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Biomedical subjects

A Horiuchi

Publications and source records attributed to A Horiuchi.

At least 199 records · Page 11Linked to original sources

The relationship between the defect in the syngeneic mixed lymphocyte reaction and thymic abnormality in New Zealand mice.

Whether a defect the syngeneic mixed lymphocyte reaction (SMLR) is caused by an abnormality in the recognition of autoantigen (Ia antigen) by T cells or by an abnormality in macrophages (Mø) which provides the Ia antigen was examined using New Zealand black (NZB) mice, a model animal for human autoimmune diseases. The level of activation of T cells by Ia antigen was lower in NZB mice than in normal mice, despite the fact that the quantity of Ia antigen expressed on the surface of Mø was much the same in the NZB mice. Furthermore, less Ia antigen was expressed on thymic reticuloepithelial cells (TRC) in NZB mice than in normal mice. These findings suggest that the defect in the SMLR in NZB mice is mainly due to T cells, namely, to abnormality in the activation of the Ia antigen receptors on the T cells, which occurs as a result of the contact between T cells and TRC in the process of T cell maturation and differentiation.

Animals↗

Effects of forskolin on pancreatic exocrine secretion and cyclic nucleotide concentrations of the dog pancreas.

The effects of forskolin on the secretion of pancreatic juice and on the intracellular levels of cyclic nucleotides were investigated in preparations of the isolated and blood-perfused dog pancreas. Forskolin (3-100 micrograms) injected intra-arterially caused a dose-dependent increase in the secretion of pancreatic juice. The concentration of bicarbonate in the pancreatic juice induced by forskolin was increased. However, protein concentration was decreased. Forskolin-induced secretion was not modified by pretreatment with atropine, phentolamine, propranolol, cimetidine, sulpiride and verapamil. Forskolin (10-30 micrograms) significantly increased cyclic AMP concentration in the pancreatic tissue before the onset of the pancreatic secretion. On the other hand, cyclic GMP concentration was not influenced significantly throughout 30 min after the administration of forskolin. From these results, it is concluded that forskolin may produce an increase in pancreatic secretion mediated through an increase of intracellular cyclic AMP concentration.

Animals↗

[Phase II study of etoposide (VP-16) in the form of intravenous injection for malignant lymphomas and acute leukemias: Hanshin Cooperative Study Group for Hematological Disorders].

Twenty patients with malignant lymphomas and 12 with acute leukemias were treated with intravenous administration of etoposide, 60-100 mg/m2/day for five days, repeated for three to four weeks. Eighteen cases of malignant lymphoma and nine of acute leukemia were evaluable. CR was achieved in three cases (16.7%) and PR in four cases (22.2%) of malignant lymphoma. Although CR was not achieved in any patients with acute leukemia, and PR was in three (33.3%), it was found that etoposide was most effective for the patients with the M4 or M5 subtype in the FAB classification. The most serious adverse effect of the drug was leukopenia in patients with lymphoma. In three patients (30.0%), the leukocyte count was lower than 1,000/mm3. Gastrointestinal complications, such as anorexia, nausea, vomiting and diarrhea occurred in 60.7% of all patients, but were not serious. Alopecia was observed in 73.1%. Intravenous administration of etoposide was apparently effective for the patients with malignant lymphoma of the diffuse mixed type, and this efficacy found in our study was the same as that for oral administration of etoposide reported by us previously.

Adult↗

The effects of macrophages on interleukin 2 production in thymocytes of New Zealand black mice.

The New Zealand Black (NZB) mouse is a model animal for human autoimmune disease. Abnormalities in Interleukin 2 (IL-2) production were studied in these mice to investigate whether they arise from disorders in T cells or from abnormalities of macrophages (M phi). T cells were separated from thymocytes using peanut agglutinin (PNA), while M phi were separated from spleen cells using the adherence method. Cultures were prepared from T cells and M phi obtained from normal control mice and NZB mice and the activity of IL-2 in the supernatant of the culture was studied. The results indicate that abnormalities in the production of IL-2 in NZB mice are due to functional disorders in both T cells and M phi.

Animals↗

[Effect of low-dose Ara-C in the treatment of refractory, atypical leukemia and myelodysplastic syndrome].

This study was designed to evaluate the effect of low-dose Ara-C in the treatment of refractory, atypical leukemia and myelodysplastic syndrome (MDS). The subjects were 33 patients (19 acute myelocytic leukemia (AML), 9 MDS, 3 atypical leukemia and 2 unclassified leukemia). The age range was 19 to 84 years with a mean age of 51.5 years. We administered low-dose Ara-C (5-10 mg/m2/12 h s.c. or i.v.) for 13 to 35 days with a mean of 16.7 days. Complete remission and partial remission were obtained in 8 of 31 (25.8%) and in 9 of 31 (29.0%) respectively. A high response rate was found in M2 types showing a tendency for mature and refractory anemia with excess blasts in MDS according to the FAB classification. In our cases, severe pancytopenia in peripheral blood as a result of Ara-C was observed before normal hematopoiesis recurred. From the above results, the mechanism of low-dose Ara-C may induce remission by a cytotoxic rather than a differentiation effect. This treatment can be offered to patients with refractory, atypical leukemia and MDS with limited toxicity.

Adolescent↗

[Phase II study on oral administration of MCNU (ranomustine) tablet. Hanshin Cooperative Study Group on Hematological Disorders].

A phase II study of MCNU tablet has been performed on 70 patients with hematological disorders including mostly myeloproliferative disorders. MCNU tablet was given p.o. at a dose of 50 mg daily for 2-6 days (total 100-300mg) as one course with average intervals of 3 to 5 months or more for patients responding to this drug. The effective rates were 72% in 18 patients with chronic myelogenous leukemia, 88% in 25 patients with polycythemia vera and 68.5% in 19 patients with essential thrombocythemia. Side effects of MCNU tablet were nausea and vomiting (31%) which had a dose-dependent relationship, mild liver dysfunction (5%) and elevation of BUN and creatinine (2%) which were not serious. The results were almost comparable to those of the phase II study of MCNU given intravenously.

Administration, Oral↗

[A phase III study of BHAC-MMP (behenoyl-ara-C, mitoxantrone, 6-mercaptopurine prednisolone) in acute leukemia. Hanshin Cooperative Study Group of Hematological Disorders].

BHAC-MMP therapy, a combination of behenoyl-ara-C, mitoxantrone, 6-mercaptopurine and prednisolone, was applied to 49 patients with acute leukemia for remission induction. Complete remission was obtained in 6 out of 11 previously untreated patients (55%), and in 16 of 38 pretreated patients (42%). Median duration of complete remission was 41 weeks in previously treated patients, while 67% of untreated patients were still in complete remission. Most frequent side effects other than hematological toxicities were gastrointestinal disturbances, and GPT elevation etc., although most of these were not severe. In conclusion, BHAC-MMP therapy seems to be very promising for remission induction or for possible intensification treatment for acute leukemia.

Acute Disease↗

[A phase II study of mitoxantrone in acute leukemia. Hanshin Cooperative Study Group of Hematological Disorders].

A phase II study of mitoxantrone was conducted on acute leukemia. Mitoxantrone 4 mg/m2/day was administered for 5 consecutive days in most cases. For cases showing insufficient decrease of leukemic cells even at nadir, a second course of the same regimen was given. Enrolled were 38 cases in total, of which 34 were evaluable. In 14 cases for first remission induction, the drug efficacy was evaluated at the completion of the first or second course, then further combination drug therapy followed immediately. Of 14 cases for first remission induction, 6, or 43%, achieved CR and of 20 cases for reinduction of remission, 4, or 20%, achieved CR. Two out of 7 cases of ALL (29%) and 8 out of 27 cases of ANLL (30%) achieved CR. Of 19 cases with previous anthracycline therapy, 4 cases, or 21%, achieved CR, showing that the cross-resistance was partial. Gastrointestinal symptoms were the main side effects, but cases of symptoms severer than grade 3 were very rare. Cardiotoxicity occurred at a rate as low as 11%. Mitoxantrone thus appears to be a promising drug for the treatment of acute leukemia.

Acute Disease↗

A phase II study of mitoxantrone in acute leukemia.

A phase II study of mitoxantrone (Novantrone; dihydroxyanthracenedione) was conducted in 35 patients (22 male: 13 female) with acute leukemia. There were 35 evaluable cases with a mean age of 34 (range 8-61). Twenty-eight patients had acute non-lymphocytic leukemia (ANLL) and seven had acute lymphocytic leukemia (ALL). Mitoxantrone was administered intravenously 2-4 mg/m2 daily for five days and after the nadir a further 2-3 doses were added if necessary. All previously treated cases (22 patients) had been treated with anthracyclines; 13 had no previous treatment. Out of the 13 untreated cases there were six complete remissions (CRs) (46.2%) and five partial remissions (PRs) (38.5%), while out of 22 pretreated cases, four CRs (18.2%) and five PRs (22.7%) were obtained. In seven of the untreated cases the decrease of leukemic cells and neutrophil leukocytes were analysed. Mitoxantrone showed a longer duration of decrease and higher log decrease of leukemic cells in the bone marrow than daunorubicin or cytosine arabinoside. Seventy-three percent of patients showed gastrointestinal disturbances such as nausea or loss of appetite. In 38.1% SGPT elevation and in 8.8% abnormal ECG findings were observed. All side-effects were mild and reversible. From this data mitoxantrone seems a very promising agent in the treatment of acute leukemia and a phase III study is now being carried out.

Aclarubicin↗