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Biomedical subjects

H Mizoguchi

Publications and source records attributed to H Mizoguchi.

At least 307 records · Page 17Linked to original sources
PubMed1990

Enhanced production of tissue-type plasminogen activator by estradiol in a novel type variant of human breast cancer MCF-7 cell line.

ES-1 cells, which showed a higher sensitivity to the cytocidal action of estradiol were isolated from a human breast cancer MCF-7 cell line. Growth of ES-1 cells was inhibited by a dose of 17-beta estradiol that stimulated the growth of the parental MCF-7 cells. Proteins secreted from MCF-7 and ES-1 cells when cultured with 17-beta estradiol were compared by sodium dodecyl sulfate-containing polyacrylamide gel electrophoresis (SDS-PAGE). Addition of estradiol to culture medium enhanced secretion of a protein of molecular mass of 52 kDa in media for both MCF-7 and ES-1 cell lines, but the secretion of a second 67 kDa protein was enhanced about 10-fold only in ES-1 cells. The analysis by SDS-PAGE of culture medium immunoprecipitated with anti-tissue-type plasminogen activator (t-PA) antibody demonstrated that the band of 67 kDa protein specifically secreted from estradiol-treated ES-1 cells contained t-PA. Zymography assays, quantitative immunoreactive assays, and Northern analysis showed about 5-fold specific increase by estradiol of t-PA with molecular mass of 65-70 kDa in ES-1 but not in its parental MCF-7 cells. Cellular level of the plasminogen activity was also specifically enhanced in ES-1 cells by estradiol, but only a slightly in MCF-7 cells. By contrast, another urokinase-type PA (u-PA) with molecular weight of 55 kDa showed very low level activity in both MCF-7 and ES-1 cell lines in the presence of estradiol. Formation of t-PA mRNA was specifically enhanced in ES-1 cells when ES-1 cells were treated for more than 12 h with 10(-8) M 17-beta estradiol. Estradiol did not elongate the lifetime of t-PA mRNA in ES-1 cells. A unique phenotype of ES-1 cells in response to estradiol is discussed in relation to activating expression of the t-PA gene.

Breast Neoplasms↗
PubMed1990

Cytotoxic T lymphocyte triggering via CD16 is regulated by CD3 and CD8 antigens. Studies with T cell receptor (TCR)-alpha beta+/CD3+16+ and TCR-gamma delta+/CD3+16+ granular lymphocytes.

The role of CD3 and CD8 Ag in CD16-mediated CTL triggering was studied in TCR-alpha beta+ and TCR-gamma delta+ granular lymphocytes (GL). In TCR-alpha beta+/CD3+4-8+16+ GL obtained from patients with GL-proliferative disorders, antibody-dependent cellular cytotoxicity was inhibited by anti-CD3 and anti-CD8 mAb. Anti-CD3 mAb also inhibited antibody-dependent cellular cytotoxicity activity of TCR-gamma delta+/CD3+4-8-16+ GL from a patient and that of TCR-gamma delta+/CD3+4-8+/-16+ T cell clones established from patients with proliferating TCR-gamma delta+ GL. In TCR-gamma delta+ T cell clones, cytotoxicity against Fc gamma R+ targets was induced by stimulation of CD16 Ag with anti-CD16 mAb, and such cytotoxicity was also inhibited by anti-CD3 mAb. These results indicate that CD3 and CD8 molecules play a regulatory role in CD16-mediated CTL triggering.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1990

Perforin gene expression in granular lymphocyte proliferative disorders.

By Northern blot analysis using a cDNA clone of the perforin gene, we studied the levels of perforin mRNA in peripheral blood mononuclear cells from 11 cases of granular lymphocyte-proliferative disorders (GLPDs). The granular lymphocytes studied were characterized by morphologic, immunophenotypic, and immunogenotypic analyses. Cytolytic functions of the lymphocytes assayed included nonmajor histocompatibility complex-requiring cytotoxicity, anti-CD3-redirected cytotoxicity, antibody-dependent cellular cytotoxicity, and lectin-dependent cellular cytotoxicity. The results showed that in lymphocytes with strong cytolytic functions high levels of perforin mRNA existed, whereas in lymphocytes with weak or undetectable levels of cytolytic functions, low levels of perforin mRNA existed. Because the levels of perforin mRNA correlated with those of cytolytic functions, perforin is probably a mediator in cytolytic functions of granular lymphocytes in patients with GLPDs. When the lymphocytes were cultured for 1 day, however, the levels of cytolytic activity were increased, and those of perforin mRNA were decreased. Therefore, we cannot rule out the possibility that factors other than perforin protein are involved in the cytolytic functions of granular lymphocytes.

Antigens, CD↗
PubMed1990

Successful treatment of refractory anemia with high-dose methylprednisolone.

Five patients with refractory anemia were treated with high-dose methylprednisolone. An immediate and long-lasting hematological improvement without serious side effects was achieved in two of the patients, although chromosomal abnormalities persisted in both. The clinical course and laboratory data of these two patients are described. Restoration of normal hematopoiesis was achieved regardless of the enhancement of colony formation of granulocyte progenitor cells by the simultaneous addition of hydrocortisone in vitro. The same treatment was given to six patients who had refractory anemia with an excess of myeloblasts (RAEB), but no improvement was observed in any of these patients. It appears that high-dose methylprednisolone can be valuable in the treatment of refractory anemia, but is not useful for RAEB.

Adult↗
PubMed1990

The effect of cytokines on the ploidy of megakaryocytes.

The effects of recombinant cytokines on the ploidy of human megakaryocytes derived from megakaryocyte progenitors were studied using serum-free agar cultures. Nonadherent and T cell-depleted marrow cells were cultured for 14 days. Megakaryocyte colonies were identified in situ by the alkaline phosphatase anti-alkaline phosphatase technique, using monoclonal antibody against platelet IIb/IIIa. The ploidy of individual megakaryocytes in colonies was determined by microfluorometry with DAPI (4',6-diamidino-2-phenylindole) staining. Recombinant human interleukin 3 (rhIL-3) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) supported megakaryocyte colony formation in a dose-dependent manner. However, both rhIL-3 and rhGM-CSF had no definite ability to increase the ploidy values. Recombinant human erythropoietin (rhEpo) or recombinant human macrophage colony-stimulating factor (rhM-CSF) by itself did not stimulate the growth of megakaryocyte progenitors. rhEpo or rhM-CSF, however, stimulated increases in the number, size and ploidy values of megakaryocyte colonies in the presence of rhIL-3 or rhGM-CSF. Recombinant human interleukin 6 (rhIL-6) showed no capacity to generate or enhance megakaryocyte colony formation when added to the culture alone or in combination with rhIL-3. rhIL-6, however, increased the ploidy values in colonies when added with rhIL-3. These results show that rhEpo, rhM-CSF and rhIL-6 affect endomitosis and that two factors are required for megakaryocyte development.

Biological Factors↗
PubMed1990

Endoscopic appearance of the colon and small intestine of a patient with hemorrhagic enteric graft-vs.-host disease.

Endoscopic appearance of the gastrointestinal tract of a patient with severe hemorrhagic enteric graft-vs.-host disease (GVHD) is presented. A 29-year-old man with chronic myelogenous leukemia suffered from severe enteric GVHD after allogeneic bone marrow transplantation. Endoscopy showed hemorrhagic ulceration of the upper jejunum, terminal ileum, and colon at the onset of melena. Sections of biopsies were compatible with acute GVHD. Repeat endoscopy showed gradual healing of the lesions after steroid pulse and antilymphocyte globulin therapy, but the patient died of cytomegalovirus pneumonitis 14 months later. Autopsy revealed submucosal fibrosis of the small intestine and colon.

Adult↗
PubMed1990

Epidermal growth factor (EGF)-nonresponsive variants of normal rat kidney cell line: response to EGF and transforming growth factor-beta.

Anchorage-independent growth in soft agar of normal rat kidney (NRK) fibroblasts depends on both transforming growth factor-beta (TGF-beta) and epidermal growth factor (EGF) (or TGF-alpha). We have isolated two EGF-nonresponsive cell lines, N-3 and N-9, from chemically mutagenized NRK cells, after selection of mitogen-specific nonproliferative variants in the presence of EGF and colchicine. Saturation binding kinetics with 125I-EGF showed one-half or fewer EGF receptors in N-3 and N-9 than in their parental NRK. Cellular uptake of 2-deoxy-D-glucose was enhanced in all NRK, N-3, and N-9 cell lines by TGF-beta treatment, whereas treatment with EGF significantly enhanced the cellular uptake of the glucose analog in NRK cells, but not in N-3 and N-9 cells. DNA synthesis of NRK during the quiescent state, but not that of N-3 and N-9, was stimulated by EGF. Anchorage-independent growth of N-9 could not be observed even in the presence of both EGF and TGF-beta, whereas that of N-3 was significantly enhanced by TGF-beta alone. EGF stimulated phosphorylation of a membrane protein with molecular size 170 kDa of NRK, but not of N-3, when immunoprecipitates reacting with anti-phosphotyrosine antibody were analyzed. Exposure of NRK cells to EGF increased cellular levels of TGF-beta mRNA, but there appeared little expression of TGF-beta mRNA in N-3 and N-9 cells. Exposure of N-3 cells to EGF or TGF-beta enhanced the secretion of EGF into culture medium, but exposure of NRK or N-9 cells did not. Altered response to EGF of N-3 or N-9 might be related to their aberrant growth behaviors.

Animals↗
PubMed1990

Effects of various cytokines on proliferation of acute lymphoblastic leukemia cells.

We investigated the effects of recombinant human interleukins 1 to 6 (rIL-1 to -6) on the proliferation of blast cells from patients with acute lymphoblastic leukemia (ALL). The 3H-TdR incorporation in the presence of various cytokines was examined in cells from 14 patients: 12 with B-lineage ALL, 1 with T-lineage ALL and 1 with biphenotypic leukemia. In B-lineage ALL, a significant increase in 3H-TdR incorporation was observed in 5/12 cases (42%) in the presence of rIL-1 alpha, in 10/12 cases (83%) with rIL-2, in 9/12 cases (75%) with rIL-3, in 3/6 cases (50%) with rIL-4, in 4/6 cases (67%) with rIL-5, and in 4/12 cases (33%) with rIL-6. The mean stimulation index of the cells showing a positive response was 1.74 for rIL-1 alpha, 3.40 for rIL-2, 2.55 for rIL-3, 1.86 for IL-4, 1.56 for rIL-5, and 2.97 for rIL-6. T-lineage ALL cells were stimulated only in the presence of rIL-2, and biphenotypic leukemia cells were not stimulated by any of the cytokines tested.

Antigens, CD↗
PubMed1990

c-myb gene analysis in T-cell malignancies with del(6q).

Three T-cell malignancies with del(6q) were analyzed for karyotypes and alteration of the oncogene c-myb that is assigned to 6q22-q24. Patients were diagnosed as having non-Hodgkin T-cell lymphoblastic lymphoma, adult T-cell leukemia, and acute T-cell lymphoblastic leukemia, and the deletions of chromosome 6 were del(6)(q21q25), del(6)(q21q23), and del(6)(q21) or del(6)(q21q27), respectively. Tumor cell DNAs were obtained from cultured pleural fluid or from fresh peripheral blood and marrow samples and were analyzed by Southern blot hybridization, using c-myb oncogene probes. Rearrangements, deletions, or amplifications were absent in these tumor DNAs, thereby indicating that the del(6q) breakpoint in these T-cell malignancies was located outside of the c-myb gene. Northern blot analysis revealed the elevated expression of c-myb in the non-Hodgkin lymphoma patient, in accord with lineage characteristics.

Adolescent↗
PubMed1990

Cutaneous extramedullary hematopoiesis in myelofibrosis.

Erythematous papulonodules that resembled a malignant lymphoma developed in a 62-year-old man. Further examination revealed that he had primary myelofibrosis with cutaneous extramedullary hematopoiesis. All three marrow elements (myeloid, erythroid, and megakaryocytic series) were present in the skin lesions. Although extramedullary hematopoiesis of the skin is a rare complication of myelofibrosis, 13 similar cases have been reported. In nine cases, including ours, all three marrow elements were present in the cutaneous lesions.

Aged↗
PubMed1990

Induction of eosinophilic colonies by interleukin-5 on acute myeloblastic leukaemic cells.

The effect of interleukin-5 (IL-5) on blast colony formation of acute myeloblastic leukaemia (AML) cells was studied. IL-5 showed a weak but significant colony stimulatory effect in one out of six cases studied. IL-5 induced eosinophilic colony growth in this case, and chromosomal and histochemical analyses strongly suggested that these eosinophilic colonies were derived from leukaemic blast progenitor cells. To our knowledge, this is the first report that IL-5 induces eosinophilic colonies on fresh AML cells. A possible induction of differentiation of AML blast cells by IL-5 is suggested.

Adult↗
PubMed1990

Enhanced growth of clonogenic cells from acute myeloblastic leukaemia by erythropoietin.

The effect of erythropoietin (Epo) on colony formation by blast progenitors in acute myeloblastic leukaemia other than erythroleukaemia was studied using a blast colony assay. Epo alone did not induce colony formation, but when it was used together with phytohaemagglutinin-stimulated leucocyte-conditioned medium (PHA-LCM) the number of leukaemic colonies significantly increased in nine out of 12 cases studies. Preincubation of Epo with anti-Epo antibody completely abolished this enhancement, indicating that the increase in colony numbers was caused by Epo itself. Cell surface phenotype analysis of colonies produced by Epo plus PHA-LCM showed no increase in percentages of erythroid and megakaryocyte lineages. The addition of Epo also increased the self-renewal capacity of leukaemic blast cells. Fresh leukaemic cells did not express Epo receptors, but they were induced after incubation with PHA-LCM. The present study thus showed that the proliferative response to Epo is not restricted only to the erythroid lineage, but also extends to AML blast cells other than those in erythroleukaemia in the presence of colony stimulating factors.

Antibodies↗
PubMed1990

[Therapeutic evaluation of combination therapy using C-425, human native immunoglobulin liquid preparation for i.v. administration, with antibiotics in severe infections in the field of internal medicine].

A novel human native immunoglobulin liquid preparation for intravenous injection, C-425, was used in combination with antibiotics to study its efficacy, safety, and usefulness in 262 patients with severe infections which had not responded to antibiotic therapy of 3-day or more duration. As a result of the Committee judgement, 12 of the 262 patients were excluded from this study; 87 were included only in safety analysis; 163 (62.2%) were included in efficacy, safety, and usefulness analyses (complete inclusion). The complete analysis of 163 patients consisted of 93 patients (57.1%) with suspected septicemia, 33 (20.2%) with pneumonia, and 18 (11.0%) with septicemia. Eighty percent or more of the patients had severe underlying diseases such as leukemia and malignant lymphoma. Clinical efficacy of C-425 was judged by the doctors in charge to be "excellent" or "good" in 49.1% of the total cases. The rate of effectiveness was calculated at 74.8% when "excellent", "good" and "fair" cases were all included. Similarly, the rate of effectiveness calculated from the results of Committee judgment was 53.4% when "excellent" and "good" cases were included, and 68.7% when "excellent", "good" and "fair" cases were included. Microbiological assessment was conducted in 19 patients. Causative organisms were eliminated in 11 patients, decreased in number in 1, persisted in 5, and replaced in 2. The rate of elimination was 57.9%. Side effects appeared in 6 of 250 patients (2.4%). It was judged that 3 patients (1.2%) of the 6 were affected by the drug or suspected to be affected, but they were not considered clinically important. Hepatic disfunction was found in 4 patients (1.6%) of the 250; but it was not clarified whether this was related to the drug. From these results, C-425 was considered to be an effective and very safe drug for treating severe internal infections.

Adolescent↗
PubMed1990

Renal tissue and urinary kallikrein activity in two-kidney, one-clip hypertensive rats.

Renal tissue and urinary kallikrein activity were studied to assess the role of the renal kallikrein-kinin system in two-kidney, one-clip hypertensive rats. Body weight, urine volume, systolic blood pressure and urinary kallikrein activity were measured in 11 hypertensive rats and 6 normotensive rats 1, 4, 8 and 12 weeks after clipping or sham operation. The hypertensive rats used in the present study had systolic blood pressures of over 180 mm Hg 12 weeks after the operation and presented polyuria with a reduction in weight gain, which placed them in the malignant hypertension category. Urinary kallikrein activity in hypertensive rats significantly decreased from 21.7 +/- 13.3 nkat/day at 1 week to 11.6 +/- 5.5 nkat/day at 12 weeks after clipping (p less than 0.05), while urinary kallikrein activity in normotensive rats significantly increased from 23.6 +/- 8.9 nkat/day at 1 week to 43.7 +/- 16.2 nkat/day at 4 weeks after the sham operation. Significant differences were observed in urinary kallikrein activity between hypertensive rats and normotensive rats 4 and 12 weeks after the operation (p less than 0.05). Renal tissue kallikrein activity from bilaterally nephrectomized kidneys was investigated 12 weeks after the operation. No significant difference in tissue kallikrein activity was found between the two kidneys of the hypertensive rats. However, tissue kallikrein activity was significantly lower in the contralateral kidney of hypertensive rats as compared to the same kidney of normotensive rats (2.13 +/- 0.73 nkat/g in hypertensive rats vs. 3.05 +/- 0.69 nkat/g in normotensive rats, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Bradykinin and respiratory mucous membranes. Analysis of bradykinin binding site distribution and secretory responses in vitro and in vivo.

Bradykinin (BK) and lysyl-BK (lys-BK, kallidin) have been proposed as potentially important mediators of rhinorrhea. Possible mechanisms by which BK might contribute to rhinorrhea were investigated by several approaches. (1) The autoradiographic distribution of 125I-BK binding sites in human inferior turbinate nasal mucosa was determined. (2) The effects of BK and lys-BK and antagonists on radiolabeled respiratory glycoconjugate (RGC) release from human nasal mucosa was measured. (3) The secretory effects of BK were studied in cat tracheal mucosa maintained in short-term explant culture, and in ferret trachea maintained in Ussing chambers. (4) The effects of BK on macromolecule secretion in guinea pig nasal mucosa was studied in vivo. Autoradiographic examination of human nasal mucosa revealed that 125I-BK specifically bound to small muscular arteries, venous sinusoids, and submucosal fibers. No specific binding to submucosal glands or goblet cells was noted. Human nasal fragments secreted significantly increased amounts of RGC in response to 10 microM BK (15.0% +/- 1.8 compared with control values; mean +/- standard error of the mean; n = 7; p less than 0.01 by Student's unpaired t test), 10 microM lys-BK (12.2% +/- 3.3; n = 5; p less than 0.05), and 100 microM methacholine (35.7% +/- 2.3; p less than 0.0001). The addition of 1 microM BK, or 1 microM lys-BK, did not induce release. The addition of the BK receptor antagonist des-Arg9-[Leu8]-BK (10 microM) or inhibition of arachidonic acid metabolism with 50 microM nordihydroguaiaretic acid or 65 microM ibuprofen inhibited the prosecretory effect of 10 microM BK.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1990

[A phase III study of KRN 8601 (rhG-CSF) on neutropenia induced by chemotherapy for malignant lymphoma--a multi-institutional placebo controlled double-blind comparative study].

The clinical usefulness of KRN 8601 (rhG-CSF) was evaluated in patients with neutropenia induced by chemotherapy for non-Hodgkin lymphoma in a double-blind study. The same chemotherapeutic regimens repeated for twice in 3 to 4 weeks interval. During the first cycle of chemotherapy, changes of leukopenia (neutropenia) were observed, and KRN 8601 at a dose of 75 micrograms/body or placebo was started to administer subcutaneously 72 hours after the termination of the second cycle and continued for 14 days. Elevations of nadirs of absolute neutrophil counts (ANC) and significant shorting of neutropenic periods of ANC below 2,000/mm3 were observed with patients given KRN 8601. KRN 8601 is significantly superior over placebo (p less than 0.0001), while overall safety evaluation showed no significant difference between the two groups. All the above results indicate that KRN 8601 is extremely usefull for the neutropenia induced by chemotherapy.

Adult↗