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Biomedical subjects

Y Ohe

Publications and source records attributed to Y Ohe.

At least 163 records · Page 9Linked to original sources

[Cardiovascular changes after intubation and at the time of incision during nitrous oxide-oxygen anesthesia with epidural buprenorphine].

The cardiovascular changes after intubation and at the time of incision under nitrous oxide-oxygen anesthesia with epidural buprenorphine (Bn) were examined. The subjects were 56 patients who underwent abdominal surgery. The patients were divided into two groups in terms of the epidural drugs used, i.e., group I (Bn 0.2 mg + saline 9 ml, n = 31) and group II (Bn 0.2 mg + 1% lidocaine 10 ml, n = 25). The systolic pressure increased significantly (P less than 0.05) to 169 +/- 29 mmHg (mean +/- SD) after intubation and to 162 +/- 28 mmHg after incision in group I, with no decrease in blood pressure during the non-stimulation period. In group II, although there was a significant decrease in blood pressure to 114 +/- 24 mmHg just before incision (P less than 0.05), no elevation of blood pressure was noted after intubation or incision. There was no significant difference between groups I and II with regard to the heart rate and respiratory rate. We were unable to block the cardiovascular reaction after intubation and incision under nitrous oxide-oxygen anesthesia with epidural Bn, requiring local anesthetics or volatile anesthetics. This method, however, is useful for patients in whom a fall of blood pressure should be avoided, e.g., for those with hypovolemia.

Abdomen↗

[Epidural buprenorphine with nitrous oxide-oxygen-enflurane anesthesia].

Epidural buprenorphine (Bn) with nitrous oxide-oxygen-enflurane (GOE) anesthesia was investigated as an anesthetic method in 63 patients who underwent upper abdominal surgery over three hours. The patients were divided randomly into three groups. The first group received only GOE anesthesia (group A, n = 13), the second group was given GOE anesthesia and 0.2 mg epidural Bn every three hours during operation (group B, n = 23) and the third group was administered GOE anesthesia and 0.2 mg epidural Bn every six hours (group C, n = 27). The patients were rated according to intraoperative anesthetic dosage, awakening from anesthesia, postoperative respiratory depression and postoperative analgesia. The administered enflurane concentration declined approximately 0.4% in group B and C as compared that in group A (P less than 0.05). And there was no intra-group difference in the awakening time from anesthesia. Postoperative respiratory depression was noted in group B. The respiratory rate 18.7 +/- 1.0 (mean +/- SE) min-1 in group B was significantly lower compared with the rates 22.8 +/- 1.5 min-1 in group A and 22.1 +/- 1.1 min-1 in group C (P less than 0.05). The PaCO2 value 44.1 +/- 1.0 mmHg in group B was significantly higher compared with the values 39.8 +/- 0.8 mmHg in group A and 41.3 +/- 0.9 mmHg in group C (P less than 0.01). Postoperative analgesia was remarkably prolonged in group B and C; 542 +/- 97 minutes and 504 +/- 97 minutes, respectively, as compared with 55 +/- 20 minutes in group A (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

[Is epidural buprenorphine with nitrous oxide-oxygen-enflurane anesthesia indicated for surgery of short-duration?].

The effects of duration of surgeries on epidural buprenorphine (Bn) with nitrous oxide-oxygen enflurane anesthesia were examined. The subjects were 64 patients who underwent upper abdominal surgery. The patients were divided into two groups in terms of the time required for surgery: i.e., group I (surgery of short duration, n = 18) and group II (surgery of long duration, n = 46). They were given 0.2 mg epidural Bn just before induction and then general anesthesia with nitrous oxide-oxygen-enflurane was performed. The patients were rated with intraoperative anesthetic dosage, time required for arousing from anesthesia, postoperative respiratory depression and postoperative analgesia. There was no significant difference between groups I and II with regard to the dose of Bn, maximum concentration of inhaled enflurane and time required for arousal from anesthesia. There were, however, significant differences in postoperative respiratory state between the two groups. The mean tidal volume was 307.6 ml in group I, which is lower than the corresponding value, 429.5 ml in group II (P less than 0.01), and PaCO2 was higher in group I (mean 44.9 mmHg) than in group II (42.3 mmHg) (P less than 0.05). Although no difference was found in the time from Bn administration to the first analgesic supplement between the two groups, the postoperative analgesic time was longer in group I than in group II (P less than 0.05). From these results we conclude that considerable care should be taken for surgery of short duration under epidural buprenorphine with nitrous oxide-oxygen-enflurane anesthesia.

Abdomen↗

Involvement of an AFP1-binding site in cell-specific transcription of the pre-S1 region of the human hepatitis B virus surface antigen gene.

Human hepatitis B virus infection is characterized by a high degree of hepatotropism which may be due to the dependency of viral genes on specific host factors for their expression. To learn more about such a requirement and the molecular basis of the viral tissue tropism we analyzed the promoter function in the pre-S1 region of the surface antigen gene. DNase I footprinting and competition gel retardation assays showed that a sequence with an AT-rich core (AT motif) in the pre-S1 promoter region interacts with AFP1, a hepatoma nuclear factor that binds to the alpha-fetoprotein enhancer and promoter. Functional analysis of the pre-S1 AT motif by transient transfection assays showed that this element is important in cell-specific transcriptional initiation. These results suggest that AFP1 may be one of the factors determining the liver specificity of human hepatitis B virus.

Base Sequence↗

In vitro evaluation of the new anticancer agents KT6149, MX-2, SM5887, menogaril, and liblomycin using cisplatin- or adriamycin-resistant human cancer cell lines.

A new model to predict antitumor activity of new analogues was developed, and the cross-resistance against cisplatin (CDDP) and Adriamycin (ADM) was examined. A preclinical evaluation of various new analogues using this new model was performed. The antitumor activities of KT6149, MX-2 (KRN8602), SM5887, menogaril (TUT-7), and liblomycin (NK313) were evaluated against four non-small cell lung cancer cell lines, PC-7, -9, -13, and -14; two small cell lung cancer cell lines, H69 and N231; four CDDP-resistant cell lines, PC-7/1.0, PC-9/0.5, PC-14/1.5, and H69/0.4; a human myelogenous leukemia cell line, K562; and its ADM-resistant subline, K562/ADM by clonogenic assay. The relative antitumor activities of these new analogues were compared with those of parental agents, mitomycin C, ADM, bleomycin, and several anticancer drugs, CDDP, daunomycin, vindesine, and etoposide. KT6149 was more active than mitomycin C against all lung cancer cell lines and the human myelogenous leukemia cell line. Menogaril showed greater activity than ADM, and MX-2 showed activity similar to ADM. However, the antitumor activity of SM5887 was lower than that of ADM. SM5887 and menogaril showed cross-resistance to K562/ADM. Nevertheless, the antitumor activity against K562/ADM of MX-2 was similar to that of the parental cell lines. The activity of liblomycin was similar to that of bleomycin. Thus, KT6149 appears to be the best analogue for use in a clinical trial against lung cancer. MX-2 was active even against ADM-resistant cancer cells. The values of relative resistance to CDDP or ADM were 4.7, 8.1, 7.5, 20.0, and 13.6 for PC-7/1.0, PC-9/0.5, PC-14/1.5, H69/0.4, and K562/ADM, respectively. CDDP-resistant cell lines showed no cross-resistance with other drugs in this study. K562/ADM showed cross-resistance against daunomycin, etoposide, and vindesine. In contrast, mitomycin C and bleomycin had nearly equal activity against K562 and K562/ADM. However, K562/ADM was 2.4-fold more sensitive to CDDP than its parental cell line, K562 (P less than 0.001). These results suggested that the mechanism of CDDP resistance is different from that of multidrug resistance.

Anthracyclines↗

Pharmacokinetics of (glycolate-0,0')-diammine platinum (II), a new platinum derivative, in comparison with cisplatin and carboplatin.

The pharmacokinetics of (glycolato-0,0')-diammine platinum (II) (254-S; NSC 375101D), one of the new platinum analogues, was examined in a phase I study of this drug and compared with that of cisplatin and carboplatin. All drugs were given in short-term (30-min) i.v. drip infusions; the doses of 254-S, cisplatin, and carboplatin were 100, 80, and 450 mg/m2, respectively. Platinum concentrations in whole plasma, plasma ultrafiltrate, and urine were determined by atomic absorption spectrometry. After the infusion, the plasma concentration of total platinum for the three agents decayed biphasically. Ultrafilterable platinum in plasma decreased in a biexponential mode after infusions of 254-S and carboplatin, whereas the free platinum of cisplatin showed a monoexponential disappearance. The peak plasma concentrations and AUC for free platinum were 5.31 micrograms/ml and 959 micrograms/min per ml for 254-S, 3.09 micrograms/ml and 208 micrograms/min per ml for cisplatin, and 19.90 micrograms/ml and 3446 micrograms/min per ml for carboplatin, respectively. The mean ratio of plasma ultrafilterable platinum to total platinum were calculated, and the results showed that the protein-binding abilities of 254-S and carboplatin were almost identical. More than 50% of the 254-S was excreted in the urine within the first 480 min after its administration. Thrombocytopenia was reported as a dose-limiting toxicity for both 254-S and carboplatin. This similarity in side effects may mainly be due to the comparable pharmacokinetic behavior of these two platinum compounds.

Antineoplastic Agents↗

Human spleen histone H1. Isolation and amino acid sequences of three minor variants, H1a, H1c, and H1d.

Following the previous determination of the main variant H1b of human spleen histone H1, we have determined the complete amino acid sequence of another variant, H1d. Limited chymotryptic digestion of H1d produced four fragments, I to IV, and one partial fragment I-II, as in the case of H1b. These fragments were aligned with two overlapping peptides, produced by another enzyme from the intact H1d. We also confirmed the C-terminal sequence of H1d by carboxypeptidase digestion. This H1d has an acetylated N-terminal serine, equimolar alanine or valine residue at 17, and is composed of 212 residues. The molecular weight was 21,233 for the alanine variant and 21,261 for the valine variant in the unmodified form. We also deduced the total sequences of H1a and H1c in a similar way, considering the maximum homology with H1b and H1d. Each N-terminal serine residue is acetylated, too. H1a consists of 222 amino acid residues and has a molecular weight of 22,178 in its unmodified form; the H1c consists of 220 residues and has a molecular weight of 22,218 in that form. The human spleen H1 sequences varied to about the same extent in the N-terminal 40 and C-terminal 110 residues. However, the sequences of the about 70 internal residues are well conserved between the variants. The extent of differences among the human H1 variants is similar to, or rather smaller than, those among the mammalian somatic H1 species. The implications of these differences in the sequence for H1 function are discussed from the evolutionary viewpoint.

Amino Acid Sequence↗

Inhibition of colony formation of drug-resistant human tumor cell lines by combinations of interleukin-2-activated killer cells and antitumor drugs.

The cytotoxicity of interleukin-2-activated killer (LAK) cells with or without anticancer drugs against cell lines with acquired drug resistance was evaluated in vitro by colony assay. Human non-small cell lung cancer cell lines, PC-9 and PC-14, human leukemia cell line, K-562, and their sublines resistant to cisplatin (CDDP), PC-9/CDDP and PC-14/CDDP, and to adriamycin (ADM), K-562/ADM, were used as target cells. PC-9/CDDP demonstrated a marked increase in susceptibility to killing by both peripheral blood lymphocytes (PBL) and LAK cells, as compared to the parental cell line, PC-9. The cytotoxicity of PBL and LAK cells against PC-14/CDDP and K-562/ADM was similar to that against their parental cell lines. Moreover, the combination of LAK and CDDP had a synergistic effect on PC-14 and PC-14/CDDP.

Adenocarcinoma↗

[Clinical evaluation of PIVKA-II as a marker of hepatocellular carcinoma].

PIVKA-II (protein induced vitamin K absence or antagonist-II) levels in plasma were measured using ELISA in patients with hepatocellular carcinoma (HCC). PIVKA-II was detected in 53 of 97 patients (54.6%) of HCC, and the combination assay of PIVKA-II and AFP identified 69 of 97 patients (71.1%) with HCC. However, the positive rate of PIVKA-II (6.1%) was lower than that of AFP (37.5%) in patients with HCC less than 2 cm in diameter. The concentration of PIVKA-II was markedly reduced within 2 weeks after treatment in patients with HCC showing a favorable response to Lp-TAE or Lp-TAI. Although PIVKA-II is a valuable marker for the diagnosis and follow-up of patients with HCC, it must be noted that the change to negative concentration of PIVKA-II after treatment does not mean complete necrosis of the tumor.

Aged↗

[New acrylic resins with very low residual monomer].

New experimental acrylic resins were prepared by polymerization of MMA in the presence of vinylidene fluoride/hexafluoropropylene copolymer. The amount of residual monomer in the resins prepared by visible light curing, cold curing, and heat curing, at various polymer/monomer ratios, was measured and compared with the usual MMA/PMMA resin. In the visible light cured resins containing 60 or 70 wt% of the fluoropolymer, the amount of residual monomer was less than 0.1%. In the cold cured resins, the amount of residual monomer was very low: 0.2% and 0.7% for the resins containing 70 and 60 wt% of the polymer, respectively. These values were comparable to the usual heat cured MMA/PMMA resins. In the heat cured resins, the amount of residual monomer was the lowest; less than 0.1%, even in the resin consisting of 50 wt% polymer. Thus, we prepared new acrylic resins with much less residual monomer than the usual MMA/PMMA resins.

Acrylic Resins↗

Phase II study of carboplatin in non-small cell lung cancer.

Forty four patients with advanced non-small cell lung cancer (NSCLC) were treated with carboplatin (CBDCA; cis-diammine-1, 1-cyclobutane dicarboxylate platinum II) at a dose of 400-450 mg/m2 intravenously every four weeks in a phase II study. Forty three patients were evaluated for response and toxicity. Two patients achieved responses resulting in an overall response rate of 4.7% (95% confidence limits: 0.6-15.8%); one of these had not been treated previously and the other had been treated previously with vinblastine. The durations of their responses were 5 and 7 months, respectively. The response rate in 28 previously untreated patients was 3.6% (1/28; 95% confidence limits: 0.1-18.3%). Myelosuppression was the most commonly found toxicity, and thrombocytopenia especially was dose-limiting. Thrombocytopenia (less than 75,000/mm3) was observed in 12 patients (28%). Leukopenia (less than 3,000/mm3) was observed in 14 patients (33%). No serious infection or bleeding occurred, however. Treatment with 400-450 mg CBDCA/m2 was well tolerated in the good risk patients in this study. Mild to moderate emesis was observed in 28 patients (65%). No renal toxicity, neurotoxicity or ototoxicity was seen. It was demonstrated that CBDCA had little efficacy in NSCLC at the dose and schedule given in the present study.

Adult↗

[Assay of erythropoietin in plasma by enzyme-linked immunosorbent assay].

Using an enzyme linked immunosolvent assay kit supplied by Toyobo Co., erythropoietin (EPO) concentration in plasma was measured. Normal 100 samples showed a logarithmic distribution in EPO concentrations and normal range was between 5.4-32.5 mU/ml (mean +/- 2 SD). Coefficient variations (C.V.) of 3 samples continuously assayed were 3.8%, 6.5%, and 9.1% and C.V. of 3 samples assayed day by day were 3.6%, 7.2%, and 11.5%. Dilution test revealed that 3 samples diluted to 75%, 50%, and 25% were on each line which go through zero point. After the addition of 5.0, 15.0, and 35.0 mU/ml of EPO to the 3 samples, assay of EPO revealed 95.5 +/- 6.3% (mean +/- SD) of recovery. Assay of EPO in plasma from 19 patients with aplastic anemia revealed that all samples were higher than normal range and that 4 samples from the patients with severe aplastic anemia (less than 8.0 g/dl of hemoglobin) showed higher than 3,000 mU/ml. Furthermore, 67% (14/21) of samples from patients with leukemia showed higher than normal range in EPO concentration. EPO concentration in plasma from 17 patients with chronic renal failure were within normal range although the patients showed anemia.

Adult↗

[Anesthesia for aorto-coronary bypass graft surgery in children with Kawasaki disease].

We investigated anesthetic management of aorto-coronary bypass graft surgery (CABG) in the children who have coronary disease due to acute febrile mucocutaneous lymph node syndrome (Kawasaki disease). A retrospective observation was made on anesthetic management of 17 patients with Kawasaki disease. They were 13 boys and 4 girls and their ages ranged from 5 to 13 years. They underwent CABG during the past 10 years (1976-1986) in Tokyo Women's Medical College Daini Hospital. Induction of anesthesia was carried out with halothane-nitrous oxide-oxygen (GOF) in 16 patients and morphine-nitrous oxide-oxygen (GOM) in one patient. Anesthesia was maintained with GOF in 11 patients, and in 6 patients with GOF and narcotics. High-dose fentanyl was not used for anesthetic induction in children with Kawasaki disease. Pulse rate increased significantly after endotracheal intubation. Blood pressure increased after endotracheal intubation in 5 patients and after sternotomy in one patient. Hypotension developed in 2 patients. Coronary spasm did not occur during the all procedures. Control of blood pressure during CABG in children was easier than in adult patients. But the control of pulse rate offers a problem in anesthetic management of the children with Kawasaki disease.

Adolescent↗

Control of cisplatin-induced delayed emesis with metoclopramide and dexamethasone: a randomized controlled trial.

Forty-two patients with advanced lung cancer undergoing chemotherapy containing cisplatin (80 mg/m2) were submitted to a randomized controlled trial to evaluate the effect of the combination of metoclopramide and dexamethasone for the treatment of delayed cisplatin-induced emesis occurring more than 24 hours after cisplatin administration. All patients received intravenously (i.v.) high-dose metoclopramide and dexamethasone on the day of cisplatin treatment. Excellent emetic control (no emesis during the 24 hours following cisplatin administration) was achieved in 30 out of 41 patients (73%) with this combination. Patients treated i.v. with metoclopramide and dexamethasone on days 2-7 experienced less delayed emesis, nausea and anorexia compared to those treated with a placebo (delayed emesis, 25 vs 50%, respectively, P = 0.105; more than four days of nausea, 10 vs 35%, respectively, P = 0.059; less than three days of anorexia, 80 vs 50%, respectively, P = 0.048). Although the results of the study showed no statistically significant advantage with the combination of i.v. metoclopramide and dexamethasone for patients treated with cisplatin, in view of the short duration of anorexia and the marginal reduction in nausea. Female patients tended to have more emetic episodes and extrapyramidal side effects (except akathisia) than male patients, but the differences were not statistically significant except for acute emesis (P less than 0.005).

Adult↗

Glycolipid-directed FH6 monoclonal antibody recognizes high molecular weight glycoprotein antigen carrying sialyl Lex-i determinant in the culture supernatant of PC-9 cells.

The properties of the antigen recognized by monoclonal antibody FH6 have been analyzed. FH6 was originally generated against a glycolipid, i.e. a difucoganglioside isolated from human colonic adenocarcinoma, and specifically reacts with sialyl Lex-i determinant. Several culture supernatants of human carcinoma cell line cells were found to have high levels of FH6-reactive antigen, and PC-9, a human lung carcinoma cell line was used for the analysis. A solid-phase sandwich radioimmunoassay was performed to detect the antigen. The antigenic activity was extractable in 0.6 M PCA or 7% TCA, and was sensitive to mild alkaline treatment and to Pronase digestion. Most of the antigen was eluted in the void volume of a Sepharose CL-2B column, which indicates that its molecular weight is greater than several million. It was eluted from a DEAE-cellulose column at a NaCl concentration in the range of 0.2-0.25 M. The immunoaffinity-purified antigen has a high carbohydrate content of more than 80%. These data indicate that the antigen recognized by FH6 in the culture supernatant of PC-9 is not a glycolipid, but a high molecular weight glycoprotein which could be referred to as a mucin, or a proteoglycan, which contains keratan-sulfate like glycosaminoglycan chains, as judged from the results of the glycosidase treatments.

Antibodies, Monoclonal↗

Comparative study of the antitumor effect of two types of murine recombinant interferons, (beta) and (gamma), against B16-F10 melanoma.

A comparative study of the antitumor effect of murine recombinant interferon(beta) less than Mu-rIFN(beta) greater than and murine recombinant interferon(gamma) less than Mu-rIFN(gamma) greater on B16-F10 melanoma was conducted. Administration of Mu-rIFN(gamma) i.p. into C57BL/6 mice on days 1 to 7 produced a higher suppressive effect than Mu-rIFN(beta) both on the growth of s.c. implanted tumor and on the formation of artificial pulmonary metastasis. Pharmacokinetic study of Mu-rIFN(gamma) demonstrated that high plasma levels were retained for a long time. In clonogenic assay, Mu-rIFN(gamma) at 1000 units/ml showed about 80% inhibition of colonies of B16-F10 melanoma. However, Mu-rIFN(beta) hardly inhibited the colonies, even at 1000 units/ml. Augmentation of natural killer (NK) cytotoxicity was much greater with Mu-rIFN(beta) than Mu-rIFN(gamma), whereas Mu-rIFN(gamma) enhanced the cytotoxicity of peritoneal macrophages more strongly than Mu-rIFN(beta). Injection of Mu-rIFN(gamma) i.p. 1 day before tumor challenge also inhibited the formation of pulmonary metastasis of B16-F10 melanoma. However, pretreatment of mice with carrageenan significantly suppressed the inhibitory effect of Mu-rIFN(gamma). From these results, it is suggested that the inhibitory effect of Mu-rIFN(gamma) on the tumor growth and metastases of B16-F10 melanoma is mediated partly by direct antitumor effect and partly by the activation of macrophages, and that the augmentation of NK activity contributes mainly to the antitumor effect of Mu-rIFN(beta).

Animals↗

In vitro antitumor activity of mitomycin C derivative (RM-49) and new anticancer antibiotics (FK973) against lung cancer cell lines determined by tetrazolium dye (MTT) assay.

Seven small- (SCLC) and four non-small-cell (NSCLC) lung cancer cell lines were used to examine the in vitro cytotoxicity of cytotoxic drugs such as (1aS-(1a alpha,8 beta,8a alpha,8b alpha]-8-[aminocarbonyl)oxy)methyl)-4,8a- dimethoxy-1,1a,2,8,8a,8b-hexahydro-7-hydroxy-5-methyl-6- nitrosoazirino(2',3':3,4)-pyrrolo-(1,2-a)indole (RM-49) and 11-acetyl-8-carboxymethyl-4-formyl-14oxa-1,11-diaze- tetracyclo(7.4.1.0(2,7),0(10,12]tetradeca-2-4-6-trien-6,9-++ +diyl-diacetate (FK973). In vitro cytotoxicities of RM-49 and FK973 were compared with those of mitomycin C (MMC), cisplatin (CDDP), carboplatin (CBDCA), etoposide (VP16), adriamycin (ADM) and vindesin (VDS). Drug sensitivity was determined using a tetrazolium (MTT)-based assay. Average IC50 values of these two drugs were not statistically different compared with that of MMC, although FK973 showed strong antitumor activity against SCLC cell lines such as LT3, N857, and H69 at the same concentration. The predicted peak plasma concentration (predicted PPC) calculated by the formula proposed by Scheithauer, log (predicted PPC) = -0.788 + (0.755 x log(LD50], and relative antitumor activity, RAA (PPC/IC50), of RM-49 were higher than those of other drugs such as MMC, CDDP, CBDCA, and ADM against SCLC cell lines (P less than or equal to 0.05), and those of FK973 were also higher than those of other drugs such as MMC, CDDP, CBDCA, and ADM against SCLC cell lines (P less than or equal to 0.05). Based on these promising in vitro studies, the clinical trials of RM-49 and FK973 were warranted.

Antibiotics, Antineoplastic↗