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Biomedical subjects

H Kanamori

Publications and source records attributed to H Kanamori.

At least 19 recordsLinked to original sources
PubMed1992

Low-dose cytosine arabinoside for treating hypocellular acute leukemia in the elderly.

Ten previously untreated elderly patients with hypocellular acute leukemia received a low dose of cytosine arabinoside (Ara-C), 10 mg/m2 injected subcutaneously every 12 hours for 14-28 days. Six patients achieved a complete remission (CR) for periods ranging for 6-23 months (median 8.5 months) and the others had a partial remission (PR). Relapse has occurred in three patients to date. The median survival ranged from 10-24 months (median 14.5 months). Only two of the six patients, in whom bone marrow biopsy was performed at CR, had a normal cellularity. This change, however, did not appear to be a significant prognostic factor in those patients. In seven patients who achieved a CR or PR low-dose Ara-C was administrated as maintenance therapy at the same low dose for 10 days each month. Treatment was well tolerated in all patients despite for myelosuppression. There were no drug-related deaths. These observations suggest that low-dose Ara-C is effective in treating elderly patients with hypocellular acute leukemia.

Acute Disease↗
PubMed1992

Case report: fulminant hepatitis C viral infection after allogeneic bone marrow transplantation.

The authors describe two patients with acute leukemia who died of fulminant hepatitis caused by hepatitis C virus (HCV) after an allogeneic bone marrow transplant, the first such cases reported in Japan. Both had developed posttransfusion hepatitis during chemotherapy to induce remission and for consolidation. Six months after blood transfusion, the blood serum of each patient was positive for HCV antibody and HCV RNA. In each case, there was a transient improvement in liver function after the transplant. However, within 5 months of receiving the transplant and coincident with the withdrawal of cyclosporin A, each patient developed an acute exacerbation of hepatitis. The fulminant hepatitis in our patients may, therefore, have been caused by the reactivation of HCV induced by the immunosuppressive therapy followed by a reconstitution of the immune system.

Adult↗
PubMed1992

[Malignant histiocytosis associated with central neurological symptoms and cerebrospinal fluid involvement].

A 53-year-old woman was admitted with fever and general fatigue in December, 1988. A diagnosis of malignant histiocytosis (MH) was made based on her high level of LDH, thrombocytopenia, mild splenomegaly without systemic lymphadenopathy. There was also bone marrow infiltration large atypical cells and erythro-phagocytosis. VEPA therapy resulted in complete remission. Visual disturbance and left lagophthalmos were recognized in March 1990. These signs indicated central nervous system (CNS) relapse which disappeared after intrathecal methotrexate injection. The same symptoms and signs appeared after another, 5 months. Tumor cells were found not only in the central spinal fluid but also in bone marrow. CNS and bone marrow recurrence were treated with intrathecal methotrexate injection VEPA therapy and cranial irradiation. We diagnosed this case as MH, based on the clinical features which did not include systemic lymphadenopathy and laboratory findings although TcR-gamma rearrangement was observed in bone marrow cells. Only one case of CNS infiltration diagnosed when alive has previously been reported in Japan. We report here a very rare case in which by medical treatment CNS infiltrations was improved twice.

Facial Nerve Diseases↗
PubMed1992

[Myelodysplastic syndrome associated with marked eosinophilia and basophilia].

Myelodysplastic syndrome (refractory anemia with excess of blasts; RAEB) with marked basophilia and eosinophilia is described. An 82-year-old male was admitted to our hospital because of severe normocytic normochromic anemia (Hb 5.6 g/dl). The white cell count was 9,200/microliters with marked basophilia (34.5%) and eosinophilia (19.5%). The bone marrow aspiration also revealed both basophilia and eosinophilia, with blast contents of 9%. Diagnosis of RAEB was established. Although the treatment with red cell transfusion and ubenimex (Bastatin) was started, anemia was not improved. A karyotype of the bone marrow cells from this patient showed 47, XY, +8, i (17q), which has been observed as additional chromosomal abnormalities in blastic crisis of chronic myelogenous leukemia. The diagnosis of CML was not compatible with this case, because Ph1 chromosome and bcr gene rearrangement were negative. It is concluded that eosinophilia and basophilia might be derived from clonal abnormalities associated with MDS.

Aged↗
PubMed1991

The nucleolar localisation signal of the HTLV-I protein p27rex is important for stabilisation of IL-2 receptor alpha subunit mRNA by p27rex.

In this study we investigated the mechanism of stabilisation of IL-2 receptor alpha subunit mRNA by the HTLV-I protein p27rex. We tested the role of the nucleolar targetting signal in rex by introducing mutations. Three deletion mutants could not express rex protein in the nucleolus and although protein was still expressed in the nucleoplasm none of the mutants could stabilise IL-2R alpha mRNA. A substitution mutant could be expressed in the nucleolus and could also stabilise IL-2R alpha mRNA. The data show that the nucleolar targetting signal is crucial for stabilisation of IL-2R alpha mRNA by rex and raise the possibility that transport of mRNA from nucleus to cytoplasm can involve the nucleolus.

Animals↗
PubMed1991

The effect of 1-hydroxyvitamin D3 for prolongation of leukemic transformation-free survival in myelodysplastic syndromes.

Leukemic transformation (LT) free survival was studied in 30 patients with myelodysplastic syndromes (MDS). In 15 cases, 4-6 micrograms/day of 1-hydroxyvitamin D3 was administered, for a median duration of 17 months (D-group), other subjects had no therapy (N group). LT free survival of the D group had significant advantage over that of the N group according to the Kaplan-Meier method (P less than 0.001). In addition, 7 cases in the N group developed acute leukemia, in contrast to only one in the D group (P less than 0.05). These results suggest that oral administration of 1-hydroxyvitamin D3 prevents the progression of MDS to overt leukemia under the effect of differentiation capacity from blasts to monocytes.

Acute Disease↗
PubMed1991

The transient appearance of small blastoid cells in the marrow after bone marrow transplantation.

Of 14 patients who underwent allogeneic or syngeneic bone marrow transplantation, 6 had a transient appearance of small blastoid cells in the bone marrow after transplantation. Most of these patients (11) had leukemia, although 3 had severe aplastic anemia. The cells were 8-18 micron in diameter and had scant cytoplasm and dense nuclei with smooth, homogeneous chromatin. They often had distinct nuclear clefts. These cells constituted 4.0-21.3% of the total number of bone marrow cells. They were not reactive with peroxidase, alpha-naphtyl butylate esterase, naphthol AS-D chloroacetate esterase, or periodic acid-Schiff stains. Immunocytochemical analysis revealed that the small blastoid cells expressed terminal deoxynucleotidyl transferase, Ia-like, CD19, and CD10 antigens and cytoplasmic mu heavy chains, indicating a precursor B-cell phenotype. CD20 antigen was not expressed on these cells. The data suggest that cytoplasmic mu may be expressed earlier than CD20 antigen in the differentiation of B-cell lineage. The morphologic, cytochemical, and immunophenotypic characteristics did not distinguish these nonneoplastic cells distinctly from leukemic lymphoblastic cells. The increase of small blastoid cells was a transient and self-limited phenomenon, in contrast to that of neoplastic blasts. These cells should be recognized as a common component of the bone marrow of marrow transplant recipients. The significance and role of these cells in immune recovery and hematopoiesis remain uncertain.

Bone Marrow↗
PubMed1991

[Clinical effects of low-dose Ara-C in acute nonlymphocytic leukemia and myelodysplastic syndromes].

Forty-eight patients with acute nonlymphocytic leukemia (ANLL) and myelodysplastic syndromes (MDS) were treated with low-dose Ara-C regimen (LDAC) (10 mg/m2 or 10 mg/body subcutaneously every 12 hours). Complete remission (CR) was obtained in sixteen patients (33%) and partial remission (PR) in six (16%). Seven of eight patients with hypoplastic leukemia entered CR. However, LDAC was not effective in MDS and ANLL developing from MDS. The rate of CR was 20% in relapsed or refractory ANLL. Relapse was occurred in thirteen patients until now. The median duration of remission was 7 months (range: 3-20 months). Seven of the sixteen patients who achieved CR were received LDAC at the same dose for 10 days every month as a maintenance therapy. The duration of CR of these patients was shown to be longer than that of the patients without any maintenance therapy. Myelosuppression was observed in nearly all of them and the other clinical findings including cytogenetic analysis indicated cytotoxicity rather than differentiation as the mechanism of LDAC. LDAC was effective especially in hypoplastic leukemia and the maintenance therapy was found to prolong the duration of CR.

Adult↗
PubMed1991

Donor-HLA-incompatible marrow transplantation with an anti-donor cytotoxic antibody in the serum of the patient.

A 42-year-old female with acute mixed lineage leukemia received a marrow transplantation from an HLA non-identical sibling. The serum of the patient showed a positive crossmatch for anti-donor lymphocytotoxic antibody and exhibited a complement-mediated cytotoxicity to donor hematopoietic progenitor cells. In an attempt to reduce the risk of graft rejection, a large volume plasma exchange was performed, which was followed by an infusion of irradiated donor lymphocytes to eliminate remaining antibodies from her serum. The level of anti-donor antibody fell below the sensitivity of the anti-human immunoglobulin lymphocytotoxicity test after the infusion of donor lymphocytes. The cytotoxic activity against donor progenitor cells also disappeared from the serum. Cyclosporin had been administered for 2 weeks before marrow infusion, and methylprednisolone and prednisolone for 1 week before the initiation of conditioning chemoradiotherapy. Conditioning comprised cytosine arabinoside 5.6 g/m2, cyclophosphamide 4500 mg/m2 and fractionated total body irradiation with 15 Gy followed by an infusion of 4.0 x 10(8) cells/kg of unmodified marrow cells. Engraftment of donor cells was documented by HLA typing of peripheral lymphocytes. A sustained engraftment may be obtained in a donor-incompatible HLA non-identical marrow transplantation with anti-donor antibody by elimination of the antibody and achieving an intensive immunosuppression in the recipient before marrow infusion.

Adult↗
PubMed1990

Control of IL-2 receptor-alpha expression by IL-1, tumor necrosis factor, and IL-2. Complex regulation via elements in the 5' flanking region.

We have analyzed the mechanisms by which IL-1, IL-2, and TNF regulate expression of IL-2R alpha chain in a rodent T cell line. All three cytokines induce detectable IL-2R alpha mRNA by themselves, but there is strong synergy between IL-1 or TNF, on the one hand, and IL-2, on the other. The earliest phase of induction by IL-1 is independent of protein synthesis. IL-1, but not TNF, also stimulates transient secretion of IL-2. This leads to an autocrine stimulation of a further increase in IL-2R alpha mRNA levels. When IL-2 secretion has dropped off, continued IL-2R alpha expression requires both IL-2 and IL-1. Most or all of this regulation is due to changes in the rate of transcription of the IL-2R alpha gene. The response to IL-1 and IL-2 depends on a segment in the IL-2R alpha 5' flanking region, upstream of all cis-acting regulatory elements previously identified in the human gene.

Animals↗
PubMed1990

HTLV-1 p27rex stabilizes human interleukin-2 receptor alpha chain mRNA.

Expression of the pX gene products (p40tax, p27rex and p21X-III) of human T cell leukemia virus type 1 (HTLV-1), which is known to be a causative agent of adult T cell lymphoma/leukemia, induces expression of the interleukin-2 receptor alpha chain (IL-2R alpha) on infected T cells. Comparison of IL-2R alpha promoter activities has revealed that the transcriptional activation of the promoter alone cannot explain the large numbers of IL-2R alpha expressed on HTLV-1 infected cells. We found that the rates of the IL-2R alpha mRNA degradation were greatly reduced in pX-positive cells as compared with pX-negative cells. Simultaneous transfection of the expression vector plasmid containing IL-2R alpha cDNA and similar plasmids containing various pX sequences showed that p27rex elongated the half life of IL-2R alpha mRNA. As p27rex did not affect the transport of the IL-2R alpha mRNA from nucleus to cytoplasm, prolongation of the IL-2R alpha mRNA half life by p27rex is ascribed to stabilization of the mRNA. Experiments using deletion mutants and chimeric constructs of the IL-2R alpha cDNA demonstrated that the coding sequence but not the 5' or 3' untranslated region of the IL-2R alpha mRNA sequence is responsible for its protection by p27rex.

Cell Line↗
PubMed1990

Human macrophage scavenger receptors: primary structure, expression, and localization in atherosclerotic lesions.

Two types of cDNAs for human macrophage scavenger receptors were cloned from a cDNA library derived from the phorbol ester-treated human monocytic cell line THP-1. The type I and type II human scavenger receptors encoded by these cDNAs are homologous (73% and 71% amino acid identity) to their previously characterized bovine counterparts and consist of six domains: cytoplasmic (I), membrane-spanning (II), spacer (III), alpha-helical coiled-coil (IV), collagen-like (V), and a type-specific C-terminal (VI). The receptor gene is located on human chromosome 8. The human receptors expressed in CHO-K1 cells mediated endocytosis of modified low density lipoproteins. Two mRNAs, 4.0 and 3.2 kilobases, have been detected in human liver, placenta, and brain. Immunohistochemical studies using an anti-peptide antibody which recognizes human scavenger receptors indicated the presence of the scavenger receptors in the macrophages of lipid-rich atherosclerotic lesions, suggesting the involvement of scavenger receptors in atherogenesis.

Amino Acid Sequence↗
PubMed1990

[Hypercalcemia associated with blast crisis of chronic myeloid leukemia].

We describe a patient with CML who developed hypercalcemia in his course of blast crisis. A 25-years-old man was diagnosed as CML with priapism in April 1985, and controlled with BHAC-DVP, VMP, busulfan therapy. In December 1987, he readmitted to our hospital with abdominal pain. Investigations at that time showed: white blood cell count 11600/microliters (blast cells 9%); hemoglobin 8.4 g/microliters; platelets 19.0 X 10(4)/microliters; serum calcium 13.2 mg/dl; BUN 44 mg/dl; creatinine 2.7 mg/dl. Treatment with predonine, 6-MP and vincristine was begun. But serum calcium level rose gradually up to 16.5 mg/dl. So we tried middle dose Ara-c therapy, serum calcium decreased to 6.8 mg/dl. At once he was in a chronic phase, but he relapsed and died of heart failure. Necropsy showed extensive leukemic blast-cell infiltration of the bone marrow, liver, spleen, lung, and kidney. The cause of hypercalcemia in our case was suspected of local osteolytic hypercalcemia, because multiple bone destruction was found.

Adult↗
PubMed1989

Transcriptional regulation alone does not explain the constitutive expression of the interleukin 2 receptor (Tac/L-chain) in HTLV-1 infected cells.

We have identified a suppressive element in the upstream region of the interleukin 2 (IL-2) receptor L chain (Tac) promoter. The inhibitory activity of this element was retained in human T cell leukemia virus type-1 (HTLV-1)-infected T cell lines which express constitutively a large number of IL-2 receptors on the cell surface. The promoter activities of the IL-2 receptor gene did not always correlate with the strong expression of the receptor and its mRNA in the HTLV-1-infected T cell lines we analysed. The results indicate that the constitutive up-regulation of the IL-2 receptor in HTLV-1-infected T cells may be ascribed to not only the transcriptional but also post-transcriptional regulation.

Gene Expression Regulation↗
PubMed1989

Production of sterile transcripts of C gamma genes in an IgM-producing human neoplastic B cell line that switches to IgG-producing cells.

A human neoplastic B cell line SSK41 that expresses IgM on its surface switches spontaneously to IgG-producing cells. The SSK41 line contains a single immunoglobulin heavy-chain locus, the constant region (C) genes of which retain the germline configuration. The IgG-producing SSK41 line was purified by sorting, and shown to have undergone S-S recombination with deletion of the C mu gene. This line produced secretory and membrane-bound forms of gamma-chain mRNA. From cDNA libraries of a mixed population of IgM+/IgG+ SSK41 cells, we have isolated cDNA clones encoding the mature membrane-bound and secretory forms of the mu and gamma 1 heavy chains, all of which share the same variable region sequence. cDNA clones containing the mature gamma 3 chain were identified as well. We also isolated cDNA clones containing C gamma 1 and C gamma 3 sterile transcripts from the SSK41 line. These sterile transcripts contained additional exon sequences designated 'I' which were localized upstream of the C gamma 1 and C gamma 3 switch regions and homologous to murine counterparts. The I sequences were precisely spliced to the 5' ends of the corresponding C gamma exon sequences. These features of germline CH transcripts, i.e. the isotype specificity to class switching, location of exons, and sequences per se, are highly conserved between man and mouse.

Amino Acid Sequence↗
PubMed1989

[Sepsis in patients with hematological diseases].

Sepsis is one of the important complications on the treatment of severe hematological diseases. In this report, we analyzed sepsis in 309 patients with hematological diseases who were admitted to the First Department of Internal Medicine of Yokohama City University Hospital from 1979 to 1986. Positive blood culture were found in 17.8% (55/309 cases) and total positive cases were 73 including recurrent patients. Positive rate by underlying diseases was 30.3% in acute leukemia, 20.8% in chronic myelocytic leukemia, 17.2% in aplastic anemia, 8.0% in multiple myeloma, 6.0% in malignant lymphoma and 6.5% in others. The organisms causing sepsis were as follows; gram negative bacilli 56.4%, gram positive organisms 34.6%, fungus 6.4% and anaerobic bacteria 2.6%. Pseudomonas aeruginosa was found in 19.2%. The mortality rate of patients with sepsis was 34.2% (25/73 cases). The significant prognostic factors in patients with sepsis were the degree of neutropenia, duration of neutropenia (500 less than microliters), the species of organisms, simultaneous complication with shock and the site of other infections.

Hematologic Diseases↗
PubMed1989

[Allogeneic bone marrow transplantation as primary treatment in acute myelofibrosis].

A 20-year-old man with acute myelofibrosis received ablative chemotherapy consisting of busulfan, Ara-C and cyclophosphamide followed by bone marrow transplantation from his histocompatible sister. There was a prompt engraftment with a rising WBC and platelet count and with donor karyotype in specimen of marrow. A bone marrow examination on day 29 showed a prominent decrease in marrow fibrosis. However, fibrosis was again exacerbated with leukemic relapse as overt acute megakaryoblastic leukemia on day 110, The patient died on day 126. Marrow fibrosis was found to be reversible by ablation of malignant cells and repopulation of normal hemopoietic cells after bone marrow transplantation.

Acute Disease↗