Background: Oxidative stress, the imbalance between pro- and antioxidants, has been implicated in the etiology and pathophysiology of the incidence and mortality of many diseases. We aim to investigate the relations of dietary intakes of vitamin C and

and main carotenoids with all-cause mortality in Japanese men and women.

Methods: The Japan Collaborative Cohort Study for Evaluation of Cancer Risk had

,795 men and 35,539 women, aged 40–79 years at baseline (1988–1990), who completed a valid food frequency questionnaire and were followed up to the end of 2009.

Results: There were 6,179 deaths in men and

,355 deaths in women during the median follow-up of 18.9 years for men and 19.4 years for women. Multivariate hazard ratios for the highest versus lowest quintile intakes in women were 0. (% confidence interval [CI], 0.76–0.; P for trend < 0.0001) for vitamin C, 0.85 (% CI, 0.78–0.93; P for trend < 0.0001) for vitamin , 0.88 (% CI, 0.81–0.96; P for trend = 0.0006) for β-carotene, and 0. (% CI, 0.82–0.98; P for trend = 0.0002) for β-cryptoxanthin. The joint effect of any two of these highly correlated micronutrients showed significant 12–17% reductions in risk in the high-intake group compared with the low-intake group in women. These significant associations were also observed in the highest quintile intakes of vitamin C, vitamin , and β-carotene in female non-smokers but were not observed in female smokers, male smokers, and non-smokers.

Conclusions: Higher dietary intakes of antioxidant vitamins may reduce the risk of all-cause mortality in middle-aged Japanese women, especially female non-smokers.

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Ferri-ghoseite（フェリゴース閃石）が和歌山県飯盛鉱山より見出された．X線実験に使用された部分はEPMAにより分析され，その化学式は，^A(Na_0.16K_0.02)_Σ0.18^B(+_1.08)_Σ2.00^C(Mg_3.78Mn²⁺_0.52Fe³⁺
_0.66Al_0.04)

Σ5.00^T

(

Si_7.95Al_0.05

)

Σ8.00O₂₂^W

[(OH)

1.90F_0.10

] _Σ2.00である．単結晶X線回折実験により得られた格子定数は， a = 9.6389(7), b = 18.0534(10), c =

5

.3138(3) angstrorm and beta = 102.896(2) degreeである．

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Paired box transcription factor

() is essential for thyroid organogenesis and development. Heterozygous pathogenic variants of typically cause congenital hypothyroidism (CH) due to thyroid hypoplasia. Additionally, pathogenic variants have been identified in patients with gland in situ (GIS). This study was conducted to analyze the in vitro functional consequences of four variants (p.D94N, p.del, p.V58I, and p.L186Hfs*) previously identified in patients with CH and GIS. The transcriptional activity of variants on the thyroglobulin (TG) promoter was assessed in a luciferase reporter assay. The levels of transcriptional activity on the TG promoter of p.del and p.L186Hfs* were significantly reduced, whereas p.D94N and p.V58I showed residual activation. In addition, a dominant negative effect on the wild-type (WT) was not detected in any variant using a luciferase reporter assay. Two variants (p.del and p.L186Hfs*) may be pathogenic causes of CH with GIS.

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This work studied the antinociceptive effects of the hydroalcoholic extracts (HAEs) from Erythrina velutina (Ev) and Erythrina mulungu (Em) in three experimental models of nociception in mice. The extract was administered intraperitoneally to female mice at the doses of 200 and 400 mg/kg. Inhibitions of abdominal contractions were observed with the doses of 200 (88.6%; 86.%) and 400 (.%; .%) mg/kg of

E

. velutina and

E

. mulungu, respectively, as compared to controls.

E

. velutina and

E

. mulungu, at both doses, reduced the nociception produced by formalin in the 1st and 2nd phases and this effect was not reversed by the pretreatment with naloxone. In the hot plate test an increase of the reaction time was observed only at 60 (Ev=18.0±2.2; Em=20.±2.52) and min (Ev=20.4±1.71; Em=23.7±2.32) after the treatment with

E

. velutina and

E

. mulungu at the dose of 400 mg/kg as compared to controls (T60=11.1±0.74; T=11.9±0.86). This effect was not reversed by naloxone. We conclude that

E

. velutina and

E

. mulungu presents antinociceptive effects, which are independent of the opioid system.

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Background: Mannose-binding lectin2 (MBL2) is implicated in the host immune response, but there are limited data about MBL2 polymorphisms and hepatocellular carcinoma (HCC) risk. This study aimed to investigate the relationship between the MBL2 rs7096206 polymorphism and HCC risk in a Chinese Han population.
Methods: A population-based case-control study of 220 HCC patients and 220 age- and gender-matched healthy control subjects from a Chinese Han population was conducted. Genomic DNA was extracted from blood samples, and the presence of the MBL2 polymorphism rs7096206 was assessed using matrix-assisted laser desorption-ionization time-of-flight mass spectrometry. Conditional logistic regression was performed to assess the risk of HCC by determining odds ratios and % confidence intervals (CIs).
Results: The odds of HCC among carriers of CG and GG genotypes were 7.33 (% CI, 2.53–21.29) and 12.48 (% CI, 2.08–74.), respectively. In the dominant genetic model, GG+CG carriers had an approximately -fold increased risk (% CI, 2.–.62) compared with those with the CC genotype. The G allele was significantly associated with elevated HCC risk, with an odds ratio of 6. (% CI, 2.–16.10).
Conclusions: Our findings suggest that the MBL2 polymorphism rs7096206 is associated with HCC susceptibility and has the potential to serve as a biomarker to detect populations at increased HCC risk.

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Background: Angiographic fractional flow reserve (angioFFR) is a novel artificial intelligence (AI)-based angiography-derived fractional flow reserve (FFR) application. We investigated the diagnostic accuracy of angioFFR to detect hemodynamically relevant coronary artery disease.

Methods and Results: Consecutive patients with 30–

% angiographic stenoses and invasive FFR measurements were included in this prospective, single-center study conducted between November 2018 and February 2020. Diagnostic accuracy was assessed using invasive FFR as the reference standard. In patients undergoing percutaneous coronary intervention, gradients of invasive FFR and angioFFR in the pre-senting segments were compared. We assessed 253 vessels (200 patients). The accuracy of angioFFR was 87.7% (% confidence interval [CI] .1–91.%), with a sensitivity of 76.% (% CI 67.1–84.9%), specificity of 94.3% (% CI 89.–97.4%), and area under the curve of 0. (% CI 0.86–0.93%). AngioFFR was well correlated with invasive FFR (r=0.76; % CI 0.71–0.81; P<0.001). The agreement was 0.003 (limits of agreement: −0.13, 0.14). The FFR gradients of angioFFR and invasive FFR were comparable (n=51; mean [±SD] 0.±0.10 vs. 0.±0.11, respectively; P=0.87).

Conclusions: AI-based angioFFR showed good diagnostic accuracy for detecting hemodynamically relevant stenosis using invasive FFR as the reference standard. The gradients of invasive FFR and angioFFR in the pre-stenting segments were comparable.

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In the first part of the present work the interaction of glycophorin with dimyristoylphosphatidylcholine (DMPC) is studied by freeze fracture electron microscopy, densitometry, calorimetry, and ° static light scattering. An exothermic lipid/protein interaction energy of W_P=190 kJ•mol^-1 was found by application of the well known Van Laar relation for the displacement of the freezing point and the Gibbs-Duhem relationship. Secondly, the effects of Ca²⁺ on the lipid/protein interaction were studied. Following Ca²⁺ addition a remarkable decoupling of the interaction of the glycophorin head group with the bilayer surface was revealed by densitometry and gold-labeling electron microscopy. It is estimated that about 80% of lipid once disturbed by the adsorption of glycophorin head groups is decoupled after addition of Ca²⁺. Thirdly, the selective interaction of glycophorin with binary lipid mixtures was studied, including the mixtures of DMPC with dimyristoylphosphatidylserine (DMPS) and dilauroylphosphatidylcholine (DLPC), and the mixture of dipalmitoylphosphatidylcholine (DPPC) with DLPC.

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Arabidopsis dwf4 is a brassinosteroid deficient mutant, and the DWF4 gene has been reported to encode a cytochrome P450, CYPB1. Here, we report the catalytic activity and substrate specificity of the CYPB1 protein. The recombinant CYPB1 was produced in . coli. The measurement of type I substrate binding spectra of CYPB1 demonstrated that sterols showed 10 times stronger affinity to the P450 than the corresponding stanols. CYPB1 activity was measured in an assay reconstituted with NADPH-P450 reductase, and the reaction products were analyzed by GC-MS. The recombinant CYPB1 catalyzed the C- hydroxylation of campestanol to produce 6-deoxocathasterone. Substrate specificity of the CYPB1 revealed that campesterol was much better substrate than campestanol, suggesting that the early C- hydroxylation pathway is a main route in the BR biosynthetic pathway. In addition, CYPB1 showed the C- hydroxylation activity toward various C_<27>, C_<28>, and C_<29> sterols, indicating that CYPB1 functions in the biosynthesis of C_<27>, C_<28>, and C_<29> brassinosteroids. To our knowledge, this is the first report of the biochemical evidence for the C- hydroxylation by the P450.

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In the present study, we developed a novel color scale for visual assessment, conforming to theoretical color changes of a gum, to evaluate m a s t i c a t o r y p r f o r m a n c ; m o r o v r , w investigated the reliability and validity of this evaluation method using the color scale. Ten participants (aged 26–30 years) with natural dentition chewed the gum at several chewing strokes. Changes in color were measured using a c o l o r i m t r , a n d t h n , l i n a r r g r s s i o n expressions that represented changes in gum color were derived. The color scale was developed using these regression expressions. Thirty-two chewed gums were evaluated using colorimeter and were assessed three times using the color scale by six dentists aged 25–27 (mean, 25.) years, six preclinical dental students aged 21–23 (mean, .2) years, and six elderly individuals aged 68–84 (mean, 74.0) years. The intrarater and interrater reliability of evaluations was assessed using intraclass correlation coefficients. Validity of the method compared with a colorimeter was assessed using Spearman’s rank correlation coefficient. All intraclass correlation coefficients were > 0., and Spearman’s rank-correlation coefficients were > 0. in all groups. These results indicated that the evaluation method of the color-changeable chewing gum using the newly developed color scale is reliable and valid.

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We screened the differentiation-inducing activities of 39 mushroom extracts from Akita prefecture, Japan, on the mouse osteoblastic cell line, MC3T3-1. Sixteen phosphate buffered saline (PBS), boiled PBS, 14 ethanol and 12 methanol extracts induced alkaline phosphatase (ALP) activities, an indicator of MC3T3-1 cell differentiation. The enzyme activities were markedly induced by extracts of Tricholoma auratum, and we isolated the active compound from methanol extracts of this mushroom. Physical data for the isolated active compound were identical to those for (,24R)-ergosta-7,-diene-3β,,6β-triol (1). 1 induced ALP activities of MC3T3-1 cells and promoted cell proliferation. To investigate the relationships between the chemical structure and differentiation-inducing activity of the compound, ALP-inducing activities of MC3T3-1 cells by 1, ergosterol (2), ergocalciferol (3), cholesta-3β,,6β-triol (4), 7-dehydrocholesterol () and cholecalciferol (6) were tested. The enzyme activities of MC3T3-1 cells were increased 3.0-fold by 10 μM 1 and 2.4-fold by 10 μM 4. However, 2, 3, and 6 did not induce MC3T3-1 cell ALP activity at 0.1—10 μM. These results suggested that the OH groups at C- and/or C-6 of 1 and 4 played an important role in their differentiation-inducing activities on MC3T3-1 cells. Furthermore, 1 suppressed induction of MC3T3-1 cell apoptosis by serum starvation.

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We characterized a new cytochrome P450 monooxygenase (P450), CYP724B2, from tomato (Lycopersicon esculentum). CYP724B2 showed 42% and 62% amino acid sequence identity with Arabidopsis DWARF4/CYPB1 and rice DWARF11/CYP724B1 respectively. Functional assay of CYP724B2 heterologously expressed in insect cells revealed that CYP724B2 catalyzes C- hydroxylation of campesterol, indicating that CYP724B2 is a C- hydroxylase. We also isolated a tomato CYPB homolog (CYPB3) and found that CYPB3 is a C- hydroxylase as well. CYP724B2 and CYPB3 showed substrate specificities similar to each other toward the biosynthetic intermediate compounds from campesterol to campestanol. Campesterol was the best substrate, and (24R)-ergost-4-en-3-one was also metabolized to the C- hydroxylated product to some extent. On the other hand, the P450s catalyzed C- hydroxylation of (24R)--ergostan-3-one and campestanol at a trace level, indicating that the compounds after C- reduction are poor substrates of CYP724B2 and CYPB3. In addition, cholesterol (C₂₇ sterol) and sitosterol (C₂₉ sterol) were also converted to C- hydroxylated products by the P450s. Furthermore, CYP724B2 and genes were ubiquitously expressed, and their transcript levels were down-regulated by the exogenous application of brassinolide. These findings strongly suggest that CYP724B2 and CYPB3 function in the early C- hydroxylation steps of brassinosteroid biosynthetic pathway in tomato.

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Possible individual variations in the sympathetic nervous system response to sound stimuli were investigated using the auditory evoked plethysmogram response (AEPGR). This study consists of the following 3 experiments; (EXP 1) the sound level-response relationships between white noise at 50, 70, and dB (A) and AEPGRmax as defined below, (EXP 2) individual variations of AEPGRmax to white noise at dB (A), and (EXP 3) the relationship between the AEPGR pattern and the urinary catecholamine (CA) excretion rate during sleep on the preceding night. The subjects were 35 young persons in (EXP 1), and 79 young (18-28yrs. old) and 35 old (60-yrs. old) persons in (EXP 2) and (EXP 3), respectively.
The results were: (1) a good sound level-response relationship between the sound levels of 50, 70, and dB (A) and AEPGRmax was obtained on average; (2) an AEPGRmax of more than 100% in response to the dB (A) white noise was found in about 10% of the subjects, whereas it was below 100% in % of them. The time prior to the maximum response in the former case varied from 4.6 to .2sec, which was quite a contrast to that of 3.0-9.0sec in the latter case; (3) The NE (norepinephrine), (epinephrine) and DA (dopamine) excretion rates were shown to be significantly higher in the former group in (2) than in the other groups, regardless of adjustment for age, blood pressure and/or ECG findings.
Thus, it is suggested that the cardiac response to secreted from the adrenals due to white noise stimuli was predominant in the former group in (2). Therefore, this response pattern was called the AEPGR“βtype”, whereas the other group was designated the“αtype”, since its AEPGR appeared to reflect only vasoconstriction. The suggested individual differences in AEPGR associated with increased night-rest catecholamine secretion were also discussed in relation to their possible relevance to chronic stress, neuroticism and other conditions.

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