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Biomedical subjects

M Hiyoshi

Publications and source records attributed to M Hiyoshi.

At least 37 records · Page 2Linked to original sources

Long-term survival in a case of high-risk type IgD myeloma; a possibility of effectiveness of interferon-alpha and erythropoietin.

The prognosis of patients with IgD myeloma is poorest among all types of multiple myeloma. We report a case of a patient with IgD myeloma who survived for an extraordinarily long period post-diagnosis (65 months). According to the new risk grouping of IgD myeloma (Shimamoto Y. et al., Eur. J. Haematol. 47, 262 (1991), he was classified as being in the high-risk group, with a zero percent expected 5-yr survival. Nevertheless, he survived for 65 months. We discuss the usefulness of interferon-alpha and erythropoietin for the treatment of IgD myeloma.

Antineoplastic Agents↗

A new type of major aminopeptidase in bovine brain.

A new type of major aminopeptidase was purified from bovine brain by ammonium sulfate fractionation and TMAE-fractogel (anion exchange), arginine-Sepharose 4B, Sephadex G-150, and Sephadex G-100 column chromatography. The purified enzyme showed a maximum activity at pH 7.2, and its molecular size was estimated to be 98,000 by gel filtration and 104,000 by SDS-PAGE with or without 2-mercaptoethanol. Further properties were activation by thiol reagents; inhibition by EDTA, puromycin, bestatin, amastatin, actinonin, leuhistin and probestin; and very low concentrations of Cu2+, Cd2+, Pb2+, Al3+, Fe3+, and Zn2+ inhibited activity. The enzyme hydrolyzed several amino acyl-7-amido-4-methylcoumalin derivatives (amino acid-MCA). The order of MCA-substrate specificity expressed as kcat/Km is Lys-MCA > Arg-MCA > Leu-MCA > Met-MCA > Phe-MCA > Tyr-MCA > Ala-MCA >> Gly-MCA, Pro-MCA, Ser-MCA, Asn-MCA. Immunoreactivity of the antibody against the purified aminopeptidase was observed in human brain and most rat tissues examined including brain, liver, kidney, lung, heart, and skeletal muscle at the same molecular size as in bovine brain aminopeptidase. Most of the Lys-, Leu-, Met-, and Phe-MCA degrading activity in crude bovine and human brain extracts was absorbed by the aminopeptidase IgG, suggesting that this aminopeptidase is a major enzyme, sharing at least Lys-, Leu-, Met-, and Phe-MCA degrading aminopeptidase activities in the brains.

Amino Acids↗

Experimental Chlamydia psittaci infection of Japanese quail.

Japanese quail were used for the infection model of avian chlamydiosis. One-day-old Japanese quail were highly susceptible to lethal infection by a Chlamydia psittaci strain of budgerigar origin upon inoculation via the air sac route with 10(4.1) FFU of the organism, showing an acute and lethal course with chlamydial propagation. In contrast, 7-day-old quail developed resistance to the infection as shown by the lack of lethal effect with the same dose. The resistance of 7-day-old birds was abolished by immunosuppressive treatment with cyclophosphamide. Upon inoculation with a sublethal dose of 10(2.1) FFU, latent infection was established in 1-day-old birds with a minimum number of the organism. The latent infection in the birds was converted to the lethal form by treatment with cyclophosphamide along with chlamydial propagation and suppression of antibody production.

Aging↗

Establishment and characterization of IRTA17 and IRTA21, two novel acute non-lymphocytic leukaemia cell lines with t(16;21) translocation.

The t(16;21)(p11;q22) translocation is an infrequent chromosomal abnormality, but seems specific to acute non-lymphocytic leukaemia (ANLL). We established two cell lines with t(16;21)(p11;q22) from the bone marrow of a patient with ANL in relapse. Their morphological, karyotypic, immunohistochemical and genetic features are examined. Although both cell lines show monocytoid features morphologically, they express only CD13 (My7) and CD34, and neither expressed monocytoid or lymphoid markers. Reverse transcription-polymerase chain reaction showed that both cell lines expressed a similar TLS-ERG chimaeric mRNA as a result of the t(16;21)(p11;q22) translocation. As far as we know, there is no report of a leukaemia cell line with t(16;21). These cell lines represent a useful tool for leukaemia research.

Adult↗

Acute non-lymphoblastic leukaemia with t(16;21): case report with a review of the literature.

A rare case of acute non-lymphoblastic leukaemia with chromosomal t(16;21)(p11;q22) translocation was studied at the molecular level. Most of the previous reports about the translocation have been described at a karyotypic level. Blast cells of this patient expressed the TLS-ERG chimeric mRNA. The clinical, morphological, karyotypic, and immunohistochemical aspects of this leukaemia are also presented with a review of the literature.

Adult↗

Assay of DNA denaturation by polymerase chain reaction-driven fluorescent label incorporation and fluorescence resonance energy transfer.

We have developed a simple and sensitive assay method to monitor DNA denaturation. This method is based on (i) incorporation of fluorescent labels onto complementary DNA strands during target-specific amplification by polymerase chain reaction and (ii) detection of DNA denaturation by fluorescence resonance energy transfer. Fluorescein-11-dUTP and rhodamine-4-dUTP were used to label complementary DNA strands as the energy transfer donors and acceptors, respectively. The complementary DNA strands thus labeled were then annealed by incubation at a constant temperature, and the energy transfer efficiency was monitored during DNA denaturation experiments. Both heat denaturation and alkali denaturation could be monitored by this assay. Some factors affecting the DNA denaturation were also investigated.

DNA↗

Treatment with cytosine arabinoside and granulocyte colony-stimulating factor in patients with myelodysplastic syndrome and its leukemic phase.

Twenty-one patients with myelodysplastic syndrome (MDS) or overt leukemia resulting from MDS were treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) and cytosine arabinoside (Ara-C). Ara-C was administered in a dose of 20 mg/m2 every 12 h for 5 days and after 2 days 125 micrograms of rhG-CSF was administered for 10 days. After recovery of the leukocyte count the therapy was repeated, doubling the dose of Ara-C serially when possible. Of 13 patients with MDS, four achieved complete remission (CR), two good response (GR), two minor response (MR), and five no response (NR). Of eight patients with overt leukemia from MDS, only one with hyperplastic bone marrow achieved a partial response (PR) and the remaining seven achieved NR. The efficacy of the combination of rhG-CSF and Ara-C in the treatment of MDS and its leukemic phase is discussed, including at which time rhG-CSF should be administered: before, after or concomitantly with Ara-C. Multicenter randomized studies are needed in the evaluation of this combination therapy.

Adult↗

Comparison of two monoclonal antibodies, H6B11 and GS2C4, against human plasma gelsolin.

We compared the properties of a new monoclonal antibody developed in our laboratory, H6B11, against human plasma gelsolin with those of GS2C4, which is commercially available. Both antibodies recognize human plasma gelsolin in an enzyme-linked immunosorbent assay (ELISA), and demonstrated similar interference activity for actin gelation, but exhibited differing behaviors toward gel electrophoresis and electroblotting. H6B11 did not bind to gelsolin on an electroblotted membrane after electrophoresis on sodium dodecyl sulfate-polyacrylamide gel, in contrast to GS2C4. However, under certain milder conditions, H6B11 was able to bind to gelsolin. H6B11 was thus judged to be capable of partially recognizing gelsolin conformation, while GS2C4 recognized part of the amino acid-sequence of gelsolin. The faster reaction of H6B11 in the ELISA and the linearity of the results, indicates that the ELISA for plasma gelsolin can be used in routine laboratory testing.

Antibodies, Monoclonal↗

Vestibular compensation in vestibular neuronitis: evaluation of positional nystagmus and caloric nystagmus.

We evaluated the vestibular functions, especially for positional nystagmus and caloric nystagmus, in 43 cases of vestibular neuronitis for long periods after its onset. It is shown that in the cases of vestibular neuronitis that were studied more than 10 years after the onset of the disease, the completed vestibular compensation changed or the vestibular compensation was still incomplete.

Caloric Tests↗

An anti-platelet activating factor antibody and its effects on platelet aggregation.

Production of antibodies against platelet activating factor (PAF) has been difficult, probably because of the low antigenicity of PAF, a low-molecular-weight phospholipid. We therefore used colloidal gold as a hapten carrier to produce anti-PAF polyclonal and monoclonal antibodies. Both antibodies reacted with PAF, lyso PAF, and L-alpha-lysophosphatidyl choline palmitoyl (lyso PCP), but they did not react phosphorylcholine chloride (PCC). Their affinities were higher for PAF than for lyso PAF and lyso PCP. When the antibodies were tested on PAF-induced platelet aggregation, they suppressed aggregation in a dose-dependent manner.

Animals↗

Monoclonal antibody to human plasma gelsolin.

Human plasma gelsolin was purified by column chromatography. The method yielded a protein of high purity and activity. Using this protein, we produced monoclonal antibody (Mab H6B11) against human plasma gelsolin by somatic cell fusion. This monoclonal antibody reacted in a dose-dependent manner with gelsolin derived from human plasma and platelets and neutralized depolymerizing activity to F-actin. It differed from the commercially available substance (Mab G4896; Sigma) in that the time required for the reaction between the antigen and antibody in the enzyme-linked immunosorbent assay could be shortened by one-third. The antibody was judged to be useful in assays for elucidating the physiological role of plasma gelsolin.

Animals↗

[Timing of administration of granulocyte colony stimulating factor after cytotoxic chemotherapy in hematological malignancies].

We evaluated the effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) given to 30 patients with hematological malignancies after cytotoxic chemotherapy. The first course of chemotherapy was not treated with rhG-CSF (control), and in the second to fourth courses, rhG-CSF was given by one of the following three ways to the patients (not necessarily in this order): 1) 10 days of administration starting 48 hr after chemotherapy, 2) 5 days of administration starting 48 hr after chemotherapy, and 3) 5 days of administration after the leukocyte counts reached to less than 2,000/microliters. The leukocyte nadirs were significantly higher in the course with 10 days of administration compared with the control course. The time needed for recovery from the leukocyte nadir was significantly shorter in 10-day course and 5-day course after the leukocyte counts reached to less than 2,000/microliters. The therapy spans became significantly shorter with all of the three patterns of administration of rhG-CSF compared with the control course. The number of days on which the leukocyte counts became less than 2,000/microliters were significantly fewer in 10-day course and 5-day course after the leukocyte counts became less than 2,000/microliters. These findings showed that rhG-CSF prevented severe neutropenia after cytotoxic chemotherapy, and (or) assisted the rapid recovery from neutropenia. These effects depend on the timing of its administration.

Acute Disease↗

Therapy with mitoxantrone, ifosfamide, vindesine, and prednisolone for malignant lymphoma with adjustable doses and timing of courses.

Thirty-seven patients with malignant lymphoma were treated with mitoxantrone, ifosfamide, vindesine, and prednisolone. The time among courses was not fixed, being decided by the time for recovery from the leukopenia caused by the treatment. The drug dose was adjusted after the initial course. Of the 12 patients treated for the first time, eight had a complete remission and two had a partial response. Of the 18 patients who relapsed after another drug regimen, six had a complete remission and seven had a partial response. The SD of the leukocyte nadirs decreased after the first course, and time needed for recovery from leukopenia tended to shorten during treatment. Side effects seemed mild, and we can use many drugs safely in a short term without long drug-free intervals. Response rates were satisfactory, compared with other report, so this method of timing the start of courses with adjustment of the dose seems useful.

Antineoplastic Combined Chemotherapy Protocols↗

Interleukin-2 induces motility of human lymphocytes, but not their mobility.

Interleukin-2 induces cytotoxic and antitumor activities of human lymphocytes. For the expression of these activities, the cytoskeletal system is probably activated. This study was do;ne to find if interleukin-2 causes cell movement. Lymphocytes were incubated with interleukin-2, and their morphology and motile activities were studied. After 72 hr of incubation, some 29% of lymphocytes were larger than before; nucleoli had formed and the microvilli were well-developed. The membrane potential of the lymphocytes increased during incubation. Motility under agar after 3 days of incubation with interleukin-2 was examined. Cells aggregated in clumps in the incubation well, and migration was not observed. When mobility was examined with Boyden's method, fewer cells incubated with interleukin-2 migrated than in control preparations. Cells incubated with interleukin-2 were extracted with Triton X-100. The extract obtained had three more bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis than the controls. The band were at the positions for the molecular weights of 270,000-300,000. We concluded that interleukin-2 activated the motility of lymphocytes, but not their mobility.

Cell Aggregation↗

Evaluation of serum sialyl Lewisx-i in hematologic disorders.

Sialyl Lewisx-i (SLX) was found in more than 40% of patients with acute leukemia or chronic myelogenous leukemia, and in about 20% of those with myelodysplastic syndrome or malignant lymphoma. This tumor marker was absent in all patients with polycythemia vera, essential thrombocythemia, primary myelofibrosis, chronic lymphatic leukemia, multiple myeloma, and those with acute leukemia or malignant lymphoma in remission. The marker was found in 8% and of the patients with idiopathic thrombocytopenic purpura and 33% of those with autoimmune hemolytic anemia but in no patient with aplastic anemia or megaloblastic anemia. Immunostaining with SLX antibody showed that tumor cells of the patients with high levels of serum SLX were producing the SLX antigen. The detection of this marker in the serum is thought to be useful not only in the diagnosis but also in the observation of the recurrence of the diseases.

Antigens↗

Evaluation of 117 patients with non-Hodgkin's lymphoma in the past ten years at our department.

We did a retrospective statistical study of 117 patients with non-Hodgkin's lymphoma admitted to our hospital from January 1979 to December 1988. Five-year survival was 83% for patients in stage I at diagnosis, which was significantly better than the 55% in stage II, 37% in stage III, and 34% in stage IV. Five-year survival was 74% for patients with B-cell lymphoma (74%), which was significantly better than with the 32% for T-cell lymphoma. For patients in stage I or II, five-year survival was 46% for those with nasal lymphoma, which was significantly worse than the 72% with nodal lymphoma and the 82% for those with Waldeyer's lymphoma. Sixty-eight patients were treated initially with radiation only. The relapse frequency was 20% in stage I and 40% in stage II. All of the relapses occurred outside the irradiated area treated on the other side of the diaphragm. Of all 48 patients with combination chemotherapy such as vincristine, cyclophosphamide, predonisolone, and Adriamycin (VEPA), mitoxantrone, cyclophosphamide, vincristine, and predonisolone (MCOP), and mitoxantrone, ifosfamide, vindesine, and predonisolone (MIFP), 33 (69%) achieved complete remission.

Adolescent↗