Structural and functional analyses of the Arg-Gly-Asp sequence introduced into human lysozyme

This research was originally published in the Journal of Biological Chemistry. T Yamada, M Matsushima, K Inaka, T Ohkubo, A Uyeda, T Maeda, K Titani, K Sekiguchi and M Kikuchi. Structural and functional analyses of the Arg-Gly-Asp sequence introduced into human lysozyme. J. Biol. Chem. 1993; 268: 10588-10592 © the American Society for Biochemistry and Molecular Biolog

Effects of tomato juice on the pharmacokinetics of CYP3A4-substrate drugs

We previously demonstrated that tomato juice (TJ) contains potent mechanism-based inhibitor(s) of CYP3A4. In this study, we investigated the effects of TJ and grapefruit juice (GFJ) on the pharmacokinetics of the CYP3A4-substrate drugs, nifedipine (NFP) and midazolam (MDZ), in male Wistar rats. Oral administration of GFJ 90 min before the intraduodenal administration of NFP or MDZ increased the area under the concentration–time curves (AUCs) of NFP and MDZ by 32.4% and 89.4%, respectively. TJ increased MDZ blood concentrations and AUC after intraduodenal MDZ administration; however, it had no effect on NFP. When MDZ and NFP were intravenously administered, GFJ significantly increased the AUC of MDZ, but only slightly increased that of NFP. In contrast, TJ only slightly increased the AUC of MDZ. These results suggest that, similar to GFJ, TJ influences the pharmacokinetics of CYP3A4-substrate drugs; however, it may be a drug-dependent partial effect

Structural and functional analyses of the Arg-Gly-Asp sequence introduced into human lysozyme

To determine the functional conformation of the Arg-Gly-Asp (RGD) sequence, we have constructed mutant proteins by inserting 4-12 amino acid residues from the RGD region of human fibronectin between Val74 and Asn75 of human lysozyme. RGDS-, GRGDSP-, TGRGDSPA-, VTGRGDSPAS-, and AVTGRGDS-PASS-introduced mutant lysozymes were expressed in yeast, purified, and designated as RGD4, -6, -8, -10, and -12, respectively. Using baby hamster kidney cells, RGD8, RGD10, and RGD12 were shown to possess high cell adhesion activity nearly equal to 10% of human vitronectin activity. RGD4 and RGD6 exhibited somewhat lower cell adhesion activity. The activities of these mutant proteins were inhibited by the addition of either GRGDSP peptide or polyclonal antibody against vitronectin receptor, as was the case for the vitronectin activity. The results suggest that the cell adhesion signals are transduced to cells through the interaction with the vitronectin receptor. The three-dimensional structures of RGD4 and RGD8 were determined at 1.8-A resolution by x-ray crystallography. A model of the inserted region in RGD4 could be built in the electron density map, but the positions of the preceding residues, Ala73-Val74, were uncertain. The inserted region in RGD8 did not demonstrate continuous electron densities. The results suggest that these RGD sequence-containing regions are highly flexible and that such flexibility could allow the conformation of the RGD regions to be induced to fit into the binding pocket of the integrin receptor.This research was originally published in the Journal of Biological Chemistry. T Yamada, M Matsushima, K Inaka, T Ohkubo, A Uyeda, T Maeda, K Titani, K Sekiguchi and M Kikuchi. Structural and functional analyses of the Arg-Gly-Asp sequence introduced into human lysozyme. J. Biol. Chem. 1993; 268: 10588-10592 © the American Society for Biochemistry and Molecular Biolog

Mediators of the effects of rice intake on health in individuals consuming a traditional Japanese diet centered on rice

Although the Japanese diet is believed to be balanced and healthy, its benefits have been poorly investigated, especially in terms of effects on mental health. We investigated dietary patterns and physical and mental health in the Japanese population using an epidemiological survey to determine the health benefits of the traditional Japanese diet. Questionnaires to assess dietary habits, quality of life, sleep quality, impulsivity, and depression severity were distributed to 550 randomly selected middle-aged and elderly individuals. Participants with any physical or mental disease were excluded. Two-hundred and seventy-eight participants were selected for the final statistical analysis. We determined rice to be one of the most traditional foods in Japanese cuisine. Scores for each questionnaire were computed, and the correlations between rice intake and health indices were assessed. When analyzing the direct correlations between rice intake and health indices, we found only two correlations, namely those with quality of life (vitality) and sleep quality. Path analysis using structural equation modeling was performed to investigate the association between rice intake and health, with indirect effects included in the model. Additional associations between rice intake and health were explained using this model when compared to those using direct correlation analysis. Path analysis was used to identify mediators of the rice-health association. These mediators were miso (soybean paste) soup, green tea, and natto (fermented soybean) intake. Interestingly, these mediators have been major components of the Japanese diet since 1975, which has been considered one of the healthiest diets since the 1960s. Our results indicate that the combination of rice with other healthy foods, which is representative of the traditional Japanese diet, may contribute to improvements in physical and mental health

Two Forms of NAD-Dependent d-Mandelate Dehydrogenase in Enterococcus faecalis IAM 10071

Two forms of NAD-dependent d-mandelate dehydrogenase (d-ManDHs) were purified from Enterococcus faecalis IAM 10071. While these two enzymes consistently exhibited high activity toward large 2-ketoacid substrates that were branched at the C3 or C4 position, they gave distinctly different K(m) and V(max) values for these substrates and had distinct molecular weights by gel electrophoresis and gel filtration

家庭血圧測定実施状況と関連する生活習慣行動および基本的特性の探索的検討：職域横断研究

目的：我が国の一般集団における家庭血圧測定実施状況はほとんど報告されていない．本研究は職域集団において家庭血圧測定の実施状況と家庭血圧測定を実施している者の生活習慣行動および基本的特性を探索的に明らかにすることを目的とした．方法：総合小売業の単一職域集団において2018年に実施された定期健康診断データを用い，40–65歳の4,664名を対象とした．降圧薬服用の有無別，性別に家庭血圧計保有の有無と測定頻度を算出し，多変量ロジスティック回帰分析より家庭血圧測定実施と基本特性，生活習慣行動との関連を検討した．独立変数は年齢，血圧，雇用形態，同居者有無，喫煙習慣，飲酒習慣，食習慣，運動習慣，歩行速度，脂質異常症治療有無，糖尿病治療有無とし，従属変数は降圧薬非服用者では家庭血圧測定機会あり（家庭血圧測定頻度が月2回以上），服用者では家庭血圧測定習慣あり（家庭血圧測定頻度がほぼ毎日）とした．結果：降圧薬非服用者で家庭血圧測定機会のある者は男性8.7％，女性12.4％で，男女とも年齢（1歳上昇毎のオッズ比：男性1.11，女性1.06）と血圧（＜130/80 mmHgと比較した ≥ 140/90 mmHgのオッズ比：男性7.42，女性：4.71）が家庭血圧測定機会と正に関連した．さらに女性では脂質異常症治療を受けている者（受けていない者と比較してオッズ比1.77），歩く速度が速い者（遅い者と比較してオッズ比：1.49），運動習慣のある者（ない者と比較してオッズ比：1.79）で測定機会ありのオッズ比が有意に高く，夕食後の間食の回数が多い者（少ない者と比較してオッズ比：0.65）で有意に低かった．降圧薬服用者で家庭血圧測定習慣ありの者は男性21.6％，女性25.5％であった．男性では糖尿病治療を受けている者（受けていない者と比較してオッズ比：0.23）で測定習慣ありのオッズ比が有意に低かった．女性では，脂質異常症の治療を受けている者（受けていない者と比較してオッズ比：0.53），血圧管理不良者（＜130/80 mmHgと比較した ≥ 140/90 mmHgのオッズ比：0.58），飲酒習慣のある者（ない者と比較してオッズ比：0.60），就寝前2時間以内の夕食回数が多い者（少ない者と比較してオッズ比：0.54）で測定習慣ありのオッズ比が有意に低く，独居者（同居者がいる者と比較してオッズ比：2.43）で有意に高かった．結論：降圧薬非服用者で家庭血圧測定機会ありの者は約10％で，男女とも年齢と血圧が，女性では加えて健康的な生活習慣が正に関連していた．降圧薬服用者で家庭血圧測定習慣ありの者は約25％で，他の生活習慣病治療や女性では血圧管理不良，不健康な生活習慣が負に関連した．Objectives:The current status of home blood pressure (HBP) measurement is unknown at a Japanese worksite. We aimed to calculate the proportion of individuals who periodically measured HBP and to explore the demographic and lifestyle characteristics of these workers.Methods:The study included 4,664 employees aged 40-65 years who worked at a retail company and underwent health check-ups in 2018. Multivariable logistic regression models were used to estimate odds ratios (ORs) of participant\u27s demographics and lifestyle characteristics and habits for HBP measurement by sex and medical treatment for hypertension. Periodic HBP measurement was defined as HBP measurements performed two times or more per month (opportunistic HBP measurement) among participants not being treated for hypertension, and daily measurement of HBP (everyday HBP measurement) among participants treated for hypertension.Results:The percentages of opportunistic HBP measurement were 8.7% in males and 12.4% in females not being treated for hypertension. In both sexes, age (ORs per 1-year increment: 1.11 in males and 1.06 in females) and blood pressure (ORs of ≥ 140/90 mmHg: 7.42 in males and 4.71 in females compared with < 130/80 mmHg) were positively associated with opportunistic HBP measurement. Females treated for dyslipidemia (OR: 1.77), who had a self-described fast walking speed (OR: 1.49), and who exercised habitually (OR: 1.79) had significantly high ORs for opportunistic HBP measurement. Females who frequently consumed snacks after dinner had significantly lower ORs (0.65) than those who did not. The percentages of workers who did everyday HBP measurement were 21.6% in males and 25.5% in females treated for hypertension. Males treated for diabetes (OR: 0.23) had significantly lower OR than those who did not. Females treated for dyslipidemia (OR was 0.53), who had uncontrolled hypertension (OR: 0.58), consumed alcohol (OR: 0.60), and frequently ate within two hours before bed (OR: 0.54) had significantly lower ORs. Females who lived alone had significantly higher ORs (2.43) than those who did not.Conclusion:Approximately 10% of individuals not treated for hypertension periodically measured HBP. Age and blood pressure in males and females, and healthy lifestyles in females, were associated with having opportunistic HBP measurement. Approximately 25% of individuals treated for hypertension measured HBP every day. Individuals treated for dyslipidemia or diabetes and females with unhealthy lifestyle and uncontrolled hypertension were less likely to measure HBP every day