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Biomedical subjects

K Tainaka

Publications and source records attributed to K Tainaka.

At least 19 recordsLinked to original sources
PubMed1998

Stability of the Escherichia coli ATP synthase F0F1 complex is dependent on interactions between gamma Gln-269 and the beta subunit loop beta Asp-301-beta Asp-305.

The role of the conserved sequence motif 301DDLTDP306 in the F0F1 ATP synthase beta subunit was assessed by mutagenic analysis in the Escherichia coli enzyme. Mutations gave variable effects on F1 sector activity, stability, and membrane binding to the F0 sector. Upon solubilization, F1 sectors of the betaD302E and betaD305E mutants (betaAsp-302 and betaAsp-305 replaced by glutamate) dissociated into subunits, while mutants with other beta305 substitutions failed to assemble. Membrane ATPase activities of beta301 and 302 mutants were 20-70% of wild type. Replacements of the gamma subunit Gln-269 had similar effects. The membrane ATPase activities of the gammaQ269E or gammaQ269D mutants were significantly lower and their F1 sectors dissociated into subunits upon solubilization. These results suggest that the beta301-305 loop and the gamma subunit region around Gln-269 form a key region for the assembly of alpha3 beta3 gamma complex. These results are consistent with the X-ray crystallographic structure of bovine F1 (J. P. Abrahams, A. G. W. Leslie, R. Lutter, and J. E. Walker (1994) Nature 370, 621-628) where the beta301DDLTD305 loop directly interacts with gammaGln-269.

Amino Acid Substitution↗
PubMed1996

Anti-tumor effects of hyperthermia plus granulocyte colony-stimulating factor.

The role of neutrophils in the anti-tumor effects of hyperthermia was investigated in an experimental rat model, and the efficacy of hyperthermia combined with recombinant human granulocyte colony-stimulating factor (G-CSF) was similarly investigated. AH109A carcinoma cells were transplanted into the hind legs of Donryu rats, then heated by a radio-frequency dielectric heater. In this study, because the myeloperoxidase (MPO) activity of neutrophils was not affected by heating or G-CSF, MPO activity was measured as an index of neutrophil migration into tumor tissue. After hyperthermia, MPO activity in tumor tissue increased significantly, suggesting migration of neutrophils into tumor tissue. Depletion of circulating neutrophils by the intraperitoneal injection of anti-rat neutrophil antibody decreased the anti-tumor effects of hyperthermia. Subsequently, we used hyperthermia plus intraarterial G-CSF to enhance the anti-tumor effect. Hyperthermia was induced 1 h after injection of G-CSF, a time when MPO activity in tumor tissue was maximal. A satisfactory thermal effect was noted even in cases where tissue could not be heated sufficiently. In conclusion, neutrophils have an important role in the anti-tumor effects of hyperthermia, and administration of G-CSF enhances these effects.

Animals↗
PubMed1995

A novel cancer therapy based on oxygen radicals.

The antitumor effect of oxygen radicals produced by hypoxanthine and xanthine oxidase reaction was studied in an experimental rabbit model. VX2 carcinomas were transplanted into rabbit hind legs. Hypoxanthine was administered continuously through the ear vein, while xanthine oxidase was administered simultaneously through the femoral artery. As a result, hypoxanthine and xanthine oxidase reacted only in the hind leg, and superoxide was produced in that area. The volume of the VX2 carcinoma was measured immediately prior to treatment and 7 days later. As an index of lipid peroxidation, thiobarbituric acid-reactive substances in the tumor tissue were measured 60 min following infusion of hypoxanthine and xanthine oxidase. Tumor growth was suppressed significantly by the hypoxanthine-xanthine oxidase reaction, and thiobarbituric acid-reactive substances in the tumor tissue infused with hypoxanthine and xanthine oxidase were significantly increased. In addition, the antitumor effect of the hypoxanthine and xanthine oxidase reaction was significantly inhibited by the administration of superoxide dismutase and catalase. Pathological examination showed that oxygen radicals produced by hypoxanthine and xanthine oxidase reaction were selectively more destructive for VX2 carcinoma tissue than muscle tissue surrounding the tumor region. These results suggest that oxygen radicals produced by hypoxanthine and xanthine oxidase reaction produce an anticancer effect and that the VX2 carcinoma used in this study was more sensitive to oxygen radicals than normal muscle tissue.

Animals↗
PubMed1993

Cloning and sequence of an alkaline serine protease-encoding gene from the marine bacterium Alteromonas sp. strain O-7.

The gene (aprII) encoding alkaline serine protease (AprII; subtilase) from Alteromonas sp. strain O-7 was cloned in plasmid pUC19 and transformed into Escherichia coli JM109. The nucleotide (nt) sequence of aprII has been determined. A single open reading frame (ORF) encoded a protein consisting of 621 amino acids (aa) with a M(r) of 63,958. The results of aa sequence analysis indicated that AprII is produced as a large precursor consisting of four domains: the signal sequence, the N-terminal pro-region (AprII-N), the mature AprII (AprII-M) and the C-terminal pro-region (AprII-C). The aa sequence of AprII-M shows high sequence homology with those of class-II subtilases. Two conserved sequences were found in AprII-N which might play a critical role in the maintenance of chaperone-like activity. Repeated aa sequences were observed in AprII-C (AprII-C1 and AprII-C2). The aa sequences of AprII-C1 and AprII-C2 show high sequence homology with those of the C-terminal pro-region of the other known proteases.

Amino Acid Sequence↗
PubMed1993

The role of active oxygen species and lipid peroxidation in the antitumor effect of hyperthermia.

The role of active oxygen species and lipid peroxidation in the antitumor effect of hyperthermia was studied in an experimental rabbit model. VX2 tumors were transplanted into rabbit hind legs, and the effect of hyperthermia on tumor growth was measured at 7 and 14 days after heating. As an index of lipid peroxidation, thiobarbituric acid-reactive substances in the tumor tissue were measured prior to hyperthermia and 3, 6, 12, and 24 h after hyperthermia. Tumor growth in rabbits treated with hyperthermia was significantly reduced, and thiobarbituric acid-reactive substances in the tumor tissue treated with hyperthermia were significantly increased until 6 h after hyperthermia. In addition, alpha-tocopherol in the tumor tissue was significantly decreased after hyperthermia. The antitumor effect of hyperthermia and the increase of thiobarbituric acid-reactive substances in the tumor tissue treated with hyperthermia were significantly inhibited by the administration of superoxide dismutase and catalase or dimethyl sulfoxide. These results suggest that lipid peroxidation mediated by active oxygen species plays an important role in the antitumor effect of hyperthermia.

Animals↗
PubMed1992

[Role of polymorphonuclear leukocytes (PMN) and active oxygen species in hyperthermia--antitumor effect of hyperthermia combined with rhG-CSF].

We have reported that polymorphonuclear leukocytes (PMN) and active oxygen species from PMN may play an important role in the mechanism of the antitumor effect of hyperthermia. At this time, we focused our experimental studies on rat AH109A carcinoma treated with hyperthermia combined with arterial injection of rhG-CSF. Rats with transplantable AH109A carcinoma at the hind leg received hyperthermia. These tumors showed mild suppression of further development only by hyperthermia. However, when arterial injection of rhG-CSF was applied together with hyperthermia, marked suppression of tumor development was observed. Our data suggest that hyperthermia combined with rhG-CSF is closely related to the generation of free radical-mediated tumor cell killing, and it can be an effective treatment for cancer.

Animals↗
PubMed1992

[Role of polymorphonuclear leukocytes (PMN) and active oxygen species in hyperthermia--enhancing effect of G-CSF on superoxide generation from PMN].

We examined in vitro the effect of G-CSF and temperature on superoxide (O2-) generation by Cypridina luciferin analog (CLA) dependent chemiluminescence. PMN significantly generated O2- at the concentration of G-CSF 25 ng/ml or more at 37 degrees C within the range of 0.1 from 1,000 ng/ml. O2- generation from PMN was remarkably enhanced, stimulated by opsonized zymosan (OZ) and phorbol myristate acetate (PMA), at 41 degrees C as compared with 37 degrees C. O2- generation was enhanced with the addition of 25 ng/ml of G-CSF at 41 degrees C as compared to without it at 41 degrees C. A significant enhancement of O2- generation from PMN was observed at 25 ng/ml G-CSF and 41 degrees C.

Granulocyte Colony-Stimulating Factor↗
PubMed1991

[Chemoembolization with degradable starch microspheres for liver metastases of colorectal cancer].

Transcatheter chemoembolization using degradable starch microspheres (DSM) was performed in 17 patients with liver metastases of colorectal cancer. DSM, 45 microns in diameter, which are easily degraded by serum amylase, and therefore obstruct arterial blood flow temporarily at the arteriolar capillary bed. DSM mixed with mitomycin C were administered through the catheter introduced by Seldinger's method in 13 cases, and through subcutaneously implanted drug delivery system (Port-A-Cath) in 4 cases. The treatment was repeated 5 times on the average at intervals of 2 to 4 weeks. The therapeutic effect of this chemoembolization was evaluated by the change in tumor size measured by angiography or computed tomography. Tumor regression of over 50% was observed in 9 of 17 cases (53%). Elevated serum CEA levels (greater than 10 ng/ml) decreased in 10 of 15 cases (67%). One-year survival rate was 48% in 17 cases, and among them it was 100% in 7 cases with the extent of several liver metastases (H2). Extrahepatic metastasis was observed in 3 of 17 cases (18%) before the treatment, and in 8 cases (47%) after the treatment. Abdominal pain occurred in 36% of the cases by the administration of DSM, but the pain disappeared within 2 hours. No major side effects such as bone marrow suppression or hepatotoxicity were observed. Our results suggest that chemoembolization using DSM is effective and safe in the treatment of liver metastases from colorectal cancer.

Carcinoembryonic Antigen↗
PubMed1990

[Role of active oxygen species and lipid peroxidation in liver injury induced by ischemia-reperfusion].

The role of superoxide and lipid peroxidation in liver injury induced by ischemia-reperfusion was investigated in rats. Ischemic condition of the liver was created by applying small clamps to the right branch of portal vein and the right hepatic artery for 15 min. Clamping of hepatic artery and portal vein could decrease the hepatic blood flow to about 30% of that measured before the clamping. Levels of serum GPT and thiobarbituric acid (TBA) reactive substances in the liver tissue were significantly increased 30 min after the reperfusion following 15 min of ischemia. The increase in serum GPT and TBA reactants in the liver tissue was significantly inhibited by the treatment with superoxide dismutase combined with catalase. The treatment with allopurinol significantly inhibited the elevation of serum GPT levels and showed a tendency to inhibit the increase in TBA reactants in liver tissue. These results suggest that active oxygen species and lipid peroxidation may play an important role in the pathogenesis of ischemia-reperfusion injury in the liver, and hypoxanthine-xanthine oxidase system may be one of the main sources of active oxygen species.

Animals↗
PubMed1989

[Clinical results of hyperthermia alone in the treatment of refractory human tumors].

Retrospective analysis of patients with refractory tumors which were treated with hyperthermia alone in five institutions was performed. Hyperthermia was applied to 30 refractory tumors including 19 deep-seated tumors for a total of 427 sessions by 8 MHz or 13.56 MHz radiofrequency capacitive heating devices. Of the 30 tumors treated, 3 (10%) showed complete regression and 2 (7%) more than 50% regression. Although tumor regression was observed in small tumors, large deep-seated tumors did not respond to heat alone. Thus, response rate of hyperthermia alone was lower than expected, although subjective improvement by hyperthermia was noted in 53% patients. We consider that hyperthermia should be combined with radiation or chemotherapy whenever possible.

Adult↗
PubMed1989

[Antitumor effect and indication of chemoembolization using degradable starch microspheres and regional hyperthermia in patients with hepatocellular carcinoma].

Antitumor effects and indications of chemoembolization using degradable starch microspheres (DSM) and regional hyperthermia were investigated in patients with unresectable hepatocellular carcinoma. Chemoembolization using DSM was performed in 40 cases and fourteen cases were treated with the combination of hyperthermia. Tumor regression rate over 50% was 48% (chemoembolization alone: 42%, combined hyperthermia: 57%). Though one and two year survival rates were 62% and 54% respectively in the treatment with chemoembolization alone, one year survival rate was 91% in the treatment with combined hyperthermia. From the viewpoint of antitumor effect, it was thought that effectual indications of chemoembolization using DSM alone were the cases whose tumor size were below 7 cm and portal invasion were negative. These indications however were spread by the combination of hyperthermia. The DSM, temporary embolus, is suitable for combination of hyperthermia because chemoembolization using DSM can be performed many times. The cases with clinical stage III and obstruction of the first branch of portal veins did not become severe hepatic failure because DSM was temporary embolus. Therefore, from the viewpoint of safety, chemoembolization using DSM has almost the same indications as intra-arterial infusion therapy. These results suggested that chemoembolization using DSM will be a beneficial methods as combination therapy for unresectable hepatocellular carcinoma.

Carcinoma, Hepatocellular↗
PubMed1989

[Chemoembolization with degradable starch microspheres for liver metastases in colorectal cancer].

Transcatheter chemoembolization using Degradable Starch Microspheres (DSM) was performed in 17 patients with liver metastases of colorectal cancer. Mitomycin C mixed with DSM was injected into the proper hepatic artery. Tumor regression of over 50% was observed in 9 of 17 cases (53%). Elevated serum CEA levels (greater than 10 ng/ml) decreased in 10 of 15 cases (67%). One-year survival rate was 50% in 17 cases. One-year survival rate was 100% in 7 cases with several liver metastases (H2). Abdominal pain occurred in 36%, mostly disappearing within 2 hours. No major side effects such as bone marrow suppression or hepatotoxicity were observed. Our results suggest that chemoembolization using DSM is effective and safe in the treatment of liver metastases from colorectal cancer.

Colorectal Neoplasms↗
PubMed1989

[Chemo-embolization using degradable starch microspheres and regional hyperthermia in unresectable hepatocellular carcinoma].

Antitumor effects and prognosis of the patients with unresectable hepatocellular carcinoma were investigated in the treatment of chemo-embolization using degradable starch microspheres (DSM) and regional hyperthermia. Twenty-six cases were treated with chemo-embolization using DSM alone (Group A) and eighteen cases were treated with combination of chemo-embolization and hyperthermia (Group B). Tumor regression rates over 50% were 42% (11/26) and 56% (10/18) in Group A and Group B, respectively. In the patients with tumors over 7 cm in diameter, no favorable response was obtained in Group A (0/11), but the response rate was increased to 56% (5/9) by the combination of hyperthermia. In the patients with arterio-portal shunt, therapeutic effects were observed in 17% (1/6) and 50% (1/2) of Group A and Group B, respectively. In the patients with portal invasion (Vp2 and Vp3), no favorable response was demonstrated in Group A (0/4), but tumor response was demonstrated in one out of 3 cases in Group B. One- and two-year survival rates were 59% and 53%, respectively, in Group A, and 93% and 45%, respectively, in Group B. The DSM, temporary embolus, is suitable for the combination of hyperthermia because chemo-embolization using DSM can be performed many times. Therefore, these results suggested that chemo-embolization using DSM should be beneficial as combination therapy for unresectable hepatocellular carcinoma.

Carcinoma, Hepatocellular↗
PubMed1989

[Role of lipid peroxidation and polymorphonuclear leukocytes-derived oxygen radicals in acute gastric lesions induced by hyperthermic treatment].

Acute gastric lesions were experimentally induced by local hyperthermic treatment (42 degrees C, 40 min). Thiobarbituric acid (TBA) reactants in the gastric mucosa were significantly increased 40 min after the hyperthermia. There were no changes in gastric mucosal blood flow and gastric acid secretion. The total area of gastric erosions and TBA reactant in gastric mucosa of rats deficient in vitamin E were significantly increased compared with those of rats supplemented with vitamin E. The increase in the total area of gastric erosions and TBA reactants in gastric mucosa were significantly inhibited by the treatment of bovine Cu, Zn-SOD and bovine catalase, and by the depletion of polymorphonuclear leukocytes (PMN). Allopurinol did not show any influence on these pathological changes induced by hyperthermia. These results suggest that lipid peroxidation and PMN-derived oxygen radicals may play an important role in the pathogenesis of gastric lesions induced by hyperthermic treatment.

Acute Disease↗
PubMed1988

Esophageal candidiasis.

Among 3,501 individuals receiving endoscopic examination for the upper digestive tract, 41 were found to have esophageal candidiasis including 17 malignancies, 14 immunological disorders, 4 diabetes mellitus, 7 other underlying diseases and 7 apparently healthy subjects. The diagnosis was made either by brushing of the esophagus or by histological examination of the biopsied specimen. Systemic invasion of fungi was observed mainly in patients with malignancy involving the hematopoietic system, and most of them had been treated by corticosteroids, antibiotics or anticancer agents. Although complications associated with esophageal candidiasis are rare, it is emphasized that those patients with malignancy as well as impared immunity should be carefully examined for esophageal candidiasis, in order to prevent the fungi from developing invasive candidiasis. It should be noted that a few cases of gastric ulcer treated by H2 blocker revealed esophageal candidiasis, suggesting that decrease of gastric acidity might be one of the factors involved in this pathological condition.

Amphotericin B↗