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Biomedical subjects

M Miyazaki

Publications and source records attributed to M Miyazaki.

At least 847 records · Page 47Linked to original sources

[Anticancer treatment with a combination of antimetabolites of polyamine and pyrimidine].

A combined efficacy of the polyamine antimetabolites, alpha-difluoromethylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG) with two fluorinated pyrimidines was studied. DFMO, MGBG, 5-FU and 5'-deoxy-5-fluorouridine (5'-DFUR) were administered intraperitoneally to BALB/c nu/nu mice bearing xenotransplanted human gastric cancer for 5 consecutive days. Similar antitumor efficacies were observed in 3 groups treated with DFMO plus MGBG, DFMO, MGBG plus 5-FU as well as DFMO, MGBG plus 5'-DFUR. The two groups on 5-FU or 5'-DFUR alone did not differ in antitumor effects from the control, although reasonable levels of 5-FU were involved in tumor tissues. Hepatic and splenic 5-FU levels after 5-FU administration were significantly higher than those after 5'-DFUR, and marked decrease in mouse body weight was caused by 5-FU alone as well as 5-FU plus polyamine antimetabolites for 5 consecutive days. DNA biosynthesis and spermine levels in the tumor tissues on day 2 after cessation of the treatments dropped in 3 groups with DFMO plus MGBG, DFMO, MGBG plus 5'-DFUR as well as DFMO, MGBG plus 5-FU, while on day 6 there was little difference between the control and treated groups. These data suggest that combination with 5-FU or 5'-DFUR does not enhance the antitumor activity of polyamine antimetabolites by this experimental regimen.

Animals↗

Neuroeffector actions of prostaglandins on isolated arteries.

PGD2, PGF2 alpha, and CTA2 are compounds that increase vascular contractility indirectly by potentiating responses to nerve stimulation or vasoconstrictor agents and directly by acting on vascular smooth-muscle receptors. The direct vasoconstrictor potency is in the order of CTA2 greater than PGF2 alpha greater than PGD2 (5,6,9). The ratio of concentrations for directly- and indirectly-induced contractions is approximately 1,000 with PDG2, 100 with PGF2 alpha, and 10 with CTA2. PGD2, PGF2 alpha, and TXA2 may contribute to provoking coronary vasospasm because of potentiating actions on responses to adrenergic and other vasoconstrictor stimuli and to their vasoconstrictor actions. The former effect is induced by appreciably lower concentrations. On the other hand, PGI2 appears to counteract responses to the vasoconstrictor interventions. PGD2 and PGF2 alpha act on presynaptic receptors and increase the release of norepinephrine; these actions are resistant to diphloretin, a PG antagonist. In contrast, CTA2 and PGI2 act on postsynaptic receptors and alter smooth-muscle reactivity to vasoconstrictors; these actions are sensitive to the PG antagonist.

Animals↗

Vascular neuroeffector function in two-kidney, one clip hypertensive dogs.

In control dogs and those made hypertensive for 1 and 8 months by partially occluding a renal artery, contractile responses of mesenteric artery strips to adrenergic nerve stimulation and to norepinephrine, plasma renin activity and vascular angiotensin converting enzyme (ACE) activity were compared. Contractile responses to norepinephrine were potentiated in the artery strips from 8-month-hypertensive dogs; however, the response to electrical stimulation of adrenergic nerves was not influenced. Contractions induced by the nerve stimulation were potentiated by a low concentration (2 X 10(-10) mol/l) of angiotensin (ANG) II; the potentiating effect was enhanced in 8-month-hypertensive dog arteries. 3H-overflow evoked by adrenergic nerve stimulation was increased by ANG II to a greater extent in superfused mesenteric artery strips obtained from hypertensive (8-month) dogs, previously soaked in 3H-norepinephrine. Angiotensin converting enzyme activity was markedly greater in 8-month-hypertensive dog mesenteric arteries than in normotensive dog arteries. It may be concluded that the hypertension is maintained by increased sensitivity of post-synaptic alpha 1-adrenoceptors and pre-synaptic ANG receptors and increased vascular ACE activity, possibly promoting the production of ANG II in the vascular wall.

Adrenergic Fibers↗

[Cyclic AMP- and ATP-mediated stimulation of DNA synthesis following partial hepatectomy by prostaglandin-E1 in D-galactosamine injured liver].

D-galactosamine (D-gal) damaged rats were infused with Prostaglandin E1 (PGE1) through a peripheral vein for 40 min. before and after partial hepatectomy. DNA synthesis following 68% partial hepatectomy was severely inhibited by the pretreatment of D-galactosamine. PGE1 infusion (0.5, 1.0 microgram/kg/min) enhanced the DNA synthesis inhibited by D-gal 600 mg/kg significantly (p less than 0.01). After 20 min. of PGE1 infusion cyclic AMP levels of liver tissue was increased as compared with saline infusion in D-gal (600 mg/kg)-damaged rat (p less than 0.05). Also 20 min. and 3 hour after partial hepatectomy. ATP levels of liver tissue was enhanced in PGE1 treated group (p less than 0.05). However the doses of PGE1 infused in this investigation could not increase the hepatic tissue blood flow measured by hydrogen gas clearance method. These results suggest that PGE1 enhance DNA synthesis of injured liver after partial hepatectomy by the mechanism which PGE1 stimulate cyclic AMP production and increase ATP level in hepatic tissue.

Adenosine Triphosphate↗

Interaction between non-steroidal antiinflammatory agents and sodium salicylate in the relaxant response of dog renal arteries to angiotensin II.

Angiotensin (ANG) II produced a slight, transient contraction followed by a moderate relaxation in dog renal artery strips precontracted with prostaglandin (PG) F2 alpha. Treatment with acetylsalicylic acid indomethacin, ibuprofen and sodium meclofenamate reduced the relaxant response to ANG II or reversed the relaxation to a contraction, but did not significantly alter the relaxant response to PGI2. The inhibitory potencies were in the order of meclofenamate greater than indomethacin greater than ibuprofen greater than acetylsalicylic acid. Sodium salicylate and gentisic acid, metabolites of acetylsalicylic acid, in concentrations up to 5 X 10(-4)M did not influence the ANG II-induced relaxation. Treatment with salicylate (5 X 10(-4)M) prevented the inhibitory effect of acetylsalicylic acid, indomethacin or meclofenamate, whereas combined treatment with salicylate and ibuprofen elicited an inhibition of ANG II-induced relaxations to a similar extent to that seen in preparations treated with ibuprofen alone. It appears that acetylsalicylic acid, indomethacin and meclofenamate share the same mechanism for inhibiting the cyclooxygenase activity, but the mechanism of inhibitory action of ibuprofen differs.

Angiotensin II↗

Interaction of yeast polypeptide chain elongation factor-3 (EF-3) with different nucleotides.

ATPase and GTPase activities of EF-3 were similarly inhibited by various nucleotides including CTP, UTP and four dNTP's. The low specificity of EF-3 was in remarkable contrast with the high specificity of EF-1 alpha and EF-2 directed only to quanine nucleotides. The pH-activity and salt concentration-activity profiles as well as the above inhibition experiments coincidently supported that the same active site functions for ATPase and GTPase of EF-3. The stimulation of poly(Phe) synthesis was not observed with AMPPNP in place of ATP. The stimulation required ATP hydrolysis, probably catalyzed by ATPase of EF-3. Reflecting the low specificity of the ATPase, UTP, dTTP, dATP and dGTP stimulated the poly(Phe) synthesis. EF-3 appears to drive yeast elongation cycle using the energy from ATP hydrolysis by its ATPase without serving for GTP regeneration.

Deoxyribonucleotides↗

[Preoperative cancer chemotherapy for gastric cancer].

Preoperative cancer chemotherapy for gastric cancer was reviewed with special emphasis on histologic findings and survival. Preoperative chemotherapy with intravenous, split administration of MMC 40 mg caused considerable damage to "micro-solitary metastatic foci" in metastatic lymph nodes. In view of the lipid-adsorbing ability of the lymphatic stream, emulsified 5-FU was used orally in 182 patients with gastric cancer; histologic findings revealed that the emulsified 5-FU enhanced the antitumor efficacy for metastatic lymph nodes as well as the primary lesion. However, the 5-year survival rate for gastric cancer patients undergoing preoperative emulsified 5-FU therapy did not differ from the control, with only the exception of patients with Stage III gastric cancer. On the other hand, combined therapy involving preoperative intra-arterial infusion and surgery was carried out in 62 patients with gastric cancer. These preoperative treatments using MMC, 5-FU, VLB, MTX and/or cytosine arabinoside entailed continuous infusion for 15 to 20 hours; the histologic changes observed revealed marked antitumor effects on the primary focus as well as metastatic lymph nodes. The five-year survival rate for the 62 patients was compared with that for 99 patients with gastric cancer in the corresponding period. The survival rate was analyzed based on the degree of serosal invasion. The overall survivals in the 62 patients were higher than those in the controls for the first 3 years. At 4 to 5 years, the survival rates for both the treated and control groups were approximately equal. In patients without serosal invasion, the survival rates were higher in treated cases than in the controls for the first 2 years. Thirty-nine patients with serosal invasion had significantly higher survival rates than the controls for the first 3 years. The survival rates for the treated patients with cancerous infiltration of ther organs were about the same as those for the corresponding control patients.

Administration, Oral↗

[Multimodality therapy of colorectal cancer].

Multimodality therapy for colorectal cancer is composed of surgery, chemotherapy and irradiation; and hyperthermia joins them recently. As patients with operable colorectal cancer are a good candidate for a chemotherapeutic approach, we began postoperative adjuvant chemotherapy since 1971. On the other hand, our treatment policy towards inoperable cases is various treatments combined with the four therapies described above. The most patients with hepatic metastasis are unamenable for surgery, and they have been mainly treated with intra-arterial chemotherapy. With conventional infusion treatment, however, the infusion drugs are eliminated rapidly from the drainage vein. Thus, we prepared biodegradable albumin microspheres containing MMC (mean diameter 45 +/- 8 micron); and in 6 patients with liver metastasis, we infused MMC microspheres into the proper hepatic artery, with marked tumor regression. Hyperthermia treatment has been performed with ThermaTech 2000 (International Institute for Medical Sciences, U.S.A.), which has a complete capacitive, 3-channel, "crossfire" heating system operating by RF at 13.56 MHz. Six patients with local recurrence and/or hepatic metastasis were treated by hyperthermia combined with chemotherapy or irradiation, with a fair success in tumor response and improvement of subjective symptoms.

Aged↗

[Treatment of post-infarction ventricular septal perforation].

Recently clinical course of ventricular septal perforation following myocardial infarction is made clear. It is concluded that postinfarction ventricular septal perforation constitutes a surgical emergency. However, cardiac function of these patients are not fully evaluated, as full-cardiac catheterization including coronary angiography is hazardous. The timing of surgical intervention must be determined according to the non-invasive evaluation such as echocardiogram. In this report, we review our experience with postinfarction ventricular septal perforation and attempt to determine from this review the management of these patients. Our cases are classified into three categories. Group 1 showed cardiogenic shock state after onset of ventricular septal perforation. Group 2 had severe congestive heart failure and required inotropic support. Group 3 had moderate congestive heart failure. Group 1 need emergency operation. Group 2 need intraaortic balloon support and respiratory support after the onset. After then surgical intervention should be considered. Group 3 can be operated on more than 6 weeks after myocardial infarction on an elective basis.

Aged↗

[Long-term follow-up study of selective VIM-thalamotomy].

To evaluate the effect of the physiologically defined selective Vim-thalamotomy on tremor type Parkinson's disease (PA, 26 cases) and essential tremor (ESS-T, 16 cases), a long-term follow-up study was conducted. The follow-up time extended from 4 months to 7 years (mean: 3.6 years). On 42 cases a total of 49 operations (4 bilateral surgery and 3 reoperations) were carried out. After identifying kinesthetic neuron, the coagulative lesion was made by using Leksell's apparatus between two needles of 4 mm effective tip length located with 3 mm interval including the recording point. One coagulation (unit lesion) destroyed about 20 mm3 brain tissue taking account of the mechanical damage by the needles themselves. The unit lesion was added around an imaginary cylinder of 3 mm radius, until the tremor was abolished completely. On the basis of number of unit lesion and its extent within an imaginary cylinder, these 49 operations were divided into the following group. Group I (minimal lesion group): coagulative lesion of 1 to 3 units within a quadrant of the imaginary cylinder. Group II: 3 to 5 units within 1/2 to one cylinder. The early (14 days after operation) and the late results on the tremor were evaluated clinically and electromyographically by 4 different categories: complete abolition, slight residual, residual, and recurrence in a strict sense. The late results in 13 PA cases of group I (similar to the early results) were: 10 complete abolition, 2 slight residual and one recurred, this case was reoperated 3 months after first operation and therefore categolized in group II. The late results in 11 ESS-T cases of group I were: 6 complete arrest, 4 slight residual, and one recurred case, which had been reoperated 2 years after operation. Therefore in a total of 24 minimal lesioned cases with PA and ESS-T complete abolition in 16, slight residual in 6, and 2 reoperated cases. In these successful 22 cases with minimal lesion, the tremor was abolished without noticeable long-lasting side effect. In other 20 cases with PA and ESS-T of group II, the tremor was almost completely relieved and maintained. In conclusion, by radiographically and physiologically controlled selective Vim thalamotomy for Parkinsonian and essential tremor, it was shown that the effect of minimal lesion was valid and well maintained on the long-term follow-up base.

Adult↗