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Biomedical subjects

K Ono

Publications and source records attributed to K Ono.

At least 829 records · Page 46Linked to original sources

[Application of a slow release system of anti-cancer drug retained in calcium hydroxyapatite ceramic against experimental bone and soft tissue sarcoma].

Cis-platinum enclosed into porous calcium hydroxyapatite ceramics (CDDP-CHA) has already been reported to be an excellent slow releasing drug preparation in vivo and in vitro study. In this paper, CDDP-CHA tried to apply for experimental bone and soft tissue sarcoma. When CDDP-CHA were implanted into solid tumors (Dunn osteosarcoma cells) transplanted subcutaneously in mice, high concentration of CDDP was found and a prolonged retention of the drug in the tumor as same pattern as in normal muscle. In contrast, CDDP concentration in other organs such as liver, kidney were significantly lower than in the tumor. Tumor growth was markedly inhibited at 30 days after CDDP-CHA implantation into the tumor compared to that after intraperitoneal administration. CDDP-CHA showed a similar effect to experimental bone tumor (mammary carcinoma) as that of soft tissue tumor. These result suggests that this delivery system will be able to apply clinically for bone and soft tissue sarcoma.

Animals↗

[Changes of Cu, Zn-SOD and LPO in the regenerating liver after partial hepatectomy--effect of coenzyme Q10 administration].

We have investigated the effect of CoQ10 to lipid peroxide (LPO) and Cu, Zn-SOD in the regenerating liver in rats. Cu, Zn-SOD was investigated in biochemical activity, and immunohistochemical localization. In normal control liver, Cu, Zn-SOD was diffusely stained throughout the hepatic lobules, with predominance in the centrilobular area and with vicinity of thick portal vein. In early stage of regenerating liver. LPO was increased and Cu, Zu-SOD was decreased. Destruction of the membrane of hepatocyte was confirmed by electron microscopy in the early stage of regenerating liver, Cu, Zn-SOD might be speculated to leak out into extra cellular spaces. CoQ10 suppressed the mentioned phenomenon in regenerating liver.

Animals↗

Involvement of the retinoblastoma gene in primary osteosarcomas and other bone and soft-tissue tumors.

The retinoblastoma (Rb) gene, thought by some to be associated with tumor formation of retinoblastoma as a recessive human oncogene, was investigated in 57 cases using DNA and RNA from primary osteosarcomas and other bone and soft-tissue tumors. Eight of 23 osteosarcoma cases (35%) showed structural alterations of the Rb gene. Three of the eight demonstrated homozygous deletions, and the remaining five cases showed heterozygous deletions. Seven out of eight cases represented deletion of a 7.5-kb HindIII fragment. Northern blot analysis of five cases of osteosarcoma showed that four demonstrated no detectable Rb gene transcription, and one case had a truncated 3.5-kb fragment with a faint 4.7-kb band. In the other 34 cases of bone and soft-tissue tumors, two cases of three malignant fibrous histiocytomas showed an Rb gene abnormality by Southern blot analysis. These results strongly suggest that Rb gene alteration is pertinent to the tumorigenesis of most osteosarcoma cases and some other bone and soft-tissue tumors.

Adolescent↗

[Continuous hyperthermic peritoneal perfusion (CHPP) therapy in advanced gastric cancer].

In CHPP therapy for advanced gastric cancer, a perfusate containing 20 mg CDDP and 8 mg MMC in 1,000 ml physiologic saline warmed at 47 degrees C was infused at a constant rate of 200 ml/min into the pouch of Douglas. The intraperitoneal temperature at the supra-pancreatic region was around 39.0 degrees C. To obtain a more stable and higher intraperitoneal temperature, the infusing rate was increased to 400 ml/min. This yielded a 3 degrees C higher temperature (42 degrees C) at the same measuring site. However, the temperature recorded at various intraperitoneal sites did not always reach such an effective range. The maximal plasma concentrations of MMC determined during CHPP at the 200 and 400 ml/min infusion were 0.09 +/- 0.03 and 0.11 +/- 0.03 microgram/ml, and those of CDDP 1.6 +/- 0.4 and 1.7 +/- 0.3 microgram/ml, respectively, all of which were not significantly different. When an intraperitoneal dosage of 20 mg MMC was given to 3 patients, the portal venous blood, at 10 min after the administration, produced a 1.7 times higher concentration of the agent than did the peripheral venous blood. This discrepancy between the two concentrations was much smaller than found by other investigators in animal experiments.

Adult↗

[A basic study on cefpirome].

The antibacterial activity of cefpirome (CPR), a new parenteral cephalosporin antibiotic having a cyclopentenopyridine group in the 3-position side chain, was evaluated against Neisseria gonorrhoeae and concentrations in human kidney and prostate was determined. The minimum inhibitory concentrations (MICs) of CPR against N. gonorrhoeae isolated clinically in our out-clinic (34 strains of non-PPNG and 20 of PPNG) were less than or equal to 0.003-0.1 microgram/ml in non-PPNG group and 0.006-0.1 microgram/ml in PPNG group. The 90% of MICs (MIC90s) was 0.1 microgram/ml in the non-PPNG group and 0.05 microgram/ml in the PPNG group. The concentration in the prostate was determined in 30 cases with benign prostatic hypertrophy. The maximum values was 52.8 micrograms/g at 15 minutes after administration of 1 g of CPR. The levels of CPR were gradually decreased with the lapse of time. The prostatic tissue concentration was 17.9 micrograms/g at 60 min., 10.1 micrograms/g at 180 min., 7.22 micrograms/g at 320 min. and 2.70 micrograms/g at 360 min. There was a positive correlation between concentration of the prostate and plasma collected at the time of the prostate. The concentration of CPR in human kidney, 90-100 min. after administration of 1 g to 4 cases with renal tumor, was 107-148 micrograms/g in the renal cortex, and 80.6-88.6 micrograms/g in the renal medulla. The concentration in kidney was higher than that in the plasma in all cases. In conclusion, CPR is suggested to be a useful drug for urological infection.

Cephalosporins↗

[Bacteriological and clinical studies on fleroxacin in male gonococcal urethritis].

We performed basic and clinical studies on the effects of a new oral antimicrobial agent, fleroxacin (FLRX), a new quinolone derivative in male gonococcal urethritis. The antibacterial activity of FLRX against clinical strains of Neisseria gonorrhoeae was roughly comparable to that of norfloxacin and ofloxacin. FLRX was administered to 58 males with gonococcal urethritis. Two different schedules of administration were adopted. One was a single-dose of 300 mg given orally (17 cases) and the other was the oral administration of 200 mg once a day for 3 to 10 days (41 cases). Clinical evaluation was made according to the criteria of the Japanese UTI Committee. The overall efficacy rate was 98% (49/50). For complications of Chlamydia trachomatis (11 cases), the efficacy rate was 90.9% (10/11). No subjective or objective adverse reaction occurred.

Administration, Oral↗

[Neural plasticity after neonatal hypoxic and ischemic insult in rats].

Rats with huge porencephaly occupying the left cerebral hemisphere were used for this study. Porencephaly was caused experimentally by the ligation of the left common carotid artery and subsequent hypoxic exposure at the age of 7 days. A large band of horseradish peroxidase (HRP) positive fibers was found crossing at the pyramidal decussation to reach the contra-lateral corticospinal tract and the deeper part of the funiculus, in the cervical cord. However, a small band of HRP positive fibers was noticed to reach the ipsilateral corticospinal tract without crossing at the pyramidal decussation. This result indicates that the developing pyramidal neurons in the right hemisphere carry the plasticity even after suffering from considerable hypoxia.

Animals↗

[A case of unstable diabetes mellitus after total pancreatectomy controlled by CSII].

Continuous subcutaneous insulin injection (CSII) is one of good methods to control unstable diabetes. In this paper, we reported a case of a patient with unstable diabetes after total pancreatectomy, to whom CSII was very effective. The case was 53 years of age, lean woman. In 1980, she had pancreatoduodenectomy for the treatment of cancer of duodenal papilla. In June, 1986, she was diagnosed as recurrence of the cancer, and undertaken total pancreatectomy. And then, insulin treatment was commended. But she readily developed hypoglycemic reactions by ordinary insulin injection once or twice a day, and glycemic control was very poor. On April 22, 1987, CSII was started. 8 units of regular insulin were given during 24 hours, and 2 units of regular insulin were added before every meal. Thereafter, the frequency of hypoglycemic reaction decreased dramatically, and HbA1c level decreased from 8.5% to 8.1% three months later. This report indicated usefulness of CSII to patients with unstable diabetes, who couldn't be controlled by ordinary insulin injection.

Aged↗

Purification and characterization of a sea squirt beta-galactosidase.

A beta-galactosidase was extracted from the internal organs of a sea squirt, Styela plicata, and purified 959-fold, with an 18% yield, by successive gel chromatography, anion-exchange chromatography, chromatofocusing, and affinity chromatography on a Con A-Sepharose column. The purified enzyme was fairly homogeneous, as judged on disc PAGE, SDS-PAGE, and gel chromatography on a Sephadex G-200 column. The molecular weight of the enzyme was estimated to be 77,000 and 75,000 by gel chromatography and SDS-PAGE, respectively, and its isoelectric point was determined to be 4.9 by the isoelectric focusing method. The enzyme was substantially stable in the pH range of 3.5 to 7.5, the optimum pH being 4.0. The enzyme was significantly inhibited by 9 mM HgCl2 and 9 mM DFP, while the inhibition by 0.9% PCMB was only 60% at 0 degrees C for 30 min. The purified beta-galactosidase apparently liberated galactose from a sea squirt antigen (H-antigen), two allergenically active glycopeptides (Gp-1 and Gp-2) derived from another sea squirt antigen (Gi-rep), asialo-ovomucoid glycopeptide, asialo-fetuin glycopeptide, GA1, CDH, and an ABEE-derivative (Gal beta 1----3ThrNAc-ABEE) of Gal beta 1----3GalNAc-ol isolated from bovine submaxillary gland mucin.

Animals↗

[T-cell type non-Hodgkin's lymphoma associated with eosinophilia].

A 65-year-old man was admitted to our hospital in January 1990, because of weakness of upper limbs. On admission he was found to have generalized lymphadenopathy and leukocytosis. His WBC count was 40,900/microliters with 88% eosinophils. The bone marrow showed an increased number of eosinophils and their precursors but no other abnormalities. A diagnosis of non-Hodgkin's lymphoma (diffuse, medium sized cell type) was made by biopsy of his inguinal lymph node. The result of marker analysis was consistent with CD3+4+8-. The antibody to human T-lymphotropic virus type I was negative. A stomach biopsy revealed lymphoma cell infiltration. Extensive studies to identify the cause of the eosinophilia were undertaken, with consistently negative results. Combination chemotherapy was begun, and resulted in a dramatic resolution of the eosinophilia and the lymphadenopathy. The association of hypereosinophilia with non-Hodgkin's lymphoma is unusual. We report a patient with eosinophilia and non-Hodgkin's lymphoma, and discussed its possible etiology.

Aged↗

[Immunotherapy using high concentration purified antigen showed remarkable effect in all cases].

Hoya (sea-squirt) asthma is a typical type I occupational asthma. A total of 22 females with this disease whose age ranged from 22 to 69 years were treated for two years with high concentration purified sea-squirt antigen named Ei-M having a molecular weight of 22,800. One case who developed ordinary bronchial asthma abandoned the immunotherapy during the early stage of the therapy, but in the remaining 21 cases remarkable effects were rapidly observed from the early stage of treatment. These cases did not develop asthmatic attacks even through they engaged in oyster shucking work and no symptomatic therapy was indicated. Serum anti-Ei-M IgG antibody was significantly elevated after the therapy. None of the treated cases developed any side effects.

Adult↗

[Left ventricular-right atrial shunt due to infective endocarditis--report of a case].

Acquired left ventricular-right atrial shunt is a very rare cardiac disease. Infective endocarditis, cardiac operative procedures, and thoracic trauma were reported as origins. We report a case of a patient with left ventricular-right atrial shunt due to infective endocarditis. A 53-year-old male who had aortic regurgitation due to infective endocarditis developed suddenly severe congestive heart failure. Two-dimensional and pulsed doppler echocardiography demonstrated left ventricular-right atrial shunt. Emergency operation was done. The fistula was found through the atrioventricular membranous septum. The position from the left view was just below the commissure between the right coronary cusp and non coronary cusp and the opening position from the right view was just above the septal leaflet of tricuspid valve. Aortic valve replacement and direct closure of fistula were done and patient's recovery was uneventful. Case reports of left ventricular-right atrial shunt due to infective endocarditis have been rarely seen, most of which were followed by poor prognosis. Surgical intervention in acute phase is recommended.

Endocarditis, Bacterial↗

[Successful reinduction of complete remission in a patient with ALL associated with multiple liver abscesses who relapsed after 6 years].

We reported on a 35 year-old patient suffering from ALL with multiple liver abscesses (Journal of Kyusyu Hematological Society, Vol. 31, No. 3 & 4, Dec., 1983). He experienced six years of complete hematological remission from 1983 to 1989, with low fever, positive CRP, polyclonal gamma-globulinemia and elevated alkaline phosphatase. A relapse occurred in June of 1989. A subsequent biopsy revealed fibrosis of the liver attributed to inflammation. At present, he has returned to the complete remission stage with no exacerbation of the liver abscesses.

Adult↗

Regulation by induction of branched-chain 2-oxo acid dehydrogenase complex in clofibrate-fed rat liver.

The activity of branched-chain 2-oxo acid dehydrogenase complex increased 3.0-fold in liver of rats fed on 0.1%(w/w) clofibrate. Immunotitration experiments with antibodies against the constituent enzymes of the complex revealed that this increase resulted mainly from the increased amounts of only two(a decarboxylase and a lipoate acyltransferase) of three components of the complex and that the other component(dihydrolipoamide dehydrogenase) remained unchanged in its content, irrespective of clofibrate administration. The increases of both enzyme components were associated with increases in their mRNA levels which were estimated by in vitro translation with poly(A)+ RNA.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

Potent inhibitory effects of the 5'-triphosphates of (E)-5-(2-bromovinyl)-2'-deoxyuridine and (E)-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil on DNA polymerase gamma.

(E)-5-(2-Bromovinyl)-2'-deoxyuridine 5'-triphosphate (BrVdUTP) and (E)-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil 5'-triphosphate (BrVarafUTP), which are known as specific inhibitors of herpes simplex viral (type 1 and 2) DNA polymerase, were found to be strong inhibitors of DNA polymerase gamma from human KB and murine myeloma cells. In fact BrVdUTP and BrVarafUTP were found to be stronger inhibitors of DNA polymerase gamma than of other DNA polymerases having viral (herpes simplex virus or retrovirus) origin or cellular (eukaryotic alpha and beta, or prokaryotic) origin. The mode of inhibition of DNA polymerase gamma by BrVdUTP and BrVarafUTP was competitive with respect to dTTP, the normal substrate. Whereas BrVdUTP was an efficient substrate for DNA polymerase gamma and other DNA polymerases that were examined, BrVarafUTP failed to serve as a substrate for DNA synthesis. Ki values for BrVdUTP (40 nM) and BrVarafUTP (7 nM) with DNA polymerase gamma, as determined with (rA)n.(dT) as the template.primer, were much smaller than the Km values for dTTP (0.16 microM and 0.71 microM for murine and human DNA polymerase gamma, respectively). Thus, the affinity of BrVdUTP or BrVarafUTP for DNA polymerase gamma was much stronger than that of dTTP.

Animals↗

Differential inhibitory effects of various flavonoids on the activities of reverse transcriptase and cellular DNA and RNA polymerases.

Four flavonoids, 5,6,7-trihydroxyflavone (baicalein), 3,3',4',5,7-pentahydroxyflavone (quercetin), 3,3',4',5,6,7-hexahydroxyflavone (quercetagetin) and 3,3',4',5,5',7-hexahydroxyflavone (myricetin), were found to be potent inhibitors of reverse transcriptases from Rauscher murine leukemia virus (RLV) and human immunodeficiency virus (HIV). Under the reaction conditions employed, any one of these flavonoids almost completely inhibited the activity of RLV reverse transcriptase at a concentration of 1 microgram/ml. HIV reverse transcriptase was inhibited by 100%, 100%, 90% and 70% in the presence of 2 micrograms/ml quercetin, myricetin, quercetagetin and baicalein, respectively. The mode of inhibition of these flavonoids was competitive (RLV reverse transcriptase) or partially competitive (HIV reverse transcriptase) with respect to the template.primer complex, (rA)n.(dT), and noncompetitive with respect to the triphosphate substrate, dTTP. The Ki values for RLV reverse transcriptase were found to be 0.37 microM and 0.08 microM for baicalein and quercetin, respectively and those for HIV reverse transcriptase were 2.52 microM, 0.52 microM, 0.46 microM and 0.08 microM for baicalein, quercetin, quercetagetin and myricetin, respectively. Comparative studies with other flavonoids (hydroxyflavones, dihydroxyflavones and polyhydroxyflavones and flavanones) carried out to clarify the structure/activity relationships, revealed that the presence of both the unsaturated double bond between positions 2 and 3 of the flavonoid pyrone ring, and the three hydroxyl groups introduced on positions 5, 6 and 7, (i.e. baicalein) were a prerequisite for the inhibition of reverse transcriptase activity. Removal of the 6-hydroxyl group of baicalein required the introduction of three additional hydroxyl groups at positions 3, 3' and 4' (quercetin), to afford a compound still capable of inhibiting the reverse transcriptase activity. Quercetagetin which contains the structures of both baicalein and quercetin, and myricetin which has the structure of quercetin with an additional hydroxyl group on the 5' position also proved strong inhibitors of reverse transcriptase activity. The inhibition by baicalein of reverse transcriptase is highly specific, whereas quercetin and quercetagetin were also strong inhibitors of DNA polymerase beta and DNA polymerase I, respectively. Myricetin was also a potent inhibitor of both DNA polymerase alpha and DNA polymerase I.

Animals↗