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Biomedical subjects

K Yano

Publications and source records attributed to K Yano.

At least 883 records · Page 49Linked to original sources

Prediction of substances of weak toxicity from chemical structures. An epidemiological approach.

A global structure set of acute toxicity (LD50, mouse, i.v.) was constructed from databases. The common structural features of low toxicity substances were obtained from 1495 structure-toxicity data by applying the substructural balance method (SBM). This set contained 111 low toxicity (> ca. 1000 mg/kg) and 817 high toxicity substances (< ca. 30 mg/kg). The result was expressed by a control chart which is made to control the structural causes to obtain the desired effect (low toxicity). Within the control limits, 100% of low toxic and 20% of high toxic substances were found. The control chart was tested with another set of 81 structures of low toxicity selected among 718 structures retrieved from RTECS. Seventy-eight structures were found within the control limits and the predictability was 96.3% (78/81). SBM employs a new paradigm of descriptors, the ratios of numbers of substructures, which were selected through a descriptor-screening process. The results confirm that the new paradigm is applicable for structure-based toxicity prediction. This "epidemiological" approach suggests key structural criteria where no reliable mechanism of toxicity is available and serves to reduce the search space of organic structures. A theory supporting SBM was discussed.

Animals↗

How prevalence of hypertension varies as diagnostic criteria change.

In a effort to determine what impact diagnostic criteria might have in defining the magnitude of the "hypertensive" population, various definitions of high blood pressure were applied to the same population. At the initial encounter, 23.3 per cent of the subjects had blood pressures greater than or equal to 160/95 mm Hg, but less than half of these sustained that level on two subsequent occasions over the next three weeks. When an initial diastolic blood pressure of greater than or equal to 105 mm Hg was used to define hypertension, prevalence fell by more than two thirds (23.3 to 7.2 per cent). These results clearly demonstrate that even a very simple modification of diagnostic criteria can markedly alter the prevalence of "hypertension."

Adolescent↗

Usefulness of multiangle MRI in aortic arch dissection.

A multiangle scan technique was used in combination with usual spin echo and cine MR techniques to study a patient with aortic arch dissection. The intimal flap was seen with each technique and the jet into the entry site was observed with cine MR technique. Exact short axis images of aortic arch were obtained only with multiangle scan. Retrograde dissection and involvement of left subclavian artery were detected clearly on the short axis images.

Adult↗

Effect of verapamil directly administered into A-V node artery on A-V junctional automaticity and A-V conduction in dogs.

We investigated the direct effects verapamil, which was infused into the A-V node artery at two doses of 0.01 and 0.1 microgram/kg/min on the A-V conduction and the A-V junctional automaticity in the dog with experimentally induced A-V junctional rhythm. Verapamil significantly prolonged the A-H interval, but not the H-V interval, in the His bundle electrogram during atrial pacing at a rate of 100 beats/min. Effective and functional refractory periods of the A-V node also were prolonged significantly by verapamil. On the other hand, verapamil showed less propensity to decrease the spontaneous A-V junctional rate and to prolong the A-V junctional recovery time after atrial overdrive at a rate of 100 beats/min for 60 s. These results indicate that suppressive effects of verapamil on the A-V junctional automaticity are much weaker when compared with that on the A-V conduction.

Animals↗

Biological and dietary correlates of plasma lipids and lipoproteins among elderly Japanese men in Hawaii.

The relationships of plasma total cholesterol (total-C), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and triglyceride (TG) to a variety of personal attributes were investigated cross-sectionally in a random sample of approximately 1360 elderly Japanese men, aged 60-81 years, in Hawaii. In multivariate analyses, total-C was positively related to hematocrit (p less than 0.01); LDL-C was positively related to hematocrit (p less than 0.0001), and inversely related to alcohol consumption (p less than 0.0001); HDL-C was positively related to alcohol consumption (p less than 0.0001) and physical activity index (p less than 0.05), and inversely related to body mass index (p less than 0.0001) and antihypertensive medication (p less than 0.05); and LogTG was positively related to body mass index (p less than 0.0001), alcohol consumption (p less than 0.0001), antihypertensive medication (p less than 0.0001), and diastolic blood pressure (p less than 0.01), and inversely related to physical activity index (p less than 0.01). Body mass index and alcohol consumption were the most important correlates of plasma lipids and lipoproteins. Several dietary variables were significantly related to each lipid or lipoprotein fraction after controlling for nondietary variables, but their independent contributions were generally quite modest.

Aged↗

Biological and social correlates of blood pressure among Japanese men in Hawaii.

A cohort of more than 8,000 Japanese men living in Hawaii was studied for factors associated with blood pressure levels, with an emphasis on biological and sociocultural variables. Bivariate and multivariate analyses of more than 50 variables indicated that obesity, age, hematocrit, heart rate, forced vital capacity, serum triglyceride, serum uric acid, cigarette consumption, and family history of hypertension were independently associated with both cross-sectional levels and longitudinal changes in blood pressure. Serum glucose and alcohol consumption were associated with cross-sectional levels only. There was little evidence of association for specific dietary items, type of diet, diet changes, or use of salt. Furthermore, there was no support for the psychosocial hypotheses of elevated blood pressure from the stress of migration, acculturation, or status incongruity.

Acculturation↗

Incidence of transient cerebral ischemic attack in Hawaii Japanese men. The Honolulu Heart Study.

At the Honolulu Heart Study 7,895 men of Japanese ancestry, 45--68 year-old, who were free of previous stroke at the baseline examination (1965--1968) were followed 6 years for the development of transient cerebral ischemic attacks (TIA). Fifty-one men developed probable or possible episodes. In multivariate analysis TIA was associated with preceding hypertension, cigarette smoking and coronary heart disease. It was less common in men who were facile with written Japanese language, in those who consumed alcohol, and in those who were physically active. During an average follow up of 3 years after these TIA events 2 strokes occurred, vs 0.7 expected. This prognosis is more favorable than that reported by other studies.

Aged↗

Dietary and other risk factors for stroke in Hawaiian Japanese men.

As part of an on-going longitudinal study, 7895 men of Japanese ancestry living on the island of Oahu, aged 45-68 and free of evidence of prior stroke at entry examination, have been followed by re-examinations and surveillance. During ten years of follow-up 154 men developed thromboembolic stroke, 65 developed intracranial hemorrhage, and 19 developed stroke of unknown type. There were 79 deaths attributed to stroke. The independent risk factors for thrombo-embolic stroke were elevated blood pressure, glucose intolerance, age, electrocardiographic evidence of left ventricular hypertrophy or strain, cigarette smoking and proteinuria. Attributes associated with increased risk of intracranial hemorrhage were age, elevated blood pressure, cigarette smoking, serum uric acid and, inversely, serum cholesterol level. Electrocardiographic evidence of left ventricular hypertrophy or strain significantly increased the risk of cerebral hemorrhage, but was not associated with subarachnoid hemorrhage. In univariate analysis, there was an inverse relation between dietary fat intake and thrombo-embolic and total stroke incidence. An inverse relation was also shown between protein intake and total stroke incidence. These dietary relations became statistically not significant in multivariate analysis. No relation was found between salt intake and the incidence of stroke.

Age Factors↗

Evaluations of p53 immunoreactivity, nucleolar organizer regions, and proliferating cell nuclear antigen in non-small cell lung carcinoma.

We examined p53 protein expression, proliferating cell nuclear antigen (PCNA), and argyrophilic nuclear organizer regions (AgNOR), in 102 patients with surgically-treated non-small cell lung cancer (NSCLC). p53 positive cases with DO-1 were defined when more than 10% of the tumor cell nuclei were stained. Mean AgNOR count and PCNA LI were 2.80 and 40.7 and there were no significant differences of AgNOR count and PCNA LI between p53 positive and negative cases. We assessed the relationship between the p53 immunoreactivity and various clinical or pathological parameters. p53 positive rate of stage III disease (46.3%) was significantly higher than that of stage II disease (28.6%). The p53 positive rate of squamous cell carcinoma (42.1%) tended to be higher than that of adenocarcinoma (33.9%). In the survival curves of patients with NSCLC according to the p53 immunoreactivity, there was no significant difference between p53 positive and negative cases. Eight potential prognostic parameters (p53 immunoreactivity, AgNOR count, PCNA LI, sex, age, year of operation, histology, and stage) were also estimated, using univariate and multivariate analysis. In univariate analysis, PCNA LI and AgNOR count, and stage were significantly related to shortened survival. In multivariate analysis, PCNA LI, Age, and stage were independently associated with shortened survival of NSCLC patients. PCNA staining may be more useful than p53 and AgNOR staining in assessing the aggressiveness of surgically-treated NSCLC, although the most useful clinical prognostic parameter should be achieved by the combined analysis of several prognostic indicators.

Adult↗

Inferior vena cava injury after catheterization: report of a case.

We present a patient with retroperitoneal hematoma suspicious of inferior vena cava injury after catheterization for hemodialysis. Emergency computed tomography revealed extensive retroperitoneal hematoma and inferior vena cava angiography revealed extravasation. Emergent laparotomy was performed and repaired the perforation of inferior vena cava. His postoperative courses were uneventful and he remains well after the operation.

Adult↗

Diet, blood pressure, and multicollinearity.

Recent reports of an inverse association between dietary calcium intake and hypertension stimulated this analysis of the relationship of blood pressure to more than 20 dietary factors among a group of 8000 Japanese men in Hawaii. Reported intakes of potassium, calcium, protein, and milk were all inversely associated with blood pressure levels when examined one at a time while controlling for other risk factors. Alcohol intake was directly associated with blood pressure, and was treated as a confounding variable in the analysis. The association of potassium intake with blood pressure was relatively stronger than the associations for other nutrients, but the intake of potassium was so highly correlated with intakes of calcium, milk, and protein that it was not statistically possible to identify the independent association of potassium and blood pressure. Calcium intake was strongly correlated with milk and potassium intakes, and only calcium from dairy sources was associated with blood pressure. These data thus indicate that several dietary factors are inversely related to blood pressure levels independently of other risk factors such as age, body mass, and alcohol intake. The high degree of intercorrelation (multicollinearity) among these dietary factors, however, indicates that the independent role of any specific nutrient cannot be conclusively separated from the possible effects of other nutrients in this type of study.

Adult↗

Advantage of combined treatment of CPT-11 and 5-fluorouracil.

The combined chemotherapy of SN-38, active metabolite of CPT-11, and 5-FU in vitro was examined using human cell lines and primarily cultured cells obtained at surgery. The percent survival of the Suit-2 cell line treated with a single modality of SN-38 at the concentration of 0.95-61 nM was 70% to 86%, while, when treated with SN-38 and 5-FU, the percent survival of these cells decreased at even 1 microM of 5-FU. The enhanced ratios (percent survival at 0 nM SN-38/percent survival at 61 nM SN-38) at 1 microM and 4 microM of 5-FU were 1.56 and 1.33, respectively. The enhanced ratio became lower when the concentration of 5-FU was increased. When topoisomerase I activity in Suit-2 cells incubated with 5-FU was examined, 5-FU at a high dose (> or = 4 microM) in the medium caused a strong inhibition of the relaxation of Suit-2 DNA by topoisomerase I, but 5-FU at low dose (< or = 2 microM) barely inhibited topoisomerase I activity. These results indicated that topoisomerase I synthesis in the Suit-2 cell line might be suppressed by a high dose of 5-FU in the medium but not by a clinically achievable level of 5-FU. The cancer cells obtained from clinical cancer tissues were treated with these drugs at a clinically achievable dose in the medium. Judging from the results of a sensitivity test, in 7 out of 10 cases, the percent survivals under the combined treatment were lower than those estimated under the single modality treatment. Therefore, by the addition of 5-FU, the antitumor effect of CPT-11 would seem to be further enhanced.

Aged↗

Cytotoxicity of paclitaxel in comparison with other anticancer agents against neoplastic cells obtained from clinical gastrointestinal carcinoma tissue.

We examined the activity of paclitaxel against primary cultured cells from gastrointestinal neoplasmas, such as stomach, colon, hepatocellular and pancreatic cancer, and estimated the clinical use of paclitaxel. Antitumor activity, expressed as reduction in cell survival rates mediated by anticancer agents, was measured using [3H]thymidine incorporation into primary cell cultured. Percent survival rates for stomach, colon and hepatocellular cancer cells in the presence of 0.5 microM paclitaxel were 68.1%, 58.4% and 65.1%, respectively. Proportions of gastrointestinal cancer cases having percent survival rates of < or = 70% for paclitaxel, CDDP, MMC and ADM were 48.3%, 17.4%, 28.0% and 21.1%, respectively. The rate for paclitaxel was the highest of all. The proportion of stomach, colon, liver and pancreatic cancer cases having a percent survival rate of < or = 70% in the percentage of paclitaxel were 55.6%, 66.7%, 50.0% and 20.0%, respectively. In particular, the proportions of stomach and colonal cases having survival rates of < or = 70% for paclitaxel in spite of having survival rates of > 70% for other anticancer drugs were 75% (3/4) and 50% (2/4), respectively. From these results, it is probable that paclitaxel will demonstrate clinical activity in gastrointestinal tract cancers, such as stomach, colon, hepatocellular and pancreatic cancer.

3T3 Cells↗

Usefulness of lymphocyte subset change as an indicator for predicting survival time and effectiveness of treatment with the immunopotentiator lentinan.

The usefulness of lymphocyte subset change as an indicator for predicting survival time and the effectiveness of combined treatment with an immunopotentiator, lentinan, and carboplatin (CBDCA) were investigated. Of 13 patients with advanced unresectable cancer entered in this study, 9 were administered 2 mg/body lentinan and 450 mg/m2 CBDCA, and 4 were administered a single modality of CBDCA. The mean survival time of all 13 cases was 9.89 months. Lymphocyte subsets of CD11(-)CD8(+), CD11(+)CD8(+), CD57(-)CD16(+) and CD57(+)CD16(+,-) were measured by two-color flow cytometry. In five cases surviving longer than 9.89 months, CD11(-)CD8(+)/CD11(+)CD8(+) on post-treatment showed an increase two-fold higher than on pre-treatment, but in all cases surviving less than 9.89 months the rate on post-treatment did not increase two fold higher than on pre-treatment. The mean (1.78) of (post-treatment/pre-treatment) ratios of CD57(-)CD16(+)/CD57(+) in long survival cases was significantly higher (p < 0.01) than that (0.46) in short survival cases. Moreover, the mean of (post-treatment/pre-treatment) ratios of CD11(-)CD8(+)/CD11(+)CD8(+) and CD57(-) CD16(+)/CD57(+) showed a good correlation with survival time. These results indicate that changes of lymphocyte subsets of killer T cell/suppressor T cell and natural killer cell on posttreatment compared to pre-treatment are clinically useful indicators for predicting and monitoring the effectiveness of combined treatment with lentinan and CBDCA.

Adjuvants, Immunologic↗

Restorative effect of romurtide for thrombocytopenia associated with intensive anticancer drug treatment and/or irradiation in patients with gastrointestinal cancer.

In 55 gastrointestinal cancer patients the mean change ratios for platelets were, respectively, 1.22 +/- 0.75 and 0.67 +/- 0.45, in the romurtide administration (30 cases) and non-administration (25 cases) groups, [statistically significant difference (p < 0.005)]. The number of cases in each group with a decrease in platelet count was 13 (43%) and 20 (80%) with and without romurtide, respectively. The difference was statistically significant, (p < 0.01). In addition, the number of cases with a marked decrease ( < 6 x 10(4)/mm3) in platelet count was 2 (7%) and 7 (28%) with and without romurtide, respectively, reaching statistical significance (p < 0.05). For patients treated with a bolus administration of 450 mg/m2 carboplatin (27 cases), the mean change ratios for leukocytes and platelets in the romurtide administration group (13 cases) were 1.10 +/- 0.52 and 1.23 +/- 0.59, respectively. Meanwhile, in the romurtide non-administration group the mean change ratios for leukocytes and platelets were, respectively, 0.74 +/- 0.27 and 0.74 +/- 0.42, a statistically significant reduction (p < 0.05) compared with the romurtide administration group. The number of cases with an increase in the number of lymphocytes after i.v. administration was significantly more than that observed after s.c. administration (p < 0.01). These results indicate that romurtide has a restorative effect on thrombocytopenia similar to that displayed for leukocytopenia when given as concomitant therapy with anticancer drugs and/or irradiation in patients undergoing intensive treatment for gastrointestinal cancer.

Acetylmuramyl-Alanyl-Isoglutamine↗

Cytotoxicity of CPT-11 against a Taxol-resistant cell line.

We examined the cytotoxic changes of CPT-11 (SN-38) against a Suit-2 cell line after a long-term culture (more than 4 passages) with Taxol (Taxol-resistant cells). The percentage survival of the Suit-2 cells with and without resistance to 0.8 microM Taxol were 20% and 96%, respectively, after treatment with 0.1 microM Taxol for 24 hours. When Suit-2 cells resistant to 0.6, 0.8, and 1.0 yM of Taxol were treated with 15 pM SN-38 for 2 hours, the percentages of survival were 59%, 72%, and 62%, respectively, and no statistical difference was observed with the percentage survival (77%) of Suit-2 cells cultured without Taxol (parent cells). Moreover, Taxol-resistant cells did not cause an inhibition of the relaxation of DNA by topoisomerase I. Therefore, the cytotoxic level of SN-38 between Suit-2 cells with and without resistance to Taxol was almost equal. The percentage survival of SN-38-resistant Suit-2 cells decreased markedly with the increase in the dose of Taxol, and no statistical difference was observed in comparison to that of the parent Suit-2 cells. These results thus indicated that the cross-resistance to SN-38 and Taxol would therefore be very difficult to induce in Suit-2 cells.

Antineoplastic Agents, Phytogenic↗