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Supplementary Data I from Deletion of the COOH-Terminal Domain of CXC Chemokine Receptor 4 Leads to the Down-regulation of Cell-to-Cell Contact, Enhanced Motility and Proliferation in Breast Carcinoma Cells

The CXC chemokine receptor 4 (CXCR4) contributes to the metastasis of human breast cancer cells. The CXCR4 COOH-terminal domain (CTD) seems to play a major role in regulating receptor desensitization and down-regulation. We expressed either wild-type CXCR4 (CXCR4-WT) or CTD-truncated CXCR4 (CXCR4-ΔCTD) in MCF-7 human mammary carcinoma cells to determine whether the CTD is involved in CXCR4-modulated proliferation of mammary carcinoma cells. CXCR4-WT-transduced MCF-7 cells (MCF-7/CXCR4-WT cells) do not differ from vector-transduced MCF-7 control cells in morphology or growth rate. However, CXCR4-ΔCTD-transduced MCF-7 cells (MCF-7/CXCR4-ΔCTD cells) exhibit a higher growth rate and altered morphology, potentially indicating an epithelial-to-mesenchymal transition. Furthermore, extracellular signal-regulated kinase (ERK) activation and cell motility are increased in these cells. Ligand induces receptor association with β-arrestin for both CXCR4-WT and CXCR4-ΔCTD in these MCF-7 cells. Overexpressed CXCR4-WT localizes predominantly to the cell surface in unstimulated cells, whereas a significant portion of overexpressed CXCR4-ΔCTD resides intracellularly in recycling endosomes. Analysis with human oligomicroarray, Western blot, and immunohistochemistry showed that E-cadherin and Zonula occludens are down-regulated in MCF-7/CXCR4-ΔCTD cells. The array analysis also indicates that mesenchymal marker proteins and certain growth factor receptors are up-regulated in MCF-7/CXCR4-ΔCTD cells. These observations suggest that (a) the overexpression of CXCR4-ΔCTD leads to a gain-of-function of CXCR4-mediated signaling and (b) the CTD of CXCR4-WT may perform a feedback repressor function in this signaling pathway. These data will contribute to our understanding of how CXCR4-ΔCTD may promote progression of breast tumors to metastatic lesions. (Cancer Res 2006; 66(11): 5665-75)

Objective: The aim of this study was to examine the effects of nutrition education programme using the Convenient, Attractive, Normative (CAN) framework to facilitate changes in mindset, attitudes and behaviours towards food among high-school male baseball players. Design: Quasi-experimental design. Setting: Two public high schools in Osaka, Japan. Methods: Students in two high schools (mean age ± SD, 16.6 ± .5 years) participated in the study. One school served as an intervention group ( n = 28) and received the CAN nutrition education programme. The other school served as a control group ( n = 22), and students within it did not receive the intervention. Students in the intervention group received three nutrition lecture sessions and face-to-face individual nutritional guidance over a 4 month intervention period. Before and after the intervention, all students were asked to record their food and beverage intake by taking food pictures, recording portion weights and sending these to the project dietitian. They were also asked to develop a dietary behaviour plan for meeting their goals. At the end of the intervention, they were asked about their experiences. Results: Students in the intervention improved their food intake, dietary balance and athletic performance. Bat swing speed was significantly faster following the intervention. Body weight increased without changing lean body mass in both groups. Conclusion: Results suggest that a CAN nutrition education programme may be effective in increasing motivation and promote dietary behaviour change among male adolescent athletes. Future interventions should examine these motivational processes and investigate the factors contributing to well-balanced meals.

BACKGROUND Clinical studies have clarified the usefulness of moisturizers for dry skin diseases. However, few reports exist on the appropriate application of moisturizers with respect to the skin physiological functions. AIMS To clarify the optimal moisturizer application method on the basis of skin physiological functions. METHODS This study investigated the appropriate time, dose, and frequency of moisturizer application from the perspective of skin physiology. In healthy subjects, the stratum corneum water content (SCW) was compared between different moisturizer application times (immediately [≤5 min] and 90 min after bathing), doses (0.5, 1.0, and 2.0 mg/cm2 ), and frequencies (once and twice daily). Thereafter, patients with dry skin were treated with the moisturizer once or twice daily for 8 weeks at the time, and application dose was determined to be optimal for the healthy subjects; the moisturizing effect was evaluated based on the SCW, trypsin activity, and desmoglein 1 localization score in the stratum corneum. RESULTS In healthy subjects, compared to at control sites, the SCW was significantly higher at sites treated with the moisturizer immediately after bathing, with 1.0 and 2.0 mg/cm2 of the moisturizer, and with once- and twice-daily applications. In patients with dry skin, the SCW was significantly higher compared to control sites and the desmoglein 1 localization score was significantly lower after 8 weeks only when the moisturizer was applied twice daily. CONCLUSIONS Moisturizer application of ≥1.0 mg/cm2 twice daily (immediately after bathing at night and in the morning) had a moisturizing effect, as verified from the skin physiological functions.

Aim Stress during the perinatal period may result in failure to thrive in the newborn. A possible preventive effect of two kampo formulae, saikokaryukotsuboreito (SRB) and hachimijiogan (HJG) on the incidence of hind-leg paraparesis and mortality in newborns, including that due to maternal cannibalism, were examined in neurotoxin-treated rats. Methods Female Wistar/ST rats treated with SRB or HJG during pregnancy and the lactation period were separated from their pups for 6 h daily and then reunited. The pups were treated daily with a neurotoxin, l-β- N -oxalyl-α,β-diaminopropionic acid (l-β-ODAP), to cause neurolathyrism-like symptoms, a motor defect leading to hind-leg paraparesis. Results Although SRB and HJG treatment in mother rats did not affect the incidence of motor defect (paraparesis) in the pups, pup mortality was greatly and significantly decreased during the treatment period in the SRB group but not in the HJG group. Conclusion SRB treatment in mother rats is effective in decreasing pup mortality mainly due to cannibalism, thus suggesting its potential for anxiety disorder during the perinatal period in humans.

Aim The Great East Japan Earthquake and in particular, the Fukushima Daiichi Nuclear Power Plant accident, have had a serious psychological impact on not only residents, but also relief workers in Fukushima. Although public employees work in highly stressful situations and play a very important role in long-term relief, their psychiatric features have yet to be clarified. The two aims of this study were to identify the current prevalence rate of depression and post-traumatic stress disorder among public employees working in the disaster area using diagnostic interviews, and to speculate on the psychosocial factors affecting their mental condition. Methods We conducted diagnostic interviews and self-administered questionnaires with 168 public employees working in two coastal towns in Fukushima. Results Results showed that the current prevalence of depression among public employees is as high as 17.9%, in contrast to the relatively low prevalence of post-traumatic stress disorder (4.8%). Based on the results of self-administered questionnaires and interview contents, frequent exposure to strong complaints or anger from residents and role conflicts were considered the cause of the high prevalence of depression. Conclusion The present study reveals the serious mental status of public employees working in Fukushima and sheds light on the urgent need to establish an efficient care network to provide adequate psychiatric intervention.

The expression of Notch in 30 cases of pleomorphic adenoma was examined by immunohistochemistry. Comparing the results of our study with previous literatures, from the partial CK7 expression and substantial Notch expression in ductal epithelial cells as well as the Notch expression in solid tumor nests, it can be inferred that Notch is involved in cell differentiation. CK13 expression was observed in cells undergoing squamous metaplasia and Notch expression was seen in the nucleus of basal and squamous cells. The intense Notch expression in basal cells and weak expression in squamous cells suggests that Notch is involved in the differentiation from basal to squamous cell. Moreover, the loss of nuclear expression on the inner layer would signify that differentiation is about to end or has been terminated. Notch was expressed in the cytoplasm of cartilage cells and in the cell membrane of mucous cells but not in the nucleus indicating that differentiation has been concluded. Notch involvement is suspected in cell differentiation in areas showing ductal structures and squamous metaplasia. In summary, Notch is involved in cell differentiation of ductal cells in PA. Nuclear expression was shown in tumor cells in solid nests and surrounding structures. Moreover, Notch is expressed by basal cells undergoing squamous metaplasia suggesting the participation of Notch in cell differentiation in PA.

Aim Within the Kampo medical system, there exists a system specific to Japan of abdominal diagnosis called abdominal palpation, or Fukushin, which is used to obtain a holistic picture, called an abdominal pattern, of the physical indications in the abdominal area. In order to educate students in this system, we have devised and continued to develop a Fukushin simulator, incorporating various improvements as appropriate. The present study describes some recent additions to the model with the aim of increasing its applicability across a broad range of abdominal patterns. Methods The simulator is modeled on the abdomen of a healthy adult man, from which we took a mold using flexible silicon resin. To increase the resistance in some areas, we used urethane foam mixed with silicon rubber or attached parts consisting of silicon rubber; to reduce the resistance to pressure in other areas, we used urethane foam in small quantities. Results By such adjustments, we were able to reproduce patterns seen frequently in abdominal palpation, that is, stuffiness and rigidity below the heart, rectus muscle tension, fullness in the chest and hypochondrium, and lower abdominal fullness, each marked by localized increases in resistance to touch; and lower abdominal numbness, marked by a localized reduction in resistance to touch. Conclusion It is expected that the simulator will make an important contribution not only to medical education but also to the standardization of abdominal diagnosis.

We present seven cases of a relatively rare swan neck deformity resulting from chronic radial collateral ligament (RCL) injury of the proximal interphalangeal (PIP) joint in the little finger. All patients were middle-aged women (mean 51 years old, range 42–55), and the duration between the initial injury and surgery was 20 years (range 5–40). The chief complaint was painful snapping of the PIP joint. All patients had hyperextension and ulnar deviation of the PIP joint with mobile swan neck deformities that had not improved with conservative treatment. Radiographs revealed osteoarthritis and ulnar deviation of the PIP joints in all cases. We describe a method for reconstruction of both the palmar plate and the RCL of the affected PIP joint using a distally-based ulnar slip of flexor superficialis tendon. The prevention of PIP joint hyperextension was critical for successful resolution of symptoms; the aim of RCL augmentation was to prevent the recurrence of the deformity. Level of evidence: IV

Introduction: Randomized usual-case controlled studies on Japanese dementia patients with behavioral and psychological symptoms were conducted to examine the effects of Kampo medicine Yokukan-San (YKS) on the behavioral and psychological symptoms of dementia (BPSD). These studies showed that YKS is effective in treating BPSD. Yokukan-San-Ka-Chimpi-Hange is a Kampo medicine made by adding dried citrus peel and pinellia tuber to YKS. In Japan, we usually administer Yokukan-San-Ka-Chimpi-Hange as Kracie Yokukan-San-Ka-Chimpi-Hange extract granules (KB-83), produced by Kracie Pharma, Ltd. (Tokyo, Japan). Methods: We investigated 3 trials carried out on the use of KB-83 for the treatment of severe dementia in elderly. Results: KB-83 showed no change in core symptoms after administration in cases of dementia, but significant improvements in BPSD were reported. KB-83 was particularly effective in treating aggressive symptoms such as restlessness or abusive language. Conclusion: In the treatment of dementia, we think that the administration of KB-83 is effective in mitigating the BPSD, and that further studies are need to investigate the effects of EK-83.

専業主婦については、活動量や運動量の制限などが報告されている一方、若年期からの地域とのつながりにより外出頻度は維持されやすいと考えられる. そこで高齢者で報告されている外出頻度と主観的健康感との関連が専業主婦でもみられるのか、年齢による影響を明らかにすることを目的とした. 研究は大阪府堺市南区の一地区内の全世帯(3,069世帯)に無記名自記式の質問紙調査を行い、回答数1,820(回収率58.0%)の中から専業主婦701名を分析対象とした. 質問項目は最近1週間の外出頻度、主観的健康感について尋ねた. その結果、外出頻度は60代、70代後半、80代以上と段階的に減少した. 主観的健康感は加齢とともに不安あり群が増加した. 外出頻度と主観的健康感の関連は50代以上で外出頻度が減少するとともに主観的健康感が低下する傾向を認めた. 以上より、健康維持、増進のためには50代から年代ごとの取り組みが必要であることが示唆された., Physical activity levels and the amount of exercise in housewives are reportedly low; however, a high frequency of outings is likely to be maintained due to connection with local residents. This study aimed to identify the relationship between the frequency of outings and self-rated health in housewives, and investigate age-related effects. Anonymous self-administered questionnaires were distributed to 3,069 households in one district of Minami-ku, Sakai-shi, Osaka, and, of the 1,820 responses (response rate: 58.0%), 701 housewives were analyzed. Questionnaire items included the frequency of outings and self-rated health over the past one week. As the results of the questionnaire, the frequency of outings gradually decreased as the age advanced from their 60s to 80s or over. Regarding self-rated health, the number of subjects with anxiety increased with age. Among the subjects aged 50 or over, there was a decreasing trend in the frequency of outings and self-rated health. The findings suggest the need to take appropriate measures to maintain and promote the health of housewives aged 50 and over according to their age group.

学校や一般社会で健康教育活動を将来担う大学生を対象として，漢方医学についての講義を行う機会があった。このような学生に対する漢方医学教育の目標の設定は検討されていない。我々は漢方医学の必要性を理解し，将来これに関する適切な助言ができることを目標として講義を行った。講義の前後のアンケート調査を検討すると，漢方医学に関する我々の考えている望ましい認識は講義前の58.0 ± 15.4％から講義には88.5 ± 10.2％と増加した。現在行われている漢方医学の有用性に関しては，極めて有用，あるいは有用という認識に関して，講義前は58.4％であったが，講義後には95.9％となった。講義により漢方医学に関する充分な認識にもとづいて，将来，彼らが学校や社会において，漢方医学に関しても適切な健康教育活動を行うことが期待される。

Rizzi(1997) proposed a sprit CP system on the basis of the syntactic facts of Italian discourse elements on left periphery such as topic and focus. This paper explores the Japanese CP system by means of the right peripheral elements such as modal forms an

To evaluate the use of receipt information in the strategic management of lifestyle related diseases under healthcare system reforms, we investigated the use of National Health Insurance (NHI) receipts in B City of A Prefecture.Receipt information was compiled and analyzed. The status of participation in NIH programs and status of diabetes and diabetes-related disorders was ascertained to identify target patients for diabetes management. Coexisting disorders were analyzed to identify those requiring points for management. In addition, diagnosis and treatment facilities were reviewed to identify medical institutions that should be linked in managing diabetes care, and household units were reviewed to establish directions for family health education in cooperation with medical institutions.These results indicate that use of receipt information is essential with respect to specific health check up and guidance. The analysis methodology and data in our study can be used to examine strategic management of lifestyle related diseases at the regional level.

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn disease (CD), is a disorder characterized by diffuse inflammation of the gastrointestinal tract. The immune response and inflammation are mediated by polyunsaturated fatty acids and influenced by dietary fats and lipid metabolism. This study examined the qualitative and quantitative fat intake of IBD patients and healthy controls on plasma phospholipid and erythrocyte membrane phospholipid (EMP) fatty acid content. Measurement of the fatty acid composition of plasma phospholipid and EMP were performed in 29 UC patients, 20 CD patients, and 31 healthy controls. Anthropometric characteristics and data on dietary intake were also collected. We observed significantly lower lipid intake in UC and CD patients vs controls. The UC and CD patients had significantly higher levels of linoleic acid in their EMP than did controls. There were no significant differences in the levels of n-3 polyunsaturated fatty acids, but there were significantly higher levels of the n-6 in the EMP of UC and CD patients compared with controls. The significant differences persisted after the data were adjusted for potential confounders and lipid intake. Higher levels of linoleic acids and n-6 fatty acids, which are involved in production of proinflammatory mediators, were found in IBD patients compared with controls, thereby implicating n-6 fatty acids in the pathophysiology of the disease.

Japanese modality has been one of the hottest issues in traditional Japanese linguistics. It has been explored in the round and mainly discussed semantically and pragmatically. This paper argues for assuming at least two independent phrasal categories headed by modal forms, Utterance-modal Phrase (henceforth U-modalP) and Epistemic-modal Phrase (henceforth E-modalP), in terms of the following three points: (i) their occurrence in an embedded clause, (ii) person restrictions and (iii) the EPP-satisfaction in C. We would not presume to criticize previous meaning-based fruitful outcomes, but attempt to focus our attention on forms and syntactic positions of Japanese modals.

The Great East Japan Earthquake and in particular, the Fukushima Daiichi Nuclear Power Plant accident, have had a serious psychological impact on not only residents, but also relief workers in Fukushima. Although public employees work in highly stressful situations and play a very important role in long-term relief, their psychiatric features have yet to be clarified. The two aims of this study were to identify the current prevalence rate of depression and post-traumatic stress disorder among public employees working in the disaster area using diagnostic interviews, and to speculate on the psychosocial factors affecting their mental condition.We conducted diagnostic interviews and self-administered questionnaires with 168 public employees working in two coastal towns in Fukushima.Results showed that the current prevalence of depression among public employees is as high as 17.9%, in contrast to the relatively low prevalence of post-traumatic stress disorder (4.8%). Based on the results of self-administered questionnaires and interview contents, frequent exposure to strong complaints or anger from residents and role conflicts were considered the cause of the high prevalence of depression.The present study reveals the serious mental status of public employees working in Fukushima and sheds light on the urgent need to establish an efficient care network to provide adequate psychiatric intervention.

It is widely recognized that tobacco smoke causes skin pigmentation. No studies, however, have directly evaluated the mechanisms of the changes in smoker's skin pigmentation. In this study, when cultured with water-soluble tobacco smoke extract, the human epidermal melanocytes grew to a large size and produced more melanins. We evaluated melanocyte activation by quantifying microphthalmia-associated transcription factor (MITF) expression by real-time polymerase chain reaction. MITF expression was significantly and dose-dependently increased by exposure to tobacco smoke extract. The Wnt/β-catenin signalling pathway seemed to mediate the tobacco smoke extract-induced melanocyte activation. Immunocytochemical studies revealed that the activated melanocytes actively expressed aryl hydrocarbon receptors (AhR) around the nuclear membrane. The tobacco smoke extract-induced MITF activation was inhibited by RNA silencing of the AhR. This study provides the evidence that tobacco smoke enhances pigmentation in vitro and that the increase in pigmentation may involve β-catenin- and AhR-mediated mechanisms inside human melanocytes.

Ueda (2000, 2002, 2003a, 2003b) propose a new scope calculation system named a phase-based approach. The new system treats scope calculation as a feature-matching operation in C_. We call this matching operation F_-matching. On the basis of our new approach to scope calculation, this paper explores scope interpretation in sentences with floating quantifiers (henceforth FQs), focusing on the case in which FQs appear in the subject position. We call subjects of this type FQ subjects. We observe interesting scope phenomena concerning FQs, which are problematic data for previous analyses. It is demonstrated that the mysterious scope facts in FQ subject constructions with and without scrambling are reducible to our phase-based approach.

This paper proposes a new scope calculation system named a phase-based approach. The new system treats scope calculation as a feature-matching operation between more than one interpretable feature related to quantification (henceforth F_). We call this matching operation F_-matching. It is shown that the working space of F_-matching is restricted by a syntactic unit phase. Given the matching operation for scope calculation in C_, scope interpretation can be derivationally determined In narrow syntax as far as it is permitted by the Phase Impenetrability Condition (PIC) proposed in Chomsky (2001). It is demonstrated that various mysterious scope facts in both English and Japanese are reducible to our phase-based scope system without any other special implement.

Niemann–Pick C1-like 1 (NPC1L1), ATP-binding cassette (ABC)G5, and ABCG8 are all involved in intestinal cholesterol absorption. It is unclear whether a high-cholesterol (HC) diet affects the expression of these transporters in rats and mice as well as humans. We examined the effects of an HC diet on their expression in small intestine and the differences between rats and mice in the responsive of this expression to an HC diet. In addition to these transporters, alterations in six representative drug and nutrient transporters (multidrug resistance-associated protein, breast cancer resistance protein, peptide transporter, sodium-glucose linked transporter, glucose transporter, and l-type amino acid transporter) and transcriptional factors such as hepatocyte nuclear factor (HNF)4α, sterol regulatory element-binding protein (SREBP)2, and liver X receptor (LXR)α were determined. In rats and mice fed an HC diet for 7 days, the mRNA and protein levels of NPC1L1 in the small intestine were determined by real-time reverse transcription polymerase chain reaction and western blotting, respectively. The mRNA levels of ABCG5 and ABCG8, six representative transporters, and transcriptional factors such as HNF4α, SREBP2, and LXR were examined. Significant decreases in the expression levels of NPC1L1 were observed in mice, but not rats, fed the HC diet. The mRNA levels of ABCG5 and ABCG8 were significantly increased in HC rats but not in mice. Only minor changes in the mRNA levels of the other transporters were seen in HC rats and mice. Decreased mRNA levels of HNF4α and SREBP2 in mice could be involved in the reduction in NPC1L1 expression observed upon the introduction of an HC diet. These results indicate that the effects of an HC diet on the expression levels of NPC1L1, ABCG5, and ABCG8 differ between mice and rats.

This paper provides some evidence for the non-movement hypothesis that Japanese nominals are licensed in situ and do not undergo movement for Case-feature checking (Fukui 1986,Takano 1996,Ikawa 1997,and Fukui and Takano 1998). We focus on three scopal contrasts between English and Japanese : (i) scope rigidity in Japanese, (ii) distribution of Negative Polarity Items (henceforth NPIs) and Positive Polarity Items (henceforth PPIs) in negative sentences, and (iii) lack of scope ambiguity between an o-marked Accusative object and a Postpositional phrase in Japanese. Those facts are simultaneously accounted for by the assumption that Japanese nominals undergo no movement from a theta-position to a Case-checking position. This leads one to conclude that Japanese has no Agr projection.

Serum concentrations of carotenoids, such as β-carotene, α-carotene, lycopene, cryptoxanthin, and lutein/zeaxanthin, and additionally the concentrations of retinol and α-tocopherol, were investigated by high-performance liquid chromatography (HPLC) of samples from 90 Japanese (56 males and 34 females) who took part in a mass examination held in 1997. At the same time, their serum lipid peroxides were measured by the hemoglobin-methylene blue (Hb-MB) method. Serum α-carotene, β-carotene, cryptoxanthin, and total carotenoids were significantly higher in females (151.6±23.8 pmol/ml, 327.8±58.4 pmol/ml, 375.4±97.8 pmol/ ml, and 1.9±0.3 nmol/ml, respectively) than in males (84.1±11.5 pmol/ ml, 120.0±15.6 pmol/ml, 135.0±18.2 pmol/ml, and 1.3±0.1 nmol/ml, respectively). These differences may be mainly due to increased intake of carotenoids in females. On the other hand, serum lipid peroxides in females were 81% of those in males. There was no correlation between fat-soluble vitamins and lipid peroxides in males and females. In the subjects high in serum total-cholesterol (≥ 220 mg/dl), there was a negative correlation between lipid peroxides and lycopene in the females, suggesting that lipid peroxidation in the serum of females high in total-cholesterol may be inhibited by the fat-soluble antioxidant lycopene.

This chapter explores relative scope phenomena cross‐linguistically. First, we observe the facts that the head licensing each QP is closely related to the possibility of creating inverse scope readings in English, Greek/Catalan, and Japanese and further point out that the relative scope interpretation does not rely on whether the languages undergo Quantifier Raising (henceforth QR) or not. The facts observed in the three languages lead us to a new scope calculation system, named a phase‐based approach, and provide further evidence for the purely syntactic scope system. The system treats inverse scope calculation as a feature‐matching operation between more than one interpretable feature related to quantification. We call this matching operation F‐quant matching. The operation is restricted by syntactic unit phases and is subject to the Phase Impenetrability Condition. Given the matching operation, scope interpretation can be determined in the following two ways: (i) c‐command relation between QPs at the end of a derivation D, namely, the LF‐input structure, (ii) through F‐quant matching in a derivation D. As a result, if (i) and (ii) predict different scope relations, then the sentence is ambiguous. If (i) and (ii) predict the same scope relation, then the sentence is unambiguous. Different scope phenomena between languages follow from a currently acknowledged basic apparatus for structure building, match, and the PIC, without any other special implement.

This paper discusses the reconstruction effects and binding of zibun in relative clause head positions. We propose two different structures for "zibun no X" : AGENT zibun is in Spec of DP; non-AGENT zibun (e. g. THEME zibun) is a sister position of the relative clause. We claim that the relative clauses with AGENT zibun are derived by IP scrambling at S-Structure. This structural relation between the scrambled relative clause and its head is very similar to nonrestrictive relatives. Thus, we will conclude, at least, that a relative clause with AGENT zibun is non-restrictive one. By assuming our proposed structure of relative clauses and the obligatory undoing of the scrambled IP in the sense of Saito (1992), the disjoint interpretation between zibun and the subject in the relative clause results from the condition (C) type of reconstruction effects.

Obesity is associated with increased markers of oxidative stress. We examined whether oxidative stress is reduced within the first week after Roux-en-Y gastric bypass (RYGB) surgery and could be related to changes in adipose tissue depots. The reactive oxygen species (ROS) marker 8-iso-prostaglandin F2α (8-iso-PGF2α) and activity of antioxidant glutathione peroxidases (GPX) in plasma were compared before and ~1 week after RYGB. The effects of RYGB on subcutaneous adipose tissue and interstitial fluid 8-iso-PGF2α levels and subcutaneous adipose tissue expression of GPX-3 were also assessed. Levels of 8-iso-PGF2α in subcutaneous and visceral adipose tissue were determined. Plasma 8-iso-PGF2α levels decreased (122 ± 75 to 56 ± 15 pg/ml, P = 0.001) and GPX activity increased (84 ± 18 to 108 ± 25 nmol/min/ml, P = 0.003) in the first week post-RYGB. RYGB also resulted in reductions of 8-iso-PGF2α in subcutaneous adipose tissue (1,742 ± 931 to 1,132 ± 420 pg/g fat, P = 0.046) and interstitial fluid (348 ± 118 to 221 ± 83 pg/ml, P = 0.046) that were comparable to plasma (26–33%, P = 0.74). Adipose GPX-3 expression was increased (6.7 ± 4.7-fold, P = 0.004) in the first postoperative week. The improvements in oxidative stress occurred with minimal weight loss (2.4 ± 3.4%, P = 0.031) and elevations in plasma interleukin-6 (18.0 ± 46.8 to 28.0 ± 58.9 pg/ml, P = 0.004). Subcutaneous and visceral adipose tissues express comparable 8-iso-PGF2α levels (1,204 ± 470 and 1,331 ± 264 pg/g fat, respectively; P = 0.34). These data suggest that RYGB affects adipose tissue leading to the restoration of adipose redox balance within the first postoperative week and that plasma 8-iso-PGF2α is primarily derived from subcutaneous adipose tissue.

Objective The aim of the present study was to evaluate the effects of dietary zinc deprivation on zinc concentration, the activity of angiotensin converting enzyme (ACE) and ratio of apo/holo-activities of ACE (ACE ratio) in the serum of mice. Methods Twenty-two male mice were deprived of dietary zinc for up to 9 days. Zinc concentration in the serum was measured by means of atomic absorption spectrometry. Also, the activity of ACE in the serum was measured by HPLC as the activity of holo-ACE. After addition of zinc to the serum in vitro, the increase of ACE activity over the initial value was determined as that of apo-ACE. Finally, the ratio of apo/holo-ACE activities was calculated. Results There was a significant decrease of zinc concentration, but a slight decrease of the activity of ACE in the serum of mice by intake of zinc-deficient diet for 9 days. ACE ratio tended to increase on day 5 and was significantly increased on day 9 in mice deprived of dietary zinc. Conclusion These findings suggest that ACE ratio is as sensitive as serum zinc concentration for the evaluation of zinc deficiency and can be used for the biochemical diagnosis of zinc nutritional status in patients with zinc deficiency-induced taste impairment.

Nutrition may play an important role in the pathogenesis and treatment of ulcerative colitis. Several studies suggest an association between dietary factors and the onset of ulcerative colitis; however, only few studies have examined the relationship between dietary intake and relapse of ulcerative colitis. The aim of this study was to assess the dietary intake and antioxidative capacity of ulcerative colitis patients and to elucidate the efficacy of dietary therapy for ulcerative colitis. Dietary intake, fatty acid composition of phospholipids in plasma and neutrophils, serum fat-soluble vitamin levels, and oxygen radical absorbance capacity were analyzed in 29 ulcerative colitis patients (7 males and 22 females), who were treated at the Department of Gastroenterology, Okayama University Hospital. Total fat intake, fat energy ratio and linoleic acid intake were significantly lower, while protein and carbohydrate intakes were significantly higher, in the patients than age- and sex-matched controls. In the neutrophil phospholipids of ulcerative colitis patients, significantly higher levels of linoleic aicd and arachidonic acid and a lower level of eicosapentaenoic acid were observed. The concentrations of serum retinol and beta-carotene but not alpha-tocopherol were significantly lower and serum oxygen radical absorbance capacity was also lower than in the controls. Significant correlations between serum oxygen radical absorbance capacity and retinol (r = 0.567, p = 0.0031), alpha-tocopherol (r = 0.560, p = 0.0036) and beta-carotene (r = 0.440, p = 0.0279) concentrations were observed in the ulcerative colitis patients. A diet restricting the intake of linoleic acid and supplemented with eicosapentaenoic acid and antioxidative vitamins may be recommendable for the nutritional management of ulcerative colitis patients.

Members of the nuclear factor-kappa beta (NF-kappaB) family maintain cellular homeostasis by enhancing the transcription of genes involved in inflammation, immune response, cell proliferation, and apoptosis. Melanoma tumor cells often express inflammatory mediators through enhanced activation of NF-kappaB. The NF-kappaB activation appears to result from the enhancer formation including NF-kappaB and lysine acetyl transferases such as p300, CREB (cyclic AMP-responsive element binding protein)-binding protein (CBP), and/or p300/CBP associating factor (PCAF). We observed that proteins expressed by Hs294T metastatic melanoma cells are highly acetylated compared with normal melanocytes, and dominant-negative PCAF reduced the basal and tumor necrosis factor-alpha-stimulated transcriptional activity of NF-kappaB. The promoter activity of NF-kappaB-regulated chemokines was also reduced by the expression of dominant-negative PCAF. The promoters of these chemokines contain a CCAAT displacement protein (CDP)-binding site near the NF-kappaB element. compared with vector-transduced cells, in CDP-transduced Hs294T cells: (i) over-expressed CDP bound efficiently to PCAF, (ii) tumor necrosis factor-alpha-stimulated chemokine expression and NF-kappaB-mediated transcription were reduced, and (iii) the binding of CBP to Rel A was reduced. These data suggest that CDP inhibits cytokine-induced NF-kappaB-regulated chemokine transcription. This study contributes to our understanding of the role of CDP in an enhanceosome of NF-kappaB-mediated chemokine transcription in human melanoma cells.

Metastatic melanoma is an aggressive skin cancer that is notoriously resistant to current cancer therapies. In human melanoma, nuclear factor-kappa B (NF-kappaB) is upregulated, leading to the deregulation of gene transcription. In this review, we discuss (i) the relationship between gene alteration in melanoma and upregulation of NF-kappaB, (ii) mechanisms by which activated NF-kappaB switch from pro-apoptotic to anti-apoptotic functions in melanoma and (iii) autocrine mechanisms that promote constitutive activation of NF-kappaB in metastatic melanoma.

1. The present study was undertaken to investigate the effect of smoking habits on dietary intake, serum oxygen radical absorbance capacity (ORAC) and lifestyle in Japanese adults. 2. Lifestyle factors were recorded by questionnaire and dietary intake was measured by a single 24 h food recall. Blood was collected under fasting conditions for analysis. 3. Smokers had lower intakes of vitamin C, fruits and dark green and yellow vegetables (DGYV), higher consumption of alcohol, lower physical activity and lower ORAC values than non-smokers. Body mass index (BMI), serum total cholesterol (TC) and triacylglycerol (TG) increased, whereas high-density lipoprotein-cholesterol (HDL-C) decreased with an increase in the amount smoked, but there were no significant differences between smokers and non-smokers. 4. It is considered that high cancer and cardiovascular risks among smokers are also reinforced by undesirable lifestyle factors other than smoking.