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Biomedical subjects

K Aoki

Publications and source records attributed to K Aoki.

At least 613 records · Page 34Linked to original sources

Sociomedical factors affecting participation in screening program on cerebro- and cardio- vascular disease.

In 1984 the Public Health Bureau of Nagoya City began a new health check-up program to encourage citizens aged 40 years to have a medical examination. The rate of participation was 46.6% greater than that of the previous program; however, at about 16%, it was still low. From the survey in Moriyama Ward following results were suggested. Housewives and female part-time workers who had not had a health examination during the previous year showed participation rates of 32.7% and 42.4%, respectively. It would seem that the low rate of participation in the health examination program conducted in the metropolitan area by the municipal Public Health Bureau is due to the existence of many medical care facilities, and the fact that 64.6% of men and 52.6% of women had undergone a medical examination in the year preceding the program. Total screening rates became 69.7% in males and 66.0% in females. Participation rates of 32.7% and 42.4% were achieved by unemployed women and by women with part-time employment, respectively, who had no experience of screening in the previous year. Total screening rates were 63.7% for the unemployed women and 82.1% for the part-time women.

Cardiovascular Diseases↗

Tropomyosin-caldesmon/actomyosin systems in platelets and arterial smooth muscle: results from exchange experiments.

Tropomyosin and caldesomon reciprocally control the actomyosin system in smooth muscle and some non-muscle cells. To compare this mechanism between arterial smooth muscle and platelets, we carried out extensive exchange experiments. Actin, myosin, tropomyosin from arterial smooth muscle cells and platelets were recombined and the effects of two species of caldesmon ('caldesmon77' and 'caldesmon140') on the ATPase activities of both systems were examined and analyzed by the method of analysis of variance. (a) The actomyosin system itself is different between artery and platelets, the difference being determined by myosin (P less than 0.05) and not by actin. (b) Platelet tropomyosin differentiates platelet actin from arterial actin (P less than 0.01), while arterial tropomyosin does not. Neither does tropomyosin differentiate myosin. (c) The effect of caldesmon77 differentiates the origins of myosin (P less than 0.01), actin (P less than 0.05) and tropomyosin (P less than 0.05). The effect of caldesmon140 differentiates the origin of myosin (P less than 0.05) and the actin-myosin 'interaction' (combination) (P less than 0.01), but not the origin of tropomyosin (P greater than 0.1). (1) It is concluded that actomyosin/tropomyosin-caldesmon system is distinguishable between platelets and artery. (2) It is suggested that caldesmon is an actomyosin inhibitor which may interact with myosin, in addition to actin and tropomyosin.

Actins↗

Efficacy of two-route chemotherapy using cis-diamminedichloroplatinum(II) and its antidote, sodium thiosulfate, in combination with angiotensin II for rat liver tumor.

To improve the therapeutic effects of conventional TRC using i.a. CDDP plus simultaneous i.v. STS in a rat liver tumor, we made use of the AT-II-induced hypertension method, in combination with TRC. The decrease in tumor area (-15%), measured 8 days after the TRC using CDDP 12 mg/kg i.a. plus i.v. post-administration (5 min later) of STS 1,264 mg/kg, was much greater than that (+ 13%) seen in the conventional TRC, but BUN level was elevated (44.9 mg/dl). AT-II (15 micrograms/kg) administered i.a. simultaneously with CDDP normalized the BUN level (20.3 mg/dl) and further decreased (-15% to -31%) the tumor area (modified TRC). The modified TRC also exhibited a higher anti-tumor effect than did CDDP 3 mg/kg with AT-II i.a. (5%) at a similar BUN level (22.2 mg/dl). Loss of body weight, decrease in WBC count and changes in serum transaminases of rats treated with the modified TRC were tolerable. The improved therapeutic effect of the modified TRC was explained as follows: during AT-II-induced hypertension, (I) CDDP delivery to the tumor was increased by 150% and (2) CDDP delivery to the kidney was decreased by 35%. The latter effect of AT-II made feasible the post-administration of STS to CDDP.

Angiotensin II↗

Serum concentration of beta-carotene and intake frequency of green-yellow vegetables among healthy inhabitants of Japan.

Serum levels of beta-carotene were measured among healthy inhabitants (671 males and 948 females) of 2 towns in Japan to determine the association between the levels and intake frequency of green-yellow vegetables. Those individuals who consumed green-yellow vegetables frequently showed higher levels of serum beta-carotene than those who ate them less often. The influences of alcohol drinking, smoking, obesity and age on serum beta-carotene levels were similarly observed for the 2 areas. The factors listed above were used for adjustment, giving a significant association between intake frequency of green-yellow vegetables and serum beta-carotene level. The proportion of the subjects who rarely consumed green-yellow vegetables was larger among smokers than among non-smokers. There was a large difference in serum beta-carotene levels between the 2 towns, which could not be explained by alcohol drinking and smoking. Women showed statistically significantly higher serum beta-carotene levels than men.

Adult↗

[Hazard ratio estimated from a proportional hazard model including two strongly correlated prognostic factors].

Estimates of hazard ratio from hypothetical survival data were examined, under the condition that the survival is affected by two prognostic factors X1 and X2 with two discrete values (0, 1) which are strongly correlated. Survival curves from the data were assumed to fit an exponential function. As an example, following numbers of subjects were used; 100 cases with X1 = 0 and X2 = 0, 10 cases with X1 = 1 and X2 = 0, 10 cases with X1 = 0 and X2 = 1, and 100 cases with X1 = 1 and X2 = 1. When the hazard ratio of X1 = 1 or X2 = 1 to X1 = 0 and X2 = 0 was 3, univariate analysis gave reasonable estimates around 3. Under the same condition, estimates of hazard ratio from multivariate analysis including the two variables X1 and X2 varied widely, depending on the survivals of 20 cases with X1 = 1 X2 = 0 or X1 = 0 X2 = 1. Probability of having extremely deviated estimates was demonstrated. The result illustrated successfully some points we should take into account when proportional hazard models including strongly correlated variables are applied.

Actuarial Analysis↗

[Explanatory essay for researchers who plan to analyse their clinical data using Cox's proportional hazard model].

Proportional hazard model was proposed by Cox as a multivariate model suitable for evaluation of prognostic factors and/or therapeutic effects. This paper aims at explaining fundamental concepts of the model for clinical researchers, as clear as possible. The relationship between hazard ratio and survival curves is demonstrated using an example of survivals calculated from an exponential function. Usage of computer programme SAS is described in brief for the readers who plan to analyse their own clinical data by this model.

Analysis of Variance↗

Characterization of N-linked oligosaccharides of human urinary kallikrein molecules.

The micro-heterogeneity due to varied N-linked oligosaccharides of both active- and pro-types of human urinary kallikrein (HUK) in normal subjects and some patients were investigated by the methods of serial lectin affinity chromatography and crossed affino-immunoelectrophoresis. In the case of both types of normal HUK, the species carrying tri- and/or tetra-antennary oligosaccharide(s), corefucosylated bi-antennary oligosaccharide(s), and bi-antennary oligosaccharides containing outer galactose residues and an N-acetylglucosamine residue linked beta 1,4 to a beta-linked mannose residue (bisecting N-acetylglucosamine residue) amounted to approximately 36, 33 and 17% of the total of each type of HUK, respectively. On the other hand, in some diseases, i.e. essential hypertension, Bartter's syndrome and acute pancreatitis, alterations of the chromatographic and electrophoretic patters were observed and are assumed to correspond to glycosylation changes in each HUK molecule.

Chromatography, Affinity↗

Characterization of human pancreatic kallikrein.

Human pancreatic kallikrein (H.Panc.K.) was purified from human pancreas by ion exchange chromatography on DEAE-cellulose, affinity chromatographies on p-aminobenzamidine Sepharose 6B and aprotinin aminocellulofine, followed by gel filtration on Sephacryl S-200. The final preparation had a specific activity of 9.2 AU/A280 (AU; amidase unit for H-Pro-Phe-Arg-MCA) and its N-terminal sequence coincided with the reported sequence for H.Panc.K.. In HPLC (gel filtration), one symmetrical peak corresponding to a molecular weight of 48,000 was obtained. In SDS-PAGE without 2-mercaptoethanol (2-ME), one band corresponding to a molecular weight of 52,000 was obtained, but with 2-ME, 2 bands, 52,000 and 30,000, were obtained. Km value for MCA was 4.9 x 10(-2) mM. Proteinase inhibitor specificities of H.Panc.K. were the same as those of human urinary kallikrein (HUK) and hog pancreatic kallikrein (hog Panc.K.), while anti-HUK antibody inhibited the activities of H.Panc.K. and HUK, but not that of hog Panc.K.. From the analysis of affinity for concanavalin A (Con A) and erythroagglutinating phytohemagglutinin (E-PHA), the carbohydrate parts of H.Panc.K. are relatively rich in biantennary complex type sugar chains with bisecting GlcNAc compared with those of human salivary kallikrein (H.Saliv.K.) and HUK.

Amino Acid Sequence↗

Enzyme-linked immunosorbent assays for human tissue kallikrein and analysis of immunoreactive kallikrein in the plasma by them.

In order to study immunoreactive tissue kallikrein (TK) in human plasma, three kinds of enzyme-linked immunosorbent assay (ELISA) systems for human urinary kallikrein (HUK) were developed. All three types of TK in the plasma, i.e., active kallikrein, prokallikrein and kallikrein-alpha 1 antitrypsin (alpha 1 AT) complex, could be measured by the competitive ELISA (C-ELISA). However, the sandwich ELISA (S-ELISA) showed more strict specificity. Namely, both active and prokallikreins were able to be measured by the S-ELISA, while kallikrein-alpha 1 AT complex was hardly measurable. Measurement of this kallikrein-alpha 1 AT complex was made possible by using horseradish peroxidase (HRP)-labeled anti-alpha 1 AT IgG instead of HRP-labeled anti-HUK Fab' as the second antibody (HS-ELISA). Using these ELISAs we studied TK in plasma and the following observations were made. 1) The greater part of TK in the plasma was found in a form of a complex with alpha 1 AT. 2) The amount of free type TK was very small and the most part of this type TK in normal plasma was prokallikrein.

Chromatography, Affinity↗

"Two-route chemotherapy" using cis-diamminedichloroplatinum(II) and its antidote, sodium thiosulfate, combined with angiotensin II is effective against peritoneally disseminated cancer in rats.

"Two-route chemotherapy" (TRC) using cis-diamminedichloroplatinum(II) (DDP) and its antidote, sodium thiosulfate (STS), combined with the angiotensin II (AT-II)-induced hypertension method was evaluated for its efficacy against peritoneally disseminated tumors in rats. A bolus i.p. injection of DDP (15 mg/kg) was given 1 min after the initiation of an AT-II (16.5 micrograms/kg) i.v. infusion lasting 11 min. Immediately after the termination of the AT-II infusion, 1,580 mg/kg STS was injected i.v. over a further 5 min. This modified TRC significantly improved the antitumor effect, evaluated by survival (increase in life span, 273%), compared with that achieved with other treatments, as follows: 15 mg/kg DDP i.p. and the concomitant i.v. infusion of 1,580 mg/kg STS (conventional TRC), 153% increase in life span; 5 mg/kg DDP i.p. with or without AT-II i.v. (167% and 107% increases in life span, respectively). As an index of nephrotoxicity, blood urea nitrogen (BUN) levels seen after modified TRC (21.1 mg/dl) were as low as those observed after conventional TRC (19.1 mg/dl), despite the postadministration of STS, and were much lower than those seen after DDP alone or DDP plus AT-II (35.6 and 35.7 mg/dl, respectively). Further evaluation of the effectiveness of modified TRC using various doses of DDP gave similar results. The feasibility of the administration of STS 10 min after DDP treatment was explained by the significant inhibition of DDP delivery to the kidney during the AT-II-induced hypertension. Thus, TRC combined with AT-II has a superior therapeutic effect against peritonitis carcinomatosa induced in rats.

Angiotensin II↗

Conformational change of bovine serum albumin by heat treatment.

The thermal denaturation of bovine serum albumin (BSA) was studied at pH 2.8 and 7.0 in the range of 2-65 degrees C. The relative proportions of alpha-helix, beta-structure, and disordered structure in the protein conformation were determined as a function of temperature, by the curve-fitting method of circular dichroism spectra. With the rise of temperature at pH 7.0, the proportion of alpha-helix decreased above 30 degrees C and those of beta-structure and disordered structure increased in the same temperature range. The structural change was reversible in the temperature range below 45 degrees C. However, the structural change was partially reversible upon cooling to room temperature subsequent to heating at 65 degrees C. On the other hand, the structural change of BSA at pH 2.8 was completely reversible in the temperature range of 2-65 degrees C, probably because the interactions between domains and between subdomains might disappear due to the acid expansion. The secondary structure of disulfide bridges-cleaved BSA remained unchanged during the heat treatment up to 65 degrees C at pH 2.8 and 7.0.

Animals↗

Pleiotropy and preadaptation in the evolution of human language capacity.

The capacity for spoken language in the human is a genetic trait, but the information communicated by this means is to a large extent culturally determined. Using a gene-culture coevolutionary approach, we model the hypothesis that speech evolved as a channel for the communication of adaptive cultural traits from parent to offspring. The motivation for this paper is a condition obtained previously that initial increase of communication would require at least a two-fold advantage for the transmitted trait. Here, we show that under reasonable assumptions the invasion condition becomes less stringent. In Model 1, we assume that two adaptive cultural traits can be transmitted. A gene which permits communication of the second adaptive trait. In Model 2, we assume that a related function such as greater memory capacity is a prerequisite for speech, and that this function confers an advantage independent of its association with speech. In both models we assume haploid sexual genetics and a simple scheme of vertical transmission. The stability properties of all corner and edge equilibria of the models are analyzed. The two models taken together suggest a possible scenario for the initial stages of the evolution of speech.

Adaptation, Biological↗

Age and strain dependence of O6-methylguanine DNA methyltransferase activity in mice.

The activity of the DNA repair protein O6-methylguanine DNA methyltransferase (MT) was compared in liver extracts from female ICR and male C57BL/6 mice at various ages (3-130 weeks old). Similar patterns of overall enzyme activity were observed in both strains with O6-MT activity being relatively low in young mice (3 or 8 weeks old). However, the activity significantly increased after adolescence (middle age), thereafter decreasing with old age (over 100 weeks old) to a level equivalent to that found in young mice. In an additional strain difference study, O6-MT activities in liver extracts from 4 strains of mice were compared at 5 and 30 weeks of age. Although a similar age-associated increase of enzyme activity in adolescence was confirmed in all 4 strains investigated, the closed-colony ICR mice differed from the inbred strains in demonstrating significantly higher levels of O6-MT activity in females than in males. However, the same tendency was also observed in a comparison of the sexes in 30-week-old C3H/HeN, C57BL/6 and BALB/c mice.

Aging↗

Decrease in alpha 1-adrenoceptor reserve in mesenteric arteries isolated from spontaneously hypertensive rats.

The characterization of alpha-adrenoceptor-mediated contractile responses and the effects of the calcium channel blocker nifedipine on these responses were investigated in mesenteric arterial strips from 13-week-old male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Contractile responses to the alpha-adrenoceptor agonists phenylephrine and clonidine were mediated through the activation of alpha 1-adrenoceptors. The dose producing a half-maximum response (ED50) for the agonists was higher in SHR than in WKY. Affinities of alpha 1-adrenoceptors were similar between the two strains. When arterial strips from both strains were treated with the same concentration of phenoxybenzamine, the maximum response to each agonist was weaker in SHR. The alpha 1-adrenoceptor occupancy-response relationship for phenylephrine was hyperbolic and less steep in SHR, while the relationship for clonidine was linear in SHR but not in WKY. Alpha 1-adrenoceptor occupancy at a half-maximum response to each agonist was greater in SHR. Nifedipine inhibited the maximum responses to the agonists more profoundly in SHR than in WKY. This inhibition was greater in the response to clonidine than in the response to phenylephrine in both strains. When the maximum response to phenylephrine was reduced to the same extent in both strains by treatment with different concentrations of phenoxybenzamine, the responses to phenylephrine were more susceptible to inhibition by nifedipine. Under these conditions, the effects of nifedipine were similar between SHR and WKY. These results suggest that alpha 1-adrenoceptor reserve is reduced in SHR mesenteric artery compared with WKY, which may be responsible for the greater inhibition by nifedipine of the alpha 1-adrenoceptor-mediated contractions in SHR.

Adrenergic alpha-Agonists↗

Glycosylated proteins of skin, nail and hair: application as an index for long-term control of diabetes mellitus.

The purpose of the present study was to compare the degrees of nonenzymatically glycosylated proteins in the skin (stratum corneum), the nail, the hair, and hemoglobin obtained simultaneously from the same subject and to evaluate the most useful sample for management of diabetic complications. Fifty-one diabetic patients and 20 control patients were examined, utilizing furosine determination. Furosine value of the skin in diabetics was 2.14 +/- 1.70%, whereas that in controls was 1.65 +/- 0.47%. Furosine value of the nail in diabetics was 6.67 +/- 3.30%, whereas that in controls was 4.16 +/- 1.62%. Furosine value of the hair in diabetics was 1.30 +/- 1.11%, whereas that in controls was 1.29 +/- 1.71%. Close correlations were detected between HbA1 (glycosylated hemoglobin) and furosine of the nail (r = 0.58, p less than 0.001), HbA1 and furosine of the skin (r = 0.48, p less than 0.001), and HbA1 and furosine of the hair (r = 0.43, p less than 0.01); however, poor correlations were found between furosine of the hair and the skin (r = 0.35, p less than 0.05) and furosine of the nail and the hair (r = 0.33, p less than 0.05). Furosine of the nail was significantly correlated with the FBS (fasting blood sugar) of the same time, previous 6, and previous 12 months. Furosine value of the nail, we believe, is the most useful indicator for evaluating long term control of diabetics and may provide useful information for management of diabetic complications.

Adult↗

Life-span studies on spontaneous tumor development in the medaka (Oryzias latipes).

A total of 961 medaka, separated chronologically from the first to the fifth year of life, were examined for spontaneous tumor development. While no liver tumors were found in either male or female medaka under the age of 1 year and the incidence in 2-year-old fish was relatively low (males 1.9% and females 1.7%), they became more common with advancing age. The incidence was higher in females than in males from 3 to 5 years of age, reaching 7.1% in 5-year-old female stock. These liver tumors included a total of 12 adenomas and 9 hepatocellular carcinomas. The hepatocellular carcinomas were histologically well differentiated and were all observed in female medaka. Spontaneous tumors occurring in organs other than the liver were rare and sporadic. Four squamous cell carcinomas, 5 melanomas and 4 lymphosarcomas were observed with no sexual or pronounced age bias being evident. The squamous cell carcinomas developed in the surface epithelium with local invasion into the dermis. Melanomas occurred in the abdominal cavity and demonstrated systemic invasion into various parts of the body. Three out of the 4 lymphosarcomas arose from the inner part of the operculum suggesting that these tumors were of thymic origin. They also showed extensive invasion. The data indicate a particular susceptibility of older female medaka to liver but not other tumor development.

Adenoma↗

Efficacy of two-route chemotherapy using intraperitoneal neocarzinostatin and its antidote, intravenous tiopronin, for peritoneally disseminated tumors in mice.

We assessed the efficacy of "two-route chemotherapy (TRC)" using neocarzinostatin (NCS) given ip and its antidote, N-(2-mercaptopropionyl)-glycine (tiopronin), given iv for peritoneally disseminated tumors in mice. Whether or not the single iv administration of tiopronin (800 mg/kg) at various times after NCS ip would decrease the lethal toxicity induced by NCS ip was given attention. When compared with the LD50 (4.4 mg/kg) of NCS ip alone, simultaneous or postadministration of tiopronin together with NCS ip increased the LD50 of NCS ip by 2.8 to 7.6 fold in a time-dependent manner. Chemotherapy experiments on ip disseminated tumors in mice were done to compare the antitumor effects of the following treatments, at two dose levels (75 and 100% of LD10) of NCS, with or without tiopronin: treatment with NCS ip alone and combined chemotherapy using NCS ip plus tiopronin iv, simultaneously or postadministered. Based on the survival time of the treated mice, the groups given NCS plus tiopronin (postadministration, 15 or 25 min later) showed a significantly superior survival time to that of the group given NCS ip alone. The side effects, evaluated in terms of the changes in body weight and number of WBC of the mice, were not significantly different among the groups treated with 100% of LD10 of NCS.

Animals↗

Acute changes in the properties of baroreflexes in man after beta-blockade.

1. To clarify whether acute changes in the properties of baroreflexes can occur in man, we evaluated the time course of baroreflex control of heart rate and cardiopulmonary baroreflex control of forearm vascular resistance (FVR) over 240 min after intravenous administration of propranolol (0.2 mg/kg) in 13 healthy young men. 2. Systolic and diastolic blood pressure remained unchanged after propranolol. Propranolol significantly decreased cardiac index and heart rate, and significantly increased total peripheral resistance. These effects remained unchanged for 240 min after propranolol. 3. Baroreflex control of heart rate was significantly augmented immediately after, and at 30, 60 min after propranolol, but partly reverted to the initial level afterwards. Cardiopulmonary baroreflex control of FVR was reduced immediately after, and at 30, 60 min after propranolol, but partly reverted to the initial level afterwards. Pressor responses to phenylephrine was reduced immediately after propranolol, but no significant differences were observed after 30 min. 4. These results suggest that acute changes in the properties of baroreflexes occur in man after propranolol.

Adrenergic beta-Antagonists↗