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Biomedical subjects

M Harada

Publications and source records attributed to M Harada.

At least 847 records · Page 47Linked to original sources

Evidence of sex difference in DNA synthesis in hepatocellular carcinoma.

To clarify sex differences in DNA synthesis in hepatocellular carcinoma (HCC), bromodeoxyuridine labeling indices (BrdU LI) of HCC cells included in tumor biopsy specimens from 12 consecutive male patients and from 5 consecutive female patients all with liver cirrhosis and HCC were examined using an in vitro labeling technique. The mean BrdU LI +/- SE of HCC from male patients (7.7 +/- 0.8%) was significantly (P less than 0.05) higher than that from female patients (4.4 +/- 1.0%). While 7 of the 12 male HCC patients belonged to the high DNA synthesis group (BrdU LI greater than or equal to 7.0%), none of the 5 female HCC patients showed high DNA synthesis (P less than 0.05). We conclude that DNA synthesis in HCC was higher in males than in females.

Aged↗

Characterization of leukaemic basophil progenitors from chronic myelogenous leukaemia.

We describe the unique characteristics of leukaemic basophils from a patient with chronic myelogenous leukaemia (CML). The leukaemic cells were immature basophil-like blasts and expressed CD4, CD7 and HLA-DR in addition to CD13 and CD33. Both immunoglobulin and T cell receptor genes were retained in germline configurations. Interleukin-1 (IL-1) or granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as IL-3 or IL-4 enhanced the proliferation and differentiation of leukaemic cells and only basophils were generated from in vitro culture. These results suggest that basophil progenitors expressing CD4, CD7 and HLA-DR may be involved in the development of basophilic crisis of CML and that both IL-1 and GM-CSF may act on basophil progenitors as well as IL-3 or IL-4.

Antigens, CD↗

Human granulocyte colony-stimulating factor receptors in acute myelogenous leukemia.

Human granulocyte colony-stimulating factor (G-CSF) receptors on human acute leukemia cells were investigated using human G-CSF iodolabeled by the lactoperoxidase method. Among various human leukemic cell lines, only cells of myelogenous lineage including HL-60, THP-1 and U937 had one type of high-affinity receptor for G-CSF, as shown by Scatchard analysis. Fresh leukemia cells from 19 patients with acute myelogenous leukemia (AML) were then studied. Specific receptors for G-CSF were demonstrated on blast cells in all 19 cases, the mean number of G-CSF receptors per AML cell ranging from 95 to 1436. G-CSF receptors on AML cells appeared to be a single affinity type, although some variations were observed. The mean number of G-CSF receptors on leukemic cells from patients with either FAB M3 or FAB M2 was greater than that of cells from patients with M1 (p less than 0.01, p less than 0.10, respectively). Moreover, the mean number of receptors for G-CSF on CD13- and CD34-positive AML cells was higher than that on CD13-negative and CD34-positive AML cells (p less than 0.01), and the mean number of G-CSF receptors on CD7-positive AML cells was lower than that for CD7-negative AML cells (p less than 0.10). Since the FAB classification and surface phenotypes reflect maturation stages, our findings indicate that the distribution of G-CSF receptors, even on AML cells, may be related to the maturation process.

Adolescent↗

Role of interleukin-4 in the negative regulation of proliferation of chronic myelomonocytic leukemia cells.

We studied the effects of interleukin-4 (IL-4) on the spontaneous proliferation of chronic myelomonocytic leukemia (CMMoL) cells in vitro to clarify whether IL-4 can act as a negative regulator of hematopoiesis. The results clearly show that IL-4 suppressed spontaneous DNA synthesis and colony formation by CMMoL cells in vitro. Colony formation by CMMoL cells was substantially suppressed by adding either an anti-IL-6 or anti-GM-CSF antibody to the colony assay system. This suppression was abrogated by the treatment of IL-4 with an anti-IL-4 antibody. Furthermore, the production of IL-6 or GM-CSF was markedly inhibited by adding IL-4 to the culture system. These observations indicate that IL-4 can act as a negative regulator for the autocrine growth of CMMoL cells by inhibiting their production of IL-6 and/or GM-CSF.

Aged↗

Differences in alpha 1-adrenoceptor mechanisms for phenylephrine and tizanidine in rabbit thoracic aorta and common iliac artery.

Based on affinity for WB4101 and susceptibility to chloroethylclonidine, we evaluated the subtype of alpha 1-adrenoceptors activated by phenylephrine (a full agonist) and tizanidine (a partial agonist). The rabbit thoracic aorta and common iliac artery contain both alpha 1A- and alpha 1B-adrenoceptors, but the alpha 1B-subtype may be more predominantly in the common iliac artery than in the thoracic aorta. In rabbit thoracic aorta and common iliac artery, phenylephrine induced contraction through both alpha 1A- and alpha 1B-subtypes and tizanidine through only the alpha 1A-subtype. The subtype activated by phenylephrine may be partly different from that activated by tizanidine in the preparations used herein.

Animals↗

Acute eosinophilic leukemia in a patient with preexistent myelodysplastic syndrome.

A case of acute eosinophilic leukemia (EoL) that occurred in a patient with preexistent myelodysplastic syndrome is reported. The patient was initially diagnosed as having refractory anemia (RA) on the basis of pancytopenia with dysplasia and chromosomal abnormalities. Two years later, he was readmitted because of progression of pancytopenia, and bone marrow and peripheral blood showed immature dysplastic eosinophils. Clonal assay of peripheral blood mononuclear cells revealed autonomous growth of colony-forming unit eosinophils. Cytotoxic chemotherapy did not induce remission, and extensive myelofibrosis developed. Cytogenetic analysis in the RA state showed +1p- and -7 whereas complicated abnormalities including +1p-, 3q- and 7p- dominated in the EoL state.

Cells, Cultured↗

Human recombinant granulocyte colony-stimulating factor for the treatment of autoimmune neutropenia.

We have recently treated a case of autoimmune neutropenia in a 57-year-old male. Because neutropenia persisted despite the administration of prednisolone for 30 days, daily subcutaneous injection of human recombinant granulocyte colony-stimulating factor (rhG-CSF) at a dosage of 100 micrograms was started. Neutrophil count increased gradually and reached a plateau of 5,000/microliters by day 25 after administration of rhG-CSF. This observation suggests that rhG-CSF is effective for the treatment of autoimmune neutropenia.

Autoimmune Diseases↗

Immunological analysis of acquired factor VIII inhibitor in a case with immunologic disorder.

Coagulation factor VIII inhibitor arising in a patient with autoimmune disease was immunologically analyzed. A 63-year-old man who had been diagnosed as suffering from polyarteritis nodosa was treated with prednisolone for 10 years. Severe bleeding tendency developed and coagulation studies demonstrated a high titer of inhibitor to factor VIII:C. As a result of immunological analysis, the inhibitor was found to be IgG type autoantibody having both kappa and lambda light chains. The subclasses were IgG1 and IgG4. The inhibitor recognized the COOH-terminal light chain (72-kDa thrombin fragment) on the factor VIII molecule as an epitope.

Autoantibodies↗

Combined cisplatin and radiation therapy for advanced bladder cancer.

Since September 1985, 44 patients with advanced urinary bladder cancer have been treated by combined cisplatin and full-dose radiotherapy. The patients were 32 males and 12 females, and their ages ranged from 33 to 83 years, with a median of 67.4 years. Radiotherapy consisting of a tumor dose of 50-60 Gy was administered with cobalt-60. Cisplatin was infused 5 days at a daily dose of 20 mg on the 1st and 4th weeks of treatment. Of the 39 evaluable patients 27 (69.2%) achieved a complete response. Toxicity was also evaluated for those 44 patients. Mainly gastrointestinal toxicity was noted: loss of appetite in 28 (64%), nausea and/or vomiting in 21 (48%), and diarrhea in 8 (18%). Leukocytopenia was noted in 16 (33%) and mild thrombocytopenia in 5 (11%). Mild dermatitis was noted in 8 (18%).

Aged↗

Interleukin 4 suppresses the spontaneous growth of chronic myelomonocytic leukemia cells.

We studied the effects of IL-4 on the spontaneous proliferation of chronic myelomonocytic leukemia (CMMoL) cells in vitro. IL-4 (100 U/ml) suppressed the spontaneous DNA synthesis by approximately 50% in 5 of 8 cases examined. IL-4 (100 U/ml) also inhibited the spontaneous colony formation by CMMoL cells in a methylcellulose culture by 50-97% in all of the 10 cases in which spontaneous colonies were formed. This IL-4-mediated suppression of the growth of CMMoL cells was completely abolished by the addition of anti-IL-4 neutralizing antibodies. The spontaneous CMMoL colonies were substantially suppressed by the addition of either anti-IL-6 or anti-granulocyte/macrophage colony-stimulating factor (GM-CSF) antibodies to the colony assay system: the addition of both anti-IL-6 and anti-GM-CSF antibodies resulted in greater than 80% inhibition of the colony formation by CMMoL cells. On the other hand, none of anti-IL-1-beta, anti-granulocyte-CSF, anti-macrophage-CSF, or anti-tumor necrosis factor-alpha antibodies affected the CMMoL colony formation. In the supernatants from 24-h cultures of CMMoL cells, high levels of IL-6 and GM-CSF were demonstrated in 9 of 9 and 2 of 9 cases examined, respectively. IL-4 (100 U/ml) almost completely inhibited the secretion of IL-6 and GM-CSF by CMMoL cells. These observations suggest that IL-4 suppresses the spontaneous proliferation of CMMoL cells by inhibiting their production of IL-6 and/or GM-CSF, both of which could act in vitro as an autocrine growth factor for CMMoL cells.

Adult↗

Anti-inflammatory effect of Zingiber cassumunar Roxb. and its active principles.

The present study was carried out to elucidate the anti-inflammatory effect of the methanol extract obtained from the rhizomes of Zingiber cassumunar Roxb. and its active principles. The methanol extract was partitioned between ether and water, and then the ether-soluble fraction was extracted with n-hexane. The n-hexane-soluble fraction was chromatographed and part of the fraction was rechromatographed by silica gel column. Three compounds were isolated from the n-hexane-soluble fraction and the chemical structures of these compounds were identified as (E)-1-(3,4-dimethoxyphenyl)but-1-ene, (E)-1-(3,4-dimethoxyphenyl)butadiene and zerumbone. The anti-inflammatory activity of these fractions was investigated on carrageenin-induced edema in rats, as well as on acetic acid-induced vascular permeability and writhing symptoms in mice. The methanol extract (p.o.) showed both anti-inflammatory activity and analgesic activity. These activities shifted successively to ether-soluble and n-hexane-soluble fractions and to (E)-1-(3,4-dimethoxyphenyl)but-1-ene. These results suggest that the anti-inflammatory action and analgesic action of Zingiber cassumunar is the result of the (E)-1-(3,4-dimethoxyphenyl)but-1-ene that it contains.

Animals↗

A difference in receptor mechanisms for muscarinic full and partial agonists.

Concentration-response curves of 4 muscarinic full agonists were progressively inhibited by 10 to 50-min treatments of the longitudinal muscle of guinea pig ileum with propylbenzilylcholine mustard (PrBCM, 3 x 10(-6) M). A 90-min treatment with PrBCM had no further significant inhibitory effect on their curves. The 50-min treatment with PrBCM (3 x 10(-6) M) completely inhibited the concentration-response curves of 6 partial agonists. The limiting effect of PrBCM observed on the concentration-response curves of the full agonists was not found on the curves of the partial agonists. These results suggest that there are two subtypes of M3-cholinoceptors, PrBCM-sensitive receptors and PrBCM-resistant ones. Pilocarpine, a partial agonist, shifted the concentration-response curve of carbachol, a full agonist, in a parallel fashion in the strips treated with PrBCM (3 x 10(-6) M) for 50 min, suggesting that an interaction of pilocarpine with PrBCM-resistant cholinoceptors does not induce contraction. The full agonists contract the longitudinal muscle through the interaction of two cholinoceptors, PrBCM-sensitive and -resistant ones, while the partial agonists produce the contraction through the activation of PrBCM-sensitive ones.

Animals↗

Inhibition of ion channels by hirsutine in rat pheochromocytoma cells.

Effects of hirsutine, an alkaloid that produces a potent ganglion blocking effect, were investigated using rat pheochromocytoma PC12 cells. Hirsutine (1 to 10 microM) suppressed dopamine-release evoked by 100 microM nicotine. In voltage-clamped cells, hirsutine (1 to 10 microM) inhibited the inward current activated by 100 microM nicotine. Hirsutine was equipotent to hexamethonium in blocking the nicotine-activated current. The voltage-dependency of the nicotine activated current was not modified by hirsutine. Effects of hirustine on other ion channels were tested to determine its selectivity. Inward currents mediated through ATP-activated channels were scarcely affected by hirsutine (up to 100 microM). However, hirustine (10 microM) inhibited Ba currents passing through Ca channels and K currents activated by depolarizing voltage steps. The results suggest that hirsutine potently blocks nicotinic receptor-channels, but hirsutine also inhibits voltage-gated Ca and K channels. Roles of the inhibition of these channels in the pharmacological effects of hirsutine were discussed.

Adrenal Gland Neoplasms↗

High susceptibility of cataract Shionogi (CTS) mice to passive anaphylactic shock mediated by allogeneic IgE and IgG1 monoclonal antibodies.

The susceptibility of cataract Shionogi (CTS) mice as young as 8 to 10 weeks of age to passive anaphylactic shock mediated by anti-benzylpenicilloyl IgE and IgG1 monoclonal antibodies was compared with those of other strains of the same age including sister strains such as nonobese-diabetic (NOD) and nonobese-nondiabetic (NON). When the animals had been treated with killed Bordetella pertussis organisms, potent sensitization, enough to cause lethal shock, was produced by either monoclonal antibody preparation in CTS, NOD, C57BL/6J and DS/Shi strains, but not at all in C3H/He, DBA/2 and BALB/c strains. In the NON strain, lethal shock was elicited in the animals sensitized with the IgG1 antibody but not in those sensitized with the IgE antibody. Without the pertussis pretreatment, sensitization sufficient to cause lethal shock was produced at a high frequency by the IgG1 antibody in CTS and NOD mice but not in the other strains. When the IgE antibody was used, lethal shock was not observed in any of the mouse strains tested except for one CTS mouse. These results indicate that CTS as well as NOD are highly susceptible strains, and that IgG1 antibody is more effective than IgE antibody for producing systemic sensitization for anaphylactic shock. In addition to these findings, the results revealed an age-dependent potentiation of anaphylactic shock in CTS mice. The IgE antibody-mediated lethal shock was produced in all the aged animals of this mouse strain tested without the Bp treatment, but not in aged NOD and NON mice.

Age Factors↗

Synthesis and assignment of novel [125I]-labeled 1 alpha,25-dihydroxyvitamin D3 derivatives.

This paper describes the synthesis and structural assignment of noval 125I-1 alpha,25-dihydroxyvitamin D3 derivatives (1a) and (1b) labeled with 125I-Bolton-Hunter reagent [N-succinimidyl 3-(4-hydroxy-3-iodo[125I]phenyl)propionate] (1), which is known as a protein-labeling reagent, as tracers for radioimmunoassay (RIA). The radiospecific activities of these tracers (1a) and (1b) were calculated as 2,200 Ci/mmol (81.4 TBq/mmol).

Calcitriol↗

[Prostate cancer: retrospective study of long-term follow-up cases. Is it possible to discontinue hormonal medications?].

We reviewed retrospectively the medical records of 70 patients treated for prostate cancer who were followed for more than 10 years or until they died. All patients were treated by hormonal therapy and 54 of 70 patients (77 per cent) were combined with castration. Of 70 patients 10 (14.3 per cent) are alive now with an average follow up for 180.5 months. Of 60 patients with stage A and B only 3 died of the tumor. Of 56 patients with stage C and D, 10 and 18 patients died of the tumor, respectively. From the point of pathology, none of the patients with well differentiated adenocarcinoma died of the tumor. And in patients with stage A and B, pathologically well and moderately differentiated adenocarcinoma, there were no cancer death. On the other hand, a group of patients of poorly differentiated adenocarcinoma had a poor prognosis. In cases with well differentiated adenocarcinoma who discontinued hormonal medication (diethylstilbestrol diphosphate) no patients died of the tumor. From these observations we consider that, after long term hormonal medication, we can stop the hormonal medication for patients who have no positive prostate biopsy results for 4 years with well differentiated adenocarcinoma of stage A and B.

Adenocarcinoma↗