[Clinical application of the thermal effect of lasers. 1. Application of the Nd-YAG laser in inducing hyperthermia].
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Biomedical subjects
Publications and source records attributed to T Nobori.
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Patients with 2,8-dihydroxyadenine urolithiasis are either completely or partially deficient in adenine phosphoribosyltransferase activities. Patients with partial enzyme deficiencies, all of whom have been found among Japanese, are homozygotes having a unique mutant adenine phosphoribosyltransferase gene (APRT*J) in double dose (Japanese type deficiency). We have established B-cell lines from heterozygotes and homozygotes of complete and Japanese type adenine phosphoribosyltransferase deficiencies as well as normal individuals. Characterization of the cell lines indicated that all homozygous cells were deficient in adenine phosphoribosyltransferase function while all heterozygous and normal cells had functional adenine phosphoribosyltransferase.
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Allyl group serves as a useful protecting group for an protection of sugar hydroxyls and amino and imide moieties of by brief treatment with a palladium catalyst and a variety of nucleophiles at room temperature.
We have been treating cancer since 1980 with a CO2 laser and since 1983 have added a Nd-YAG laser. We are applying the contact YAG laser with a new ceramics tip to cancer therapy. This ceramics laser is markedly different in its point of contact or noncontact from conventional lasers. In addition, one can use this laser at relatively low power (under 10 W). Also, we have recently developed a new ceramics tip for localized laser hyperthermia. The head and neck region is very irregular and present equipment is difficult to apply to this region. This type of hyperthermia was used on human thyroid anaplastic carcinoma transplanted into the necks of nude mice. In two of five nude mice decreased tumor size was observed 2 weeks after hyperthermia. Thereafter this technique has also been used in combination with radio-chemotherapy for patients with head and neck cancer. This localized laser hyperthermia was applied to the treatment of a patient with tongue cancer. This patient was given two localized hyperthermic treatments combined with 4,000 rads of radiation therapy and 5-Fu-administration for 4 weeks. A hemiglossectomy was performed using the contact YAG laser technique. A histological examination of the excised specimen failed to find evidence of tumor cells.
The effect of a macrolide antibiotic on experimentally induced sinusitis in rabbits was evaluated. Compared with the control group, the effect on sinus mucosal pathology was significantly superior in the drug-treated groups. Inflammation models as used in the present study will contribute to the establishment of a suitable pharmacotherapy for sinusitis.
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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.
The contact Nd-YAG laser system with ceramic rods which has been developed by us was applied to animal experiments and clinical practice. It was confirmed that: 1) this method can be performed at low power of 6 to 8 W in contact laser incision of soft tissue and at 3 to 4 W in localized laser hyperthermia; 2) it permits accurate and precise incision because mis-shots of laser irradiation can be eliminated in the target tissue; 3) it causes less bleeding with minimal damage to adjacent tissue; and 4) it has remarkably high controllability. The contact Nd-YAG laser systems are very useful as one of the new modalities for surgical procedures as well as localized laser hyperthermia in head and neck tumors.
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With advances in the understanding of intracellular nucleic acid metabolism, the biochemical modulation of the action of antimetabolites by MTX was discussed as an approach towards the development of more selective chemotherapy. Using high-performance liquid chromatography, the sequential changes occurring in the acid-soluble intra cellular nucleotide pools of L1210 mouse leukemic cells were analysed after treatment with MTX, and a reduction of the dTTP pool to 46% of the control level was observed. Declines in the dCTP, ATR and GTP pools were also reduced to 36%, 30% and 24%, respectively, of the control level after treatment with MTX. Using MTX-5-FU combination chemotherapy, pretreatment with MTX enhanced the intracellular level of FUTP which is one of the active metabolites of 5-FU. There was, however, no significant difference in the value of dTTP levels between MTX-5-FU and 5-FU alone. One of the mechanisms of the synergistic interaction between MTX and 5-FU might therefore be stimulated phosphorylation of 5-FU with an increased PRPP level, which occurs as a result of the MTX-blocked purine de novo pathway. Using MTX-ara C combination chemotherapy, MTX enhanced the intracellular production of ara-CTP, which occurs as a result of MTX reducing the intracellular dCTP pools, following activation of deoxycytidine kinase. More clarification of the effects on intracellular nucleic acid metabolism will aid the development new and increasingly effective drug combinations involving thiopurines. The methods of combination chemotherapy will become more sophisticated as the biochemical modulation effect of the drug is clarified.
Fundamental and clinical studies were performed with aspoxicillin (ASPC), a new developed injectable broad penicillin, in pediatric infectious diseases, and the following results were obtained. Pharmacokinetics ASPC was administered to 2 cases at a dose of 20 mg/kg by one shot intravenous injection. The mean half-life (T 1/2) was 1.17 hours. The mean urinary excretion rate was 58.4% during 6 hours after ASPC treatment. In 3 cases of intravenous drip infusion with a period of 1 hour at a dose of 10 mg/kg (2 cases) and 20 mg/kg (1 case), the half-lives (T 1/2) were 1.7 hours, 3.5 hours and 1.0 hour, respectively. The urinary recovery rate during 6 hours after administration was 57.7%, 32.6% and 42.7%, respectively. At only one case treated with 10 mg/kg intravenous drip infusion, the half-life was prolonged and urinary excretion rate was lower than other 2 cases. Clinical study ASPC was administered 50-80 mg/kg/day for 4-8 days to 22 children comprising 6 tonsillitis, 2 bronchitis, 6 pneumonia and 8 urinary tract infections. Clinical efficacy was excellent in 13 cases, good in 8 cases and fair in 1 case, the total cure rate was 95%. As for the clinical response classified by diagnosis, the each efficacy rate of tonsillitis, bronchitis and pneumonia was 100%, and that of urinary tract infection was 87.5%. Clinical side effect and abnormal laboratory findings were not observed in any cases. From the above results, it was concluded that ASPC was one of the useful secure drug for treatment of infections in pediatric field.
Analogs of 2'5'-oligiadenylates (2-5As) have been prepared on the basis of the recently developed internucleotide-linkage formation via selective hydroxyl activation of N-unprotected nucleosides. The analogs synthesized include the trimeric cores having 2'-deoxyadenosine, cordycepin (3'-deoxyadenosine), and 2',3'-bisdeoxyadenosine at the 2' termini, and the tetramer with 2'-end 2'-deoxyadenosine.
Macrocyst (spherule) formation was induced in synchronized suspension cultures of microplasmodia of Physarum polycephalum under conditions where DNA synthesis was inhibited. Plasmodia in early G2 phase of nuclear cycle were able to differentiate to spherules in the presence of an inhibitor of DNA synthesis, whereas those in late G2 phase required another round of DNA replication before they could enter into the spherulation process. These facts suggest that commitment to DNA synthesis occurred about halfway through G2 phase. The idea was also supported by the results of autoradiographic study in which spherulating plasmodia were fed with radioactive thymidine and labelled plasmodia were scored at the terminal differentiation stage.