bluuebunny/crossref_metadata_2025 huggingface dataset:
THAP5 is a human cardiac-specific inhibitor of cell cycle that is cleaved by the proapoptotic Omi/HtrA2 protease during cell death
Authors: Balakrishnan Meenakshi P. , Cilenti Lucia , Mashak Zineb , Popat Paiyal , Alnemri Emad S. , Zervos Antonis S.
Published: June 2009

Omi/HtrA2 is a mitochondrial serine protease that has a dual function: while confined in the mitochondria, it promotes cell survival, but when released into the cytoplasm, it participates in caspase-dependent as well as caspase-independent cell death. To investigate the mechanism of Omi/HtrA2's function, we set out to isolate and characterize novel substrates for this protease. We have identified Thanatos-associated protein 5 (THAP5) as a specific interactor and substrate of Omi/HtrA2 in cells undergoing apoptosis. This protein is an uncharacterized member of the THAP family of proteins. THAP5 has a unique pattern of expression and is found predominantly in the human heart, although a very low expression is also seen in the human brain and muscle. THAP5 protein is localized in the nucleus and, when ectopically expressed, induces cell cycle arrest. During apoptosis, THAP5 protein is degraded, and this process can be blocked using a specific Omi/HtrA2 inhibitor, leading to reduced cell death. In patients with coronary artery disease, THAP5 protein levels substantially decrease in the myocardial infarction area, suggesting a potential role of this protein in human heart disease. This work identifies human THAP5 as a cardiac-specific nuclear protein that controls cell cycle progression. Furthermore, during apoptosis, THAP5 is cleaved and removed by the proapoptotic Omi/HtrA2 protease. Taken together, we provide evidence to support that THAP5 and its regulation by Omi/HtrA2 provide a new link between cell cycle control and apoptosis in cardiomyocytes.
sGCα1β1attenuates cardiac dysfunction and mortality in murine inflammatory shock models
Authors: Buys Emmanuel S. , Cauwels Anje , Raher Michael J. , Passeri Jonathan J. , Hobai Ion , Cawley Sharon M. , Rauwerdink Kristen M. , Thibault Helene , Sips Patrick Y. , Thoonen Robrecht , Scherrer-Crosbie Marielle , Ichinose Fumito , Brouckaert Peter , Bloch Kenneth D.
Published: June 2009

Altered cGMP signaling has been implicated in myocardial depression, morbidity, and mortality associated with sepsis. Previous studies, using inhibitors of soluble guanylate cyclase (sGC), suggested that cGMP generated by sGC contributed to the cardiac dysfunction and mortality associated with sepsis. We used sGCα1-deficient (sGCα1−/−) mice to unequivocally determine the role of sGCα1β1in the development of cardiac dysfunction and death associated with two models of inflammatory shock: endotoxin- and TNF-induced shock. At baseline, echocardiographic assessment and invasive hemodynamic measurements of left ventricular (LV) dimensions and function did not differ between wild-type (WT) mice and sGCα1−/−mice on the C57BL/6 background (sGCα1−/−B6mice). At 14 h after endotoxin challenge, cardiac dysfunction was more pronounced in sGCα1−/−B6than WT mice, as assessed using echocardiographic and hemodynamic indexes of LV function. Similarly, Ca2+handling and cell shortening were impaired to a greater extent in cardiomyocytes isolated from sGCα1−/−B6than WT mice after endotoxin challenge. Importantly, morbidity and mortality associated with inflammatory shock induced by endotoxin or TNF were increased in sGCα1−/−B6compared with WT mice. Together, these findings suggest that cGMP generated by sGCα1β1protects against cardiac dysfunction and mortality in murine inflammatory shock models.
20-HETE can act as a nonhypoxic regulator of HIF-1α in human microvascular endothelial cells
Authors: Guo Austin M. , Scicli Gloria , Sheng Ju , Falck John C. , Edwards Paul A. , Scicli A. Guillermo
Published: June 2009

20-HETE increases the expression of VEGF in human dermal microvascular endothelial cells (ECs). Since VEGF is regulated by hypoxia inducible factor (HIF)-1, we studied whether 20-HETE also upregulates HIF-1α using the stable 20-HETE analog 20-hydroxyeicosa-5( Z),14( Z)dienoic acid (WIT003; 1–10 μM) and found that it induced a marked increase in HIF-1α protein levels. The increases in VEGF after the addition of WIT003 preceded the changes in HIF-1α, and the increases in HIF-1α were prevented by a VEGF neutralizing antibody. This suggests that 20-HETE first causes increases in VEGF, which then, in turn, cause the upregulation of HIF-1α. Stimulation with exogenously added VEGF also led to an upregulation of HIF-1α. Incubation with the MEK1/ERK1/2 inhibitor U-0126 (10 μM) completely abolished the increases in VEGF and thus HIF-1α, suggesting the involvement of ERK1/2 activation. The addition of WIT003 resulted in a rapid and sustained increase in superoxide formation. When WIT003 was added in the presence of the nitric oxide (NO) synthase (NOS) inhibitor N-nitro-l-arginine, no changes in superoxide, VEGF, or HIF-1α were observed. This suggests that NOS is responsible for the early changes in superoxide induced by WIT003. Furthermore, WIT003 induced the expression of the NADPH oxidase subunit p47 phox in ECs before the increases in HIF-1α. Incubation with polyethylene glycol-superoxide dismutase (400 U/ml), apocynin (100 μM), diphenylene iodonium (10 μM), or p47 phox downregulation with small interfering (si)RNA all inhibited the increases in HIF-1α expression. This indicates that the early changes in superoxide lead to VEGF increases and thereby NADPH oxidase-dependent superoxide production, which is required for HIF-1α upregulation. We also found that the higher HIF-1α expression induced by WIT003 was accompanied by higher expression of erythropoietin receptor and angiopoietin-2 proteins. These increases were caused by HIF-1α because their levels were markedly decreased by siRNA downregulation of HIF-1α. 20-HETE may be a novel nonhypoxic regulator of HIF-1α and HIF-1α-regulated genes in ECs.
Sarcalumenin is essential for maintaining cardiac function during endurance exercise training
Authors: Jiao Qibin , Bai Yunzhe , Akaike Toru , Takeshima Hiroshi , Ishikawa Yoshihiro , Minamisawa Susumu
Published: June 2009

Sarcalumenin (SAR), a Ca2+-binding protein located in the longitudinal sarcoplasmic reticulum (SR), regulates Ca2+reuptake into the SR by interacting with cardiac sarco(endo)plasmic reticulum Ca2+-ATPase 2a (SERCA2a). We have previously demonstrated that SAR deficiency induced progressive heart failure in response to pressure overload, despite mild cardiac dysfunction in sham-operated SAR knockout (SARKO) mice ( 26 ). Since responses to physiological stresses often differ from those to pathological stresses, we examined the effects of endurance exercise on cardiac function in SARKO mice. Wild-type (WT) and SARKO mice were subjected to endurance treadmill exercise training (∼65% of maximal exercise ability for 60 min/day) for 12 wk. After exercise training, maximal exercise ability was significantly increased by 5% in WT mice ( n = 6), whereas it was significantly decreased by 37% in SARKO mice ( n = 5). Cardiac function assessed by echocardiographic examination was significantly decreased in accordance with upregulation of biomarkers of cardiac stress in SARKO mice after training. After training, expression levels of SERCA2a protein were significantly downregulated by 30% in SARKO hearts, whereas they were significantly upregulated by 59% in WT hearts. Consequently, SERCA2 activity was significantly decreased in SARKO hearts after training. Furthermore, the expression levels of other Ca2+-handling proteins, including phospholamban, ryanodine receptor 2, calsequestrin 2, and sodium/calcium exchanger 1, were significantly decreased in SARKO hearts after training. These results indicate that SAR plays a critical role in maintaining cardiac function under physiological stresses, such as endurance exercise, by regulating Ca2+transport activity into the SR. SAR may be a primary target for exercise-related adaptation of the Ca2+storage system in the SR to preserve cardiac function.
Adipocyte-derived factor reduces vasodilatory capability in ob−/ob− mice
Authors: Xiang Lusha , Hester Robert L.
Published: June 2009

Obesity is associated with impaired functional hyperemic response. We have shown that ATP-sensitive potassium (KATP) channels are important in mediating functional vasodilation. Adipocyte-derived factors (ADFs) can alter vascular tone via opening KATP channels. We hypothesize that, in an animal model of obesity, ADFs will decrease basal arteriolar tone by opening KATP channels, resulting in an attenuated functional vasodilation. We used wild-type (WT) mice and ob−/ ob− mice ( ob) to test this hypothesis. The spinotrapezius muscle was prepared for the microcirculatory observation of arcade arterioles, and we measured the vasodilatory responses to muscle stimulation. The basal arteriolar diameter was larger in ob mice compared with WT mice. The KATP channel inhibitor glibenclamide (10 μM) decreased arteriolar diameter in ob mice with no effect in WT mice. The increase in arteriolar diameter induced by muscle stimulation was attenuated in ob mice compared with WT mice. To determine the mechanisms for the opening of KATP channels, fat was collected from the ob mice, subcutaneous fat from around the spinotrapezius muscle (OBSF) or visceral fat (OBVF) and was incubated in physiological saline solution (PSS). The vasodilatory responses to the fat-conditioned PSS were determined in WT mice. Treatment with OBSF- or OBVF -conditioned PSS increased the arteriolar diameters in WT mice, a dilation that was inhibited by glibenclamide. The absolute diameters induced by muscle stimulation were not altered by the fat-conditioned PSS. These results suggest that, in ob mice, local ADFs reduce the functional vasodilatory capability via opening KATP channels.
FGF signaling is required for myofibroblast differentiation during alveolar regeneration
Authors: Perl Anne-Karina T. , Gale Emily
Published: June 2009

Normal alveolarization has been studied in rodents using detailed morphometric techniques and loss of function approaches for growth factors and their receptors. However, it remains unclear how these growth factors direct the formation of secondary septae. We have previously developed a transgenic mouse model in which expression of a soluble dominant-negative FGF receptor (dnFGFR) in the prenatal period results in reduced alveolar septae formation and subsequent alveolar simplification. Retinoic acid (RA), a biologically active derivative of vitamin A, can induce regeneration of alveoli in adult rodents. In this study, we demonstrate that RA induces alveolar reseptation in this transgenic mouse model and that realveolarization in adult mice is FGF dependent. Proliferation in the lung parenchyma, an essential prerequisite for lung regrowth was enhanced after 14 days of RA treatment and was not influenced by dnFGFR expression. During normal lung development, formation of secondary septae is associated with the transient presence of α-smooth muscle actin (αSMA)-positive interstitial myofibroblasts. One week after completion of RA treatment, αSMA expression was detected in interstitial fibroblasts, supporting the concept that RA-initiated realveolarization recapitulates aspects of septation that occur during normal lung development. Expression of dnFGFR blocked realveolarization with increased PDGF receptor-α (PDGFRα)-positive cells and decreased αSMA-positive cells. Taken together, our data demonstrate that FGF signaling is required for the induction of αSMA in the PDGFRα-positive myofibroblast progenitor and the progression of alveolar regeneration.
Erythromycin-induced CXCR4 expression on microvascular endothelial cells
Authors: Takagi Yasuyuki , Hashimoto Naozumi , Phan Sem H. , Imaizumi Kazuyoshi , Matsuo Masaki , Nakashima Harunori , Hashimoto Izumi , Hayashi Yuta , Kawabe Tsutomu , Shimokata Kaoru , Hasegawa Yoshinori
Published: June 2009

Although stromal-derived factor-1 (SDF-1) via its cognate receptor CXCR4 is assumed to play a critical role in migration of endothelial cells during new vessel formation after tissue injury, CXCR4 expression on endothelial cells is strictly regulated. Erythromycin (EM), a 14-membered ring macrolide, has an anti-inflammatory effect that may account for its clinical benefit in the treatment of chronic inflammatory diseases. However, the effects of EM on endothelial cells and especially their expression of CXCR4 have not been fully evaluated. In this study, we demonstrated that EM markedly induced CXCR4 surface expression on microvascular endothelial cells in vitro and lung capillary endothelial cells in vivo. This ability to induce CXCR4 surface expression on endothelial cells was restricted to 14-membered ring macrolides and was not observed in other antibiotics including a 16-membered ring macrolide, josamycin. Furthermore, this EM-induced expression of CXCR4 on endothelial cells was functionally significant as demonstrated by chemotaxis assays in vitro. These findings suggest that EM-induced CXCR4 surface expression on endothelial cells may promote migration of CXCR4-expressing endothelial cells into sites of tissue injury, which may be associated with the known anti-inflammatory activity of this macrolide.
On (N, p, q)(E, 1) Summability of Fourier Series
Authors: Nigam H. K. , Sharma Ajay
Published: June 2009

A new theorem on (N, p, q)(E, 1) summability of Fourier series has been established.
Genetic Variation in the Chromosome 17q23 Amplicon and Breast Cancer Risk
Authors: Kelemen Linda E. , Wang Xianshu , Fredericksen Zachary S. , Pankratz V. Shane , Pharoah Paul D.P. , Ahmed Shahana , Dunning Alison M. , Easton Douglas F. , Vierkant Robert A. , Cerhan James R. , Goode Ellen L. , Olson Janet E. , Couch Fergus J.
Published: June 2009

Background: Gene amplification leading to overexpression is a common event in breast tumors that is linked to tumor development and progression. The 17q23 region is amplified in >40% of breast tumors and contains several candidate oncogenes. Because common genetic variation in several oncogenes has been associated with cancer risk, we assessed the relevance of common variants in the 17q23 candidate oncogenes to breast cancer.

Methods: We investigated 60 polymorphisms in the TUBD1, SEPT4, PRKCA, TBX2, TBX4, TEX14, TLK2, YPEL2, and PPM1E genes from this amplicon for association with breast cancer risk among 798 Caucasian breast cancer cases and 843 unaffected Caucasian controls from the Mayo Clinic.

Results: Eight polymorphisms in PRKCA, TBX4, TLK2, and YPEL2 displayed significant dose-response associations with breast cancer risk (Ptrend < 0.05). Of these, PRKCA rs7342847 and TLK2 rs2245092 and rs733025 were also associated with hormone receptor–positive breast cancer: PRKCA rs7342847 (odds ratio, 0.7; 95% confidence interval, 0.6-0.9; Ptrend = 0.002) and TLK2 rs733025 and rs2245092 (both: odds ratio, 0.8; 95% confidence interval, 0.7-1.0; Ptrend = 0.03). Interactions between SEPT4 rs758377 and TEX14 rs302864 (Pinteraction = 0.0003) and between TLK2 rs733025 and YPEL2 rs16943468 (Pinteraction = 0.05) for risk of breast cancer were also observed.

Conclusion: These findings suggest that single polymorphisms and combinations of polymorphisms within candidate oncogenes from the 17q23 amplicon may influence risk of breast cancer overall and possibly specific molecular subtypes of breast tumors. The findings are discussed within the context of the results from two independent data sets. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1864–8)
Cancer Risk in Long-term Users of Valproate: A Population-Based Case-Control Study
Authors: Hallas Jesper , Friis Søren , Bjerrum Lars , Støvring Henrik , Narverud Sverre Flatabø , Heyerdahl Thomas , Grønbæk Kirsten , Andersen Morten
Published: June 2009

Background: Inhibitors of histone deacetylases (HDAC) have shown promise as targeted cancer therapy. Valproate, an older anticonvulsant, has been shown to possess HDAC inhibitory activity. We undertook this case-control study to clarify whether long-term users of valproate had a reduced cancer incidence. If so, it would support HDAC inhibition as a pharmacologic principle in chemoprevention.

Methods: We identified 149,417 incident cancer cases in Denmark during the study period 2000 through 2005, and 597,668 age- and gender-matched controls. Data on history of cancer, past hospital admission diagnoses, and prescription history were obtained from the Danish Cancer Registry, the Danish National Patient Registry, and the Danish Prescription Registry. Primary exposure to valproate was defined as a cumulative dose of minimum 1,500 g within the past 5 years. Confounders were controlled by conditional logistic regression.

Results: Among the cases and controls, 81 (0.05%) and 260 (0.04%), respectively, were long-term users of valproate. For cancer overall, the crude and adjusted odds ratios were 1.25 [95% confidence interval (95% CI), 0.97-1.60] and 1.21 (95% CI, 0.95-1.56), respectively. Subgroup analyses revealed no dose or duration effect for overall cancer incidence, and no specific cancer site was found to be inversely associated with long-term use of valproate. For lung cancer, we found a positive but imprecise association (adjusted odds ratio, 2.32; 95% CI, 1.12-4.79).

Conclusion: Long-term valproate use is not associated with a reduced cancer risk. Our study does not support HDAC inhibition as a pharmacologic principle for general chemoprevention. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1714–9)
Melanoma in Maori, Asian, and Pacific Peoples in New Zealand
Authors: Sneyd Mary Jane , Cox Brian
Published: June 2009

New Zealand Maori, Pacific, and Asian people develop melanoma less frequently than New Zealand Europeans, but little is known about melanomas that develop in these people. We examined the characteristics of melanoma in these minority ethnic groups in New Zealand. In 2007, all first primary melanomas diagnosed from January 1996 to December 2006 were extracted from the New Zealand Cancer Registry database. Melanoma was more commonly diagnosed in Maori than Asian or Pacific peoples. Age-adjusted incidence rates increased annually from 1996 to 2006 by 0.37 per 100,000 in the total population and 0.20 per 100,000 in Maori, a 12% (from 30.9 to 34.6) and 90% (from 2.3 to 4.3) increase, respectively, over the 11 years. Nodular melanoma occurred more often in Maori (15.9%) and Pacific peoples (17.1%) compared with Asians (8.7%) and New Zealand Europeans (10.5%). In Pacific peoples, acral lentiginous melanoma (22.9%) was the most common subtype. The median thickness of melanoma was 0.78 mm in New Zealand Europeans, 1.2 mm in Maori, 2.5 mm in Pacific peoples, and 0.73 mm in Asians (P < 0.001, difference in medians). Thirty-seven percent of melanomas in Pacific peoples were >4 mm thick compared with 7.9% in New Zealand Europeans. About 13% of Asians and 11% of Pacific peoples, compared with 4% of New Zealand Europeans with melanoma, were diagnosed by histology of metastases rather than the primary lesion. Minority ethnicities in New Zealand have a higher than expected risk of thick and more advanced melanoma, with poorer prognosis. Melanoma campaigns should include messages that incorporate the unique features of melanoma in minorities. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1706–13)
Toll-like Receptor Signaling Pathway Variants and Prostate Cancer Mortality
Authors: Stark Jennifer R. , Wiklund Fredrik , Grönberg Henrik , Schumacher Fredrick , Sinnott Jennifer A. , Stampfer Meir J. , Mucci Lorelei A. , Kraft Peter
Published: June 2009

An understanding of factors associated with prostate cancer (PCa) mortality is increasingly important given the biological heterogeneity of disease. Previous studies have shown that genetic variation in the Toll-like receptor (TLR) signaling pathway is associated with PCa incidence, but any role in progression and mortality is unclear. Among 1,252 PCa cases from the Cancer Prostate in Sweden study, we conducted time-to-event analyses of PCa mortality for 99 individual tagging SNPs and haploytpes from 20 genes in the TLR pathway. Cox proportional hazards models were used to estimate hazard ratios (HR) and 99% confidence intervals (99% CI). Global P values were estimated from a likelihood ratio test. During a median follow-up of 5.1 years, 191 PCa deaths occurred. Controlling for age and geographic location, two polymorphisms were statistically significantly associated with PCa mortality (P < 0.01). Compared with homozygous wild-type carriers of the TLR-9 polymorphism (rs187084), the HR (99% CI) was 1.57 (1.02, 2.41) for heterozygotes and 1.02 (0.57, 1.84) for rare homozygotes (P = 0.009). For a MIC-1 SNP (rs1227732), the HR comparing carriers of at least one copy of the minor allele to wild-type homozygotes was 0.54 (99% CI: 0.34, 0.87). Only the MIC-1 SNP remained significant after additional adjustment for treatment. No significant associations were observed for common haplotypes and PCa mortality. This study highlights the importance of studies of PCa mortality because risk factors for incidence and mortality may differ. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1859–63)
Dietary Folate and Folate Vitamers and the Risk of Pancreatic Cancer in the Netherlands Cohort Study
Authors: Keszei András P. , Verhage Bas A.J. , Heinen Mirjam M. , Goldbohm Royle A. , van den Brandt Piet A.
Published: June 2009

An association between high intake of folate and reduced risk of cancer has been suggested by previous research. However, epidemiologic data from cohort studies regarding the relationship between dietary folate and pancreatic cancer are sparse and inconsistent. We examined the association between dietary folate intake and risk of pancreatic cancer within the Netherlands Cohort Study on diet and cancer. Men and women (120,852), ages 55 to 69 years, were recruited. Information on diet was collected at baseline by means of food frequency questionnaires, and the cohort was followed for 13.3 years. Total folate and vitamer intake were calculated using folate contents of food items derived from a validated liquid chromatography trienzyme method. Cases (n = 363) were identified by record linkage with regional cancer registries and the Dutch National Database of Pathology Reports. A case-cohort approach was used using the follow-up data of a random subcohort (n = 5,000) identified at the onset of the cohort. Multivariable hazard ratios with 95% confidence intervals were estimated using Cox proportional hazards model. After adjusting for age, gender, smoking status, number of years smoked, number of cigarettes smoked per day, and intake of added sugar multivariate hazard ratio comparing the highest and lowest quintiles of folate intake for pancreatic cancer risk was 1.37 (confidence interval, 0.97-1.94; Ptrend = 0.07). When folate vitamers were analyzed separately, results did not show a difference in association. Our results do not support a protective association of total dietary folate or individual folate vitamers on the risk of pancreatic cancer.(Cancer Epidemiol Biomarkers Prev 2009;18(6):1785–91)
International Trends in Colorectal Cancer Incidence Rates
Authors: Center Melissa M. , Jemal Ahmedin , Ward Elizabeth
Published: June 2009

Background: Previous studies have documented significant variations in colorectal cancer incidence rates and trends regionally and across countries. However, no study has examined the worldwide pattern using the most recently updated incidence data from the IARC.

Methods: We obtained sex-specific colorectal cancer incidence for 1953-57 through 1998-2002 by cancer registry from Cancer Incidence in Five Continents (CI5) databases. For 51 cancer registries with long-term incidence data, we assessed the change in the incidence rates over the past 20 years by calculating the ratio of the incidence rates in 1998-2002 to that in 1983-87.

Results: Colorectal cancer incidence rates for both males and females statistically significantly increased from 1983-87 to 1998-2002 for 27 of 51 cancer registries considered in the analysis, largely confined to economically transitioning countries including Eastern European countries, most parts of Asia, and select countries of South America. These increases were more prominent for men than for women. We also observed substantial variations in colorectal cancer incidence trends within countries such as Japan. Similarly, trends in Israel and Singapore varied significantly according to ethnicity. The United States is the only country where colorectal cancer incidence rates declined in both males and females.

Conclusions: Colorectal cancer incidence rates continue to increase in economically transitioning countries, with incidence rates among men in the Czech Republic and Slovakia exceeding the peak incidence observed in the United States and other long-standing developed nations. Targeted prevention and early detection programs could help reverse the trend in these countries. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1688–94)
Vitamin D Pathway Gene Variants and Prostate Cancer Risk
Authors: Holt Sarah K. , Kwon Erika M. , Peters Ulrike , Ostrander Elaine A. , Stanford Janet L.
Published: June 2009

Vitamin D has antiproliferative, antiangiogenic, and apoptotic properties. There is some evidence supporting an association between vitamin D–related gene variants and prostate cancer risk. We report results from this population-based case-control study of genes encoding for the vitamin D receptor (VDR), the vitamin D activating enzyme 1-α-hydroxylase (CYP27B1), and deactivating enzyme 24-hydroxylase (CYP24A1). Forty-eight tagging single nucleotide polymorphisms (tagSNP) were analyzed in 827 incident prostate cancer cases diagnosed from 2002 to 2005, and in 787 age-matched controls. Contrary to some earlier studies, we found no strong evidence of altered risk of developing prostate cancer overall or within clinical measures of tumor aggressiveness for any of the tagSNPs when they were assessed individually or in haplotypes. (Cancer Epidemiol NBiomarkers Prev 2009;18(6):1929–33)
Association of Genetic Polymorphisms, mRNA Expression ofp53andp21with Chronic Benzene Poisoning in a Chinese Occupational Population
Authors: Sun Pin , Qiu Yulan , Zhang Zhongbin , Wan Junxiang , Wang Tong , Jin Xipeng , Lan Qing , Rothman Nathaniel , Xia Zhao-lin
Published: June 2009

DNA damage induced by benzene reactive metabolites is thought of as an important mechanism underlying benzene hematotoxicity and genotoxicity, and genetic variation in cell-cycle control genes may contribute to susceptibility to chronic benzene poisoning (CBP). Using a case-control study that included 307 benzene-poisoned patients and 299 workers occupationally exposed to benzene in south China, we aimed to investigate the association between genetic polymorphisms of p53 and p21 and the odds of CBP. To investigate whether benzene exposure may influence mRNA expression of p53 and p21 in benzene-exposed workers, we also chose 39 CBP workers, 38 occupationally benzene-exposure workers, and 37 nonexposure workers in the same region of China. PCR-restriction fragment length polymorphism technique was applied to detect polymorphisms of p53 (rs17878362, rs1042522, and rs1625895) and p21 (rs1801270 and rs1059234), and real-time PCR was applied to detect the quantity of gene mRNA expression. We found that p21 C98A variant genotypes (CA+AA) or C70T variant genotypes (CT+TT) were associated with decreased odds of CBP [odds ratio (OR), 0.51; 95% confidence interval (95% CI), 0.32-0.83, and OR, 0.53; 95% CI, 0.29-0.95, respectively. Further analysis showed the decreased odds of CBP in the subjects with p21 CC/AT diplotype (OR, 0.51; 95% CI, 0.30-0.85). In addition, p53 mRNA expression of CBP workers or benzene-exposure workers was significantly lower than that of nonexposure workers. Although these results require confirmation and extension, our results show that polymorphisms in p21 may be protective against the risk of CBP in the Chinese occupational population. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1821–8)
A Cohort Study of p27 Localization in Colon Cancer, Body Mass Index, and Patient Survival
Authors: Ogino Shuji , Shima Kaori , Nosho Katsuhiko , Irahara Natsumi , Baba Yoshifumi , Wolpin Brian M. , Giovannucci Edward L. , Meyerhardt Jeffrey A. , Fuchs Charles S.
Published: June 2009

Energy balance and the AKT pathway are important in colorectal cancer development and regulate p27 (cyclin-dependent kinase inhibitor-1B/CDKN1B/KIP1), which plays a role in preventing cell cycle progression. However, little is known on the clinical outcome or prognostic significance of p27 alterations in relation to patient body mass index (BMI). Among 630 colon cancers (stage I-IV) in two prospective cohort studies, we detected p27 alterations (cytoplasmic p27 localization or p27 loss) in 500 tumors (79%) by immunohistochemistry. The remaining 130 (21%) tumors were “p27-nuclear+.” Cox proportional hazard models computed hazard ratios (HR) of deaths, adjusted for patient and tumoral characteristics, including p53, p21, cyclin D1, KRAS, BRAF, PIK3CA, cyclooxygenase-2, fatty acid synthase (FASN), β-catenin, microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and long interspersed nucleotide element-1 (LINE-1) hypomethylation. Compared with p27-nuclear+ patients, p27-altered patients experienced low colon cancer–specific [adjusted HR, 0.63; 95% confidence interval (95% CI), 0.42-0.94] and overall mortality (adjusted HR, 0.70; 95% CI, 0.51-0.95), independent of FASN, MSI, CIMP, LINE-1 methylation, and other potential confounders. The effect of p27 alteration on overall mortality significantly differed by BMI (Pinteraction = 0.013); adjusted HR (p27-altered versus p27-nuclear+ tumors) was 0.28 (95% CI, 0.13-0.59) for BMI ≥30 kg/m2, 0.67 (95% CI, 0.40-1.14) for BMI 25 to 29 kg/m2, and 0.91 (95% CI, 0.57-1.46) for BMI <25 kg/m2. Obesity was associated with inferior overall survival among p27-nuclear+ cases (adjusted HR, 3.07; 95% CI, 1.49-6.32; versus nonobese cases), but not among p27-altered cases (adjusted HR, 1.08). In conclusion, p27 alterations in colon cancer are associated with superior prognosis. Adverse prognostic effect of obesity seems limited to patients with nuclear p27 expression, suggesting a host-tumor interaction. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1849–58)
Use of Thiazolidinediones Does Not Affect Prostate-Specific Antigen Levels in Men with Diabetes
Authors: Pini Tunghi M. , Griffin Marie R. , Roumie Christianne L. , Huizinga Mary Margaret , Fowke Jay H. , Greevy Robert , Liu Xulei , Murff Harvey J.
Published: June 2009

Thiazolidinediones (TZD) have been shown to down-regulate prostate-specific antigen (PSA) levels in prostate cancer cell lines and decrease PSA velocity among prostate cancer patients; however, the effect of TZDs on serum PSA levels among men with diabetes at risk for prostate cancer is unknown. We conducted a retrospective cohort study of veterans receiving care for diabetes between 1999 and 2005 to determine if TZD use affects PSA levels in veterans at risk for prostate cancer. Eligible patients were male, ≥45 years old, taking at least one oral antidiabetic medication, and with two or more recorded PSA values. Patients with a prior history of prostate cancer or prostatectomy were excluded. Of the 13,791 patients included in the adjusted analysis, 2,016 (14.6%) were prescribed a TZD. No effect of cumulative TZD dose on change in PSA was detected (P = 0.26). Increased TZD exposure was not associated with a change in PSA, suggesting that TZD treatment for diabetes is unlikely to affect prostate cancer detection. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1937–8)
Is Circumcision a Modified Ritual of Castration?
Authors: Mordeniz Cengiz , Verit Ayhan
Published: June 2009

Aim: In the earliest records of human religion, castration was regarded as an act of devotion. Moreover, the ritual of circumcision is still followed by many modern religions. In this article, we have exposed the archeological, historical, cultural and religious evidence between the ancient ritual of castration and circumcision. Materials and Methods: We reviewed the reports about circumcision and castration in the English, French, and Turkish literature. Result: Both the rituals of circumcision and castration had similar aims in human religions. Conclusion: The ritual of castration evolved into circumcision as a less-invasive and bloody procedure than castration.
Clinical Management of Bladder Dysfunction Caused by Sexual Abuse
Authors: Pannek Jürgen , Einig Eva-Maria , Einig Werner
Published: June 2009

Background: Victims of sexual abuse are prone to develop posttraumatic stress disorder and lower urinary tract symptoms. Conservative treatment is recommended in these patients. We reviewed the treatment results of patients in which drug treatment failed. Patients and Methods: In a retrospective study, results of 5 women with chronic posttraumatic stress disorder and symptoms of dysfunctional voiding were evaluated. Results: One patient was successfully treated by electrostimulation. After failure of conservative treatment, 3 patients received a sacral neuromodulator, which was revised and finally explanted in all patients. One patient received botulinum toxin-A injections in the detrusor, 2 patients underwent urinary diversion. With a follow-up of 1 year, these 2 patients are asymptomatic. Conclusions: Although conservative treatment is recommended in these patients, surgical treatment may be inevitable in some cases. Successful surgical treatment is possible if an interdisciplinary approach with a close collaboration between psychotherapists and urologists is utilized.
Causes of Food-Induced Anaphylaxis in Italian Adults: A Multi-Centre Study
Authors: Asero R. , Antonicelli L. , Arena A. , Bommarito L. , Caruso B. , Colombo G. , Crivellaro M. , De Carli M. , Della Torre E. , Della Torre F. , Heffler E. , Lodi Rizzini F. , Longo R. , Manzotti G. , Marcotulli M. , Melchiorre A. , Minale P. , Morandi P. , Moreni B. , Moschella A. , Murzilli F. , Nebiolo F. , Poppa M. , Randazzo S. , Rossi G. , Senna G.E.
Published: June 2009

Background: Data about food-induced anaphylaxis in Italy are missing. Objective: It was the aim of this study to detect the main foods/food allergens causing anaphylaxis in Italy. Methods: The frequency of anaphylaxis and the relative importance of many offending foods were assessed in 1,110 adult patients with food allergy diagnosed by common criteria at 19 allergy centres scattered throughout Italy from 1 January to 31 December 2007. Results: Fifty-eight of 1,110 (5%) food-allergic patients experienced at least 1 episode of anaphylaxis. On average, they were older than other food-allergic patients (34 vs. 31 years; p < 0.05). The majority of anaphylactic episodes occurred in patients sensitized to lipid transfer protein (LTP; n = 19), followed by shrimp (n = 10), tree nuts (n = 9), legumes other than peanut (n = 4), and seeds (n = 2); peanut, spinach, celery, buckwheat, wheat, avocado, tomato, fish, meat, and Anisakis caused an anaphylactic reaction in single patients. Among LTP-hypersensitive patients, peach caused 13/19 anaphylactic episodes. Shrimp-allergic patients were significantly older than other patients with food-induced anaphylaxis (p < 0.05), whereas patients allergic to LTP experienced their anaphylactic episodes at a younger age (p < 0.001). The frequency of anaphylaxis among patients sensitized to LTP, shrimp or tree nuts did not differ between northern and central/southern Italy. Conclusion: LTP is the most important allergen causing food-induced anaphylaxis in Italy, peach being the most frequently offending food. Peanut-induced anaphylaxis seems very uncommon. Geographic and environmental differences both between Italy and other countries and within Italy seem to play a relevant role in the pattern of sensitization to foods.
Interaction of Lymphocytes and Thyrocytes in Graves’ Disease and Nonautoimmune Thyroid Diseases in Immunohistochemical and Ultrastructural Investigations
Authors: Ben-Skowronek Iwona , Sierocinska-Sawa Jadwiga , Szewczyk Leszek , Korobowicz Elzbieta
Published: June 2009

Background: Graves’ disease is the archetype for organ-specific autoimmune disorders. It is very important for our understanding of the mechanisms responsible for progression of autoimmunity. The aim of this study was to present interactions of lymphocytes and thyrocytes in the thyroid tissue in Graves’ disease and nonautoimmune thyroid diseases. Methods: The study involved 30 children with Graves’ disease, 30 children with nodular goiter, 30 with simple goiter and 30 healthy children. After thyroidectomy, T cells were detected in the thyroid specimens by CD3, CD4, CD8 antibodies, B cells by CD79α antibodies and the antigen-presenting dendritic cells with CD1a antibodies (DakoCytomation) and were examined in the EM 900 Zeiss Germany Electron Microscope. Results: The most enhanced immune reaction was observed in the thyroid from children with Graves’ disease. The cells of the immune system infiltrated the thyroid follicles and interfollicular compartments; they also formed lymph follicles. Conclusion: The immune reaction in Graves’ disease and migration of lymphocytes T and B between thyrocytes results in the thickening of the basal membrane of the thyroid follicle. No cytotoxic effect of T cytotoxic/suppressor CD8+ cells on thyrocytes was observed in Graves’ disease, while a mild cytotoxic effect was observed in non-autoimmune thyroid disease.
Diagnostic Evaluation of Dementia in the Secondary Health Care Sector
Authors: Phung Thien Kieu Thi , Andersen Birgitte Bo , Kessing Lars Vedel , Mortensen Preben Bo , Waldemar Gunhild
Published: June 2009

Background: We conducted a nationwide registry-based study of the quality of diagnostic evaluation for dementia in the secondary health care sector. Method: Two hundred patients were randomly selected from the patient population (4,682 patients) registered for the first time with a dementia diagnosis in the nationwide hospital registries during the last 6 months of 2003. Through medical record review, we evaluated the completeness of the work-up on which the dementia diagnosis was based, using evidence-based dementia guidelines as reference standards. Results: Satisfactory or acceptable completion of the basic dementia work-up was documented in 51.3% of the patients. Only 11.5% of those with unsatisfactory work-up were referred to follow-up investigations. Dementia syndrome was confirmed in 88.5% of the cases, but correct subtypes were diagnosed in only 35.1%. Conclusion: The adherence to clinical guidelines concerning dementia work-up is inadequate in the secondary health care sector. Our findings call for improvement in the organization of clinical dementia care, for education of specialists and for changes in attitude towards making a diagnosis of dementia.
Understandings and Experiences of Involved Fathering in the United Kingdom: Exploring Classed Dimensions
Authors: Gillies Val
Published: June 2009

In the United Kingdom, current family policy seeks to prioritize fathering as a social issue. The author critically examines the assumptions and expectations that underpin this approach, comparing and contrasting it with data from qualitative interviews with fathers. It highlights the class-specific nature of fathers' everyday values and experiences, pointing to the way policy-sanctioned models of fatherhood are grounded in middle-class perspectives. The author also argues that the policy discourse of the “involved father” promotes a particular role for fathers as educational facilitators, overlooking the more mundane aspects of care most often associated with motherhood.
Men's Relations with Kids: Exploring and Promoting the Mosaic of Youth Work and Fathering
Authors: Marsiglio William
Published: June 2009

Using qualitative in-depth interviews with a sample of adult male youth workers ( n = 55), including a subset of twenty-nine fathers, the author explores how men's fathering and youth experiences can be viewed as part of a larger, integrated social mosaic. Informed selectively by social constructionist, symbolic interactionist, life course, and generativity themes, the analysis expands the fatherhood literature by connecting it to men's volunteering and work with kids in public settings. While extending his framework of fathering trajectories (self-as-father, father-child, and coparental) to examine similar processes defining men's youth work, the author explores key points of intersection between youth work and fathering: youth work as inspiration and training for fathering, reciprocal influences between youth work and fathering, and men's contributions to social capital for kids in public settings. The author also sketches several ideas to foster conceptual and practical ties between youth work and fathering to benefit youth.
Determinants of Police Strength in Large U.S. Cities During the 1990s
Authors: McCarty William P. , Ren Ling , Zhao Jihong “Solomon”
Published: June 2009

The 1990s represented a unique decade in which to analyze the determinants of police strength in the United States. This decade was a time in which crime initially increased, then substantially decreased. Furthermore, this decade also was characterized by increases in the minority population throughout large American cities. Finally, the 1990s were characterized by increasing police budgets. These realities have direct implications for the competing theories of police growth. This research examines the determinants of police strength in large U.S. cities from 1990 to 2000. A fixed-effects panel analysis was used to assess the number of sworn police officers per 100,000 population. The findings support the resource dependency and social conflict perspectives. Additionally, no support was found for the rational public choice perspective.
Semimetallic Brake Friction Materials Containing ZrSiO4: Friction Performance and Friction Layers Evaluation
Authors: Matějka Vlastimil , Simha Martynková Gražyna , Yuning Ma  , Yafei Lu
Published: June 2009

The effect of ZrSiO4 (zircon) content on friction performance and friction surfaces of semimetallic brake friction materials is discussed. The experimental results indicate that the varying content of zircon affects the friction performance as well as plays crucial role in the iron film formation on the friction surfaces. The friction layers, formed during friction process, were carefully characterized using scanning electron microscopy with energy dispersive X-ray microanalysis, and X-ray diffraction methods. The phenomenon of two different types of iron film formation (film I and film II) on the friction surfaces is proposed and their formation and destruction mechanism is described. Despite the compositions of both iron films being similar, film I is formed by steel wool itself and film II by the debris from either disc or steel wool. The relationships among formulation, friction performance, and friction surfaces are summarized.
Towards an Ontology of Media
Authors: Kittler Friedrich
Published: June 2009

This paper addresses the exclusion of physical and technical media from questions of ontology. It is argued, first, that from Aristotle onwards ontology has dealt with the matter and form of things rather than the relations between things in time and space. Second, it is argued that because the Greeks did not distinguish between speech elements and alphabetic letters there has been a tendency for philosophy to neglect writing as its own technical medium. This paper traces these tendencies through a range of philosophical sources: from Aquinas and Descartes to Fichte and Hegel. It is argued, by way of response, that it is only with Heidegger that a philosophical consciousness for technical media first arose, and that today the connections of mathematics and media, and of media and ontology are to be formulated in more precise terms.
Fiction and the `Unrepresentable'
Authors: Hasumi Shigehiko
Published: June 2009

In this article I argue that basic characteristics of the medium of cinema formed during the relatively brief era of silent movies continued to characterize film throughout the 20th century. Despite the development of talkies in the 1920s, sound was never truly integrated into the composition of cinema in the sense implied by the term `audiovisual'. This is a reflection not only of technological constraints but also of a fundamental ideological orientation that prohibited the direct representation of the voice. This `prohibition' of the voice is not a phenomenon confined entirely to cinema. Through a critique of the debate begun by Godard and Lanzmann on representation of the Auschwitz gas chambers in film, I consider how the issue of the `unrepresentable' must be extended beyond the issue of visual representation so as to also include the matter of representation in sound. It is only now that we have entered the 21st century that the `visibility' of this larger issue of representation is presented to us.
The Cool Brand, Affective Activism and Japanese Youth
Authors: Allison Anne
Published: June 2009

Japanese youth goods have become globally popular over the past 15 years. Referred to as `cool', their contribution to the national economy has been much hyped under the catchword Japan's `GNC' (gross national cool). While this new national brand is indebted to youth — youth are the intended consumers for such products and sometimes the creators — young Japanese today are also chastised for not working hard, failing at school and work, and being insufficiently productive or reproductive. Using the concept of immaterial labor, the article argues that such `J-cool' products as Pokémon are both based on, and generative of, a type of socio-power also seen in the very behaviors of youth — flexible sociality, instantaneous communication, information juggling — that are so roundly condemned in public discourse. The article examines the contradictions between these two different ways of assessing and calibrating the value of youth today. It also looks at the emergence of youth activism around the very precariousness, for them, of socio-economic conditions of flexibility.
Methylphenidate Induction of Complex Visual Hallucinations
Authors: Halevy Ayelet , Shuper Avinoam
Published: June 2009

A 15-year-old boy with attention-deficit hyperactivity disorder (ADHD) presented with complex visual hallucinations of rats running around and touching and smelling him soon after receiving a first low dose of methylphenidate. The hallucinations resolved upon discontinuation of the drug. Reintroduction of the drug 7 years later at an even lower dose had the same effect. Other cases of vivid complex hallucinations of living creatures associated with methylphenidate have been reported in the literature. The pathogenetic mechanism is still unknown. In our case, the occurrence of hallucinations after a very low dose of the drug on 2 occasions may suggest an idiosyncratic reaction. The phenomenon might also be explained by a drug-induced dysfunction of the monoamine transmitters. Given the wide use of methylphenidate, clinicians should be aware of this possible side effect.