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Biomedical subjects

T Miyoshi

Publications and source records attributed to T Miyoshi.

At least 19 recordsLinked to original sources

Characterization of region Ic in site I on human serum albumin. Microenvironmental analysis using fluorescence spectroscopy.

Characteristics of region Ic among at least three overlapping binding regions (regions Ia, Ib and Ic) in site I on human serum albumin (HSA) were analysed using n-alkyl p-aminobenzoates (n-alkyl p-ABEs), all of which are specific fluorescent probes for region Ic. In the interaction processes between n-alkyl p-ABEs and HSA, hydrophobic interaction, van der Waals interaction and local structural changes in region Ic were found to be involved based on the results obtained by analyses of the fluorescence spectra, structure-activity relationships and thermodynamic parameters. In addition, comparison of the fluorescence spectra of n-alkyl p-ABEs in HSA and detergents indicated that the possibility of a hydrophobic region Ic around which an amino acid with cationic charge locates could not be denied because of the similarity of fluorescence spectra between n-alkyl p-ABEs in HSA and in neutral and cationic detergents. The deviation of n-alkyl p-ABEs with long alkyl chains (C9-C12) in the relationships between association constants and physicochemical properties of a series of n-alkyl p-ABEs (C1-C12) suggested that region Ic possess an optimal depth. A conformational change of HSA with increasing pH (pH 6-9) generated an increase in hydrophobicity and adaptability of the binding region and made interaction easy, with an increase in adaptability of the binding region Ic; consequently, it enhanced the binding of n-alkyl p-ABEs to HSA.

Binding Sites

Assessment of the mechanical properties of peripheral arteries in chain saw operators using a photosensor.

In order to evaluate the severity of peripheral vascular disorders, and to detect changes in the digital arteries of workers who use chain saws, the mechanical properties of the digital arteries of 22 such workers were examined using a photosensor. The elastic properties and the nonlinearity of digital arteries were assessed through observation of the changes in the vascular volume ratio (V/Vo) against the volume (Vo) at mean blood pressure (Pm). A significant negative correlation was found between age and V/Vo at a transmural pressure of 30 mmHg (V30/Vo), which suggested that V30/Vo tended to decrease with aging. Although it was impossible to calculate V30/Vo for chain saw operators because of the vague changes in the volume pulse wave, this nonlinearity was more clearly observed through changes in the relative vascular volume (V/V40) along with a reduction in cuff pressure (Pc) to 40 mmHg below systolic blood pressure. A group of similarly aged healthy controls and three groups of workers with a different severity of vibration-induced white finger (VWF), i.e., no symptoms of VWF, mild VWF and severe VWF, were classified according to the changes in their V/V40 and the reduction in Pc. The results obtained in the present study suggest that the peripheral vascular disorders in workers using chain saws are due to the opening disturbance of the arteries with nonlinear changes in the peripheral artery, which is related to functional and organic abnormality of the arteries.

Adult

Epidemiological study on relationship between breast cancer mortality and dietary factors.

To elucidate the effects of nutritional factors on regional differences in breast cancer mortality in Japan, the statistical analysis was made using the results of the national nutrition surveys in 12 districts from 1966 to 1980 and age-adjusted mortality from breast cancer from 1966 to 1990. The correlation analysis between food or nutrient intake and breast cancer mortality was performed with a fixed time lag of 10 years. Dietary factors such as wheat, milk, meats, animal fat, animal protein, total fat, saturated fatty acid (SF) and monounsaturated fatty acid (MUF) were correlated highly positively with breast cancer mortality. The correlation analysis between increase rates in age-adjusted mortality from breast cancer and increase rates in food or nutrient intake was also examined. Highly positive correlations were obtained between breast cancer mortality and following dietary factors; oils and fats, fruits, milk, total fat, vegetable fat, SF, MUF and n-6 polyunsaturated fatty acid. Factor analysis using fat intake by 12 districts revealed the factor representing the intake of fat component resulting from ingestion of animal fat. This factor showed a positive correlation with age-adjusted mortality from breast cancer. The findings suggested that the dietary factors due to intake of Westernized meals, especially SF had the effect on breast cancer mortality in Japan.

Adult

Epidemiological studies on regional differences in suicide mortality and its correlation with socioeconomic factors.

To investigate regional differences in suicide mortality and its correlation with socioeconomic factors during the 1975-1990 period, we analyzed annual change in suicide mortality and 18 socioeconomic indicators among each prefectures in Japan. Annual course of age-adjusted mortality from suicide during the 1975-1985 period differed between males (increasing) and females (decreasing), because of rapidly increase in suicide mortality for middle-aged males. During the 1986-1990 period, suicide mortality decreased in both males and females. A census characteristic that suicide mortality was higher in rural districts than in urban districts intensified annually until 1985 and weakened thereafter. The factor analysis of socioeconomic indicators revealed that 1st factor was recognized as the industrial and economic activity. A high inverse correlation was observed between age-adjusted mortality from suicide and the 1st factor for males and females. In males this tendency continued until the end of the 1980s. On the whole, correlation coefficients between age-adjusted mortality from suicide and the socioeconomic indicators in males were much higher than that in females. The indicators whose annual change differed remarkably between the prefectures with an increase and a decrease in suicide mortality for males were amount of savings and frequency of bankruptcy. Therefore they were considered to be closely related to suicide mortality.

Adolescent

Relationship between physical exercise and health of the elderly people in a rural community.

The significance of life style and regular physical exercise for health of elderly people in a rural community was evaluated by questionnaires. The subjects studied were a group who had been playing gate ball (such as croquet) for more than three years (N = 86) and a group who had not (N = 255). Significantly more males in the group playing gate ball (GB group) than in the group not playing gate ball (n-GB group) reported feeling healthier than three years before. The average overall score for life style which indicates a healthier life style was analyzed. The score for life style of males was significantly lower in the GB group than in the n-GB group. Significantly more males in the GB group did not take snacks or smoke than those in the n-GB group. Regarding regular physical exercise, significantly fewer females in the GB group went for a daily walk than those in the n-GB group. The average score for integrated regular physical exercise was significantly higher in the GB group than in the n-GB group. The scores for regular physical exercise of females in the GB group, even in spite of disability or hypertension, were significantly higher than those in the n-GB group. From this survey it appears that regular physical exercise including gate ball may be beneficial for health of elderly people in a rural community.

Aged

Characteristic differences in the mode of quinone reduction and stability between energy-coupled and -uncoupled NADH-quinone reductases from bacterial respiratory chain.

Bacterial respiratory chain has two types of NADH-quinone reductase (NQR): one is energy-coupled (type-1) and the other had no energy-transducing capacity, that is, energy-uncoupled (type-2). Each of the NADH-reacting flavoprotein subunits of NQR-1 from Escherichia coli and the marine Vibrio alginolyticus reduced quinone to semiquinone radicals by the one-electron transfer pathway and was very sensitive to preincubation with NADH. On the other hand, the NQR-2 from these bacteria reduced quinone to quinol by the two-electron transfer pathway and was insensitive to preincubation with NADH. Since the NQR-1 from E. coli functions as a proton pump, whereas that from the marine V. alginolyticus functions as a sodium pump, the formation of semiquinone radicals as an intermediate is likely to be a common mechanism to functioning as either proton or sodium pump.

Escherichia coli

Characterization of aldehyde reductase of Sporobolomyces salmonicolor.

An NADPH-dependent aldehyde reductase (EC 1.1.1.2) isolated from Sporobolomyces salmonicolor AKU 4429 was further characterized. The enzyme also catalyzed the reductions of D-glucuronate, D-glucose, D-xylose and D-galactose at high concentrations. Km values for D-glucuronate and D-glucose are 345 and 4270 mM, respectively. Quercetin, dicoumarol and some SH-reagents inhibited the enzyme activity. NH2-terminal amino acid sequence analysis showed that the S. salmonicolor enzyme is partially the same as the aldo-keto reductase family proteins in primary protein structure.

Alcohol Oxidoreductases

Further characterization of reversal of signs of induced cotton effects of dicumarol derivatives-alpha 1-acid glycoprotein systems by protriptyline.

The interaction of dicumarol derivatives and protriptyline with respect to the binding to alpha 1-acid glycoprotein (AGP) has been investigated by circular dichroism (CD), equilibrium dialysis and ultrafiltration. Investigation of the induced CD spectra of dicumarol derivatives bound to AGP indicated that the conformations of these compounds were different when bound to AGP. Though all the dicumarol derivatives, protriptyline and AGP formed a ternary complex, interaction modes were different, depending upon the substituent groups at position 3 of the dicumarol molecule. On the basis of the protriptyline effect on the CD spectra of all dicumarol derivatives bound to AGP, the compounds were classified in the following way: (1) Dicumarol, ethylidenebis 4-hydroxycoumarin and propylidenebis 4-hydroxycoumarin caused reversal of the sign of ellipticity. This interaction was explained by cooperative binding. (2) Butylidenebis 4-hydroxycoumarin and pentylidenebis 4-hydroxycoumarin generated new band and disappeared ellipticity of the original Cotton effect. This interaction was also explained by the cooperative binding mode. (3) Ethylbiscoumacetate which generated the CD band similar to that of dicumarol in the absence of protriptyline, reversed the sign of the CD spectrum only at 325 nm. The interaction was anticooperative in nature. (4) Benzylidenebis 4-hydroxycoumarin represented type four which had no change in the CD spectrum by the addition of protriptyline. This interaction was explained by the two-state model accompanying the conformational change of AGP. These results suggested that all compounds, except for benzylidenebis 4-hydroxycoumarin, induced negative Cotton effects at 325 nm by taking the same asymmetrical perturbation by the addition of protriptyline and the interaction was carried out according to model 2. An attempt to study the interaction mechanism of two or more drugs with regard to the binding to protein using these models is thought to help in understanding drug-protein interactions.

Binding Sites

Properties of respiratory chain-linked Na(+)-independent NADH-quinone reductase in a marine Vibrio alginolyticus.

The respiratory chain of a marine Vibrio alginolyticus contains two types of NADH-quinone reductase (NQR): one is an Na(+)-dependent NQR functioning as an Na+ pump (NQR-1) and the other is an Na(+)-independent NQR (NQR-2). NQR-2 was purified about 55-fold from the membrane of mutant Nap-1 which is devoid of NQR-1, and its properties were compared with those of NQR-1. In contrast to NQR-1, the purified NQR-2 does not require any salts for activity and is not inhibited by up to 0.4 M salts. The optimum pH of NQR-2 is between 6.8 and 7.8, which is about 0.7 ph units lower than that of NQR-1. NQR-2 is insensitive to strong inhibitors of NQR-1 such as p-chloromercuribenzoate, Ag+ and 2-heptyl-4-hydroxyquinoline N-oxide. Using inverted membrane vesicles, it was confirmed that NQR-2 has no capacity to generate a membrane potential. NQR-2 reduces menadione and ubiquinone-1 by a two-electron reduction pathway. Since the NADH-reacting FAD-containing beta-subunit of NQR-1 reduces quinones by a one-electron reduction pathway, the mode of quinone reduction is closely related to energy coupling; the formation of semiquinone radicals as an intermediate is likely to be essential to functioning as an ion pump.

Electron Transport Complex II

Reversal of signs of induced cotton effects of dicumarol-alpha 1-acid glycoprotein systems by phenothiazine neuroleptics through ternary complexation.

The interaction of dicumarol and phenothiazine neuroleptics binding to alpha 1-acid glycoprotein (AGP) was investigated by circular dichroism (CD) and equilibrium dialysis. The induced CD spectra of the dicumarol-AGP complex were affected differently by the different substituents of the phenothiazine molecule. The sign of the induced Cotton effect of dicumarol bound to AGP was reversibly changed with the introduction of the propyldimethylamine substituent at position 10 or chloride group at position 2 of the phenothiazine molecule. Chlorpromazine, which contains both of these substituents reversed the sign of the induced Cotton effect with the highest intensity. The addition of trifluoperazine, fluphenazine, and promethazine containing neither of the two substituents generated a new negative CD band. However, the addition of opromazine, which contains sulfoxide at position 5, decreased the CD intensity of the dicumarol-AGP complex without changing the shape of the CD spectra. Equilibrium dialysis studies revealed that the interaction of dicumarol-AGP with phenothiazine derivatives occurred simultaneously, and the interaction followed a cooperative and anticooperative binding model. Further, among the six phenothiazine derivatives that reversed the signs of the induced Cotton effects of the dicumarol-AGP complex, a linear relationship was observed between coupling constants and the difference in the induced optical ellipticity. The opromazine and dicumarol interaction was competitive for a common binding site on the AGP molecule. Removal of sialic acid did not have any effect on this interaction. These data support the hypothesis that the acidic and the basic drug binding sites overlap each other.

Antipsychotic Agents

Significance of the serum CA125 level in recurrent ovarian cancer.

Thirty-four recurrent cases of 89 patients with ovarian cancer treated in our department between 1985 and 1989 were examined for changes in serum CA125 level. 1) Upon confirmation of recurrence, 17 patients were positive for CA125 and 15 were negative. 2) According to the histopathological type, the rate of CA125 positivity in patients with recurrence was high for serous adenocarcinoma, suggesting that determination of CA125 is useful for detection of recurrence. In contrast, all patients with mucinous adenocarcinoma or endometrioid adenocarcinoma were negative for CA125. 3) The CA125 positivity rate upon confirmation of recurrence was 9% in patients whose CA125 was less than 1,000 U/ml on initial examination, suggesting that close management of such patients is necessary. 4) Elevation of CA125 by 3 steps or more within the normal range (less than 35 U/ml) was useful for predicting recurrence. 5) The cut-off level of CA125 during follow-up should be set at 16 U/ml. 6) It was difficult to evaluate remission with only the serum CA125 level. It is impossible to avoid second look operation at present. These results indicate that pretreatment values and changes of the parameter within the normal range (less than 35 U/ml) have to be considered when using CA125 as a marker of tumor recurrence.

Adenocarcinoma

Investigation of the interaction mode of phenothiazine neuroleptics with alpha 1-acid glycoprotein.

The interaction of phenothiazine neuroleptics with alpha 1-acid glycoprotein (AGP) and desialylated AGP (asialoAGP) has been investigated by fluorescence, circular dichroism spectroscopy and by equilibrium dialysis. The binding parameters of phenothiazines obtained from fluorescence agreed closely with those obtained from circular dichroism and equilibrium dialysis. The binding affinities (nK) to AGP were slightly higher than binding affinities to asialoAGP. Attempts to correlate binding affinities with partition coefficients suggested that hydrophobic forces were mainly involved in the binding of phenothiazine neuroleptics to AGP and asialoAGP. However, electrostatic interaction was also found to be involved as suggested by experimental data obtained from the influence of oleic acid and caesium chloride on the drug binding to the two proteins.

Antipsychotic Agents

Interaction mode of dicumarol and its derivatives with human serum albumin, alpha 1-acid glycoprotein and asialo alpha 1-acid glycoprotein.

The interaction of dicumarol and its seven other derivatives with human serum albumin (HSA), alpha 1-acid glycoprotein (AGP) and desialylatedAGP (asialoAGP) has been investigated by circular dichroism (CD) and fluorescence. The binding parameters of dicumarol and its derivatives obtained from fluorescence almost agreed with those obtained from CD. The binding data indicated that the total binding affinities (nK) to HSA were higher than the binding affinities to AGP and asialoAGP. Hydrophobic interaction was the driving force for the binding to all the three proteins and nK values in the binding process were found to be increased with the increase of hydrophobicity of the compound. This was evidenced by the attempts taken to correlate binding affinities with partition coefficients. Both electrostatic and van der Waals interactions were not found to play any significant role in the binding of these compounds to any of these three proteins. However, in case of the AGP and asialoAGP binding, apart from the hydrophobic interaction, some other forces may be involved as evidenced from the experimental data. Binding was exothermic, entropy driven and spontaneous. The change of enthalpy (delta H degree) was compensated for by the change in entropy (delta S degree). Relative contribution of hydrophobic interactions in the binding of these compounds to HSA was higher than to AGP or asialoAGP. Sialic acid was not found to impart any significant role in the binding of these compounds to AGP.

Asialoglycoproteins

Enhancing effect of sodium chloride on in vitro adsorption of paraquat onto activated carbon.

The enhancing effect of sodium chloride addition on the adsorption of paraquat onto activated carbon was discussed from the standpoints of equilibrium amount adsorbed and adsorption rate in vitro. The amount of paraquat adsorbed was increased by the addition of sodium chloride. The amount adsorbed with 0.1% addition was about five times greater than that in sodium chloride-free solution at an equilibrium concentration of 1 mg/L. The adsorption rate of paraquat onto activated carbon was also accelerated by sodium chloride addition. Kinetic constants in 0.1% and 0.9% sodium chloride solution were about 1.4 and 2.0 times greater, respectively, than that in sodium chloride-free solution. It was confirmed that paraquat removal by activated carbon was enhanced by sodium chloride addition. The reason was assumed to be the interrupted dissociation of paraquat in solution caused by sodium chloride addition.

Adsorption

[Changes of nutritional factors related to regional differences in the mortality of cardiovascular disease between 1966 and 1985 in Japan].

Cardiovascular disease has been the leading cause of death since 1946 in Japan. In this paper, the relationship between mortality and nutritional factors was analyzed by 12 different regions in Japan during the period 1966-1985. Data in the Reports of the National Nutritional Survey in Japan were used as the nutritional factors, and calculation was made of age-adjusted mortality from ischemic heart disease (IHD), cerebral hemorrhage (CH) and cerebral infarction (CI). The results obtained were as follows: 1. Correlation coefficients were calculated based on the average value of 20 years in each 12 different regions. Correlation coefficients between the mortality from IHD and intake of total fat and n3-polyunsaturated fatty acids were positively significant for both sexes. Between the mortality from CH and vegetable protein and salt, they were positively significant (p < 0.01) while cholesterol was negatively significant (p < 0.01). Between the mortality from CI and vegetable protein, salt and carbohydrate, they were positively significant (p < 0.01). 2. Correlation coefficients between slopes of CH and slopes of nutrients intakes, indicated cholesterol to be negatively significant (p < 0.05) for women from 1966-1970, and salt to be positively significant for men (p < 0.01) and women (p < 0.05) from 1974-1985. In the period 1966-1970, the correlation coefficient between slopes of IHD and those of Keys' factor was positively significant (p < 0.05) for women. 3. To clarify changes in the relationship between mortality and nutrients, correlation coefficients were calculated each year from 1966 to 1985. Significant positive correlation coefficients for IHD were found with animal protein and saturated fat starting from about 1975. Salt was associated with IHD in the 1960s but not following 1970. Those of nutrients for CH and CI did not change markedly during 18 years. 4. Multiple regression analysis with intake of salt and Keys' factor indicated that the influence of salt on cardiovascular disease to decreased and that that of low serum cholesterol on CH declined. Multiple correlation coefficients with salt and Keys' factor decreased for IHD (men) and CH (women).

Cardiovascular Diseases

[Two cases of acute promyelocytic leukemia in pregnancy and the effect of anthracyclines on fetal development].

Two patients with acute promyelocytic leukemia (APL) in 2nd and 3rd trimester of pregnancy are reported on. Case 1: 38-year-old female consulted our hospital because of bleeding tendency and pancytopenia in April, 1988. She was diagnosed as having APL with disseminated intravascular coagulopathy (DIC) and was found to be in the 14th week of gestation. Combined chemotherapy (BHAC-DMP) including the total dose (440 mg) of daunorubicin (DNR) resulted in intrauterine fetal death at 19 weeks of gestation. The fetus was severely anemic and the bone marrow was hypoplastic. Case 2: A 27-year-old female was diagnosed as having APL with DIC at 29 weeks of gestation. BHAC-DMP including 440 mg DNR achieved complete remission. At 35 weeks of gestation, she delivered a normal infant by Caesarean section. The child had normal hematological findings and showed normal growth. Both cases developed APL accompanied by DIC during pregnancy and were treated with a similar regimen including high dose of anthracyclines. Case 2 treated in the late period of gestation delivered a normal infant, while fetal death resulted in case 1, treated in the early period of gestation. We reviewed the literature regarding chemotherapy using anthracyclines during pregnancy.

Adult