rare fragile sites, at least in the etiology of these preleukemic or myeloproliferative disorders.

Adult↗
PubMed1987

Clonal origin of radiation-induced myeloid leukemia in mice with cellular mosaicism.

The clonal origin of radiation-induced myeloid leukemia was studied in mice with cellular mosaicism for phosphoglycerate kinase (PGK). A single whole-body X-irradiation of 3 Gy resulted in development of 11 myeloid leukemias in 198 mosaic mice (5.6%). PGK of spleen cells from 9 myeloid leukemias assayed gave only a single band on electrophoresis. PGK of red blood cells (RBC) from one myeloid leukemia gave a single band identical to that of PGK of leukemic cells, while PGK of RBC from 4 other myeloid leukemias gave two bands. From these results, we concluded that radiation-induced myeloid leukemias in mice were of single cell origin, and that the origin of some myeloid leukemias might be a progenitor cell capable of differentiating into both erythroid and myeloid series.

Animals↗
PubMed1987

Hairy cell leukemia in Japanese patients: a study with monoclonal antibodies.

Using a panel of monoclonal antibodies and three anti-hairy cell sera (alpha HC1 and alpha HC2 of Posnett and 4B122 prepared by the authors), hairy cells were phenotyped on frozen sections of cell pellets from blood and spleen of 11 Japanese patients with hairy cell leukemia (HCL). The results were quite similar to those reported for HCL of non-Japanese patients inasmuch as hairy cells in the majority of these patients were B1+, B2-, FMC7+, and IL-2R1+. However, they were more often than not J5+, Leu-1+, alpha HC1-, alpha HC2-, and 4B122+ in contrast to the pattern reported for non-Japanese patients. In conclusion, HCL in the Japanese constitutes a special variant of HCL because of its rareness, unusual immunophenotype, and atypical clinicohematologic features.

Aged↗