[Studies on portal blood flow using an ultrasonic pulsed Doppler system and correlation between portal blood flow and cardiac output].
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Biomedical subjects
Publications and source records attributed to M Miyazaki.
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Whereas the ribosome-dependent ATPase activity of EF-3 required highly active ribosomes for its full activity, a catalytic site for ATP hydrolysis may reside in the EF-3 as being supported by the activity-EF-3/ribosome amount profiles. The direct interaction of EF-3 with various nucleotides such as GTP, UTP, CTP, dATP, ADP and AMPPNP as well as ATP was analyzed by protection experiments against trypsin digestion of the factor according to SDS-gel electrophoresis. The protection effect varied with the used nucleotides roughly in accordance with the inhibitory effect of those on the ribosome-dependent ATPase. The ATPase activity of EF-3 alone in the absence of ribosome was observed by using large amounts of the factor and the rate was two orders of magnitude lower than that of the ribosome-dependent.
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Hyperthermic treatment using ACNU combined with a thermosensitizing drug, methylglyoxal-bis-guanylhydrazone (MGBG), was studied in human gastric cancer xenotransplanted into nude mice. In order to increase the intra-cellular MGBG content, intraperitoneal injection of alpha-difluoromethylornithine(DFMO) 1000 mg/kg was performed twice with an interval of 6 hours and 50 mg/kg of MGBG was given at the time of the second administration of DFMO. After 6 hours of MGBG administration, ACNU 20 mg/kg was given intraperitoneally and, subsequently a 23-minute hyperthermia was carried out in a water bath at 43.5 degrees C. After 48 hours a second hyperthermia was performed by the same method. Tumor weight was estimated using Battelle's Columbus Institute protocol and the inoculated tumors, which were extirpated 60 minutes after 3H-thymidine injection at a prescribed interval after cessation of hyperthermia, were assayed biochemically for the determination of DNA biosynthesis. In mice given ACNU, DFMO, MGBG plus heat, considerably superior results were obtained. Although the DFMO plus MGBG group was inferior in antitumor activity to the ACNU only or heat only group, the DFMO, MGBG plus heat group showed much the same antitumor effects, compared to the ACNU plus heat group. These data suggest that the thermosensitizing efficacy of MGBG may be applicable for clinical use.
Antitumor therapy using the polyamine antimetabolites, alpha-difluoromethylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG), combined with ACNU was studied in human gastric cancer xenotransplanted into nude mice. DFMO 1,000 mg/kg (in two divided doses) and MGBG 50 mg/kg were given i.p. for 6 successive days from the time when the xenotransplanted tumor weighed about 100 mg, and ACNU 20 mg/kg was given i.p. every other day from the same time. Antitumor efficacy was assessed by the time course of tumor weight as well as of DNA biosynthesis and polyamine levels in tumor tissue. Tumor weight was estimated using Battelle's Columbus Institute protocol and DNA biosynthesis was assayed biochemically by 3H-TdR injection at a prescribed interval after termination of therapy. Furthermore, tumoral polyamine levels were assayed by HPLC. This three-drug regimen showed a favorable antitumor effect, compared to those of the other two therapies with DFMO plus MGBG as well as ACNU only. These data suggest that this combined regimen may have a synergistic efficacy judging from the action mechanisms of these three drugs.
The combined antitumor effects of the polyamine antimetabolites, alpha-difluoro methylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG), with CDDP were studied using human gastric cancer cells xenotransplanted into nude mice. DFMO (1000 mg/kg in two divided doses) and MGBG (50 mg/kg) were given IP for six consecutive days from the time when the xenotransplanted tumor weighted about 100 mg, and CDDP (3.0 mg/kg) was given IP every other day from the same time. Animals treated with DFMO plus MGBG with or without CDDP as well as with CDDP only displayed suppressed tumor growth, compared to untreated mice. In mice treated with these three drugs, however, tumor growth was rather rapid compared to those treated with CDDP only, although tumoral CDDP levels in animals given DFMO, MGBG and CDDP were higher than those given CDDP only. When DFMO, MGBG and CDDP or DFMO and MGBG were administered, tumoral spermidine and spermine levels decreased markedly. On the other hand, tumor DNA biosynthesis in the CDDP only group dropped markedly 24 hours after the termination of therapy. These results suggest that an alteration in the DNA structure caused by polyamine deficiency may prevent cross-link formation in DNA by CDDP.
In helical strips of proximal and distal coronary arteries from beagles of different ages (30 days, 3 months and 1 and 3 years old) precontracted partially with prostaglandin F2 alpha, responses to catecholamines, transmural electrical stimulation, tyramine and acetylcholine were compared. Proximal coronary arteries from infant beagles responded to norepinephrine and epinephrine with contractions, whereas those from adult (1 and 3 years old) beagles responded with dose-related relaxations. Isoproterenol-induced relaxations were in the order of infant less than young less than adult beagle arteries. Norepinephrine produced contractions in the proximal arteries from infant beagles but relaxations in the distal arteries. Relaxations induced by norepinephrine and isoproterenol were in the order of small greater than medium greater than large-size arteries from adult beagles. Transmural stimulation and tyramine produced contractions in the infant and young beagle arteries of proximal portion but only relaxations in the adult beagle arteries. The contractions induced by transmural stimulation and norepinephrine were suppressed by prazosin but not by yohimbine. Acetylcholine produced similar magnitude of relaxations in the arteries from beagles of different ages. It may be concluded that contractions of coronary arteries mediated by alpha-1 adrenoceptors decrease with age, whereas beta receptor-mediated relaxations increase with age. Alpha-1 adrenoceptor functions appear to be in the order of large greater than medium greater than small-size coronary arteries from beagles of different ages, and beta receptor functions to be in the reverse order.
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The 3rd coronary artery, whose anatomical significance is defined, is a normal variant of the conus branch of the right coronary artery. This study involved the stereoscopic comparative investigation of human fetal hearts from 13 to 40 weeks of age and human adult hearts from 18 to 88 a of age. The incidence of the 3rd coronary artery in human fetuses was 45 out of 218 or 20.6%. No clear sexual differences were observed. Anastomoses had already developed between the 3rd coronary and the branches of the left anterior descending artery during the fetal stage. The 3rd coronary artery orifices in human fetuses was located at 9 o'clock (+/- 0 degree) most frequent (48.9%), and at 8 o'clock (-30 degrees) most infrequent (22.2%). The incidence of the 3rd coronary artery in human adults was 36.8%. In the human adult's normal group, the orifice was located at 9 o'clock (+/- 0 degree) most frequent (59.0%), and at 8 o'clock (-30 degrees) most infrequent (14.8%), while on the other hand in the pathologic group, the orifice was located at 9 o'clock (+/- 0 degree) most frequent (54.9%) and at 10 o'clock (+30 degrees) most infrequent (11.5%). Further, multiple 3rd coronary artery orifices, which were not observed in human fetal hearts, were observed in the human adults' heart. Furthermore, the existence of multiple orifices and the fact that human adult hearts had a higher incidence than human fetal hearts suggests the possibility that the 3rd coronary artery develops after birth.
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Cefixime (CFIX) was evaluated for pharmacokinetics, therapeutic effectiveness on infection, safety, and bacteriological effectiveness in pediatrics. The following is a summary of the results. Pharmacokinetics in 4 children, 2 each receiving a single dose of 1.5 mg or 6.0 mg per kg body weight, were examined. Peak serum CFIX concentrations after the dose of 1.5 mg/kg were 1.12 and 1.34 micrograms/ml, and the serum half-lives were 1.83 and 3.53 hours. For the children administered with 6.0 mg/kg of CFIX, the respective figures were 2.50 and 7.46 micrograms/ml, and 6.77 and 6.64 hours. The 12-hour urinary recoveries were 4.9 and 34.1% and 9.4 and 25.4% for the small and the large doses, respectively. Therapeutic effectiveness in 19 children with infections was "excellent" in 14 and "good" in 5, with an effectiveness rate of 100%. Bacteriological effectiveness was evaluated in 10 children. Classified by causative organisms, 5 cases had H. influenzae, 2 each H. parainfluenzae and S. pyogenes, and 1 mixed infection by H. influenzae and S. pneumoniae. Only the H. influenzae in the child with mixed infection resisted the therapy, and all the other pathogens were successfully eradicated. No side effects were recorded. The only abnormal laboratory test finding attributed to CFIX was eosinophilia in 2 children.
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