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Biomedical subjects

K Miyake

Publications and source records attributed to K Miyake.

At least 163 records · Page 9Linked to original sources
PubMed1997

Neonatal alloimmune thrombocytopenia associated with anti-human platelet antigen-3a antibody.

A sister and brother with neonatal alloimmune thrombocytopenic purpura (NAITP) caused by maternal anti-human platelet antigen (HPA)-3a are reported. The children had transient severe thrombocytopenia in the newborn period, and were treated with intravenous gamma-globulin and platelet concentrates from random donors. Although the sister had intracranial hemorrhage on day 2 postnatally, the development of the child has been normal and no neurological sequelae have been observed. The brother only had bloody stool when the platelet count was low, and did not have severe hemorrhagic manifestations. The diagnosis of NAITP was made by the sera from the mother, which contained anti-HPA-3a antibody directed against platelets of the children. The rate of recurrence might be high in this family, because the father of the patients was found to be homozygous for the HPA-3a gene.

Antigens, Human Platelet↗
PubMed1997

Human herpesvirus 7 infection of lymphoid and myeloid cell lines transduced with an adenovirus vector containing the CD4 gene.

It has been reported recently that CD4 is a major component of the receptor for human herpesvirus 7 (HHV-7), which has been newly identified as a T-lymphotropic virus. To investigate further the role of CD4 in HHV-7 infection, we examined the susceptibility to HHV-7 infection of various CD4-negative or weakly positive cell lines into which the cDNA for CD4 was transferred using an adenovirus vector (Adex1CACD4). Of 13 cell lines transduced with Adex1CACD4, including T-lymphoid, B-lymphoid, monocytoid, and myeloid cell lines, one T-lymphoid cell line, one monocytoid cell line, and two cell lines established from the blast crisis of chronic myelogenous leukemia showed high susceptibility to HHV-7 infection. Taken together with the results of previous studies, these data suggest strongly that CD4 is a major component of the binding receptor for HHV-7. This study also shows that HHV-7 may be able to infect CD4-positive hematopoietic precursor cells as well as T lymphocytes.

Adenoviridae↗
PubMed1997

Effects of nebracetam on synaptosomal monoamine uptake of striatal and hippocampal regions in rats.

Effects of nebracetam, a novel nootorpic agent, on the synaptosomal uptake of neurotransmitter monoamines of the brain regions were examined. Striatal and hippocampal synaptosomes were isolated by the Percoll gradient method, and the striatal dopamine uptake and hippocampal serotonin uptake were measured in the presence of different concentrations (1 to 1000 microM) of nebracetam in vitro. A significant reduction in dopamine uptake in the striatum and serotonin uptake in the hippocampus was seen at concentrations of 100 microM or above. In in vivo microdialysis study, there were no appreciable changes in the extracellular concentrations of striatal dopamine and hippocampal serotonin when this agent at a dose of 30 mg/kg, which was effective in improving ischemic brain energy metabolism, was applied i.p. to the rat. The ineffectiveness of nebracetam in the in vivo microdialysis may be due to low levels of the concentration of nebracetam when the agent was administered i.p. at a dose of 30 mg/kg, since the brain blood concentration of this agent is pharmacokinetically estimated to be no more than 15 microM when this dose of nebracetam is employed. Thus, it is unlikely that this agent at a pharmacologically effective dose alters dopamine or serotonin uptake in the brain nerve terminal under normal conditions.

Animals↗
PubMed1997

M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for poor prognosis patients with urothelial tumors and effect of dose intensity.

The effects of the M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) regimen, which has been reported to improve the outcome of patients with urothelial cancers, were studied on 41 patients treated at our hospital. The patients were divided into adjuvant (24 patients), neoadjuvant (5 patients), and salvage (12 patients) groups. We investigated the dose intensity, the cause-specific survival, response rate and toxicities in the three groups. Although 36 patients received > or = 95% of the initial doses projected, the mean dose intensity (+/-standard deviation) in the adjuvant, neoadjuvant, and the salvage groups was 77 (+/-11), 73 (+/-4), and 74 (+/-12)%, respectively. The five-year cause-specific survival in the adjuvant group was 69% (95% confidence limit: 50-88%). Only 2 of the 5 patients (40%) in the neoadjuvant group survived 23 months after the initiation of the treatment, and all patients in the salvage group died of cancer or treatment-related toxicity within 33 months. The median survival was 38 months in the adjuvant group, 21 months in the neoadjuvant group, and 7 months in the salvage group. A dose intensity > or = 75% did not improve survival in any group. The overall response rate was 33% in 15 patients with evaluable lesions. A complete response was noted in 1 patient and a partial response was noted in 1 patients. Two patients died of treatment-related complications. Nausea and vomiting were observed in all patients. Leukopenia, thrombocytopenia and anemia > or = WHO grade 3 were observed in 25 (61%), 4 (10%), and 7 (17%) patients, respectively. Thrombocytopenia, anemia, and pyrexia > or = grade 3 were seen relatively more often in the patients receiving a dose intensity < 75%. Stomatitis > or = grade 3 appeared to be more frequent in the patients receiving a dose intensity > or = 75%. Adjuvant M-VAC might be beneficial, while its efficacy was limited in the neoadjuvant and salvage settings. Although dose intensity is considered to be important, it did not appear to be related to survival, the response rate, or the toxicity of M-VAC.

Adult↗
PubMed1997

Effect of interferon on GB virus C and hepatitis C virus in hepatitis patients with the co-infection.

Of 74 patients who were infected with hepatitis C virus (HCV) and received interferon, 12 (16%) were positive for RNA of GB virus C (GBV-C). RNA of GBV-C was determined in sera from the co-infected patients retrospectively, and the effect of interferon on GBV-C was compared with that on HCV in them. Titers of both GBV-C and HCV RNAs decreased during interferon in all of them. Two patients lost both GBV-C and HCV RNAs and remained clear until 6 months after treatment with interferon, while 2 lost RNA for GBV-C only and 2 for HCV RNA alone. Low pretreatment RNA titers of GBV-C and HCV correlated with the efficacy of interferon in clearing. Alanine aminotransferase returned to normal only in the patients who lost HCV RNA, regardless of the persistence or loss of GBV-C RNA. These results indicate that the response to interferon of GBV-C is comparable to but independent of that of HCV and that the persistence of GBV-C would not prevent the normalization of aminotransferases in response to interferon in patients with chronic hepatitis C.

Adult↗
PubMed1997

[Clinical investigation of prostatic cancer patients who underwent radical prostatectomy: analysis of patients in the Tokai Urological Cancer Registry].

Between 1989 and 1991, 815 cases of prostatic carcinoma were registered in the Tokai Urological Cancer Registry. We investigated the clinical features and prognosis of 69 patients who underwent radical prostatectomy. The median age and clinical stage, were 65.9 +/- 4.7 years and A in 7 patients, 66.3 +/- 5.8 years and B in 31, 68.2 +/- 2.7 years and C in 26, 63.4 +/- 13.5 years and N(+) in 5. Neoadjuvant therapy consisting of endocrine therapy and chemoendocrine therapy was administered to 28 and 14 patients, respectively. In comparison to the clinical stage, pathologically, 4 cases (9.5%) showed downstaging or overstaging, 15 (35.7%) understaging and 23 (54.8%) accurate staging in the neoadjuvant therapy group, and, respectively, 2 (7.4%), 12 (44.4%) and 13 (48.2%) in the non-neoadjuvant therapy group. There was a significant difference in the pretreatment prostatic antigen (PA) value between pT0 and pT3 (p < 0.05), between pT0 and pN(+) (p < 0.01) and between pT2 and pN(+) (p < 0.05). In addition, the pretreatment PA value in the recurrence group was higher than that in the non-recurrence group in both neoadjuvant and non-neoadjuvant groups, with a significant difference (p < 0.01) in the neoadjuvant group. Cancer recurrence was noticed in 2 patients given non-neoadjuvant therapy and 3 given neoadjuvant therapy. There was no significant difference in the non-recurrence rate with the pathological stage either with or without neoadjuvant therapy. However, the non-recurrence rate in the neoadjuvant therapy group was higher than that in the non-neoadjuvant therapy group.

Adenocarcinoma↗
PubMed1996

Molecular cloning of a human RP105 homologue and chromosomal localization of the mouse and human RP105 genes (Ly64 and LY64).

RP105 is a mouse B cell surface molecule that transmits a growth-promoting signal and is implicated in the life/death decision of B cells. RP105 has tandem repeats of a leucine-rich motif in the extracellular domain that is expected to be involved in protein-protein interactions. In the present study, a cDNA clone encoding the human homologue of RP105 was isolated. The amino acid sequence of human RP105 is highly homologous to that of mouse RP105 with 74% identity, and the leucine-rich repeats are well conserved. The expression of the human RP105 transcript was detected in some B cell lines, a histiocytic leukemia cell line, and peripheral blood leukocytes. We also determined the chromosomal locations of the mouse RP105 gene (Ly64 locus) and the human RP105 gene (LY64 locus). Interspecific mouse backcross analysis was used to map the Ly64 locus at the distal region of chromosome 13. The human LY64 locus was localized to 5q12 by fluorescence in situ hybridization, confirming the syntenic relationship between these regions of the mouse and human chromosomes.

Amino Acid Sequence↗
PubMed1996

Two-step gene transfer using an adenoviral vector carrying the CD4 gene and human immunodeficiency viral vectors.

Human immunodeficiency virus-1 (HIV-1) belongs to the lentivirus subfamily of retroviruses and has several interesting features, including T cell tropism and the ability to infect nondividing cells. Replication-incompetent HIV vectors were developed and were shown to be capable of targeted gene transfer into CD4+T cells. This strict T cell tropism may be important for the development of gene therapy of acquired immunodeficiency syndrome (AIDS), but it hampers the use of the HIV vector for other gene transfer applications. To expand the host range of the HIV vector, we established the two-step gene transfer system, which allows us to transduce non-T cells stably. In the first step, the CD4 gene was introduced into target cells using a replication-defective adenoviral vector. Transient but high-level expression of CD4 molecules was detected in both adherent and floating cells. In the subsequent step, the cells were incubated with HIV vectors. Stable integration of the HIV vector was demonstrated in cells transduced with the adenoviral vector. These results indicate that transient expression of CD4 molecules by the adenoviral vector is sufficient to render non-T cells susceptible to HIV-mediated gene transfer. This two-step gene transfer strategy may be used as a general method to transduce various types of human cells stably including nondividing cells.

Adenoviridae↗
PubMed1996

Cell adhesion via murine alpha4 human beta1 integrin chimera on transfected K562 cells to endothelial cells.

To evaluate the property of binding activity of alpha4beta1 integrin in cell-cell interaction, we newly established a cell line, alpha4mK562, by transfecting cDNA of murine integrin alpha4 subunit into human erythroleukemic K562 cells. alpha4mK562 transfectant expressed both murine alpha4 and human beta1 subunit, which generated a functional heterodimer. alpha4mK562 cells more efficiently bound to murine endothelial cell lines and recombinant human TNFalpha (rhTNF)-treated human umbilical vein endothelial cells (HUVEC) than the parental K562 cells. These adhesion resulted from the interaction between alpha4beta1 and VCAM-1. Interestingly, treatment with mAb against human beta1 (4B4 clone), which has been known as inhibitory mAb, enhanced binding of alpha4mK562 cells to rhTNF-treated HUVEC but not to murine endothelial cells. This increase in binding induced by 4B4 mAb was completely inhibited by another mAb against human beta1 (mAb13), but only partially by anti-alpha4 mAb (PSsolidus2). The increase in binding induced by 4B4 mAb was also abolished by metabolic inhibitors, indicating that the increased binding is energy dependent. These observations suggest that the binding of 4B4 mAb to the chimeric alpha4beta1 induces an unique outside-in signaling and enhances the specific binding of alpha4mK562 cells to rhTNF-treated HUVEC.

Animals↗
PubMed1996

Activation mediated by RP105 but not CD40 makes normal B cells susceptible to anti-IgM-induced apoptosis: a role for Fc receptor coligation.

Signals through the B cell antigen receptor lead to a variety of cellular events such as activation, anergy, and apoptosis. B cells select these outcomes to establish and maintain self-tolerance, and to mount adequate antibody responses. However, it is not fully understood how one and the same signal causes such different consequences. In the present study, we have studied the effect of activation signals on the outcome of responses to antigen receptor ligation. Two distinct growth-promoting signals were used to activate B cells. Ligation of either RP105, a newly discovered B cell surface molecule, or the CD40 molecule, drove B cells to proliferate. Resultant blastic cells were then exposed to anti-immunoglobulin M (IgM). Blast cells that had been stimulated with anti-RP105 ceased growing and underwent apoptosis after cross-linking of surface IgM. Coligation of the Fc gamma receptor IIB with surface IgM augmented, rather than aborted, this response. In contrast to RP105-activated B cells, blast cells that had been activated by CD40 ligation were unaltered by anti-IgM. On the other hand, CD40-activated B cells became extremely susceptible to Fas-mediated apoptosis, whereas RP105-activated B cells were much less sensitive. Anti-IgM-induced apoptosis in RP105 blasts was independent of Fas, because it was demonstrable with Fas-deficient MRL-lpr/lpr mice. These results demonstrate that the nature of an initial activation signal has a great influence on the fate of activated B cells after (re)engagement of the antigen receptor. RP105, as well as CD40, may be important in this life/death decision.

Animals↗
PubMed1996

Antibody ligation of CD9 modifies production of myeloid cells in long-term cultures.

The KMC8.8 monoclonal antibody was made by immunizing rats with the BMS2 stromal cell clone, and was selected for further study because its ability to inhibit production of myeloid cells in Dexter cultures but not that of lymphoid cells in Whitlock-Witte cultures. The influence on myeloid progenitors might have been indirect, since the antibody did not prevent responsiveness to colony-stimulating factors in semisolid agar cultures. Furthermore, there was no inhibition, and some augmentation, of cell production when the antibody was added to established Dexter cultures. A cDNA clone that encoded the KMC8.8-recognized molecule was isolated by expression cloning and found to be identical in sequence to a previously published murine CD9 homologue. The antibody and cDNA clone were used to establish that CD9 is expressed by stromal cells, megakaryocytes, platelets, myeloid cells, and subpopulations of mature lymphocytes in mice. Treatment with the KMC8.8/CD9 antibody slightly augmented adhesion between myeloid cells and stromal cells, consistent with previous reports that this member of the tetraspan family of proteins can transmit proadhesive signals to human platelets and lymphoid cells. CD9 might participate in cell-cell interactions critical for correct orientation and movement of maturing myeloid cells in bone marrow.

Animals↗
PubMed1996

DCC protein expression in hematopoietic cell populations and its relation to leukemogenesis.

Using flow cytometry and immunoprecipitation (IP), we have investigated the deleted in colon cancer (DCC) protein expression on the bone marrow (BM) and peripheral blood (PB) cells of 16 normal subjects, 17 myelodysplastic syndrome (MDS) patients, and 10 acute myelogenous leukemia (AML) patients. With regard to the BM mononuclear cells (BM-MNCs) of normal subjects, the DCC protein expression ranged from 6.6 to 57.0%. Two-color flow cytometry revealed that among the IBM-MNCs the DCC protein was clearly expressed on the CD14+, CD13+, and factor 8+ cells, whereas it was low on the CD19+ and CD7+ cells and did not express on the CD34+, CD8+, and the glycophorin A+ cells. Further, the DCC protein expression was not seen on the PB CD11b+ and CD13+ cells. The IP results revealed that the 180-kD DCC protein was detected on the MNCs of both the BM and PB cells by the antibodies AF5, specific for the DCC extracellular domain, and G97-449, specific for the cytoplasmic domain. In contrast, flow cytometry did not detect the DCC protein on any BM-MNC MDS lineages (0.1-1.5%) or on AML leukemic cells (0.1-0.9%). The IP results indicated that the AF5 antibody did not detect the DCC protein on BM-MNCs of three of five MDS patients and four of five AML patients; however, the G97-449 antibody detected the 180-kD DCC protein in two MDS patients in whom AF5 had detected greatly reduced DCC band. These findings suggest that the DCC protein presence appears to be associated with normal hematopoiesis, and that its absence on the surfaces of the BM-MNCs and AML cells may contribute to the MDS and AML pathogenesis.

Antigens, CD↗
PubMed1996

Treatment of high-risk acute lymphoblastic leukemia in children using the AL851 and ALHR88 protocols: a report from the Kyushu-Yamaguchi Children's Cancer Study Group in Japan.

A total of 125 children, who were diagnosed as having high-risk acute lymphoblastic leukemia (ALL), were treated with two consecutive protocols designated as AL851 (1985-1988) and ALHR88 (1988-1990). All patients received induction therapy consisting of vincristine (VCR), prednisolone (PSL), daunorubicin (DNR), and I-asparaginase (I-Asp). In the ALHR88 protocol, the patients whose blasts in the bone marrow (BM) were > or = 25% on day 14 of induction therapy and who were classified into T-cell type received additional cytosine arabinoside (AraC). After consolidation with intermediate-dose methotrexate (MTX), reinduction therapy including VCR, dexamethasone, and adriamycin followed by high-dose AraC was done for all patients. Intrathecal MTX and 24Gy of cranial irradiation were used to prevent central nervous system leukemia. A maintenance therapy consisting of 6-mercaptopurine, cyclophosphamide, MTX, DNR, VCR, and AraC was administered for 3 years after achieving a complete remission (CR). CR was achieved in 51/55 (92.7%) for AL851 and 68/70 (97.1%) for ALHR88. The 5-year event-free survival rates were 49.1 +/- 6.7% in AL851 and 62.5 +/- 6.1% in ALHR88. The factors related to a poor prognosis were a high initial leukocyte count of greater than 50 x 10(9)/L (P < 0.001), an L2 morphology of leukemic cells by FAB classification (P = 0.009), the chromosomal abnormality (P = 0.004) and high residual leukemic cells in BM (> or = 25%) on day 14 of induction therapy (P < 0.001). Taking these factors into consideration, more intensive protocols were started in 1990 for the patients with high-risk ALL.

Adolescent↗