Gender-Specific Associations of Perceived Stress and Coping Strategies with C-Reactive Protein in Middle-Aged and Older Men and Women

Background

Perceived stress and coping strategies may influence the risk of cardiovascular disease through their possible association with inflammation, but data remain controversial for perceived stress or scanty for coping strategies.

Purpose

We examined the associations of perceived stress and coping strategies with serum high-sensitivity C-reactive protein (CRP) in a Japanese general population.

Methods

This cross-sectional study included 2,971 men and 4,902 women aged 40–69 years who were enrolled between 2005 and 2007. Subjects with possible inflammation-related disease, CRP levels ≥3,000 ng/mL, or currently used analgesics or lipid-lowering drugs were excluded. Analyses were performed by gender with adjustment for lifestyle, socioeconomic, and psychosocial factors.

Results

Unexpectedly, elevated perceived stress was significantly associated with lower CRP levels in men (P _trend?P _trend?=?0.90) after adjustment for age and covariates. Among five items of coping strategies evaluated, “disengagement” showed a significant inverse association with CRP in men only (P _trend?=?0.027). In addition, a possible interaction between “emotional support seeking” and perceived stress on CRP was detected in men (P _interaction?=?0.021); “emotional support seeking” was associated with lower CRP at the high stress level only (P _trend?=?0.028).

Conclusions

Both perceived stress and coping strategies may be associated with systemic inflammation in Japanese men, yet caution must be exercised before accepting the stress–inflammation–disease pathway.     

Human astrocytes express 14-3-3 sigma in response to oxidative and DNA-damaging stresses

The 14-3-3 protein family consists of seven isoforms, most of which are expressed abundantly in neurons and glial cells, although the sigma isoform, a p53 target gene originally identified as an epithelium-specific marker, has not been identified in the human central nervous system. Here, we show that human astrocytes in culture expressed 14-3-3sigma under stress conditions. By Western blot, the expression of 14-3-3sigma, p53 and p21 was coordinately upregulated in astrocytes following exposure to hydrogen peroxide, 4-hydroxy-2-nonenal (4-HNE) or etoposide, a topoisomerase II inhibitor. 14-3-3sigma was induced by treatment with 5-aza-2'-deoxycytidine, suggesting a hypermethylated status of the gene promoter in astrocytes. In vivo, a small subset of hypertrophic reactive astrocytes, often showing a multinucleated morphology, expressed 14-3-3sigma in active demyelinating lesions of multiple sclerosis (MS) and ischemic lesions of cerebral infarction, where the expression of 4-HNE and 8-hydroxy-2'-deoxyguanosine was enhanced in reactive astrocytes. Microarray analysis of etoposide-treated astrocytes verified upregulation of p53-responsive genes and concurrent downregulation of mitotic checkpoint-regulatory genes. These observations suggest that 14-3-3sigma might serve as a marker of oxidative and DNA-damaging stresses inducing the mitotic checkpoint dysfunction in reactive astrocytes under pathological conditions.     

Dietary Patterns and Serum Gamma-Glutamyl Transferase in Japanese Men and Women

Background

Although specific foods and nutrients have been examined as potential determinants of serum gamma-glutamyl transferase (GGT) concentrations, the relationship between dietary patterns and GGT remains unknown. The present cross-sectional study aimed to determine relationships between dietary patterns and GGT concentrations, and the effects of lifestyle factors on GGT.

Methods

Relationships between dietary patterns and GGT were analyzed in 9803 Japanese individuals (3723 men and 6080 women age 40–69 years) without a history of liver diseases or elevated serum aminotransferase. We examined major dietary patterns by factor analysis of 46 items determined from a validated, short food frequency questionnaire.

Results

We defined dietary patterns as healthy, Western, seafood, bread, and dessert. The healthy pattern was inversely related to GGT in men (odds ratio [OR] for highest vs lowest quartile, 0.72; 95% confidence interval [CI], 0.57–0.92; P < 0.01 for trend) and women (OR 0.82; 95% CI, 0.66–1.0; P = 0.05 for trend), whereas the seafood pattern was positively related to GGT in men (OR 1.27; 95% CI, 1.01–1.61; P = 0.03 for trend) and women (OR 1.21; 95% CI, 0.98–1.49; P = 0.05 for trend). Male-specific inverse associations with GGT were found for bread and dessert patterns (OR 0.63; 95% CI, 0.50–0.80 and OR 0.53; 95% CI, 0.41–0.68, respectively; P < 0.01 for both trends). Seafood or bread patterns and alcohol consumption significantly interacted with GGT in men (P = 0.03 and <0.01 for interaction, respectively) and between the dessert pattern and body mass index or smoking habit in women (P = 0.03 and <0.01, respectively, for interaction).

Conclusions

Dietary patterns may be important determinants of GGT, and their possible clinical implications warrant further investigation.Key words: dietary pattern, gamma-glutamyl transferase, factor analysis     

The combination therapy of α‐galactosylceramide and 5‐fluorouracil showed antitumor effect synergistically against liver tumor in mice

α‐Galactosylceramide (α‐GalCer) has been reported to be therapeutic against metastatic liver tumors in mice. However, little is known regarding the efficacy of combined chemo‐immunotherapy using α‐GalCer and anticancer drugs. In this study, we evaluated the antitumor effect of the combination therapy of α‐GalCer and 5‐fluorouracil (5‐FU) against liver tumors of MC38 colon cancer cells. The liver weights of tumor‐bearing mice treated with the combination were significantly lower than those of nontreated mice and of mice treated with 5‐FU or α‐GalCer alone. No toxic effects on the liver and renal functions were observed in any of the treatment groups. α‐GalCer treatment induced significant activation of liver NK cells in vivo, but 5‐FU treatment did not. 5‐FU treatment resulted in a significant upregulation of NKG2D activating molecules (Rae‐1 and H60) and DNAM‐1 ligands (CD112 and CD155) on MC38 cells, but α‐GalCer did not. The cytolytic activity of α‐GalCer‐activated liver mononuclear cells against 5‐FU‐treated MC38 cells was significantly higher than that against nontreated cells. The increase of the cytolytic activity induced by 5‐FU partially depended on NKG2D‐Rae‐1 or H60 signals. Depletion of NK cells significantly inhibited the antitumor efficacy of 5‐FU against MC38 liver tumors, which suggested that the antitumor effect of 5‐FU partially depended on the cytolytic activity of NK cells. These results demonstrated that the combination therapy of α‐GalCer and 5‐FU produced synergistic antitumor effects against liver tumors by increasing the expression of NK activating molecules on cancer cells. This study suggests a promising new chemo‐immunotherapy against metastatic liver cancer.     

Prevalence of deep venous thrombosis detected by ultrasonography before surgery in patients with gastric cancer: a retrospective study of 1140 consecutive patients

Background

The prevalence of deep venous thrombosis (DVT) in patients with gastric cancer before surgery is unknown. This study aimed to clarify the risk factors for DVT of the lower extremities in patients with gastric cancer before surgery and to evaluate the usefulness of ultrasonographic screening for prevention of postoperative pulmonary thromboembolism (PTE).

Methods

Patients who had undergone lower-extremity venous ultrasonography before surgery for gastric cancer were retrospectively analyzed. Univariate and multivariate logistic regression analyses were performed to identify the predictors of DVT before surgery. Perioperative management of patients with DVTs and the incidence of postoperative PTE were investigated.

Results

Of the total 1140 patients, 86 had DVT preoperatively. On univariate analysis, the incidence of DVT was significantly higher with: female sex; age ≥80 years; PS ≥ 1 (vs. PS = 0); stage IV (vs. stages I–III); history of preoperative chemotherapy; and the presence of a central venous catheter (CVC). Multivariate logistic regression analysis demonstrated that sex, age ≥80 years, PS ≥ 1, history of preoperative chemotherapy, and the presence of CVC were significantly correlated with DVT before surgery. Postoperative PTE occurred in 2 patients with proximal DVT. No patients in whom DVT was not detected developed PTE.

Conclusions

Female sex, older age, worse PS, the presence of CVC, and a history of preoperative chemotherapy were the independent risk factors for DVT. Routine lower-extremity venous ultrasonographic screening is useful for prevention of PTE because it can identify patients at high or low risk for PTE.

     

Availability of 2VO rats as a model for chronic cerebrovascular disease

We have established a chronic cerebral hypoperfusion model that is produced by permanent occlusion of bilateral common carotid arteries (2VO) in rats. 2VO rats exhibited rarefaction in the white matter, shrinkage of neurons in the cerebral cortex and hippocampus 1-3 days after 2VO and infarctions in the striatum 7 days after 2VO. These histological changes in the cortex and hippocampus were accompanied by a decrease in immunoreactivity for microtubule-associated protein 2 (MAP2). Immunoreactivity for glial fibrillary acid protein (GFAP) was observed at 3-7 days after 2VO. Marked increase in GFAP staining in astrocytes in the cerebral cortex and hippocampus was found 30 days after ligation. In the 8-arm radial maze performance, the 2VO rats showed a higher rate of errors than the sham-operated control during repeated training periods. THA (9-amino-1,2,3,4-tetrahydroacridine), a cholinesterase inhibitor and GTS-21 (3-(2,4-dimethoxybenzylidene)-anabaseine dihydrochloride), a central nicotinic acetylcholine-receptor agonist improved the learning impairment in the radical maze task of 2VO rats. GTS-21 administration exerted a protective effect against the neuropathological changes that followed 2VO. Taken together, the 2VO rat appears to be a useful model for investigating the pathophysiology of human dementia and to elucidate the therapeutic potential of drugs for this disease.     

Perfusion and mechanical analysis with technetium-99m 2-methoxy-isobutyl-isonitrile in a case of dilated cardiomyopathy

With technetium-99m 2-methoxy-isobutyl-isonitrile (99mTc-MIBI), regional wall thickening in a patient with dilated cardiomyopathy was analyzed by the first component Fourier method. The regional wall thickening was compared with thallium-201 and 99mTc-MIBI SPECT imaging. Thallium-201 SPECT images showed mildly reduced perfusion in the posterior wall and redistribution in the septum, whereas 99mTc-MIBI images showed heterogeneous accumulation around the left ventricular circumference. By means of phase analysis, diffusely decreased wall thickening and discontinuity of percent wall thickening in neighboring segments were observed throughout the left ventricle. Regional wall motion and wall thickening correlated roughly. However, discrepancies between the mechanical function and myocardial perfusion, and discrepancies in regional myocardial perfusion between thallium-201 and 99mTc-MIBI were observed.     

Temporal course of the development of obesity in Japanese school children: a cohort study based on the Keio Study.

OBJECTIVE: To demonstrate the temporal course of obesity development in Japanese school children by conducting a school-site cohort study over 12 years. METHODS: From 1981 to 1984, height and weight of 479 subjects (343 boys and 136 girls) were measured every year from entrance into primary school until graduation from high school in Tokyo. Obese children were defined as those with a body mass index (BMI) at or above the age-sex-specific standard value, derived from Japanese nationwide data. RESULTS: Approximately 50% of the children who were obese in the primary school period were obese at age 17. Likewise, 40% who were obese in the junior high school period and 70% who were obese in the high school period were obese at age 17. Among 44 children who were obese at age 17, 14 showed tracking of obesity from the preschool period, 14 showed tracking from ages 7 to 11 years, 10 showed tracking from the junior high school period, and 6 showed tracking from the high school period. CONCLUSIONS: Among children who were obese at age 17, most tracked from the primary school age or earlier. The earlier the tracking commenced, the greater the BMI at age 17. This indicates the importance of conducting health education for school children at an early age.