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Sample records for factor receptor gender

  1. Response to Therapy and Outcomes in Oropharyngeal Cancer Are Associated With Biomarkers Including Human Papillomavirus, Epidermal Growth Factor Receptor, Gender, and Smoking

    Kumar, Bhavna; Cordell, Kitrina G.; Lee, Julia S.; Prince, Mark E.; Tran, Huong H.; Wolf, Gregory T.; Urba, Susan G.; Worden, Francis P.; Chepeha, Douglas B.; Teknos, Theodoros N.; Eisbruch, Avraham; Tsien, Christina I.; Taylor, Jeremy; D'Silva, Nisha J.; Yang, Kun; Kurnit, David M.; Bradford, Carol R.

    2007-01-01

    Induction chemotherapy and concurrent chemoradiation for responders or immediate surgery for non-responders is an effective treatment strategy head and neck squamous cell carcinoma (HNSCC) of the larynx and oropharynx. Biomarkers that predict outcome would be valuable in selecting patients for therapy. In this study, the presence and titer of high risk human papilloma virus (HPV) and expression of epidermal growth factor receptor (EGFR) in pre-treatment biopsies, as well as smoking and gender were examined in oropharynx cancer patients enrolled in an organ sparing trial. HPV16 copy number was positively associated with response to therapy and with overall and disease specific survival, whereas EGFR expression, current or former smoking behavior, and female gender (in this cohort) were associated with poor response and poor survival in multivariate analysis. Smoking cessation and strategies to target EGFR may be useful adjuncts for therapy to improve outcome in the cases with the poorest biomarker profile

  2. Fibroblast growth factor receptors in breast cancer.

    Wang, Shuwei; Ding, Zhongyang

    2017-05-01

    Fibroblast growth factor receptors are growth factor receptor tyrosine kinases, exerting their roles in embryogenesis, tissue homeostasis, and development of breast cancer. Recent genetic studies have identified some subtypes of fibroblast growth factor receptors as strong genetic loci associated with breast cancer. In this article, we review the recent epidemiological findings and experiment results of fibroblast growth factor receptors in breast cancer. First, we summarized the structure and physiological function of fibroblast growth factor receptors in humans. Then, we discussed the common genetic variations in fibroblast growth factor receptors that affect breast cancer risk. In addition, we also introduced the potential roles of each fibroblast growth factor receptors isoform in breast cancer. Finally, we explored the potential therapeutics targeting fibroblast growth factor receptors for breast cancer. Based on the biological mechanisms of fibroblast growth factor receptors leading to the pathogenesis in breast cancer, targeting fibroblast growth factor receptors may provide new opportunities for breast cancer therapeutic strategies.

  3. Gender differences and lateralization in the distribution pattern of insulin-like growth factor-1 receptor in developing rat hippocampus: an immunohistochemical study.

    Hami, Javad; Kheradmand, Hamed; Haghir, Hossein

    2014-03-01

    Numerous investigators have provided data supporting essential roles for insulin-like growth factor-I (IGF-I) in development of the brain. The aim of this study was to immunohistochemically determine the distinct regional distribution pattern of IGF-1 receptor (IGF-IR) expression in various portions of newborn rat hippocampus on postnatal days 0 (P0), 7 (P7), and 14 (P14), with comparison between male/female and right/left hippocampi. We found an overall significant increase in distribution of IGF-IR-positive (IGF-IR+) cells in CA1 from P0 until P14. Although, no marked changes in distribution of IGF-IR+ cells in areas CA2 and CA3 were observed; IGF-IR+ cells in DG decreased until P14. The smallest number of immunoreactive cells was present in CA2 and the highest number in DG at P0. Moreover, in CA1, CA3, and DG, the number of IGF-IR+ cells was markedly higher in both sides of the hippocampus in females. Our data also showed a higher mean number of IGF-IR+ cells in the left hippocampus of female at P7. By contrast, male pups showed a significantly higher number of IGF-IR+ cells in the DG of the right hippocampus. At P14, the mean number of immunoreactive cells in CA1, CA3, and DG areas found to be significantly increased in left side of hippocampus of males, compared to females. These results indicate the existence of a differential distribution pattern of IGF-IR between left-right and male-female hippocampi. Together with other mechanisms, these differences may underlie sexual dimorphism and left-right asymmetry in the hippocampus.

  4. Motivational factors, gender and engineering education

    Kolmos, Anette; Mejlgaard, Niels; Haase, Sanne; Egelund Holgaard, Jette

    2013-06-01

    Based on survey data covering the full population of students enrolled in Danish engineering education in autumn 2010, we explore the motivational factors behind educational choice, with a particular aim of comparing male and female students1 reasons for choosing a career in engineering. We find that women are significantly more influenced by mentors than men, while men tend to be more motivated by intrinsic and financial factors, and by the social importance of the engineering profession. Parental influence is low across all programmes and by differentiating between specific clusters of engineering programmes, we further show that these overall gender differences are subtle and that motivational factors are unequally important across the different educational programmes. The findings from this study clearly indicate that intrinsic and social motivations are the most important motivational factors; however, gender and programme differentiation needs to be taken into account, and points towards diverse future strategies for attracting students to engineering education.

  5. Gendered Pathways? Gender, Mediating Factors, and the Gap in Boys' and Girls' Substance Use

    Whaley, Rachel Bridges; Hayes-Smith, Justin; Hayes-Smith, Rebecca

    2013-01-01

    A gender gap in alcohol and drug use exists but is somewhat smaller than the gender gap in other forms of delinquency. This article extends studies that examine the gender-delinquency relationship to substance use in particular and estimate the extent to which major risk and protective factors mediate the association between gender and alcohol and…

  6. Gender Inequality and Emigration: Push factor or Selection process?

    Baudassé, Thierry; Bazillier, Rémi

    2012-01-01

    Our objective in this research is to provide empirical evidence relating to the linkages between gender equality and international emigration. Two theoretical hypotheses can be made for the purpose of analyzing such linkages. The fi rst is that gender inequality in origin countries could be a push factor for women. The second one is that gender inequality may create a \\gender bias" in the selection of migrants within a household or a community. An improvement of gender equality would then inc...

  7. Motivational factors, gender and engineering education

    Kolmos, Anette; Mejlgaard, Niels; Haase, Sanne Schioldann

    2013-01-01

    Based on survey data covering the full population of students enrolled in Danish engineering education in autumn 2010, we explore the motivational factors behind educational choice, with a particular aim of comparing male and female students1 reasons for choosing a career in engineering. We find...... that women are significantly more influenced by mentors than men, while men tend to be more motivated by intrinsic and financial factors, and by the social importance of the engineering profession. Parental influence is low across all programmes and by differentiating between specific clusters of engineering......; however, gender and programme differentiation needs to be taken into account, and points towards diverse future strategies for attracting students to engineering education....

  8. Gender factors affecting female labour input in the Nigerian ...

    Gender factors affecting female labour input in the Nigerian University system. ... which mostly affect women‟s job performance in the Nigerian university system. ... are essential in building a gender-friendly university work environment.

  9. Do Social and Cultural Factors Perpetuate Gender Based Violence ...

    Gender based violence in Malawi exist at a level that requires special acknowledgement. A survey was conducted to assess how social and cultural factors affect gender-based violence in Malawi. The study revealed that both men and women are victims of gender based violence although women bare the brunt of the ...

  10. Determinant factors of gender identity: a commentary.

    Liao, Lih-Mei; Audi, Laura; Magritte, Ellie; Meyer-Bahlburg, Heino F L; Quigley, Charmian A

    2012-12-01

    Paediatric specialists involved in the care of children with disorders of sex development may be expected to provide straightforward answers to questions concerning the "true sex" of a child, reflecting common perceptions of sex/gender as an immutable binary biological reality. This article highlights how much more broad and complex the topic of gender identity and its development is. Many theories have been put forward to advance knowledge of gender identity. Against the breadth and depth of this vast topic, the current overview is inevitably incomplete. It begins by arguing for a more consistent use of 'sex' and 'gender'. It considers in turn three influential theoretical frameworks that lend themselves to empirical research. These are: 1) the role of the brain; 2) the role of socialisation; and 3) multi-dimensional gender development. The article ends by suggesting potentially fruitful questions and areas for future research. Copyright © 2012 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  11. The persistence of gender inequality in Zimbabwe: factors that ...

    The persistence of gender inequality in Zimbabwe: factors that impede the ... Specifically, we sought to identify the factors perceived by women school heads to be causes ... all other roles; and lack of support from the home and the workplace.

  12. Gender-related factors influencing perceptions of homosexuality.

    Wong, F Y; McCreary, D R; Carpenter, K M; Engle, A; Korchynsky, R

    1999-01-01

    There is a long history linking gender role conformity to perceived homosexuality. However, the lack of a systematic theoretical model hinders the elucidation of the interrelationships among gender stereotypes, conformity to gender stereotypes, and perceived homosexuality, as well as other factors which may mediate these relationships. The purpose of the present study was to propose such a model by combining theories of gender stereotype formation and maintenance with research investigating perceptions of homosexuality. Specifically, this study examined college students' perceptions of gender role characteristics in male and female adult target persons and these students' perceptions of the likelihood that the targets were homosexual. Path analysis demonstrated that the sex and occupation of the target person were significantly related to perceived masculinity, femininity, and homosexuality of the target person. Furthermore, individual differences in these relationships were observed, indicating that the sex and gender role characteristics of the participant influenced perceptions of the gender role attributes and homosexuality of the target person.

  13. Gender Factors and Inclusive Economic Growth: The Silent Revolution

    Laura Cabeza-García

    2018-01-01

    Full Text Available The gender factors that trigger economic growth in both high- and low-income countries were investigated in this study. To address these gender factors, four characteristic dimensions of gender inclusion were considered: education, access to the labor market, fertility, and democracy. The relationship between economic growth and gender factors was analyzed in a sample of 127 countries. Value and robustness were added to the results using dynamic models applied to panel data while accounting for endogeneity. We conclude that high fertility in women has negative effects on economic growth. However, when women have greater access to secondary education and the labor market in conditions of equality, the effects are positive. Similarly, the access of women to active political participation has significant effects on economic growth. Overall, this study helps identify which gender factors may promote inclusive economic growth, which is economic growth achieved when both men and women are incorporated in equal conditions.

  14. Epidermal Growth Factor Receptor in Pancreatic Cancer

    Oliveira-Cunha, Melissa; Newman, William G.; Siriwardena, Ajith K.

    2011-01-01

    Pancreatic cancer is the fourth leading cause of cancer related death. The difficulty in detecting pancreatic cancer at an early stage, aggressiveness and the lack of effective therapy all contribute to the high mortality. Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, which is expressed in normal human tissues. It is a member of the tyrosine kinase family of growth factors receptors and is encoded by proto-oncogenes. Several studies have demonstrated that EGFR is over-expressed in pancreatic cancer. Over-expression correlates with more advanced disease, poor survival and the presence of metastases. Therefore, inhibition of the EGFR signaling pathway is an attractive therapeutic target. Although several combinations of EGFR inhibitors with chemotherapy demonstrate inhibition of tumor-induced angiogenesis, tumor cell apoptosis and regression in xenograft models, these benefits remain to be confirmed. Multimodality treatment incorporating EGFR-inhibition is emerging as a novel strategy in the treatment of pancreatic cancer

  15. Factors contributing to physical Gender Based Violence reported at ...

    46987.2

    violence, and poverty as well as income disparities and gender inequality stand out as important community and. 4 societal factors. Copperbelt ... of all urban married women had to seek hospital treatment. 9 following domestic violence.

  16. GENDER FACTORS OF SOCIAL AND ECONOMIC DEVELOPMENT OF A COUNTRY

    N. Kochkina

    2016-06-01

    Full Text Available The article discusses the impact of gender asymmetry on the socio-economic development of the country. Authors detected factors that determine with high level of the probability social development of the society. Econometric relationship between the level of GDP per capita in comparative prices and the socio-cultural and gender factors are developed and estimated. The analysis showed that the level of individualism, indulgence, economic participation, and political empowerment of women in the society have direct linear correlation with GDP per capita. Power distance has opposite inverse correlation with the level of GDP. Application of regression analysis gave the possibility to divide all countries into 9 clusters with similar features. Two-dimensional matrix included GDP per capita and coefficient of implementation of a country gender and sociocultural potential. The recommendations for stimulating economic growth by smoothing gender gaps are proposed.

  17. Outdoor Advertising and Gender Differences : Factors Influencing Perception and Attitudes

    Belinskaya, Yulia

    2015-01-01

    The thesis examines attitudes towards outdoor advertising, with strong emphasis on gender-based differences. The research intends to reveal the most influencing factors, including gender, format, different images and recall. Earlier researchers have argued that females are inclined to rate advertisements more positively than men. Five different, but interconnected studies, one content analysis and four surveys, were implicated in order to measure the responses to advertising. It is further su...

  18. Gender dependent association between perinatal morbidity and estrogen receptor-alpha Pvull polymorphism.

    Derzbach, László; Treszl, András; Balogh, Adám; Vásárhelyi, Barna; Tulassay, Tivadar; Rigó J, János

    2005-01-01

    Assuming the importance of estrogen in perinatal physiology, we tested the association of an estrogen receptor-alpha (ER-alpha) gene Pvull pP polymorphism with perinatal morbidity in premature infants. The ER-alpha Pp genotype was determined in 69 low-birth weight (LBW) boys and 72 LBW girls, 86 term boys and 81 term girls. The association between risk factors, genotype, gender and perinatal morbidity was tested with binary logistic regression analysis. Boys carrying "p" allele were at lower risk for necrotizing enterocolitis (OR [95% Cl]: 0.24 [0.07-0.83]) and patent ductus arteriosus (OR [95% Cl]: 0.24 [0.05-0.97]). The carrier state of the "p" allele was associated with a 34-h shorter period of oxygen supplementation on average (P=0.0018). Boys with pp genotype were at greater risk for intraventricular hemorrhage (OR [95% Cl]: 4.39 [1.15-16.82]). No association between ER-alpha Pvull polymorphism and morbidity was present in girls. Since homozygocity for any Pvull alleles (i.e. having PP or pp genotype) increases the risk for at least one of the most common perinatal complications, it is likely that the heterozygous carrier state of Pvull genotypes has a protective effect, which is gender-dependent.

  19. A comparative gender study of the factors affecting motivation of ...

    The purpose of the study is to identify the key factors of motivation for professional and paraprofessional library staff based on their gender and to identify how they rate the various motivational factors. The descriptive survey method was employed and five university libraries were selected for the study. The respondents ...

  20. Pattern of hormone receptors and human epidermal growth factor ...

    Introduction: Breast cancer is the most common cancer among women globally. With immunohistochemistry (IHC), breast cancer is classified into four groups based on IHC profile of estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2/neu) expression, positive (+) and/or ...

  1. Motivational Factors, Gender and Engineering Education

    Kolmos, Anette; Mejlgaard, Niels; Haase, Sanne; Holgaard, Jette Egelund

    2013-01-01

    Based on survey data covering the full population of students enrolled in Danish engineering education in autumn 2010, we explore the motivational factors behind educational choice, with a particular aim of comparing male and female students reasons for choosing a career in engineering. We find that women are significantly more influenced by…

  2. Pregnane X Receptor-Humanized Mice Recapitulate Gender Differences in Ethanol Metabolism but Not Hepatotoxicity.

    Spruiell, Krisstonia; Gyamfi, Afua A; Yeyeodu, Susan T; Richardson, Ricardo M; Gonzalez, Frank J; Gyamfi, Maxwell A

    2015-09-01

    Both human and rodent females are more susceptible to developing alcoholic liver disease following chronic ethanol (EtOH) ingestion. However, little is known about the relative effects of acute EtOH exposure on hepatotoxicity in female versus male mice. The nuclear receptor pregnane X receptor (PXR; NR1I2) is a broad-specificity sensor with species-specific responses to toxic agents. To examine the effects of the human PXR on acute EtOH toxicity, the responses of male and female PXR-humanized (hPXR) transgenic mice administered oral binge EtOH (4.5 g/kg) were analyzed. Basal differences were observed between hPXR males and females in which females expressed higher levels of two principal enzymes responsible for EtOH metabolism, alcohol dehydrogenase 1 and aldehyde dehydrogenase 2, and two key mediators of hepatocyte replication and repair, cyclin D1 and proliferating cell nuclear antigen. EtOH ingestion upregulated hepatic estrogen receptor α, cyclin D1, and CYP2E1 in both genders, but differentially altered lipid and EtOH metabolism. Consistent with higher basal levels of EtOH-metabolizing enzymes, blood EtOH was more rapidly cleared in hPXR females. These factors combined to provide greater protection against EtOH-induced liver injury in female hPXR mice, as revealed by markers for liver damage, lipid peroxidation, and endoplasmic reticulum stress. These results indicate that female hPXR mice are less susceptible to acute binge EtOH-induced hepatotoxicity than their male counterparts, due at least in part to the relative suppression of cellular stress and enhanced expression of enzymes involved in both EtOH metabolism and hepatocyte proliferation and repair in hPXR females. U.S. Government work not protected by U.S. copyright.

  3. Molecular analysis of the nerve growth factor receptor

    Hempstead, B.; Patil, N.; Olson, K.; Chao, M.

    1988-01-01

    An essential molecule in the translocation of information by nerve growth factor (NGF) to responsive cells is the cell-surface receptor for NGF. This paper presents information on the genomic structure of the NGF receptor gene, NGF receptor models, and transfection of NGF receptors. Equilibrium binding of [ 125 I]NGF to cells reveals two distinct affinity states for the NGF receptor. The human NGF receptor gene is a single-copy gene, consisting of six exons that span 23 kb. The receptor gene is capable of being transferred to fibroblast cells from human genomic DNA and expressed at high levels. The constitutive nature of the receptor promoter sequence is a partial explanation of why this tissue-specific gene is expressed efficiently in a variety of nonneuronal cells after genomic gene transfer. The two kinetic forms of the NGF receptor appear to be encoded by the same protein, which is the product of a single gene

  4. Interaction of epidermal growth factor receptors with the cytoskeleton is related to receptor clustering

    van Belzen, N.; Spaargaren, M.; Verkleij, A. J.; Boonstra, J.

    1990-01-01

    Recently it has been established that cytoskeleton-associated epidermal growth factor (EGF) receptors are predominantly of the high-affinity class and that EGF induces a recruitment of low-affinity receptors to the cytoskeleton. The nature of this EGF-induced receptor-cytoskeleton interaction,

  5. Factors Influencing the Gender Breakdown of Academic Radiology Residency Programs.

    Campbell, James C; Yoon, Sora C; Cater, Sarah Wallace; Grimm, Lars J

    2017-07-01

    To determine the gender distribution of radiology residency programs and identify associations with radiology departmental factors. The residency programs affiliated with the top 50 research medical school from US News and World Report were identified. The gender of all radiology residency graduates from each program from 2011 to 2015 were collected. Radiology departmental factors were collected: gender of chairperson, gender of program director, gender of faculty, geographic location, and city population of the residency program. The median percentage of female radiology faculty and residents were calculated and classified as above or below the median. Comparisons were made between residency programs and departmental factors via a Pearson χ 2 univariate test or logistic regression. There were 618 (27.9%) female and 1,598 (72.1%) male residents in our study, with a median female representation of 26.4% in each program. Programs with a female residency program director were significantly more likely to have an above-median percentage of female residents versus a male program director (68.4% versus 38.7%, P = .04). Programs in the Northeast (70.6%) and West (70.0%) had higher above-median female representation than the South (10.0%) and Midwest (38.5%, P < .01). There was no association with city population size (P = .40), gender of faculty (P = .40), residency size (P = .91), or faculty size (P = .15). Radiology residency programs with a female residency program director and those in the Northeast or West have a greater concentration of female residents. Residency programs that aim to increase female representation should investigate modifiable factors that can improve their recruitment practices. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  6. Prevalence and risk factors for gender based violence during ...

    Background: Gender Based Violence (GBV) is a pervasive and systemic public health problem affecting pregnant women but there is paucity of data on the magnitude of GBV during pregnancy and the factors associated with it in Kenya, particularly in areas where the prevalence of GBV in the general population is ...

  7. Gender Factors in Capital Sourcing and Accessibility by Arable Crop ...

    Female farmers' access to loan was positively influenced by their level of education and length of loan repayment period. The access to loan by the female farmers was significantly and negatively influenced by value of required collaterals, size of their households, and interest charges on the loans. Gender related factors ...

  8. Factors Influencing Gender Based Violence among Men and ...

    This study determined the factors associated with gender based violence among 3000 men and women in selected states in Nigeria. Respondents who had experienced physical violence were 806(26.9%), comprising 353(11.8%) males and 453(15.1%) females (p<0.001). Respondents who had experienced sexual ...

  9. Urokinase-type plasminogen activator receptor (uPAR), tissue factor (TF) and epidermal growth factor receptor (EGFR)

    Christensen, Anders; Kiss, Katalin; Lelkaitis, Giedrius

    2017-01-01

    Background: Tumor-specific biomarkers are a prerequisite for the development of targeted imaging and therapy in oral squamous cell carcinoma (OSCC). urokinase-type Plasminogen Activator Receptor (uPAR), Tissue Factor (TF) and Epidermal Growth Factor Receptor (EGFR) are three biomarkers that exhib...... with a reduced survival. uPAR seems to be a prognostic biomarker in oral cancer....

  10. Radiotherapy and receptor of epidermal growth factor

    Deberne, M.

    2009-01-01

    The expression level of the receptor of the epidermal growth factor is in correlation with the tumor cells radiosensitivity. An overexpression of the E.G.F.R. is often present in the bronchi cancer, epidermoid carcinomas of the O.R.L. sphere, esophagus, uterine cervix, and anal duct but also in the rectum cancers and glioblastomas. At the clinical level, the E.G.F.R. expression is in correlation with an unfavourable prognosis after radiotherapy in numerous tumoral localizations. In the rectum cancers it is an independent prognosis factor found in multifactorial analysis: increase of the rate of nodes and local recurrence when the E.G.F.R. is over expressed. In the uterine cervix cancers, the survival is is negatively affected in multifactorial analysis by the E.G.F.R. membranes expression level. At the therapy level, the development of anti E.G.F.R. targeted therapies (tyrosine kinase inhibitors and monoclonal antibodies) opens a new therapy field at radio-sensitivity potentiality. The irradiation makes an activation of the E.G.F.R. way that would be partially responsible of the post irradiation tumoral repopulation. This activation leads the phosphorylation of the PI3 kinase ways and M.A.P. kinase ones, then the Akt protein one that acts an apoptotic modulator part. It has been shown that blocking the E.G.F.R. way acts on three levels: accumulation of ells in phase G1, reduction of the cell repair and increasing of apoptosis. he inhibition of post irradiation action of the E.G.F.R. signal way is a factor explaining the ionizing radiation - anti E.G.F.R. synergy. The preclinical data suggest that the E.G.F.R. blocking by the monoclonal antibodies is more important than the use of tyrosine kinase inhibitors. A first positive randomized study with the cetuximab, published in 2006 in the epidermoid carcinomas of the O.R.L. sphere lead to its authorization on the market with the radiotherapy for this localization. The use of cetuximab in other indication with or in

  11. Effects of serotonin-2A receptor binding and gender on personality traits and suicidal behavior in borderline personality disorder.

    Soloff, Paul H; Chiappetta, Laurel; Mason, Neale Scott; Becker, Carl; Price, Julie C

    2014-06-30

    Impulsivity and aggressiveness are personality traits associated with a vulnerability to suicidal behavior. Behavioral expression of these traits differs by gender and has been related to central serotonergic function. We assessed the relationships between serotonin-2A receptor function, gender, and personality traits in borderline personality disorder (BPD), a disorder characterized by impulsive-aggression and recurrent suicidal behavior. Participants, who included 33 BPD patients and 27 healthy controls (HC), were assessed for Axis I and II disorders with the Structured Clinical Interview for DSM-IV and the International Personality Disorders Examination, and with the Diagnostic Interview for Borderline Patients-Revised for BPD. Depressed mood, impulsivity, aggression, and temperament were assessed with standardized measures. Positron emission tomography with [(18)F]altanserin as ligand and arterial blood sampling was used to determine the binding potentials (BPND) of serotonin-2A receptors in 11 regions of interest. Data were analyzed using Logan graphical analysis, controlling for age and non-specific binding. Among BPD subjects, aggression, Cluster B co-morbidity, antisocial PD, and childhood abuse were each related to altanserin binding. BPND values predicted impulsivity and aggression in BPD females (but not BPD males), and in HC males (but not HC females.) Altanserin binding was greater in BPD females than males in every contrast, but it did not discriminate suicide attempters from non-attempters. Region-specific differences in serotonin-2A receptor binding related to diagnosis and gender predicted clinical expression of aggression and impulsivity. Vulnerability to suicidal behavior in BPD may be related to serotonin-2A binding through expression of personality risk factors. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Racial and gender discrimination: risk factors for high blood pressure?

    Krieger, N

    1990-01-01

    Despite controversy as to the biologic and/or social meaning of 'race' and 'sex', few public health studies have directly examined the impact of racial or gender discrimination on health. One plausible condition they might affect is hypertension, since stress and internalized anger may constitute important risk factors for this disease. The present investigation therefore sought to determine the feasibility of asking questions pertaining to race- and gender-biased treatment plus response to unfair treatment, and to assess their predictive value regarding self-reported high blood pressure. Using random-digit dialing, 51 black and 50 white women, ages 20-80, who resided in Alameda County, CA in 1987, were identified and interviewed by phone. Among black respondents, those who stated they usually accepted and kept quiet about unfair treatment were 4.4 times more likely to report hypertension than women who said they took action and talked to others (P = 0.01 for linear trend); no clear association existed among white respondents. The age-adjusted risk of high blood pressure among black respondents who recounted experiencing zero instances of race- and gender-biased treatment was 2.6 times greater than that of black women who reported one or more such instances (95% CI = 0.7, 10.5). Among white respondents, gender discrimination was not associated with hypertension. These results suggest that an internalized response to unfair treatment, plus non-reporting of race and gender discrimination, may constitute risk factors for high blood pressure among black women. They also bolster the view that subjective appraisal of stressors may be inversely associated with risk of hypertension.

  13. Steroid hormone and epidermal growth factor receptors in meningiomas.

    Horsfall, D J; Goldsmith, K G; Ricciardelli, C; Skinner, J M; Tilley, W D; Marshall, V R

    1989-11-01

    A prospective study of steroid hormone and epidermal growth factor receptor expression in 57 meningiomas is presented. Scatchard analysis of radioligand binding identified 20% of meningiomas as expressing classical oestrogen receptors (ER) at levels below that normally accepted for positivity, the remainder being negative. ER could not be visualized in any meningioma using immunocytochemistry. Alternatively, 74% of meningiomas demonstrated the presence of progesterone receptors (PR) by Scatchard analysis, the specificity of which could not be attributed to glucocorticoid or androgen receptors. Confirmation of classical PR presence was determined by immunocytochemical staining. The presence of epidermal growth factor receptor (EGFR) was demonstrated in 100% of meningiomas using immunocytochemical staining. These data are reviewed in the context of previously reported results and are discussed in relation to the potential for medical therapy as an adjunct to surgery.

  14. Andrographolide regulates epidermal growth factor receptor and transferrin receptor trafficking in epidermoid carcinoma (A-431) cells

    Tan, Y; Chiow, KH; Huang, D; Wong, SH

    2010-01-01

    Background and purpose: Andrographolide is the active component of Andrographis paniculata, a plant used in both Indian and Chinese traditional medicine, and it has been demonstrated to induce apoptosis in different cancer cell lines. However, not much is known about how it may affect the key receptors implicated in cancer. Knowledge of how andrographolide affects receptor trafficking will allow us to better understand new mechanisms by which andrographolide may cause death in cancer cells. Experimental approach: We utilized the well-characterized epidermal growth factor receptor (EGFR) and transferrin receptor (TfR) expressed in epidermoid carcinoma (A-431) cells as a model to study the effect of andrographolide on receptor trafficking. Receptor distribution, the total number of receptors and surface receptors were analysed by immunofluorescence, Western blot as well as flow-cytometry respectively. Key results: Andrographolide treatment inhibited cell growth, down-regulated EGFRs on the cell surface and affected the degradation of EGFRs and TfRs. The EGFR was internalized into the cell at an increased rate, and accumulated in a compartment that co-localizes with the lysosomal-associated membrane protein in the late endosomes. Conclusion and implications: This study sheds light on how andrographolide may affect receptor trafficking by inhibiting receptor movement from the late endosomes to lysosomes. The down-regulation of EGFR from the cell surface also indicates a new mechanism by which andrographolide may induce cancer cell death. PMID:20233216

  15. Gender differences in risk factors for coronary heart disease.

    Tan, Yen Y; Gast, Gerrie-Cor M; van der Schouw, Yvonne T

    2010-02-01

    Coronary heart disease (CHD), traditionally considered a male disease, is also a major threat to women. This review article addresses independent risk factors for CHD that are specific for women as well as non-gender-specific risk factors and how their effects differ between men and women. Although polycystic ovary syndrome (PCOS) in women is associated with an adverse metabolic risk profile, current evidence regarding future risk of CHD is conflicting. Preeclampsia is consistently associated with higher risk of CHD later in life. Menopause is associated with an increased risk of CHD, and the earlier the onset of menopause, the larger the risk. Existing data on postmenopausal hormone therapy (HT) was inconclusive with regard to possible protection when HT is initiated close to menopause in young peri- or postmenopausal women. Evidence on use of low-dose oral contraceptives strongly suggests no increased risk of CHD. Although levels of physical inactivity are similar for men and women, the higher prevalences of hypertension, diabetes, and obesity in older women portends a greater risk in women than in men. Additionally, risk factors like smoking, hypertriglyceridemia and low high-density lipoprotein cholesterol levels have greater impact in women than in men. This review indicates that acknowledgement of non-gender-specific risk factors in addition to those that are unique to women would help optimize diagnosis, treatment and earlier prevention of CHD in women. Further research is needed to ascertain if incorporating these gender-specific risks into a clinically used risk stratification model would change outcome in women. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  16. Risk Factors for Gambling Problems: An Analysis by Gender.

    Hing, Nerilee; Russell, Alex; Tolchard, Barry; Nower, Lia

    2016-06-01

    Differences in problem gambling rates between males and females suggest that associated risk factors vary by gender. Previous combined analyses of male and female gambling may have obscured these distinctions. This study aimed to develop separate risk factor models for gambling problems for males and for females, and identify gender-based similarities and differences. It analysed data from the largest prevalence study in Victoria Australia (N = 15,000). Analyses determined factors differentiating non-problem from at-risk gamblers separately for women and men, then compared genders using interaction terms. Separate multivariate analyses determined significant results when controlling for all others. Variables included demographics, gambling behaviour, gambling motivations, money management, and mental and physical health. Significant predictors of at-risk status amongst female gamblers included: 18-24 years old, not speaking English at home, living in a group household, unemployed or not in the workforce, gambling on private betting, electronic gaming machines (EGMs), scratch tickets or bingo, and gambling for reasons other than social reasons, to win money or for general entertainment. For males, risk factors included: 18-24 years old, not speaking English at home, low education, living in a group household, unemployed or not in the workforce, gambling on EGMs, table games, races, sports or lotteries, and gambling for reasons other than social reasons, to win money or for general entertainment. High risk groups requiring appropriate interventions comprise young adults, especially males; middle-aged female EGM gamblers; non-English speaking populations; frequent EGM, table games, race and sports gamblers; and gamblers motivated by escape.

  17. Signal transduction by the platelet-derived growth factor receptor

    Williams, L.T.; Escobedo, J.A.; Keating, M.T.; Coughlin, S.R.

    1988-01-01

    The mitogenic effects of platelet-derived growth factor (PDGF) are mediated by the PDGF receptor. The mouse PDGF receptor was recently purified on the basis of its ability to become tyrosine phosphorylated in response to the A-B human platelet form of PDGF, and the receptor amino acid sequence was determined from a full-length cDNA clone. Both the human and mouse receptor cDNA sequences have been expressed in Chinese hamster ovary fibroblast (CHO) cells that normally lack PDGF receptors. This paper summarizes recent results using this system to study signal transduction by the PDGF receptor. Some of the findings show that the KI domain of the PDGF receptor plays an important role in the stimulation of DNA synthesis by PDGF. Surprisingly, the kinase insert region is not essential for PDGF stimulation of PtdIns turnover, pH change, increase in cellular calcium, and receptor autophosphorylation. In addition, PDGF stimulates a conformational change in the receptor

  18. Novel Drosophila receptor that binds multiple growth factors

    Rosner, M.R.; Thompson, K.L.; Garcia, V.; Decker, S.J.

    1986-01-01

    The authors have recently reported the identification of a novel growth factor receptor from Drosophila cell cultures that has dual binding specificity for both insulin and epidermal growth factor (EGF). This 100 kDa protein is also antigenically related to the cytoplasmic region of the mammalian EGF receptor-tyrosine kinase. They now report that this protein binds to mammalian nerve growth factor and human transforming growth factor alpha as well as insulin and EGF with apparent dissociation constants ranging from 10 -6 to 10 -8 M. The 100 kDa protein can be affinity-labeled with these 125 I-labeled growth factors after immunoprecipitation with anti-EGF receptor antiserum. These four growth factors appear to share a common binding site, as evidenced by their ability to block affinity labelling by 125 I-insulin. No significant binding to the 100 kDa protein was observed with platelet-derived growth factor, transforming growth factor beta, or glucagon. The 100 kDa Drosophila protein has a unique ligand-binding spectrum with no direct counterpart in mammalian cells and may represent an evolutionary precursor of the mammalian receptors for these growth factors

  19. Assembly and activation of neurotrophic factor receptor complexes.

    Simi, Anastasia; Ibáñez, Carlos F

    2010-04-01

    Neurotrophic factors play important roles in the development and function of both neuronal and glial elements of the central and peripheral nervous systems. Their functional diversity is in part based on their ability to interact with alternative complexes of receptor molecules. This review focuses on our current understanding of the mechanisms that govern the assembly and activation of neurotrophic factor receptor complexes. The realization that many, if not the majority, of these complexes exist in a preassembled form at the plasma membrane has forced the revision of classical ligand-mediated oligomerization models, and led to the discovery of novel mechanisms of receptor activation and generation of signaling diversity which are likely to be shared by many different classes of receptors.

  20. Topical administration of adrenergic receptor pharmaceutics and nerve growth factor

    Jena J Steinle

    2010-06-01

    Full Text Available Jena J SteinleDepartments of Ophthalmology and Anatomy and Neurobiology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN 38163, USAAbstract: Topical application of nerve growth factor (NGF and adrenergic receptor pharmaceutics are currently in use for corneal ulcers and glaucoma. A recent interest in the neuroprotective abilities of NGF has led to a renewed interest in NGF as a therapeutic for retinal and choroidal diseases. NGF can promote cell proliferation through actions of the TrkA receptor or promote apoptosis through receptor p75NTR. This understanding has led to novel interest in the role of NGF for diseases of the posterior eye. The role of β-adrenergic receptor agonists and antagonists for treatments of glaucoma, diabetic retinopathy, and their potential mechanisms of action, are still under investigation. This review discusses the current knowledge and applications of topical NGF and adrenergic receptor drugs for ocular disease.Keywords: NGF, β-adrenergic receptor agents, α-adrenergic receptor agents, retina, cornea, glaucoma

  1. A model of gender prejudice, power, and discrimination: How hierarchy-enhancing factors predominate over hierarchy-attenuating factors

    Kleinlogel, E. P.; Dietz, J.

    2015-01-01

    Gender inequalities remain an issue in our society and particularly in the workplace. Several factors can explain this gender difference in top-level managerial positions such as career ambitions but also biases against women. In our chapter, we propose a model explaining why gender inequalities and particularly discrimination against women is still present in our societies despite social norms and existing legislation on gender equality. To this purpose, we review research on discrimination ...

  2. The diminished expression of proangiogenic growth factors and their receptors in gastric ulcers of cirrhotic patients.

    Luo, Jiing-Chyuan; Peng, Yen-Ling; Hou, Ming-Chih; Huang, Kuang-Wei; Huang, Hui-Chun; Wang, Ying-Wen; Lin, Han-Chieh; Lee, Fa-Yauh; Lu, Ching-Liang

    2013-01-01

    The pathogenesis of the higher occurrence of peptic ulcer disease in cirrhotic patients is complex. Platelets can stimulate angiogenesis and promote gastric ulcer healing. We compared the expressions of proangiogenic growth factors and their receptors in the gastric ulcer margin between cirrhotic patients with thrombocytopenia and those of non-cirrhotic patients to elucidate possible mechanisms. Eligible cirrhotic patients (n = 55) and non-cirrhotic patients (n = 55) who had gastric ulcers were enrolled. Mucosa from the gastric ulcer margin and non-ulcer areas were sampled and the mRNA expressions of the proangiogenic growth factors (vascular endothelial growth factor [VEGF], platelet derived growth factor [PDGF], basic fibroblast growth factor [bFGF]) and their receptors (VEGFR1, VEGFR2, PDGFRA, PDGFRB, FGFR1, FGFR2) were measured and compared. Platelet count and the expressions of these growth factors and their receptors were correlated with each other. The two groups were comparable in terms of gender, ulcer size and infection rate of Helicobacter pylori. However, the cirrhotic group were younger in age, had a lower platelet count than those in the non-cirrhotic group (pexpressions of PDGFB, VEGFR2, FGFR1, and FGFR2 in gastric ulcer margin when compared with those of the non-cirrhotic patients (pexpressions of PDGFB and VEGFR2, FGFR1, and FGFR2 were well correlated with the degree of thrombocytopenia in these cirrhotic patients (ρ>0.5, pimplied that diminished activity of proangiogenic factors and their receptors may contribute to the pathogenesis of gastric ulcers in cirrhotic patients.

  3. Examining the Impact of Gender on the Factor Structure of the Psychopathic Personality Inventory--Revised

    Anestis, Joye C.; Caron, Kelly M.; Carbonell, Joyce L.

    2011-01-01

    Research on the factor structure of psychopathy has yielded mixed results, supporting anywhere from one to three factors. Additionally, most of this research has used all-male samples, and the possibility of structural invariance across gender has not been examined. Using a mixed-gender sample of 360 undergraduates, the factor structure of the…

  4. The influence of social factors on gender health.

    2016-08-01

    Male births exceed female births by 5-6% (for a sex ratio at birth of 1.05-1.06) while a women's life expectancy, on a global scale, is about 6 years longer. Thus within various age groups the male:female ratio changes over time. Until age 50 years men outnumber women; thereafter their numbers show a sharp decline. Consequently at age 80 years, there are many more women than men. An estimated 25% of this male excess mortality is due to biological causes, the rest being explained by behavioural, cultural and environmental factors. For both women and men, the main health risks related to lifestyle are smoking, alcohol, unhealthy diet and physical inactivity. In the year 2010, overweight (BMI: 25-29 kg/m(2)) and obesity (BMI: >30 kg/m(2)) were responsible for over 3 million deaths, with similar relative risks in men and women for overweight and obesity. Smoking and alcohol are the major causes of the global gender gap in mortality. For women in some parts of the world however pregnancy is also hazardous. On a global scale, in 2013 about 300 000 deaths were related to pregnancy, with sub-Saharan Africa registering the highest maternal mortality: over 500 maternal deaths per 100 000 births. Additional woman's health risks arise from gender discrimination, including sex-selective abortion, violence against women and early child marriage. Providers should be aware of the effect that these risks can have on both reproductive and general health. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Factor Structure of a Multidimensional Gender Identity Scale in a Sample of Chinese Elementary School Children

    Lu Yu

    2012-01-01

    Full Text Available This study examined the factor structure of a scale based on the four-dimensional gender identity model (Egan and Perry, 2001 in 726 Chinese elementary school students. Exploratory factor analyses suggested a three-factor model, two of which corresponded to “Felt Pressure” and “Intergroup Bias” in the original model. The third factorGender Compatibility” appeared to be a combination of “Gender Typicality” and “Gender Contentment” in the original model. Follow-up confirmatory factor analysis (CFA indicated that, relative to the initial four-factor structure, the three-factor model fits the current Chinese sample better. These results are discussed in light of cross-cultural similarities and differences in development of gender identity.

  6. Insulin and insulin-like growth factor receptors and responses

    Roth, R.A.; Steele-Perkins, G.; Hari, J.; Stover, C.; Pierce, S.; Turner, J.; Edman, J.C.; Rutter, W.J.

    1988-01-01

    Insulin is a member of a family of structurally related hormones with diverse physiological functions. In humans, the best-characterized members of this family include insulin, insulin-like growth factor (IGF)-I, and IGF-II. Each of these three polypeptide hormones has its own distinct receptor. The structures of each of these receptors have now been deduced from analyses of isolated cDNA clones. To study further the responses mediated through these three different receptors, the authors have been studying cells expressing the proteins encoded by these three cDNAs. The isolated cDNAs have been transfected into Chinese hamster ovary (CHO) cells, and the resulting transfected cell lines have been characterized as to the ligand-binding activities and signal-transducing activities of the expressed proteins

  7. Distribution of corticotropin-releasing factor receptors in primate brain

    Millan, M.A.; Jacobowitz, D.M.; Hauger, R.L.; Catt, K.J.; Aguilera, G.

    1986-01-01

    The distribution and properties of receptors for corticotropin-releasing factor (CRF) were analyzed in the brain of cynomolgus monkeys. Binding of [ 125 I]tyrosine-labeled ovine CRF to frontal cortex and amygdala membrane-rich fractions was saturable, specific, and time- and temperature-dependent, reaching equilibrium in 30 min at 23 0 C. Scatchard analysis of the binding data indicated one class of high-affinity sites with a K/sub d/ of 1 nM and a concentration of 125 fmol/mg. As in the rat pituitary and brain, CRF receptors in monkey cerebral cortex and amygdala were coupled to adenylate cyclase. Autoradiographic analysis of specific CRF binding in brain sections revealed that the receptors were widely distributed in the cerebral cortex and limbic system. Receptor density was highest in the pars tuberalis of the pituitary and throughout the cerebral cortex, specifically in the prefrontal, frontal, orbital, cingulate, insular, and temporal areas, and in the cerebellar cortex. A low binding density was present in the superior colliculus, locus coeruleus, substantia gelatinosa, preoptic area, septal area, and bed nucleus of the stria terminalis. These data demonstrate that receptors for CRF are present within the primate brain at areas related to the central control of visceral function and behavior, suggesting that brain CRF may serve as a neurotransmitter in the coordination of endocrine and neural mechanisms involved in the response to stress

  8. Platelet-derived growth factor receptors in the human central nervous system : autoradiographic distribution and receptor densities in multiple sclerosis

    De Keyser, J; Wilczak, N

    1997-01-01

    Platelet derived growth factor (PDGF) receptors were studied in postmortem adult human brain and cervical spinal cord using autoradiography with human recombinant I-125-PDGF-BB. PDGF-BB binds to the three different dimers of PDGF receptors (alpha alpha, alpha beta and beta beta) PDGF receptors were

  9. Gender Difference as a Factor in Teachers' Perceptions of Students.

    Prawat, Richard S.; Jarvis, Robert

    1980-01-01

    Teacher perceptions of students as influenced by differences in student gender are examined. Elementary school teachers' perceptions of students were assessed by their rating children in their classes on various dimensions. Results showed student ability/achievement are more potent in teacher perceptions than gender. (Author/GK)

  10. Epidermal growth factor receptor expression in urinary bladder cancer

    Dayalu S.L. Naik

    2011-01-01

    Full Text Available Objective : To evaluate the expression pattern of epidermal growth factor receptor (EGFR in urinary bladder cancer and its association with human epidermal growth factor receptor 2 (HER2, epidermal growth factor (EGF, interleukin-6 (IL-6, and high risk human papilloma virus (HPV types 16 and 18. Materials and Methods : Thirty cases of urothelial carcinoma were analyzed. EGFR, HER2, EGF, and IL-6 expressions in the tissue were evaluated by immunohistochemical staining. For HPV, DNA from tissue samples was extracted and detection of HPV was done by PCR technique. Furthermore, evaluation of different intracellular molecules associated with EGFR signaling pathways was performed by the western blot method using lysates from various cells and tissues. Results : In this study, the frequencies of immunopositivity for EGFR, HER2, EGF, and IL-6 were 23%, 60%, 47%, and 80%, respectively. No cases were positive for HPV-18, whereas HPV-16 was detected in 10% cases. Overall, expression of EGFR did not show any statistically significant association with the studied parameters. However, among male patients, a significant association was found only between EGFR and HER2. Conclusions : Overexpression of EGFR and/or HER2, two important members of the same family of growth factor receptors, was observed in a considerable proportion of cases. Precise knowledge in this subject would be helpful to formulate a rational treatment strategy in patients with urinary bladder cancer.

  11. Topical administration of adrenergic receptor pharmaceutics and nerve growth factor

    Steinle, Jena

    2010-01-01

    Jena J SteinleDepartments of Ophthalmology and Anatomy and Neurobiology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN 38163, USAAbstract: Topical application of nerve growth factor (NGF) and adrenergic receptor pharmaceutics are currently in use for corneal ulcers and glaucoma. A recent interest in the neuroprotective abilities of NGF has led to a renewed interest in NGF as a therapeutic for retinal and choroidal diseases. NGF can promote cell proliferati...

  12. Multiple autophosphorylation sites of the epidermal growth factor receptor are essential for receptor kinase activity and internalization. Contrasting significance of tyrosine 992 in the native and truncated receptors

    Sorkin, A; Helin, K; Waters, C M

    1992-01-01

    The role of epidermal growth factor (EGF) receptor autophosphorylation sites in the regulation of receptor functions has been studied using cells transfected with mutant EGF receptors. Simultaneous point mutation of 4 tyrosines (Y1068, Y1086, Y1148, Y1173) to phenylalanine, as well as removal of ...

  13. Decreased expression of serum and microvascular vascular endothelial growth factor receptor-2 in meningococcal sepsis*.

    Flier, M. van der; Baerveldt, E.M.; Miedema, A.; Hartwig, N.G.; Hazelzet, J.A.; Emonts, M.; Groot, R. de; Prens, E.P.; Vught, A.J. van; Jansen, N.J.

    2013-01-01

    OBJECTIVES: To determine the skin microvessel expression of vascular endothelial growth factor receptor 2 and serum-soluble vascular endothelial growth factor receptor 2 levels in children with meningococcal sepsis. DESIGN: Observational study. SETTING: Two tertiary academic children hospital PICUs.

  14. 287 Factors That Promote Gender Imbalance in the Teaching of ...

    User

    good working environment to teachers and equip the laboratories for effective ... Ibibio women at the early part of this century scarcely had access to education yet .... is still gender disparity in enrolment, performance and completion of science.

  15. Gender analysis of factors affecting facilitation of agricultural ...

    It ascertained the perception of the gender groups on the organizational, job related and ... and ensure balanced working conditions for both men and women facilitators in the NFDP III. This will help to ultimately improve their job performance.

  16. Teachers' Attitude and Gender Factor as Determinant of Pupils ...

    Nekky Umera

    Abstract. Teachers are regarded as the basic tools in education and curriculum .... The analysis in table 1 showed that teachers' attitude have significant effect ... Iroegbu, T.O (1998) Problem based learning, numerical ability and gender as.

  17. Home and Motivational Factors Related to Science-Career Pursuit: Gender differences and gender similarities

    Shin, Jongho; Lee, Hyunjoo; McCarthy-Donovan, Alexander; Hwang, Hyeyoung; Yim, Sonyoung; Seo, EunJin

    2015-06-01

    The purpose of the study was to examine whether gender differences exist in the mean levels of and relations between adolescents' home environments (parents' view of science, socio-economic status (SES)), motivations (intrinsic and instrumental motivations, self-beliefs), and pursuit of science careers. For the purpose, the Programmed for International Student Assessment 2006 data of Korean 15-year-old students were analysed. The results of the study showed that girls had lower levels of science intrinsic and instrumental motivations, self-beliefs, and science-career pursuit (SCP) as well as their parents' values in science less than boys. Gender similarities, rather than gender differences, existed in patterns of causal relationship among home environments, motivations, and SCP. The results showed positive effects for parents' higher value in science and SES on motivations, SCP, and for intrinsic and instrumental motivations on SCP for girls and boys. These results provide implications for educational interventions to decrease gender differences in science motivations and SCP, and to decrease adolescents' gender stereotypes.

  18. Gender and the use of hormonal contraception in women are not associated with cerebral cortical 5-HT 2A receptor binding

    Frokjaer, V G; Erritzoe, D; Madsen, J

    2009-01-01

    to frontolimbic 5-HT(2A) receptor binding and to be more pronounced in women, again, the effect of gender was not significant (P=0.42, n=127). Also, the use of hormonal contraception (n=14) within the group of pre-menopausal women (total n=29) was not associated with cortical 5-HT(2A) receptor binding (P=0.......31). In conclusion, neither gender, nor the use of hormonal contraception in premenopausal women was associated with cortical 5-HT(2A) receptor binding....... binding it is not clear if gender or use of hormonal contraception exhibits associations with 5-HT(2A) receptor binding. We found no significant effect of gender on cortical 5-HT(2A) receptor binding (P=0.15, n=132). When adjusting for the personality trait neuroticism, known to be positively correlated...

  19. Epidermal Growth Factor Receptor (EGFR) Crosstalks in Liver Cancer

    Berasain, Carmen; Latasa, María Ujue; Urtasun, Raquel; Goñi, Saioa; Elizalde, María; Garcia-Irigoyen, Oihane; Azcona, María; Prieto, Jesús; Ávila, Matías A.

    2011-01-01

    Hepatocarcinogenesis is a complex multistep process in which many different molecular pathways have been implicated. Hepatocellular carcinoma (HCC) is refractory to conventional chemotherapeutic agents, and the new targeted therapies are meeting with limited success. Interreceptor crosstalk and the positive feedback between different signaling systems are emerging as mechanisms of targeted therapy resistance. The identification of such interactions is therefore of particular relevance to improve therapeutic efficacy. Among the different signaling pathways activated in hepatocarcinogenesis the epidermal growth factor receptor (EGFR) system plays a prominent role, being recognized as a “signaling hub” where different extracellular growth and survival signals converge. EGFR can be transactivated in response to multiple heterologous ligands through the physical interaction with multiple receptors, the activity of intracellular kinases or the shedding of EGFR-ligands. In this article we review the crosstalk between the EGFR and other signaling pathways that could be relevant to liver cancer development and treatment

  20. Epidermal growth factor receptor in primary human lung cancer

    Yu Xueyan; Hu Guoqiang; Tian Keli; Wang Mingyun

    1996-01-01

    Cell membranes were prepared from 12 human lung cancers for the study of the expression of epidermal growth factor receptors (EGFR). EGFR concentration was estimated by ligand binding studies using 125 I-radiolabeled EGF. The dissociation constants of the high affinity sites were identical, 1.48 nmol and 1.1 nmol in cancer and normal lung tissues, the EGFR contents were higher in lung cancer tissues (range: 2.25 to 19.39 pmol·g -1 membrane protein) than that in normal tissues from the same patients (range: 0.72 to 7.43 pmol·g -1 membrane protein). These results suggest that EGF and its receptor may play a role in the regulatory mechanisms in the control of lung cellular growth and tumor promotion

  1. Tyrosine 769 of the keratinocyte growth factor receptor is required for receptor signaling but not endocytosis

    Ceridono, Mara; Belleudi, Francesca; Ceccarelli, Simona; Torrisi, Maria Rosaria

    2005-01-01

    Keratinocyte growth factor receptor (KGFR) is a receptor tyrosine kinase expressed on epithelial cells which belongs to the family of fibroblast growth factor receptors (FGFRs). Following ligand binding, KGFR is rapidly autophosphorylated on specific tyrosine residues in the intracellular domain, recruits substrate proteins, and is rapidly internalized by clathrin-mediated endocytosis. The role of different autophosphorylation sites in FGFRs, and in particular the role of the tyrosine 766 in FGFR1, first identified as PLCγ binding site, has been extensively studied. We analyzed here the possible role of the tyrosine 769 in KGFR, corresponding to tyrosine 766 in FGFR1, in the regulation of KGFR signal transduction and MAPK activation as well as in the control of the endocytic process of KGFR. A mutant KGFR in which tyrosine 769 was substituted by phenylalanine was generated and transfected in NIH3T3 and HeLa cells. Our results indicate that tyrosine 769 is required for the binding to KGFR and tyrosine phosphorylation of PLCγ as well as for the full activation of MAPKs and for cell proliferation through the regulation of FRS2 tyrosine phosphorylation, suggesting that this residue represents a key regulator of KGFR signal transduction. Our data also show that tyrosine 769 is not involved in the regulation of the endocytic process of KGFR

  2. Home and Motivational Factors Related to Science-Career Pursuit: Gender Differences and Gender Similarities

    Shin, Jongho; Lee, Hyunjoo; McCarthy-Donovan, Alexander; Hwang, Hyeyoung; Yim, Sonyoung; Seo, EunJin

    2015-01-01

    The purpose of the study was to examine whether gender differences exist in the mean levels of and relations between adolescents' home environments (parents' view of science, socio-economic status (SES)), motivations (intrinsic and instrumental motivations, self-beliefs), and pursuit of science careers. For the purpose, the Programmed for…

  3. Age and gender might influence big five factors of personality: a preliminary report in Indian population.

    Magan, Dipti; Mehta, Manju; Sarvottam, Kumar; Yadav, Raj Kumar; Pandey, R M

    2014-01-01

    Age and gender are two important physiological variables which might influence the personality of an individual. The influence of age and gender on big five personality domains in Indian population was assessed in this cross-sectional study that included 155 subjects (female = 76, male = 79) aged from 16-75 years. Big five personality factors were evaluated using 60-item NEO-Five Factor Inventory (NEO-FFI) at a single point in time. Among the big five factors of personality, Conscientiousness was positively correlated (r = 0.195; P personality traits might change with age, and is gender-dependent.

  4. More than Numbers: Individual and Contextual Factors in How Gender Diversity Affects Women's Well-Being

    Miner-Rubino, Kathi; Settles, Isis H.; Stewart, Abigail J.

    2009-01-01

    This study examined factors related to workplace gender diversity in a sample of 87 college-educated White women. Specifically, we investigated the moderating effects of one individual difference variable (sensitivity to sexism) and one contextual variable (perceptions of the workplace climate) in the relationship between the gender composition at…

  5. Autism Spectrum Disorder Risk Factors and Autistic Traits in Gender Dysphoric Children

    VanderLaan, Doug P.; Leef, Jonathan H.; Wood, Hayley; Hughes, S. Kathleen; Zucker, Kenneth J.

    2015-01-01

    Gender dysphoria (GD) and autism spectrum disorder (ASD) are associated. In 49 GD children (40 natal males), we examined ASD risk factors (i.e., birth weight, parental age, sibling sex ratio) in relation to autistic traits. Data were gathered on autistic traits, birth weight, parents' ages at birth, sibling sex ratio, gender nonconformity, age,…

  6. Gender-Specific Risk Factors for Intimate Partner Homicide: A Nationwide Register-Based Study

    Weizmann-Henelius, Ghitta; Gronroos, Matti; Putkonen, Hanna; Eronen, Markku; Lindberg, Nina; Hakkanen-Nyholm, Helina

    2012-01-01

    The present study examined gender differences in intimate partner homicide (IPH) and offender characteristics with the focus on putative gender-specific risk factors in a nationwide consecutive sample of homicide offenders. Data on all offenders (N = 642; 91 females, 551 males) convicted of homicide and subjected to a forensic psychiatric…

  7. Gender as a factor in delivering sustainable energy

    Clancy, Joy S.; Islam, A.K.M.S.; Infield, D.G.

    2002-01-01

    This paper reviews the role of energy in contributing to the solution of a major development objective: moving people out of poverty. Understanding gender issues, especially the crucial role women play in household energy provision, is important in the design and implementation of appropriate energy

  8. Self Efficacy, Self Esteem, and Gender as Factors Predicting ...

    For most new students, adjusting to an unfamiliar academic setting can induce homesickness. While most studies have investigated homesickness as a negative outcome of relocation, the present study extended the literature by examining the influence of self esteem, self efficacy, and gender on homesickness among ...

  9. Identification of Factors Contributing to Gender Disparity in an ...

    in absolute numbers while female dismissal rates soared alarmingly between 2000/01-2004/05. To bridge the gender disparity in participation, the paper recommends intervention strategies aimed at bolstering academic achievement and positive self-concept among female students. East African Social Science Research ...

  10. Differences among Age, Gender and School Factors in Ghanaian ...

    The conclusion of the study was that there were differences with respect to age, gender, course of study and school type in students' aspirations for entrepreneurial careers, while there was none regarding form/class level. Among the counselling implications are that counsellors must take into consideration personal and ...

  11. Epidermal growth factor and its receptors in human pancreatic carcinoma

    Chen, Y.F.; Pan, G.Z.; Hou, X.; Liu, T.H.; Chen, J.; Yanaihara, C.; Yanaihara, N.

    1990-01-01

    The role of epidermal growth factor (EGF) in oncogenesis and progression of malignant tumors is a subject of vast interest. In this study, radioimmunoassay and radioreceptor assay of EGF were established. EGF contents in malignant and benign pancreatic tumors, in normal pancreas tissue, and in culture media of a human pancreatic carcinoma cell line were determined. EGF receptor binding studies were performed. It was shown that EGF contents in pancreatic carcinomas were significantly higher than those in normal pancreas or benign pancreatic tumors. EGF was also detected in the culture medium of a pancreatic carcinoma cell line. The binding of 125I-EGF to the pancreatic carcinoma cells was time and temperature dependent, reversible, competitive, and specific. Scatchard analysis showed that the dissociation constant of EGF receptor was 2.1 X 10(-9) M, number of binding sites was 1.3 X 10(5) cell. These results indicate that there is an over-expression of EGF/EGF receptors in pancreatic carcinomas, and that an autocrine regulatory mechanism may exist in the growth-promoting effect of EGF on tumor cells

  12. Expression of epidermal growth factor receptors in human endometrial carcinoma

    Nyholm, H C; Nielsen, Anette Lynge; Ottesen, B

    1993-01-01

    Little data exist on the expression of epidermal growth factor receptors (EGF-Rs) in human endometrial cancer. EGF-R status was studied in 65 patients with endometrial carcinomas and in 26 women with nonmalignant postmenopausal endometria, either inactive/atrophic endometrium or adenomatous...... hyperplasia. EGF-R was identified on frozen tissue sections by means of an indirect immunoperoxidase technique with a monoclonal antibody against the external domain of the EGF-R. Seventy-one percent of the carcinomas expressed positive EGF-R immunoreactivity. In general, staining was most prominent...

  13. Epidermal growth factor receptor (EGFR) and EGFR mutations, function and possible role in clinical trials

    Voldborg, B R; Damstrup, L; Spang-Thomsen, M

    1997-01-01

    The epidermal growth factor receptor (EGFR) is a growth factor receptor that induces cell differentiation and proliferation upon activation through the binding of one of its ligands. The receptor is located at the cell surface, where the binding of a ligand activates a tyrosine kinase in the intr...... aspects of therapeutic targeting of EGFR....

  14. Changing the insulin receptor to possess insulin-like growth factor I ligand specificity

    Andersen, A.S.; Kjeldsen, T.; Wiberg, F.C.; Christensen, P.M.; Rasmussen, J.S.; Norris, K.; Moeller, K.B.; Moeller, N.P.H.

    1990-01-01

    To examine the role of the N-terminal part of the insulin-like growth factor I (IGF-I) receptor and insulin receptor in determining ligand specificity, the authors prepared an expression vector encoding a hybrid receptor where exon 1 (encoding the signal peptide and seven amino acids of the α-subunit), exon 2, and exon 3 of the insulin receptor were replaced with the corresponding IGF-I receptor cDNA (938 nucleotides). To allow direct quantitative comparison of the binding capabilities of this hybrid receptor with those of the human IGF-I receptor and the insulin receptor, all three receptors were expressed in baby hamster kidney (BHK) cells as soluble molecules and partially purified before characterization. The hybrid IGF-I/insulin receptor bound IGF-I with an affinity comparable to that of the wild-type IGF-I receptor. In contrast, the hybrid receptor no longer displayed high-affinity binding of insulin. These results directly demonstrate that it is possible to change the specificity of the insulin receptor to that of the IGF-I receptor and, furthermore, that the binding specificity for IGF-I is encoded within the nucleotide sequence from 135 to 938 of the IGF-I receptor cDNA. Since the hybrid receptor only bound insulin with low affinity, the insulin binding region is likely to be located within exons 2 and 3 of the insulin receptor

  15. Factor structure of PTSD, and relation with gender in trauma survivors from India

    Charak, Ruby; Armour, Cherie; Elklit, Ask; Angmo, Disket; Elhai, Jon D.; Koot, Hans M.

    2014-01-01

    Background The factor structure of posttraumatic stress disorder (PTSD) has been extensively studied in Western countries. Some studies have assessed its factor structure in Asia (China, Sri Lanka, and Malaysia), but few have directly assessed the factor structure of PTSD in an Indian adult sample. Furthermore, in a largely patriarchal society in India with strong gender roles, it becomes imperative to assess the association between the factors of PTSD and gender. Objective The purpose of the present study was to assess the factor structure of PTSD in an Indian sample of trauma survivors based on prevailing models of PTSD defined in the DSM-IV-TR (APA, 2000), and to assess the relation between PTSD factors and gender. Method The sample comprised of 313 participants (55.9% female) from Jammu and Kashmir, India, who had experienced a natural disaster (N=200) or displacement due to cross-border firing (N=113). Results Three existing PTSD models—two four-factor models (Emotional Numbing and Dysphoria), and a five-factor model (Dysphoric Arousal)—were tested using Confirmatory Factor Analysis with addition of gender as a covariate. The three competing models had similar fit indices although the Dysphoric Arousal model fit significantly better than Emotional Numbing and Dysphoria models. Gender differences were found across the factors of Re-experiencing and Anxious arousal. Conclusions Findings indicate that the Dysphoric Arousal model of PTSD was the best model; albeit the fit indices of all models were fairly similar. Compared to males, females scored higher on factors of Re-experiencing and Anxious arousal. Gender differences found across two factors of PTSD are discussed in light of the social milieu in India. PMID:25413575

  16. Factor structure of PTSD, and relation with gender in trauma survivors from India.

    Charak, Ruby; Armour, Cherie; Elklit, Ask; Angmo, Disket; Elhai, Jon D; Koot, Hans M

    2014-01-01

    The factor structure of posttraumatic stress disorder (PTSD) has been extensively studied in Western countries. Some studies have assessed its factor structure in Asia (China, Sri Lanka, and Malaysia), but few have directly assessed the factor structure of PTSD in an Indian adult sample. Furthermore, in a largely patriarchal society in India with strong gender roles, it becomes imperative to assess the association between the factors of PTSD and gender. The purpose of the present study was to assess the factor structure of PTSD in an Indian sample of trauma survivors based on prevailing models of PTSD defined in the DSM-IV-TR (APA, 2000), and to assess the relation between PTSD factors and gender. The sample comprised of 313 participants (55.9% female) from Jammu and Kashmir, India, who had experienced a natural disaster (N=200) or displacement due to cross-border firing (N=113). Three existing PTSD models-two four-factor models (Emotional Numbing and Dysphoria), and a five-factor model (Dysphoric Arousal)-were tested using Confirmatory Factor Analysis with addition of gender as a covariate. The three competing models had similar fit indices although the Dysphoric Arousal model fit significantly better than Emotional Numbing and Dysphoria models. Gender differences were found across the factors of Re-experiencing and Anxious arousal. Findings indicate that the Dysphoric Arousal model of PTSD was the best model; albeit the fit indices of all models were fairly similar. Compared to males, females scored higher on factors of Re-experiencing and Anxious arousal. Gender differences found across two factors of PTSD are discussed in light of the social milieu in India.

  17. Factor structure of PTSD, and relation with gender in trauma survivors from India

    Ruby Charak

    2014-11-01

    Full Text Available Background: The factor structure of posttraumatic stress disorder (PTSD has been extensively studied in Western countries. Some studies have assessed its factor structure in Asia (China, Sri Lanka, and Malaysia, but few have directly assessed the factor structure of PTSD in an Indian adult sample. Furthermore, in a largely patriarchal society in India with strong gender roles, it becomes imperative to assess the association between the factors of PTSD and gender. Objective: The purpose of the present study was to assess the factor structure of PTSD in an Indian sample of trauma survivors based on prevailing models of PTSD defined in the DSM-IV-TR (APA, 2000, and to assess the relation between PTSD factors and gender. Method: The sample comprised of 313 participants (55.9% female from Jammu and Kashmir, India, who had experienced a natural disaster (N=200 or displacement due to cross-border firing (N=113. Results: Three existing PTSD models—two four-factor models (Emotional Numbing and Dysphoria, and a five-factor model (Dysphoric Arousal—were tested using Confirmatory Factor Analysis with addition of gender as a covariate. The three competing models had similar fit indices although the Dysphoric Arousal model fit significantly better than Emotional Numbing and Dysphoria models. Gender differences were found across the factors of Re-experiencing and Anxious arousal. Conclusions: Findings indicate that the Dysphoric Arousal model of PTSD was the best model; albeit the fit indices of all models were fairly similar. Compared to males, females scored higher on factors of Re-experiencing and Anxious arousal. Gender differences found across two factors of PTSD are discussed in light of the social milieu in India.

  18. Expression of nerve growth factor and its receptor, tyrosine kinase receptor A, in rooster testes.

    Ma, Wei; Wang, Chunqiang; Su, Yuhong; Tian, Yumin; Zhu, Hongyan

    2015-10-01

    Nerve growth factor (NGF), which is required for the survival and differentiation of the nervous system, is also thought to play an important role in the development of mammalian reproductive tissues. To explore the function of NGF in the male reproductive system of non-mammalian animals, we determined the presence of NGF and its receptor, tyrosine kinase receptor A (TrkA), in rooster testes and investigated the regulation of NGF and TrkA expression by follicle-stimulating hormone (FSH). The mRNA and protein levels of NGF and TrkA in 6-week-old rooster testes were lower than those in 12-, 16- or 20-week age groups; levels were highest in the 16-week group. Immunohistochemistry showed that NGF and TrkA were both detected in spermatogonia, spermatocytes and spermatids. NGF immunoreactivity was observed in Leydig cells and strong TrkA signals were present in Sertoli cells. Meanwhile, FSH increased TrkA transcript levels in rooster testes in a dose-dependent manner. We present novel evidence for the developmental and FSH-regulated expression of the NGF/TrkA system, and our findings suggest that the NGF/TrkA system may play a prominent role in chicken spermatogenesis. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Personalized Radiation Oncology: Epidermal Growth Factor Receptor and Other Receptor Tyrosine Kinase Inhibitors.

    Higgins, Geoff S; Krause, Mechthild; McKenna, W Gillies; Baumann, Michael

    Molecular biomarkers are currently evaluated in preclinical and clinical studies in order to establish predictors for treatment decisions in radiation oncology. The receptor tyrosine kinases (RTK) are described in the following text. Among them, the most data are available for the epidermal growth factor receptor (EGFR) that plays a major role for prognosis of patients after radiotherapy, but seems also to be involved in mechanisms of radioresistance, specifically in repopulation of tumour cells between radiotherapy fractions. Monoclonal antibodies against the EGFR improve locoregional tumour control and survival when applied during radiotherapy, however, the effects are heterogeneous and biomarkers for patient selection are warranted. Also other RTK´s such as c-Met and IGF-1R seem to play important roles in tumour radioresistance. Beside the potential to select patients for molecular targeting approaches combined with radiotherapy, studies are also needed to evluate radiotherapy adaptation approaches for selected patients, i.e. adaptation of radiation dose, or, more sophisticated, of target volumes.

  20. Nerve growth factor receptor immunostaining suggests an extrinsic origin for hypertrophic nerves in Hirschsprung's disease.

    Kobayashi, H; O'Briain, D S; Puri, P

    1994-01-01

    The expression of nerve growth factor receptor in colon from 20 patients with Hirshsprung's disease and 10 controls was studied immunohistochemically. The myenteric and submucous plexuses in the ganglionic bowel and hypertrophic nerve trunks in the aganglionic bowel displayed strong expression of nerve growth factor receptor. The most important finding was the identical localisation of nerve growth factor receptor immunoreactivity on the perineurium of both hypertrophic nerve trunks in Hirshs...

  1. Gender identity outcomes in children with disorders/differences of sex development: Predictive factors.

    Bakula, Dana M; Mullins, Alexandria J; Sharkey, Christina M; Wolfe-Christensen, Cortney; Mullins, Larry L; Wisniewski, Amy B

    2017-06-01

    Disorders/differences of sex development (DSD) comprise multiple congenital conditions in which chromosomal, gonadal, and/or anatomical sex are discordant. The prediction of future gender identity (i.e., self-identifying as male, female, or other) in children with DSD can be imprecise, and current knowledge about the development of gender identity in people with, and without DSD, is limited. However, sex of rearing is the strongest predictor of gender identity for the majority of individuals with various DSD conditions. When making decisions regarding sex of rearing biological factors (e.g., possession of a Y chromosome, degree and duration of pre- and postnatal androgen exposure, phenotypic presentation of the external genitalia, and fertility potential), social and cultural factors, as well as quality of life should be considered. Information on gender identity outcomes across a range of DSD diagnoses is presented to aid in sex of rearing assignment. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Antibody-induced dimerization activates the epidermal growth factor receptor tyrosine kinase

    Spaargaren, M.; Defize, L. H.; Boonstra, J.; de Laat, S. W.

    1991-01-01

    The relationship between epidermal growth factor receptor (EGF-R) protein tyrosine kinase activation and ligand-induced receptor dimerization was investigated using several bivalent anti-EGF-R antibodies directed against various receptor epitopes. In A431 membrane preparations and permeabilized

  3. Understanding Factors that Shape Gender Attitudes in Early Adolescence Globally: A Mixed-Methods Systematic Review

    Gibbs, Susannah; Blum, Robert Wm; Moreau, Caroline; Chandra-Mouli, Venkatraman; Herbert, Ann; Amin, Avni

    2016-01-01

    Background Early adolescence (ages 10–14) is a period of increased expectations for boys and girls to adhere to socially constructed and often stereotypical norms that perpetuate gender inequalities. The endorsement of such gender norms is closely linked to poor adolescent sexual and reproductive and other health-related outcomes yet little is known about the factors that influence young adolescents’ personal gender attitudes. Objectives To explore factors that shape gender attitudes in early adolescence across different cultural settings globally. Methods A mixed-methods systematic review was conducted of the peer-reviewed literature in 12 databases from 1984–2014. Four reviewers screened the titles and abstracts of articles and reviewed full text articles in duplicate. Data extraction and quality assessments were conducted using standardized templates by study design. Thematic analysis was used to synthesize quantitative and qualitative data organized by the social-ecological framework (individual, interpersonal and community/societal-level factors influencing gender attitudes). Results Eighty-two studies (46 quantitative, 31 qualitative, 5 mixed-methods) spanning 29 countries were included. Ninety percent of studies were from North America or Western Europe. The review findings indicate that young adolescents, across cultural settings, commonly express stereotypical or inequitable gender attitudes, and such attitudes appear to vary by individual sociodemographic characteristics (sex, race/ethnicity and immigration, social class, and age). Findings highlight that interpersonal influences (family and peers) are central influences on young adolescents’ construction of gender attitudes, and these gender socialization processes differ for boys and girls. The role of community factors (e.g. media) is less clear though there is some evidence that schools may reinforce stereotypical gender attitudes among young adolescents. Conclusions The findings from this

  4. Understanding Factors that Shape Gender Attitudes in Early Adolescence Globally: A Mixed-Methods Systematic Review.

    Kågesten, Anna; Gibbs, Susannah; Blum, Robert Wm; Moreau, Caroline; Chandra-Mouli, Venkatraman; Herbert, Ann; Amin, Avni

    2016-01-01

    Early adolescence (ages 10-14) is a period of increased expectations for boys and girls to adhere to socially constructed and often stereotypical norms that perpetuate gender inequalities. The endorsement of such gender norms is closely linked to poor adolescent sexual and reproductive and other health-related outcomes yet little is known about the factors that influence young adolescents' personal gender attitudes. To explore factors that shape gender attitudes in early adolescence across different cultural settings globally. A mixed-methods systematic review was conducted of the peer-reviewed literature in 12 databases from 1984-2014. Four reviewers screened the titles and abstracts of articles and reviewed full text articles in duplicate. Data extraction and quality assessments were conducted using standardized templates by study design. Thematic analysis was used to synthesize quantitative and qualitative data organized by the social-ecological framework (individual, interpersonal and community/societal-level factors influencing gender attitudes). Eighty-two studies (46 quantitative, 31 qualitative, 5 mixed-methods) spanning 29 countries were included. Ninety percent of studies were from North America or Western Europe. The review findings indicate that young adolescents, across cultural settings, commonly express stereotypical or inequitable gender attitudes, and such attitudes appear to vary by individual sociodemographic characteristics (sex, race/ethnicity and immigration, social class, and age). Findings highlight that interpersonal influences (family and peers) are central influences on young adolescents' construction of gender attitudes, and these gender socialization processes differ for boys and girls. The role of community factors (e.g. media) is less clear though there is some evidence that schools may reinforce stereotypical gender attitudes among young adolescents. The findings from this review suggest that young adolescents in different cultural

  5. Understanding Factors that Shape Gender Attitudes in Early Adolescence Globally: A Mixed-Methods Systematic Review.

    Anna Kågesten

    Full Text Available Early adolescence (ages 10-14 is a period of increased expectations for boys and girls to adhere to socially constructed and often stereotypical norms that perpetuate gender inequalities. The endorsement of such gender norms is closely linked to poor adolescent sexual and reproductive and other health-related outcomes yet little is known about the factors that influence young adolescents' personal gender attitudes.To explore factors that shape gender attitudes in early adolescence across different cultural settings globally.A mixed-methods systematic review was conducted of the peer-reviewed literature in 12 databases from 1984-2014. Four reviewers screened the titles and abstracts of articles and reviewed full text articles in duplicate. Data extraction and quality assessments were conducted using standardized templates by study design. Thematic analysis was used to synthesize quantitative and qualitative data organized by the social-ecological framework (individual, interpersonal and community/societal-level factors influencing gender attitudes.Eighty-two studies (46 quantitative, 31 qualitative, 5 mixed-methods spanning 29 countries were included. Ninety percent of studies were from North America or Western Europe. The review findings indicate that young adolescents, across cultural settings, commonly express stereotypical or inequitable gender attitudes, and such attitudes appear to vary by individual sociodemographic characteristics (sex, race/ethnicity and immigration, social class, and age. Findings highlight that interpersonal influences (family and peers are central influences on young adolescents' construction of gender attitudes, and these gender socialization processes differ for boys and girls. The role of community factors (e.g. media is less clear though there is some evidence that schools may reinforce stereotypical gender attitudes among young adolescents.The findings from this review suggest that young adolescents in different

  6. Arctigenin induced gallbladder cancer senescence through modulating epidermal growth factor receptor pathway.

    Zhang, Mingdi; Cai, Shizhong; Zuo, Bin; Gong, Wei; Tang, Zhaohui; Zhou, Di; Weng, Mingzhe; Qin, Yiyu; Wang, Shouhua; Liu, Jun; Ma, Fei; Quan, Zhiwei

    2017-05-01

    Gallbladder cancer has poor prognosis and limited therapeutic options. Arctigenin, a representative dibenzylbutyrolactone lignan, occurs in a variety of plants. However, the molecular mechanisms involved in the antitumor effect of arctigenin on gallbladder cancer have not been fully elucidated. The expression levels of epidermal growth factor receptor were examined in 100 matched pairs of gallbladder cancer tissues. A positive correlation between high epidermal growth factor receptor expression levels and poor prognosis was observed in gallbladder cancer tissues. Pharmacological inhibition or inhibition via RNA interference of epidermal growth factor receptor induced cellular senescence in gallbladder cancer cells. The antitumor effect of arctigenin on gallbladder cancer cells was primarily achieved by inducing cellular senescence. In gallbladder cancer cells treated with arctigenin, the expression level of epidermal growth factor receptor significantly decreased. The analysis of the activity of the kinases downstream of epidermal growth factor receptor revealed that the RAF-MEK-ERK signaling pathway was significantly inhibited. Furthermore, the cellular senescence induced by arctigenin could be reverted by pcDNA-epidermal growth factor receptor. Arctigenin also potently inhibited the growth of tumor xenografts, which was accompanied by the downregulation of epidermal growth factor receptor and induction of senescence. This study demonstrates arctigenin could induce cellular senescence in gallbladder cancer through the modulation of epidermal growth factor receptor pathway. These data identify epidermal growth factor receptor as a key regulator in arctigenin-induced gallbladder cancer senescence.

  7. Factors Relating to Managerial Stereotypes: The Role of Gender of the Employee and the Manager and Management Gender Ratio.

    Stoker, Janka I; Van der Velde, Mandy; Lammers, Joris

    2012-03-01

    PURPOSE: Several studies have shown that the traditional stereotype of a "good" manager being masculine and male still exists. The recent changes in the proportion of women and female managers in organizations could affect these two managerial stereotypes, leading to a stronger preference for feminine characteristics and female leaders. This study examines if the gender of an employee, the gender of the manager, and the management gender ratio in an organization are related to employees' managerial stereotypes. DESIGN/METHODOLOGY/APPROACH: 3229 respondents working in various organizations completed an electronic questionnaire. FINDINGS: The results confirm our hypotheses that, although the general stereotype of a manager is masculine and although most prefer a man as a manager, female employees, employees with a female manager, and employees working in an organization with a high percentage of female managers, have a stronger preference for feminine characteristics of managers and for female managers. Moreover, we find that proximal variables are much stronger predictors of these preferences than more distal variables. IMPLICATIONS: Our study suggests that managerial stereotypes could change as a result of personal experiences and changes in the organizational context. The results imply that increasing the proportion of female managers is an effective way to overcome managerial stereotyping. ORIGINALITY/VALUE: This study examines the influence on managerial stereotypes of various proximal and distal factors derived from theory among a large group of employees (in contrast to students).

  8. Gender determination from diagnostic factors on anteroposterior pelvic radiographs

    Azadeh Memarian

    2017-03-01

    Conclusion: The results of this study revealed that the evaluation of the radiographic images of pelvic bones by assessing the mentioned factors can be useful for sex determination from skeletal remains. However, ethical considerations should also be taken into account while using these factors.

  9. The gender difference on the Mental Rotations test is not due to performance factors.

    Masters, M S

    1998-05-01

    Men score higher than women on the Mental Rotations test (MRT), and the magnitude of this gender difference is the largest of that on any spatial test. Goldstein, Haldane, and Mitchell (1990) reported finding that the gender difference on the MRT disappears when "performance factors" are controlled--specifically, when subjects are allowed sufficient time to attempt all items on the test or when a scoring procedure that controls for the number of items attempted is used. The present experiment also explored whether eliminating these performance factors results in a disappearance of the gender difference on the test. Male and female college students were allowed a short time period or unlimited time on the MRT. The tests were scored according to three different procedures. The results showed no evidence that the gender difference on the MRT was affected by the scoring method or the time limit. Regardless of the scoring procedure, men scored higher than women, and the magnitude of the gender difference persisted undiminished when subjects completed all items on the test. Thus there was no evidence that performance factors produced the gender difference on the MRT. These results are consistent with the results of other investigators who have attempted to replicate Goldstein et al.'s findings.

  10. Developmental regulation of human truncated nerve growth factor receptor

    DiStefano, P.S.; Clagett-Dame, M.; Chelsea, D.M.; Loy, R. (Abbott Laboratories, Abbott Park, IL (USA))

    1991-01-01

    Monoclonal antibodies (designated XIF1 and IIIG5) recognizing distinct epitopes of the human truncated nerve growth factor receptor (NGF-Rt) were used in a two-site radiometric immunosorbent assay to monitor levels of NGF-Rt in human urine as a function of age. Urine samples were collected from 70 neurologically normal subjects ranging in age from 1 month to 68 years. By using this sensitive two-site radiometric immunosorbent assay, NGF-Rt levels were found to be highest in urine from 1-month old subjects. By 2.5 months, NGF-Rt values were half of those seen at 1 month and decreased more gradually between 0.5 and 15 years. Between 15 and 68 years, urine NGF-Rt levels were relatively constant at 5% of 1-month values. No evidence for diurnal variation of adult NGF-Rt was apparent. Pregnant women in their third trimester showed significantly elevated urine NGF-Rt values compared with age-matched normals. Affinity labeling of NGF-Rt with 125I-NGF followed by immunoprecipitation with ME20.4-IgG and gel autoradiography indicated that neonatal urine contained high amounts of truncated receptor (Mr = 50 kd); decreasingly lower amounts of NGF-Rt were observed on gel autoradiograms with development, indicating that the two-site radiometric immunosorbent assay correlated well with the affinity labeling technique for measuring NGF-Rt. NGF-Rt in urines from 1-month-old and 36-year-old subjects showed no differences in affinities for NGF or for the monoclonal antibody IIIG5. These data show that NGF-Rt is developmentally regulated in human urine, and are discussed in relation to the development and maturation of the peripheral nervous system.

  11. Developmental regulation of human truncated nerve growth factor receptor

    DiStefano, P.S.; Clagett-Dame, M.; Chelsea, D.M.; Loy, R.

    1991-01-01

    Monoclonal antibodies (designated XIF1 and IIIG5) recognizing distinct epitopes of the human truncated nerve growth factor receptor (NGF-Rt) were used in a two-site radiometric immunosorbent assay to monitor levels of NGF-Rt in human urine as a function of age. Urine samples were collected from 70 neurologically normal subjects ranging in age from 1 month to 68 years. By using this sensitive two-site radiometric immunosorbent assay, NGF-Rt levels were found to be highest in urine from 1-month old subjects. By 2.5 months, NGF-Rt values were half of those seen at 1 month and decreased more gradually between 0.5 and 15 years. Between 15 and 68 years, urine NGF-Rt levels were relatively constant at 5% of 1-month values. No evidence for diurnal variation of adult NGF-Rt was apparent. Pregnant women in their third trimester showed significantly elevated urine NGF-Rt values compared with age-matched normals. Affinity labeling of NGF-Rt with 125I-NGF followed by immunoprecipitation with ME20.4-IgG and gel autoradiography indicated that neonatal urine contained high amounts of truncated receptor (Mr = 50 kd); decreasingly lower amounts of NGF-Rt were observed on gel autoradiograms with development, indicating that the two-site radiometric immunosorbent assay correlated well with the affinity labeling technique for measuring NGF-Rt. NGF-Rt in urines from 1-month-old and 36-year-old subjects showed no differences in affinities for NGF or for the monoclonal antibody IIIG5. These data show that NGF-Rt is developmentally regulated in human urine, and are discussed in relation to the development and maturation of the peripheral nervous system

  12. Gender Differences in Risk Factors for Single and Recurrent Falls Among the Community-Dwelling Elderly

    Yu Mei O

    2015-08-01

    Full Text Available The purpose of this study was to identify gender differences in risk factors of fall accidents among older people, and whether these factors differ between single and recurrent fallers. A total of 4,426 individuals aged ≥65 years from two large-scale health surveys provided data. Logistic regression analyses were used to identify risk factors and to determine the risk model for falling and recurrent falling in men and women separately. Three major risk factors for falling regardless of gender or fall history are fear of falling, limitations in activities of daily living (ADL, and age ≥75 years. Fear of falling remains one of the common modifiable risk factors. Among those without a fall history, the use of sedatives or tranquilizers increases the risk of falling. Regarding gender differences, ADL limitations and fear of falling appear to be stronger fall risk factors for men than for women. Among women, alcohol use and educational level are significant risk factors for falling, while loneliness is associated with recurrent falling. Men with fear of falling or ADL limitations are at higher risk to have a recurrent fall accident than women with these conditions. Having a visual impairment or living with someone is associated with recurrent falling among men. Our findings emphasize the importance of multifactorial fall interventions, taking into account a variety of subgroup characteristics such as gender and fall history.

  13. Gender differences in factors associated with sexual intercourse among Estonian adolescents.

    Part, Kai; Rahu, Kaja; Rahu, Mati; Karro, Helle

    2011-06-01

    To examine factors associated with early sexual intercourse among 15 to 16-year-old adolescents by gender. The data were collected from a random sample of Estonian basic schools' ninth grade pupils in 1999 using self-completed questionnaires. A multivariate logistic regression analysis for boys and girls was used to test for associations between sexual intercourse, and personal gender role-related attitudes, attitudes towards sexual intercourse, pubertal timing, smoking status and experience of drunkenness. Of the respondents, 14.6% of boys and 13.1% of girls had experienced sexual intercourse. Traditional gender role-related attitudes were associated with sexual intercourse among girls, but not among boys. Smoking and experience of drunkenness was strongly associated with sexual intercourse for both genders. Gender differences in the association between gender role-related attitudes and early sexual intercourse were observed among 15 to 16-year-olds in Estonia. Smoking and experience of drunkenness were strongly related to sexual intercourse for both genders.

  14. Factors affecting cognitive function according to gender in community-dwelling elderly individuals

    Miwon Kim

    2017-11-01

    Full Text Available OBJECTIVES This study aimed to identify the factors affecting the cognitive function of elderly people in a community by gender. METHODS We obtained 4,878 secondary data of people aged ≥65 years in 2016 at a dementia prevention center in Gyeyang-gu, Incheon. Data were obtained through Mini-Mental Status Examination optimized for screening dementia and a questionnaire. The data were statistically analyzed using analysis of variance, analysis of covariance, and hierarchical regression. RESULTS There were significant differences in cognitive function according to gender, and the differences were significant even when age was controlled, but gender differences disappeared when education was controlled. Age, education, social activities, number of comorbid diseases, and alcohol drinking affected cognitive function through interaction with gender, but interaction with gender disappeared when education was controlled. Regression analysis showed that depression, cohabitant, social activities etc., had a significant impact on both men and women under controlled education and age. In men, the effect of social activities was greater than that of women, and hyperlipidemia had the effect only in women. CONCLUSIONS The differences in gender-related cognitive functions were due to differences in gender education period. The period of education is considered to have a great influence on cognitive function in relation to the economic level, occupation, and social activity.

  15. Analysis of receptor signaling pathways by mass spectrometry: identification of vav-2 as a substrate of the epidermal and platelet-derived growth factor receptors

    Pandey, A; Podtelejnikov, A V; Blagoev, B

    2000-01-01

    Oligomerization of receptor protein tyrosine kinases such as the epidermal growth factor receptor (EGFR) by their cognate ligands leads to activation of the receptor. Transphosphorylation of the receptor subunits is followed by the recruitment of signaling molecules containing src homology 2 (SH2...

  16. Role of Actors and Gender Factor in Disaster Management

    Gundogdu, Oguz; Isik, Ozden; Ozcep, Ferhat; Goksu, Goksel

    2014-05-01

    In Turkey, the discussions in the modern sense about disaster management begun after the 1992 Erzincan and the 1995 Dinar earthquakes, faulting in terms of features and effects. These earthquakes are "Urban Earthquakes'' with effects and faulting charectristics, and have led to radical changes in terms of disaster and disaster management. Disaster Management, to become a science in the world, but with the 1999 Izmit and Duzce earthquakes in Turkey has begun to take seriously on the agenda. Firstly, such as Civil Defense and Red Crescent organizations, by transforming its own, have entered into a new organizing effort. By these earthquakes, NGO's have contributed the search-rescue efforts in the field and to the process of normalization of life. Because "the authority and responsibilities" of NGO's could not be determined, and could not be in planning and scenario studies, we faced the problems. Thus, to the citizens of our country-specific "voluntary" has not benefited enough from the property. The most important development in disaster management in 2009, the Disaster and Emergency Management Presidency (AFAD) has been the establishment. However, in terms of coordination and accreditation to the target point has been reached yet. Another important issue in disaster management (need to be addressed along with disaster actors) is the role of women in disasters. After the Golcuk Earthquake, successful field works of women and women's victimization has attracted attention in two different directions. Gender-sensitive policies should be noted by the all disaster actors due to the importance of the mitigation, and these policies should take place in laws, regulations and planning.

  17. Haploinsufficiency in the PPARα and LDL receptor genes leads to gender- and age-specific obesity and hyperinsulinemia

    Sugiyama, Eiko; Tanaka, Naoki; Nakajima, Tamie; Kamijo, Yuji; Yokoyama, Shin; Li Yufeng; Gonzalez, Frank J.; Aoyama, Toshifumi

    2006-01-01

    When preparing peroxisome proliferator-activated receptor (PPAR)α:low-density lipoprotein receptor (LDLR) (-/-) double knockout mice, we unexpectedly found a unique gender- and age-specific obesity in the F1 generation, PPARα (+/-):LDLR (+/-), even in mice fed standard chow. Body weights of the male heterozygous mice increased up to about 60 g at 75 weeks of age, then decreased by about 30 g at 100 weeks of age. More than 95% of the heterozygous mice between 35- and 75-week-olds were overweight. Of interest, the obese heterozygous mice also exhibited hyperinsulinemia correlating with moderate insulin resistance. Hepatic gene expression of LDLR was lower than expected in the heterozygous mice, particularly at 50 and 75 weeks of age. In contrast, the hepatic expression of PPARα was higher than expected in obese heterozygous mice, but decreased in non-obese older heterozygous mice. Modulated expression of these genes may be partially associated with the onset of the hyperinsulinemia

  18. Development of real-time reverse transcription polymerase chain reaction assays to quantify insulin-like growth factor receptor and insulin receptor expression in equine tissue

    Stephen B. Hughes

    2013-08-01

    Full Text Available The insulin-like growth factor system (insulin-like growth factor 1, insulin-like growth factor 2, insulin-like growth factor 1 receptor, insulin-like growth factor 2 receptor and six insulin-like growth factor-binding proteins and insulin are essential to muscle metabolism and most aspects of male and female reproduction. Insulin-like growth factor and insulin play important roles in the regulation of cell growth, differentiation and the maintenance of cell differentiation in mammals. In order to better understand the local factors that regulate equine physiology, such as muscle metabolism and reproduction (e.g., germ cell development and fertilisation, real-time reverse transcription polymerase chain reaction assays for quantification of equine insulin-like growth factor 1 receptor and insulin receptor messenger ribonucleic acid were developed. The assays were sensitive: 192 copies/µLand 891 copies/µL for insulin-like growth factor 1 receptor, messenger ribonucleic acid and insulin receptor respectively (95%limit of detection, and efficient: 1.01 for the insulin-like growth factor 1 receptor assay and 0.95 for the insulin receptor assay. The assays had a broad linear range of detection (seven logs for insulin-like growth factor 1 receptor and six logs for insulin receptor. This allowed for analysis of very small amounts of messenger ribonucleic acid. Low concentrations of both insulin-like growth factor 1 receptor and insulin receptor messenger ribonucleic acid were detected in endometrium, lung and spleen samples, whilst high concentrations were detected in heart, muscle and kidney samples, this was most likely due to the high level of glucose metabolism and glucose utilisation by these tissues. The assays developed for insulin-like growth factor 1 receptor and insulin receptor messenger ribonucleic acid expression have been shown to work on equine tissue and will contribute to the understanding of insulin and insulin-like growth factor 1

  19. Sedentary risk factors across genders and job roles within a university campus workplace: preliminary study.

    Alkhatib, Ahmad

    2013-01-01

    The aim of this study was to investigate whether sedentary job role and gender are reflected by sedentary risk factors within a university campus. Following institutional ethical approval, 80 U.K. university campus employees were recruited, and 34 of them (age 47.8 ± 11.9 years, height 169 ± 1.0 cm, body mass 72.0 ± 14.1 kg) were measured for their systolic (SBP) and diastolic blood pressure (DBP), blood glucose (Glu), total serum blood cholesterol (Cho), dominant (DHG) and nondominant handgrip strength (NHG), body fat percentage (Fat%), trunk flexibility (Flex), peak cardiorespiratory capacity (V.O2max), and answered a physical activity questionnaire (IPAQ). The data were analyzed using two-way ANOVA with job role and gender as independent factors, and each measured risk as a dependent factor. Gender had significant effects (pworkplace.

  20. Gender factors influencing technical efficiency of cassava farmers in ...

    This work was therefore conducted in Akwa Ibom state to examine factors influencing the technical efficiency of farmer groups in cassava production. In carrying out the study, 120 respondents were randomly selected from two agricultural zones in the State and interviewed with interview schedule. Data were analyzed using ...

  1. Gender differences in the developmental trajectories, risk factors ...

    Research suggests that neonatal insults were found to be better predictors of male antisocial behaviors relative to females. Research also suggests that neurocognitive differences (e.g., ADHD) were more predictive of antisocial behaviors in males than in females. Social factors (i.e., family-related and peer related) were ...

  2. gender and school types as factors responsible for job stress

    Emeka Egbochuku

    public Universities should be looked into so that all factors responsible for stress might be .... universities in Malaysia, university academic staffs faced more problems .... adjustment with different coping styles. .... in college students: The role of rumination and stress. ... International Journal of Stress Management, 8, 285–29.

  3. Gender Differences in How Retirees Perceive Factors Influencing Unretirement

    Armstrong-Stassen, Marjorie; Staats, Sara

    2012-01-01

    Returning to paid employment after retirement is occurring in many developed countries and can be expected to increase in the future. This study compared how women (n = 202) and men (n = 347) who had retired from a managerial or professional career occupation perceived factors associated with unretirement. Retired professional women perceived…

  4. Glycosylation as a Main Regulator of Growth and Death Factor Receptors Signaling

    Inês Gomes Ferreira

    2018-02-01

    Full Text Available Glycosylation is a very frequent and functionally important post-translational protein modification that undergoes profound changes in cancer. Growth and death factor receptors and plasma membrane glycoproteins, which upon activation by extracellular ligands trigger a signal transduction cascade, are targets of several molecular anti-cancer drugs. In this review, we provide a thorough picture of the mechanisms bywhich glycosylation affects the activity of growth and death factor receptors in normal and pathological conditions. Glycosylation affects receptor activity through three non-mutually exclusive basic mechanisms: (1 by directly regulating intracellular transport, ligand binding, oligomerization and signaling of receptors; (2 through the binding of receptor carbohydrate structures to galectins, forming a lattice thatregulates receptor turnover on the plasma membrane; and (3 by receptor interaction with gangliosides inside membrane microdomains. Some carbohydrate chains, for example core fucose and β1,6-branching, exert a stimulatory effect on all receptors, while other structures exert opposite effects on different receptors or in different cellular contexts. In light of the crucial role played by glycosylation in the regulation of receptor activity, the development of next-generation drugs targeting glyco-epitopes of growth factor receptors should be considered a therapeutically interesting goal.

  5. Gender Differences in Risk Factors for Single and Recurrent Falls Among the Community-Dwelling Elderly

    Yu Mei O; Fatima El Fakiri

    2015-01-01

    The purpose of this study was to identify gender differences in risk factors of fall accidents among older people, and whether these factors differ between single and recurrent fallers. A total of 4,426 individuals aged ≥65 years from two large-scale health surveys provided data. Logistic regression analyses were used to identify risk factors and to determine the risk model for falling and recurrent falling in men and ...

  6. Epidermal growth factor receptor mutation in gastric cancer.

    Liu, Zhimin; Liu, Lina; Li, Mei; Wang, Zhaohui; Feng, Lu; Zhang, Qiuping; Cheng, Shihua; Lu, Shen

    2011-04-01

    Epidermal growth factor receptor (EGFR) and Kirsten-RAS (KRAS) mutations have been identified as predictors of response to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer. We aimed to screen the mutations of both genes in gastric carcinoma to detect the suitability of EGFR TKIs for patients with gastric carcinoma. We screened EGFR mutation in exons 19-21 and KRAS mutation in exon 2 in 58 gastric adenocarcinomas from China using high resolution melting analysis (HRMA). Positive samples were confirmed by DNA sequencing. Three EGFR missense mutations (5.2%) and 22 single nucleotide polymorphisms (SNP, Q787Q, 37.9%) were identified. To our knowledge, we report for the first time three mutation patterns of EGFR, Y801C, L858R and G863D, in gastric carcinoma. Two samples with EGFR mutation were mucinous adenocarcinoma. These three samples were collected from male patients aged over 75 years old. The frequency of KRAS mutation was 10.3% (6/58). The exclusiveness of EGFR and KRAS mutations was proven for the first time in gastric cancer. Gastric carcinoma of the mucinous adenocarcinoma type collected from older male patients may harbour EGFR mutations. The small subset of gastric adenocarcinoma patients may respond to EGFR TKIs.

  7. Association of coatomer proteins with the beta-receptor for platelet-derived growth factor

    Hansen, Klaus; Rönnstrand, L; Rorsman, C

    1997-01-01

    The nonreceptor tyrosine kinase Src binds to and is activated by the beta-receptor for platelet-derived growth factor (PDGF). The interaction leads to Src phosphorylation of Tyr934 in the kinase domain of the receptor. In the course of the functional characterization of this phosphorylation, we...... of intracellular vesicle transport. In order to explore the functional significance of the interaction between alpha- and beta'-COP and the PDGF receptor, a receptor mutant was made in which the conserved histidine residue 928 was mutated to an alanine residue. The mutant receptor, which was unable to bind alpha...

  8. Gender differences in (metacognitive and motivational-emotional factors of reading comprehension

    Svjetlana Kolić-Vehovec

    2008-12-01

    Full Text Available The aim of our study was to establish, from the aspect of gender, the degree to which reading comprehension is connected with students' academic achievement, potential gender differences between (metacognitive and motivational-emotional factors of reading comprehension, and to identify the most important predictors of reading comprehension for exploratory and narrative texts. The results of study, which included 380 Slovenian and Croatian students with the average age of 10;6 years, showed that: (i reading comprehension significantly determines academic achievement regardless of students' gender; (ii there are significant gender differences in most of the factors of reading comprehension (girls summarize texts better, have more metacognitive knowledge of reading, show greater reading interest, feel more competent for reading and in general feel better while reading; (iii the predictive value of cognitive, motivational, and emotional predictors differ for exploratory and narrative texts (for exploratory texts metacognitive factors have the greatest predictive value; for narrative texts motivatonal-emotional factors have the greatest predictive value for boys, and metacognitive factors for girls.

  9. Influence of gender and other factors on medical student specialty interest.

    Boyle, Veronica; Shulruf, Boaz; Poole, Phillippa

    2014-09-12

    Medical schools must select and educate to meet anticipated health needs. Factors influencing career choice include those of the student and their background as well as subsequent experience. Women have comprised over 50% of medical classes for over 20 years. This study describes gender patterns of current specialty interest among medical students at the University of Auckland, and models the predictive effect of gender compared to other career influencing factors. The study analysed career intention survey data from 711 graduating medical students (response rate, 79%) from 2006 to 2011. Interest level was highest for medicine, followed by subspecialty surgery, general practice and paediatrics. There were differences by gender for most specialties, but not for general practice. Women were more likely than men to be interested in Obstetrics and Gynaecology, Paediatrics, Geriatrics, Public Health or General Medicine, and less interested in Surgery, Anaesthesia, Emergency Medicine or post graduate study. Each specialty had a different pattern of influencing factors with the most important factor being the experience on a clinical attachment. Factors in career choice are complex and vary by gender and specialty. General practice levels of interest are too low for workforce needs. Predictive models need to be validated in longer term studies but may help guide selection and curriculum design.

  10. Gender differences in the factor structure of posttraumatic stress disorder symptoms in war-exposed adolescents.

    Armour, Cherie; Elhai, Jon D; Layne, Christopher M; Shevlin, Mark; Duraković-Belko, Elvira; Djapo, Nermin; Pynoos, Robert S

    2011-05-01

    DSM-IV's three-factor model of posttraumatic stress disorder (PTSD) is rarely empirically supported, whereas other four-factor models (King et al., 1998; Simms, Watson, & Doebbeling, 2002) have proven to be better representations of PTSD's latent structure. To date, a clear consensus as to which model provides the best representation of PTSD's underlying dimensions has yet to be reached. The current study investigated whether gender is associated with factor structure differences using the King et al. (1998) model of reexperiencing, avoidance, numbing, and hyperarousal PTSD symptoms. Participants were war-exposed Bosnian secondary/high school boys and girls (N=1572) assessed nearly two years after the 1992-1995 Bosnian conflict. Confirmatory factor analytic tests of measurement invariance across PTSD model parameters revealed many significant sex-linked differences. Implications regarding the potential role of gender as a moderator of the King et al. (1998) model's factor structure are discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. The Pseudo signal peptide of the corticotropin-releasing factor receptor type 2A prevents receptor oligomerization.

    Teichmann, Anke; Rutz, Claudia; Kreuchwig, Annika; Krause, Gerd; Wiesner, Burkhard; Schülein, Ralf

    2012-08-03

    N-terminal signal peptides mediate the interaction of native proteins with the translocon complex of the endoplasmic reticulum membrane and are cleaved off during early protein biogenesis. The corticotropin-releasing factor receptor type 2a (CRF(2(a))R) possesses an N-terminal pseudo signal peptide, which represents a so far unique domain within the large protein family of G protein-coupled receptors (GPCRs). In contrast to a conventional signal peptide, the pseudo signal peptide remains uncleaved and consequently forms a hydrophobic extension at the N terminus of the receptor. The functional consequence of the presence of the pseudo signal peptide is not understood. Here, we have analyzed the significance of this domain for receptor dimerization/oligomerization in detail. To this end, we took the CRF(2(a))R and the homologous corticotropin-releasing factor receptor type 1 (CRF(1)R) possessing a conventional cleaved signal peptide and conducted signal peptide exchange experiments. Using single cell and single molecule imaging methods (fluorescence resonance energy transfer and fluorescence cross-correlation spectroscopy, respectively) as well as biochemical experiments, we obtained two novel findings; we could show that (i) the CRF(2(a))R is expressed exclusively as a monomer, and (ii) the presence of the pseudo signal peptide prevents its oligomerization. Thus, we have identified a novel functional domain within the GPCR protein family, which plays a role in receptor oligomerization and which may be useful to study the functional significance of this process in general.

  12. Factor structure of the CES-D and measurement invariance across gender in Mainland Chinese adolescents.

    Wang, Mengcheng; Armour, Cherie; Wu, Yan; Ren, Fen; Zhu, Xiongzhao; Yao, Shuqiao

    2013-09-01

    The primary aim was to examine the depressive symptom structure of Mainland China adolescents using the Center for Epidemiologic Studies Depression Scale (CES-D). Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were simultaneously conducted to determine the structure of the CES-D in a large scale, representative adolescent samples recruited from Mainland China. Multigroup CFA (N = 5059, 48% boys, mean = 16.55±1.06) was utilized to test the factorial invariance of the depressive symptom structure, which was generated by EFA and confirmed by CFA across gender. The CES-D can be interpreted in terms of 3 symptom dimensions. Additionally, factorial invariance of the new proposed model across gender was supported at all assuming different degrees of invariance. Mainland Chinese adolescents have specific depressive symptom structure, which is consistent across gender. © 2013 Wiley Periodicals, Inc.

  13. A transcription factor active on the epidermal growth factor receptor gene

    Kageyama, R.; Merlino, G.T.; Pastan, I.

    1988-01-01

    The authors have developed an in vitro transcription system for the epidermal growth factor receptor (EGFR) oncogene by using nuclear extracts of A431 human epidermoid carcinoma cells, which overproduce EGFR. They found that a nuclear factor, termed EGFR-specific transcription factor (ETF), specifically stimulated EGFR transcription by 5- to 10-fold. In this report, ETF, purified by using sequence-specific oligonucleotide affinity chromatography, is shown by renaturing material eluted from a NaDodSO 4 /polyacrylamide gel to be a protein with a molecular mass of 120 kDa. ETF binds to the promoter region, as measured by DNase I footprinting and gel-mobility-shift assays, and specifically stimulates the transcription of the EGFR gene in a reconstituted in vitro transcription system. These results suggest that ETF could play a role in the overexpression of the cellular oncogene EGFR

  14. Phenobarbital indirectly activates the constitutive active androstane receptor (CAR) by inhibition of epidermal growth factor receptor signaling.

    Mutoh, Shingo; Sobhany, Mack; Moore, Rick; Perera, Lalith; Pedersen, Lee; Sueyoshi, Tatsuya; Negishi, Masahiko

    2013-05-07

    Phenobarbital is a central nervous system depressant that also indirectly activates nuclear receptor constitutive active androstane receptor (CAR), which promotes drug and energy metabolism, as well as cell growth (and death), in the liver. We found that phenobarbital activated CAR by inhibiting epidermal growth factor receptor (EGFR) signaling. Phenobarbital bound to EGFR and potently inhibited the binding of EGF, which prevented the activation of EGFR. This abrogation of EGFR signaling induced the dephosphorylation of receptor for activated C kinase 1 (RACK1) at Tyr(52), which then promoted the dephosphorylation of CAR at Thr(38) by the catalytic core subunit of protein phosphatase 2A. The findings demonstrated that the phenobarbital-induced mechanism of CAR dephosphorylation and activation is mediated through its direct interaction with and inhibition of EGFR.

  15. Gender Differences in Risk Factors for Adolescent Binge Drinking and Implications for Intervention and Prevention

    Allyson L. Dir

    2017-12-01

    Full Text Available Alcohol use, particularly binge drinking (BD, is a major public health concern among adolescents. Recent national data show that the gender gap in alcohol use is lessening, and BD among girls is rising. Considering the increase in BD among adolescent girls, as well as females’ increased risk of experiencing more severe biopsychosocial negative effects and consequences from BD, the current review sought to examine gender differences in risk factors for BD. The review highlights gender differences in (1 developmental-related neurobiological vulnerability to BD, (2 psychiatric comorbidity and risk phenotypes for BD, and (3 social-related risk factors for BD among adolescents, as well as considerations for BD prevention and intervention. Most of the information gleaned thus far has come from preclinical research. However, it is expected that, with recent advances in clinical imaging technology, neurobiological effects observed in lower mammals will be confirmed in humans and vice versa. A synthesis of the literature highlights that males and females experience unique neurobiological paths of development, and although there is debate regarding the specific nature of these differences, literature suggests that these differences in turn influence gender differences in psychiatric comorbidity and risk for BD. For one, girls are more susceptible to stress, depression, and other internalizing behaviors and, in turn, these symptoms contribute to their risk for BD. On the other hand, males, given gender differences across the lifespan as well as gender differences in development, are driven by an externalizing phenotype for risk of BD, in part, due to unique paths of neurobiological development that occur across adolescence. With respect to social domains, although social and peer influences are important for both adolescent males and females, there are gender differences. For example, girls may be more sensitive to pressure from peers to fit in and

  16. Host factors that modify Plasmodium falciparum adhesion to endothelial receptors.

    Mahamar, Almahamoudou; Attaher, Oumar; Swihart, Bruce; Barry, Amadou; Diarra, Bacary S; Kanoute, Moussa B; Cisse, Kadidia B; Dembele, Adama B; Keita, Sekouba; Gamain, Benoît; Gaoussou, Santara; Issiaka, Djibrilla; Dicko, Alassane; Duffy, Patrick E; Fried, Michal

    2017-10-24

    P. falciparum virulence is related to adhesion and sequestration of infected erythrocytes (IE) in deep vascular beds, but the endothelial receptors involved in severe malaria remain unclear. In the largest ever study of clinical isolates, we surveyed adhesion of freshly collected IE from children under 5 years of age in Mali to identify novel vascular receptors, and examined the effects of host age, hemoglobin type, blood group and severe malaria on levels of IE adhesion to a panel of endothelial receptors. Several novel molecules, including integrin α3β1, VE-cadherin, ICAM-2, junctional adhesion molecule-B (JAM-B), laminin, and cellular fibronectin, supported binding of IE from children. Severe malaria was not significantly associated with levels of IE adhesion to any of the 19 receptors. Hemoglobin AC, which reduces severe malaria risk, reduced IE binding to the receptors CD36 and integrin α5β1, while hemoglobin AS did not modify IE adhesion to any receptors. Blood groups A, AB and B significantly reduced IE binding to ICAM-1. Severe malaria risk varies with age, but age significantly impacted the level of IE binding to only a few receptors: IE binding to JAM-B decreased with age, while binding to CD36 and integrin α5β1 significantly increased with age.

  17. Gender dependent rate of metabolism of the opioid receptor-PET ligand [18F]fluoroethyl-diprenorphine

    Henriksen, G.; Spilker, M.E.; Hauser, A.I.; Boecker, H.; Schwaiger, M.; Wester, H.J.; Sprenger, T.; Platzer, S.; Toelle, T.R.

    2006-01-01

    Aim: The morphinane-derivate 6-O-(2-[ 18 F]fluoroethyl)-6-O-desmethyldiprenorphine ([ 18 F]FDPN) is a non-selective opioid receptor ligand currently used in positron emission tomography (PET). Correction for plasma metabolites of the arterial input function is necessary for quantitative measurements of [ 18 ]FDPN binding. A study was undertaken to investigate if there are gender dependent differences in the rate of metabolism of [ 18 F]FDPN. Methods: The rate of metabolism of [ 18 F]FDPN was mathematically quantified by fitting a bi-exponential function to each individual's dynamic metabolite data. Results: No statistically significant gender differences were found for age, weight, body mass index or dose. However, significant differences (p 18 F]FDPN faster than men. These differences were found in the contribution of the fast and slow kinetic components of the model describing the distribution of radioactive species in plasma, indicating a higher rate of enzyme-dependent degradation of [ 18 F]FDPN in women than in men. Conclusion: The findings reinforce the need for individualized metabolite correction during [ 18 F]FDPN-PET scans and also indicate that in certain cases, grouping according to gender could be performed in order to minimize methodological errors of the input function prior to kinetic analyses. (orig.)

  18. Factors Associated with Gender-Affirming Surgery and Age of Hormone Therapy Initiation Among Transgender Adults

    Beckwith, Noor; Reisner, Sari L.; Zaslow, Shayne; Mayer, Kenneth H.; Keuroghlian, Alex S.

    2017-01-01

    Abstract Purpose: Gender-affirming surgeries and hormone therapy are medically necessary treatments to alleviate gender dysphoria; however, significant gaps exist in the research and clinical literature on surgery utilization and age of hormone therapy initiation among transgender adults. Methods: We conducted a retrospective review of electronic health record data from a random sample of 201 transgender patients of ages 18–64 years who presented for primary care between July 1, 2010 and June 30, 2015 (inclusive) at an urban community health center in Boston, MA. Fifty percent in our analyses were trans masculine (TM), 50% trans feminine, and 24% reported a genderqueer/nonbinary gender identity. Regression models were fit to assess demographic, gender identity-related, sexual history, and mental health correlates of gender-affirming surgery and of age of hormone therapy initiation. Results: Overall, 95% of patients were prescribed hormones by their primary care provider, and the mean age of initiation of masculinizing or feminizing hormone prescriptions was 31.8 years (SD=11.1). Younger age of initiation of hormone prescriptions was associated with being TM, being a student, identifying as straight/heterosexual, having casual sexual partners, and not having past alcohol use disorder. Approximately one-third (32%) had a documented history of gender-affirming surgery. Factors associated with increased odds of surgery were older age, higher income levels, not identifying as bisexual, and not having a current psychotherapist. Conclusion: This study extends our understanding of prevalence and factors associated with gender-affirming treatments among transgender adults seeking primary care. Findings can inform future interventions to expand delivery of clinical care for transgender patients. PMID:29159310

  19. Gender differences in the influence of economic, lifestyle, and psychosocial factors on later-life health.

    Prus, Steven G; Gee, Ellen

    2003-01-01

    Gender differences in exposure to social resources play a significant role in influencing gender inequalities in health. A related question--and our focus--asks whether these inequalities are also influenced by gendered vulnerabilities to social forces. Specifically, this paper examines the differential impact of social forces on the health of elderly (65+) men and women. Multiple linear regression analysis is used to estimate gender differences in the influence of socioeconomic, lifestyle, and psychosocial factors on both self-rated health and overall functional health using data from the 1994-1995 National Population Health Survey. Key findings include: 1) the relationship between income and health is significant for older women only, whereas the converse holds for education; 2) having an acceptable body weight is positively associated with health for elderly women only; and 3) stress-related factors are stronger determinants of health for older women. Our findings shed light on the processes of healthy aging for men and women, and suggest that interventions to improve the health of elderly Canadians need to be gender-specific.

  20. Factor structure and gender stability in the multidimensional condom attitudes scale.

    Starosta, Amy J; Berghoff, Christopher R; Earleywine, Mitch

    2015-06-01

    Sexually transmitted infections continue to trouble the United States and can be attenuated through increased condom use. Attitudes about condoms are an important multidimensional factor that can affect sexual health choices and have been successfully measured using the Multidimensional Condom Attitudes Scale (MCAS). Such attitudes have the potential to vary between men and women, yet little work has been undertaken to identify if the MCAS accurately captures attitudes without being influenced by underlying gender biases. We examined the factor structure and gender invariance on the MCAS using confirmatory factor analysis and item response theory, within-subscale differential item functioning analyses. More than 770 participants provided data via the Internet. Results of differential item functioning analyses identified three items as differentially functioning between the genders, and removal of these items is recommended. Findings confirmed the previously hypothesized multidimensional nature of condom attitudes and the five-factor structure of the MCAS even after the removal of the three problematic items. In general, comparisons across genders using the MCAS seem reasonable from a methodological standpoint. Results are discussed in terms of improving sexual health research and interventions. © The Author(s) 2014.

  1. The Higher Order Factor Structure and Gender Invariance of the Pathological Narcissism Inventory

    Wright, Aidan G. C.; Lukowitsky, Mark R.; Pincus, Aaron L.; Conroy, David E.

    2010-01-01

    The Pathological Narcissism Inventory (PNI) is a recently developed multidimensional inventory for the assessment of pathological narcissism. The authors describe and report the results of two studies that investigate the higher order factor structure and gender invariance of the PNI. The results of the first study indicate that the PNI has a…

  2. Diversity in Primary Teacher Education Gender Differences in Student Factors and Curriculum Perception

    Geerdink, Gerda; Bergen, Theo; Dekkers, Hetty

    2011-01-01

    In the Netherlands only a small number of male students opt for primary school teaching and a relatively large percentage of them leave without graduating. A small-scale research project was set up to explore the question: Can gender-specific student factors be identified in relation to the initial teacher education curriculum that leads to the…

  3. Diversity in Primary Teacher Education : Gender differences in Student Factors and Curriculum perception

    Gerda Geerdink; H. Dekkers; T. Bergen

    2011-01-01

    In the Netherlands only a small number of male students opt for primary school teaching and a relatively large percentage of them leave without graduating. A small-scale research project was set up to explore the question: Can gender-specific student factors be identified in relation to the initial

  4. Effect of Child Gender and Psychosocial Factors on Physical Activity From Fifth to Sixth Grade.

    Forthofer, Melinda; Dowda, Marsha; O'Neill, Jennifer R; Addy, Cheryl L; McDonald, Samantha; Reid, Lauren; Pate, Russell R

    2017-12-01

    Gender differences in physical activity (PA) trajectories during adolescence are well documented, yet little research has examined whether the determinants of these trajectories vary by child's gender. This study is one of few prospective examinations of gender differences in the influences of psychosocial and socioenvironmental factors on changes in objectively measured PA. Students and parents from elementary and middle schools located in 2 school districts in South Carolina were enrolled in a prospective cohort study of changes in children's PA from elementary to middle school. Measures included children's and/or parents' ratings of various psychosocial and socioenvironmental factors as well as objectively measured PA, children's anthropometric characteristics, and neighborhood factors at fifth and sixth grades. Parents' reports of children's sport and class participation, parent-reported support for PA, and neighborhood resources for PA were protective against declines in PA for both boys and girls. The effects of 2 factors-children's self-efficacy and parents' leisure-time PA-on changes in PA over time were moderated by the child's gender. A better understanding of these dynamics may inform the development of interventions.

  5. Gender Differences in Factors Related to Parenting Styles: A Study of High Performing Science Students.

    Hein, Carol; Lewko, John H.

    1994-01-01

    Examined parenting styles within families of high performing science students and explored gender differences in the factors associated with authoritative parenting style. Found that the authoritative parenting style was predominant among study participants and that a greater number of family-related variables emerge for females, whereas more…

  6. Are There Gender-Specific Risk Factors for Suicidal Activity among Patients with Schizophrenia and Depression?

    Kaplan, Kalman J.; Harrow, Martin; Faull, Robert N.

    2012-01-01

    Are there gender-specific risk factors for suicidal activity among patients with schizophrenia and depression? A total of 74 schizophrenia patients (51 men, 23 women) and 77 unipolar nonpsychotic depressed patients (26 men, 51 women) from the Chicago Follow-up Study were studied prospectively at 2 years posthospitalization and again at 7.5 years.…

  7. [Socioeconomic inequalities and age and gender differences in cardiovascular risk factors].

    López-González, Ángel A; Bennasar-Veny, Miquel; Tauler, Pedro; Aguilo, Antoni; Tomàs-Salvà, Matias; Yáñez, Aina

    2015-01-01

    To describe the cardiovascular risk factors in a working population in the Balearic Islands and to examine whether differences by social class vary according to age and gender. A cross-sectional study was carried out in a sample of active workers aged 20-65 years in the Balearic Islands. The participants were included in the study during their annual work health assessment in 2011. The following variables were collected: occupation, social class, age, gender, height, weight, smoking, blood pressure, lipid profile, and glucose levels. Cardiovascular risk was calculated using two different equations (Framingham and REGICOR). Differences by social class were observed for most cardiovascular risk factors. The pattern of these differences differed depending on age group and gender. Differences in obesity by social class increased with age in women but decreased in men. More differences in hypertension by social class were found among women than among men, with differences increasing with age in both genders. Significant differences by social class were found among women in lipid profile, and these differences increased with age, mainly for low levels of high-density lipoprotein-cholesterol. Inequalities in cardiovascular risk factors by social class were higher among women than among men. Some cardiovascular risk factors such as smoking and obesity showed significant inequalities from a very early age. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

  8. Factor Structure and Gender Stability of the Brazilian Version of the Pornography Consumption Inventory.

    Baltieri, Danilo Antonio; de Oliveira, Vitor Henrique; de Souza Gatti, Ana Luísa; Junqueira Aguiar, Ana Saito; de Souza Aranha E Silva, Renata Almeida

    2016-10-02

    There are a few instruments available to measure pornograhy consumption-related constructs, and this lack of instruments can compromise the validity of research findings. The Pornography Consumption Inventory (PCI) assesses four motivations for pornography consumption, and it has been validated in hypersexual men and medical students. However, whether the psychometric properties of this instrument are comparable across genders remains unclear. Multigroup confirmatory factor analysis (MGCFA) was used to verify the invariance of the structure of the PCI across male (100) and female (105) university students. The confirmatory factor analysis (CFA) for each group showed a reasonably good fit of the data to the four-factor model. The MGCFA model included only factor loadings constrained to be equal between both genders (ΔCFI 0.05). However, the ΔCFI did not support a strong and strict factorial invariance, ΔCFI > 0.01. Although both genders seemed to agree with the conceptualization of pornography and motivations for consuming it, the PCI was not gender-invariant, as men showed a stronger degree of motivation to consume pornographic material than women did. The implications of these findings regarding the measurement of motivations for pornography use are outlined.

  9. Explaining IT Professionals' Organizational Commitment Based on Age, Gender, and Personality Trait Factor

    Syed, Javaid A.

    2017-01-01

    The purpose of the present study was to test the Emotional Stability dimension of the Big Five factors of personality traits theory to predict or explain a relationship with Employee Organizational Commitment, when the relationship between Emotional Stability (ES) and Employee Organizational Commitment (EOC) was moderated by Gender and AgeGroup.…

  10. Diversity in primary teacher education gender differences in student factors and curriculum perception

    Geerdink, G.; Bergen, T.C.M.; Dekkers, Hetty

    2010-01-01

    In the Netherlands only a small number of male students opt for primary school teaching and a relatively large percentage of them leave without graduating. A small-scale research project was set up to explore the question: Can gender-specific student factors be identified in relation to the initial

  11. The Strengths and Difficulties Questionnaire (SDQ: Factor Structure and Gender Equivalence in Norwegian Adolescents.

    Tormod Bøe

    Full Text Available Although frequently used with older adolescents, few studies of the factor structure, internal consistency and gender equivalence of the SDQ exists for this age group, with inconsistent findings. In the present study, confirmatory factor analysis (CFA was used to evaluate the five-factor structure of the SDQ in a population sample of 10,254 16-18 year-olds from the youth@hordaland study. Measurement invariance across gender was assessed using multigroup CFA. A modestly modified five-factor solution fitted the data acceptably, accounting for one cross loading and some local dependencies. Importantly, partial measurement non-invariance was identified, with differential item functioning in eight items, and higher correlations between emotional and conduct problems for boys compared to girls. Implications for use clinically and in research are discussed.

  12. The Strengths and Difficulties Questionnaire (SDQ): Factor Structure and Gender Equivalence in Norwegian Adolescents.

    Bøe, Tormod; Hysing, Mari; Skogen, Jens Christoffer; Breivik, Kyrre

    2016-01-01

    Although frequently used with older adolescents, few studies of the factor structure, internal consistency and gender equivalence of the SDQ exists for this age group, with inconsistent findings. In the present study, confirmatory factor analysis (CFA) was used to evaluate the five-factor structure of the SDQ in a population sample of 10,254 16-18 year-olds from the youth@hordaland study. Measurement invariance across gender was assessed using multigroup CFA. A modestly modified five-factor solution fitted the data acceptably, accounting for one cross loading and some local dependencies. Importantly, partial measurement non-invariance was identified, with differential item functioning in eight items, and higher correlations between emotional and conduct problems for boys compared to girls. Implications for use clinically and in research are discussed.

  13. Targeting fibroblast growth factor receptor signaling inhibits prostate cancer progression.

    Feng, Shu; Shao, Longjiang; Yu, Wendong; Gavine, Paul; Ittmann, Michael

    2012-07-15

    Extensive correlative studies in human prostate cancer as well as studies in vitro and in mouse models indicate that fibroblast growth factor receptor (FGFR) signaling plays an important role in prostate cancer progression. In this study, we used a probe compound for an FGFR inhibitor, which potently inhibits FGFR-1-3 and significantly inhibits FGFR-4. The purpose of this study is to determine whether targeting FGFR signaling from all four FGFRs will have in vitro activities consistent with inhibition of tumor progression and will inhibit tumor progression in vivo. Effects of AZ8010 on FGFR signaling and invasion were analyzed using immortalized normal prostate epithelial (PNT1a) cells and PNT1a overexpressing FGFR-1 or FGFR-4. The effect of AZ8010 on invasion and proliferation in vitro was also evaluated in prostate cancer cell lines. Finally, the impact of AZ8010 on tumor progression in vivo was evaluated using a VCaP xenograft model. AZ8010 completely inhibits FGFR-1 and significantly inhibits FGFR-4 signaling at 100 nmol/L, which is an achievable in vivo concentration. This results in marked inhibition of extracellular signal-regulated kinase (ERK) phosphorylation and invasion in PNT1a cells expressing FGFR-1 and FGFR-4 and all prostate cancer cell lines tested. Treatment in vivo completely inhibited VCaP tumor growth and significantly inhibited angiogenesis and proliferation and increased cell death in treated tumors. This was associated with marked inhibition of ERK phosphorylation in treated tumors. Targeting FGFR signaling is a promising new approach to treating aggressive prostate cancer.

  14. Human corpus luteum: presence of epidermal growth factor receptors and binding characteristics

    Ayyagari, R.R.; Khan-Dawood, F.S.

    1987-01-01

    Epidermal growth factor receptors are present in many reproductive tissues but have not been demonstrated in the human corpus luteum. To determine the presence of epidermal growth factor receptors and its binding characteristics, we carried out studies on the plasma cell membrane fraction of seven human corpora lutea (days 16 to 25) of the menstrual cycle. Specific epidermal growth factor receptors were present in human corpus luteum. Insulin, nerve growth factor, and human chorionic gonadotropin did not competitively displace epidermal growth factor binding. The optimal conditions for corpus luteum-epidermal growth factor receptor binding were found to be incubation for 2 hours at 4 degrees C with 500 micrograms plasma membrane protein and 140 femtomol 125 I-epidermal growth factor per incubate. The number (mean +/- SEM) of epidermal growth factor binding sites was 12.34 +/- 2.99 X 10(-19) mol/micrograms protein; the dissociation constant was 2.26 +/- 0.56 X 10(-9) mol/L; the association constant was 0.59 +/- 0.12 X 10(9) L/mol. In two regressing corpora lutea obtained on days 2 and 3 of the menstrual cycle, there was no detectable specific epidermal growth factor receptor binding activity. Similarly no epidermal growth factor receptor binding activity could be detected in ovarian stromal tissue. Our findings demonstrate that specific receptors for epidermal growth factor are present in the human corpus luteum. The physiologic significance of epidermal growth factor receptors in human corpus luteum is unknown, but epidermal growth factor may be involved in intragonadal regulation of luteal function

  15. Napsin A and Thyroid Transcription Factor-1-Positive Cerebellar Tumor with Epidermal Growth Factor Receptor Mutation

    Taiji Kuwata

    2011-12-01

    Full Text Available We present a very rare case of cerebellar metastasis of unknown origin, in which a primary lung adenocarcinoma was diagnosed by pathological examination of a cerebellar metastatic tumor, using immunohistochemical markers and epidermal growth factor receptor (EGFR mutation of primary lung cancer. A 69-year-old woman was admitted to our hospital because of a hemorrhagic cerebellar tumor and multiple small brain tumors. She underwent cerebellar tumor resection. On pathological examination, the tumor was diagnosed as adenocarcinoma. However, the primary tumor site was unidentifiable even with several imaging inspections. On immunohistochemical analysis, the resected tumor was positive for napsin A and thyroid transcription factor-1. In addition, an EGFR mutation was detected in the tumor. Therefore, primary lung cancer was diagnosed and the patient was started on gefitinib (250 mg/day therapy.

  16. Gender differences in extreme mathematical achievement: an international perspective on biological and social factors.

    Penner, Andrew M

    2008-01-01

    Genetic and other biological explanations have reemerged in recent scholarship on the underrepresentation of women in mathematics and the sciences. This study engages this debate by using international data-including math achievement scores from the Third International Mathematics and Sciences Study and country-level data from the World Bank, the United Nations, the International Labour Organization, the World Values Survey, and the International Social Survey Programme-to demonstrate the importance of social factors and to estimate an upper bound for the impact of genetic factors. The author argues that international variation provides a valuable opportunity to present simple and powerful arguments for the continued importance of social factors. In addition, where previous research has, by and large, focused on differences in population means, this work examines gender differences throughout the distribution. The article shows that there is considerable variation in gender differences internationally, a finding not easily explained by strictly biological theories. Modeling the cross-national variation in gender differences with country-level predictors reveals that differences among high achievers are related to gender inequality in the labor market and differences in the overall status of men and women.

  17. Prognostic significance of epidermal growth factor receptor (EGFR) over expression in urothelial carcinoma of urinary bladder.

    Hashmi, Atif Ali; Hussain, Zubaida Fida; Irfan, Muhammad; Khan, Erum Yousuf; Faridi, Naveen; Naqvi, Hanna; Khan, Amir; Edhi, Muhammad Muzzammil

    2018-06-07

    Epidermal growth factor receptor (EGFR) has been shown to have abnormal expression in many human cancers and is considered as a marker of poor prognosis. Frequency of over expression in bladder cancer has not been studied in our population; therefore we aimed to evaluate the frequency and prognostic significance of EGFR immunohistochemical expression in locoregional population. We performed EGFR immunohistochemistry on 126 cases of bladder cancer and association of EGFR expression with tumor grade, lamina propria invasion, deep muscle invasion and recurrence of disease was evaluated. High EGFR expression was noted in 26.2% (33 cases), 15.1% (19 cases) and 58.7% (74 cases) revealed low and no EGFR expression respectively. Significant association of EGFR expression was noted with tumor grade, lamina propria invasion, deep muscle invasion and recurrence status while no significant association was seen with age, gender and overall survival. Kaplan- Meier curves revealed significant association of EGFR expression with recurrence while no significant association was seen with overall survival. Significant association of EGFR overexpression with tumor grade, muscularis propria invasion and recurrence signifies its prognostic value; therefore EGFR can be used as a prognostic biomarker in Urothelial bladder carcinoma.

  18. Gender differences in the relations between work-related physical and psychosocial risk factors and musculoskeletal complaints

    Hooftman, W.E.; Poppel, M.N.M. van; Beek, A.J. van der; Bongers, P.M.; Mechelen, W. van

    2004-01-01

    Gender differences in the prevalence of musculoskeletal complaints might be explained by differences in the effect of exposure to work-related physical and psychosocial risk factors. A systematic review was conducted to examine gender differences in the relations between these risk factors and

  19. Oxygen dependency of epidermal growth factor receptor binding and DNA synthesis of rat hepatocytes

    Hirose, Tetsuro; Terajima, Hiroaki; Yamauchi, Akira

    1997-01-01

    Background/Aims: Changes in oxygen availability modulate replicative responses in several cell types, but the effects on hepatocyte replication remain unclear. We have studied the effects of transient nonlethal hypoxia on epidermal growth factor receptor binding and epidermal growth factor-induced DNA synthesis of rat hepatocytes. Methods: Lactate dehydrogenase activity in culture supernatant, intracellular adenosine triphosphate content, 125 I-epidermal growth factor specific binding, epidermal growth factor receptor protein expression, and 3 H-thymidine incorporation were compared between hepatocytes cultured in hypoxia and normoxia. Results: Hypoxia up to 3 h caused no significant increase in lactate dehydrogenase activity in the culture supernatant, while intracellular adenosine triphosphate content decreased time-dependently and was restored to normoxic levels by reoxygenation (nonlethal hypoxia). Concomitantly, 125 I-epidermal growth factor specific binding to hepatocytes decreased time-dependently (to 54.1% of normoxia) and was restored to control levels by reoxygenation, although 125 I-insulin specific binding was not affected. The decrease in 125 I-epidermal growth factor specific binding was explained by the decrease in the number or available epidermal growth factor receptors (21.37±3.08 to 12.16±1.42 fmol/10 5 cells), while the dissociation constant of the receptor was not affected. The change in the number of available receptors was not considered to be due to receptor degradation-resynthesis, since immuno-detection of the epidermal growth factor receptor revealed that the receptor protein expression did not change during hypoxia and reoxygenation, and since neither actinomycin D nor cycloheximide affected the recovery of 125 I-epidermal growth factor binding by reoxygenation. Inhibition of epidermal growth factor-induced DNA synthesis after hypoxia (to 75.4% of normoxia by 3 h hypoxia) paralleled the decrease in 125 I-epidermal growth factor binding

  20. Hepatocyte and keratinocyte growth factors and their receptors in human lung emphysema

    Marchal Joëlle

    2005-10-01

    Full Text Available Abstract Background Hepatocyte and keratinocyte growth factors are key growth factors in the process of alveolar repair. We hypothesized that excessive alveolar destruction observed in lung emphysema involves impaired expression of hepatocyte and keratinocyte growth factors or their respective receptors, c-met and keratinocyte growth factor receptor. The aim of our study was to compare the expression of hepatocyte and keratinocyte growth factors and their receptors in lung samples from 3 groups of patients: emphysema; smokers without emphysema and non-smokers without emphysema. Methods Hepatocyte and keratinocyte growth factor proteins were analysed by immunoassay and western blot; mRNA expression was measured by real time quantitative polymerase chain reaction. Results Hepatocyte and keratinocyte growth factors, c-met and keratinocyte growth factor receptor mRNA levels were similar in emphysema and non-emphysema patients. Hepatocyte growth factor mRNA correlated negatively with FEV1 and the FEV1/FVC ratio both in emphysema patients and in smokers with or without emphysema. Hepatocyte and keratinocyte growth factor protein concentrations were similar in all patients' groups. Conclusion The expression of hepatocyte and keratinocyte growth factors and their receptors is preserved in patients with lung emphysema as compared to patients without emphysema. Hepatocyte growth factor mRNA correlates with the severity of airflow obstruction in smokers.

  1. Sexual Minority Health and Health Risk Factors: Intersection Effects of Gender, Race, and Sexual Identity.

    Hsieh, Ning; Ruther, Matt

    2016-06-01

    Although population studies have documented the poorer health outcomes of sexual minorities, few have taken an intersectionality approach to examine how sexual orientation, gender, and race jointly affect these outcomes. Moreover, little is known about how behavioral risks and healthcare access contribute to health disparities by sexual, gender, and racial identities. Using ordered and binary logistic regression models in 2015, data from the 2013 and 2014 National Health Interview Surveys (n=62,302) were analyzed to study disparities in self-rated health and functional limitation. This study examined how gender and race interact with sexual identity to create health disparities, and how these disparities are attributable to differential exposure to behavioral risks and access to care. Conditional on sociodemographic factors, all sexual, gender, and racial minority groups, except straight white women, gay white men, and bisexual non-white men, reported worse self-rated health than straight white men (pnon-white men, were more likely to report a functional limitation than straight white men (pgender, and racial minority groups. Sexual, gender, and racial identities interact with one another in a complex way to affect health experiences. Efforts to improve sexual minority health should consider heterogeneity in health risks and health outcomes among sexual minorities. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  2. Receptores do factor estimulante de colónias de macrófagos do robalo

    Oliveira, Márcio Adriano Guiomar de

    2010-01-01

    O receptor do factor estimulante de colónias de macrófagos, também conhecido como receptor do factor estimulante de colónias-1 (CSF1R), é um receptor de um factor de crescimento hematopoiético que é especificamente expresso em células do sistema fagocítico-mononuclear e desempenha um papel essencial no desenvolvimento e regulação destas células. O CSF1R já foi descrito em vários mamíferos e a sua biologia tem sido exaustivamente caracterizada nestes vertebrados mas o conheci...

  3. The influence of gender on entrepreneurial intention: The mediating role of perceptual factors

    Carmen Camelo-Ordaz

    2016-10-01

    Full Text Available The empirical evidence devoted to analyze the impact of perceptual factors in explaining the differences in the entrepreneurial intention of men and women is still limited and not entirely conclusive (Shinnar et al., 2012; Wilson et al., 2009. This non-conclusive research is significantly more noteworthy when the analysis is focused on the entrepreneurial intention of men and women once they become entrepreneurs. Drawing on this gap and taking as starting point the premises of Social Feminist Theory, our paper aims to examine the mediating role of perceptual factors on the relationship between gender and entrepreneurial intention of non-entrepreneurs and entrepreneurs. Drawing on a sample provided by the Global Entrepreneurship Monitor Project of 21,697 Spanish non-entrepreneurs and 2899 Spanish entrepreneurs, our results have shown that, in general terms, perceptual factor fully mediate the relationship between gender and the entrepreneurial intention of non-entrepreneurs, whereas such mediating impact disappears when people become entrepreneurs.

  4. Multistep change in epidermal growth factor receptors during spontaneous neoplastic progression in Chinese hamster embryo fibroblasts

    Wakshull, E.; Kraemer, P.M.; Wharton, W.

    1985-01-01

    Whole Chinese hamster embryo lineages have been shown to undergo multistep spontaneous neoplastic progression during serial passage in culture. The authors have studied the binding, internalization, and degradation of 125 I-labeled epidermal growth factor at four different stages of transformation. The whole Chinese hamster embryo cells lost cell surface epidermal growth factor receptors gradually during the course of neoplastic progression until only 10% of the receptor number present in the early-passage cells (precrisis) were retained in the late-passage cells (tumorigenic). No differences in internalization rates, chloroquine sensitivity, or ability to degrade hormone between the various passage levels were seen. No evidence for the presence in conditioned medium of transforming growth factors which might mask or down-regulate epidermal growth factor receptor was obtained. These results suggest that a reduction in cell surface epidermal growth factor receptor might be an early event during spontaneous transformation in whole Chinese hamster embryo cells

  5. Racial and gender discrimination, early life factors, and chronic physical health conditions in midlife.

    McDonald, Jasmine A; Terry, Mary Beth; Tehranifar, Parisa

    2014-01-01

    Most studies of perceived discrimination have been cross-sectional and focused primarily on mental rather than physical health conditions. We examined the associations of perceived racial and gender discrimination reported in adulthood with early life factors and self-reported physician diagnosis of chronic physical health conditions. We used data from a racially diverse birth cohort of U.S. women (n = 168; average age, 41 years) with prospectively collected early life data (e.g., parental socioeconomic factors) and adult reported data on perceived discrimination, physical health conditions, and relevant risk factors. We performed modified robust Poisson regression owing to the high prevalence of the outcomes. Fifty percent of participants reported racial and 39% reported gender discrimination. Early life factors did not have strong associations with perceived discrimination. In adjusted regression models, participants reporting at least three experiences of gender or racial discrimination had a 38% increased risk of having at least one physical health condition (relative risk, 1.38; 95% confidence interval, 1.01-1.87). Using standardized regression coefficients, the magnitude of the association of having physical health condition(s) was larger for perceived discrimination than for being overweight or obese. Our results suggest a substantial chronic disease burden associated with perceived discrimination, which may exceed the impact of established risk factors for poor physical health. Copyright © 2014 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  6. Hierarchical classification strategy for Phenotype extraction from epidermal growth factor receptor endocytosis screening

    L. Cao (Lu); M. Graauw (Marjo de); K. Yan (Kuan); L.C.J. Winkel (Leah C.J.); F.J. Verbeek (Fons)

    2016-01-01

    textabstractBackground: Endocytosis is regarded as a mechanism of attenuating the epidermal growth factor receptor (EGFR) signaling and of receptor degradation. There is increasing evidence becoming available showing that breast cancer progression is associated with a defect in EGFR endocytosis. In

  7. Targeting of the tumor necrosis factor receptor superfamily for cancer immunotherapy

    Bremer, Edwin

    2013-01-01

    The tumor necrosis factor (TNF) ligand and cognate TNF receptor superfamilies constitute an important regulatory axis that is pivotal for immune homeostasis and correct execution of immune responses. TNF ligands and receptors are involved in diverse biological processes ranging from the selective

  8. Expression of growth factor receptors and targeting of EGFR in cholangiocarcinoma cell lines

    Xu, Ling; Hausmann, Martin; Dietmaier, Wolfgang; Kellermeier, Silvia; Pesch, Theresa; Stieber-Gunckel, Manuela; Lippert, Elisabeth; Klebl, Frank; Rogler, Gerhard

    2010-01-01

    Cholangiocarcinoma (CC) is a malignant neoplasm of the bile ducts or the gallbladder. Targeting of growth factor receptors showed therapeutic potential in palliative settings for many solid tumors. The aim of this study was to determine the expression of seven growth factor receptors in CC cell lines and to assess the effect of blocking the EGFR receptor in vitro. Expression of EGFR (epithelial growth factor receptor), HGFR (hepatocyte growth factor receptor) IGF1R (insulin-like growth factor 1 receptor), IGF2R (insulin-like growth factor 2 receptor) and VEGFR1-3 (vascular endothelial growth factor receptor 1-3) were examined in four human CC cell lines (EGI-1, HuH28, OZ and TFK-1). The effect of the anti-EGFR-antibody cetuximab on cell growth and apoptosis was studied and cell lines were examined for KRAS mutations. EGFR, HGFR and IGFR1 were present in all four cell lines tested. IGFR2 expression was confirmed in EGI-1 and TFK-1. No growth-inhibitory effect was found in EGI-1 cells after incubation with cetuximab. Cetuximab dose-dependently inhibited growth in TFK-1. Increased apoptosis was only seen in TFK-1 cells at the highest cetuximab dose tested (1 mg/ml), with no dose-response-relationship at lower concentrations. In EGI-1 a heterozygous KRAS mutation was found in codon 12 (c.35G>A; p.G12D). HuH28, OZ and TFK-1 lacked KRAS mutation. CC cell lines express a pattern of different growth receptors in vitro. Growth factor inhibitor treatment could be affected from the KRAS genotype in CC. The expression of EGFR itself does not allow prognoses on growth inhibition by cetuximab

  9. Expression of growth factor receptors and targeting of EGFR in cholangiocarcinoma cell lines

    Kellermeier Silvia

    2010-06-01

    Full Text Available Abstract Background Cholangiocarcinoma (CC is a malignant neoplasm of the bile ducts or the gallbladder. Targeting of growth factor receptors showed therapeutic potential in palliative settings for many solid tumors. The aim of this study was to determine the expression of seven growth factor receptors in CC cell lines and to assess the effect of blocking the EGFR receptor in vitro. Methods Expression of EGFR (epithelial growth factor receptor, HGFR (hepatocyte growth factor receptor IGF1R (insulin-like growth factor 1 receptor, IGF2R (insulin-like growth factor 2 receptor and VEGFR1-3 (vascular endothelial growth factor receptor 1-3 were examined in four human CC cell lines (EGI-1, HuH28, OZ and TFK-1. The effect of the anti-EGFR-antibody cetuximab on cell growth and apoptosis was studied and cell lines were examined for KRAS mutations. Results EGFR, HGFR and IGFR1 were present in all four cell lines tested. IGFR2 expression was confirmed in EGI-1 and TFK-1. No growth-inhibitory effect was found in EGI-1 cells after incubation with cetuximab. Cetuximab dose-dependently inhibited growth in TFK-1. Increased apoptosis was only seen in TFK-1 cells at the highest cetuximab dose tested (1 mg/ml, with no dose-response-relationship at lower concentrations. In EGI-1 a heterozygous KRAS mutation was found in codon 12 (c.35G>A; p.G12D. HuH28, OZ and TFK-1 lacked KRAS mutation. Conclusion CC cell lines express a pattern of different growth receptors in vitro. Growth factor inhibitor treatment could be affected from the KRAS genotype in CC. The expression of EGFR itself does not allow prognoses on growth inhibition by cetuximab.

  10. Gender differences in risk factors for cigarette smoking initiation in childhood.

    Sylvestre, Marie-Pierre; Wellman, Robert J; O'Loughlin, Erin K; Dugas, Erika N; O'Loughlin, Jennifer

    2017-09-01

    We investigated whether established risk factors for initiating cigarette smoking during adolescence (parents, siblings, friends smoke; home smoking rules, smokers at home, exposure to smoking in cars, academic performance, susceptibility to smoking, depressive symptoms, self-esteem, school connectedness, use of other tobacco products) are associated with initiation in preadolescents, and whether the effects of these factors differ by gender. In spring 2005, baseline data were collected in self-report questionnaires from 1801 5th grade students including 1553 never-smokers (mean age=10.7years), in the longitudinal AdoQuest I Study in Montréal, Canada. Follow-up data were collected in the fall and spring of 6th grade (2005-2006). Poisson regression analyses with robust variance estimated the effects of each risk factor on initiation and additive interactions with gender were computed to assess the excess risk of each risk factor in girls compared to boys. 101 of 1399 participants in the analytic sample (6.7% of boys; 7.7% of girls) initiated smoking during follow-up. After adjustment for age, gender and maternal education, all risk factors except academic performance and school connectedness were statistically significantly associated with initiation. Paternal and sibling smoking were associated with initiation in girls only, and girls with lower self-esteem had a significant excess risk of initiating smoking in 6th grade. Risk factors for smoking initiation in preadolescents mirror those in adolescents; their effects do not differ markedly by gender. Preventive programs targeting children should focus on reducing smoking in the social environment and the dangers of poly-tobacco use. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Sulindac metabolites inhibit epidermal growth factor receptor activation and expression

    Ahnen Dennis

    2005-01-01

    Full Text Available Abstract Background Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs is associated with a decreased mortality from colorectal cancer (CRC. NSAIDs induce apoptotic cell death in colon cancer cells in vitro and inhibit growth of neoplastic colonic mucosa in vivo however, the biochemical mechanisms required for these growth inhibitory effects are not well defined. We previously reported that metabolites of the NSAID sulindac downregulate extracellular-signal regulated kinase 1/2 (ERK1/2 signaling and that this effect is both necessary and sufficient for the apoptotic effects of these drugs. The goal of this project was to specifically test the hypothesis that sulindac metabolites block activation and/or expression of the epidermal growth factor (EGF receptor (EGFR. Methods HT29 human colon cancer cells were treated with EGF, alone, or in the presence of sulindac sulfide or sulindac sulfone. Cells lysates were assayed by immunoblotting for phosphorylated EGFR (pEGFR, pY1068, total EGFR, phosphorylated ERK1/2 (pERK1/2, total ERK1/2, activated caspase-3, and α-tubulin. Results EGF treatment rapidly induced phosphorylation of both EGFR and ERK1/2 in HT29 colon cancer cells. Pretreatment with sulindac metabolites for 24 h blocked EGF-induced phosphorylation of both EGFR and ERK1/2 and decreased total EGFR protein expression. Under basal conditions, downregulation of pEGFR and total EGFR was detected as early as 12 h following sulindac sulfide treatment and persisted through at least 48 h. Sulindac sulfone induced downregulation of pEGFR and total EGFR was detected as early as 1 h and 24 h, respectively, following drug treatment, and persisted through at least 72 h. EGFR downregulation by sulindac metabolites was observed in three different CRC cell lines, occurred prior to the observed downregulation of pERK1/2 and induction of apoptosis by these drugs, and was not dependent of caspase activation. Conclusion These results suggest that

  12. Regulation of insulin-like growth factor I receptors on vascular smooth muscle cells by growth factors and phorbol esters.

    Ververis, J J; Ku, L; Delafontaine, P

    1993-06-01

    Insulin-like growth factor I (IGF I) is an important mitogen for vascular smooth muscle cells. To characterize regulation of vascular IGF I receptors, we performed radioligand displacement experiments using rat aortic smooth muscle cells (RASMs). Serum deprivation for 48 hours caused a 40% decrease in IGF I receptor number. Exposure of quiescent RASMs to platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), or angiotensin II (Ang II) caused a 1.5-2.0-fold increase in IGF I receptors per cell. After FGF exposure, there was a marked increase in the mitogenic response to IGF I. IGF I downregulated its receptors in the presence of platelet-poor plasma. Stimulation of protein kinase C (PKC) by exposure of quiescent RASMs to phorbol 12-myristate 13-acetate caused a biphasic response in IGF I binding; there was a 42% decrease in receptor number at 45 minutes and a 238% increase at 24 hours. To determine the role of PKC in growth factor-induced regulation of IGF I receptors, we downregulated PKC by exposing RASMs to phorbol 12,13-dibutyrate (PDBu) for 48 hours. PDGF- and FGF- but not Ang II-mediated upregulation of IGF I receptors was completely inhibited in PDBu-treated cells. Thus, acute PKC activation by phorbol esters inhibits IGF I binding, whereas chronic PKC activation increases IGF I binding. PDGF and FGF but not Ang II regulate vascular IGF I receptors through a PKC-dependent pathway. These data provide new insights into the regulation of vascular smooth muscle cell IGF I receptors in vitro and are of potential importance in characterizing vascular proliferative responses in vivo.

  13. Female migrant sex workers in Moscow: gender and power factors and HIV risk.

    Weine, Stevan; Golobof, Alexandra; Bahromov, Mahbat; Kashuba, Adrianna; Kalandarov, Tohir; Jonbekov, Jonbek; Loue, Sana

    2013-01-01

    This study aimed to build formative knowledge regarding HIV risks in female migrant sex workers in Moscow, focusing on gender and power. This was a collaborative ethnographic study, informed by the theory of gender and power, in which researchers conducted minimally structured interviews with 24 female sex workers who were migrants to Moscow and who provided sexual services to male migrant laborers. Overall, the female migrant sex workers engaged in HIV risk behaviors and practiced inadequate HIV protection with their clients. These behaviors were shaped by gender and power factors in the realms of labor, behavior, and cathexis. In the labor realm, because some female migrants were unable to earn enough money to support their families, they were pushed or pulled into sex work providing service to male migrants. In the behavior realm, many female migrant sex workers were intimidated by their male clients, feared violence, and lacked access to women's health care and prevention. In the cathexis realm, many had a sense of shame, social isolation, emotional distress, and lacked basic HIV knowledge and prevention skills. To prevent HIV transmission requires addressing the gender and power factors that shape HIV/AIDS risks among female migrant sex workers through multilevel intervention strategies.

  14. An examination of multilevel factors that may explain gender differences in children's physical activity.

    Crespo, Noe C; Corder, Kirsten; Marshall, Simon; Norman, Gregory J; Patrick, Kevin; Sallis, Jim F; Elder, John P

    2013-09-01

    Girls are less physically active than boys, yet no single study has examined the factors that may explain gender differences in children's physical activity (PA). This study was a cross-sectional analysis of data from 116 caregivers and their children aged 5-8 years who participated in the MOVE study. Caregivers reported various factors that may relate to children's PA (eg, encouragement for child PA and PA equipment at home). Child PA was measured by 7-day accelerometry. Linear regression tested for the variance in moderate-to-vigorous physical activity (MVPA) explained by gender and several variables. Gender and ethnicity interactions were examined. Caregivers were mostly female (97%), mean age 38 ± 6 years, mean BMI 28 ± 6 (kg/m2). Child's mean age was 8.1 ± 0.7, 54% were female and 40% were overweight/obese. Girls were less physically active than boys (54.1 ± 19.7 vs. 65.2 ± 28.0 daily minutes of MVPA, respectively). Among girls, more days of PE/week was associated with greater MVPA. Among boys, greater parent support for PA, greater parent modeling for PA, and greater number of PA equipment in the home were associated with greater MVPA. This study supports that boys and girls have different correlates for MVPA, which may partly explain gender differences in PA.

  15. Gender differences and related factors affecting online gaming addiction among Taiwanese adolescents.

    Ko, Chih-Hung; Yen, Ju-Yu; Chen, Cheng-Chung; Chen, Sue-Huei; Yen, Cheng-Fang

    2005-04-01

    The aim of this study was to evaluate the extent to which gender and other factors predict the severity of online gaming addiction among Taiwanese adolescents. A total of 395 junior high school students were recruited for evaluation of their experiences playing online games. Severity of addiction, behavioral characteristics, number of stressors, and level of satisfaction with daily life were compared between males and females who had previously played online games. Multiple regression analysis was used to explore gender differences in the relationships between severity of online gaming addiction and a number of variables. This study found that subjects who had previously played online games were predominantly male. Gender differences were also found in the severity of online gaming addiction and motives for playing. Older age, lower self-esteem, and lower satisfaction with daily life were associated with more severe addiction among males, but not among females. Special strategies accounting for gender differences must be implemented to prevent adolescents with risk factors from becoming addicted to online gaming.

  16. Gender differences in depression risk and coping factors in a clinical sample.

    Wilhelm, K; Roy, K; Mitchell, P; Brownhill, S; Parker, G

    2002-07-01

    To examine gender differences in depression risk and coping factors in a clinical sample of patients with a diagnosis of DSM-IV major depression. Patients were assessed for substance use and abuse, family history of psychiatric disorder, interpersonal depressogenic factors and lifetime history of anxiety disorders. Trait anxiety, coping styles when depressed, parental bonding, marital features and personality style were also measured. Patients were reassessed at 12-month follow-up. There were few gender differences in experience of depression (either in duration, type or severity prior to treatment) in a group with established episodes of major depression but women reported more emotional arousability when depressed. Women reported higher rates of dysfunctional parenting and childhood sexual abuse, and rated their partners as less caring and as more likely to be a depressogenic stressor. Men were more likely to have a generalized anxiety disorder at assessment, to use recreational drugs prior to presentation. Men were rated as having a more rigid personality style and 'Cluster A' personality traits both at assessment and follow-up. There were few gender differences in severity or course of established episodes of major depression. Gender differences were related to levels of arousal, anxiety disorders, and repertoires for dealing with depression, rather than depressive symptoms per se.

  17. Factors Relating to Managerial Stereotypes: The Role of Gender of the Employee and the Manager and Management Gender Ratio

    Stoker, Janka I.; Van der Velde, Mandy; Lammers, Joris

    2011-01-01

    Purpose Several studies have shown that the traditional stereotype of a ?good? manager being masculine and male still exists. The recent changes in the proportion of women and female managers in organizations could affect these two managerial stereotypes, leading to a stronger preference for feminine characteristics and female leaders. This study examines if the gender of an employee, the gender of the manager, and the management gender ratio in an organization are related to employees? manag...

  18. EphA2 is a functional receptor for the growth factor progranulin.

    Neill, Thomas; Buraschi, Simone; Goyal, Atul; Sharpe, Catherine; Natkanski, Elizabeth; Schaefer, Liliana; Morrione, Andrea; Iozzo, Renato V

    2016-12-05

    Although the growth factor progranulin was discovered more than two decades ago, the functional receptor remains elusive. Here, we discovered that EphA2, a member of the large family of Ephrin receptor tyrosine kinases, is a functional signaling receptor for progranulin. Recombinant progranulin bound with high affinity to EphA2 in both solid phase and solution. Interaction of progranulin with EphA2 caused prolonged activation of the receptor, downstream stimulation of mitogen-activated protein kinase and Akt, and promotion of capillary morphogenesis. Furthermore, we found an autoregulatory mechanism of progranulin whereby a feed-forward loop occurred in an EphA2-dependent manner that was independent of the endocytic receptor sortilin. The discovery of a functional signaling receptor for progranulin offers a new avenue for understanding the underlying mode of action of progranulin in cancer progression, tumor angiogenesis, and perhaps neurodegenerative diseases. © 2016 Neill et al.

  19. Signal transduction by growth factor receptors: signaling in an instant

    Dengjel, Joern; Akimov, Vyacheslav; Blagoev, Blagoy

    2007-01-01

    Phosphorylation-based signaling events happening within the first minute of receptor stimulation have so far only been analyzed by classical cell biological approaches like live-cell microscopy. The development of a quench flow system with a time resolution of one second coupled to a read...

  20. Gender Differences in Psychosocial Risk and Protective Factors for Adolescent Alcohol Use and Misuse in Jamaica

    P Whitehorne-Smith

    2015-03-01

    Full Text Available Objective: The present study sought to determine if there were gender differences in the impact of five psychosocial risk and protective factors for adolescent alcohol use. The five factors considered by the study were family relationships, self-esteem, peer pressure, religious involvement and school performance. Method: This was a cross-sectional quantitative study which utilized a 96-item self-administered questionnaire. The questionnaire captured key demographic and alcohol-related information. It also consisted of three standardized scales: the Cernkovich and Giordano’s Family Relationship Scale, Rosenberg Self-esteem Scale and the CAGE questionnaire. Data were collected from students 12−18 years old in three schools in the Kingston and St Andrew area in Jamaica. Results: There were 240 participants in the study, 121 males and 119 females. The findings revealed that there were no significant differences between male and female adolescent alcohol use in the last 30 days. There was also no significant difference between male and female adolescent risk of substance abuse. Logistic regression analysis of risk factor for each gender revealed that for males, their family relationship, peer pressure and self-esteem were significant predictors for alcohol use, while for females, peer pressure and school performance were significant predictors for alcohol use. Religious involvement was not found to be a significant protective factor for either gender. Conclusion: Gender differences in risk and protective factors exist among Jamaican adolescents. Further research needs to be done to determine the extent of these differences which need to be considered in the development of prevention and intervention programmes.

  1. A First Look at Gender Inequality as a Societal Risk Factor for Dating Violence.

    Gressard, Lindsay A; Swahn, Monica H; Tharp, Andra Teten

    2015-09-01

    One of ten U.S. high school students is a victim of adolescent dating violence (ADV). Understanding ADV risk factors guides prevention efforts; however, research examining community- and societal-level risk factors is scant. Societal gender inequality is a known risk factor for violence against women, but has yet to be explored in relation to ADV. This study aims to determine whether the Gender Inequality Index (GII) correlates with levels of physical and sexual ADV victimization across U.S. states. State-representative prevalence rates of self-reported physical and sexual ADV victimization were obtained from the 2013 Youth Risk Behavior Survey. The state GII includes five indicators: (1) maternal mortality; (2) adolescent birth rate; (3) government representation; (4) educational attainment; and (5) labor force participation. Pearson correlation coefficients determined the association between physical and sexual ADV victimization, the GII, and GII indicators. Analyses were conducted in August 2014. Among U.S. states, the prevalence of physical ADV victimization in 2013 ranged from 7.0% to 14.8%, and the prevalence of sexual ADV victimization ranged from 7.8% to 13.8%. The GII was significantly associated with the state prevalence of female physical ADV victimization (r=0.48, pgender inequality may be a societal-level risk factor for female physical ADV victimization. As ADV prevention strategies are implemented at the state level, further research examining the effect of gender inequality on ADV is needed. Published by Elsevier Inc.

  2. Are new medical students' specialty preferences gendered? Related motivational factors at a Dutch medical school.

    van Tongeren-Alers, Margret; van Esch, Maartje; Verdonk, Petra; Johansson, Eva; Hamberg, Katarina; Lagro-Janssen, Toine

    2011-01-01

    Female students currently outnumber male students in most medical schools. Some medical specialties are highly gender segregated. Therefore, it is interesting to know whether medical students have early specialization preferences based on their gender. Consequently, we like to know importance stipulated to motivational factors. Our study investigates new medical students' early specialization preferences and motivational factors. New students at a Dutch medical school (n = 657) filled in a questionnaire about specialty preferences (response rate = 94%; 69.5% female, 30.5% male). The students chose out of internal medicine, psychiatry, neurology, pediatrics, surgery, gynecology and family medicine, "other" or "I don't know." Finally, they valued ten motivational factors. Forty percent of the medical students reported no specialty preference yet. Taken together, female medical students preferred pediatrics and wished to combine work and care, whereas male students opted for surgery and valued career opportunities. Gender-driven professional preferences in new medical students should be noticed in order to use competencies. Changes in specialty preferences and motivational factors in pre- and post graduates should further assess the role of medical education.

  3. Tumor necrosis factor receptor- associated factor 6 (TRAF6) regulation of development, function, and homeostasis of the immune system.

    Walsh, Matthew C; Lee, JangEun; Choi, Yongwon

    2015-07-01

    Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) is an adapter protein that mediates a wide array of protein-protein interactions via its TRAF domain and a RING finger domain that possesses non-conventional E3 ubiquitin ligase activity. First identified nearly two decades ago as a mediator of interleukin-1 receptor (IL-1R)-mediated activation of NFκB, TRAF6 has since been identified as an actor downstream of multiple receptor families with immunoregulatory functions, including members of the TNFR superfamily, the Toll-like receptor (TLR) family, tumor growth factorreceptors (TGFβR), and T-cell receptor (TCR). In addition to NFκB, TRAF6 may also direct activation of mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and interferon regulatory factor pathways. In the context of the immune system, TRAF6-mediated signals have proven critical for the development, homeostasis, and/or activation of B cells, T cells, and myeloid cells, including macrophages, dendritic cells, and osteoclasts, as well as for organogenesis of thymic and secondary lymphoid tissues. In multiple cellular contexts, TRAF6 function is essential not only for proper activation of the immune system but also for maintaining immune tolerance, and more recent work has begun to identify mechanisms of contextual specificity for TRAF6, involving both regulatory protein interactions, and messenger RNA regulation by microRNAs. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Tumor necrosis factor receptor associated factor 6 (TRAF6) regulation of development, function, and homeostasis of the immune system

    Walsh, Matthew C.; Lee, JangEun; Choi, Yongwon

    2016-01-01

    Summary Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) is an adaptor protein that mediates a wide array of protein-protein interactions via its TRAF domain and a RING finger domain that possesses non-conventional E3 ubiquitin ligase activity. First identified nearly two decades ago as a mediator of IL-1 receptor (IL-1R)-mediated activation of NFκB, TRAF6 has since been identified as an actor downstream of multiple receptor families with immunoregulatory functions, including members of the TNFR superfamily, the toll-like receptor (TLR) family, tumor growth factorreceptors (TGFβR), and T cell receptor (TCR). In addition to NFκB, TRAF6 may also direct activation of mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and interferon regulatory factor (IRF) pathways. In the context of the immune system, TRAF6-mediated signals have proven critical for the development, homeostasis, and/or activation of B cells, T cells, and myeloid cells, including macrophages, dendritic cells, and osteoclasts, as well as for organogenesis of thymic and secondary lymphoid tissues. In multiple cellular contexts, TRAF6 function is essential not only for proper activation of the immune system, but also for maintaining immune tolerance, and more recent works have begun to identify mechanisms of contextual specificity for TRAF6, involving both regulatory protein interactions, and messenger RNA regulation by microRNAs. PMID:26085208

  5. Factors Affecting Gender-based Experiences for Residents in Radiation Oncology

    Barry, Parul N.; Miller, Karen H.; Ziegler, Craig; Hertz, Rosanna; Hanna, Nevine; Dragun, Anthony E.

    2016-01-01

    Purpose: Although women constitute approximately half of medical school graduates, an uneven gender distribution exists among many specialties, including radiation oncology, where women fill only one third of residency positions. Although multiple social and societal factors have been theorized, a structured review of radiation oncology resident experiences has yet to be performed. Methods and Materials: An anonymous and voluntary survey was sent to 611 radiation oncology residents practicing in the United States. Residents were asked about their gender-based experiences in terms of mentorship, their professional and learning environment, and their partnerships and personal life. Results: A total of 203 participants submitted completed survey responses. Fifty-seven percent of respondents were men, and 43% were women, with a mean age of 31 years (standard deviation=3.7 years). Although residents in general value having a mentor, female residents prefer mentors of the same gender (P<.001), and noted having more difficulty finding a mentor (P=.042). Women were more likely to say that they have observed preferential treatment based on gender (P≤.001), and they were more likely to perceive gender-specific biases or obstacles in their professional and learning environment (P<.001). Women selected residency programs based on gender ratios (P<.001), and female residents preferred to see equal numbers of male and female faculty (P<.001). Women were also more likely to perceive work-related strain than their male counterparts (P<.001). Conclusions: Differences in experiences for male and female radiation oncology residents exist with regard to mentorship and in their professional and learning environment.

  6. Factors Affecting Gender-based Experiences for Residents in Radiation Oncology

    Barry, Parul N., E-mail: pnbarr01@louisville.edu [Department of Radiation Oncology, University of Louisville, School of Medicine, Louisville, Kentucky (United States); Miller, Karen H.; Ziegler, Craig [Department of Graduate Medical Education, University of Louisville, School of Medicine, Louisville, Kentucky (United States); Hertz, Rosanna [Departments of Women' s and Gender Studies and Sociology, Wellesley College, Wellesley, Massachusetts (United States); Hanna, Nevine [Department of Radiation Oncology, University of Utah, School of Medicine, Salt Lake City, Utah (United States); Dragun, Anthony E. [Department of Radiation Oncology, University of Louisville, School of Medicine, Louisville, Kentucky (United States)

    2016-07-01

    Purpose: Although women constitute approximately half of medical school graduates, an uneven gender distribution exists among many specialties, including radiation oncology, where women fill only one third of residency positions. Although multiple social and societal factors have been theorized, a structured review of radiation oncology resident experiences has yet to be performed. Methods and Materials: An anonymous and voluntary survey was sent to 611 radiation oncology residents practicing in the United States. Residents were asked about their gender-based experiences in terms of mentorship, their professional and learning environment, and their partnerships and personal life. Results: A total of 203 participants submitted completed survey responses. Fifty-seven percent of respondents were men, and 43% were women, with a mean age of 31 years (standard deviation=3.7 years). Although residents in general value having a mentor, female residents prefer mentors of the same gender (P<.001), and noted having more difficulty finding a mentor (P=.042). Women were more likely to say that they have observed preferential treatment based on gender (P≤.001), and they were more likely to perceive gender-specific biases or obstacles in their professional and learning environment (P<.001). Women selected residency programs based on gender ratios (P<.001), and female residents preferred to see equal numbers of male and female faculty (P<.001). Women were also more likely to perceive work-related strain than their male counterparts (P<.001). Conclusions: Differences in experiences for male and female radiation oncology residents exist with regard to mentorship and in their professional and learning environment.

  7. Increased Epidermal Growth Factor Receptor (EGFR Associated with Hepatocyte Growth Factor (HGF and Symptom Severity in Children with Autism Spectrum Disorders (ASDs

    Anthony J. Russo

    2014-01-01

    Full Text Available Background One in 88 children in the US is thought to have one of the autism spectrum disorders (ASDs. ASDs are characterized by social impairments and communication problems. Growth factors and their receptors may play a role in the etiology of ASDs. Research has shown that epidermal growth factor receptor (EGFR activation is associated with nerve cell development and repair. This study was designed to measure plasma levels of EGFR in autistic children and correlate these levels with its ligand, epidermal growth factor, other related putative biomarkers such as hepatocyte growth factor (HGF, the ligand for MET (MNNG HOS transforming gene receptor, as well as the symptom severity of 19 different behavioral symptoms. Subjects and Methods Plasma EGFR concentration was measured in 33 autistic children and 34 age- and gender-similar neurotypical controls, using an enzyme-linked immunosorbent assay. Plasma EGFR levels were compared to putative biomarkers known to be associated with EGFR and MET and severity levels of 19 autism-related symptoms. Results We found plasma EGFR levels significantly higher in autistic children, when compared to neurotypical controls. EGFR levels correlated with HGF and high-mobility group protein B1 (HMGB1 levels, but not other tested putative biomarkers, and EGFR levels correlated significantly with severity of expressive language, conversational language, focus/attention, hyperactivity, eye contact, and sound sensitivity deficiencies. Conclusions These results suggest a relationship between increased plasma EGFR levels and designated symptom severity in autistic children. A strong correlation between plasma EGFR and HGF and HMGB1 suggests that increased EGFR levels may be associated with the HGF/Met signaling pathway, as well as inflammation.

  8. Economic Reforms and Gender-based Wage Inequality in the Presence of Factor Market Distortions

    Chaudhuri, Sarbajit; Roychowdhury, Somasree

    2014-01-01

    A simple three-sector general equilibrium model has been developed with both male and female labour and factor market distortions. The effects of different liberalized economic policies have been examined on the gender-based wage inequality. The analysis finds that credit market reform and tariff reform produce favourable effects on the wage inequality while the liberalized investment policy becomes counterproductive. These results have important policy implications for a small open developin...

  9. SH2 domains of the p85 alpha subunit of phosphatidylinositol 3-kinase regulate binding to growth factor receptors.

    McGlade, C J; Ellis, C; Reedijk, M; Anderson, D; Mbamalu, G; Reith, A D; Panayotou, G; End, P; Bernstein, A; Kazlauskas, A

    1992-01-01

    The binding of cytoplasmic signaling proteins such as phospholipase C-gamma 1 and Ras GTPase-activating protein to autophosphorylated growth factor receptors is directed by their noncatalytic Src homology region 2 (SH2) domains. The p85 alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase, which associates with several receptor protein-tyrosine kinases, also contains two SH2 domains. Both p85 alpha SH2 domains, when expressed individually as fusion proteins in bacteria, bound stably to the activated beta receptor for platelet-derived growth factor (PDGF). Complex formation required PDGF stimulation and was dependent on receptor tyrosine kinase activity. The bacterial p85 alpha SH2 domains recognized activated beta PDGF receptor which had been immobilized on a filter, indicating that SH2 domains contact autophosphorylated receptors directly. Several receptor tyrosine kinases within the PDGF receptor subfamily, including the colony-stimulating factor 1 receptor and the Steel factor receptor (Kit), also associate with PI 3-kinase in vivo. Bacterially expressed SH2 domains derived from the p85 alpha subunit of PI 3-kinase bound in vitro to the activated colony-stimulating factor 1 receptor and to Kit. We infer that the SH2 domains of p85 alpha bind to high-affinity sites on these receptors, whose creation is dependent on receptor autophosphorylation. The SH2 domains of p85 are therefore primarily responsible for the binding of PI 3-kinase to activated growth factor receptors. Images PMID:1372092

  10. Choosing a Surgeon: An Exploratory Study of Factors Influencing Selection of a Gender Affirmation Surgeon.

    Ettner, Randi; Ettner, Frederic; White, Tonya

    2016-01-01

    Purpose: Selecting a healthcare provider is often a complicated process. Many factors appear to govern the decision as to how to select the provider in the patient-provider relationship. While the possibility of changing primary care physicians or specialists exists, decisions regarding surgeons are immutable once surgery has been performed. This study is an attempt to assess the importance attached to various factors involved in selecting a surgeon to perform gender affirmation surgery (GAS). It was hypothesized that owing to the intimate nature of the surgery, the expense typically involved, the emotional meaning attached to the surgery, and other variables, decisions regarding choice of surgeon for this procedure would involve factors other than those that inform more typical healthcare provider selection or surgeon selection for other plastic/reconstructive procedures. Methods: Questionnaires were distributed to individuals who had undergone GAS and individuals who had undergone elective plastic surgery to assess decision-making. Results: The results generally confirm previous findings regarding how patients select providers. Conclusion: Choosing a surgeon to perform gender-affirming surgery is a challenging process, but patients are quite rational in their decision-making. Unlike prior studies, we did not find a preference for gender-concordant surgeons, even though the surgery involves the genital area. Providing strategies and resources for surgical selection can improve patient satisfaction.

  11. [Gender-determinant factors in contraception: design and validation of a questionnaire].

    Yago Simón, Teresa; Tomás Aznar, Concepción

    2013-10-01

    To design and validate a questionnaire for young women on gender-determinant factors in contraception. A questionnaire was developed from conversations with young women attending contraception clinic in the Health Promotion Municpal Centre, Zaragoza. A total of 200 young women between the ages of 13 and 24 self-completed the questionnaire, with only one no response. Several items were analysed: reliability, using Cronbach's alpha coefficient, and construct validity by analysis of the main components with eigenvalues above 1, and Quartimax rotation with Kaiser normalisation. The questionnaire contained 36 items and took 10minutes to self-complete. There was good internal consistency, with a Cronbach's alpha 0,853. Twelve factors were established with an explanation of 61.42% variance, and three descriptive lines: relationship dimension («submissive attitude», «blind attitude», «let go due to affection», «dominant partner»), gender identity («maternity as identity», «non-idealised maternity», «traditional role», «insecurity», «shame») and caring. This questionnaire enabled gender determinant-factors that take part in contraception to be identified, and will be useful to find out how the different ways of relating between the sexes influence the problems of sexual and reproductive health in young women in our environment. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  12. Increase of tumor necrosis factor receptor 1 expression in women with unexplained early spontaneous abortion

    YAN Chun-fang; YU Xue-wen; JIN Hui; LI Xu

    2004-01-01

    To investigate membrane tumor necrosis factor receptor 1 protein expression level in decidua andconcentration of soluble tumor necrosis factor receptor 1 in serum in women with unexplained early spontaneous abortion,threatened abortion, and compare the levels with healthy pregnant women. Methods: Thirty-seven women with unexplainedearly spontaneous abortion, 27 women with threatened abortion, and 34 healthy pregnant women undergoing artificial abortionof pregnancy at 6 - 10 weeks of gestation were selected. Decidual samples were collected when women were undergoing arti-ficial abortion, and blood samples were collected at the same time. The level of membrane tumor necrosis factor receptor 1 indecidua was detected by flow cytometer, and the concentration of soluble tumor necrosis factor receptor 1 in sera was mea-sured with an enzyme-linked immunosorbent assay. Results: The ercentages of membrane tumor necrosis factor receptor 1positive decidual cells were 16.42 ± 7.10 Mean ± SD for women with unexplained early spontaneous abortion and 13.14 ±6.30 for healthy pregnant women ( P < 0.05). Serum oncentration of soluble tumor necrosis factor receptor 1 was signifi-cantly higher in women with unexplained early spontaneous abortion than in healthy pregnant women and in women withthreatened abortion, and no difference was found between healthy pregnant women and women with threatened abortion.Conclusion: Women with unexplained early spontaneous abortion present significantly higher expression of tumor necrosisfactor receptor 1 than healthy pregnant women, suggesting that over-expression of tumor necrosis factor receptor 1 may cont-ribute to the development of early spontaneous abortion.

  13. Immunoautoradiographic analysis of epidermal growth factor receptors: a sensitive method for the in situ identification of receptor proteins and for studying receptor specificity

    Fernandez-Pol, J.A.

    1982-01-01

    The use of an immunoautoradiographic system for the detection and analysis of epidermal growth factor (EGF) receptors in human epidermoid carcinoma A-431 cells is reported. By utilizing this technique, the interaction between EGF and its membrane receptor in A-431 cells can be rapidly visualized. The procedure is simple, rapid, and very sensitive, and it provides conclusive evidence that the 150K dalton protein is the receptor fo EGF in A-431 cells. In summary, the immunoautoradiographic procedure brings to the analysis of hormone rceptor proteins the power that the radioimmunoassay technique has brought to the analysis of hormones. Thus, this assay system is potentially applicable in a wide spectrum in many fields of nuclear medicine and biology

  14. GENDER DIFFERENTIALS IN FACTORS AFFECTING PERFORMANCE OF SMALL-SCALE ENTERPRISES IN LAGOS STATE – NIGERIA

    Yusuff Olabisi Sherifat

    2013-05-01

    Full Text Available There is a lack of empirical data segregation on factors affecting gender as the variable of interest. However, previous research had indicated several factors that affect business performances among small-scale enterprise owners. Using feminist theory and a descriptive survey research design, data were collected from fifty (50 small-scale enterprise owners that were purposively chosen across the study area. The findings show that the factors that were significant for female were significantly different from male. For female small scale enterprise owners, marital status (64% Age of Children (68%, Role Model/ advisors (58% were significant factors that affect their business performance. For male small-scale enterprise owners, Friends (70%, a lack of Government support (80%, inability to display innovativeness (78% and Risk-Taking (84% were significant for male. Lack of availability of capital and finances were significant for the two. Other factors that affect performance include friends, inadequate training and business location. Adequate knowledge of factors that affect gender enterprise performance will go a long way in alleviating these problems. Small-scale enterprises should be supported for poverty alleviation, especially among women and for the nation’s economic development

  15. Altered [125I]epidermal growth factor binding and receptor distribution in psoriasis

    Nanney, L.B.; Stoscheck, C.M.; Magid, M.; King, L.E. Jr.

    1986-01-01

    Stimulation of growth and differentiation of human epidermis by epidermal growth factor (EGF) is mediated by its binding to specific receptors. Whether EGF receptors primarily mediate cell division or differentiation in hyperproliferative disease such as psoriasis vulgaris is unclear. To study the pathogenesis of psoriasis, 4-mm2 punch biopsy specimens of normal, uninvolved, and involved psoriatic skin were assayed for EGF receptors by autoradiographic, immunohistochemical, and biochemical methods. Using autoradiographic and immunohistochemical methods, basal keratinocytes were found to contain the greatest number of EGF binding sites and immunoreactive receptors as compared to the upper layers of the epidermis in both normal epidermis and psoriatic skin. No EGF receptor differences between normal and psoriatic epidermis were observed in this layer. In the upper layers of the epidermis, a 2-fold increase in EGF binding capacity was observed in psoriatic skin as compared with normal thin or thick skin. Biochemical methods indicated that [ 125 I]EGF binding was increased in psoriatic epidermis as compared with similar thickness normal epidermis when measured on a protein basis. Epidermal growth factor was shown to increase phosphorylation of the EGF receptor in skin. EGF receptors retained in the nonmitotic stratum spinosum and parakeratotic stratum corneum may reflect the incomplete, abnormal differentiation that occurs in active psoriatic lesions. Alternatively, retained EGF receptors may play a direct role in inhibiting cellular differentiation in the suprabasal layers

  16. Hormonal receptors and vascular endothelial growth factor in juvenile nasopharyngeal angiofibroma: immunohistochemical and tissue microarray analysis.

    Liu, Zhuofu; Wang, Jingjing; Wang, Huan; Wang, Dehui; Hu, Li; Liu, Quan; Sun, Xicai

    2015-01-01

    This work demonstrated that juvenile nasopharyngeal angiofibromas (JNAs) express high levels of hormone receptors and vascular endothelial growth factor (VEGF) compared with normal nasal mucosa. The interaction between hormone receptors and VEGF may be involved in the initiation and growth of JNA. JNA is a rare benign tumor that occurs almost exclusively in male adolescents. Although generally regarded as a hormone-dependent tumor, this has not been proven in previous studies. The aim of this study was to investigate the role of hormone receptors in JNA and the relationship with clinical characteristics. Standard immunohistochemical microarray analysis was performed on 70 JNA samples and 10 turbinate tissue samples. Specific antibodies for androgen receptor (AR), estrogen receptor-α (ER-α), estrogen receptor-β (ER-β), progesterone receptor (PR), and VEGF were examined, and the relationships of receptor expression with age, tumor stage, and bleeding were evaluated. RESULTS showed that JNA expressed ER-α (92.9%), ER-β (91.4%), AR (65.7%), PR (12.8%), and VEGF (95.7%) at different levels. High level of VEGF was linked to elevated ER-α and ER-β. There was no significant relationship between hormonal receptors and age at diagnosis, tumor stage or bleeding. However, overexpression of ER-α was found to be an indicator of poor prognosis (p = 0.031).

  17. Dopamine receptor gene d4 polymorphisms and early sexual onset: gender and environmental moderation in a sample of african-american youth.

    Kogan, Steven M; Lei, Man-Kit; Beach, Steven R H; Brody, Gene H; Windle, Michael; Lee, Sunbok; MacKillop, James; Chen, Yi-Fu

    2014-08-01

    Early sexual onset and its consequences disproportionately affect African-American youth, particularly male youth. The dopamine receptor D4 gene (DRD4) has been linked to sexual activity and other forms of appetitive behavior, particularly for male youth and in combination with environmental factors (gene × environment [G × E] effects). The differential susceptibility perspective suggests that DRD4 may exert this effect by amplifying the effects of both positive and negative environments. We hypothesized that DRD4 status would amplify the influence of both positive and negative neighborhood environments on early sexual onset among male, but not female, African-Americans. Hypotheses were tested with self-report, biospecimen, and census data from five prospective studies of male and female African-American youth in rural Georgia communities, N = 1,677. Early sexual onset was defined as intercourse before age 14. No significant G × E findings emerged for female youth. Male youth with a DRD4 long allele were more likely than those with two DRD4 short alleles to report early sexual onset in negative community environments and not to report early onset in positive community environments. Dopaminergic regulation of adolescent sexual behaviors may operate differently by gender. DRD4 operated as an environmental amplification rather than a vulnerability factor. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  18. Insulin-like growth factor-II receptors in cultured rat hepatocytes: regulation by cell density

    Scott, C.D.; Baxter, R.C.

    1987-01-01

    Insulin-like growth factor-II (IGF-II) receptors in primary cultures of adult rat hepatocytes were characterized and their regulation by cell density examined. In hepatocytes cultured at 5 X 10(5) cells per 3.8 cm2 plate [ 125 I]IGF-II bound to specific, high affinity receptors (Ka = 4.4 +/- 0.5 X 10(9) l/mol). Less than 1% cross-reactivity by IGF-I and no cross-reactivity by insulin were observed. IGF-II binding increased when cells were permeabilized with 0.01% digitonin, suggesting the presence of an intracellular receptor pool. Determined by Scatchard analysis and by polyacrylamide gel electrophoresis after affinity labeling, the higher binding was due solely to an increase in binding sites present on 220 kDa type II IGF receptors. In hepatocytes cultured at low densities, the number of cell surface receptors increased markedly, from 10-20,000 receptors per cell at a culture density of 6 X 10(5) cells/well to 70-80,000 receptors per cell at 0.38 X 10(5) cells/well. The increase was not due simply to the exposure of receptors from the intracellular pool, as a density-related increase in receptors was also seen in cells permeabilized with digitonin. There was no evidence that IGF binding proteins, either secreted by hepatocytes or present in fetal calf serum, had any effect on the measurement of receptor concentration or affinity. We conclude that rat hepatocytes in primary culture contain specific IGF-II receptors and that both cell surface and intracellular receptors are regulated by cell density

  19. Gender aspects of the role of the metabolic syndrome as a risk factor for cardiovascular disease.

    Regitz-Zagrosek, Vera; Lehmkuhl, Elke; Mahmoodzadeh, Shokufeh

    2007-01-01

    The interaction of the risk factors of abdominal obesity, disturbed glucose homeostasis, dyslipidemia, and hypertension is believed to represent a distinct entity, termed the metabolic syndrome (MetS), that leads to a greater increase in cardiovascular risk than does the sum of its components. We reviewed currently available information regarding gender differences in the role of the MetS as a risk factor for cardiovascular disease (CVD). Using the search terms women, men, sex, gender, sex differences, and gender differences in combination with the metabolic syndrome, we conducted a systematic review of the available literature on sex differences in the MetS. The National Institutes of Health, PubMed, and MEDLINE databases were searched retrospectively from 2007 to 1987. Reference lists of identified articles were also used as a source, and articles were not restricted to the English language. In recent years, the MetS has been more prevalent in men than in women but has risen particularly in young women, where it is mainly driven by obesity. Diagnostic criteria for the MetS vary for the cutoff points and definition of its components in a gender-specific manner. Based on the definition of impaired glucose homeostasis and pathologic abdominal circumference or waist/hip ratio, more or fewer women are included. Glucose and lipid metabolism are directly modulated by estrogen and testosterone, with a lack of estrogen or a relative increase in testosterone inducing insulin resistance and a proatherogenic lipid profile. Hypertension is a strong risk factor in both sexes, but the prevalence of hypertension increases more rapidly in aging women than in men. Menopause and polycystic ovary syndrome contribute to the development of MetS by the direct effects of sex hormones. Some components of the MetS (eg, diabetes and hypertension) carry a greater risk for CVD in women. Future gender-related clinical and research activities should focus on the identification of sex- and

  20. Molecular and functional characterization of pigeon (Columba livia) tumor necrosis factor receptor-associated factor 3.

    Zhou, Yingying; Kang, Xilong; Xiong, Dan; Zhu, Shanshan; Zheng, Huijuan; Xu, Ying; Guo, Yaxin; Pan, Zhiming; Jiao, Xinan

    2017-04-01

    Tumor necrosis factor receptor-associated factor 3 (TRAF3) plays a key antiviral role by promoting type I interferon production. We cloned the pigeon TRAF3 gene (PiTRAF3) according to its predicted mRNA sequence to investigate its function. The 1704-bp full-length open reading frame encodes a 567-amino acid protein. One Ring finger, two TRAF-type Zinc fingers, one Coiled coil, and one MATH domain were inferred. RT-PCR showed that PiTRAF3 was expressed in all tissues, with relatively weak expression in the heart and liver. In HEK293T cells, over-expression of wild-type, △Ring, △Zinc finger, and △Coiled coil PiTRAF3, but not a △MATH form, significantly increased IFN-β promoter activity. Zinc finger and Coiled coil domains were essential for NF-κB activation. In chicken HD11 cells, PiTRAF3 increased IFN-β promoter activity and four domains were all contributing. R848 stimulation of pigeon peripheral blood mononuclear cells and splenocytes significantly increased expression of PiTRAF3 and the inflammatory cytokine genes CCL5, IL-8, and IL-10. These data demonstrate TRAF3's innate immune function and improve understanding of its involvement in poultry antiviral defense. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. The Relationship between Demographic Factors and Gender Role Attitudes in Women Referring to Mashhad Health Care Centers in 2014

    Elham Fazeli

    2015-01-01

    Full Text Available Background & aim:  Gender roles are affected by biosocial and cultural factors. These roles have significant impacts on one’s professional, social, and family life. Therefore, given the recent changes in gender roles in Iran, we aimed to determine the relationship between demographic factors and gender role attitudes among women. Methods:This cross-sectional study was conducted on 712 females, selected via stratified sampling. Data were collected using a demographic checklist and a gender role questionnaire including 2 sections: gender role stereotypes and gender egalitarianism. The validity of this questionnaire was confirmed by content validity and its reliability was verified by internal consistency (α=0.77. For data analysis, ANOVA and correlation coefficient tests were performed, using SPSS version16. Results: The mean scores of gender role stereotypes and egalitarianism were 29.55±4.33 and 112.55±14.64, respectively. Stereotypic and egalitarian attitudes were significantly correlated with age, family size, duration of marriage, women’s age at first childbirth, educational level, intentions to pursue education in future, and occupational status. Conclusion: As to the finding, gender role attitudes were influenced by social, economic, and demographic factors in Iran. By paying attention to these factors, we can implement proper interventions in order to promote personal and social health among women.

  2. Association Study of Tumor Necrosis Factor Receptor 1 (TNFR1 Gene Polymorphisms with Schizophrenia in the Polish Population

    Renata Suchanek-Raif

    2017-01-01

    Full Text Available Schizophrenia is a devastating mental disorder with undetermined aetiology. Previous research has suggested that dysregulation of proinflammatory cytokines and their receptors plays a role in developing schizophrenia. We examined the association of the three single nucleotide polymorphisms (SNPs; rs4149576, rs4149577, and rs1860545 in the tumor necrosis factor receptor 1 (TNFR1 gene with the development and psychopathology of paranoid schizophrenia in the Polish Caucasian sample consisting of 388 patients and 657 control subjects. The psychopathology was assessed using a five-factor model of the Positive and Negative Syndrome Scale (PANSS. SNPs were genotyped using the TaqMan 5′-exonuclease allelic discrimination assay. The SNPs tested were not associated with a predisposition to paranoid schizophrenia in either the entire sample or after stratification according to gender. However, rs4149577 and rs1860545 SNPs were associated with the intensity of the PANSS excitement symptoms in men, which may contribute to the risk of violent behavior. Polymorphisms in the TNFR1 gene may have an impact on the symptomatology of schizophrenia in men.

  3. Gender difference in sickness absence from work: a multiple mediation analysis of psychosocial factors.

    Casini, Annalisa; Godin, Isabelle; Clays, Els; Kittel, France

    2013-08-01

    Previous research has shown that job characteristics, private life and psychosocial factors partially account for gender difference in work absences because of sickness. Most studies have analysed these factors separately. The aim of the present study was to evaluate whether these explanatory factors act as mediators when they are considered simultaneously. The evaluated data set comprises the merger of two Belgian longitudinal studies, BELSTRESS III and SOMSTRESS. It includes 3821 workers (1541 men) aged 21-66 years, employed in eight organizations. A multiple mediation analysis was performed to explain the higher prevalence among women. Estimated factors were occupational grade, total number of paid working hours per week, job strain, overcommitment, home-work interference and social support at and outside work. Prospective data concerning duration and frequency of medically justified sickness absence (registered by the organizations) were used as outcomes. Overall, the mediating factors partially account for gender difference in sickness absence. The strongest mediator for both outcomes is job strain. In addition, difference in absence duration is mediated by social support at work, whereas difference in frequency is mediated by professional grade and home-work interference. Our results call attention to the necessity to elaborate actual preventive actions aiming at favouring a better positioning of women on the labour market in term of hierarchical level as well as in terms of quality of work for reducing sickness absence in this group.

  4. Gender Differences in Cognitive and Noncognitive Factors Related to Achievement in Organic Chemistry

    Turner, Ronna C.; Lindsay, Harriet A.

    2003-05-01

    For many college students in the sciences, organic chemistry poses a difficult challenge. Indeed, success in organic chemistry has proven pivotal in the careers of a vast number of students in a variety of science disciplines. A better understanding of the factors that contribute to achievement in this course should contribute to efforts to increase the number of students in the science disciplines. Further, an awareness of gender differences in factors associated with achievement should aid efforts to bolster the participation of women in chemistry and related disciplines. Using a correlation research design, the individual relationships between organic chemistry achievement and each of several cognitive variables and noncognitive variables were assessed. In addition, the relationships between organic chemistry achievement and combinations of these independent variables were explored. Finally, gender- and instructor-related differences in the relationships between organic chemistry achievement and the independent variables were investigated. Cognitive variables included the second-semester general chemistry grade, the ACT English, math, reading, and science-reasoning scores, and scores from a spatial visualization test. Noncognitive variables included anxiety, confidence, effectance motivation, and usefulness. The second-semester general chemistry grade was found to be the best indicator of performance in organic chemistry, while the effectiveness of other predictors varied between instructors. In addition, gender differences were found in the explanations of organic chemistry achievement variance provided by this study. In general, males exhibited stronger correlations between predictor variables and organic chemistry achievement than females.

  5. Problematic internet use among high school students: Prevalence, associated factors and gender differences.

    Vigna-Taglianti, Federica; Brambilla, Romeo; Priotto, Bruna; Angelino, Remo; Cuomo, GianLuca; Diecidue, Roberto

    2017-11-01

    This study aimed to measure the prevalence of Problematic Internet Use (PIU) among high school students and to identify factors associated with PIU underlining gender differences. The students filled a self-administered, anonymous questionnaire collecting information on demographic characteristics and patterns of Internet use. Multiple logistic regression analysis was performed to identify factors associated with PIU in the overall sample and by gender. Twenty-five schools and 2022 students participated in the survey. Prevalence of PIU was 14.2% among males and 10.1% among females. Males 15-year-olds and females 14-year-olds had the highest PIU prevalence that progressively lowered with age among females. Only 13.5% of pupils declared parents controlled their Internet use. The sensation of feeling lonely, the frequency of use, the number of hours of connection, and visiting pornographic websites were associated with the risk of PIU in both genders. Attending vocational schools, the activities of chatting and file downloading, and the location of use at Internet point among males, and younger age among females were associated with PIU, whilst information searching was protective among females. PIU could become a public health problem in the next years. The physical and mental health consequences should be studied. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Sebum, acne, skin elasticity, and gender difference - which is the major influencing factor for facial pores?

    Kim, B Y; Choi, J W; Park, K C; Youn, S W

    2013-02-01

    Enlarged facial pores have been esthetic problems and have become a matter of cosmetic concern. Several factors are supposed to be related to the enlargement of facial pores, although scientific evaluations were not performed yet. To assess the correlation between facial pores and possible relating factors such as age, gender, sebum secretion, skin elasticity, and the presence of acne, using objective bioengineering instruments. Sixty volunteers, 30 males and 30 females, participated in this study. Various parameters of facial pores were assessed using the Robo Skin Analyzer. The facial sebum secretion and skin elasticity were measured using the Sebumeter and the Cutometer, respectively. These data were compared and correlated to examine the possible relationship between facial pores and age, sebum secretion and skin elasticity, according to gender and the presence of acne. Male gender and the existence of acne were correlated with higher number of facial pores. Sebum secretion levels showed positive correlation with facial pores. The R7 parameter of skin elasticity was negatively correlated with facial pores, suggesting increased facial pores with decreased skin elasticity. However, the age and the severity of acne did not show a definite relationship with facial pores. Male, increased sebum and decreased skin elasticity were mostly correlated with facial pore development. Further studies on population with various demographic profiles and more severe acne may be helpful to elucidate the potential effect of aging and acne severity on facial pores. © 2011 John Wiley & Sons A/S.

  7. Risk and Protective Factors in the Lives of Transgender/Gender Nonconforming Adolescents.

    Eisenberg, Marla E; Gower, Amy L; McMorris, Barbara J; Rider, G Nicole; Shea, Glynis; Coleman, Eli

    2017-10-01

    Research suggests that transgender and gender nonconforming (TGNC) youth may be at greatly increased risk of high-risk health behaviors compared with cisgender youth, but existing studies are limited by convenience samples and small numbers. This study uses a large school-based sample of adolescents to describe the prevalence of TGNC identity, associations with health risk behaviors and protective factors, and differences across birth-assigned sex. This study analyzes existing surveillance data provided by 9th and 11th grade students in Minnesota in 2016 (N = 81,885). Students who were transgender, genderqueer, genderfluid, or unsure about their gender identity (TGNC) were compared with those who were not, using χ 2 and t-tests. Outcome measures included four domains of high-risk behaviors and experiences and four protective factors. The prevalence of TGNC identity was 2.7% (n = 2,168) and varied significantly across gender, race/ethnicity, and economic indicators. Involvement in all types of risk behaviors and experiences was significantly higher, and reports of four protective factors were significantly lower among TGNC than cisgender youth. For example, almost two-thirds (61.3%) of TGNC youth reported suicidal ideation, which is over three times higher than cisgender youth (20.0%, χ 2  = 1959.9, p < .001). Among TGNC youth, emotional distress and bullying experience were significantly more common among birth-assigned females than males. This research presents the first large-scale, population-based evidence of substantial health disparities for TGNC adolescents in the United States, highlighting numerous multilevel points of intervention through established protective factors. Health care providers are advised to act as allies by creating a safe space for young people, bolstering protective factors, and supporting their healthy development. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  8. Suicidal ideation in transgender people: Gender minority stress and interpersonal theory factors.

    Testa, Rylan J; Michaels, Matthew S; Bliss, Whitney; Rogers, Megan L; Balsam, Kimberly F; Joiner, Thomas

    2017-01-01

    Research has revealed alarmingly high rates of suicidal ideation (SI) and suicide attempts among transgender and gender nonconforming (TGNC) people. This study aims to analyze the role of factors from the gender minority stress and resilience (GMSR) model (Testa, Habarth, Peta, Balsam, & Bockting, 2015), the interpersonal-psychological theory of suicide (IPTS; Joiner, 2005; Van Orden et al., 2010), and the potential integration of these factors, in explaining SI in this population. A convenience sample of 816 TGNC adults responded to measures of current SI, gender minority stressors, and IPTS factors. Path analysis was utilized to test 2 models. Model 1 evaluated the associations between external minority stressors and SI through internal minority stressors. Model 2 examined the relationships between internal minority stressors and SI through IPTS variables (perceived burdensomeness and thwarted belongingness). All GMSR external stressors (rejection, nonaffirmation, victimization, and discrimination), internal stressors (internalized transphobia, negative expectations, and nondisclosure), and IPTS factors (thwarted belongingness and perceived burdensomeness) were related to SI. Both models demonstrated good fit. Model 1 revealed that rejection, nonaffirmation, and victimization were related to SI through experiences of internalized transphobia and negative expectations. Model 2 indicated that internalized transphobia and negative expectations were associated with SI through IPTS factors. The models demonstrate pathways through which GMSR and IPTS constructs relate to one another and confer risk for SI among TGNC individuals. These pathways and several recently proposed constructs examined here provide promising directions for future research and clinical interventions in this area. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  9. Distinct phosphotyrosines on a growth factor receptor bind to specific molecules that mediate different signaling pathways.

    Fantl, W J; Escobedo, J A; Martin, G A; Turck, C W; del Rosario, M; McCormick, F; Williams, L T

    1992-05-01

    The receptor for platelet-derived growth factor (PDGF) binds two proteins containing SH2 domains, GTPase activating protein (GAP) and phosphatidylinositol 3-kinase (PI3-kinase). The sites on the receptor that mediate this interaction were identified by using phosphotyrosine-containing peptides representing receptor sequences to block specifically binding of either PI3-kinase or GAP. These results suggested that PI3-kinase binds two phosphotyrosine residues, each located in a 5 aa motif with an essential methionine at the fourth position C-terminal to the tyrosine. Point mutations at these sites caused a selective elimination of PI3-kinase binding and loss of PDGF-stimulated DNA synthesis. Mutation of the binding site for GAP prevented the receptor from associating with or phosphorylating GAP, but had no effect on PI3-kinase binding and little effect on DNA synthesis. Therefore, GAP and PI3-kinase interact with the receptor by binding to different phosphotyrosine-containing sequence motifs.

  10. Internalization mechanisms of the epidermal growth factor receptor after activation with different ligands.

    Lasse Henriksen

    Full Text Available The epidermal growth factor receptor (EGFR regulates normal growth and differentiation, but dysregulation of the receptor or one of the EGFR ligands is involved in the pathogenesis of many cancers. There are eight ligands for EGFR, however most of the research into trafficking of the receptor after ligand activation focuses on the effect of epidermal growth factor (EGF and transforming growth factor-α (TGF-α. For a long time it was believed that clathrin-mediated endocytosis was the major pathway for internalization of the receptor, but recent work suggests that different pathways exist. Here we show that clathrin ablation completely inhibits internalization of EGF- and TGF-α-stimulated receptor, however the inhibition of receptor internalization in cells treated with heparin-binding EGF-like growth factor (HB-EGF or betacellulin (BTC was only partial. In contrast, clathrin knockdown fully inhibits EGFR degradation after all ligands tested. Furthermore, inhibition of dynamin function blocked EGFR internalization after stimulation with all ligands. Knocking out a number of clathrin-independent dynamin-dependent pathways of internalization had no effect on the ligand-induced endocytosis of the EGFR. We suggest that EGF and TGF-α lead to EGFR endocytosis mainly via the clathrin-mediated pathway. Furthermore, we suggest that HB-EGF and BTC also lead to EGFR endocytosis via a clathrin-mediated pathway, but can additionally use an unidentified internalization pathway or better recruit the small amount of clathrin remaining after clathrin knockdown.

  11. Internalization Mechanisms of the Epidermal Growth Factor Receptor after Activation with Different Ligands

    Henriksen, Lasse; Grandal, Michael Vibo; Knudsen, Stine Louise Jeppe; van Deurs, Bo; Grøvdal, Lene Melsæther

    2013-01-01

    The epidermal growth factor receptor (EGFR) regulates normal growth and differentiation, but dysregulation of the receptor or one of the EGFR ligands is involved in the pathogenesis of many cancers. There are eight ligands for EGFR, however most of the research into trafficking of the receptor after ligand activation focuses on the effect of epidermal growth factor (EGF) and transforming growth factor-α (TGF-α). For a long time it was believed that clathrin-mediated endocytosis was the major pathway for internalization of the receptor, but recent work suggests that different pathways exist. Here we show that clathrin ablation completely inhibits internalization of EGF- and TGF-α-stimulated receptor, however the inhibition of receptor internalization in cells treated with heparin-binding EGF-like growth factor (HB-EGF) or betacellulin (BTC) was only partial. In contrast, clathrin knockdown fully inhibits EGFR degradation after all ligands tested. Furthermore, inhibition of dynamin function blocked EGFR internalization after stimulation with all ligands. Knocking out a number of clathrin-independent dynamin-dependent pathways of internalization had no effect on the ligand-induced endocytosis of the EGFR. We suggest that EGF and TGF-α lead to EGFR endocytosis mainly via the clathrin-mediated pathway. Furthermore, we suggest that HB-EGF and BTC also lead to EGFR endocytosis via a clathrin-mediated pathway, but can additionally use an unidentified internalization pathway or better recruit the small amount of clathrin remaining after clathrin knockdown. PMID:23472148

  12. Growth factor receptors as molecular targets for cancer diagnosis and therapy

    Zalutsky, M. R.

    1997-01-01

    Growth factor receptors are of great interest as molecular targets for the diagnosis and treatment of cancer. Growth factor receptors are frequently over expressed on malignant cell populations since many cellular oncogenes encode either growth factors of their receptors. The wild-type epidermal growth factor receptor has a molecular weight of 170 kD and is over expressed on gliomas, bladder tumors, squamous cells carcinomas and breast carcinomas. Another growth factor oncogene, c-erb B-2, encodes a 185-kD glycoprotein found on the surface of gliomas, breast and ovarian cancers as well as other carcinomas of epithelial origin. In addition to causing over expression, oncogenic transformation also can result in genomic re-arrangements. An important example from the perspective of targeting is EGFRvIII, a deletion mutant which lacks amino acids 6-273 in the extracellular domain of the epiderma growth factor receptor. The EGFRvIII molecule (145 kD) may be of great value for targeting because it appears to be tumor-specific. Antibodies have been developed with specific reactivity with these growth factor receptors. Since these antibodies are internalized into the cell after receptor binding, it is necessary to use radiolabeling methods which residualize the radioactivity in the tumor cell after intracellular catabolism. To investigate this problem they have evaluated the effect of radioiodination method on the in vitro an in vivo properties of an anti-EGFRvIII antibody. Methods studied were Iodogen, tyramine-cellobiose, and N-succinimidyl 5-iodo-3-pyridine-carboxylate with the last offering optimal localization in a human xenograft model

  13. Genes, Gender, Environment, and Novel Functions of Estrogen Receptor Beta in the Susceptibility to Neurodevelopmental Disorders

    Mukesh Varshney

    2017-02-01

    Full Text Available Many neurological disorders affect men and women differently regarding prevalence, progression, and severity. It is clear that many of these disorders may originate from defective signaling during fetal or perinatal brain development, which may affect males and females differently. Such sex-specific differences may originate from chromosomal or sex-hormone specific effects. This short review will focus on the estrogen receptor beta (ERβ signaling during perinatal brain development and put it in the context of sex-specific differences in neurodevelopmental disorders. We will discuss ERβ’s recent discovery in directing DNA de-methylation to specific sites, of which one such site may bear consequences for the susceptibility to the neurological reading disorder dyslexia. We will also discuss how dysregulations in sex-hormone signaling, like those evoked by endocrine disruptive chemicals, may affect this and other neurodevelopmental disorders in a sex-specific manner through ERβ.

  14. Epidermal growth factor receptor: an independent predictor of survival in astrocytic tumors given definitive irradiation

    An Zhu; Shaeffer, James; Leslie, Susan; Kolm, Paul; El-Mahdi, Anas M.

    1996-01-01

    Purpose: To determine whether the expression of epidermal growth factor receptor (EGFR) protein was predictive of patient survival independently of other prognostic factors in astrocytic tumors. Methods and Materials: Epidermal growth factor receptor protein expression was investigated immunohistochemically in formalin-fixed, paraffin-embedded surgical specimens of 55 glioblastoma multiforme, 14 anaplastic astrocytoma, and 2 astrocytomas given definitive irradiation. We evaluated the relationship of EGFR protein expression and tumor grade, histologic features, age at diagnosis, sex, patient survival, and recurrence-free survival. Results: The percentage of tumor cells which were EGFR positive related to reduced survival by Cox regression analysis in both univariate (p = 0.0424) and multivariate analysis (p = 0.0016). Epidermal growth factor receptor positivity was the only 1 of 11 clinical and histological variables associated with decreased recurrence-free survival by either univariate (p = 0.0353) or multivariate (p = 0.0182) analysis. Epidermal growth factor receptor protein expression was not related to patient age, sex, or histologic features. Conclusion: Epidermal growth factor receptor positivity was a significant and independent prognostic indicator for overall survival and recurrence-free survival for irradiated patients with astrocytic gliomas

  15. Inhibition of the release of soluble tumor necrosis factor receptors in experimental endotoxemia by an anti-tumor necrosis factor-alpha antibody

    Jansen, J.; van der Poll, T.; Levi, M. [=Marcel M.; ten Cate, H.; Gallati, H.; ten Cate, J. W.; van Deventer, S. J.

    1995-01-01

    The role of tumor necrosis factor-alpha in the shedding of soluble tumor necrosis factor receptors in endotoxemia was investigated. The appearance of the soluble tumor necrosis factor receptors was assessed in four healthy volunteers following an intravenous injection of tumor necrosis factor-alpha

  16. Male gender preference, female gender disadvantage as risk factors for psychological morbidity in Pakistani women of childbearing age - a life course perspective

    Medhin Girmay

    2011-09-01

    Full Text Available Abstract Background In Pakistan, preference for boys over girls is deeply culturally embedded. From birth, many women experience gendered disadvantages; less access to scarce resources, poorer health care, higher child mortality, limited education, less employment outside of the home and circumscribed autonomy. The prevalence of psychological morbidity is exceptionally high among women. We hypothesise that, among women of childbearing age, gender disadvantage is an independent risk factor for psychological morbidity Methods A cross-sectional catchment area survey of 525 women aged 18 to 35 years living in Islamabad and Rawalpindi. The effect of gender disadvantage was assessed as a latent variable using structural equation modelling. Indicators were parental gender preference, low parental care, parental overprotection, limited education, early age at marriage, marital dissatisfaction and low autonomy. Psychological morbidity was assessed using the 20 item Self Reporting Questionnaire (SRQ. Results Gender disadvantage was independently predictive of psychological morbidity. Among married women, socio-economic status did not predict psychological morbidity, and the effect of education was mediated through gender disadvantage rather than socioeconomic status (SES. The women's own preference for a male child was strongly predicted by their perceptions of having been disadvantaged by their gender in their families of origin. Conclusions The high prevalence of psychological morbidity among women in Pakistan is concerning given recently reported strong associations with low birth weight and infant stunting. Social action, public policies and legislation are indicated to reduce culturally embedded preferences. Neglect of these fundamentals will entrench consequent inequities including gender bias in access to education, a key millennium development goal.

  17. Embryonic expression of the transforming growth factor beta ligand and receptor genes in chicken.

    Cooley, James R; Yatskievych, Tatiana A; Antin, Parker B

    2014-03-01

    Transforming growth factor-beta (TGFβ) signaling regulates a myriad of biological processes during embryogenesis, in the adult, and during the manifestation of disease. TGFβ signaling is propagated through one of three TGFβ ligands interacting with Type I and Type II receptors, and Type III co-receptors. Although TGFβ signaling is regulated partly by the combinatorial expression patterns of TGFβ receptors and ligands, a comprehensive gene expression analysis has not been published. Here we report the embryonic mRNA expression patterns in chicken embryos of the canonical TGFβ ligands (TGFB1, TGFB2, and TGFB3) and receptors (TGFBR1, TGFBR2, TGFBR3), plus the Activin A receptor, type 1 (ACVR1) and co receptor Endoglin (ENG) that also transduce TGFβ signaling. TGFB ligands and receptors show dynamic and frequently overlapping expression patterns in numerous embryonic cell layers and structures. Integrating expression information identifies combinations of ligands and receptors that are involved in specific developmental processes including somitogenesis, cardiogenesis and vasculogenesis. Copyright © 2013 Wiley Periodicals, Inc.

  18. ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2 and TRAF5.

    Hsu, H; Solovyev, I; Colombero, A; Elliott, R; Kelley, M; Boyle, W J

    1997-05-23

    Members of tumor necrosis factor receptor (TNFR) family signal largely through interactions with death domain proteins and TRAF proteins. Here we report the identification of a novel TNFR family member ATAR. Human and mouse ATAR contain 283 and 276 amino acids, respectively, making them the shortest known members of the TNFR superfamily. The receptor is expressed mainly in spleen, thymus, bone marrow, lung, and small intestine. The intracellular domains of human and mouse ATAR share only 25% identity, yet both interact with TRAF5 and TRAF2. This TRAF interaction domain resides at the C-terminal 20 amino acids. Like most other TRAF-interacting receptors, overexpression of ATAR activates the transcription factor NF-kappaB. Co-expression of ATAR with TRAF5, but not TRAF2, results in synergistic activation of NF-kappaB, suggesting potentially different roles for TRAF2 and TRAF5 in post-receptor signaling.

  19. Gender differences in factors influencing alcohol use and drinking progression among adolescents.

    Schulte, Marya T; Ramo, Danielle; Brown, Sandra A

    2009-08-01

    While prevalence rates for alcohol use and related disorders differ widely between adult men and women, male and female adolescents do not exhibit the same disparity in alcohol consumption. Previous research and reviews do not address the emergence of differences in drinking patterns that occur during late adolescence. Therefore, a developmental perspective is presented for understanding how various risk and protective factors associated with problematic drinking affect diverging alcohol trajectories as youth move into young adulthood. This review examines factors associated with risk for developing an alcohol use disorder in adolescent girls and boys separately. Findings indicate that certain biological (i.e., genetic risk, neurological abnormalities associated with P300 amplitudes) and psychosocial (i.e., impact of positive drinking expectancies, personality characteristics, and deviance proneness) factors appear to impact boys and girls similarly. In contrast, physiological and social changes particular to adolescence appear to differentially affect boys and girls as they transition into adulthood. Specifically, boys begin to manifest a constellation of factors that place them at greater risk for disruptive drinking: low response to alcohol, later maturation in brain structures and executive function, greater estimates of perceived peer alcohol use, and socialization into traditional gender roles. On an individual level, interventions which challenge media-driven stereotypes of gender roles while simultaneously reinforcing personal values are suggested as a way to strengthen adolescent autonomy in terms of healthy drinking decisions. Moreover, parents and schools must improve consistency in rules and consequences regarding teen drinking across gender to avoid mixed messages about acceptable alcohol use for boys and girls.

  20. Age, gender and hypertension as major risk factors in development of subclinical atherosclerosis

    Ajla Rahimić Ćatić

    2013-04-01

    Full Text Available Introduction: Intima-media thickness (IMT measurement of the common carotid artery (CCA is considered as useful indicator of carotid atherosclerosis. Early detection of atherosclerosis and its associated risk factors is important to prevent stroke and heart diseases. The aim of the present study was to investigate which risk factors are better determinants of subclinical atherosclerosis, measured by common carotidartery intima media thickness (CCA-IMT.Methods: A total of 74 subjects were randomly selected in this cross – sectional study. Information on the patient’s medical history and laboratory fi ndings were obtained from their clinical records. Risk factors relevant to this study were age, gender, cigarette smoking status, diabetes, hypertension and dyslipidemia. Ultrasound scanning of carotid arteries was performed with a 7,5 MHz linear array transducer (GE Voluson730 pro. The highest value of six common carotid artery measurements was taken as the fi nal IMT. Increased CCA-IMT was defi ned when it was > 1 mm.Results: Our data demonstrated higher CCA-IMT values in male patients compared with female patients. Increased CCA-IMT was the most closely related to age (PConclusion: Age, gender and hypertension are the most important risk factors in development of carotid atherosclerosis. Early detection of atherosclerosis among high-risk populations is important in order to prevent stroke and heart diseases, which are leading causes of death worldwide.

  1. Factors associated with desistence and persistence of childhood gender dysphoria: a quantitative follow-up study.

    Steensma, Thomas D; McGuire, Jenifer K; Kreukels, Baudewijntje P C; Beekman, Anneke J; Cohen-Kettenis, Peggy T

    2013-06-01

    To examine the factors associated with the persistence of childhood gender dysphoria (GD), and to assess the feelings of GD, body image, and sexual orientation in adolescence. The sample consisted of 127 adolescents (79 boys, 48 girls), who were referred for GD in childhood (orientation. We examined contributions of childhood factors on the probability of persistence of GD into adolescence. We found a link between the intensity of GD in childhood and persistence of GD, as well as a higher probability of persistence among natal girls. Psychological functioning and the quality of peer relations did not predict the persistence of childhood GD. Formerly nonsignificant (age at childhood assessment) and unstudied factors (a cognitive and/or affective cross-gender identification and a social role transition) were associated with the persistence of childhood GD, and varied among natal boys and girls. Intensity of early GD appears to be an important predictor of persistence of GD. Clinical recommendations for the support of children with GD may need to be developed independently for natal boys and for girls, as the presentation of boys and girls with GD is different, and different factors are predictive for the persistence of GD. Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  2. Gender differences in metabolic risk factor prevalence in a South African student population.

    Smith, Carine; Essop, M Faadiel

    2009-01-01

    We determined selected risk factors for the metabolic syndrome and assessed the metabolic risk status (using IDF criteria) of third-year physiology students at Stellenbosch University (88 males and 178 females). Outcome measures included anthropometry [body mass index (BMI), waist circumference, waist-to-hip ratio], blood pressure (BP), resting pulse rate, and fasting blood glucose, total cholesterol and triglyceride levels. In addition, students completed a lifestyle questionnaire. A number of gender-based differences were found, with male students displaying a greater incidence of risk factors for the metabolic syndrome: 6% of males versus 3% of females displayed a cluster of three risk factors. Twenty-five per cent of female students (but only 14% of males) exhibited waist circumferences above the accepted range, which was positively correlated, for males and females, with both systolic and diastolic BP, and in females only, also with total cholesterol levels. Male students on average exercised more than their female counterparts, but also exhibited poorer eating habits. Average blood triglyceride levels for both male and female students exceeded the accepted threshold (1.85 +/- 1.62 mmol/l and 2.15 +/- 1.79 mmol/l, respectively). We concluded that metabolic risk factors were evident in a much younger population than commonly expected. Moreover, the gender-specific differences observed may impact on future risk assessment and preventative measures adopted.

  3. The development of epidermal growth factor receptor molecular imaging in cancer

    Zhou Xiaoliang; Wang Hao; Shi Peiji; Liu Jianfeng; Meng Aimin

    2013-01-01

    In vivo epidermal growth factor receptor (EGFR) targeted therapy has great potential for cancer diagnosis and the evaluation of curative effects. Enhancement of EGFR-targeted therapy needs a reliable quantitative molecular imaging method which could enable monitoring of receptor drug binding and receptor occupancy in vivo, and identification of the mutation in EGFR. PET or SPECT is the most advanced molecular imaging technology of non-invasively selecting responders, predicting therapeutic outcome and monitoring EGFR-targeted treatment. This review analyzed the present situation and research progress of molecular imaging agents. (authors)

  4. Male gender and prematurity are risk factors for incarceration in pediatric inguinal hernia: A study of 922 children

    Amine Ksia

    2017-01-01

    Conclusion: IH occurs mainly in male infants. Prematurity and male gender were identified as risk factors of incarceration. Contralateral metachronous hernia was reported, especially in female infants and after a left side surgical repair of the hernia.

  5. Functional and structural stability of the epidermal growth factor receptor in detergent micelles and phospholipid nanodiscs

    Mi, Li-Zhi; Grey, Michael J; Nishida, Noritaka

    2008-01-01

    Cellular signaling mediated by the epidermal growth factor receptor (EGFR or ErbB) family of receptor tyrosine kinases plays an important role in regulating normal and oncogenic cellular physiology. While structures of isolated EGFR extracellular domains and intracellular protein tyrosine kinase...... differential functional stability in Triton X-100 versus dodecyl maltoside. Furthermore, the kinase activity can be significantly stabilized by reconstituting purified EGF-bound EGFR dimers in phospholipid nanodiscs or vesicles, suggesting that the environment around the hydrophobic transmembrane...

  6. Expression of platelet-derived growth factor and its receptors in proliferative disorders of fibroblastic origin.

    Smits, A.; Funa, K.; Vassbotn, F. S.; Beausang-Linder, M.; af Ekenstam, F.; Heldin, C. H.; Westermark, B.; Nistér, M.

    1992-01-01

    Platelet-derived growth factor (PDGF) is known to stimulate the proliferation of connective tissue-derived cells in vitro. Less is known about its functions in vivo, and the role of PDGF in the development of human tumors has not been clarified. The authors have investigated the occurrence of PDGF and PDGF receptors in a series of proliferative disorders of fibroblastic origin using immunohistochemical and in situ hybridization techniques. High expression of PDGF beta-receptor mRNA and protei...

  7. A receptor model for urban aerosols based on oblique factor analysis

    Keiding, Kristian; Sørensen, Morten S.; Pind, Niels

    1987-01-01

    A procedure is outlined for the construction of receptor models of urban aerosols, based on factor analysis. The advantage of the procedure is that the covariation of source impacts is included in the construction of the models. The results are compared with results obtained by other receptor......-modelling procedures. It was found that procedures based on correlating sources were physically sound as well as in mutual agreement. Procedures based on non-correlating sources were found to generate physically obscure models....

  8. Targeting the epidermal growth factor receptor in solid tumor malignancies

    Nedergaard, Mette K; Hedegaard, Chris J; Poulsen, Hans S

    2012-01-01

    been proposed as valid targets in many cancer therapy settings. Different strategies have been developed in order to either inhibit EGFR/EGFRvIII activity or to ablate EGFR/EGFRvIII-positive tumor cells. Drugs that inhibit these receptors include monoclonal antibodies (mAbs) that bind...... to the extracellular part of EGFR, blocking the binding sites for the EGFR ligands, and intracellular tyrosine kinase inhibitors (TKIs) that block the ATP binding site of the tyrosine kinase domain. Besides an EGFRvIII-targeted vaccine, conjugated anti-EGFR mAbs have been used in different settings to deliver lethal...... agents to the EGFR/EGFRvIII-positive cells; among these are radio-labelled mAbs and immunotoxins. This article reviews the current status and efficacy of EGFR/EGFRvIII-targeted therapies....

  9. Mechanisms of integrin-vascular endothelial growth factor receptor cross-activation in angiogenesis.

    Mahabeleshwar, Ganapati H; Feng, Weiyi; Reddy, Kumar; Plow, Edward F; Byzova, Tatiana V

    2007-09-14

    The functional responses of endothelial cells are dependent on signaling from peptide growth factors and the cellular adhesion receptors, integrins. These include cell adhesion, migration, and proliferation, which, in turn, are essential for more complex processes such as formation of the endothelial tube network during angiogenesis. This study identifies the molecular requirements for the cross-activation between beta3 integrin and tyrosine kinase receptor 2 for vascular endothelial growth factor (VEGF) receptor (VEGFR-2) on endothelium. The relationship between VEGFR-2 and beta3 integrin appears to be synergistic, because VEGFR-2 activation induces beta3 integrin tyrosine phosphorylation, which, in turn, is crucial for VEGF-induced tyrosine phosphorylation of VEGFR-2. We demonstrate here that adhesion- and growth factor-induced beta3 integrin tyrosine phosphorylation are directly mediated by c-Src. VEGF-stimulated recruitment and activation of c-Src and subsequent beta3 integrin tyrosine phosphorylation are critical for interaction between VEGFR-2 and beta3 integrin. Moreover, c-Src mediates growth factor-induced beta3 integrin activation, ligand binding, beta3 integrin-dependent cell adhesion, directional migration of endothelial cells, and initiation of angiogenic programming in endothelial cells. Thus, the present study determines the molecular mechanisms and consequences of the synergism between 2 cell surface receptor systems, growth factor receptor and integrins, and opens new avenues for the development of pro- and antiangiogenic strategies.

  10. Interactions between Type III receptor tyrosine phosphatases and growth factor receptor tyrosine kinases regulate tracheal tube formation in Drosophila

    Mili Jeon

    2012-04-01

    The respiratory (tracheal system of the Drosophila melanogaster larva is an intricate branched network of air-filled tubes. Its developmental logic is similar in some ways to that of the vertebrate vascular system. We previously described a unique embryonic tracheal tubulogenesis phenotype caused by loss of both of the Type III receptor tyrosine phosphatases (RPTPs, Ptp4E and Ptp10D. In Ptp4E Ptp10D double mutants, the linear tubes in unicellular and terminal tracheal branches are converted into bubble-like cysts that incorporate apical cell surface markers. This tube geometry phenotype is modulated by changes in the activity or expression of the epidermal growth factor receptor (Egfr tyrosine kinase (TK. Ptp10D physically interacts with Egfr. Here we demonstrate that the Ptp4E Ptp10D phenotype is the consequence of the loss of negative regulation by the RPTPs of three growth factor receptor TKs: Egfr, Breathless and Pvr. Reducing the activity of any of the three kinases by tracheal expression of dominant-negative mutants suppresses cyst formation. By competing dominant-negative and constitutively active kinase mutants against each other, we show that the three RTKs have partially interchangeable activities, so that increasing the activity of one kinase can compensate for the effects of reducing the activity of another. This implies that SH2-domain downstream effectors that are required for the phenotype are likely to be able to interact with phosphotyrosine sites on all three receptor TKs. We also show that the phenotype involves increases in signaling through the MAP kinase and Rho GTPase pathways.

  11. Association of gender disadvantage factors and gender preference with antenatal depression in women: a cross-sectional study from rural Maharashtra.

    Shidhaye, Pallavi; Shidhaye, Rahul; Phalke, Vaishali

    2017-06-01

    Maternal depression is a major public health problem in low- and middle-income countries including India. Very few studies have assessed association of various risk factors with antenatal depression in rural Indian women, especially the effect of marital conflict, gender disadvantage and gender preference on antenatal depression. This paper describes the prevalence of probable antenatal depression in rural Maharashtra, a state in the western part of India and specifically assesses the association of marital and gender disadvantage factors and gender preference for a male child with antenatal depression. Primary Health Centre-based cross-sectional survey of antenatal women in rural Maharashtra was carried out. The outcome of interest was a probable diagnosis of depression in antenatal women which was measured using the Edinburgh postnatal depression scale (EPDS). Data were analyzed using simple and multiple logistic regression. 302 women in their antenatal period were included in this study. The outcome of antenatal depression (EPDS > 12) was found in 51 women (16.9%, 95% CI 12.6-21.1%). Feeling pressurized to deliver a male child was strongly associated with the outcome of antenatal depression (adjusted odds ratio (OR): 3.0; 95% CI 1.4-6.5). Unsatisfactory reaction of in-laws to dowry (adjusted OR 11.2; 95% CI 2.4-52.9) and difficult relationship with in-laws (adjusted OR 5.3; 95% CI 2.4-11.6) were also significantly associated with antenatal depression. Our findings demonstrate that antenatal depression in rural women of Western Maharashtra is associated with gender disadvantage factors, especially related to preference for a male child. The agenda to improve maternal mental health should be ultimately linked to address the broader social development goals and gender empowerment.

  12. Gender and Middle School Science: An Examination of Intrinsic and Extrinsic Factors Affecting Achievement

    Austin, Jennifer

    Gender differences in middle school science were examined utilizing a mixed-methods approach. The intrinsic and extrinsic experiences of male and female non-gifted high-achieving students were investigated through the administration of the CAIMI, student interviews, teacher questionnaires, observations, and document examination. Male and female students were selected from a rural Northeast Georgia school district based on their high performance and high growth during middle school science. Eighty-three percent of the student participants were white and 17% were Hispanic. Half of the male participants and one third of the female participants were eligible for free and reduced meals. Findings revealed that male participants were highly motivated, whereas female participants exhibited varying levels of motivation in science. Both male and female students identified similar instructional strategies as external factors that were beneficial to their success. Due to their selection by both genders, these instructional strategies were considered to be gender-neutral and thereby useful for inclusion within coeducational middle school science classrooms.

  13. Factors related to gender differences in toothbrushing among Lithuanian middle-aged university employees.

    Sakalauskienė, Zana; Vehkalahti, Miira M; Murtomaa, Heikki; Mačiulskienė, Vita

    2011-01-01

    BACKGROUND AND OBJECTIVES. Many previous studies showed clear gender differences in the percentages of adults reporting toothbrushing more than once a day. This study evaluated the factors determining gender differences in toothbrushing among Lithuanian middle-aged university employees. MATERIAL AND METHODS. A questionnaire survey was anonymously conducted among 35- to 44-year-old employees (n=862) of four universities in Lithuania in 2005. The response rate was 64% (n=553). Data covered toothbrushing frequency, habitual dental attendance, dental health attitudes and knowledge, and subject's background information. RESULTS. Of all respondents, 68% reported brushing their teeth more than once a day (73% of women and 49% of men, Pimportant to them and poor oral health as injurious to general health. Of all respondents, 44% indicated that "Lack of time is the main reason for incomplete oral self-care" (61% of men and 40% of women, Pimportance of good dental health to them (OR, 1.6; 95% CI, 1.1-2.4; P=0.02) among women and statement that "Poor oral health can be injurious to general health" (OR, 2.6; 95% CI, 1.2-5.5; P=0.01) and checkup-based habitual dental attendance (OR, 2.4; 95% CI, 1.0-5.9; P=0.06) among men. CONCLUSIONS. Due to different determinants affecting toothbrushing frequency among men and women, different oral health motivation programs by gender should be developed.

  14. Perceived Parental Attitudes of Gender Expansiveness: Development and Preliminary Factor Structure of a Self-Report Youth Questionnaire.

    Hidalgo, Marco A; Chen, Diane; Garofalo, Robert; Forbes, Catherine

    2017-01-01

    Purpose: Parental acceptance of gender identity/expression in lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ+) youth moderates the effects of minority stress on mental health outcomes. Given this association, mental health clinicians of gender-expansive adolescents often assess the degree to which these youth perceive their parents/primary caregivers as accepting or nonaffirming of their gender identity and expression. While existing measures may reliably assess youth's perceptions of general family support, no known tool aids in the assessment an adolescent's perceived parental support related to adolescent gender-expansive experiences. Methods: To provide both clinicians and researchers with an empirically derived tool, the current study used factor analysis to explore an underlying factor structure of a brief questionnaire developed by subject-matter experts and pertaining to multiple aspects of perceived parental support in gender-expansive adolescents and young adults. Respondents were gender-expansive adolescents and young adults seeking care in an interdisciplinary gender-health clinic within a pediatric academic medical center in the Midwestern United States. Results: Exploratory factor analysis resulted in a 14-item questionnaire comprised of two subscales assessing perceived parental nonaffirmation and perceived parental acceptance. Internal consistency and construct validity results provided support for this new questionnaire. Conclusion: This study provides preliminary evidence of the factor structure, reliability and validity of the Parental Attitudes of Gender Expansiveness Scale for Youth (PAGES-Y). These findings demonstrate both the clinical and research utility of the PAGES-Y, a tool that can yield a more nuanced understanding of family-related risk and protective factors in gender-expansive adolescents.

  15. Gender gap on concept inventories in physics: What is consistent, what is inconsistent, and what factors influence the gap?

    Madsen, Adrian; McKagan, Sarah B.; Sayre, Eleanor C.

    2013-12-01

    We review the literature on the gender gap on concept inventories in physics. Across studies of the most commonly used mechanics concept inventories, the Force Concept Inventory and Force and Motion Conceptual Evaluation, men’s average pretest scores are always higher than women’s, and in most cases men’s posttest scores are higher as well. The weighted average gender difference on these tests is 13% for pretest scores, 12% for posttest scores, and 6% for normalized gain. This difference is much smaller than the average difference in normalized gain between traditional lecture and interactive engagement (25%), but it is large enough that it could impact the results of studies comparing the effectiveness of different teaching methods. There is sometimes a gender gap on commonly used electricity and magnetism concept inventories, the Brief Electricity and Magnetism Assessment and Conceptual Survey of Electricity and Magnetism, but it is usually much smaller and sometimes is zero or favors women. The weighted average gender difference on these tests is 3.7% for pretest scores, 8.5% for posttest scores, and 6% for normalized gain. There are far fewer studies of the gender gap on electricity and magnetism concept inventories and much more variation in the existing studies. Based on our analysis of 26 published articles comparing the impact of 30 factors that could potentially influence the gender gap, no single factor is sufficient to explain the gap. Several high-profile studies that have claimed to account for or reduce the gender gap have failed to be replicated in subsequent studies, suggesting that isolated claims of explanations of the gender gap should be interpreted with caution. For example, claims that the gender gap could be eliminated through interactive engagement teaching methods or through a “values affirmation writing exercise” were not supported by subsequent studies. Suggestions that the gender gap might be reduced by changing the wording of

  16. Gender gap on concept inventories in physics: What is consistent, what is inconsistent, and what factors influence the gap?

    Adrian Madsen

    2013-11-01

    Full Text Available We review the literature on the gender gap on concept inventories in physics. Across studies of the most commonly used mechanics concept inventories, the Force Concept Inventory and Force and Motion Conceptual Evaluation, men’s average pretest scores are always higher than women’s, and in most cases men’s posttest scores are higher as well. The weighted average gender difference on these tests is 13% for pretest scores, 12% for posttest scores, and 6% for normalized gain. This difference is much smaller than the average difference in normalized gain between traditional lecture and interactive engagement (25%, but it is large enough that it could impact the results of studies comparing the effectiveness of different teaching methods. There is sometimes a gender gap on commonly used electricity and magnetism concept inventories, the Brief Electricity and Magnetism Assessment and Conceptual Survey of Electricity and Magnetism, but it is usually much smaller and sometimes is zero or favors women. The weighted average gender difference on these tests is 3.7% for pretest scores, 8.5% for posttest scores, and 6% for normalized gain. There are far fewer studies of the gender gap on electricity and magnetism concept inventories and much more variation in the existing studies. Based on our analysis of 26 published articles comparing the impact of 30 factors that could potentially influence the gender gap, no single factor is sufficient to explain the gap. Several high-profile studies that have claimed to account for or reduce the gender gap have failed to be replicated in subsequent studies, suggesting that isolated claims of explanations of the gender gap should be interpreted with caution. For example, claims that the gender gap could be eliminated through interactive engagement teaching methods or through a “values affirmation writing exercise” were not supported by subsequent studies. Suggestions that the gender gap might be reduced by

  17. Measurement Invariance of Second-Order Factor Model of the Multifactor Leadership Questionnaire (MLQ) across K-12 Principal Gender

    Xu, Lihua; Wubbena, Zane; Stewart, Trae

    2016-01-01

    Purpose: The purpose of this paper is to investigate the factor structure and the measurement invariance of the Multifactor Leadership Questionnaire (MLQ) across gender of K-12 school principals (n=6,317) in the USA. Design/methodology/approach: Nine first-order factor models and four second-order factor models were tested using confirmatory…

  18. The aryl hydrocarbon receptor (AHR) transcription factor regulates megakaryocytic polyploidization.

    Lindsey, Stephan; Papoutsakis, Eleftherios T

    2011-02-01

    We propose that the aryl hydrocarbon receptor (AHR) is a novel transcriptional regulator of megakaryopoietic polyploidization. Functional evidence was obtained that AHR impacts in vivo megakaryocytic differentiation and maturation; compared to wild-type mice, AHR-null mice had lower platelet counts, fewer numbers of newly synthesized platelets, increased bleeding times and lower-ploidy megakaryocytes (Mks). AHR mRNA increased 3·6-fold during ex vivo megakaryocytic differentiation, but reduced or remained constant during parallel isogenic granulocytic or erythroid differentiation. We interrogated the role of AHR in megakaryopoiesis using a validated Mk model of megakaryopoiesis, the human megakaryoblastic leukaemia CHRF cell line. Upon CHRF Mk differentiation, AHR mRNA and protein levels increased, AHR protein shifted from the cytoplasm to the nucleus and AHR binding to its consensus DNA binding sequence increased. Protein and mRNA levels of the AHR transcriptional target HES1 also increased. Mk differentiation of CHRF cells where AHR or HES1 was knocked-down using RNAi resulted in lower ploidy distributions and cells that were incapable of reaching ploidy classes ≥16n. AHR knockdown also resulted in increased DNA synthesis of lower ploidy cells, without impacting apoptosis. Together, these data support a role for AHR in Mk polyploidization and in vivo platelet function, and warrant further detailed investigations. © 2011 Blackwell Publishing Ltd.

  19. Internalization mechanisms of the epidermal growth factor receptor after activation with different ligands

    Henriksen, Lasse; Grandal, Michael Vibo; Knudsen, Stine Louise Jeppe

    2013-01-01

    after ligand activation focuses on the effect of epidermal growth factor (EGF) and transforming growth factor-α (TGF-α). For a long time it was believed that clathrin-mediated endocytosis was the major pathway for internalization of the receptor, but recent work suggests that different pathways exist....... Here we show that clathrin ablation completely inhibits internalization of EGF- and TGF-α-stimulated receptor, however the inhibition of receptor internalization in cells treated with heparin-binding EGF-like growth factor (HB-EGF) or betacellulin (BTC) was only partial. In contrast, clathrin knockdown...... fully inhibits EGFR degradation after all ligands tested. Furthermore, inhibition of dynamin function blocked EGFR internalization after stimulation with all ligands. Knocking out a number of clathrin-independent dynamin-dependent pathways of internalization had no effect on the ligand...

  20. Soluble tumor necrosis factor receptor-1 in preterm infants with chronic lung disease.

    Sato, Miho; Mori, Masaaki; Nishimaki, Shigeru; An, Hiromi; Naruto, Takuya; Sugai, Toshiyuki; Shima, Yoshio; Seki, Kazuo; Yokota, Shumpei

    2010-04-01

    It is clear that inflammation plays an important role in developing chronic lung disease in preterm infants. The purpose of the present study is to investigate changes of serum soluble tumor necrosis factor receptor-1 levels over time in infants with chronic lung disease. The serum levels of soluble tumor necrosis factor receptor-1 were measured after delivery, and at 7, 14, 21 and 28 days of age in 10 infants with chronic lung disease and in 18 infants without chronic lung disease. The serum level of soluble tumor necrosis factor receptor-1 was significantly higher in infants with chronic lung disease than in infants without chronic lung disease after delivery. The differences between these two groups remained up to 28 days of age. Prenatal inflammation with persistence into postnatal inflammation may be involved in the onset of chronic lung disease.

  1. Identification of a second putative receptor of platelet activating factor on human polymorphonuclear leukocytes

    Hwang, S.B.

    1987-01-01

    Due to multiple molecular species of platelet activating factor (PAF) and the existence of high affinity binding sites in a variety of cells and tissues, possible existence of PAF receptor subtypes has been suggested. This report shows differences between specific PAF receptors on human leukocytes and platelets. Human PMN leukocyte membranes showed high affinity binding sites for PAF with an equilibrium dissociation constant (Kd) of 4.7 (+/- 1.4) x 10 -10 M. The maximal number (B/sub max/) of receptor sites was estimated to be 3.13 (+/- 1.4) x 10 -13 mol/mg protein. They compared the relative potencies of several PAF agonists and receptor antagonists between human platelet and human leukocyte membranes. One antagonist (Ono-6240) was found to be 8 times less potent at inhibiting the [ 3 H]PAF specific receptor binding to human leukocytes than to human platelets. Mg 2+ , Ca 2+ and K + ions potentiated the [ 3 H]PAF specific binding in both systems. Na + ions inhibited the [ 3 H]PAF specific binding to human platelets but showed no effects in human leukocytes. K + ions decreased the Mg 2+ -potentiated [ 3 H]PAF binding in human leukocytes but showed no effects in human platelets. These results suggest that the PAF specific receptors in human leukocytes are different structurally and possibly functionally from the receptors identified in human platelets

  2. Expression of the epidermal growth factor receptor in human small cell lung cancer cell lines

    Damstrup, L; Rygaard, K; Spang-Thomsen, M

    1992-01-01

    of EGF receptor mRNA in all 10 cell lines that were found to be EGF receptor-positive and in one cell line that was found to be EGF receptor-negative in the radioreceptor assay and affinity labeling. Our results provide, for the first time, evidence that a large proportion of a broad panel of small cell......Epidermal growth factor (EGF) receptor expression was evaluated in a panel of 21 small cell lung cancer cell lines with radioreceptor assay, affinity labeling, and Northern blotting. We found high-affinity receptors to be expressed in 10 cell lines. Scatchard analysis of the binding data...... demonstrated that the cells bound between 3 and 52 fmol/mg protein with a KD ranging from 0.5 x 10(-10) to 2.7 x 10(-10) M. EGF binding to the receptor was confirmed by affinity-labeling EGF to the EGF receptor. The cross-linked complex had a M(r) of 170,000-180,000. Northern blotting showed the expression...

  3. Ric-8A, a Gα protein guanine nucleotide exchange factor potentiates taste receptor signaling

    Claire J Fenech

    2009-10-01

    Full Text Available Taste receptors for sweet, bitter and umami tastants are G-protein coupled receptors (GPCRs. While much effort has been devoted to understanding G-protein-receptor interactions and identifying the components of the signalling cascade downstream of these receptors, at the level of the G-protein the modulation of receptor signal transduction remains relatively unexplored. In this regard a taste-specific regulator of G-protein signaling (RGS, RGS21, has recently been identified. To study whether guanine nucleotide exchange factors (GEFs are involved in the transduction of the signal downstream of the taste GPCRs we investigated the expression of Ric-8A and Ric-8B in mouse taste cells and their interaction with G-protein subunits found in taste buds. Mammalian Ric-8 proteins were initially identified as potent GEFs for a range of Gα subunits and Ric-8B has recently been shown to amplify olfactory signal transduction. We find that both Ric-8A and Ric-8B are expressed in a large portion of taste bud cells and that most of these cells contain IP3R-3 a marker for sweet, umami and bitter taste receptor cells. Ric-8A interacts with Gα-gustducin and Gαi2 through which it amplifies the signal transduction of hTas2R16, a receptor for bitter compounds. Overall, these findings are consistent with a role for Ric-8 in mammalian taste signal transduction.

  4. Direct and Indirect Effects of Five Factor Personality and Gender on Depressive Symptoms Mediated by Perceived Stress.

    Kim, Song E; Kim, Han-Na; Cho, Juhee; Kwon, Min-Jung; Chang, Yoosoo; Ryu, Seungho; Shin, Hocheol; Kim, Hyung-Lae

    2016-01-01

    This study was designed to investigate associations among five factor personality traits, perceived stress, and depressive symptoms and to examine the roles of personality and perceived stress in the relationship between gender and depressive symptoms. The participants (N = 3,950) were part of a cohort study for health screening and examination at the Kangbuk Samsung Hospital. Personality was measured with the Revised NEO Personality Inventory (NEO-PI-R). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Perceived stress level was evaluated with a self-reported stress questionnaire developed for the Korea National Health and Nutrition Examination Survey. A higher degree of neuroticism and lower degrees of extraversion, agreeableness, and conscientiousness were significantly associated with greater perceived stress and depressive symptoms. Neuroticism and extraversion had significant direct and indirect effects (via stress as a mediator) on depressive symptoms in both genders. Agreeableness and conscientiousness had indirect effects on depression symptoms in both genders. Multiple mediation models were used to examine the mediational roles of each personality factor and perceived stress in the link between gender and depressive symptoms. Four of the personality factors (except openness) were significant mediators, along with stress, on the relationship between gender and depressive symptoms. Our findings suggest that the links between personality factors and depressive symptoms are mediated by perceived stress. As such, personality is an important factor to consider when examining the link between gender and depression.

  5. Direct and Indirect Effects of Five Factor Personality and Gender on Depressive Symptoms Mediated by Perceived Stress

    Kim, Song E.; Cho, Juhee; Kwon, Min-Jung; Chang, Yoosoo; Ryu, Seungho; Shin, Hocheol

    2016-01-01

    This study was designed to investigate associations among five factor personality traits, perceived stress, and depressive symptoms and to examine the roles of personality and perceived stress in the relationship between gender and depressive symptoms. The participants (N = 3,950) were part of a cohort study for health screening and examination at the Kangbuk Samsung Hospital. Personality was measured with the Revised NEO Personality Inventory (NEO-PI-R). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Perceived stress level was evaluated with a self-reported stress questionnaire developed for the Korea National Health and Nutrition Examination Survey. A higher degree of neuroticism and lower degrees of extraversion, agreeableness, and conscientiousness were significantly associated with greater perceived stress and depressive symptoms. Neuroticism and extraversion had significant direct and indirect effects (via stress as a mediator) on depressive symptoms in both genders. Agreeableness and conscientiousness had indirect effects on depression symptoms in both genders. Multiple mediation models were used to examine the mediational roles of each personality factor and perceived stress in the link between gender and depressive symptoms. Four of the personality factors (except openness) were significant mediators, along with stress, on the relationship between gender and depressive symptoms. Our findings suggest that the links between personality factors and depressive symptoms are mediated by perceived stress. As such, personality is an important factor to consider when examining the link between gender and depression. PMID:27120051

  6. ErbB2 resembles an autoinhibited invertebrate epidermal growth factor receptor

    Alvarado, Diego; Klein, Daryl E.; Lemmon, Mark A.; (UPENN-MED)

    2009-09-25

    The orphan receptor tyrosine kinase ErbB2 (also known as HER2 or Neu) transforms cells when overexpressed, and it is an important therapeutic target in human cancer. Structural studies have suggested that the oncogenic (and ligand-independent) signalling properties of ErbB2 result from the absence of a key intramolecular 'tether' in the extracellular region that autoinhibits other human ErbB receptors, including the epidermal growth factor (EGF) receptor. Although ErbB2 is unique among the four human ErbB receptors, here we show that it is the closest structural relative of the single EGF receptor family member in Drosophila melanogaster (dEGFR). Genetic and biochemical data show that dEGFR is tightly regulated by growth factor ligands, yet a crystal structure shows that it, too, lacks the intramolecular tether seen in human EGFR, ErbB3 and ErbB4. Instead, a distinct set of autoinhibitory interdomain interactions hold unliganded dEGFR in an inactive state. All of these interactions are maintained (and even extended) in ErbB2, arguing against the suggestion that ErbB2 lacks autoinhibition. We therefore suggest that normal and pathogenic ErbB2 signalling may be regulated by ligands in the same way as dEGFR. Our findings have important implications for ErbB2 regulation in human cancer, and for developing therapeutic approaches that target novel aspects of this orphan receptor.

  7. Peptides derived from specific interaction sites of the fibroblast growth factor 2 - FGF receptor complexes induce receptor activation and signaling

    Manfè, Valentina; Kochoyan, Artur; Bock, Elisabeth

    2010-01-01

    J. Neurochem. (2010) 10.1111/j.1471-4159.2010.06718.x Abstract Basic fibroblast growth factor (FGF2, bFGF) is the most extensively studied member of the FGF family and is involved in neurogenesis, differentiation, neuroprotection, and synaptic plasticity in the CNS. FGF2 executes its pleiotropic...... biologic actions by binding, dimerizing, and activating FGF receptors (FGFRs). The present study reports the physiologic impact of various FGF2-FGFR1 contact sites employing three different synthetic peptides, termed canofins, designed based on structural analysis of the interactions between FGF2 and FGFR1...

  8. Thyroid hormone and retinoic acid nuclear receptors: specific ligand-activated transcription factors

    Brtko, J.

    1998-01-01

    Transcriptional regulation by both the thyroid hormone and the vitamin A-derived 'retinoid hormones' is a critical component in controlling many aspects of higher vertebrate development and metabolism. Their functions are mediated by nuclear receptors, which comprise a large super-family of ligand-inducible transcription factors. Both the thyroid hormone and the retinoids are involved in a complex arrangement of physiological and development responses in many tissues of higher vertebrates. The functions of 3,5,3'-triiodothyronine (T 3 ), the thyromimetically active metabolite of thyroxine as well as all-trans retinoic acid, the biologically active vitamin A metabolite are mediated by nuclear receptor proteins that are members of the steroid/thyroid/retinoid hormone receptor family. The functions of all members of the receptor super family are discussed. (authors)

  9. Factors signifying gender differences in clinical presentation of sarcoidosis among Estonian population.

    Lill, Hille; Kliiman, Kai; Altraja, Alan

    2016-05-01

    Sarcoidosis is endemically prevalent in Northern Europe, but gender differences among the sarcoidosis population have not yet been compositely addressed. To reveal independent factors that formulate gender differences in the presentation of sarcoidosis. All Caucasian patients with confirmed sarcoidosis were recruited from the outpatient department of the Lung Clinic of the Tartu University Hospital, Estonia, between February 2009 and April 2011. Data on demographics, complaints, symptoms, clinical presentation, extrapulmonary manifestations, radiographic stage, lung function parameters and sarcoidosis-related laboratory indices were all drawn from patients' clinical records at presentation. Factors characteristic of female gender were estimated using multivariate logistic regression analysis. Of 230 cases included, there were significantly more females (56.5%, P = 0.005). After adjustment for age, females appeared distinguishable from males by older age [adjusted odds ratio (OR) 1.04, 95% confidence interval (CI) 1.02-1.07], less frequent smoking (OR 0.25, 95% CI 0.13-0.49), higher probability of extrapulmonary complaints (OR 2.06, 95% CI 1.16-3.65) and musculoskeletal sarcoidosis (OR 3.22, 95% CI 1.65-6.29), and after adjustment for both age and smoking status lower forced expiratory volume in 1 s and lung carbon monoxide diffusing coefficient % predicted (OR 0.89, 95% CI 0.82-0.97 and OR 0.98, 95% CI 0.96-0.995, respectively), but by higher forced vital capacity % predicted (OR 1.12, 95% CI 1.03-1.22). Women with sarcoidosis are independently characterized by greater airflow obstruction, lower lung diffusing coefficient, older age, less smoking, and more frequent extrapulmonary complaints and musculoskeletal involvement. This may urge special attention when addressing female patients in both differential diagnostic and management settings. © 2014 John Wiley & Sons Ltd.

  10. Factors associated with gender difference in the intima-media thickness of the common carotid artery

    Tan, T.-Y.; Lu, C.-H.; Lin, T.-K.; Liou, C.-W. [Department of Neurology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Chuang, Y.-C., E-mail: tengyeowtan@yahoo.co [Department of Neurology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Schminke, U. [Department of Neurology, Ernst Moritz Arndt University, Greifswald (Germany)

    2009-11-15

    Aim: To investigate the gender differences associated with a thinner intima-media thickness (IMT) of the common carotid artery (CCA) in women. Materials and methods: In a sample of 218 consecutive healthy volunteers comprising 110 men and 108 women, the IMT of the CCA was measured using B-mode ultrasonography. Blood pressure, fasting blood sugar, body mass index (BMI), blood lipid profile, homocysteine, folic acid, uric acid, high sensitive C-reactive protein, and thiobarbituric acid reactive substances (TBARS) levels were measured and compared with each other in both genders. Results: The IMT of the CCA was significantly thinner in women than in men (p = 0.012). Blood pressure, fasting plasma glucose, BMI, low-density lipoprotein cholesterol, triglycerides, homocysteine, uric acid, and TBARS were significantly (p < 0.05) lower, folic acid and high-density lipoprotein cholesterol (HDL-C) were significantly (p < 0.0001) higher in women compared with men. Multivariable logistic regression analysis revealed that higher serum levels of homocysteine, uric acid, and TBARS, and lower serum levels of HDL-C were significantly (p < 0.05) associated with male sex. Multiple linear regression analysis further revealed that age, sex, and BMI were independently associated with CCA IMT. Conclusions: The IMT of the CCA was thinner in women than in men. Traditional vascular risk factors explain only a small amount of variance in multivariate regression models supporting the hypothesis that other behavioural, sex hormone-related or genetic factors, which have not been sufficiently explored so far, may play a role in the gender differences of IMT.

  11. Factors associated with gender difference in the intima-media thickness of the common carotid artery

    Tan, T.-Y.; Lu, C.-H.; Lin, T.-K.; Liou, C.-W.; Chuang, Y.-C.; Schminke, U.

    2009-01-01

    Aim: To investigate the gender differences associated with a thinner intima-media thickness (IMT) of the common carotid artery (CCA) in women. Materials and methods: In a sample of 218 consecutive healthy volunteers comprising 110 men and 108 women, the IMT of the CCA was measured using B-mode ultrasonography. Blood pressure, fasting blood sugar, body mass index (BMI), blood lipid profile, homocysteine, folic acid, uric acid, high sensitive C-reactive protein, and thiobarbituric acid reactive substances (TBARS) levels were measured and compared with each other in both genders. Results: The IMT of the CCA was significantly thinner in women than in men (p = 0.012). Blood pressure, fasting plasma glucose, BMI, low-density lipoprotein cholesterol, triglycerides, homocysteine, uric acid, and TBARS were significantly (p < 0.05) lower, folic acid and high-density lipoprotein cholesterol (HDL-C) were significantly (p < 0.0001) higher in women compared with men. Multivariable logistic regression analysis revealed that higher serum levels of homocysteine, uric acid, and TBARS, and lower serum levels of HDL-C were significantly (p < 0.05) associated with male sex. Multiple linear regression analysis further revealed that age, sex, and BMI were independently associated with CCA IMT. Conclusions: The IMT of the CCA was thinner in women than in men. Traditional vascular risk factors explain only a small amount of variance in multivariate regression models supporting the hypothesis that other behavioural, sex hormone-related or genetic factors, which have not been sufficiently explored so far, may play a role in the gender differences of IMT.

  12. Gender differences in factors influencing insulin resistance in elderly hyperlipemic non-diabetic subjects

    Hrebícek Jirí

    2002-10-01

    Full Text Available Abstract Background The increase in the prevalence of insulin resistance-related metabolic syndrome, a disorder that greatly increases the risk of diabetes, heart attack and stroke, is alarming. One of the most frequent and early symptoms of metabolic syndrome is hypertriglyceridemia. We examined the gender differences between various metabolic factors related to insulin resistance in elderly non-diabetic men and postmenopausal women of comparable age suffering from hypertriglyceridemia, and compared them with healthy subjects of equal age. Results The indexes of insulin resistance HOMA IR and QUICKI were significantly higher in both hyperlipemic men and women than in controls; 95% confidence limits of hyperlipemic subjects did not overlap with controls. In both normolipemic and hyperlipemic men and women serum leptin correlated significantly with insulin resistance, while HDL-cholesterol correlated inversely with HOMA-IR only in women (both normo- and hyperlipemic, and serum tumor necrosis factor α (TNFα only in hyperlipemic women. According to results of multiple regression analysis with HOMA-IR as a dependent variable, leptin played a significant role in determining insulin resistance in both genders, but – aside from leptin – triglycerides, TNFα and decreased HDL-cholesterol were significant determinants in women, while body mass index and decreased HDL-cholesterol were significant determinants in men. The coefficient of determination (R2 of HOMA IR by above mentioned metabolic variables was in women above 60%, in men only about 40%. Conclusion The significant role of serum leptin in determination of insulin resistance in both elderly men and postmenopausal women of equal age was confirmed. However, the study also revealed significant gender differences : in women a strong influence of triglycerides, TNFα and decreased HDL-cholesterol, in men only a mild role of BMI and decreased HDL-cholesterol.

  13. Inactivation of the transforming growth factor beta type II receptor in human small cell lung cancer cell lines

    Hougaard, S; Nørgaard, P; Abrahamsen, N

    1999-01-01

    Transforming growth factor beta (TGF-beta) exerts a growth inhibitory effect on many cell types through binding to two types of receptors, the type I and II receptors. Resistance to TGF-beta due to lack of type II receptor (RII) has been described in some cancer types including small cell lung...

  14. Exploring risk factors in Latino cardiovascular disease: the role of education, nativity, and gender.

    Dinwiddie, Gniesha Y; Zambrana, Ruth E; Garza, Mary A

    2014-09-01

    We examined 3 cardiovascular disease risk factors by nativity and gender, evaluating evidence for education and health behaviors in explaining the "Hispanic Health Paradox." We analyzed 2001-2008 National Health and Nutrition Examination Survey data for adults (n = 6032) to compare hypertension, high waist circumference, and diabetes for US- and foreign-born Mexican men and women. We controlled for age, depression, and health insurance. Cardiovascular disease risk factors differed by education, nativity, and gender. Higher education was associated with higher odds of hypertension and high waist circumference for men and women regardless of nativity. As education increased, the odds of diabetes increased for US-born women, showing a gradient for this population. Finally, foreign-born Mexican women with 5 to 19 years in the United States conferred the highest odds of having diabetes, whereas foreign-born men with less than 5 years in the United States had the lowest odds for high waist circumference and presence of diabetes. Results contest assumptions of the Hispanic Health Paradox and suggest new approaches. New research can yield accurate information to ensure the development of appropriate interventions, decreasing health disparities endemic to a subgroup of Latinos.

  15. Resiliency as a factor protecting youths from risky behaviour: Moderating effects of gender and sport.

    Lipowski, Mariusz; Lipowska, Małgorzata; Jochimek, Magdalena; Krokosz, Daniel

    2016-01-01

    We hypothesised that resiliency may protect adolescents against risky behaviours, and that both the practicing of sports, and gender are moderating variables in relationships between resiliency and risky behaviours. The study included 18-year-old pupils from a selection of secondary schools (n = 556). A total of 188 individuals practiced competitive sports and the remaining 368 participants were non-athletes. The participants were examined with the Resiliency Assessment Scale for Children and Adolescents (SPP-18) and with a survey containing questions and statements related to high-risk "experiments with adulthood". Adolescent athletes showed higher levels of resiliency than their peers. The power of the "Determination and Persistence in Action" effect on "Alcohol" scale differed significantly between male athletes and male non-athletes. Only in the athletes groups were higher scores on this scale reflected by lower values on the "Drugs" scale. Moreover, it is possible to observe differences in undertaking risky behaviour between male and female athletes. The analysis of risky sexual behaviour suggests that sport is a risk factor for men, and a protective factor for women. These data suggest that consistent prophylactic and psycho-educative activities, with a special attention to differences between genders, should be provided to all the adolescents, irrespective of their sport performance levels.

  16. Gender-specific hierarchy in nuage localization of PIWI-interacting RNA factors in Drosophila

    Mikiko C Siomi

    2011-08-01

    Full Text Available PIWI-interacting RNAs (piRNAs are germline-specific small non-coding RNAs that form piRNA-induced silencing complexes (piRISCs by associating with PIWI proteins, a subclade of the Argonaute proteins predominantly expressed in the germline. piRISCs protect the integrity of the germline genome from invasive transposable DNA elements by silencing them. Multiple piRNA biogenesis factors have been identified in Drosophila. The majority of piRNA factors are localized in the nuage, electron-dense non-membranous cytoplasmic structures located in the perinuclear regions of germ cells. Thus, piRNA biogenesis is thought to occur in the nuage in germ cells. Immunofluorescence analyses of ovaries from piRNA factor mutants have revealed a localization hierarchy of piRNA factors in female nuage. However, whether this hierarchy is female-specific or can also be applied in male gonads remains undetermined. Here, we show by immunostaining of both ovaries and testes from piRNA factor mutants that the molecular hierarchy of piRNA factors shows gender-specificity, especially for Krimper (Krimp, a Tudor-domain containing protein of unknown function(s: Krimp is dispensable for PIWI protein Aubergine (Aub nuage localization in ovaries but Krimp and Aub require each other for their proper nuage localization in testes. This suggests that the functional requirement of Krimp in piRNA biogenesis may be different in male and female gonads.

  17. Gender Differences in Pay

    Francine D. Blau; Lawrence M. Kahn

    2000-01-01

    We consider the gender pay gap in the United States. Both gender-specific factors, including gender differences in qualifications and discrimination, and overall wage structure, the rewards for skills and employment in particular sectors, importantly influence the gender pay gap. Declining gender differentials in the U.S., and the more rapid closing of the gender pay gap in the U.S. than elsewhere, appear to be primarily due to gender-specific factors. However, the relatively large gender pay...

  18. Type-I Insulin-Like Growth Factor Receptor (IGF1R)-Estrogen Receptor (ER) Crosstalk Contributes to Antiestrogen Therapy Resistance in Breast Cancer Cells

    2013-02-01

    vitro have downregulated J GF1R making antibodies directed agai nst th is receptor ineffective. Inhlbition of IH may be necessary to manage ...monoclonal antibody to insulin-like growth factor receptor 1. J Clin Oncol 2009;27:580Q-7. 31. Drury s. Detre s. Leary A, Salter J, Reis-Filho J

  19. Up-regulation of proproliferative genes and the ligand/receptor pair placental growth factor and vascular endothelial growth factor receptor 1 in hepatitis C cirrhosis.

    Huang, Xiao X; McCaughan, Geoffrey W; Shackel, Nicholas A; Gorrell, Mark D

    2007-09-01

    Cirrhosis can lead to hepatocellular carcinoma (HCC). Non-diseased liver and hepatitis C virus (HCV)-associated cirrhosis with or without HCC were compared. Proliferation pathway genes, immune response genes and oncogenes were analysed by a quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and immunostaining. Real-time RT-PCR showed up-regulation of genes in HCV cirrhosis including the proliferation-associated genes bone morphogenetic protein 3 (BMP3), placental growth factor 3 (PGF3), vascular endothelial growth factor receptor 1 (VEGFR1) and soluble VEGFR1, the oncogene FYN, and the immune response-associated genes toll-like receptor 9 (TLR9) and natural killer cell transcript 4 (NK4). Expressions of TLR2 and the oncogenes B-cell CLL/lymphoma 9 (BCL9) and PIM2 were decreased in HCV cirrhosis. In addition, PIM2 and TLR2 were increased in HCV cirrhosis with HCC compared with HCV cirrhosis. The ligand/receptor pair PGF and VEGFR1 was intensely expressed by the portal tract vascular endothelium. VEGFR1 was expressed in reactive biliary epithelial structures in fibrotic septum and in some stellate cells and macrophages. PGF and VEGFR1 may have an important role in the pathogenesis of the neovascular response in cirrhosis.

  20. Age, gender and hypertension as major risk factors in development of subclinical atherosclerosis

    Ajla Rahimić Ćatić

    2013-04-01

    Full Text Available Introduction: Intima-media thickness (IMT measurement of the common carotid artery (CCA is considered as useful indicator of carotid atherosclerosis. Early detection of atherosclerosis and its associated risk factors is important to prevent stroke and heart diseases. The aim of the present study was to investigate which risk factors are better determinants of subclinical atherosclerosis, measured by common carotidartery intima media thickness (CCA-IMT.Methods: A total of 74 subjects were randomly selected in this cross – sectional study. Information on the patient’s medical history and laboratory fi ndings were obtained from their clinical records. Risk factors relevant to this study were age, gender, cigarette smoking status, diabetes, hypertension and dyslipidemia. Ultrasound scanning of carotid arteries was performed with a 7,5 MHz linear array transducer (GE Voluson730 pro. The highest value of six common carotid artery measurements was taken as the fi nal IMT. Increased CCA-IMT was defi ned when it was > 1 mm.Results: Our data demonstrated higher CCA-IMT values in male patients compared with female patients. Increased CCA-IMT was the most closely related to age (P<0.001, followed by systolic blood pressure (P=0.001, diastolic blood pressure (P=0.003 and glucose blood level (P=0.048.Conclusion: Age, gender and hypertension are the most important risk factors in development of carotid atherosclerosis. Early detection of atherosclerosis among high-risk populations is important in order to prevent stroke and heart diseases, which are leading causes of death worldwide.

  1. Characterization of receptors for recombinant human tumor necrosis factor-alpha from human placental membranes

    Aiyer, R.A.; Aggarwal, B.B.

    1990-01-01

    High affinity receptors for recombinant human tumor necrosis factor-alpha (rhTNF-alpha) were identified on membranes prepared from full term human placenta. Highly purified rhTNF-alpha iodinated by the iodogen method was found to bind placental membranes in a displaceable manner with an approximate dissociation constant (KD) of 1.9 nM. The membrane bound TNF-alpha receptor could be solubilized by several detergents with optimum extraction being obtained with 1% Triton X-100. The binding of 125I-rhTNF-alpha to the solubilized receptor was found to be time and temperature dependent, yielding maximum binding within 1 h, 24 h and 48 h at 37 degrees C, 24 degrees C and 4 degrees C, respectively. However, the maximum binding obtainable at 4 degrees C was only 40% of that at 37 degrees C. The binding 125I-rhTNF-alpha to solubilized placental membrane extracts was displaceable by unlabeled rhTNF-alpha, but not by a related protein recombinant human tumor necrosis factor-beta (rhTNF-beta; previously called lymphotoxin). This is similar to the behavior of TNF-alpha receptors derived from detergent-solubilized cell extracts, although on intact cells, both rhTNF-alpha and rhTNF-beta bind with equal affinity to TNF receptors. The Scatchard analysis of the binding data of the solubilized receptor revealed high affinity binding sites with a KD of approximately 0.5 nM and a receptor concentration of about 1 pmole/mg protein. Gel filtration of the solubilized receptor-ligand complexes on Sephacryl S-300 revealed two different peaks of radioactivity at approximate molecular masses of 50,000 Da and 400,000 Da. The 400,000 dalton peak corresponded to the receptor-ligand complex. Overall, our results suggest that high affinity receptors for TNF-alpha are present on human placental membranes and provide evidence that these receptors may be different from that of rhTNF-beta

  2. Gender differences in the factors predicting initial engagement at cardiac rehabilitation.

    Galdas, Paul Michael; Harrison, Alexander Stephen; Doherty, Patrick

    2018-01-01

    To determine whether there are gender differences in the factors that predict attendance at the initial cardiac rehabilitation baseline assessment (CR engagement) after referral. Using data from the National Audit of Cardiac Rehabilitation, we analysed data on 95 638 patients referred to CR following a cardiovascular diagnosis/treatment between 2013 and 2016. Eighteen factors that have been shown in previous research to be important predictors of CR participation were investigated and grouped into four categories: sociodemographic factors, cardiac risk factors, patient medical status and service-level factors. Logistic binary regression models were built for male patients and female patients, assessing the likelihood for CR engagement. Each included predictors such as age, number of comorbidities and social deprivation score. There were no important differences in the factors that predict the likelihood of CR engagement in men and women. Seven factors associated with a reduced probability of CR engagement, and eight factors associated with increased probability, were identified. Fourteen of the 15 factors identified as predicting the likelihood for engagement/non-engagement were the same for both men and women. Increasing age, being South Asian or non-white ethnicity (other than Black) and being single were all associated with a reduced likelihood of attending an initial CR baseline assessment in both men and women. Male patients with diabetes were 11% less likely to engage with CR; however, there was no significant association in women. Results showed that the overwhelmingly important determinant of CR engagement observed in both men and women was receiving an invitation to attend an assessment session (OR 4.223 men/4.033women; pgender differences in predictors of CR uptake should probably be more nuanced and informed by the stage of the patient care pathway.

  3. Factors that affect college students' perceptions of rape: what is the role of gender and other situational factors?

    Vandiver, Donna M; Dupalo, Jessica Rager

    2013-05-01

    Prior research has shown that various situational factors and behaviors can affect one's perception of whether a rape has occurred. Moreover, some hold false beliefs about rape. This can also affect one's perception of ambiguous situations. This study included the administration of a survey to 584 college students; the survey examined the prevalence of rape myths and responses to vignettes of potential rape scenarios. It was found that although the majority of this sample did not support rape myths, male students were significantly more likely than female students to support rape myths. Furthermore, approximately 20% of students did support one subscale of the rape myth scale: He didn't mean to [commit rape]. The results also revealed an interaction effect between the observer's sex and the victim's sex, suggesting a complex gender relationship.

  4. Insulin-like growth factor-II (IGF II) receptor from rat brain is of lower apparent molecular weight than the IGF II receptor from rat liver

    McElduff, A.; Poronnik, P.; Baxter, R.C.

    1987-01-01

    The binding subunits of the insulin and insulin-like growth factor-I (IGF I) receptors from rat brain are of lower molecular weight than the corresponding receptor in rat liver, possibly due to variations in sialic acid content. We have compared the IGF II receptor from rat brain and rat liver. The brain receptor is of smaller apparent mol wt (about 10 K) on sodium dodecyl sulfate polyacrylamide gel electrophoresis. This size difference is independent of ligand binding as it persists in iodinated and specifically immunoprecipitated receptors. From studies of wheat germ agglutinin binding and the effect of neuraminidase on receptor mobility, we conclude that this difference is not simply due to variations in sialic acid content. Treatment with endoglycosidase F results in reduction in the molecular size of both liver and brain receptors and after this treatment the aglycoreceptors are of similar size. We conclude that in rat brain tissue the IGF II receptor like the binding subunits of the insulin and IGF I receptors is of lower molecular size than the corresponding receptors in rat liver. This difference is due to differences in N-linked glycosylation

  5. Self-phosphorylation of epidermal growth factor receptor: evidence for a model of intermolecular allosteric activation

    Yarden, Y.; Schlessinger, J.

    1987-01-01

    The membrane receptor for epidermal growth factor (EGF) is a 170,000 dalton glycoprotein composed of an extracellular EGF-binding domain and a cytoplasmic kinase domain connected by a stretch of 23 amino acids traversing the plasma membrane. The binding of EGF to the extracellular domain activates the cytoplasmic kinase function even in highly purified preparations of EGF receptor, suggesting that the activation occurs exclusively within the EGF receptor moiety. Conceivably, kinase activation may require the transfer of a conformational change through the single transmembrane region from the ligand binding domain to the cytoplasmic kinase region. Alternatively, ligand-induced receptor-receptor interactions may activate the kinase and thus bypass this requirement. Both mechanisms were contrasted by employing independent experimental approaches. On the basis of these results, an allosteric aggregation model is formulated for the activation of the cytoplasmic kinase function of the receptor by EGF. This model may be relevant to the mechanism by which the mitogenic signal of EGF is transferred across the membrane

  6. Sperm Impairment by Sperm Agglutinating Factor Isolated from Escherichia coli: Receptor Specific Interactions

    Kiranjeet Kaur

    2013-01-01

    Full Text Available In an earlier work done in our laboratory, we have been able to isolate a sperm agglutinating strain of Escherichia coli from the semen sample of a male attending infertility clinic. Further, factor responsible for sperm agglutination (SAF was isolated and purified, and, using SAF as a tool, corresponding SAF binding receptor from human spermatozoa has been purified. Characterization of SAF and SAF binding receptor using MALDI-TOF showed homology to glutamate decarboxylase and MHC class I molecule, respectively. Coincubation of SAF with spermatozoa not only resulted in spermagglutination but could also compromise other sperm parameters, namely, Mg2+ dependent ATPase activity and apoptosis. Intravaginal administration of SAF could lead to infertility in Balb/c mice. SAF induced impairment of sperm parameters, and infertility was observed to be due to interaction of SAF with sperm surface receptor component as, when purified receptor was introduced, receptor completely inhibited all the detrimental effects induced by SAF. From these results, it could be concluded that interaction of SAF with spermatozoa is receptor mediated.

  7. The under-appreciated promiscuity of the epidermal growth factor receptor family.

    Sean P Kennedy

    2016-08-01

    Full Text Available Each member of the epidermal growth factor receptor (EGFR family plays a key role in normal development, homeostasis and a variety of pathophysiological conditions, most notably in cancer. According to the prevailing dogma, these four receptor tyrosine kinases (RTKs; EGFR, ERBB2, ERBB3 and ERBB4 function exclusively through the formation of homodimers and heterodimers within the EGFR family. These combinatorial receptor interactions are known to generate increased interactome diversity and therefore influence signalling output, subcellular localization and function of the heterodimer. This molecular plasticity is also thought to play a role in the development of resistance towards targeted cancer therapies aimed at these known oncogenes. Interestingly, many studies now challenge this dogma and suggest that the potential for EGFR family receptors to interact with more distantly related RTKs is much greater than currently appreciated. Here we discuss how the promiscuity of these oncogenic receptors may lead to the formation of many unexpected receptor pairings and the significant implications for the efficiency of many targeted cancer therapies.

  8. Association of nerve growth factor receptors with the triton X-100 cytoskeleton of PC12 cells

    Vale, R.D.; Ignatius, M.J.; Shooter, E.M.

    1985-01-01

    Triton X-100 solubilizes membranes of PC12 cells and leaves behind a nucleus and an array of cytoskeletal filaments. Nerve growth factor (NGF) receptors are associated with this Triton X-100-insoluble residue. Two classes of NGF receptors are found on PC12 cells which display rapid and slow dissociating kinetics. Although rapidly dissociating binding is predominant (greater than 75%) in intact cells, the majority of binding to the Triton X-100 cytoskeleton is slowly dissociating (greater than 75%). Rapidly dissociating NGF binding on intact cells can be converted to a slowly dissociating form by the plant lectin wheat germ agglutinin (WGA). This lectin also increases the number of receptors which associate with the Triton X-100 cytoskeleton by more than 10-fold. 125 I-NGF bound to receptors can be visualized by light microscopy autoradiography in Triton X-100-insoluble residues of cell bodies, as well as growth cones and neurites. The WGA-induced association with the cytoskeleton, however, is not specific for the NGF receptor. Concentrations of WGA which change the Triton X-100 solubility of membrane glycoproteins are similar to those required to alter the kinetic state of the NGF receptor. Both events may be related to the crossbridging of cell surface proteins induced by this multivalent lectin

  9. Design and Synthesis of Benzimidazoles As Novel Corticotropin-Releasing Factor 1 Receptor Antagonists.

    Mochizuki, Michiyo; Kori, Masakuni; Kobayashi, Katsumi; Yano, Takahiko; Sako, Yuu; Tanaka, Maiko; Kanzaki, Naoyuki; Gyorkos, Albert C; Corrette, Christopher P; Cho, Suk Young; Pratt, Scott A; Aso, Kazuyoshi

    2016-03-24

    Benzazole derivatives with a flexible aryl group bonded through a one-atom linker as a new scaffold for a corticotropin-releasing factor 1 (CRF1) receptor antagonist were designed, synthesized, and evaluated. We expected that structural diversity could be expanded beyond that of reported CRF1 receptor antagonists. In a structure-activity relationship study, 4-chloro-N(2)-(4-chloro-2-methoxy-6-methylphenyl)-1-methyl-N(7),N(7)-dipropyl-1H-benzimidazole-2,7-diamine 29g had the most potent binding activity against a human CRF1 receptor and the antagonistic activity (IC50 = 9.5 and 88 nM, respectively) without concerns regarding cytotoxicity at 30 μM. Potent CRF1 receptor-binding activity in brain in an ex vivo test and suppression of stress-induced activation of the hypothalamus-pituitary-adrenocortical (HPA) axis were also observed at 138 μmol/kg of compound 29g after oral administration in mice. Thus, the newly designed benzimidazole 29g showed in vivo CRF1 receptor antagonistic activity and good brain penetration, indicating that it is a promising lead for CRF1 receptor antagonist drug discovery research.

  10. Characterization of cell-surface receptors for monoclonal-nonspecific suppressor factor (MNSF)

    Nakamura, M.; Ogawa, H.; Tsunematsu, T.

    1990-01-01

    Monoclonal-nonspecific suppressor factor (MNSF) is a lymphokine derived from murine T cell hybridoma. The target tissues are both LPS-stimulated B cells and Con A-stimulated T cells. Since the action of MNSF may be mediated by its binding to specific cell surface receptors, we characterized the mode of this binding. The purified MNSF was labeled with 125 I, using the Bolton-Hunter reagent. The labeled MNSF bound specifically to a single class of receptor (300 receptors per cell) on mitogen-stimulated murine B cells or T cells with an affinity of 16 pM at 24 degrees C, in the presence of sodium azide. Competitive experiments showed that MNSF bound to the specific receptor and that the binding was not shared with IL2, IFN-gamma, and TNF. Various cell types were surveyed for the capacity to specifically bind 125 I-MNSF. 125 I-MNSF bound to MOPC-31C (a murine plasmacytoma line) and to EL4 (a murine T lymphoma line). The presence of specific binding correlates with the capacity of the cells to respond to MNSF. These data support the view that like other polypeptide hormones, the action of MNSF is mediated by specific cell surface membrane receptor protein. Identification of these receptors will provide insight into the apparently diverse activities of MNSF

  11. Soluble receptors for tumor necrosis factor as markers of disease activity in visceral leishmaniasis

    Zijlstra, E. E.; van der Poll, T.; Mevissen, M.

    1995-01-01

    Serum concentrations of soluble receptors for tumor necrosis factor (sTNFRs) were measured before and after antimony therapy in 25 Sudanese patients with active visceral leishmaniasis (VL). Both sTNFR types I and II were significantly elevated in patients with VL compared with healthy controls from

  12. Brain-derived neurotrophic factor in human subjects with function-altering melanocortin-4 receptor variants

    In rodents, hypothalamic brain-derived neurotrophic factor (BDNF) expression appears to be regulated by melanocortin-4 receptor (MC4R) activity. The impact of MC4R genetic variation on circulating BDNF in humans is unknown. The objective of this study is to compare BDNF concentrations of subjects wi...

  13. Changes in epidermal growth factor receptor expression during chemotherapy in non-small cell lung cancer

    Jakobsen, Jan Nyrop; Santoni-Rugiu, Eric; Sørensen, Jens Benn

    2014-01-01

    BACKGROUND: Antibodies targeting epidermal growth factor receptor (EGFR), such as cetuximab, may potentially improve outcome in non-small cell lung cancer (NSCLC) patients with high EGFR expression. The EGFR expression may be heterogeneously distributed within tumors, and small biopsies may thus...

  14. Amplification of epidermal growth factor receptor gene in renal cell carcinoma

    El-Hariry, Iman; Powles, Thomas; Lau, Mike R

    2010-01-01

    Expression of epidermal growth factor receptor (EGFR) may be of prognostic value in renal cell cancer (RCC). Gene amplification of EGFR was investigated in a cohort of 315 patients with advanced RCC from a previously reported randomised study. Using fluorescent in situ hybridisation, only 2...

  15. Localization and functional roles of corticotropin-releasing factor receptor type 2 in the cerebellum

    Gounko, Natalia V.; Gramsbergen, Albert; van der Want, Johannes J. L.

    The corticotropin-releasing factor (CRF) type 2 receptor has three splice variants alpha, beta, and gamma. In the rodent brain only CRF-R2 alpha is present. In the cerebellum, CRF-R2 alpha has two different isoforms: a full-length form (fl) and truncated (tr). Both forms CRF-R2 have a unique

  16. Orphan nuclear receptor TR4 and fibroblast growth factor 1 in metabolism

    Liu, Weilin

    2016-01-01

    Metabolic homeostasis is achieved, in part, through the coordinated activities of members of the Nuclear Receptor (NR) family, a superfamily of ligand-modulated transcription factors (TFs) that mediate responses to a wide range of lipophilic signaling molecules including lipids, steroids, retinoids,

  17. Cell-Cell Adhesion and Insulin-Like Growth Factor I Receptor in Breast Cancer

    Bartucci, Monica

    2001-01-01

    .... Our goal was to study the role of the insulin-like growth factor I receptor (IGF-IR) in breast cancer. The IGF-IR is a multifunctional tyrosine kinase that has been recently implicated in breast tumor development and progression...

  18. Palliation of bone cancer pain by antagonists of platelet-activating factor receptors.

    Katsuya Morita

    Full Text Available Bone cancer pain is the most severe among cancer pain and is often resistant to current analgesics. Thus, the development of novel analgesics effective at treating bone cancer pain are desired. Platelet-activating factor (PAF receptor antagonists were recently demonstrated to have effective pain relieving effects on neuropathic pain in several animal models. The present study examined the pain relieving effect of PAF receptor antagonists on bone cancer pain using the femur bone cancer (FBC model in mice. Animals were injected with osteolytic NCTC2472 cells into the tibia, and subsequently the effects of PAF receptor antagonists on pain behaviors were evaluated. Chemical structurally different type of antagonists, TCV-309, BN 50739 and WEB 2086 ameliorated the allodynia and improved pain behaviors such as guarding behavior and limb-use abnormalities in FBC model mice. The pain relieving effects of these antagonists were achieved with low doses and were long lasting. Blockade of spinal PAF receptors by intrathecal injection of TCV-309 and WEB 2086 or knockdown of the expression of spinal PAF receptor protein by intrathecal transfer of PAF receptor siRNA also produced a pain relieving effect. The amount of an inducible PAF synthesis enzyme, lysophosphatidylcholine acyltransferase 2 (LPCAT2 protein significantly increased in the spinal cord after transplantation of NCTC 2472 tumor cells into mouse tibia. The combination of morphine with PAF receptor antagonists develops marked enhancement of the analgesic effect against bone cancer pain without affecting morphine-induced constipation. Repeated administration of TCV-309 suppressed the appearance of pain behaviors and prolonged survival of FBC mice. The present results suggest that PAF receptor antagonists in combination with, or without, opioids may represent a new strategy for the treatment of persistent bone cancer pain and improve the quality of life of patients.

  19. Neomycin is a platelet-derived growth factor (PDGF) antagonist that allows discrimination of PDGF alpha- and beta-receptor signals in cells expressing both receptor types.

    Vassbotn, F S; Ostman, A; Siegbahn, A; Holmsen, H; Heldin, C H

    1992-08-05

    The aminoglycoside neomycin has recently been found to affect certain platelet-derived growth factor (PDGF) responses in C3H/10T1/2 C18 fibroblasts. Using porcine aortic endothelial cells transfected with PDGF alpha- or beta-receptors, we explored the possibility that neomycin interferes with the interaction between the different PDGF isoforms and their receptors. We found that neomycin (5 mM) inhibited the binding of 125I-PDGF-BB to the alpha-receptor with only partial effect on the binding of 125I-PDGF-AA; in contrast, the binding of 125I-PDGF-BB to the beta-receptor was not affected by the aminoglycoside. Scatchard analyses showed that neomycin (5 mM) decreased the number of binding sites for PDGF-BB on alpha-receptor-expressing cells by 87%. Together with cross-competition studies with 125I-labeled PDGF homodimers, the effect of neomycin indicates that PDGF-AA and PDGF-BB bind to both common and unique structures on the PDGF alpha-receptor. Neomycin specifically inhibited the autophosphorylation of the alpha-receptor by PDGF-BB, with less effect on the phosphorylation induced by PDGF-AA and no effect on the phosphorylation of the beta-receptor by PDGF-BB. Thus, neomycin is a PDGF isoform- and receptor-specific antagonist that provides a possibility to compare the signal transduction pathways of alpha- and beta-receptors in cells expressing both receptor types. This approach was used to show that activation of PDGF beta-receptors by PDGF-BB mediated a chemotactic response in human fibroblasts, whereas activation of alpha-receptors by the same ligand inhibited chemotaxis.

  20. Gender is a risk factor in patients with gastroesophageal reflux disease.

    Fakhre Yaseri, Hashem

    2017-01-01

    Background: Prevalence of gastroesophageal reflux disease (GERD) has increased in the last decades, and it is now one of the most common chronic and recurrent diseases. The present study aimed at determining the frequency of gender (sex) and age in Iranian patients with GERD symptoms. Methods: In this study, 803 patients aged 11 to 84 years, with erosive and nonerosive gastroesophageal reflux diseases, based on the questionnaire and esophagogastroduodenoscopy findings, participated. The female group was compared with the male group with respect to age, symptoms, esophageal injury, and hiatus hernia. Results: Of the 803 participants, 60.5% (n= 486) were female, and 69.2% (n= 555) were younger than 50 years. Of those patients older than 50 years, 32.8% (n= 81) were female. Moreover, 31.0% (n= 249) of the patients had erosive esophagitis (ERD), and 69.0% (n= 254) had normal esophageal mucosa (NERD).The female to male ratio was 1/1.06 and 1.94/1 in ERD and NERD patients, respectively. Hiatal hernia was more prevalent in females than in males. Conclusion: Nonerosive reflux disease, as a gastroesophageal reflux disease (GERD), was more common in females than in males. GERD became more prevalent with increase in age. Gender and hiatal hernias were 2 potential risk factors of GERD.

  1. Problematic Internet Use in University Students: associated factors and differences of gender.

    Fernández-Villa, Tania; Alguacil Ojeda, Juan; Almaraz Gómez, Ana; Cancela Carral, José María; Delgado-Rodríguez, Miguel; García-Martín, Miguel; Jiménez-Mejías, Eladio; Llorca, Javier; Molina, Antonio José; Ortíz Moncada, Rocío; Valero-Juan, Luiz Félix; Martín, Vicente

    2015-12-15

    The aim of this paper is to make a descriptive analysis of Problematic Internet Use in college students, evaluating the possible association with health problems and addictive behaviors, as well as gender differences in user types. A total of 2,780 students participated in the study between 2011 and 2014, 29% of them being males (age 20.8 ± 5.1 years) and 71% females (age 20.3 ± 4.4 years). The prevalence of Problematic Internet Use (PIU) assessed by the Internet Addiction Test was 6.08%. Being under 21 years of age and studying for degrees in subjects other than the health sciences were associated factors with a higher frequency of this problem, no differences by gender or type of address were found. The results show a significant association with some health problems (migraines, back pain, excess weight or obesity, insufficient rest), psychological aspects (risk of eating disorders, risk of mental disorder, depression), family problems and discrimination; with no associations with substance use (alcohol, cannabis or tobacco) being found. Concerning the time of Internet use, weekly hours were significantly higher in women than in men, both the total time as for leisure. The analysis of the profile use in problematic users revealed that males are related to aspects of entertainment such as games or shopping online and females are related to aspects of socialization, such as chats and social networks.

  2. Non-medical opioid use in youth: Gender differences in risk factors and prevalence.

    Osborne, Vicki; Serdarevic, Mirsada; Crooke, Hannah; Striley, Catherine; Cottler, Linda B

    2017-09-01

    Non-medical use (NMU) of prescription opioids in youth is of concern since they may continue this pattern into adulthood and become addicted or divert medications to others. Research into risk factors for NMU can help target interventions to prevent non-medical use of opioids in youth. The National Monitoring of Adolescent Prescription Stimulants Study (N-MAPSS) was conducted from 2008 to 2011. Participants 10-18years of age were recruited from entertainment venues in urban, rural and suburban areas of 10 US cities. Participants completed a survey including questions on their use of prescription opioids. NMU was defined as a non-labeled route of administration or using someone else's prescription. Information on age, gender, alcohol, marijuana and tobacco use was also collected. Summary descriptive, chi-square statistics and logistic regression were conducted using SAS 9.4. Of the 10,965 youth who provided information about past 30day prescription opioid use, prevalence of reported opioid use was 4.8% with 3.2% reported as NMU (n=345) and 1.6% as medical use (MU) only (n=180). More males than females (55.7% vs. 44.4%) reported opioid NMU (pgender differences in opioid NMU is needed; interventions for opioid NMU may need to be gender specific to obtain the best results. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Moroccans in Spain: an analysis by gender of the determinant factors on family migration

    Carolina Montoro-Gurich

    2018-02-01

    Full Text Available This work analyses the most influential factors over the migratory calendar of Moroccan married people moving to Spain from the gender-related perspective. It uses data coming from an ethnographic survey (=262 individuals applied in 2013 to Moroccan population in Navarre. Logistic regression models are estimated to forecast which variables have more influence on the accelerated family reunification of such individuals. Results show that in both models, male and female, the most relevant determinant is the fact about if women do work in the same year of the reunification, followed by the time interval between the reunification and year 2008. Moreover, in the male model, the opinion of men about female occupation outside the home is very important, while in the female one there are remarkable variables related to social capital such as: spouse’s age, having small children and being the head of householdor not. The conclusion is that early family reunification in Moroccans reveals a reality wich is conditioned both by economic motivations and gender differences.

  4. Indigenous food security revival strategies at the village level: The gender factor implications

    Wilfred Lunga

    2016-01-01

    Full Text Available This article is based on an evaluation concerning the practice of the Zunde raMambo concept (commonly referred to as Zunde in four of Zimbabwe’s 52 districts; (Mangwe, Lupane, Guruve and Hwedza. Zunde is a social security system providing protection against food shortages to vulnerable families and is coordinated by chiefs. The Zunde concept identifies with Ndebele and Shona rural communities in Zimbabwe. Thus, this evaluation sought to determine the relevance and fulfilment of the Zunde project objectives, namely: efficiency, effectiveness, impact and sustainability. The revived Zunde practice extends a long way in reducing food insecurity in vulnerable communities. Although the concept may be as old as the Zimbabwean culture, it had been abandoned as communities became urbanised. The Chief’s Council of Zimbabwe, in collaboration with the Nutrition Unit of the Ministry of Health and Child Welfare have rekindled it. However, to revive this indigenous knowledge practice, there is need to assess the nature of existing social and economic structures, leadership, gender roles and the availability of resources such as land, inputs and implements. This article, which is based on both qualitative and quantitative data, collected between September 2013 and March 2014, goes on to reflect on policy issues surrounding disaster risk reduction (DRR and survival strategies used by vulnerable communities in rural areas of Zimbabwe. It recommends that the gender factor approach offers the best means possible to understand peoples’ needs and challenges as well as how these can be satisfied and resolved respectively.

  5. Gender and other factors associated with the use of hearing protection devices at work

    Tatiane Costa Meira

    2015-01-01

    Full Text Available OBJECTIVE To analyze whether sociodemographic, occupational, and health-related data are associated with the use of hearing protection devices at work, according to gender.METHODS A cross-sectional study was conducted in 2006, using a random sample of 2,429 workers, aged between 18 and 65 years old, from residential sub-areas in Salvador, BA, Northeastern Brazil. Questionnaires were used to obtain sociodemographic, occupational, and health-related data. Workers who reported that they worked in places where they needed to shout in order to be heard were considered to be exposed to noise. Exposed workers were asked whether they used hearing protection devices, and if so, how frequently. Analyses were conducted according to gender, with estimates made about prevalence of the use of hearing protection devices, prevalence ratios, and their respective 95% confidence intervals.RESULTS Twelve percent (12.3% of study subjects reported that they were exposed to noise while working. Prevalence of the use of hearing protection devices was 59.3% for men and 21.4% for women. Men from higher socioeconomic levels (PR = 1.47; 95%CI 1.14;1.90 and who had previous audiometric tests (PR = 1.47; 95%CI 1.15;1.88 were more likely to use hearing protection devices. For women, greater perceived safety was associated with the use of protection devices (PR = 2.92; 95%CI 1.34;6.34. This perception was specifically related to the presence of supervisors committed to safety (PR = 2.09; 95%CI 1.04;4.21, the existence of clear rules to prevent workplace injuries (PR = 2.81; 95%CI 1.41;5.59, and whether they were informed about workplace safety (PR = 2.42; 95%CI 1.23;4.76.CONCLUSIONS There is a gender bias regarding the use of hearing protection devices that is less favorable to women. The use of such devices among women is positively influenced by their perception of a safe workplace, suggesting that gender should be considered as a factor in hearing conservation programs.

  6. Linking γ-aminobutyric acid A receptor to epidermal growth factor receptor pathways activation in human prostate cancer.

    Wu, Weijuan; Yang, Qing; Fung, Kar-Ming; Humphreys, Mitchell R; Brame, Lacy S; Cao, Amy; Fang, Yu-Ting; Shih, Pin-Tsen; Kropp, Bradley P; Lin, Hsueh-Kung

    2014-03-05

    Neuroendocrine (NE) differentiation has been attributed to the progression of castration-resistant prostate cancer (CRPC). Growth factor pathways including the epidermal growth factor receptor (EGFR) signaling have been implicated in the development of NE features and progression to a castration-resistant phenotype. However, upstream molecules that regulate the growth factor pathway remain largely unknown. Using androgen-insensitive bone metastasis PC-3 cells and androgen-sensitive lymph node metastasis LNCaP cells derived from human prostate cancer (PCa) patients, we demonstrated that γ-aminobutyric acid A receptor (GABA(A)R) ligand (GABA) and agonist (isoguvacine) stimulate cell proliferation, enhance EGF family members expression, and activate EGFR and a downstream signaling molecule, Src, in both PC-3 and LNCaP cells. Inclusion of a GABA(A)R antagonist, picrotoxin, or an EGFR tyrosine kinase inhibitor, Gefitinib (ZD1839 or Iressa), blocked isoguvacine and GABA-stimulated cell growth, trans-phospohorylation of EGFR, and tyrosyl phosphorylation of Src in both PCa cell lines. Spatial distributions of GABAAR α₁ and phosphorylated Src (Tyr416) were studied in human prostate tissues by immunohistochemistry. In contrast to extremely low or absence of GABA(A)R α₁-positive immunoreactivity in normal prostate epithelium, elevated GABA(A)R α₁ immunoreactivity was detected in prostate carcinomatous glands. Similarly, immunoreactivity of phospho-Src (Tyr416) was specifically localized and limited to the nucleoli of all invasive prostate carcinoma cells, but negative in normal tissues. Strong GABAAR α₁ immunoreactivity was spatially adjacent to the neoplastic glands where strong phospho-Src (Tyr416)-positive immunoreactivity was demonstrated, but not in adjacent to normal glands. These results suggest that the GABA signaling is linked to the EGFR pathway and may work through autocrine or paracine mechanism to promote CRPC progression. Copyright © 2013 Elsevier

  7. Are new medical students' specialty preferences gendered? Related motivational factors at a Dutch medical school.

    Tongeren-Alers, M.L.G. van; Esch, M. van der; Verdonk, P.; Johansson, E.; Hamberg, K.; Lagro-Janssen, T.

    2011-01-01

    BACKGROUND: Female students currently outnumber male students in most medical schools. Some medical specialties are highly gender segregated. Therefore, it is interesting to know whether medical students have early specialization preferences based on their gender. Consequently, we like to know

  8. Wnt signalling via the epidermal growth factor receptor: a role in breast cancer?

    Musgrove, Elizabeth A

    2004-01-01

    Recent data have suggested the epidermal-growth-factor receptor (EGFR) as a point of convergence for several different classes of receptor. Civenni and colleagues have now demonstrated crosstalk between Wnt signalling and the EGFR, showing that in breast epithelial cells Wnts activate downstream targets of the EGFR, including cyclin D1. Given the role of members of these pathways in the aetiology of breast cancer and as markers of outcome and potential therapeutic targets in breast cancer, this observation has a number of potential implications important for both the basic biology of breast cancer and the clinical management of the disease

  9. Emotional intelligence, personality, and gender as factors in disordered eating patterns.

    Zysberg, Leehu

    2014-08-01

    We examined the hypotheses that proposing higher levels of emotional intelligence (ability test and self-report) and lower neuroticism, extraversion, and agreeableness associate with lower levels of disordered eating. In a correlational study, 126 Israeli college students completed two measures of emotional intelligence, a brief five-factor personality test, demographic data questionnaires, and questionnaires assessing food preoccupation, namely, the Body Weight, Image and Self-Esteem Scale and the Appearance Schema Inventory. Results suggested that ability emotional intelligence is associated with disordered eating beyond gender and personality. Self-reported emotional intelligence did not associate with any of the outcomes after controlling for personality. Implications and applications are briefly discussed. © The Author(s) 2013.

  10. Gender Role and Social Identifications: The Two Major Factors to Shape Turkish Women

    Erden-Imamoglu, Seval

    2013-01-01

    The process of being a woman starts with biological gender but it is shaped by learning the social gender roles. Besides social gender role; age, education, marriage, and motherhood supply social roles and attributions and they have an impact on women identification and their interpersonal relationships. The aim of the study is to investigate…

  11. Two signaling molecules share a phosphotyrosine-containing binding site in the platelet-derived growth factor receptor.

    Nishimura, R; Li, W; Kashishian, A; Mondino, A; Zhou, M; Cooper, J; Schlessinger, J

    1993-11-01

    Autophosphorylation sites of growth factor receptors with tyrosine kinase activity function as specific binding sites for Src homology 2 (SH2) domains of signaling molecules. This interaction appears to be a crucial step in a mechanism by which receptor tyrosine kinases relay signals to downstream signaling pathways. Nck is a widely expressed protein consisting exclusively of SH2 and SH3 domains, the overexpression of which causes cell transformation. It has been shown that various growth factors stimulate the phosphorylation of Nck and its association with autophosphorylated growth factor receptors. A panel of platelet-derived growth factor (PDGF) receptor mutations at tyrosine residues has been used to identify the Nck binding site. Here we show that mutation at Tyr-751 of the PDGF beta-receptor eliminates Nck binding both in vitro and in living cells. Moreover, the Y751F PDGF receptor mutant failed to mediate PDGF-stimulated phosphorylation of Nck in intact cells. A phosphorylated Tyr-751 is also required for binding of phosphatidylinositol-3 kinase to the PDGF receptor. Hence, the SH2 domains of p85 and Nck share a binding site in the PDGF receptor. Competition experiments with different phosphopeptides derived from the PDGF receptor suggest that binding of Nck and p85 is influenced by different residues around Tyr-751. Thus, a single tyrosine autophosphorylation site is able to link the PDGF receptor to two distinct SH2 domain-containing signaling molecules.

  12. Characterization of a receptor for human monocyte-derived neutrophil chemotactic factor/interleukin-8

    Grob, P.M.; David, E.; Warren, T.C.; DeLeon, R.P.; Farina, P.R.; Homon, C.A.

    1990-01-01

    Monocyte-derived neutrophil chemotactic factor/interleukin-8 (MDNCF/IL-8) is an 8,000-dalton protein produced by monocytes which exhibits activity as a chemoattractant for neutrophils with maximal activity achieved at a concentration of 50 ng/ml. This polypeptide has been iodinated by chloramine-T methodology (350 Ci/mM), and specific receptors for MDNCF/IL-8 have been detected on human neutrophils, U937 cells, THP-1 cells, and dimethyl sulfoxide-differentiated HL-60 cells. The binding of MDNCF/IL-8 to human neutrophils is not inhibited by interleukin-1 alpha, tumor necrosis factor-alpha, insulin, or epidermal growth factor. In addition, chemoattractants such as C5a, fMet-Leu-Phe, leukotriene B4, and platelet-activating factor fail to inhibit binding, suggesting that MDNCF/IL-8 utilizes a unique receptor. The receptor for MDNCF/IL-8 is apparently glycosylated since ligand binding is inhibited by the presence of wheat germ agglutinin, a lectin with a binding specificity for N-acetylglucosamine and neuraminic acid. Steady state binding experiments indicate Kd values of 4 and 0.5 nM and receptor numbers of 75,000 and 7,400 for human neutrophils and differentiated HL-60 cells, respectively. 125I-MDNCF/IL-8 bound to human neutrophils is rapidly internalized and subsequently released from cells as trichloroacetic acid-soluble radioactivity. Affinity labeling experiments suggest that the human neutrophil MDNCF/IL-8 receptor exhibits a mass of approximately 58,000 daltons

  13. Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes

    Andersen, Christian Brix Folsted; Madsen, Mette; Storm, Tina

    2010-01-01

    Cobalamin (Cbl, vitamin B(12)) is a bacterial organic compound and an essential coenzyme in mammals, which take it up from the diet. This occurs by the combined action of the gastric intrinsic factor (IF) and the ileal endocytic cubam receptor formed by the 460-kilodalton (kDa) protein cubilin...... and the 45-kDa transmembrane protein amnionless. Loss of function of any of these proteins ultimately leads to Cbl deficiency in man. Here we present the crystal structure of the complex between IF-Cbl and the cubilin IF-Cbl-binding-region (CUB(5-8)) determined at 3.3 A resolution. The structure provides...... of how Cbl indirectly induces ligand-receptor coupling. Finally, the comparison of Ca(2+)-binding CUB domains and the low-density lipoprotein (LDL) receptor-type A modules suggests that the electrostatic pairing of a basic ligand arginine/lysine residue with Ca(2+)-coordinating acidic aspartates...

  14. FTZ-Factor1 and Fushi tarazu interact via conserved nuclear receptor and coactivator motifs

    Schwartz, Carol J.E.; Sampson, Heidi M.; Hlousek, Daniela; Percival-Smith, Anthony; Copeland, John W.R.; Simmonds, Andrew J.; Krause, Henry M.

    2001-01-01

    To activate transcription, most nuclear receptor proteins require coactivators that bind to their ligand-binding domains (LBDs). The Drosophila FTZ-Factor1 (FTZ-F1) protein is a conserved member of the nuclear receptor superfamily, but was previously thought to lack an AF2 motif, a motif that is required for ligand and coactivator binding. Here we show that FTZ-F1 does have an AF2 motif and that it is required to bind a coactivator, the homeodomain-containing protein Fushi tarazu (FTZ). We also show that FTZ contains an AF2-interacting nuclear receptor box, the first to be found in a homeodomain protein. Both interaction motifs are shown to be necessary for physical interactions in vitro and for functional interactions in developing embryos. These unexpected findings have important implications for the conserved homologs of the two proteins. PMID:11157757

  15. Characterization of the epidermal growth factor receptor associated with cytoskeletons of A431 cells

    Roy, L.M.; Gittinger, C.K.; Landreth, G.E.

    1989-01-01

    Epidermal growth factor receptors (EGF-R) have been shown to be associated with the detergent-insoluble cytoskeleton of A431 cells, where they retained both a functional ligand-binding domain and tyrosine kinase activity. In the present study we have characterized the tyrosine kinase and ligand binding activities of this cytoskeletally associated EGF-R. The tyrosine kinase activity of the cytoskeletally associated EGF-R was stimulated by EGF treatment of intact cells as evidenced by increased autophosphorylation and phosphorylation of the exogenous substrate angiotensin II (AII). The kinetic behavior of the EGF-R associated with cytoskeletons of EGF-treated cells was similar to that of purified receptors. The stimulation of the receptor kinase activity required EGF treatment of intact cells prior to Triton extraction. If cytoskeletons were prepared from untreated cells and then incubated with EGF, there was no stimulation of the detergent-insoluble receptor kinase activity, indicating that the immobilized receptor was unable to undergo EGF-stimulated activation. Comparison of peptide maps from soluble and cytoskeletally associated EGF-R revealed qualitatively similar patterns; however, they are distinguished by a prominent 46 kD band in digests of the cytoskeletal EGF-R. Saturable binding of 125I-EGF to A431 cytoskeletons prepared from adherent and suspended cells demonstrated the presence of specific receptors on the cytoskeleton. High-affinity EGF-R were preferentially retained upon detergent extraction of adherent cells, whereas both low- and high-affinity receptors were solubilized from the cytoskeletons of suspended cells. Suspension of cells resulted in the solubilization of an additional 15% of the EGF-R to that solubilized in adherent cells, indicating that EGF-R can reversibly associate with the structural elements of the cell

  16. Expression of platelet-derived growth factor and its receptors in proliferative disorders of fibroblastic origin.

    Smits, A; Funa, K; Vassbotn, F S; Beausang-Linder, M; af Ekenstam, F; Heldin, C H; Westermark, B; Nistér, M

    1992-03-01

    Platelet-derived growth factor (PDGF) is known to stimulate the proliferation of connective tissue-derived cells in vitro. Less is known about its functions in vivo, and the role of PDGF in the development of human tumors has not been clarified. The authors have investigated the occurrence of PDGF and PDGF receptors in a series of proliferative disorders of fibroblastic origin using immunohistochemical and in situ hybridization techniques. High expression of PDGF beta-receptor mRNA and protein was found in the malignant tumors, and also in some benign lesions, such as dermatofibroma. In all these cases, benign as well as malignant, the PDGF B-chain mRNA, and less clearly, the PDGF A-chain mRNA, were coexpressed with the beta-receptor. In contrast, high expression of PDGF alpha-receptor mRNA was only found in fully malignant lesions, i.e., malignant fibrous histiocytoma. These data indicate that an autocrine growth stimulation via the PDGF beta-receptor could occur in an early phase of tumorigenesis, and may be a necessary but insufficient event for the progression into fully malignant human connective tissue lesions.

  17. A Plant Immune Receptor Detects Pathogen Effectors that Target WRKY Transcription Factors.

    Sarris, Panagiotis F; Duxbury, Zane; Huh, Sung Un; Ma, Yan; Segonzac, Cécile; Sklenar, Jan; Derbyshire, Paul; Cevik, Volkan; Rallapalli, Ghanasyam; Saucet, Simon B; Wirthmueller, Lennart; Menke, Frank L H; Sohn, Kee Hoon; Jones, Jonathan D G

    2015-05-21

    Defense against pathogens in multicellular eukaryotes depends on intracellular immune receptors, yet surveillance by these receptors is poorly understood. Several plant nucleotide-binding, leucine-rich repeat (NB-LRR) immune receptors carry fusions with other protein domains. The Arabidopsis RRS1-R NB-LRR protein carries a C-terminal WRKY DNA binding domain and forms a receptor complex with RPS4, another NB-LRR protein. This complex detects the bacterial effectors AvrRps4 or PopP2 and then activates defense. Both bacterial proteins interact with the RRS1 WRKY domain, and PopP2 acetylates lysines to block DNA binding. PopP2 and AvrRps4 interact with other WRKY domain-containing proteins, suggesting these effectors interfere with WRKY transcription factor-dependent defense, and RPS4/RRS1 has integrated a "decoy" domain that enables detection of effectors that target WRKY proteins. We propose that NB-LRR receptor pairs, one member of which carries an additional protein domain, enable perception of pathogen effectors whose function is to target that domain. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Insulin-like growth factor II: complexity of biosynthesis and receptor binding

    Gammeltoft, S; Christiansen, Jan; Nielsen, F C

    1991-01-01

    Insulin-like growth factor II (IGF-II) belongs to the insulin family of peptides and acts as a growth factor in many fetal tissues and tumors. The gene expression of IGF-II is initiated at three different promoters which gives rise to multiple transcripts. In a human rhabdomyosarcoma cell line......, Man-6-P induces cellular responses. We have studied rat brain neuronal precursor cells where Man-6-P acted as a mitogen suggesting that phosphomannosylated proteins may act as growth factors via the Man-6-P/IGF-II receptor. In conclusion, the gene expression and mechanism of action of IGF-II is very...

  19. Role of tissue factor and protease-activated receptors in a mouse model of endotoxemia.

    Pawlinski, Rafal; Pedersen, Brian; Schabbauer, Gernot; Tencati, Michael; Holscher, Todd; Boisvert, William; Andrade-Gordon, Patricia; Frank, Rolf Dario; Mackman, Nigel

    2004-02-15

    Sepsis is associated with a systemic activation of coagulation and an excessive inflammatory response. Anticoagulants have been shown to inhibit both coagulation and inflammation in sepsis. In this study, we used both genetic and pharmacologic approaches to analyze the role of tissue factor and protease-activated receptors in coagulation and inflammation in a mouse endotoxemia model. We used mice expressing low levels of the procoagulant molecule, tissue factor (TF), to analyze the effects of TF deficiency either in all tissues or selectively in hematopoietic cells. Low TF mice had reduced coagulation, inflammation, and mortality compared with control mice. Similarly, a deficiency of TF expression by hematopoietic cells reduced lipopolysaccharide (LPS)-induced coagulation, inflammation, and mortality. Inhibition of the down-stream coagulation protease, thrombin, reduced fibrin deposition and prolonged survival without affecting inflammation. Deficiency of either protease activated receptor-1 (PAR-1) or protease activated receptor-2 (PAR-2) alone did not affect inflammation or survival. However, a combination of thrombin inhibition and PAR-2 deficiency reduced inflammation and mortality. These data demonstrate that hematopoietic cells are the major pathologic site of TF expression during endotoxemia and suggest that multiple protease-activated receptors mediate crosstalk between coagulation and inflammation.

  20. Emerging growth factor receptor antagonists for the treatment of renal cell carcinoma.

    Zahoor, Haris; Rini, Brian I

    2016-12-01

    The landscape of systemic treatment for metastatic renal cell carcinoma (RCC) has dramatically changed with the introduction of targeted agents including vascular endothelial growth factor (VEGF) inhibitors. Recently, multiple new agents including growth factor receptor antagonists and a checkpoint inhibitor were approved for the treatment of refractory metastatic RCC based on encouraging benefit shown in clinical trials. Areas covered: The background and biological rationale of existing treatment options including a brief discussion of clinical trials which led to their approval, is presented. This is followed by reviewing the limitations of these therapeutic options, medical need to develop new treatments and major goals of ongoing research. We then discuss two recently approved growth factor receptor antagonists i.e. cabozantinib and lenvatinib, and a recently approved checkpoint inhibitor, nivolumab, and issues pertaining to drug development, and future directions in treatment of metastatic RCC. Expert opinion: Recently approved growth factor receptor antagonists have shown encouraging survival benefit but associated drug toxicity is a major issue. Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, has similarly shown survival benefit and is well tolerated. With multiple options now available in this patient population, the right sequence of these agents remains to be determined.

  1. Gender perspective on the factors predicting recycling behavior: Implications from the theory of planned behavior.

    Oztekin, Ceren; Teksöz, Gaye; Pamuk, Savas; Sahin, Elvan; Kilic, Dilek Sultan

    2017-04-01

    This study aimed to assess the role of some socio-psychological attributes in explaining recycling behavior of Turkish university community from a gender perspective within the context of the theory of planned behavior with an additional variable (past experience). The recycling behavior of whole sample, females and males, has been examined in 3 sessions -depending on the arguments that explain gendered pattern of private and public environmental behavior and sticking to the fact why females' stronger environmental values, beliefs, and attitudes do not translate consistently into greater engagement in public behavior. As a result of model runs, different variables shaping intention for behavior have been found, namely perceived behavior control for females and past behavior for males. Due to the low percent of the variance in explaining recycling behavior of females, they have been identified as the ones who do not carry out intentions (non-recyclers). Since intentions alone are capable of identifying recyclers accurately but not non-recyclers, there may be other factors to be considered to understand the reason for females not carrying out the intentions. The results of descriptive statistics supported the identification by attitudes toward recycling. Female attitudes were innate (recycling is good, necessary, useful and sensitive), whereas those of males were learnt (recycling is healthy, valuable and correct). Thus, it has been concluded that males' intention for recycling is shaped by their past behavior and the conclusion is supported by males having learnt attitude toward recycling whereas females' lack of intention for recycling is shaped by their perceived behavior control and is supported by their innate attitude for recycling. All in all, the results of the present study provide further support for the utility of the TPB as a model of behavioral prediction and concur with other studies examining the utility of the TPB in the context of recycling

  2. Cognitive disorder and changes in cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury

    Weiliang Zhao; Dezhi Kang; Yuanxiang Lin

    2008-01-01

    BACKGROUND: Learning and memory damage is one of the most permanent and the severest symptoms of traumatic brain injury; it can seriously influence the normal life and work of patients. Some research has demonstrated that cognitive disorder is closely related to nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor. OBJECTIVE: To summarize the cognitive disorder and changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury. RETRIEVAL STRATEGY: A computer-based online search was conducted in PUBMED for English language publications containing the key words "brain injured, cognitive handicap, acetylcholine, N-methyl-D aspartate receptors, neural cell adhesion molecule, brain-derived neurotrophic factor" from January 2000 to December 2007. There were 44 papers in total. Inclusion criteria: ① articles about changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury; ② articles in the same researching circle published in authoritative journals or recently published. Exclusion criteria: duplicated articles.LITERATURE EVALUATION: References were mainly derived from research on changes in these four factors following brain injury. The 20 included papers were clinical or basic experimental studies. DATA SYNTHESIS: After craniocerebral injury, changes in these four factors in brain were similar to those during recovery from cognitive disorder, to a certain degree. Some data have indicated that activation of nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor could greatly improve cognitive disorder following brain injury. However, there are still a lot of questions remaining; for example, how do these

  3. Gender and age effects on risk factor-based prediction of coronary artery calcium in symptomatic patients

    Nicoll, R; Wiklund, U; Zhao, Y

    2016-01-01

    BACKGROUND AND AIMS: The influence of gender and age on risk factor prediction of coronary artery calcification (CAC) in symptomatic patients is unclear. METHODS: From the European Calcific Coronary Artery Disease (EURO-CCAD) cohort, we retrospectively investigated 6309 symptomatic patients, 62......, diabetes and smoking were independently predictive of CAC presence in both genders. In addition to a progressive increase in CAC with age, the most important predictors of CAC presence were dyslipidaemia and diabetes (β = 0.64 and 0.63, respectively) in males and diabetes (β = 1.08) followed by smoking (β...... = 0.68) in females; these same risk factors were also important in predicting increasing CAC scores. There was no difference in the predictive ability of diabetes, hypertension and dyslipidaemia in either gender for CAC presence in patients aged 70, only...

  4. Co-occurring eating and psychiatric symptoms in Taiwanese college students: effects of gender and parental factors.

    Tseng, Mei-Chih Meg; Gau, Susan Shur-Fen; Tseng, Wan-Ling; Hwu, Hai-Gwo; Lee, Ming-Been

    2014-03-01

    To test whether gender and parental factors moderate the relationships between symptoms of eating disorder (ED) and other psychiatric symptoms. A total of 5,015 new entrants completed several questionnaires and 541 individuals with ED symptoms were identified by the Adult Self-Report Inventory-4 that assessed a wide range of Diagnostic and Statistical Manual of Mental Disorders Fourth Edition psychopathology. The participants also reported on their parents' attitude toward them before their ages of 16. ED symptoms, female gender, less parental care, and more parental protection were associated with more severe co-occurring psychiatric symptoms. Gender and parental factors also demonstrated differential moderating effects on the relationships between ED and co-occurring psychiatric symptoms. Parenting counseling may be individualized to young adults with ED symptoms and different co-occurring psychiatric symptoms. © 2013 Wiley Periodicals, Inc.

  5. Gender issues in malaysian education: Factors influencing male and female students’ academic achievement through cognitive processes in public examinations

    Suppiah Nachiappan

    2013-07-01

    Full Text Available Gender issues in the field of education has been a continuos debated issue for generations. In the present context, the gender issue is being debated heatedly based on the differences in the achievements among male and female students in public exams.The objective of this study is to obtain views from (N=120 secondary school students randomly selected from various location in Malaysia. Hermeneutic analysis was used in order to analyse the students’ written essays on the factors which contributed to the achievement of the two genders in examinations. The findings of the study clearly indicated that female students outperform male students in examinations. The sample also summed up the factors leading to the failure of male students in performing well and ways to overcome this setback.

  6. Cloning and expression of a cDNA coding for the human platelet-derived growth factor receptor: Evidence for more than one receptor class

    Gronwald, R.G.K.; Grant, F.J.; Haldeman, B.A.; Hart, C.E.; O'Hara, P.J.; Hagen, F.S.; Ross, R.; Bowen-Pope, D.F.; Murray, M.J.

    1988-01-01

    The complete nucleotide sequence of a cDNA encoding the human platelet-derived growth factor (PDGF) receptor is presented. The cDNA contains an open reading frame that codes for a protein of 1106 amino acids. Comparison to the mouse PDGF receptor reveals an overall amino acid sequence identity of 86%. This sequence identity rises to 98% in the cytoplasmic split tyrosine kinase domain. RNA blot hybridization analysis of poly(A) + RNA from human dermal fibroblasts detects a major and a minor transcript using the cDNA as a probe. Baby hamster kidney cells, transfected with an expression vector containing the receptor cDNA, express an ∼ 190-kDa cell surface protein that is recognized by an anti-human PDGF receptor antibody. The recombinant PDGF receptor is functional in the transfected baby hamster kidney cells as demonstrated by ligand-induced phosphorylation of the receptor. Binding properties of the recombinant PDGF receptor were also assessed with pure preparations of BB and AB isoforms of PDGF. Unlike human dermal fibroblasts, which bind both isoforms with high affinity, the transfected baby hamster kidney cells bind only the BB isoform of PDGF with high affinity. This observation is consistent with the existence of more than one PDGF receptor class

  7. RECREATIONAL TENDENCIES AND THE FACTORS PREVENTING UNIVERSITY STUDENTS PARTICIPATING TO RECREATIONAL ACTIVITES ACCORDING TO GENDER

    Yaşar ÇORUH

    2014-07-01

    Full Text Available The purpose of the study of university students according to gender; recreational activity participation trends and participation in these events in the factors which may impede the examination of population of the study, Agri Ibrahim Chechen University 2012 - 2013 academic year, students who are studying the sample group the Islamic Sciences Faculty, Faculty of Arts and Education at the Faculty of normal and used in teaching students selected by the random sampling method and volunteered to participate in the research consisted of 490 individuals . Working as a data collection tool "Leisure Barriers" scale is used. Working for the analysis of two independent sample t - test and ANOVA were applied, no significant differences found as a result of these practices in order to determine the source of the Duncan test was performed. The scale used in the study in three of the six factors of the variations observed according to the specified arguments, but this perspective more " time and lack of interest in" the focus has been understood that.

  8. [Economic factors and gender differences in the prevalence of smoking among adults].

    Paes, Nelson Leitão

    2016-01-01

    This article presents a study that seeks to identify the relevant economic variables in the prevalence of smoking in a group of 37 countries. The chosen methodology was to estimate multiple linear regression using the least square approach. The econometric exercise is performed by gender, seeking to examine whether there are different motivations for cigarette smoking among the adult population of men and women. The results show that although taxation is a common element in the decision of both sexes, the decision to smoke among women is also sensitive to price and other social and cultural factors. These factors were based on the fact that women who live in countries that are part of the Organization for Economic Cooperation and Development reveal a significantly higher prevalence of cigarette consumption. The evidence presented in this study, therefore, reinforces the perception that taxation is in fact a crucial tool in the control of smoking, but in the specific case of women, higher prices and the promotion of greater equality with men, are also important.

  9. Protective versus risk factors for self-objectification in different age and gender cohorts

    Rollero Chiara

    2018-01-01

    Full Text Available The harmful effects of objectification and self-objectification have been widely investigated, but few studies have examined factors that may predict self-objectification. This research intends to assess the protective versus risk role of sociodemographic and physical characteristics (age, BMI, psychosocial variables (self-esteem; self-oriented perfectionism and socially prescribed perfectionism, and social factors (influence of family and friends; internalization of media standards on self-objectification in men and women. The selfobjectification was assessed with two subscales of the Objectified Body Consciousness Scale: Body Shame and Body Surveillance. Participants were 812 Italian adults of different age cohorts (age range 21–60 years; 50.7% females recruited via a quota sampling method. Two regression models separately for males and females were performed. Results showed that mass media influence was the strongest predictor for body surveillance and body shame in both men and women, whereas gender-related patterns emerged for physical, psychological, and relational variables with age as moderator.

  10. Metabotropic glutamate receptor 2 and corticotrophin-releasing factor receptor-1 gene expression is differently regulated by BDNF in rat primary cortical neurons

    Jørgensen, Christinna V; Klein, Anders B; El-Sayed, Mona

    2013-01-01

    Brain-derived neurotrophic factor (BDNF) is important for neuronal survival and plasticity. Incorporation of matured receptor proteins is an integral part of synapse formation. However, whether BDNF increases synthesis and integration of receptors in functional synapses directly is unclear. We...... are particularly interested in the regulation of the 5-hydroxytryptamine receptor 2A (5-HT2A R). This receptor form a functional complex with the metabotropic glutamate receptor 2 (mGluR2) and is recruited to the cell membrane by the corticotrophin-releasing factor receptor 1 (CRF-R1). The effect of BDNF on gene...... expression for all these receptors, as well as a number of immediate-early genes, was pharmacologically characterized in primary neurons from rat frontal cortex. BDNF increased CRF-R1 mRNA levels up to fivefold, whereas mGluR2 mRNA levels were proportionally downregulated. No effect on 5-HT2A R mRNA was seen...

  11. Fibroblast growth factor 10-fibroblast growth factor receptor 2b mediated signaling is not required for adult glandular stomach homeostasis.

    Allison L Speer

    Full Text Available The signaling pathways that are essential for gastric organogenesis have been studied in some detail; however, those that regulate the maintenance of the gastric epithelium during adult homeostasis remain unclear. In this study, we investigated the role of Fibroblast growth factor 10 (FGF10 and its main receptor, Fibroblast growth factor receptor 2b (FGFR2b, in adult glandular stomach homeostasis. We first showed that mouse adult glandular stomach expressed Fgf10, its receptors, Fgfr1b and Fgfr2b, and most of the other FGFR2b ligands (Fgf1, Fgf7, Fgf22 except for Fgf3 and Fgf20. Fgf10 expression was mesenchymal whereas FGFR1 and FGFR2 expression were mostly epithelial. Studying double transgenic mice that allow inducible overexpression of Fgf10 in adult mice, we showed that Fgf10 overexpression in normal adult glandular stomach increased epithelial proliferation, drove mucous neck cell differentiation, and reduced parietal and chief cell differentiation. Although a similar phenotype can be associated with the development of metaplasia, we found that Fgf10 overexpression for a short duration does not cause metaplasia. Finally, investigating double transgenic mice that allow the expression of a soluble form of Fgfr2b, FGF10's main receptor, which acts as a dominant negative, we found no significant changes in gastric epithelial proliferation or differentiation in the mutants. Our work provides evidence, for the first time, that the FGF10-FGFR2b signaling pathway is not required for epithelial proliferation and differentiation during adult glandular stomach homeostasis.

  12. Frequency and physical factors associated with gender-based violence in the internally displaced people of Pakistan.

    Qayum, Mehran; Mohmand, Sundas; Arooj, Hina

    2012-01-01

    Gender-based violence frequency and associated physical factors were determined in internally displaced people camp of Jalozai (Pakistan). Majority of families reported that security conditions were lacking and washrooms were neither illuminated (68%, n=29) nor locked (82%, n=31). Reported incidents of emotional violence were 56% (n=35), physical violence 42% (n=26) and sexual violence 18% (n=11). Health facilities reported 12 cases of gender-based violence/ month. No health education on prevention of gender-based violence (93%, n=56) neither psychologist was provided by any health facility. There was no refugee committee (95%, n=59) for women protection and health education (93%, n=56) for prevention of gender-based violence was done. To safeguard women and children proper lightening of passage, lock facilities in washrooms and timely reporting of gender-based violence cases should be ensured. This can be established by creating women protection committees and by conducting health education programs for gender-based violence.

  13. Serum concentrations of brain-derived neurotrophic factor in patients diagnosed with gender dysphoria undergoing sex reassignment surgery

    Maiko A. Schneider

    Full Text Available Abstract Introduction: Transsexualism (ICD-10 is a condition characterized by a strong and persistent dissociation with one's assigned gender. Sex reassignment surgery (SRS and hormone therapy provide a means of allowing transsexual individuals to feel more congruent with their gender and have played a major role in treatment over the past 70 years. Brain-derived neurotrophic factor (BDNF appears to play a key role in recovery from acute surgical trauma and environmentally mediated vulnerability to psychopathology. We hypothesize that BDNF may be a biomarker of alleviation of gender incongruence suffering. Objectives: To measure preoperative and postoperative serum BDNF levels in transsexual individuals as a biomarker of alleviation of stress related to gender incongruence after SRS. Methods: Thirty-two male-to-female transsexual people who underwent both surgery and hormonal treatment were selected from our initial sample. BDNF serum levels were assessed before and after SRS with sandwich enzyme linked immunosorbent assay (ELISA. The time elapsed between the pre-SRS and post-SRS blood collections was also measured. Results: No significant difference was found in pre-SRS or post-SRS BDNF levels or with relation to the time elapsed after SRS when BDNF levels were measured. Conclusion: Alleviation of the suffering related to gender incongruence after SRS cannot be assessed by BDNF alone. Surgical solutions may not provide a quick fix for psychological distress associated with transsexualism and SRS may serve as one step toward, rather than as the conclusion of, construction of a person's gender identity.

  14. The half-life of 25(OH)D after UVB exposure depends on gender and vitamin D receptor polymorphism but mainly on the start level

    Datta, Pameli; Philipsen, Peter A.; Olsen, Peter

    2017-01-01

    The 25-hydroxy vitamin D (25(OH)D) production caused by UVB exposure is usually underestimated as the concurrent degradation of 25(OH)D is not considered. Therefore, the decrease in 25(OH)D was investigated during a 7-week period in winter when ambient UVB is negligible. Twenty-two healthy Danish....... This suggests a quantitatively larger elimination of 25(OH)D at high 25(OH)D start levels. A linear model (logarithm of 25(OH)D) including personal start levels as intercepts and a slope influenced by gender and the vitamin D receptor gene polymorphism rs2228570 explained 87.8% of the observed variation...

  15. Optimal experimental design in an epidermal growth factor receptor signalling and down-regulation model.

    Casey, F P; Baird, D; Feng, Q; Gutenkunst, R N; Waterfall, J J; Myers, C R; Brown, K S; Cerione, R A; Sethna, J P

    2007-05-01

    We apply the methods of optimal experimental design to a differential equation model for epidermal growth factor receptor signalling, trafficking and down-regulation. The model incorporates the role of a recently discovered protein complex made up of the E3 ubiquitin ligase, Cbl, the guanine exchange factor (GEF), Cool-1 (beta -Pix) and the Rho family G protein Cdc42. The complex has been suggested to be important in disrupting receptor down-regulation. We demonstrate that the model interactions can accurately reproduce the experimental observations, that they can be used to make predictions with accompanying uncertainties, and that we can apply ideas of optimal experimental design to suggest new experiments that reduce the uncertainty on unmeasurable components of the system.

  16. Anti-epidermal growth factor receptor skin toxicity: a matter of topical hydration.

    Ferrari, Daris; Codecà, Carla; Bocci, Barbara; Crepaldi, Francesca; Violati, Martina; Viale, Giulia; Careri, Carmela; Caldiera, Sarah; Bordin, Veronica; Luciani, Andrea; Zonato, Sabrina; Cassinelli, Gabriela; Foa, Paolo

    2016-02-01

    Skin toxicity is a frequent complication of anti-epidermal growth factor receptor therapy, which can be an obstacle in maintaining the dose intensity and may negatively impact on the clinical outcome of cancer patients. Skin lesions depend on the disruption of the keratinocyte development pathways and no treatment is clearly effective in resolving the cutaneous alterations frequently found during anti-epidermal growth factor receptor therapy. Among systemic treatments, oral tetracycline proved to be useful in preventing skin manifestations. We describe the case of a patient affected by metastatic colorectal cancer, for whom a combination of chemotherapy and cetuximab was used as second-line treatment. The patient developed a symptomatic papulopustular skin rash that disappeared completely after a twice-daily application of a hydrating and moisturizing cream, mainly consisting of a mixture of paraffin, silicone compounds, and macrogol. The marked cutaneous amelioration allowed the patient to continue cetuximab without any further symptoms and was associated with a partial radiological response.

  17. Explaining gender differences in ill-health in South Korea: the roles of socio-structural, psychosocial, and behavioral factors.

    Chun, Heeran; Khang, Young-Ho; Kim, Il-Ho; Cho, Sung-Il

    2008-09-01

    This study examines and explains the gender disparity in health despite rapid modernization in South Korea where the social structure is still based on traditional gender relations. A nationally representative sample of 2897 men and 3286 women aged 25-64 from the 2001 Korean National Health and Nutrition Examination Survey was analyzed. Health indicators included self rated health and chronic disease. Age-adjusted prevalence was computed according to a gender and odds ratios (OR) derived from logistic regression. Percentage changes in OR by inclusion of determinant variables (socio-structural, psychosocial, and behavioral) into the base logistic regression model were used to estimate the contributions to the gender gap in two morbidity measures. Results showed a substantial female excess in ill-health in both measures, revealing an increasing disparity in the older age group. Group-specific age-adjusted prevalence of ill-health showed an inverse relationship to socioeconomic position. When adjusting for each determinant, employment status, education, and depression contributed the greatest to the gender gap. After adjusting for all suggested determinants, 78% for self rated health and 86% for chronic disease in excess OR could be explained. After stratifying for age, the full model provided a complete explanation for the female excess in chronic illness, but for self rated health a female excess was still evident for the younger age group. Socio-structural factors played a crucial role in accounting for female excess in ill-health. This result calls for greater attention to gender-based health inequality stemming from socio-structural determinants in South Korea. Cross-cultural validation studies are suggested for further discussion of the link between changing gender relations and the gender health gap in morbidity in diverse settings.

  18. It's not just economic factors...: The pervasive gender gap in 21st century Japan

    GRIMES-MACLELLAN,, Dawn

    2014-01-01

    More than twenty-five years have passed since the Japanese government introduced legislation to address gender discrimination in the workplace. This has been followed by other legal measures to safeguard employment during childcare or eldercare leave, and most recently to promote the formation of a "gender-equal society." Yet, official policies and legal provisions have had only little impact on reshaping gender attitudes and role expectations, suggesting that top-down efforts to effect chang...

  19. Gender-related factors influencing tuberculosis control in shantytowns: a qualitative study

    Onifade, Dami A; Bayer, Angela M; Montoya, Rosario; Haro, Marie; Alva, Jessica; Franco, Jessica; Sosa, Rosario; Valiente, Betty; Valera, Enit; Ford, Carolyn M; Acosta, Colleen D; Evans, Carlton A

    2010-01-01

    Abstract Background There is evidence that female gender is associated with reduced likelihood of tuberculosis diagnosis and successful treatment. This study aimed to characterize gender-related barriers to tuberculosis control in Peruvian shantytowns. Methods We investigated attitudes and experiences relating gender to tuberculosis using the grounded theory approach to describe beliefs amongst key tuberculosis control stakeholders. These issues were explored in 22 semi-structured interviews ...

  20. Insulin-Insulin-like Growth Factors Hybrids as Molecular Probes of Hormone:Receptor Binding Specificity

    Křížková, Květoslava; Chrudinová, Martina; Povalová, Anna; Selicharová, Irena; Collinsová, Michaela; Vaněk, Václav; Brzozowski, A. M.; Jiráček, Jiří; Žáková, Lenka

    2016-01-01

    Roč. 55, č. 21 (2016), s. 2903-2913 ISSN 0006-2960 R&D Projects: GA ČR GA15-19018S Institutional support: RVO:61388963 Keywords : alanine scanning mutagenesis * high-affinity binding * type 1 IGF receptor Subject RIV: CE - Biochemistry Impact factor: 2.938, year: 2016 http://pubs.acs.org/doi/pdf/10.1021/acs.biochem.6b00140

  1. Insulin-like Growth Factor Receptor Inhibitors: Baby or the Bathwater?

    Yee, Douglas

    2012-01-01

    The success of targeted therapies for cancer is undisputed; strong preclinical evidence has resulted in the approval of several new agents for cancer treatment. The type I insulin-like growth factor receptor (IGF1R) appeared to be one of these promising new targets. Substantial population and preclinical data have all pointed toward this pathway as an important regulator of tumor cell biology. Although early results from clinical trials that targeted the IGF1R showed some evidence of response...

  2. Optimal Therapeutic Strategy for Non-small Cell Lung Cancer with Mutated Epidermal Growth Factor Receptor

    Zhong SHI

    2015-02-01

    Full Text Available Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs have been widely used in non-small cell lung cancer (NSCLC patients, it is still controversial about how to combine EGFR-TKI with chemotherapy and other targeted drugs. We have made a summary on the current therapeutic models of EGFR-TKI combined with chemotherapy/bevacizumab in this review and aimed to find the optimal therapeutic strategy for NSCLC patients with EGFR mutation.

  3. Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor.

    Roskoski, Robert

    2005-11-11

    Signaling by stem cell factor and Kit, its receptor, plays important roles in gametogenesis, hematopoiesis, mast cell development and function, and melanogenesis. Moreover, human and mouse embryonic stem cells express Kit transcripts. Stem cell factor exists as both a soluble and a membrane-bound glycoprotein while Kit is a receptor protein-tyrosine kinase. The complete absence of stem cell factor or Kit is lethal. Deficiencies of either produce defects in red and white blood cell production, hypopigmentation, and sterility. Gain-of-function mutations of Kit are associated with several human neoplasms including acute myelogenous leukemia, gastrointestinal stromal tumors, and mastocytomas. Kit consists of an extracellular domain, a transmembrane segment, a juxtamembrane segment, and a protein kinase domain that contains an insert of about 80 amino acid residues. Binding of stem cell factor to Kit results in receptor dimerization and activation of protein kinase activity. The activated receptor becomes autophosphorylated at tyrosine residues that serve as docking sites for signal transduction molecules containing SH2 domains. The adaptor protein APS, Src family kinases, and Shp2 tyrosyl phosphatase bind to phosphotyrosine 568. Shp1 tyrosyl phosphatase and the adaptor protein Shc bind to phosphotyrosine 570. C-terminal Src kinase homologous kinase and the adaptor Shc bind to both phosphotyrosines 568 and 570. These residues occur in the juxtamembrane segment of Kit. Three residues in the kinase insert domain are phosphorylated and attract the adaptor protein Grb2 (Tyr703), phosphatidylinositol 3-kinase (Tyr721), and phospholipase Cgamma (Tyr730). Phosphotyrosine 900 in the distal kinase domain binds phosphatidylinositol 3-kinase which in turn binds the adaptor protein Crk. Phosphotyrosine 936, also in the distal kinase domain, binds the adaptor proteins APS, Grb2, and Grb7. Kit has the potential to participate in multiple signal transduction pathways as a result of

  4. A sensitive electrochemiluminescence cytosensor for quantitative evaluation of epidermal growth factor receptor expressed on cell surfaces

    Tang, Yanjuan; Zhang, Shaolian; Wen, Qingqing; Huang, Hongxing; Yang, Peihui, E-mail: typh@jnu.edu.cn

    2015-06-30

    Highlights: • EGF-cytosensor was used for evaluating EGFR expression level on cell surfaces. • CdSQDs and EGF were coated on magnetic beads (MBs) for ECL-probe. • Good sensitivity was achieved due to the signal amplification of ECL-probe. - Abstract: A sensitive electrochemiluminescence (ECL) strategy for evaluating the epidermal growth factor receptor (EGFR) expression level on cell surfaces was designed by integrating the specific recognition of EGFR expressed on MCF-7 cell surfaces with an epidermal growth factor (EGF)-funtionalized CdS quantum dots (CdSQDs)-capped magnetic bead (MB) probe. The high sensitivity of ECL probe of EGF-funtionalized CdSQD-capped-MB was used for competitive recognition with EGFR expressed on cell surfaces with recombinant EGFR protein. The changes of ECL intensity depended on both the cell number and the expression level of EGFR receptor on cell surfaces. A wide linear response to cells ranging from 80 to 4 × 10{sup 6} cells mL{sup −1} with a detection limit of 40 cells mL{sup −1} was obtained. The EGF-cytosensor was used to evaluate EGFR expression levels on MCF-7 cells, and the average number of EGFR receptor on single MCF-7 cells was 1.35 × 10{sup 5} with the relative standard deviation of 4.3%. This strategy was further used for in-situ and real-time evaluating EGFR receptor expressed on cell surfaces in response to drugs stimulation at different concentration and incubation time. The proposed method provided potential applications in the detection of receptors on cancer cells and anticancer drugs screening.

  5. Hepatocyte growth factor enhances death receptor-induced apoptosis by up-regulating DR5

    Li, Yang; Fan, Xing; Goodwin, C Rory; Laterra, John; Xia, Shuli

    2008-01-01

    Hepatocyte growth factor (HGF) and its receptor c-MET are commonly expressed in malignant gliomas and embryonic neuroectodermal tumors including medulloblastoma and appear to play an important role in the growth and dissemination of these malignancies. Dependent on cell context and the involvement of specific downstream effectors, both pro- and anti-apoptotic effects of HGF have been reported. Human medulloblastoma cells were treated with HGF for 24–72 hours followed by death receptor ligand TRAIL (Tumor necrosis factor-related apoptosis-inducing ligand) for 24 hours. Cell death was measured by MTT and Annexin-V/PI flow cytometric analysis. Changes in expression levels of targets of interest were measured by Northern blot analysis, quantitative reverse transcription-PCR, Western blot analysis as well as immunoprecipitation. In this study, we show that HGF promotes medulloblastoma cell death induced by TRAIL. TRAIL alone triggered apoptosis in DAOY cells and death was enhanced by pre-treating the cells with HGF for 24–72 h prior to the addition of TRAIL. HGF (100 ng/ml) enhanced TRAIL (10 ng/ml) induced cell death by 36% (P < 0.001). No cell death was associated with HGF alone. Treating cells with PHA-665752, a specific c-Met receptor tyrosine kinase inhibitor, significantly abrogated the enhancement of TRAIL-induced cell death by HGF, indicating that its death promoting effect requires activation of its canonical receptor tyrosine kinase. Cell death induced by TRAIL+HGF was predominately apoptotic involving both extrinsic and intrinsic pathways as evidenced by the increased activation of caspase-3, 8, 9. Promotion of apoptosis by HGF occurred via the increased expression of the death receptor DR5 and enhanced formation of death-inducing signal complexes (DISC). Taken together, these and previous findings indicate that HGF:c-Met pathway either promotes or inhibits medulloblastoma cell death via pathway and context specific mechanisms

  6. Identification of fibroblast growth factor receptor 3 (FGFR3 as a protein receptor for botulinum neurotoxin serotype A (BoNT/A.

    Birgitte P S Jacky

    Full Text Available Botulinum neurotoxin serotype A (BoNT/A causes transient muscle paralysis by entering motor nerve terminals (MNTs where it cleaves the SNARE protein Synaptosomal-associated protein 25 (SNAP25206 to yield SNAP25197. Cleavage of SNAP25 results in blockage of synaptic vesicle fusion and inhibition of the release of acetylcholine. The specific uptake of BoNT/A into pre-synaptic nerve terminals is a tightly controlled multistep process, involving a combination of high and low affinity receptors. Interestingly, the C-terminal binding domain region of BoNT/A, HC/A, is homologous to fibroblast growth factors (FGFs, making it a possible ligand for Fibroblast Growth Factor Receptors (FGFRs. Here we present data supporting the identification of Fibroblast Growth Factor Receptor 3 (FGFR3 as a high affinity receptor for BoNT/A in neuronal cells. HC/A binds with high affinity to the two extra-cellular loops of FGFR3 and acts similar to an agonist ligand for FGFR3, resulting in phosphorylation of the receptor. Native ligands for FGFR3; FGF1, FGF2, and FGF9 compete for binding to FGFR3 and block BoNT/A cellular uptake. These findings show that FGFR3 plays a pivotal role in the specific uptake of BoNT/A across the cell membrane being part of a larger receptor complex involving ganglioside- and protein-protein interactions.

  7. Abundant immunohistochemical expression of dopamine D{sub 2} receptor and p53 protein in meningiomas: follow-up, relation to gender, age, tumor grade, and recurrence

    Trott, G.; Pereira-Lima, J.F.S.; Leães, C.G.S. [Programa de Graduação em Patologia, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Centro de Neuroendocrinologia, Complexo Hospitalar Santa Casa de Porto Alegre, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Ferreira, N.P. [Centro de Neuroendocrinologia, Complexo Hospitalar Santa Casa de Porto Alegre, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Barbosa-Coutinho, L.M. [Programa de Graduação em Patologia, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Oliveira, M.C. [Programa de Graduação em Patologia, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Centro de Neuroendocrinologia, Complexo Hospitalar Santa Casa de Porto Alegre, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil)

    2015-03-03

    Meningiomas are common, usually benign tumors, with a high postoperative recurrence rate. However, the genesis and development of these tumors remain controversial. We aimed to investigate the presence and implications of a mutated p53 protein and dopamine D{sub 2} receptor in a representative series of meningiomas and to correlate these findings with age, gender, tumor grade, and recurrence. Tumor tissue samples of 157 patients diagnosed with meningioma (37 males and 120 females, mean age 53.6±14.3 years) who underwent surgical resection between 2003 and 2012 at our institution were immunohistochemically evaluated for the presence of p53 protein and dopamine D{sub 2} receptor and were followed-up to analyze tumor recurrence or regrowth. Tumors were classified as grades I (n=141, 89.8%), II (n=13, 8.3%), or grade III (n=3, 1.9%). Dopamine D{sub 2} receptor and p53 protein expression were positive in 93.6% and 49.7% of the cases, respectively. Neither of the markers showed significant expression differences among different tumor grades or recurrence or regrowth statuses. Our findings highlight the potential role of p53 protein in meningioma development and/or progression. The high positivity of dopamine D{sub 2} receptor observed in this study warrants further investigation of the therapeutic potential of dopamine agonists in the evolution of meningiomas.

  8. Abundant immunohistochemical expression of dopamine D2 receptor and p53 protein in meningiomas: follow-up, relation to gender, age, tumor grade, and recurrence

    Trott, G.; Pereira-Lima, J.F.S.; Leães, C.G.S.; Ferreira, N.P.; Barbosa-Coutinho, L.M.; Oliveira, M.C.

    2015-01-01

    Meningiomas are common, usually benign tumors, with a high postoperative recurrence rate. However, the genesis and development of these tumors remain controversial. We aimed to investigate the presence and implications of a mutated p53 protein and dopamine D 2 receptor in a representative series of meningiomas and to correlate these findings with age, gender, tumor grade, and recurrence. Tumor tissue samples of 157 patients diagnosed with meningioma (37 males and 120 females, mean age 53.6±14.3 years) who underwent surgical resection between 2003 and 2012 at our institution were immunohistochemically evaluated for the presence of p53 protein and dopamine D 2 receptor and were followed-up to analyze tumor recurrence or regrowth. Tumors were classified as grades I (n=141, 89.8%), II (n=13, 8.3%), or grade III (n=3, 1.9%). Dopamine D 2 receptor and p53 protein expression were positive in 93.6% and 49.7% of the cases, respectively. Neither of the markers showed significant expression differences among different tumor grades or recurrence or regrowth statuses. Our findings highlight the potential role of p53 protein in meningioma development and/or progression. The high positivity of dopamine D 2 receptor observed in this study warrants further investigation of the therapeutic potential of dopamine agonists in the evolution of meningiomas

  9. Granulocyte-Colony Stimulating Factor Receptor, Tissue Factor, and VEGF-R Bound VEGF in Human Breast Cancer In Loco.

    Wojtukiewicz, Marek Z; Sierko, Ewa; Skalij, Piotr; Kamińska, Magda; Zimnoch, Lech; Brekken, Ralf A; Thorpe, Philip E

    2016-01-01

    Doxorubicin and docetaxel-based chemotherapy regimens used in breast cancer patients are associated with high risk of febrile neutropenia (FN). Granulocyte colony-stimulating factors (G-CSF) are recommended for both treating and preventing chemotherapy-induced neutropenia. Increased thrombosis incidence in G-CSF treated patients was reported; however, the underlying mechanisms remain unclear. The principal activator of blood coagulation in cancer is tissue factor (TF). It additionally contributes to cancer progression and stimulates angiogenesis. The main proangiogenic factor is vascular endothelial growth factor (VEGF). The aim of the study was to evaluate granulocyte-colony stimulating factor receptor (G-CSFR), tissue factor (TF) expression and vascular endothelial growth factor receptor (VEGF-R) bound VEGF in human breast cancer in loco. G-CSFR, TF and VEGFR bound VEGF (VEGF: VEGFR) were assessed in 28 breast cancer tissue samples. Immunohistochemical (IHC) methodologies according to ABC technique and double staining IHC procedure were employed utilizing antibodies against G-CSFR, TF and VEGF associated with VEGFR (VEGF: VEGFR). Expression of G-CSFR was demonstrated in 20 breast cancer tissue specimens (71%). In 6 cases (21%) the expression was strong (IRS 9-12). Strong expression of TF was observed in all investigated cases (100%). Moreover, expression of VEGF: VEGFR was visualized in cancer cells (IRS 5-8). No presence of G-CSFR, TF or VEGF: VEGFR was detected on healthy breast cells. Double staining IHC studies revealed co-localization of G-CSFR and TF, G-CSFR and VEGF: VEGFR, as well as TF and VEGF: VEGFR on breast cancer cells and ECs. The results of the study indicate that GCSFR, TF and VEGF: VEGFR expression as well as their co-expression might influence breast cancer biology, and may increase thromboembolic adverse events incidence.

  10. Selective binding and oligomerization of the murine granulocyte colony-stimulating factor receptor by a low molecular weight, nonpeptidyl ligand.

    Doyle, Michael L; Tian, Shin-Shay; Miller, Stephen G; Kessler, Linda; Baker, Audrey E; Brigham-Burke, Michael R; Dillon, Susan B; Duffy, Kevin J; Keenan, Richard M; Lehr, Ruth; Rosen, Jon; Schneeweis, Lumelle A; Trill, John; Young, Peter R; Luengo, Juan I; Lamb, Peter

    2003-03-14

    Granulocyte colony-stimulating factor regulates neutrophil production by binding to a specific receptor, the granulocyte colony-stimulating factor receptor, expressed on cells of the granulocytic lineage. Recombinant forms of granulocyte colony-stimulating factor are used clinically to treat neutropenias. As part of an effort to develop granulocyte colony-stimulating factor mimics with the potential for oral bioavailability, we previously identified a nonpeptidyl small molecule (SB-247464) that selectively activates murine granulocyte colony-stimulating factor signal transduction pathways and promotes neutrophil formation in vivo. To elucidate the mechanism of action of SB-247464, a series of cell-based and biochemical assays were performed. The activity of SB-247464 is strictly dependent on the presence of zinc ions. Titration microcalorimetry experiments using a soluble murine granulocyte colony-stimulating factor receptor construct show that SB-247464 binds to the extracellular domain of the receptor in a zinc ion-dependent manner. Analytical ultracentrifugation studies demonstrate that SB-247464 induces self-association of the N-terminal three-domain fragment in a manner that is consistent with dimerization. SB-247464 induces internalization of granulocyte colony-stimulating factor receptor on intact cells, consistent with a mechanism involving receptor oligomerization. These data show that small nonpeptidyl compounds are capable of selectively binding and inducing productive oligomerization of cytokine receptors.

  11. Explaining Gender Gaps in English Composition and College Algebra in College: The Mediating Role of Psychosocial Factors

    Ndum, Edwin; Allen, Jeff; Way, Jason; Casillas, Alex

    2018-01-01

    We examined the role of six psychosocial factors (PSFs) in explaining gender gaps in English Composition (n = 8,633) and College Algebra (n = 2,261) using data of first-year female (55%) and male students from 42 colleges. Using a multilevel model and controlling for prior achievement, we found that PSFs mediated between 3% and 41% of the gender…

  12. Understanding the Decision to Enroll in Graduate Business Programs: Influence of Sociological and Economic Factors and Gender

    Douglas, Stephanie

    2017-01-01

    This ex post facto study describes the associations of economic factors as well as social and cultural capital variables on enrollment in business master's degree programs and differences of associations by gender and race/ethnicity. Data from the 2008/2012 Baccalaureate and Beyond Longitudinal Study (B&B: 08/12) of those who completed a…

  13. Thyroid hormone regulation of epidermal growth factor receptor levels in mouse mammary glands

    Vonderhaar, B.K.; Tang, E.; Lyster, R.R.; Nascimento, M.C.

    1986-01-01

    The specific binding of iodinated epidermal growth factor ([ 125 I]iodo-EGF) to membranes prepared from the mammary glands and spontaneous breast tumors of euthyroid and hypothyroid mice was measured in order to determine whether thyroid hormones regulate the EGF receptor levels in vivo. Membranes from hypothyroid mammary glands of mice at various developmental ages bound 50-65% less EGF than those of age-matched euthyroid controls. Treatment of hypothyroid mice with L-T4 before killing restored binding to the euthyroid control level. Spontaneous breast tumors arising in hypothyroid mice also bound 30-40% less EGF than tumors from euthyroid animals even after in vitro desaturation of the membranes of endogenous growth factors with 3 M MgCl2 treatment. The decrease in binding in hypothyroid membranes was due to a decrease in the number of binding sites, not to a change in affinity of the growth factor for its receptor, as determined by Scatchard analysis of the binding data. Both euthyroid and hypothyroid membranes bound EGF primarily to a single class of high affinity sites [dissociation constant (Kd) = 0.7-1.8 nM]. Euthyroid membranes bound 28.4 +/- (SE) 0.6 fmol/mg protein, whereas hypothyroid membranes bound 15.5 +/- 1.0 fmol/mg protein. These data indicate that EGF receptor levels in normal mammary glands and spontaneous breast tumors in mice are subject to regulation by thyroid status

  14. Matched-pair analysis of a multi-institutional cohort reveals that epidermal growth factor receptor mutation is not a risk factor for postoperative recurrence of lung adenocarcinoma.

    Matsumura, Yuki; Suzuki, Hiroyuki; Ohira, Tetsuya; Shiono, Satoshi; Abe, Jiro; Sagawa, Motoyasu; Sakurada, Akira; Katahira, Masato; Machida, Yuichiro; Takahashi, Satomi; Okada, Yoshinori

    2017-12-01

    It is unclear whether epidermal growth factor receptor (EGFR) mutation status is a risk factor for postoperative recurrence of surgically resected lung adenocarcinoma (ADC). Therefore, we conducted a multi-institutional study employing matched-pair analysis to compare recurrence-free survival (RFS) and overall survival (OS) of patients with lung ADC according to EGFR mutation status. We collected the records of 909 patients who underwent surgical resection for lung ADC between 2005 and 2012 at five participating institutions and were also examined their EGFR mutation status. For each patient with an EGFR mutation, we selected one with the wild-type EGFR sequence and matched them according to institution, age, gender, smoking history, pathological stage (pStage), and adjuvant treatment. We compared RFS and OS of the matched cohort. The patients were allocated into groups (n=181 each) with mutated or wild-type EGFR sequences. Both cohorts had identical characteristics as follows: institution, median age (68 years), men (85, 47%), ever smokers (77, 43%), and pStage (IA, 108, 60%; IB, 48, 27%; II, 14, 8%; III, 11, 6%). The 3- and 5-year RFS rates of patients with mutated or wild-type EGFR sequence were 79%, 68% and 77%, 68%, respectively (p=0.557). The respective OS rates were 92%, 81%, and 89%, 79% (p=0.574). Matched-pair and multi-institutional analysis reveals that an EGFR mutation was not a significant risk factor for recurrence of patients with surgically resected lung adenocarcinoma. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Regulation of platelet activating factor receptor coupled phosphoinositide-specific phospholipase C activity

    Morrison, W.J.

    1988-01-01

    The major objectives of this study were two-fold. The first was to establish whether binding of platelet activating factor (PAF) to its receptor was integral to the stimulation of polyphosphoinositide-specific phospholipase C (PLC) in rabbit platelets. The second was to determine regulatory features of this receptor-coupled mechanism. [ 3 H]PAF binding demonstrated two binding sites, a high affinity site with a inhibitory constant (Ki) of 2.65 nM and a low affinity site with a Ki of 0.80 μM. PAF receptor coupled activation of phosphoinositide-specific PLC was studied in platelets which were made refractory, by short term pretreatments, to either PAF or thrombin. Saponin-permeabilized rabbit platelets continue to regulate the mechanism(s) coupling PAF receptors to PLC stimulation. However, TRPγS and GDPβS, which affect guanine nucleotide regulatory protein functions, were unable to modulate the PLC activity to any appreciable extent as compared to PAF. The possible involvement of protein kinase C (PKC) activation in regulating PAF-stimulated PLC activity was studied in rabbit platelets pretreated with staurosporine followed by pretreatments with PAF or phorbol 12-myristate 13-acetate (PMA)

  16. Structural analysis of the receptors for granulocyte colony-stimulating factor on neutrophils

    Hanazono, Y.; Hosoi, T.; Kuwaki, T.; Matsuki, S.; Miyazono, K.; Miyagawa, K.; Takaku, F.

    1990-01-01

    We investigated granulocyte colony-stimulating factor (G-CSF) receptors on neutrophils from three patients with chronic myelogenous leukemia (CML) in the chronic phase, in comparison with four normal volunteers. Because we experienced some difficulties in radioiodinating intact recombinant human G-CSF, we developed a new derivative of human G-CSF termed YPY-G-CSF. It was easy to iodinate this protein using the lactoperoxidase method because of two additional tyrosine residues, and its radioactivity was higher than that previously reported. The biological activity of YPY-G-CSF as G-CSF was fully retained. Scatchard analysis demonstrated that CML neutrophils had a single class of binding sites (1400 +/- 685/cell) with a dissociation constant (Kd) of 245 +/- 66 pM. The number of sites and Kd value of CML neutrophils were not significantly different from those of normal neutrophils (p greater than 0.9). Cross-linking studies revealed two specifically labeled bands of [125I]YPY-G-CSF-receptor complexes with apparent molecular masses of 160 and 110 kd on both normal and CML neutrophils. This is the first report describing two receptor proteins on neutrophils. According to the analyses of the proteolytic process of these cross-linked complexes and proteolytic mapping, we assume that alternative splicing or processing from a single gene may generate two distinct receptor proteins that bind specifically to G-CSF but have different fates in intracellular metabolism

  17. Targeting of liposomes to cells bearing nerve growth factor receptors mediated by biotinylated NGF

    Rosenberg, M.B.

    1986-01-01

    Previous studies of liposome targeting have concentrated on immunological systems, the use of ligand-receptor interactions has received little attention. The protein hormone beta-nerve growth factor (NGF) was modified by biotinylation via carboxyl group substitution (C-bio-NGF) under reaction conditions that yielded an average of 3 biotin additions per NGF subunit. NGF was also biotinylated through amino group substitution to produce derivatives with ratios of 1, 2 and 4 biotin moieties per NGF subunit (N-bio-NGF). These derivatives were compared with native NGF for their ability to compete with 125 I-NGF for binding to NGF receptors on rat pheochromocytoma (PC 12) cells at 4 0 C. C-bio-NGF was as effective as native NGF in binding to NGF receptors, while N-bio-NGF containing 1 biotin per NGF subunit was only 28% as active in binding as native NGF. C-bio-NGF, but not N-bio-NGF, mediated the specific binding of 125 I-streptavidin to PC12 cells. Biocytin-NGF, a derivative of C-bio-NGF with an extended spacer chain, was also synthesized and retained full biological and receptor binding activities. C-bio-NGF and biocytin-NGF were as effective as native NGF in a bioassay involving induction of neurite outgrowth from PC12 cells

  18. Molecular Recognition of Corticotropin releasing Factor by Its G protein-coupled Receptor CRFR1

    Pioszak, Augen A.; Parker, Naomi R.; Suino-Powell, Kelly; Xu, H. Eric (Van Andel)

    2009-01-15

    The bimolecular interaction between corticotropin-releasing factor (CRF), a neuropeptide, and its type 1 receptor (CRFR1), a class B G-protein-coupled receptor (GPCR), is crucial for activation of the hypothalamic-pituitary-adrenal axis in response to stress, and has been a target of intense drug design for the treatment of anxiety, depression, and related disorders. As a class B GPCR, CRFR1 contains an N-terminal extracellular domain (ECD) that provides the primary ligand binding determinants. Here we present three crystal structures of the human CRFR1 ECD, one in a ligand-free form and two in distinct CRF-bound states. The CRFR1 ECD adopts the alpha-beta-betaalpha fold observed for other class B GPCR ECDs, but the N-terminal alpha-helix is significantly shorter and does not contact CRF. CRF adopts a continuous alpha-helix that docks in a hydrophobic surface of the ECD that is distinct from the peptide-binding site of other class B GPCRs, thereby providing a basis for the specificity of ligand recognition between CRFR1 and other class B GPCRs. The binding of CRF is accompanied by clamp-like conformational changes of two loops of the receptor that anchor the CRF C terminus, including the C-terminal amide group. These structural studies provide a molecular framework for understanding peptide binding and specificity by the CRF receptors as well as a template for designing potent and selective CRFR1 antagonists for therapeutic applications.

  19. Imbalance of tumor necrosis factor receptors during progression in bovine leukemia virus infection

    Konnai, Satoru; Usui, Tatsufumi; Ikeda, Manabu; Kohara, Junko; Hirata, Toh-ichi; Okada, Kosuke; Ohashi, Kazuhiko; Onuma, Misao

    2005-01-01

    Previously, we found an up-regulation of tumor necrosis factor alpha (TNF)-α and an imbalance of TNF receptors in sheep experimentally infected with bovine leukemia virus (BLV). In order to investigate the different TNF-α-induced responses, in this study we examined the TNF-α-induced proliferative response and the expression levels of two distinct TNF receptors on peripheral blood mononuclear cells (PBMC) derived from BLV-uninfected cattle and BLV-infected cattle that were aleukemic (AL) or had persistent lymphocytosis (PL). The proliferative response of PBMC isolated from those cattle with PL in the presence of recombinant bovine TNF-α (rTNF-α) was significantly higher than those from AL cattle and uninfected cattle and the cells from PL cattle expressed significantly higher mRNA levels of TNF receptor type II (TNF-RII) than those from AL and BLV-uninfected cattle. No difference was found in TNF-RI mRNA levels. Most cells expressing TNF-RII in PL cattle were CD5 + or sIgM + cells and these cells showed resistance to TNF-α-induced apoptosis. Additionally, there were significant positive correlations between the changes in provirus load and TNF-RII mRNA levels, and TNF-α-induced proliferation and TNF-RII mRNA levels. These data suggest that imbalance in the expression of TNF receptors could at least in part contribute to the progression of lymphocytosis in BLV infection

  20. Expression of transforming growth factor alpha and epidermal growth factor receptor in rat lung neoplasms induced by plutonium-239

    Stegelmeier, B.L.; Gillett, N.A.; Hahn, F.F.; Kelly, G.; Rebar, A.H.

    1994-01-01

    Ninety-two rat lung proliferative lesions and neoplasms induced by inhaled 239 PuO 2 were evaluated for aberrant expression of transforming growth factor alpha (TGF-α) and epidermal growth factor receptor (EGFR). Expression of TGF-α protein, measured by immunohistochemistry, was higher in 94% of the squamous cell carcinomas and 87% of the foci of alveolar epithelial squamous metaplasia than that exhibited by the normal-appearing, adjacent lung parenchyma. In contrast, only 20% of adenocarcinomas and foci of epithelial hyperplasia expressed elevated levels of TGF-α. Many neoplasms expressing TGF-α also expressed excessive levels of EGFR mRNA. Southern and DNA slot blot analyses showed that the elevated EGFR expression was not due to amplification of the EGFR gene. These data suggest that increased amounts of TGF-α were early alterations in the progression of plutonium-induced squamous cell carcinoma, and these increases may occur in parallel with overexpression of the receptor for this growth factor. Together, these alterations create a potential autocrine loop for sustaining clonal expansion of cells initiated by high-LET radiation. 44 refs., 4 figs., 1 tab

  1. Tissue factor is an angiogenic-specific receptor for factor VII-targeted immunotherapy and photodynamic therapy.

    Hu, Zhiwei; Cheng, Jijun; Xu, Jie; Ruf, Wolfram; Lockwood, Charles J

    2017-02-01

    Identification of target molecules specific for angiogenic vascular endothelial cells (VEC), the inner layer of pathological neovasculature, is critical for discovery and development of neovascular-targeting therapy for angiogenesis-dependent human diseases, notably cancer, macular degeneration and endometriosis, in which vascular endothelial growth factor (VEGF) plays a central pathophysiological role. Using VEGF-stimulated vascular endothelial cells (VECs) isolated from microvessels, venous and arterial blood vessels as in vitro angiogenic models and unstimulated VECs as a quiescent VEC model, we examined the expression of tissue factor (TF), a membrane-bound receptor on the angiogenic VEC models compared with quiescent VEC controls. We found that TF is specifically expressed on angiogenic VECs in a time-dependent manner in microvessels, venous and arterial vessels. TF-targeted therapeutic agents, including factor VII (fVII)-IgG1 Fc and fVII-conjugated photosensitizer, can selectively bind angiogenic VECs, but not the quiescent VECs. Moreover, fVII-targeted photodynamic therapy can selectively and completely eradicate angiogenic VECs. We conclude that TF is an angiogenic-specific receptor and the target molecule for fVII-targeted therapeutics. This study supports clinical trials of TF-targeted therapeutics for the treatment of angiogenesis-dependent diseases such as cancer, macular degeneration and endometriosis.

  2. Design and characteristics of cytotoxic fibroblast growth factor 1 conjugate for fibroblast growth factor receptor-targeted cancer therapy

    Szlachcic A

    2016-08-01

    Full Text Available Anna Szlachcic, Malgorzata Zakrzewska, Michal Lobocki, Piotr Jakimowicz, Jacek Otlewski Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland Abstract: Fibroblast growth factor receptors (FGFRs are attractive candidate cancer therapy targets as they are overexpressed in multiple types of tumors, such as breast, prostate, bladder, and lung cancer. In this study, a natural ligand of FGFR, an engineered variant of fibroblast growth factor 1 (FGF1V, was conjugated to a potent cytotoxic drug, monomethyl auristatin E (MMAE, and used as a targeting agent for cancer cells overexpressing FGFRs, similar to antibodies in antibody–drug conjugates. The FGF1V–valine–citrulline–MMAE conjugate showed a favorable stability profile, bound FGFRs on the cell surface specifically, and efficiently released the drug (MMAE upon cleavage by the lysosomal protease cathepsin B. Importantly, the conjugate showed a prominent cytotoxic effect toward cell lines expressing FGFR. FGF1V–vcMMAE was highly cytotoxic at concentrations even an order of magnitude lower than those found for free MMAE. This effect was FGFR-specific as cells lacking FGFR did not show any increased mortality. Keywords: fibroblast growth factor 1, FGF receptor, targeted cancer therapy, cytotoxic conjugates, FGFR-dependent cancer, MMAE, auristatin

  3. Gender Implications in Curriculum and Entrance Exam Grouping: Institutional Factors and Their Effects

    Hsaieh, Hsiao-Chin; Yang, Chia-Ling

    2014-01-01

    While access to higher education has reached gender parity in Taiwan, the phenomenon of gender segregation and stratification by fields of study and by division of labor persist. In this article, we trace the historical evolution of Taiwan's education system and data using large-scale educational databases to analyze the association of…

  4. In-vivo fluorescence detection of breast cancer growth factor receptors by fiber-optic probe

    Bustamante, Gilbert; Wang, Bingzhi; DeLuna, Frank; Sun, LuZhe; Ye, Jing Yong

    2018-02-01

    Breast cancer treatment options often include medications that target the overexpression of growth factor receptors, such as the proto-oncogene human epidermal growth factor receptor 2 (HER2/neu) and epidermal growth factor receptor (EGFR) to suppress the abnormal growth of cancerous cells and induce cancer regression. Although effective, certain treatments are toxic to vital organs, and demand assurance that the pursued receptor is present at the tumor before administration of the drug. This requires diagnostic tools to provide tumor molecular signatures, as well as locational information. In this study, we utilized a fiber-optic probe to characterize in vivo HER2 and EGFR overexpressed tumors through the fluorescence of targeted dyes. HER2 and EGFR antibodies were conjugated with ICG-Sulfo-OSu and Alexa Fluor 680, respectively, to tag BT474 (HER2+) and MDA-MB-468 (EGFR+) tumors. The fiber was inserted into the samples via a 30-gauge needle. Different wavelengths of a supercontinuum laser were selected to couple into the fiber and excite the corresponding fluorophores in the samples. The fluorescence from the dyes was collected through the same fiber and quantified by a time-correlated single photon counter. Fluorescence at different antibody-dye concentrations was measured for calibration. Mice with subcutaneous HER2+ and/or EGFR+ tumors received intravenous injections of the conjugates and were later probed at the tumor sites. The measured fluorescence was used to distinguish between tumor types and to calculate the concentration of the antibody-dye conjugates, which were detectable at levels as low as 40 nM. The fiber-optic probe presents a minimally invasive instrument to characterize the molecular signatures of breast cancer in vivo.

  5. Macrophage colony-stimulating factor, CSF-1, and its proto-oncogene-encoded receptor

    Sherr, C.J.; Rettenmier, C.W.; Roussel, M.F.

    1988-01-01

    The macrophage colony-stimulating factor, CSF-1, or M-CSF, is one of a family of hematopoietic growth factors that stimulates the proliferation of monocytes, macrophages, and their committed bone marrow progenitors. Unlike pluripotent hemopoietins such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3 or multi-CSF), which affect the growth of myeloid cells of several different hematopoietic lineages, CSF-1 acts only on cells of the mononuclear phagocyte series to stimulate their growth and enhance their survival. Retroviral transduction of the feline c-fms gene in the Susan McDonough and Hardy Zuckerman-5 (HZ-5) strains of feline sarcoma virus (FeSV) led to genetic alterations that endowed the recombined viral oncogene (v-fms) with the ability to transform cells in culture morphologically and to induce firbrosarcomas and hematopoietic neoplasms in susceptible animals. The v-fms oncogene product differs from the normal CSF-1 receptor in certain of its cardinal biochemical properties, most notably in exhibiting constitutively high basal levels of tyrosine kinase activity in the absence of its ligand. Comparative studies of the c-fms and v-fms genes coupled with analyses of engineered mutants and receptor chimeras have begun to pinpoint pertinent genetic alterations in the normal receptor gene that unmask its latent oncogenic potential. In addition, the availability of biologically active c-fms, v-fms, and CSF-1 cDNAs has allowed these genes to be mobilized and expressed in naive cells, thereby facilitating assays for receptor coupling with downstream components of the mitogenic pathway in diverse cell types

  6. Regional and national differences in stressful life events: The role of cultural factors, economic development, and gender.

    Vázquez, José Juan; Panadero, Sonia; Martín, Rosa M

    2015-07-01

    The study analyzed differences in the risk of experiencing stressful life events (SLE) according to cultural factors, the level of economic development of the region inhabited, and gender. Information was gathered on the number and nature of SLE experienced by a sample of 604 undergraduates from 3 regions with very different levels of economic development: Madrid (Spain), León (Nicaragua), and Bilwi (Nicaragua). The results indicated a greater risk of experiencing SLE among undergraduates from Nicaragua, but few differences attributed to the undergraduates' gender or the level of economic development in the region they inhabit within the same country. (c) 2015 APA, all rights reserved).

  7. Gender Differences in the VDR-FokI Polymorphism and Conventional Non-Genetic Risk Factors in Association with Lumbar Spine Pathologies in an Italian Case-Control Study

    Colombini, Alessandra; Brayda-Bruno, Marco; Ferino, Lucia; Lombardi, Giovanni; Maione, Vincenzo; Banfi, Giuseppe; Cauci, Sabina

    2015-01-01

    Recently, the FokI polymorphism (rs2228570) in the vitamin D receptor gene (VDR) and conventional risk factors were associated with spine disorders in the Italian population, but without gender analysis. Two-hundred and sixty-seven patients (149 males, 118 females) with lumbar spine disorders were assessed by magnetic resonance imaging (MRI) and 254 (127 males, 127 females) asymptomatic controls were enrolled. The exposure to putative risk factors was evaluated and FokI polymorphism was detected by PCR-restriction fragment length polymorphism (PCR-RFLP). An association between lumbar spine pathologies and higher than average age; overweight; family history; lower leisure physical activity; smoking habit; higher number of hours/day exposure to vibration and more sedentary or intense physical job demand was observed in male patients. In contrast, in females, only higher age, overweight, family history and lower leisure physical activity were risk factors. FF genotype was a 2-fold risk factor to develop discopathies and/or osteochondrosis concomitant with disc herniation for both gender patients, while heterozygous Ff was protective for females only. In males only ff genotype was protective for discopathies and/or osteochondrosis and F allele was a 2-fold risk factor for hernia; discopathies; discopathies and/or osteochondrosis. Sex-related differences in voluntary behaviors, exposure to environmental risks and genetic background could be crucial for a gender-differentiated management of patients with spine disorders. PMID:25671813

  8. Gender Differences in the VDR-FokI Polymorphism and Conventional Non-Genetic Risk Factors in Association with Lumbar Spine Pathologies in an Italian Case-Control Study

    Alessandra Colombini

    2015-02-01

    Full Text Available Recently, the FokI polymorphism (rs2228570 in the vitamin D receptor gene (VDR and conventional risk factors were associated with spine disorders in the Italian population, but without gender analysis. Two-hundred and sixty-seven patients (149 males, 118 females with lumbar spine disorders were assessed by magnetic resonance imaging (MRI and 254 (127 males, 127 females asymptomatic controls were enrolled. The exposure to putative risk factors was evaluated and FokI polymorphism was detected by PCR-restriction fragment length polymorphism (PCR-RFLP. An association between lumbar spine pathologies and higher than average age; overweight; family history; lower leisure physical activity; smoking habit; higher number of hours/day exposure to vibration and more sedentary or intense physical job demand was observed in male patients. In contrast, in females, only higher age, overweight, family history and lower leisure physical activity were risk factors. FF genotype was a 2-fold risk factor to develop discopathies and/or osteochondrosis concomitant with disc herniation for both gender patients, while heterozygous Ff was protective for females only. In males only ff genotype was protective for discopathies and/or osteochondrosis and F allele was a 2-fold risk factor for hernia; discopathies; discopathies and/or osteochondrosis. Sex-related differences in voluntary behaviors, exposure to environmental risks and genetic background could be crucial for a gender-differentiated management of patients with spine disorders.

  9. Gender Roles, Masculinity, And Militarism: Factors Contributing To Rape Being Used As A Weapon Of War In The Eastern Democratic Republic Of The Congo

    2014-04-01

    Messerschmidt, J. “ Hegemonic Masculinity : Rethinking the Concept.” Gender and Society 19, no.6 (2005). http://www.jstor.org.aufric.idm.oclc.org...AIR COMMAND AND STAFF COLLEGE AIR UNIVERSITY GENDER ROLES, MASCULINITY , AND MILITARISM: FACTORS CONTRIBUTING TO RAPE...the sexual violence against women. The factors that will be critically explored in this paper are the gender roles, masculinity , and militarism of the

  10. Antibody-induced activation of the epidermal growth factor receptor tyrosine kinase requires the presence of detergent

    Spaargaren, M.; Defize, L. H.; de Laat, S. W.; Boonstra, J.

    1990-01-01

    Activation of the epidermal growth factor receptor (EGF-R) tyrosine kinase was investigated in membrane preparations as well as intact A431 cells, using anti-EGF-R antibodies directed against extra- and intracellular receptor domains. In vitro assay conditions were mimicked on whole cells by a mild

  11. Blockade of epidermal growth factor receptors chemosensitizes breast cancer cells through up-regulation of Bnip3L

    Real, PJ; Benito, A; Cuevas, J; Berciano, MT; de Juan, A; Coffer, P; Gomez-Roman, J; Lafarga, M; Lopez-Vega, JM; Fernandez-Luna, JL

    2005-01-01

    Epidermal growth factor receptor-1 (EGFR) and EGFR-2 (HER2) have become major targets for cancer treatment. Blocking antibodies and small-molecule inhibitors are being used to silence the activity of these receptors in different tumors with varying efficacy. Thus, a better knowledge on the signaling

  12. Gender differences in factors associated with suicidal ideation and depressive symptoms among middle-aged workers in Japan.

    Sugawara, Norio; Yasui-Furukori, Norio; Sasaki, Giro; Tanaka, Osamu; Umeda, Takashi; Takahashi, Ippei; Danjo, Kazuma; Matsuzaka, Masashi; Kaneko, Sunao; Nakaji, Shigeyuki

    2013-01-01

    The purpose of this study was to assess middle-aged Japanese workers for possible gender differences in the risk factors associated with depressive symptoms and suicidal ideation. 5,878 workers (40-60 yr of age) (3,631 males and 2,247 females) were recruited from randomly selected companies in northern Japan. Demographic and lifestyle factors, suicidal ideation rate, and the data for the Brief Job Stress Questionnaire (BJSQ) and the Center for Epidemiologic Studies for Depression scale (CES-D) were obtained from the self-report questionnaires. After adjusting for possible confounding variables, marital status, absent of stress reduction technique and low job compatibility were significant independent risk factors for suicidal ideation among males. In females, marital status, feeling of insufficient sleep and absence of stress reduction techniques were significant independent risk factors after adjusting for all variables. Under the same adjustments, temporary employment also showed a protective effect against female suicidal ideation. In conclusion, our results suggest that factors related to suicidal ideation differed by gender. Different approaches for each gender might be useful in the development of suicide prevention programs. However, interpretation of work-related effects, such as temporary employment, interpersonal conflict and transportation industry, was hampered by lack of data concerning personal income, working hours and organizational commitment. Additional studies are needed to examine the longitudinal relationships between the risk factors associated with suicidal ideation and depressive symptoms.

  13. Suicide in Northern Ireland: An Analysis of Gender Differences in Demographic, Psychological, and Contextual Factors.

    O'Neill, Siobhan; Corry, Colette; McFeeters, Danielle; Murphy, Sam; Bunting, Brendan

    2016-01-01

    The circumstances surrounding death by suicide can give us insight into the factors affecting suicide risk in particular regions. This study examined gender and circumstances surrounding death by suicide in Northern Ireland from 2005 to 2011. The study analyzed 1,671 suicides (77% male and 23% female cases) using information contained from the coroner's files on suicides and undetermined deaths. Hanging was the most common method and more than one third of the deceased had prior suicide attempts. There was evidence of alcohol use in 41% of the cases. Only, 61% of cases had recorded adverse events; most had multiple and complex combinations of experiences. Relationship and interpersonal difficulties were the most common category of adverse event (40.3%). However, illness and bereavement, employment /financial crisis, and health problems were also common. One third of those who died by suicide were employed, compared with 50.3% who were not in employment. Just over half (50.1%) were known to have a mental health disorder. The results provide the first profile of deaths by suicide in Northern Ireland. They highlight the need to target people who have difficult life experiences in suicide prevention work, notably men, people with employment, financial and relationship crises, and those with mental disorders.

  14. Gender Disparities in Faculty Rank: Factors that Affect Advancement of Women Scientists at Academic Medical Centers

    Cristina M. López

    2018-04-01

    Full Text Available While a significant portion of women within academic science are employed within medical schools, women faculty in these academic medical centers are disproportionately represented in lower faculty ranks. The medical school setting is a critical case for both understanding and advancing women in basic sciences. This study highlights the findings from focus groups conducted with women faculty across Assistant, Associate, and Full Professor ranks (n = 35 in which they discussed barriers and facilitators for advancement of women basic scientists at an academic medical center. Qualitative analysis demonstrated several emergent themes that affect women’s advancement, including gendered expectation norms (e.g., good citizenship, volunteerism, work-life balance, mentorship/sponsorship, adoption of a team science approach, tenure process milestones, soft money research infrastructure, institution specific policies (or lack thereof, and operating within an MD-biased culture. These findings are compared with the extant literature of women scientists in STEM institutions. Factors that emerged from these focus groups highlight the need for evidence-based interventions in the often overlooked STEM arena of academic medical centers.

  15. Prognostic factors in advanced breast cancer: Race and receptor status are significant after development of metastasis.

    Ren, Zhiyong; Li, Yufeng; Shen, Tiansheng; Hameed, Omar; Siegal, Gene P; Wei, Shi

    2016-01-01

    Prognostic factors are well established in early-stage breast cancer (BC), but less well-defined in advanced disease. We analyzed 323 BC patients who had distant relapse during follow-up from 1997 to 2010 to determine the significant clinicopathologic factors predicting survival outcomes. By univariate analysis, race, tumor grade, estrogen and progesterone receptors (ER/PR) and HER2 status were significantly associated with overall survival (OS) and post-metastasis survival (PMS). Applying a Cox regression model revealed that all these factors remained significant for PMS, while race, tumor grade and HER2 were independent factors for OS. Tumor grade was the only significant factor for metastasis-free survival by univariate and multivariate analyses. Our findings demonstrated that being Caucasian, hormonal receptor positive (HR+) and HER2 positive (HER2+) were all associated with a decreased hazard of death and that patients with HR+/HER2+ tumors had superior outcomes to those with HR+/HER2- disease. Further, PR status held a prognostic value over ER, thus reflecting the biologic mechanism of the importance of the functional ER pathway and the heterogeneity in the response to endocrine therapy. These observations indicate that the patients' genetic makeup and the intrinsic nature of the tumor principally govern BC progression and prognosticate the long-term outcomes in advanced disease. Copyright © 2015 Elsevier GmbH. All rights reserved.

  16. Gender-specific effects of endogenous testosterone: female alpha-estrogen receptor-deficient C57Bl/6J mice develop glomerulosclerosis.

    Elliot, S J; Berho, M; Korach, K; Doublier, S; Lupia, E; Striker, G E; Karl, M

    2007-08-01

    Young female mice on a C57Bl/6J (B6) background are considered glomerulosclerosis (GS)-resistant but aging B6 mice develop mild GS. Estrogen deficiency accelerates while estrogen replacement retards GS in young sclerosis-prone oligosyndactyly mutant mice on an ROP background. To explore the effects of sex hormones on glomerular structure and function in the context of gender and genetic background, we studied mice in which the estrogen-receptor (ER) genes alpha- or -beta were deleted (alpha- or betaER knockout (KO)) and crossed into the B6 background. We also studied ovariectomized (Ovx) B6 mice given testosterone. Male and female betaERKO and male alphaERKO mice had no glomerular dysfunction at 9 months of age; however, alphaERKO female mice displayed albuminuria and GS. Ovx prevented glomerular dysfunction in alphaERKO female mice by eliminating endogenous testosterone production while exogenous testosterone induced GS in Ovx B6 mice. Androgen receptor (AR) expression and function was found in microdissected glomeruli and cultured mesangial cells. Testosterone compared to placebo increased both AR expression and TGF-beta1 mRNA levels in glomeruli isolated from female B6 mice. Estrogen deficiency had no deleterious effects on the glomeruli in B6 mice. Our study shows that genetic traits strongly influence the GS-promoting effects of estrogen deficiency while testosterone induces GS in a gender-specific manner.

  17. Differential role of tumor necrosis factor receptors in mouse brain inflammatory responses in cryolesion brain injury

    Quintana, Albert; Giralt, Mercedes; Rojas, Santiago

    2005-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is one of the mediators dramatically increased after traumatic brain injury that leads to the activation, proliferation, and hypertrophy of mononuclear, phagocytic cells and gliosis. Eventually, TNF-alpha can induce both apoptosis and necrosis via intracell......Tumor necrosis factor-alpha (TNF-alpha) is one of the mediators dramatically increased after traumatic brain injury that leads to the activation, proliferation, and hypertrophy of mononuclear, phagocytic cells and gliosis. Eventually, TNF-alpha can induce both apoptosis and necrosis via...... intracellular signaling. This cytokine exerts its functions via interaction with two receptors: type-1 receptor (TNFR1) and type-2 receptor (TNFR2). In this work, the inflammatory response after a freeze injury (cryolesion) in the cortex was studied in wild-type (WT) animals and in mice lacking TNFR1 (TNFR1 KO...... signaling also affected the expression of apoptosis/cell death-related genes (Fas, Rip, p53), matrix metalloproteinases (MMP3, MMP9, MMP12), and their inhibitors (TIMP1), suggesting a role of TNFR1 in extracellular matrix remodeling after injury. However, GDNF, NGF, and BDNF expression were not affected...

  18. Regulation of oxidative enzyme activity and eukaryotic elongation factor 2 in human skeletal muscle: influence of gender and exercise

    Roepstorff, Carsten; Schjerling, P.; Vistisen, Bodil

    2005-01-01

    AIM: To investigate gender-related differences in the responses of oxidative enzymes and eukaryotic elongation factor-2 (eEF2) to exercise. METHODS: The influence of exercise (90 min, 60%VO(2peak)) on citrate synthase (CS) and beta-hydroxyacyl-CoA dehydrogenase (HAD) activity and mRNA content...... expression and phosphorylation were unaffected by training status (NS). CONCLUSION: Basal transcriptional, translational, and/or post-translational control of CS and HAD seems to be gender-dependent. Also, gender differences in translation and/or post-translational protein modification of CS occur during...... not differ between females and males (NS). In females only, CS activity was enhanced (P differ between UT and ET but, nevertheless, CS activity was 56% higher in ET than in UT volunteers (P

  19. Expression, purification, and characterization of a diabody against the most important angiogenesis cell receptor: Vascular endothelial growth factor receptor 2

    Mahdi Behdani

    2012-01-01

    Full Text Available Antibodies and their derivative fragments have long been used as tools in a variety of applications, in fundamental research work, biotechnology, diagnosis, and therapy. Camels produce single heavy-chain antibodies (VHH in addition to usual antibodies. These minimal-sized binders are very robust and bind the antigen with high affinity in a monomeric state. Vascular endothelial growth factor recepror-2 (VEGFR2 is an important tumor-associated receptor that blockade of its signaling can lead to the inhibition of neovascularization and tumor metastasis. Here, we describe the construction, expression, and purification VEGFR2-specific Diabody. Two variable fragments of a same camel anti-VEGFR2 antibody were linked together by the upper hinge segment of antibody to make a diabody. We showed the ability of diabody to recognition of VEGFR2 on the cell surface by FACS. Diabodies can be produced in the low-cost prokaryotic expression system, so they are suitable molecules for diagnostic and therapeutic issues.

  20. Purification of rat intestinal receptor for intrinsic factor-vitamin B12 complex

    Yamada, Shoji; Itaya, Harutaka; Nakazawa, Osamu; Fukuda, Morimichi.

    1977-01-01

    The intrinsic factor (IF) in a rat gastric mucosal extract was bound efficiently to vitamin B 12 -sepharose without significant change in its nature to produce IF-vitamin B 12 -sepharose. The purification of the intestinal receptor for the IF-vitamin B 12 complex was performed by the affinity chromatography using the IF-vitamin B 12 -sepharose as the affinity adsorbent. As a result of admixing the gastric mucosal extract sample with B 12 -sepharose while stirring for 4 hours, the adsorption was performed without any break through. Further, it was recognized that the B 12 -bound protein purified by the affinity chromatography using B 12 -sepharose was not much changed as compared with that before purification. Furthermore, it was recognized that IF-B 12 -sepharose was able to be made by binding IF with B 12 -sepharose which was made by coupling B 12 with the market-available AH-sepharose. The IF-B 12 -sepharose was washed with buffer solution, and then was loaded with the small intestine mucosal extract. Thereafter, the receptor was eluted by making di-valent cation inert with the buffer solution. After the removal of EDTA in the eluted solution by dialysis, the activity of the receptor was measured. 48.5% of the receptor activity loaded was recovered by the elution with EDTA. The specific activity of the receptor represented by the final amount of B 12 (pg)/the amount of protein (mg) in the purified substance was 335 folds of the original activity. (Iwakiri, K.)

  1. Platelet activating factor receptor binding plays a critical role in jet fuel-induced immune suppression

    Ramos, Gerardo; Kazimi, Nasser; Nghiem, Dat X.; Walterscheid, Jeffrey P.; Ullrich, Stephen E.

    2004-01-01

    Applying military jet fuel (JP-8) or commercial jet fuel (Jet-A) to the skin of mice suppresses the immune response in a dose-dependant manner. The release of biological response modifiers, particularly prostaglandin E 2 (PGE 2 ), is a critical step in activating immune suppression. Previous studies have shown that injecting selective cyclooxygenase-2 inhibitors into jet fuel-treated mice blocks immune suppression. Because the inflammatory phospholipid mediator, platelet-activating factor (PAF), up-regulates cyclooxygenase-2 production and PGE 2 synthesis by keratinocytes, we tested the hypothesis that PAF-receptor binding plays a role in jet fuel-induced immune suppression. Treating keratinocyte cultures with PAF and/or jet fuel (JP-8 and Jet-A) stimulates PGE 2 secretion. Jet fuel-induced PGE 2 production was suppressed by treating the keratinocytes with specific PAF-receptor antagonists. Injecting mice with PAF, or treating the skin of the mice with JP-8, or Jet-A, induced immune suppression. Jet fuel-induced immune suppression was blocked when the jet fuel-treated mice were injected with PAF-receptor antagonists before treatment. Jet fuel treatment has been reported to activate oxidative stress and treating the mice with anti-oxidants (Vitamins C, or E or beta-hydroxy toluene), before jet fuel application, interfered with immune suppression. These findings confirm previous studies showing that PAF-receptor binding can modulate immune function. Furthermore, they suggest that PAF-receptor binding may be an early event in the induction of immune suppression by immunotoxic environmental agents that target the skin

  2. Does Performance in Digital Reading Relate to Computer Game Playing? A Study of Factor Structure and Gender Patterns in 15-Year-Olds' Reading Literacy Performance

    Rasmusson, Maria; Åberg-Bengtsson, Lisbeth

    2015-01-01

    Data from a Swedish PISA-sample were used (1) to identify a digital reading factor, (2) to investigate gender differences in this factor (if found), and (3) to explore how computer game playing might relate to digital reading performance and gender. The analyses were conducted with structural equation modeling techniques. In addition to an overall…

  3. A gender perspective on factors that influence outdoor recreational physical activity among the elderly

    Sjögren Katarina

    2010-06-01

    Full Text Available Abstract Background Physical activity (PA is part of a healthy lifestyle and prevents many chronic health problems, in addition to promoting mental health. PA performed outdoors has been found particularly good for promoting one's well-being. The aim of this study was to investigate the extent to which outdoor recreational PA was carried out during 1 year, and the factors influencing such activities from a gender perspective among persons ≥ 60 years of age. Methods This study included 999 individuals 60-96 years of age living in the south eastern part of Sweden. Data collection was carried out during the years of 2001-2003. We measured the amount of regular light and/or intense outdoor recreational PA performed during the last year and determined the probability of performing PA as a function of 10 variables covering individual and socioeconomic factors. Results Our results suggest that being independent physically and healthy enough to manage one's personal hygiene and having access to areas for country walks were the most important factors associated with the probability of engaging in outdoor recreational PA for both men and women. Despite the level of performance being almost equal for the sexes as two-thirds of both had performed outdoor recreational PA during the preceding year more factors, i.e., living alone, being unable to cover an unexpected cost, fear of being violated, and fear of falling, were associated with the possibilities of engaging in outdoor recreational PA among women. Also increasing age seems to affect activities among women negatively to a higher extent than men. Conclusion Men and women seem to have different opportunities and needs with respect to performing PA. These considerations do not seem to be sufficiently taken into account today and improvements could be made concerning e.g., health-promoting activities suggested to the elderly by healthcare personnel and spatial planning within society. Promoting outdoor

  4. Parenthood and factors that influence outdoor recreational physical activity from a gender perspective

    Hansson Eva

    2011-02-01

    Full Text Available Abstract Background A physically active life promotes both physical and mental health, increasing well-being and quality of life. Physical activity (PA performed outdoors has been found to be particularly good for promoting well-being. However, participation in PA can change during the course of a lifetime. Parenthood has been found to be a life event associated with decreased PA, especially among women, although studies in the field are sparse. The aim of this study was to investigate participation in outdoor recreational PA, and factors influencing participation among parents-to-be, with and without previous children, from a gender perspective. Methods This study included baseline data from parents-to-be, 224 women and 208 men, from the municipality of Karlskrona in south-east Sweden. Data collection was carried out during 2008-2009. We measured the self-reported amount of outdoor recreational PA undertaken during the last year and analysed the probability of participating in this PA using 25 variables covering individual and socioeconomic factors. Results Seventy-six per cent of the women and 65% of the men had participated in outdoor recreational PA, varying from several times per month to every day, over a 12-month period prior to one month before pregnancy. Participation in PA indoors and owning a dog or a horse emerged as the most important factors associated with the probability of participation in outdoor recreational PA. Men were affected by a greater number of factors than women, for example men who had a family situation that permitted outdoor recreational PA participated in activities to a greater extent than men without such a family situation. The physical aspect, i.e. improved physical condition, staying power and vigour, also played a significant role with regard to participation among men. Conclusions Becoming a parent is a life-changing event that affects participation in PA. By offering family-oriented PA choices that involve

  5. Flow cytometric detection of growth factor receptors in autografts and analysis of growth factor concentrations in autologous stem cell transplantation: possible significance for platelet recovery

    Schiødt, I; Jensen, Charlotte Harken; Kjaersgaard, E

    2000-01-01

    In order to improve prediction of hematopoietic recovery, we conducted a pilot study, analyzing the significance of growth factor receptor expression in autografts as well as endogenous growth factor levels in blood before, during and after stem cell transplantation. Three early acting (stem cell......-CSF receptor positive, CD34+ progenitor cells were measured by flow cytometry in the leukapheresis product used for transplantation in a subgroup of 15 patients (NHL, n = 8, MM, n = 7). Three factors were identified as having a significant impact on platelet recovery. First, the level of Tpo in blood...... at the time of the nadir (day +7). Second, the percentage of re-infused thrombopoietin receptor positive progenitors and finally, the percentage of Flt3 receptor positive progenitors. On the other hand, none of the analyzed factors significantly predicted myeloid or erythroid recovery. These findings need...

  6. Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism interacts with gender to influence cortisol responses to mental stress.

    Jiang, Rong; Babyak, Michael A; Brummett, Beverly H; Siegler, Ilene C; Kuhn, Cynthia M; Williams, Redford B

    2017-05-01

    Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with cortisol responses to stress with gender differences reported, although the findings are not entirely consistent. To evaluate the role of Val66Met genotype and gender on cortisol responses to stress, we conducted a 45-min mental stress protocol including four tasks and four rest periods. Blood cortisol was collected for assay immediately before and after each task and rest period. A significant two-way interaction of Val66Met genotype×gender (P=0.022) was observed on the total area under the curve (AUC), a total cortisol response over time, such that the Val/Val genotype was associated with a larger cortisol response to stress as compared to the Met group in women but not in men. Further contrast analyses between the Val/Val and Met group for each stress task showed a similar increased cortisol pattern among women Val/Val genotype but not among men. The present findings indicate the gender differences in the effect of Val66Met genotype on the cortisol responses to stress protocol, and extend the evidence for the importance of gender and the role of Val66Met in the modulation of stress reactivity and subsequent depression prevalence. Further studies and the underlying mechanism need to be investigated, which may provide an insight for prevention, intervention, and treatment strategies that target those at high risk. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. A Premature Termination of Human Epidermal Growth Factor Receptor Transcription in Escherichia coli

    Jihene Elloumi-Mseddi

    2014-01-01

    Full Text Available Our success in producing an active epidermal growth factor receptor (EGFR tyrosine kinase in Escherichia coli encouraged us to express the full-length receptor in the same host. Despite its large size, we were successful at producing the full-length EGFR protein fused to glutathione S-transferase (GST that was detected by Western blot analysis. Moreover, we obtained a majoritarian truncated GST-EGFR form detectable by gel electrophoresis and Western blot. This truncated protein was purified and confirmed by MALDI-TOF/TOF analysis to belong to the N-terminal extracellular region of the EGFR fused to GST. Northern blot analysis showed two transcripts suggesting the occurrence of a transcriptional arrest.

  8. Recent Advances of Colony-Stimulating Factor-1 Receptor (CSF-1R) Kinase and Its Inhibitors.

    El-Gamal, Mohammed I; Al-Ameen, Shahad K; Al-Koumi, Dania M; Hamad, Mawadda G; Jalal, Nouran A; Oh, Chang-Hyun

    2018-01-17

    Colony stimulation factor-1 receptor (CSF-1R), which is also known as FMS kinase, plays an important role in initiating inflammatory, cancer, and bone disorders when it is overstimulated by its ligand, CSF-1. Innate immunity, as well as macrophage differentiation and survival, are regulated by the stimulation of the CSF-1R. Another ligand, interlukin-34 (IL-34), was recently reported to activate the CSF-1R receptor in a different manner. The relationship between CSF-1R and microglia has been reviewed. Both CSF-1 antibodies and small molecule CSF-1R kinase inhibitors have now been tested in animal models and in humans. In this Perspective, we discuss the role of CSF-1 and IL-34 in producing cancer, bone disorders, and inflammation. We also review the newly discovered and improved small molecule kinase inhibitors and monoclonal antibodies that have shown potent activity toward CSF-1R, reported from 2012 until 2017.

  9. Mactosylceramide Prevents Glial Cell Overgrowth by Inhibiting Insulin and Fibroblast Growth Factor Receptor Signaling

    Gerdøe-Kristensen, Stine; Lund, Viktor K; Wandall, Hans H

    2017-01-01

    , in which the mannosyltransferase Egghead controls conversion of glucosylceramide (GlcCer) to mactosylceramide (MacCer). Lack of elongated GSL in egghead (egh) mutants causes overgrowth of subperineurial glia (SPG), largely due to aberrant activation of phosphatidylinositol 3-kinase (PI3K). However, to what...... of the Drosophila Insulin Receptor (InR) and the FGFR homolog Heartless (Htl) in wild type SPG, and is suppressed by inhibiting Htl and InR activity in egh. Knockdown of GlcCer synthase in the SPG fails to suppress glial overgrowth in egh nerves, and slightly promotes overgrowth in wild type, suggesting that RTK...... hyperactivation is caused by absence of MacCer and not by GlcCer accumulation. We conclude that an early product in GSL biosynthesis, MacCer, prevents inappropriate activation of Insulin and Fibroblast Growth Factor Receptors in Drosophila glia. This article is protected by copyright. All rights reserved....

  10. Detection and Quantification of Vascular Endothelial Growth Factor Receptor Tyrosine Kinases in Primary Human Endothelial Cells.

    Fearnley, Gareth W; Wheatcroft, Stephen B; Ponnambalam, Sreenivasan

    2015-01-01

    Proteins differ widely in their pattern of expression depending on organism, tissue, and regulation in response to changing conditions. In the mammalian vasculature, the endothelium responds to vascular endothelial growth factors (VEGFs) via membrane-bound receptor tyrosine kinases (VEGFRs) to modulate many aspects of vascular physiology including vasculogenesis, angiogenesis, and blood pressure. Studies on VEGFR biology are thus dependent on detecting expression levels in different cell types and evaluating how changes in protein levels correlate with changing conditions including circulating VEGF levels. Here, we present a robust immunoblot-based protocol for detecting and quantifying VEGFRs in human endothelial cells. Using internal and external standards, we can rapidly evaluate receptor copy number and assess how this is altered in response to the cellular environment.

  11. Gender-related factors influencing tuberculosis control in shantytowns: a qualitative study.

    Onifade, Dami A; Bayer, Angela M; Montoya, Rosario; Haro, Marie; Alva, Jessica; Franco, Jessica; Sosa, Rosario; Valiente, Betty; Valera, Enit; Ford, Carolyn M; Acosta, Colleen D; Evans, Carlton A

    2010-06-29

    There is evidence that female gender is associated with reduced likelihood of tuberculosis diagnosis and successful treatment. This study aimed to characterize gender-related barriers to tuberculosis control in Peruvian shantytowns. We investigated attitudes and experiences relating gender to tuberculosis using the grounded theory approach to describe beliefs amongst key tuberculosis control stakeholders. These issues were explored in 22 semi-structured interviews and in four focus group discussions with 26 tuberculosis patients and 17 healthcare workers. We found that the tuberculosis program was perceived not to be gender discriminatory and provided equal tuberculosis diagnostic and treatment care to men and women. This contrasted with stereotypical gender roles in the broader community context and a commonly expressed belief amongst patients and healthcare workers that female health inherently has a lower priority than male health. This belief was principally associated with men's predominant role in the household economy and limited employment for women in this setting. Women were also generally reported to experience the adverse psychosocial and economic consequences of tuberculosis diagnosis more than men. There was a common perception that women's tuberculosis care was of secondary importance to that of men. This reflected societal gender values and occurred despite apparent gender equality in care provision. The greatest opportunities for improving women's access to tuberculosis care appear to be in improving social, political and economic structures, more than tuberculosis program modification.

  12. Gender-related factors influencing tuberculosis control in shantytowns: a qualitative study

    Alva Jessica

    2010-06-01

    Full Text Available Abstract Background There is evidence that female gender is associated with reduced likelihood of tuberculosis diagnosis and successful treatment. This study aimed to characterize gender-related barriers to tuberculosis control in Peruvian shantytowns. Methods We investigated attitudes and experiences relating gender to tuberculosis using the grounded theory approach to describe beliefs amongst key tuberculosis control stakeholders. These issues were explored in 22 semi-structured interviews and in four focus group discussions with 26 tuberculosis patients and 17 healthcare workers. Results We found that the tuberculosis program was perceived not to be gender discriminatory and provided equal tuberculosis diagnostic and treatment care to men and women. This contrasted with stereotypical gender roles in the broader community context and a commonly expressed belief amongst patients and healthcare workers that female health inherently has a lower priority than male health. This belief was principally associated with men's predominant role in the household economy and limited employment for women in this setting. Women were also generally reported to experience the adverse psychosocial and economic consequences of tuberculosis diagnosis more than men. Conclusions There was a common perception that women's tuberculosis care was of secondary importance to that of men. This reflected societal gender values and occurred despite apparent gender equality in care provision. The greatest opportunities for improving women's access to tuberculosis care appear to be in improving social, political and economic structures, more than tuberculosis program modification.

  13. Receptors for insulin-like growth factors I and II: autoradiographic localization in rat brain and comparison to receptors for insulin

    Lesniak, M.A.; Hill, J.M.; Kiess, W.; Rojeski, M.; Pert, C.B.; Roth, J.

    1988-01-01

    Receptors for insulin-like growth factor I (IGF-I) in rat brain were visualized using autoradiography with [125I]IGF-I. The binding of the labeled peptide was competed for fully by high concentrations of unlabeled IGF-I. At intermediate concentrations of unlabeled peptide the binding of [125I]IGF-I was competed for by unlabeled IGF-I more effectively than by IGF-II or insulin, which is typical of receptors for IGF-I. Essentially every brain section shows specific binding of IGF-I, and the pattern of binding of IGF-I to its receptors correlated well with the cytoarchitectonic structures. In parallel studies we showed that [125I]IGF-II was bound to tissue sections of rat brain and that the binding was competed for by an excess of unlabeled IGF-II. However, intermediate concentrations of unlabeled peptides gave inconclusive results. To confirm that the binding of [125I]IGF-II was to IGF-II receptors, we showed that antibodies specific for the IGF-II receptor inhibited the binding of labeled IGF-II. Furthermore, the binding of the antibody to regions of the brain section, visualized by the application of [125I]protein-A, gave patterns indistinguishable from those obtained with [125I]IGF-II alone. Again, the binding was very widely distributed throughout the central nervous system, and the patterns of distribution corresponded well to the underlying neural structures. Densitometric analysis of the receptors enabled us to compare the distribution of IGF-I receptors with that of IGF-II receptors as well as retrospectively with that of insulin receptors

  14. Sensitivity to epidermal growth factor receptor tyrosine kinase inhibitors in males, smokers, and non-adenocarcinoma lung cancer in patients with EGFR mutations.

    Zeng, Zhu; Chen, Hua-Jun; Yan, Hong-Hong; Yang, Jin-Ji; Zhang, Xu-Chao; Wu, Yi-Long

    2013-09-27

    The demographical/clinical characteristics of being Asian, having an adenocarcinoma, being female, and being a "never-smoker" are regarded as favorable predictors for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) efficacy in non-small cell lung cancer (NSCLC) with unknown EGFR gene status. In this study, we examined the effects of the supposedly unfavorable clinical variables in EGFR-mutant patients. In total, 159 EGFR-mutant NSCLC patients' clinical features were correlated with progression-free survival (PFS), response rate (RR), and overall survival (OS). Multivariate analysis of clinical characteristics was performed using the Cox and logistic regression methods. There were 90 females (56.6%), 112 never-smokers (70.4%), and 153 patients with adenocarcinomas (96.2%). All patients were treated with EGFR-TKI, and 52.8% received TKI in a first-line setting. The median PFS of patients receiving first-line TKI was similar, regardless of gender (males vs females: 9.1 vs 9.7 months, p=0.793), smoking status (never-smokers vs smokers: 9.9 vs 9.1 months, p=0.570), or histology (adenocarcinoma vs non-adenocarcinoma: 9.7 vs 9.2 months, p=0.644). OS curves of first-line TKI-treated patients were also not associated with gender (p=0.722), smoking status (p=0.579), or histology (p=0.480). Similar results of PFS and OS were obtained for patients who received TKI beyond first-line. Multivariate analysis indicated that none of these clinical factors was an independent predictor of survival. The supposedly 'favorable' clinical factors of female gender, non-smoking status, and adenocarcinoma were not independent predictive factors for PFS or OS in this population of EGFR-mutant NSCLC patients.

  15. Changing rates of suicide ideation and attempts among Inuit youth: a gender-based analysis of risk and protective factors.

    Fraser, Sarah L; Geoffroy, Dominique; Chachamovich, Eduardo; Kirmayer, Laurence J

    2015-04-01

    Inuit in Canada currently suffer from one of the highest rates of suicide in the world. The objective of this study was to explore the prevalence of suicide ideations and attempts among 15-24 year olds living in Nunavik, Québec, and to explore risk and protective factors of suicide attempts as a function of gender. A cross-sectional survey was conducted in 2004 across Nunavik. Univariate and multivariate logistic regressions were conducted. A total of 22% of young males and 39% of females adults reported past suicidal attempts. Gender differences were observed in relation to associated risk and protective factors as well as degree of exposure to risk factors. Suicide prevention must include alcohol and drug prevention programs and rehabilitation services, interventions to reduce physical and sexual violence and their long-term impacts on Inuit youth, as well as exposure to culturally meaningful activities. © 2014 The American Association of Suicidology.

  16. receptores

    Salete Regina Daronco Benetti

    2006-01-01

    Full Text Available Se trata de un estudio etnográfico, que tuvo lo objetivo de interpretar el sistema de conocimiento y del significado atribuidos a la sangre referente a la transfusión sanguínea por los donadores y receptores de un banco de sangre. Para la colecta de las informaciones se observaron los participantes y la entrevista etnográfica se realizó el análisis de dominio, taxonómicos y temáticos. Los dominios culturales fueron: la sangre es vida: fuente de vida y alimento valioso; creencias religiosas: fuentes simbólicas de apoyos; donación sanguínea: un gesto colaborador que exige cuidarse, gratifica y trae felicidad; donación sanguínea: fuente simbólica de inseguridad; estar enfermo es una condición para realizar transfusión sanguínea; transfusión sanguínea: esperanza de vida; Creencias populares: transfusión sanguínea como riesgo para la salud; donadores de sangre: personas benditas; donar y recibir sangre: como significado de felicidad. Temática: “líquido precioso que origina, sostiene, modifica la vida, provoca miedo e inseguridad”.

  17. Advanced Research of Fibroblast Growth Factor Receptor 
in Non-small Cell Lung Cancer

    Dan PU

    2013-11-01

    Full Text Available Lung cancer is severely threatening human health. In recent years, the treatment for lung adenocarcinoma has made a great progress, targeted therapy has been widely applied in clinic, and benefits amount of patients. However, in squamous cell lung cancer, the incidence of epidermal growth factor receptor (EGFR gene mutant and ALK fusion gene are low,and targeted therapy like Tarceva and crizotinib, can hardly work. Since the fibroblast growth factors (fibroblast growth factor, FGF pathway is considered to be related to tumor cell proliferation, metastasis and angiogenesis, more and more researches proved the amplification of fibroblast growth factor receptor (FGFR in squamous cell lung cancer. Experiments in vivo and in vitro found that blocking FGF pathway could reduce the proliferation of tumor cells and inhibit metastasis. The FGF pathway might be a new target for treatment of squamous cell lung cancer. This article reviews the effect of FGFR in tumorigenesis,as well as the prospect as a therapeutic target in non-small cell lung cancer.

  18. Stimulation of LDL receptor activity in Hep-G2 cells by a serum factor(s)

    Ellsworth, J.L.; Brown, C.; Cooper, A.D.

    1988-01-01

    The regulation of low-density lipoprotein (LDL) receptor activity in the human hepatoma cell line Hep-G2 by serum components was examined. Incubation of dense monolayers of Hep-G2 cells with fresh medium containing 10% fetal calf serum (FM) produced a time-dependent increase in LDL receptor activity. Uptake and degradation of 125I-LDL was stimulated two- to four-fold, as compared with that of Hep-G2 cells cultured in the same media in which they had been grown to confluence (CM); the maximal 125I-LDL uptake plus degradation increased from 0.2 microgram/mg cell protein/4 h to 0.8 microgram/mg cell protein/4 h. In addition, a two-fold increase in cell surface binding of 125I-LDL to Hep-G2 cells was observed when binding was measured at 4 degrees C. There was no change in the apparent Kd. The stimulation of LDL receptor activity was suppressed in a concentration-dependent manner by the addition of cholesterol, as LDL, to the cell medium. In contrast to the stimulation of LDL receptor activity, FM did not affect the uptake or degradation of 125I-asialoorosomucoid. Addition of FM increased the protein content per dish, and DNA synthesis was stimulated approximately five-fold, as measured by [3H]thymidine incorporation into DNA; however, the cell number did not change. Cellular cholesterol biosynthesis was also stimulated by FM; [14C]acetate incorporation into unesterified and esterified cholesterol was increased approximately five-fold. Incubation of Hep-G2 cells with high-density lipoproteins (200 micrograms protein/ml) or albumin (8.0 mg/ml) in the absence of the serum factor did not significantly increase the total processed 125I-LDL. Stimulation of LDL receptor activity was dependent on a heat-stable, nondialyzable serum component that eluted in the inclusion volume of a Sephadex G-75 column

  19. Cloning of human tumor necrosis factor (TNF) receptor cDNA and expression of recombinant soluble TNF-binding protein

    Gray, P.W.; Barrett, K.; Chantry, D.; Turner, M.; Feldmann, M.

    1990-01-01

    The cDNA for one of the receptors for human tumor necrosis factor (TNF) has been isolated. This cDNA encodes a protein of 455 amino acids that is divided into an extracellular domain of 171 residues and a cytoplasmic domain of 221 residues. The extracellular domain has been engineered for expression in mammalian cells, and this recombinant derivative binds TNFα with high affinity and inhibits its cytotoxic activity in vitro. The TNF receptor exhibits similarity with a family of cell surface proteins that includes the nerve growth factor receptor, the human B-cell surface antigen CD40, and the rat T-cell surface antigen OX40. The TNF receptor contains four cysteine-rich subdomains in the extracellular portion. Mammalian cells transfected with the entire TNF receptor cDNA bind radiolabeled TNFα with an affinity of 2.5 x 10 -9 M. This binding can be competitively inhibited with unlabeled TNFα or lymphotoxin (TNFβ)

  20. Novel targeted approaches to treating biliary tract cancer: the dual epidermal growth factor receptor and ErbB-2 tyrosine kinase inhibitor NVP-AEE788 is more efficient than the epidermal growth factor receptor inhibitors gefitinib and erlotinib.

    Wiedmann, Marcus; Feisthammel, Jürgen; Blüthner, Thilo; Tannapfel, Andrea; Kamenz, Thomas; Kluge, Annett; Mössner, Joachim; Caca, Karel

    2006-08-01

    Aberrant activation of the epidermal growth factor receptor is frequently observed in neoplasia, notably in tumors of epithelial origin. Attempts to treat such tumors with epidermal growth factor receptor antagonists resulted in remarkable success in recent studies. Little is known, however, about the efficacy of this therapy in biliary tract cancer. Protein expression of epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 was assessed in seven human biliary tract cancer cell lines by immunoblotting. In addition, histological sections from 19 patients with extrahepatic cholangiocarcinoma were analyzed for epidermal growth factor receptor, ErbB-2 and vascular endothelial growth factor receptor-2 expression by immunohistochemistry. Moreover, we sequenced the cDNA products representing the entire epidermal growth factor receptor coding region of the seven cell lines, and searched for genomic epidermal growth factor receptor amplifications and polysomy by fluorescence in-situ hybridization. Cell growth inhibition by gefitinib erlotinib and NVP-AEE788 was studied in vitro by automated cell counting. In addition, the anti-tumoral effect of erlotinib and NVP-AEE788 was studied in a chimeric mouse model. The anti-tumoral drug mechanism in this model was assessed by MIB-1 antibody staining, terminal deoxynucleotidyl transfer-mediated dUTP nick end-labelling assay, von Willebrand factor staining, and immunoblotting for p-p42/44 (p-Erk1/2, p-MAPK) and p-AKT. Immunoblotting revealed expression of epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 in all biliary tract cancer cell lines. EGFR was detectable in six of 19 (32%) extrahepatic human cholangiocarcinoma tissue samples, ErbB-2 in 16 of 19 (84%), and vascular endothelial growth factor receptor-2 in nine of 19 (47%). Neither epidermal growth factor receptor mutations nor amplifications or polysomy were found in the seven biliary tract cancer

  1. Does Depth Matter? Factors Affecting Choice of Vulvoplasty Over Vaginoplasty as Gender-Affirming Genital Surgery for Transgender Women.

    Jiang, David; Witten, Jonathan; Berli, Jens; Dugi, Daniel

    2018-04-26

    Gender-affirming vaginoplasty aims to create the external female genitalia (vulva) as well as the internal vaginal canal; however, not all patients desire nor can safely undergo vaginal canal creation. Our objective is to describe the factors influencing patient choice or surgeon recommendation of vulvoplasty and to assess the patient's satisfaction with this choice. Gender-affirming genital surgery consults were reviewed from March 2015 until December 2017, and patients scheduled for or who had completed vulvoplasty were interviewed by telephone. We report demographic data and the reasons for choosing vulvoplasty as gender-affirming surgery for patients who either completed or were scheduled for surgery, in addition to patient reports of satisfaction with choice of surgery, satisfaction with the surgery itself, and sexual activity after surgery. In total, 486 patients were seen in consultation for trans-feminine gender-affirming genital surgery: 396 requested vaginoplasty and 39 patients requested vulvoplasty. 30 Patients either completed or are scheduled for vulvoplasty. Vulvoplasty patients were older and had higher body mass index than those seeking vaginoplasty. The majority (63%) of the patients seeking vulvoplasty chose this surgery despite no contra-indications to vaginoplasty. The remaining patients had risk factors leading the surgeon to recommend vulvoplasty. Of those who completed surgery, 93% were satisfied with the surgery and their decision for vulvoplasty. Vulvoplasty creates the external appearance of female genitalia without creation of a neovaginal canal; it is associated with high satisfaction and low decision regret. This is the first study of factors impacting a patient's choice of or a surgeon's recommendation for vulvoplasty over vaginoplasty as gender-affirming genital surgery; it also is the first reported series of patients undergoing vulvoplasty only. Limitations of this study include its retrospective nature, non-validated questions

  2. Adenovirus E4-ORF1 Dysregulates Epidermal Growth Factor and Insulin/Insulin-Like Growth Factor Receptors To Mediate Constitutive Myc Expression

    Kong, Kathleen; Kumar, Manish; Taruishi, Midori; Javier, Ronald T.

    2015-01-01

    The E4-ORF1 protein encoded by human adenovirus stimulates viral replication in human epithelial cells by binding and activating cellular phosphatidylinositol 3-kinase (PI3K) at the plasma membrane and cellular Myc in the nucleus. In this study, we showed that E4-ORF1 hijacks the tyrosine kinase activities of cellular epidermal growth factor receptor (EGFR) and insulin receptor (InsR)/insulin-like growth factor receptor 1 (IGF1R), as well as the lipid kinase activity of PI3K, to mediate const...

  3. Mammary tumors that become independent of the type I insulin-like growth factor receptor express elevated levels of platelet-derived growth factor receptors

    Campbell Craig I

    2011-11-01

    Full Text Available Abstract Background Targeted therapies are becoming an essential part of breast cancer treatment and agents targeting the type I insulin-like growth factor receptor (IGF-IR are currently being investigated in clinical trials. One of the limitations of targeted therapies is the development of resistant variants and these variants typically present with unique gene expression patterns and characteristics compared to the original tumor. Results MTB-IGFIR transgenic mice, with inducible overexpression of the IGF-IR were used to model mammary tumors that develop resistance to IGF-IR targeting agents. IGF-IR independent mammary tumors, previously shown to possess characteristics associated with EMT, were found to express elevated levels of PDGFRα and PDGFRβ. Furthermore, these receptors were shown to be inversely expressed with the IGF-IR in this model. Using cell lines derived from IGF-IR-independent mammary tumors (from MTB-IGFIR mice, it was demonstrated that PDGFRα and to a lesser extent PDGFRβ was important for cell migration and invasion as RNAi knockdown of PDGFRα alone or PDGFRα and PDGFRβ in combination, significantly decreased tumor cell migration in Boyden chamber assays and suppressed cell migration in scratch wound assays. Somewhat surprisingly, concomitant knockdown of PDGFRα and PDGFRβ resulted in a modest increase in cell proliferation and a decrease in apoptosis. Conclusion During IGF-IR independence, PDGFRs are upregulated and function to enhance tumor cell motility. These results demonstrate a novel interaction between the IGF-IR and PDGFRs and highlight an important, therapeutically relevant pathway, for tumor cell migration and invasion.

  4. Culture beats gender? The importance of controlling for identity- and parenting-related risk factors in adolescent psychopathology.

    Seiffge-Krenke, Inge; Persike, Malte; Besevegis, Elias; Chau, Cecilia; Karaman, Neslihan Güney; Lannegrand-Willems, Lyda; Lubiewska, Katharzyna; Rohail, Iffat

    2018-02-01

    This study analyzed the unique effects of gender and culture on psychopathology in adolescents from seven countries after controlling for factors which might have contributed to variations in psychopathology. In a sample 2259 adolescents (M = 15 years; 54% female) from France, Germany, Turkey, Greece, Peru, Pakistan, and Poland identity stress, coping with identity stress, maternal parenting (support, psychological control, anxious rearing) and psychopathology (internalizing, externalizing and total symptomatology) were assessed. Due to variations in stress perception, coping style and maternal behavior, these covariates were partialed out before the psychopathology scores were subjected to analyses of variance with gender and country as factors. These analyses leveled out the main effect of country and revealed country-specific gender effects. In four countries, males reported higher internalizing and total symptomatology than females. Partialing out the covariates resulted in a clearer picture of culture-specific and gender-dependent effects on psychopathology, which is helpful in designing interventions. Copyright © 2017 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  5. Gender as a risk factor for adverse intraoperative and postoperative outcomes of elective pancreatectomy.

    Mazmudar, Aditya; Vitello, Dominic; Chapman, Mackenzie; Tomlinson, James S; Bentrem, David J

    2017-02-01

    Patient selection remains paramount when developing and adopting quality-based assessment and reimbursement models, and enhanced recovery protocols. Gender is a patient characteristic known before surgery which can inform risk stratification. Our aim was to evaluate the effect of gender on intraoperative blood transfusions, operative time, length of hospital stay, estimated blood loss (EBL) as well as postoperative surgical site infections (SSIs), and mortality. Patients undergoing elective pancreatectomy from 2005 to 2013 were identified in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) and Northwestern institutional databases. Multivariable analyses were conducted to identify the association between gender and these outcomes. Analyses demonstrated that male gender was independently associated with blood transfusion (OR 1.23), operative time >6 hr (OR 1.76), length of stay greater than 11 days (OR 1.17), and all-type SSIs (OR 1.17), especially superficial SSIs (OR 1.15) and organ space SSIs (OR 1.18). Analysis of the institutional cohort found that male gender was independently associated with increased odds of EBL > 1 L for Whipple procedures (OR 2.85). Male gender is a significant predictor of increased operative time, length of stay, transfusions, EBL > 1L, as well as postoperative organ space surgical site infections in these patients. J. Surg. Oncol. 2017;115:131-136. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Self-renewal of human embryonic stem cells requires insulin-like growth factor-1 receptor and ERBB2 receptor signaling

    Wang, Linlin; Schulz, Thomas C.; Sherrer, Eric S.; Dauphin, Derek S.; Shin, Soojung; Nelson, Angelique M.; Ware, Carol B.; Zhan, Mei; Song, Chao-Zhong; Chen, Xiaoji; Brimble, Sandii N.; McLean, Amanda; Galeano, Maria J.; Uhl, Elizabeth W.; D'Amour, Kevin A.; Chesnut, Jonathan D.; Rao, Mahendra S.

    2007-01-01

    Despite progress in developing defined conditions for human embryonic stem cell (hESC) cultures, little is known about the cell-surface receptors that are activated under conditions supportive of hESC self-renewal. A simultaneous interrogation of 42 receptor tyrosine kinases (RTKs) in hESCs following stimulation with mouse embryonic fibroblast (MEF) conditioned medium (CM) revealed rapid and prominent tyrosine phosphorylation of insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R); less prominent tyrosine phosphorylation of epidermal growth factor receptor (EGFR) family members, including ERBB2 and ERBB3; and trace phosphorylation of fibroblast growth factor receptors. Intense IGF1R and IR phosphorylation occurred in the absence of MEF conditioning (NCM) and was attributable to high concentrations of insulin in the proprietary KnockOut Serum Replacer (KSR). Inhibition of IGF1R using a blocking antibody or lentivirus-delivered shRNA reduced hESC self-renewal and promoted differentiation, while disruption of ERBB2 signaling with the selective inhibitor AG825 severely inhibited hESC proliferation and promoted apoptosis. A simple defined medium containing an IGF1 analog, heregulin-1β (a ligand for ERBB2/ERBB3), fibroblast growth factor-2 (FGF2), and activin A supported long-term growth of multiple hESC lines. These studies identify previously unappreciated RTKs that support hESC proliferation and self-renewal, and provide a rationally designed medium for the growth and maintenance of pluripotent hESCs. PMID:17761519

  7. Age- and Gender-Specific Prevalence of Risk Factors in Patients with First-Ever Ischemic Stroke in China

    Xiao-ying Yao

    2012-01-01

    Full Text Available Background. Evidences are accumulating that age and gender have great impact on the distribution of stroke risk factors. Such data are lacking in Chinese population. Methods. 1027 patients with first-ever ischemic stroke (IS were recruited and divided into young adult (80 years groups according to stroke onset ages. Vascular risk factors were collected and compared among groups. Results. Female patients were globally older than male patients at stroke onset and having higher prevalence of diabetes mellitus (DM, heart diseases, and atrial fibrillation (AF. However, females were less likely to drink heavily or smoke than males. Young patients had a much higher proportion of smoking and drinking than middle-aged and very old patients and the highest family history of hypertension, while very old patients had the highest prevalence of heart diseases and AF but lowest proportion of positive family history of vascular diseases. Hypertension and DM were equally frequent among three groups. Conclusion. Our study showed that vascular risk factors had a specific age and gender distribution pattern in Chinese IS patients. Secondary prevention strategy should emphasize on the control of different risk factors based on patient’s age and gender.

  8. Involvement of macrophage migration inhibitory factor and its receptor (CD74) in human breast cancer.

    Richard, Vincent; Kindt, Nadège; Decaestecker, Christine; Gabius, Hans-Joachim; Laurent, Guy; Noël, Jean-Christophe; Saussez, Sven

    2014-08-01

    Macrophage migration inhibitory factor (MIF) and its receptor CD74 appear to be involved in tumorigenesis. We evaluated, by immunohistochemical staining, the tissue expression and distribution of MIF and CD74 in serial sections of human invasive breast cancer tumor specimens. The serum MIF level was also determined in breast cancer patients. We showed a significant increase in serum MIF average levels in breast cancer patients compared to healthy individuals. MIF tissue expression, quantified by a modified Allred score, was strongly increased in carcinoma compared to tumor-free specimens, in the cancer cells and in the peritumoral stroma, with fibroblasts the most intensely stained. We did not find any significant correlation with histoprognostic factors, except for a significant inverse correlation between tumor size and MIF stromal positivity. CD74 staining was heterogeneous and significantly decreased in cancer cells but increased in the surrounding stroma, namely in lymphocytes, macrophages and vessel endothelium. There was no significant variation according to classical histoprognostic factors, except that CD74 stromal expression was significantly correlated with triple-negative receptor (TRN) status and the absence of estrogen receptors. In conclusion, our data support the concept of a functional role of MIF in human breast cancer. In addition to auto- and paracrine effects on cancer cells, MIF could contribute to shape the tumor microenvironment leading to immunomodulation and angiogenesis. Interfering with MIF effects in breast tumors in a therapeutic perspective remains an attractive but complex challenge. Level of co-expression of MIF and CD74 could be a surrogate marker for efficacy of anti-angiogenic drugs, particularly in TRN breast cancer tumor.

  9. Tumor necrosis factor receptor-associated factor 6 (TRAF6) participates in anti-lipopolysaccharide factors (ALFs) gene expression in mud crab.

    Sun, Wan-Wei; Zhang, Xin-Xu; Wan, Wei-Song; Wang, Shu-Qi; Wen, Xiao-Bo; Zheng, Huai-Ping; Zhang, Yue-Ling; Li, Sheng-Kang

    2017-02-01

    Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a key cytoplasm signal adaptor that mediates signals activated by tumor necrosis factor receptor (TNFR) superfamily and the Interleukin-1 receptor/Toll-like receptor (IL-1/TLR) superfamily. The full-length 2492 bp TRAF6 (Sp-TRAF6) from Scylla paramamosain contains 1800 bp of open reading frame (ORF) encoding 598 amino acids, including an N-terminal RING-type zinc finger, two TRAF-type zinc fingers and a conserved C-terminal meprin and TRAF homology (MATH) domain. Multiple alignment analysis shows that the putative amino acid sequence of Sp-TRAf6 has highest identity of 88% with Pt-TRAF6 from Portunus trituberculatus, while the similarity of Sp-TRAF6 with other crustacean sequences was 54-55%. RT-PCR analysis indicated that Sp-TRAF6 transcripts were predominantly expressed in the hepatopancreas and stomach, whereas it was barely detected in the heart and hemocytes in our study. Moreover, Sp-TRAF6 transcripts were significantly up-regulated after Vibrio parahemolyticus and LPS challenges. RNA interference assay was carried out used by siRNA to investigate the genes expression patterns regulated by Sp-TRAF6. The qRT-PCR results showed that silencing Sp-TRAF6 gene could inhibit SpALF1, SpALF2, SpALF5 and SpALF6 expression in hemocytes, while inhibit SpALF1, SpALF3, SpALF4, SpALF5 and SpALF6 expression in hepatopancreas. Taken together, the acute-phase response to immune challenges and the inhibition of SpALFs gene expression indicate that Sp-TRAF6 plays an important role in host defense against pathogen invasions via regulation of ALF gene expression in S. paramamosain. Copyright © 2016. Published by Elsevier Ltd.

  10. A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus.

    Alejo, Alí; Ruiz-Argüello, M Begoña; Ho, Yin; Smith, Vincent P; Saraiva, Margarida; Alcami, Antonio

    2006-04-11

    Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis.

  11. Orexin–Corticotropin-Releasing Factor Receptor Heteromers in the Ventral Tegmental Area as Targets for Cocaine

    Navarro, Gemma; Quiroz, César; Moreno-Delgado, David; Sierakowiak, Adam; McDowell, Kimberly; Moreno, Estefanía; Rea, William; Cai, Ning-Sheng; Aguinaga, David; Howell, Lesley A.; Hausch, Felix; Cortés, Antonio; Mallol, Josefa; Casadó, Vicent; Lluís, Carme; Canela, Enric I.

    2015-01-01

    Release of the neuropeptides corticotropin-releasing factor (CRF) and orexin-A in the ventral tegmental area (VTA) play an important role in stress-induced cocaine-seeking behavior. We provide evidence for pharmacologically significant interactions between CRF and orexin-A that depend on oligomerization of CRF1 receptor (CRF1R) and orexin OX1 receptors (OX1R). CRF1R–OX1R heteromers are the conduits of a negative crosstalk between orexin-A and CRF as demonstrated in transfected cells and rat VTA, in which they significantly modulate dendritic dopamine release. The cocaine target σ1 receptor (σ1R) also associates with the CRF1R–OX1R heteromer. Cocaine binding to the σ1R–CRF1R–OX1R complex promotes a long-term disruption of the orexin-A–CRF negative crosstalk. Through this mechanism, cocaine sensitizes VTA cells to the excitatory effects of both CRF and orexin-A, thus providing a mechanism by which stress induces cocaine seeking. PMID:25926444

  12. Orexin-corticotropin-releasing factor receptor heteromers in the ventral tegmental area as targets for cocaine.

    Navarro, Gemma; Quiroz, César; Moreno-Delgado, David; Sierakowiak, Adam; McDowell, Kimberly; Moreno, Estefanía; Rea, William; Cai, Ning-Sheng; Aguinaga, David; Howell, Lesley A; Hausch, Felix; Cortés, Antonio; Mallol, Josefa; Casadó, Vicent; Lluís, Carme; Canela, Enric I; Ferré, Sergi; McCormick, Peter J

    2015-04-29

    Release of the neuropeptides corticotropin-releasing factor (CRF) and orexin-A in the ventral tegmental area (VTA) play an important role in stress-induced cocaine-seeking behavior. We provide evidence for pharmacologically significant interactions between CRF and orexin-A that depend on oligomerization of CRF1 receptor (CRF1R) and orexin OX1 receptors (OX1R). CRF1R-OX1R heteromers are the conduits of a negative crosstalk between orexin-A and CRF as demonstrated in transfected cells and rat VTA, in which they significantly modulate dendritic dopamine release. The cocaine target σ1 receptor (σ1R) also associates with the CRF1R-OX1R heteromer. Cocaine binding to the σ1R-CRF1R-OX1R complex promotes a long-term disruption of the orexin-A-CRF negative crosstalk. Through this mechanism, cocaine sensitizes VTA cells to the excitatory effects of both CRF and orexin-A, thus providing a mechanism by which stress induces cocaine seeking. Copyright © 2015 the authors 0270-6474/15/356639-15$15.00/0.

  13. Receptors for insulin-like growth factor II (IGF-II) in the rat kidney glomerulus

    Haskell, J.F.; Pillion, D.J.; Meezan, E.

    1986-01-01

    Renal glomeruli were isolated by a technique involving renal perfusion with a solution containing magnetic iron oxide particles, followed by homogenization, sieving and isolation over a strong magnet. Isolated glomeruli were treated with 1% Triton X-100 to solubilize plasma membrane components while insoluble basement membrane components were removed by centrifugation. [ 125 I]Insulin-like growth factor-II (IGF-II) binding to this preparation was competitively inhibited by increasing amounts of unlabelled IGF-II, with 50% inhibition of binding observed at an IGF-II concentration of 1 ng/ml. [ 125 I]IGF-II was covalently cross-linked to its receptor with disuccinimidyl suberate in two tissues known to contain IGF-II receptors, the rat chondrosarcoma chondrocyte and the rat kidney tubule, as well as in rat renal glomeruli. In all three cases, a specific high-molecular weight (Mr = 255,000) band could be identified on autoradiograms of dodecyl sulfate polyacrylamide gels. These results indicate that the rat glomerulus contains a high-affinity receptor for IGF-II. This finding is consistent with the hypothesis that IGF-II plays a role in glomerular growth and differentiation

  14. Nuclear functions and subcellular trafficking mechanisms of the epidermal growth factor receptor family

    2012-01-01

    Accumulating evidence suggests that various diseases, including many types of cancer, result from alteration of subcellular protein localization and compartmentalization. Therefore, it is worthwhile to expand our knowledge in subcellular trafficking of proteins, such as epidermal growth factor receptor (EGFR) and ErbB-2 of the receptor tyrosine kinases, which are highly expressed and activated in human malignancies and frequently correlated with poor prognosis. The well-characterized trafficking of cell surface EGFR is routed, via endocytosis and endosomal sorting, to either the lysosomes for degradation or back to the plasma membrane for recycling. A novel nuclear mode of EGFR signaling pathway has been gradually deciphered in which EGFR is shuttled from the cell surface to the nucleus after endocytosis, and there, it acts as a transcriptional regulator, transmits signals, and is involved in multiple biological functions, including cell proliferation, tumor progression, DNA repair and replication, and chemo- and radio-resistance. Internalized EGFR can also be transported from the cell surface to several intracellular compartments, such as the Golgi apparatus, the endoplasmic reticulum, and the mitochondria, in addition to the nucleus. In this review, we will summarize the functions of nuclear EGFR family and the potential pathways by which EGFR is trafficked from the cell surface to a variety of cellular organelles. A better understanding of the molecular mechanism of EGFR trafficking will shed light on both the receptor biology and potential therapeutic targets of anti-EGFR therapies for clinical application. PMID:22520625

  15. Specific, high affinity receptors for insulin-like growth factor II in the rat kidney glomerulus

    Haskell, J.F.; Pillion, D.J.; Meezan, E.

    1988-01-01

    Rat renal glomeruli were isolated by a technique involving kidney perfusion with a solution containing magnetic iron oxide particles, followed by homogenization, sieving, and concentration over a strong magnet. Isolated glomeruli were treated with 1% Triton X-100 to solubilize plasma membrane components, while insoluble basement membrane components were removed by centrifugation. [ 125 I]Insulin-like growth factor II (IGF-II) binding to this preparation was competitively inhibited by increasing amounts of unlabeled IGF-II, with 50% inhibition at an IGF-II concentration of 1 ng/ml. [ 125 I]IGF-II was covalently cross-linked with disuccinimidyl suberate to its receptor in rat renal glomeruli and a specific high mol wt (255,000) band could be identified on autoradiograms of dodecyl sulfate-polyacrylamide gels. [ 125 I]IGF-II binding and cross-linking to this band was inhibited by a polyclonal antibody against the type II IGF receptor. These results demonstrate for the first time that the isolated rat renal glomerulus contains a high affinity receptor for IGF-II

  16. A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus

    Alejo, Alí; Ruiz-Argüello, M. Begoña; Ho, Yin; Smith, Vincent P.; Saraiva, Margarida; Alcami, Antonio

    2006-01-01

    Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis. PMID:16581912

  17. Receptor activator of nuclear factor kappa B ligand and osteoprotegerin levels in gingival crevicular fluid

    Sarlati, Fatemeh; Sattari, Mandana; Razzaghi, Shilan; Nasiri, Malihe

    2012-01-01

    Background: Osteoclastogenesis is coordinated by the interaction of three members of the tumor necrosis factor (TNF) superfamily: Osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B ligand (RANKL)/receptor activator of nuclear factor kappa B (RANK). The aim of this study was to investigate RANKL and OPG levels, and their relative ratio in gingival crevicular fluid (GCF) of patients with chronic and aggressive periodontitis, as well as healthy controls. Materials and Methods: In this analytical study, GCF was obtained from healthy (n = 10), mild chronic periodontitis (n = 18), moderate chronic periodontitis (n = 18), severe chronic periodontitis (n = 20), and generalized aggressive periodontitis (n = 20) subjects. RANKL and OPG concentrations were measured by enzyme-linked immunosorbent assay. Statistical tests used were Kruskal–Wallis test, Mann–Whitney U rank sum test, and Spearman's rank correlation analysis. The level of statistical significance was set at P chronic periodontitis (mild, moderate, severe), and aggressive periodontitis (P = 0.41). There was statistically significant correlation between the concentration of sRANKL and Clinical Attachment Level (CAL) in moderate chronic periodontitis patients (R = 0.48, P = 0.04). There was also negative correlation between OPG concentration and CAL in moderate chronic periodontitis patients, although not significant (R = −0.13). Conclusion: RANKL was prominent in periodontitis sites, especially in moderate periodontitis patients, whereas OPG was not detectable in some diseased sites with bleeding on probing, supporting the role of these two molecules in the bone loss developed in this disease. PMID:23559954

  18. Involvement of growth factors and their receptors in radon-induced rat lung tumors

    Leung, F.C.; Dagle, G.E.; Cross, F.T.

    1992-01-01

    In this paper we examine the role of growth factors (GF) and their receptors (GFR) in radon-induced rat lung tumors. Inhalation exposure of radon and its daughters induced lung tumors in rats, but the molecule/cellular mechanisms are not known. Recent evidence suggests that GF/GFR play a critical role in the growth and development of lung cancer in humans and animals. We have developed immunocytochemical methods for identifying sites of production and action of GF/GFR at the cellular level; for example, the avidin-biotin horseradish peroxidase technique. In radon-induced rat epidermoid carcinomas, epidermal growth factor (EGF), EGF-receptors (EGF-R), transforming growth factor alpha (TGF-α), and bombesin were found to be abnormally expressed. These abnormal expressions, mainly associated with epidermoid carcinomas of the lung, were not found in any other lung tumor types. Our data suggest that EGF, EGF-R, TGF-α, and bombesin are involved in radon oncogenesis in rat lungs, especially in epidermoid carcinomas, possibly through the autocrine/paracrine pathway

  19. Eps15 is recruited to the plasma membrane upon epidermal growth factor receptor activation and localizes to components of the endocytic pathway during receptor internalization

    Torrisi, M R; Lotti, L V; Belleudi, F

    1999-01-01

    Eps15 is a substrate for the tyrosine kinase of the epidermal growth factor receptor (EGFR) and is characterized by the presence of a novel protein:protein interaction domain, the EH domain. Eps15 also stably binds the clathrin adaptor protein complex AP-2. Previous work demonstrated an essential...

  20. Divergent effects of insulin-like growth factor-1 receptor expression on prognosis of estrogen receptor positive versus triple negative invasive ductal breast carcinoma

    Hartog, Hermien; Horlings, Hugo M; van der Vegt, Bert; Kreike, Bas; Ajouaou, Abderrahim; van de Vijver, Marc J; Boezen, Hendrika; de Bock, Geertruida H; van der Graaf, Wilhelmina; Wesseling, Jelle

    2011-01-01

    The insulin-like growth factor type 1 receptor (IGF1R) is involved in progression of breast cancer and resistance to systemic treatment. Targeting IGF1R signaling may, therefore, be beneficial in systemic treatment. We report the effect of IGF1R expression on prognosis in invasive ductal breast

  1. P55 tumour necrosis factor receptor in bone marrow-derived cells promotes atherosclerosis development in low-density lipoprotein receptor knock-out mice

    Xanthoulea, Sofia; Gijbels, Marion J. J.; van der Made, Ingeborg; Mujcic, Hilda; Thelen, Melanie; Vergouwe, Monique N.; Ambagts, Matheus H. C.; Hofker, Marten H.; de Winther, Menno P. J.

    2008-01-01

    Tumour necrosis factor (TNF) is a pivotal pro-inflammatory cytokine with a clear pathogenic role in many chronic inflammatory diseases, and p55 TNF receptor (TNFR) mediates the majority of TNF responses. The aim of the current study was to investigate the role of p55 TNFR expression in bone

  2. The aryl hydrocarbon receptor and estrogen receptor alpha differentially modulate nuclear factor erythroid-2-related factor 2 transactivation in MCF-7 breast cancer cells

    Lo, Raymond; Matthews, Jason, E-mail: jason.matthews@utoronto.ca

    2013-07-15

    Nuclear factor erythroid-2-related factor 2 (NRF2; NFE2L2) plays an important role in mediating cellular protection against reactive oxygen species. NRF2 signaling is positively modulated by the aryl hydrocarbon receptor (AHR) but inhibited by estrogen receptor alpha (ERα). In this study we investigated the crosstalk among NRF2, AHR and ERα in MCF-7 breast cancer cells treated with the NRF2 activator sulforaphane (SFN), a dual AHR and ERα activator, 3,3′-diindolylmethane (DIM), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 17β-estradiol (E2). SFN-dependent increases in NADPH-dependent oxidoreductase 1 (NQO1) and heme oxygenase I (HMOX1) mRNA levels were significantly reduced after co-treatment with E2. E2-dependent repression of NQO1 and HMOX1 was associated with increased ERα but reduced p300 recruitment and reduced histone H3 acetylation at both genes. In contrast, DIM + SFN or TCDD + SFN induced NQO1 and HMOX1 mRNA expression to levels higher than SFN alone, which was prevented by RNAi-mediated knockdown of AHR. DIM + SFN but not TCDD + SFN also induced recruitment of ERα to NQO1 and HMOX1. However, the presence of AHR at NQO1 and HMOX1 restored p300 recruitment and histone H3 acetylation, thereby reversing the ERα-dependent repression of NRF2. Taken together, our study provides further evidence of functional interplay among NRF2, AHR and ERα signaling pathways through altered p300 recruitment to NRF2-regulated target genes. - Highlights: • We examined crosstalk among ERα, AHR, and NRF2 in MCF-7 breast cancer cells. • AHR enhanced the mRNA expression levels of two NRF2 target genes – HMOX1 and NQO1. • ERα repressed HMOX1 and NQO1 expression via decreased histone acetylation. • AHR prevented ERα-dependent repression of HMOX1 and NQO1.

  3. Lack of Evidence for a Direct Interaction of Progranulin and Tumor Necrosis Factor Receptor-1 and Tumor Necrosis Factor Receptor-2 From Cellular Binding Studies

    Isabell Lang

    2018-04-01

    Full Text Available Progranulin (PGRN is a secreted anti-inflammatory protein which can be processed by neutrophil proteases to various granulins. It has been reported that at least a significant portion of the anti-inflammatory effects of PGRN is due to direct high affinity binding to tumor necrosis factor receptor-1 (TNFR1 and TNFR2 and inhibition of tumor necrosis factor (TNF-induced TNFR1/2 signaling. Two studies failed to reproduce the interaction of TNFR1 and TNFR2 with PGRN, but follow up reports speculated that this was due to varying experimental circumstances and/or the use of PGRN from different sources. However, even under consideration of these speculations, there is still a striking discrepancy in the literature between the concentrations of PGRN needed to inhibit TNF signaling and the concentrations required to block TNF binding to TNFR1 and TNFR2. While signaling events induced by 0.2–2 nM of TNF have been efficiently inhibited by low, near to equimolar concentrations (0.5–2.5 nM of PGRN in various studies, the reported inhibitory effects of PGRN on TNF-binding to TNFR1/2 required a huge excess of PGRN (100–1,000-fold. Therefore, we investigated the effect of PGRN on TNF binding to TNFR1 and TNFR2 in highly sensitive cellular binding studies. Unlabeled TNF inhibited >95% of the specific binding of a Gaussia princeps luciferase (GpL fusion protein of TNF to TNFR1 and TNFR2 and blocked binding of soluble GpL fusion proteins of TNFR1 and TNFR2 to membrane TNF expressing cells to >95%, too. Purified PGRN, however, showed in both assays no effect on TNF–TNFR1/2 interaction even when applied in huge excess. To rule out that tags and purification- or storage-related effects compromise the potential ability of PGRN to bind TNF receptors, we directly co-expressed PGRN, and as control TNF, in TNFR1- and TNFR2-expressing cells and looked for binding of GpL-TNF. While expression of TNF strongly inhibited binding of GpL-TNF to TNFR1/2, co

  4. The aryl hydrocarbon receptor and estrogen receptor alpha differentially modulate nuclear factor erythroid-2-related factor 2 transactivation in MCF-7 breast cancer cells

    Lo, Raymond; Matthews, Jason

    2013-01-01

    Nuclear factor erythroid-2-related factor 2 (NRF2; NFE2L2) plays an important role in mediating cellular protection against reactive oxygen species. NRF2 signaling is positively modulated by the aryl hydrocarbon receptor (AHR) but inhibited by estrogen receptor alpha (ERα). In this study we investigated the crosstalk among NRF2, AHR and ERα in MCF-7 breast cancer cells treated with the NRF2 activator sulforaphane (SFN), a dual AHR and ERα activator, 3,3′-diindolylmethane (DIM), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 17β-estradiol (E2). SFN-dependent increases in NADPH-dependent oxidoreductase 1 (NQO1) and heme oxygenase I (HMOX1) mRNA levels were significantly reduced after co-treatment with E2. E2-dependent repression of NQO1 and HMOX1 was associated with increased ERα but reduced p300 recruitment and reduced histone H3 acetylation at both genes. In contrast, DIM + SFN or TCDD + SFN induced NQO1 and HMOX1 mRNA expression to levels higher than SFN alone, which was prevented by RNAi-mediated knockdown of AHR. DIM + SFN but not TCDD + SFN also induced recruitment of ERα to NQO1 and HMOX1. However, the presence of AHR at NQO1 and HMOX1 restored p300 recruitment and histone H3 acetylation, thereby reversing the ERα-dependent repression of NRF2. Taken together, our study provides further evidence of functional interplay among NRF2, AHR and ERα signaling pathways through altered p300 recruitment to NRF2-regulated target genes. - Highlights: • We examined crosstalk among ERα, AHR, and NRF2 in MCF-7 breast cancer cells. • AHR enhanced the mRNA expression levels of two NRF2 target genes – HMOX1 and NQO1. • ERα repressed HMOX1 and NQO1 expression via decreased histone acetylation. • AHR prevented ERα-dependent repression of HMOX1 and NQO1.

  5. Co-inhibition of epidermal growth factor receptor and insulin-like growth factor receptor 1 enhances radiosensitivity in human breast cancer cells

    Li, Ping; Veldwijk, Marlon R; Zhang, Qing; Li, Zhao-bin; Xu, Wen-cai; Fu, Shen

    2013-01-01

    Over-expression of epidermal growth factor receptor (EGFR) or insulin-like growth factor-1 receptor (IGF-1R) have been shown to closely correlate with radioresistance of breast cancer cells. This study aimed to investigate the impact of co-inhibition of EGFR and IGF-1R on the radiosensitivity of two breast cancer cells with different profiles of EGFR and IGF-1R expression. The MCF-7 (EGFR +/−, IGF-1R +++) and MDA-MB-468 (EGFR +++, IGF-1R +++) breast cancer cell lines were used. Radiosensitizing effects were determined by colony formation assay. Apoptosis and cell cycle distribution were measured by flow cytometry. Phospho-Akt and phospho-Erk1/2 were quantified by western blot. In vivo studies were conducted using MDA-MB-468 cells xenografted in nu/nu mice. In MDA-MB-468 cells, the inhibition of IGF-1R upregulated the p-EGFR expression. Either EGFR (AG1478) or IGF-1R inhibitor (AG1024) radiosensitized MDA-MB-468 cells. In MCF-7 cells, radiosensitivity was enhanced by AG1024, but not by AG1478. Synergistical radiosensitizing effect was observed by co-inhibition of EGFR and IGF-1R only in MDA-MB-468 cells with a DMF 10% of 1.90. The co-inhibition plus irradiation significantly induced more apoptosis and arrested the cells at G0/G1 phase in MDA-MB-468 cells. Only co-inhibition of EGFR and IGF-1R synergistically diminished the expression of p-Akt and p-Erk1/2 in MDA-MB-468 cells. In vivo studies further verified the radiosensitizing effects by co-inhibition of both pathways in a MDA-MB-468 xenograft model. Our data suggested that co-inhibition of EGFR and IGF-1R synergistically radiosensitized breast cancer cells with both EGFR and IGF-1R high expression. The approach may have an important therapeutic implication in the treatment of breast cancer patients with high expression of EGFR and IGF-1R

  6. Regulation of the ligand-dependent activation of the epidermal growth factor receptor by calmodulin

    Li, Hongbing; Panina, Svetlana; Kaur, Amandeep

    2012-01-01

    Calmodulin (CaM) is the major component of calcium signaling pathways mediating the action of various effectors. Transient increases in the intracellular calcium level triggered by a variety of stimuli lead to the formation of Ca2+/CaM complexes, which interact with and activate target proteins....... In the present study the role of Ca2+/CaM in the regulation of the ligand-dependent activation of the epidermal growth factor receptor (EGFR) has been examined in living cells. We show that addition of different cell permeable CaM antagonists to cultured cells or loading cells with a Ca2+ chelator inhibited...

  7. Strong association of epidermal growth factor receptor status with breast cancer FDG uptake

    Lee, Joohee; Moon, Seung Hwan; Hyun, Seung Hyup; Cho, Young Seok; Choi, Joon Young; Kim, Byung-Tae; Lee, Kyung-Han [Sungkyunkwan University School of Medicine, Department of Nuclear Medicine, Samsung Medical Center, Seoul (Korea, Republic of); Lee, Eun Jeong [Seoul Medical Center, Department of Nuclear Medicine, Seoul (Korea, Republic of); Kim, Seokhwi [Sungkyunkwan University School of Medicine, Department of Pathology, Samsung Medical Center, Seoul (Korea, Republic of)

    2017-08-15

    Imaging tumor FDG uptake could complement breast cancer biomarkers of risk and treatment response. Although breast cancer FDG uptake is reputedly influenced by major biomarker states, the role of epidermal growth factor receptor (EGFR) expression remains largely unexplored. This is a retrospective study that included 499 patients with primary breast cancer at initial presentation. Tumor FDG uptake was measured on pretreatment PET/CT as maximum standardized uptake value (SUVmax), and biomarkers were assessed by immunohistochemistry of tumor tissue. Regression analysis was performed for predictors of high tumor FDG uptake (SUVmax ≥ 8.6). SUVmax was higher in ER- (36.5%; 11.2 ± 6.0 vs. 8.3 ± 5.3), PR- (42.3%; 10.9 ± 6.0 vs. 8.2 ± 5.2), and triple-negative tumors (19.8%; 12.0 ± 6.9 vs. 8.7 ± 5.2; all p < 0.0001). EGFR expression (28.5%) was more frequent in ER-, PR-, triple-negative, cytokeratin 5/6 (CK5/6) + and mutant P53 (mP53) + tumors (all p < 0.0001). EGFR+ was associated with higher SUVmax among all tumors (11.9 ± 6.0 vs. 8.3 ± 5.3), ER- tumors (p < 0.0001), PR- and + tumors (p < 0.0001 and 0.027), hormone receptor- and + tumors (p < 0.0001 and 0.004), human epidermal growth factor receptor 2 (HER2)- and + tumors (p < 0.0001 and 0.006), non-triple negative tumors (p < 0.0001), CK5/6- and + tumors (p = 0.021 and <0.0001), and mP53- and + tumors (p < 0.0001 and 0.008). Tumors had high FDG uptake in 73.2% of EGFR+ and 40.6% of EGFR- tumors. On regression analysis, significant multivariate predictors of high tumor FDG uptake were large size, EGFR+ and CK5/6+ for the entire subjects, and EGFR+ and CK5/6+ for ER- and hormone receptor negative subgroups. High FDG uptake was able to sub-stratify EGFR+ tumors that were more likely to be ER- and CK5/6+, and EGFR- tumors more likely to be mP53 +. Primary breast tumor FDG uptake is strongly influenced by EGFR status beyond that by other major biomarkers including hormone receptor and HER2 status, and EGFR

  8. Rab GTPases Regulate Endothelial Cell Protein C Receptor-Mediated Endocytosis and Trafficking of Factor VIIa

    Nayak, Ramesh C.; Keshava, Shiva; Esmon, Charles T.; Pendurthi, Usha R.; Rao, L. Vijaya Mohan

    2013-01-01

    Recent studies have established that factor VIIa (FVIIa) binds to the endothelial cell protein C receptor (EPCR). FVIIa binding to EPCR may promote the endocytosis of this receptor/ligand complex. Rab GTPases are known to play a crucial role in the endocytic and exocytic pathways of receptors or receptor/ligand complexes. The present study was undertaken to investigate the role of Rab GTPases in the intracellular trafficking of EPCR and FVIIa. CHO-EPCR cells and human umbilical vein endothelial cells (HUVEC) were transduced with recombinant adenoviral vectors to express wild-type, constitutively active, or dominant negative mutant of various Rab GTPases. Cells were exposed to FVIIa conjugated with AF488 fluorescent probe (AF488-FVIIa), and intracellular trafficking of FVIIa, EPCR, and Rab proteins was evaluated by immunofluorescence confocal microscopy. In cells expressing wild-type or constitutively active Rab4A, internalized AF488-FVIIa accumulated in early/sorting endosomes and its entry into the recycling endosomal compartment (REC) was inhibited. Expression of constitutively active Rab5A induced large endosomal structures beneath the plasma membrane where EPCR and FVIIa accumulated. Dominant negative Rab5A inhibited the endocytosis of EPCR-FVIIa. Expression of constitutively active Rab11 resulted in retention of accumulated AF488-FVIIa in the REC, whereas expression of a dominant negative form of Rab11 led to accumulation of internalized FVIIa in the cytoplasm and prevented entry of internalized FVIIa into the REC. Expression of dominant negative Rab11 also inhibited the transport of FVIIa across the endothelium. Overall our data show that Rab GTPases regulate the internalization and intracellular trafficking of EPCR-FVIIa. PMID:23555015

  9. The social patterns of a biological risk factor for disease: race, gender, socioeconomic position, and C-reactive protein.

    Herd, Pamela; Karraker, Amelia; Friedman, Elliot

    2012-07-01

    Understand the links between race and C-reactive protein (CRP), with special attention to gender differences and the role of class and behavioral risk factors as mediators. This study utilizes the National Social Life, Health, and Aging Project data, a nationally representative study of older Americans aged 57-85 to explore two research questions. First, what is the relative strength of socioeconomic versus behavioral risk factors in explaining race differences in CRP levels? Second, what role does gender play in understanding race differences? Does the relative role of socioeconomic and behavioral risk factors in explaining race differences vary when examining men and women separately? When examining men and women separately, socioeconomic and behavioral risk factor mediators vary in their importance. Indeed, racial differences in CRP among men aged 57-74 are little changed after adjusting for both socioeconomic and behavioral risk factors with levels 35% higher for black men as compared to white men. For women aged 57-74, however, behavioral risk factors explain 30% of the relationship between race and CRP. The limited explanatory power of socioeconomic position and, particularly, behavioral risk factors, in elucidating the relationship between race and CRP among men, signals the need for research to examine additional mediators, including more direct measures of stress and discrimination.

  10. Gender-specific risk factors for virologic failure in KwaZulu-Natal: automobile ownership and financial insecurity.

    Hare, Anna Q; Ordóñez, Claudia E; Johnson, Brent A; Del Rio, Carlos; Kearns, Rachel A; Wu, Baohua; Hampton, Jane; Wu, Peng; Sunpath, Henry; Marconi, Vincent C

    2014-11-01

    We sought to examine which socioeconomic indicators are risk factors for virologic failure among HIV-1 infected patients receiving antiretroviral therapy (ART) in KwaZulu-Natal, South Africa. A case-control study of virologic failure was conducted among patients recruited from the outpatient clinic at McCord Hospital in Durban, South Africa between October 1, 2010 and June 30, 2012. Cases were those failing first-line ART, defined as viral load >1,000 copies/mL. Univariate logistic regression was performed on sociodemographic data for the outcome of virologic failure. Variables found significant (p ownership was a risk factor among males, while variables of financial insecurity (unemployment, non-spouse family paying for care, staying with family) were risk factors for women. In this cohort, financial insecurity among women and automobile ownership among men were risk factors for virologic failure. Risk factor differences between genders demonstrate limitations of generalized risk factor analysis.

  11. Expression of Vascular Endothelial Growth Factor Receptors in Benign Vascular Lesions of the Orbit: A Case Series.

    Atchison, Elizabeth A; Garrity, James A; Castillo, Francisco; Engman, Steven J; Couch, Steven M; Salomão, Diva R

    2016-01-01

    Vascular lesions of the orbit, although not malignant, can cause morbidity because of their location near critical structures in the orbit. For the same reason, they can be challenging to remove surgically. Anti-vascular endothelial growth factor (VEGF) drugs are increasingly being used to treat diseases with prominent angiogenesis. Our study aimed to determine to what extent VEGF receptors and their subtypes are expressed on selected vascular lesions of the orbit. Retrospective case series of all orbital vascular lesions removed by one of the authors (JAG) at the Mayo Clinic. A total of 52 patients who underwent removal of vascular orbital lesions. The pathology specimens from the patients were retrieved, their pathologic diagnosis was confirmed, demographic and clinical information were gathered, and sections from vascular tumors were stained with vascular endothelial growth factor receptor (VEGFR), vascular endothelial growth factor receptor type 1 (VEGFR1), vascular endothelial growth factor receptor type 2 (VEGFR2), and vascular endothelial growth factor receptor type 3 (VEGFR3). The existence and pattern of staining with VEGF and its subtypes on these lesions. There were 28 specimens of venous malformations, 4 capillary hemangiomas, 7 lymphatic malformations, and 6 lymphaticovenous malformations. All samples stained with VEGF, 55% stained with VEGFR1, 98% stained with VEGFR2, and 96% stained with VEGFR3. Most (94%) of the VEGFR2 staining was diffuse. Most orbital vascular lesions express VEGF receptors, which may suggest a future target for nonsurgical treatment. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  12. Risk Factors for Smoking in Rural Women: The Role of Gender-Based Sexual and Intimate Partner Violence

    Nemeth, Julianna M.; Bonomi, Amy E.; Lu, Bo; Lomax, Richard G.; Wewers, Mary Ellen

    2016-01-01

    Background: Women living in Ohio Appalachia experience cervical cancer at disproportionately high rates. Intimate partner and sexual gender-based violence (GBV) and smoking are independent risk factors for cervical cancer and interact to heighten risk. Appalachian women smoke at higher rates than other Ohio women, but little is known about GBV exposure in the region. The purpose of this study was to establish prevalence of women's exposure to GBV in Ohio Appalachia and examine the association...

  13. Adenosine inhibits neutrophil vascular endothelial growth factor release and transendothelial migration via A2B receptor activation.

    Wakai, A

    2012-02-03

    The effects of adenosine on neutrophil (polymorphonuclear neutrophils; PMN)-directed changes in vascular permeability are poorly characterized. This study investigated whether adenosine modulates activated PMN vascular endothelial growth factor (vascular permeability factor; VEGF) release and transendothelial migration. PMN activated with tumour necrosis factor-alpha (TNF-alpha, 10 ng\\/mL) were incubated with adenosine and its receptor-specific analogues. Culture supernatants were assayed for VEGF. PMN transendothelial migration across human umbilical vein endothelial cell (HUVEC) monolayers was assessed in vitro. Adhesion molecule receptor expression was assessed flow cytometrically. Adenosine and some of its receptor-specific analogues dose-dependently inhibited activated PMN VEGF release. The rank order of potency was consistent with the affinity profile of human A2B receptors. The inhibitory effect of adenosine was reversed by 3,7-dimethyl-1-propargylxanthine, an A2 receptor antagonist. Adenosine (100 microM) or the A2B receptor agonist 5\\'-N-ethylcarboxamidoadenosine (NECA, 100 microM) significantly reduced PMN transendothelial migration. However, expression of activated PMN beta2 integrins and HUVEC ICAM-1 were not significantly altered by adenosine or NECA. Adenosine attenuates human PMN VEGF release and transendothelial migration via the A2B receptor. This provides a novel target for the modulation of PMN-directed vascular hyperpermeability in conditions such as the capillary leak syndrome.

  14. Fibroblast growth factor 21, fibroblast growth factor receptor 1, and β-Klotho expression in bovine growth hormone transgenic and growth hormone receptor knockout mice.

    Brooks, Nicole E; Hjortebjerg, Rikke; Henry, Brooke E; List, Edward O; Kopchick, John J; Berryman, Darlene E

    Although growth hormone (GH) and fibroblast growth factor 21 (FGF21) have a reported relationship, FGF21 and its receptor, fibroblast growth factor receptor 1 (FGFR1) and cofactor β-Klotho (KLB), have not been analyzed in chronic states of altered GH action. The objective of this study was to quantify circulating FGF21 and tissue specific expression of Fgf21, Fgfr1, and Klb in mice with modified GH action. Based on previous studies, we hypothesized that bovine GH transgenic (bGH) mice will be FGF21 resistant and GH receptor knockout (GHR-/-) mice will have normal FGF21 action. Seven-month-old male bGH mice (n=9) and wild type (WT) controls (n=10), and GHR-/- mice (n=8) and WT controls (n=8) were used for all measurements. Body composition was determined before dissection, and tissue weights were measured at the time of dissection. Serum FGF21 levels were evaluated by ELISA. Expression of Fgf21, Fgfr1, and Klb mRNA in white adipose tissue (AT), brown AT, and liver were evaluated by reverse transcription quantitative PCR. As expected, bGH mice had increased body weight (p=3.70E -8 ) but decreased percent fat mass (p=4.87E -4 ). Likewise, GHR-/- mice had decreased body weight (p=1.78E -10 ) but increased percent fat mass (p=1.52E -9 ), due to increased size of the subcutaneous AT depot when normalized to body weight (p=1.60E -10 ). Serum FGF21 levels were significantly elevated in bGH mice (p=0.041) and unchanged in GHR-/- mice (p=0.88). Expression of Fgf21, Fgfr1, and Klb mRNA in white AT and liver were downregulated or unchanged in both bGH and GHR-/- mice. The only exception was Fgf21 expression in brown AT of GHR-/-, which trended toward increased expression (p=0.075). In accordance with our hypothesis, we provide evidence that circulating FGF21 is increased in bGH animals, but remains unchanged in GHR-/- mice. Downregulation or no change in Fgf21, Fgfr1, and Klb expression are seen in white AT, brown AT, and liver of bGH and GHR-/- mice when compared to their

  15. Market Openness and Culture as Factors that Shape the Gender Gap: a Comparative Study of Urban Latin America and East Asia (1960-2000)

    Enriqueta Camps

    2013-01-01

    In this paper we present: 1. The available data on comparative gender inequality at the macroeconomic level and 2. Gender inequality measures at the microeconomic and case study level. We see that market openness has a significant effect on the narrowing of the human capital gender gap. Globalization and market openness stand as factors that improve both the human capital endowments of women and their economic position. But we also see that the effects of culture and religious beliefs are ver...

  16. Gender differences in natural language factors of subjective intoxication in college students: an experimental vignette study.

    Levitt, Ash; Schlauch, Robert C; Bartholow, Bruce D; Sher, Kenneth J

    2013-12-01

    Examining the natural language college students use to describe various levels of intoxication can provide important insight into subjective perceptions of college alcohol use. Previous research (Levitt et al., Alcohol Clin Exp Res 2009; 33: 448) has shown that intoxication terms reflect moderate and heavy levels of intoxication and that self-use of these terms differs by gender among college students. However, it is still unknown whether these terms similarly apply to other individuals and, if so, whether similar gender differences exist. To address these issues, the current study examined the application of intoxication terms to characters in experimentally manipulated vignettes of naturalistic drinking situations within a sample of university undergraduates (n = 145). Findings supported and extended previous research by showing that other-directed applications of intoxication terms are similar to self-directed applications and depend on the gender of both the target and the user. Specifically, moderate intoxication terms were applied to and from women more than men, even when the character was heavily intoxicated, whereas heavy intoxication terms were applied to and from men more than women. The findings suggest that gender differences in the application of intoxication terms are other-directed as well as self-directed and that intoxication language can inform gender-specific prevention and intervention efforts targeting problematic alcohol use among college students. Copyright © 2013 by the Research Society on Alcoholism.

  17. Male gender and sonographic gall bladder wall thickness: important predictable factors for empyema and gangrene in acute cholecystitis

    Khan, M.L.U.; Jawed, M.; Shaikh, U.; Abbassi, M.R.

    2014-01-01

    Objective: To underline the status of male gender and gall bladder wall thickness as significant risk factors for acute cholecystitis complications. Methods: The retrospective study, with purposive sampling of the patients of acute cholecystits in age above 18 years, who were operated within 10 days of onset of symptoms, was conducted at the Department of Surgery, Dow University Hospital, Karachi, by reviewing the patients' medical record from March 2010 to August 2012. Correlation of incidence of acute cholecystitis complications (empyema and gangrene) to male gender and to the sonographic gall bladder wall thickness more than 4.5mm was analysed using SPSS 16. Result: Out of 62 patients, 8 (13%) patients had gangrene while 10 (16.12%) had empyema. Overall, there were 21 (33.87%) males in the study. Ten (47.6%) of the male patients developed empyema or gangrene of the gall bladder as a complication of acute cholecystitis. Of the 41 (66.12%) female patients, only 8 (19.5%) developed these complications. There were 22 (35.48%) cases of gall bladders with sonographic wall thickness more than 4.5mm who were operated for acute cholecystitis. Of them, 16 (72.7%) had empyema or gangrene. Conclusion: Male gender and sonographic gall bladder wall thickness more than 4.5mm were statistically significant risk factors for suspicion of complicated acute cholecystitis (empyema/gangrene) and by using these risk factors, we can prioritise patients for surgery in the emergency room. (author)

  18. Gender differences of the influential factors on the mental health condition of teachers in the A university.

    Kataoka, Mika; Ozawa, Kazuhiro; Tanioka, Tetsuya; Okuda, Kikuko; Chiba, Shinichi; Tomotake, Masahito; King, Beth

    2015-01-01

    The purpose of this research was to investigate the gender differences of the influential factors on the mental health condition among university teachers in the A university in Japan. A questionnaire survey was mailed to 924 university teachers in Japan, with a survey return rate of 43.8% (N=405). The General Health Questionnaire 28 (GHQ-28), Multidimensional Scale of Perceived Social Support (MSPSS), the Japanese version of the Brief Coping Orientation to Problems Experienced (COPE) and the Work Situation Questionnaire (WSQ) developed by the authors were administered to subjects. The GHQ-28 total score and all of sub-score of the woman was significantly higher than men. In the correlated factor of mental health, level of job satisfaction and job control, social support of significant others was observed in the both sexes. However, gender differences was observed in the coping style. Some copings including self-distraction and self-blame were related to the men, but the woman was related to the substance use. University teachers had some gender differences in the factors affecting their mental health condition. In order to improve university teacher's mental health condition, it is necessary to increase their level of job satisfaction and feeling of job control in the workplace. Especially, it was considered women's coping using substance use was important.

  19. Gender Differences in Patients' Beliefs About Biological, Environmental, Behavioral, and Psychological Risk Factors in a Cardiac Rehabilitation Program

    Mozhgan Saeidi

    2014-11-01

    Full Text Available Introduction: There are significant gender differences in the epidemiology and presentation of cardiovascular diseases (CVDs, physiological aspects of CVDs, response to diagnostic tests or interventions, and prevalence or incidence of the associated risk factors. Considering the independent influence of gender on early dire consequences of such diseases, this study was conducted to investigate gender differences in patients' beliefs about biological, environmental, behavioral, and psychological risk factors in a cardiac rehabilitation program. Materials and Methods: This study has cross sectional design. The sample was composed of 775 patients referred to cardiac rehabilitation unit in Imam Ali Hospital in Kermanshah, Iran. The data were collected using clinical interview and patients’ medical records. The data were analyzed using descriptive statistics such as mean, standard deviation, and chi-square test​​. To do the statistical analysis, SPSS version 20 was utilized. Results: As the results indicated, there was a significant difference between the beliefs of men and women about risk factors of heart disease (X2= 48.36; P

  20. Adolescent eating disorder behaviours and cognitions: gender-specific effects of child, maternal and family risk factors

    Micali, N.; De Stavola, B.; Ploubidis, G.; Simonoff, E.; Treasure, J.; Field, A. E.

    2015-01-01

    Background Eating disorder behaviours begin in adolescence. Few longitudinal studies have investigated childhood risk and protective factors. Aims To investigate the prevalence of eating disorder behaviours and cognitions and associated childhood psychological, physical and parental risk factors among a cohort of 14-year-old children. Method Data were collected from 6140 boys and girls aged 14 years. Gender-stratified models were used to estimate prospective associations between childhood body dissatisfaction, body mass index (BMI), self-esteem, maternal eating disorder and family economic disadvantage on adolescent eating disorder behaviours and cognitions. Results Childhood body dissatisfaction strongly predicted eating disorder cognitions in girls, but only in interaction with BMI in boys. Higher self-esteem had a protective effect, particularly in boys. Maternal eating disorder predicted body dissatisfaction and weight/shape concern in adolescent girls and dieting in boys. Conclusions Risk factors for eating disorder behaviours and cognitions vary according to gender. Prevention strategies should be gender-specific and target modifiable predictors in childhood and early adolescence. PMID:26206865

  1. Gender-related differences in cardiometabolic risk factors and lifestyle behaviors in treatment-seeking adolescents with severe obesity.

    Barstad, Lisa Ha; Júlíusson, Pétur B; Johnson, Line Kristin; Hertel, Jens Kristoffer; Lekhal, Samira; Hjelmesæth, Jøran

    2018-02-14

    Obesity during adolescence is associated with cardiovascular mortality in adulthood. The adverse obesity-related cardiometabolic risk profile is already observed in adolescence. We aimed to examine possible gender differences in cardiometabolic risk factors and lifestyle behaviors among adolescents with severe obesity, hypothesizing that boys would have both a higher prevalence of the metabolic syndrome as well as less healthy lifestyle behaviors than girls. Cross-sectional study of treatment-seeking adolescents with severe obesity who attended the Morbid Obesity Centre at Vestfold Hospital Trust and who were consecutively enrolled in the Vestfold Register of Obese Children between September 2009 and September 2015. A total of 313 adolescents aged 12 to 18 years were recruited, whereof 268 subjects (49% boys) completed a food and activity frequency questionnaire and were included in the analysis. Mean (SD) age, BMI and BMI SDS were 15 (1.6) years, 38.6 (5.9) kg/m 2 and 3.5 (0.6). Levels of LDL cholesterol, fasting insulin and glucose and diastolic blood pressure (DBP) did not differ between genders. Compared to girls, boys had significantly higher triglycerides (p = 0.037) and systolic blood pressure (SBP) (p = 0.003), as well as lower HDL cholesterol (p = 0.002). The metabolic syndrome was present in 27% of the boys and 19% of the girls (p = 0.140), and the prevalence of high DBP, dyslipidemia and dysglycemia also did not differ significantly between genders. The prevalence of high SBP was higher in boys than in girls (19% vs. 9%, p = 0.021). Gender was associated with a number of lifestyle habits, as a larger proportions of boys had higher screen time (p = 0.032), more regular breakfast eating (p = 0.023), higher intake of sugar sweetened soda (p = 0.036), and lower intake of vegetables than girls (p = 0.011). By contrast, physical activity level and intake of fruit and berries did not differ between genders. Male treatment

  2. Dietary Risk Factors by Race/Ethnicity, Age-Group, and Gender in a Representative Sample of US Older Adults.

    Vaccaro, J A; Huffman, F G

    2017-01-01

    To explore the relationships among ethnicity/race, gender, demographics, age-group and dietary health in a nationally representative sample of older adults. Cross-sectional study. Data for this study were collected by interview in the mobile examination centers from the National Health and Nutrition Examination Surveys, 2011 - 2012. U.S. representative sample of adults aged 55 years and older (N = 1860) from five ethnic/racial groups. All participants read, understood, and signed informed consent forms under data collection procedures by trained individuals. Sociodemographics were collected by trained interviewers using a general questionnaire. Food groups were determined by 24-hour recall using the validated USDA Automated Multiple-Pass Method. Data were presented by cross-tabulation and logistic regression to investigate relationships among race/ethnicity, gender, and age groups. Over 70% of older adults failed to consume 2.75 cups of combined fruits and vegetables. Other Hispanics (Hispanics excluding Mexican Americans) had higher Odds of sugar-containing food consumption compared to non-Hispanic Whites (adjusted model). Being older and female were protective factors for over-consumption of sugar. Older Americans are not meeting dietary guidelines and there are differences by gender and ethnicity. Since diet has been associated with quality of life and medical costs, public health interventions can benefit by knowing age-, gender- and racial/ethnic- specific dietary behaviors.

  3. Europium-labeled epidermal growth factor and neurotensin: novel probes for receptor-binding studies.

    Mazor, Ohad; Hillairet de Boisferon, Marc; Lombet, Alain; Gruaz-Guyon, Anne; Gayer, Batya; Skrzydelsky, Delphine; Kohen, Fortune; Forgez, Patricia; Scherz, Avigdor; Rostene, William; Salomon, Yoram

    2002-02-01

    We investigated the possibility of labeling two biologically active peptides, epidermal growth factor (EGF) and neurotensin (NT), with europium (Eu)-diethylenetriaminepentaacetic acid. More specifically, we tested them as probes in studying receptor binding using time-resolved fluorescence of Eu3+. The relatively simple synthesis yields ligands with acceptable binding characteristics similar to isotopically labeled derivatives. The binding affinity (Kd) of labeled Eu-EGF to human A431 epidermal carcinoid cells was 3.6 +/- 1.2 nM, similar to the reported Kd values of EGF, whereas the Kd of Eu-NT to human HT29 colon cancer cells (7.4 +/- 0.5 nM) or to Chinese hamster ovary (CHO) cells transfected with the high-affinity NT receptor (CHO-NT1) were about 10-fold higher than the Kd values of NT. The bioactivity of the Eu-labeled EGF as determined by stimulation of cultured murine D1 hematopoietic cell proliferation was nearly the same as that obtained with native EGF. The maximal stimulation of Ca2+ influx with NT and Eu-NT in CHO-NT1 cells was similar, but the respective K0.5 values were 20 pM and 1 nM, corresponding to differences in the binding affinities previously described. The results of these studies indicate that Eu labeling of peptide hormones and growth factor molecules ranging from 10(3) to 10(5) Da can be conveniently accomplished. Importantly, the Eu-labeled products are stable for approximately 2 years and are completely safe for laboratory use compared to the biohazardous radioligands. Thus, Eu-labeled peptides present an attractive alternative for commonly used radiolabeled ligands in biological studies in general and in receptor assays in particular.

  4. Fibroblast growth factor receptor 4 regulates tumor invasion by coupling fibroblast growth factor signaling to extracellular matrix degradation

    Sugiyama, Nami; Varjosalo, Markku; Meller, Pipsa

    2010-01-01

    /stroma border and tumor invasion front. The strongest overall coexpression was found in prostate carcinoma. Studies with cultured prostate carcinoma cell lines showed that the FGFR4-R388 variant, which has previously been associated with poor cancer prognosis, increased MT1-MMP-dependent collagen invasion......Aberrant expression and polymorphism of fibroblast growth factor receptor 4 (FGFR4) has been linked to tumor progression and anticancer drug resistance. We describe here a novel mechanism of tumor progression by matrix degradation involving epithelial-to-mesenchymal transition in response...... to membrane-type 1 matrix metalloproteinase (MT1-MMP, MMP-14) induction at the edge of tumors expressing the FGFR4-R388 risk variant. Both FGFR4 and MT1-MMP were upregulated in tissue biopsies from several human cancer types including breast adenocarcinomas, where they were partially coexpressed at the tumor...

  5. Gender and Space: Analysis of Factors Conditioning Equity in the Public Space

    Pablo Paramo Bernal

    2011-01-01

    Full Text Available This article discusses gender research in urban public space through three different perspectives: the social representations and differentiated uses of space, the division of roles in public and private spaces, and urban planning of public space. The paper gathers and analyses some studies that complement the state of art and literature on women and space giving evidence on how women have been segregated from public space and are victim of gender inequalities. Public space does not exist absolutely nor gender; instead both are socially constructed by social order and reproduced by social practices. Finally, some suggestions for urban planning and research are given in order to respond women’s needs in public space.

  6. [Gender-specific influencing factors on incidence, risk factors and outcome of carcinoma of the liver, gallbladder, extrahepatic bile duct and pancreas].

    Grundmann, R T; Meyer, F

    2014-04-01

    This overview comments on gender-specific differences in incidence, risk factors and prognosis in patients with carcinoma of the liver, gallbladder, extrahepatic bile duct and pancreas. For the literature review, the MEDLINE database (PubMed) was searched under the key words "liver cancer", "gallbladder cancer", "extrahepatic bile duct carcinoma", "pancreatic cancer" AND "gender". There were significant gender differences in the epidemiology of the analysed carcinomas. The incidence of hepatocellular carcinoma (HCC) is much higher in men than in women, one of 86 men, but only 1 out of 200 women develop a malignant primary liver tumour in Germany in the course of their life. The lifetime risk for carcinomas of the gallbladder and extrahepatic bile ducts in Germany amounts to about 0.6 % for women and 0.5 % for men, specifically gallbladder carcinomas are observed more frequently in women than in men. For pancreatic cancer, no clear gender preference exists in Germany, although the mortality risk for men is higher than that for women (age-adjusted standardised death rate in men 12.8/100, 000 persons, in women 9.5). Remarkable is furthermore the shift of the tumour incidence in the last decades. Liver cancer has increased among men in Germany by about 50 % in the last 30 years, the incidence of gallbladder carcinoma has inversely dropped. The prognosis of these cancers across all tumour stages is uniformly bad in an unselected patient population. This is probably the main reason why only little - if any - gender differences in survival are described. In addition to avoiding the known risk factors such as hepatitis B and C virus infection, alcohol abuse, and smoking, the avoidance of overweight and obesity plays an increasingly important role in the prevention of these cancers. Georg Thieme Verlag KG Stuttgart · New York.

  7. Male gender is not a risk factor for the outcome of laparoscopiccholecystectomy: A single surgeon experience

    Al-Mulhim, Abdulmohsen A.

    2008-01-01

    Previous studies regarding the outcome of laparoscopic cholecystectomy(LC) in men have reported inconsistent findings. We conducted thisprospective study to test the hypothesis that the outcome of LC is worse inmen than women. Between 1997 and 2002, a total of 391 consecutive LCs wereperformed by a single surgeon at King Fahd Hospital of the University. Wecollected and analyzed data including age, gender, body mass index (kg/m2),the American Society of Anesthesiologists (ASA) class, mode of admission(elective or emergency), indication for LC (chronic or acute) cholecystitis[AC]), comorbid disease, previous abdominal surgery, conversion to opencholecystectomy, complications, operation time and length of postoperativehospital stay. Bivariate analysis showed that both genders were matched forage, ASA class and mode of admission. The incidence of AC (P=0.003) andcomobrid disease (P=0.031) were significantly higher in men. Women weresignificantly more obese than men (P<0.001) and had a higher incidence ofprevious abdominal surgery (P=0.017). There were no statistical differencesbetween genders with regards to rate of conversion (P=0.372) andcomplications (P=0.647) and operation time (P=0.063). The postoperative staywas significantly longer in men than women (P=0.001). Logistic regressionanalysis showed that male gender was not an independent predictor ofconversion (Odds ratio [or] = 0.37 and P=0.43) or complications (OR=0.42,P=0.42). Linear regression analysis showed that male gender was not anindependent predictor of the operation time, but was associated with a longerpostoperative stay (P=0.02). Male gender is not an independent risk factorfor satisfactory outcome of LC in the experience of a single surgeon. (author)

  8. Development of epidermal growth factor receptor targeted therapy in pancreatic cancer.

    Qing, Liu; Qing, Wang

    2018-02-01

    The epidermal growth factor receptor (EGFR) family are a series of important cancer therapeutic targets involved in cancer biology. These genes play an important role in tumor biological characteristics including angiogenesis, cell survival, invasion and glucose metabolism. In recent years, progresses have been achieved upon the cellular and molecular biological characteristics of EGFR and its role in cancer development based on the study of tumor specimens and experimental animal model. EGFR(HER1/ErbB) is overexpressed in over sixty percent of triple-negative breast cancers and occurs in pancreatic, bladder, lung and head-and-neck cancers. Up to now, EGFR inhibitors have been applied in various of cancer, such as lung, breast, bladder and head and neck cancers etc., in which the combination of EGFR inhibitors plus chemotherapeutic agents is now seen as the standard of care for advanced/metastatic pancreatic cancer. For these reasons, EGFR inhibitors and their therapeutic effect for pancreatic cancer is becoming the focus in Laboratory and clinical research. In this paper, research progress of the development of epidermal growth factor receptor targeted therapy in pancreatic cancer is introduced.

  9. Therapies based on inhibitors of the epidermal growth factor receptor: enclosing the future

    Diaz, Arlhee; Lage, Agustin

    2007-01-01

    The Epidermal Growth Factor Receptor (EGFR) is considered an important target for rational drug design due to its key role in numerous tumors. Potential contribution of EGFR-related signaling pathways to promote tumorigenic processes, including cell proliferation, angiogenesis, and resistance to apoptosis has been well established. Two classes of anti-EGFR agents in late-stage clinical testing include monoclonal antibodies against extracellular EGFR domain (Cetuximab, Nimotuzumab) and small molecules tyrosine kinase inhibitors, which inhibit the receptor enzyme activity (Gefitinib, Erlotinib). A considerable body of evidence has emerged since its introduction in the treatment of cancer patients. However, important questions such as reliable surrogate markers to predict response to the treatment, or optimal sequence and combination of these agents with conventional therapies remain to be addressed. Identify and validate predictive factors to select patients likely to respond to EGFR inhibitors, such as mutations that confer resistance versus those associated with sensitivity is required. A better understanding of molecular mechanisms associated with antitumor activity will useful to predict the interaction of these agents with other therapies in order to avoid antagonisms or overlapping effects resulting in no adding effects. Finally, the benefits derived from EGFR inhibitors as first-line therapy in selected populations, and the optimal doses and ways to delivery to the tumor site resulting in optimal target modulation should be established by the ongoing investigation. (Author)

  10. Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer

    Matsuda, Naoko; Lim, Bora; Wang, Xiaoping; Ueno, Naoto T.

    2018-01-01

    Introduction Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer. This review article aims to consider the knowledge of the biological background of EGFR pathways in dissecting clinical studies of EGFR targeted treatment in breast cancer. Areas covered This review focuses on the role of the EGFR pathway and the investigational drugs that target EGFR for breast cancer. Expert opinion Recent studies have indicated that EGFR targeted therapy for breast cancer has some promising effects for patients with triple-negative breast cancer, basal-like breast cancer, and inflammatory breast cancer. However, predictive and prognostic biomarkers for EGFR targeted therapy have not been identified. The overexpression or amplification of EGFR itself may not be the true factor of induction of the canonical pathway as an oncogenic driver of breast cancer. Instead, downstream, non-canonical pathways related to EGFR may contribute to some aspects of the biological behavior of breast cancer; therefore, the blockade of the receptor could result in sufficient suppression of downstream pathways to inhibit the aggressive behavior of breast cancer. Mechanistic studies to investigate the dynamic interaction between the EGFR pathway and non-canonical pathways are warranted. PMID:28271910

  11. Recurrent exposure to nicotine differentiates human bronchial epithelial cells via epidermal growth factor receptor activation

    Martinez-Garcia, Eva; Irigoyen, Marta; Anso, Elena; Martinez-Irujo, Juan Jose; Rouzaut, Ana

    2008-01-01

    Cigarette smoking is the major preventable cause of lung cancer in developed countries. Nicotine (3-(1-methyl-2-pyrrolidinyl)-pyridine) is one of the major alkaloids present in tobacco. Besides its addictive properties, its effects have been described in panoply of cell types. In fact, recent studies have shown that nicotine behaves as a tumor promoter in transformed epithelial cells. This research focuses on the effects of acute repetitive nicotine exposure on normal human bronchial epithelial cells (NHBE cells). Here we show that treatment of NHBE cells with recurrent doses of nicotine up to 500 μM triggered cell differentiation towards a neuronal-like phenotype: cells emitted filopodia and expressed neuronal markers such as neuronal cell adhesion molecule, neurofilament-M and the transcription factors neuronal N and Pax-3. We also demonstrate that nicotine treatment induced NF-kB translocation to the nucleus, phosphorylation of the epidermal growth factor receptor (EGFR), and accumulation of heparin binding-EGF in the extracellular medium. Moreover, addition of AG1478, an inhibitor of EGFR tyrosine phosphorylation, or cetuximab, a monoclonal antibody that precludes ligand binding to the same receptor, prevented cell differentiation by nicotine. Lastly, we show that differentiated cells increased their adhesion to the extracellular matrix and their protease activity. Given that several lung pathologies are strongly related to tobacco consumption, these results may help to better understand the damaging consequences of nicotine exposure

  12. Stepwise Progress in Epidermal Growth Factor Receptor/Radiation Studies for Head and Neck Cancer

    Harari, Paul M.

    2007-01-01

    The U.S. Food and Drug Administration approval of four new epidermal growth factor receptor (EGFR) inhibitors for cancer therapy (cetuximab, panitumumab, gefitinib, and erlotinib) over the last 3 years is a remarkable milestone in oncology. Indeed, molecular inhibition of EGFR signaling represents one of the most promising current arenas for the development of molecular-targeted cancer therapies. Epidermal growth factor receptor inhibitors from both the monoclonal antibody and tyrosine kinase inhibitor class have demonstrated clinical activity in the treatment of a broad spectrum of common human malignancies. For the discipline of radiation oncology, the 2006 report of a phase III trial demonstrating a survival advantage for advanced head and neck cancer patients with the addition of weekly cetuximab during a 7-week course of radiation is particularly gratifying. Indeed, this is the first phase III trial to confirm a survival advantage with the addition of a molecular-targeted agent to radiation. Furthermore, this result seems to have been achieved with only a modest increment in overall treatment toxicity and with very high compliance to the prescribed treatment regimen. Nevertheless, much remains to be learned regarding the rational integration of EGFR inhibitors into cancer treatment regimens, as well as methods to optimize the selection of patients most likely to benefit from EGFR inhibitor strategies

  13. Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer.

    Matsuda, Naoko; Lim, Bora; Wang, Xiaoping; Ueno, Naoto T

    2017-04-01

    Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer. This review article aims to consider the knowledge of the biological background of EGFR pathways in dissecting clinical studies of EGFR targeted treatment in breast cancer. Areas covered: This review focuses on the role of the EGFR pathway and the investigational drugs that target EGFR for breast cancer. Expert opinion: Recent studies have indicated that EGFR targeted therapy for breast cancer has some promising effects for patients with triple-negative breast cancer, basal-like breast cancer, and inflammatory breast cancer. However, predictive and prognostic biomarkers for EGFR targeted therapy have not been identified. The overexpression or amplification of EGFR itself may not be the true factor of induction of the canonical pathway as an oncogenic driver of breast cancer. Instead, downstream, non-canonical pathways related to EGFR may contribute to some aspects of the biological behavior of breast cancer; therefore, the blockade of the receptor could result in sufficient suppression of downstream pathways to inhibit the aggressive behavior of breast cancer. Mechanistic studies to investigate the dynamic interaction between the EGFR pathway and non-canonical pathways are warranted.

  14. Physiological epidermal growth factor concentrations activate high affinity receptors to elicit calcium oscillations.

    Béatrice Marquèze-Pouey

    Full Text Available Signaling mediated by the epidermal growth factor (EGF is crucial in tissue development, homeostasis and tumorigenesis. EGF is mitogenic at picomolar concentrations and is known to bind its receptor on high affinity binding sites depending of the oligomerization state of the receptor (monomer or dimer. In spite of these observations, the cellular response induced by EGF has been mainly characterized for nanomolar concentrations of the growth factor, and a clear definition of the cellular response to circulating (picomolar concentrations is still lacking. We investigated Ca2+ signaling, an early event in EGF responses, in response to picomolar doses in COS-7 cells where the monomer/dimer equilibrium is unaltered by the synthesis of exogenous EGFR. Using the fluo5F Ca2+ indicator, we found that picomolar concentrations of EGF induced in 50% of the cells a robust oscillatory Ca2+ signal quantitatively similar to the Ca2+ signal induced by nanomolar concentrations. However, responses to nanomolar and picomolar concentrations differed in their underlying mechanisms as the picomolar EGF response involved essentially plasma membrane Ca2+ channels that are not activated by internal Ca2+ store depletion, while the nanomolar EGF response involved internal Ca2+ release. Moreover, while the picomolar EGF response was modulated by charybdotoxin-sensitive K+ channels, the nanomolar response was insensitive to the blockade of these ion channels.

  15. Physiological epidermal growth factor concentrations activate high affinity receptors to elicit calcium oscillations.

    Marquèze-Pouey, Béatrice; Mailfert, Sébastien; Rouger, Vincent; Goaillard, Jean-Marc; Marguet, Didier

    2014-01-01

    Signaling mediated by the epidermal growth factor (EGF) is crucial in tissue development, homeostasis and tumorigenesis. EGF is mitogenic at picomolar concentrations and is known to bind its receptor on high affinity binding sites depending of the oligomerization state of the receptor (monomer or dimer). In spite of these observations, the cellular response induced by EGF has been mainly characterized for nanomolar concentrations of the growth factor, and a clear definition of the cellular response to circulating (picomolar) concentrations is still lacking. We investigated Ca2+ signaling, an early event in EGF responses, in response to picomolar doses in COS-7 cells where the monomer/dimer equilibrium is unaltered by the synthesis of exogenous EGFR. Using the fluo5F Ca2+ indicator, we found that picomolar concentrations of EGF induced in 50% of the cells a robust oscillatory Ca2+ signal quantitatively similar to the Ca2+ signal induced by nanomolar concentrations. However, responses to nanomolar and picomolar concentrations differed in their underlying mechanisms as the picomolar EGF response involved essentially plasma membrane Ca2+ channels that are not activated by internal Ca2+ store depletion, while the nanomolar EGF response involved internal Ca2+ release. Moreover, while the picomolar EGF response was modulated by charybdotoxin-sensitive K+ channels, the nanomolar response was insensitive to the blockade of these ion channels.

  16. Insulin-like growth factor receptor inhibitors: baby or the bathwater?

    Yee, Douglas

    2012-07-03

    The success of targeted therapies for cancer is undisputed; strong preclinical evidence has resulted in the approval of several new agents for cancer treatment. The type I insulin-like growth factor receptor (IGF1R) appeared to be one of these promising new targets. Substantial population and preclinical data have all pointed toward this pathway as an important regulator of tumor cell biology. Although early results from clinical trials that targeted the IGF1R showed some evidence of response, larger randomized phase III trials have not shown clear clinical benefit of targeting this pathway in combination with conventional strategies. These disappointing results have resulted in the discontinuation of several anti-IGF1R programs. However, the conduct of these trials has brought to the forefront several important factors that need to be considered in the conduct of future clinical trials. The need to develop biomarkers, a clearer understanding of insulin receptor function, and defining rational combination regimens all require further consideration. In this commentary, the current state of IGF1R inhibitors in cancer therapy is reviewed.

  17. Inhibition of fibroblast growth factor receptor 3-dependent lung adenocarcinoma with a human monoclonal antibody

    Yongjun Yin

    2016-05-01

    Full Text Available Activating mutations in fibroblast growth factor receptor 3 (FGFR3 have been identified in multiple types of human cancer and in congenital birth defects. In human lung cancer, fibroblast growth factor 9 (FGF9, a high-affinity ligand for FGFR3, is overexpressed in 10% of primary resected non-small cell lung cancer (NSCLC specimens. Furthermore, in a mouse model where FGF9 can be induced in lung epithelial cells, epithelial proliferation and ensuing tumorigenesis is dependent on FGFR3. To develop new customized therapies for cancers that are dependent on FGFR3 activation, we have used this mouse model to evaluate a human monoclonal antibody (D11 with specificity for the extracellular ligand-binding domain of FGFR3, that recognizes both human and mouse forms of the receptor. Here, we show that D11 effectively inhibits signaling through FGFR3 in vitro, inhibits the growth of FGFR3-dependent FGF9-induced lung adenocarcinoma in mice, and reduces tumor-associated morbidity. Given the potency of FGF9 in this mouse model and the absolute requirement for signaling through FGFR3, this study validates the D11 antibody as a potentially useful and effective reagent for treating human cancers or other pathologies that are dependent on activation of FGFR3.

  18. Parental and Infant Gender Factors in Parent–Infant Interaction: State-Space Dynamic Analysis

    M. Angeles Cerezo; Purificación Sierra-García; Gemma Pons-Salvador; Rosa M. Trenado

    2017-01-01

    This study aimed to investigate the influence of parental gender on their interaction with their infants, considering, as well, the role of the infant’s gender. The State Space Grid (SSG) method, a graphical tool based on the non-linear dynamic system (NDS) approach was used to analyze the interaction, in Free-Play setting, of 52 infants, aged 6 to 10 months, divided into two groups: half of the infants interacted with their fathers and half with their mothers. There were 50% boys in each gro...

  19. Immunohistochemical detection of epidermal growth factor receptor in radiation-induced lung tumors in Beagle dogs

    Gillett, N A; Haley, P J; Hahn, F F

    1988-12-01

    Increased levels of epidermal growth factor receptor have been reported in a variety of tumors, including pulmonary squamous cell carcinomas in man. The purpose of this study was to determine if increased levels of epidermal growth factor (EGFR) were present in lung tumors from Beagle dogs that had been exposed to {sup 239}PuO{sub 2}- Using immunohistochemical techniques, sections from 17 lung tumors were examined for the presence of EGFR. Seven of the tumors were strongly positive for EGFR; the remainder of the tumors and the normal lung sections were negative. The positive immunostaining could not be correlated with the histologic phenotype of the tumors. Work is in progress to determine the level of EGFR in preneoplastic, proliferative epithelial foci in the Iung. (author)

  20. Sex, Receptors and Attachment: A Review of Individual Factors Influencing Response to Oxytocin

    Kai S Macdonald

    2013-01-01

    Full Text Available As discussed in the larger review in this special issue (MacDonald and Feifel, intranasal oxytocin (IN OT is demonstrating a growing potential as a therapeutic agent in psychiatry. Importantly, research suggests that a variety of individual factors may influence a person’s response to OT. In this mini-review, I provides a review of three: (1 sex and hormonal status; (2 genetic variation in aspects of the OT system (i.e. OT receptors; and (3 attachment history. Each of these factors will be important to monitor as we strive to develop a richer understanding of OT's role in human development, brain-based disease, and the potential for individualized, OT-targeted treatments.

  1. Mothers, fathers, sons, and daughters: gender differences in factors associated with parent-child communication about sexual topics.

    Wilson, Ellen K; Koo, Helen P

    2010-12-14

    In the United States, nearly half of high school students are sexually active, and adolescents experience high rates of unintended pregnancy and sexually transmitted diseases. Parents can have an important influence on their children's sexual behaviour, but many parents do not talk with their children about sexual topics. Research has shown significant differences in parent-child communication about sexual topics depending on the gender of both the parent and the child. Little is known, however, about the reasons for these gender differences. The purpose of this paper is to describe how factors associated with parent-child communication about sexual topics differ by gender. Data are from a nationwide online survey with 829 fathers and 1,113 mothers of children aged 10 to 14. For each of the four gender groups (fathers of sons, fathers of daughters, mothers of sons, mothers of daughters), we calculated the distribution of responses to questions assessing (1) parent-child communication about sex-related topics, and (2) factors associated with that communication. We used chi-square tests to determine whether the distributions differed and the false discovery rate control to reduce the likelihood of type I errors. With both sons and daughters, fathers communicated less about sexual topics than mothers did. Fathers also had lower levels of many characteristics that facilitate communication about sex (e.g., lower self-efficacy and lower expectations that talking to their children about sex would have positive outcomes). Compared with parents of sons, parents of daughters (both mothers and fathers) talked more about sexual topics, were more concerned about potential harmful consequences of sexual activity, and were more disapproving of their child having sex at an early age. Using a large national sample, this study confirms findings from previous studies showing gender differences in parent-child communication about sexual topics and identifies gender differences in

  2. Mothers, fathers, sons, and daughters: gender differences in factors associated with parent-child communication about sexual topics

    Koo Helen P

    2010-12-01

    Full Text Available Abstract Background In the United States, nearly half of high school students are sexually active, and adolescents experience high rates of unintended pregnancy and sexually transmitted diseases. Parents can have an important influence on their children's sexual behaviour, but many parents do not talk with their children about sexual topics. Research has shown significant differences in parent-child communication about sexual topics depending on the gender of both the parent and the child. Little is known, however, about the reasons for these gender differences. The purpose of this paper is to describe how factors associated with parent-child communication about sexual topics differ by gender. Methods Data are from a nationwide online survey with 829 fathers and 1,113 mothers of children aged 10 to 14. For each of the four gender groups (fathers of sons, fathers of daughters, mothers of sons, mothers of daughters, we calculated the distribution of responses to questions assessing (1 parent-child communication about sex-related topics, and (2 factors associated with that communication. We used chi-square tests to determine whether the distributions differed and the false discovery rate control to reduce the likelihood of type I errors. Results With both sons and daughters, fathers communicated less about sexual topics than mothers did. Fathers also had lower levels of many characteristics that facilitate communication about sex (e.g., lower self-efficacy and lower expectations that talking to their children about sex would have positive outcomes. Compared with parents of sons, parents of daughters (both mothers and fathers talked more about sexual topics, were more concerned about potential harmful consequences of sexual activity, and were more disapproving of their child having sex at an early age. Conclusions Using a large national sample, this study confirms findings from previous studies showing gender differences in parent

  3. Mechanical stretch augments insulin-induced vascular smooth muscle cell proliferation by insulin-like growth factor-1 receptor

    Liu, Gang [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang (China); Hitomi, Hirofumi, E-mail: hitomi@kms.ac.jp [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Hosomi, Naohisa [Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Kagawa (Japan); Lei, Bai; Nakano, Daisuke [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Deguchi, Kazushi; Mori, Hirohito; Masaki, Tsutomu [Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Ma, Hong [Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang (China); Griendling, Kathy K. [Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA (United States); Nishiyama, Akira [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan)

    2011-10-15

    Insulin resistance and hypertension have been implicated in the pathogenesis of cardiovascular disease; however, little is known about the roles of insulin and mechanical force in vascular smooth muscle cell (VSMC) remodeling. We investigated the contribution of mechanical stretch to insulin-induced VSMC proliferation. Thymidine incorporation was stimulated by insulin in stretched VSMCs, but not in un-stretched VSMCs. Insulin increased 2-deoxy-glucose incorporation in both stretched and un-stretched VSMCs. Mechanical stretch augmented insulin-induced extracellular signal-regulated kinase (ERK) and Akt phosphorylation. Inhibitors of epidermal growth factor (EGF) receptor tyrosine kinase and Src attenuated insulin-induced ERK and Akt phosphorylation, as well as thymidine incorporation, whereas 2-deoxy-glucose incorporation was not affected by these inhibitors. Moreover, stretch augmented insulin-like growth factor (IGF)-1 receptor expression, although it did not alter the expression of insulin receptor and insulin receptor substrate-1. Insulin-induced ERK and Akt activation, and thymidine incorporation were inhibited by siRNA for the IGF-1 receptor. Mechanical stretch augments insulin-induced VSMC proliferation via upregulation of IGF-1 receptor, and downstream Src/EGF receptor-mediated ERK and Akt activation. Similar to in vitro experiment, IGF-1 receptor expression was also augmented in hypertensive rats. These results provide a basis for clarifying the molecular mechanisms of vascular remodeling in hypertensive patients with hyperinsulinemia. -- Highlights: {yields} Mechanical stretch augments insulin-induced VSMC proliferation via IGF-1 receptor. {yields} Src/EGFR-mediated ERK and Akt phosphorylation are augmented in stretched VSMCs. {yields} Similar to in vitro experiment, IGF-1 receptor is increased in hypertensive rats. {yields} Results provide possible mechanisms of vascular remodeling in hypertension with DM.

  4. Influences of ABO blood group, age and gender on plasma coagulation factor VIII, fibrinogen, von Willebrand factor and ADAMTS13 levels in a Chinese population.

    Wang, Zongkui; Dou, Miaomiao; Du, Xi; Ma, Li; Sun, Pan; Cao, Haijun; Ye, Shengliang; Jiang, Peng; Liu, Fengjuan; Lin, Fangzhao; Zhang, Rong; Li, Changqing

    2017-01-01

    ABO blood group is a hereditary factor of plasma levels of coagulation factor VIII (FVIII) and von Willebrand factor (VWF). Age and gender have been shown to influence FVIII, VWF, fibrinogen (Fbg), and ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 motif, 13). We investigated the effects of ABO type, age, and gender on plasma levels of FVIII, Fbg, VWF, and ADAMTS13 in a Chinese population. A total of 290 healthy volunteers were eligible for this study. ABO blood group was determined by indirect technique. FVIII:C and Fbg were measured by clotting assays. VWF antigen (VWF:Ag), collagen-binding activity (VWF:CBA), and ADAMTS13 antigen were assessed by ELISA, whereas VWF ristocetin cofactor activity (VWF:Rcof) was performed by agglutination of platelets with ristocetin. Mean FVIII:C and VWF levels (VWF:Ag, VWF:CBA, and VWF:Rcof) were significantly higher in non-O than in O type subjects ( p  blood group, age, and gender showed different effects on plasma levels of FVIII:C, Fbg, VWF:Ag, VWF:CBA, VWF:Rcof, and ADAMTS13 antigen. These new data on a Chinese population are quite helpful to compare with other ethnic groups.

  5. Potent and long-acting corticotropin releasing factor (CRF) receptor 2 selective peptide competitive antagonists.

    Rivier, J; Gulyas, J; Kirby, D; Low, W; Perrin, M H; Kunitake, K; DiGruccio, M; Vaughan, J; Reubi, J C; Waser, B; Koerber, S C; Martinez, V; Wang, L; Taché, Y; Vale, W

    2002-10-10

    We present evidence that members of the corticotropin releasing factor (CRF) family assume distinct structures when interacting with the CRF(1) and CRF(2) receptors. Predictive methods, physicochemical measurements, and structure-activity relationship studies have suggested that CRF, its family members, and competitive antagonists such as astressin [cyclo(30-33)[DPhe(12),Nle(21),Glu(30),Lys(33),Nle(38)]hCRF((12-41))] assume an alpha-helical conformation when interacting with their receptors. We had shown that alpha-helical CRF((9-41)) and sauvagine showed some selectivity for CRF receptors other than that responsible for ACTH secretion(1) and later for CRF2.(2) More recently, we suggested the possibility of a helix-turn-helix motif around a turn encompassing residues 30-33(3) that would confer high affinity for both CRF(1) and CRF(2)(2,4) in agonists and antagonists of all members of the CRF family.(3) On the other hand, the substitutions that conferred ca. 100-fold CRF(2) selectivity to the antagonist antisauvagine-30 [[DPhe(11),His(12)]sauvagine((11-40))] did not confer such property to the corresponding N-terminally extended agonists. We find here that a Glu(32)-Lys(35) side chain to side chain covalent lactam constraint in hCRF and the corresponding Glu(31)-Lys(34) side chain to side chain covalent lactam constraint in sauvagine yield potent ligands that are selective for CRF(2). Additionally, we introduced deletions and substitutions known to increase duration of action to yield antagonists such as cyclo(31-34)[DPhe(11),His(12),C(alpha)MeLeu(13,39),Nle(17),Glu(31),Lys(34)]Ac-sauvagine((8-40)) (astressin(2)-B) with CRF(2) selectivities greater than 100-fold. CRF receptor autoradiography was performed in rat tissue known to express CRF(2) and CRF(1) in order to confirm that astressin(2)-B could indeed bind to established CRF(2) but not CRF(1) receptor-expressing tissues. Extended duration of action of astressin(2)-B vs that of antisauvagine-30 is demonstrated in

  6. Human epidermal growth factor receptor 2 status of gastric cancer patients in Asia: results from a large, multicountry study.

    Pathmanathan, Nirmala; Geng, Jing-Shu; Li, Wencai; Nie, Xiu; Veloso, Januario; Wang, John; Hill, Julie; Mccloud, Philip; Bilous, Michael

    2017-06-01

    Current estimates of the human epidermal growth factor receptor 2 (HER2)-positivity rate in gastric cancer vary widely in the literature, and there are limited data from countries in Asia. The primary aim of this study was to conduct a clinical audit of laboratories across seven countries in Asia to determine the incidence of HER2-positive gastric cancer in this region. Pathologists were asked to collect data on patient gender, age, cancer site, specimen type, tumor spread, type and grade, HER2 test results, including protein and/or gene copy enumeration, and final HER2 status on consecutive gastric cancer cases tested for HER2 in their laboratory over a 2-year period. HER2 results from 5,301 gastric cancers were submitted by 50 laboratories. The overall HER2-positivity rate was 9.7% which, after the exclusion of China, increased to 18.1%. The rate between countries ranged from 0% to 23.1%, and from 0% to 50.0% between laboratories. An equivocal HER2 result was recorded in 19.5% of cases. Despite the lack of centralized testing to confirm the accuracy of HER2 diagnoses, the incidence of HER2-positive gastric cancer observed here was comparable to that reported in the literature. Nevertheless, rates were highly variable between countries and laboratories, which suggests a lack of HER2 testing expertise in gastric cancer. Given that the mortality rates for gastric cancer in Eastern Asia are the highest in the world, efforts should focus on improving HER2 testing expertise in the region so that patients receive the appropriate treatment early in their disease. © 2016 The Authors. Asia-Pacific Journal of Clinical Oncology Published by John Wiley & Sons Australia, Ltd.

  7. Coagulation factor VII is regulated by androgen receptor in breast cancer.

    Naderi, Ali

    2015-02-01

    Androgen receptor (AR) is widely expressed in breast cancer; however, there is limited information on the key molecular functions and gene targets of AR in this disease. In this study, gene expression data from a cohort of 52 breast cancer cell lines was analyzed to identify a network of AR co-expressed genes. A total of 300 genes, which were significantly enriched for cell cycle and metabolic functions, showed absolute correlation coefficients (|CC|) of more than 0.5 with AR expression across the dataset. In this network, a subset of 35 "AR-signature" genes were highly co-expressed with AR (|CC|>0.6) that included transcriptional regulators PATZ1, NFATC4, and SPDEF. Furthermore, gene encoding coagulation factor VII (F7) demonstrated the closest expression pattern with AR (CC=0.716) in the dataset and factor VII protein expression was significantly associated to that of AR in a cohort of 209 breast tumors. Moreover, functional studies demonstrated that AR activation results in the induction of factor VII expression at both transcript and protein levels and AR directly binds to a proximal region of F7 promoter in breast cancer cells. Importantly, AR activation in breast cancer cells induced endogenous factor VII activity to convert factor X to Xa in conjunction with tissue factor. In summary, F7 is a novel AR target gene and AR activation regulates the ectopic expression and activity of factor VII in breast cancer cells. These findings have functional implications in the pathobiology of thromboembolic events and regulation of factor VII/tissue factor signaling in breast cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. MiR-125a TNF receptor-associated factor 6 to inhibit osteoclastogenesis

    Guo, Li-Juan; Liao, Lan; Yang, Li; Li, Yu; Jiang, Tie-Jian

    2014-01-01

    MicroRNAs (miRNAs) play important roles in osteoclastogenesis and bone resorption. In the present study, we found that miR-125a was dramatically down-regulated during macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) induced osteoclastogenesis of circulating CD14+ peripheral blood mononuclear cells (PBMCs). Overexpression of miR-125a in CD14+ PBMCs inhibited osteoclastogenesis, while inhibition of miR-125a promoted osteoclastogenesis. TNF receptor-associated factor 6 (TRAF6), a transduction factor for RANKL/RANK/NFATc1 signal, was confirmed to be a target of miR-125a. EMSA and ChIP assays confirmed that NFATc1 bound to the promoter of the miR-125a. Overexpression of NFATc1 inhibited miR-125a transcription, and block of NFATc1 expression attenuated RANKL-regulated miR-125a transcription. Here, we reported that miR-125a played a biological function in osteoclastogenesis through a novel TRAF6/ NFATc1/miR-125a regulatory feedback loop. It suggests that regulation of miR-125a expression may be a potential strategy for ameliorating metabolic disease. - Highlights: • MiR-125a was significantly down-regulated in osteoclastogenesis of CD14+ PBMCs. • MiR-125a inhibited osteoclast differentiation by targeting TRAF6. • NFATc1 inhibited miR-125a transciption by binding to the promoter of miR-125a. • TRAF6/NFATc1 and miR-125a form a regulatory feedback loop in osteoclastogenesis

  9. The SRC homology 2 domain of Rin1 mediates its binding to the epidermal growth factor receptor and regulates receptor endocytosis.

    Barbieri, M Alejandro; Kong, Chen; Chen, Pin-I; Horazdovsky, Bruce F; Stahl, Philip D

    2003-08-22

    Activated epidermal growth factor receptors (EGFRs) recruit intracellular proteins that mediate receptor signaling and endocytic trafficking. Rin1, a multifunctional protein, has been shown to regulate EGFR internalization (1). Here we show that EGF stimulation induces a specific, rapid, and transient membrane recruitment of Rin1 and that recruitment is dependent on the Src homology 2 (SH2) domain of Rin1. Immunoprecipitation of EGFR is accompanied by co-immunoprecipitation of Rin1 in a time- and ligand-dependent manner. Association of Rin1 and specifically the SH2 domain of Rin1 with the EGFR was dependent on tyrosine phosphorylation of the intracellular domain of the EGFR. The recruitment of Rin1, observed by light microscopy, indicated that although initially cytosolic, Rin1 was recruited to both plasma membrane and endosomes following EGF addition. Moreover, the expression of the SH2 domain of Rin1 substantially impaired the internalization of EGF without affecting internalization of transferrin. Finally, we found that Rin1 co-immunoprecipitated with a number of tyrosine kinase receptors but not with cargo endocytic receptors. These results indicate that Rin1 provides a link via its SH2 domain between activated tyrosine kinase receptors and the endocytic pathway through the recruitment and activation of Rab5a.

  10. Authoritarianism as an element of social character and a factor of gendered social interaction

    Jovančević Saša

    2003-01-01

    Full Text Available The immediacy of daily encounters with gender roles, as well as the specific features of authoritarian mediation in their social shaping, make an analysis of gendered social interaction indispensable. In this paper the analysis is centered on the concept of social character, with special emphasis on authoritarianism as a continuous determinant of the transformation of natural sex into social construct of gender. It is precisely the authoritarian personality type that is the basis for alienated gender, dominated by sexism, a “natural” belonging to the private or the public sphere of social life, suppression of individual human capacities, and reduction of choice. After a review of the theoretical conceptions of social character and authoritarianism, a historical-comparative analysis of authoritarianism is offered, where the latter is seen as an element of the social character within the perspective of the typology traditional - modern - postmodern society. It is argued in conclusion that, in spite of certain emancipatory achievements, men and women still tend to escape into the security of authoritarian alienation. Feminist theory remains a basic source for reflecting on these processes; therefore the author pleads for a wider acceptance of feminist insights as contributions to establishing a postmodern, interpretive “sociology in a new key”.

  11. Returning to STEM: Gendered Factors Affecting Employability for Mature Women Students

    Herman, Clem

    2015-01-01

    This paper adds to current discourses around employability by arguing for an explicit recognition of gender, in particular in relation to women's employment in male-dominated sectors such as science, engineering and technology. This is not limited to young first-time graduates but continues and evolves throughout the life course. Mature women…

  12. Female Gender and Reproductive Factors Affecting Risk, Relapses and Progression in Multiple Sclerosis

    D'hooghe, M. B.; D'Hooghe, T.; De Keyser, J.

    2013-01-01

    Multiple sclerosis (MS), a chronic inflammatory demyelinating and degenerative disease of the central nervous system, is a frequent cause of neurological disability in young adults. Female predominance has increased over the last decades. Although female gender carries a higher risk of developing

  13. Is gender a risk factor for pesticide intoxications among farmers in Bolivia?

    Jørs, Erik; Hay-Younes, Jasmin; Condarco, Madelaine A

    2013-01-01

    This study compares gender differences regarding knowledge, practice, and symptoms of intoxication when handling pesticides in farming. Data were gathered in La Paz County, Bolivia, in 2008 and 2009. Poor knowledge on safe handling, hazardous working practices, and use of very toxic pesticides were...... symptoms. To minimize this gap, education and agricultural services should be made more accessible to female farmers in Bolivia....

  14. Factors That Influence Student Pursuit of Science Careers; the Role of Gender, Ethnicity, Family and Friends

    Rodrigues, Susan; Jindal-Snape, Divya; Snape, Jonathan B.

    2011-01-01

    This study adds to a body of research reporting on pupils' choices and outcomes in relation to science. The article reports on 536 Scottish pupils' perceptions regarding reported intention to choose careers in science, with further analysis in terms of family, friends, gender and ethnicity. The pupils, aged 14-15, from 5 schools in one Scottish…

  15. Age, gender and risk factor disparities in first-stroke Jewish and Arab patients in Israel undergoing rehabilitation.

    Greenberg, Elina; Treger, Iuly; Schwarz, Juliana

    2011-11-01

    Little is known of the risk factor disparities in first stroke among Jewish and Arab patients undergoing rehabilitation in Israel. To investigate the age, gender and risk factor disparities in first stroke among Jewish (immigrant and non-immigrant) and Arab patients undergoing rehabilitation and to compare the prevalence and odds ratio of stroke risk factors in these patients. The database of the Department of Neurological Rehabilitation C at Loewenstein Rehabilitation Center was used to investigate first ischemic and hemorrhagic stroke patients admitted for hospital rehabilitation over a 15 year period, January 1993 to December 2008. Particular attention was paid to age, gender and risk factor disparities. The 2000 patients with first stroke who were included in the study were grouped as Jewish (immigrant and non-immigrant) orArab; there were 237 Arabs, 370 non-immigrant Jews and 1393 immigrant Jews. A high percentage of Arab patients were found to have hypertension and diabetes mellitus, while a high percentage of Jewish immigrants had stenosis of the internal carotid artery. The study demonstrated some differences in the effect of risk factors between the groups. It may be important to address such differences when developing stroke preventative strategies in this population of Jewish and Arab stroke survivors in Israel.

  16. Sexuality Within Female Same-Gender Couples: Definitions of Sex, Sexual Frequency Norms, and Factors Associated with Sexual Satisfaction.

    Scott, Shelby B; Ritchie, Lane; Knopp, Kayla; Rhoades, Galena K; Markman, Howard J

    2018-04-01

    Despite a growing number of female same-gender (FSG) relationships, couples-based research and interventions have focused primarily on mixed-gender couples. Consequently, research has applied a heteronormative lens to understanding some relationship factors, including sexuality. The current study sought to provide descriptive data regarding frequency and conceptualizations of sex across partners in FSG relationships, as well as to analyze how relationship factors are associated with sexual satisfaction in this population. Participants (N = 206) were 103 adult FSG couples who had been together for at least 2 months. Individuals provided self-report data on how they conceptualized sex, and actor-partner models were utilized to assess relationship factors associated with sexual satisfaction. Findings indicated that women in FSG relationships hold broad definitions of sex, with the majority of behaviors conceptualized as sex, including acts that involved partnered genital touching. In dyadic actor-partner models, sexual satisfaction was predicted by several factors including sexual frequency, emotional intimacy, and sexual intimacy. Unexpectedly, higher desired sexual frequency was associated with lower sexual satisfaction; however, this finding only emerged after controlling for actual sexual frequency, suggesting that discrepancies between desired and actual sex frequency may be important for FSG couples. Implications for clinical practice with FSG couples are explored, including a strength-based focus on broad conceptualizations of sex within this population and targeting relationship factors associated with sexual satisfaction.

  17. Nature and regulation of the receptors for insulin-like growth factors

    Rechler, M.M.; Nissley, S.P.

    1985-01-01

    Two subtypes of IGF receptors have been identified. Type I IGF receptors have a Mr greater than 300,000 and are composed of disulfide-linked 130,000-dalton (alpha) and approximately 90,000-dalton (beta) subunits. Type I receptors preferentially bind IGF-I but also bind IGF-II and, more weakly, insulin. Type II IGF receptors consist of a 250,000-dalton protein that contains internal disulfide bonds but is not linked to other membrane components. Type II receptors bind IGF-II with higher affinity than IGF-I. They do not interact with even very high concentrations of insulin. Type I IGF receptors and insulin receptors are homologous structures. Type II IGF receptors do not appear to be homologous to type I receptors. Type II receptors do not appear to be downregulated. Insulin acutely upregulates type II IGF receptors in intact rat adipose cells by effecting a redistribution of receptors cycling between a large intracellular pool and the plasma membrane. Insulin and the IGFs elicit the same biological responses, either by cross-reacting with one of the receptors for the heterologous ligand or by concurrent activation of convergent effector pathways by binding to the homologous receptor. Which mechanism is utilized appears to depend more on the tissue than on the biological response. Insulin desensitizes rat hepatoma cells to the actions of insulin and IGFs, mediated by both insulin and IGF receptors, by mechanisms distal to hormone binding and possibly common to IGF and insulin effector pathways

  18. Direct demonstration of rapid insulin-like growth factor II receptor internalization and recycling in rat adipocytes. Insulin stimulates 125I-insulin-like growth factor II degradation by modulating the IGF-II receptor recycling process

    Oka, Y.; Rozek, L.M.; Czech, M.P.

    1985-01-01

    The photoactive insulin-like growth factor (IGF)-II analogue 4-azidobenzoyl- 125 I-IGF-II was synthesized and used to label specifically and covalently the Mr = 250,000 Type II IGF receptor. When rat adipocytes are irradiated after a 10-min incubation with 4-azidobenzoyl- 125 I-IGF-II at 10 degrees C and immediately homogenized, most of the labeled IGF-II receptors are associated with the plasma membrane fraction, indicating that receptors accessible to the labeling reagent at low temperature are on the cell surface. However, when the photolabeled cells are incubated at 37 degrees C for various times before homogenization, labeled IGF-II receptors are rapidly internalized with a half-time of 3.5 min as evidenced by a loss from the plasma membrane fraction and a concomitant appearance in the low density microsome fraction. The steady state level of cell surface IGF-II receptors in the presence or absence of IGF-II remains constant under these conditions, demonstrating that IGF-II receptors rapidly recycle back to the cell surface at the same rate as receptor internalization. Using the above methodology, it is shown that acute insulin action: 1) increases the steady state number of cell surface IGF-II receptors; 2) increases the number of ligand-bound IGF-II receptors that are internalized per unit of time; and 3) increases the rate of cellular 125 I-IGF-II degradation by a process that is blocked by anti-IGF-II receptor antibody

  19. The relationship between employment and veteran status, disability and gender from 2004-2011 Behavioral Risk Factor Surveillance System (BRFSS).

    Smith, Diane L

    2014-01-01

    In 2011, about 1.8 million or 8 percent of the 22.2 million veterans were women in the US. The unemployment rate for female veterans of the wars in Iraq and Afghanistan rose to 13.5%, above the 8.4% for non-veteran adult women. To examine data from the Behavioral Risk Factor Surveillance System (BRFSS), from 2004-2011 to determine the relationship between employment and veteran status, disability and gender. Chi square analysis was used to determine if significant differences existed between the employment rate of female veterans with disabilities and female veterans without disabilities, female non-veterans with disabilities and male veterans with disabilities. Binomial logistic regression analysis was used to determine how veteran status, disability and gender affected the likelihood of not being employed. Significant differences were found in employment rate between female veterans with disabilities and female veterans without disabilities, but not when compared to female non-veterans with disabilities or male veterans with disabilities. Disability was the strongest factor increasing the likelihood of not being employed, though veteran status and female gender were also predictive. Female veterans with disabilities experience low levels of employment. Policies and programs are needed to address the unique needs of these veterans.

  20. Factors associated with sexual orientation and gender disparities in chronic pain among U.S. adolescents and young adults

    Sabra L. Katz-Wise

    2015-01-01

    Full Text Available This research investigated factors associated with sexual orientation disparities in chronic pain frequency among youth. Data were analyzed from 4534 female and 3785 male youth from Waves I–IV (1995–2009 of the U.S. National Longitudinal Study of Adolescent to Adult Health. Gender-stratified weighted logistic regression models controlled for sociodemographic characteristics and included sexual orientation (primary predictor and frequency of three types of chronic pain (outcomes. Models with sexual orientation only were compared to models with factors hypothesized to increase or decrease risk of pain. Significant odds ratios (OR for chronic pain frequency (daily/weekly vs. rarely with confidence intervals (CI and associated factors are reported. Compared to same-gender heterosexual females, mostly heterosexuals were more likely to report headaches (OR = 1.40, CI = 1.09, 1.79 and mostly heterosexuals and bisexuals were more likely to report muscle/joint pain (mostly heterosexual OR = 1.69, CI = 1.29, 2.20; bisexual OR = 1.87, CI = 1.03, 3.38. Compared to same-gender heterosexual males, gay males were more likely to report headaches (OR = 2.00, CI = 1.06, 3.82, but less likely to report muscle/joint pain (OR = 0.28, CI = 0.11, 0.74. Significant disparities were attenuated by up to 16% when associated factors were added to the model. Sexual orientation disparities in chronic pain were partially explained by associated factors, but more research is needed to develop intervention and prevention strategies.

  1. Two signaling molecules share a phosphotyrosine-containing binding site in the platelet-derived growth factor receptor.

    Nishimura, R; Li, W; Kashishian, A; Mondino, A; Zhou, M; Cooper, J; Schlessinger, J

    1993-01-01

    Autophosphorylation sites of growth factor receptors with tyrosine kinase activity function as specific binding sites for Src homology 2 (SH2) domains of signaling molecules. This interaction appears to be a crucial step in a mechanism by which receptor tyrosine kinases relay signals to downstream signaling pathways. Nck is a widely expressed protein consisting exclusively of SH2 and SH3 domains, the overexpression of which causes cell transformation. It has been shown that various growth fac...

  2. The Int7G24A variant of transforming growth factor-beta receptor type I is a risk factor for colorectal cancer in the male Spanish population: a case-control study

    Castillejo, Adela; Guillén-Ponce, Carmen; Carrato, Alfredo; Soto, José-Luís; Mata-Balaguer, Trinidad; Guarinos, Carla; Castillejo, María-Isabel; Martínez-Cantó, Ana; Barberá, Víctor-Manuel; Montenegro, Paola; Ochoa, Enrique; Lázaro, Rafael

    2009-01-01

    The Int7G24A variant of transforming growth factor-beta receptor type I (TGFBR1) has been shown to increase the risk for kidney, ovarian, bladder, lung and breast cancers. Its role in colorectal cancer (CRC) has not been established. The aims of this study were to assess the association of TGFBR1*Int7G24A variant with CRC occurrence, patient age, gender, tumour location and stage. We performed a case-control study with 504 cases of sporadic CRC; and 504 non-cancerous age, gender and ethnically matched controls. Genotyping analysis was performed using allelic discrimination assay by real time PCR. The Int7G24A variant was associated with increased CRC incidence in an additive model of inheritance (P for trend = 0.005). No significant differences were found between Int7G24A genotypes and tumour location or stage. Interestingly, the association of the Int7G24A variant with CRC risk was significant in men (odds ratio 4.10 with 95% confidence intervals 1.41-11.85 for homozygous individuals; P for trend = 0.00023), but not in women. We also observed an increase in susceptibility to CRC for individuals aged less than 70 years. Our data suggest that the Int7G24A variant represents a risk factor for CRC in the male Spanish population

  3. The Int7G24A variant of transforming growth factor-beta receptor type I is a risk factor for colorectal cancer in the male Spanish population: a case-control study

    Lázaro Rafael

    2009-11-01

    Full Text Available Abstract Background The Int7G24A variant of transforming growth factor-beta receptor type I (TGFBR1 has been shown to increase the risk for kidney, ovarian, bladder, lung and breast cancers. Its role in colorectal cancer (CRC has not been established. The aims of this study were to assess the association of TGFBR1*Int7G24A variant with CRC occurrence, patient age, gender, tumour location and stage. Methods We performed a case-control study with 504 cases of sporadic CRC; and 504 non-cancerous age, gender and ethnically matched controls. Genotyping analysis was performed using allelic discrimination assay by real time PCR. Results The Int7G24A variant was associated with increased CRC incidence in an additive model of inheritance (P for trend = 0.005. No significant differences were found between Int7G24A genotypes and tumour location or stage. Interestingly, the association of the Int7G24A variant with CRC risk was significant in men (odds ratio 4.10 with 95% confidence intervals 1.41-11.85 for homozygous individuals; P for trend = 0.00023, but not in women. We also observed an increase in susceptibility to CRC for individuals aged less than 70 years. Conclusion Our data suggest that the Int7G24A variant represents a risk factor for CRC in the male Spanish population.

  4. Functional variation in the arginine vasopressin 2 receptor as a modifier of human plasma von Willebrand factor levels

    Nossent, Anne Yaël; Robben, J H; Deen, P M T

    2010-01-01

    SUMMARY OBJECTIVES: Stimulation of arginine vasopressin 2 receptor (V2R) with arginine vasopressin (AVP) results in a rise in von Willebrand factor (VWF) and factor VIII plasma levels. We hypothesized that gain-of-function variations in the V2R gene (AVPR2) would lead to higher plasma levels of V...

  5. Expression and Regulation of Corticotropin-Releasing Factor Receptor Type 2 beta in Developing and Mature Mouse Skeletal Muscle

    Kuperman, Yael; Issler, Orna; Vaughan, Joan; Bilezikjian, Louise; Vale, Wylie; Chen, Alon

    Corticotropin-releasing factor receptor type 2 (CRFR2) is highly expressed in skeletal muscle (SM) tissue where it is suggested to inhibit interactions between insulin signaling pathway components affecting whole-body glucose homeostasis. However, little is known about factors regulating SM CRFR2

  6. Expression of receptors for putative anabolic growth factors in human intervertebral disc: implications for repair and regeneration of the disc.

    Le Maitre, Christine L; Richardson, Stephen M A; Baird, Pauline; Freemont, Anthony J; Hoyland, Judith A

    2005-12-01

    Low back pain (LBP) is a common, debilitating and economically important disorder. Current evidence implicates loss of intervertebral disc (IVD) matrix consequent upon 'degeneration' as a major cause of LBP. Degeneration of the IVD involves increases in degradative enzymes and decreases in the extracellular matrix (ECM) component in a process that is controlled by a range of cytokines and growth factors. Studies have suggested using anabolic growth factors to regenerate the normal matrix of the IVD, hence restoring disc height and reversing degenerative disc disease. However, for such therapies to be successful it is vital that the target cells (i.e. the disc cells) express the appropriate receptors. This immunohistochemical study has for the first time investigated the expression and localization of four potentially beneficial growth factor receptors (i.e. TGFbetaRII, BMPRII, FGFR3 and IGFRI) in non-degenerate and degenerate human IVDs. Receptor expression was quantified across regions of the normal and degenerate disc and showed that cells of the nucleus pulposus (NP) and inner annulus fibrosus (IAF) expressed significantly higher levels of the four growth factor receptors investigated. There were no significant differences between the four growth factor expression in non-degenerate and degenerate biopsies. However, expression of TGFbetaRII, FGFR3 and IGFRI, but not BMP RII, were observed in the ingrowing blood vessels that characterize part of the disease aetiology. In conclusion, this study has demonstrated the expression of the four growth factor receptors at similar levels in the chondrocyte-like cells of the NP and IAF in both non-degenerate and degenerate discs, implicating a role in normal disc homeostasis and suggesting that the application of these growth factors to the degenerate human IVD would stimulate matrix production. However, the expression of some of the growth factor receptors on ingrowing blood vessels might be problematic in a therapeutic

  7. NF-κB Protects NKT Cells from Tumor Necrosis Factor Receptor 1-induced Death.

    Kumar, Amrendra; Gordy, Laura E; Bezbradica, Jelena S; Stanic, Aleksandar K; Hill, Timothy M; Boothby, Mark R; Van Kaer, Luc; Joyce, Sebastian

    2017-11-15

    Semi-invariant natural killer T (NKT) cells are innate-like lymphocytes with immunoregulatory properties. NKT cell survival during development requires signal processing by activated RelA/NF-κB. Nonetheless, the upstream signal(s) integrated by NF-κB in developing NKT cells remains incompletely defined. We show that the introgression of Bcl-x L -coding Bcl2l1 transgene into NF-κB signalling-deficient IκBΔN transgenic mouse rescues NKT cell development and differentiation in this mouse model. We reasoned that NF-κB activation was protecting developing NKT cells from death signals emanating either from high affinity agonist recognition by the T cell receptor (TCR) or from a death receptor, such as tumor necrosis factor receptor 1 (TNFR1) or Fas. Surprisingly, the single and combined deficiency in PKC-θ or CARMA-1-the two signal transducers at the NKT TCR proximal signalling node-only partially recapitulated the NKT cell deficiency observed in IκBΔN tg mouse. Accordingly, introgression of the Bcl2l1 transgene into PKC-θ null mouse failed to rescue NKT cell development. Instead, TNFR1-deficiency, but not the Fas-deficiency, rescued NKT cell development in IκBΔN tg mice. Consistent with this finding, treatment of thymocytes with an antagonist of the inhibitor of κB kinase -which blocks downstream NF-κB activation- sensitized NKT cells to TNF-α-induced cell death in vitro. Hence, we conclude that signal integration by NF-κB protects developing NKT cells from death signals emanating from TNFR1, but not from the NKT TCR or Fas.

  8. Effect of corticotropin-releasing factor receptor antagonist on psychologically suppressed masculine sexual behavior in rats.

    Miwa, Yoshiji; Nagase, Keiko; Oyama, Nobuyuki; Akino, Hironobu; Yokoyama, Osamu

    2011-03-01

    Corticotropin-releasing factor (CRF) coordinates various responses of the body to stress, and CRF receptors are important targets of treatment for stress-related disorders. To investigate the effect of a nonselective CRF receptor antagonist, astressin, on suppression of masculine sexual behavior by psychological stress in rats. First, we investigated the influence of psychological stress, induced 2 hours per day for three consecutive days, on sexual behavior. Then, rats were divided into 4 groups: a control group, an astressin administration group (A), a psychological stress loading group (PS), and a psychological stress loading and astressin administration group (PS + A). The rats were exposed to sham or psychological stress for three consecutive days. After the last stress loading, the rats were injected with vehicle or astressin, and their sexual behavior was observed. We also measured serum levels of adrenocorticotropic hormone (ACTH). The effects of astressin on sexual behavior and serum levels of ACTH in rats affected by psychological stress were determined. Sexual behavior was reduced after psychological stress loading. The PS rats had significantly longer mount, intromission, and ejaculation latencies and lower ejaculation frequency than did the control, A, and PS + A rats. The intromission latency and ejaculation frequency in the PS + A rats did not achieve the level observed in the controls. There was no significant difference in these parameters between the control and A rats. Serum ACTH levels were significantly lower in PS + A rats than in PS rats. Psychologically suppressed masculine sexual behavior could be partially recovered with astressin administration in rats. These data provide a rationale for the further study of CRF receptor antagonists as novel agents for treating psychological sexual disorders. © 2010 International Society for Sexual Medicine.

  9. Characterization of germ cell-specific expression of the orphan nuclear receptor, germ cell nuclear factor.

    Katz, D; Niederberger, C; Slaughter, G R; Cooney, A J

    1997-10-01

    Nuclear receptors, such as those for androgens, estrogens, and progesterones, control many reproductive processes. Proteins with structures similar to these receptors, but for which ligands have not yet been identified, have been termed orphan nuclear receptors. One of these orphans, germ cell nuclear factor (GCNF), has been shown to be germ cell specific in the adult and, therefore, may also participate in the regulation of reproductive functions. In this paper, we examine more closely the expression patterns of GCNF in germ cells to begin to define spatio-temporal domains of its activity. In situ hybridization showed that GCNF messenger RNA (mRNA) is lacking in the testis of hypogonadal mutant mice, which lack developed spermatids, but is present in the wild-type testis. Thus, GCNF is, indeed, germ cell specific in the adult male. Quantitation of the specific in situ hybridization signal in wild-type testis reveals that GCNF mRNA is most abundant in stage VII round spermatids. Similarly, Northern analysis and specific in situ hybridization show that GCNF expression first occurs in testis of 20-day-old mice, when round spermatids first emerge. Therefore, in the male, GCNF expression occurs postmeiotically and may participate in the morphological changes of the maturing spermatids. In contrast, female expression of GCNF is shown in growing oocytes that have not completed the first meiotic division. Thus, GCNF in the female is expressed before the completion of meiosis. Finally, the nature of the two different mRNAs that hybridize to the GCNF complementary DNA was studied. Although both messages contain the DNA binding domain, only the larger message is recognized by a probe from the extreme 3' untranslated region. In situ hybridization with these differential probes demonstrates that both messages are present in growing oocytes. In addition, the coding region and portions of the 3' untranslated region of the GCNF complementary DNA are conserved in the rat.

  10. Oncogenic role of fibroblast growth factor receptor 3 in tumorigenesis of urinary bladder cancer.

    Pandith, Arshad A; Shah, Zafar A; Siddiqi, Mushtaq A

    2013-05-01

    Bladder cancer is the second most common genitourinary tumor and constitutes a very heterogeneous disease. Molecular and pathologic studies suggest that low-grade noninvasive and high-grade invasive urothelial cell carcinoma (UCC) arise via distinct pathways. Low-grade noninvasive UCC represent the majority of tumors at presentation. A high proportion of patients with low-grade UCC develop recurrences but usually with no progression to invasive disease. At presentation, a majority of the bladder tumors (70%-80%) are low-grade noninvasive (pTa). Several genetic changes may occur in bladder cancer, but activating mutations in the fibroblast growth factor receptor 3 (FGFR3) genes are the most common and most specific genetic abnormality in bladder cancer. Interestingly, these mutations are associated with bladder tumors of low stage and grade, which makes the FGFR3 mutation the first marker that can be used for diagnosis of noninvasive bladder tumors. Since the first report of FGFR3 involvement in bladder tumors, numerous studies have been conducted to understand its function and thereby confirm the oncogenic role of this receptor particularly in noninvasive groups. Efforts are on to exploit this receptor as a therapeutic target, which holds much promise in the treatment of bladder cancer, particularly low-grade noninvasive tumors. Further studies need to explore the potential use of FGFR3 mutations in bladder cancer diagnosis, prognosis, and in surveillance of patients with bladder cancer. This review focuses on the role of FGFR3 in bladder tumors in the backdrop of various studies published. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. The epidermal growth factor receptor as a target for gastrointestinal cancer therapy.

    Tedesco, Karen L; Lockhart, A Craig; Berlin, Jordan D

    2004-10-01

    The epidermal growth factor receptor (EGFR) is a member of the family of transmembrane protein kinase receptors known as the erbB or HER receptor family. When activated, EGFR phosphorylates and activates other intracellular proteins that affect cell signaling pathways, cellular proliferation, control of apoptosis and angiogenesis. EGFR signaling is best thought of as a network of activating and inactivating proteins with EGFR as the entry point into the network. EGFR overexpression occurs in most GI malignancies and while data are not entirely consistent, EGFR overexpression often confers a poor prognosis in those GI malignancies that have been studied. It often correlates with poorly differentiated histology, more advanced stage and other known poor prognostic markers. The EGFR is a tempting target because of its presence and overexpression on so many tumor types. However, downstream of the EGFR are several proteins that may be activated without EGFR thus allowing blockade to be overcome. Therefore, while blocking the activity of the EGFR protein appears to be a promising anticancer strategy, a simplistic strategy of blocking only EGFR is likely to only impact a minority of patients. It is time for the laboratory and clinical researchers to work closely together to develop this treatment strategy, moving back and forth from clinical to laboratory to best understand how to block this network effectively enough to produce a broader antitumor effect. While multiple methods of targeting the EGFR pathway are under development, including the inhibition of downstream proteins, only two modalities have entered clinical trials in GI malignancies: small molecule inhibitors of the intracellular kinase domain of EGFR and antibodies designed to block the extracellular ligand-binding domain of EGFR. EGFR inhibitors are still experimental in every GI malignancy with the notable exception of cetuximab that is approved for second or third-line therapy of metastatic colorectal

  12. Targeting the epidermal growth factor receptor in radiotherapy: radiobiological mechanisms, preclinical and clinical results

    Baumann, Michael; Krause, Mechthild

    2004-01-01

    Background and purpose: Inhibition of the epidermal growth factor receptor (EGFR) is a fastly developing field in preclinical and clinical cancer research. This review presents the current status of knowledge and discusses radiobiological mechanisms which may underly the efficacy of EGFR inhibitors combined with irradiation. Materials and methods: Preclinical and clinical results on combined targeting of the EGFR and irradiation from the literature and from this laboratory are reviewed. Focus is given to the radiobiological rationale of this approach and to endpoints of experimental radiotherapy. Results: Overexpression of the EGFR is associated with decreased local tumour control after radiotherapy, especially when the overall treatment time is long. Inhibition of the EGFR either alone or in combination with irradiation decreases the growth rate of tumours expressing this receptor. Preclinical data provide proof-of-principle that local tumour control may be improved by combining irradiation with C225 mAb. In a randomised phase III clinical trial, simultaneous irradiation and treatment with the EGFR antibody Cetuximab (Erbitux[reg]; C225) in head and neck cancer patients resulted in significantly improved locoregional tumour control and survival compared to curative irradiation alone. Acute skin reactions increased in the experimental arm. The underlying mechanisms of enhanced radiation effects of combined EGFR inhibition with irradiation and of the partly conflicting results in different studies are poorly understood. There is increasing evidence, that important intertumoral heterogeneity in the response to EGFR inhibition alone and combined with irradiation exists, which appears to be at least partly dependent on specific mutations of the receptor as well as of molecules that are involved in the intracellular signal transduction pathway. Conclusions and outlook: Further investigations at all levels of the translational research chain exploring the mechanisms of

  13. Amphiregulin triggered epidermal growth factor receptor activation confers in vivo crizotinib-resistance of EML4-ALK lung cancer and circumvention by epidermal growth factor receptor inhibitors.

    Taniguchi, Hirokazu; Takeuchi, Shinji; Fukuda, Koji; Nakagawa, Takayuki; Arai, Sachiko; Nanjo, Shigeki; Yamada, Tadaaki; Yamaguchi, Hiroyuki; Mukae, Hiroshi; Yano, Seiji

    2017-01-01

    Crizotinib, a first-generation anaplastic lymphoma kinase (ALK) tyrosine-kinase inhibitor, is known to be effective against echinoderm microtubule-associated protein-like 4 (EML4)-ALK-positive non-small cell lung cancers. Nonetheless, the tumors subsequently become resistant to crizotinib and recur in almost every case. The mechanism of the acquired resistance needs to be deciphered. In this study, we established crizotinib-resistant cells (A925LPE3-CR) via long-term administration of crizotinib to a mouse model of pleural carcinomatous effusions; this model involved implantation of the A925LPE3 cell line, which harbors the EML4-ALK gene rearrangement. The resistant cells did not have the secondary ALK mutations frequently occurring in crizotinib-resistant cells, and these cells were cross-resistant to alectinib and ceritinib as well. In cell clone #2, which is one of the clones of A925LPE3-CR, crizotinib sensitivity was restored via the inhibition of epidermal growth factor receptor (EGFR) by means of an EGFR tyrosine-kinase inhibitor (erlotinib) or an anti-EGFR antibody (cetuximab) in vitro and in the murine xenograft model. Cell clone #2 did not have an EGFR mutation, but the expression of amphiregulin (AREG), one of EGFR ligands, was significantly increased. A knockdown of AREG with small interfering RNAs restored the sensitivity to crizotinib. These data suggest that overexpression of EGFR ligands such as AREG can cause resistance to crizotinib, and that inhibition of EGFR signaling may be a promising strategy to overcome crizotinib resistance in EML4-ALK lung cancer. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  14. Fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) autocrine enhance breast cancer cells survival.

    Tiong, Kai Hung; Tan, Boon Shing; Choo, Heng Lungh; Chung, Felicia Fei-Lei; Hii, Ling-Wei; Tan, Si Hoey; Khor, Nelson Tze Woei; Wong, Shew Fung; See, Sze-Jia; Tan, Yuen-Fen; Rosli, Rozita; Cheong, Soon-Keng; Leong, Chee-Onn

    2016-09-06

    Basal-like breast cancer is an aggressive tumor subtype with poor prognosis. The discovery of underlying mechanisms mediating tumor cell survival, and the development of novel agents to target these pathways, is a priority for patients with basal-like breast cancer. From a functional screen to identify key drivers of basal-like breast cancer cell growth, we identified fibroblast growth factor receptor 4 (FGFR4) as a potential mediator of cell survival. We found that FGFR4 mediates cancer cell survival predominantly via activation of PI3K/AKT. Importantly, a subset of basal-like breast cancer cells also secrete fibroblast growth factor 19 (FGF19), a canonical ligand specific for FGFR4. siRNA-mediated silencing of FGF19 or neutralization of extracellular FGF19 by anti-FGF19 antibody (1A6) decreases AKT phosphorylation, suppresses cancer cell growth and enhances doxorubicin sensitivity only in the FGFR4+/FGF19+ breast cancer cells. Consistently, FGFR4/FGF19 co-expression was also observed in 82 out of 287 (28.6%) primary breast tumors, and their expression is strongly associated with AKT phosphorylation, Ki-67 staining, higher tumor stage and basal-like phenotype. In summary, our results demonstrated the presence of an FGFR4/FGF19 autocrine signaling that mediates the survival of a subset of basal-like breast cancer cells and suggest that inactivation of this autocrine loop may potentially serve as a novel therapeutic intervention for future treatment of breast cancers.

  15. Association of Polymorphisms in Connective Tissue Growth Factor and Epidermal Growth Factor Receptor Genes With Human Longevity.

    Donlon, Timothy A; Morris, Brian J; He, Qimei; Chen, Randi; Masaki, Kamal H; Allsopp, Richard C; Willcox, D Craig; Tranah, Gregory J; Parimi, Neeta; Evans, Daniel S; Flachsbart, Friederike; Nebel, Almut; Kim, Duk-Hwan; Park, Joobae; Willcox, Bradley J

    2017-08-01

    Growth pathways play key roles in longevity. The present study tested single-nucleotide polymorphisms (SNPs) in the connective tissue growth factor gene (CTGF) and the epidermal growth factor receptor gene (EGFR) for association with longevity. Comparison of allele and genotype frequencies of 12 CTGF SNPs and 41 EGFR SNPs between 440 American men of Japanese ancestry aged ≥95 years and 374 men of average life span revealed association with longevity at the p cases, consistent with heterozygote advantage in living to extreme old age. No associations of the most significant SNPs were observed in whites or Koreans. In conclusion, the present findings indicate that genetic variation in CTGF and EGFR may contribute to the attainment of extreme old age in Japanese. More research is needed to confirm that genetic variation in CTGF and EGFR contributes to the attainment of extreme old age across human populations. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Binding characteristics of brain-derived neurotrophic factor to its receptors on neurons from the chick embryo

    Rodriguez-Tebar, A.; Barde, Y.A.

    1988-09-01

    Brain-derived neurotrophic factor (BDNF), a protein known to support the survival of embryonic sensory neurons and retinal ganglion cells, was derivatized with 125I-Bolton-Hunter reagent and obtained in a biologically active, radioactive form (125I-BDNF). Using dorsal root ganglion neurons from chick embryos at 9 d of development, the basic physicochemical parameters of the binding of 125I-BDNF with its receptors were established. Two different classes of receptors were found, with dissociation constants of 1.7 x 10(-11) M (high-affinity receptors) and 1.3 x 10(-9) M (low-affinity receptors). Unlabeled BDNF competed with 125I-BDNF for binding to the high-affinity receptors with an inhibition constant essentially identical to the dissociation constant of the labeled protein: 1.2 x 10(-11) M. The association and dissociation rates from both types of receptors were also determined, and the dissociation constants calculated from these kinetic experiments were found to correspond to the results obtained from steady-state binding. The number of high-affinity receptors (a few hundred per cell soma) was 15 times lower than that of low-affinity receptors. No high-affinity receptors were found on sympathetic neurons, known not to respond to BDNF, although specific binding of 125I-BDNF to these cells was detected at a high concentration of the radioligand. These results are discussed and compared with those obtained with nerve growth factor on the same neuronal populations.

  17. Binding characteristics of brain-derived neurotrophic factor to its receptors on neurons from the chick embryo

    Rodriguez-Tebar, A.; Barde, Y.A.

    1988-01-01

    Brain-derived neurotrophic factor (BDNF), a protein known to support the survival of embryonic sensory neurons and retinal ganglion cells, was derivatized with 125I-Bolton-Hunter reagent and obtained in a biologically active, radioactive form (125I-BDNF). Using dorsal root ganglion neurons from chick embryos at 9 d of development, the basic physicochemical parameters of the binding of 125I-BDNF with its receptors were established. Two different classes of receptors were found, with dissociation constants of 1.7 x 10(-11) M (high-affinity receptors) and 1.3 x 10(-9) M (low-affinity receptors). Unlabeled BDNF competed with 125I-BDNF for binding to the high-affinity receptors with an inhibition constant essentially identical to the dissociation constant of the labeled protein: 1.2 x 10(-11) M. The association and dissociation rates from both types of receptors were also determined, and the dissociation constants calculated from these kinetic experiments were found to correspond to the results obtained from steady-state binding. The number of high-affinity receptors (a few hundred per cell soma) was 15 times lower than that of low-affinity receptors. No high-affinity receptors were found on sympathetic neurons, known not to respond to BDNF, although specific binding of 125I-BDNF to these cells was detected at a high concentration of the radioligand. These results are discussed and compared with those obtained with nerve growth factor on the same neuronal populations

  18. Increased expression of protease-activated receptor 4 and Trefoil factor 2 in human colorectal cancer.

    Guoyu Yu

    Full Text Available Protease-activated receptor 4 (PAR4, a member of G-protein coupled receptors family, was recently reported to exhibit decreased expression in gastric cancer and esophageal squamous cancer, yet increased expression during the progression of prostate cancer. Trefoil factor 2 (TFF2, a small peptide constitutively expressed in the gastric mucosa, plays a protective role in restitution of gastric mucosa. Altered TFF2 expression was also related to the development of gastrointestinal cancer. TFF2 has been verified to promote cell migration via PAR4, but the roles of PAR4 and TFF2 in the progress of colorectal cancer are still unknown. In this study, the expression level of PAR4 and TFF2 in colorectal cancer tissues was measured using real-time PCR (n = 38, western blotting (n=38 and tissue microarrays (n = 66. The mRNA and protein expression levels of PAR4 and TFF2 were remarkably increased in colorectal cancer compared with matched noncancerous tissues, especially in positive lymph node and poorly differentiated cancers. The colorectal carcinoma cell LoVo showed an increased response to TFF2 as assessed by cell invasion upon PAR4 expression. However, after intervention of PAR4 expression, PAR4 positive colorectal carcinoma cell HT-29 was less responsive to TFF2 in cell invasion. Genomic bisulfite sequencing showed the hypomethylation of PAR4 promoter in colorectal cancer tissues and the hypermethylation in the normal mucosa that suggested the low methylation of promoter was correlated to the increased PAR4 expression. Taken together, the results demonstrated that the up-regulated expression of PAR4 and TFF2 frequently occurs in colorectal cancer tissues, and that overexpression of PAR4 may be resulted from promoter hypomethylation. While TFF2 promotes invasion activity of LoVo cells overexpressing PAR4, and this effect was significantly decreased when PAR4 was knockdowned in HT-29 cells. Our findings will be helpful in further investigations into the

  19. Emerging role of epidermal growth factor receptor inhibition in therapy for advanced malignancy: focus on NSCLC

    Langer, Corey J.

    2004-01-01

    Combination chemotherapy regimens have emerged as the standard approach in advanced non-small-cell lung cancer. Meta-analyses have demonstrated a 2-month increase in median survival after platinum-based therapy vs. best supportive care, and an absolute 10% improvement in the 1-year survival rate. Just as importantly, cytotoxic therapy has produced benefits in symptom control and quality of life. Newer agents, including the taxanes, vinorelbine, gemcitabine, and irinotecan, have expanded our therapeutic options in the treatment of advanced non-small-cell lung cancer. Despite their contributions, we have reached a therapeutic plateau, with response rates seldom exceeding 30-40% in cooperative group studies and 1-year survival rates stable between 30% and 40%. It is doubtful that substituting one agent for another in various combinations will lead to any further improvement in these rates. The thrust of current research has focused on targeted therapy, and epidermal growth factor receptor inhibition is one of the most promising clinical strategies. Epidermal growth factor receptor inhibitors currently under investigation include the small molecules gefitinib (Iressa, ZD1839) and erlotinib (Tarceva, OSI-774), as well as monoclonal antibodies such as cetuximab (IMC-225, Erbitux). Agents that have only begun to undergo clinical evaluation include CI-1033, an irreversible pan-erbB tyrosine kinase inhibitor, and PKI166 and GW572016, both examples of dual kinase inhibitors (inhibiting epidermal growth factor receptor and Her2). Preclinical models have demonstrated synergy for all these agents in combination with either chemotherapy or radiotherapy, leading to great enthusiasm regarding their ultimate contribution to lung cancer therapy. However, serious clinical challenges persist. These include the identification of the optimal dose(s); the proper integration of these agents into popular, established cytotoxic regimens; and the selection of the optimal setting(s) in which

  20. Pluripotency factors and Polycomb Group proteins repress aryl hydrocarbon receptor expression in murine embryonic stem cells

    Chia-I Ko

    2014-01-01

    Full Text Available The aryl hydrocarbon receptor (AHR is a transcription factor and environmental sensor that regulates expression of genes involved in drug-metabolism and cell cycle regulation. Chromatin immunoprecipitation analyses, Ahr ablation in mice and studies with orthologous genes in invertebrates suggest that AHR may also play a significant role in embryonic development. To address this hypothesis, we studied the regulation of Ahr expression in mouse embryonic stem cells and their differentiated progeny. In ES cells, interactions between OCT3/4, NANOG, SOX2 and Polycomb Group proteins at the Ahr promoter repress AHR expression, which can also be repressed by ectopic expression of reprogramming factors in hepatoma cells. In ES cells, unproductive RNA polymerase II binds at the Ahr transcription start site and drives the synthesis of short abortive transcripts. Activation of Ahr expression during differentiation follows from reversal of repressive marks in Ahr promoter chromatin, release of pluripotency factors and PcG proteins, binding of Sp factors, establishment of histone marks of open chromatin, and engagement of active RNAPII to drive full-length RNA transcript elongation. Our results suggest that reversible Ahr repression in ES cells holds the gene poised for expression and allows for a quick switch to activation during embryonic development.

  1. Insulin and insulin-like growth factor receptors in the brain: physiological and pathological aspects.

    Werner, Haim; LeRoith, Derek

    2014-12-01

    The involvement of insulin, the insulin-like growth factors (IGF1, IGF2) and their receptors in central nervous system development and function has been the focus of scientific interest for more than 30 years. The insulin-like peptides, both locally-produced proteins as well as those transported from the circulation into the brain via the blood-brain barrier, are involved in a myriad of biological activities. These actions include, among others, neuronal survival, neurogenes, angiogenesis, excitatory and inhibitory neurotransmission, regulation of food intake, and cognition. In recent years, a linkage between brain insulin/IGF1 and certain neuropathologies has been identified. Epidemiological studies have demonstrated a correlation between diabetes (mainly type 2) and Alzheimer׳s disease. In addition, an aberrant decline in IGF1 values was suggested to play a role in the development of Alzheimer׳s disease. The present review focuses on the expression and function of insulin, IGFs and their receptors in the brain in physiological and pathological conditions. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  2. DNA homologous recombination factor SFR1 physically and functionally interacts with estrogen receptor alpha.

    Yuxin Feng

    Full Text Available Estrogen receptor alpha (ERα, a ligand-dependent transcription factor, mediates the expression of its target genes by interacting with corepressors and coactivators. Since the first cloning of SRC1, more than 280 nuclear receptor cofactors have been identified, which orchestrate target gene transcription. Aberrant activity of ER or its accessory proteins results in a number of diseases including breast cancer. Here we identified SFR1, a protein involved in DNA homologous recombination, as a novel binding partner of ERα. Initially isolated in a yeast two-hybrid screen, the interaction of SFR1 and ERα was confirmed in vivo by immunoprecipitation and mammalian one-hybrid assays. SFR1 co-localized with ERα in the nucleus, potentiated ER's ligand-dependent and ligand-independent transcriptional activity, and occupied the ER binding sites of its target gene promoters. Knockdown of SFR1 diminished ER's transcriptional activity. Manipulating SFR1 expression by knockdown and overexpression revealed a role for SFR1 in ER-dependent and -independent cancer cell proliferation. SFR1 differs from SRC1 by the lack of an intrinsic activation function. Taken together, we propose that SFR1 is a novel transcriptional modulator for ERα and a potential target in breast cancer therapy.

  3. The transcription factor ERG increases expression of neurotransmitter receptors on prostate cancer cells

    Kissick, Haydn T.; On, Seung T.; Dunn, Laura K.; Sanda, Martin G.; Asara, John M.; Pellegrini, Kathryn L.; Noel, Jonathan K.; Arredouani, Mohamed S.

    2015-01-01

    The TMPRSS2-ERG gene fusion occurs in about half of prostate cancer (PCa) cases and results in overexpression of the transcription factor ERG. Overexpression of ERG has many effects on cellular function. However, how these changes enhance cell growth and promote tumor development is unclear. To investigate the role of ERG, LNCaP and PC3 cells were transfected with ERG and gene expression and metabolic profile were analyzed. Our data show that expression of ERG induces overexpression of many nicotinicacetylcholine receptors (nAChRs). In addition, metabolic profiling by LC-MS/MS revealed elevated production of several neurotransmitters in cells expressing ERG. Consistently, treatment of ERG-expressing cells with nicotine induced elevated calcium influx, GSK3β (Ser9) phosphorylation and cell proliferation. Finally, we show that PCa patientswho are smokers have larger tumors if their tumors are TMPRSS2-ERG gene fusion positive. Collectively, our data suggest that ERG sensitizes prostate tumor cells to neurotransmitter receptor agonists like nicotine. The online version of this article (doi:10.1186/s12885-015-1612-3) contains supplementary material, which is available to authorized users

  4. Characterization of the receptors for mycobacterial cord factor in Guinea pig.

    Kenji Toyonaga

    Full Text Available Guinea pig is a widely used animal for research and development of tuberculosis vaccines, since its pathological disease process is similar to that present in humans. We have previously reported that two C-type lectin receptors, Mincle (macrophage inducible C-type lectin, also called Clec4e and MCL (macrophage C-type lectin, also called Clec4d, recognize the mycobacterial cord factor, trehalose-6,6'-dimycolate (TDM. Here, we characterized the function of the guinea pig homologue of Mincle (gpMincle and MCL (gpMCL. gpMincle directly bound to TDM and transduced an activating signal through ITAM-bearing adaptor molecule, FcRγ. Whereas, gpMCL lacked C-terminus and failed to bind to TDM. mRNA expression of gpMincle was detected in the spleen, lymph nodes and peritoneal macrophages and it was strongly up-regulated upon stimulation of zymosan and TDM. The surface expression of gpMincle was detected on activated macrophages by a newly established monoclonal antibody that also possesses a blocking activity. This antibody potently suppressed TNF production in BCG-infected macrophages. Collectively, gpMincle is the TDM receptor in the guinea pig and TDM-Mincle axis is involved in host immune responses against mycobacteria.

  5. Characterization of the receptors for mycobacterial cord factor in Guinea pig.

    Toyonaga, Kenji; Miyake, Yasunobu; Yamasaki, Sho

    2014-01-01

    Guinea pig is a widely used animal for research and development of tuberculosis vaccines, since its pathological disease process is similar to that present in humans. We have previously reported that two C-type lectin receptors, Mincle (macrophage inducible C-type lectin, also called Clec4e) and MCL (macrophage C-type lectin, also called Clec4d), recognize the mycobacterial cord factor, trehalose-6,6'-dimycolate (TDM). Here, we characterized the function of the guinea pig homologue of Mincle (gpMincle) and MCL (gpMCL). gpMincle directly bound to TDM and transduced an activating signal through ITAM-bearing adaptor molecule, FcRγ. Whereas, gpMCL lacked C-terminus and failed to bind to TDM. mRNA expression of gpMincle was detected in the spleen, lymph nodes and peritoneal macrophages and it was strongly up-regulated upon stimulation of zymosan and TDM. The surface expression of gpMincle was detected on activated macrophages by a newly established monoclonal antibody that also possesses a blocking activity. This antibody potently suppressed TNF production in BCG-infected macrophages. Collectively, gpMincle is the TDM receptor in the guinea pig and TDM-Mincle axis is involved in host immune responses against mycobacteria.

  6. Regulation of granulocyte colony-stimulating factor receptor-mediated granulocytic differentiation by C-mannosylation.

    Otani, Kei; Niwa, Yuki; Suzuki, Takehiro; Sato, Natsumi; Sasazawa, Yukiko; Dohmae, Naoshi; Simizu, Siro

    2018-04-06

    Granulocyte colony-stimulating factor (G-CSF) receptor (G-CSFR) is a type I cytokine receptor which is involved in hematopoietic cell maturation. G-CSFR has three putative C-mannosylation sites at W253, W318, and W446; however, it is not elucidated whether G-CSFR is C-mannosylated or not. In this study, we first demonstrated that G-CSFR was C-mannosylated at only W318. We also revealed that C-mannosylation of G-CSFR affects G-CSF-dependent downstream signaling through changing ligand binding capability but not cell surface localization. Moreover, C-mannosylation of G-CSFR was functional and regulated granulocytic differentiation in myeloid 32D cells. In conclusion, we found that G-CSFR is C-mannosylated at W318 and that this C-mannosylation has role(s) for myeloid cell differentiation through regulating downstream signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Targeting Epidermal Growth Factor Receptor-Related Signaling Pathways in Pancreatic Cancer.

    Philip, Philip A; Lutz, Manfred P

    2015-10-01

    Pancreatic cancer is aggressive, chemoresistant, and characterized by complex and poorly understood molecular biology. The epidermal growth factor receptor (EGFR) pathway is frequently activated in pancreatic cancer; therefore, it is a rational target for new treatments. However, the EGFR tyrosine kinase inhibitor erlotinib is currently the only targeted therapy to demonstrate a very modest survival benefit when added to gemcitabine in the treatment of patients with advanced pancreatic cancer. There is no molecular biomarker to predict the outcome of erlotinib treatment, although rash may be predictive of improved survival; EGFR expression does not predict the biologic activity of anti-EGFR drugs in pancreatic cancer, and no EGFR mutations are identified as enabling the selection of patients likely to benefit from treatment. Here, we review clinical studies of EGFR-targeted therapies in combination with conventional cytotoxic regimens or multitargeted strategies in advanced pancreatic cancer, as well as research directed at molecules downstream of EGFR as alternatives or adjuncts to receptor targeting. Limitations of preclinical models, patient selection, and trial design, as well as the complex mechanisms underlying resistance to EGFR-targeted agents, are discussed. Future clinical trials must incorporate translational research end points to aid patient selection and circumvent resistance to EGFR inhibitors.

  8. Job stress, occupational position and gender as factors differentiating workplace bullying experience.

    Drabek, Marcin; Merecz, Dorota

    2013-01-01

    The results of our research broaden the knowledge concerning the correlates of mobbing. The study is aimed at finding out whether an employee's gender, his/her occupational position and level of occupational stress are related to bullying experience. 1313 employees of a transport company participated in the study. The relationships between gender, occupational position, the level of stress and bullying were analysed. Bullying was measured by the use of the MD)M Questionnaire, while work environment was assessed using the Subjective Assessment of Work Questionnaire. It was found that women were generally more exposed to bullying than men (Z = -1.999; p company, its organisational culture as well as its situation. Therefore it's difficult to talk about irrefutable individual correlates of bullying at work.

  9. Epidermal growth factor receptor coexpression modulates susceptibility to Herceptin in HER2/neu overexpressing breast cancer cells via specific erbB-receptor interaction and activation

    Diermeier, Simone; Horvath, Gabor; Knuechel-Clarke, Ruth; Hofstaedter, Ferdinand; Szoellosi, Janos; Brockhoff, Gero

    2005-01-01

    Background: Growth factors and Herceptin specifically and differentially modulate cell proliferation of tumor cells. However, the mechanism of action on erbB-receptor level is incompletely understood. We evaluated Herceptin's capacity to modulate erbB-receptor activation and interaction on the cell surface level and thereby potentially impair cell proliferation of HER2/neu (c-erbB2) overexpressing breast cancer cells, both in the presence and absence of relevant growth factors. Methods: BT474 and SK-BR-3 breast cancer cell lines were treated with Epidermal Growth Factor (EGF), Heregulin, and with Herceptin in different combinations. Kinetics of cell proliferation were evaluated flow cytometrically based on BrdU-labeling. Fluorescence Resonance Energy Transfer, ELISAs and phosphorylation site specific Western Blotting was performed to investigate erbB-receptor interaction and activation. Results: EGF induced EGFR/EGFR and EGFR/c-erbB2 interactions correlate with stimulation of cell proliferation in BT474 cells. Both homo- and heterodimerization are considerably less pronounced in SK-BR-3 cells and heterointeraction is additionally reduced by EGF treatment, causing inhibition of cell proliferation. Heregulin stimulates cell proliferation extensively in both cell lines. Herceptin drives BT474 cells more efficiently into quiescence than it does with SK-BR-3 cells and thereby blocks cell cycle progress. In SK-BR-3 Herceptin treatment causes c-erbB2 phosphorylation of Y877 and Y1248, EGF induces Y877 and Y1112 phosphorylation. The Y1112 phosphorylation site, activated by EGF in SK-BR-3 cell, is bypassed in BT474. In addition the inhibitory capacity of Herceptin on BT474 and SK-BR-3 cell proliferation depends on the presence and absence of growth factors to a various extent. Conclusion: The growth inhibitory effect of Herceptin on c-erbB2 overexpressing breast cancer cells is considerably modulated by EGFR coexpression and consequently EGFR/c-erbB2 homo- and

  10. Gender as a factor in differentiating strategies of coping with stress used by physical education students

    Monika Guszkowska; Adriana Zagórska-Pachucka; Anna Kuk; Katarzyna Skwarek

    2016-01-01

    Background Students are exposed to numerous stressors associated with their integration into their university education, their relationships with friends, and anxiety about the future. Given that stress may be related to university students’ academic performance, understanding the coping strategies used by students may be important in facilitating a positive transition to a university setting. The aim of this study was to determine the gender-based variation of strategies for coping with...

  11. Depression Vulnerability Predicts Cigarette Smoking among College Students: Gender and Negative Reinforcement Expectancies as Contributing Factors

    Morrell, Holly E. R.; Cohen, Lee M.; McChargue, Dennis E.

    2010-01-01

    This study examined the association between vulnerability to depression and smoking behavior in college students in 1214 college students (54% female), and evaluated gender and expectancies of negative affect reduction as moderators or mediators of this relationship. Depression vulnerability predicted smoking in females, but not males. The relationship between depression vulnerability and smoking status was mediated by expectancies of negative affect reduction in females only. Female college ...

  12. [Gender identity, a factor of inequality forgotten by Spanish health information systems].

    Gil-Borrelli, Christian; Velasco, César; Martí-Pastor, Marc; Latasa, Pello

    The Spanish Health Information System (HIS) collects health information. Trans people have poorer health status. This paper aimed to assess the adequacy of the HIS to collect the health data on trans individuals. The HIS sources available in the Statistical Portal of the National Health System were reviewed. The sources containing population health data were selected. The variables "sex" and "gender identity" were searched. Nineteen sources were identified. In all of them the variable "sex" was found, whereas "gender identify" did not appear in any of the 19. In two sources, the variable "sex" allowed values of "transsexual". The SIS contains little information regarding gender identity. This leads to the invisibility of trans people in Spanish health statistics. Obtaining this information would allow for a better understanding of the barriers to health care access, and the health needs of one of the most discriminated groups in our society. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Activated factor X signaling via protease-activated receptor 2 suppresses pro-inflammatory cytokine production from LPS-stimulated myeloid cells.

    Gleeson, Eimear M

    2013-07-19

    Vitamin K-dependent proteases generated in response to vascular injury and infection enable fibrin clot formation, but also trigger distinct immuno-regulatory signaling pathways on myeloid cells. Factor Xa, a protease crucial for blood coagulation, also induces protease-activated receptor-dependent cell signaling. Factor Xa can bind both monocytes and macrophages, but whether factor Xa-dependent signaling stimulates or suppresses myeloid cell cytokine production in response to Toll-like receptor activation is not known. In this study, exposure to factor Xa significantly impaired pro-inflammatory cytokine production from lipopolysaccharide-treated peripheral blood mononuclear cells, THP-1 monocytic cells and murine macrophages. Furthermore, factor Xa inhibited nuclear factor-kappa B activation in THP-1 reporter cells, requiring phosphatidylinositide 3-kinase activity for its anti-inflammatory effect. Active-site blockade, γ-carboxyglutamic acid domain truncation and a peptide mimic of the factor Xa inter-epidermal growth factor-like region prevented factor Xa inhibition of lipopolysaccharide-induced tumour necrosis factor-α release. In addition, factor Xa anti-inflammatory activity was markedly attenuated by the presence of an antagonist of protease-activated receptor 2, but not protease-activated receptor 1. The key role of protease-activated receptor 2 in eliciting factor Xa-dependent anti-inflammatory signaling on macrophages was further underscored by the inability of factor Xa to mediate inhibition of tumour necrosis factor-α and interleukin-6 release from murine bone marrow-derived protease-activated receptor 2-deficient macrophages. We also show for the first time that, in addition to protease-activated receptor 2, factor Xa requires a receptor-associated protein-sensitive low-density lipoprotein receptor to inhibit lipopolysaccharide-induced cytokine production. Collectively, this study supports a novel function for factor Xa as an endogenous, receptor

  14. Increased Eps15 homology domain 1 and RAB11FIP3 expression regulate breast cancer progression via promoting epithelial growth factor receptor recycling.

    Tong, Dandan; Liang, Ya-Nan; Stepanova, A A; Liu, Yu; Li, Xiaobo; Wang, Letian; Zhang, Fengmin; Vasilyeva, N V

    2017-02-01

    Recent research indicates that the C-terminal Eps15 homology domain 1 is associated with epithelial growth factor receptor-mediated endocytosis recycling in non-small-cell lung cancer. The aim of this study was to determine the clinical significance of Eps15 homology domain 1 gene expression in relation to phosphorylation of epithelial growth factor receptor expression in patients with breast cancer. Primary breast cancer samples from 306 patients were analyzed for Eps15 homology domain 1, RAB11FIP3, and phosphorylation of epithelial growth factor receptor expression via immunohistochemistry. The clinical significance was assessed via a multivariate Cox regression analysis, Kaplan-Meier curves, and the log-rank test. Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor were upregulated in 60.46% (185/306) and 53.92% (165/306) of tumor tissues, respectively, as assessed by immunohistochemistry. The statistical correlation analysis indicated that Eps15 homology domain 1 overexpression was positively correlated with the increases in phosphorylation of epithelial growth factor receptor ( r = 0.242, p breast cancer for the overall survival in the total, chemotherapy, and human epidermal growth factor receptor 2 (-) groups. However, the use of combined expression of Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor markers is more effective for the disease-free survival in the overall population, chemotherapy, and human epidermal growth factor receptor 2 (-) groups. Moreover, the combined markers are also significant prognostic markers of breast cancer in the human epidermal growth factor receptor 2 (+), estrogen receptor (+), and estrogen receptor (-) groups. Eps15 homology domain 1 has a tumor suppressor function, and the combined marker of Eps15 homology domain 1/phosphorylation of epithelial growth factor receptor expression was identified as a better prognostic marker in breast cancer diagnosis

  15. Single-domain antibodies that compete with the natural ligand fibroblast growth factor block the internalization of the fibroblast growth factor receptor 1

    Veggiani, Gianluca; Ossolengo, Giuseppe; Aliprandi, Marisa; Cavallaro, Ugo [IFOM-IEO Campus, Via Adamello 16, 20139 Milano (Italy); Marco, Ario de, E-mail: ario.demarco@ung.si [IFOM-IEO Campus, Via Adamello 16, 20139 Milano (Italy); Dept. Environmental Sciences, University of Nova Gorica (UNG), Vipavska 13, P.O. Box 301-SI-5000, Rozna Dolina, Nova Gorica (Slovenia)

    2011-05-20

    Highlights: {yields} Recombinant antibodies for FGFR1 were isolated from a llama naive library in VHH format. {yields} These antibodies compete with the natural ligand FGF-2 for the same epitope on FGFR1. {yields} The antibody competition inhibits the FGF-2-dependent internalization of FGFR1. -- Abstract: Single-domain antibodies in VHH format specific for fibroblast growth factor receptor 1 (FGFR1) were isolated from a phage-display llama naive library. In particular, phage elution in the presence of the natural receptor ligand fibroblast growth factor (FGF) allowed for the identification of recombinant antibodies that compete with FGF for the same region on the receptor surface. These antibodies posses a relatively low affinity for FGFR1 and were never identified when unspecific elution conditions favoring highly affine binders were applied to panning procedures. Two populations of competitive antibodies were identified that labeled specifically the receptor-expressing cells in immunofluorescence and recognize distinct epitopes. Antibodies from both populations effectively prevented FGF-dependent internalization and nuclear accumulation of the receptor in cultured cells. This achievement indicates that these antibodies have a capacity to modulate the receptor physiology and, therefore, constitute powerful reagents for basic research and a potential lead for therapeutic applications.

  16. Single-domain antibodies that compete with the natural ligand fibroblast growth factor block the internalization of the fibroblast growth factor receptor 1

    Veggiani, Gianluca; Ossolengo, Giuseppe; Aliprandi, Marisa; Cavallaro, Ugo; Marco, Ario de

    2011-01-01

    Highlights: → Recombinant antibodies for FGFR1 were isolated from a llama naive library in VHH format. → These antibodies compete with the natural ligand FGF-2 for the same epitope on FGFR1. → The antibody competition inhibits the FGF-2-dependent internalization of FGFR1. -- Abstract: Single-domain antibodies in VHH format specific for fibroblast growth factor receptor 1 (FGFR1) were isolated from a phage-display llama naive library. In particular, phage elution in the presence of the natural receptor ligand fibroblast growth factor (FGF) allowed for the identification of recombinant antibodies that compete with FGF for the same region on the receptor surface. These antibodies posses a relatively low affinity for FGFR1 and were never identified when unspecific elution conditions favoring highly affine binders were applied to panning procedures. Two populations of competitive antibodies were identified that labeled specifically the receptor-expressing cells in immunofluorescence and recognize distinct epitopes. Antibodies from both populations effectively prevented FGF-dependent internalization and nuclear accumulation of the receptor in cultured cells. This achievement indicates that these antibodies have a capacity to modulate the receptor physiology and, therefore, constitute powerful reagents for basic research and a potential lead for therapeutic applications.

  17. Aberrant Receptor Internalization and Enhanced FRS2-dependent Signaling Contribute to the Transforming Activity of the Fibroblast Growth Factor Receptor 2 IIIb C3 Isoform*

    Cha, Jiyoung Y.; Maddileti, Savitri; Mitin, Natalia; Harden, T. Kendall; Der, Channing J.

    2009-01-01

    Alternative splice variants of fibroblast growth factor receptor 2 (FGFR2) IIIb, designated C1, C2, and C3, possess progressive reduction in their cytoplasmic carboxyl termini (822, 788, and 769 residues, respectively), with preferential expression of the C2 and C3 isoforms in human cancers. We determined that the progressive deletion of carboxyl-terminal sequences correlated with increasing transforming potency. The highly transforming C3 variant lacks five tyrosine r...

  18. 99m Tc-anti-epidermal growth factor receptor nanobody for tumor imaging.

    Piramoon, Majid; Hosseinimehr, Seyed Jalal; Omidfar, Kobra; Noaparast, Zohreh; Abedi, Seyed Mohammad

    2017-04-01

    Nanobodies are important biomolecules for tumor targeting. In this study, we synthesized and labeled anti-epidermal growth factor receptor (EGFR) nanobody OA-cb6 with 99m Tc(CO) 3 + and evaluated its characteristics for targeting the EGFR in the A431 human epidermal carcinoma cell line. Nanobody radiolabeling was achieved with high yield and radiochemical purity, and the radioconjugate was stable. Biodistribution results in nude mice exhibited a favorable tumor-to-muscle ratio at 4-hr postinjection, and tumor location was visualized at 4 hr after injection of radiolabeled nanobody. Our result showed that the OA-cb6- 99m Tc-tricarbonyl radiolabeled nanobody is a promising radiolabeled biomolecule for tumor imaging in cancers with high EGFR overexpression. © 2016 John Wiley & Sons A/S.

  19. No evidence for a role of the serotonin 4 receptor in five-factor personality traits

    Stenbæk, Dea Siggaard; Dam, Vibeke Høyrup; Fisher, Patrick MacDonald

    2017-01-01

    Serotonin (5-HT) brain architecture appears to be implicated in normal personality traits as supported by genetic associations and studies using molecular brain imaging. However, so far, no studies have addressed potential contributions to variation in normal personality traits from in vivo...... serotonin 4 receptor (5-HT4R) brain availability, which has recently become possible to image with Positron Emission Tomography (PET). This is particularly relevant since availability of 5-HT4R has been shown to adapt to synaptic levels of 5-HT and thus offers information about serotonergic tone...... in the healthy brain. In 69 healthy participants (18 females), the associations between personality traits assessed with the five-factor NEO Personality Inventory-Revised (NEO PI-R) and regional cerebral 5-HT4R binding in neocortex, amygdala, hippocampus, and anterior cingulate cortex (ACC) were investigated...

  20. Urokinase plasminogen activator receptor on invasive cancer cells: A prognostic factor in distal gastric adenocarcinoma

    Alpizar, Warner Enrique Alpizar; Christensen, Ib Jarle; Santoni-Rugiu, Eric

    2012-01-01

    Gastric cancer is the second cancer causing death worldwide. The five-year survival for this malignancy is below 25% and few parameters have shown an impact on the prognosis of the disease. The receptor for urokinase plasminogen activator (uPAR) is involved in extracellular matrix degradation...... by mediating cell surface associated plasminogen activation, and its presence on gastric cancer cells is linked to micrometastasis and poor prognosis. Using immunohistochemistry, the prognostic significance of uPAR was evaluated in tissue samples from a retrospective series of 95 gastric cancer patients. u...... association between the expression of uPAR on tumor cells in the peripheral invasion zone and overall survival of gastric cancer patients (HR = 2.16; 95% CI: 1.13-4.14; p = 0.02). Multivariate analysis showed that uPAR immunoreactivity in cancer cells at the invasive front is an independent prognostic factor...

  1. Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans

    Jinah Han

    2015-02-01

    Full Text Available Neural stem cells (NSCs continuously produce new neurons within the adult mammalian hippocampus. NSCs are typically quiescent but activated to self-renew or differentiate into neural progenitor cells. The molecular mechanisms of NSC activation remain poorly understood. Here, we show that adult hippocampal NSCs express vascular endothelial growth factor receptor (VEGFR 3 and its ligand VEGF-C, which activates quiescent NSCs to enter the cell cycle and generate progenitor cells. Hippocampal NSC activation and neurogenesis are impaired by conditional deletion of Vegfr3 in NSCs. Functionally, this is associated with compromised NSC activation in response to VEGF-C and physical activity. In NSCs derived from human embryonic stem cells (hESCs, VEGF-C/VEGFR3 mediates intracellular activation of AKT and ERK pathways that control cell fate and proliferation. These findings identify VEGF-C/VEGFR3 signaling as a specific regulator of NSC activation and neurogenesis in mammals.

  2. Molecular interactions between chondroitin-dermatan sulfate and growth factors/receptors/matrix proteins.

    Mizumoto, Shuji; Yamada, Shuhei; Sugahara, Kazuyuki

    2015-10-01

    Recent functional studies on chondroitin sulfate-dermatan sulfate (CS-DS) demonstrated its indispensable roles in various biological events including brain development and cancer. CS-DS proteoglycans exert their physiological activity through interactions with specific proteins including growth factors, cell surface receptors, and matrix proteins. The characterization of these interactions is essential for regulating the biological functions of CS-DS proteoglycans. Although amino acid sequences on the bioactive proteins required for these interactions have already been elucidated, the specific saccharide sequences involved in the binding of CS-DS to target proteins have not yet been sufficiently identified. In this review, recent findings are described on the interaction between CS-DS and some proteins which are especially involved in the central nervous system and cancer development/metastasis. Copyright © 2015. Published by Elsevier Ltd.

  3. Upregulation of vascular endothelial growth factor receptor-1 contributes to sevoflurane preconditioning–mediated cardioprotection

    Qian B

    2018-04-01

    Full Text Available Bin Qian,1 Yang Yang,2 Yusheng Yao,3 Yanling Liao,3 Ying Lin3 1Department of Anesthesiology, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China; 2Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; 3Department of Anesthesiology, The Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China Purpose: Sevoflurane preconditioning (SPC can provide myocardial protective effects similar to ischemic preconditioning. However, the exact mechanism of SPC remains unclear. Previous studies indicate that vascular endothelial growth factor receptor 1 (VEGFR-1 is involved in ischemic preconditioning-mediated cardioprotection. This study was designed to determine the significance of VEGFR-1 signaling in SPC-mediated cardioprotection.Materials and methods: Myocardial ischemia–reperfusion (I/R rat model was established using the Langendorff isolated heart perfusion apparatus. Additionally, after 15 min of baseline equilibration, the isolated hearts were pretreated with 2.5% sevoflurane, 2.5% sevoflurane+MF1 10 µmol/L, or 2.5% sevoflurane+placental growth factor 10 µmol/L, and then subjected to 30 min of global ischemia and 120 min of reperfusion. The changes in hemodynamic parameters, myocardial infarct size, and the levels of creatine kinase-MB, lactate dehydrogenase, cardiac troponin-I, tumor necrosis factor-α, and interleukin 6 in the myocardium were evaluated.Results: Compared to the I/R group, pretreatment with 2.5% sevoflurane significantly improved the cardiac function, limited myocardial infarct size, reduced cardiac enzyme release, upregulated VEGFR-1 expression, and decreased inflammation. In addition, the selective VEGFR-1 agonist, placental growth factor, did not enhance the cardioprotection and anti-inflammation effects of sevoflurane, while the specific VEGFR-1 inhibitor, MF1, completely reversed these effects

  4. Mechanisms of Inhibition of the Epidermal Growth Factor Receptor: Implications for Novel Anti-Cancer Therapies

    Klein, Daryl E

    2005-01-01

    .... No secreted or extracellular ErbB receptor inhibitors have been reported in mammals. However, two natural inhibitors of the highly homologous Drosophila EGF receptor are found in Drosophila melanogaster...

  5. Epidermal Growth Factor Receptor Activating Mutations in Squamous Histology of Lung Cancer Patients of Southern Bulgaria

    Genova Silvia N.

    2015-12-01

    Full Text Available There is only limited data on the prevalence of epidermal growth factor receptor (EGFR activating mutations in squamous cell carcinomas and adenosquamous carcinomas of the lung in patients of the Southern Bulgarian region and the efficacy of EGFR tyrosine kinase inhibitors. AIM: Previous reports for Bulgarian population showed high incidence of EGFR mutations in the squamous cell carcinomas, so we set the goal to investigate their frequency in Southern Bulgaria, after precise immunohistochemical verification of lung cancers. MATERIALS AND METHODS: Two hundred and thirty-six lung carcinomas were included in this prospective study. All biopsies were initially analysed with p63, TTF1, Napsin A, CK7, CK34βE12, synaptophysin, CK20 and CDX2. Two hundred and twenty-five non-small cell lung carcinomas were studied with real-time PCR technology to assess the status of the EGFR gene. RESULTS: We detected 132 adenocarcinomas (58.7%, 89 squamous cell carcinomas (39.2%, 4 adenosquamous carcinomas (1.8%, 9 large cell neuroendocrine carcinomas (3.8% and 2 metastatic colorectal adenocarcinomas (0.8%. Activating mutations in the EGF receptor had 3 out of 89 squamous cell carcinomas (3.37%. We have established mutations in L858R, deletion in exon 19 and rare mutation in S7681. One out of four adenosquamous carcinomas had a point mutation in the L858R (25%. CONCLUSIONS: The frequency of EGFR mutations we found in lung squamous cell carcinomas in a Southern Bulgarian region is lower than that in European countries. Ethnic diversity in the region does not play role of an independent predictive factor in terms of mutation frequency.

  6. Retinal hypoxia induces vascular endothelial growth factor through induction of estrogen-related receptor γ

    Do, Ji Yeon; Choi, Young Keun [Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University School of Medicine, Kyungpook National University, Daegu (Korea, Republic of); Kook, Hyun [Department of Pharmacology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Suk, Kyoungho [Department of Pharmacology, Brain Science & Engineering Institute, Kyungpook National University School of Medicine, Daegu (Korea, Republic of); Lee, In-Kyu [Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University School of Medicine, Kyungpook National University, Daegu (Korea, Republic of); Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Aging and Metabolism, Kyungpook National University School of Medicine, Daegu (Korea, Republic of); Park, Dong Ho, E-mail: sarasate2222@gmail.com [Department of Ophthalmology, Kyungpook National University School of Medicine, Daegu (Korea, Republic of)

    2015-05-01

    Ischemic retinopathies causing overexpression of pro-angiogenic factors, including vascular endothelial growth factor (VEGF), are the most common cause of blindness. Thus, understanding the pathophysiology of targetable pathways that regulate retinal VEGF is of great interest. A conserved binding site for estrogen-related receptor γ (ERRγ) has been identified in the promoter of the Vegfa gene. ERRγ is a constitutively active orphan nuclear receptor and its expression is increased by hypoxic stimuli in metabolically active tissues. This study evaluated the role of ERRγ in the ischemic retina and the anti-VEGF potential of GSK5182, a selective inverse agonist of ERRγ. In an oxygen-induced retinopathy (OIR) mouse model, immunohistochemistry showed significantly increased ERRγ expression in the ganglion cell layer at postnatal day (P) 17. In a ganglion cell line (RGC-5), mRNA and protein levels of ERRγ were increased by desferrioxamine treatment and hypoxic conditions (1% O{sub 2}). Transient transfection of RGC-5 cells revealed that ERRγ regulated Vegfa expression and this was inhibited by GSK5182. Intravitreal injection of GSK5182 into the OIR model at P14 inhibited retinal Vegfa mRNA expression at P17. GSK5182 suppresses hypoxia-induced VEGF expression via ERRγ; therefore, ERRγ could be a treatment target for ischemic retinopathies. - Highlights: • OIR mice exhibited increased ERRγ expression in the ganglion cell layer. • Hypoxia-induced ERRγ expression was observed in retinal ganglion cells. • ERRγ overexpression increased VEGFA expression in retinal ganglion cells. • An ERRγ inverse agonist suppressed VEGFA expression in retinal ganglion cells. • Intravitreal injection of an ERRγ inverse agonist suppressed VEGFA in OIR mice.

  7. Molecular Cloning and Characterization of Growth Factor Receptor Bound-Protein in Clonorchis sinensis

    Bai, Xuelian; Lee, Ji-Yun; Kim, Tae Im; Dai, Fuhong; Lee, Tae-Jin; Hong, Sung-Jong

    2014-01-01

    Background Clonorchis sinensis causes clonorchiasis, a potentially serious disease. Growth factor receptor-bound protein 2 (Grb2) is a cytosolic protein conserved among animals and plays roles in cellular functions such as meiosis, organogenesis and energy metabolism. In the present study, we report first molecular characters of growth factor receptor bound-protein (CsGrb2) from C. sinensis as counter part of Grb2 from animals and its possible functions in development and organogenesis of C. sinensis. Methodology/Principal Findings A CsGrb2 cDNA clone retrieved from the C. sinensis transcriptome encoded a polypeptide with a SH3-SH2-SH3 structure. Recombinant CsGrb2 was bacterially produced and purified to homogeneity. Native CsGrb2 with estimated molecular weight was identified from C. sinensis adult extract by western blotting using a mouse immune serum to recombinant CsGrb2. CsGrb2 transcripts was more abundant in the metacercariae than in the adults. Immunohistochemical staining showed that CsGrb2 was localized to the suckers, mesenchymal tissues, sperms in seminal receptacle and ovary in the adults, and abundantly expressed in most organs of the metacercariae. Recombinant CsGrb2 was evaluated to be little useful as a serodiagnostic reagent for C. sinesis human infections. Conclusion Grb2 protein found in C. sinensis was conserved among animals and suggested to play a role in the organogenesis, energy metabolism and mitotic spermatogenesis of C. sinensis. These findings from C. sinensis provide wider understanding on diverse function of Grb2 in lower animals such as platyhelminths. PMID:24454892

  8. Molecular cloning and characterization of growth factor receptor bound-protein in Clonorchis sinensis.

    Xuelian Bai

    Full Text Available BACKGROUND: Clonorchis sinensis causes clonorchiasis, a potentially serious disease. Growth factor receptor-bound protein 2 (Grb2 is a cytosolic protein conserved among animals and plays roles in cellular functions such as meiosis, organogenesis and energy metabolism. In the present study, we report first molecular characters of growth factor receptor bound-protein (CsGrb2 from C. sinensis as counter part of Grb2 from animals and its possible functions in development and organogenesis of C. sinensis. METHODOLOGY/PRINCIPAL FINDINGS: A CsGrb2 cDNA clone retrieved from the C. sinensis transcriptome encoded a polypeptide with a SH3-SH2-SH3 structure. Recombinant CsGrb2 was bacterially produced and purified to homogeneity. Native CsGrb2 with estimated molecular weight was identified from C. sinensis adult extract by western blotting using a mouse immune serum to recombinant CsGrb2. CsGrb2 transcripts was more abundant in the metacercariae than in the adults. Immunohistochemical staining showed that CsGrb2 was localized to the suckers, mesenchymal tissues, sperms in seminal receptacle and ovary in the adults, and abundantly expressed in most organs of the metacercariae. Recombinant CsGrb2 was evaluated to be little useful as a serodiagnostic reagent for C. sinesis human infections. CONCLUSION: Grb2 protein found in C. sinensis was conserved among animals and suggested to play a role in the organogenesis, energy metabolism and mitotic spermatogenesis of C. sinensis. These findings from C. sinensis provide wider understanding on diverse function of Grb2 in lower animals such as platyhelminths.

  9. Inhibition of fibroblast growth factor receptor with AZD4547 mitigates juvenile nasopharyngeal angiofibroma.

    Le, Tran; New, Jacob; Jones, Joel W; Usman, Shireen; Yalamanchali, Sreeya; Tawfik, Ossama; Hoover, Larry; Bruegger, Dan E; Thomas, Sufi Mary

    2017-10-01

    Juvenile nasopharyngeal angiofibroma (JNA) is a benign tumor that presents in adolescent males. Although surgical excision is the mainstay of treatment, recurrences complicate treatment. There is a need to develop less invasive approaches for management. JNA tumors are composed of fibroblasts and vascular endothelial cells. We identified fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor (VEGF) expression in JNA-derived fibroblasts. FGFR influences fibroblast proliferation and VEGF is necessary for angiogenesis. We hypothesized that targeting FGFR would mitigate JNA fibroblast proliferation, invasion, and migration, and that targeting the VEGF receptor would attenuate endothelial tubule formation. After informed consent, fibroblasts from JNA explants of 3 patients were isolated. Fibroblasts were treated with FGFR inhibitor AZD4547, 0 to 25 μg/mL for 72 hours and proliferation was quantified using CyQuant assay. Migration and invasion of JNA were assessed using 24-hour transwell assays with subsequent fixation and quantification. Mitigation of FGFR and downstream signaling was evaluated by immunoblotting. Tubule formation was assessed in human umbilical vein endothelial cells (HUVECs) treated with vehicle control (dimethylsulfoxide [DMSO]) or semaxanib (SU5416) as well as in serum-free media (SFM) or JNA conditioned media (CM). Tubule length was compared between treatment groups. Compared to control, AZD4547 inhibited JNA fibroblast proliferation, migration, and invasion through inhibition of FGFR and downstream signaling, specifically phosphorylation of - p44/42 mitogen activated protein kinase (p44/42 MAPK). JNA fibroblast CM significantly increased HUVEC tubule formation (p = 0.0039). AZD4547 effectively mitigates FGFR signaling and decreases JNA fibroblast proliferation, migration, and invasion. SU5416 attenuated JNA fibroblast-induced tubule formation. AZD4547 may have therapeutic potential in the treatment of JNA. © 2017 ARS

  10. Retinal hypoxia induces vascular endothelial growth factor through induction of estrogen-related receptor γ

    Do, Ji Yeon; Choi, Young Keun; Kook, Hyun; Suk, Kyoungho; Lee, In-Kyu; Park, Dong Ho

    2015-01-01

    Ischemic retinopathies causing overexpression of pro-angiogenic factors, including vascular endothelial growth factor (VEGF), are the most common cause of blindness. Thus, understanding the pathophysiology of targetable pathways that regulate retinal VEGF is of great interest. A conserved binding site for estrogen-related receptor γ (ERRγ) has been identified in the promoter of the Vegfa gene. ERRγ is a constitutively active orphan nuclear receptor and its expression is increased by hypoxic stimuli in metabolically active tissues. This study evaluated the role of ERRγ in the ischemic retina and the anti-VEGF potential of GSK5182, a selective inverse agonist of ERRγ. In an oxygen-induced retinopathy (OIR) mouse model, immunohistochemistry showed significantly increased ERRγ expression in the ganglion cell layer at postnatal day (P) 17. In a ganglion cell line (RGC-5), mRNA and protein levels of ERRγ were increased by desferrioxamine treatment and hypoxic conditions (1% O 2 ). Transient transfection of RGC-5 cells revealed that ERRγ regulated Vegfa expression and this was inhibited by GSK5182. Intravitreal injection of GSK5182 into the OIR model at P14 inhibited retinal Vegfa mRNA expression at P17. GSK5182 suppresses hypoxia-induced VEGF expression via ERRγ; therefore, ERRγ could be a treatment target for ischemic retinopathies. - Highlights: • OIR mice exhibited increased ERRγ expression in the ganglion cell layer. • Hypoxia-induced ERRγ expression was observed in retinal ganglion cells. • ERRγ overexpression increased VEGFA expression in retinal ganglion cells. • An ERRγ inverse agonist suppressed VEGFA expression in retinal ganglion cells. • Intravitreal injection of an ERRγ inverse agonist suppressed VEGFA in OIR mice

  11. Stage specific requirement of platelet-derived growth factor receptor-α in embryonic development.

    Chen Qian

    Full Text Available Platelet-derived growth factor receptor alpha (PDGFRα is a cell-surface receptor tyrosine kinase for platelet-derived growth factors. Correct timing and level of Pdgfra expression is crucial for embryo development, and deletion of Pdgfra caused developmental defects of multiple endoderm and mesoderm derived structures, resulting in a complex phenotypes including orofacial cleft, spina bifida, rib deformities, and omphalocele in mice. However, it is not clear if deletion of Pdgfra at different embryonic stages differentially affects these structures.To address the temporal requirement of Pdgfra in embryonic development.We have deleted the Pdgfra in Pdgfra-expressing tissues at different embryonic stages in mice, examined and quantified the developmental anomalies.Current study showed that (i conditional deletion of Pdgfra at different embryonic days (between E7.5 and E10.5 resulted in orofacial cleft, spina bifida, rib cage deformities, and omphalocele, and (ii the day of Pdgfra deletion influenced the combinations, incidence and severities of these anomalies. Deletion of Pdgfra caused apoptosis of Pdgfra-expressing tissues, and developmental defects of their derivatives.Orofacial cleft, spina bifida and omphalocele are among the commonest skeletal and abdominal wall defects of newborns, but their genetic etiologies are largely unknown. The remarkable resemblance of our conditional Pdgfra knockout embryos to theses human congenital anomalies, suggesting that dysregulated PDGFRA expression could cause these anomalies in human. Future work should aim at defining (a the regulatory elements for the expression of the human PDGFRA during embryonic development, and (b if mutations / sequence variations of these regulatory elements cause these anomalies.

  12. Gender as a prognostic factor and its impact on the incidence of multiple sclerosis in Lorraine, France.

    Debouverie, M

    2009-11-15

    We sought to identify (a) the change of incidence rates among gender from 1990 to 2002 from the LORSEP (Lorraine Multiple Sclerosis) population-based cohort, and (b) the role of gender as a predictive demographic factor of disability during the initial course of the disease among multiple sclerosis (MS) patients. The incidence rates of multiple sclerosis (MS) in Lorraine, France, have significantly increased in women, but not in men, from 1990 to 2002 but this increase in incidence of MS was not related to a better ascertainment of patients with mild disability. A total of 2871 MS patients were analyzed. For relapsing-remitting (RR) patients, a multivariate analysis showed that a shorter time to the assignment of an EDSS score of 3 and 4 was associated with the late onset MS, incomplete recovery from the first relapse and a high number of relapses during the first 5 years after the MS onset. Median times were not influenced by gender or by time between the first two relapses. The data were very different for the time between the assignment of scores of 4 and 6, since the median times were not influenced by any of the predicting variables.

  13. Computer Breakdown as a Stress Factor during Task Completion under Time Pressure: Identifying Gender Differences Based on Skin Conductance

    René Riedl

    2013-01-01

    Full Text Available In today’s society, as computers, the Internet, and mobile phones pervade almost every corner of life, the impact of Information and Communication Technologies (ICT on humans is dramatic. The use of ICT, however, may also have a negative side. Human interaction with technology may lead to notable stress perceptions, a phenomenon referred to as technostress. An investigation of the literature reveals that computer users’ gender has largely been ignored in technostress research, treating users as “gender-neutral.” To close this significant research gap, we conducted a laboratory experiment in which we investigated users’ physiological reaction to the malfunctioning of technology. Based on theories which explain that men, in contrast to women, are more sensitive to “achievement stress,” we predicted that male users would exhibit higher levels of stress than women in cases of system breakdown during the execution of a human-computer interaction task under time pressure, if compared to a breakdown situation without time pressure. Using skin conductance as a stress indicator, the hypothesis was confirmed. Thus, this study shows that user gender is crucial to better understanding the influence of stress factors such as computer malfunctions on physiological stress reactions.

  14. Gender perspective of risk factors associated with disclosure of HIV status, a cross-sectional study in Soweto, South Africa.

    Longinetti, Elisa; Santacatterina, Michele; El-Khatib, Ziad

    2014-01-01

    Human Immunodeficiency Virus (HIV) status disclosure has been shown to provide several benefits, both at the individual and societal levels. To determine risk factors associated with disclosing HIV status among antiretroviral therapy (ART) recipients in South Africa. A cross-sectional study on risk factors for viremia and drug resistance took place at two outpatient HIV clinics in 2008, at a large hospital located in Soweto, South Africa. We conducted a secondary data analysis on socio-economic characteristics and HIV status disclosure to anyone, focusing on gender differences. Descriptive and multivariable logistic regression analyses were performed to model the associations between risk factors and HIV status disclosure. Additionally, descriptive analysis was conducted to describe gender differences of HIV status disclosure to partner, parents, parents in law, partner, child, family, employer, and other. A total of 883 patients were interviewed. The majority were women (73%) with median age of 39 years. Employed patients were less likely to disclose than unemployed (odds ratio (OR) 0.36; 95% confidence interval (CI) 0.1-1.0; p = 0.05)). Women with higher income were more likely to disclose (OR 3.25; 95% CI 0.90-11.7; p = 0.07) than women with lower income, while men with higher income were less likely (OR 0.20; 95% CI 0.02-1.99; p = 0.17) than men with lower income. Men were more likely than women to disclose to their partner (pwomen were more likely than men to disclose to child and family (pgender and income on disclosure. Interventions designed to reduce workplace discrimination and gender-sensitive interventions promoting disclosure are strongly recommended.

  15. Epidermal growth factor treatment of A431 cells alters the binding capacity and electrophoretic mobility of the cytoskeletally associated epidermal growth factor receptor

    Roy, L.M.; Gittinger, C.K.; Landreth, G.E.

    1991-01-01

    Epidermal growth factor receptor interacts with structural elements of A431 cells and remains associated with the cytoskeleton following extraction with nonionic detergents. Extraction of cells with 0.15% Triton X-100 resulted in detection of only approximately 40% of the EGF binding sites on the cytoskeleton. If the cells were exposed to EGF prior to extraction, approximately twofold higher levels of low-affinity EGF binding sites were detected. The difference in number of EGF binding sites was not a consequence of differences in numbers of EGF receptors associated with the cytoskeleton; equal amounts of 35S-labeled receptor were immunoprecipitated from the cytoskeletons of both control and EGF-treated cells. The effect of EGF pretreatment on binding activity was coincident with a change in the mobility of the receptor from a doublet of Mr approximately 160-180 kDa to a single sharp band at 180 kDa. The alteration in receptor mobility was not a simple consequence of receptor phosphorylation in that the alteration was not reversed by alkaline phosphatase treatment, nor was the shift produced by treatment of the cells with phorbol ester. The two EGF receptor species demonstrated differential susceptibility to V8 proteinase digestion. The EGF-induced 180 kDa species was preferentially digested by the proteinase relative to the 160 kDa species, indicating that EGF binding results in a conformational change in the receptor. The EGF-mediated preservation of binding activity and altered conformation may be related to receptor oligomerization

  16. Structure and function of the Juxta membrane domain of the human epidermal growth factor receptor by NMR spectroscopy

    Choowongkomon, Kiattawee; Carlin, Cathleen; Sonnichsen, Frank D.

    2005-10-01

    The epidermal growth factor receptor (EGFR) is a member of the receptor tyrosine kinase family involved in the regulation of cellular proliferation and differentiation. Its juxta membrane domain (JX), the region located between the transmembrane and kinase domains, plays important roles in receptor trafficking since both basolateral sorting in polarized epithelial cells and lysosomal sorting signals are identified in this region. In order to understand the regulation of these signals, we characterized the structural properties of recombinant JX domain in dodecyl phosphocholine detergent (DPC) by nuclear magnetic resonance (NMR) spectroscopy. In DPC micelles, structures derived from NMR data showed three amphipathic, helical segments. Two equivalent average structural models on the surface of micelles were obtained that differ only in the relative orientation between the first and second helices. Our data suggests that the activity of sorting signals may be regulated by their membrane association and restricted accessibility in the intact receptor

  17. Transmembrane signalling at the epidermal growth factor receptor. Positive regulation by the C-terminal phosphotyrosine residues

    Magni, M; Pandiella, A; Helin, K

    1991-01-01

    a positive role in the regulation of transmembrane signalling at the EGF receptor. The stepwise decrease in signal generation observed in single, double and triple point mutants suggest that the role of phosphotyrosine residues is not in the participation in specific amino acid sequences, but rather...... in the double and the triple mutants. In the latter mutant, expression of the EGF-receptor-activated lipolytic enzyme phospholipase C gamma was unchanged, whereas its tyrosine phosphorylation induced by the growth factor was lowered to approx. 25% of that in the controls. In all of the cell clones employed......, the accumulation of inositol phosphates induced by treatment with fetal calf serum varied only slightly, whereas the same effect induced by EGF was consistently lowered in those lines expressing mutated receptors. This decrease was moderate for those receptors missing only the distal tyrosine (point and deletion...