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Biomedical subjects

H Hirota

Publications and source records attributed to H Hirota.

87 records · Page 5Linked to original sources
PubMed1985

Enhanced production of intracellular ara-CTP after sequential use of methotrexate and 1-beta-D-arabinofuranosylcytosine.

Synergistic antiproliferative effect has been proven in vitro when mouse leukemic cells were sequentially treated with MTX and ara-C. The mechanism of this combination effect not well elucidated but the intracellular uptake of ara-C was higher when cells were pre-exposed to MTX. In this experiment, the intracellular ara-CTP was measured by HPLC after MTX and ara-C were sequentially administered to BDF1 mice bearing L1210 leukemic cell, either being sensitive or resistant to MTX. When MTX at the dose of 12 mg/kg was preceded 6 h and 3 h to ara-C at the dose of 25 mg/kg, the intracellular levels of ara-CTP were found to be significantly higher as compared with those of ara-C alone as control group. At 1 h after ara-C, ara-CTP was measured about 165 and 130% of the control levels, respectively, and at 12 h, ara-CTP was over 4 times higher of control level with group of mice to which MTX was preceded 6 h prior to MTX. On the contrary, the enhancement of ara-CTP production was definitely diminished with MTX-resistant cells in the same administrative model. From our present experiment, the time sequential modulation of intracellular ara-CTP production by MTX was reconfirmed in vivo, and this modulation might depend upon the sensitivity of MTX of leukemic cells.

Animals↗
PubMed1985

[The effect of methotrexate on intracellular nucleotide pools].

In a previous study, we showed that methotrexate (MTX) enhanced the intracellular production of ara-CTP. The study described in the present paper has elucidated the mechanism of this MTX-enhanced ara-CTP production, which occurs as a result of MTX reducing the intracellular dCTP pool, and the decreased dCTP pool then allowing activation of deoxycytidine Kinase. One of the mechanisms of synergistic interaction between 1-beta-D-arabinofuranosylcytosine (ara-C) and MTX might therefore be the stimulated phosphorylation of ara-C with MTX-activated deoxy-cytidine kinase. Using high-pressure liquid chromatography, the sequential changes occurring in the acid-soluble intracellular nucleotide pools of L1210 mouse leukemic cells were analysed after treatment with MTX (12mg/kg). At 3 hr after treatment with MTX a reduction of the dTTP pool to 46% of the control level was observed. The dCTP pool was also reduced to 36% of the control level after treatment with MTX. The levels of the dATP and dGTP pools were not significantly changed, at least during the observation period. Pyrimidine ribonucleotide pools were almost unchanged at 3 hr, but in the sequential changes observed in purine ribonucleotide pools after treatment with MTX, both diphosphate and triphosphate pools were seen to be on the decline, the reduction of triphosphate pools being especially marked. A decline in ATP and GPT to 24-30% of control levels was observed at 3 hr after treatment with MTX.

Adenosine Triphosphate↗
PubMed1982

[Experience with high-dose methotrexate therapy for malignant solid tumors].

Thirteen patients with malignant solid tumors, mainly osteogenic sarcomas, were treated by high-dose MTX therapy, 50-400 mg/kg, in a total of 72 cycles. It has been proved that this therapy was relatively safe provided careful clinical surveillance were assured. Of 8 patients with osteogenic sarcomas, 6 had no metastatic lesions on the chest X-rays before this therapy: three were alive without any evidence of disease for 18-25 months after high-dose MTX therapy. In some cases of other malignant solid tumors, particularly intracranial tumors, clinical efficacy was observed. Dose-time relationships, etc. should further be studied for more therapeutic efficacies of high-dose MTX therapy.

Adolescent↗
PubMed1981

Reduced antitumor and immune-adjuvant activities of the sub-cellular fractions from Group A Streptococcus.

The sub-cellular fractions from Group A streptococcus (Su-strain) were prepared, and their antitumor and biological activities were examined. The cell wall fraction (CWF) and the protoplast membrane fraction (PMF) were slightly effective in retarding the growth of Ehrlich ascites carcinoma in outbred ddY mice when either fraction was used in combination with 5-FU. The cytoplasmic particle fraction (CPF) and the cytoplasmic soluble fraction (CSF), however, were not effective. In the B6D2F1 mice-L 1210 leukemia system, none of the subcellular fractions were beneficial even when combined with 5-FU. Further, the antitumor effect of OK-432 was completely abolished by disruption of the preparation, indicating that antitumor activity of OK-432 may depend on the structural integrity of the cocci in the preparation. Despite the general lack of anti-tumor activity in the mouse systems, the subcellular fractions, including those of OK-432, inhibited the growth of Yoshida sarcoma cells in culture and the uptake of [2H]-UR and [3H]-TdR by L 1210 cells in vitro. The immunopotentiating activities of these fractions, however, were demonstrated to be markedly diminished as compared with those of OK-432 and heated Su-cocci (60 degrees C, 30 min). The present study, therefore, shows that the decreased antitumor activity of the subcellular fractions closely correlate to the decrease of their immunopotentiating activities.

Adjuvants, Immunologic↗
PubMedDate not supplied

Clinical evaluation of newly developed CRT viewing station: CT reading and observer's performance.

The clinical performance of the new viewing station with six CRT monitors (17-inch, 1,024 x 1,280) was evaluated. In the primary interpretation of CT images, time measurements were carried out for eight radiologists. No significant differences in reading time existed between CRT and film in 3 of 4 readers in head CT series, and in 2 of 6 readers in body CT series. Compared with the previous system, the new prototype system achieved an approximately 30% decrease in reading time in both head and body CT studies and could reduce mental and eye fatigue.

Computer Systems↗
PubMedDate not supplied

Display method can affect interobserver agreement: comparison of 'zoom-and-pan' and 'browse-and-paste' for primary CT interpretation.

Eight radiologists interpreted body CT images of 30 cases using a viewing station (six 17-in. monitors, 1024x1280). Using two different display methods, 'zoom-and-pan' and 'browse-and-paste', the readers described the presence or absence of liver tumors using a five-point rating scale and temporal changes between the current and previous studies using a seven-point rating scale. There was no significant difference in kappa values for tumor detection between the two display modes. However, in describing temporal changes, the kappa value of the browse-and-paste was significantly lower than that of zoom-and-pan (p<0.01). Browse-and-paste may have the disadvantage of greater interobserver variation.

Data Display↗
PubMedDate not supplied

Neural control of blood pressure following 1,1,1-trichloroethane inhalation: a role of sympathetic nervous system.

The effects of 1,1,1-trichloroethane (1,1,1-TCE) inhalation on arterial blood pressure and renal sympathetic nerve activity were investigated in anesthetized dogs. In acute inhalation experiments, the threshold concentration of 1,1,1-TCE required to produce a decrease in blood pressure was 0.4 to 0.5% in inspired air; moreover, a dose-response relationship between the decrease in blood pressure and 1,1,1-TCE concentration which exceeded the threshold level was observed. In addition, renal nerve activity increased and was associated with a slight decrease in blood pressure following inhalation of relatively low concentrations of 1,1,1-TCE. Following inhalation of relatively high concentrations of 1,1,1-TCE, however, renal nerve activity decreased and was accompanied by a marked decrease in blood pressure. Opposite reactions of renal nerve activity were observed when blood pressure decreased to 70-80 mm Hg following inhalation. It is suggested that systemic hypotension resulting from 1,1,1-TCE inhalation may be controlled by two different reactions of sympathetic nerve activity.

Animals↗