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Sample records for family cytokines implications

  1. Interleukin-1 Family Cytokines in Liver Diseases

    PubMed Central

    Tsutsui, Hiroko; Cai, Xianbin; Hayashi, Shuhei

    2015-01-01

    The gene encoding IL-1 was sequenced more than 30 years ago, and many related cytokines, such as IL-18, IL-33, IL-36, IL-37, IL-38, IL-1 receptor antagonist (IL-1Ra), and IL-36Ra, have since been identified. IL-1 is a potent proinflammatory cytokine and is involved in various inflammatory diseases. Other IL-1 family ligands are critical for the development of diverse diseases, including inflammatory and allergic diseases. Only IL-1Ra possesses the leader peptide required for secretion from cells, and many ligands require posttranslational processing for activation. Some require inflammasome-mediated processing for activation and release, whereas others serve as alarmins and are released following cell membrane rupture, for example, by pyroptosis or necroptosis. Thus, each ligand has the proper molecular process to exert its own biological functions. In this review, we will give a brief introduction to the IL-1 family cytokines and discuss their pivotal roles in the development of various liver diseases in association with immune responses. For example, an excess of IL-33 causes liver fibrosis in mice via activation and expansion of group 2 innate lymphoid cells to produce type 2 cytokines, resulting in cell conversion into pro-fibrotic M2 macrophages. Finally, we will discuss the importance of IL-1 family cytokine-mediated molecular and cellular networks in the development of acute and chronic liver diseases. PMID:26549942

  2. AIDS: Implications for Families.

    ERIC Educational Resources Information Center

    Macklin, Eleanor D.

    1988-01-01

    Reviews facts about Acquired Immune Deficiency Syndrome (AIDS) and its epidemiology. Discusses implications for families (social stigma and isolation, fears of contagion, infection and abandonment, guilt, anger, grief, and economic hardship) and for human service professionals (public education, voluntary, anonymous testing with counseling, and…

  3. Clinical implication of perioperative inflammatory cytokine alteration.

    PubMed

    Hsing, Chung-Hsi; Wang, Jhi-Joung

    2015-03-01

    Cytokines are key modulators of inflammatory responses, and play an important role in the defense and repair mechanisms following trauma. After traumatic injury, an immuno-inflammatory response is initiated immediately, and cytokines rapidly appear and function as a regulator of immunity. In pathologic conditions, imbalanced cytokines may provide systemic inflammatory responses or immunosuppression. Expression of perioperative cytokines vary by different intensities of surgical trauma and types of anesthesia and anesthetic agents. Inflammatory cytokines play important roles in postoperative organ dysfunction including central nervous system, cardiovascular, lung, liver, and kidney injury. Inhibition of cytokines could protect against traumatic injury in some circumstances, therefore cytokine inhibitors or antagonists might have the potential for reducing postoperative tissue/organ dysfunction. Cytokines are also involved in wound healing and post-traumatic pain. Application of cytokines for the improvement of surgical wound healing has been reported. Anesthesia-related immune response adjustment might reduce perioperative morbidity because it reduces proinflammatory cytokine expression; however, the overall effects of anesthetics on postoperative immune-inflammatory responses needs to be further investigated. PMID:25837846

  4. Tumor suppression in mice lacking GABARAP, an Atg8/LC3 family member implicated in autophagy, is associated with alterations in cytokine secretion and cell death

    PubMed Central

    Salah, F S; Ebbinghaus, M; Muley, V Y; Zhou, Z; Al-Saadi, K R D; Pacyna-Gengelbach, M; O'Sullivan, G A; Betz, H; König, R; Wang, Z-Q; Bräuer, R; Petersen, I

    2016-01-01

    GABARAP belongs to an evolutionary highly conserved gene family that has a fundamental role in autophagy. There is ample evidence for a crosstalk between autophagy and apoptosis as well as the immune response. However, the molecular details for these interactions are not fully characterized. Here, we report that the ablation of murine GABARAP, a member of the Atg8/LC3 family that is central to autophagosome formation, suppresses the incidence of tumor formation mediated by the carcinogen DMBA and results in an enhancement of the immune response through increased secretion of IL-1β, IL-6, IL-2 and IFN-γ from stimulated macrophages and lymphocytes. In contrast, TGF-β1 was significantly reduced in the serum of these knockout mice. Further, DMBA treatment of these GABARAP knockout mice reduced the cellularity of the spleen and the growth of mammary glands through the induction of apoptosis. Gene expression profiling of mammary glands revealed significantly elevated levels of Xaf1, an apoptotic inducer and tumor-suppressor gene, in knockout mice. Furthermore, DMBA treatment triggered the upregulation of pro-apoptotic (Bid, Apaf1, Bax), cell death (Tnfrsf10b, Ripk1) and cell cycle inhibitor (Cdkn1a, Cdkn2c) genes in the mammary glands. Finally, tumor growth of B16 melanoma cells after subcutaneous inoculation was inhibited in GABARAP-deficient mice. Together, these data provide strong evidence for the involvement of GABARAP in tumorigenesis in vivo by delaying cell death and its associated immune-related response. PMID:27124579

  5. Tumor suppression in mice lacking GABARAP, an Atg8/LC3 family member implicated in autophagy, is associated with alterations in cytokine secretion and cell death.

    PubMed

    Salah, F S; Ebbinghaus, M; Muley, V Y; Zhou, Z; Al-Saadi, K R D; Pacyna-Gengelbach, M; O'Sullivan, G A; Betz, H; König, R; Wang, Z-Q; Bräuer, R; Petersen, I

    2016-01-01

    GABARAP belongs to an evolutionary highly conserved gene family that has a fundamental role in autophagy. There is ample evidence for a crosstalk between autophagy and apoptosis as well as the immune response. However, the molecular details for these interactions are not fully characterized. Here, we report that the ablation of murine GABARAP, a member of the Atg8/LC3 family that is central to autophagosome formation, suppresses the incidence of tumor formation mediated by the carcinogen DMBA and results in an enhancement of the immune response through increased secretion of IL-1β, IL-6, IL-2 and IFN-γ from stimulated macrophages and lymphocytes. In contrast, TGF-β1 was significantly reduced in the serum of these knockout mice. Further, DMBA treatment of these GABARAP knockout mice reduced the cellularity of the spleen and the growth of mammary glands through the induction of apoptosis. Gene expression profiling of mammary glands revealed significantly elevated levels of Xaf1, an apoptotic inducer and tumor-suppressor gene, in knockout mice. Furthermore, DMBA treatment triggered the upregulation of pro-apoptotic (Bid, Apaf1, Bax), cell death (Tnfrsf10b, Ripk1) and cell cycle inhibitor (Cdkn1a, Cdkn2c) genes in the mammary glands. Finally, tumor growth of B16 melanoma cells after subcutaneous inoculation was inhibited in GABARAP-deficient mice. Together, these data provide strong evidence for the involvement of GABARAP in tumorigenesis in vivo by delaying cell death and its associated immune-related response. PMID:27124579

  6. PCTAIRE1-knockdown sensitizes cancer cells to TNF family cytokines.

    PubMed

    Yanagi, Teruki; Shi, Ranxin; Aza-Blanc, Pedro; Reed, John C; Matsuzawa, Shu-ichi

    2015-01-01

    While PCTAIRE1/PCTK1/Cdk16 is overexpressed in malignant cells and is crucial in tumorigenesis, its function in apoptosis remains unclear. Here we investigated the role of PCTAIRE1 in apoptosis, especially in the extrinsic cell death pathway. Gene-knockdown of PCTAIRE1 sensitized prostate cancer PPC1 and Du145 cells, and breast cancer MDA-MB-468 cells to TNF-family cytokines, including TNF-related apoptosis-inducing ligand (TRAIL). Meanwhile, PCTAIRE1-knockdown did not sensitize non-malignant cells, including diploid fibroblasts IMR-90 and the immortalized prostate epithelial cell line 267B1. PCTAIRE1-knockdown did not up-regulate death receptor expression on the cell surface or affect caspase-8, FADD and FLIP expression levels. PCTAIRE1-knockdown did promote caspase-8 cleavage and RIPK1 degradation, while RIPK1 mRNA knockdown sensitized PPC1 cells to TNF-family cytokines. Furthermore, the kinase inhibitor SNS-032, which inhibits PCTAIRE1 kinase activity, sensitized PPC1 cells to TRAIL-induced apoptosis. Together these results suggest that PCTAIRE1 contributes to the resistance of cancer cell lines to apoptosis induced by TNF-family cytokines, which implies that PCTAIRE1 inhibitors could have synergistic effects with TNF-family cytokines for cytodestruction of cancer cells. PMID:25790448

  7. PCTAIRE1-Knockdown Sensitizes Cancer Cells to TNF Family Cytokines

    PubMed Central

    Yanagi, Teruki; Shi, Ranxin; Aza-Blanc, Pedro; Reed, John C.; Matsuzawa, Shu-ichi

    2015-01-01

    While PCTAIRE1/PCTK1/Cdk16 is overexpressed in malignant cells and is crucial in tumorigenesis, its function in apoptosis remains unclear. Here we investigated the role of PCTAIRE1 in apoptosis, especially in the extrinsic cell death pathway. Gene-knockdown of PCTAIRE1 sensitized prostate cancer PPC1 and Du145 cells, and breast cancer MDA-MB-468 cells to TNF-family cytokines, including TNF-related apoptosis-inducing ligand (TRAIL). Meanwhile, PCTAIRE1-knockdown did not sensitize non-malignant cells, including diploid fibroblasts IMR-90 and the immortalized prostate epithelial cell line 267B1. PCTAIRE1-knockdown did not up-regulate death receptor expression on the cell surface or affect caspase-8, FADD and FLIP expression levels. PCTAIRE1-knockdown did promote caspase-8 cleavage and RIPK1 degradation, while RIPK1 mRNA knockdown sensitized PPC1 cells to TNF-family cytokines. Furthermore, the kinase inhibitor SNS-032, which inhibits PCTAIRE1 kinase activity, sensitized PPC1 cells to TRAIL-induced apoptosis. Together these results suggest that PCTAIRE1 contributes to the resistance of cancer cell lines to apoptosis induced by TNF-family cytokines, which implies that PCTAIRE1 inhibitors could have synergistic effects with TNF-family cytokines for cytodestruction of cancer cells. PMID:25790448

  8. Cytokines of the LIF/CNTF family and metabolism.

    PubMed

    Pasquin, Sarah; Sharma, Mukut; Gauchat, Jean-François

    2016-06-01

    The incidence of obesity is increasing worldwide. Obesity is accompanied by a chronic inflammatory state that increases the risk of metabolic diseases such as insulin-resistance and type 2 diabetes. Over the past two decades, interest in immunomodulatory cytokines as potential mediators and/or targets for treatment or prevention of obesity and metabolic syndrome has increased. In this review, we summarize studies that revealed the effects of LIF family cytokines on adipose tissue, energy expenditure and food intake, highlighting the importance of gp130/LIFRβ signaling in obesity and obesity-related metabolic diseases. PMID:26817395

  9. Interleukin 12 (IL-12) family cytokines: Role in immune pathogenesis and treatment of CNS autoimmune disease.

    PubMed

    Sun, Lin; He, Chang; Nair, Lekha; Yeung, Justine; Egwuagu, Charles E

    2015-10-01

    Cytokines play crucial roles in coordinating the activities of innate and adaptive immune systems. In response to pathogen recognition, innate immune cells secrete cytokines that inform the adaptive immune system about the nature of the pathogen and instruct naïve T cells to differentiate into the appropriate T cell subtypes required to clear the infection. These include Interleukins, Interferons and other immune-regulatory cytokines that exhibit remarkable functional redundancy and pleiotropic effects. The focus of this review, however, is on the enigmatic Interleukin 12 (IL-12) family of cytokines. This family of cytokines plays crucial roles in shaping immune responses during antigen presentation and influence cell-fate decisions of differentiating naïve T cells. They also play essential roles in regulating functions of a variety of effector cells, making IL-12 family cytokines important therapeutic targets or agents in a number of inflammatory diseases, such as the CNS autoimmune diseases, uveitis and multiple sclerosis. PMID:25796985

  10. Family Capital: Implications for Interventions with Families

    ERIC Educational Resources Information Center

    Belcher, John R.; Peckuonis, Edward V.; Deforge, Bruce R.

    2011-01-01

    Social capital has been extensively discussed in the literature as building blocks that individuals and communities utilize to leverage system resources. Similarly, some families also create capital, which can enable members of the family, such as children, to successfully negotiate the outside world. Families in poverty confront serious…

  11. Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications.

    PubMed

    Felger, J C; Lotrich, F E

    2013-08-29

    Mounting evidence indicates that inflammatory cytokines contribute to the development of depression in both medically ill and medically healthy individuals. Cytokines are important for development and normal brain function, and have the ability to influence neurocircuitry and neurotransmitter systems to produce behavioral alterations. Acutely, inflammatory cytokine administration or activation of the innate immune system produces adaptive behavioral responses that promote conservation of energy to combat infection or recovery from injury. However, chronic exposure to elevated inflammatory cytokines and persistent alterations in neurotransmitter systems can lead to neuropsychiatric disorders and depression. Mechanisms of cytokine behavioral effects involve activation of inflammatory signaling pathways in the brain that results in changes in monoamine, glutamate, and neuropeptide systems, and decreases in growth factors, such as brain-derived neurotrophic factor. Furthermore, inflammatory cytokines may serve as mediators of both environmental (e.g. childhood trauma, obesity, stress, and poor sleep) and genetic (functional gene polymorphisms) factors that contribute to depression's development. This review explores the idea that specific gene polymorphisms and neurotransmitter systems can confer protection from or vulnerability to specific symptom dimensions of cytokine-related depression. Additionally, potential therapeutic strategies that target inflammatory cytokine signaling or the consequences of cytokines on neurotransmitter systems in the brain to prevent or reverse cytokine effects on behavior are discussed. PMID:23644052

  12. Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications

    PubMed Central

    Felger, Jennifer C.; Lotrich, Francis E.

    2013-01-01

    Mounting evidence indicates that inflammatory cytokines contribute to the development of depression in both medically ill and medically healthy individuals. Cytokines are important for development and normal brain function, and have the ability to influence neurocircuitry and neurotransmitter systems to produce behavioral alterations. Acutely, inflammatory cytokine administration or activation of the innate immune system produces adaptive behavioral responses that promote conservation of energy to combat infection or recovery from injury. However, chronic exposure to elevated inflammatory cytokines and persistent alterations in neurotransmitter systems can lead to neuropsychiatric disorders and depression. Mechanisms of cytokine behavioral effects involve activation of inflammatory signaling pathways in the brain that results in changes in monoamine, glutamate, and neuropeptide systems, and decreases in growth factors, e.g. brain derived neurotrophic factor. Furthermore, inflammatory cytokines may serve as mediators of both environmental (e.g. childhood trauma, obesity, stress, and poor sleep) and genetic (functional gene polymorphisms) factors that contribute to depression’s development. This review explores the idea that specific gene polymorphisms and neurotransmitter systems can confer protection from or vulnerability to specific symptom dimensions of cytokine-related depression. Additionally, potential therapeutic strategies that target inflammatory cytokine signaling or the consequences of cytokines on neurotransmitter systems in the brain to prevent or reverse cytokine effects on behavior are discussed. PMID:23644052

  13. Optimized Expression of IL-12 Cytokine Family | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute's Human Retrovirus Section is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize methods for improved expression of IL-12 family cytokines.

  14. The IL-1 cytokine family and its role in inflammation and fibrosis in the lung.

    PubMed

    Borthwick, L A

    2016-07-01

    The IL-1 cytokine family comprises 11 members (7 ligands with agonist activity, 3 receptor antagonists and 1 anti-inflammatory cytokine) and is recognised as a key mediator of inflammation and fibrosis in multiple tissues including the lung. IL-1 targeted therapies have been successfully employed to treat a range of inflammatory conditions such as rheumatoid arthritis and gouty arthritis. This review will introduce the members of the IL-1 cytokine family, briefly discuss the cellular origins and cellular targets and provide an overview of the role of these molecules in inflammation and fibrosis in the lung. PMID:27001429

  15. Zinc and regulation of inflammatory cytokines: implications for cardiometabolic disease.

    PubMed

    Foster, Meika; Samman, Samir

    2012-07-01

    In atherosclerosis and diabetes mellitus, the concomitant presence of low-grade systemic inflammation and mild zinc deficiency highlights a role for zinc nutrition in the management of chronic disease. This review aims to evaluate the literature that reports on the interactions of zinc and cytokines. In humans, inflammatory cytokines have been shown both to up- and down-regulate the expression of specific cellular zinc transporters in response to an increased demand for zinc in inflammatory conditions. The acute phase response includes a rapid decline in the plasma zinc concentration as a result of the redistribution of zinc into cellular compartments. Zinc deficiency influences the generation of cytokines, including IL-1β, IL-2, IL-6, and TNF-α, and in response to zinc supplementation plasma cytokines exhibit a dose-dependent response. The mechanism of action may reflect the ability of zinc to either induce or inhibit the activation of NF-κB. Confounders in understanding the zinc-cytokine relationship on the basis of in vitro experimentation include methodological issues such as the cell type and the means of activating cells in culture. Impaired zinc homeostasis and chronic inflammation feature prominently in a number of cardiometabolic diseases. Given the high prevalence of zinc deficiency and chronic disease globally, the interplay of zinc and inflammation warrants further examination. PMID:22852057

  16. Immunotherapeutic implications of IL-6 blockade for cytokine storm.

    PubMed

    Tanaka, Toshio; Narazaki, Masashi; Kishimoto, Tadamitsu

    2016-07-01

    IL-6 contributes to host defense against infections and tissue injuries. However, exaggerated, excessive synthesis of IL-6 while fighting environmental stress leads to an acute severe systemic inflammatory response known as 'cytokine storm', since high levels of IL-6 can activate the coagulation pathway and vascular endothelial cells but inhibit myocardial function. Remarkable beneficial effects of IL-6 blockade therapy using a humanized anti-IL-6 receptor antibody, tocilizumab were recently observed in patients with cytokine release syndrome complicated by T-cell engaged therapy. In this review we propose the possibility that IL-6 blockade may constitute a novel therapeutic strategy for other types of cytokine storm, such as the systemic inflammatory response syndrome including sepsis, macrophage activation syndrome and hemophagocytic lymphohistiocytosis. PMID:27381687

  17. Policy implications for familial searching

    PubMed Central

    2011-01-01

    In the United States, several states have made policy decisions regarding whether and how to use familial searching of the Combined DNA Index System (CODIS) database in criminal investigations. Familial searching pushes DNA typing beyond merely identifying individuals to detecting genetic relatedness, an application previously reserved for missing persons identifications and custody battles. The intentional search of CODIS for partial matches to an item of evidence offers law enforcement agencies a powerful tool for developing investigative leads, apprehending criminals, revitalizing cold cases and exonerating wrongfully convicted individuals. As familial searching involves a range of logistical, social, ethical and legal considerations, states are now grappling with policy options for implementing familial searching to balance crime fighting with its potential impact on society. When developing policies for familial searching, legislators should take into account the impact of familial searching on select populations and the need to minimize personal intrusion on relatives of individuals in the DNA database. This review describes the approaches used to narrow a suspect pool from a partial match search of CODIS and summarizes the economic, ethical, logistical and political challenges of implementing familial searching. We examine particular US state policies and the policy options adopted to address these issues. The aim of this review is to provide objective background information on the controversial approach of familial searching to inform policy decisions in this area. Herein we highlight key policy options and recommendations regarding effective utilization of familial searching that minimize harm to and afford maximum protection of US citizens. PMID:22040348

  18. Multiple Serum Cytokine Profiling to Identify Combinational Diagnostic Biomarkers in Attacks of Familial Mediterranean Fever.

    PubMed

    Koga, Tomohiro; Migita, Kiyoshi; Sato, Shuntaro; Umeda, Masataka; Nonaka, Fumiaki; Kawashiri, Shin-Ya; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Nakamura, Hideki; Origuchi, Tomoki; Ueki, Yukitaka; Masumoto, Junya; Agematsu, Kazunaga; Yachie, Akihiro; Yoshiura, Koh-Ichiro; Eguchi, Katsumi; Kawakami, Atsushi

    2016-04-01

    The precise cytokine networks in the serum of individuals with familial Mediterranean fever (FMF) that are associated with its pathogenesis have been unknown. Here, we attempted to identify specific biomarkers to diagnose or assess disease activity in FMF patients. We measured serum levels of 45 cytokines in 75 FMF patients and 40 age-matched controls by multisuspension cytokine array. FMF in "attack" or "remission" was classified by Japan College of Rheumatology-certified rheumatologists according to the Tel Hashomer criteria. Cytokines were ranked by their importance by a multivariate classification algorithm. We performed a logistic regression analysis to determine specific biomarkers for discriminating FMF patients in attack. To identify specific molecular networks, we performed a cluster analysis of each cytokine. Twenty-nine of the 45 cytokines were available for further analyses. Eight cytokines' serum levels were significantly elevated in the FMF attack versus healthy control group. Nine cytokines were increased in FMF attack compared to FMF remission. Multivariate classification algorithms followed by a logistic regression analysis revealed that the combined measurement of IL-6, IL-18, and IL-17 distinguished FMF patients in attack from the controls with the highest accuracy (sensitivity 89.2%, specificity 100%, and accuracy 95.5%). Among the FMF patients, the combined measurement of IL-6, G-CSF, IL-10, and IL-12p40 discriminated febrile attack periods from remission periods with the highest accuracy (sensitivity 75.0%, specificity 87.9%, and accuracy 84.0%). Our data identified combinational diagnostic biomarkers in FMF patients based on the measurement of multiple cytokines. These findings help to improve the diagnostic performance of FMF in daily practice and extend our understanding of the activation of the inflammasome leading to enhanced cytokine networks. PMID:27100444

  19. The roles and functional mechanisms of interleukin-17 family cytokines in mucosal immunity

    PubMed Central

    Song, Xinyang; He, Xiao; Li, Xiaoxia; Qian, Youcun

    2016-01-01

    The mucosal immune system serves as our front-line defense against pathogens. It also tightly maintains immune tolerance to self-symbiotic bacteria, which are usually called commensals. Sensing both types of microorganisms is modulated by signalling primarily through various pattern-recognition receptors (PRRs) on barrier epithelial cells or immune cells. After sensing, proinflammatory molecules such as cytokines are released by these cells to mediate either defensive or tolerant responses. The interleukin-17 (IL-17) family members belong to a newly characterized cytokine subset that is critical for the maintenance of mucosal homeostasis. In this review, we will summarize recent progress on the diverse functions and signals of this family of cytokines at different mucosal edges. PMID:27018218

  20. Multiple Serum Cytokine Profiling to Identify Combinational Diagnostic Biomarkers in Attacks of Familial Mediterranean Fever

    PubMed Central

    Koga, Tomohiro; Migita, Kiyoshi; Sato, Shuntaro; Umeda, Masataka; Nonaka, Fumiaki; Kawashiri, Shin-Ya; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Nakamura, Hideki; Origuchi, Tomoki; Ueki, Yukitaka; Masumoto, Junya; Agematsu, Kazunaga; Yachie, Akihiro; Yoshiura, Koh-Ichiro; Eguchi, Katsumi; Kawakami, Atsushi

    2016-01-01

    Abstract The precise cytokine networks in the serum of individuals with familial Mediterranean fever (FMF) that are associated with its pathogenesis have been unknown. Here, we attempted to identify specific biomarkers to diagnose or assess disease activity in FMF patients. We measured serum levels of 45 cytokines in 75 FMF patients and 40 age-matched controls by multisuspension cytokine array. FMF in “attack” or “remission” was classified by Japan College of Rheumatology-certified rheumatologists according to the Tel Hashomer criteria. Cytokines were ranked by their importance by a multivariate classification algorithm. We performed a logistic regression analysis to determine specific biomarkers for discriminating FMF patients in attack. To identify specific molecular networks, we performed a cluster analysis of each cytokine. Twenty-nine of the 45 cytokines were available for further analyses. Eight cytokines’ serum levels were significantly elevated in the FMF attack versus healthy control group. Nine cytokines were increased in FMF attack compared to FMF remission. Multivariate classification algorithms followed by a logistic regression analysis revealed that the combined measurement of IL-6, IL-18, and IL-17 distinguished FMF patients in attack from the controls with the highest accuracy (sensitivity 89.2%, specificity 100%, and accuracy 95.5%). Among the FMF patients, the combined measurement of IL-6, G-CSF, IL-10, and IL-12p40 discriminated febrile attack periods from remission periods with the highest accuracy (sensitivity 75.0%, specificity 87.9%, and accuracy 84.0%). Our data identified combinational diagnostic biomarkers in FMF patients based on the measurement of multiple cytokines. These findings help to improve the diagnostic performance of FMF in daily practice and extend our understanding of the activation of the inflammasome leading to enhanced cytokine networks. PMID:27100444

  1. Inflammatory Cytokines and Antipsychotic-Induced Weight Gain: Review and Clinical Implications.

    PubMed

    Fonseka, Trehani M; Müller, Daniel J; Kennedy, Sidney H

    2016-05-01

    Antipsychotic medications (APs), particularly second-generation APs, are associated with significant weight gain in schizophrenia patients. Recent evidence suggests that the immune system may contribute to antipsychotic-induced weight gain (AIWG) via AP-mediated alterations of cytokine levels. Antipsychotics with a high propensity for weight gain, such as clozapine and olanzapine, influence the expression of immune genes, and induce changes in serum cytokine levels to ultimately down-regulate neuroinflammation. Since inflammatory cytokines are normally involved in anorexigenic responses, reduced inflammation has been independently shown to mediate changes in feeding behaviours and other metabolic parameters, resulting in obesity. Genetic variation in pro-inflammatory cytokines is also associated with both general obesity and weight change during AP treatment, and thus, may be implicated in the pharmacogenetics of AIWG. At this time, preliminary data support a cytokine-mediated model of AIWG which may have clinical utility in developing more effective metabolic monitoring guidelines and prevention measures. However, further research is still needed to clearly elucidate the validity of this immune model. This article reviews the evidence implicating inflammatory cytokines in AIWG and its potential clinical relevance. PMID:27606316

  2. Stressor-dependent Alterations in Glycoprotein 130: Implications for Glial Cell Reactivity, Cytokine Signaling and Ganglion Cell Health in Glaucoma

    PubMed Central

    Echevarria, FD; Walker, CC; Abella, SK; Won, M; Sappington, RM

    2013-01-01

    Objective: The interleukin-6 (IL-6) family of cytokines is associated with retinal ganglion cell (RGC) survival and glial reactivity in glaucoma. The purpose of this study was to evaluate glaucoma-related changes in glycoprotein-130 (gp130), the common signal transducer of the IL-6 family of cytokines, as they relate to RGC health, glial reactivity and expression of IL-6 cytokine family members. Methods: For all experiments, we examined healthy retina (young C57), aged retina (aged C57), retina predisposed to glaucoma (young DBA/2) and retina with IOP-induced glaucoma (aged DBA/2). We determined retinal gene expression of gp130 and IL-6 family members, using quantitative PCR, and protein expression of gp130, using multiplex ELISA. For protein localization and cell-specific expression, we performed co-immunolabeling for gp130 and cell type-specific markers. We used quantitative microscopy to measure layer-specific expression of gp130 and its relationships to astrocyte and Müller glia reactivity and RGC axonal transport, as determined by uptake and transport of cholera toxin β-subunit (CTB). Results: Gene expression of gp130 was elevated with all glaucoma-related stressors, but only normal aging increased protein levels. In healthy retina, gp130 localized primarily to the inner retina, where it was expressed by astrocytes, Müller cells and RGCs. Layer-specific analysis of gp130 expression revealed increased expression in aging retina and decreased expression in glaucomatous retina that was eccentricity-dependent. These glaucoma-related changes in gp130 expression correlated with the level of GFAP and glutamine synthetase expression, as well as axonal transport in RGCs. The relationships between gp130, glial reactivity and RGC health could impact signaling by many IL-6 family cytokines, which exhibited overall increased expression in a stressor-dependent manner. Conclusions: Glaucoma-related stressors, including normal aging, glaucoma predisposition and IOP

  3. Evaluating the levels of interleukin-1 family cytokines in sporadic amyotrophic lateral sclerosis

    PubMed Central

    2014-01-01

    Background Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease leading to the death of affected individuals within years. The involvement of inflammation in the pathogenesis of neurodegenerative diseases, including ALS, is increasingly recognized but still not well understood. The aim of this study is to evaluate the levels of inflammation-related IL-1 family cytokines (IL-1β, IL-18, IL-33, IL-37) and their endogenous inhibitors (IL-1Ra, sIL-1R2, IL-18BP, sIL-1R4) in patients with sporadic ALS (sALS), Methods Sera were collected from 144 patients (125 patients were characterized by disease form, duration, and disability, using the revised ALS functional rating scale (ALSFRS-R) and from 40 matched controls. Cerebrospinal fluid (CSF) was collected from 54 patients with sALS and 65 patients with other non-infectious non-oncogenic diseases as controls. Cytokines and inhibitors were measured by commercial ELISA. Results Among the IL-1 family cytokines tested total IL-18, its endogenous inhibitor IL-18BP, and the active form of the cytokine (free IL-18) were significantly higher in the sALS sera than in controls. No correlation between these soluble mediators and different clinical forms of sALS or the clinical setting of the disease was found. IL-18BP was the only mediator detectable in the CSF of patients. Conclusions Among the IL-1 family cytokines, only IL-18 correlates with this disease and may therefore have a pathological role in sALS. The increase of total IL-18 suggests the activation of IL-18-cleaving inflammasome. Whether IL-18 upregulation in circulation of sALS patients is a consequence of inflammation or one of the causes of the pathology still needs to be addressed. PMID:24884937

  4. Interleukin-1 family cytokines and their regulatory proteins in normal pregnancy and pre-eclampsia.

    PubMed

    Southcombe, J H; Redman, C W G; Sargent, I L; Granne, I

    2015-09-01

    Maternal systemic inflammation is a feature of pre-eclampsia, a condition in pregnancy characterized by hypertension and proteinuria. Pre-eclampsia is caused by the placenta; many placental factors contribute to the syndrome's progression, and proinflammatory cytokines have been identified previously as one such mediator. The interleukin (IL)-1 family of cytokines are key regulators of the inflammatory network, and two naturally occurring regulatory molecules for IL-1 family cytokines, IL-1RA and sST2, have been found previously to be elevated in maternal blood from women with pre-eclampsia. Here we investigate more recently identified IL-1 family cytokines and regulatory molecules, IL-1RAcP, IL-37, IL-18BP, IL-36α/β/γ/Ra and IL-38 in pre-eclampsia. Pregnant women have more circulating IL-18BP and IL-36Ra than non-pregnant women, and sIL-1RAcP is elevated from women with pre-eclampsia compared to normal pregnancies. The placenta expresses all the molecules, and IL-37 and IL-18BP are up-regulated significantly in pre-eclampsia placentas compared to those from normal pregnancies. Together, these changes contribute to the required inhibition of maternal systemic cytotoxic immunity in normal pregnancy; however, in pre-eclampsia the same profile is not seen. Interestingly, the increased circulating levels of sIL-1RAcP and increased placental IL-18BP and IL-37, the latter of which we show to be induced by hypoxic damage to the placenta, are all factors which are anti-inflammatory. While the placenta is often held responsible for the damage and clinical symptoms of pre-eclampsia by the research community, here we show that the pre-eclampsia placenta is also trying to prevent inflammatory damage to the mother. PMID:25693732

  5. The TNF-family cytokine TL1A: from lymphocyte costimulator to disease co-conspirator.

    PubMed

    Richard, Arianne C; Ferdinand, John R; Meylan, Françoise; Hayes, Erika T; Gabay, Odile; Siegel, Richard M

    2015-09-01

    Originally described in 2002 as a T cell-costimulatory cytokine, the tumor necrosis factor family member TNF-like factor 1A (TL1A), encoded by the TNFSF15 gene, has since been found to affect multiple cell lineages through its receptor, death receptor 3 (DR3, encoded by TNFRSF25) with distinct cell-type effects. Genetic deficiency or blockade of TL1A-DR3 has defined a number of disease states that depend on this cytokine-receptor pair, whereas excess TL1A leads to allergic gastrointestinal inflammation through stimulation of group 2 innate lymphoid cells. Noncoding variants in the TL1A locus are associated with susceptibility to inflammatory bowel disease and leprosy, predicting that the level of TL1A expression may influence host defense and the development of autoimmune and inflammatory diseases. PMID:26188076

  6. The TNF-family cytokine TL1A: from lymphocyte costimulator to disease co-conspirator

    PubMed Central

    Richard, Arianne C.; Ferdinand, John R.; Meylan, Françoise; Hayes, Erika T.; Gabay, Odile; Siegel, Richard M.

    2015-01-01

    Originally described in 2002 as a T cell-costimulatory cytokine, the tumor necrosis factor family member TNF-like factor 1A (TL1A), encoded by the TNFSF15 gene, has since been found to affect multiple cell lineages through its receptor, death receptor 3 (DR3, encoded by TNFRSF25) with distinct cell-type effects. Genetic deficiency or blockade of TL1A-DR3 has defined a number of disease states that depend on this cytokine-receptor pair, whereas excess TL1A leads to allergic gastrointestinal inflammation through stimulation of group 2 innate lymphoid cells. Noncoding variants in the TL1A locus are associated with susceptibility to inflammatory bowel disease and leprosy, predicting that the level of TL1A expression may influence host defense and the development of autoimmune and inflammatory diseases. PMID:26188076

  7. Computational EST database analysis identifies a novel member of the neuropoietic cytokine family.

    PubMed

    Shi, Y; Wang, W; Yourey, P A; Gohari, S; Zukauskas, D; Zhang, J; Ruben, S; Alderson, R F

    1999-08-19

    A novel member of the neuropoietic cytokine family has been cloned and the protein expressed and characterized. In an effort to identify novel secreted proteins, an algorithm incorporating neural network algorithms was applied to a large EST database. A full-length clone was identified that is 1710 bp in length and has a single open reading frame of 225 amino acids. This new cytokine is most homologous to cardiotrophin-1, having a similarity and an identity of 46 and 29%, respectively, and therefore we have named it cardiotrophin-like cytokine (CLC). Northern hybridization analysis identified a 1.4-kb messenger RNA that is highly expressed in spleen and peripheral leukocytes. Purified recombinant CLC induced the activation of NFkappaB and SRE reporter constructs in the TF-1, U937, and M1 cell lines. Furthermore, the signal transduction pathway for CLC was characterized in the neuroblastoma cell line SK-N-MC and found to involve tyrosine phosphorylation of gp130 and STAT-1. PMID:10448081

  8. Small Molecule Inhibition of the TNF Family Cytokine CD40 Ligand Through a Subunit Fracture Mechanism

    SciTech Connect

    L Silvian; J Friedman; K Strauch; T Cachero; E Day; F Qian; B Cunningham; A Fung; L Sun; et al.

    2011-12-31

    BIO8898 is one of several synthetic organic molecules that have recently been reported to inhibit receptor binding and function of the constitutively trimeric tumor necrosis factor (TNF) family cytokine CD40 ligand (CD40L, aka CD154). Small molecule inhibitors of protein-protein interfaces are relatively rare, and their discovery is often very challenging. Therefore, to understand how BIO8898 achieves this feat, we characterized its mechanism of action using biochemical assays and X-ray crystallography. BIO8898 inhibited soluble CD40L binding to CD40-Ig with a potency of IC{sub 50} = 25 {mu}M and inhibited CD40L-dependent apoptosis in a cellular assay. A co-crystal structure of BIO8898 with CD40L revealed that one inhibitor molecule binds per protein trimer. Surprisingly, the compound binds not at the surface of the protein but by intercalating deeply between two subunits of the homotrimeric cytokine, disrupting a constitutive protein-protein interface and breaking the protein's 3-fold symmetry. The compound forms several hydrogen bonds with the protein, within an otherwise hydrophobic binding pocket. In addition to the translational splitting of the trimer, binding of BIO8898 was accompanied by additional local and longer-range conformational perturbations of the protein, both in the core and in a surface loop. Binding of BIO8898 is reversible, and the resulting complex is stable and does not lead to detectable dissociation of the protein trimer. Our results suggest that a set of core aromatic residues that are conserved across a subset of TNF family cytokines might represent a generic hot-spot for the induced-fit binding of trimer-disrupting small molecules.

  9. Fibrosis Related Inflammatory Mediators: Role of the IL-10 Cytokine Family

    PubMed Central

    Sziksz, Erna; Pap, Domonkos; Lippai, Rita; Béres, Nóra Judit; Fekete, Andrea; Szabó, Attila J.; Vannay, Ádám

    2015-01-01

    Importance of chronic fibroproliferative diseases (FDs) including pulmonary fibrosis, chronic kidney diseases, inflammatory bowel disease, and cardiovascular or liver fibrosis is rapidly increasing and they have become a major public health problem. According to some estimates about 45% of all deaths are attributed to FDs in the developed world. Independently of their etiology the common hallmark of FDs is chronic inflammation. Infiltrating immune cells, endothelial, epithelial, and other resident cells of the injured organ release an orchestra of inflammatory mediators, which stimulate the proliferation and excessive extracellular matrix (ECM) production of myofibroblasts, the effector cells of organ fibrosis. Abnormal amount of ECM disturbs the original organ architecture leading to the decline of function. Although our knowledge is rapidly expanding, we still have neither a diagnostic tool to detect nor a drug to specifically target fibrosis. Therefore, there is an urgent need for the more comprehensive understanding of the pathomechanism of fibrosis and development of novel diagnostic and therapeutic strategies. In the present review we provide an overview of the common key mediators of organ fibrosis highlighting the role of interleukin-10 (IL-10) cytokine family members (IL-10, IL-19, IL-20, IL-22, IL-24, and IL-26), which recently came into focus as tissue remodeling-related inflammatory cytokines. PMID:26199463

  10. Distinctive expression pattern of interleukin-17 cytokine family members in colorectal cancer.

    PubMed

    Al-Samadi, Ahmed; Moossavi, Shirin; Salem, Abdelhakim; Sotoudeh, Masoud; Tuovinen, Sarianna M; Konttinen, Yrjö T; Salo, Tuula; Bishehsari, Faraz

    2016-02-01

    Colorectal cancer (CRC) is one of the most common cancers in both genders. Even though interleukin (IL)-17A was shown to play an important role in intestinal tumourigenesis and CRC, other IL-17 family members were not studied well. We therefore studied the expression of IL-17 cytokine family members in CRC. Ten healthy colons and ten CRC mucosa were immunostained for IL-17B, IL-17C, IL-17E, and IL-17F, and their receptors IL-17RA, IL-17RB, and IL-17RC. Double immunofluorescence staining of the CRC mucosa was done for IL-17B with markers of neutrophils, endothelial cells, macrophages, T cells, mast cells, or fibroblasts. While IL-17B was increased in CRC with a strong presence both in the epithelial and stromal compartments, IL-17C showed different expression depending on the grade of differentiation and IL-17E remained unchanged. In contrast, IL-17F was decreased in CRC compared to healthy control. Colon epithelial cells stained positive for IL-17RA, IL-17RB, and IL-17RC in both healthy control and CRC. Neutrophils were the main source of IL-17B in the stroma. IL-17 family members demonstrated distinct expression patterns in CRC, suggesting a differential role exerted by each member in colon carcinogenesis. PMID:26304506

  11. A new member of the cytokine receptor gene family maps on chromosome 21 at less than 35 kb from IFNAR

    SciTech Connect

    Lutfalla, G.; Uze, G.; Gardiner, K.

    1993-05-01

    A full-length cDNA corresponding to a gene mapping to the D21S58 locus was cloned. The encoded protein, called CRF2-4, was shown to be a typical class II member of the cytokine receptor family. The gene encoding CRF2-4 spans more than 30 kb. Its intron/exon structure was determined and shown to be conserved with all other members of the cytokine receptor family. The physical distance between the CRF2-4 gene and its IFNAR neighbor has been narrowed to less than 35 kb. 41 refs., 4 figs., 1 tab.

  12. Revisiting the regulatory roles of the TGF-β family of cytokines.

    PubMed

    Fujio, Keshi; Komai, Toshihiko; Inoue, Mariko; Morita, Kaoru; Okamura, Tomohisa; Yamamoto, Kauzhiko

    2016-09-01

    TGF-β family members are multipotent cytokines that are involved in many cellular processes, including cell differentiation, organ development, wound healing and immune regulation. TGF-β has pleiotropic effects on adaptive immunity, especially in the regulation of CD4(+) T cell and B cell responses. Furthermore, identification of CD4(+) T cell subsets that produce TGF-β3 revealed unexpected roles of TGF-β3 in the control of adaptive immunity. In contrast to TGF-β1, which induces extensive fibrosis, TGF-β3 induces non-scarring wound healing and counteracts tissue fibrosis. Recent progress in the understanding of the activation mechanism of TGF-β may enable us to develop novel biologic therapies based on advanced protein engineering. PMID:27392504

  13. The Transformation of the Family: Implications for Child Care Policy.

    ERIC Educational Resources Information Center

    Hill-Scott, Karen

    This paper summarizes theories of American family organization, points out social changes that have had an impact on family structure, and discusses implications of current social and political conditions for child care policy. It is suggested that monistic characterizations of the family, emphasizing self-sufficiency and only one kind of family…

  14. Proinflammatory cytokines promote glial heme oxygenase-1 expression and mitochondrial iron deposition: implications for multiple sclerosis.

    PubMed

    Mehindate, K; Sahlas, D J; Frankel, D; Mawal, Y; Liberman, A; Corcos, J; Dion, S; Schipper, H M

    2001-06-01

    Proinflammatory cytokines, pathological iron deposition, and oxidative stress have been implicated in the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). HO-1 mRNA levels and mitochondrial uptake of [(55)Fe]Cl(3)-derived iron were measured in rat astroglial cultures exposed to interleukin-1beta (IL-1beta) or tumor necrosis factor-alpha (TNF-alpha) alone or in combination with the heme oxygenase-1 (HO-1) inhibitors, tin mesoporphyrin (SnMP) or dexamthasone (DEX), or interferon beta1b (INF-beta). HO-1 expression in astrocytes was evaluated by immunohistochemical staining of spinal cord tissue derived from MS and control subjects. IL-1beta or TNF-alpha promoted sequestration of non-transferrin-derived (55)Fe by astroglial mitochondria. HO-1 inhibitors, mitochondrial permeability transition pore (MTP) blockers and antioxidants significantly attenuated cytokine-related mitochondrial iron sequestration in these cells. IFN-beta decreased HO-1 expression and mitochondrial iron sequestration in IL-1beta- and TNF-alpha-challenged astroglia. The percentage of astrocytes coexpressing HO-1 in affected spinal cord from MS patients (57.3% +/- 12.8%) was significantly greater (p < 0.05) than in normal spinal cord derived from controls subjects (15.4% +/- 8.4%). HO-1 is over-expressed in MS spinal cord astroglia and may promote mitochondrial iron deposition in MS plaques. In MS, IFN-beta may attenuate glial HO-1 gene induction and aberrant mitochondrial iron deposition accruing from exposure to proinflammatory cytokines. PMID:11389189

  15. The Changing Family: Implications for Education.

    ERIC Educational Resources Information Center

    Rubin, Linda J.; Borgers, Sherry B.

    1991-01-01

    Changes in the composition of the American family and shifts in family members' roles and responsibilities are weakening the family support system essential for children's healthy development. Financial issues (income and poverty levels and working mothers) have a similar effect. To cope with changing families' needs, good teacher-administrator…

  16. Antibody blockade of IL-17 family cytokines in immunity to acute murine oral mucosal candidiasis.

    PubMed

    Whibley, Natasha; Tritto, Elaine; Traggiai, Elisabetta; Kolbinger, Frank; Moulin, Pierre; Brees, Dominique; Coleman, Bianca M; Mamo, Anna J; Garg, Abhishek V; Jaycox, Jillian R; Siebenlist, Ulrich; Kammüller, Michael; Gaffen, Sarah L

    2016-06-01

    Antibodies targeting IL-17A or its receptor, IL-17RA, are approved to treat psoriasis and are being evaluated for other autoimmune conditions. Conversely, IL-17 signaling is critical for immunity to opportunistic mucosal infections caused by the commensal fungus Candida albicans, as mice and humans lacking the IL-17R experience chronic mucosal candidiasis. IL-17A, IL-17F, and IL-17AF bind the IL-17RA-IL-17RC heterodimeric complex and deliver qualitatively similar signals through the adaptor Act1. Here, we used a mouse model of acute oropharyngeal candidiasis to assess the impact of blocking IL-17 family cytokines compared with specific IL-17 cytokine gene knockout mice. Anti-IL-17A antibodies, which neutralize IL-17A and IL-17AF, caused elevated oral fungal loads, whereas anti-IL-17AF and anti-IL-17F antibodies did not. Notably, there was a cooperative effect of blocking IL-17A, IL-17AF, and IL-17F together. Termination of anti-IL-17A treatment was associated with rapid C. albicans clearance. IL-17F-deficient mice were fully resistant to oropharyngeal candidiasis, consistent with antibody blockade. However, IL-17A-deficient mice had lower fungal burdens than anti-IL-17A-treated mice. Act1-deficient mice were much more susceptible to oropharyngeal candidiasis than anti-IL-17A antibody-treated mice, yet anti-IL-17A and anti-IL-17RA treatment caused equivalent susceptibilities. Based on microarray analyses of the oral mucosa during infection, only a limited number of genes were associated with oropharyngeal candidiasis susceptibility. In sum, we conclude that IL-17A is the main cytokine mediator of immunity in murine oropharyngeal candidiasis, but a cooperative relationship among IL-17A, IL-17AF, and IL-17F exists in vivo. Susceptibility displays the following hierarchy: IL-17RA- or Act1-deficiency > anti-IL-17A + anti-IL-17F antibodies > anti-IL-17A or anti-IL-17RA antibodies > IL-17A deficiency. PMID:26729813

  17. The gp130 Receptor Cytokine Family: Regulators of Adipocyte Development and Function

    PubMed Central

    White, Ursula A.; Stephens, Jacqueline M.

    2011-01-01

    Gp130 cytokines are involved in the regulation of numerous biological processes, including hematopoiesis, immune response, inflammation, cardiovascular action, and neuronal survival. These cytokines share glycoprotein 130 as a common signal transducer in their receptor complex and typically activate STAT3. Most gp130 cytokines have paracrine or endocrine actions, and their levels can be measured in circulation in rodents and humans. In recent years, various laboratories have conducted studies to demonstrate that gp130 cytokines can modulate adipocyte development and function. Therefore, these studies suggest that some gp130 cytokines may be viable anti-obesity therapeutics. In this review, we will summarize the reported effects of gp130 cytokines on adipocyte differentiation and adipocyte function. In addition, the modulation of gp130 cytokines in conditions of obesity, insulin resistance, and Type 2 diabetes will be presented. PMID:21375496

  18. Implications of Change in Mexican American Families.

    ERIC Educational Resources Information Center

    Knowlton, Clark S.

    The Mexican American bilateral extended family system was a part of the cultural heritage from Mexico or Spain and a family system developed as a social and cultural response to the cultural isolation and frontier environment of the Borderlands. As a social system, it mobilized members to work the land, protect family members and property against…

  19. Identification of the salmon somatolactin receptor, a new member of the cytokine receptor family.

    PubMed

    Fukada, Haruhisa; Ozaki, Yuichi; Pierce, Andrew L; Adachi, Shinji; Yamauchi, Kohei; Hara, Akihiko; Swanson, Penny; Dickhoff, Walton W

    2005-05-01

    Somatolactin (SL) is a pituitary hormone of the GH/prolactin (PRL) family that so far has been found only in fish. Compared with GH and PRL, the primary structure of SL is highly conserved among divergent fish species, suggesting it has an important function and a discriminating receptor that constrains structural change. However, SL functions are poorly understood, and receptors for SL have not yet been identified. During cloning of GH receptor cDNA from salmon, we found a variant with relatively high (38-58%) sequence identity to vertebrate GH receptors and low (28-33%) identity to PRL receptors; however, the recombinant protein encoding the extracellular domain showed only weak binding of GH. Ligand binding of the recombinant extracellular domain for this receptor confirmed that the cDNA encoded a specific receptor for SL. The SL receptor (SLR) has common features of a GH receptor including FGEFS motif, six cysteine residues in the extracellular domain, a single transmembrane region, and Box 1 and 2 regions in the intracellular domain. These structural characteristics place the SLR in the cytokine receptor type I homodimeric group, which includes receptors for GH, PRL, erythropoietin, thrombopoietin, granulocyte-colony stimulating factor, and leptin. Transcripts for SLR were found in 11 tissues with highest levels in liver and fat, supporting the notion that a major function of SL is regulation of lipid metabolism. Cloning SLR cDNA opens the way for discovery of new SL functions and target tissues in fish, and perhaps novel members of this receptor family in other vertebrates. PMID:15718271

  20. IMPLICATIONS OF SPANISH-AMERICAN CULTURE ON FAMILY LIFE.

    ERIC Educational Resources Information Center

    VALDEZ, BERNARD

    FAMILY PATTERNS AND ROLES OF SPANISH-AMERICANS AND IMPLICATIONS OF TRANSFERENCE OF FOLK CULTURE TO AN URBAN SETTING ARE ANALYZED. STRONG FAMILY COHESIVENESS IS CREATED BY ISOLATION, LACK OF MOBILITY, AN AGRARIAN ECONOMY, AND THE PUEBLO INDIAN INFLUENCE OF SMALL VILLAGES. BLOOD KINSHIPS ARE SOUGHT OUT AND MAINTAINED, AND ARE EXTENDED BY A SYSTEM OF…

  1. Induction of proinflammatory cytokines by a soluble factor of Propionibacterium acnes: implications for chronic inflammatory acne.

    PubMed

    Vowels, B R; Yang, S; Leyden, J J

    1995-08-01

    Although many cytokines have been implicated in the development and persistence of inflammatory immune responses, it is unknown if any of these are important in inflammatory acne. This study investigated the production of the proinflammatory cytokines interleukin-8 (IL-8), IL-1 beta, and tumor necrosis factor alpha (TNF-alpha) by human monocytic cell lines, ThP-1 and U937, and by freshly isolated peripheral blood mononuclear cells from acne patients. Both Propionibacterium acnes and supernatants obtained from 72-h P. acnes cultures could induce significant concentrations of IL-1 beta, TNF-alpha, and IL-8 by both cell lines and by peripheral blood mononuclear cells as determined by enzyme-linked immunosorbent assay. There was no significant difference between acne and non-acne subjects. Endotoxin quantification and addition of polymyxin B to assays indicated no lipopolysaccharide (LPS) contamination. P. acnes supernatant was fractionated into components with molecular weights of < 3,000, < 10,000, and < 30,000 and assayed for the ability to induce IL-8 and TNF production in ThP-1 cells. Nearly 90% of the original activity was found in the < 30,000-molecular-weight fraction, 50% was in the < 10,000-molecular-weight fraction, and only 15% remained in the < 3,000-molecular-weight fraction. The effluent from the < 3,000-molecular-weight fraction contained about 70% activity, indicating that the inducing factor was not retained in the membrane. Incubation of P. acnes supernatant with various concentrations of mutanolysin or lysozyme resulted in a loss of 60% of the original activity. The addition of jimson lectin, which binds peptidoglycan, resulted in a loss of 70% of the activity in a dose-response manner, whereas peanut lectin had little or no effect on the activity. Heating of the P. acnes supernatant to 65 degrees C also had no effect on the activity. Blocking of CD14, a receptor for both LPS and peptidoglycan, reduced cytokine production by > 50%, suggesting that

  2. Grandparents' Rights: Implications for Family Specialists.

    ERIC Educational Resources Information Center

    Purnell, Marie; Bagby, Beatrice H.

    1993-01-01

    Notes that every state has passed laws giving grandparents right to petition courts for privilege of visiting their grandchildren. Family specialists need to understand nature of grandparents' rights laws because these laws affect their duties. Asserts that research findings and expert witness testimonies of family specialists should be included…

  3. Work/Family Conflicts: Policy Implications.

    ERIC Educational Resources Information Center

    Baker, Maureen

    In the past 20 years, the percentage of married women in the Canadian labor force has risen dramatically. Despite women's increased participation in the labor force, child care and housework are still largely done by women. While the difficulty of combining work and family responsibilities can result in work/family conflicts, a variety of…

  4. Cell death and inflammation: the case for IL-1 family cytokines as the canonical DAMPs of the immune system.

    PubMed

    Martin, Seamus J

    2016-07-01

    It is well known that necrotic cells are capable of promoting inflammation through releasing so-called endogenous 'danger signals' that can promote activation of macrophages, dendritic cells, and other sentinel cells of the innate immune system. However, the identity of these endogenous proinflammatory molecules, also called damage-associated molecular patterns (DAMPs), has been debated since the 'danger model' was first advanced 20 years ago. While a relatively large number of molecules have been proposed to act as DAMPs, little consensus has emerged concerning which of these represent the key activators of sterile inflammation. Here I argue that the canonical DAMPs have long been hiding in plain sight, in the form of members of the extended IL-1 cytokine family (IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β, and IL-36γ). The latter cytokines possess all of the characteristics expected of endogenous DAMPs and initiate inflammation in a manner strikingly similar to that utilized by the other major category of inflammatory triggers, pathogen-associated molecular patterns (PAMPs). Furthermore, many PAMPs upregulate the expression of IL-1 family DAMPs, enabling robust synergy between these distinct classes of inflammatory triggers. Thus, multiple lines of evidence now suggest that IL-1 family cytokines represent the key initiators of necrosis-initiated sterile inflammation, as well as amplifiers of inflammation in response to infection-associated tissue injury. PMID:27273805

  5. Family Mode Deactivation Therapy Results and Implications

    ERIC Educational Resources Information Center

    Apsche, Jack A.; Bass, Christopher K.

    2006-01-01

    This article highlights the inclusion of Mode Deactivation Therapy as a treatment modality for families in crisis. As an empirically validated treatment, Mode Deactivation Therapy has been effective in treating a wide variety of psychological issues. Mode Deactivation Therapy, (MDT) was developed to treat adolescents with disorders of conduct…

  6. Family Matters Update: Design, Baseline Findings, Policy Implications and Program Developments from a Family Supports Study.

    ERIC Educational Resources Information Center

    Cochran, Moncrieff

    The major portion of this presentation describes research results and policy implications of the Family Matters Project, a longitudinal study of social contexts as they affect children and families during the period of transition from home to school. Also provided in this portion are highlights of what was learned from delivering to 160 families…

  7. Familialism, Social Support, and Stress: Positive Implications for Pregnant Latinas

    PubMed Central

    Campos, Belinda; Schetter, Christine Dunkel; Abdou, Cleopatra M.; Hobel, Calvin J.; Glynn, Laura M.; Sandman, Curt A.

    2010-01-01

    This study examined the association of familialism, a cultural value that emphasizes close family relationships, with social support, stress, pregnancy anxiety, and infant birth weight. Foreign-born Latina (n = 31), U.S.-born Latina (n = 68), and European American (n = 166) women living in the United States participated in a prospective study of pregnancy in which they completed measures of familialism, social support, stress, and pregnancy anxiety during their second trimester. As expected, Latinas scored higher on familialism than European Americans. Familialism was positively correlated with social support and negatively correlated with stress and pregnancy anxiety in the overall sample. As predicted, however, the associations of familialism with social support and stress were significantly stronger among Latinas than European Americans. Moreover, higher social support was associated with higher infant birth weight among foreign-born Latinas only. Implications of cultural values for relationships and health are discussed. PMID:18426288

  8. Control of Cytokine Production by Human Fc Gamma Receptors: Implications for Pathogen Defense and Autoimmunity

    PubMed Central

    Vogelpoel, Lisa T. C.; Baeten, Dominique L. P.; de Jong, Esther C.; den Dunnen, Jeroen

    2015-01-01

    Control of cytokine production by immune cells is pivotal for counteracting infections via orchestration of local and systemic inflammation. Although their contribution has long been underexposed, it has recently become clear that human Fc gamma receptors (FcγRs), which are receptors for the Fc region of immunoglobulin G (IgG) antibodies, play a critical role in this process by controlling tissue- and pathogen-specific cytokine production. Whereas individual stimulation of FcγRs does not evoke cytokine production, FcγRs cell-type specifically interact with various other receptors for selective amplification or inhibition of particular cytokines, thereby tailoring cytokine responses to the immunological context. The physiological function of FcγR-mediated control of cytokine production is to counteract infections with various classes of pathogens. Upon IgG opsonization, pathogens are simultaneously recognized by FcγRs as well as by various pathogen-sensing receptors, leading to the induction of pathogen class-specific immune responses. However, when erroneously activated, the same mechanism also contributes to the development of autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. In this review, we discuss control of cytokine production as a novel function of FcγRs in human innate immune cells in the context of homeostasis, infection, and autoimmunity and address the possibilities for future therapeutic exploitation. PMID:25759693

  9. The SOCS box encodes a hierarchy of affinities for Cullin5: implications for ubiquitin ligase formation and cytokine signalling suppression

    PubMed Central

    Babon, Jeffrey J.; Sabo, Jennifer K.; Zhang, Jian-Guo; Nicola, Nicos A.; Norton, Raymond S.

    2009-01-01

    Summary The SOCS (Suppressors of Cytokine Signalling) family of proteins inhibit the cytokine induced signalling cascade, in part by promoting the ubiquitination of signalling intermediates that are then targeted for proteasomal degradation. This activity relies upon an interaction between the SOCS box domain, the adapter complex elonginBC and a member of the Cullin family, the scaffold protein of an E3 ubiquitin ligase. Here we dissect this interaction, in vitro, using purified components. We show that all eight SOCS proteins bound Cullin5, but required prior recruitment of elonginBC. Neither SOCS nor elonginBC bound Cullin5 when in isolation. Interestingly, the affinity of each SOCS/elonginBC complex for Cullin5 varied by two orders of magnitude across the SOCS family. Unexpectedly, the most potent suppressors of signalling, SOCS-1 and SOCS-3, bound most weakly to the E3 ligase scaffold, with affinities 100- and 10-fold lower, respectively, than than the rest of the family. The remaining six SOCS proteins all bound Cullin5 with high affinity (KD ∼ 10 nM), due to a slower off-rate, and hence a longer half-life of the complex. This difference in affinity may reflect a difference in mode-of-action, as only SOCS-1 and -3 have been shown to suppress signalling using both SOCS box dependent and independent mechanisms. This is not the case with the other six SOCS proteins and our data imply the existence of two distinct sub-classes of SOCS proteins, with a high affinity for Cullin5, the E3 ligase scaffold, possibly reflecting complete dependence upon ubiquitination for suppression of cytokine signalling. PMID:19385048

  10. The IL-6 family of cytokines modulates STAT3 activation by desumoylation of PML through SENP1 induction

    SciTech Connect

    Ohbayashi, Norihiko; Kawakami, Shiho; Muromoto, Ryuta; Togi, Sumihito; Ikeda, Osamu; Kamitani, Shinya; Sekine, Yuichi; Honjoh, Tsutomu; Matsuda, Tadashi

    2008-07-11

    Post-translational modification by small ubiquitin-like modifier (SUMO) plays an important role in the regulation of different signaling pathways and is involved in the formation of promyelocytic leukemia (PML) protein nuclear bodies following sumoylation of PML. In the present study, we found that IL-6 induces desumoylation of PML and dissociation between PML and SUMO1 in hepatoma cells. We also found that IL-6 induces mRNA expression of SENP1, a member of the SUMO-specific protease family. Furthermore, wild-type SENP1 but not an inactive SENP1 mutant restored the PML-mediated suppression of STAT3 activation. These results indicate that the IL-6 family of cytokines modulates STAT3 activation by desumoylation and inactivation PML through SENP1 induction.

  11. Perceived Family Functioning and Family Resources of Hong Kong Families: Implications for Social Work Practice

    ERIC Educational Resources Information Center

    Ma, Joyce L. C.; Wong, Timothy K. Y.; Lau, Luk King; Pun, Shuk Han

    2009-01-01

    This article reports the results of a telephone survey (n = 1,015 respondents) that aims to identify the perceived general family functioning and family resources of Hong Kong Chinese families and their linkage to each other in a rapidly transforming society. The perceived general family functioning of the respondents was average, and the five…

  12. Progesterone modulates pro-inflammatory cytokine expression profile after spinal cord injury: Implications for neuropathic pain.

    PubMed

    Coronel, María F; Raggio, María C; Adler, Natalia S; De Nicola, Alejandro F; Labombarda, Florencia; González, Susana L

    2016-03-15

    Neuropathic pain is a frequent complication of spinal cord injury (SCI), still refractory to conventional treatment. Glial cell activation and cytokine production contribute to the pathology of central neuropathic syndromes. In this study we evaluated the effects of progesterone, a neuroactive steroid, on pain development and the spinal expression of IL-1β, its receptors (IL-1RI and IL-1RII) and antagonist (IL-1ra), IL-6 and TNFα, and NR1 subunit of NMDAR. Our results show that progesterone, by modulating the expression of pro-inflammatory cytokines and neuronal IL-1RI/NR1 colocalization, emerges as a promising agent to prevent chronic pain after SCI. PMID:26943964

  13. Regulation and function of the IL-1 family cytokine IL-1F9 in human bronchial epithelial cells.

    PubMed

    Chustz, Regina T; Nagarkar, Deepti R; Poposki, Julie A; Favoreto, Silvio; Avila, Pedro C; Schleimer, Robert P; Kato, Atsushi

    2011-07-01

    The IL-1 family of cytokines, which now includes 11 members, is well known to participate in inflammation. Although the most recently recognized IL-1 family cytokines (IL-1F5-11) have been shown to be expressed in airway epithelial cells, the regulation of their expression and function in the epithelium has not been extensively studied. We investigated the regulation of IL-1F5-11 in primary normal human bronchial epithelial cells. Messenger (m)RNAs for IL-1F6 and IL-1F9, but not IL-1F5, IL-1F8 or IL-1F10, were significantly up-regulated by TNF, IL-1β, IL-17 and the Toll-like receptor (TLR)3 ligand double-stranded (ds)RNA. mRNAs for IL-1F7 and IL-1F11 (IL-33) were weakly up-regulated by some of the cytokines tested. Notably, mRNAs for IL-1F6 and IL-1F9 were synergistically enhanced by the combination of TNF/IL-17 or dsRNA/IL-17. IL-1F9 protein was detected in the supernatant following stimulation with dsRNA or a combination of dsRNA and IL-17. IL-1F6 protein was detected in the cell lysate but was not detected in the supernatant. We screened for the receptor for IL-1F9 and found that lung fibroblasts expressed this receptor. We found that IL-1F9 activated mitogen-activated protein kinases and the transcription factor NF-κB in primary normal human lung fibroblasts. IL-1F9 also stimulated the expression of the neutrophil chemokines IL-8 and CXCL3 and the Th17 chemokine CCL20 in lung fibroblasts. These results suggest that epithelial activation by TLR3 (e.g., by respiratory viral infection) and exposure to cytokines from Th17 cells (IL-17) and inflammatory cells (TNF) may amplify neutrophilic inflammation in the airway via induction of IL-1F9 and activation of fibroblasts. PMID:20870894

  14. Misoprostol modulates cytokine expression through a cAMP pathway: Potential therapeutic implication for liver disease.

    PubMed

    Gobejishvili, Leila; Ghare, Smita; Khan, Rehan; Cambon, Alexander; Barker, David F; Barve, Shirish; McClain, Craig; Hill, Daniell

    2015-12-01

    Dysregulated cytokine metabolism plays a critical role in the pathogenesis of many forms of liver disease, including alcoholic and non-alcoholic liver disease. In this study we examined the efficacy of Misoprostol in modulating LPS-inducible TNFα and IL-10 expression in healthy human subjects and evaluated molecular mechanisms for Misoprostol modulation of cytokines in vitro. Healthy subjects were given 14day courses of Misoprostol at doses of 100, 200, and 300μg four times a day, in random order. Baseline and LPS-inducible cytokine levels were examined ex vivo in whole blood at the beginning and the end of the study. Additionally, in vitro studies were performed using primary human PBMCs and the murine macrophage cell line, RAW 264.7, to investigate underlying mechanisms of misoprostol on cytokine production. Administration of Misoprostol reduced LPS inducible TNF production by 29%, while increasing IL-10 production by 79% in human subjects with no significant dose effect on ex vivo cytokine activity; In vitro, the effect of Misoprostol was largely mediated by increased cAMP levels and consequent changes in CRE and NFκB activity, which are critical for regulating IL-10 and TNF expression. Additionally, chromatin immunoprecipitation (ChIP) studies demonstrated that Misoprostol treatment led to changes in transcription factor and RNA Polymerase II binding, resulting in changes in mRNA levels. In summary, Misoprostol was effective at beneficially modulating TNF and IL-10 levels both in vivo and in vitro; these studies suggest a potential rationale for Misoprostol use in ALD, NASH and other liver diseases where inflammation plays an etiologic role. PMID:26408955

  15. Lymphoid-Tissue-Resident Commensal Bacteria Promote Members of the IL-10 Cytokine Family to Establish Mutualism.

    PubMed

    Fung, Thomas C; Bessman, Nicholas J; Hepworth, Matthew R; Kumar, Nitin; Shibata, Naoko; Kobuley, Dmytro; Wang, Kelvin; Ziegler, Carly G K; Goc, Jeremy; Shima, Tatsuichiro; Umesaki, Yoshinori; Sartor, R Balfour; Sullivan, Kaede V; Lawley, Trevor D; Kunisawa, Jun; Kiyono, Hiroshi; Sonnenberg, Gregory F

    2016-03-15

    Physical separation between the mammalian immune system and commensal bacteria is necessary to limit chronic inflammation. However, selective species of commensal bacteria can reside within intestinal lymphoid tissues of healthy mammals. Here, we demonstrate that lymphoid-tissue-resident commensal bacteria (LRC) colonized murine dendritic cells and modulated their cytokine production. In germ-free and antibiotic-treated mice, LRCs colonized intestinal lymphoid tissues and induced multiple members of the IL-10 cytokine family, including dendritic-cell-derived IL-10 and group 3 innate lymphoid cell (ILC3)-derived IL-22. Notably, IL-10 limited the development of pro-inflammatory Th17 cell responses, and IL-22 production enhanced LRC colonization in the steady state. Furthermore, LRC colonization protected mice from lethal intestinal damage in an IL-10-IL-10R-dependent manner. Collectively, our data reveal a unique host-commensal-bacteria dialog whereby selective subsets of commensal bacteria interact with dendritic cells to facilitate tissue-specific responses that are mutually beneficial for both the host and the microbe. PMID:26982365

  16. Cytokine gene associations with self-report ratings of morning and evening fatigue in oncology patients and their family caregivers.

    PubMed

    Dhruva, Anand; Aouizerat, Bradley E; Cooper, Bruce; Paul, Steven M; Dodd, Marylin; West, Claudia; Wara, William; Lee, Kathryn; Dunn, Laura B; Langford, Dale J; Merriman, John D; Baggott, Christina; Cataldo, Janine; Ritchie, Christine; Kober, Kord M; Leutwyler, Heather; Miaskowski, Christine

    2015-03-01

    The purpose of this study was to evaluate for differences in variations in pro- and anti-inflammatory cytokine genes between participants who were classified as having low and high levels of morning and evening fatigue and to evaluate for differences in phenotypic characteristics between these two groups. In a sample of 167 oncology outpatients with breast, prostate, lung, or brain cancer and 85 of their family caregivers, growth mixture modeling was used to identify latent classes of individuals based on ratings of morning and evening fatigue obtained prior to, during, and for 4 months following completion of radiation therapy. Differences in single nucleotide polymorphisms and haplotypes in 15 cytokine genes were evaluated between the latent classes. Multiple logistic regression was used to assess the effect of phenotypic and genotypic characteristics on morning and evening fatigue class membership. Associations were found between morning fatigue and number of comorbidities as well as variations in tumor necrosis factor alpha (TNFA) rs1800629 and rs3093662. Evening fatigue was associated with caring for children at home and variations in interleukin 4 (IL4) rs2243248 and TNFA rs2229094. Younger age and lower performance status were associated with both morning and evening fatigue. These findings suggest that inflammatory mediators are associated with the development of morning and evening fatigue. However, because different phenotypic characteristics and genomic markers are associated with diurnal variations in fatigue, morning and evening fatigue may be distinct but related symptoms. PMID:24872120

  17. Uninephrectomy in rats on a fixed food intake results in adipose tissue lipolysis implicating spleen cytokines

    PubMed Central

    Arsenijevic, Denis; Cajot, Jean-François; Dulloo, Abdul G.; Montani, Jean-Pierre

    2015-01-01

    The role of mild kidney dysfunction in altering lipid metabolism and promoting inflammation was investigated in uninephrectomized rats (UniNX) compared to Sham-operated controls rats. The impact of UniNX was studied 1, 2, and 4 weeks after UniNX under mild food restriction at 90% of ad libitum intake to ensure the same caloric intake in both groups. UniNX resulted in the reduction of fat pad weight. UniNX was associated with increased circulating levels of beta-hydroxybutyrate and glycerol, as well as increased fat pad mRNA of hormone sensitive lipase and adipose triglyceride lipase, suggesting enhanced lipolysis. No decrease in fat pad lipogenesis as assessed by fatty acid synthase activity was observed. Circulating hormones known to regulate lipolysis such as leptin, T3, ghrelin, insulin, corticosterone, angiotensin 1, and angiotensin 2 were not different between the two groups. In contrast, a select group of circulating lipolytic cytokines, including interferon-gamma and granulocyte macrophage–colony stimulating factor, were increased after UniNX. These cytokine levels were elevated in the spleen, but decreased in the kidney, liver, and fat pads. This could be explained by anti-inflammatory factors SIRT1, a member of the sirtuins, and the farnesoid x receptor (FXR), which were decreased in the spleen but elevated in the kidney, liver, and fat pads (inguinal and epididymal). Our study suggests that UniNX induces adipose tissue lipolysis in response to increased levels of a subset of lipolytic cytokines of splenic origin. PMID:26217234

  18. Human Cytomegalovirus-Induces Cytokine Changes in the Placenta with Implications for Adverse Pregnancy Outcomes

    PubMed Central

    Hamilton, Stuart T.; Scott, Gillian; Naing, Zin; Iwasenko, Jenna; Hall, Beverley; Graf, Nicole; Arbuckle, Susan; Craig, Maria E.; Rawlinson, William D.

    2012-01-01

    Human cytomegalovirus (CMV) infection of the developing fetus can result in adverse pregnancy outcomes including death in utero. Fetal injury results from direct viral cytopathic damage to the CMV-infected fetus, although evidence suggests CMV placental infection may indirectly cause injury to the fetus, possibly via immune dysregulation with placental dysfunction. This study investigated the effects of CMV infection on expression of the chemokine MCP-1 (CCL2) and cytokine TNF-α in placentae from naturally infected stillborn babies, and compared these changes with those found in placental villous explant histocultures acutely infected with CMV ex vivo. Tissue cytokine protein levels were assessed using quantitative immunohistochemistry. CMV-infected placentae from stillborn babies had significantly elevated MCP-1 and TNF-α levels compared with uninfected placentae (p = 0.001 and p = 0.007), which was not observed in placentae infected with other microorganisms (p = 0.62 and p = 0.71) (n = 7 per group). Modelling acute clinical infection using ex vivo placental explant histocultures showed infection with CMV laboratory strain AD169 (0.2 pfu/ml) caused significantly elevated expression of MCP-1 and TNF-α compared with uninfected explants (p = 0.0003 and p<0.0001) (n = 25 per group). Explant infection with wild-type Merlin at a tenfold lower multiplicity of infection (0.02 pfu/ml), caused a significant positive correlation between increased explant infection and upregulation of MCP-1 and TNF-α expression (p = 0.0001 and p = 0.017). Cytokine dysregulation has been associated with adverse outcomes of pregnancy, and can negatively affect placental development and function. These novel findings demonstrate CMV infection modulates the placental immune environment in vivo and in a multicellular ex vivo model, suggesting CMV-induced cytokine modulation as a potential initiator and/or exacerbator of placental and fetal injury. PMID

  19. Informed consent and its implications in family practice.

    PubMed

    Mangold, W J

    1975-04-01

    The doctrine of informed consent has had its practical introduction to medical malpractice litigation in the past five years. Its definition has not changed since the days when its definitive application was only a fond dream of the malpractice plaintiffs attorneys. However, with neh new methods of presenting this theory to the courts, and with the newly emerging practice fo having rulings on matters of law substituted by judges for prevailing standards of medical practice, the implications for family physicians have become tremendous. Hopefullum by understanding the principles involved in its application in the pertinent landmark cases, family physicians will be better able to abid the pitfalls engendered by the doctrine of informed consent. PMID:1127387

  20. Nursing workloads in family health: implications for universal access1

    PubMed Central

    de Pires, Denise Elvira Pires; Machado, Rosani Ramos; Soratto, Jacks; Scherer, Magda dos Anjos; Gonçalves, Ana Sofia Resque; Trindade, Letícia Lima

    2016-01-01

    Objective to identify the workloads of nursing professionals of the Family Health Strategy, considering its implications for the effectiveness of universal access. Method qualitative study with nursing professionals of the Family Health Strategy of the South, Central West and North regions of Brazil, using methodological triangulation. For the analysis, resources of the Atlas.ti software and Thematic Content Analysis were associated; and the data were interpreted based on the labor process and workloads as theorical approaches. Results the way of working in the Family Health Strategy has predominantly resulted in an increase in the workloads of the nursing professionals, with emphasis on the work overload, excess of demand, problems in the physical infrastructure of the units and failures in the care network, which hinders its effectiveness as a preferred strategy to achieve universal access to health. On the other hand, teamwork, affinity for the work performed, bond with the user, and effectiveness of the assistance contributed to reduce their workloads. Conclusions investments on elements that reduce the nursing workloads, such as changes in working conditions and management, can contribute to the effectiveness of the Family Health Strategy and achieving the goal of universal access to health. PMID:27027679

  1. Nursing workloads in family health: implications for universal access.

    PubMed

    Pires, Denise Elvira Pires de; Machado, Rosani Ramos; Soratto, Jacks; Scherer, Magda Dos Anjos; Gonçalves, Ana Sofia Resque; Trindade, Letícia Lima

    2016-01-01

    Objective to identify the workloads of nursing professionals of the Family Health Strategy, considering its implications for the effectiveness of universal access. Method qualitative study with nursing professionals of the Family Health Strategy of the South, Central West and North regions of Brazil, using methodological triangulation. For the analysis, resources of the Atlas.ti software and Thematic Content Analysis were associated; and the data were interpreted based on the labor process and workloads as theorical approaches. Results the way of working in the Family Health Strategy has predominantly resulted in an increase in the workloads of the nursing professionals, with emphasis on the work overload, excess of demand, problems in the physical infrastructure of the units and failures in the care network, which hinders its effectiveness as a preferred strategy to achieve universal access to health. On the other hand, teamwork, affinity for the work performed, bond with the user, and effectiveness of the assistance contributed to reduce their workloads. Conclusions investments on elements that reduce the nursing workloads, such as changes in working conditions and management, can contribute to the effectiveness of the Family Health Strategy and achieving the goal of universal access to health. PMID:27027679

  2. Proinflammatory cytokines induce bronchial hyperplasia and squamous metaplasia in smokers: implications for chronic obstructive pulmonary disease therapy.

    PubMed

    Herfs, Michael; Hubert, Pascale; Poirrier, Anne-Lise; Vandevenne, Patricia; Renoux, Virginie; Habraken, Yvette; Cataldo, Didier; Boniver, Jacques; Delvenne, Philippe

    2012-07-01

    Tracheobronchial squamous metaplasia is common in smokers, and is associated with both airway obstruction in chronic obstructive pulmonary disease (COPD) and increased risk of lung cancer. Although this reversible epithelial replacement is almost always observed in association with chronic inflammation, the role of inflammatory mediators in the pathogenesis of squamous metaplasia remains unclear. In the present study, we investigated the implication of cigarette smoke-mediated proinflammatory cytokine up-regulation in the development and treatment of tracheobronchial epithelial hyperplasia and squamous metaplasia. Using immunohistological techniques, we showed a higher epithelial expression of TNF-α, IL-1β, and IL-6, as well as an activation of NF-κB and activator protein-1/mitogen-activated protein kinase signaling pathways in the respiratory tract of smoking patients, compared with the normal ciliated epithelium of nonsmoking patients. In addition, we demonstrated that these signaling pathways strongly influence the proliferation and differentiation state of in vitro-generated normal human airway epithelial basal cells. Finally, we exposed mice to cigarette smoke for 16 weeks, and demonstrated that anti-TNF-α (etanercept), anti-IL-1β (anakinra), and/or anti-IL-6R (tocilizumab) therapies significantly reduced epithelial hyperplasia and the development of squamous metaplasia. These data highlight the importance of soluble inflammatory mediators in the pathogenesis of tracheobronchial squamous metaplasia. Therefore, the administration of proinflammatory cytokine antagonists may have clinical applications in the management of patients with COPD. PMID:22343222

  3. Upregulation of mitochondrial ferritin by proinflammatory cytokines: implications for a role in Alzheimer's disease.

    PubMed

    Yang, Hongkuan; Guan, Hongpeng; Yang, Mingchun; Liu, Ziyi; Takeuchi, Shigeko; Yanagisawa, Daijiro; Vincent, Steven R; Zhao, Shiguang; Tooyama, Ikuo

    2015-01-01

    Studies have shown an increased expression of mitochondrial ferritin (FtMt) and an antioxidant role for the protein in the brains of Alzheimer's disease (AD) patients. However, little information is available concerning the role of FtMt in other AD pathologies, including inflammation and amyloidogenesis. Therefore, we investigated the regulation and function of FtMt in inflammation and amyloidogenesis. FtMt protein expression was increased by proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin 6 (IL-6), whereas FtMt mRNA levels were increased by TNF-α but not by IL-1β or IL-6 in IMR-32 cells. The transcription factor nuclear factor-κB (NF-κB) inhibitor, Bay 11-7082, suppressed this TNF-α-induced FtMt expression. FtMt overexpression increased NF-κB activity and translocation of p65 into the nucleus in HEK293 cells. Conversely, knockdown of FtMt attenuated TNF-α-induced NF-κB activity. Overexpression of FtMt inhibited TNF-α-induced apoptosis in the cell culture. FtMt overexpression reduced iron-mediated expression of amyloid-β protein precursor and decreased NF-κB-dependent increases in β- and γ-secretase, leading to decreased amyloid-β production. Our data provide new insights into the mechanism underlying the regulation of FtMt expression by proinflammatory cytokines and indicate further roles for FtMt in AD. PMID:25624418

  4. Elderly adult survivors of family violence. Implications for clinical practice.

    PubMed

    Anetzberger, G J

    1997-10-01

    This article on elderly adult survivors of domestic violence (usually women) reviews the literature that examines the impact on later life of domestic violence experienced earlier in life and that examines the effects of elder abuse perpetrated by adult family members. The discussion is illustrated with case studies and figures that list the physical, psychological, behavioral, and social effects of each type of violence as well as intervening variables. Next, the paper reviews the influence of culture and ethnicity on the meaning attached to elder abuse and on help-seeking or accepting behavior. The article then proposes a conceptual framework that uses contributing factors (cultural background, individual influences, and cohort influences), modifying factors (the nature of violence, personal circumstances, and relationship with perpetrator), the meaning of violence, and the effects on the survivor to explain the effects of early or late family violence on elderly adult survivors. The discussion notes that the framework focuses on negative effects but that survivors of domestic violence can experience positive effects, such as the development of personal coping skills. The article ends by noting that this proposed framework has clinical implications because it recognizes that the effects of domestic violence on elderly adults may be complicated, it helps practitioners link symptoms to domestic violence, it helps practitioners realize that the meaning of domestic violence may vary among elderly victims, and it shows that family violence occurs in a social context. PMID:12322016

  5. Transcriptome Changes Affecting Hedgehog and Cytokine Signalling in the Umbilical Cord: Implications for Disease Risk

    PubMed Central

    Stünkel, Walter; Tng, Emilia; Tan, Jun Hao; Chen, Li; Joseph, Roy; Cheong, Clara Y.; Ong, Mei-Lyn; Lee, Yung Seng; Chong, Yap-Seng; Saw, Seang Mei; Meaney, Michael J.; Kwek, Kenneth; Sheppard, Allan M.; Gluckman, Peter D.; Holbrook, Joanna D.

    2012-01-01

    Background Babies born at lower gestational ages or smaller birthweights have a greater risk of poorer health in later life. Both the causes of these sub-optimal birth outcomes and the mechanism by which the effects are transmitted over decades are the subject of extensive study. We investigated whether a transcriptomic signature of either birthweight or gestational age could be detected in umbilical cord RNA. Methods The gene expression patterns of 32 umbilical cords from Singaporean babies of Chinese ethnicity across a range of birthweights (1698–4151 g) and gestational ages (35–41 weeks) were determined. We confirmed the differential expression pattern by gestational age for 12 genes in a series of 127 umbilical cords of Chinese, Malay and Indian ethnicity. Results We found that the transcriptome is substantially influenced by gestational age; but less so by birthweight. We show that some of the expression changes dependent on gestational age are enriched in signal transduction pathways, such as Hedgehog and in genes with roles in cytokine signalling and angiogenesis. We show that some of the gene expression changes we report are reflected in the epigenome. Conclusions We studied the umbilical cord which is peripheral to disease susceptible tissues. The results suggest that soma-wide transcriptome changes, preserved at the epigenetic level, may be a mechanism whereby birth outcomes are linked to the risk of adult metabolic and arthritic disease and suggest that greater attention be given to the association between premature birth and later disease risk. PMID:22808055

  6. The inflammasome and danger associated molecular patterns (DAMPs) are implicated in cytokine and chemokine responses following stressor exposure.

    PubMed

    Maslanik, Thomas; Mahaffey, Lucas; Tannura, Kate; Beninson, Lida; Greenwood, Benjamin N; Fleshner, Monika

    2013-02-01

    Exposure to stressors or trauma in the absence of pathogenic challenge can stimulate a systemic sterile inflammatory response characterized by high concentrations of blood and tissue cytokines, chemokines, and danger associated molecular patterns (DAMPs) such as heat shock protein-72 (Hsp72), and uric acid. The signaling pathways responsible for these responses remain unclear, however, the inflammasome may play a role. In vitro, DAMPs are known to stimulate the inflammasome in the presence of LPS to activate caspase-1 which cleaves immature precursors of interleukin (IL)-1β and IL-18 into their mature releasable forms. Furthermore, in vivo neutralization of the LPS selectively attenuates the stress-induced increase in the inflammasome-dependent cytokines IL-1β and IL-18. Thus, the current experiments tested the hypothesis that inflammasome-mediated processes are necessary for a systemic stress-induced inflammatory response to an acute stressor. The data presented (1) establish that male F344 rats exposed to an acute severe stressor (100 tail shocks) have elevated plasma concentrations of inflammatory proteins (IL-1β, IL-18, IL-6, IL-10, and monocyte chemotactic protein (MCP)-1), and DAMPs (uric acid and Hsp72); (2) demonstrate that inhibiting caspase-1 in vivo, using the caspase-1 inhibitor ac-YVAD-cmk, attenuates stress-induced production of IL-1β, IL-18, and IL-6 in both the circulation and peripheral tissues; and (3) implicates the DAMPs uric acid and Hsp72 as important signals contributing to inflammasome-dependent inflammatory responses using a stepwise multiple regression. The results increase our mechanistic understanding of systemic sterile inflammatory responses, and provide novel evidence that the inflammasome may be an important pharmacological target for treatment of these conditions. PMID:23103443

  7. The βc receptor family - Structural insights and their functional implications.

    PubMed

    Broughton, Sophie E; Nero, Tracy L; Dhagat, Urmi; Kan, Winnie L; Hercus, Timothy R; Tvorogov, Denis; Lopez, Angel F; Parker, Michael W

    2015-08-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) and IL-5 are members of a small family of cytokines that share a beta receptor subunit (βc). These cytokines regulate the growth, differentiation, migration and effector function activities of many hematopoietic cells in bone marrow, blood and sites of inflammation. Excessive or aberrant signaling can result in chronic inflammatory conditions and myeloid leukemias. The crystal structures of the GM-CSF ternary complex, the IL-5 binary complex and the very recent IL-3 receptor alpha subunit build upon decades of structure-function studies, giving new insights into cytokine-receptor specificity and signal transduction. Selective modulation of receptor function is now a real possibility and the structures of the βc receptor family are being used to discover novel and disease-specific therapeutics. PMID:25982846

  8. A Possible Change Process of Inflammatory Cytokines in the Prolonged Chronic Stress and Its Ultimate Implications for Health

    PubMed Central

    Tian, Rui; Hou, Gonglin; Li, Dan; Yuan, Ti-Fei

    2014-01-01

    Sustained stress triggers series of changes in the brain and the body. At the early stage of stress, the activated hypothalamus-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) axis can upregulate the levels of glucocorticoid (GCs) and catecholamines (CAs), respectively, and then they in turn inhibit the secretion of proinflammatory cytokines directly or indirectly while promoting the secretion of anti-inflammatory cytokines. At the prolonged stage, the sustained activated HPA demonstrates cortisol-resistance. At the same time, the inflammation related transcription pathway, such as nuclear-factor kappa-B (NF-κB) signaling, may be inhibited. Additionally, the inflammatory cytokines mediate a negative feedback regulation on themselves. Collectively, these regulations may increase the proinflammatory cytokines while decreasing the anti-inflammatory cytokines. This may further activate NF-κB and increase the proinflammation cytokines, which in turn reduce the inflammatory responses, contributing to various diseases. PMID:24995360

  9. Child Abuse and Neglect in Cambodian Refugee Families: Characteristics and Implications for Practice

    ERIC Educational Resources Information Center

    Chang, Janet; Rhee, Siyon; Berthold, S. Megan

    2008-01-01

    This study examines the characteristics and patterns of child maltreatment among Cambodian refugee families in Los Angeles and assesses the implications for child welfare practice with Cambodian refugee families. Data were extracted from 243 active Cambodian case files maintained by the Los Angeles County Department of Children and Family Services…

  10. Synergy between Common γ Chain Family Cytokines and IL-18 Potentiates Innate and Adaptive Pathways of NK Cell Activation

    PubMed Central

    Nielsen, Carolyn M.; Wolf, Asia-Sophia; Goodier, Martin R.; Riley, Eleanor M.

    2016-01-01

    Studies to develop cell-based therapies for cancer and other diseases have consistently shown that purified human natural killer (NK) cells secrete cytokines and kill target cells after in vitro culture with high concentrations of cytokines. However, these assays poorly reflect the conditions that are likely to prevail in vivo in the early stages of an infection and have been carried out in a wide variety of experimental systems, which has led to contradictions within the literature. We have conducted a detailed kinetic and dose–response analysis of human NK cell responses to low concentrations of IL-12, IL-15, IL-18, IL-21, and IFN-α, alone and in combination, and their potential to synergize with IL-2. We find that very low concentrations of both innate and adaptive common γ chain cytokines synergize with equally low concentrations of IL-18 to drive rapid and potent NK cell CD25 and IFN-γ expression; IL-18 and IL-2 reciprocally sustain CD25 and IL-18Rα expression in a positive feedback loop; and IL-18 synergizes with FcγRIII (CD16) signaling to augment antibody-dependent cellular cytotoxicity. These data indicate that NK cells can be rapidly activated by very low doses of innate cytokines and that the common γ chain cytokines have overlapping but distinct functions in combination with IL-18. Importantly, synergy between multiple signaling pathways leading to rapid NK cell activation at very low cytokine concentrations has been overlooked in prior studies focusing on single cytokines or simple combinations. Moreover, although the precise common γ chain cytokines available during primary and secondary infections may differ, their synergy with both IL-18 and antigen–antibody immune complexes underscores their contribution to NK cell activation during innate and adaptive responses. IL-18 signaling potentiates NK cell effector function during innate and adaptive immune responses by synergy with IL-2, IL-15, and IL-21 and immune complexes. PMID:27047490

  11. Evidence of associations between cytokine genes and subjective reports of sleep disturbance in oncology patients and their family caregivers.

    PubMed

    Miaskowski, Christine; Cooper, Bruce A; Dhruva, Anand; Dunn, Laura B; Langford, Dale J; Cataldo, Janine K; Baggott, Christina R; Merriman, John D; Dodd, Marylin; Lee, Kathryn; West, Claudia; Paul, Steven M; Aouizerat, Bradley E

    2012-01-01

    The purposes of this study were to identify distinct latent classes of individuals based on subjective reports of sleep disturbance; to examine differences in demographic, clinical, and symptom characteristics between the latent classes; and to evaluate for variations in pro- and anti-inflammatory cytokine genes between the latent classes. Among 167 oncology outpatients with breast, prostate, lung, or brain cancer and 85 of their FCs, growth mixture modeling (GMM) was used to identify latent classes of individuals based on General Sleep Disturbance Scale (GSDS) obtained prior to, during, and for four months following completion of radiation therapy. Single nucleotide polymorphisms (SNPs) and haplotypes in candidate cytokine genes were interrogated for differences between the two latent classes. Multiple logistic regression was used to assess the effect of phenotypic and genotypic characteristics on GSDS group membership. Two latent classes were identified: lower sleep disturbance (88.5%) and higher sleep disturbance (11.5%). Participants who were younger and had a lower Karnofsky Performance status score were more likely to be in the higher sleep disturbance class. Variation in two cytokine genes (i.e., IL6, NFKB) predicted latent class membership. Evidence was found for latent classes with distinct sleep disturbance trajectories. Unique genetic markers in cytokine genes may partially explain the interindividual heterogeneity characterizing these trajectories. PMID:22844404

  12. Distribution of interleukin-10 family cytokines in serum and synovial fluid of patients with inflammatory arthritis reveals different contribution to systemic and joint inflammation

    PubMed Central

    Scrivo, R; Conigliaro, P; Riccieri, V; Di Franco, M; Alessandri, C; Spadaro, A; Perricone, R; Valesini, G

    2015-01-01

    Evidence exists that interleukin (IL)-10 family cytokines may be involved in the pathogenesis of rheumatoid arthritis (RA). We sought to determine whether or not these cytokines are involved in psoriatic arthritis (PsA). We conducted a prospective study on patients with PsA, RA and osteoarthritis (OA); healthy controls (HC) were also included. We analysed IL-20, IL-24 and IL-19 serum and synovial fluid (SF) levels and change of serum levels following treatment with biological agents. IL-20 serum levels were increased in PsA and RA compared with OA patients and HC and with matched SF levels. IL-24 serum levels in PsA, RA and OA patients were higher than those in HC and also with respect to matched SF in PsA. IL-19 serum levels were higher in HC and OA compared with PsA and RA patients; IL-19 SF levels were higher in PsA and RA compared with OA patients, and in PsA compared with RA patients. PsA and RA patients showed a reduction of IL-19 serum levels after biological treatment. Therefore, IL-19 seems to be involved mainly in the joint inflammation, whereas IL-20 and IL-24 appear to participate mainly in the systemic responses. These findings may further the comprehension of the contribution of these cytokines to the inflammatory response involved in chronic arthritis, as well as to the development of novel therapeutic strategies. PMID:25178435

  13. How Families Experience the Phenomenon of Adolescent Pregnancy and Parenting: Implications for Family Therapists and Educators

    ERIC Educational Resources Information Center

    Boyer, Glenda J.

    2012-01-01

    The purpose of this qualitative study was to describe how family members experience the phenomenon of adolescent pregnancy and parenting in the family unit, over time, and to examine the meanings family members attach to the experience. The participants were six nuclear families (20 individuals) of six adolescent mothers who had previously…

  14. Observations of a Working Class Family: Implications for Self-Regulated Learning Development

    ERIC Educational Resources Information Center

    Vassallo, Stephen

    2012-01-01

    Guardians have been implicated in the development of children's academic self-regulation. In this case study, which involved naturalistic observations and interviews, the everyday practices of a working class family were considered in the context of self-regulated learning development. The family's practices, beliefs, dispositions and home…

  15. Breast Cancer-Related Lymphedema: Implications for Family Leisure Participation

    ERIC Educational Resources Information Center

    Radina, M. Elise

    2009-01-01

    An estimated 20% of breast cancer survivors face the chronic condition of breast cancer-related lymphedema. This study explored the ways in which women with this condition experienced changes in their participation in family leisure as one indicator of family functioning. Participants (N = 27) were interviewed regarding lifestyles before and after…

  16. Family Disengagement of Youth Offenders: Implications for Counselors

    ERIC Educational Resources Information Center

    Coll, Kenneth M.; Juhnke, Gerald A.; Thobro, Patti; Haas, Robin; Smith Robinson, Megan

    2008-01-01

    This study investigated the differences among youth offenders for family engagement (as measured by the Family Adaptability and Cohesion Evaluation Scales--III) and conduct-disordered behaviors (as measured by "Diagnostic and Statistical Manual of Mental Disorders" [4th ed., text revision] criteria) by means of the Youth Comprehensive Risk…

  17. Parental Incarceration and Child Wellbeing: Implications for Urban Families

    PubMed Central

    Geller, Amanda; Garfinkel, Irwin; Cooper, Carey E.; Mincy, Ronald B.

    2010-01-01

    Objective Using a population-based, longitudinal family survey (N=4,898), we identify economic, residential, and developmental risks particular to the children of incarcerated parents. Methods We use parental reports of incarceration history, demographic background, and a rich set of child and family outcomes, in a series of multivariate regression models. Results Children of incarcerated parents face more economic and residential instability than their counterparts. Sons of incarcerated fathers display more behavior problems, though other developmental differences are insignificant. Conclusions We find that incarceration identifies families facing severe hardship, which cannot be explained by other observed family characteristics. Given the prevalence of incarceration, our findings suggest that a large population of children suffers unmet material needs, residential instability, and behavior problems. These risks may be best addressed by using the point of incarceration as an opportunity for intervention and the administration of age-appropriate social services. PMID:20228880

  18. Cytokines, atherogenesis, and hypercatabolism in chronic kidney disease: a dreadful triad.

    PubMed

    Carrero, Juan Jesus; Park, Sun-Hee; Axelsson, Jonas; Lindholm, Bengt; Stenvinkel, Peter

    2009-01-01

    The term cytokine clusters denotes a copious family of molecules and correspondent receptors implicated in numerous processes mediating health and disease. In the context of chronic kidney disease (CKD), generation and metabolism of most of these cytokines are disturbed. Available evidence suggests that cytokine imbalances contribute to the progression of common CKD complications, such as atherosclerosis, mineral-bone disease, and protein-energy wasting via pleiotropic effects. The belief that cytokine CKD research is solely represented by interleukins (IL) and tumor-necrosis factors (TNF) (mainly IL-6 and TNF-alpha) is a common misconception among nephrologists. We here explore recent findings concerning the pathophysiological role of various cytokines in uremic complications, and discuss how cytokines could be used as novel potential therapeutic targets in CKD. At the same time, we provide a brief overview of current discoveries in the main transforming growth factors and chemokines. PMID:19708986

  19. Successful implementation of Thai Family Matters: strategies and implications.

    PubMed

    Rosati, Michael J; Cupp, Pamela K; Chookhare, Warunee; Miller, Brenda A; Byrnes, Hilary F; Fongkaew, Warunee; Vanderhoff, Jude; Chamratrithirong, Aphichat; Rhucharoenpornpanich, Orratai; Atwood, Katharine A

    2012-05-01

    This article discusses the successful process used to assess the feasibility of implementing the Family Matters program in Bangkok, Thailand. This is important work since adopting and adapting evidence-based programs is a strategy currently endorsed by leading prevention funding sources, particularly in the United States. The original Family Matters consists of four booklets designed to increase parental communication with their adolescent children in order to delay onset of or decrease alcohol, tobacco, and other drug use. As part of the program, health educators contact parents by telephone to support them in the adoption of the program. Each booklet addresses a key aspect of strengthening families and protecting young people from unhealthy behaviors related to alcohol and other drug use. Adaptation of the program for Bangkok focused on cultural relevance and the addition of a unit targeting adolescent dating and sexual behavior. A total of 170 families entered the program, with the majority (85.3%) completing all five booklets. On average, the program took 16 weeks to complete, with families reporting high satisfaction with the program. This article provides greater detail about the implementation process and what was learned from this feasibility trial. PMID:22090152

  20. T cell factor-1 negatively regulates expression of IL-17 family of cytokines and protects mice from experimental autoimmune encephalomyelitis.

    PubMed

    Yu, Qing; Sharma, Archna; Ghosh, Amalendu; Sen, Jyoti Misra

    2011-04-01

    Activated CD4 T cells are associated with protective immunity and autoimmunity. The manner in which the inflammatory potential of T cells and resultant autoimmunity is restrained is poorly understood. In this article, we demonstrate that T cell factor-1 (TCF1) negatively regulates the expression of IL-17 and related cytokines in activated CD4 T cells. We show that TCF1 does not affect cytokine signals and expression of transcription factors that have been shown to regulate Th17 differentiation. Instead, TCF1 regulates IL-17 expression, in part, by binding to the regulatory regions of the Il17 gene. Moreover, TCF1-deficient Th17 CD4 T cells express higher levels of IL-7Rα, which potentially promotes their survival and expansion in vivo. Accordingly, TCF1-deficient mice are hyperresponsive to experimental autoimmune encephalomyelitis. Thus, TCF1, a constitutively expressed T cell-specific transcription factor, is a critical negative regulator of the inflammatory potential of TCR-activated T cells and autoimmunity. PMID:21339363

  1. Custodial evaluations of Native American families: implications for forensic psychiatrists.

    PubMed

    Wills, Cheryl D; Norris, Donna M

    2010-01-01

    Native American children in the United States have been adopted by non-Indian families at rates that threaten the preservation of their Indian history, traditions, and culture. The Indian Child Welfare Act (ICWA), which established restrictive parameters that govern the placement of Native American children into foster care and adoptive homes, was ratified in an effort to keep American Indian families intact. This article addresses matters of importance to psychiatrists who conduct custody evaluations of Native American children and families. A summary of events that preceded enactment of the ICWA is given, along with guidelines for forensic psychiatrists who conduct foster and adoptive care evaluations of Native American children. We use clinical vignettes to illustrate how the ICWA informs the custody evaluation process as well as approaches to cultural concerns, including biases that forensic evaluators may encounter during these evaluations. PMID:21156915

  2. Family Background of Beginning Education Students: Implications for Teacher Educators

    ERIC Educational Resources Information Center

    Stewart, Roger A.; Coll, Kenneth M.; Osguthorpe, Richard

    2013-01-01

    Teacher education has not historically focused on the social and emotional development of teachers even though there is evidence that such variables influence student success (Jennings & Greenberg, 2009). We believe such a focus is important and we explored variables in teacher education students' families of origin that underpin social…

  3. Hispanic Families and Their Culture: Implications for FCS Educators

    ERIC Educational Resources Information Center

    Allison, Barbara N.; Bencomo, Angelina

    2015-01-01

    Hispanic children constitute the largest population of racial/ethnic minority students in the nation's public schools. By the year 2023, the Hispanic enrollment is expected to increase to 30% of the total school population (pre-K through 12) in the United States. Because cultural background affects student learning, family and consumer sciences…

  4. The California Family Choice Initiatives: Implications for Urban Education.

    ERIC Educational Resources Information Center

    Koshiyama, Albert Noboru

    Three constitutional amendments proposed for the June and November, 1980, ballots in California are discussed in this paper. The amendments, all of which would channel public funds to private schools, are: (1) the "Family Choice Initiative," also known as the Sugarman-Coons proposal, which would permit parents to use public funds to send their…

  5. Farm Families in Transition: Implications for Rural Communities.

    ERIC Educational Resources Information Center

    Leistritz, F. Larry; And Others

    1989-01-01

    A study of 169 North Dakota families (from a sample of 260) who quit farming for economic reasons describes (1) the demographic characteristics of former operators and the structural and financial character of their farms, (2) the financial circumstances of their departure from farming, and (3) their current employment situation and perceived…

  6. Experiences of Families Transmitting Values in a Rapidly Changing Society: Implications for Family Therapists.

    PubMed

    Akyil, Yudum; Prouty, Anne; Blanchard, Amy; Lyness, Kevin

    2016-06-01

    Intergenerational value transmission affects parent-child relationships and necessitates constant negotiation in families. Families with adolescents from rapidly changing societies face unique challenges in balancing the traditional collectivistic family values that promote harmony with emerging values that promote autonomy. Using modern Turkey as an example of such a culture, the authors examine the transmission process in families that hold more traditional and collectivistic values than their adolescent children. Special consideration is given to generational and cultural differences in the autonomy and relatedness dimensions. PMID:26133038

  7. Multi-Family Groups for Multi-Stressed Families: Initial Outcomes and Future Implications

    ERIC Educational Resources Information Center

    Jackson, Jerrold M.

    2015-01-01

    Purpose: To examine the influence of caregiver stress on attendance among urban families involved in a multiple family group (MFG) intervention, as well as pre/post changes in childhood behavioral difficulties, caregiver stress, caregiver depressive symptoms, caregiver coping by substance use, and caregiver motivation to change. Methods:…

  8. Multiple family member visits to family physicians. Terminology, classification, and implications.

    PubMed

    Knishkowy, B; Furst, A; Fassberg, Y; Anor, E; Matthews, S; Paz, Y

    1991-01-01

    A study was designed to investigate "the family as the unit of care" in family medicine consultations from the patient's end of the physician-patient axis, unlike most previous related studies, which have concentrated on it from the physician's perspective. During 2 separate weeks in November 1987 and February 1988, nine Israeli family physicians collected demographic and family-related data concerning the spontaneous visiting patterns generated by 1156 persons (899 patients and 257 nonpatients) who attended 796 separate consultations at their clinics during this time. More than one patient attended 12% of the consultations, and more than one person, patient or nonpatient, was present at 36%. At 31% of the consultations children alone or children and adults were recorded as patients (child consultations), and at 69% only adult patients were present (adult consultations). Adults were recorded as second or third patients at 19% of the child consultations but at only 5% of the adult consultations. The child consultations alone yielded 86% of all the nonpatients documented. Basic terminology and methodology for investigating such multiple family member visits to family physicians is discussed as well as the composition of the different family units encountered and their possible significance. PMID:1985136

  9. The perspectives of older Greek-Australians toward changes in the nature of family support: implications for family care policies.

    PubMed

    Walker, Ruth; Newman, Lareen; Tsianikas, Michael; Panagiotopoulos, Georgia; Hurley, Catherine

    2013-01-01

    Internationally, public policies encourage "aging in place," and the majority of older Australians requiring care in the community receive informal care, supplemented by publicly subsidized formal services. The effect of contemporary social changes on informal care in aging migrant communities is poorly understood. This articles explores the perceptions of older Greek-Australians toward changes in the nature of family support. Bicultural and bilingual researchers carried out in-depth interviews (n = 27) and five focus groups (n = 63 total participants) with older Greek-Australians in modern Greek. While "cultures of care" remain among Greek-Australian families, the means for a family to assist have shifted, and these compromises are met with considerable powerlessness among older Greek-Australians. Implications for policy include the need to better involve older migrants and their families in decisions about their care needs, potentially involving consumer-directed care models. Service providers may also need to adopt the use of new technologies to communicate with increasingly time-pressured family members. PMID:24059927

  10. Sexually Explicit Material on the Internet: Implications for Family Life Educators.

    ERIC Educational Resources Information Center

    Sanders, Gregory; Deal, James; Myers-Bowman, Karen

    1999-01-01

    Describes a content analysis of sexually explicit Internet material at three times (1995, 1996, and 1998), which found that material became more explicit between 1995 and 1996 but declined somewhat between 1996 and 1998 and that these sites had no barriers to access. Addresses implications for family-life educators. (SK)

  11. Home Economists Working with Low-Income Families and Implications for College Food and Nutrition Curriculum.

    ERIC Educational Resources Information Center

    Kopel, Bernice Helene

    To identify implications for college food and nutrition curriculum, multiple-choice questionnaires were developed to provide general characteristics of home economists and the concerns they had in their work with low-income families. Job concerns were ranked and analyzed according to the degree of concern expressed by the 129 respondents (70.8…

  12. Implications of Shift Work for Parent-Adolescent Relationships in Dual-Earner Families

    ERIC Educational Resources Information Center

    Davis, Kelly D.; Crouter, Ann C.; McHale, Susan M.

    2006-01-01

    This investigation examined the implications of shift work for parent-adolescent relationship quality--intimacy, conflict, parental knowledge, and involvement--in a sample of 376 dual-earner families. The findings suggested that mothers' relationships with their adolescents were not negatively impacted by their working nonstandard schedules but…

  13. Occupational Training Families. Their Implications for FE. An FEU Occasional Paper.

    ERIC Educational Resources Information Center

    Johnson, Ron

    This occasional paper appraises the implications of occupational training families (OTF) for further education (FE) in Great Britain. In the early sections, the document sketches the background of OTFs and appraises the advantages and disadvantages of the concept. In so doing, four possible approaches to helping young people acquire flexibility,…

  14. Family Violence and Migrant Women: Implications for Practice. Migrant Clinicians Network Clinical Supplement.

    ERIC Educational Resources Information Center

    Rodriguez, Rachel; And Others

    1993-01-01

    This newsletter supplement is devoted to the theme of domestic violence affecting migrant women. It contains four articles describing programs providing violence prevention education to migrant women and children. "Family Violence and Migrant Women: Implications for Practice" (Rachel Rodriguez) discusses the social isolation of migrant women;…

  15. The implications of the Human Genome Project for family practice.

    PubMed

    Whittaker, L A

    1992-09-01

    The Human Genome Project is an international effort to map and sequence the human genome. The information it will generate has been referred to by some as the "new anatomy," and may play an important role in the future of medicine. However, as with any new technological advancement, the outcome of the Human Genome Project and the subsequent availability of new technology will raise a myriad of ethical, legal, and social concerns. The fear is that this technology will be applied in the clinical setting before the appropriate infrastructure is in place to deal with the issues it will raise. The family physician, far from being merely an interested observer in this process, will be responsible for the delivery of much of this technology as it becomes available. As an intermediary between the technology and the individual patient, the physician has a unique obligation to join in the thoughtful consideration and debate of these issues. PMID:1517727

  16. The Extended Granin Family: Structure, Function, and Biomedical Implications

    PubMed Central

    Bartolomucci, Alessandro; Possenti, Roberta; Mahata, Sushil K.; Fischer-Colbrie, Reiner; Loh, Y. Peng

    2011-01-01

    The chromogranins (chromogranin A and chromogranin B), secretogranins (secretogranin II and secretogranin III), and additional related proteins (7B2, NESP55, proSAAS, and VGF) that together comprise the granin family subserve essential roles in the regulated secretory pathway that is responsible for controlled delivery of peptides, hormones, neurotransmitters, and growth factors. Here we review the structure and function of granins and granin-derived peptides and expansive new genetic evidence, including recent single-nucleotide polymorphism mapping, genomic sequence comparisons, and analysis of transgenic and knockout mice, which together support an important and evolutionarily conserved role for these proteins in large dense-core vesicle biogenesis and regulated secretion. Recent data further indicate that their processed peptides function prominently in metabolic and glucose homeostasis, emotional behavior, pain pathways, and blood pressure modulation, suggesting future utility of granins and granin-derived peptides as novel disease biomarkers. PMID:21862681

  17. Cytokines and autoimmunity.

    PubMed Central

    Cavallo, M G; Pozzilli, P; Thorpe, R

    1994-01-01

    Although the immunopathology of most autoimmune diseases has been well defined, the mechanisms responsible for the breakdown of self-tolerance and which lead to the development of systemic and organ-specific autoaggression are still unclear. Evidence has accumulated which supports a role for a disregulated production of cytokines by leucocytes and possibly other cells in the pathogenesis of some autoimmune diseases. However, due to the complexity and heterogeneity of cytokine effects in the regulation of the immune response, it is difficult to determine whether abnormalities in the patterns of cytokine production are primary or secondary to the pathological process. Confusion is also caused by the fact that the biological activities of cytokines are multiple and often overlapping, and consequently it is difficult to focus on a unique effect of any one cytokine. Characterization of the potential and actual involvement of cytokines is important not only for a better understanding of the pathogenesis of autoimmune conditions, but particularly because of the implications for the development of immunotherapeutic strategies for the prevention and treatment of the diseases. PMID:8149655

  18. Genetic testing and familial implications in breast-ovarian cancer families.

    PubMed

    Oosterwijk, Jan C; de Vries, Jakob; Mourits, Marian J; de Bock, Geertruida H

    2014-08-01

    DNA-testing for BRCA1 and BRCA2 has become incorporated in the diagnostic procedure of patients with breast and/or ovarian cancer. Since 1994 an immense amount of information has been gathered on mutation spectra, mutation risk assessment, cancer risks for mutation carriers, factors that modify these risks, unclassified DNA variants, surveillance strategies and preventive options. For the patient and family the main determinator still is whether a mutation is found or not. When a pathogenic mutation is detected in an index case, relatives can opt for pre-symptomatic DNA testing. However in the vast majority no mutation, or only unclear mutations are detectable yet. This means that a hereditary cause cannot be excluded, but pre-symptomatic DNA-testing is still unavailable for relatives. Surveillance for both index cases and relatives is based of the family history of cancer. Next generation genetic testing may help to elucidate genetic causes in these families. PMID:24894332

  19. Protein Interaction Screening for the Ankyrin Repeats and Suppressor of Cytokine Signaling (SOCS) Box (ASB) Family Identify Asb11 as a Novel Endoplasmic Reticulum Resident Ubiquitin Ligase*

    PubMed Central

    Andresen, Christina Aaen; Smedegaard, Stine; Sylvestersen, Kathrine Beck; Svensson, Charlotte; Iglesias-Gato, Diego; Cazzamali, Giuseppe; Nielsen, Tine Kragh; Nielsen, Michael Lund; Flores-Morales, Amilcar

    2014-01-01

    The ankyrin and SOCS (suppressor of cytokine signaling) box (ASB) family of proteins function as the substrate recognition subunit in a subset of Elongin-Cullin-SOCS (ECS) E3 ubiquitin ligases. Despite counting 18 members in humans, the identity of the physiological targets of the Asb proteins remains largely unexplored. To increase our understanding of the function of ASB proteins, we conducted a family-wide SILAC (stable isotope labeling by amino acids in cell culture)-based protein/protein interaction analysis. This investigation led to the identification of novel as well as known ASB-associated proteins like Cullin 5 and Elongins B/C. We observed that several proteins can be bound by more than one Asb protein. The additional exploration of this phenomenon demonstrated that ASB-Cullin 5 complexes can oligomerize and provides evidence that Cullin 5 forms heterodimeric complexes with the Cullin 4a-DDB1 complex. We also demonstrated that ASB11 is a novel endoplasmic reticulum-associated ubiquitin ligase with the ability to interact and promote the ubiquitination of Ribophorin 1, an integral protein of the oligosaccharyltransferase (OST) glycosylation complex. Moreover, expression of ASB11 can increase Ribophorin 1 protein turnover in vivo. In summary, we provide a comprehensive protein/protein interaction data resource that can aid the biological and functional characterization of ASB ubiquitin ligases. PMID:24337577

  20. Toll-like receptor and pro-inflammatory cytokine expression during prolonged hyperinsulinaemia in horses: implications for laminitis.

    PubMed

    de Laat, M A; Clement, C K; McGowan, C M; Sillence, M N; Pollitt, C C; Lacombe, V A

    2014-01-15

    Equine laminitis, a disease of the lamellar structure of the horse's hoof, can be incited by numerous factors that include inflammatory and metabolic aetiologies. However, the role of inflammation in hyperinsulinaemic laminitis has not been adequately defined. Toll-like receptor (TLR) activation results in up-regulation of inflammatory pathways and the release of pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α), and may be a pathogenic factor in laminitis. The aim of this study was to determine whether TLR4 expression and subsequent pro-inflammatory cytokine production is increased in lamellae and skeletal muscle during equine hyperinsulinaemia. Standardbred horses were treated with either a prolonged, euglycaemic hyperinsulinaemic clamp (p-EHC) or a prolonged, glucose infusion (p-GI), which induced marked and moderate hyperinsulinaemia, respectively. Age-matched control horses were treated simultaneously with a balanced electrolyte solution. Treated horses developed clinical (p-EHC) or subclinical (p-GI) laminitis, whereas controls did not. Skeletal muscle and lamellar protein extracts were analysed by Western blotting for TLR4, IL-6, TNF-α and suppressor of cytokine signalling 3 (SOCS3) expression. Lamellar protein expression of TLR4 and TNF-α, but not IL-6, was increased by the p-EHC, compared to control horses. A significant positive correlation was found between lamellar TLR4 and SOCS3. Skeletal muscle protein expression of TLR4 signalling parameters did not differ between control and p-EHC-treated horses. Similarly, the p-GI did not result in up-regulation of lamellar protein expression of any parameter. The results suggest that insulin-sensitive tissues may not accurately reflect lamellar pathology during hyperinsulinaemia. While TLR4 is present in the lamellae, its activation appears unlikely to contribute significantly to the developmental pathogenesis of hyperinsulinaemic laminitis. However

  1. The Consequences of Witnessing Family Violence on Children and Implications for Family Counselors

    ERIC Educational Resources Information Center

    Adams, Christopher M.

    2006-01-01

    Although a large number of children are directly abused, an even larger number may indirectly experience the effects of abuse as witnesses of family violence. However, the effects on children who witness such violence have long been unaddressed, although a growing body of research indicates that these children are affected in various domains,…

  2. Schools, Families, and Communities Affecting the Dropout Rate: Implications and Strategies for Family Counselors

    ERIC Educational Resources Information Center

    Ziomek-Daigle, Jolie

    2010-01-01

    Serious social and economic consequences affect the local and national levels when students drop out of school. Research has shown that collaboration among schools, families, and communities in the academic progression of students can decrease their drop out probability. The author presents findings related to a qualitative study conducted in…

  3. Family Review. Politics and Education: Implications for America's Children and Families.

    ERIC Educational Resources Information Center

    Lindjord, Denise

    1996-01-01

    Examines the pros and cons of several family-oriented initiatives offered by President Clinton and Senator Bob Dole during their 1996 campaigns. These include tuition tax credits, volunteer tutoring programs, across-the-board tax breaks, and school voucher programs. (HTH)

  4. Baker's yeast β-glucan supplementation increases monocytes and cytokines post-exercise: implications for infection risk?

    PubMed

    Carpenter, K C; Breslin, W L; Davidson, T; Adams, A; McFarlin, B K

    2013-02-14

    Strenuous aerobic exercise is known to weaken the immune system, and while many nutritional supplements have been proposed to boost post-exercise immunity, few are known to be effective. The purpose of the present study was to evaluate whether 10 d of supplementation with a defined source of baker's yeast β-glucan (BG, Wellmune WGP®) could minimise post-exercise immunosuppression. Recreationally active men and women (n 60) completed two 10 d trial conditions using a cross-over design with a 7 d washout period: placebo (rice flour) and baker's yeast BG (250 mg/d of β-1,3/1,6-glucans derived from Saccharomyces cerevisiae) before a bout of cycling (49 ± 6 min) in a hot (38 ± 2°C), humid (45 ± 2 % relative humidity) environment. Blood was collected at baseline (before supplement), pre- (PRE), post- (POST) and 2 h (2H) post-exercise. Total and subset monocyte concentration was measured by four-colour flow cytometry. Plasma cytokine levels and lipopolysaccharide (LPS)-stimulated cytokine production were measured using separate multiplex assays. Total (CD14⁺) and pro-inflammatory monocyte concentrations (CD14⁺/CD16⁺) were significantly greater at POST and 2H (P<0·05) with BG supplementation. BG supplementation boosted LPS-stimulated production of IL-2, IL-4, IL-5 and interferon-γ (IFN-γ) at PRE and POST (P<0·05). Plasma IL-4, IL-5 and IFN-γ concentrations were greater at 2H following BG supplementation. It appears that 10 d of supplementation with BG increased the potential of blood leucocytes for the production of IL-2, IL-4, IL-5 and IFN-γ. The key findings of the present study demonstrate that BG may have potential to alter immunity following a strenuous exercise session. PMID:22575076

  5. Ethnic identity development of internationally adopted children and adolescents: implications for family therapists.

    PubMed

    Friedlander, M L

    1999-01-01

    The life story of the internationally adopted child tends to be an emotional one. How the story is told and retold in the family can have lasting consequences for the child's adjustment and well-being. In telling the story, parents are faced with a unique challenge: To what extent is it desirable to encourage their children, who already struggle with identity issues related to adoption, to identify with their cultures of origin? Therapists working on these issues with multiethnic adoptive families can find little guidance in the family systems literature. To fill this gap, the present article reviews the literature on racial/ethnic identity development and the available research on ethnic identification, self-esteem, and the psychological adjustment of cross-ethnically adopted children and adolescents. Implications for practice include developmental considerations, identifying children and families at risk, and recommendations for those in need of intervention. PMID:9990519

  6. N-Palmitoylethanolamine Prevents the Run-down of Amplitudes in Cortical Spreading Depression Possibly Implicating Proinflammatory Cytokine Release.

    PubMed

    Richter, Frank; Koulen, Peter; Kaja, Simon

    2016-01-01

    Cortical spreading depression (CSD), a wave of neuronal depolarization in the cerebral cortex following traumatic brain injury or cerebral ischemia, significantly aggravates brain damage. Here, we tested whether N-palmitoylethanolamine (PEA), a substance that effectively reduces lesion volumes and neurological deficits after ischemic stroke, influences CSD. CSD was elicited chemically in adult rats and occurrence, amplitude, duration and propagation velocity of CSD was determined prior to and for 6 hours after intraperitoneal injection of PEA. The chosen systemic administration of PEA stabilized the amplitude of CSD for at least four hours and prevented the run-down of amplitudes that is typically observed and was also seen in untreated controls. The propagation velocity of the CSD waves was unaltered indicating stable neuronal excitability. The stabilization of CSD amplitudes by PEA indicates that inhibition or prevention of CSD does not underlie PEA's profound neuroprotective effect. Rather, PEA likely inhibits proinflammatory cytokine release thereby preventing the run-down of CSD amplitudes. This contribution of PEA to the maintenance of neuronal excitability in healthy tissue during CSD potentially adds to neuroprotection outside a damaged area, while other mechanisms control PEA-mediated neuroprotection in damaged tissue resulting from traumatic brain injury or cerebral ischemia. PMID:27004851

  7. N-Palmitoylethanolamine Prevents the Run-down of Amplitudes in Cortical Spreading Depression Possibly Implicating Proinflammatory Cytokine Release

    PubMed Central

    Richter, Frank; Koulen, Peter; Kaja, Simon

    2016-01-01

    Cortical spreading depression (CSD), a wave of neuronal depolarization in the cerebral cortex following traumatic brain injury or cerebral ischemia, significantly aggravates brain damage. Here, we tested whether N-palmitoylethanolamine (PEA), a substance that effectively reduces lesion volumes and neurological deficits after ischemic stroke, influences CSD. CSD was elicited chemically in adult rats and occurrence, amplitude, duration and propagation velocity of CSD was determined prior to and for 6 hours after intraperitoneal injection of PEA. The chosen systemic administration of PEA stabilized the amplitude of CSD for at least four hours and prevented the run-down of amplitudes that is typically observed and was also seen in untreated controls. The propagation velocity of the CSD waves was unaltered indicating stable neuronal excitability. The stabilization of CSD amplitudes by PEA indicates that inhibition or prevention of CSD does not underlie PEA’s profound neuroprotective effect. Rather, PEA likely inhibits proinflammatory cytokine release thereby preventing the run-down of CSD amplitudes. This contribution of PEA to the maintenance of neuronal excitability in healthy tissue during CSD potentially adds to neuroprotection outside a damaged area, while other mechanisms control PEA-mediated neuroprotection in damaged tissue resulting from traumatic brain injury or cerebral ischemia. PMID:27004851

  8. In vivo imaging visualizes discoid platelet aggregations without endothelium disruption and implicates contribution of inflammatory cytokine and integrin signaling

    PubMed Central

    Manabe, Ichiro; Nagasaki, Mika; Kakuta, Shigeru; Iwakura, Yoichiro; Takayama, Naoya; Ooehara, Jun; Otsu, Makoto; Kamiya, Akihide; Petrich, Brian G.; Urano, Tetsumei; Kadono, Takafumi; Sato, Shinichi; Aiba, Atsu; Yamashita, Hiroshi; Sugiura, Seiryo; Kadowaki, Takashi; Nakauchi, Hiromitsu; Nagai, Ryozo

    2012-01-01

    The mechanism by which thrombotic vessel occlusion occurs independently of plaque development or endothelial cell (EC) disruption remains unclear, largely because of an inability to visualize the formation of thrombus, especially at the single-platelet level in real time. Here we demonstrate that rapidly developing thrombi composed of discoid platelets can be induced in the mesenteric capillaries, arterioles, and large-sized arteries of living mice, enabling characterization of the kinetics of thrombosis initiation and the multicellular interrelationships during thrombus development. Platelet aggregation without EC disruption was triggered by reactive oxygen species (ROS) photochemically induced by moderate power laser irradiation. The inflammatory cytokines TNF-α and IL-1 could be key components of the EC response, acting through regulation of VWF mobilization to the cell surface. Thrombus formation was then initiated by the binding of platelet GPIbα to endothelial VWF in our model, and this effect was inhibited by the ROS scavenger N-acetylcysteine. Actin linker talin-dependent activation of alphaIIb-beta3 integrin or Rac1 in platelets was required for late-phase thrombus stability. Our novel imaging technology illustrates the molecular mechanism underlying inflammation-based thrombus formation by discoid platelets on undisrupted ECs and suggests control of ROS could be a useful therapeutic target for the prevention of thrombotic diseases. PMID:22096246

  9. Cytokine signaling for proliferation, survival, and death in hematopoietic cells.

    PubMed

    Miyajima, A; Ito, Y; Kinoshita, T

    1999-04-01

    The survival, proliferation, and differentiation of hematopoietic cells are regulated by cytokines. In the absence of cytokines, hematopoietic cells not only stop proliferation, but undergo apoptosis. This strict dependency of hematopoietic cells on cytokines is an important mechanism that maintains the homeostasis of blood cells. Cytokines induce various intracellular signaling pathways by activating the receptor-associated Janus kinases (Jaks), and distinct signals are responsible for cell cycle progression and cell survival. Induction of signals for cell cycle progression without suppressing apoptosis results in apoptotic cell death, indicating the essential role of anti-apoptotic signaling for cell growth. In hematopoietic cells, Ras, a cellular protooncogen product, and phosphatidylinositol 3 kinase are involved in the suppression of apoptosis. Cytokine depletion not only turns off anti-apoptotic signaling, but also actively induces cell death by activating caspases, a distinct family of cysteine proteases. Alterations in the mechanisms of cytokine signaling for cell cycle progression and anti-apoptotic function are implicated in hematological disorders. PMID:10222650

  10. Histoplasma capsulatum-Induced Cytokine Secretion in Lung Epithelial Cells Is Dependent on Host Integrins, Src-Family Kinase Activation, and Membrane Raft Recruitment.

    PubMed

    Maza, Paloma K; Suzuki, Erika

    2016-01-01

    Histoplasma capsulatum var. capsulatum is a dimorphic fungus that causes histoplasmosis, a human systemic mycosis with worldwide distribution. In the present work, we demonstrate that H. capsulatum yeasts are able to induce cytokine secretion by the human lung epithelial cell line A549 in integrin- and Src-family kinase (SFK)-dependent manners. This conclusion is supported by small interfering RNA (siRNA) directed to α3 and α5 integrins, and PP2, an inhibitor of SFK activation. siRNA and PP2 reduced IL-6 and IL-8 secretion in H. capsulatum-infected A549 cell cultures. In addition, α3 and α5 integrins from A549 cells were capable of associating with H. capsulatum yeasts, and this fungus promotes recruitment of these integrins and SFKs to A549 cell membrane rafts. Corroborating this finding, membrane raft disruption with the cholesterol-chelator methyl-β-cyclodextrin reduced the levels of integrins and SFKs in these cell membrane domains. Finally, pretreatment of A549 cells with the cholesterol-binding compound, and also a membrane raft disruptor, filipin, significantly reduced IL-6 and IL-8 levels in A549-H.capsulatum cultures. Taken together, these results indicate that H. capsulatum yeasts induce secretion of IL-6 and IL-8 in human lung epithelial cells by interacting with α3 and α5 integrins, recruiting these integrins to membrane rafts, and promoting SFK activation. PMID:27148251

  11. Histoplasma capsulatum-Induced Cytokine Secretion in Lung Epithelial Cells Is Dependent on Host Integrins, Src-Family Kinase Activation, and Membrane Raft Recruitment

    PubMed Central

    Maza, Paloma K.; Suzuki, Erika

    2016-01-01

    Histoplasma capsulatum var. capsulatum is a dimorphic fungus that causes histoplasmosis, a human systemic mycosis with worldwide distribution. In the present work, we demonstrate that H. capsulatum yeasts are able to induce cytokine secretion by the human lung epithelial cell line A549 in integrin- and Src-family kinase (SFK)-dependent manners. This conclusion is supported by small interfering RNA (siRNA) directed to α3 and α5 integrins, and PP2, an inhibitor of SFK activation. siRNA and PP2 reduced IL-6 and IL-8 secretion in H. capsulatum-infected A549 cell cultures. In addition, α3 and α5 integrins from A549 cells were capable of associating with H. capsulatum yeasts, and this fungus promotes recruitment of these integrins and SFKs to A549 cell membrane rafts. Corroborating this finding, membrane raft disruption with the cholesterol-chelator methyl-β-cyclodextrin reduced the levels of integrins and SFKs in these cell membrane domains. Finally, pretreatment of A549 cells with the cholesterol-binding compound, and also a membrane raft disruptor, filipin, significantly reduced IL-6 and IL-8 levels in A549-H.capsulatum cultures. Taken together, these results indicate that H. capsulatum yeasts induce secretion of IL-6 and IL-8 in human lung epithelial cells by interacting with α3 and α5 integrins, recruiting these integrins to membrane rafts, and promoting SFK activation. PMID:27148251

  12. IL-6 Amplifies TLR Mediated Cytokine and Chemokine Production: Implications for the Pathogenesis of Rheumatic Inflammatory Diseases

    PubMed Central

    Caiello, Ivan; Minnone, Gaetana; Holzinger, Dirk; Vogl, Thomas; Prencipe, Giusi; Manzo, Antonio; De Benedetti, Fabrizio; Strippoli, Raffaele

    2014-01-01

    The role of Interleukin(IL)-6 in the pathogenesis of joint and systemic inflammation in rheumatoid arthritis (RA) and systemic juvenile idiopathic arthritis (s-JIA) has been clearly demonstrated. However, the mechanisms by which IL-6 contributes to the pathogenesis are not completely understood. This study investigates whether IL-6 affects, alone or upon toll like receptor (TLR) ligand stimulation, the production of inflammatory cytokines and chemokines in human peripheral blood mononuclear cells (PBMCs), synovial fluid mononuclear cells from JIA patients (SFMCs) and fibroblast-like synoviocytes from rheumatoid arthritis patients (RA synoviocytes) and signalling pathways involved. PBMCs were pre-treated with IL-6 and soluble IL-6 Receptor (sIL-6R). SFMCs and RA synoviocytes were pre-treated with IL-6/sIL-6R or sIL-6R, alone or in combination with Tocilizumab (TCZ). Cells were stimulated with LPS, S100A8-9, poly(I-C), CpG, Pam2CSK4, MDP, IL-1β. Treatment of PBMCs with IL-6 induced production of TNF-α, CXCL8, and CCL2, but not IL-1β. Addition of IL-6 to the same cells after stimulation with poly(I-C), CpG, Pam2CSK4, and MDP induced a significant increase in IL-1β and CXCL8, but not TNF-α production compared with TLR ligands alone. This enhanced production of IL-1β and CXCL8 paralleled increased p65 NF-κB activation. In contrast, addition of IL-6 to PBMCs stimulated with LPS or S100A8-9 (TLR-4 ligands) led to reduction of IL-1β, TNF-α and CXCL8 with reduced p65 NF-κB activation. IL-6/IL-1β co-stimulation increased CXCL8, CCL2 and IL-6 production. Addition of IL-6 to SFMCs stimulated with LPS or S100A8 increased CXCL8, CCL2 and IL-1β production. Treatment of RA synoviocytes with sIL-6R increased IL-6, CXCL8 and CCL2 production, with increased STAT3 and p65 NF-κB phosphorylation. Our results suggest that IL-6 amplifies TLR-induced inflammatory response. This effect may be relevant in the presence of high IL-6 and sIL-6R levels, such as in arthritic joints

  13. IL-6 amplifies TLR mediated cytokine and chemokine production: implications for the pathogenesis of rheumatic inflammatory diseases.

    PubMed

    Caiello, Ivan; Minnone, Gaetana; Holzinger, Dirk; Vogl, Thomas; Prencipe, Giusi; Manzo, Antonio; De Benedetti, Fabrizio; Strippoli, Raffaele

    2014-01-01

    The role of Interleukin(IL)-6 in the pathogenesis of joint and systemic inflammation in rheumatoid arthritis (RA) and systemic juvenile idiopathic arthritis (s-JIA) has been clearly demonstrated. However, the mechanisms by which IL-6 contributes to the pathogenesis are not completely understood. This study investigates whether IL-6 affects, alone or upon toll like receptor (TLR) ligand stimulation, the production of inflammatory cytokines and chemokines in human peripheral blood mononuclear cells (PBMCs), synovial fluid mononuclear cells from JIA patients (SFMCs) and fibroblast-like synoviocytes from rheumatoid arthritis patients (RA synoviocytes) and signalling pathways involved. PBMCs were pre-treated with IL-6 and soluble IL-6 Receptor (sIL-6R). SFMCs and RA synoviocytes were pre-treated with IL-6/sIL-6R or sIL-6R, alone or in combination with Tocilizumab (TCZ). Cells were stimulated with LPS, S100A8-9, poly(I-C), CpG, Pam2CSK4, MDP, IL-1β. Treatment of PBMCs with IL-6 induced production of TNF-α, CXCL8, and CCL2, but not IL-1β. Addition of IL-6 to the same cells after stimulation with poly(I-C), CpG, Pam2CSK4, and MDP induced a significant increase in IL-1β and CXCL8, but not TNF-α production compared with TLR ligands alone. This enhanced production of IL-1β and CXCL8 paralleled increased p65 NF-κB activation. In contrast, addition of IL-6 to PBMCs stimulated with LPS or S100A8-9 (TLR-4 ligands) led to reduction of IL-1β, TNF-α and CXCL8 with reduced p65 NF-κB activation. IL-6/IL-1β co-stimulation increased CXCL8, CCL2 and IL-6 production. Addition of IL-6 to SFMCs stimulated with LPS or S100A8 increased CXCL8, CCL2 and IL-1β production. Treatment of RA synoviocytes with sIL-6R increased IL-6, CXCL8 and CCL2 production, with increased STAT3 and p65 NF-κB phosphorylation. Our results suggest that IL-6 amplifies TLR-induced inflammatory response. This effect may be relevant in the presence of high IL-6 and sIL-6R levels, such as in arthritic joints

  14. The influence of family history on prostate cancer risk: implications for clinical management.

    PubMed

    Madersbacher, Stephan; Alcaraz, Antonio; Emberton, Mark; Hammerer, Peter; Ponholzer, Anton; Schröder, Fritz H; Tubaro, Andrea

    2011-03-01

    • The most recent evidence for the link between a family history of prostate cancer and individual risk for future disease was examined, with the aim of understanding what the existence and nature of a family history of prostate cancer does to a man's risk of developing the disease. • Our findings highlighted the clear association between a family history of prostate cancer and increased risk of developing the disease; with a greater proximity of relatedness, greater number of family members affected and/or earlier age at diagnosis of the family member elevating risk further. • These findings have important clinical implications for the identification and subsequent management of men deemed to be at increased risk of developing prostate cancer. The evidence for prostate cancer risk reduction with the mono 5α-reductase inhibitor (5ARI) finasteride in a low-risk population and, more recently, with the dual 5ARI dutasteride in a population at increased risk of developing the disease, has potential to expand management options for men at risk of developing prostate cancer beyond more frequent and/or earlier surveillance. • Given that family history can be easily assessed in routine clinical practice, it should be regarded as an important parameter to consider alongside PSA level for prostate cancer risk assessment. PMID:21166744

  15. Cytokines and antitumor immunity.

    PubMed

    Müller, Ludmila; Pawelec, Graham

    2003-06-01

    Currently, the notion of immunosurveillance against tumors is enjoying something of a renaissance. Even if we still refuse to accept that tumors arising in the normal host are unable to trigger an immune response because of the lack of initiation ("danger") signals, there is no doubt that the immune system can be manipulated experimentally and by implication therapeutically to exert anti-tumor effects. For this activity to be successful, the appropriate cytokine milieu has to be provided, making cytokine manipulation central to immunotherapy. On the other hand, the major hurdle currently preventing successful immunotherapy is the ability of tumors to evolve resistant variants under the pressure of immune selection. Here, too, the cytokine milieu plays an essential role. The purpose of this brief review is to consider the current status of the application of cytokines in facilitating antitumor immunity, as well their role in inhibiting responses to tumors. Clearly, encouraging the former but preventing the latter will be the key to the effective clinical application of cancer immunotherapy. PMID:12779349

  16. Characterization of the Deleted in Autism 1 Protein Family: Implications for Studying Cognitive Disorders

    PubMed Central

    Aziz, Azhari; Harrop, Sean P.; Bishop, Naomi E.

    2011-01-01

    Autism spectrum disorders (ASDs) are a group of commonly occurring, highly-heritable developmental disabilities. Human genes c3orf58 or Deleted In Autism-1 (DIA1) and cXorf36 or Deleted in Autism-1 Related (DIA1R) are implicated in ASD and mental retardation. Both gene products encode signal peptides for targeting to the secretory pathway. As evolutionary medicine has emerged as a key tool for understanding increasing numbers of human diseases, we have used an evolutionary approach to study DIA1 and DIA1R. We found DIA1 conserved from cnidarians to humans, indicating DIA1 evolution coincided with the development of the first primitive synapses. Nematodes lack a DIA1 homologue, indicating Caenorhabditis elegans is not suitable for studying all aspects of ASD etiology, while zebrafish encode two DIA1 paralogues. By contrast to DIA1, DIA1R was found exclusively in vertebrates, with an origin coinciding with the whole-genome duplication events occurring early in the vertebrate lineage, and the evolution of the more complex vertebrate nervous system. Strikingly, DIA1R was present in schooling fish but absent in fish that have adopted a more solitary lifestyle. An additional DIA1-related gene we named DIA1-Like (DIA1L), lacks a signal peptide and is restricted to the genomes of the echinoderm Strongylocentrotus purpuratus and cephalochordate Branchiostoma floridae. Evidence for remarkable DIA1L gene expansion was found in B. floridae. Amino acid alignments of DIA1 family gene products revealed a potential Golgi-retention motif and a number of conserved motifs with unknown function. Furthermore, a glycine and three cysteine residues were absolutely conserved in all DIA1-family proteins, indicating a critical role in protein structure and/or function. We have therefore identified a new metazoan protein family, the DIA1-family, and understanding the biological roles of DIA1-family members will have implications for our understanding of autism and mental retardation. PMID

  17. Black Families' Lay Views on Health and the Implications for Health Promotion: A Community-Based Study in the UK

    ERIC Educational Resources Information Center

    Ochieng, Bertha

    2012-01-01

    Many studies focusing on beliefs about health and health promotion have paid little attention to the life experiences of Black and other visible minority ethnic families in western societies. This paper is a report of a study exploring Black families' beliefs about health and the implications of such beliefs for health promotion. Ten Black…

  18. Trajectories of Adolescent Hostile-Aggressive Behavior and Family Climate: Longitudinal Implications for Young Adult Romantic Relationship Competence

    ERIC Educational Resources Information Center

    Fosco, Gregory M.; Van Ryzin, Mark J.; Xia, Mengya; Feinberg, Mark E.

    2016-01-01

    The formation and maintenance of young adult romantic relationships that are free from violence and are characterized by love, connection, and effective problem-solving have important implications for later well-being and family functioning. In this study, we examined adolescent hostile-aggressive behavior (HAB) and family relationship quality as…

  19. Familial adenomatous polyposis in an adolescent with coexisting schizophrenia: treatment strategies and implications

    PubMed Central

    Gonzalez, Luisa; Alvarez, Jose; Weinstein, Erica; Korenis, Panagiota

    2015-01-01

    Schizophrenia is associated with high mortality and morbidity. The etiology of schizophrenia remains unclear, studies implicate a multifactorial origin with genetic and environmental factors. The adenomatous polyposis coli (APC) gene has been associated with FAP (familial adenomatous polyposis), and studies have linked it to schizophrenia. However, there are few studies which examine the association between FAP and schizophrenia. Limited data exist regarding recommendations for genetic counseling of adolescents with comorbid psychiatric illness. A case of an adolescent with FAP who developed psychotic symptoms is presented. This case hopes to add to the literature about mental illness in those with FAP. A review of literature about the role of APC in schizophrenia as well as implications of genetic counseling on those who suffer with mental illness will be discussed. PMID:26436104

  20. Meal skipping children in low-income families and community practice implications

    PubMed Central

    Kim, Meesook; Hong, Soon Myoung

    2008-01-01

    We examined dietary habits, food intakes, health status, and school and community life of meal skipping children, and investigated factors predicting meal skipping of children. A sample was composed of 944 children in low-income families who were provided with public meal service. The sample was obtained from the Survey of Meal Service for Poor Children conducted by the Korea Institute for Health and Social Affairs in 2007. Meal skipping was significantly associated with a lower nutrition and health status, and poor school performance of children, as hypothesized. The school age of child, family structure, region, job of caretaker, concern about diet, and the child's visit to welfare center significantly predicted frequency of meal skipping. We suggested a few implications for community practice to reduce meal skipping of children. PMID:20126373

  1. Child abuse and neglect in Cambodian refugee families: characteristics and implications for practice.

    PubMed

    Chang, Janet; Rhee, Siyon; Berthold, S Megan

    2008-01-01

    This study examines the characteristics and patterns of child maltreatment among Cambodian refugee families in Los Angeles and assesses the implications for child welfare practice with Cambodian refugee families. Data were extracted from 243 active Cambodian case files maintained by the Los Angeles County Department of Children and Family Services (LAC-DCFS). Some of the major findings include (1) Cambodian child maltreatment cases were most frequently reported to the LAC-DCFS among various Asian Pacific ethnic groups; (2) Cambodian refugee families were more likely to be charged with neglect, while their Asian Pacific counterparts were more likely charged with physical abuse; (3) the circumstances under which maltreatment occurred most frequently were parental substance abuse and mental illness; and (4) while fathers who maltreated their child were likely to use alcohol, mothers were also more likely to have a mental health problem such as depression. This study suggests the importance of collaboration between Child Protective Service agencies, substance abuse programs, traditional healers, mental health services, and other social service agencies for effective child abuse prevention and intervention efforts. PMID:18575261

  2. High glucose driven expression of pro-inflammatory cytokine and chemokine genes in lymphocytes: molecular mechanisms of IL-17 family gene expression.

    PubMed

    Kumar, Prabhakaran; Natarajan, Kartiga; Shanmugam, Narkunaraja

    2014-03-01

    High glucose is an independent risk factor that alters the expression pattern of cytokines/chemokine leading to leukocyte activation in diabetes. Fluctuation of cytokine milieu in lymphocytes may lead to differentiation into a particular subset. Our objectives were to profile high glucose induced inflammatory gene expression in lymphocytes, to examine in vivo relevance in diabetes and to identify the key transcription factors and signaling pathways involved. Cytokine gene arrays and T-helper (Th1/Th2/Th17) cytokine profiler RT(2)-PCR arrays used for cytokine expression profiling followed by validation using Real Time-qPCR and relative RT-PCR in Jurkat T-lymphocytes, peripheral blood lymphocytes (PBLCs) from normal and diabetes subjects. Luciferase reporter plasmid, pharmacological inhibitors and mutant plasmids were used for promoter activation and signaling pathway studies. High glucose induced gene profiling in Jurkat T-lymphocytes showed significantly increased expression of 64 proinflammatory genes including IL-6 and IL-17A and most of these genes were Nuclear Factor (NF)-κB and AP-1 regulated. RT(2)-PCR array results suggested the transcriptional activation of IL-17 and its downstream signaling in Jurkat T-lymphocytes upon high glucose treatment. Candidate genes like Interleukin (IL)-17A, IL-17E IL-17F and IL-6 were up-regulated in both Jurkat T-lymphocytes and PBLCs from normal and diabetes subjects. This high glucose induced cytokine expression was due to promoter activation. Pharmacology inhibitor studies showed the involvement of NF-κB, protein kinase-C, p38 Mitogen activated protein kinase; Janus activated kinase-signal transducer and activator of transcription and extracellular regulated kinase signaling pathways. Further, high glucose treatment increased the adhesion of lymphocytes to human umbilical vein endothelial cells. These results show that IL-17 cytokines are induced by high glucose via key signaling pathways leading to lymphocyte activation

  3. Involvement of purinergic receptors and NOD-like receptor-family protein 3-inflammasome pathway in the adenosine triphosphate-induced cytokine release from macrophages.

    PubMed

    Gicquel, Thomas; Victoni, Tatiana; Fautrel, Alain; Robert, Sacha; Gleonnec, Florence; Guezingar, Marie; Couillin, Isabelle; Catros, Véronique; Boichot, Elisabeth; Lagente, Vincent

    2014-04-01

    Adenosine triphosphate (ATP) has been described as a danger signal activating the NOD-like receptor-family protein 3 (NLRP3)-inflammasome leading to the pro-inflammatory cytokine, interleukin (IL)-1β, release in the lung. The NLRP3-inflammasome pathway has been previously described to be involved in experimental collagen deposition and the development of pulmonary fibrosis. The aim of the present study was to investigate the role of the NLRP3 inflammasome pathway and P2X7 purinergic receptor in the activation of human macrophages in vitro by ATP. We showed that adenosine 5'-[γ-thio]triphosphate tetralithium salt (ATPγS) and 2',3'-O-(4-benzoylbenzoyl) adenosine 5'-triphosphate (BzATP), two stable analogs of ATP, are able to potentiate the release of IL-1β from human monocyte-derived macrophages induced by low concentration of lipopolysaccharide (LPS). However, in the same conditions no increase in IL-1α and IL-6 was observed. Immunochemistry has shown that human macrophages natively express NLRP3 and purinergic P2X7 receptors (P2X7 R). NLRP3 and IL-1β mRNA expression were induced from LPS-primed macrophages, but also after 5-h treatment of BzATP as analysed by reverse transcription quantitative polymerase chain reaction. However, other inflammasome pathways (NLRP1, NLRP2, NLRC4, NLRP6 and AIM2) and P2X7 R were not induced by BzATP. We observed that P2X7 R antagonists, A-438079 and A-740003, were able to reduce the release of IL-1β, but not of IL-1α and IL-6 from macrophages stimulated by ATPγS or BzATP. The present results showed the involvement of the P2X7 R-NLRP3 inflammasome pathway in the secretion of IL-1β from ATP-stimulated human macrophages, and suggest that P2X7 R were not involved in IL-1α and IL-6 release. This study also points out that repression of the P2X7 R represents a novel potential therapeutic approach to control fibrosis in lung injury. PMID:24472059

  4. Functional characterization of novel ABCB6 mutations and their clinical implications in familial pseudohyperkalemia.

    PubMed

    Andolfo, Immacolata; Russo, Roberta; Manna, Francesco; De Rosa, Gianluca; Gambale, Antonella; Zouwail, Soha; Detta, Nicola; Pardo, Catia Lo; Alper, Seth L; Brugnara, Carlo; Sharma, Alok K; De Franceschi, Lucia; Iolascon, Achille

    2016-08-01

    Isolated familial pseudohyperkalemia is a dominant red cell trait characterized by cold-induced 'passive leak' of red cell potassium ions into plasma. The causative gene of this condition is ABCB6, which encodes an erythrocyte membrane ABC transporter protein bearing the Langereis blood group antigen system. In this study analyzing three new families, we report the first functional characterization of ABCB6 mutants, including the homozygous mutation V454A, heterozygous mutation R276W, and compound heterozygous mutations R276W and R723Q (in trans). All these mutations are annotated in public databases, suggesting that familial pseudohyperkalemia could be common in the general population. Indeed, we identified variant R276W in one of 327 random blood donors (0.3%). Four weeks' storage of heterozygous R276W blood cells resulted in massive loss of potassium compared to that from healthy control red blood cells. Moreover, measurement of cation flux demonstrated greater loss of potassium or rubidium ions from HEK-293 cells expressing ABCB6 mutants than from cells expressing wild-type ABCB6. The R276W/R723Q mutations elicited greater cellular potassium ion efflux than did the other mutants tested. In conclusion, ABCB6 missense mutations in red blood cells from subjects with familial pseudohyperkalemia show elevated potassium ion efflux. The prevalence of such individuals in the blood donor population is moderate. The fact that storage of blood from these subjects leads to significantly increased levels of potassium in the plasma could have serious clinical implications for neonates and infants receiving large-volume transfusions of whole blood. Genetic tests for familial pseudohyperkalemia could be added to blood donor pre-screening. Further study of ABCB6 function and trafficking could be informative for the study of other pathologies of red blood cell hydration. PMID:27151991

  5. Functional characterization of novel ABCB6 mutations and their clinical implications in familial pseudohyperkalemia

    PubMed Central

    Andolfo, Immacolata; Russo, Roberta; Manna, Francesco; De Rosa, Gianluca; Gambale, Antonella; Zouwail, Soha; Detta, Nicola; Pardo, Catia Lo; Alper, Seth L.; Brugnara, Carlo; Sharma, Alok K.; De Franceschi, Lucia; Iolascon, Achille

    2016-01-01

    Isolated familial pseudohyperkalemia is a dominant red cell trait characterized by cold-induced ‘passive leak’ of red cell potassium ions into plasma. The causative gene of this condition is ABCB6, which encodes an erythrocyte membrane ABC transporter protein bearing the Langereis blood group antigen system. In this study analyzing three new families, we report the first functional characterization of ABCB6 mutants, including the homozygous mutation V454A, heterozygous mutation R276W, and compound heterozygous mutations R276W and R723Q (in trans). All these mutations are annotated in public databases, suggesting that familial pseudohyperkalemia could be common in the general population. Indeed, we identified variant R276W in one of 327 random blood donors (0.3%). Four weeks’ storage of heterozygous R276W blood cells resulted in massive loss of potassium compared to that from healthy control red blood cells. Moreover, measurement of cation flux demonstrated greater loss of potassium or rubidium ions from HEK-293 cells expressing ABCB6 mutants than from cells expressing wild-type ABCB6. The R276W/R723Q mutations elicited greater cellular potassium ion efflux than did the other mutants tested. In conclusion, ABCB6 missense mutations in red blood cells from subjects with familial pseudohyperkalemia show elevated potassium ion efflux. The prevalence of such individuals in the blood donor population is moderate. The fact that storage of blood from these subjects leads to significantly increased levels of potassium in the plasma could have serious clinical implications for neonates and infants receiving large-volume transfusions of whole blood. Genetic tests for familial pseudohyperkalemia could be added to blood donor pre-screening. Further study of ABCB6 function and trafficking could be informative for the study of other pathologies of red blood cell hydration. PMID:27151991

  6. Putting Families in the Center: Family Perspectives on Decision Making and ADHD and Implications for ADHD Care

    ERIC Educational Resources Information Center

    Davis, Catherine C.; Claudius, Milena; Palinkas, Lawrence A.; Wong, John B.; Leslie, Laurel K.

    2012-01-01

    Objective: To examine components of family-centered care in families' stories about treatment decision making for their child with ADHD. Method: Twenty-eight families participated in qualitative interviews that addressed families' perspectives on (a) the treatment decision-making process, (b) the cause and impact of their child's symptoms, and (c)…

  7. Evolution of Cytokine Receptor Signaling.

    PubMed

    Liongue, Clifford; Sertori, Robert; Ward, Alister C

    2016-07-01

    Cytokines represent essential mediators of cell-cell communication with particularly important roles within the immune system. These secreted factors are produced in response to developmental and/or environmental cues and act via cognate cytokine receptors on target cells, stimulating specific intracellular signaling pathways to facilitate appropriate cellular responses. This review describes the evolution of cytokine receptor signaling, focusing on the class I and class II receptor families and the downstream JAK-STAT pathway along with its key negative regulators. Individual components generated over a long evolutionary time frame coalesced to form an archetypal signaling pathway in bilateria that was expanded extensively during early vertebrate evolution to establish a substantial "core" signaling network, which has subsequently undergone limited diversification within discrete lineages. The evolution of cytokine receptor signaling parallels that of the immune system, particularly the emergence of adaptive immunity, which has likely been a major evolutionary driver. PMID:27317733

  8. Cytokines in immunity and allograft rejection.

    PubMed

    Benjamin, Louis C; Allan, James S; Madsen, Joren C

    2002-01-01

    Cytokines are highly potent regulatory molecules that are secreted by a variety of cells into the local microenvironment. These chemical messengers participate in the activation and regulation of immune function by a variety of mechanisms, including the stimulation and inhibition of cellular proliferation and differentiation. Cytokines also may have chemotactic activity. Six cytokine receptor families have been described, on the basis of their conserved structural features. Many cytokines are classified as proinflammatory cytokines, which promote both innate and adaptive immune responses. Solid-organ transplantation presents several unique challenges to the immune system, and cytokines play an important role in both antigen-dependent and antigen-independent immune recognition. The selective blockade of cytokine-mediated immune responses is a cornerstone of modern immunosuppressive therapy. PMID:12678428

  9. Innate Multigene Family Memories Are Implicated in the Viral-Survivor Zebrafish Phenotype

    PubMed Central

    Estepa, Amparo; Coll, Julio

    2015-01-01

    Since adaptive features such as memory were discovered in mammalian innate immunity, interest in the immunological status of primitive vertebrates after infections has grown. In this context, we used zebrafish (Danio rerio), a primitive vertebrate species suited to molecular and genetic studies to explore transcriptional memories of the immune system in long-term survivors of viral haemorrhagic septicemia virus infections. Immune-gene targeted microarrays designed in-house, multipath genes, gene set enrichment, and leading-edge analysis, reveal unexpected consistent correlations between the viral-survivor phenotype and several innate multigene families. Thus, here we describe in survivors of infections the upregulation of the multigene family of proteasome subunit macropains, zebrafish-specific novel gene sets, mitogen activated protein kinases, and epidermal growth factor. We also describe the downregulation of the multigene families of c-reactive proteins, myxovirus-induced proteins and novel immunoglobulin-type receptors. The strength of those immunological memories was reflected by the exceptional similarity of the transcriptional profiles of survivors before and after re-infection compared with primary infected fish. On the other hand, the high levels of neutralizing antibodies in the blood plasma of survivors contrasted with the depletion of transcripts specific for most cell types present in lymphoid organs. Therefore, long-term survivors maintained unexpected molecular/cellular memories of previous viral encounters by modulating the expression levels of innate multigene families as well as having specific adaptive antibodies. The implications of the so-called "trained immunity" for future research in this field are also discussed. PMID:26270536

  10. Altered expression of IL-10 family cytokines in monocytes from CRMO patients result in enhanced IL-1β expression and release.

    PubMed

    Hofmann, S R; Kubasch, A S; Ioannidis, C; Rösen-Wolff, A; Girschick, H J; Morbach, H; Hedrich, C M

    2015-12-01

    Chronic recurrent multifocal osteomyelitis (CRMO) is characterized by reduced activation of protein kinases ERK1 and 2 in monocytes resulting in impaired IL-10 expression. IL10 and its homologs IL19 and IL20 are organized in the IL10 cluster on chromosome 1q32. IL-10 and IL-19 are immune-regulatory cytokines, while IL-20 acts in a pro-inflammatory manner. The NLRP3 inflammasome, a multi-protein complex forming in response to innate stimuli, mediates IL-1β cleavage and release. Here, we investigated IL-10-related cytokine expression in CRMO monocytes, underlying molecular events, and effects on inflammatory responses. We observed reduced anti-inflammatory IL-10 and IL-19 expression, and enhanced IL-20 expression in CRMO monocytes. Reduced IL-10 and IL-19 expression was associated with impaired Sp-1 recruitment to regulatory regions, contributing to NLRP3 inflammasome activation, which may induce inflammatory bone-loss. Our findings underscore the importance of balanced receptor-, cell-, and tissue-specific cytokine expression for immune homeostasis, providing additional arguments for cytokine blocking strategies in CRMO. PMID:26404542

  11. The genetic basis of familial adenomatous polyposis and its implications for clinical practice and risk management

    PubMed Central

    Leoz, Maria Liz; Carballal, Sabela; Moreira, Leticia; Ocaña, Teresa; Balaguer, Francesc

    2015-01-01

    Familial adenomatous polyposis (FAP) is an inherited disorder that represents the most common gastrointestinal polyposis syndrome. Germline mutations in the APC gene were initially identified as responsible for FAP, and later, several studies have also implicated the MUTYH gene as responsible for this disease, usually referred to as MUTYH-associated polyposis (MAP). FAP and MAP are characterized by the early onset of multiple adenomatous colorectal polyps, a high lifetime risk of colorectal cancer (CRC), and in some patients the development of extracolonic manifestations. The goal of colorectal management in these patients is to prevent CRC mortality through endoscopic and surgical approaches. Individuals with FAP and their relatives should receive appropriate genetic counseling and join surveillance programs when indicated. This review is focused on the description of the main clinical and genetic aspects of FAP associated with germline APC mutations and MAP. PMID:25931827

  12. Partner violence, depression, and practice implications with families of Chinese descent.

    PubMed

    Yick, Alice G; Shibusawa, Tazuko; Agbayani-Siewert, Pauline

    2003-01-01

    Because the Chinese tend to display psychological problems such as depression in somatic This article examines cultural aspects, experiences, and the mental health consequences of partner violence among families of Chinese descent. A total of 262 Chinese men and women participated in a telephone survey about partner violence and psychological well-being. Symptoms, two indicators of mental health were employed in the research study. Findings indicated a high level of verbal aggression both perpetrated and sustained by participants. Rates of physical abuse were lower; however, these figures dispel the model minority myth associated with Asian Americans. In addition, findings showed a positive correlation between depression and partner violence. Those who experienced verbal and physical aggression by a spouse/intimate partner in the last 12 months were more likely to experience depression. Those who perpetrated physical aggression were more likely to experience somatic symptoms. Practice and research implications are highlighted. PMID:14692179

  13. MAPK-dependent regulation of IL-1- and β-adrenoreceptor-induced inflammatory cytokine production from mast cells: Implications for the stress response

    PubMed Central

    Chi, David S; Fitzgerald, S Matthew; Pitts, Shannon; Cantor, Karen; King, Ellis; Lee, Steven A; Huang, Shau-Ku; Krishnaswamy, Guha

    2004-01-01

    Background Catecholamines, such as epinephrine, are elaborated in stress responses, and mediate vasoconstriction to cause elevation in systemic vascular resistance and blood pressure. Our previous study has shown that IL-1 can induce mast cells to produce proinflammatory cytokines which are involved in atherogenesis. The aim of this study was to determine the effects of epinephrine on IL-1-induced proatherogenic cytokine production from mast cells. Results Two ml of HMC-1 (0.75 × 106 cells/ml) were cultured with epinephrine (1 × 10-5 M) in the presence or absence of IL-1β (10 ng/ml) for 24 hrs. HMC-1 cultured alone produced none to trace amounts of IL-6, IL-8, and IL-13. IL-1β significantly induced production of these cytokines in HMC-1, while epinephrine alone did not. However, IL-6, IL-8, and IL-13 production induced by IL-1β were significantly enhanced by addition of epinephrine. The enhancing effect appears to involve NF-κB and p38 MAPK pathways. Flow cytometry showed the presence of β1 and β2 adrenoreceptors on resting mast cells. The enhancing effect of proatherogenic cytokine production by epinephrine was down regulated by the β1 and β2 adrenoceptor antagonist, propranolol, but not by the β1 adrenoceptor antagonist, atenolol, suggesting the effect involved β2 adrenoceptors. The enhancing effect of epinephrine on proatherogenic cytokine production was also down regulated by the immunosuppressive drug, dexamethasone. Conclusions These results not only confirm that an acute phase cytokine, IL-1β, regulates mast cell function, but also show that epinephrine up regulates the IL-1β induction of proatherogenic cytokines in mast cells. These data provide a novel role for epinephrine, a stress hormone, in inflammation and atherogenesis. PMID:15383152

  14. Side effects of cytokines approved for therapy.

    PubMed

    Baldo, Brian A

    2014-11-01

    Cytokines, currently known to be more than 130 in number, are small MW (<30 kDa) key signaling proteins that modulate cellular activities in immunity, infection, inflammation and malignancy. Key to understanding their function is recognition of their pleiotropism and often overlapping and functional redundancies. Classified here into 9 main families, most of the 20 approved cytokine preparations (18 different cytokines; 3 pegylated), all in recombinant human (rh) form, are grouped in the hematopoietic growth factor, interferon, platelet-derived growth factor (PDGF) and transforming growth factor β (TGFβ) families. In the hematopoietin family, approved cytokines are aldesleukin (rhIL-2), oprelvekin (rhIL-11), filgrastim and tbo-filgrastim (rhG-CSF), sargramostim (rhGM-CSF), metreleptin (rh-leptin) and the rh-erythropoietins, epoetin and darbepoietin alfa. Anakinra, a recombinant receptor antagonist for IL-1, is in the IL-1 family; recombinant interferons alfa-1, alfa-2, beta-1 and gamma-1 make up the interferon family; palifermin (rhKGF) and becaplermin (rhPDGF) are in the PDGF family; and rhBMP-2 and rhBMP-7 represent the TGFβ family. The main physicochemical features, FDA-approved indications, modes of action and side effects of these approved cytokines are presented. Underlying each adverse events profile is their pleiotropism, potency and capacity to release other cytokines producing cytokine 'cocktails'. Side effects, some serious, occur despite cytokines being endogenous proteins, and this therefore demands caution in attempts to introduce individual members into the clinic. This caution is reflected in the relatively small number of cytokines currently approved by regulatory agencies and by the fact that 14 of the FDA-approved preparations carry warnings, with 10 being black box warnings. PMID:25270293

  15. Ankylosing spondylitis patients display altered dendritic cell and T cell populations that implicate pathogenic roles for the IL-23 cytokine axis and intestinal inflammation

    PubMed Central

    Wright, Pamela B.; McEntegart, Anne; McCarey, David; McInnes, Iain B.; Siebert, Stefan

    2016-01-01

    Objective. AS is a systemic inflammatory disease of the SpA family. Polymorphisms at loci including HLA-B27, IL-23R and ERAP-1 directly implicate immune mechanisms in AS pathogenesis. Previously, in an SpA model, we identified HLA-B27–mediated effects on dendritic cells that promoted disease-associated Th17 cells. Here we extend these studies to AS patients using deep immunophenotyping of candidate pathogenic cell populations. The aim of our study was to functionally characterize the immune populations mediating AS pathology. Methods. Using 11-parameter flow cytometry, we characterized the phenotype and functions of lymphocyte and myeloid cells from peripheral blood, and the synovial phenotype of AS patients and age-matched healthy controls. Results. Significantly fewer circulating CD1c-expressing dendritic cells were observed in AS patients, offset by an increase in CD14− CD16+ mononuclear cells. Ex vivo functional analysis revealed that this latter population induced CCR6 expression and promoted secretion of IL-1β and IL-6 when co-cultured with naive CD4+ T cells. Additionally, systemic inflammation in AS patients significantly correlated with increased proportions of activated CCR9+ CD4+ T cells. Conclusion. CD14− CD16+ mononuclear cells may contribute to AS by promoting Th17 responses, and antigen-presenting cells of mucosal origin are likely to contribute to systemic inflammation in AS. PMID:26320138

  16. Regulation of ADAMTS-1, -4 and -5 expression in human macrophages: differential regulation by key cytokines implicated in atherosclerosis and novel synergism between TL1A and IL-17.

    PubMed

    Ashlin, Tim G; Kwan, Alvin P L; Ramji, Dipak P

    2013-10-01

    Atherosclerosis is an inflammatory disease of the vasculature regulated by cytokines. Macrophages play a crucial role at all stages of this disease, including regulation of foam cell formation, the inflammatory response and stability of atherosclerotic plaques. For example, matrix metalloproteinases produced by macrophages play an important role in modulating plaque stability. More recently, the ADAMTS proteases, which are known to play a key role in the control of cartilage degradation during arthritis, have been found to be expressed in atherosclerotic lesions and suggested to have potentially important functions in the control of plaque stability. Unfortunately, the action of cytokines on the expression of ADAMTS family in macrophages is poorly understood. We have investigated the effect of classical cytokines (IFN-γ and TGF-β) and those that have been recently identified (TL1A and IL-17) on the expression of ADAMTS-1, -4 and -5 in human macrophages. The expression of all three ADAMTS members was induced during differentiation of monocytes into macrophages. TGF-β had a differential action with induction of ADAMTS-1 and -5 expression and attenuation in the levels of ADAMTS-4. In contrast, IFN-γ suppressed the expression of ADAMTS-1 without having an effect on ADAMTS-4 and -5. Although TL-1A or IL-17A alone had little effect on the expression of all the members, they induced their expression synergistically when present together. These studies provide new insight into the regulation of key ADAMTS family members in human macrophages by major cytokines in relation to atherosclerosis. PMID:23859810

  17. Unmet Need for Family Planning: Implication for Under-five Mortality in Nigeria

    PubMed Central

    Odimegwu, Clifford; Imasiku, Eunice Ntwala; Ononokpono, Dorothy Ngozi

    2015-01-01

    ABSTRACT There are gaps in evidence on whether unmet need for family planning has any implication for under-five mortality in Nigeria. This study utilized 2008 Nigeria Demographic and Health Survey data to examine the effect of unmet need on under-five mortality. Cox regression analysis was performed on 28,647 children born by a nationally-representative sample of 18,028 women within the five years preceding the survey. Findings indicated elevated risks of under-five death for children whose mothers had unmet need for spacing [Hazard ratio (HR): 1.60, confidence interval (CI) 1.37-1.86, p<0.001] and children whose mothers had unmet need for limiting (HR: 1.78, CI 1.48-2.15, p<0.001) compared to children whose mothers had met need. These findings were consistent after adjusting for the effects of factors that could confound the association. Findings of this study underscore the need to address the present level of unmet need for family planning in Nigeria, if the country would achieve meaningful reduction in under-five mortality. PMID:25995735

  18. Trajectories of adolescent hostile-aggressive behavior and family climate: Longitudinal implications for young adult romantic relationship competence.

    PubMed

    Fosco, Gregory M; Van Ryzin, Mark J; Xia, Mengya; Feinberg, Mark E

    2016-07-01

    The formation and maintenance of young adult romantic relationships that are free from violence and are characterized by love, connection, and effective problem-solving have important implications for later well-being and family functioning. In this study, we examined adolescent hostile-aggressive behavior (HAB) and family relationship quality as key individual and family level factors that may forecast later romantic relationship functioning. Guided by a family systems framework, we evaluated the reciprocal influences of adolescent hostility and family climate, to provide a more comprehensive picture of the etiology of romantic relationship functioning. We drew on a large sample (N = 974) of young adults (mean age = 19.5) that were followed starting in the fall of 6th grade, and subsequently in spring of 6th, 7th, 8th, 9th, and 10th grades prior to the young adult assessment. Using a latent difference score cross-lag model (McArdle, 2009), our results indicated that a more positive family climate was associated with decreases in HAB, but HAB was not associated with changes in family climate. Further, the influence of the family climate on HAB was consistent across all time points. HAB and family climate had different predictions for young adult romantic relationships: Increasing HAB over adolescence predicted relationship violence, while maintenance in family climate was a key predictor of relationship problem-solving skills. The only predictor of love and connection in relationships was early family functioning. Implications for developmental theory and prevention science are discussed. (PsycINFO Database Record PMID:27337516

  19. Whole exome sequencing in extended families with autism spectrum disorder implicates four candidate genes.

    PubMed

    Chapman, Nicola H; Nato, Alejandro Q; Bernier, Raphael; Ankenman, Katy; Sohi, Harkirat; Munson, Jeff; Patowary, Ashok; Archer, Marilyn; Blue, Elizabeth M; Webb, Sara Jane; Coon, Hilary; Raskind, Wendy H; Brkanac, Zoran; Wijsman, Ellen M

    2015-10-01

    Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders, characterized by impairment in communication and social interactions, and by repetitive behaviors. ASDs are highly heritable, and estimates of the number of risk loci range from hundreds to >1000. We considered 7 extended families (size 12-47 individuals), each with ≥3 individuals affected by ASD. All individuals were genotyped with dense SNP panels. A small subset of each family was typed with whole exome sequence (WES). We used a 3-step approach for variant identification. First, we used family-specific parametric linkage analysis of the SNP data to identify regions of interest. Second, we filtered variants in these regions based on frequency and function, obtaining exactly 200 candidates. Third, we compared two approaches to narrowing this list further. We used information from the SNP data to impute exome variant dosages into those without WES. We regressed affected status on variant allele dosage, using pedigree-based kinship matrices to account for relationships. The p value for the test of the null hypothesis that variant allele dosage is unrelated to phenotype was used to indicate strength of evidence supporting the variant. A cutoff of p = 0.05 gave 28 variants. As an alternative third filter, we required Mendelian inheritance in those with WES, resulting in 70 variants. The imputation- and association-based approach was effective. We identified four strong candidate genes for ASD (SEZ6L, HISPPD1, FEZF1, SAMD11), all of which have been previously implicated in other studies, or have a strong biological argument for their relevance. PMID:26204995

  20. Cytokines and immune surveillance in humans

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald

    1993-01-01

    Evidence from both human and rodent studies has indicated that alterations in immunological parameters occur after space flight. Among the parameters shown, by us and others, to be affected is the production of interferons. Interferons are a family of cytokines that are antiviral and play a major role in regulating immune responses that control resistance to infection. Alterations in interferon and other cytokine production and activity could result in changes in immunity and a possible compromise of host defenses against both opportunistic and external infections. The purpose of the present study is to further explore the effects of space flight on cytokines and cytokine-directed immunological function.

  1. Post-War Trauma and Reconciliation in Bosnia-Herzegovina: Observations, Experiences, and Implications for Marriage and Family Therapy.

    ERIC Educational Resources Information Center

    Nelson, Briana S.

    2003-01-01

    The 1992-1995 war in Bosnia-Herzegovina caused mush devastation in that region of the world. This article describes the themes and issues that emerged from information gained from interviews with Bosnian professionals through a project entitled "Trauma and Reconciliation in Bosnia-Herzegovina." Recommendations and implications for family and…

  2. Structural design and molecular evolution of a cytokine receptor superfamily.

    PubMed Central

    Bazan, J F

    1990-01-01

    A family of cytokine receptors comprising molecules specific for a diverse group of hematopoietic factors and growth hormones has been principally defined by a striking homology of binding domains. This work proposes that the approximately 200-residue binding segment of the canonical cytokine receptor is composed of two discrete folding domains that share a significant sequence and structural resemblance. Analogous motifs are found in tandem approximately 100-amino acid domains in the extracellular segments of a receptor family formed by the interferon-alpha/beta and -gamma receptors and tissue factor, a membrane tether for a coagulation protease. Domains from the receptor supergroup reveal clear evolutionary links to fibronectin type III structures, approximately 90-amino acid modules that are typically found in cell surface molecules with adhesive functions. Predictive structural analysis of the shared receptor and fibronectin domains locates seven beta-strands in conserved regions of the chain; these strands are modeled to fold into antiparallel beta-sandwiches with a topology that is similar to immunoglobulin constant domains. These findings have strong implications for understanding the evolutionary emergence of an important class of regulatory molecules from primitive adhesive modules. In addition, the resulting double-barrel design of the receptors and the spatial clustering of conserved residues suggest a likely binding site for cytokine ligands. Images PMID:2169613

  3. The Dual-Earner Family's Impact on the Child and the Family System: Review and Implications for Counseling Practice.

    ERIC Educational Resources Information Center

    Bennett, Bert; Reardon, Robert

    In recent years there has been a rapid increase in the number of American families in which both spouses work. The literature regarding preschoolers suggests that one cannot say that being from a dual-earner family will necessarily harm a child. Key issues center not on whether both parents work, but on the quality of substitute care and how well…

  4. Developing a Parent-Centered Obesity Prevention Program for 4-H Families: Implications for Extension Family Programming

    ERIC Educational Resources Information Center

    Benke, Carrie J.; Bailey, Sandra J.; Martz, Jill; Paul, Lynn; Lynch, Wesley; Eldridge, Galen

    2013-01-01

    Planning youth and family programming in the 21st century is daunting given family members' busy schedules. This is even more challenging when planning programs in rural areas, where there are vast distances between communities. This article discusses a research and educational outreach project that uses best practices in program development…

  5. Work-supportive family, family-supportive supervision, use of organizational benefits, and problem-focused coping: implications for work-family conflict and employee well-being.

    PubMed

    Lapierre, Laurent M; Allen, Tammy D

    2006-04-01

    Employees (n = 230) from multiple organizations and industries were involved in a study assessing how work-family conflict avoidance methods stemming from the family domain (emotional sustenance and instrumental assistance from the family), the work domain (family-supportive supervision, use of telework and flextime), and the individual (use of problem-focused coping) independently relate to different dimensions of work-family conflict and to employees' affective and physical well-being. Results suggest that support from one's family and one's supervisor and the use of problem-focused coping seem most promising in terms of avoiding work-family conflict and/or decreased well-being. Benefits associated with the use of flextime, however, are relatively less evident, and using telework may potentially increase the extent to which family time demands interfere with work responsibilities. PMID:16649850

  6. The glutamate and neutral amino acid transporter family: physiological and pharmacological implications.

    PubMed

    Kanai, Yoshikatsu; Hediger, Matthias A

    2003-10-31

    The solute carrier family 1 (SLC1) is composed of five high affinity glutamate transporters, which exhibit the properties of the previously described system XAG-, as well as two Na+-dependent neutral amino acid transporters with characteristics of the so-called "ASC" (alanine, serine and cysteine). The SLC1 family members are structurally similar, with almost identical hydropathy profiles and predicted membrane topologies. The transporters have eight transmembrane domains and a structure reminiscent of a pore loop between the seventh and eighth domains [Neuron 21 (1998) 623]. However, each of these transporters exhibits distinct functional properties. Glutamate transporters mediate transport of L-Glu, L-Asp and D-Asp, accompanied by the cotransport of 3 Na+ and one 1 H+, and the countertransport of 1 K+, whereas ASC transporters mediate Na+-dependent exchange of small neutral amino acids such as Ala, Ser, Cys and Thr. Given the high concentrating capacity provided by the unique ion coupling pattern of glutamate transporters, they play crucial roles in protecting neurons against glutamate excitotoxicity in the central nervous system (CNS). The regulation and manipulation of their function is a critical issue in the pathogenesis and treatment of CNS disorders involving glutamate excitotoxicity. Loss of function of the glial glutamate transporter GLT1 (SLC1A2) has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), resulting in damage of adjacent motor neurons. The importance of glial glutamate transporters in protecting neurons from extracellular glutamate was further demonstrated in studies of the slc1A2 glutamate transporter knockout mouse. The findings suggest that therapeutic upregulation of GLT1 may be beneficial in a variety of pathological conditions. Selective inhibition of the neuronal glutamate transporter EAAC1 (SLC1A1) but not the glial glutamate transporters may be of therapeutic interest, allowing blockage of glutamate exit from

  7. Examining reciprocal influences among family climate, school attachment, and academic self-regulation: Implications for school success.

    PubMed

    Xia, Mengya; Fosco, Gregory M; Feinberg, Mark E

    2016-06-01

    Guided by family systems and ecological theories, this study examined the multicontextual implications of family, school, and individual domains for adolescents' school success. The first goal of this study was to examine reciprocal influences among family climate, school attachment, and academic self-regulation (ASR) during the middle school years. The second goal was to test the relative impact of each of these domains on adolescents' school adjustment and academic achievement after the transition to high school. We applied a cross-lag structural equation modeling approach to longitudinal data from 979 students in the 6th grade and their families, followed over 5 measurement occasions, from 6th through 9th grade. Controlling for family income, parent education, and adolescent gender, the results revealed reciprocal relationships between the family climate and school attachment over time; both of these factors were related to increases in ASR over time. In turn, ASR was a robust predictor of academic success, with unique associations with school adjustment and academic achievement. Family climate and school adjustment had modest to marginal associations with school adjustment, and no association with academic achievement. Applications of these findings for family school interventions are discussed. (PsycINFO Database Record PMID:26376426

  8. Implications of parental affiliate stigma in families of children with ADHD.

    PubMed

    Mikami, Amori Yee; Chong, Gua Khee; Saporito, Jena M; Na, Jennifer Jiwon

    2015-01-01

    This study examined parents' perceptions/awareness and internalization of public courtesy stigma (affiliate stigma) about their children's inattentive and hyperactive/impulsive symptoms, and associations between parental affiliate stigma, parental negativity expressed toward the child, and child social functioning. Participants were families of 63 children (ages 6-10; 42 boys) with attention-deficit/hyperactivity disorder, assessed in a cross-sectional design. After statistical control of children's severity of inattentive and hyperactive/impulsive symptoms (as reported by parents and teachers), parents' self-reports of greater affiliate stigma were associated with more observed negative parenting. The associations between high parental affiliate stigma and children's poorer adult informant-rated social skills and greater observed aggression were partially mediated by increased parental negativity. As well, the positive association between children's adult informant-rated aggressive behavior and parental negativity was partially mediated by parents' increased affiliate stigma. Parental affiliate stigma about their children's inattentive and hyperactive/impulsive symptoms may have negative ramifications for parent-child interactions and children's social functioning. Clinical implications for parent training interventions are discussed. PMID:24697640

  9. Characterization and Clinical Implication of Th1/Th2/Th17 Cytokines Produced from Three-Dimensionally Cultured Tumor Tissues Resected from Breast Cancer Patients

    PubMed Central

    Kiyomi, Anna; Makita, Masujiro; Ozeki, Tomoko; Li, Na; Satomura, Aiko; Tanaka, Sachiko; Onda, Kenji; Sugiyama, Kentaro; Iwase, Takuji; Hirano, Toshihiko

    2015-01-01

    OBJECTIVES: Several cytokines secreted from breast cancer tissues are suggested to be related to disease prognosis. We examined Th1/Th2/Th17 cytokines produced from three-dimensionally cultured breast cancer tissues and related them with patient clinical profiles. METHODS: 21 tumor tissues and 9 normal tissues surgically resected from breast cancer patients were cultured in thermoreversible gelatin polymer–containing medium. Tissue growth and Th1/Th2/Th17 cytokine concentrations in the culture medium were analyzed and were related with hormone receptor expressions and patient clinical profiles. RESULTS: IL-6 and IL-10 were expressed highly in culture medium of both cancer and normal tissues. However, IFN-γ, TNF-α, IL-2, and IL-17A were not detected in the supernatant of the three-dimensionally cultured normal mammary gland and are seemed to be specific to breast cancer tissues. The growth abilities of hormone receptor–negative cancer tissues were significantly higher than those of receptor-positive tissues (P = 0.0383). Cancer tissues of stage ≥ IIB patients expressed significantly higher TNF-α levels as compared with those of patients with stage < IIB (P = 0.0096). CONCLUSIONS: The tumor tissues resected from breast cancer patients can grow in the three-dimensional thermoreversible gelatin polymer culture system and produce Th1/Th2/Th17 cytokines. Hormone receptor–positive cancer tissues showed less growth ability. TNF-α is suggested to be a biomarker for the cancer stage. PMID:26310378

  10. Membrane-proximal TRAIL species are incapable of inducing short circuit apoptosis signaling: Implications for drug development and basic cytokine biology

    PubMed Central

    Tatzel, Katharina; Kuroki, Lindsay; Dmitriev, Igor; Kashentseva, Elena; Curiel, David T.; Goedegebuure, S. Peter; Powell, Matthew A.; Mutch, David G.; Hawkins, William G.; Spitzer, Dirk

    2016-01-01

    TRAIL continues to garner substantial interest as a recombinant cancer therapeutic while the native cytokine itself serves important tumor surveillance functions when expressed in membrane-anchored form on activated immune effector cells. We have recently developed the genetically stabilized TRAIL platform TR3 in efforts to improve the limitations associated with currently available drug variants. While in the process of characterizing mesothelin-targeted TR3 variants using a single chain antibody (scFv) delivery format (SS-TR3), we discovered that the membrane-tethered cytokine had a substantially increased activity profile compared to non-targeted TR3. However, cell death proceeded exclusively via a bystander mechanism and protected the mesothelin-positive targets from apoptosis rather than leading to their elimination. Incorporation of a spacer-into the mesothelin surface antigen or the cancer drug itself-converted SS-TR3 into a cis-acting phenotype. Further experiments with membrane-anchored TR3 variants and the native cytokine confirmed our hypothesis that membrane-proximal TRAIL species lack the capacity to physically engage their cognate receptors coexpressed on the same cell membrane. Our findings not only provide an explanation for the “peaceful” coexistence of ligand and receptor of a representative member of the TNF superfamily but give us vital clues for the design of activity-enhanced TR3-based cancer therapeutics. PMID:26935795

  11. An Islet-Targeted Genome-Wide Association Scan Identifies Novel Genes Implicated in Cytokine-Mediated Islet Stress in Type 2 Diabetes

    PubMed Central

    Sharma, Poonam R.; Mackey, Aaron J.; Dejene, Eden A.; Ramadan, James W.; Langefeld, Carl D.; Palmer, Nicholette D.; Taylor, Kent D.; Wagenknecht, Lynne E.; Watanabe, Richard M.; Rich, Stephen S.

    2015-01-01

    Genome-wide association studies in human type 2 diabetes (T2D) have renewed interest in the pancreatic islet as a contributor to T2D risk. Chronic low-grade inflammation resulting from obesity is a risk factor for T2D and a possible trigger of β-cell failure. In this study, microarray data were collected from mouse islets after overnight treatment with cytokines at concentrations consistent with the chronic low-grade inflammation in T2D. Genes with a cytokine-induced change of >2-fold were then examined for associations between single nucleotide polymorphisms and the acute insulin response to glucose (AIRg) using data from the Genetics Underlying Diabetes in Hispanics (GUARDIAN) Consortium. Significant evidence of association was found between AIRg and single nucleotide polymorphisms in Arap3 (5q31.3), F13a1 (6p25.3), Klhl6 (3q27.1), Nid1 (1q42.3), Pamr1 (11p13), Ripk2 (8q21.3), and Steap4 (7q21.12). To assess the potential relevance to islet function, mouse islets were exposed to conditions modeling low-grade inflammation, mitochondrial stress, endoplasmic reticulum (ER) stress, glucotoxicity, and lipotoxicity. RT-PCR revealed that one or more forms of stress significantly altered expression levels of all genes except Arap3. Thapsigargin-induced ER stress up-regulated both Pamr1 and Klhl6. Three genes confirmed microarray predictions of significant cytokine sensitivity: F13a1 was down-regulated 3.3-fold by cytokines, Ripk2 was up-regulated 1.5- to 3-fold by all stressors, and Steap4 was profoundly cytokine sensitive (167-fold up-regulation). Three genes were thus closely associated with low-grade inflammation in murine islets and also with a marker for islet function (AIRg) in a diabetes-prone human population. This islet-targeted genome-wide association scan identified several previously unrecognized candidate genes related to islet dysfunction during the development of T2D. PMID:26018251

  12. Family Therapy and Children of Alcoholics Implications for Continuing Education and Certification in Substance Abuse Practice

    ERIC Educational Resources Information Center

    Crespi, Tony D.; Rueckert, Quentin H.

    2006-01-01

    Clinicians involved in family therapy are increasingly concerned with the impact of parental alcoholism on individual development and family functioning. With more than 20 million adults raised within an alcoholic family, and with widespread problems associated with parental alcoholism, clinicians providing family treatment have a potentially…

  13. Comparing families and staff in nursing homes and assisted living: implications for social work practice.

    PubMed

    Zimmerman, Sheryl; Cohen, Lauren W; Reed, David; Gwyther, Lisa P; Washington, Tiffany; Cagle, John G; Beeber, Anna S; Sloane, Philip D

    2013-01-01

    Nursing homes and residential care/assisted living settings provide care to 2.4 million individuals. Few studies compare the experience of, and relationships between, family and staff in these settings, despite ongoing family involvement and evidence that relationships are problematic. Data from 488 families and 397 staff members in 24 settings examined family involvement and family and staff burden, depressive symptoms, and perceptions; and staff absenteeism and turnover. There were few differences across setting types. Although conflict rarely occurred, there was room for improvement in family-staff relations; this area, and preparing family for their caregiving roles, are appropriate targets for social work intervention. PMID:23869592

  14. Social Class, Work, and the Family: Some Implications of the Father's Occupation for Familial Relationships and Sons' Career Decisions.

    ERIC Educational Resources Information Center

    Mortimer, Jeylan T.

    The effects of both vertical and nonvertical dimensions of fathers' work on family relations and vocational socialization are explored through a multivariate analysis of data collected from several hundred male student participants enrolled in a Michigan College from 1962-1967. Social class and occupationally-related differences in family…

  15. Social Class, Work and the Family: Some Implications of the Father's Occupation for Familial Relationships and Sons' Career Decisions

    ERIC Educational Resources Information Center

    Mortimer, Jeylan T.

    1976-01-01

    The effects of both vertical and nonvertical dimensions of fathers' work on family relations and vocational socialization are explored through a multivariate analysis of data from several hundred male participants in the 1962-1967 Michigan Student Study. Closeness to father emerged as an important, structurally-related intervening variable.…

  16. Cytokines and fever.

    PubMed

    Conti, Bruno; Tabarean, Iustin; Andrei, Cristina; Bartfai, Tamas

    2004-05-01

    Cytokines are highly inducible, secreted proteins mediating intercellular communication in the nervous and immune system. Fever is the multiphasic response of elevation and decline of the body core temperature regulated by central thermoregulatory mechanisms localized in the preoptic area of the hypothalamus. The discovery that several proinflammatory cytokines act as endogenous pyrogens and that other cytokines can act as antipyretic agents provided a link between the immune and the central nervous systems and stimulated the study of the central actions of cytokines. The proinflammatory cytokines interleukin 1 (IL-1), interleukin 6 (IL-6) and the tumor necrosis factor alpha (TNF) as well as the antiinflammatory cytokines interleukin 1 receptor antagonist (IL-1ra) and interleukin 10 (IL-10) have been most investigated for their pyrogenic or antipyretic action. The experimental evidence demonstrating the role of these secreted proteins in modulating the fever response is as follows: 1) association between cytokine levels in serum and CSF and fever; 2) finding of the presence of cytokine receptors on various cell types in the brain and demonstration of the effects of pharmacological application of cytokines and of their neutralizing antibodies on the fever response; 3) fever studies on cytokine- and cytokine receptor- transgenic models. Studies on the peripheral and the central action of cytokines demonstrated that peripheral cytokines can communicate with the brain in several ways including stimulation of afferent neuronal pathways and induction of the synthesis of a non cytokine pyrogen, i.e. PGE2, in endothelial cells in the periphery and in the brain. Cytokines synthesized in the periphery may act by crossing the blood brain barrier and acting directly via neuronal cytokine receptors. The mechanisms that ultimately mediate the central action of cytokines and of LPS on the temperature-sensitive neurons in the preoptic hypothalamic region involved in

  17. Transmembrane TNF-α Reverse Signaling Inhibits Lipopolysaccharide-Induced Proinflammatory Cytokine Formation in Macrophages by Inducing TGF-β: Therapeutic Implications.

    PubMed

    Pallai, Anna; Kiss, Beáta; Vereb, György; Armaka, Marietta; Kollias, George; Szekanecz, Zoltán; Szondy, Zsuzsa

    2016-02-01

    TNF-α, a potent proinflammatory cytokine, is generated in a precursor form called transmembrane (m)TNF-α that is expressed as a type II polypeptide on the surface of certain cells. mTNF-α was shown to act both as a ligand by binding to TNF-α receptors, as well as a receptor that transmits outside-to-inside (reverse) signals back into the mTNF-α-bearing cells. In this study, we show that nonactivated macrophages express basal levels of mTNF-α and respond to anti-TNF-α Abs by triggering the MAPK kinase 4 signaling pathway. The pathway induces TGF-β. Based on inhibitory experiments, the production of TGF-β1 is regulated via Jun kinases, whereas that of other TGF-βs is regulated via p38 MAPKs. Exposure to LPS further induced the expression of mTNF-α, and triggering of mTNF-α strongly suppressed the LPS-induced proinflammatory response. Neutralizing TGF-β by Abs prevented the mTNF-α-mediated suppression of LPS-induced proinflammatory cytokine formation, indicating that the immune-suppressive effect of mTNF-α is mediated via TGF-β. Although apoptotic cells are also known to suppress LPS-induced proinflammatory cytokine formation in macrophages by upregulating TGF-β, we show that they do not use the mTNF-α signaling pathway. Because TGF-β possesses a wide range of immune-suppressive effects, our data indicate that upregulation of TGF-β synthesis by those TNF-α-targeting molecules, which are able to trigger mTNF-α, might contribute to their therapeutic effect in the treatment of certain inflammatory diseases such as Crohn's disease, Wegener's granulomatosis, or sarcoidosis. Additionally, none of the TNF-α-targeting molecules is expected to interfere with the immune-silencing effects of apoptotic cells. PMID:26729808

  18. Concerted action of Nrf2-ARE pathway, MRN complex, HMGB1 and inflammatory cytokines - Implication in modification of radiation damage

    PubMed Central

    Anuranjani; Bala, Madhu

    2014-01-01

    Whole body exposure to low linear energy transfer (LET) ionizing radiations (IRs) damages vital intracellular bio-molecules leading to multiple cellular and tissue injuries as well as pathophysiologies such as inflammation, immunosuppression etc. Nearly 70% of damage is caused indirectly by radiolysis of intracellular water leading to formation of reactive oxygen species (ROS) and free radicals and producing a state of oxidative stress. The damage is also caused by direct ionization of biomolecules. The type of radiation injuries is dependent on the absorbed radiation dose. Sub-lethal IR dose produces more of DNA base damages, whereas higher doses produce more DNA single strand break (SSBs), and double strand breaks (DSBs). The Nrf2-ARE pathway is an important oxidative stress regulating pathway. The DNA DSBs repair regulated by MRN complex, immunomodulation and inflammation regulated by HMGB1 and various types of cytokines are some of the key pathways which interact with each other in a complex manner and modify the radiation response. Because the majority of radiation damage is via oxidative stress, it is essential to gain in depth understanding of the mechanisms of Nrf2-ARE pathway and understand its interactions with MRN complex, HMGB1 and cytokines to increase our understanding on the radiation responses. Such information is of tremendous help in development of medical radiation countermeasures, radioprotective drugs and therapeutics. Till date no approved and safe countermeasure is available for human use. This study reviews the Nrf2-ARE pathway and its crosstalk with MRN-complex, HMGB1 and cytokines (TNF-a, IL-6, IFN-? etc.). An attempt is also made to review the modification of some of these pathways in presence of selected antioxidant radioprotective compounds or herbal extracts. PMID:25009785

  19. A new member of the GP138 multigene family implicated in cell interactions in Dictyostelium discoideum.

    PubMed

    Hata, T; Yamaguchi, N; Tanaka, Y; Urushihara, H

    1999-06-01

    The cellular slime mold Dictyostelium discoideum reproduces sexually under submerged and dark conditions. Its mating system is polymorphic and particularly interesting with respect to mechanisms of cell recognition. The cell-surface glycoprotein gp138 has been implicated in sexual cell interactions, as it was identified as a target molecule for the antibodies that block sexual cell fusion in D. discoideum. Two mutually homologous genes, GP138A and GP138B, have been cloned, but gene disruption experiments to clarify their functional relationships suggested that there is at least one more gene for gp138. Further protein analysis including peptide mapping also revealed that gp138 exists as three isoforms, DdFRP1, DdFRP2, and DdFRP3. GP138A encodes DdFRP2 and GP138B, DdFRP3, and the presence of a third gp138 gene encoding DdFRP1 was suggested. Here, we isolated and characterized a third GP138 gene, GP138C. Although the deduced amino acid sequences of GP138C matched completely with those of peptide fragments of DdFRP1 in the N-terminal half, the rest did not give complete matches. Overexpression of GP138C caused an increase in the intensity of DdFRP1, but disruption of this gene did not diminish DdFRP1. Our results indicate that GP138C encodes a protein very similar to but distinct from DdFRP1. The GP138 multigene family is thus composed of more members than previously expected, and their functional relationships are of special interest. PMID:10462174

  20. The complex nature of family support across the life span: Implications for psychological well-being.

    PubMed

    Fuller-Iglesias, Heather R; Webster, Noah J; Antonucci, Toni C

    2015-03-01

    This study examines the complex role of family networks in shaping adult psychological well-being over time. We examine the unique and interactive longitudinal influences of family structure (i.e., composition and size) and negative family relationship quality on psychological well-being among young (ages 18-34), middle-aged (ages 35-49), and older adults (ages 50+). A sample of 881 adults (72% White; 26% Black) was drawn from the longitudinal Social Relations, Age, and Health Study. Structural equation modeling indicated that among young and middle-aged adults, increasing family negativity was associated with increases in depressive symptoms over time. In contrast, among older adults, lowered proportion of family in network and an increasing number of family members in the network (i.e., family size) were associated with decreases in depressive symptoms. These findings were moderated by family negativity. Among older adults with low family negativity, having a lower proportion of family and larger family size were associated with decreasing depressive symptoms, but there was no effect among those reporting high family negativity. Overall, these results contribute to an increased understanding of the complex, developmental nature of how family support influences well-being across the life span and highlights unique age differences. PMID:25602936

  1. The Complex Nature of Family Support across the Life Span: Implications for Psychological Well-Being

    ERIC Educational Resources Information Center

    Fuller-Iglesias, Heather R.; Webster, Noah J.; Antonucci, Toni C.

    2015-01-01

    This study examines the complex role of family networks in shaping adult psychological well-being over time. We examine the unique and interactive longitudinal influences of family structure (i.e., composition and size) and negative family relationship quality on psychological well-being among young (ages 18-34), middle-aged (ages 35-49), and…

  2. Intrafamilial Separations in the Immigrant Family: Implications for Cross-Cultural Counseling.

    ERIC Educational Resources Information Center

    Sciarra, Daniel T.

    1999-01-01

    Describes a structural family-therapy (SFT) approach combined with the paradigm of acculturation to increase counselors' sensitivity to immigrant families whose members arrive at different times. The focus is on those families in which parents have preceded children in the immigration experience. Provides culturally sensitive counseling strategies…

  3. A Humanistic Approach towards Family Interaction: An Implication to Mental Health and Caring Society.

    ERIC Educational Resources Information Center

    Harun, Lily Mastura Hj.

    In an effort to develop stability in a community's mental health and establish a resilient and caring society, work must begin with the family itself. This paper discusses the dimensions and types of family interactions prevalent among the Malay families in Malaysia. An integration of the humanistic, systemic, and Islamic approaches form the main…

  4. Implications of the Schiavo Case for Understanding Family Caregiving Issues at the End of Life

    ERIC Educational Resources Information Center

    Roscoe, Lori A.; Osman, Hana; Haley, William E.

    2006-01-01

    The case of Mrs. Terri Schiavo illustrates common themes in family caregiving at the end of life but is distinctive from most family caregiving situations in other ways. As occurred in Mrs. Schiavo's case, family members do act as both caregivers and decisionmakers for their loved ones at the end of life, often without the benefit of written…

  5. Broadening the Concept of Adolescent Promiscuity: Male Accountability Made Visible and the Implications for Family Therapists.

    ERIC Educational Resources Information Center

    Dankoski, Mary E.; Payer, Rosemary; Steinberg, Marilyn

    1996-01-01

    Looks at male promiscuity and the gender bias that holds females accountable for sexual activity. Examines communication patterns, family structure, and other factors. Argues that family therapists can alter family communication patterns, redefine boundaries, and promote healthy parental involvement to make an impact on the issue of male sexual…

  6. Structure, Genomic Organization, and Phylogenetic Implications of Six New VH Families in the Channel Catfish

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To define members of previously unknown VH gene families, a channel catfish immunoglobulin heavy chain cDNA library was constructed and screened with probes specific for the seven known catfish VH families. Reiterative screening and sequence studies defined six new VH families, designated VH8–VH13, ...

  7. Understanding Contexts of Family Violence in Rural, Farming Communities: Implications for Rural Women's Health

    ERIC Educational Resources Information Center

    Wendt, Sarah; Hornosty, Jennie

    2010-01-01

    Research on family violence in rural communities in Australia and Canada has shown that women's experience of family violence is shaped by social and cultural factors. Concern for economic security and inheritance for children, closeness and belonging, and values of family unity and traditional gender roles are factors in rural communities that…

  8. Becoming a Family: Parents' Stories and Their Implications for Practice, Policy, and Research.

    ERIC Educational Resources Information Center

    Harold, Rena D.

    Noting that the movement from young adulthood through coupling and the transition to parenthood may be among the most universal adult developmental transitions, this book uses a qualitative analysis of family narratives to examine the meanings that family members ascribe to the developmental process of becoming a family. Addressing issues of…

  9. The Chinese Family in Transition: Implications for Education and Society in Modern Taiwan.

    ERIC Educational Resources Information Center

    Smith, Douglas C.

    This paper investigates the challenges facing the modern Chinese family in Taiwan. An understanding of how culture and family life interact in other cultures may be useful in helping to understand such interactions in one's own society. Confucianism and family stability have been two enduring features of the protracted civilizations of China. In…

  10. Implications of oxidative stress and hepatic cytokine (TNF-{alpha} and IL-6) response in the pathogenesis of hepatic collagenesis in chronic arsenic toxicity

    SciTech Connect

    Das, Subhankar; Santra, Amal; Lahiri, Sarbari; Guha Mazumder, D.N. . E-mail: dngm@apexmail.com

    2005-04-01

    Introduction: Noncirrhotic portal fibrosis has been reported to occur in humans due to prolonged intake of arsenic contaminated water. Further, oxystress and hepatic fibrosis have been demonstrated by us in chronic arsenic induced hepatic damage in murine model. Cytokines like tumor necrosis factor {alpha} (TNF-{alpha}) and interleukin 6 (IL-6) are suspected to play a role in hepatic collagenesis. The present study has been carried out to find out whether increased oxystress and cytokine response are associated with increased accumulation of collagen in the liver due to prolonged arsenic exposure and these follow a dose-response relationship. Methods: Male BALB/c mice were given orally 200 {mu}l of water containing arsenic in a dose of 50, 100, and 150 {mu}g/mouse/day for 6 days a week (experimental group) or arsenic-free water (<0.01 {mu}g/l, control group) for 3, 6, 9 and 12 months. Hepatic glutathione (GSH), protein sulfhydryl (PSH), glutathione peroxidase (GPx), Catalase, lipid peroxidation (LPx), protein carbonyl (PC), interleukin (IL-6), tumor necrosis factor (TNF-{alpha}), arsenic and collagen content in the liver were estimated from sacrificed animals. Results: Significant increase of lipid peroxidation and protein oxidation in the liver associated with depletion of hepatic thiols (GSH, PSH), and antioxidant enzymes (GPx, Catalase) occurred in mice due to prolonged arsenic exposure in a dose-dependent manner. Significant elevation of hepatic collagen occurred at 9 and 12 months in all the groups associated with significant elevation of TNF-{alpha} and IL-6. However, arsenic level in the liver increased progressively from 3 months onwards. There was a positive correlation between the hepatic arsenic level and collagen content (r = 0.8007), LPx (r = 0.779) and IL-6 (r = 0.7801). Further, there was a significant negative correlation between GSH and TNF-{alpha} (r = -0.5336)) and LPx (r = -0.644). Conclusion: Increasing dose and duration of arsenic exposure in

  11. Cytokine Regulation of Metastasis and Tumorigenicity.

    PubMed

    Yao, M; Brummer, G; Acevedo, D; Cheng, N

    2016-01-01

    The human body combats infection and promotes wound healing through the remarkable process of inflammation. Inflammation is characterized by the recruitment of stromal cell activity including recruitment of immune cells and induction of angiogenesis. These cellular processes are regulated by a class of soluble molecules called cytokines. Based on function, cell target, and structure, cytokines are subdivided into several classes including: interleukins, chemokines, and lymphokines. While cytokines regulate normal physiological processes, chronic deregulation of cytokine expression and activity contributes to cancer in many ways. Gene polymorphisms of all types of cytokines are associated with risk of disease development. Deregulation RNA and protein expression of interleukins, chemokines, and lymphokines have been detected in many solid tumors and hematopoetic malignancies, correlating with poor patient prognosis. The current body of literature suggests that in some tumor types, interleukins and chemokines work against the human body by signaling to cancer cells and remodeling the local microenvironment to support the growth, survival, and invasion of primary tumors and enhance metastatic colonization. Some lymphokines are downregulated to suppress tumor progression by enhancing cytotoxic T cell activity and inhibiting tumor cell survival. In this review, we will describe the structure/function of several cytokine families and review our current understanding on the roles and mechanisms of cytokines in tumor progression. In addition, we will also discuss strategies for exploiting the expression and activity of cytokines in therapeutic intervention. PMID:27613135

  12. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy.

    PubMed

    Czabotar, Peter E; Lessene, Guillaume; Strasser, Andreas; Adams, Jerry M

    2014-01-01

    The BCL-2 protein family determines the commitment of cells to apoptosis, an ancient cell suicide programme that is essential for development, tissue homeostasis and immunity. Too little apoptosis can promote cancer and autoimmune diseases; too much apoptosis can augment ischaemic conditions and drive neurodegeneration. We discuss the biochemical, structural and genetic studies that have clarified how the interplay between members of the BCL-2 family on mitochondria sets the apoptotic threshold. These mechanistic insights into the functions of the BCL-2 family are illuminating the physiological control of apoptosis, the pathological consequences of its dysregulation and the promising search for novel cancer therapies that target the BCL-2 family. PMID:24355989

  13. Oclacitinib (APOQUEL®) is a novel Janus kinase inhibitor with activity against cytokines involved in allergy

    PubMed Central

    Gonzales, A J; Bowman, J W; Fici, G J; Zhang, M; Mann, D W; Mitton-Fry, M

    2014-01-01

    Janus kinase (JAK) enzymes are involved in cell signaling pathways activated by various cytokines dysregulated in allergy. The objective of this study was to determine whether the novel JAK inhibitor oclacitinib could reduce the activity of cytokines implicated in canine allergic skin disease. Using isolated enzyme systems and in vitro human or canine cell models, potency and selectivity of oclacitinib was determined against JAK family members and cytokines that trigger JAK activation in cells. Oclacitinib inhibited JAK family members by 50% at concentrations (IC50's) ranging from 10 to 99 nm and did not inhibit a panel of 38 non-JAK kinases (IC50's > 1000 nm). Oclacitinib was most potent at inhibiting JAK1 (IC50 = 10 nm). Oclacitinib also inhibited the function of JAK1-dependent cytokines involved in allergy and inflammation (IL-2, IL-4, IL-6, and IL-13) as well as pruritus (IL-31) at IC50's ranging from 36 to 249 nm. Oclacitinib had minimal effects on cytokines that did not activate the JAK1 enzyme in cells (erythropoietin, granulocyte/macrophage colony-stimulating factor, IL-12, IL-23; IC50's > 1000 nm). These results demonstrate that oclacitinib is a targeted therapy that selectively inhibits JAK1-dependent cytokines involved in allergy, inflammation, and pruritus and suggests these are the mechanisms by which oclacitinib effectively controls clinical signs associated with allergic skin disease in dogs. PMID:24495176

  14. The Distribution among the States of School-Age Children in Poor Families, 1990 versus 1980: Implications for Chapter 1. CRS Report for Congress.

    ERIC Educational Resources Information Center

    Riddle, Wayne Clifton

    This review and comparison of census data on the distribution among states of school-age children in poor families for 1990 and 1980 explores implications in the changes for Chapter 1 funding and administration. Numbers of school-age children in poor families represent the primary factor in the allocation of most funds under the federal Elementary…

  15. Nitric oxide and superoxide mediate diesel particle effects in cytokine-treated mice and murine lung epithelial cells — implications for susceptibility to traffic-related air pollution

    PubMed Central

    2012-01-01

    Background Epidemiologic studies associate childhood exposure to traffic-related air pollution with increased respiratory infections and asthmatic and allergic symptoms. The strongest associations between traffic exposure and negative health impacts are observed in individuals with respiratory inflammation. We hypothesized that interactions between nitric oxide (NO), increased during lung inflammatory responses, and reactive oxygen species (ROS), increased as a consequence of traffic exposure ─ played a key role in the increased susceptibility of these at-risk populations to traffic emissions. Methods Diesel exhaust particles (DEP) were used as surrogates for traffic particles. Murine lung epithelial (LA-4) cells and BALB/c mice were treated with a cytokine mixture (cytomix: TNFα, IL-1β, and IFNγ) to induce a generic inflammatory state. Cells were exposed to saline or DEP (25 μg/cm2) and examined for differential effects on redox balance and cytotoxicity. Likewise, mice undergoing nose-only inhalation exposure to air or DEP (2 mg/m3 × 4 h/d × 2 d) were assessed for differential effects on lung inflammation, injury, antioxidant levels, and phagocyte ROS production. Results Cytomix treatment significantly increased LA-4 cell NO production though iNOS activation. Cytomix +  DEP-exposed cells incurred the greatest intracellular ROS production, with commensurate cytotoxicity, as these cells were unable to maintain redox balance. By contrast, saline + DEP-exposed cells were able to mount effective antioxidant responses. DEP effects were mediated by: (1) increased ROS including superoxide anion (O2˙-), related to increased xanthine dehydrogenase expression and reduced cytosolic superoxide dismutase activity; and (2) increased peroxynitrite generation related to interaction of O2˙- with cytokine-induced NO. Effects were partially reduced by superoxide dismutase (SOD) supplementation or by blocking iNOS induction. In mice, cytomix +  DEP

  16. Symposium: Social Implications and Alternatives for Families and Children in the Next Decade.

    ERIC Educational Resources Information Center

    Weisberg, Phyllis G.

    A number of major social and demographic trends are having a profound effect on American families with young children. Among these are changes in the characteristics of poverty in families with preschool-age children, curtailment of formerly available financial support or changes in the means of obtaining such support, and the increasing cost of…

  17. Integrating Training in Family-Centered Practices in Context: Implications for Implementing Change Activities.

    ERIC Educational Resources Information Center

    Granlund, Mats; Bjorck-Akesson, Eva

    2000-01-01

    This article discusses in-service training of Swedish professionals in family-centered intervention for families with children with disabilities. The training, which has been implemented on an interdisciplinary team basis in the context of ordinary habilitation services, is described as one of several options for fostering improvement within an…

  18. The Myth of the Nuclear Family: Historical Background and Clinical Implications.

    ERIC Educational Resources Information Center

    Uzoka, Azubike Felix

    1979-01-01

    Research reviewed indicates that the concept of the nuclear family is inadequate and misleading for an understanding of family dynamics or a guide for therapeutic intervention. Nonetheless, clinical practitioners and psychological theorists foster the nuclear myth. A new approach to the study of human relationships is needed. (Author/GC)

  19. Filial Piety by Contract? The Emergence, Implementation, and Implications of the "Family Support Agreement" in China

    ERIC Educational Resources Information Center

    Chou, Rita Jing-Ann

    2011-01-01

    China has the largest aging population in the world today. Despite the Chinese tradition of filial piety, economic, social, cultural, and familial changes have made it increasingly difficult for older Chinese to receive support from adult children. To ensure parental support, the Family Support Agreement (FSA) emerged from a local community in the…

  20. Family History of Speech and Language Impairment in African American Children: Implications for Assessment

    ERIC Educational Resources Information Center

    Pruitt, Sonja L.; Garrity, April W.; Oetting, Janna B.

    2010-01-01

    Purpose: We explored the prevalence of a positive family history of speech and language impairment in African American children as a function of their socioeconomic status (SES), receipt of speech-language services, and diagnosis of specific language impairment (SLI). Method: Data were collected in 2 phases. Phase 1 included family questionnaires…

  1. Predicting Suicide Risks among Outpatient Adolescents Using the Family Environment Scale: Implications for Practice and Research

    ERIC Educational Resources Information Center

    Lucey, Christopher F.; Lam, Sarah K. Y.

    2012-01-01

    This study was designed to identify characteristics of family functioning that relate to suicide potential in an outpatient adolescent population. Participants included 51 adolescents between the ages of 14 and 18 who were involved in outpatient counselling. The Family Environment Scale and the Suicide Probability Scale were used to assess…

  2. Canada's Families Today: Some Policy Implications of Changing Forms and Patterns.

    ERIC Educational Resources Information Center

    Glossop, Robert

    A summary review of facts, figures, and trends concerning family life in Canada reveals patterns of continuity and patterns of change. Generalizations about the average family no longer suffice (if ever they did) as the basis for government policies and programs, corporate personnel practices, and the organization and administration of schools.…

  3. The Implications of Family Size and Birth Order for Test Scores and Behavioral Development

    ERIC Educational Resources Information Center

    Silles, Mary A.

    2010-01-01

    This article, using longitudinal data from the National Child Development Study, presents new evidence on the effects of family size and birth order on test scores and behavioral development at age 7, 11 and 16. Sibling size is shown to have an adverse causal effect on test scores and behavioral development. For any given family size, first-borns…

  4. Impact of Health-Related Family Factors on School Enrollment in Bolivia: Implications for Health Education

    ERIC Educational Resources Information Center

    Madanat, Hala; Dearden, Kirk; Heaton, Tim; Forste, Renata

    2005-01-01

    This study identified the extent to which family factors increase school enrollment in Bolivia, after adjusting for human and financial capital. The sample was drawn from the 1998 Demographic and Health Survey. Logistic regression models were used to determine the effect of human capital, financial capital and family factors on school enrollment.…

  5. Protective Families in High- and Low-Risk Environments: Implications for Adolescent Substance Use

    ERIC Educational Resources Information Center

    Cleveland, Michael J.; Feinberg, Mark E.; Greenberg, Mark T.

    2010-01-01

    This study used data from a sample of 6th to 12th grade students (N = 48,641, 51% female), nested in 192 schools, to determine if the influence of family-based protective factors varied across different school contexts. Hierarchical logistic regression models were used to examine the effects of individual-level family protective factors, relative…

  6. Adolescent Homicide and Family Pathology: Implications for Research and Treatment with Adolescents.

    ERIC Educational Resources Information Center

    Crespi, Tony D.; Rigazio-DiGilio, Sandra A.

    1996-01-01

    The number of felony-murder convictions of adolescents on death row in the United States is arguably a warning beacon about the serious nature of juvenile homicide. Reviews the research on adolescent homicide and highlights significant family variables. The contribution of a family studies perspective for understanding adolescent homicide is…

  7. Work-Family Interface for Same-Sex, Dual-Earner Couples: Implications for Counselors

    ERIC Educational Resources Information Center

    Perrone, Kristin M.

    2005-01-01

    The author highlights information for career counselors to consider when addressing work-family interface with individuals who are members of same-sex, dual-earner couples or families. D. E. Super's (1990) life-span, life-space theory is the framework used to organize the literature review and discussion of current trends. Issues related to the…

  8. Challenges to parenting in a new culture: Implications for child and family welfare.

    PubMed

    Lewig, Kerry; Arney, Fiona; Salveron, Mary

    2010-08-01

    Increasing numbers of families arriving through Australia's humanitarian settlement scheme are coming into contact with Australian child protection systems. A large number of these families come from African and Middle Eastern countries and have common experiences of trauma, dislocation, loss and many are victims of genocide, war, and torture. Pre-migration experiences together with the considerable challenges of settling into a new country can significantly affect family well-being and parenting practices. It is therefore important that child and family welfare service planners are well informed about how best to support refugee families using culturally competent family intervention and community development practices. This paper draws on the findings of a research project designed to examine why recently arrived families from refugee backgrounds are presenting in the South Australian child protection system and to identify culturally appropriate strategies for intervention. The paper presents findings from the project that relate to (1) refugee parents', community members' and child protection practitioners' perspectives on the challenges to being a refugee parent in Australia and (2) strategies and resources relevant to prevention and early intervention in refugee families before statutory child protection intervention becomes necessary. PMID:19552958

  9. Fathers' Involvement in Young Children's Literacy Development: Implications for Family Literacy Programmes

    ERIC Educational Resources Information Center

    Morgan, Anne; Nutbrown, Cathy; Hannon, Peter

    2009-01-01

    Relatively few studies of family literacy programmes have investigated parents' experiences and whilst a number of such programmes have been specifically aimed at fathers, little is known about the involvement of fathers in programmes which target both mothers and fathers. This article reports fathers' involvement in a family literacy programme…

  10. Cytokines in the perinatal period - Part I.

    PubMed

    Chau, A; Markley, J C; Juang, J; Tsen, L C

    2016-05-01

    Successful pregnancy requires a state of immune homeostasis. Maternal tolerance of the genetically distinct fetoplacental unit is in part mediated by maternal and fetal pro- and anti-inflammatory cytokines; these cytokines have also been implicated in different pregnancy-related pathologic states. This two-part series seeks to provide anesthesiologists with an overview on selected perinatal cytokines in an effort to identify opportunities for research and improvements in clinical care. In part one, we review basic and pregnancy-related elements of the immune system, with an emphasis on the role of cytokines. From this foundation, we offer a perspective of a unique phenomenon witnessed within obstetric anesthesia - maternal temperature elevation associated with labor epidural analgesia. PMID:26970932

  11. Src family kinase expression and subcellular localization in macrophages: implications for their role in CSF-1-induced macrophage migration.

    PubMed

    Dwyer, Amy R; Mouchemore, Kellie A; Steer, James H; Sunderland, Andrew J; Sampaio, Natalia G; Greenland, Eloise L; Joyce, David A; Pixley, Fiona J

    2016-07-01

    A major role of colony-stimulating factor-1 is to stimulate the differentiation of mononuclear phagocytic lineage cells into adherent, motile, mature macrophages. The colony-stimulating factor-1 receptor transduces colony-stimulating factor-1 signaling, and we have shown previously that phosphatidylinositol 3-kinase p110δ is a critical mediator of colony-stimulating factor-1-stimulated motility through the colony-stimulating factor-1 receptor pY721 motif. Src family kinases are also implicated in the regulation of macrophage motility and in colony-stimulating factor-1 receptor signaling, although functional redundancy of the multiple SFKs expressed in macrophages makes it challenging to delineate their specific functions. We report a comprehensive analysis of individual Src family kinase expression in macrophage cell lines and primary macrophages and demonstrate colony-stimulating factor-1-induced changes in Src family kinase subcellular localization, which provides clues to their distinct and redundant functions in macrophages. Moreover, expression of individual Src family kinases is both species specific and dependent on colony-stimulating factor-1-induced macrophage differentiation. Hck associated with the activated colony-stimulating factor-1 receptor, whereas Lyn associated with the receptor in a constitutive manner. Consistent with this, inhibitor studies revealed that Src family kinases were important for both colony-stimulating factor-1 receptor activation and colony-stimulating factor-1-induced macrophage spreading, motility, and invasion. Distinct colony-stimulating factor-1-induced changes in the subcellular localization of individual SFKs suggest specific roles for these Src family kinases in the macrophage response to colony-stimulating factor-1. PMID:26747837

  12. Validating the revised Health Belief Model for young families: implications for nurses' health promotion practice.

    PubMed

    Roden, Janet

    2004-12-01

    By modifying the Health Belief Model (HBM) nurses can provide health promotion guidance for families through the revised HBM for young families. The constructs 'perceived behavioral control' and 'behavioral intention' from Ajzen's Theory of Planned Behavior were added to the HBM to provide a health orientation. An initial qualitative study informed the second quantitative study through thematic data obtained by interviewing parents about family health. The second comparative study of low and high socioeconomic status families of preschool-aged children living in western Sydney, Australia, measured family health through the Parental Health Behavior Questionnaire (PHBQ). After a small pilot study, the researcher distributed 150 questionnaires to center directors from preschools, kindergartens and long day care, who then handed out questionnaires to interested parents. Data collection occurred in 1998 with consenting parents returning the questionnaires for collection by the researchers. A convenience sample of 103 was obtained with a 69% return rate. Analysis was undertaken through MANCOVA. Justification for validity occurred through logical analysis and hypothesis testing, based on the literature, while reliability was acknowledged by undertaking Cronbach coefficient alphas on small variable clusters. Results support the constructs 'perceived behavioral control' and 'behavioral intention' in the revised model, suggesting that for families of different socioeconomic background, differences emerge in terms of their perceived control over their child's health and the initiation of health behaviors for their child. Recommendations for further research are for refinement of the PHBQ, new research with different families, and further testing of all the model constructs. PMID:15507045

  13. Female inmates, family caregivers, and young children's adjustment: A research agenda and implications for corrections programming

    PubMed Central

    Cecil, Dawn K.; McHale, James; Strozier, Anne; Pietsch, Joel

    2008-01-01

    Attendant to the exponential increase in rates of incarceration of mothers with young children in the United States, programming has been established to help mothers attend to parenting skills and other family concerns while incarcerated. Unfortunately, most programs overlook the important, ongoing relationship between incarcerated mothers and family members caring for their children—most often, the inmates' own mothers. Research reveals that children's behavior problems escalate when different co-caregivers fail to coordinate parenting efforts and interventions, work in opposition, or disparage or undermine one another. This article presents relevant research on co-caregiving and child adjustment, highlights major knowledge gaps in need of study to better understand incarcerated mothers and their families, and proposes that existing interventions with such mothers can be strengthened through targeting and cultivating functional coparenting alliances in families. PMID:19884977

  14. Implications of New Marriages and Children for Coparenting in Nonresident Father Families

    PubMed Central

    MCGENE, JULIANA; KING, VALARIE

    2011-01-01

    Prior research has noted that although cooperative coparenting between resident and nonresident parents is beneficial to children, this form of shared parenting is relatively uncommon. Relying on nationally representative data from two waves of the National Survey of Families and Households (N = 628), we examine the importance of nonresident fathers’ and resident mothers’ new marriages and new children for levels of cooperative coparenting and test whether changes in coparenting are linked to changes in parents’ marital or fertility statuses. Consistent with prior studies, our data suggest that cooperative coparenting does not occur in most nonresident father families. Results suggest that changes to the nonresident father’s family structure are of primary importance for cooperative coparenting, but that mother’s family structure is relatively unimportant. PMID:23794773

  15. Implication of combined PD-L1/PD-1 blockade with cytokine-induced killer cells as a synergistic immunotherapy for gastrointestinal cancer

    PubMed Central

    Geng, Ruixuan; Ge, Xiaoxiao; Tang, Wenbo; Chang, Jinjia; Wu, Zheng; Liu, Xinyang; Lin, Ying; Zhang, Zhe; Li, Jin

    2016-01-01

    Cytokine-induced killer (CIK) cells represent a realistic approach in cancer immunotherapy with confirmed survival benefits in the context of metastatic solid tumors. However, therapeutic effects are limited to a fraction of patients. In this study, immune-resistance elements and ideal combination therapies were explored. Initially, phenotypic analysis was performed to document CD3, CD56, NKG2D, DNAM-1, PD-L1, PD-1, CTLA-4, TIM-3, 2B4, and LAG-3 on CIK cells. Upon engagement of CIK cells with the tumor cells, expression of PD-1 on CIK cells and PD-L1 on both cells were up-regulated. Over-expression of PD-L1 levels on tumor cells via lentiviral transduction inhibited tumoricidal activity of CIK cells, and neutralizing of PD-L1/PD-1 signaling axis could enhance their tumor-killing effect. Conversely, blockade of NKG2D, a major activating receptor of CIK cells, largely caused dysfunction of CIK cells. Functional study showed an increase of NKG2D levels along with PD-L1/PD-1 blockade in the presence of other immune effector molecule secretion. Additionally, combined therapy of CIK infusion and PD-L1/PD-1 blockade caused a delay of in vivo tumor growth and exhibited a survival advantage over untreated mice. These results provide a preclinical proof-of-concept for simultaneous PD-L1/PD-1 pathways blockade along with CIK infusion as a novel immunotherapy for unresectable cancers. PMID:26871284

  16. 'Train the trainer' model: implications for health professionals and farm family health in Australia.

    PubMed

    Brumby, Susan; Smith, Andrew

    2009-01-01

    Australia is a large country with 60% of land used for agricultural production. Its interior is sparsely populated, with higher morbidity and mortality recorded in rural areas, particularly farmers, farm families, and agricultural workers. Rural health professionals in addressing health education gaps of farming groups have reported using behavioralist approaches. These approaches in isolation have been criticized as disempowering for participants who are identified as passive learners or 'empty vessels.' A major challenge in rural health practice is to develop more inclusive and innovative models in building improved health outcomes. The Sustainable Farm Families Train the Trainer (SFFTTT) model is a 5-day program developed by Western District Health Service designed to enhance practice among health professionals working with farm families in Australia. This innovative model of addressing farmer health asks health professionals to understand the context of the farm family and encourages them to value the experience and existing knowledge of the farmer, the family and the farm business. The SFFTTT program has engaged with health agencies, community, government, and industry groups across Australia and over 120 rural nurses have been trained since 2005. These trainers have successfully delivered programs to 1000 farm families, with high participant completion, positive evaluation, and improved health indicators. Rural professionals report changes in how they approach health education, clinical practice, and promotion with farm families and agricultural industries. This paper highlights the success of SFFTTT as an effective tool in enhancing primary health practice in rural and remote settings. The program is benefiting not only drought ravaged farmers but assisting rural nurses, health agencies, and health boards to engage with farm families at a level not identified previously. Furthermore, nurses and health professionals are now embracing a more 'farmer

  17. Neutrophil Elastase Modulates Cytokine Expression

    PubMed Central

    Benabid, Rym; Wartelle, Julien; Malleret, Laurette; Guyot, Nicolas; Gangloff, Sophie; Lebargy, François; Belaaouaj, Azzaq

    2012-01-01

    There is accumulating evidence that following bacterial infection, the massive recruitment and activation of the phagocytes, neutrophils, is accompanied with the extracellular release of active neutrophil elastase (NE), a potent serine protease. Using NE-deficient mice in a clinically relevant model of Pseudomonas aeruginosa-induced pneumonia, we provide compelling in vivo evidence that the absence of NE was associated with decreased protein and transcript levels of the proinflammatory cytokines TNF-α, MIP-2, and IL-6 in the lungs, coinciding with increased mortality of mutant mice to infection. The implication of NE in the induction of cytokine expression involved at least in part Toll-like receptor 4 (TLR-4). These findings were further confirmed following exposure of cultured macrophages to purified NE. Together, our data suggest strongly for the first time that NE not only plays a direct antibacterial role as it has been previously reported, but released active enzyme can also modulate cytokine expression, which contributes to host protection against P. aeruginosa. In light of our findings, the long held view that considers NE as a prime suspect in P. aeruginosa-associated diseases will need to be carefully reassessed. Also, therapeutic strategies aiming at NE inhibition should take into account the physiologic roles of the enzyme. PMID:22927440

  18. A Family-Focused Delirium Educational Initiative With Practice and Research Implications

    PubMed Central

    Paulson, Christina May; Monroe, Todd; Mcdougall, Graham J.; Fick, Donna M.

    2015-01-01

    Delirium is burdensome and psychologically distressing for formal and informal caregivers, yet family caregivers often have very little understanding or knowledge about delirium. As part of a large multisite intervention study, the Early Nurse Detection of Delirium Superimposed on Dementia (END-DSD), the authors identified a need for family educational materials. This educational initiative’s purpose was to develop a delirium admission brochure for family members to aid in the prevention and earlier identification of delirium during hospitalization. A brochure was developed using an iterative approach with an expert panel. Following three iterations, a final brochure was approved. The authors found that an iterative expert consensus approach can be used to develop a brochure for families. Major content areas were helping families understand the difference between delirium and dementia, signs and symptoms of delirium, causes of delirium, and strategies family members can use to prevent delirium. A caregiver-focused educational brochure is one intervention to use in targeting older adults hospitalized with delirium. PMID:26165565

  19. Comparative binding of biotinylated neurotrophins to alpha(2)-macroglobulin family of proteins: relationship between cytokine-binding and neuro-modulatory activities of the macroglobulins.

    PubMed

    Skornicka, Erin L; Shi, Xiaoqing; Koo, Peter H

    2002-02-01

    Human alpha(2)-macroglobulin (alpha(2)M), pregnancy zone protein (PZP), rat alpha(1)M and acute-phase rat alpha(2)M belong to the alpha(2)M gene family of proteins, which can react covalently with nucleophilic monoamines to yield monoamine-activated (MA) macroglobulins. The MA forms of human alpha(2)M, PZP and rat alpha(2)M have been demonstrated previously to inhibit various neurotrophin-promoted neuronal activities, whereas MA-alpha(1)M is neurostimulatory and all native macroglobulins are generally inactive. The mechanism of neuromodulation is unknown, but it has been postulated that MA macroglobulins might inhibit neurons via their binding and sequestration of neurotrophins. This study employed a novel biotinylation-Western blot technique to compare the neurotrophin-binding properties of the four macroglobulins, and to correlate their binding activities with their known neuro-modulatory activities. In comparison with their respective native counterparts, human and rat MA-alpha(2)M bound slightly more NGF, but significantly less BDNF or NT-3. Native human alpha(2)M and PZP in general have no neuro-modulatory activity, but native PZP bound significantly more NGF, BDNF or NT-3 than either native alpha(2)M or MA-alpha(2)M, which is neuro-inhibitory. It is known that MA-PZP is neuro-inhibitory, but it fails to bind more NGF, BDNF, or NT-3 than native PZP. MA-alpha(1)M is the only macroglobulin known to stimulate NGF-promoted neurite outgrowth, but it bound NGF with similar affinities as native alpha(1)M and rat alpha(2)M; in addition, it bound significantly less BDNF or NT-3 than native alpha(1)M. All the bindings were non-covalent and appeared specific. In conclusion, PZP and rat macroglobulins are versatile carriers of neurotrophins with diverse binding capacities, and the neurotrophin-binding property does not appear to mediate the neuro-modulatory activity of these human and rat macroglobulins. PMID:11813239

  20. Prognostic implications of novel beta cardiac myosin heavy chain gene mutations that cause familial hypertrophic cardiomyopathy.

    PubMed Central

    Anan, R; Greve, G; Thierfelder, L; Watkins, H; McKenna, W J; Solomon, S; Vecchio, C; Shono, H; Nakao, S; Tanaka, H

    1994-01-01

    Three novel beta cardiac myosin heavy chain (MHC) gene missense mutations, Phe513Cys, Gly716Arg, and Arg719Trp, which cause familial hypertrophic cardiomyopathy (FHC) are described. One mutation in exon 15 (Phe513Cys) does not alter the charge of the encoded amino acid, and affected family members have a near normal life expectancy. The Gly716Arg mutation (exon 19; charge change of +1) causes FHC in three family members, one of whom underwent transplantation for heart failure. The Arg719Trp mutation (exon 19; charge change of -1) was found in four unrelated FHC families with a high incidence of premature death and an average life expectancy in affected individuals of 38 yr. A comparable high frequency of disease-related deaths in four families with the Arg719Trp mutation suggests that this specific gene defect directly accounts for the observed malignant phenotype. Further, the significantly different life expectancies associated with the Arg719Trp vs. Phe513Cys mutation (P < 0.001) support the hypothesis that mutations which alter the charge of the encoded amino acid affect survival more significantly than those that produce a conservative amino acid change. Images PMID:8282798

  1. Phylogenetic relationships within the eared seals (Otariidae: Carnivora): implications for the historical biogeography of the family.

    PubMed

    Wynen, L P; Goldsworthy, S D; Insley, S J; Adams, M; Bickham, J W; Francis, J; Gallo, J P; Hoelzel, A R; Majluf, P; White, R W; Slade, R

    2001-11-01

    Phylogenetic relationships within the family Otariidae were investigated using two regions of the mitochondrial genome. A 360-bp region of the cytochrome b gene was employed for the primary phylogenetic analysis, while a 356-bp segment of the control region was used to enhance resolution of the terminal nodes. Traditional classification of the family into the subfamilies Arctocephalinae (fur seals) and Otariinae (sea lions) is not supported, with the fur seal Callorhinus ursinus having a basal relationship relative to the rest of the family. This is consistent with the fossil record which suggests that this genus diverged from the line leading to the remaining fur seals and sea lions about 6 million years ago (mya). There is also little evidence to support or refute the monophyly of sea lions. Four sea lion clades and five fur seal clades were observed, but relationships among these clades are unclear. Similar genetic divergences between the sea lion clades (D(a) = 0.054-0.078), as well as between the major Arctocephalus fur seal clades (D(a) = 0.040-0.069) suggest that these groups underwent periods of rapid radiation at about the time they diverged from each other. Rapid radiations of this type make the resolution of relationships between the resulting species difficult and indicate the requirement for additional molecular data from both nuclear and mitochondrial genes. The phylogenetic relationships within the family and the genetic distances among some taxa highlight inconsistencies in the current taxonomic classification of the family. PMID:11697921

  2. Unique Loss of the PYHIN Gene Family in Bats Amongst Mammals: Implications for Inflammasome Sensing

    PubMed Central

    Ahn, Matae; Cui, Jie; Irving, Aaron T.; Wang, Lin-Fa

    2016-01-01

    Recent genomic analysis of two bat species (Pteropus alecto and Myotis davidii) revealed the absence of the PYHIN gene family. This family is recognized as important immune sensors of intracellular self and foreign DNA and activators of the inflammasome and/or interferon pathways. Further assessment of a wider range of bat genomes was necessary to determine if this is a universal pattern for this large mammalian group. Here we expanded genomic analysis of this gene family to include ten bat species. We confirmed the complete loss of this gene family, with only a truncated AIM2 remaining in one species (Pteronotus parnellii). Divergence of the PYHIN gene loci between the bat lineages infers different loss-of-function histories during bat evolution. While all other major groups of placental mammals have at least one gene member, only bats have lost the entire family. This removal of inflammasome DNA sensors may indicate an important adaptation that is flight-induced and related, at least in part, to pathogen-host co-existence. PMID:26906452

  3. Efficacy studies in natural family planning: issues and management implications illustrated with data from five studies.

    PubMed

    Labbok, M H; Klaus, H; Perez, A

    1991-12-01

    Studies of method effectiveness must be carefully assessed for comparability of findings. Several parameters are identified that are important in the assurance of comparable results. This article discusses these issues with the use of data from previously published studies and emphasizes the management implications of use-effectiveness data. PMID:1755468

  4. Cytokines in Cancer Immunotherapy

    PubMed Central

    Lee, Sylvia; Margolin, Kim

    2011-01-01

    Cytokines are molecular messengers that allow the cells of the immune system to communicate with one another to generate a coordinated, robust, but self-limited response to a target antigen. The growing interest over the past two decades in harnessing the immune system to eradicate cancer has been accompanied by heightened efforts to characterize cytokines and exploit their vast signaling networks to develop cancer treatments. The goal of this paper is to review the major cytokines involved in cancer immunotherapy and discuss their basic biology and clinical applications. The paper will also describe new cytokines in pre-clinical development, combinations of biological agents, novel delivery mechanisms, and potential directions for future investigation using cytokines. PMID:24213115

  5. Service needs among Latino immigrant families: implications for social work practice.

    PubMed

    Ayón, Cecilia

    2014-01-01

    This study sought to learn from Latino immigrant families what services they need to promote their families' well-being within a context of stringent anti-immigrant legislation. Fifty-two Latino immigrant parents participated in focus groups. Focus groups took place following the passage of Senate Bill 1070. Findings reveal five major categories of need: mental health, physical health care, education, information and support services, and community efforts. Participants' experiences as immigrants played a significant role in their narratives. The narratives reveal that families need assistance navigating systems of care, coping with discrimination and oppressive environments, strengthening ties among community members, and advocating for policy change. Social workers are called to address the needs of this community and advocate for human rights and social justice. PMID:24640227

  6. Dynamics of ADHD in familial contexts: perspectives from children and parents and implications for practitioners.

    PubMed

    Wong, Hui Mei; Goh, Esther C L

    2014-01-01

    This article provides in-depth insights on the bidirectional dynamics between parents and their children with attention deficit hyperactivity disorder (ADHD). Five family units (8 parents, 5 children, N = 13) participated in this study. Parents and their child with ADHD were interviewed individually in their homes. Stressful moments of parent-child dynamics revolved around managing their child's behavior and doing homework. Findings highlight the child's agency and power of influence, and the possible recovery of negative dynamics. It is recommended that practitioners adopt the strengths perspective in working with these families and incorporate child's agency and bidirectional dynamics in interventions. PMID:25133296

  7. Phylogenetic analysis of the thiolase family. Implications for the evolutionary origin of peroxisomes.

    PubMed

    Igual, J C; González-Bosch, C; Dopazo, J; Pérez-Ortín, J E

    1992-08-01

    The thiolase family is a widespread group of proteins present in prokaryotes and three cellular compartments of eukaryotes. This fact makes this family interesting in order to study the evolutionary process of eukaryotes. Using the sequence of peroxisomal thiolase from Saccharomyces cerevisiae recently obtained by us and the other known thiolase sequences, a phylogenetic analysis has been carried out. It shows that all these proteins derived from a primitive enzyme, present in the common ancestor of eubacteria and eukaryotes, which evolved into different specialized thiolases confined to various cell compartments. The evolutionary tree obtained is compatible with the endosymbiotic theory for the origin of peroxisomes. PMID:1354266

  8. Giving hope to families in palliative care and implications for practice.

    PubMed

    Smith, Helen

    2014-06-01

    Caring for a dying child and the family is one of the greatest nursing challenges. The way in which care is delivered will shape the experience they are about to face. Hope plays a crucial role in helping people cope, and healthcare professionals can foster appropriate hopes ethically, while maintaining open and honest communication. If palliative care is discussed with clients and families from the time of diagnosis, they can face realistic decisions better and not feel that they are 'giving up'. They need to know that everything possible is being done to improve the quality of the time left to them. PMID:24914668

  9. The Impact of Financial Stress in Marriage: Implications for Marriage and Family Therapists.

    ERIC Educational Resources Information Center

    Arguello, Sandra Crews

    Many couples who come in for family counseling report that financial difficulty is a factor contributing to their current struggles. Yet few therapists spend much time, or even feel qualified to help couples in this critical area. The purpose of this study was to interview subjects who were married or who are married to discern their financial…

  10. Implications of New Marriages and Children for Coparenting in Nonresident Father Families

    ERIC Educational Resources Information Center

    McGene, Juliana; King, Valarie

    2012-01-01

    Prior research has noted that although cooperative coparenting between resident and nonresident parents is beneficial to children, this form of shared parenting is relatively uncommon. Relying on nationally representative data from two waves of the National Survey of Families and Households (N = 628), this study examines the importance of…

  11. The Dynamics of Families Who Are Homeless: Implications for Early Childhood Educators

    ERIC Educational Resources Information Center

    Swick, Kevin J.

    2004-01-01

    Family homelessness has emerged as a serious global problem (Stronge, 2000). Over the past 25 years in the United States, the makeup of the homeless population has changed significantly. As De Angelis (1994) reports: The landscape of homelessness has changed since the early 1980s, when nearly all homeless people were men. Today,…

  12. Ethnicity, Family Socioeconomic Inequalities, and Prevalence of Vaginal Douching among College Students: The Implication for Health

    ERIC Educational Resources Information Center

    Ekpenyong, Christopher E.; Etukumana, Etiobong A.

    2013-01-01

    Objective: This study assessed the association between ethnicity and family socioeconomic status (SES) as it relates to the prevalence of vaginal douching among female undergraduates in a university community. Participants and Methods: This was a cross-sectional survey conducted between September 2011 and February 2012 among 1,535 female…

  13. Patterns of Maternal Behavior among Neglectful Families: Implications for Research and Intervention

    ERIC Educational Resources Information Center

    Wilson, Samantha L.; Kuebli, Janet E.; Hughes, Honore M.

    2005-01-01

    Objective: The heterogeneity within neglecting caregivers has not been explored in an empirical fashion. The current study sought to address this limitation by utilizing archival data in order to explore variability of maternal behavior among neglectful families. Method: The current study utilized archival data containing caseworker and…

  14. The Implications of Psychosocial Theory for Personal Growth in the Family.

    ERIC Educational Resources Information Center

    Newman, Philip R.; Newman, Barbara M.

    Psychosocial theory, based on the ideas of Erik Erikson and Robert Havighurst, is proposed as a useful framework for conceptualizing the potential for growth within the family. Erikson's (1950) eight stage theory of psychosocial development and Havighurst's (1959) concept of developmental tasks are used to take account of the stages of development…

  15. Parents as Scholars: Education Works. Outcomes for Maine Families and Implications for TANF Reauthorization.

    ERIC Educational Resources Information Center

    Smith, Rebekah J.; Deprez, Luisa S.; Butler, Sandra S.

    Maine's Parents as Scholars (PaS) program provides parents who are eligible for Temporary Assistance for Needy Families (TANF) with cash assistance and support services while they attend a two-year or four-year postsecondary degree program. PaS participants receive the same cash benefits and access to support services as TANF recipients receive.…

  16. Prenatal Diagnosis: Current Procedures and Implications for Early Interventionists Working with Families.

    ERIC Educational Resources Information Center

    Blasco, Patricia M.; And Others

    1994-01-01

    This article provides an overview of procedures commonly used in prenatal screening and diagnosis including ultrasound, amniocentesis, chorionic villus biopsy, maternal serum alpha-fetoprotein, and deoxyribonucleic acid (DNA) analysis. Emphasis is on the role of the early interventionist in supporting families during prenatal diagnosis. (Author/DB)

  17. Saturday Morning at the Jail: Implications of Incarceration for Families and Children.

    ERIC Educational Resources Information Center

    Arditti, Joyce A.; Lambert-Shute, Jennifer; Joest, Karen

    2003-01-01

    Using a conceptual framework that acknowledges the losses associated with a parent's incarceration, 56 caregivers visiting an incarcerated family member during children's visiting hours were interviewed. Problems believed to be created by incarceration included parenting strain, emotional stress, and concerns about children's loss of involvement…

  18. Parents' Definition of Effective Child Disability Support Services: Implications for Implementing Family-Centered Practice

    ERIC Educational Resources Information Center

    Hiebert-Murphy, Diane; Trute, Barry; Wright, Alexandra

    2011-01-01

    The current study examined parents' perspectives of services within a community-based childhood disability program in the process of enhancing the family centeredness of its services. Qualitative interviews were conducted with 39 mothers and 22 fathers approximately 18 months after entering the service delivery system. Parents reported that…

  19. Ethnic Identity and Parenting Stress in South Asian Families: Implications for Culturally Sensitive Counselling

    ERIC Educational Resources Information Center

    Shariff, Aneesa

    2009-01-01

    The South Asian culture is one in which family obligation and loyalty, as well as self-sacrifice and obedience toward one's elders, are paramount. These values can be different from those of the more individualistically oriented Euro-Canadian dominant culture, and can prompt challenges of cultural adjustment among Canadian-born South Asian youth…

  20. A Structural Theory of Social Exchange: Implications for Family Theory and Research.

    ERIC Educational Resources Information Center

    McDonald, Gerald W.

    This paper explores the potential contributions of social exchange theory in investigations of marriage and family relationships. The basic premise of social exchange is that individuals in social interaction attempt to maximize rewards and minimize costs to obtain the most profitable outcomes. Research has shown that five factors must be…

  1. Mothers' and Fathers' Racial Socialization in African American Families: Implications for Youth

    ERIC Educational Resources Information Center

    McHale, Susan M.; Crouter, Ann C.; Kim, Ji-Yeon; Burton, Linda M.; Davis, Kelly D.; Dotterer, Aryn M.; Swanson, Dena P.

    2006-01-01

    Mothers' and fathers' cultural socialization and bias preparation with older (M=13.9 years) and younger (M=10.31 years) siblings were studied in 162 two-parent, African American families. Analyses examined whether parental warmth and offspring age and gender were linked to parental practices and whether parents' warmth, spouses' racial…

  2. The Changing Rural Appalachian Community and Low-Income Family: Implications for Community Development.

    ERIC Educational Resources Information Center

    Photiadis, John D.

    Pressures on rural Appalachian families to function as an integral part of the larger American society have led to internal discord and a "Culture of Poverty"; consequently, a new vehicle for rural community reorganization is needed, particularly for low-income rural Appalachian communities. An alternative for non-conventional development should…

  3. Parents' Experiences with Childhood Deafness: Implications for Family-Centered Services

    ERIC Educational Resources Information Center

    Jackson, Carla Wood; Traub, Randi J.; Turnbull, Ann P.

    2008-01-01

    In response to the need for family-centered follow-up, this study examined parents' experiences with deafness after early identification. Qualitative inquiry methods were used to explore and describe the perceptions and experiences of nine parents of children identified with severe to profound deafness. Parents participated in face-to-face…

  4. African American Factors for Student Success: Implications for Families and Counselors

    ERIC Educational Resources Information Center

    Herndon, Michael K.; Moore, James L., III

    2002-01-01

    Many students who navigate the terrain of higher education often seek support during their journeys through college. The purpose of this article is to examine the different kinds of support African American students receive from family during the college years. After doing a comprehensive review of the literature on word combinations such as…

  5. Identification and Characterization of New Family Members in the Tautomerase Superfamily: Analysis and Implications

    PubMed Central

    Huddleston, Jamison P.; Burks, Elizabeth A.; Whitman, Christian P.

    2014-01-01

    Tautomerase superfamily members are characterized by a β–α–β building block and a catalytic amino terminal proline. 4-oxalocrotonate tautomerase (4-OT) and malonate semialdehyde decarboxylase (MSAD) are the title enzymes of two of the five known families in the superfamily. Two recent developments in these families indicate that there might be more metabolic diversity in the tautomerase superfamily than previously thought. 4-OT homologues have been identified in three biosynthetic pathways, whereas all previously characterized 4-OTs are found in catabolic pathways. In the MSAD family, homologues have been characterized that lack decarboxylase activity, but have a modest hydratase activity using 2-oxo-3-pentynoate. This observation stands in contrast to the first characterized MSAD, which is a proficient decarboxylase and a less efficient hydratase. The hydratase activity was thought to be a vestigial and promiscuous activity. However, this recent discovery suggests that the hydratase activity might reflect a new activity in the MSAD family for an unknown substrate. These discoveries open up new avenues of research in the tautomerase superfamily. PMID:25219626

  6. Transnational Intergenerationalities: Cultural Learning in Polish Migrant Families and Its Implications for Pedagogy

    ERIC Educational Resources Information Center

    Sime, Daniela; Pietka-Nykaza, Emilia

    2015-01-01

    In this qualitative study, we examine the impact of family migration on intergenerational learning, especially in relation to the transmission of cultural values and practices. Drawing on data collected through in-depth case studies with migrant Polish children and their parents, we explore the influence of intergenerationality on children's…

  7. Understanding Stepfamilies: Implications for Assessment and Treatment. Family Psychology and Counseling Series.

    ERIC Educational Resources Information Center

    Huntley, Debra K., Ed.; Carlson, Jon, Ed.

    It is estimated that between 33% and 40% of all United States children will live with a stepfamily. Due to the complexity, ambiguous roles, negative perceptions, and unrealistic expectations of many stepfamilies, members of such families are increasingly being seen by mental health professionals. This monograph is aimed at professionals to help…

  8. Interpersonal Relatedness and Psychological Functioning Following Traumatic Brain Injury: Implications for Marital and Family Therapists

    ERIC Educational Resources Information Center

    Bay, Esther H.; Blow, Adrian J.; Yan, Xie

    2012-01-01

    Recovery from a mild-to-moderate traumatic brain injury (TBI) is a challenging process for injured persons and their families. Guided by attachment theory, we investigated whether relationship conflict, social support, or sense of belonging were associated with psychological functioning. Community-dwelling persons with TBI (N = 75) and their…

  9. Family Mobility and Neighborhood Change: New Evidence and Implications for Community Initiatives

    ERIC Educational Resources Information Center

    Coulton, Claudia; Theodos, Brett; Turner, Margery A.

    2009-01-01

    Americans change residences frequently. Residential mobility can reflect positive changes in a family's circumstances or be a symptom of instability and insecurity. Mobility may also change neighborhoods as a whole. To shed light on these challenges, this report uses a unique survey conducted for the "Making Connections" initiative. The first…

  10. [The relation between the nursing team and patient's family: implications for care].

    PubMed

    Squassante, Nilcéia Dadalto; Alvim, Neide Aparecida Titonelli

    2009-01-01

    Study of qualitative nature, developed along with the nursing team and the accompanying relatives of interned customers in a public hospital at Vitória/ES. The objectives were to describe the bases that sustain the relations among those subjects; to analyze the dynamics of this relation; and to discuss its implications for the nursing care. The theoretical reference was linked to the studies of power relations in the disciplined hospital environment and the care in a humanized perspective concept. The data collection was through a participant observation and semi-structured interviews. The results pointed out that those relations don't happen lineally. At same time that conflicting experiences emerge, there is another whose position of one and other subject reveals sensibility and solidarity that implicate directly in the delivered care to the hospitalized customer. PMID:19219348

  11. Production of MMP-9 and inflammatory cytokines by Trypanosoma cruzi-infected macrophages.

    PubMed

    de Pinho, Rosa Teixeira; da Silva, Wellington Seguins; de Castro Côrtes, Luzia Monteiro; da Silva Vasconcelos Sousa, Periela; de Araujo Soares, Renata Oliveira; Alves, Carlos Roberto

    2014-12-01

    Matrix metalloproteinases (MMPs) constitute a large family of Zn(2+) and Ca(2+) dependent endopeptidases implicated in tissue remodeling and chronic inflammation. MMPs also play key roles in the activation of growth factors, chemokines and cytokines produced by many cell types, including lymphocytes, granulocytes, and, in particular, activated macrophages. Their synthesis and secretion appear to be important in a number of physiological processes, including the inflammatory process. Here, we investigated the interaction between human and mouse macrophages with T. cruzi Colombian and Y strains to characterize MMP-9 and cytokine production in this system. Supernatants and total extract of T. cruzi infected human and mouse macrophages were obtained and used to assess MMP-9 profile and inflammatory cytokines. The presence of metalloproteinase activity was determined by zymography, enzyme-linked immunosorbent assay and immunoblotting assays. The effect of cytokines on MMP-9 production in human macrophages was verified by previous incubation of cytokines on these cells in culture, and analyzed by zymography. We detected an increase in MMP-9 production in the culture supernatants of T. cruzi infected human and mouse macrophages. The addition of IL-1β or TNF-α to human macrophage cultures increased MMP-9 production. In contrast, MMP-9 production was down-modulated when human macrophage cultures were treated with IFN-γ or IL-4 before infection. Human macrophages infected with T. cruzi Y or Colombian strains produced increased levels of MMP-9, which was related to the production of cytokines such as IL-1β, TNF-α and IL-6. PMID:25448360

  12. The cytokine network in HIV infection.

    PubMed

    Alfano, M; Poli, G

    2002-12-01

    Cytokines are major controller of HIV replication and represent, at the same time, a target for viral-induced immune dysregulation. This mutual relationship has profound implications for both active HIV replication and immune-mediated governance of latency; in addition, cytokines have therapeutic value in the perspective of immune reconstitution. In the current article we will review the most relevant aspects emerged in almost 20 years of research in this area with particular reference to the distinct, but interconnected contribution of the most simple (cell lines) to the most complex (animal) models of HIV infection. PMID:12462389

  13. Cytokines in the perinatal period - Part II.

    PubMed

    Chau, A; Markley, J C; Juang, J; Tsen, L C

    2016-05-01

    A contemporary, robust immunologic explanation for common obstetric conditions remains elusive; why some pregnant women are more susceptible to developing preeclampsia or preterm labor is not completely understood. We explore the immunology behind four important and commonly encountered pregnancy-related conditions: preeclampsia, recurrent miscarriage, preterm labor and gestational diabetes. For each condition, we summarize the current understanding of cytokines implicated in the pathogenesis, discuss the impact of anesthesia and analgesia on selected cytokine profiles, and suggest potential opportunities for clinical and research interventions. PMID:26971652

  14. Increased Th2 cytokine secretion, eosinophilic airway inflammation, and airway hyperresponsiveness in neurturin-deficient mice.

    PubMed

    Michel, Tatiana; Thérésine, Maud; Poli, Aurélie; Domingues, Olivia; Ammerlaan, Wim; Brons, Nicolaas H C; Hentges, François; Zimmer, Jacques

    2011-06-01

    Neurotrophins such as nerve growth factor and brain-derived neurotrophic factor have been described to be involved in the pathogenesis of asthma. Neurturin (NTN), another neurotrophin from the glial cell line-derived neurotrophic factor family, was shown to be produced by human immune cells: monocytes, B cells, and T cells. Furthermore, it was previously described that the secretion of inflammatory cytokines was dramatically stimulated in NTN knockout (NTN(-/-)) mice. NTN is structurally similar to TGF-β, a protective cytokine in airway inflammation. This study investigates the implication of NTN in a model of allergic airway inflammation using NTN(-/-) mice. The bronchial inflammatory response of OVA-sensitized NTN(-/-) mice was compared with wild-type mice. Airway inflammation, Th2 cytokines, and airway hyperresponsiveness (AHR) were examined. NTN(-/-) mice showed an increase of OVA-specific serum IgE and a pronounced worsening of inflammatory features. Eosinophil number and IL-4 and IL-5 concentration in the bronchoalveolar lavage fluid and lung tissue were increased. In parallel, Th2 cytokine secretion of lung draining lymph node cells was also augmented when stimulated by OVA in vitro. Furthermore, AHR was markedly enhanced in NTN(-/-) mice after sensitization and challenge when compared with wild-type mice. Administration of NTN before challenge with OVA partially rescues the phenotype of NTN(-/-) mice. These findings provide evidence for a dampening role of NTN on allergic inflammation and AHR in a murine model of asthma. PMID:21508262

  15. [Cytokines and osteogenesis].

    PubMed

    Fujiwara, Makoto; Ozono, Keiichi

    2014-06-01

    Many cytokines associate with proliferation, differentiation and activation of osteoblasts which have an important role in osteogenesis. TGF-β, BMP, IGF, FGF, Hedgehog, Notch, IL and WNT signaling pathways and their inhibitors have been revealed to correlate to osteogenesis, and those gene mutations have been shown to cause various bone disorders. It has been suggested that there are common pathways or crosstalk in these cytokine signaling each other, but mechanism of their complicated regulation on osteogenesis has been unclear. It was expected that the knowledge about these cytokines will apply to clinical therapies of bone diseases. PMID:24870835

  16. Autism in DSM-5 under the microscope: implications to patients, families, clinicians, and researchers.

    PubMed

    Fung, Lawrence K; Hardan, Antonio Y

    2014-10-01

    The changes in the diagnostic classification of the pervasive developmental disorders from the 4th edition of the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV) to DSM-5 are expected to affect patients with autism, their families, as well as clinicians and researchers in the field of autism. This article reviews the new DSM-5 diagnostic criteria for Autism Spectrum Disorder (ASD) and Social Communication Disorder (SCD), and discusses potential consequences in the perspectives of major stakeholders. PMID:25219947

  17. An extinct Eocene taxon of the daisy family (Asteraceae): evolutionary, ecological and biogeographical implications

    PubMed Central

    Barreda, Viviana D.; Palazzesi, Luis; Katinas, Liliana; Crisci, Jorge V.; Tellería, María C.; Bremer, Kåre; Passala, Mauro G.; Bechis, Florencia; Corsolini, Rodolfo

    2012-01-01

    Background and Aims Morphological, molecular and biogeographical information bearing on early evolution of the sunflower alliance of families suggests that the clade containing the extant daisy family (Asteraceae) differentiated in South America during the Eocene, although palaeontological studies on this continent failed to reveal conclusive support for this hypothesis. Here we describe in detail Raiguenrayun cura gen. & sp. nov., an exceptionally well preserved capitulescence of Asteraceae recovered from Eocene deposits of northwestern Patagonia, Argentina. Methods The fossil was collected from the 47·5 million-year-old Huitrera Formation at the Estancia Don Hipólito locality, Río Negro Province, Argentina. Key Results The arrangement of the capitula in a cymose capitulescence, the many-flowered capitula with multiseriate–imbricate involucral bracts and the pappus-like structures indicate a close morphological relationship with Asteraceae. Raiguenrayun cura and the associated pollen Mutisiapollis telleriae do not match exactly any living member of the family, and clearly represent extinct taxa. They share a mosaic of morphological features today recognized in taxa phylogenetically close to the root of Asteraceae, such as Stifftieae, Wunderlichioideae and Gochnatieae (Mutisioideae sensu lato) and Dicomeae and Oldenburgieae (Carduoideae), today endemic to or mainly distributed in South America and Africa, respectively. Conclusions This is the first fossil genus of Asteraceae based on an outstandingly preserved capitulescence that might represent the ancestor of Mutisioideae–Carduoideae. It might have evolved in southern South America some time during the early Palaeogene and subsequently entered Africa, before the biogeographical isolation of these continents became much more pronounced. The new fossil represents the first reliable point for calibration, favouring an earlier date to the split between Barnadesioideae and the rest of Asteraceae than previously

  18. Suicidal Ideation in a Population-Based Sample of Adolescents: Implications for Family Medicine Practice

    PubMed Central

    Hamelin, Gail P.; Granger, Stephen J. R.

    2013-01-01

    Introduction. This study investigated the relationship between suicidal ideation and demographic characteristics, health conditions, depression, and health care utilization patterns among adolescents. Methods. Secondary analysis of the regionally representative Canadian Community Health Survey conducted in 2000/2001 (response rate 85%). Adolescents aged 15 to 19 who reported suicidal ideation in the previous year (n = 260) were compared with their peers who did not (n = 5528). The association between suicidal ideation and socio-demographic and health characteristics were investigated. Findings. Almost three-quarters (73%) of suicidal adolescents had not spoken with any health professional about mental health issues in the preceding year. Despite the fact that 80% of suicidal adolescents had regular contact with their family doctor, only 5% had consulted with them about mental health issues. In addition to the well-known risk factors of depression and stress, suicidal ideation was highly elevated in adolescents with two or more chronic health conditions, self-reported poor health, migraines, and back pain and those whose activities were prevented by pain (P < .05). Other characteristics significantly correlated with suicidal ideation included smoking, living in single parent families, and having lower levels of social support. Conclusions. Family physicians should regularly screen for suicidal thoughts in their adolescent patients with these characteristics. PMID:24967322

  19. Implications of living with a strong family history of breast cancer.

    PubMed

    Maheu, Christine

    2009-06-01

    The findings presented here are from a qualitative study in which data were gathered from 20 women who had received inconclusive genetic testing results for inherited breast cancer susceptibility. Before describing the significance, for them, of their genetic test results, all of the participants related what it was like to live with a strong family history of breast cancer. The focus of this article is the women's experience of living with a personal and strong family history of breast cancer. For these women, having such a history had become a fact of life that could not be ignored.Three themes were identified in the data: expecting and dealing with a diagnosis of breast cancer protecting oneself and others, and increasing exposure to cancer screening procedures. These themes address the underlying reality that having a personal and family history of breast cancer is not an isolated situation but part of one's journey in choosing to undergo genetic testing for inherited breast cancer susceptibility. PMID:19650516

  20. Emerging roles of NudC family: from molecular regulation to clinical implications.

    PubMed

    Fu, Qiqin; Wang, Wei; Zhou, Tianhua; Yang, Yuehong

    2016-05-01

    Nuclear distribution gene C (NudC) was first found in Aspergillus nidulans as an upstream regulator of NudF, whose mammalian homolog is Lissencephaly 1 (Lis1). NudC is conserved from fungi to mammals. Vertebrate NudC has three homologs: NudC, NudC-like protein (NudCL), and NudC-like protein 2 (NudCL2). All members of the NudC family share a conserved p23 domain, which possesses chaperone activity both in conjunction with and independently of heat shock protein 90 (Hsp90). Our group and the others found that NudC homologs were involved in cell cycle regulation by stabilizing the components of the LIS1/dynein complex. Additionally, NudC plays important roles in cell migration, ciliogenesis, thrombopoiesis, and the inflammatory response. It has been reported that NudCL is essential for the stability of the dynein intermediate chain and ciliogenesis via its interaction with the dynein 2 complex. Our data showed that NudCL2 regulates the LIS1/dynein pathway by stabilizing LIS1 with Hsp90 chaperone. The fourth distantly related member of the NudC family, CML66, a tumor-associated antigen in human leukemia, contains a p23 domain and appears to promote oncogenesis by regulating the IGF-1R-MAPK signaling pathway. In this review, we summarize our current knowledge of the NudC family and highlight its potential clinical relevance. PMID:26965524

  1. Role of HLA, KIR, MICA, and Cytokines Genes in Leprosy

    PubMed Central

    Jarduli, Luciana Ribeiro; Sell, Ana Maria; Reis, Pâmela Guimarães; Ayo, Christiane Maria; Mazini, Priscila Saamara; Alves, Hugo Vicentin; Teixeira, Jorge Juarez Vieira; Visentainer, Jeane Eliete Laguila

    2013-01-01

    Many genes including HLA, KIR, and MICA genes, as well as polymorphisms in cytokines have been investigated for their role in infectious disease. HLA alleles may influence not only susceptibility or resistance to leprosy, but also the course of the disease. Some combinations of HLA and KIR may result in negative as well as positive interactions between NK cells and infected host cells with M. leprae, resulting in activation or inhibition of NK cells and, consequently, in death of bacillus. In addition, studies have demonstrated the influence of MICA genes in the pathogenesis of leprosy. Specifically, they may play a role in the interaction between NK cells and infected cells. Finally, pro- and anti-inflammatory cytokines have been influencing the clinical course of leprosy. Data from a wide variety of sources support the existence of genetic factors influencing the leprosy pathogenesis. These sources include twin studies, segregation analyses, family-based linkage and association studies, candidate gene association studies, and, most recently, genome-wide association studies (GWAS). The purpose of this brief review was to highlight the importance of some immune response genes and their correlation with the clinical forms of leprosy, as well as their implications for disease resistance and susceptibility. PMID:23936864

  2. Research Review: The Role of Cytokines in Depression in Adolescents: A Systematic Review

    ERIC Educational Resources Information Center

    Mills, Natalie T.; Scott, James G.; Wray, Naomi R.; Cohen-Woods, Sarah; Baune, Bernhard T.

    2013-01-01

    Background: While cytokines have been implicated in the pathophysiology of depression in adults, the potential role in younger age groups such as adolescents is less clear. This article therefore reviews the literature (a) to explore the relationship between cytokines and depression in adolescents, and (b) to examine how cytokines may be related…

  3. Clinical and Translational Implications for the Caveolin Gene Family: Lessons from Mouse Models and Human Genetic Disorders

    PubMed Central

    Mercier, Isabelle; Jasmin, Jean Francois; Pavlides, Stephanos; Minetti, Carlo; Flomenberg, Neal; Pestell, Richard G.; Frank, Philippe G.; Sotgia, Federica; Lisanti, Michael P.

    2009-01-01

    Here, we review the clinical and translational implications of the caveolin gene family for understanding the pathogenesis of human diseases, including breast and prostate cancers, pulmonary hypertension, cardiomyopathy, diabetes, and muscular dystrophy. Detailed phenotypic analysis of caveolin knock-out mice has served to highlight the crucial role of a caveolin-deficiency in the pathogenesis of many human disease processes. Mutations in the human caveolin genes are associated with a number of established genetic disorders (such as breast cancer, lipodystrophy, muscular dystrophy, and cardiomyopathy), making the caveolins important and novel targets for drug development. The implementation of new strategies for caveolin-replacement therapy—including caveolin-mimetic peptides—is ongoing. PMID:19333235

  4. Functional conservation of suppressors of cytokine signaling proteins between teleosts and mammals: Atlantic salmon SOCS1 binds to JAK/STAT family members and suppresses type I and II IFN signaling.

    PubMed

    Skjesol, Astrid; Liebe, Theresa; Iliev, Dimitar B; Thomassen, Ernst I S; Tollersrud, Linn Greiner; Sobhkhez, Mehrdad; Lindenskov Joensen, Lisbeth; Secombes, Christopher J; Jørgensen, Jorunn B

    2014-07-01

    Suppressor of cytokine signaling (SOCS) proteins are crucially involved in the control of inflammatory responses through their impact on various signaling pathways including the JAK/STAT pathway. Although all SOCS protein family members are identified in teleost fish, their functional properties in non-mammalian vertebrates have not been extensively studied. To gain further insight into SOCS functions in bony fish, we have identified and characterized the Atlantic salmon (Salmo salar) SOCS1, SOCS2 and CISH genes. These genes exhibited sequence conservation with their mammalian counterparts and they were ubiquitously expressed. SOCS1 in mammalian species has been recognized as a key negative regulator of interferon (IFN) signaling and recent data for the two model fish Tetraodon (Tetraodon nigroviridis) and zebrafish (Danio rerio) suggest that these functions are conserved from teleost to mammals. In agreement with this we here demonstrate a strong negative regulatory activity of salmon SOCS1 on type I and type II IFN signaling, while SOCS2a and b and CISH only moderately affected IFN responses. SOCS1 also inhibited IFNγ-induced nuclear localization of STAT1 and a direct interaction between SOCS1 and STAT1 and between SOCS1 and the Tyk2 kinase was found. Using SOCS1 mutants lacking either the KIR domain or the ESS, SH2 and SOCS box domains showed that all domains affected the ability of SOCS1 to inhibit IFN-mediated signaling. These results are the first to demonstrate that SOCS1 is a potent inhibitor of IFN-mediated JAK-STAT signaling in teleost fish. PMID:24582990

  5. [Immunostimulating drugs and cytokines].

    PubMed

    Lehners, Nicola; Goldschmidt, Hartmut; Raab, Marc S

    2011-11-01

    Cytokines are essential regulators of hematopoesis and the immune system. Genetic engineering of recombinant cytokines has facilitated their implementation in many clinical areas. In the field of oncology the granulopoetic human growth factors G-CSF and GM-CSF are of particular importance. They can be applied to prevent chemotherapy induced neutropenia. Furthermore, they allow for mobilization of hematopoetic stem cells in order to obtain peripheral blood stem cell transplants. Another class of cytokines, the interferons, possess immunomodulating, antiproliferative, and antiviral properties. While the significance of interferon alfa as an antitumor agent is dwindling, it still plays a very important role in the therapy of chronic hepatitis b and c. Interferon beta is successfully used to treat multiple sclerosis. Among the heterogenous group of interleukines in particular interleukin 2 has reached clinical practice as an immunostimulating agent in the therapy of metastatic renal cell carcinoma. Many other cytokines have yet to undergo clinical trials. PMID:22045528

  6. Alternative Reproductive Technologies: Implications for Children and Families. Hearing before the Select Committee on Children, Youth, and Families. House of Representatives, One Hundredth Congress, First Session (May 21, 1987).

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. House Select Committee on Children, Youth, and Families.

    A hearing was held for the purpose of receiving testimony about alternative reproductive technologies and their implications for children, families, and society. Testimony provided: (1) a comparison of in vitro fertilization and gamete intrafallopian transfer, and trends in in vitro fertilization; (2) a summary of definitions, statistics, and the…

  7. Meeting demand for family planning within a generation: prospects and implications at country level

    PubMed Central

    Choi, Yoonjoung; Fabic, Madeleine Short; Hounton, Sennen; Koroma, Desmond

    2015-01-01

    Background In order to track progress towards the target of universal access to sexual and reproductive health care services of the post-2015 Sustainable Development Goals (SDGs), a measure (demand for family planning satisfied with modern contraceptive methods) and a benchmark (at least 75% by 2030 in all countries) have been recommended. Objectives The goal of this study was to assess the prospects of reaching the benchmark at the country level. Such information can facilitate strategic planning, including resource allocation at global and country levels. Design We selected 63 countries based on their status as least developed according to the United Nations or as a priority country in global family planning initiatives. Using United Nations estimates and projections of family planning indicators between 1970 and 2030, we calculated percent demand for family planning satisfied with modern contraceptive methods for each year and country. We then calculated the annual percentage point changes between 2014 and 2030 required to meet the benchmark. The required rates of change were compared to current projections as well as estimates between 1970 and 2010. Results To reach the benchmark on average across the 63 countries, demand satisfied with modern methods must increase by 2.2 percentage points per year between 2014 and 2030 – more than double current projections. Between 1970 and 2010, such rapid progress was observed in 24 study countries but typically spanning 5–10 years. At currently projected rates, only 9 of the 63 study countries will reach the benchmark. Meanwhile, the gap between projected and required changes is largest in the Central and West African regions, 0.9 and 3.0 percentage points per year, respectively. If the benchmark is achieved, 334 million women across the study countries will use a modern contraceptive method in 2030, compared to 226 million women in 2014. Conclusions In order to achieve the component of the SDGs calling for universal

  8. All subtypes of the Pmp adhesin family are implicated in chlamydial virulence and show species-specific function

    PubMed Central

    Becker, Elisabeth; Hegemann, Johannes H

    2014-01-01

    The bacterial pathogens Chlamydia trachomatis and C. pneumoniae are obligate intracellular parasites, cause a number of serious diseases, and can infect various cell types in humans. Chlamydial infections are probably initiated by binding of the bacterial outer membrane protein OmcB to host cell glycosaminoglycans (GAGs). Here, we show that all nine members of the polymorphic membrane protein (Pmp) family of C. trachomatis mediate adhesion to human epithelial and endothelial cells. Importantly, exposure of infectious particles to soluble recombinant Pmps blocks subsequent infection, thus implicating an important function of the entire protein family in the infection process. Analogous experiments with pairs of recombinant Pmps or a combination of Pmp and OmcB revealed that all Pmps probably act in an adhesion pathway that is distinct from the OmcB-GAG pathway. Finally, we provide evidence that the Pmps of C. trachomatis and C. pneumoniae exhibit species and tissue specificity. These findings argue for the involvement of C. trachomatis Pmps in the initial phase of infection and suggest that they may interact with a receptor other than the epidermal growth factor receptor recently identified for their counterparts in C. pneumoniae. PMID:24985494

  9. Familial glaucoma iridogoniodysplasia maps to a 6p25 region implicated in primary congenital glaucoma and iridogoniodysgenesis anomaly.

    PubMed Central

    Jordan, T; Ebenezer, N; Manners, R; McGill, J; Bhattacharya, S

    1997-01-01

    Familial glaucoma iridogoniodysplasia (FGI) is a form of open-angle glaucoma in which developmental anomalies of the iris and irido-corneal angle are associated with a juvenile-onset glaucoma transmitted as an autosomal dominant trait. A single large family with this disorder was examined for genetic linkage to microsatellite markers. A peak LOD score of 11.63 at a recombination fraction of 0 was obtained with marker D6S967 mapping to chromosome 6p25. Haplotype analysis places the disease gene in a 6.4-cM interval between the markers D6S1713 and D6S1600. Two novel clinical appearances extend the phenotypic range and provide evidence of variable expressivity. The chromosome 6p25 region is now implicated in FGI, primary congenital glaucoma, and iridogoniodysgenesis anomaly. This may indicate the presence of a common causative gene or, alternatively, a cluster of genes involved in eye development/function. Images Figure 2 PMID:9382099

  10. A Novel Predicted Calcium-Regulated Kinase Family Implicated in Neurological Disorders

    PubMed Central

    Dudkiewicz, Małgorzata; Lenart, Anna; Pawłowski, Krzysztof

    2013-01-01

    The catalogues of protein kinases, the essential effectors of cellular signaling, have been charted in Metazoan genomes for a decade now. Yet, surprisingly, using bioinformatics tools, we predicted protein kinase structure for proteins coded by five related human genes and their Metazoan homologues, the FAM69 family. Analysis of three-dimensional structure models and conservation of the classic catalytic motifs of protein kinases present in four out of five human FAM69 proteins suggests they might have retained catalytic phosphotransferase activity. An EF-hand Ca2+-binding domain in FAM69A and FAM69B proteins, inserted within the structure of the kinase domain, suggests they may function as Ca2+-dependent kinases. The FAM69 genes, FAM69A, FAM69B, FAM69C, C3ORF58 (DIA1) and CXORF36 (DIA1R), are by large uncharacterised molecularly, yet linked to several neurological disorders in genetics studies. The C3ORF58 gene is found deleted in autism, and resides in the Golgi. Unusually high cysteine content and presence of signal peptides in some of the family members suggest that FAM69 proteins may be involved in phosphorylation of proteins in the secretory pathway and/or of extracellular proteins. PMID:23840464

  11. Family-based association analysis implicates IL-4 in susceptibility to Kawasaki disease

    PubMed Central

    Burns, JC; Shimizu, C; Shike, H; Newburger, JW; Sundel, RP; Baker, AL; Matsubara, T; Ishikawa, Y; Brophy, VA; Cheng, S; Grow, MA; Steiner, LL; Kono, N; Cantor, RM

    2010-01-01

    Several compelling lines of evidence suggest an important influence of genetic variation in susceptibility to Kawasaki disease (KD), an acute vasculitis that causes coronary artery aneurysms in children. We performed a family-based genotyping study to test for association between KD and 58 genes involved in cardiovascular disease and inflammation. By analysis of a cohort of 209 KD trios using the transmission disequilibrium test, we documented the asymmetric transmission of five alleles including the interleukin-4 (IL-4) C(−589)T allele (P = 0.03). Asymmetric transmission of the IL-4 C(−589)T was replicated in a second, independent cohort of 60 trios (P = 0.05, combined P = 0.002). Haplotypes of alleles in IL-4, colony-stimulating factor 2 (CSF2), IL-13, and transcription factor 7 (TCF7), all located in the interleukin gene cluster on 5q31, were also asymmetrically transmitted. The reported associations of KD with atopic dermatitis and allergy, elevated serum IgE levels, eosinophilia, and increased circulating numbers of monocyte/macrophages expressing the low-affinity IgE receptor (FCεR2) may be related to effects of IL-4. Thus, the largest family-based genotyping study of KD patients to date suggests that genetic variation in the IL-4 gene, or regions linked to IL-4, plays an important role in KD pathogenesis and disease susceptibility. PMID:15889128

  12. Asymmetry in Family History Implicates Nonstandard Genetic Mechanisms: Application to the Genetics of Breast Cancer

    PubMed Central

    Weinberg, Clarice R.; Shi, Min; DeRoo, Lisa A.; Taylor, Jack A.; Sandler, Dale P.; Umbach, David M.

    2014-01-01

    Genome-wide association studies typically target inherited autosomal variants, but less studied genetic mechanisms can play a role in complex disease. Sex-linked variants aside, three genetic phenomena can induce differential risk in maternal versus paternal lineages of affected individuals: 1. maternal effects, reflecting the maternal genome's influence on prenatal development; 2. mitochondrial variants, which are inherited maternally; 3. autosomal genes, whose effects depend on parent of origin. We algebraically show that small asymmetries in family histories of affected individuals may reflect much larger genetic risks acting via those mechanisms. We apply these ideas to a study of sisters of women with breast cancer. Among 5,091 distinct families of women reporting that exactly one grandmother had breast cancer, risk was skewed toward maternal grandmothers (p<0.0001), especially if the granddaughter was diagnosed between age 45 and 54. Maternal genetic effects, mitochondrial variants, or variant genes with parent-of-origin effects may influence risk of perimenopausal breast cancer. PMID:24651610

  13. SHOX nullizygosity and haploinsufficiency in a Japanese family: implication for the development of Turner skeletal features.

    PubMed

    Ogata, Tsutomu; Muroya, Koji; Sasaki, Goro; Nishimura, Gen; Kitoh, Hiroshi; Hattori, Tadashi

    2002-03-01

    We report on clinical and molecular findings in a Japanese family consisting of a male infant with SHOX nullizygosity and his four family members with SHOX haploinsufficiency. The male infant had Langer mesomelic dysplasia, the prepubertal sister had idiopathic short stature phenotype with no discernible skeletal features, the father had mild Léri-Weill dyschondrosteosis (LWDC), and the mother and the maternal grandmother had moderate LWDC. The five subjects lacked clinically recognizable short metacarpals, cubitus valgus, high arched palate, short neck, and micrognathia, as well as recurrent otitis media and hearing loss. Fluorescence in situ hybridization and sequence analyses showed that the proband had a pseudoautosomal microdeletion involving SHOX and a C502T missense mutation in the homeobox domain at exon 4, and that the father was heterozygous for the SHOX deletion, and the sister, the mother, and the grandmother were heterozygous for the C502T mutation. The results, in conjunction with the previous findings, suggest that mesomelic skeletal features such as Langer mesomelic dysplasia and LWDC, which are absent or rare in Turner syndrome, are primarily caused by the SHOX dosage effect and the bone maturing effect of gonadal estrogens, whereas other skeletal features such as short metacarpals, cubitus valgus, and various craniofacial and cervical skeletal stigmata, which are common in Turner syndrome, are largely contributed by a compressive effect of distended lymphatics and lymphedema on the developing skeletal tissues. PMID:11889214

  14. The "Stolen Generations" and Cultural Genocide: The Forced Removal of Australian Indigenous Children from Their Families and Its Implications for the Sociology of Childhood.

    ERIC Educational Resources Information Center

    van Krieken, Robert

    1999-01-01

    Examined the development and outcomes of Australian government policy of forced child removal from Aboriginal families. Discusses policy antecedents, its surrounding philosophy and politics, and the emergence of a more critical understanding of this policy in recent years. Examines the general implications of this history for the sociology of…

  15. [Plant-Producers Of Recombinant Cytokines (Review)].

    PubMed

    Burlakovskii, M S; Yemel'yanov, V V; Lutova, L A

    2016-01-01

    Cytokines are a family of signaling polypeptides involved in cell-cell interactions in the process of the immune response, as well as in the regulation of a number of normal physiological functions. Cytokines are used in medicine for the treatment of cancer, immune disorders, viral infections, and other socially significant diseases, but the extent of their use is limited by the high production cost of the active agent. The development of this area of pharmacology is associated with the success of genetic engineering, which allows the production of significant amounts of protein by transgenic organisms. The review discusses the latest advances in the production of various cytokines with the use of genetically modified plants. PMID:27266244

  16. Destabilization of DJ-1 by familial substitution and oxidative modifications: implications for Parkinson's disease.

    PubMed

    Hulleman, John D; Mirzaei, Hamid; Guigard, Emmanuel; Taylor, Kellie L; Ray, Soumya S; Kay, Cyril M; Regnier, Fred E; Rochet, Jean-Christophe

    2007-05-15

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by oxidative stress and protein aggregation. Both toxic phenomena are mitigated by DJ-1, a homodimeric protein with proposed antioxidant and chaperone activities. The neuroprotective function of DJ-1 is modulated by oxidation of cysteine 106, a residue that may act as an oxidative stress sensor. Loss-of-function mutations in the DJ-1 gene have been linked to early onset PD, and age-dependent over-oxidation of DJ-1 is thought to contribute to sporadic PD. The familial mutant L166P fails to dimerize and is rapidly degraded, suggesting that protein destabilization accounts for the dysfunction of this mutant. In this study, we investigated how the structure and stability of DJ-1 are impacted by two other pathogenic substitutions (M26I and E64D) and by over-oxidation with H2O2. Whereas the recombinant wild-type protein and E64D both adopted a stable dimeric structure, M26I showed an increased propensity to aggregate and decreased secondary structure. Similar to M26I, over-oxidized wild-type DJ-1 exhibited reduced secondary structure, and this property correlated with destabilization of the dimer. The engineered mutant C106A had a greater thermodynamic stability and was more resistant to oxidation-induced destabilization than the wild-type protein. These results suggest that (i) the M26I substitution and over-oxidation destabilize dimeric DJ-1, and (ii) the oxidation of cysteine 106 contributes to DJ-1 destabilization. Our findings provide a structural basis for DJ-1 dysfunction in familial and sporadic PD, and they suggest that dimer stabilization is a reasonable therapeutic strategy to treat both forms of this disorder. PMID:17451229

  17. Cytokine inhibition in the treatment of COPD.

    PubMed

    Caramori, Gaetano; Adcock, Ian M; Di Stefano, Antonino; Chung, Kian Fan

    2014-01-01

    Cytokines play an important part in many pathobiological processes of chronic obstructive pulmonary disease (COPD), including the chronic inflammatory process, emphysema, and altered innate immune response. Proinflammatory cytokines of potential importance include tumor necrosis factor (TNF)-α, interferon-γ, interleukin (IL)-1β, IL-6, IL-17, IL-18, IL-32, and thymic stromal lymphopoietin (TSLP), and growth factors such as transforming growth factor-β. The current objectives of COPD treatment are to reduce symptoms, and to prevent and reduce the number of exacerbations. While current treatments achieve these goals to a certain extent, preventing the decline in lung function is not currently achievable. In addition, reversal of corticosteroid insensitivity and control of the fibrotic process while reducing the emphysematous process could also be controlled by specific cytokines. The abnormal pathobiological process of COPD may contribute to these fundamental characteristics of COPD, and therefore targeting cytokines involved may be a fruitful endeavor. Although there has been much work that has implicated various cytokines as potentially playing an important role in COPD, there have been very few studies that have examined the effect of specific cytokine blockade in COPD. The two largest studies that have been reported in the literature involve the use of blocking antibody to TNFα and CXCL8 (IL-8), and neither has provided benefit. Blocking the actions of CXCL8 through its CXCR2 receptor blockade was not successful either. Studies of antibodies against IL-17, IL-18, IL-1β, and TSLP are currently either being undertaken or planned. There is a need to carefully phenotype COPD and discover good biomarkers of drug efficacy for each specific target. Specific groups of COPD patients should be targeted with specific anticytokine therapy if there is evidence of high expression of that cytokine and there are features of the clinical expression of COPD that will respond

  18. Cytokines, phagocytes, and pentoxifylline.

    PubMed

    Mandell, G L

    1995-01-01

    Phagocytic cells, such as polymorphonuclear neutrophils, monocytes, and macrophages, are essential for defense against infection caused by a variety of microorganisms. The mechanisms used by these cells to destroy microbes comprise a potent oxidative armamentarium including superoxide, hydrogen peroxide, and hypochlorous acid. In addition, granule contents such as proteolytic enzymes, lysozyme, lactoferrin, and myeloperoxidase are released into the phagosome to destroy ingested microorganisms. Inflammatory cytokines, such as tumor necrosis factor (TNF), interleukin-1 (IL-1), and IL-6, enhance the phagocytic and microbicidal activity of the cells and increase their stickiness. It has been demonstrated in a variety of animal and clinical studies that activated phagocytes can damage the host they are designed to protect, using the mechanisms described above. Alkylxanthines, including pentoxifylline, are potent inhibitors of this inflammatory damage by two major actions: (a) reduction of the production of inflammatory cytokines (especially TNF) by phagocytes stimulated with a variety of microbial products (e.g., endotoxin); and (b) reversal of the effect of these cytokines on phagocytes. Thus, pentoxifylline counteracts the following effects of inflammatory cytokines on phagocytes: increased adherence, shape change resulting in larger size and rigidity, increased oxidative burst, priming for an enhanced oxidative burst, increased degranulation, and decreased chemotactic movement. In addition, these activities synergize with the normal anti-inflammatory mediator adenosine. Alkylxanthines have the potential to be effective therapy for conditions in which inflammatory cytokines and phagocytes cause damage, including the sepsis syndrome, ARDS, AIDS, and arthritis. PMID:8699856

  19. A family of metal-dependent phosphatases implicated in metabolite damage-control.

    PubMed

    Huang, Lili; Khusnutdinova, Anna; Nocek, Boguslaw; Brown, Greg; Xu, Xiaohui; Cui, Hong; Petit, Pierre; Flick, Robert; Zallot, Rémi; Balmant, Kelly; Ziemak, Michael J; Shanklin, John; de Crécy-Lagard, Valérie; Fiehn, Oliver; Gregory, Jesse F; Joachimiak, Andrzej; Savchenko, Alexei; Yakunin, Alexander F; Hanson, Andrew D

    2016-08-01

    DUF89 family proteins occur widely in both prokaryotes and eukaryotes, but their functions are unknown. Here we define three DUF89 subfamilies (I, II, and III), with subfamily II being split into stand-alone proteins and proteins fused to pantothenate kinase (PanK). We demonstrated that DUF89 proteins have metal-dependent phosphatase activity against reactive phosphoesters or their damaged forms, notably sugar phosphates (subfamilies II and III), phosphopantetheine and its S-sulfonate or sulfonate (subfamily II-PanK fusions), and nucleotides (subfamily I). Genetic and comparative genomic data strongly associated DUF89 genes with phosphoester metabolism. The crystal structure of the yeast (Saccharomyces cerevisiae) subfamily III protein YMR027W revealed a novel phosphatase active site with fructose 6-phosphate and Mg(2+) bound near conserved signature residues Asp254 and Asn255 that are critical for activity. These findings indicate that DUF89 proteins are previously unrecognized hydrolases whose characteristic in vivo function is to limit potentially harmful buildups of normal or damaged phosphometabolites. PMID:27322068

  20. Nuclear lamin A inhibits adipocyte differentiation: implications for Dunnigan-type familial partial lipodystrophy.

    PubMed

    Boguslavsky, Revekka L; Stewart, Colin L; Worman, Howard J

    2006-02-15

    Mutations in the LMNA gene encoding A-type lamins cause several diseases, including Emery-Dreifuss muscular dystrophy and Dunnigan-type familial partial lipodystrophy (FPLD). We analyzed differentiation of 3T3-L1 preadipocytes to adipocytes in cells overexpressing wild-type lamin A as well as lamin A with amino acid substitutions at position 482 that cause FPLD. We also examined adipogenic conversion of mouse embryonic fibroblasts lacking A-type lamins. Overexpression of both wild-type and mutant lamin A inhibited lipid accumulation, triglyceride synthesis and expression of adipogenic markers. This was associated with inhibition of expression of peroxisome-proliferator-activated receptor gamma 2 (PPARgamma2) and Glut4. In contrast, embryonic fibroblasts lacking A-type lamins accumulated more intracellular lipid and exhibited elevated de novo triglyceride synthesis compared with wild-type fibroblasts. They also had increased basal phosphorylation of AKT1, a mediator of insulin signaling. We conclude that A-type lamins act as inhibitors of adipocyte differentiation, possibly by affecting PPARgamma2 and insulin signaling. PMID:16415042

  1. Evolutionary Implications and Physicochemical Analyses of Selected Proteins of Type III Polyketide Synthase Family

    PubMed Central

    Mallika, V.; Sivakumar, K.C.; Soniya, E.V.

    2011-01-01

    Type III polyketide synthases have a substantial role in the biosynthesis of various polyketides in plants and microorganisms. Comparative proteomic analysis of type III polyketide synthases showed evolutionarily and structurally related positions in a compilation of amino acid sequences from different families. Bacterial and fungal type III polyketide synthase proteins showed <50% similarity but in higher plants, it exhibited >80% among chalcone synthases and >70% in the case of non-chalcone synthases. In a consensus phylogenetic tree based on 1000 replicates; bacterial, fungal and plant proteins were clustered in separate groups. Proteins from bryophytes and pteridophytes grouped immediately near to the fungal cluster, demonstrated how evolutionary lineage has occurred among type III polyketide synthase proteins. Upon physicochemical analysis, it was observed that the proteins localized in the cytoplasm and were hydrophobic in nature. Molecular structural analysis revealed comparatively stable structure comprising of alpha helices and random coils as major structural components. It was found that there was a decline in the structural stability with active site mutation as prophesied by the in silico mutation studies. PMID:21697991

  2. Intracellular localization of the BCL-2 family member BOK and functional implications

    PubMed Central

    Echeverry, N; Bachmann, D; Ke, F; Strasser, A; Simon, H U; Kaufmann, T

    2013-01-01

    The pro-apoptotic BCL-2 family member BOK is widely expressed and resembles the multi-BH domain proteins BAX and BAK based on its amino acid sequence. The genomic region encoding BOK was reported to be frequently deleted in human cancer and it has therefore been hypothesized that BOK functions as a tumor suppressor. However, little is known about the molecular functions of BOK. We show that enforced expression of BOK activates the intrinsic (mitochondrial) apoptotic pathway in BAX/BAK-proficient cells but fails to kill cells lacking both BAX and BAK or sensitize them to cytotoxic insults. Interestingly, major portions of endogenous BOK are localized to and partially inserted into the membranes of the Golgi apparatus as well as the endoplasmic reticulum (ER) and associated membranes. The C-terminal transmembrane domain of BOK thereby constitutes a ‘tail-anchor' specific for targeting to the Golgi and ER. Overexpression of full-length BOK causes early fragmentation of ER and Golgi compartments. A role for BOK on the Golgi apparatus and the ER is supported by an abnormal response of Bok-deficient cells to the Golgi/ER stressor brefeldin A. Based on these results, we propose that major functions of BOK are exerted at the Golgi and ER membranes and that BOK induces apoptosis in a manner dependent on BAX and BAK. PMID:23429263

  3. Microeconomic loans and health education to families in impoverished communities: implications for the HIV pandemic.

    PubMed

    Sherer, Renslow D; Bronson, John D; Teter, Caroline J; Wykoff, Randolph F

    2004-01-01

    Poverty is among the root causes of death and poor health worldwide. Project HOPE's Village Health Bank (VHB) program is a public health intervention that combines integrated microcredit lending and health education. Groups of 18 to 25 women receive small loans, and biweekly, one-hour health education sessions. Since 1993, about 50,000 women in 949 VHBs have participated in seven countries in the Americas, Africa, and Southeast Asia, receiving more than US$25 million in loans and 8,445 hours of health education. Members of VHBs are charged modest interest rates that enable them to become self-sufficient (eg, able to cover all operating charges, including the costs of the health education staff, and the necessary loan capital to continue without infusion of outside resources). The VHB program produces substantial economic improvements for individuals and groups, and benefits in health knowledge and behaviors, including increased utilization of healthcare services. Data from Guatemala, Malawi, and Thailand demonstrate that VHBs in countries with high HIV prevalence have been comparably successful in spite of the enormous added burdens of chronic illness, deaths, and orphans in need of support. For example, in 2004, 48 percent of 266 VHB members in Malawi experienced at least one death in their household in the preceding year, and 67 percent housed one or more orphans with an average of two orphans per household. Because of the unique combination of increased household economic stability and improved health knowledge, the VHB program is now being adapted to families of people affected by HIV/AIDS, including orphans. PMID:15768731

  4. FEE-SCHEDULE INCREASES IN CANADA: IMPLICATION FOR SERVICE VOLUMES AMONG FAMILY AND SPECIALIST PHYSICIANS.

    PubMed

    Ariste, Ruolz

    2015-01-01

    Physician spending has substantially increased over the last few years in Canada to reach $27.4 billion in 2010. Total clinical payment to physicians has grown at an average annual rate of 7.6% from 2004 to 2010. The key policy question is whether or not this additional money has bought more physician services. So, the purpose of this study is to understand if we are paying more for the same amount of medical services in Canada or we are getting more bangs for our buck. At the same time, the paper attempts to find out whether or not there is a productivity difference between family physician services and surgical procedures. Using the Baumol theory and data from the National Physician Database for the period 2004-2010, the paper breaks down growth in physician remuneration into growth in unit cost and number of services, both from the physician and the payer perspectives. After removing general inflation and population growth from the 7.6% growth in total clinical payment, we found that real payment per service and volume of services per capita grew at an average annual rate of 3.2% and 1.4% respectively, suggesting that payment per service was the main cost driver of physician remuneration at the national level. Taking the payer perspective, it was found that, for the fee-for-service (FFS) scheme, volume of services per physician decreased at an average annual rate of -0.6%, which is a crude indicator that labour productivity of physicians on FFS has fallen during the period. However, the situation differs for the surgical procedures. Results also vary by province. Overall, our finding is consistent with the Baumol theory, which hypothesizes higher productivity growth in technology-driven sectors. PMID:26897992

  5. The complement of family M1 aminopeptidases of Haemonchus contortus--Biotechnological implications.

    PubMed

    Mohandas, Namitha; Young, Neil D; Jabbar, Abdul; Korhonen, Pasi K; Koehler, Anson V; Hall, Ross S; Hu, Min; Hofmann, Andreas; Gasser, Robin B

    2016-01-01

    Although substantial research has been focused on the 'hidden antigen' H11 of Haemonchus contortus as a vaccine against haemonchosis in small ruminants, little is know about this and related aminopeptidases. In the present article, we reviewed genomic and transcriptomic data sets to define, for the first time, the complement of aminopeptidases (designated Hc-AP-1 to Hc-AP-13) of the family M1 with homologues in Caenorhabditis elegans, characterised by zinc-binding (HEXXH) and exo-peptidase (GAMEN) motifs. The three previously published H11 isoforms (accession nos. X94187, FJ481146 and AJ249941) had most sequence similarity to Hc-AP-2 and Hc-AP-8, whereas unpublished isoforms (accession nos. AJ249942 and AJ311316) were both most similar to Hc-AP-3. The aminopeptidases characterised here had homologues in C. elegans. Hc-AP-1 to Hc-AP-8 were most similar in amino acid sequence (28-41%) to C. elegans T07F10.1; Hc-AP-9 and Hc-AP-10 to C. elegans PAM-1 (isoform b) (53-54% similar); Hc-AP-11 and Hc-AP-12 to C. elegans AC3.5 and Y67D8C.9 (26% and 50% similar, respectively); and Hc-AP-13 to C. elegans C42C1.11 and ZC416.6 (50-58% similar). Comparative analysis suggested that Hc-AP-1 to Hc-AP-8 play roles in digestion, metabolite excretion, neuropeptide processing and/or osmotic regulation, with Hc-AP-4 and Hc-AP-7 having male-specific functional roles. The analysis also indicated that Hc-AP-9 and Hc-AP-10 might be involved in the degradation of cyclin (B3) and required to complete meiosis. Hc-AP-11 represents a leucyl/cystinyl aminopeptidase, predicted to have metallopeptidase and zinc ion binding activity, whereas Hc-AP-12 likely encodes an aminopeptidase Q homologue also with these activities and a possible role in gonad function. Finally, Hc-AP-13 is predicted to encode an aminopeptidase AP-1 homologue of C. elegans with hydrolase activity, suggested to operate, possibly synergistically with a PEPT-1 ortholog, as an oligopeptide transporter in the gut for protein uptake

  6. Longitudinal tracking of cytokines after acute exposure to tuberculosis: association of distinct cytokine patterns with protection and disease development.

    PubMed

    Hussain, Rabia; Talat, Najeeha; Shahid, Firdaus; Dawood, Ghaffar

    2007-12-01

    Household contacts (HCs) of patients with tuberculosis (TB) are at higher risk of infection as well as the development of active disease. Longitudinal tracking of antigen-specific cytokines after acute exposure may significantly advance our understanding of the dynamic changes in cytokine patterns associated with disease establishment. To achieve this objective, we carried out a prospective cohort study with healthy HCs after exposure to TB. The patterns of cytokines (gamma interferon [IFN-gamma] and interleukin 10 [IL-10]) in response to mycobacterial antigens (culture filtrate [CF] proteins) and nonspecific mitogens (phytohemagglutinin [PHA] and lipopolysaccharide [LPS]) were assessed at 0, 6, 12, and 24 months after exposure. Seven of 109 (6.4%) HCs developed active disease. Six of the seven individuals were females, and active disease developed between 12 and 15 months after exposure in 5/20 families. The most significant findings were the exponential increases ( approximately 1,000-fold) in both the CF protein- and the PHA- or LPS-induced IFN-gamma/IL-10 ratio in healthy HCs (n = 26), which peaked at 12 months, compared to the levels in HCs who developed disease (n = 7), in whom relatively flat responses were observed during the 24-month period. Linear trends for 0 to 12 and 0 to 24 months for the CF protein-induced IFN-gamma/IL-10 ratio showed significant differences between the two groups, as determined by the use of the Mantel extension test for chi(2) analysis (odds ratio = 0.45; 95% confidence interval = 0.295 to 0.685; P = 0.0002). Our results strongly suggest that the magnitude of the IFN-gamma/IL-10 ratio at 12 months after exposure may be a critical determinant in the resolution of infection. These studies provide new insights into the cytokine responses associated with disease establishment or the resolution of infection after natural exposure to TB and have implications for TB control programs as well vaccine efficacy studies. PMID:17928427

  7. Longitudinal Tracking of Cytokines after Acute Exposure to Tuberculosis: Association of Distinct Cytokine Patterns with Protection and Disease Development▿

    PubMed Central

    Hussain, Rabia; Talat, Najeeha; Shahid, Firdaus; Dawood, Ghaffar

    2007-01-01

    Household contacts (HCs) of patients with tuberculosis (TB) are at higher risk of infection as well as the development of active disease. Longitudinal tracking of antigen-specific cytokines after acute exposure may significantly advance our understanding of the dynamic changes in cytokine patterns associated with disease establishment. To achieve this objective, we carried out a prospective cohort study with healthy HCs after exposure to TB. The patterns of cytokines (gamma interferon [IFN-γ] and interleukin 10 [IL-10]) in response to mycobacterial antigens (culture filtrate [CF] proteins) and nonspecific mitogens (phytohemagglutinin [PHA] and lipopolysaccharide [LPS]) were assessed at 0, 6, 12, and 24 months after exposure. Seven of 109 (6.4%) HCs developed active disease. Six of the seven individuals were females, and active disease developed between 12 and 15 months after exposure in 5/20 families. The most significant findings were the exponential increases (∼1,000-fold) in both the CF protein- and the PHA- or LPS-induced IFN-γ/IL-10 ratio in healthy HCs (n = 26), which peaked at 12 months, compared to the levels in HCs who developed disease (n = 7), in whom relatively flat responses were observed during the 24-month period. Linear trends for 0 to 12 and 0 to 24 months for the CF protein-induced IFN-γ/IL-10 ratio showed significant differences between the two groups, as determined by the use of the Mantel extension test for χ2 analysis (odds ratio = 0.45; 95% confidence interval = 0.295 to 0.685; P = 0.0002). Our results strongly suggest that the magnitude of the IFN-γ/IL-10 ratio at 12 months after exposure may be a critical determinant in the resolution of infection. These studies provide new insights into the cytokine responses associated with disease establishment or the resolution of infection after natural exposure to TB and have implications for TB control programs as well vaccine efficacy studies. PMID:17928427

  8. Role of IL-38 and Its Related Cytokines in Inflammation

    PubMed Central

    Yuan, Xianli; Peng, Xiao; Li, Yan; Li, Mingcai

    2015-01-01

    Interleukin- (IL-) 38 is a recently discovered cytokine and is the tenth member of the IL-1 cytokine family. IL-38 shares structural features with IL-1 receptor antagonist (IL-1Ra) and IL-36Ra. IL-36R is the specific receptor of IL-38, a partial receptor antagonist of IL-36. IL-38 inhibits the production of T-cell cytokines IL-17 and IL-22. IL-38 also inhibits the production of IL-8 induced by IL-36γ, thus inhibiting inflammatory responses. IL-38-related cytokines, including IL-1Ra and IL-36Ra, are involved in the regulation of inflammation and immune responses. The study of IL-38 and IL-38-related cytokines might provide new insights for developing anti-inflammatory treatments in the near future. PMID:25873772

  9. Cytokines in Acute Chikungunya

    PubMed Central

    Venugopalan, Anuradha; Ghorpade, Ravi P.; Chopra, Arvind

    2014-01-01

    Introduction Acute chikungunya (CHIKV) is predominantly an acute onset of excruciatingly painful, self-limiting musculoskeletal (MSK) arbovirus illness and this was further reported by us during the 2006 Indian epidemic [Chopra et al. Epidemiol Infect 2012]. Selected serum cytokines profile in subjects within one month of onset of illness is being presented. Methods Out of 509 clinical CHIKV cases (43% population) identified during a rural population survey, 225 subjects consented blood investigations. 132 examined within 30 days of febrile onset are the study cohort. Anti-CHIKV IgM and IgG antibodies tested by immunochromatography and indirect immunofluorescence respectively. Interferons (IFN)-α, -β and -γ, Interferon Gamma-Induced Protein-10 (CXCL-10/IP-10), Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Interleukin-13 (IL-13), Monocyte Chemoattractant Protein-1 (MCP-1), Interleukin–4 (IL-4) and Interleukin–10 (IL-10) performed by ELISA. Samples collected from neighboring community a year prior to the epidemic used as healthy controls. Results Seropositivity for anti-CHIKV IgM and IgG was 65% and 52% respectively. IFN-α, IFN-β, IFN-γ, CXCL10/IP-10 and IL-1β showed intense response in early acute phase. Cytokines (particularly TNF-α, MCP-1, IL-4, IL-6 and IL-10) was maximum in extended symptomatic phase and remained elevated in recovered subjects. Higher (p<0.05) IFN and IL-4 seen in patients seropositive for anti-CHIKV IgG. Elderly cases (≥65 years) showed elevated cytokines (except IFN) and anti-CHIKV antibodies near similar to younger subjects. Significant correlations (p<0.05) found between cytokines and clinical features (fatigue, low back ache, myalgia) and anti-CHIKV antibodies. Conclusion An intense cytokine milieu was evident in the early and immediate persistent symptomatic phase and in recovered subjects. Early persistent IgM and lower IgG to anti-CHKV and intense Th2 cytokine phenotype seem to be

  10. Interleukin-6, a mental cytokine.

    PubMed

    Spooren, Anneleen; Kolmus, Krzysztof; Laureys, Guy; Clinckers, Ralph; De Keyser, Jacques; Haegeman, Guy; Gerlo, Sarah

    2011-06-24

    Almost a quarter of a century ago, interleukin-6 (IL-6) was discovered as an inflammatory cytokine involved in B cell differentiation. Today, IL-6 is recognized to be a highly versatile cytokine, with pleiotropic actions not only in immune cells, but also in other cell types, such as cells of the central nervous system (CNS). The first evidence implicating IL-6 in brain-related processes originated from its dysregulated expression in several neurological disorders such as multiple sclerosis, Alzheimer's disease and Parkinson's disease. In addition, IL-6 was shown to be involved in multiple physiological CNS processes such as neuron homeostasis, astrogliogenesis and neuronal differentiation. The molecular mechanisms underlying IL-6 functions in the brain have only recently started to emerge. In this review, an overview of the latest discoveries concerning the actions of IL-6 in the nervous system is provided. The central position of IL-6 in the neuroinflammatory reaction pattern, and more specifically, the role of IL-6 in specific neurodegenerative processes, which accompany Alzheimer's disease, multiple sclerosis and excitotoxicity, are discussed. It is evident that IL-6 has a dichotomic action in the CNS, displaying neurotrophic properties on the one hand, and detrimental actions on the other. This is in agreement with its central role in neuroinflammation, which evolved as a beneficial process, aimed at maintaining tissue homeostasis, but which can become malignant when exaggerated. In this perspective, it is not surprising that 'well-meant' actions of IL-6 are often causing harm instead of leading to recovery. PMID:21238488

  11. Structural basis for receptor sharing and activation by interleukin-20 receptor-2 (IL-20R2) binding cytokines

    PubMed Central

    Logsdon, Naomi J.; Deshpande, Ashlesha; Harris, Bethany D.; Rajashankar, Kanagalaghatta R.; Walter, Mark R.

    2012-01-01

    Interleukin 20 (IL-20) is a pleotropic IL-10 family cytokine that protects epithelial surfaces from pathogens. However, dysregulated IL-20 signaling is implicated in several human pathologies including psoriasis, rheumatoid arthritis, atherosclerosis, and osteoporosis. IL-20, and related cytokines IL-19 and IL-24, designated IL-20 subfamily cytokines (IL-20SFCs), induce cellular responses through an IL-20R1/IL-20R2 (type I) receptor heterodimer, whereas IL-20 and IL-24 also signal through the IL-22R1/IL-20R2 (type II) receptor complex. The crystal structure of the IL-20/IL-20R1/IL-20R2 complex reveals how type I and II complexes discriminate cognate from noncognate ligands. The structure also defines how the receptor–cytokine interfaces are affinity tuned to allow distinct signaling through a receptor complex shared by three different ligands. Our results provide unique insights into the complexity of IL-20SFC signaling that may be critical in the design of mechanistic-based inhibitors of IL-20SFC–mediated inflammatory disease. PMID:22802649

  12. Coordinate cytokine regulatory sequences

    DOEpatents

    Frazer, Kelly A.; Rubin, Edward M.; Loots, Gabriela G.

    2005-05-10

    The present invention provides CNS sequences that regulate the cytokine gene expression, expression cassettes and vectors comprising or lacking the CNS sequences, host cells and non-human transgenic animals comprising the CNS sequences or lacking the CNS sequences. The present invention also provides methods for identifying compounds that modulate the functions of CNS sequences as well as methods for diagnosing defects in the CNS sequences of patients.

  13. Perceptions of housing conditions among migrant farmworkers and their families: Implications for health, safety and social policy

    PubMed Central

    Keim-Malpass, Jessica; Spears, Chaya R.; Quandt, Sara A.; Arcury, Thomas A.

    2016-01-01

    Introduction In the United States, migrant farmworkers are a vulnerable group due to their low socioeconomic status, risk of occupational exposures and injury, lack of social mobility, lack of adequate access to health services and dependency on employer for provided housing. Previous reports have documented migrant farmworker housing conditions to be variable, but poor overall. This paper explores the perceptions of housing conditions among migrant farmworkers in rural North Carolina, as well as understanding potential impacts of their housing on health and safety. Methods This study used qualitative descriptive data and directed content analysis to analyze semi-structured interviews and photographs that were data elements of a larger community-based participatory research study designed to document housing quality and health among North Carolina farmworkers. Results Many of the study participants described poor housing conditions that were reflected in the photographic analysis of the houses and camps. Specific problems described by the participants include: exposure to pesticides, safety issues, pests, water supply and air quality, temperature and moisture. Conclusions This study describes migrant farmworkers’ perceptions of housing quality and numerous potential impacts on health and safety. Research, social policy and practice-based implications derived from this research could serve to improve the health status of these individuals and their families. This study suggests there is much room for sustained advocacy and action, given that many of the farmworkers’ descriptions and photographs depicted housing conditions below accepted standards of living. Access to adequate and safe employer-provided housing for migrant farmworkers should be considered a basic human right. PMID:25682066

  14. Cytokines and immune surveillance in humans

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald

    1994-01-01

    Evidence from both human and rodent studies has indicated that alterations in immunological parameters occur after space flight. Among the parameters shown, by us and others, to be affected is the production of interferons. Interferons are a family of cytokines that are antiviral and play a major role in regulating immune responses that control resistance to infection. Alterations in interferon and other cytokine production and activity could result in changes in immunity and a possible compromise of host defenses against both opportunistic and external infections. The purpose of the present study is to explore further the effects of space flight on cyotokines and cytokine-directed immunological function. Among the tests carried out are interferon-alpha production, interferon-gamma production, interleukin-1 and -2 production, signal transduction in neutrophils, signal transduction in monocytes, and monocyte phagocytic activity. The experiments will be performed using peripheral blood obtained from human subjects. It is our intent to eventually carry out these experiments using astronauts as subjects to determine the effects of space flight on cytokine production and activity. However, these subjects are not currently available. Until they become available, we will carry out these experiments using subjects maintained in the bed-rest model for microgravity.

  15. Cytokine Therapies in Neurological Disease.

    PubMed

    Azodi, Shila; Jacobson, Steven

    2016-07-01

    Cytokines are a heterogeneous group of glycoproteins that coordinate physiological functions. Cytokine deregulation is observed in many neurological diseases. This article reviews current research focused on human clinical trials of cytokine and anticytokine therapies in the treatment of several neurological disease including stroke, neuromuscular diseases, neuroinfectious diseases, demyelinating diseases, and neurobehavioral diseases. This research suggests that cytokine therapy applications may play an important role in offering new strategies for disease modulation and treatment. Further, this research provides insights into the causal link between cytokine deregulation and neurological diseases. PMID:27388288

  16. Cytokines and Other Mediators in Alopecia Areata

    PubMed Central

    Gregoriou, Stamatis; Papafragkaki, Dafni; Kontochristopoulos, George; Rallis, Eustathios; Kalogeromitros, Dimitrios; Rigopoulos, Dimitris

    2010-01-01

    Alopecia areata, a disease of the hair follicles with multifactorial etiology and a strong component of autoimmune origin, has been extensively studied as far as the role of several cytokines is concerned. So far, IFN-γ, interleukins, TNF-α, are cytokines that are well known to play a major role in the pathogenesis of the disease, while several studies have shown that many more pathways exist. Among them, MIG, IP-10, BAFF, HLA antigens, MIG, as well as stress hormones are implicated in disease onset and activity. Within the scope of this paper, the authors attempt to shed light upon the complexity of alopecia areata underlying mechanisms and indicate pathways that may suggest future treatments. PMID:20300578

  17. An Analysis of Bronfenbrenner's Bio-Ecological Perspective for Early Childhood Educators: Implications for Working with Families Experiencing Stress

    ERIC Educational Resources Information Center

    Swick, Kevin James; Williams, Reginald D.

    2006-01-01

    Today's families face many stressors during the early childhood years. Particular stressors like homelessness, violence, and chemical dependence, play havoc with the family system. Urie Bronfenbrenner's bio-ecological perspective offers an insightful lens for understanding and supporting families under stress. This article presents the key…

  18. Suppression of Cytokine Signaling: the SOCS perspective

    PubMed Central

    Linossi, Edmond M.; Babon, Jeffrey J.; Hilton, Douglas J.; Nicholson, Sandra E.

    2013-01-01

    The discovery of the Suppressor Of Cytokine Signaling (SOCS) family of proteins has resulted in a significant body of research dedicated to dissecting their biological functions and the molecular mechanisms by which they achieve potent and specific inhibition of cytokine and growth factor signaling. The Australian contribution to this field has been substantial, with the initial discovery of SOCS1 by Hilton, Starr and colleagues (discovered concurrently by two other groups) and the following work, providing a new perspective on the regulation of JAK/STAT signaling. In this review, we reflect on the critical discoveries that have lead to our current understanding of how SOCS proteins function and discuss what we see as important questions for future research. PMID:23545160

  19. State of volatiles in Jupiter Family Comets, and implications for outgassing and measurements by the MIRO instrument onboard Rosetta

    NASA Astrophysics Data System (ADS)

    Choukroun, M.; von Allmen, P. A.; Gulkis, S.; Hofstadter, M. D.; Kamp, L.; Keihm, S.; Lee, S.

    2012-12-01

    Comets are remnants of the early solar system formation, with a volatile content expected to represent that of the solar nebula at the location where they formed. Jupiter Family Comets, including the target of the Rosetta mission 67P/Churyumov-Gerasimenko, may have either formed close to their current location in standard solar system formation models, or originate from the Kuiper Belt according to the "Nice" model. On top of these two potential formation locations, a large uncertainty on their composition in volatiles comes from the poor understanding of the state of volatiles in the solar nebula: pure condensates may have formed if the conditions were cold enough, and/or volatiles may have been trapped (with various efficiency) in voids of amorphous ice, and/or clathrate hydrates may have formed by interaction of the nebular gas with crystalline ice. Each of these states implies different starting composition and evolutionary paths, as the properties of these icy materials vary widely. In particular, the phase behavior and the thermophysical properties of these icy materials will affect both the thermal evolution of comets along their orbit and the composition of volatiles that are emitted. Comet 67P/Churyumov-Gerasimenko is in its current orbit since 1959, and will in 2015 be followed by the Rosetta spacecraft during its 9th passage at its current perihelion, 1.3 a.u. from the Sun (to be compared to the previous 2.8-3.0 a.u. predicted perihelion). The MIRO instrument onboard the Rosetta orbiter will measure both the thermophysical properties of the nucleus (continuum channels) and the composition of volatiles emitted (spectroscopic channel, complementary to in-situ measurements), providing data that will help address the state of volatiles at depth and track the evolution through time of a fairly fresh comet. We will discuss the implications of the state of volatiles on the thermal properties of the nucleus and outgassing composition. This work has been

  20. The role of Th17 cytokines in primary mucosal immunity

    PubMed Central

    Kolls, Jay K.; Khader, Shabaana A.

    2010-01-01

    The T helper type 17 (Th17) lineage of CD4+ T-cells produce several effector molecules including IL-17A, IL-17F, IL-21, and IL-22. In addition to CD4+, αβ T-cells, these cytokines can be produced by natural killer and γδ T-cells. These effector cytokines can be produced rapidly upon infection at mucosal sites and evidence to date strongly implicates that this arm of the immune system plays a critical role in mucosal immunity to many extracellular pathogens. Moreover these cytokines can also coordinate adaptive immunity to some intracellular pathogens. In this review, we will highlight recent progress in our understanding of these cytokines, and mechanisms of their effector function in the mucosa. PMID:21095154

  1. Loss-of-Function FERMT1 Mutations in Kindler Syndrome Implicate a Role for Fermitin Family Homolog-1 in Integrin Activation

    PubMed Central

    Lai-Cheong, Joey E.; Parsons, Maddy; Tanaka, Akio; Ussar, Siegfried; South, Andrew P.; Gomathy, Sethuraman; Mee, John B.; Barbaroux, Jean-Baptiste; Techanukul, Tanasit; Almaani, Noor; Clements, Suzanne E.; Hart, Ian R.; McGrath, John A.

    2009-01-01

    Kindler syndrome is an autosomal recessive disorder characterized by skin atrophy and blistering. It results from loss-of-function mutations in the FERMT1 gene encoding the focal adhesion protein, fermitin family homolog-1. How and why deficiency of fermitin family homolog-1 results in skin atrophy and blistering are unclear. In this study, we investigated the epidermal basement membrane and keratinocyte biology abnormalities in Kindler syndrome. We identified altered distribution of several basement membrane proteins, including types IV, VII, and XVII collagens and laminin-332 in Kindler syndrome skin. In addition, reduced immunolabeling intensity of epidermal cell markers such as β1 and α6 integrins and cytokeratin 15 was noted. At the cellular level, there was loss of β4 integrin immunolocalization and random distribution of laminin-332 in Kindler syndrome keratinocytes. Of note, active β1 integrin was reduced but overexpression of fermitin family homolog-1 restored integrin activation and partially rescued the Kindler syndrome cellular phenotype. This study provides evidence that fermitin family homolog-1 is implicated in integrin activation and demonstrates that lack of this protein leads to pathological changes beyond focal adhesions, with disruption of several hemidesmosomal components and reduced expression of keratinocyte stem cell markers. These findings collectively provide novel data on the role of fermitin family homolog-1 in skin and further insight into the pathophysiology of Kindler syndrome. PMID:19762710

  2. Work in America: Implications for Families. Hearing before the Select Committee on Children, Youth, and Families. House of Representatives, Ninety-Ninth Congress, Second Session.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. House Select Committee on Children, Youth, and Families.

    This hearing explored the value of work, and how changes in the economy and the composition of the work force have affected families. Witnesses (1) reported data on such topics as the kinds of jobs currently available, women's participation in the work force, unemployment, and labor force growth over the next decade; (2) argued that the economy is…

  3. Eating breakfast and dinner together as a family: Associations with sociodemographic characteristics and implications for diet quality and weight status

    PubMed Central

    Larson, Nicole; MacLehose, Rich; Fulkerson, Jayne A.; Berge, Jerica M.; Story, Mary; Neumark-Sztainer, Dianne

    2013-01-01

    Background Research has shown that adolescents who frequently share evening meals with their families experience more positive health outcomes, including diets of higher nutritional quality. However, little is known about families eating together at breakfast. Objectives This study examined sociodemographic differences in family meal frequencies in a population-based adolescent sample. Additionally, this study examined associations of family breakfast meal frequency with dietary quality and weight status. Design Cross-sectional data from EAT 2010 (Eating and Activity in Teens) included anthropometric assessments and classroom-administered surveys completed in 2009-2010. Participants/setting Participants included 2,793 middle and high school students (53.2% girls, mean age=14.4 years) from Minneapolis/St. Paul, MN, public schools. Main outcome measures Usual dietary intake was self-reported on a food frequency questionnaire. Height and weight were measured. Statistical analyses performed Regression models adjusted for sociodemographic characteristics, family dinner frequency, family functioning, and family cohesion were used to examine associations of family breakfast frequency with dietary quality and weight status. Results On average, adolescents reported having family breakfast meals 1.5 times (SD=2.1) and family dinner meals 4.1 times (SD=2.6) in the past week. There were racial/ethnic differences in family breakfast frequency, with the highest frequencies reported by adolescents of Black, Hispanic, Native American, and mixed race/ethnicity. Family breakfast frequency was also positively associated with male sex; younger age; and living in a two-parent household. Family breakfast frequency was associated with several markers of better diet quality (such as higher intake of fruit, whole grains, and fiber) and lower risk for overweight/obesity. For example, adolescents who reported seven family breakfasts in the past week consumed an average of 0.37 additional

  4. Cytokine disbalance in common human cancers.

    PubMed

    Culig, Zoran

    2011-02-01

    Interleukin (IL)-6, -4, and -8 levels have been elevated in most patients suffering from prostate, breast, or colon cancer. There is a large body of evidence suggesting that chronic inflammation is one of the etiologic factors in these tumors. IL-6 is a multifunctional cytokine which is known to influence proliferation, apoptosis, and angiogenesis in cancer. Its transcription factor STAT3 is known as an oncogene that is constitutively phosphorylated in these malignancies. However, IL-6-induced STAT3 phosphorylation may result in growth arrest. IL-6 activation of androgen receptor in prostate cancer may yield either tumor cell proliferation or differentiation. Prolonged treatment with IL-6 results in generation of sublines which express a more malignant phenotype. Therapy options against IL-6 have been established and the antibody siltuximab has been applied in preclinical and clinical studies. Recently, investigations of the role of suppressors of cytokine signaling have been carried out. IL-4 and -8 are implicated in regulation of apoptosis, migration, and angiogenesis in cancers associated with chronic inflammation. All cytokines mentioned above regulate cellular events in stem cells. These cells could not be targeted by most conventional cancer therapies. PMID:21167870

  5. Families' Experiences in Different Homeless and Highly Mobile Settings: Implications for School and Community Practice

    ERIC Educational Resources Information Center

    Miller, Peter M.

    2015-01-01

    Family homelessness has been on the rise throughout the United States in recent years. As a result, more schools and communities than ever are challenged to serve students whose lives are touched by instability, uncertainty, and crisis. To date, there has been little inquiry into how families' particular places of homelessness might shape…

  6. Extension's Evolving Alignment of Programs Serving Families and Youth: Organizational Change and Its Implications

    ERIC Educational Resources Information Center

    Braverman, Marc T.; Franz, Nancy K.; Rennekamp, Roger A.

    2012-01-01

    Extension is experiencing a trend toward closer alignment of its programs serving families and youth, notably Family and Consumer Sciences and 4-H Youth Development. Projects are more multidisciplinary and comprehensive than in the past, and, in many states, FCS and 4-HYD are also becoming more administratively integrated. Several reasons for this…

  7. I Felt Like My Heart Was Staying behind: Psychological Implications of Family Separations & Reunifications for Immigrant Youth

    ERIC Educational Resources Information Center

    Suarez-Orozco, Carola; Bang, Hee Jin; Kim, Ha Yeon

    2011-01-01

    Though many transnational families undergo profound transformations that are often complicated by extended periods of separation between loved ones, it is challenging to establish a sense of prevalence of family separations as well as their effects on youth. Utilizing the Longitudinal Immigrant Student Adaptation data with 282 newcomer adolescents…

  8. Adolescents' Views on Families as Metaphors in Hong Kong: Implications for Pre-Counselling Assessment

    ERIC Educational Resources Information Center

    Chan, Zenobia C. Y.

    2013-01-01

    This interpretative study aims to offer metaphors that describe family meanings from the adolescent's perspective by encouraging them to give a metaphor with their own explanation on a self-administering essay form. This study has three objectives: to explore the family meanings as a metaphor from the Hong Kong adolescent's perspective;…

  9. Effects of Population Change on Family Life and the Child: Implications for Home Economics Programs in Nigeria.

    ERIC Educational Resources Information Center

    Okobiah, Omamurhomu Solomon

    1981-01-01

    Outlines some of the population-related factors and effects upon the family and child. Because of their vested interests and wealth of experience in family life, home economists are challenged to take the lead in planning and providing curriculum materials, and to promote population education in the schools. (Author)

  10. Understanding the Complexity of Child Sexual Abuse: A Review of the Literature with Implications for Family Counseling

    ERIC Educational Resources Information Center

    Hunter, Sally V

    2006-01-01

    Working with families in which there have been incidences of child sexual abuse is one of the most challenging assignments for a family counselor. Beyond ethical and legal mandates for reporting such assaults, less is understood about the long-term effects on victims. After reviewing the literature on child sexual abuse and gender differences,…

  11. Plasma infusions into porcine cerebral white matter induce early edema, oxidative stress, pro-inflammatory cytokine gene expression and DNA fragmentation: implications for white matter injury with increased blood-brain-barrier permeability.

    PubMed

    Wagner, Kenneth R; Dean, Christopher; Beiler, Shauna; Bryan, David W; Packard, Benjamin A; Smulian, A George; Linke, Michael J; de Courten-Myers, Gabrielle M

    2005-04-01

    Plasma infused into porcine cerebral white matter induces both acute interstitial and delayed vasogenic edema. Edematous white matter contains extracellular plasma proteins and rapidly induces oxidative stress as evidenced by increased protein carbonyl formation and heme oxygenase-1 induction. We tested the hypothesis that edematous white matter would also upregulate pro-inflammatory cytokine gene expression and develop DNA damage. We infused autologous plasma into the frontal hemispheric white matter of pentobarbital-anesthetized pigs. We monitored and controlled physiological variables and froze brains in situ at 1, 4 or 24 hrs. We determined edema volumes by computer-assisted morphometry. We measured white matter protein carbonyl formation by immunoblotting, cytokine gene expression by standard RT-PCR methods and DNA fragmentation by agarose gel electrophoresis. White matter edema developed acutely (1 hr) after plasma infusion and increased significantly in volume between 4 and 24 hrs. Protein carbonyl formation also occurred rapidly in edematous white matter with significant elevations (3 to 4-fold) already present at 1 hr. This increase remained through 24 hrs. Pro-inflammatory cytokine gene expression was also rapidly increased at 1 hr post-infusion. Evidence for DNA fragmentation began at 2 to 4 hrs, and a pattern indicative of both ongoing necrosis and apoptosis was robust by 24 hrs. Plasma protein accumulation in white matter induces acute edema development and a cascade of patho-chemical events including oxidative stress, pro-inflammatory cytokine gene expression and DNA damage. These results suggest that in diseases with increased blood-brain barrier (BBB) permeability or following intracerebral hemorrhage or traumatic brain injury, interstitial plasma can rapidly damage white matter. PMID:16181107

  12. Cytokines and therapeutic oligonucleotides.

    PubMed

    Hartmann, G; Bidlingmaier, M; Eigler, A; Hacker, U; Endres, S

    1997-12-01

    Therapeutic oligonucleotides - short strands of synthetic nucleic acids - encompass antisense and aptamer oligonucleotides. Antisense oligonucleotides are designed to bind to target RNA by complementary base pairing and to inhibit translation of the target protein. Antisense oligonucleotides enable specific inhibition of cytokine synthesis. In contrast, aptamer oligonucleotides are able to bind directly to specific proteins. This binding depends on the sequence of the oligonucleotide. Aptamer oligonucleotides with CpG motifs can exert strong immunostimulatory effects. Both kinds of therapeutic oligonucleotides - antisense and aptamer oligonucleotides - provide promising tools to modulate immunological functions. Recently, therapeutic oligonucleotides have moved towards clinical application. An antisense oligonucleotide directed against the proinflammatory intercellular adhesion molecule 1 (ICAM-1) is currently being tested in clinical trials for therapy of inflammatory disease. Immunostimulatory aptamer oligonucleotides are in preclinical development for immunotherapy. In the present review we summarize the application of therapeutic oligonucleotides to modulate immunological functions. We include technological aspects as well as current therapeutic concepts and clinical studies. PMID:9740353

  13. Modulation of Cytokines in Cancer Patients by Intravenous Ascorbate Therapy

    PubMed Central

    Mikirova, Nina; Riordan, Neil; Casciari, Joseph

    2016-01-01

    Background Cytokines play an important role in tumor angiogenesis and inflammation. There is evidence in the literature that high doses of ascorbate can reduce inflammatory cytokine levels in cancer patients. The objective of this study was to investigate the effect of treatment by intravenous vitamin C (IVC) on cytokines and tumor markers. Material/Methods With the availability of protein array kits allowing assessment of many cytokines in a single sample, we measured 174 cytokines and additional 54 proteins and tumor markers in 12 cancer patients before and after a series of IVC treatments. Results Presented results show for our 12 patients the effect of treatment resulted in normalization of many cytokine levels. Cytokines that were most consistently elevated prior to treatments included M-CSF-R, Leptin, EGF, FGF-6, TNF-α, β, TARC, MCP-1,4, MIP, IL-4, 10, IL-4, and TGF-β. Cytokine levels tended to decrease during the course of treatment. These include mitogens (EGF, Fit-3 ligand, HGF, IGF-1, IL-21R) and chemo-attractants (CTAC, Eotaxin, E-selectin, Lymphotactin, MIP-1, MCP-1, TARC, SDF-1), as well as inflammation and angiogenesis factors (FGF-6, IL-1β, TGF-1). Conclusions We are able to show that average z-scores for several inflammatory and angiogenesis promoting cytokines are positive, indicating that they are higher than averages for healthy controls, and that their levels decreased over the course of treatment. In addition, serum concentrations of tumor markers decreased during the time period of IVC treatment and there were reductions in cMyc and Ras, 2 proteins implicated in being upregulated in cancer. PMID:26724916

  14. RNAi Screen Reveals Potentially Novel Roles of Cytokines in Myoblast Differentiation

    PubMed Central

    Ge, Yejing; Waldemer, Rachel J.; Nalluri, Ramakrishna; Nuzzi, Paul D.; Chen, Jie

    2013-01-01

    Cytokines are cell-secreted signaling molecules that modulate various cellular functions, with the best-characterized roles in immune responses. The expression of numerous cytokines in skeletal muscle tissues and muscle cells has been reported, but their function in skeletal myogenesis, the formation of skeletal muscle, has been largely underexplored. To systematically examine the potential roles of cytokines in skeletal myogenesis, we undertook an RNAi screen of 134 mouse cytokine genes for their involvement in the differentiation of C2C12 myoblasts. Our results have uncovered 29 cytokines as strong candidates for novel myogenic regulators, potentially conferring positive and negative regulation at distinct stages of myogenesis. These candidates represent a diverse collection of cytokine families, including interleukins, TNF-related factors, and chemokines. Our findings suggest the fundamental importance of cytokines in the cell-autonomous regulation of myoblast differentiation, and may facilitate future identification of novel therapeutic targets for improving muscle regeneration and growth in health and diseases. PMID:23844157

  15. Structural basis of receptor sharing by interleukin 17 cytokines

    SciTech Connect

    Ely, Lauren K.; Fischer, Suzanne; Garcia, K. Christopher; Stanford-MED

    2010-02-19

    Interleukin 17 (IL-17)-producing helper T cells (T{sub H}-17 cells), together with their effector cytokines, including members of the IL-17 family, are emerging as key mediators of chronic inflammatory and autoimmune disorders. Here we present the crystal structure of a complex of IL-17 receptor A (IL-17RA) bound to IL-17F in a 1:2 stoichiometry. The mechanism of complex formation was unique for cytokines and involved the engagement of IL-17 by two fibronectin-type domains of IL-17RA in a groove between the IL-17 homodimer interface. Binding of the first receptor to the IL-17 cytokines modulated the affinity and specificity of the second receptor-binding event, thereby promoting heterodimeric versus homodimeric complex formation. IL-17RA used a common recognition strategy to bind to several members of the IL-17 family, which allows it to potentially act as a shared receptor in multiple different signaling complexes.

  16. Incorporating the family as a critical context in genetic studies of children: implications for understanding pathways to risky behavior and substance use.

    PubMed

    Rende, Richard; Slomkowski, Cheryl

    2009-07-01

    The availability of candidate gene markers for biobehavioral traits will undoubtedly result in increasing attention to genetic influences in studies of childhood risk factors for health behaviors. However, a strict emphasis on genomics without consideration of the social contexts that give rise to risky behaviors will miss opportunities to understand more fully the powerful effect of the family on childhood development. This article discusses the rationale for using the family as a critical context for studying the translation of genetic propensity for risky behavior into developmental pathways that span childhood and adolescence. Attention is given to the importance of family environmental factors; the emerging literature on genetic influences on potential intermediate phenotypes; the need for rich and detailed characterizations of both phenotypes and environmental risk factors embedded within genomic studies of children; and implications for interventions and preventions aimed at risky behaviors. Via discussion of these issues, pragmatic considerations of how studying families as a context may facilitate the thoughtful inclusion of children into genetic paradigms are emphasized. PMID:18556676

  17. The cys-loop ligand-gated ion channel gene family of Tetranychus urticae: implications for acaricide toxicology and a novel mutation associated with abamectin resistance.

    PubMed

    Dermauw, W; Ilias, A; Riga, M; Tsagkarakou, A; Grbić, M; Tirry, L; Van Leeuwen, T; Vontas, J

    2012-07-01

    The cys-loop ligand-gated ion channel (cysLGIC) super family of Tetranychus urticae, the two-spotted spider mite, represents the largest arthropod cysLGIC super family described to date and the first characterised one within the group of chelicerates. Genome annotation, phylogenetic analysis and comparison of the cysLGIC subunits with their counterparts in insects reveals that the T. urticae genome encodes for a high number of glutamate- and histamine-gated chloride channel genes (GluCl and HisCl) compared to insects. Three orthologues of the insect γ-aminobutyric acid (GABA)-gated chloride channel gene Rdl were detected. Other cysLGIC groups, such as the nAChR subunits, are more conserved and have clear insect orthologues. Members of cysLGIC family mediate endogenous chemical neurotransmission and they are prime targets of insecticides. Implications for toxicology associated with the identity and specific features of T. urticae family members are discussed. We further reveal the accumulation of known and novel mutations in different GluCl channel subunits (Tu_GluCl1 and Tu_GluCl3) associated with abamectin resistance in T. urticae, and provide genetic evidence for their causality. Our study provides useful toxicological insights for the exploration of the T. urticae cysLGIC subunits as putative molecular targets for current and future chemical control strategies. PMID:22465149

  18. Critically examining diversity in end-of-life family caregiving: implications for equitable caregiver support and Canada’s Compassionate Care Benefit

    PubMed Central

    2012-01-01

    Introduction Family (i.e., unpaid) caregiving has long been thought of as a ‘woman’s issue’, which ultimately results not only in gendered, but also financial and health inequities. Because of this, gender-based analyses have been prioritized in caregiving research. However, trends in current feminist scholarship demonstrate that gender intersects with other axes of difference, such as culture, socio-economic status, and geography to create diverse experiences. In this analysis we examine how formal front-line palliative care providers understand the role of such diversities in shaping Canadian family caregivers’ experiences of end-of-life care. In doing so we consider the implications of these findings for a social benefit program aimed at supporting family caregivers, namely the Compassionate Care Benefit (CCB). Methods This analysis contributes to a utilization-focused evaluation of Canada’s CCB, a social program that provides job security and limited income assistance to Canadian family caregivers who take a temporary leave from employment to provide care for a dying family member at end-of-life. Fifty semi-structured phone interviews with front-line palliative care providers from across Canada were conducted and thematic diversity analysis of the transcripts ensued. Results Findings reveal that experiences of caregiving are not homogenous and access to services and supports are not universal across Canada. Five axes of difference were commonly raised by front-line palliative care providers when discussing important differences in family caregivers’ experiences: culture, gender, geography, lifecourse stage, and material resources. Our findings reveal inequities with regard to accessing needed caregiver services and resources, including the CCB, based on these axes of difference. Conclusions We contend that without considering diversity, patterns in vulnerability and inequity are overlooked, and thus continually reinforced in health policy. Based on

  19. Characterization and Regulation of Suppressor of Cytokine Signaling (SOCS) Genes in Yellow Perch (Perca flavescens)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The suppressor of cytokine signaling (SOCS) proteins are a family of intracellular proteins that are centrally involved with vertebrate growth, development, and immunity via their effects as negative feedback regulators of cytokine (and hormone) signaling. A number of SOCS genes have been recently ...

  20. Molecular identification of duck and quail common cytokine receptor gamma chain genes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Common cytokine receptor gamma chain family cytokines play crucial roles in the regulation of innate and adaptive immune responses. Unlike mammals, chickens possess two different gamma chains transcripts. To determine if this difference is present in other avian species, gamma chain cDNA and genomic...

  1. Cytokines and their receptors in the central nervous system: physiology, pharmacology, and pathology.

    PubMed

    Rothwell, N J; Luheshi, G; Toulmond, S

    1996-01-01

    Numerous cytokines and their receptors have been identified in the brain, where they act as mediators of host defence responses and have direct effects on neuronal and glial function. Experimental tools for studying cytokine actions, their source and control of synthesis in the brain, actions and mechanisms of action will be reviewed here. In particular, the cytokines interleukin-1, interleukin-6, and tumour necrosis factor-alpha have been implicated in the central control of responses to systemic disease and injury and activation of fever, neuroendocrine, immune, and behavioural responses. The recent discovery of specific inhibitors of cytokine synthesis, release, or action may offer significant therapeutic benefit. PMID:8984509

  2. Solution assembly of cytokine receptor ectodomain complexes

    SciTech Connect

    Wu, Zining; Ciardelli, T.L.; Johnson, K.W.

    1995-09-01

    For the majority of single transmembrane-spanning cell surface receptors, signal transmission across the lipid bilayer barrier involves several discrete components of molecular recognition. The interaction between ligand and the extracellular segment of its cognate receptor (ectodomain) initiates either homomeric or heteromeric association of receptor subunits. Specific recognition among these subunits may then occur between ectodomain regions, within the membrane by interhelical contact or inside the cell between cytoplasmic domains. Any or all of these interactions may contribute to the stability of the signaling complex. It is the characteristics of ligand binding by the ectodomains of these receptors that controls the heteromeric or homomeric nature and the stoichiometry of the complex. Cytokines and their receptors belong to a growing family of macromolecular systems that exhibit these functional features and share many structural similarities as well. Interleukin-2 is a multifunctional cytokine that represents, perhaps, the most complex example to date of ligand recognition among the hematopoietin receptor family. It is the cooperative binding of IL-2 by all three proteins on the surface of activated T-lymphocytes, however, that ultimately results in crosslinking of the {beta}- and {gamma}-subunits and signaling via association of their cytoplasmic domains. Although the high-affinity IL-2R functions as a heterotrimer, heterodimers of the receptor subunits are also physiologically important. The {alpha}/{beta} heterodimer or {open_quotes}pseudo-high affinity{close_quotes} receptor captures IL-2 as a preformed cell surface complex while the {beta}/{gamma} intermediate affinity site exists, in the absence of the {alpha} subunit, on the majority of natural killer cells. We have begun to study stable complexes of cytokine receptor ectodomains of defined composition and that mimic the ligand binding characteristics of the equivalent cell surface receptor sites.

  3. Insights into pathogenesis and treatment of cytokines in cardiomyopathy.

    PubMed

    Vadlamani, L; Abraham, W T

    2000-03-01

    Our understanding of the pathophysiology of chronic heart failure is rapidly expanding. recent investigations suggest a role for various proinflammatory and vasoconstrictive cytokines in the development and progression of the disease. In particular, tumor necrosis factor-alpha, interlukin-6, and endothelin have all been implicated in heart failure desease progression. These cytokines appear to be activated in response to a remodeling, induction of programmed cell death, neurohormonal activation, and hemodynamics, these agents cause a variety of deleterious effects in the setting of ventricular dysfunction. Investigational inhibitors and antagonists of these substances show promise for the future treatment of heart failure. PMID:10980882

  4. Identification, localization, and functional implications of the microdomain-forming stomatin family in the ciliated protozoan Paramecium tetraurelia.

    PubMed

    Reuter, Alexander T; Stuermer, Claudia A O; Plattner, Helmut

    2013-04-01

    The SPFH protein superfamily is assumed to occur universally in eukaryotes, but information from protozoa is scarce. In the Paramecium genome, we found only Stomatins, 20 paralogs grouped in 8 families, STO1 to STO8. According to cDNA analysis, all are expressed, and molecular modeling shows the typical SPFH domain structure for all subgroups. For further analysis we used family-specific sequences for fluorescence and immunogold labeling, gene silencing, and functional tests. With all family members tested, we found a patchy localization at/near the cell surface and on vesicles. The Sto1p and Sto4p families are also associated with the contractile vacuole complex. Sto4p also makes puncta on some food vacuoles and is abundant on vesicles recycling from the release site of spent food vacuoles to the site of nascent food vacuole formation. Silencing of the STO1 family reduces mechanosensitivity (ciliary reversal upon touching an obstacle), thus suggesting relevance for positioning of mechanosensitive channels in the plasmalemma. Silencing of STO4 members increases pulsation frequency of the contractile vacuole complex and reduces phagocytotic activity of Paramecium cells. In summary, Sto1p and Sto4p members seem to be involved in positioning specific superficial and intracellular microdomain-based membrane components whose functions may depend on mechanosensation (extracellular stimuli and internal osmotic pressure). PMID:23376944

  5. Identification, Localization, and Functional Implications of the Microdomain-Forming Stomatin Family in the Ciliated Protozoan Paramecium tetraurelia

    PubMed Central

    Stuermer, Claudia A. O.; Plattner, Helmut

    2013-01-01

    The SPFH protein superfamily is assumed to occur universally in eukaryotes, but information from protozoa is scarce. In the Paramecium genome, we found only Stomatins, 20 paralogs grouped in 8 families, STO1 to STO8. According to cDNA analysis, all are expressed, and molecular modeling shows the typical SPFH domain structure for all subgroups. For further analysis we used family-specific sequences for fluorescence and immunogold labeling, gene silencing, and functional tests. With all family members tested, we found a patchy localization at/near the cell surface and on vesicles. The Sto1p and Sto4p families are also associated with the contractile vacuole complex. Sto4p also makes puncta on some food vacuoles and is abundant on vesicles recycling from the release site of spent food vacuoles to the site of nascent food vacuole formation. Silencing of the STO1 family reduces mechanosensitivity (ciliary reversal upon touching an obstacle), thus suggesting relevance for positioning of mechanosensitive channels in the plasmalemma. Silencing of STO4 members increases pulsation frequency of the contractile vacuole complex and reduces phagocytotic activity of Paramecium cells. In summary, Sto1p and Sto4p members seem to be involved in positioning specific superficial and intracellular microdomain-based membrane components whose functions may depend on mechanosensation (extracellular stimuli and internal osmotic pressure). PMID:23376944

  6. Role of cytokines in myocardial ischemia and reperfusion.

    PubMed

    Sharma, H S; Das, D K

    1997-01-01

    Mediators of myocardial inflammation, predominantly cytokines, have for many years been implicated in the healing processes after infarction. In recent years, however, more attention has been paid to the possibility that the inflammation may result in deleterious complications for myocardial infarction. The proinflammatory cytokines may mediate myocardial dysfunction associated with myocardial infarction, severe congestive heart failure, and sepsis. A growing body of literature suggests that inflammatory mediators could play a crucial role in ischemia-reperfusion injury. Furthermore, ischemia-reperfusion not only results in the local transcriptional and translational upregulation of cytokines but also leads to tissue infiltration by inflammatory cells. These inflammatory cells are a ready source of a variety of cytokines which could be lethal for the cardiomyocytes. At the cellular level it has been shown that hypoxia causes a series of well documented changes in cardiomyocytes that includes loss of contractility, changes in lipid metabolism and subsequent irreversible cell membrane damage leading to cell death. For instance, hypoxic cardiomyocytes produce interleukin-6 (IL-6) which could contribute to the myocardial dysfunction observed in ischemia reperfusion injury. Ischemia followed by reperfusion induces a number of other multi-potent cytokines, such as IL-1, IL-8, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1) as well as an angiogenic cytokine/ growth factor, vascular endothelial growth factor (VEGF), in the heart. Intrestingly, these multipotent cytokines (e.g. TNF-alpha) may induce an adaptive cytoprotective response in the reperfused myocardium. In this review, we have included a number of cytokines that may contribute to ventricular dysfunction and/or to the cytoprotective and adaptive changes in the reperfused heart. PMID:18472818

  7. CHARACTERISTICS OF IS401, A NEW MEMBER OF THE IS3 FAMILY IMPLICATED IN PLASMID REARRANGEMENTS IN PSEUDOMONAS CEPACIA

    EPA Science Inventory

    We have determined the nucleotide sequence of IS401, an insertion sequence implicated in rearrangements of a 170-kb cryptic plasmid from Pseudomonas cepacia. ur analysis focused on a 4066-bp plasmid fragment containing adjacent copies of IS401 and of IS408, an element reported pr...

  8. The Function of Fish Cytokines

    PubMed Central

    Zou, Jun; Secombes, Christopher J.

    2016-01-01

    What is known about the biological activity of fish cytokines is reviewed. Most of the functional studies performed to date have been in teleost fish, and have focused on the induced effects of cytokine recombinant proteins, or have used loss- and gain-of-function experiments in zebrafish. Such studies begin to tell us about the role of these molecules in the regulation of fish immune responses and whether they are similar or divergent to the well-characterised functions of mammalian cytokines. This knowledge will aid our ability to determine and modulate the pathways leading to protective immunity, to improve fish health in aquaculture. PMID:27231948

  9. The Function of Fish Cytokines.

    PubMed

    Zou, Jun; Secombes, Christopher J

    2016-01-01

    What is known about the biological activity of fish cytokines is reviewed. Most of the functional studies performed to date have been in teleost fish, and have focused on the induced effects of cytokine recombinant proteins, or have used loss- and gain-of-function experiments in zebrafish. Such studies begin to tell us about the role of these molecules in the regulation of fish immune responses and whether they are similar or divergent to the well-characterised functions of mammalian cytokines. This knowledge will aid our ability to determine and modulate the pathways leading to protective immunity, to improve fish health in aquaculture. PMID:27231948

  10. Medical Manpower Projections and Proposals: The Federal/Provincial/Territorial Report and Its Implications for Family Physicians

    PubMed Central

    Moore, Carl A.

    1986-01-01

    The Federal/Provincial/Territorial Advisory Committee on Health Manpower has projected a surplus of 4,870 family physicians in Canada by the year 2000. Among the committee's recommendations are proposals to reduce the number of family physicians in the future, and to decrease the undergraduate enrollment in Canadian medical schools by 17%. Too many physicians could lead to excessive costs for the government, and to overservicing, underemployment, low morale, and decreased incomes for physicians themselves. A shortfall in physician supply is easily overcome by opening the doors to immigrant physicians. However, quality of care may be sacrificed. The status and quality of family practice will be directly affected by the action ensuing from the advisory committee's report. PMID:21267265

  11. The Crosstalk of RAS with the TGF-β Family During Carcinoma Progression and its Implications for Targeted Cancer Therapy

    PubMed Central

    Grusch, M.; Petz, M.; Metzner, T.; Öztürk, D.; Schneller, D.; Mikulits, W.

    2010-01-01

    Both RAS and transforming growth factor (TGF)-β signaling cascades are central in tumorigenesis and show synergisms depending on tumor stage and tissue context. In this review we focus on the interaction of RAS subeffector proteins with signaling components of the TGF-β family including those of TGF-βs, activins and bone morphogenic proteins. Compelling evidence indicates that RAS signaling is essentially involved in the switch from tumor-suppressive to tumor-promoting functions of the TGF-β family leading to enhanced cancer growth and metastatic dissemination of primary tumors. Thus, the interface of these signaling cascades is considered as a promising target for the development of novel cancer therapeutics. The current pharmacological anti-cancer concepts combating the molecular cooperation between RAS and TGF-β family signaling during carcinoma progression are critically discussed. PMID:20718708

  12. Social Support and HIV-Status Disclosure to Friends and Family: Implications for HIV-Positive Youth

    PubMed Central

    Lee, Sonia; Yamazaki, Michiyo; Harris, D. Robert; Harper, Gary W.; Ellen, Jonathan

    2015-01-01

    Purpose The fear of negative reactions from friends and family members affects many HIV-positive adolescents’ decisions regarding disclosure of their HIV status. The complex relationships and interplay among social support, fear of stigma, and disclosure of HIV status needs to be better understood among youth living with HIV. Methods Social support from friends and family members, and HIV status disclosure were examined among 402 youth, aged 12 to 24 years, living with HIV. Results In separate analyses, 1) HIV positive youth who reported more than one close friend, as well as 2) HIV positive youth who reported that friends and family members continued to socialize with them after disclosure of their HIV diagnosis, had higher levels of perceived social support overall (both p<0.05). Furthermore, perceived social support did not differ significantly between those participants for whom no family member knew their HIV status and those for whom at least one family member knew their status (p=0.13). Race/ethnicity, sexual orientation, education level, and current living situation were not associated with family's knowledge of the participants’ HIV infection status (p>0.07). Conclusion This investigation adds important information concerning youth living with HIV, whose early disclosure experiences may influence their resilience and future coping mechanisms regarding experienced stigma, and thus influence the length of time they conceal their HIV status, their decision to disclose their status, and potentially their decisions regarding treatment. Interventions and support systems to assist youth living with HIV with disclosure, as well as medical care, may improve their overall quality of life. PMID:25940217

  13. Novel cytokines and cytokine-producing T cells in allergic disorders.

    PubMed

    Wisniewski, Julia A; Borish, Larry

    2011-01-01

    Allergic diseases reflect various pathways of T lymphocyte inflammation and largely comprise T helper (Th) 2-associated processes. Recent investigations have identified pathways involved in promoting Th2 responses. Additionally, novel T-cell subtypes, each with its own distinct cytokine profile, contribute to the heterogeneous presentations of allergic diseases. This article focuses on recent developments including novel effector (nuocytes, Th9, and Th22) and regulatory T-cell (Treg) families of lymphocytes as well as cytokines that are central in driving Th2 differentiation (interleukin [IL]-4, IL-9, IL-25, thymic stromal lymphopoietin [TSLP], and IL-33). Recent literature and investigations were reviewed. Unregulated IL-25, TSLP, and IL-33 activity results in activation of Th2 cells, mast cells, dendritic cells, eosinophils, and basophils, leading to inflammatory processes that define allergic disease. As such, these cytokines are central mediators capable of instigating the inflammatory processes responsible for allergen-mediated diseases. The previous paradigm of Th1/Th2 imbalance driving allergic disease is expanded by identification of novel T helper families (nuocytes, Th9, Th17, and Th22) with their signature cytokines, which provide alterative avenues for investigation of neutrophil-predominant asthma and other heterogeneous presentations of allergic diseases. IL-25, TSLP, and IL-33 are attractive targets for therapeutics designed to ameliorate Th2-mediated diseases such as allergic rhinitis and asthma. Moreover, the ability to delineate novel regulatory and effector T-cell lineages among CD4(+) T cells challenges the Th1/Th2 paradigm of allergic disease and invites further avenues of investigation into the role of these cells in allergic disease. PMID:21439160

  14. Indian Families in the U.S. Who Have Children with Disabilities: Implications for Inclusive and Culturally Responsive Practices

    ERIC Educational Resources Information Center

    Antony, Pavan John; Banks-Joseph, Susan Rae

    2010-01-01

    A grounded theory approach is used to explore the "lived experiences" of two upper-middle-class families from India who have children with disabilities. Findings provide insight into the parents' beliefs and perceptions about disabilities, their goals and expectations for their children, and their views of inclusive education programs.…

  15. Whole Exome Sequencing of Distant Relatives in Multiplex Families Implicates Rare Variants in Candidate Genes for Oral Clefts

    PubMed Central

    Bureau, Alexandre; Parker, Margaret M.; Ruczinski, Ingo; Taub, Margaret A.; Marazita, Mary L.; Murray, Jeffrey C.; Mangold, Elisabeth; Noethen, Markus M.; Ludwig, Kirsten U.; Hetmanski, Jacqueline B.; Bailey-Wilson, Joan E.; Cropp, Cheryl D.; Li, Qing; Szymczak, Silke; Albacha-Hejazi, Hasan; Alqosayer, Khalid; Field, L. Leigh; Wu-Chou, Yah-Huei; Doheny, Kimberly F.; Ling, Hua; Scott, Alan F.; Beaty, Terri H.

    2014-01-01

    A dozen genes/regions have been confirmed as genetic risk factors for oral clefts in human association and linkage studies, and animal models argue even more genes may be involved. Genomic sequencing studies should identify specific causal variants and may reveal additional genes as influencing risk to oral clefts, which have a complex and heterogeneous etiology. We conducted a whole exome sequencing (WES) study to search for potentially causal variants using affected relatives drawn from multiplex cleft families. Two or three affected second, third, and higher degree relatives from 55 multiplex families were sequenced. We examined rare single nucleotide variants (SNVs) shared by affected relatives in 348 recognized candidate genes. Exact probabilities that affected relatives would share these rare variants were calculated, given pedigree structures, and corrected for the number of variants tested. Five novel and potentially damaging SNVs shared by affected distant relatives were found and confirmed by Sanger sequencing. One damaging SNV in CDH1, shared by three affected second cousins from a single family, attained statistical significance (P = 0.02 after correcting for multiple tests). Family-based designs such as the one used in this WES study offer important advantages for identifying genes likely to be causing complex and heterogeneous disorders. PMID:24793288

  16. Rural Mexican-Americans' perceptions of family health history, genetics, and disease risk: implications for disparities-focused research dissemination.

    PubMed

    Malen, Rachel; Knerr, Sarah; Delgado, Fernanda; Fullerton, Stephanie M; Thompson, Beti

    2016-01-01

    Disseminating the results of transdisciplinary health disparities research will increasingly involve discussing family health history and/or genetic information with study participants and their communities. Often, individuals' familiarity and comfort with these topics will be unclear. To inform the dissemination activities of a Center for Population Health and Health Disparities (CPHHD) studying multilevel determinants of breast cancer disparities in Latinas, we talked with Spanish-speaking Mexican-Americans from a rural agricultural community about family health history, genetics, and disease risk. We found that participants had limited genetic literacy but were familiar with some concepts related to family health history. Participants emphasized the role of individual behavior in shaping health and expressed a strong desire for health-related information. This included genetic information about future disease risk, which participants were previously unaware of but thought could be useful for disease prevention. These findings suggest that for research dissemination to facilitate health promotion, gaps in knowledge, particularly genetic knowledge, will need to be overcome. Outreach to underserved Latino communities should take advantage of this existing knowledge of family health history and strong desire for health information, but also take care to not overstate the significance of unreplicated or low-penetrance genetic associations. PMID:26141228

  17. The Role of Community, Family, Peer, and School Factors in Group Bullying: Implications for School-Based Intervention

    ERIC Educational Resources Information Center

    Mann, Michael J.; Kristjansson, Alfgeir L.; Sigfusdottir, Inga Dora; Smith, Megan L.

    2015-01-01

    Background: Although an ecological perspective suggests the importance of multiple levels of intervention, most bullying research has emphasized individual- and school-focused strategies. This study investigated community and family factors that influence school efforts to reduce odds of group bullying behavior and victimization. Methods: We used…

  18. Child Care Subsidies and the Economic Well-Being of Recipient Families: A Survey and Implications for Kentucky

    ERIC Educational Resources Information Center

    University of Kentucky Center for Poverty Research, 2008

    2008-01-01

    The secular increase over the past several decades in the number of families where both the husband and wife work in the paid labor force, coupled with the surge in labor force participation of single mothers in the 1990s, has heightened policy focus on child care options for working parents; federal and state governments are now major players…

  19. The Role of Personal Resources in Work-Family Conflict: Implications for Young Mothers' Well-Being

    ERIC Educational Resources Information Center

    Braunstein-Bercovitz, Hedva; Frish-Burstein, Smadar; Benjamin, Benny A.

    2012-01-01

    The purpose of the current study was to examine the role that personal resources (person-environment [PE] congruence and personality types associated with resilience) and work-family conflict (WFC) play in the sense of well-being (as reflected by burnout and life-satisfaction) of mothers of young children. A sample of 146 mothers holding demanding…

  20. Is Autism a Member of a Family of Diseases Resulting from Genetic/Cultural Mismatches? Implications for Treatment and Prevention

    PubMed Central

    Bilbo, Staci D.; Jones, John P.; Parker, William

    2012-01-01

    Several lines of evidence support the view that autism is a typical member of a large family of immune-related, noninfectious, chronic diseases associated with postindustrial society. This family of diseases includes a wide range of inflammatory, allergic, and autoimmune diseases and results from consequences of genetic/culture mismatches which profoundly destabilize the immune system. Principle among these consequences is depletion of important components, particularly helminths, from the ecosystem of the human body, the human biome. Autism shares a wide range of features in common with this family of diseases, including the contribution of genetics/epigenetics, the identification of disease-inducing triggers, the apparent role of immunity in pathogenesis, high prevalence, complex etiologies and manifestations, and potentially some aspects of epidemiology. Fortunately, using available resources and technology, modern medicine has the potential to effectively reconstitute the human biome, thus treating or even avoiding altogether the consequences of genetic/cultural mismatches which underpin this entire family of disease. Thus, if indeed autism is an epidemic of postindustrial society associated with immune hypersensitivity, we can expect that the disease is readily preventable. PMID:22928103

  1. Children and Political Violence from a Social Ecological Perspective: Implications from Research on Children and Families in Northern Ireland

    ERIC Educational Resources Information Center

    Cummings, Mark E.; Goeke-Morey, Marcie C.; Schermerhorn, Alice C.; Merrilees, Christine E.; Cairns, Ed

    2009-01-01

    The effects on children of political violence are matters of international concern, with many negative effects well-documented. At the same time, relations between war, terrorism, or other forms of political violence and child development do not occur in a vacuum. The impact can be understood as related to changes in the communities, families and…

  2. DNA repair genes implicated in triple negative familial non-BRCA1/2 breast cancer predisposition

    PubMed Central

    Ollier, Marie; Radosevic-Robin, Nina; Kwiatkowski, Fabrice; Ponelle, Flora; Viala, Sandrine; Privat, Maud; Uhrhammer, Nancy; Bernard-Gallon, Dominique; Penault-Llorca, Frédérique; Bignon, Yves-Jean; Bidet, Yannick

    2015-01-01

    Among breast cancers, 10 to 15% of cases would be due to hereditary risk. In these familial cases, mutations in BRCA1 and BRCA2 are found in only 15% to 20%, meaning that new susceptibility genes remain to be found. Triple-negative breast cancers represent 15% of all breast cancers, and are generally aggressive tumours without targeted therapies available. Our hypothesis is that some patients with triple negative breast cancer could share a genetic susceptibility different from other types of breast cancers. We screened 36 candidate genes, using pyrosequencing, in all the 50 triple negative breast cancer patients with familial history of cancer but no BRCA1 or BRCA2 mutation of a population of 3000 families who had consulted for a familial breast cancer between 2005 and 2013. Any mutations were also sequenced in available relatives of cases. Protein expression and loss of heterozygosity were explored in tumours. Seven deleterious mutations in 6 different genes (RAD51D, MRE11A, CHEK2, MLH1, MSH6, PALB2) were observed in one patient each, except the RAD51D mutation found in two cases. Loss of heterozygosity in the tumour was found for 2 of the 7 mutations. Protein expression was absent in tumour tissue for 5 mutations. Taking into consideration a specific subtype of tumour has revealed susceptibility genes, most of them in the homologous recombination DNA repair pathway. This may provide new possibilities for targeted therapies, along with better screening and care of patients. PMID:26328243

  3. Cytokines in cancer drug resistance: Cues to new therapeutic strategies.

    PubMed

    Jones, Valerie Sloane; Huang, Ren-Yu; Chen, Li-Pai; Chen, Zhe-Sheng; Fu, Liwu; Huang, Ruo-Pan

    2016-04-01

    The development of oncoprotein-targeted anticancer drugs is an invaluable weapon in the war against cancer. However, cancers do not give up without a fight. They may develop multiple mechanisms of drug resistance, including apoptosis inhibition, drug expulsion, and increased proliferation that reduce the effectiveness of the drug. The collective work of researchers has highlighted the role of cytokines in the mechanisms of cancer drug resistance, as well as in cancer cell progression. Furthermore, recent studies have described how specific cytokines secreted by cancer stromal cells confer resistance to chemotherapeutic treatments. In order to gain a better understanding of mechanism of cancer drug resistance and a prediction of treatment outcome, it is imperative that correlations are established between global cytokine profiles and cancer drug resistance. Here we discuss the recent discoveries in this field of research and discuss their implications for the future development of effective anti-cancer medicines. PMID:26993403

  4. Cytokine profile in Nigerians with tubal infertility

    PubMed Central

    Charles-Davies, Mabel A.; Bello, Folashade A.; Taiwo, Victor O.; Bin, Li; Oni, Anthony A.

    2016-01-01

    Introduction Immune response to genital Chlamydia trachomatis infection is involved in both immunity and pathology. The cytokine profile during infection has been implicated in the disease outcome, either resolution or severe sequelae. Serum cytokines of Chlamydia positive Nigerian women with tubal infertility were assessed to determine their possible relationship with tubal occlusion. Material and methods One hundred and fifty age-matched consenting women (100 fertile and 50 with tubal infertility) were recruited based on C. trachomatis antibody positivity and grouped into infertile Chlamydia positive (CTpos) women (n = 50), fertile Chlamydia positive women (n = 50) and fertile Chlamydia negative (CTneg) women as controls (n = 50). High vaginal swabs and endo-cervical swabs were collected for microscopy, culture and gram staining. Cytokines [transforming growth factor β1 (TGF-β1), interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin (IL)-4, IL-10 and IL-17A] were estimated by ELISA in sera. Data were analyzed using ANOVA, χ 2 and Spearman's correlation at p = 0.05. Results Lower IFN-γ levels were observed in infertile women compared to fertile women. Fertile CTneg women had significantly higher TNF-α, and TGF-β1 compared to fertile and infertile CTpos women, respectively. Lower IL-10 levels were seen in fertile CTpos women compared to the infertile CTpos group. Vaginal discharge was negatively correlated with TNF-α and IFN-γ and positively with IL-4 in Chlamydia positive women. Conclusions Chlamydia positive women with tubal infertility have higher IL-10 and lower IFN-γ levels than controls, which may contribute to their development of tubal pathology. PMID:27095929

  5. Possible improvement in quality of human progeny by maternal dietary intervention: implications for programs of family planning and food production.

    PubMed

    Hsu, S C

    1973-05-01

    A report is made on the family planning program in Taiwan which emphasizes the integrated problems of population growth, nutrition and health, and food supplies. Nutrition and food supply have greatly improved in Taiwan since 1950, particularly in increases in food energy and protein availability. There has been a corresponding, though not necessarily resultant, decline in maternal and infant mortalities and deaths from gastrointestinal diseases. An official family planning program was instituted in Taiwan in 1964 with the goal of reducing the rate of natural increase from 3.0% to 1.5%. In 1971 the rate was 2.1%. Legalizing sterilization and abortion has been an important part of this program. A major goal is improvement in the quality of people. Reducing the size of the population results in more and better food and educational opportunities. A government study in Sui-Lin Township of Taiwan is investigating the effect of improved maternal health and nutrition on the quality of the offspring. The study is seeking to determine the minimum maternal food intake for proper health and which phase of the maternal diet (pre-pregnancy, pregnancy, lactation) or of the infant' diet is the most important to offspring quality. Also being studied is the possible existence of a maximum level of maternal nourishment beyond which detrimental effects might occur. The answers to these questions may provide important information for national nutrition policies, which are important factors in the family planning program. PMID:12276465

  6. Structural Insight into and Mutational Analysis of Family 11 Xylanases: Implications for Mechanisms of Higher pH Catalytic Adaptation

    PubMed Central

    Bai, Wenqin; Zhou, Cheng; Zhao, Yueju; Wang, Qinhong; Ma, Yanhe

    2015-01-01

    To understand the molecular basis of higher pH catalytic adaptation of family 11 xylanases, we compared the structures of alkaline, neutral, and acidic active xylanases and analyzed mutants of xylanase Xyn11A-LC from alkalophilic Bacillus sp. SN5. It was revealed that alkaline active xylanases have increased charged residue content, an increased ratio of negatively to positively charged residues, and decreased Ser, Thr, and Tyr residue content relative to non-alkaline active counterparts. Between strands β6 and β7, alkaline xylanases substitute an α-helix for a coil or turn found in their non-alkaline counterparts. Compared with non-alkaline xylanases, alkaline active enzymes have an inserted stretch of seven amino acids rich in charged residues, which may be beneficial for xylanase function in alkaline conditions. Positively charged residues on the molecular surface and ionic bonds may play important roles in higher pH catalytic adaptation of family 11 xylanases. By structure comparison, sequence alignment and mutational analysis, six amino acids (Glu16, Trp18, Asn44, Leu46, Arg48, and Ser187, numbering based on Xyn11A-LC) adjacent to the acid/base catalyst were found to be responsible for xylanase function in higher pH conditions. Our results will contribute to understanding the molecular mechanisms of higher pH catalytic adaptation in family 11 xylanases and engineering xylanases to suit industrial applications. PMID:26161643

  7. MRX87 family with Aristaless X dup24bp mutation and implication for polyAlanine expansions

    PubMed Central

    Laperuta, Carmela; Spizzichino, Letizia; D'Adamo, Pio; Monfregola, Jlenia; Maiorino, Antonio; D'Eustacchio, Angela; Ventruto, Valerio; Neri, Giovanni; D'Urso, Michele; Chiurazzi, Pietro; Ursini, Matilde Valeria; Miano, Maria Giuseppina

    2007-01-01

    Background Cognitive impairments are heterogeneous conditions, and it is estimated that 10% may be caused by a defect of mental function genes on the X chromosome. One of those genes is Aristaless related homeobox (ARX) encoding a polyA-rich homeobox transcription factor essential for cerebral patterning and its mutations cause different neurologic disorders. We reported on the clinical and genetic analysis of an Italian family with X-linked mental retardation (XLMR) and intra-familial heterogeneity, and provided insight into its molecular defect. Methods We carried out on linkage-candidate gene studies in a new MRX family (MRX87). All coding regions and exon-intron boundaries of ARX gene were analysed by direct sequencing. Results MRX87 patients had moderate to profound cognition impairment and a combination of minor congenital anomalies. The disease locus, MRX87, was mapped between DXS7104 and DXS1214, placing it in Xp22-p21 interval, a hot spot region for mental handicap. An in frame duplication of 24 bp (ARXdup24) in the second polyAlanine tract (polyA_II) in ARX was identified. Conclusion Our study underlines the role of ARXdup24 as a critical mutational site causing mental retardation linked to Xp22. Phenotypic heterogeneity of MRX87 patients represents a new observation relevant to the functional consequences of polyAlanine expansions enriching the puzzling complexity of ARXdup24-linked diseases. PMID:17480217

  8. Interventions to Improve Postpartum Family Planning in Low- and Middle-Income Countries: Program Implications and Research Priorities.

    PubMed

    Cleland, John; Shah, Iqbal H; Daniele, Marina

    2015-12-01

    This article provides programmatic guidance and identifies future research priorities through a review of interventions to improve postpartum contraception. Thirty-five interventions in low- and middle-income countries were identified and classified according to timing and nature of administration: antenatal, postnatal, both ante- and postnatal, and integration with other services. With the exception of single, short antenatal interventions, the evidence of impact is positive but incomplete. A major gap in knowledge concerns demand for, and means of promoting, immediate postpartum family planning services in Asia and Africa. Counseling before discharge is likely to have an impact on subsequent contraceptive uptake. Integration of family planning into immunization and pediatric services is justified, but policy and program obstacles remain. A case for relaxing the strict conditions of the lactational amenorrhea method (LAM) is strong, but qualitative evidence on the perspectives of women on pregnancy risks is required. Despite the gaps in knowledge, the evidence provides useful guidance for strategies to promote postpartum family planning, in ways that take different contexts into account. PMID:26643491

  9. Positive selection, molecular recombination structure and phylogenetic reconstruction of members of the family Tombusviridae: Implication in virus taxonomy

    PubMed Central

    Boulila, Moncef

    2011-01-01

    A detailed study of putative recombination events and their evolution frequency in the whole genome of the currently known members of the family Tombusviridae, comprising 79 accessions retrieved from the international databases, was carried out by using the RECCO and RDP version 3.31β algorithms. The first program allowed the detection of potential recombination sites in seven out of eight virus genera (Aureusvirus, Avenavirus, Carmovirus, Dianthovirus, Necrovirus, Panicovirus, and Tombusvirus), the second program provided the same results except for genus Dianthovirus. On the other hand, both methods failed to detect recombination breakpoints in the genome of members of genus Machlomovirus. Furthermore, based on Fisher’s Exact Test of Neutrality, positive selection exerted on protein-coding genes was detected in 17 accession pairs involving 15 different lineages. Except genera Machlomovirus, and Panicovirus along with unclassified Tombusviridae, all the other taxonomical genera and the unassigned Tombusviridae encompassed representatives under positive selection. The evolutionary history of all members of the Tombusviridae family showed that they segregated into eight distinct groups corresponding to the eight genera which constitute this family. The inferred phylogeny reshuffled the classification currently adopted by the International Committee on Taxonomy of Viruses. A reclassification was proposed. PMID:22215970

  10. Cytokine production in peripheral blood cells of patients with differentiated thyroid cancer: elevated Th2/Th9 cytokine production before and reduced Th2 cytokine production after radioactive iodine therapy.

    PubMed

    Simonovic, Snezana Zivancevic; Mihaljevic, Olgica; Majstorovic, Ivana; Djurdjevic, Predrag; Kostic, Irena; Djordjevic, Olivera Milosevic; Teodorovic, Ljiljana Mijatovic

    2015-01-01

    Cytokines play a key role in the regulation of cells of the immune system and also have been implicated in the pathogenesis of malignant diseases. The aim of this study was to evaluate cytokine profiles in patients with differentiated thyroid cancer (DTC) before and 7 days after radioactive iodine (131-I) therapy. Cytokine levels were determined in supernatants obtained from phytohemagglutinin-stimulated whole blood cultures of 13 patients with DTC and 13 control subjects. The concentrations of selected cytokines: Th1-interferon gamma (IFN-γ), interleukin 2 (IL-2) and tumor necrosis factor alpha (TNF-α); Th2-interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 13 (IL-13) and interleukin 10 (IL-10); Th9-interleukin-9 (IL-9); and Th17-interleukin 17 (IL-17A) were measured using multiplex cytokine detection systems for Human Th1/Th2/Th9/Th17/Th22. We have shown that peripheral blood cells of DTC patients produce significantly higher concentrations of Th2/Th9 cytokines (IL-5, IL-13 and IL-9) than control subjects. The 131-I therapy led to reduced secretion of Th2 cytokines (IL-4, IL-5 and IL-13). Despite this, the calculated cytokine ratios (Th1/Th2) in DTC patients before and 7 days after 131-I therapy were not different from those in healthy subjects. DTC patients have significantly higher concentrations of Th2/Th9 cytokines (IL-5, IL-13 and IL-9) than control subjects. There is no influence of hypothyroidism or stage of disease on cytokine production in DTC patients before 131-I therapy. The radioactive 131-I therapy leads to reduced secretion of Th2 cytokines (IL-4, IL-5 and IL-13). Additional studies are needed to determine the significance of these findings. PMID:25297452

  11. The role of the bcl-2/ced-9 gene family in cancer and general implications of defects in cell death control for tumourigenesis and resistance to chemotherapy.

    PubMed

    Strasser, A; Huang, D C; Vaux, D L

    1997-10-24

    Cell production within an organ is determined by the rate of immigration, proliferation, differentiation, emigration and death of cells. Abnormalities in any one of these processes will disturb normal control of cell production, thereby eliciting hyperplasia can be an early event in neoplasia. Cell death, apoptosis, is a physiological process responsible for removing unwanted cells. It is used in multi-cellular organisms for tissue remodelling during embryogenesis, regulation of cell turnover and as a defence strategy against invading pathogens. In this review article we describe the role of the bcl-2/ced-9 gene family in cancer and discuss the general implications of defects in the apoptosis program for tumourigenesis and resistance of cancer cells to chemotherapy in light of current knowledge of the molecular mechanisms of cell death. PMID:9395285

  12. The Role of Cytokines in Breast Cancer Development and Progression

    PubMed Central

    Esquivel-Velázquez, Marcela; Ostoa-Saloma, Pedro; Palacios-Arreola, Margarita Isabel; Nava-Castro, Karen E.; Castro, Julieta Ivonne

    2015-01-01

    Cytokines are highly inducible, secretory proteins that mediate intercellular communication in the immune system. They are grouped into several protein families that are referred to as tumor necrosis factors, interleukins, interferons, and colony-stimulating factors. In recent years, it has become clear that some of these proteins as well as their receptors are produced in the organisms under physiological and pathological conditions. The exact initiation process of breast cancer is unknown, although several hypotheses have emerged. Inflammation has been proposed as an important player in tumor initiation, promotion, angiogenesis, and metastasis, all phenomena in which cytokines are prominent players. The data here suggest that cytokines play an important role in the regulation of both induction and protection in breast cancer. This knowledge could be fundamental for the proposal of new therapeutic approaches to particularly breast cancer and other cancer-related disorders. PMID:25068787

  13. Integration of Cytokine Biology and Lipid Metabolism in Stroke**

    PubMed Central

    Adibhatla, Rao Muralikrishna; Dempsey, R.; Hatcher, J. F.

    2007-01-01

    Cytokines regulate the innate and adaptive immune responses and are pleiotropic, redundant and multifunctional. Expression of most cytokines, including TNF-α and IL-1α/ß, is very low in normal brain. Metabolism of lipids is of particular interest due to their high concentration in the brain. Inflammatory response after stroke suggests that cytokines (TNF-α, IL-1 α/ß, IL-6), affect the phospholipid metabolism and subsequent production of eicosanoids, ceramide, and ROS that may potentiate brain injury. Phosphatidylcholine and sphingomyelin are source for lipid messengers. Sphingomyelin synthase serves as a bridge between metabolism of glycerolipids and sphingolipids. TNF-α and IL-1 α/ß can induce phospholipases (A2, C, and D) and sphingomyelinases, and concomitantly proteolyse phosphatidylcholine and sphingomyelin synthesizing enzymes. Together, these alterations contribute to loss of phosphatidylcholine and sphingomyelin after stroke that can be attenuated by inhibiting TNF-α or IL-1 α/ß signaling. Inflammatory responses are instrumental in the formation and destabilization of atherosclerotic plaques. Secretory PLA2 IIA is found in human atherosclerotic lesions and is implicated in initiation, progression and maturation of atherosclerosis, a risk factor for stroke. Lipoprotein-PLA2, part of apolipoprotein B-100 of LDL, plays a role in vascular inflammation and coronary endothelial dysfunction. Cytokine antagonism attenuated secretory PLA2 IIA actions, suggesting cytokine-lipid integration studies will lead to new concepts contributing to bench-to-bedside transition for stroke therapy. PMID:17981627

  14. Psychosocial support intervention for HIV-affected families in Haiti: implications for programs and policies for orphans and vulnerable children.

    PubMed

    Smith Fawzi, Mary C; Eustache, Eddy; Oswald, Catherine; Louis, Ermaze; Surkan, Pamela J; Scanlan, Fiona; Hook, Sarah; Mancuso, Anna; Mukherjee, Joia S

    2012-05-01

    Given the increased access of antiretroviral therapy (ART) throughout the developing world, what was once a terminal illness is now a chronic disease for those receiving treatment. This requires a paradigmatic shift in service provision for those affected by HIV/AIDS in low-resource settings. Although there is a need for psychosocial support interventions for HIV-affected youth and their caregivers, to date there has been limited empirical evidence on the effectiveness of curriculum-based psychosocial support groups in HIV-affected families in low-income countries. Therefore, the purpose of this study is to examine the feasibility and assess the preliminary effectiveness of a psychosocial support group intervention for HIV-affected youth and their caregivers in central Haiti. The study was conducted at six Partners In Health-affiliated sites between February 2006 and September 2008 and included quantitative as well as qualitative methods. HIV-affected youth (n = 168) and their caregivers (n = 130) completed a baseline structured questionnaire prior to participation in a psychosocial support group intervention. Ninety-five percent of families completed the intervention and a follow-up questionnaire. Psychological symptoms, psychosocial functioning, social support, and HIV-related stigma at baseline were compared with outcomes one year later. Qualitative methods were also used to assess the participants' perspectives of the intervention. Comparing pre- and post-intervention assessment, youth affected by HIV experienced decreased psychological symptoms as well as improved psychosocial functioning and social support. Caregivers (95% HIV-positive) demonstrated a significant reduction in depressive symptoms, improved social support, and decreased HIV-related stigma. Although further study is needed to assess effectiveness in a randomized controlled trial, corroborative findings from qualitative data reflected reduced psychological distress, less social isolation and

  15. Comprehensive characterization of expression patterns of protein 4.1 family members in mouse adrenal gland: implications for functions.

    PubMed

    Wang, Hua; Liu, Congrong; Debnath, Gargi; Baines, Anthony J; Conboy, John G; Mohandas, Narla; An, Xiuli

    2010-10-01

    The members of the protein 4.1 family, 4.1R, 4.1G, 4.1N, and 4.1B, are encoded by four genes, all of which undergo complex alternative splicing. It is well established that 4.1R, the prototypical member of the family, serves as an adapter that links the spectrin-actin based cytoskeleton to the plasma membrane in red cells. It is required for mechanical resilience of the membrane, and it ensures the cell surface accumulation of selected membrane proteins. However, the function of 4.1 proteins outside erythrocytes remains under-explored, especially in endocrine tissues. Transcripts of all 4.1 homologs have previously been documented to be abundantly expressed in adrenal gland. In order to begin to decipher the function of 4.1 proteins in adrenal gland, we performed a detailed characterization of the expression pattern of various 4.1 proteins and their cellular localization. We show that 4.1R (~80 and ~135 kDa) splice forms are expressed on the membrane of all cells, while a ~160 kDa 4.1G splice form is distributed in the cytoplasm and the membrane of zona glomerulosa and of medullary cells. Two 4.1N splice forms, ~135 and ~95 kDa, are present in the peri-nuclear region of both zona glomerulosa and medullary cells, while a single ~130 kDa 4.1B splice form, is detected in all layers of adrenal gland in both the cytoplasm and the membrane. The characterization of distinct splice forms of various 4.1 proteins with diverse cellular and sub-cellular localization indicates multiple functions for this family of proteins in endocrine functions of adrenal gland. PMID:20890708

  16. Individual and Family Factors Associated with Intention to Quit among Male Vietnamese American Smokers: Implications for Intervention Development

    PubMed Central

    Tsoh, Janice Y.; Tong, Elisa K.; Gildengorin, Ginny; Nguyen, Tung T.; Modayil, Mary V.; Wong, Ching; McPhee, Stephen J.

    2011-01-01

    Smoking prevalence among Vietnamese American males remains higher than the U.S. general population. This study examined the associations of individual and family factors with quit intention among Vietnamese male smokers in California to guide intervention development to reduce their smoking prevalence. Data for Vietnamese male current smokers (n = 234) in the 2008 California Vietnamese Adult Tobacco Use Survey (N=1,101 males) were analyzed to describe quit intention and previous quit attempts. One-third of Vietnamese male smokers (33%) had no intention to quit at any time, 36% intended to quit soon (in the next 30 days), and 31% intended to quit later (beyond the next 30 days). Half (51.7%) of the sample was in “precontemplation,” indicating no intention to quit within 6 months. Many (71%) had made a serious quit attempt in the past year, but 68% of those who tried to quit used no cessation assistance. Multivariate logistic regression adjusting for age, depression, smoking intensity, nicotine dependence, health knowledge, children in the household and home smoking ban revealed that having smoking-related family conflicts and a quit attempt in the past year with or without assistance were independently associated with an intention to quit either in the next 30 days or later. Higher education was associated with no intention to quit. Findings underscore the importance of designing strategic interventions that meet the needs of smokers at both individual and family levels to promote quit intention and to facilitate successful quitting in this population. PMID:21177041

  17. Use of cytokines in infection.

    PubMed

    Aoki, Naoko; Xing, Zhou

    2004-11-01

    Infectious disease remains an ever-growing health concern worldwide due to increasing antibiotic-resistant microbial strains, immune-compromised populations, international traffic and globalisation, and bioterrorism. There exists an urgent need to develop novel prophylactic and therapeutic strategies. In addition to classic antibiotic therapeutics, immune-modulatory molecules such as cytokines or their inhibitors represent a promising form of antimicrobial therapeutics or immune adjuvant used for the purpose of vaccination. These molecules, in the form of either recombinant protein or transgene, exert their antimicrobial effect by enhancing infectious agent-specific immune activation or memory development, or by dampening undesired inflammatory and immune responses resulting from infection and host defence mechanisms. In the last two decades, a number of cytokine therapy-based experimental and clinical trials have been conducted, and some of these efforts have led to the routine clinical use of cytokines. For instance, although IFNs have been used to treat hepatitis C with great success, many other cytokines are yet to be fully evaluated for their antimicrobial potential. This review discusses the biology and therapeutic potential of selected immune modulatory cytokines and their inhibitors, including granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, IFN-gamma, IL-12 and TNF. PMID:15571481

  18. In-silico analysis and expression profiling implicate diverse role of EPSPS family genes in regulating developmental and metabolic processes

    PubMed Central

    2014-01-01

    Background The EPSPS, EC 2.5.1.19 (5-enolpyruvylshikimate −3-phosphate synthase) is considered as one of the crucial enzyme in the shikimate pathway for the biosynthesis of essential aromatic amino acids and secondary metabolites in plants, fungi along with microorganisms. It is also proved as a specific target of broad spectrum herbicide glyphosate. Results On the basis of structure analysis, this EPSPS gene family comprises the presence of EPSPS I domain, which is highly conserved among different plant species. Here, we followed an in-silico approach to identify and characterize the EPSPS genes from different plant species. On the basis of their phylogeny and sequence conservation, we divided them in to two groups. Moreover, the interacting partners and co-expression data of the gene revealed the importance of this gene family in maintaining cellular and metabolic functions in the cell. The present study also highlighted the highest accumulation of EPSPS transcript in mature leaves followed by young leaves, shoot and roots of tobacco. In order to gain the more knowledge about gene family, we searched for the previously reported motifs and studied its structural importance on the basis of homology modelling. Conclusions The results presented here is a first detailed in-silico study to explore the role of EPSPS gene in forefront of different plant species. The results revealed a great deal for the diversification and conservation of EPSPS gene family across different plant species. Moreover, some of the EPSPS from different plant species may have a common evolutionary origin and may contain same conserved motifs with related and important molecular function. Most importantly, overall analysis of EPSPS gene elucidated its pivotal role in immense function within the plant, both in regulating plant growth as well its development throughout the life cycle of plant. Since EPSPS is a direct target of herbicide glyphosate, understanding its mechanism for regulating

  19. Aberrant cytokine production by non-malignant cells in the pathogenesis of myeloproliferative tumors and response to JAK inhibitor therapies

    PubMed Central

    Belver, Laura; Ferrando, Adolfo A.

    2015-01-01

    SUMMARY Kleppe, Kwak, and collegues use detailed cytokine profiling analyses to investigate the role of aberrant pro-inflammatory cytokine secretion in the pathogenesis of myeloproliferative neoplasms (MPN). Their analyses implicate constitutive activation of STAT3 in both malignant and non-malignant bone marrow cell populations as a driver of aberrant cytokine secretion and as a cellular target mediating the therapeutic activity of ruxolitinib. PMID:25749974

  20. The functions of cytokines and their uses in toxicology

    PubMed Central

    Foster, John R

    2001-01-01

    Cytokines are critical controllers of cell, and hence tissue, growth, migration, development and differentiation. The family includes the inflammatory cytokines such as the interleukins and interferons, growth factors such as epidermal and hepatocyte growth factor and chemokines such as the macrophage inflammatory proteins, MIP-1α and MIP-1β. They do not include the peptide and steroid hormones of the endocrine system. Cytokines have important roles in chemically induced tissue damage repair, in cancer development and progression, in the control of cell replication and apoptosis, and in the modulation of immune reactions such as sensitization. They have the potential for being sensitive markers of chemically induced perturbations in function but from a toxicological point of view, the detection of cytokine changes in the whole animal is limited by the fact that they are locally released, with plasma measures being generally unreliable or irrelevant, and they have short half lives which require precise timing to detect. Even where methodology is adequate the interpretation of the downstream effects of high, local concentrations of a particular cytokine is problematic because of their interdependence and the pleiotropism of their action. A range of techniques exist for their measurement including those dependent upon antibodies specific for the respective cytokines, but with the introduction of genomic and proteomic technology, a more complete study of cytokine changes occurring under the influence of chemical toxicity should be possible. Their further study, as markers of chemical toxicity, will undoubtedly lead to a greater understanding of how synthetic molecules perturb normal cell biology and if, and how, this can be avoided by more intuitive molecular design in the future. PMID:11488991

  1. Tamm-Horsfall Protein Regulates Circulating and Renal Cytokines by Affecting Glomerular Filtration Rate and Acting as a Urinary Cytokine Trap*

    PubMed Central

    Liu, Yan; El-Achkar, Tarek M.; Wu, Xue-Ru

    2012-01-01

    Although few organ systems play a more important role than the kidneys in cytokine catabolism, the mechanism(s) regulating this pivotal physiological function and how its deficiency affects systemic cytokine homeostasis remain unclear. Here we show that elimination of Tamm-Horsfall protein (THP) expression from mouse kidneys caused a marked elevation of circulating IFN-γ, IL1α, TNF-α, IL6, CXCL1, and IL13. Accompanying this were enlarged spleens with prominent white-pulp macrophage infiltration. Lipopolysaccharide (LPS) exacerbated the increase of serum cytokines without a corresponding increase in their urinary excretion in THP knock-out (KO) mice. This, along with the rise of serum cystatin C and the reduced inulin and creatinine clearance from the circulation, suggested that diminished glomerular filtration may contribute to reduced cytokine clearance in THP KO mice both at the baseline and under stress. Unlike wild-type mice where renal and urinary cytokines formed specific in vivo complexes with THP, this “trapping” effect was absent in THP KO mice, thus explaining why cytokine signaling pathways were activated in renal epithelial cells in such mice. Our study provides new evidence implicating an important role of THP in influencing cytokine clearance and acting as a decoy receptor for urinary cytokines. Based on these and other data, we present a unifying model that underscores the role of THP as a major regulator of renal and systemic immunity. PMID:22451664

  2. The Brachodidae of Sub-Saharan Africa (Lepidoptera, Cossoidea), with implications for the origin of the family.

    PubMed

    Kallies, Axel

    2016-01-01

    Brachodidae are a small family of day-flying, rarely collected cossoid moths. Here, the Brachodidae fauna of Sub-Saharan Africa and the neighboring Arabian Peninsula is reviewed with special attention to the species of the subfamily Brachodinae. The origin of the African Brachodinae and their relationship to the Palaearctic genus Brachodes are discussed, and a Gondwanan origin of the family Brachodidae sensu stricto is proposed. A total of 34 brachodid species are considered in this study, most of which are figured. Two new genera, Archaeotychia gen. nov. (type species Atychia quiris Felder & Rogenhofer, 1875) and Nothobrachodes gen. nov. (type species Atychia infanda Meyrick, 1920) are described. Furthermore, 12 species are described as new to science: Archaeotychia semicuprea sp. nov., Archaeotychia dicksoni sp. nov., Archaeotychia khoisanorum sp. nov., Archaeotychia krooni sp. nov., Archaeotychia dentata sp. nov., Phycodes nigeriana sp. nov., Nigilgia scoblei sp. nov., Nigilgia agassizi sp. nov., Nigilgia ruwenzoriensis sp. nov., Nigilgia megabella sp. nov., Nigilgia arcana sp. nov. and Nigilgia crocea sp. nov. Moreover, Atychia metaspila Meyrick, 1926 syn. nov. is established as a new synonym of Archaeotychia albiciliata (Walsingham, 1891), and Atychia nycteropis Meyrick, 1920 syn. nov. as a new synonym of Nothobrachodes infanda (Meyrick, 1920). Atractoceros xanthoprocta (Meyrick, 1914) is transferred to the subfamily Phycodinae. PMID:27394217

  3. The organizational social context of mental health medicaid waiver programs with family support services: implications for research and practice.

    PubMed

    Glisson, Charles; Williams, Nathaniel J; Green, Philip; Hemmelgarn, Anthony; Hoagwood, Kimberly

    2014-01-01

    Peer family support specialists (FSS) are parents with practical experience in navigating children's mental health care systems who provide support, advocacy, and guidance to the families of children who need mental health services. Their experience and training differ from those of formally trained mental health clinicians, creating potential conflicts in priorities and values between FSS and clinicians. We hypothesized that these differences could negatively affect the organizational cultures and climates of mental health clinics that employ both FSS and mental health clinicians, and lower the job satisfaction and organizational commitment of FSS. The Organizational Social Context measure was administered on site to 209 FSS and clinicians in 21 mental health programs in New York State. The study compared the organizational-level culture and climate profiles of mental health clinics that employ both FSS and formally trained clinicians to national norms for child mental health clinics, assessed individual-level job satisfaction and organizational commitment as a function of job (FSS vs. clinician) and other individual-level and organizational-level characteristics, and tested whether FSS and clinicians job attitudes were differentially associated with organizational culture and climate. The programs organizational culture and climate profiles were not significantly different from national norms. Individual-level job satisfaction and organizational commitment were unrelated to position (FSS vs. clinician) or other individual-level and organizational-level characteristics except for culture and climate. Both FSS' and clinicians' individual-level work attitudes were associated similarly with organizational culture and climate. PMID:24065458

  4. Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling.

    PubMed Central

    Janssens, V; Goris, J

    2001-01-01

    Protein phosphatase 2A (PP2A) comprises a family of serine/threonine phosphatases, minimally containing a well conserved catalytic subunit, the activity of which is highly regulated. Regulation is accomplished mainly by members of a family of regulatory subunits, which determine the substrate specificity, (sub)cellular localization and catalytic activity of the PP2A holoenzymes. Moreover, the catalytic subunit is subject to two types of post-translational modification, phosphorylation and methylation, which are also thought to be important regulatory devices. The regulatory ability of PTPA (PTPase activator), originally identified as a protein stimulating the phosphotyrosine phosphatase activity of PP2A, will also be discussed, alongside the other regulatory inputs. The use of specific PP2A inhibitors and molecular genetics in yeast, Drosophila and mice has revealed roles for PP2A in cell cycle regulation, cell morphology and development. PP2A also plays a prominent role in the regulation of specific signal transduction cascades, as witnessed by its presence in a number of macromolecular signalling modules, where it is often found in association with other phosphatases and kinases. Additionally, PP2A interacts with a substantial number of other cellular and viral proteins, which are PP2A substrates, target PP2A to different subcellular compartments or affect enzyme activity. Finally, the de-regulation of PP2A in some specific pathologies will be touched upon. PMID:11171037

  5. HERV-K(HML-2), the Best Preserved Family of HERVs: Endogenization, Expression, and Implications in Health and Disease

    PubMed Central

    Hohn, Oliver; Hanke, Kirsten; Bannert, Norbert

    2013-01-01

    Retroviruses that have the ability to infect germ line cells can become an integral and inherited part of the host genome. About 8% of the human chromosomal DNA consists of sequences derived from infections by retroviruses that presumably circulated 2–40 millions of years ago, and some elements are actually much older. Post-insertional recombinations, deletions, and mutations have rendered all known human endogenous retroviruses (HERVs) non-infectious. However some, particularly the most recently acquired proviruses of the HERV-K(HML-2) family, can expresses viral proteins and produce viral particles. In this review we will first discuss the major aspects of the endogenization process and peculiarities of the different HERV-K families. We will then focus on the genes and proteins encoded by HERV-K(HML-2) as well as inactivation of these proviruses by postinsertional mutations and their inhibition by antiretroviral factors. After describing the evolutionary interplay between host and endogenous retrovirus we will delve deeper into the currently limited understanding of HERV-K and its possible association with disease, particularly tumorigenesis. PMID:24066280

  6. Caregivers' moral narratives of their African American children's out-of-school suspensions: implications for effective family-school collaborations.

    PubMed

    Gibson, Priscilla A; Haight, Wendy

    2013-07-01

    In this qualitative study, the authors examined the culturally nuanced meanings of out-of-school suspensions for 30 lower income caregivers of African American children suspended from school. Caregivers were invited to describe their experiences of their children's suspensions during in-depth, individual, audiotaped interviews. Caregivers generally valued their children's school success, recognized when their children had misbehaved, and supported educators' imposition of appropriate consequences. Out-of-school suspensions, however, were rarely viewed as appropriate consequences. On the contrary, caregivers produced emotionally laden moral narratives that generally characterized their children's suspensions as unjust; harmful to children; negligent in helping children with underlying problems such as bullying; undermining parents' racial socialization; and, in general, racially problematic. Suspensions also contributed to some families' withdrawal from participation in their schools. Understanding how caregivers experience children's out-of-school suspensions provides important clues to how families and schools can work together to effectively reduce racial disparities in out-of-school suspensions. PMID:24032307

  7. 5HT1Dbeta Receptor gene implicated in the pathogenesis of Obsessive-Compulsive Disorder: further evidence from a family-based association study.

    PubMed

    Mundo, E; Richter, M A; Zai, G; Sam, F; McBride, J; Macciardi, F; Kennedy, J L

    2002-01-01

    Obsessive-Compulsive Disorder (OCD) is a psychiatric condition with strong evidence for a genetic component and for the involvement of genes of the serotonin system. In a recent family-based association study we reported an association between the G allele of the G861C polymorphism of the 5HT1Dbeta receptor gene and OCD. The aim of the present study was to further investigate for the presence of linkage disequilibrium between each of two polymorphisms of the 5HT1Dbeta receptor gene and OCD in a larger sample of OCD families. In a total of 121 families the G861C and the T371G polymorphisms of the 5HT1Dbeta receptor gene were genotyped using standard protocols. The genotyping data were analyzed with a new extension of the Transmission Disequilibrium Test (FBAT). The phenotypes considered in the analyses were the diagnosis of OCD and two quantitative phenotypes related to the diagnosis and clinically relevant, ie, the age at onset and the severity of OCD symptoms. We confirmed the previously found preferential transmission of the G861 allele to the affected subjects (z = 2.262, P = 0.02). No significant association was found between the polymorphism and the quantitative phenotypes considered. These results represent a confirmation of our previous published study and thus, could have important implications for the role of the 5HT1Dbeta receptor gene in the pathogenesis and treatment of OCD. Further genetic investigations on this marker considering additional polymorphisms and other quantitative phenotypes related to OCD are warranted. PMID:12192628

  8. Global gene expression profiling of a mouse model of ovarian clear cell carcinoma caused by ARID1A and PIK3CA mutations implicates a role for inflammatory cytokine signaling

    PubMed Central

    Chandler, Ronald L.; Raab, Jesse R.; Vernon, Mike; Magnuson, Terry; Schisler, Jonathan C.

    2015-01-01

    Ovarian clear-cell carcinoma (OCCC) is an aggressive form of epithelial ovarian cancer (EOC). OCCC represents 5–25% of all EOC incidences and is the second leading cause of death from ovarian cancer (Glasspool and McNeish, 2013) [1]. A recent publication by Chandler et al. reported the first mouse model of OCCC that resembles human OCCC both genetically and histologically by inducing a localized deletion of ARID1A and the expression of the PIK3CAH1047R substitution mutation (Chandler et al., 2015) [2]. We utilized Affymetrix Mouse Gene 2.1 ST arrays for the global gene expression profiling of mouse primary OCCC tumor samples and animal-matched normal ovaries to identify cancer-dependent gene expression. We describe the approach used to generate the differentially expressed genes from the publicly available data deposited at the Gene Expression Omnibus (GEO) database under the accession number GSE57380. These data were used in cross-species comparisons to publically available human OCCC gene expression data and allowed the identification of coordinately regulated genes in both mouse and human OCCC and supportive of a role for inflammatory cytokine signaling in OCCC pathogenesis (Chandler et al., 2015) [2]. PMID:26484281

  9. Circulating low IL-23: IL-35 cytokine ratio promotes progression associated with poor prognosisin breast cancer

    PubMed Central

    Chen, Guanghui; Liang, Yanfang; Guan, Xin; Chen, Hui; Liu, Qiankun; Lin, Bihua; Chen, Can; Huang, Mingyuan; Chen, Jianan; Wu, Weiquan; Liang, Yi; Zhou, Keyuan; Zeng, Jincheng

    2016-01-01

    The interleukin (IL)-12 family, composed of heterodimeric cytokines including IL-12 (formed by IL-12p35 and IL-12p40 subunits), IL-23 (formed by IL-23p19 and IL-12p40 subunits), IL-27 (formed by IL-27p28 and EBI3 subunits) and IL-35 (formed by IL-12p35 and EBI3 subunits), establishes a link between innate and adaptive immunity that involves different immune effector cells and cytokines to tumors. However, the role of IL-12 family in breast cancer (BC) progression and prognosis remains unclear. In the present study, we demonstrated evidence indicating that EBI3, IL-12p35 and IL-12p40 but not IL-23p19 or IL-27p28 were highly expressed in BC tissues, suggested that tumor derived EBI3, IL-12p35 and IL-12p40 were associated with tumor progression. Circulating IL-12 and IL-23 low expressed, but IL-27 and IL-35 high expressed in BC patients, especially circulating IL-23 associated with IL-35 to mediate BC tumor resection. Ki-67, p53 and EGFR expression on BC tissues, as well as CA125, CA153 and CA199 levels on BC bloods increased when circulating IL-23: IL-35 ratio decreased. Together, for the first time, our data suggest that circulating IL-23: IL-35 ratio may be an important indicator association with BC progression and prognosis. However, further research should be carried out to assess the implications of circulating IL-23: IL-35 ratio in a larger sample size. PMID:27347332

  10. Inflammatory cytokines in small intestinal mucosa of patients with potential coeliac disease

    PubMed Central

    WESTERHOLM-ORMIO, M; GARIOCH, J; KETOLA, I; SAVILAHTI, E

    2002-01-01

    T helper cell type 1 (Th1) response to gluten has been implicated in the pathogenesis of coeliac disease (CD). To characterize immunological activation and mild inflammations leading to overt CD in potential coeliac patients, jejunal biopsies were obtained from family members of patients with CD or dermatitis herpetiformis (DH). Nine family members and one latent CD, eight CD patients and eight normal controls furnished jejunal biopsy specimens. Immunohistochemical staining of sections for interleukin-1α (IL-1α), IL-2, IL-4, interferon-γ (IFN-γ), tumour necrosis factor α (TNF-α), CD3, γδ-T cell receptor (γδ-TCR), and αβ-TCR was carried out with monoclonal antibodies. Further, expression of IL-4 and IFN-γ messenger RNA was detected by radioactive in situhybridization in these same samples. In lamina propria, CD patients and potential CD patients had higher densities of IL-2 (P = 0·028, P = 0·043), IL-4 (P = 0·021, P = 0·034) and IFN-γ positive cells (P = 0·000, P = 0·009) than did controls. Moreover, CD patients showed a higher density of TNF-α positive cells (P = 0·012, P = 0·001) than the other two groups, and expression of IFN-γ mRNA (P = 0·035) was higher in them than in the other two study groups. Additionally, higher densities of TNF-α and IFN-γ positive cells occurred in potential CD patients with high γδ-TCR+ intraepithelial lymphocytes (IELs). Our findings support the hypothesis that lamina propria T cells and macrophages, through their secretion of cytokines, play a central role in the pathogenesis of coeliac disease. The inflammatory cytokines found in potential CD specimens strongly suggest that these inflammatory markers can be identified long before visible villous changes have occurred. PMID:11982596

  11. Effects of Pregnancy-associated Malaria on T Cell Cytokines in Cameroonian Women.

    PubMed

    Megnekou, R; Lissom, A; Bigoga, J D; Djontu, J C

    2015-06-01

    Although Th17 cells subsets improve immunity against extra and intracellular pathogens, and in modulating Th1 and other immune responses, its role on pregnancy-associated malaria (PAM) is unknown. This study aims to investigate the effects of PAM on Th1 (IFN-γ, TNF-α), IL-10 family (IL-10, IL-19, IL-22), Th17 (IL-17A, IL-23) cytokines and on CXCL-10 chemokine profiles in pregnant women. Between 2010 and 2011, venous blood specimens from 107 volunteer pregnant Cameroonian women was used to determine parasitaemia microscopically and haemoglobin levels using HemoCue analyzer. Plasma levels of the biomarkers were determined by ELISA. Parasitaemia was higher in women with low haemoglobin levels, parity and mother's age. IL-10 and CXCL-10 plasma levels were higher in the malaria infected and in anaemic women while IFN-γ and IL-17A levels were higher in malaria non-infected and in non-anaemic women. Parasitaemia correlated positively with IL-10 and CXCL-10 levels but inversely with IFN-γ and IL-17A. Haemoglobin levels were higher in women with low IL-10 and CXCL-10 levels, and in group with high IFN-γ, IL-17A and IL-23 levels. Only IL-10 levels associated negatively with parity. Positive correlations were observed between Th17 (IL-17A) and Th1 (IFN-γ, TNF-α), IL-10 family (IL-19 and IL-22) and Th17 (IL-23) cytokines. Multivariate analysis showed association between: mother's age and IFN-γ levels, parasitaemia and IL-10 and CXCL-10 levels and haemoglobin levels, gestational age and IL-17A levels. In conclusion, during PAM, CXCL-10 and IL-10 responses are implicated in the pathogenesis while Th17 and Th1 immune responses, via IL-17A and IFN-γ might play protective roles. PMID:25736985

  12. Suppressor of cytokine signaling 3 inhibits head kidney macrophage activation and cytokine expression in Scophthalmus maximus.

    PubMed

    Zhang, Min; Xiao, Zhi-zhong; Sun, Li

    2011-02-01

    Proteins of the suppressor of cytokine signaling (SOCS) family function as inducible feedback inhibitors of cytokine signaling via the JAK/STAT pathway. Although several SOCS isoforms have been identified in teleosts, their immunological functions remain largely unknown. In this study, we identified in turbot Scophthalmus maximus a SOCS homologue (named SmSOCS3) of the mammalian SOCS3 type. The deduced amino acid sequence of SmSOCS3 contains 205 residues and shares extensive overall identities (60-82%) with those of known fish SOCS3. In silico analyses revealed that, like typical SOCS3, SmSOCS3 possesses a kinase inhibitor region (KIR), a Src homology 2 (SH2) domain, and a SOCS box domain. Under physiological conditions SmSOCS3 expression was detected, in increasing order, in blood, brain, heart, kidney, liver, spleen, muscle, and gill. Experimental infection of turbot with a bacterial pathogen induced significant SmSOCS3 expression in kidney, spleen, liver, and gill in time-dependent manners. Examination of SmSOCS3 expression in head kidney (HK) macrophages showed that SmSOCS3 transcription was significantly upregulated in the presence of purified recombinant TNF-α. On the other hand, SmSOCS3 overexpression in HK macrophages inhibited the transcription of TNF-α as well as IL-1β and CC-chemokine. In addition, SmSOCS3 overexpression significantly reduced macrophage respiratory burst activity, nitric oxide production, and bactericidal activity. Taken together, these results suggest that SmSOCS3 is a cytokine-inducible suppressor of pro-inflammatory cytokine signaling in HK macrophages and that regulated expression of SmSOCS3 is required for optimal innate immune response against bacterial infection. PMID:20869394

  13. Cytokines and persistent viral infections.

    PubMed

    Beltra, Jean-Christophe; Decaluwe, Hélène

    2016-06-01

    Intracellular pathogens such as the human immunodeficiency virus, hepatitis C and B or Epstein-Barr virus often cause chronic viral infections in humans. Persistence of these viruses in the host is associated with a dramatic loss of T-cell immune response due to functional T-cell exhaustion. Developing efficient immunotherapeutic approaches to prevent viral persistence and/or to restore a highly functional T-cell mediated immunity remains a major challenge. During the last two decades, numerous studies aimed to identify relevant host-derived factors that could be modulated to achieve this goal. In this review, we focus on recent advances in our understanding of the role of cytokines in preventing or facilitating viral persistence. We concentrate on the impact of multiple relevant cytokines in T-cell dependent immune response to chronic viral infection and the potential for using cytokines as therapeutic agents in mice and humans. PMID:26907634

  14. The ABC transporter gene family of Caenorhabditis elegans has implications for the evolutionary dynamics of multidrug resistance in eukaryotes

    PubMed Central

    Sheps, Jonathan A; Ralph, Steven; Zhao, Zhongying; Baillie, David L; Ling, Victor

    2004-01-01

    Background Many drugs of natural origin are hydrophobic and can pass through cell membranes. Hydrophobic molecules must be susceptible to active efflux systems if they are to be maintained at lower concentrations in cells than in their environment. Multi-drug resistance (MDR), often mediated by intrinsic membrane proteins that couple energy to drug efflux, provides this function. All eukaryotic genomes encode several gene families capable of encoding MDR functions, among which the ABC transporters are the largest. The number of candidate MDR genes means that study of the drug-resistance properties of an organism cannot be effectively carried out without taking a genomic perspective. Results We have annotated sequences for all 60 ABC transporters from the Caenorhabditis elegans genome, and performed a phylogenetic analysis of these along with the 49 human, 30 yeast, and 57 fly ABC transporters currently available in GenBank. Classification according to a unified nomenclature is presented. Comparison between genomes reveals much gene duplication and loss, and surprisingly little orthology among analogous genes. Proteins capable of conferring MDR are found in several distinct subfamilies and are likely to have arisen independently multiple times. Conclusions ABC transporter evolution fits a pattern expected from a process termed 'dynamic-coherence'. This is an unusual result for such a highly conserved gene family as this one, present in all domains of cellular life. Mechanistically, this may result from the broad substrate specificity of some ABC proteins, which both reduces selection against gene loss, and leads to the facile sorting of functions among paralogs following gene duplication. PMID:15003118

  15. The Organizational Social Context of Mental Health Medicaid Waiver Programs with Family Support Services: Implications for Research and Practice

    PubMed Central

    Glisson, Charles; Williams, Nathaniel J.; Green, Philip; Hemmelgarn, Anthony; Hoagwood, Kimberly

    2013-01-01

    Introduction Peer family support specialists (FSS) are parents with practical experience in navigating children’s mental health care systems who provide support, advocacy and guidance to the families of children who need mental health services. Their experience and training differ from those of formally trained mental health clinicians, creating potential conflicts in priorities and values between FSS and clinicians. We hypothesized that these differences could negatively affect the organizational cultures and climates of mental health clinics that employ both FSS and mental health clinicians, and lower the job satisfaction and organizational commitment of FSS. Method The Organizational Social Context (OSC) measure was administered on site to 209 FSS and clinicians in 21 mental health programs in New York State. The study compared the organizational-level culture and climate profiles of mental health clinics that employ both FSS and formally trained clinicians to national norms for child mental health clinics, assessed individual-level job satisfaction and organizational commitment as a function of job (FSS vs. clinician) and other individual-level and organizational-level characteristics, and tested whether FSS and clinicians’ job attitudes are differentially associated with organizational culture and climate. Results The programs’ organizational culture and climate profiles were not significantly different from national norms. Individual-level job satisfaction and organizational commitment were unrelated to position (FSS vs. clinician) or other individual-level and organizational-level characteristics except for culture and climate. Conclusions Organizational culture and climate are not related to the employment of FSS. Both FSS’ and clinicians’ individual-level work attitudes are associated similarly with organizational culture and climate. PMID:24065458

  16. A Drosophila protein family implicated in pheromone perception is related to Tay-Sachs GM2-activator protein.

    PubMed

    Starostina, Elena; Xu, Aiguo; Lin, Heping; Pikielny, Claudio W

    2009-01-01

    Low volatility, lipid-like cuticular hydrocarbon pheromones produced by Drosophila melanogaster females play an essential role in triggering and modulating mating behavior, but the chemosensory mechanisms involved remain poorly understood. Recently, we showed that the CheB42a protein, which is expressed in only 10 pheromone-sensing taste hairs on the front legs of males, modulates progression to late stages of male courtship behavior in response to female-specific cuticular hydrocarbons. Here we report that expression of all 12 genes in the CheB gene family is predominantly or exclusively gustatory-specific, and occurs in many different, often non-overlapping patterns. Only the Gr family of gustatory receptor genes displays a comparable variety of gustatory-specific expression patterns. Unlike Grs, however, expression of all but one CheB gene is sexually dimorphic. Like CheB42a, other CheBs may therefore function specifically in gustatory perception of pheromones. We also show that CheBs belong to the ML superfamily of lipid-binding proteins, and are most similar to human GM2-activator protein (GM2-AP). In particular, GM2-AP residues involved in ligand binding are conserved in CheBs but not in other ML proteins. Finally, CheB42a is specifically secreted into the inner lumen of pheromone-sensing taste hairs, where pheromones interact with membrane-bound receptors. We propose that CheB proteins interact directly with lipid-like Drosophila pheromones and modulate their detection by the gustatory signal transduction machinery. Furthermore, as loss of GM2-AP in Tay-Sachs disease prevents degradation of GM2 gangliosides and results in neurodegeneration, the function of CheBs in pheromone response may involve biochemical mechanisms critical for lipid metabolism in human neurons. PMID:18952610

  17. Parent's alcoholism severity and family topic avoidance about alcohol as predictors of perceived stigma among adult children of alcoholics: Implications for emotional and psychological resilience.

    PubMed

    Haverfield, Marie C; Theiss, Jennifer A

    2016-01-01

    Alcoholism is a highly stigmatized condition, with both alcohol-dependent individuals and family members of the afflicted experiencing stigmatization. This study examined the severity of a parent's alcoholism and family topic avoidance about alcohol as two factors that are associated with family members' perceptions of stigma. Three dimensions of stigma were considered: discrimination stigma, disclosure stigma, and positive aspect stigma. In addition, this study assessed associations between perceived stigmatization and individuals' experiences of depressive symptoms, self-esteem, and resilience. Adult children of alcoholics (N = 622) were surveyed about family conditions, perceived stigma, and their emotional and psychological well-being. Regression analyses revealed that the severity of a parent's alcoholism predicted all three types of stigma for females, but not for males. In addition, family topic avoidance about alcohol predicted all types of stigma for males and discrimination stigma and positive aspect stigma for females. With few exceptions, the three types of stigma predicted depressive symptoms, self-esteem, and resilience for both male and female adult children of alcoholics. The results are discussed in terms of their implications for promoting a family environment that mitigates stigma and encourages emotional and psychological well-being. In 2012, approximately 3.3 million deaths worldwide were due to the harmful use of alcohol (World Health Organization [WHO], 2014). Individuals who abuse alcohol are susceptible to a variety of negative health outcomes (Rehm et al., 2009) and display inappropriate social behaviors (Klingemann, 2001; Schomerus et al., 2011a). General societal perceptions tend to characterize alcohol-dependent individuals as irresponsible and lacking in self-control (Schomerus et al., 2011b). Research in the United Kingdom found that 54% of the population believes alcohol-dependent individuals are personally to blame for their own

  18. Neutral buoyancy and sleep-deprived serum factors alter expression of cytokines regulating osteogenesis

    NASA Astrophysics Data System (ADS)

    Gorczynski, Reginald M.; Gorczynski, Christopher P.; Gorczynski, Laura Y.; Hu, Jiang; Lu, Jin; Manuel, Justin; Lee, Lydia

    2005-05-01

    We examined expression of genes associated with cytokine production, and genes implicated in regulating bone metabolism, in bone stromal and osteoblast cells incubated under standard ground conditions and under conditions of neutral buoyancy, and in the presence/absence of serum from normal or sleep-deprived mice. We observed a clear interaction between these two conditions (exposure to neutral buoyancy and serum stimulation) in promoting enhanced osteoclastogenesis. Both conditions independently altered expression of a number of cytokines implicated in the regulation of bone metabolism. However, using stromal cells from IL-1 and TNF α cytokine r KO mice, we concluded that the increased bone loss under microgravity conditions was not primarily cytokine mediated.

  19. Circulating Cytokine Levels as Markers of Inflammation in Philadelphia Negative Myeloproliferative Neoplasms: Diagnostic and Prognostic Interest

    PubMed Central

    Mondet, Julie; Hussein, Kais; Mossuz, Pascal

    2015-01-01

    Cytokines are well known mediators of numerous physiological and pathological processes. They contribute to the regulation of normal hematopoiesis but increasing data suggest that they also have a clinical impact in some hematopoietic malignancies. In particular, there is evidence that cytokines are implicated in the functional symptoms of Philadelphia negative myeloproliferative neoplasms (Ph− MPNs), suggesting that evaluation of circulating levels of cytokines could be of clinical interest for the characterization of patients at the time of diagnosis and for disease prognosis. In this review, we present the current knowledge on alteration of circulating cytokine profiles in MPNs and their role in myelofibrosis pathogenesis. Phenotypic correlation, prognostic value of cytokines, and impact of JAK inhibitors are also discussed. PMID:26525644

  20. Upd3--an ancestor of the four-helix bundle cytokines.

    PubMed

    Oldefest, Mirja; Nowinski, Jana; Hung, Chien-Wen; Neelsen, Denis; Trad, Ahmad; Tholey, Andreas; Grötzinger, Joachim; Lorenzen, Inken

    2013-06-21

    The unpaired-like protein 3 (Upd3) is one of the three cytokines of Drosophila melanogaster supposed to activate the JAK/STAT signaling pathway (Janus tyrosine kinases/signal transducer and activator of transcription). This activation occurs via the type-I cytokine receptor domeless, an orthologue of gp130, the common signal transducer of all four-helix bundle interleukin-6 (IL-6) type cytokines. Both receptors are known to exist as preformed dimers in the plasma membrane and initiate the acute-phase response. These facts indicate an evolutionary relation between vertebrate IL-6 and the Drosophila protein Upd3. Here we presented data which strengthen this notion. Upd3 was recombinantly expressed, a renaturation and purification protocol was established which allows to obtain high amounts of biological active protein. This protein is, like human IL-6, a monomeric-α helical cytokine, implicating that Upd3 is an "ancestor" of the four-helix bundle cytokines. PMID:23707937

  1. Y-Family DNA polymerases may use two different dNTP shapes for insertion: a hypothesis and its implications.

    PubMed

    Chandani, Sushil; Loechler, Edward L

    2009-04-01

    Chemicals and radiation can damage DNA leading to the formation of adducts/lesions, which - if not removed by DNA repair pathways - usually block replicative DNA polymerases (DNAPs). To overcome such potentially lethal blockage, cells have lesion bypass DNAPs, which are often in the Y-Family and include several classes. One class includes human DNAP kappa and E. coli DNAP IV, and they insert dCTP in the non-mutagenic pathway opposite [+ta]-B[a]P-N(2)-dG, which is the major adduct formed by the environmental carcinogen benzo[a]pyrene. Another class includes hDNAP eta and ecDNAP V, and they insert dATP opposite [+ta]-B[a]P-N(2)-dG in the dominant G-->T mutagenic pathway. Herein we develop a hypothesis for why the IV/kappa-class preferentially does cellular dCTP insertion. On the minor groove side of the active site, Y-Family DNAPs have a cleft/hole that can be analyzed based on an analogy to a "chimney." Our models of DNAP IV show a large chimney opening from which the pyrene of [+ta]-B[a]P-N(2)-dG can protrude, which allows canonical adduct-dG:dCTP pairing. In contrast, our models of DNAP V have small chimney openings that forces adduct-dG downward in the active site such that canonical adduct-dG:dCTP pairing is not possible. Based on X-ray structures, sequence alignment and our modeled structures of Y-Family DNAPs, chimney opening size seems primarily controlled by one amino acid ("flue-handle"), which dictates whether nearby amino acids ("flue") plug the chimney or not. Based on this analysis, a correlation is apparent: the flue is closed in V/eta-class DNAPs giving small chimney openings, while the flue is open for the IV/kappa-class giving large chimney openings. Secondarily, a hypothesis is developed for why the V/eta-class might preferentially do cellular dATP insertion opposite [+ta]-B[a]P-N(2)-dG: the small chimney forces adduct-dG lower in the active site, possibly leading to catalysis using a non-canonical dNTP shape that permits syn-adenine:adduct-dG base

  2. Children and Political Violence from a Social Ecological Perspective: Implications from Research on Children and Families in Northern Ireland

    PubMed Central

    Cummings, E. Mark; Goeke-Morey, Marcie C.; Schermerhorn, Alice C.; Merrilees, Christine E.; Cairns, Ed

    2013-01-01

    The effects on children of political violence are matters of international concern, with many negative effects well-documented. At the same time, relations between war, terrorism or other forms of political violence and child development do not occur in a vacuum. The impact can be understood as related to changes in the communities, families and other social contexts in which children live, and in the psychological processes engaged by these social ecologies. To advance this process-oriented perspective, a social ecological model for the effects of political violence on children is advanced. This approach is illustrated by findings and methods from an ongoing research project on political violence and children in Northern Ireland. Aims of this project include both greater insight into this particular context for political violence and the provision of a template for study of the impact of children’s exposure to violence in other regions of the world. Accordingly, the applicability of this approach is considered for other social contexts, including (a) another area in the world with histories of political violence, and (b) a context of community violence in the US. PMID:19229611

  3. A heritable form of SMARCE1-related meningiomas with important implications for follow-up and family screening.

    PubMed

    Gerkes, E H; Fock, J M; den Dunnen, W F A; van Belzen, M J; van der Lans, C A; Hoving, E W; Fakkert, I E; Smith, M J; Evans, D G; Olderode-Berends, M J W

    2016-04-01

    Childhood meningiomas are rare. Recently, a new hereditary tumor predisposition syndrome has been discovered, resulting in an increased risk for spinal and intracranial clear cell meningiomas (CCMs) in young patients. Heterozygous loss-of-function germline mutations in the SMARCE1 gene are causative, giving rise to an autosomal dominant inheritance pattern. We report on an extended family with a pediatric CCM patient and an adult CCM patient and several asymptomatic relatives carrying a germline SMARCE1 mutation, and discuss difficulties in genetic counseling for this heritable condition. Because of the few reported cases so far, the lifetime risk of developing meningiomas for SMARCE1 mutation carriers is unclear and the complete tumor spectrum is unknown. There is no surveillance guideline for asymptomatic carriers nor a long-term follow-up recommendation for SMARCE1-related CCM patients as yet. Until more information is available about the penetrance and tumor spectrum of the condition, we propose the following screening advice for asymptomatic SMARCE1 mutation carriers: neurological examination and MRI of the brain and spine, yearly from diagnosis until the age of 18 and once every 3 years thereafter, or in between if there are clinical symptoms. This advice can also be used for long-term patient follow-up. More data is needed to optimize this proposed screening advice. PMID:26803492

  4. Gene family analysis of the Arabidopsis pollen transcriptome reveals biological implications for cell growth, division control, and gene expression regulation.

    PubMed

    Pina, Cristina; Pinto, Francisco; Feijó, José A; Becker, Jörg D

    2005-06-01

    Upon germination, pollen forms a tube that elongates dramatically through female tissues to reach and fertilize ovules. While essential for the life cycle of higher plants, the genetic basis underlying most of the process is not well understood. We previously used a combination of flow cytometry sorting of viable hydrated pollen grains and GeneChip array analysis of one-third of the Arabidopsis (Arabidopsis thaliana) genome to define a first overview of the pollen transcriptome. We now extend that study to approximately 80% of the genome of Arabidopsis by using Affymetrix Arabidopsis ATH1 arrays and perform comparative analysis of gene family and gene ontology representation in the transcriptome of pollen and vegetative tissues. Pollen grains have a smaller and overall unique transcriptome (6,587 genes expressed) with greater proportions of selectively expressed (11%) and enriched (26%) genes than any vegetative tissue. Relative gene ontology category representations in pollen and vegetative tissues reveal a functional skew of the pollen transcriptome toward signaling, vesicle transport, and the cytoskeleton, suggestive of a commitment to germination and tube growth. Cell cycle analysis reveals an accumulation of G2/M-associated factors that may play a role in the first mitotic division of the zygote. Despite the relative underrepresentation of transcription-associated transcripts, nonclassical MADS box genes emerge as a class with putative unique roles in pollen. The singularity of gene expression control in mature pollen grains is further highlighted by the apparent absence of small RNA pathway components. PMID:15908605

  5. miR-29s: a family of epi-miRNAs with therapeutic implications in hematologic malignancies

    PubMed Central

    Amodio, Nicola; Rossi, Marco; Raimondi, Lavinia; Pitari, Maria Rita; Botta, Cirino; Tagliaferri, Pierosandro; Tassone, Pierfrancesco

    2015-01-01

    A wealth of studies has highlighted the biological complexity of hematologic malignancies and the role of dysregulated signal transduction pathways. Along with the crucial role of genetic abnormalities, epigenetic aberrations are nowadays emerging as relevant players in cancer development, and significant research efforts are currently focusing on mechanisms by which histone post-translational modifications, DNA methylation and noncoding RNAs contribute to the pathobiology of cancer. As a consequence, these studies have provided the rationale for the development of epigenetic drugs, such as histone deacetylase inhibitors and demethylating compounds, some of which are currently in advanced phase of pre-clinical investigation or in clinical trials. In addition, a more recent body of evidence indicates that microRNAs (miRNAs) might target effectors of the epigenetic machinery, which are aberrantly expressed or active in cancers, thus reverting those epigenetic abnormalities driving tumor initiation and progression. This review will focus on the broad epigenetic activity triggered by members of the miR-29 family, which underlines the potential of miR-29s as candidate epi-therapeutics for the treatment of hematologic malignancies. PMID:25968566

  6. The PIM family of oncoproteins: Small kinases with huge implications in myeloid leukemogenesis and as therapeutic targets

    PubMed Central

    Shah, Parag P.; Mims, Alice S.; Lockwood, William W.; Kraft, Andrew S.; Beverly, Levi J.

    2014-01-01

    PIM kinases are a family of serine/threonine kinases involved in cell survival and proliferation. There is significant structural similarity between the three PIM kinases (PIM1, PIM2 and PIM3) and few amino acid differences. Although, several studies have specifically monitored the role of PIM1 in tumorigenesis, much less is known about PIM2 and PIM3. Therefore, in this study we have used in vitro cell culture models and in vivo bone marrow infection/transplantation to assess the comparative signaling and oncogenic potential of each of the three PIM kinases. All three PIM kinases were able to protect FL5.12 cells from IL-3 withdrawal induced death. Interestingly, the downstream signaling cascades were indistinguishable between the three kinases. Transplantation of murine bone marrow co-expressing MYC and PIM1, PIM2 or PIM3 caused rapid and uniformly lethal myeloid leukemia. De-induction of MYC 18 days following transplantation significantly increased the survival of mice, even with continual expression of PIM kinases. Alternatively, mice treated at the pre-leukemic stage with a PIM kinase inhibitor increased the lifespan of the mice, even with continual expression of the MYC transgene. These data demonstrate the role of PIM kinases in driving myeloid leukemia, and as candidate molecules for therapy against human malignancies. PMID:25238262

  7. miR-29s: a family of epi-miRNAs with therapeutic implications in hematologic malignancies.

    PubMed

    Amodio, Nicola; Rossi, Marco; Raimondi, Lavinia; Pitari, Maria Rita; Botta, Cirino; Tagliaferri, Pierosandro; Tassone, Pierfrancesco

    2015-05-30

    A wealth of studies has highlighted the biological complexity of hematologic malignancies and the role of dysregulated signal transduction pathways. Along with the crucial role of genetic abnormalities, epigenetic aberrations are nowadays emerging as relevant players in cancer development, and significant research efforts are currently focusing on mechanisms by which histone post-translational modifications, DNA methylation and noncoding RNAs contribute to the pathobiology of cancer. As a consequence, these studies have provided the rationale for the development of epigenetic drugs, such as histone deacetylase inhibitors and demethylating compounds, some of which are currently in advanced phase of pre-clinical investigation or in clinical trials. In addition, a more recent body of evidence indicates that microRNAs (miRNAs) might target effectors of the epigenetic machinery, which are aberrantly expressed or active in cancers, thus reverting those epigenetic abnormalities driving tumor initiation and progression. This review will focus on the broad epigenetic activity triggered by members of the miR-29 family, which underlines the potential of miR-29s as candidate epi-therapeutics for the treatment of hematologic malignancies. PMID:25968566

  8. An Assessment of Nutrition Practices and Attitudes in Family Child-Care Homes: Implications for Policy Implementation

    PubMed Central

    Risica, Patricia; Mena, Noereem; Lawson, Eliza; Ankoma, Angela; Gans, Kim M.

    2015-01-01

    Introduction Family child-care homes (FCCHs) provide care and nutrition for millions of US children, including 28% in Rhode Island. New proposed regulations for FCCHs in Rhode Island require competencies and knowledge in nutrition. We explored nutrition-related practices and attitudes of FCCH providers in Rhode Island and assessed whether these differed by provider ethnicity or socioeconomic status of the enrolled children. Methods Of 536 licensed FCCHs in Rhode Island, 105 randomly selected FCCH providers completed a survey about provider nutrition attitudes and practices, demographics of providers, and characteristics of the FCCH, including participation in the federal Child and Adult Care Food Program (CACFP). No differences between CACFP and non-CACFP participants were found; responses were compared by provider ethnicity using χ2 tests and multivariate models. Results Nearly 70% of FCCHs reported receiving nutrition training only 0 to 3 times during the past 3 years; however, more than 60% found these trainings to be very helpful. More Hispanic than non-Hispanic providers strongly agreed to sitting with children during meals, encouraging children to finish their plate, and being involved with parents on the topics of healthy eating and weight. These differences persisted in multivariate models. Discussion Although some positive practices are in place in Rhode Island FCCHs, there is room for improvement. State licensing requirements provide a foundation for achieving better nutrition environments in FCCHs, but successful implementation is key to translating policies into real changes. FCCH providers need culturally and linguistically appropriate nutrition-related training. PMID:26043303

  9. Personal history of dieting and family history of obesity are unrelated: implications for understanding weight gain proneness.

    PubMed

    Lowe, M R; Shank, L M; Mikorski, R; Butryn, M L

    2015-04-01

    Identifying predictors of future weight gain is important in obesity prevention efforts. Both family history of obesity and personal dieting history have been established as predictors of future weight gain; however, it is unknown if they are independent or overlapping predictors. The purpose of this study was to examine the degree of overlap between these two predictors using cross-sectional data. Baseline data from four studies were examined separately and in combination for a total of 561 female participants, and analyses were conducted to examine parent anthropometric variables by dieting status within and across studies. All participants were female university students between the ages of 17 and 30. For each study, as well as for the entire sample combined, parent anthropometric variables were examined by dieting status using factorial ANOVAs. No meaningful pattern was found when examining parent anthropometric variables by dieting status, which suggests that the two risk factors are largely independent. This suggests that the processes associated with the development of future weight gain by each variable are different; therefore, future research should use a longitudinal study to test the hypothesis that using both variables to predict future weight gain would account for more variance than using either variable alone. PMID:25725461

  10. Children and political violence from a social ecological perspective: implications from research on children and families in Northern Ireland.

    PubMed

    Cummings, E Mark; Goeke-Morey, Marcie C; Schermerhorn, Alice C; Merrilees, Christine E; Cairns, Ed

    2009-03-01

    The effects on children of political violence are matters of international concern, with many negative effects well-documented. At the same time, relations between war, terrorism, or other forms of political violence and child development do not occur in a vacuum. The impact can be understood as related to changes in the communities, families and other social contexts in which children live, and in the psychological processes engaged by these social ecologies. To advance this process-oriented perspective, a social ecological model for the effects of political violence on children is advanced. This approach is illustrated by findings and methods from an ongoing research project on political violence and children in Northern Ireland. Aims of this project include both greater insight into this particular context for political violence and the provision of a template for study of the impact of children's exposure to violence in other regions of the world. Accordingly, the applicability of this approach is considered for other social contexts, including (a) another area in the world with histories of political violence and (b) a context of community violence in the US. PMID:19229611

  11. Cytokine signaling-1 suppressor is inducible by IL-1beta and inhibits the catabolic effects of IL-1beta in chondrocytes: its implication in the paradoxical joint-protective role of IL-1beta

    PubMed Central

    2013-01-01

    Introduction Although IL-1β is believed to be crucial in the pathogenesis of osteoarthritis (OA), the IL-1β blockade brings no therapeutic benefit in human OA and results in OA aggravation in several animal models. We explored the role of a cytokine signaling 1 (SOCS1) suppressor as a regulatory modulator of IL-1β signaling in chondrocytes. Methods Cartilage samples were obtained from patients with knee OA and those without OA who underwent surgery for femur-neck fracture. SOCS1 expression in cartilage was assessed with immunohistochemistry. IL-1β-induced SOCS1 expression in chondrocytes was analyzed with quantitative polymerase chain reaction and immunoblot. The effect of SOCS1 on IL-1β signaling pathways and the synthesis of matrix metalloproteinases (MMPs) and aggrecanase-1 was investigated in SOCS1-overexpressing or -knockdown chondrocytes. Results SOCS1 expression was significantly increased in OA cartilage, especially in areas of severe damage (P < 0.01). IL-1β stimulated SOCS1 mRNA expression in a dose-dependent pattern (P < 0.01). The IL-1β-induced production of MMP-1, MMP-3, MMP-13, and ADAMTS-4 (aggrecanase-1, a disintegrin and metalloproteinase with thrombospondin motifs 4) was affected by SOCS1 overexpression or knockdown in both SW1353 cells and primary human articular chondrocytes (all P values < 0.05). The inhibitory effects of SOCS1 were mediated by blocking p38, c-Jun N-terminal kinase (JNK), and nuclear factor κB (NF-κB) activation, and by downregulating transforming growth factor-β-activated kinase 1 (TAK1) expression. Conclusions Our results show that SOCS1 is induced by IL1-β in OA chondrocytes and suppresses the IL-1β-induced synthesis of matrix-degrading enzymes by inhibiting IL-1β signaling at multiple levels. It suggests that the IL-1β-inducible SOCS1 acts as a negative regulator of the IL-1β response in OA cartilage. PMID:24238405

  12. Proposed changes to the American Psychiatric Association diagnostic criteria for autism spectrum disorder: implications for young children and their families.

    PubMed

    Grant, Roy; Nozyce, Molly

    2013-05-01

    The American Psychiatric Association has revised the diagnostic criteria for their DSM-5 manual. Important changes have been made to the diagnosis of the current (DSM-IV) category of Pervasive Developmental Disorders. This category includes Autistic Disorder (autism), Asperger's Disorder, and Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS). The DSM-5 deletes Asperger's Disorder and PDD-NOS as diagnostic entities. This change may have unintended consequences, including the possibility that the new diagnostic framework will adversely affect access to developmental interventions under Individuals with Disabilities Education Act (IDEA) programs, Early Intervention (for birth to 2 years olds) and preschool special education (for 3 and 4 years olds). Changing the current diagnosis of PDD-NOS to a "Social Communication Disorder" focused on language pragmatics in the DSM-5 may restrict eligibility for IDEA programs and limit the scope of services for affected children. Young children who meet current criteria for PDD-NOS require more intensive and multi-disciplinary services than would be available with a communication domain diagnosis and possible service authorization limited to speech-language therapy. Intensive behavioral interventions, inclusive group setting placements, and family support services are typically more available for children with an autism spectrum disorder than with diagnoses reflecting speech-language delay. The diagnostic distinction reflective of the higher language and social functioning between Asperger's Disorder and autism is also undermined by eliminating the former as a categorical diagnosis and subsuming it under autism. This change may adversely affect treatment planning and misinform parents about prognosis for children who meet current criteria for Asperger's Disorder. PMID:23456348

  13. Family Pet Ownership during Childhood: Findings from a UK Birth Cohort and Implications for Public Health Research

    PubMed Central

    Westgarth, Carri; Heron, Jon; Ness, Andy R.; Bundred, Peter; Gaskell, Rosalind M.; Coyne, Karen P.; German, Alexander J.; McCune, Sandra; Dawson, Susan

    2010-01-01

    In developed nations, approximately half of household environments contain pets. Studies of Human-Animal Interaction (HAI) have proposed that there are health benefits and risks associated with pet ownership. However, accurately demonstrating and understanding these relationships first requires a better knowledge of factors associated with ownership of different pet types. A UK birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC), were used to collect pet ownership data from the mothers, from gestation to child age 10 years old. 14,663 children were included in the study, of which mothers of 13,557 reported pet information at gestation, and 7,800 by age 10. Pet types recorded include cat, dog, rabbit, rodent, bird, fish and tortoise/turtle. The dataset also contains a number of demographic, socioeconomic and behavioural variables relevant to human health behaviour. Logistic regression was used to build multivariable models for ownership of each pet type at age 7 years. Family pet ownership increased during childhood, in particular rabbits, rodents and fish. A number of socioeconomic and demographic factors were associated with ownership of different pet types and the effects differed depending on the pet type studied. Variables which require consideration by researchers include gender, presence of older siblings, ethnicity, maternal and paternal education, maternal and paternal social class, maternal age, number of people in the household, house type, and concurrent ownership of other pets. Whether the mother had pets during her childhood was a strong predictor of pet ownership in all models. In HAI studies, care should be taken to control for confounding factors, and to treat each pet type individually. ALSPAC and other similar birth cohorts can be considered a potential resource for research into the effects of pet ownership during childhood. PMID:21139856

  14. Targeted resequencing implicates the familial Mediterranean fever gene MEFV and the toll-like receptor 4 gene TLR4 in Behçet disease.

    PubMed

    Kirino, Yohei; Zhou, Qing; Ishigatsubo, Yoshiaki; Mizuki, Nobuhisa; Tugal-Tutkun, Ilknur; Seyahi, Emire; Özyazgan, Yilmaz; Ugurlu, Serdal; Erer, Burak; Abaci, Neslihan; Ustek, Duran; Meguro, Akira; Ueda, Atsuhisa; Takeno, Mitsuhiro; Inoko, Hidetoshi; Ombrello, Michael J; Satorius, Colleen L; Maskeri, Baishali; Mullikin, James C; Sun, Hong-Wei; Gutierrez-Cruz, Gustavo; Kim, Yoonhee; Wilson, Alexander F; Kastner, Daniel L; Gül, Ahmet; Remmers, Elaine F

    2013-05-14

    Genome-wide association studies (GWAS) are a powerful means of identifying genes with disease-associated common variants, but they are not well-suited to detecting genes with disease-associated rare and low-frequency variants. In the current study of Behçet disease (BD), nonsynonymous variants (NSVs) identified by deep exonic resequencing of 10 genes found by GWAS (IL10, IL23R, CCR1, STAT4, KLRK1, KLRC1, KLRC2, KLRC3, KLRC4, and ERAP1) and 11 genes selected for their role in innate immunity (IL1B, IL1R1, IL1RN, NLRP3, MEFV, TNFRSF1A, PSTPIP1, CASP1, PYCARD, NOD2, and TLR4) were evaluated for BD association. A differential distribution of the rare and low-frequency NSVs of a gene in 2,461 BD cases compared with 2,458 controls indicated their collective association with disease. By stringent criteria requiring at least a single burden test with study-wide significance and a corroborating test with at least nominal significance, rare and low-frequency NSVs in one GWAS-identified gene, IL23R (P = 6.9 × 10(-5)), and one gene involved in innate immunity, TLR4 (P = 8.0 × 10(-4)), were associated with BD. In addition, damaging or rare damaging NOD2 variants were nominally significant across all three burden tests applied (P = 0.0063-0.045). Furthermore, carriage of the familial Mediterranean fever gene (MEFV) mutation Met694Val, which is known to cause recessively inherited familial Mediterranean fever, conferred BD risk in the Turkish population (OR, 2.65; P = 1.8 × 10(-12)). The disease-associated NSVs in MEFV and TLR4 implicate innate immune and bacterial sensing mechanisms in BD pathogenesis. PMID:23633568

  15. Proinflammatory cytokines, aging, and age-related diseases.

    PubMed

    Michaud, Martin; Balardy, Laurent; Moulis, Guillaume; Gaudin, Clement; Peyrot, Caroline; Vellas, Bruno; Cesari, Matteo; Nourhashemi, Fati

    2013-12-01

    Inflammation is a physiological process that repairs tissues in response to endogenous or exogenous aggressions. Nevertheless, a chronic state of inflammation may have detrimental consequences. Aging is associated with increased levels of circulating cytokines and proinflammatory markers. Aged-related changes in the immune system, known as immunosenescence, and increased secretion of cytokines by adipose tissue, represent the major causes of chronic inflammation. This phenomenon is known as "inflamm-aging." High levels of interleukin (IL)-6, IL-1, tumor necrosis factor-α, and C-reactive protein are associated in the older subject with increased risk of morbidity and mortality. In particular, cohort studies have indicated TNF-α and IL-6 levels as markers of frailty. The low-grade inflammation characterizing the aging process notably concurs at the pathophysiological mechanisms underlying sarcopenia. In addition, proinflammatory cytokines (through a variety of mechanisms, such as platelet activation and endothelial activation) may play a major role in the risk of cardiovascular events. Dysregulation of the inflammatory pathway may also affect the central nervous system and be involved in the pathophysiological mechanisms of neurodegenerative disorders (eg, Alzheimer disease).The aim of the present review was to summarize different targets of the activity of proinflammatory cytokines implicated in the risk of pathological aging. PMID:23792036

  16. Cytokines and Mycobacterium leprae induce apoptosis in human Schwann cells.

    PubMed

    Oliveira, Rosane B; Sampaio, Elizabeth P; Aarestrup, Fernando; Teles, Rosane M B; Silva, Tatiana P; Oliveira, Ariane L; Antas, Paulo R Z; Sarno, Euzenir N

    2005-10-01

    The development of deformities during the course of leprosy disease is a major public health concern worldwide. It is possible that cytokine production and apoptosis of Schwann cells (SCs) directly affect nerve degeneration and regeneration leading to injury of the myelin sheath and axon. In the present study, the expression of TNFalpha, TGFbeta, and their receptors, in addition to cell death triggered by cytokines or whole Mycobacterium leprae were investigated in a human SC line. The results showed the presence of TNF-Rs and TGF-RII on the SC membrane and the shedding of TNF-Rs during the culture period. Evaluation of cell death was performed through TUNEL and flow cytometry techniques. TNFalpha/TGFbeta combination as well as M. leprae infection triggered an increase in the apoptosis rate in the cultured SC. Moreover, reverse transcriptase-polymerase chain reaction assay revealed that M. leprae upregulated the expression of such cytokines and their receptors on the SC line. Despite the detection of TNFalpha mRNA, no protein was found in the culture supernatants. The data indicate that induction of SC death after cell interaction with M. leprae may, in fact, be implicated in the pathogenesis of nerve damage, which can most likely be modulated by in vivo cytokine production. PMID:16215460

  17. Evident and latent plasticity across the rice diterpene synthase family with potential implications for the evolution of diterpenoid metabolism in the cereals

    PubMed Central

    Morrone, Dana; Hillwig, Matthew L.; Mead, Matthew E.; Lowry, Luke; Fulton, D. Bruce; Peters, Reuben J.

    2013-01-01

    SYNOPSIS The evolution of natural products biosynthetic pathways can be envisioned to occur via a number of mechanisms. Here we provide evidence that latent plasticity plays a role in such metabolic evolution. In particular, rice (Oryza sativa) produces both ent- and syn-copalyl diphosphate (CPP), which are substrates for downstream diterpene synthases. Here we report that several members of this enzymatic family exhibit dual reactivity with some pairing of ent-, syn-, or normal CPP stereochemistry. Evident plasticity was observed, as a previously reported ent-sandaracopimaradiene synthase also converts syn-CPP to syn-labda-8(17),12E,14-triene, which can be found in planta. Notably, normal CPP is not naturally found in rice. Thus, the presence of diterpene synthases that react with this non-native metabolite reveals latent enzymatic/metabolic plasticity, providing biochemical capacity for utilization of such a novel substrate (i.e., normal CPP) that may arise during evolution, the implications of which are discussed. PMID:21323642

  18. Evident and latent plasticity across the rice diterpene synthase family with potential implications for the evolution of diterpenoid metabolism in the cereals.

    PubMed

    Morrone, Dana; Hillwig, Matthew L; Mead, Matthew E; Lowry, Luke; Fulton, D Bruce; Peters, Reuben J

    2011-05-01

    The evolution of natural product biosynthetic pathways can be envisioned to occur via a number of mechanisms. In the present study we provide evidence that latent plasticity plays a role in such metabolic evolution. In particular, rice (Oryza sativa) produces both ent- and syn-CPP (copalyl diphosphate), which are substrates for downstream diterpene synthases. In the present paper we report that several members of this enzymatic family exhibit dual reactivity with some pairing of ent-, syn- or normal CPP stereochemistry. Evident plasticity was observed, as a previously reported ent-sandaracopimaradiene synthase also converts syn-CPP into syn-labda-8(17),12E,14-triene, which can be found in planta. Notably, normal CPP is not naturally found in rice. Thus the presence of diterpene synthases that react with this non-native metabolite reveals latent enzymatic/metabolic plasticity, providing biochemical capacity for utilization of such a novel substrate (i.e. normal CPP) which may arise during evolution, the implications of which are discussed. PMID:21323642

  19. Testing for genetic associations in a spina bifida population: analysis of the HOX gene family and human candidate gene regions implicated by mouse models of neural tube defects.

    PubMed

    Volcik, K A; Blanton, S H; Kruzel, M C; Townsend, I T; Tyerman, G H; Mier, R J; Northrup, H

    2002-07-01

    Neural tube defects (NTDs) are among the most common severely disabling birth defects in the United States, affecting approximately 1-2 of every 1,000 live births. The etiology of NTDs is multifactorial, involving the combined action of both genetic and environmental factors. HOX genes play a central role in establishing the initial body plan by providing positional information along the anterior-posterior body and limb axis and have been implicated in neural tube closure. There are many mouse models that exhibit both naturally occurring NTDs in various mouse strains as well as NTDs that have been created by "knocking out" various genes. A nonparametric linkage method, the transmission disequilibrium test (TDT), was utilized to test the HOX gene family and human equivalents of genes (when known) or the syntenic region in humans to those in mouse models which could play a role in the formation of NTDs. DNA from 459 spina bifida (SB) affected individuals and their parents was tested for linkage and association utilizing polymorphic markers from within or very close to the HOXA, HOXB, HOXC, and HOXD genes as well as from within the genes/gene regions of eight mouse models that exhibit NTDs. No significant findings were obtained for the tested markers. PMID:12116226

  20. Cytokine Signature in Infective Endocarditis

    PubMed Central

    Araújo, Izabella Rodrigues; Ferrari, Teresa Cristina Abreu; Teixeira-Carvalho, Andréa; Campi-Azevedo, Ana Carolina; Rodrigues, Luan Vieira; Guimarães Júnior, Milton Henriques; Barros, Thais Lins Souza; Gelape, Cláudio Léo; Sousa, Giovane Rodrigo; Nunes, Maria Carmo Pereira

    2015-01-01

    Infective endocarditis (IE) is a severe disease with high mortality rate. Cytokines participate in its pathogenesis and may contribute to early diagnosis improving the outcome. This study aimed to evaluate the cytokine profile in IE. Serum concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12 and tumor necrosis factor (TNF)-α were measured by cytometric bead array (CBA) at diagnosis in 81 IE patients, and compared with 34 healthy subjects and 30 patients with non-IE infections, matched to the IE patients by age and gender. Mean age of the IE patients was 47±17 years (range, 15–80 years), and 40 (50%) were male. The IE patients had significantly higher serum concentrations of IL-1β, IL-6, IL-8, IL-10 and TNF-α as compared to the healthy individuals. The median levels of IL-1β, TNF-α and IL-12 were higher in the IE than in the non-IE infections group. TNF-α and IL-12 levels were higher in staphylococcal IE than in the non-staphylococcal IE subgroup. There was a higher proportion of both low IL-10 producers and high producers of IL-1β, TNF-α and IL-12 in the staphylococcal IE than in the non-staphylococcal IE subgroup. This study reinforces a relationship between the expression of proinflammatory cytokines, especially IL-1β, IL-12 and TNF-α, and the pathogenesis of IE. A lower production of IL-10 and impairment in cytokine network may reflect the severity of IE and may be useful for risk stratification. PMID:26225421

  1. Cytokine Signature in Infective Endocarditis.

    PubMed

    Araújo, Izabella Rodrigues; Ferrari, Teresa Cristina Abreu; Teixeira-Carvalho, Andréa; Campi-Azevedo, Ana Carolina; Rodrigues, Luan Vieira; Guimarães Júnior, Milton Henriques; Barros, Thais Lins Souza; Gelape, Cláudio Léo; Sousa, Giovane Rodrigo; Nunes, Maria Carmo Pereira

    2015-01-01

    Infective endocarditis (IE) is a severe disease with high mortality rate. Cytokines participate in its pathogenesis and may contribute to early diagnosis improving the outcome. This study aimed to evaluate the cytokine profile in IE. Serum concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12 and tumor necrosis factor (TNF)-α were measured by cytometric bead array (CBA) at diagnosis in 81 IE patients, and compared with 34 healthy subjects and 30 patients with non-IE infections, matched to the IE patients by age and gender. Mean age of the IE patients was 47±17 years (range, 15-80 years), and 40 (50%) were male. The IE patients had significantly higher serum concentrations of IL-1β, IL-6, IL-8, IL-10 and TNF-α as compared to the healthy individuals. The median levels of IL-1β, TNF-α and IL-12 were higher in the IE than in the non-IE infections group. TNF-α and IL-12 levels were higher in staphylococcal IE than in the non-staphylococcal IE subgroup. There was a higher proportion of both low IL-10 producers and high producers of IL-1β, TNF-α and IL-12 in the staphylococcal IE than in the non-staphylococcal IE subgroup. This study reinforces a relationship between the expression of proinflammatory cytokines, especially IL-1β, IL-12 and TNF-α, and the pathogenesis of IE. A lower production of IL-10 and impairment in cytokine network may reflect the severity of IE and may be useful for risk stratification. PMID:26225421

  2. Hypothalamic neuronal responses to cytokines.

    PubMed Central

    Shibata, M.

    1990-01-01

    Fever has been extensively studied in the past few decades. The hypothesis that hypothalamic thermosensitive neurons play a major role in both normal thermoregulation and in fever production and lysis has particularly helped to advance our understanding of the neuronal mechanisms underlying the response to pyrogens. Furthermore, new data in the study of host defense responses induced by pyrogenic cytokines such as interleukin 1, interferon alpha 2, tumor necrosis factor alpha, and interleukin 6 have demonstrated that those factors have multiple, yet coordinated, regulatory activities in the central nervous system, so that our understanding of the role of the brain in the activity of these agents requires a new perspective and dimension. Thus, recent evidence from our laboratory indicates that blood-borne cytokines may be detected in the organum vasculosum laminae terminalis and transduced there into neuronal signals. Such signals may then affect distinct, but partially overlapping, sets of neuronal systems in the preoptic area of the anterior hypothalamus, mediating directly and/or indirectly the array of various host defense responses characteristic of infection that are thought to be induced by blood-borne cytokines. PMID:2205055

  3. IL-33 enhances lipopolysaccharide-induced inflammatory cytokine production from mouse macrophages by regulating lipopolysaccharide receptor complex.

    PubMed

    Espinassous, Quentin; Garcia-de-Paco, Elvira; Garcia-Verdugo, Ignacio; Synguelakis, Monique; von Aulock, Sonja; Sallenave, Jean-Michel; McKenzie, Andrew N J; Kanellopoulos, Jean

    2009-07-15

    Bacterial LPS triggers monocytes and macrophages to produce several inflammatory cytokines and mediators. However, once exposed to LPS, they become hyporesponsive to a subsequent endotoxin challenge. This phenomenon is defined as LPS desensitization or tolerance. Previous studies have identified some components of the biochemical pathways involved in negative modulation of LPS responses. In particular, it has been shown that the IL-1R-related protein ST2 could be implicated in LPS tolerance. The natural ligand of ST2 was recently identified as IL-33, a new member of the IL-1 family. In this study, we investigated whether IL-33 triggering of ST2 was able to induce LPS desensitization of mouse macrophages. We found that IL-33 actually enhances the LPS response of macrophages and does not induce LPS desensitization. We demonstrate that this IL-33 enhancing effect of LPS response is mediated by the ST2 receptor because it is not found in ST2 knockout mice. The biochemical consequences of IL-33 pretreatment of mouse macrophages were investigated. Our results show that IL-33 increases the expression of the LPS receptor components MD2 (myeloid differentiation protein 2) and TLR-4, the soluble form of CD14 and the MyD88 adaptor molecule. In addition, IL-33 pretreatment of macrophages enhances the cytokine response to TLR-2 but not to TLR-3 ligands. Thus, IL-33 treatment preferentially affects the MyD88-dependent pathway activated by the TLR. PMID:19553541

  4. Student Development and Family Systems: Critical Review and Implications for Theory and Practice. Student-Environment Study Group. Student Development Monograph Series, Volume 2.

    ERIC Educational Resources Information Center

    Benjamin, Michael

    In response to a gap in the literature on student development with respect to the role of the family, and anecdotal evidence that the family's influence on the college student's development is profound, a review of the relevant literature on higher education, social psychology, psychiatry, sociology of the family, and family therapy was…

  5. Dimensions of Family Coping with Head Injury.

    ERIC Educational Resources Information Center

    Kosciulek, John F.

    1994-01-01

    Examined dimensions underlying family coping with head injury. Data from 150 families with a member with a head injury identified 3 dimensions of coping: individual-to-family versus family-to-community coping; family-respite versus head-injury-focused coping; and cognitive versus behavioral coping. Findings have implications for family stress and…

  6. Biological properties and regulation of IL-10 related cytokines and their contribution to autoimmune disease and tissue injury.

    PubMed

    Hofmann, S R; Rösen-Wolff, A; Tsokos, G C; Hedrich, C M

    2012-05-01

    The IL-10 cytokine family has nine members, four of which are located in the IL10 cluster on chromosome 1q32. These cytokines are the immune regulatory cytokine IL-10 itself, and the IL-20 subfamily members IL-19, IL-20, and IL-24. IL-10 instructs innate and adaptive immune responses and limits pro-inflammatory responses in order to prevent tissue damage. The IL-20 subfamily members are involved in host defense mechanisms, particularly from epithelial cells and seem essential for tissue integrity. Dysregulation of IL-10 family cytokines results in inflammation and autoimmune disease. Here, we discuss cellular source, gene regulation, and receptor complexes of cytokines in the IL10 cluster and their contribution to autoimmune disease and tissue damage. PMID:22459704

  7. Viruses, cytokines, antigens, and autoimmunity.

    PubMed Central

    Gianani, R; Sarvetnick, N

    1996-01-01

    To explain the pathogenesis of autoimmunity, we hypothesize that following an infection the immune response spreads to tissue-specific autoantigens in genetically predisposed individuals eventually determining progression to disease. Molecular mimicry between viral and self antigens could, in some instances, initiate autoimmunity. Local elicitation of inflammatory cytokines following infection probably plays a pivotal role in determining loss of functional tolerance to self autoantigens and the destructive activation of autoreactive cells. We also describe the potential role of interleukin 10, a powerful B-cell activator, in increasing the efficiency of epitope recognition, that could well be crucial to the progression toward disease. PMID:8637859

  8. Cytokine profiles in axial spondyloarthritis

    PubMed Central

    Madej, Marta; Nowak, Beata; Sokolik, Renata; Chlebicki, Arkadiusz; Korman, Lucyna; Woytala, Patryk; Lubiński, Łukasz; Wiland, Piotr

    2015-01-01

    Objectives Current studies concentrate on the cytokine network and its role in the pathogenesis of spondyloarthritis (SpA). In this study, we analyzed whether the serum cytokine profile (interleukins: IL-10, IL-11, IL-12, IL-15, IL-17, IL-23 and IL-33) correlates with demographic data, clinical manifestations, disease activity and treatment outcome in a group of patients with axial spondyloarthritis. Material and methods Forty-nine patients with an established diagnosis of axial spondyloarthritis (aSpA) and 19 healthy volunteers as controls were enrolled in the study. Clinical evaluation included patient's medical history, 44 joint count, back pain intensity and global disease activity in the preceding week (VAS), the duration of morning stiffness and blood tests. Disease activity was assessed using BASDAI and ASDAS-CRP. Serum concentration of IL-10, IL-11, IL-12, IL-15, IL-17, IL-23 and IL-33 was determined. Results In patients with aSpA, elevated serum concentration of IL-10, IL-15, IL-17 and IL-23 was detected. In the aSpA group we detected higher values of serum concentration of IL-23 and IL-33 in the subgroup with anterior uveitis (83.1 ±184.0 pg/ml vs. 14.0 ±17.1 pg/ml, p < 0.0001 and 45.5 ±71.9 pg/ml vs. 18.4 ±14.3 pg/ml, p < 0.0001, respectively). Additionally, in the subgroup with peripheral arthritis, elevation of serum concentration of IL-12 (249.3 ±246.9 pg/ml vs. 99.9 ±105.9 pg/ml, p = 0.0001) was detected. Patients with preradiological SpA had higher serum concentration of IL-17 than patients with established diagnosis of AS (6.37 ±8.50 pg/ml vs. 2.04 ±2.98 pg/ml, p = 0.0295). No differences in serum concentration of analyzed cytokines were found between the subgroup with low to moderate disease activity and the subgroup with high to very high disease activity. Conclusions We report that in aSpA patients, compared to controls, elevated serum concentrations of IL-10, IL-15, IL-17 and IL-23 were observed. Some cytokines may predispose to a more

  9. Granzymes regulate proinflammatory cytokine responses.

    PubMed

    Wensink, Annette C; Hack, C Erik; Bovenschen, Niels

    2015-01-15

    Granzymes (Grs) are serine proteases mainly produced by cytotoxic lymphocytes and are traditionally considered to cause apoptosis in tumor cells and virally infected cells. However, the cytotoxicity of several Grs is currently being debated, and additional, predominantly extracellular, functions of Grs in inflammation are emerging. Extracellular soluble Grs are elevated in the circulation of patients with autoimmune diseases and infections. Additionally, Grs are expressed by several types of immune cells other than cytotoxic lymphocytes. Recent research has revealed novel immunomodulatory functions of Grs. In this review, we provide a comprehensive overview on the role of Grs in inflammation, highlighting their role in cytokine induction and processing. PMID:25556251

  10. Cytoplasmic and nuclear cytokine receptor complexes.

    PubMed

    Mertani, H C; Morel, G; Lobie, P E

    1999-01-01

    Much of our understanding on how hormones and cytokines transmit their message into the cell is based on the receptor activation at the plasma membrane. Many experimental in vitro models have established the paradigm for cytokine action based upon such activation of their cell surface receptor. The signaling from the plasma membrane activated cytokine receptor is driven to the nucleus by a rapid ricochet of protein phosphorylation, ultimately integrated as a differentiative, proliferative, or transcriptional message. The Janus kinase (JAK)--signal transducers and activators of transcription (STAT) pathway that was first thought to be cytokine receptor specific now appears to be activated by other noncytokine receptors. Also, evidence is accumulating showing that cytokines modulate the signal transduction machinery of the tyrosine kinase receptors and that of the heterotrimeric guanosine triphosphate (GTP)-binding protein-coupled receptors. Thus cytokine receptor signaling has become much more complex than originally hypothesized, challenging the established model of specificity of the action of a given cytokine. This review is focused on another level of complexity emerging within cytokine receptor superfamily signaling. Over the past 10 years, data from different laboratories have shown that cytokines and their receptors localize to intracellular compartments including the nucleus, and, in some cases, biological responses have been correlated with this unexpected location, raising the possibility that cytokines act as their own messenger through inter-actions with nuclear proteins. Thus, the interplay between cytokine receptor engagement and cellular signaling turns out to be more dynamic than originally suspected. The mechanisms and regulations of intracellular translocation of the cytokines, their receptors, and their signaling proteins are discussed in the context that such compartmentalization provides some of the specificity of the responses mediated by each

  11. Cytokines and glucocorticoid receptors are associated with the antidepressant-like effect of alarin.

    PubMed

    Zhuang, Fuzhi; Zhou, Xue; Gao, Xin; Lou, Dan; Bi, Xuesheng; Qin, Shoujun; Sun, Chuxiao; Ye, Peng; Wang, Yun; Ma, Tengfei; Li, Mei; Gu, Shuling

    2016-02-01

    Little is known about the physiological or pharmacological properties of alarin, a new neuropeptide belonging to the galanin family. We previously showed that alarin has an antidepressant-like effect and is associated with a decrease in the hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis that is observed in patients with depression using unpredictable chronic mild stress (UCMS) mouse model of depression. However, the mechanisms underlying these effects have not been uncovered. Inflammatory cytokines are reportedly associated with depression. Animal studies and cytokine immune therapy in humans suggest that pro-inflammatory cytokines induce depressive symptomatology and potently activate the HPA axis, whereas anti-inflammatory cytokines may decrease activation. Thus, we first determined the levels of inflammatory cytokines in the blood and brain to evaluate whether the antidepressant-like effect of alarin in UCMS-treated mice is related to its regulation of these inflammatory cytokines. Pro-inflammatory cytokines disrupt the function and/or expression of glucocorticoid receptors (GRs), which mediate the negative feedback of glucocorticoids on the HPA axis to keep it from being overactivated. We next explored the expression level of GRs in the brains of mice subjected to UCMS and to the administration of alarin. We found that intracerebroventricular administration of alarin significantly ameliorated depression-like behaviors in the UCMS-treated mice. Alarin restored the UCMS-induced an increase in the levels of the pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor α and a decrease in the anti-inflammatory cytokine IL-10 level in the blood, prefrontal cortex, hippocampus and hypothalamus. Alarin also reversed the UCMS-induced down-regulation of GR expression in these brain regions. Thus, the antidepressant-like effects of alarin may be mediated by restoring altered pro-inflammatory and anti-inflammatory cytokine levels and GR

  12. Overview of cytokines and nitric oxide involvement in immuno-pathogenesis of inflammatory bowel diseases

    PubMed Central

    Soufli, Imene; Toumi, Ryma; Rafa, Hayet; Touil-Boukoffa, Chafia

    2016-01-01

    Inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis are complex disorders with undetermined etiology. Several hypotheses suggest that IBDs result from an abnormal immune response against endogenous flora and luminal antigens in genetically susceptible individuals. The dysfunction of the mucosal immune response is implicated in the pathogenesis of IBD. The balance between pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, and IL-17A], anti-inflammatory cytokines (IL-4 and IL-13), and immunoregulatory cytokines (IL-10 and transforming growth factors β) is disturbed. Moreover, evidence from animal and clinical studies demonstrate a positive correlation between an increased concentration of nitric oxide (NO) and the severity of the disease. Interestingly, proinflammatory cytokines are involved in the up-regulation of inducible oxide synthase (iNOS) expression in IBD. However, anti-inflammatory and immunoregulatory cytokines are responsible for the negative regulation of iNOS. A positive correlation between NO production and increased pro-inflammatory cytokine levels (TNF-α, IL-6, IL-17, IL-12, and interferon-γ) were reported in patients with IBD. This review focuses on the role of cytokines in intestinal inflammation and their relationship with NO in IBD. PMID:27602236

  13. Overview of cytokines and nitric oxide involvement in immuno-pathogenesis of inflammatory bowel diseases.

    PubMed

    Soufli, Imene; Toumi, Ryma; Rafa, Hayet; Touil-Boukoffa, Chafia

    2016-08-01

    Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis are complex disorders with undetermined etiology. Several hypotheses suggest that IBDs result from an abnormal immune response against endogenous flora and luminal antigens in genetically susceptible individuals. The dysfunction of the mucosal immune response is implicated in the pathogenesis of IBD. The balance between pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, and IL-17A], anti-inflammatory cytokines (IL-4 and IL-13), and immunoregulatory cytokines (IL-10 and transforming growth factors β) is disturbed. Moreover, evidence from animal and clinical studies demonstrate a positive correlation between an increased concentration of nitric oxide (NO) and the severity of the disease. Interestingly, proinflammatory cytokines are involved in the up-regulation of inducible oxide synthase (iNOS) expression in IBD. However, anti-inflammatory and immunoregulatory cytokines are responsible for the negative regulation of iNOS. A positive correlation between NO production and increased pro-inflammatory cytokine levels (TNF-α, IL-6, IL-17, IL-12, and interferon-γ) were reported in patients with IBD. This review focuses on the role of cytokines in intestinal inflammation and their relationship with NO in IBD. PMID:27602236

  14. Family Preservation & Family Functioning.

    ERIC Educational Resources Information Center

    McCroskey, Jacquelyn; Meezan, William

    This book reports a study of the outcomes of home-based family preservation services for abusive and neglectful families in Los Angeles County. Using the Family Assessment Form, the research project evaluated services provided by two voluntary agencies, and focused on changes in family functioning between the opening and closing of services during…

  15. American Indian Family Support Systems and Implications for the Rehabilitation Process: The Eastern Band of Cherokee Indians and the Mississippi Band of Choctaw Indians. Executive Summary.

    ERIC Educational Resources Information Center

    Marshall, Catherine A.; Cerveny, Lee K.

    This project focused on the role of the family in providing support to a relative with a disability in two American Indian cultures, the Eastern Band of Cherokee Indians and the Mississippi Band of Choctaw Indians. A review of the literature notes the documented importance of involving family in the rehabilitation process. Ten families in each…

  16. Bioanalytical Chemistry of Cytokines-A Review

    PubMed Central

    Stenken, Julie A.; Poschenrieder, Andreas J.

    2014-01-01

    Cytokines are bioactive proteins produced by many different cells of the immune system. Due to their role in different inflammatory disease states and maintaining homeostasis, there is enormous clinical interest in the quantitation of cytokines. The typical standard methods for quantitation of cytokines are immunoassay-based techniques including enzyme-linked immusorbent assays (ELISA) and bead-based immunoassays read by either standard or modified flow cytometers. A review of recent developments in analytical methods for measurements of cytokine proteins is provided. This review briefly covers cytokine biology and the analysis challenges associated with measurement of these biomarker proteins for understanding both health and disease. New techniques applied to immunoassay-based assays are presented along with the uses of aptamers, electrochemistry, mass spectrometry, optical resonator-based methods. Methods used for elucidating the release of cytokines from single cells as well as in vivo collection methods are described. PMID:25467452

  17. Analysis of intracellular cytokines using flowcytometry.

    PubMed

    Arora, Sunil K

    2002-01-01

    Characterization of T-cell clones and identification of functional subsets of the helper T-cells with polarized cytokine production is based on testing of cytokine expression. Several methods have been developed that allow cytokine expression to be measured like ELISA, RT-PCR, ELISPOT, ISH and flowcytometry. Among all these methods, monitoring of cytokine production using flowcytometric analysis has its own advantages and disadvantages. Multi-parametric characterization of cytokine production on single cell basis, without long-term culture and cloning along with high throughput of samples is main feature attached to flowcytometric analysis. The interpretation may be difficult at times due to change in the phenotype of the cells. Cells with similar surface phenotype but synthesizing different cytokines and having different functional characteristics can be analyzed with this technique. PMID:12815288

  18. Family traditions and generations.

    PubMed

    Schneiderman, Gerald; Barrera, Maru

    2009-01-01

    Currently, traditional family values that have been passed down through generations appear to be at risk. This has significant implications for the stability and health of individuals, families, and communities. This article explores selected issues related to intergenerational transmission of family values and cultural beliefs, with particular reference to Western culture and values that are rooted in Jewish and Christian traditions. It also examines family values and parenting styles as they influence the developing perspective of children and the family's adaptation to a changing world. PMID:19752638

  19. Cytokine-Modulating Strategies and Newer Cytokine Targets for Arthritis Therapy

    PubMed Central

    Venkatesha, Shivaprasad H.; Dudics, Steven; Acharya, Bodhraj; Moudgil, Kamal D.

    2014-01-01

    Cytokines are the key mediators of inflammation in the course of autoimmune arthritis and other immune-mediated diseases. Uncontrolled production of the pro-inflammatory cytokines such as interferon-γ (IFN-γ), tumor necrosis factor α (TNFα), interleukin-6 (IL-6), and IL-17 can promote autoimmune pathology, whereas anti-inflammatory cytokines including IL-4, IL-10, and IL-27 can help control inflammation and tissue damage. The pro-inflammatory cytokines are the prime targets of the strategies to control rheumatoid arthritis (RA). For example, the neutralization of TNFα, either by engineered anti-cytokine antibodies or by soluble cytokine receptors as decoys, has proven successful in the treatment of RA. The activity of pro-inflammatory cytokines can also be downregulated either by using specific siRNA to inhibit the expression of a particular cytokine or by using small molecule inhibitors of cytokine signaling. Furthermore, the use of anti-inflammatory cytokines or cytokine antagonists delivered via gene therapy has proven to be an effective approach to regulate autoimmunity. Unexpectedly, under certain conditions, TNFα, IFN-γ, and few other cytokines can display anti-inflammatory activities. Increasing awareness of this phenomenon might help develop appropriate regimens to harness or avoid this effect. Furthermore, the relatively newer cytokines such as IL-32, IL-34 and IL-35 are being investigated for their potential role in the pathogenesis and treatment of arthritis. PMID:25561237

  20. Current status and challenges of cytokine pharmacology

    PubMed Central

    Zídek, Z; Anzenbacher, P; Kmoníčková, E

    2009-01-01

    The major concern of pharmacology about cytokines has originated from plentiful data showing association between gross changes in their production and pathophysiological processes. Despite the enigmatic role of cytokines in diseases, a number of them have become a subject of cytokine and anti-cytokine immunotherapies. Production of cytokines can be influenced by many endogenous and exogenous stimuli including drugs. Cells of the immune system, such as macrophages and lymphocytes, are richly endowed with receptors for the mediators of physiological functions, such as biogenic amines, adenosine, prostanoids, steroids, etc. Drugs, agonists or antagonists of these receptors can directly or indirectly up- and down-regulate secretion of cytokines and expression of cytokine receptors. Vice versa, cytokines interfere with drug pharmacokinetics and pharmacodynamics through the interactions with cytochrome P450 and multiple drug resistance proteins. The aim of the review is to encourage more intensive studies in these fields of cytokine pharmacology. It also outlines major areas of searching promising candidates for immunotherapeutic interventions. PMID:19371342

  1. Effect of space flight on cytokine production

    NASA Astrophysics Data System (ADS)

    Sonnenfeld, Gerald

    Space flight has been shown to alter many immunological responses. Among those affected are the production of cytokines, Cytokines are the messengers of the immune system that facilitate communication among cells that allow the interaction among cells leading to the development of immune responses. Included among the cytokines are the interferons, interleukins, and colony stimulating factors. Cytokines also facilitate communication between the immune system and other body systems, such as the neuroendocrine and musculoskeletal systems. Some cytokines also have direct protective effects on the host, such as interferon, which can inhibit the replication of viruses. Studies in both humans and animals indicate that models of space flight as well as actual space flight alter the production and action of cytokines. Included among these changes are altered interferon production, altered responsiveness of bone marrow cells to granulocyte/monocyte-colony stimulating factor, but no alteration in the production of interleukin-3. This suggests that there are selective effects of space flight on immune responses, i.e. not all cytokines are affected in the same fashion by space flight. Tissue culture studies also suggest that there may be direct effects of space flight on the cells responsible for cytokine production and action. The results of the above study indicate that the effects of space flight on cytokines may be a fundamental mechanism by which space flight not only affects immune responses, but also other biological systems of the human.

  2. A Generic Mechanism for Enhanced Cytokine Signaling via Cytokine-Neutralizing Antibodies

    PubMed Central

    Shulgin, Boris; Helmlinger, Gabriel; Kosinsky, Yuri

    2016-01-01

    Enhancement or inhibition of cytokine signaling and corresponding immune cells responses are critical factors in various disease treatments. Cytokine signaling may be inhibited by cytokine-neutralizing antibodies (CNAs), which prevents further activation of cytokine receptors. However, CNAs may result in enhanced—instead of inhibitory—cytokine signaling (an “agonistic effect”) in various in vitro and in vivo experiments. This may lead to lack of efficacy or adverse events for cytokine-inhibiting based medicines. Alternatively, cytokine-antibody complexes may produce stronger signaling vs. cytokine alone, thereby increasing the efficacy of stimulating cytokine-based drugs, at equal or lower cytokine doses. In this paper, the effect of cytokine signaling enhancement by a CNA was studied in a generic mathematical model of interleukin-4 (IL-4) driven T-cell proliferation. The occurrence of the agonistic effect depends upon the antibody-to-cytokine binding affinity and initial concentrations of antibody and cytokine. Model predictions were in agreement with experimental studies. When the cytokine receptor consists of multiple subunits with substantially differing affinities (e.g., IL-4 case), the choice of the receptor chain to be blocked by the antibody is critical, for the agonistic effect to appear. We propose a generic mechanism for the effect: initially, binding of the CNA to the cytokine reduces free cytokine concentration; yet, cytokine molecules bound within the cytokine-CNA complex—and released later and over time—are “rescued” from earlier clearance via cellular internalization. Hence, although free cytokine-dependent signalling may be less potent initially, it will also be more sustained over time; and given non-linear dynamics, it will lead ultimately to larger cellular effector responses, vs. the same amount of free cytokine in the absence of CNA. We suggest that the proposed mechanism is a generic property of {cytokine, CNA, receptor

  3. Inflammatory cytokines in pulmonary hypertension

    PubMed Central

    2014-01-01

    Pulmonary hypertension is an “umbrella term” used for a spectrum of entities resulting in an elevation of the pulmonary arterial pressure. Clinical symptoms include dyspnea and fatigue which in the absence of adequate therapeutic intervention may lead to progressive right heart failure and death. The pathogenesis of pulmonary hypertension is characterized by three major processes including vasoconstriction, vascular remodeling and microthrombotic events. In addition accumulating evidence point to a cytokine driven inflammatory process as a major contributor to the development of pulmonary hypertension. This review summarizes the latest clinical and experimental developments in inflammation associated with pulmonary hypertension with special focus on Interleukin-6, and its role in vascular remodeling in pulmonary hypertension. PMID:24739042

  4. [The role of cytokines in cancer therapy].

    PubMed

    Ishida, N; Yoshida, T

    1987-05-01

    A variety of normal tissue or malignant cells can produce and/or release various biologically active substances (hormone-like mediators) now collectively called cytokines. Because immunological and non-immunological responses of malignant cells were modified by many of them, some cytokines have been employed as so-called Biological Response Modifiers (BRM) in the treatment of cancers in animals and humans. This overview discussed a few of the difficulties, probably inherent in cytokine therapy, that have already been encountered in early clinical trials as well as some of those that can be anticipated in future work. These include unexpected and undesirable reactions due to the systemic administration in relatively large amounts of a cytokine that is, under physiological conditions, supposed to act as a paracrine and/or autocrine among cells located within a limited distance. Even a pure recombinant preparation of a cytokine is now known to affect multiple target cells if they are accessible to it. Furthermore, this kind of therapy may sometimes be little more than a shot in the dark, since the physiological balance (homeostasis) among many of the cytokines present or produced in a host receiving a large quantity of exogenous cytokines is not well understood. Making the situation still more complicated, many types of tumor cells are known to release some of these cytokines spontaneously. Many challenging problems remain to be solved before we can confidently prescribe a cocktail of cytokines precisely suitable for a given patient according to the individual's in vivo cytokine profile. Nevertheless, in spite of all these reservations, cytokine therapy has been too frequently beneficial to be allowed to be discouraged. "Out of this nettle, danger, we pluck this flower, safety". PMID:3034167

  5. Role of Central β-Adrenergic Receptors in Regulating Proinflammatory Cytokine Responses to a Peripheral Bacterial Challenge

    PubMed Central

    Johnson, John D.; Cortez, Valerie; Kennedy, Sarah L.; Foley, Teresa E.; Hanson, Hugo; Fleshner, Monika

    2008-01-01

    Elevation of proinflammatory cytokines in the brain have potent effects on altering physiological, behavioral, and cognitive processes. The mechanism(s) by which brain cytokines are induced during a peripheral immune challenge remains unclear since microorganisms/cytokines do not cross the blood-brain barrier (BBB). Recent studies indicate that central β-adrenergic receptors (β-ADRs) may mediate brain interleukin-1beta (IL-1) production. This has direct implications for the production of brain cytokines during a peripheral immune response since peripheral pathogens and cytokines rapidly stimulate brainstem catecholamine neurons via peripheral nerves and circumventricular pathways. Studies here examine the role of central β-ADRs in regulating brain cytokine production following peripheral Escherichia coli (E.coli) challenge. Rats were centrally administered propranolol (β-ADR antagonist) or vehicle followed by peripheral E.coli or saline and sacrificed 6h later for measurement of cytokines. Pretreatment with propranolol completely blocked the induction of brain IL-1 following E.coli. Surprisingly, central propranolol also attenuated E.coli-induced peripheral cytokines. To examine whether the attenuated peripheral cytokine response following central propranolol administration was due leakage of propranolol into the general circulation and blockade of peripheral β-blockade, nadolol (β-ADR antagonist that does not cross the BBB) was administered peripherally prior to E.coli. Nadolol administration did not block central cytokine production following E.coli, but instead enhanced both peripheral and central proinflammatory cytokine production. Furthermore, central administration of isoproterenol (β-ADR agonist) results in a time-dependent increase in brain IL-1 production. These data demonstrate central β-ADRs may play a critical role to induce brain IL-1, while peripheral β-ADRs inhibit cytokine response to bacterial challenge. PMID:18468841

  6. The conditioning lesion effect on sympathetic neurite outgrowth is dependent on gp130 cytokines

    PubMed Central

    Sachs, H. Hyatt; Rohrer, H.; Zigmond, R.E.

    2010-01-01

    Sympathetic neurons, like sensory neurons, increase neurite outgrowth after a conditioning lesion. Studies in leukemia inhibitory factor (LIF) knockout animals showed that the conditioning lesion effect in sensory neurons is dependent in part on this cytokine; however, similar studies on sympathetic neurons revealed no such effect. Comparable studies with sensory neurons taken from mice lacking the related cytokine interleukin-6 (IL-6) have yielded conflicting results. LIF and IL-6 belong to a family of cytokines known as the gp130 family because they act on receptors containing the subunit gp130. In sympathetic ganglia, axotomy leads to increases in mRNA for four of these cytokines (LIF, IL-6, IL-11, and on-costatin M). To test the role of this family of cytokines as a whole in the conditioning lesion response in sympathetic neurons, mice in which gp130 was selectively eliminated in noradrenergic neurons were studied. The postganglionic axons of the SCG were transected, and seven days later the ganglia were removed and neurite outgrowth was measured in explant and dissociated cell cultures. In both systems, neurons from wild type animals showed enhanced growth after a conditioning lesion. In contrast, no enhancement occurred in neurons from mutant animals. This lack of stimulation of outgrowth occurred despite an increase in expression of activating transcription factor 3 (ATF3) in the mutant mice. These studies demonstrate that stimulation of enhanced growth of sympathetic neurons after a conditioning lesion is dependent on gp130 cytokine signaling and is blocked in the absence of signaling by these cytokines in spite of an increase in ATF3. PMID:20144891

  7. Family Dynamics and Female Sexual Delinquency.

    ERIC Educational Resources Information Center

    Pollack, Otto; Friedman, Alfred S.

    Papers included are marriage as the cornerstone of the family system, developmental difficulties and the family system, mental health implications of family structure, delinquency and the family system, sexual delinquency among middle class girls, developing standards of sexual conduct among deprived girls, families out of wedlock, and a community…

  8. Suppressors of Cytokine Signaling (SOCS) in T cell differentiation, maturation, and function

    PubMed Central

    Palmer, Douglas C.; Restifo, Nicholas P.

    2009-01-01

    Cytokines are key modulators of T cell biology but their influence can be attenuated by suppressors of cytokine signaling (SOCS), a family of proteins comprised of eight members, SOCS1-7 and CIS. SOCS proteins regulate cytokine signals that control the polarization of CD4+ T cells into Th1, Th2, Th17, and T regulatory cell lineages, the maturation of CD8+ T cells from naïve to “stem-cell memory” (Tscm), central memory (Tcm), and effector memory (Tem) states, and the activation of these lymphocytes. Understanding how SOCS family members regulate T cell maturation, differentiation and function might prove critical in improving adoptive immunotherapy for cancer and therapies aimed at treating autoimmune and infectious diseases. PMID:19879803

  9. Interleukin-6, a Major Cytokine in the Central Nervous System

    PubMed Central

    Erta, María; Quintana, Albert; Hidalgo, Juan

    2012-01-01

    Interleukin-6 (IL-6) is a cytokine originally identified almost 30 years ago as a B-cell differentiation factor, capable of inducing the maturation of B cells into antibody-producing cells. As with many other cytokines, it was soon realized that IL-6 was not a factor only involved in the immune response, but with many critical roles in major physiological systems including the nervous system. IL-6 is now known to participate in neurogenesis (influencing both neurons and glial cells), and in the response of mature neurons and glial cells in normal conditions and following a wide arrange of injury models. In many respects, IL-6 behaves in a neurotrophin-like fashion, and seemingly makes understandable why the cytokine family that it belongs to is known as neuropoietins. Its expression is affected in several of the main brain diseases, and animal models strongly suggest that IL-6 could have a role in the observed neuropathology and that therefore it is a clear target of strategic therapies. PMID:23136554

  10. Cytokines as Adjuvants for Vaccine and Cellular Therapies for Cancer

    PubMed Central

    Capitini, Christian M.; Fry, Terry J.; Mackall, Crystal L.

    2009-01-01

    Problem statement The development of a potent vaccine that can help treat tumors resistant to conventional cytotoxic therapies remains elusive. While part of the problem may be that trials have focused on patients with bulky residual disease, the desire to maximize responses to the vaccine remains. Approach The gamma(c) family of cytokines offer a unique opportunity to support the expansion and effector potential of vaccine-responding T-cells, as well as stimulate other effectors, such as natural killer (NK) cells, to become activated. Results Combining vaccines with cytokines seems logical but can bring unwanted toxicity, as has been observed with interleukin (IL)-2. In addition, the nonspecific activation or expansion of unwanted cell subsets, such as regulatory T-cells, can contribute to global immunosuppression and limit vaccine responses. The development of IL-7 and IL-21 for the clinic offers the promise of enhancing anti-tumor responses but with far less systemic toxicity and no expansion of regulatory T cells. Preclinical studies demonstrate that IL-15 could also improve T-cell, and especially NK-cell, responses as well. Conclusions/Recommendations Future work should expand the use of vaccines with IL-7, IL-21 and hopefully IL-15 in high-risk patients, and consider treatment while in a state of minimal residual disease to maximize benefit. Identifying tumors that can signal through gamma(c) cytokines will also be essential so that induction of relapse will be avoided. PMID:20182648

  11. Family psychology and family law: introduction to the special issue.

    PubMed

    Grossman, Neil S; Okun, Barbara F

    2003-06-01

    As part of a multilevel systemic approach, the authors appearing in this journal suggest implications for social policy and legislation extrapolated from the individual, family, legal, and larger sociocultural systems discussed. The field of family psychology can play a significant leadership role in advocating policies and legislation relevant to the emerging family types and legal dilemmas based on empirical findings. PMID:12828013

  12. Compartmentalized Cytokine Responses in Hidradenitis Suppurativa

    PubMed Central

    Savva, Athina; Kersten, Brigit; Pistiki, Aikaterini; van de Veerdonk, Frank L.; Netea, Mihai G.; van der Meer, Jos W.; Giamarellos-Bourboulis, Evangelos J.

    2015-01-01

    Background Favorable treatment outcomes with TNF blockade led us to explore cytokine responses in hidradenitis suppurativa (HS). Methods Blood monocytes of 120 patients and 24 healthy volunteers were subtyped by flow cytometry. Isolated blood mononuclear cells (PBMCs) were stimulated for cytokine production; this was repeated in 13 severe patients during treatment with etanercept. Cytokines in pus were measured. Results CD14brightCD16dim inflammatory monocytes and patrolling monocytes were increased in Hurley III patients. Cytokine production by stimulated PBMCs was low compared to controls but the cytokine gene copies did not differ, indicating post-translational inhibition. The low production of IL-17 was restored, when cells were incubated with adalimumab. In pus, high concentrations of pro-inflammatory cytokines were detected. Based on the patterns, six different cytokine profiles were discerned, which are potentially relevant for the choice of treatment. Clinical improvement with etanercept was predicted by increased production of IL-1β and IL-17 by PBMCs at week 8. Conclusions Findings indicate compartmentalized cytokine expression in HS; high in pus but suppressed in PBMCs. This is modulated through blockade of TNF. PMID:26091259

  13. Interactions between Autophagy and Inhibitory Cytokines

    PubMed Central

    Wu, Tian-tian; Li, Wei-Min; Yao, Yong-Ming

    2016-01-01

    Autophagy is a degradative pathway that plays an essential role in maintaining cellular homeostasis. Most early studies of autophagy focused on its involvement in age-associated degeneration and nutrient deprivation. However, the immunological functions of autophagy have become more widely studied in recent years. Autophagy has been shown to be an intrinsic cellular defense mechanism in the innate and adaptive immune responses. Cytokines belong to a broad and loose category of proteins and are crucial for innate and adaptive immunity. Inhibitory cytokines have evolved to permit tolerance to self while also contributing to the eradication of invading pathogens. Interactions between inhibitory cytokines and autophagy have recently been reported, revealing a novel mechanism by which autophagy controls the immune response. In this review, we discuss interactions between autophagy and the regulatory cytokines IL-10, transforming growth factor-β, and IL-27. We also mention possible interactions between two newly discovered cytokines, IL-35 and IL-37, and autophagy. PMID:27313501

  14. Cytokine Expression and Accelerated Tooth Movement

    PubMed Central

    Teixeira, C.C.; Khoo, E.; Tran, J.; Chartres, I.; Liu, Y.; Thant, L.M.; Khabensky, I.; Gart, L.P.; Cisneros, G.; Alikhani, M.

    2010-01-01

    It has been shown that inhibiting the expression of certain cytokines decreases the rate of tooth movement. Here, we hypothesized that stimulating the expression of inflammatory cytokines, through small perforations of cortical bone, increases the rate of bone remodeling and tooth movement. Forty-eight rats were divided into 4 groups: 50-cN force applied to the maxillary first molar (O), force application plus soft tissue flap (OF), force application plus flap plus 3 small perforations of the cortical plate (OFP), and a control group (C). From the 92 cytokines studied, the expression of 37 cytokines increased significantly in all experimental groups, with 21 cytokines showing the highest levels in the OFP group. After 28 days, micro-computed tomography, light and fluorescent microscopy, and immunohistochemistry demonstrated higher numbers of osteoclasts and bone remodeling activity in the OFP group, accompanied by generalized osteoporosity and increased rate of tooth movement. PMID:20639508

  15. FAMILY BACKGROUND OF RURAL YOUTH.

    ERIC Educational Resources Information Center

    COPP, JAMES H.

    FAMILY BACKGROUNDS OF RURAL YOUTH ARE DISCUSSED. THE BACKGROUND PROVIDED BY THE FAMILY HAS IMPLICATIONS FOR THE ADJUSTMENT OF RURAL YOUTH IN AN URBANIZED, HIGHLY TECHNICAL SOCIETY. THE BASIC ECOLOGICAL CONDITIONS OF RURAL AREAS INFLUENCE THE RATE OF SOCIAL CHANGE, THE IMPORTANCE OF THE FAMILY AS A SOCIAL UNIT, AND THE ORIENTATION TOWARD LEGAL…

  16. Soluble cytokine receptors in biological therapy.

    PubMed

    Fernandez-Botran, Rafael; Crespo, Fabian A; Sun, Xichun

    2002-08-01

    Due to their fundamental involvement in the pathogenesis of many diseases, cytokines constitute key targets for biotherapeutic approaches. The discovery that soluble forms of cytokine receptors are involved in the endogenous regulation of cytokine activity has prompted substantial interest in their potential application as immunotherapeutic agents. As such, soluble cytokine receptors have many advantages, including specificity, low immunogenicity and high affinity. Potential disadvantages, such as low avidity and short in vivo half-lifes, have been addressed by the use of genetically-designed receptors, hybrid proteins or chemical modifications. The ability of many soluble cytokine receptors to inhibit the binding and biological activity of their ligands makes them very specific cytokine antagonists. Several pharmaceutical companies have generated a number of therapeutic agents based on soluble cytokine receptors and many of them are undergoing clinical trials. The most advanced in terms of clinical development is etanercept (Enbrel, Immunex), a fusion protein between soluble TNF receptor Type II and the Fc region of human IgG1. This TNF-alpha; antagonist was the first soluble cytokine receptor to receive approval for use in humans. In general, most agents based on soluble cytokine receptors have been safe, well-tolerated and have shown only minor side effects in the majority of patients. Soluble cytokine receptors constitute a new generation of therapeutic agents with tremendous potential for applications in a wide variety of human diseases. Two current areas of research are the identification of their most promising applications and characterisation of their long-term effects. PMID:12171504

  17. Cytokine dysregulation in autism spectrum disorders (ASD): Possible role of the environment

    PubMed Central

    Goines, Paula E.; Ashwood, Paul

    2012-01-01

    Autism spectrum disorders (ASD) are neurodevelopmental diseases that affect an alarming number of individuals. The etiological basis of ASD is unclear, and evidence suggests it involves both genetic and environmental factors. There are many reports of cytokine imbalances in ASD. These imbalances could have a pathogenic role, or they may be markers of underlying genetic and environmental influences. Cytokines act primarily as mediators of immunological activity, but they also have significant interactions with the nervous system. They participate in normal neural development and function, and inappropriate activity can have a variety of neurological implications. It is therefore possible that cytokine dysregulation contributes directly to neural dysfunction in ASD. Further, cytokine profiles change dramatically in the face of infection, disease, and toxic exposures. Therefore, imbalances may represent an immune response to environmental contributors to ASD. The following review is presented in two main parts. First, we discuss select cytokines implicated in ASD, including IL-1Β, IL-6, IL-4, IFN-γ, and TGF-Β, and focus on their role in the nervous system. Second, we explore several neurotoxic environmental factors that may be involved in the disorders, and focus on their immunological impacts. This review represents an emerging model that recognizes the importance of both genetic and environmental factors in ASD etiology. We propose that the immune system provides critical clues regarding the nature of the gene by environment interactions that underlie ASD pathophysiology. PMID:22918031

  18. Cytokine variations and mood disorders: influence of social stressors and social support

    PubMed Central

    Audet, Marie-Claude; McQuaid, Robyn J.; Merali, Zul; Anisman, Hymie

    2014-01-01

    Stressful events have been implicated in the evolution of mood disorders. In addition to brain neurotransmitters and growth factors, the view has been offered that these disorders might be provoked by the activation of the inflammatory immune system as well as by de novo changes of inflammatory cytokines within the brain. The present review describes the impact of social stressors in animals and in humans on behavioral changes reminiscent of depressive states as well as on cytokine functioning. Social stressors increase pro-inflammatory cytokines in circulation as well as in brain regions that have been associated with depression, varying with the animal's social status and/or behavioral methods used to contend with social challenges. Likewise, in humans, social stressors that favor the development of depression are accompanied by elevated circulating cytokine levels and conversely, conditions that limit the cytokine elevations correlated with symptom attenuation or reversal. The implications of these findings are discussed in relation to the potentially powerful effects of social support, social identity, and connectedness in maintaining well-being and in diminishing symptoms of depression. PMID:25565946

  19. Characterization and evaluation of sex-specific expression of suppressors of cytokine signaling (SOCS) -1 and -3 in juvenile yellow perch (Perca flavescens) treated with lipopolysaccharide

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The suppressor of cytokine signaling (SOCS) proteins are a family of intracellular proteins that are centrally involved with vertebrate growth, development and immunity via their effects as negative feed-back regulators of cytokine (and hormone) signaling. The genes for SOCS-1 & -3 were cloned, sequ...

  20. Family Literacy: Directions in Research and Implications for Practice. Summary and Papers of a National Symposium (Washington, DC, September 7-8, 1995).

    ERIC Educational Resources Information Center

    Benjamin, L. Ann, Ed.; Lord, Jerome, Ed.

    This document contains 10 commissioned papers presented at a research design symposium on family literacy. It also contains a summary of the symposium, which was structured around five themes: assumptions and perceptions about family literacy; what we know from research and practice and how we know it; defining the characteristics of family…

  1. [White House Conference on Aging, 1981. Creating an Age Integrated Society: Implications for the Family. Report and Executive Summary of the Technical Committee.

    ERIC Educational Resources Information Center

    Lopata, Helena Z.; And Others

    This Technical Committee Report presents research on demographic trends, labor force participation, and public service programs which suggests a need to alter traditional assumptions about aging, family, and social supports required for an equitably integrated society. Demographic data on populations, families, and aging are provided, and…

  2. Inconsistencies in the Roles of Family- and Paid- Carers in Monitoring Health Issues in People with Learning Disabilities: Some Implications for the Integration of Health and Social Care

    ERIC Educational Resources Information Center

    Willis, Diane S.

    2015-01-01

    Changes in the living circumstances of people with learning disabilities have seen responsibility for their health become the provenance of paid-and family-carers. Thirteen semi-structured interviews were conducted with three family-carers and ten paid-carers. Findings revealed that the role of these carers was undefined, leading to difficulty in…

  3. Temporary Assistance for Needy Families: Implications of Recent Legislative and Economic Changes for State Programs and Work Participation Rates. Report to Congressional Requesters. GAO-10-525

    ERIC Educational Resources Information Center

    Brown, Kay E.

    2010-01-01

    The Deficit Reduction Act of 2005 (DRA) reauthorized the Temporary Assistance for Needy Families (TANF) block grant and made modifications expected to strengthen work requirements for families receiving cash assistance through state TANF programs. Both the U.S. Department of Health and Human Services (HHS) and states were required to take steps to…

  4. Spanish-Speaking Mexican-American Families' Involvement in School-Based Activities and Their Children's Literacy: The Implications of Having Teachers Who Speak Spanish and English

    ERIC Educational Resources Information Center

    Tang, Sandra; Dearing, Eric; Weiss, Heather B.

    2012-01-01

    For a sample of low-income, Spanish-speaking Mexican-American families (n = 72), we investigated associations between family involvement in school-based activities and children's literacy in their preferred language (English or Spanish) during early elementary school. We gave special attention to the potential moderating role of teacher fluency in…

  5. Beyond the Ball: Implications for HIV risk and prevention among the constructed families of African American Men who have Sex with Men

    PubMed Central

    Dickson-Gomez, Julia; Owczarzak, Jill; Lawrence, Janet St.; Sitzler, Cheryl; Quinn, Katherine; Pearson, Broderick; Kelly, Jeffrey A.; Amirkhanian, Yuri A.

    2014-01-01

    African American men who have sex with men (AAMSM) are disproportionately burdened by new and existing HIV infections. In spite of this, few HIV prevention interventions have been developed that meet the specific needs of AAMSM and that are culturally appropriate and build on strengths and resources. In this paper, we examine constructed families, including those who belong to houses and those who do not, from a three city sample of 196 AAMSM. Results show that the majority of AAMSM who belong to constructed families do not participate in houses or balls. Both house and non-house affiliated constructed families are important sources of social support among AAMSM. Participants reported limited success in spreading HIV messages at ball events, but talk about HIV within their constructed families. Social network approaches to HIV prevention may capitalize on existing social ties within constructed families to promote safer sexual behaviors. PMID:24980248

  6. Flowering Date of Taxonomic Families Predicts Phenological Sensitivity to Temperature: Implications for Forecasting the Effects of Climate Change on Unstudied Taxa

    NASA Technical Reports Server (NTRS)

    Mazer, Susan J.; Travers, Steven E.; Cook, Benjamin I.; Davies, T. Jonathan; Bolmgren, Kjell; Kraft, Nathan J. B.; Salamin, Nicolas; Inouye, David W.

    2013-01-01

    Premise of the study: Numerous long-term studies in seasonal habitats have tracked interannual variation in fi rst fl owering date (FFD) in relation to climate, documenting the effect of warming on the FFD of many species. Despite these efforts, long-term phenological observations are still lacking for many species. If we could forecast responses based on taxonomic affi nity, however, then we could leverage existing data to predict the climate-related phenological shifts of many taxa not yet studied; Methods: We examined phenological time series of 1226 species occurrences (1031 unique species in 119 families) across seven sites in North America and England to determine whether family membership (or family mean FFD) predicts the sensitivity of FFD to standardized interannual changes in temperature and precipitation during seasonal periods before fl owering and whether families differ signifi cantly in the direction of their phenological shifts; Key results: Patterns observed among species within and across sites are mirrored among family means across sites; earlyfl owering families advance their FFD in response to warming more than late-fl owering families. By contrast, we found no consistent relationships among taxa between mean FFD and sensitivity to precipitation as measured here; Conclusions: Family membership can be used to identify taxa of high and low sensitivity to temperature within the seasonal, temperate zone plant communities analyzed here. The high sensitivity of early-fl owering families (and the absence of earlyfl owering families not sensitive to temperature) may refl ect plasticity in fl owering time, which may be adaptive in environments where early-season conditions are highly variable among years.

  7. Resistin as an Intrahepatic Cytokine

    PubMed Central

    Bertolani, Cristiana; Sancho-Bru, Pau; Failli, Paola; Bataller, Ramon; Aleffi, Sara; DeFranco, Raffaella; Mazzinghi, Benedetta; Romagnani, Paola; Milani, Stefano; Ginés, Pere; Colmenero, Jordi; Parola, Maurizio; Gelmini, Stefania; Tarquini, Roberto; Laffi, Giacomo; Pinzani, Massimo; Marra, Fabio

    2006-01-01

    Obesity and insulin resistance accelerate the progression of fibrosis during chronic liver disease. Resistin antagonizes insulin action in rodents, but its role in humans is still controversial. The aims of this study were to investigate resistin expression in human liver and to evaluate whether resistin may affect the biology of activated human hepatic stellate cells (HSCs), key modulators of hepatic fibrogenesis. Resistin gene expression was low in normal human liver but was increased in conditions of severe fibrosis. Up-regulation of resistin during chronic liver damage was confirmed by immunohistochemistry. In a group of patients with alcoholic hepatitis, resistin expression correlated with inflammation and fibrosis, suggesting a possible action on HSCs. Exposure of cultured HSCs to recombinant resistin resulted in increased expression of the proinflammatory chemokines monocyte chemoattractant protein-1 and interleukin-8, through activation of nuclear factor (NF)-κB. Resistin induced a rapid increase in intracellular calcium concentration, mainly through calcium release from intracellular inositol triphosphate-sensitive pools. The intracellular calcium chelator BAPTA-AM blocked resistin-induced NF-κB activation and monocyte chemoattractant protein-1 expression. In conclusion, this study shows a role for resistin as an intrahepatic cytokine exerting proinflammatory actions in HSCs, via a Ca2+/NF-κB-dependent pathway and suggests involvement of this adipokine in the pathophysiology of liver fibrosis. PMID:17148667

  8. Perilla frutescens extract ameliorates DSS-induced colitis by suppressing proinflammatory cytokines and inducing anti-inflammatory cytokines.

    PubMed

    Urushima, Hayato; Nishimura, Junichi; Mizushima, Tsunekazu; Hayashi, Noriyuki; Maeda, Kazuhisa; Ito, Toshinori

    2015-01-01

    Anti-inflammatory effects have been reported in Perilla frutescens leaf extract (PE), which is a plant of the genus belonging to the Lamiaceae family. We examined the effect of PE on dextran sulfate sodium (DSS)-induced colitis. Preliminarily, PE was safely administered for 7 wk without any adverse effects. In the preventive protocol, mice were fed 1.5% DSS solution dissolved in distilled water (control group) or 0.54% PE solution (PE group) ad libitum for 7 days. In the therapeutic protocol, distilled water or 0.54% PE solution was given for 10 days just after administration of 1.5% DSS for 5 days. PE intake significantly improved body weight loss. The serum cytokine profile demonstrated that TNF-α, IL-17A, and IL-10 were significantly lower in the PE group than in the control group. In the therapeutic protocol, mice in the PE group showed significantly higher body weight and lower histological colitis scores compared with mice in the control group on day 15. The serum cytokine profile demonstrated that TGF-β was significantly higher in the PE group than in the control group. In distal colon mRNA expression, TNF-α, and IL-17A were significantly downregulated. In vitro analyses of biologically active ingredients, such as luteolin, apigenin, and rosmarinic acid, in PE were performed. Luteolin suppressed production of proinflammatory cytokines, such as TNF-α, IL-1β, IL-6, and IL-17A. Apigenin also suppressed secretion of IL-17A and increased the anti-inflammatory cytokine IL-10. Rosmarinic acid increased the regulatory T cell population. We conclude that PE might be useful in treatment and prevention of DSS-induced colitis. PMID:25359539

  9. Bacterial modulins: a novel class of virulence factors which cause host tissue pathology by inducing cytokine synthesis.

    PubMed Central

    Henderson, B; Poole, S; Wilson, M

    1996-01-01

    Cytokines are a diverse group of proteins and glycoproteins which have potent and wide-ranging effects on eukaryotic cell function and are now recognized as important mediators of tissue pathology in infectious diseases. It is increasingly recognized that for many bacterial species, cytokine induction is a major virulence mechanism. Until recent years, the only bacterial component known to stimulate cytokine synthesis was lipopolysaccharide (LPS). It is only within the past decade that it has been clearly shown that many components associated with the bacterial cell wall, including proteins, glycoproteins, lipoproteins, carbohydrates, and lipids, have the capacity to stimulate mammalian cells to produce a diverse array of cytokines. It has been established that many of these cytokine-inducing molecules act by mechanisms distinct from that of LPS, and thus their activities are not due to LPS contamination. Bacteria produce a wide range of virulence factors which cause host tissue pathology, and these diverse factors have been grouped into four families: adhesins, aggressins, impedins, and invasins. We suggest that the array of bacterial cytokine-inducing molecules represents a new class of bacterial virulence factor, and, by analogy with the known virulence families, we suggest the term "modulin" to describe these molecules, because the action of cytokines is to modulate eukaryotic cell behavior. This review summarizes our current understanding of cytokine biology in relation to tissue homeostasis and disease and concisely reviews the current literature on the cytokine-inducing molecules produced by gram-negative and gram-positive bacteria, with an emphasis on the cellular mechanisms responsible for cytokine induction. We propose that modulins, by controlling the host immune and inflammatory responses, maintain the large commensal flora that all multicellular organisms support. PMID:8801436

  10. Bone Loss Triggered by the Cytokine Network in Inflammatory Autoimmune Diseases

    PubMed Central

    Amarasekara, Dulshara Sachini; Yu, Jiyeon; Rho, Jaerang

    2015-01-01

    Bone remodeling is a lifelong process in vertebrates that relies on the correct balance between bone resorption by osteoclasts and bone formation by osteoblasts. Bone loss and fracture risk are implicated in inflammatory autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, and systemic lupus erythematosus. The network of inflammatory cytokines produced during chronic inflammation induces an uncoupling of bone formation and resorption, resulting in significant bone loss in patients with inflammatory autoimmune diseases. Here, we review and discuss the involvement of the inflammatory cytokine network in the pathophysiological aspects and the therapeutic advances in inflammatory autoimmune diseases. PMID:26065006

  11. The biological and clinical importance of the 'new generation' cytokines in rheumatic diseases

    PubMed Central

    Gabay, Cem; McInnes, Iain B

    2009-01-01

    A better understanding of cytokine biology over the last two decades has allowed the successful development of cytokine inhibitors against tumour necrosis factor and interleukin (IL)-1 and IL-6. The introduction of these therapies should be considered a breakthrough in the management of several rheumatic diseases. However, many patients will exhibit no or only partial response to these therapies, thus emphasising the importance of exploring other therapeutic strategies. In this article, we review the most recent information on novel cytokines that are often members of previously described cytokine families such as the IL-1 superfamily (IL-18 and IL-33), the IL-12 superfamily (IL-27 and IL-35), the IL-2 superfamily (IL-15 and IL-21), and IL-17. Several data derived from experimental models and clinical samples indicate that some of these cytokines contribute to the pathophysiology of arthritis and other inflammatory diseases. Targeting of some of these cytokines has already been tested in clinical trials with interesting results. PMID:19519923

  12. Cytokine medicines in clinical practice: current issues.

    PubMed

    Barnes, Theresa; Moots, Robert J; Goodacre, John

    2005-10-21

    Cytokine medicines have been licensed for the treatment of rheumatoid arthritis since 2000. The rheumatology community has accrued a large amount of experience in the use of these medications. This experience has led to the development of guidelines for their use that include ongoing vigilance for long term adverse events and efficacy using the Biologics Register. Delivery of these expensive therapies has prompted extensive system developments within rheumatology. The cytokine medicines have provided important tools to probe the pathogenesis of rheumatoid and other inflammatory diseases. Further cytokine medicines, in various stages of development, are on the horizon and continue to stimulate excitement within this fast expanding field. PMID:16188452

  13. The common γ-chain cytokine receptor: tricks-and-treats for T cells.

    PubMed

    Waickman, Adam T; Park, Joo-Young; Park, Jung-Hyun

    2016-01-01

    Originally identified as the third subunit of the high-affinity IL-2 receptor complex, the common γ-chain (γc) also acts as a non-redundant receptor subunit for a series of other cytokines, collectively known as γc family cytokines. γc plays essential roles in T cell development and differentiation, so that understanding the molecular basis of its signaling and regulation is a critical issue in T cell immunology. Unlike most other cytokine receptors, γc is thought to be constitutively expressed and limited in its function to the assembly of high-affinity cytokine receptors. Surprisingly, recent studies reported a series of findings that unseat γc as a simple housekeeping gene, and unveiled γc as a new regulatory molecule in T cell activation and differentiation. Cytokine-independent binding of γc to other cytokine receptor subunits suggested a pre-association model of γc with proprietary cytokine receptors. Also, identification of a γc splice isoform revealed expression of soluble γc proteins (sγc). sγc directly interacted with surface IL-2Rβ to suppress IL-2 signaling and to promote pro-inflammatory Th17 cell differentiation. As a result, endogenously produced sγc exacerbated autoimmune inflammatory disease, while the removal of endogenous sγc significantly ameliorated disease outcome. These data provide new insights into the role of both membrane and soluble γc in cytokine signaling, and open new venues to interfere and modulate γc signaling during immune activation. These unexpected discoveries further underscore the perspective that γc biology remains largely uncharted territory that invites further exploration. PMID:26468051

  14. MACROPHAGE ACTIVATION SYNDROME AND CYTOKINE DIRECTED THERAPIES

    PubMed Central

    Grom, Alexei A.

    2014-01-01

    Macrophage activation syndrome (MAS) is an episode of overwhelming inflammation that occurs most commonly in children with systemic juvenile idiopathic arthritis. It is characterized by expansion and activation of T lymphocytes and hemophagocytic macrophages, and bears great similarity to hemophagocytic lymphohistiocytosis (HLH). This disorder has substantial morbidity and mortality, and there is frequently a delay in recognition and initiation of treatment. Here, we will review what is known about the pathogenesis of MAS and in particular its similarities to HLH. The development of MAS is characterized by a cytokine storm, with the elaboration of numerous proinflammatory cytokines. We will examine the evidence for various cytokines in the initiation and pathogenesis of MAS, and discuss how new biologic therapies may alter the risk of MAS. Finally we will review current treatment options for MAS, and examine how cytokine-directed therapy could serve as novel treatment modalities. PMID:24974063

  15. Changes in proinflammatory cytokine activity after menopause.

    PubMed

    Pfeilschifter, Johannes; Köditz, Roland; Pfohl, Martin; Schatz, Helmut

    2002-02-01

    There is now a large body of evidence suggesting that the decline in ovarian function with menopause is associated with spontaneous increases in proinflammatory cytokines. The cytokines that have obtained the most attention are IL-1, IL-6, and TNF-alpha. The exact mechanisms by which estrogen interferes with cytokine activity are still incompletely known but may potentially include interactions of the ER with other transcription factors, modulation of nitric oxide activity, antioxidative effects, plasma membrane actions, and changes in immune cell function. Experimental and clinical studies strongly support a link between the increased state of proinflammatory cytokine activity and postmenopausal bone loss. Preliminary evidence suggests that these changes also might be relevant to vascular homeostasis and the development of atherosclerosis. Better knowledge of the mechanisms and the time course of these interactions may open new avenues for the prevention and treatment of some of the most prevalent and important disorders in postmenopausal women. PMID:11844745

  16. Cytokines in systemic lupus erythematosus, London, UK

    PubMed Central

    Rahman, Anisur

    2003-01-01

    The meeting consisted of 11 talks that illustrated the complexity of the pathogenetic mechanisms underlying systemic lupus erythematosus and aimed to identify ways in which cytokine modulation might affect those mechanisms. The evidence relating to the involvement of tumour necrosis factor-α, interleukin-10 and BLyS in this disease was discussed in particular detail. A final discussion explored the possible ways in which cytokine modulation might lead to new methods of treating systemic lupus erythematosus in the future. PMID:12823845

  17. Soypeptide lunasin in cytokine immunotherapy for lymphoma.

    PubMed

    Chang, Hua-Chen; Lewis, David; Tung, Chun-Yu; Han, Ling; Henriquez, Sarah M P; Voiles, Larry; Lupov, Ivan P; Pelloso, David; Sinn, Anthony L; Pollok, Karen E; de Lumen, Ben O; Li, Fang; Blum, Janice S; Srivastava, Shivani; Robertson, Michael J

    2014-03-01

    Immunostimulatory cytokines can enhance anti-tumor immunity and are part of the therapeutic armamentarium for cancer treatment. We have previously reported that post-transplant lymphoma patients have an acquired deficiency of signal transducer and activator of transcription 4, which results in defective IFNγ production during clinical immunotherapy. With the goal of further improving cytokine-based immunotherapy, we examined the effects of a soybean peptide called lunasin that synergistically works with cytokines on natural killer (NK) cells. Peripheral blood mononuclear cells of healthy donors and post-transplant lymphoma patients were stimulated with or without lunasin in the presence of IL-12 or IL-2. NK activation was evaluated, and its tumoricidal activity was assessed using in vitro and in vivo tumor models. Chromatin immunoprecipitation assay was performed to evaluate the histone modification of gene loci that are regulated by lunasin and cytokine. Adding lunasin to IL-12- or IL-2-stimulated NK cells demonstrated synergistic effects in the induction of IFNG and GZMB involved in cytotoxicity. The combination of lunasin and cytokines (IL-12 plus IL-2) was capable of restoring IFNγ production by NK cells from post-transplant lymphoma patients. In addition, NK cells stimulated with lunasin plus cytokines displayed higher tumoricidal activity than those stimulated with cytokines alone using in vitro and in vivo tumor models. The underlying mechanism responsible for the effects of lunasin on NK cells is likely due to epigenetic modulation on target gene loci. Lunasin represents a different class of immune modulating agent that may augment the therapeutic responses mediated by cytokine-based immunotherapy. PMID:24363024

  18. Anti cytokine therapy in chronic inflammatory arthritis.

    PubMed

    Thompson, Charlotte; Davies, Ruth; Choy, Ernest

    2016-10-01

    This is a review looking at anti cytokine therapy in Rheumatoid Arthritis (RA), Psoriatic Arthritis (PSA) and Ankylosing Spondylitis (AS). The review explores the similarities and differences in the clinical features, as well as treatments and cytokines involved in the development and propagation of the disease. Particular attention is paid to TNFα inhibitors IL-1ra, IL-6 and JAK kinase Inhibitors, anti IL23 and IL-12 and the new developments with anti-IL-17. PMID:27497159

  19. MicroRNA-98 and let-7 Confer Cholangiocyte Expression of Cytokine-Inducible Src Homology 2-Containing Protein in Response to Microbial Challenge1,2

    PubMed Central

    Hu, Guoku; Zhou, Rui; Liu, Jun; Gong, Ai-Yu; Eischeid, Alex N.; Dittman, Jared W.; Chen, Xian-Ming

    2010-01-01

    Posttranscriptional gene regulation by microRNAs (miRNAs) has been implicated in the fine-tuning of TLR-mediated inflammatory response. The cytokine-inducible Src homology 2-containing protein (CIS), one member of the suppressors of cytokine signaling family of proteins, is an important negative regulator for inflammatory cytokine signaling. Using in vitro models using normal human biliary epithelial cells (cholangiocytes), we demonstrated that LPS stimulation or infection with the parasitic protozoan Cryptosporidium parvum induced expression of CIS protein without a change in CIS mRNA levels by activating the TLR signaling pathway. Of those miRNAs expressed in cholangiocytes, we found that targeting of the 3′-untranslated region of CIS by microRNA-98 (miR-98) or let-7 resulted in translational repression, but not CIS mRNA degradation. LPS stimulation or C. parvum infection decreased cholangiocyte expression of miR-98 and let-7. Down-regulation of miR-98 and let-7 relieved miRNA-mediated translational suppression of CIS and contributed to LPS- and C. parvum-stimulated CIS protein expression. Moreover, gain-of-function (by overexpression of CIS) and loss-of-function (by siRNA interference) studies revealed that CIS could enhance IκBα degradation and regulate NF-κB activation in cholangiocytes in response to LPS stimulation or C. parvum infection. Our data suggest that miR-98 and let-7 confer cholangiocyte expression of CIS in response to microbial challenge, a process that may be relevant to the regulation of TLR-mediated epithelial innate immune response. PMID:19592657

  20. The role of cytokines in the pathogenesis and staging of Trypanosoma brucei rhodesiense sleeping sickness.

    PubMed

    Kato, Charles D; Matovu, Enock; Mugasa, Claire M; Nanteza, Ann; Alibu, Vincent P

    2016-01-01

    Human African trypanosomiasis due to Trypanosoma brucei rhodesiense is invariably fatal if untreated with up to 12.3 million people at a risk of developing the disease in Sub-Saharan Africa. The disease is characterized by a wide spectrum of clinical presentation coupled with differences in disease progression and severity. While the factors determining this varied response have not been clearly characterized, inflammatory cytokines have been partially implicated as key players. In this review, we consolidate available literature on the role of specific cytokines in the pathogenesis of T. b. rhodesiense sleeping sickness and further discuss their potential as stage biomarkers. Such information would guide upcoming research on the immunology of sleeping sickness and further assist in the selection and evaluation of cytokines as disease stage or diagnostic biomarkers. PMID:26807135

  1. Germline MLH1 and MSH2 mutational spectrum including frequent large genomic aberrations in Hungarian hereditary non-polyposis colorectal cancer families: Implications for genetic testing

    PubMed Central

    Papp, Janos; Kovacs, Marietta E; Olah, Edith

    2007-01-01

    AIM: To analyze the prevalence of germline MLH1 and MSH2 gene mutations and evaluate the clinical characteristics of Hungarian hereditary non-polyposis colorectal cancer (HNPCC) families. METHODS: Thirty-six kindreds were tested for mutations using conformation sensitive gel electrophoreses, direct sequencing and also screening for genomic rearrangements applying multiplex ligation-dependent probe amplification (MLPA). RESULTS: Eighteen germline mutations (50%) were identified, 9 in MLH1 and 9 in MSH2. Sixteen of these sequence alterations were considered pathogenic, the remaining two were non-conservative missense alterations occurring at highly conserved functional motifs. The majority of the definite pathogenic mutations (81%, 13/16) were found in families fulfilling the stringent Amsterdam I/II criteria, including three rearrangements revealed by MLPA (two in MSH2 and one in MLH1). However, in three out of sixteen HNPCC-suspected families (19%), a disease-causing alteration could be revealed. Furthermore, nine mutations described here are novel, and none of the sequence changes were found in more than one family. CONCLUSION: Our study describes for the first time the prevalence and spectrum of germline mismatch repair gene mutations in Hungarian HNPCC and suspected-HNPCC families. The results presented here suggest that clinical selection criteria should be relaxed and detection of genomic rearrangements should be included in genetic screening in this population. PMID:17569143

  2. Fixation, Segregation and Linkage of Allozyme Loci in Inbred Families of the Pacific Oyster Crassostrea Gigas (Thunberg): Implications for the Causes of Inbreeding Depression

    PubMed Central

    McGoldrick, D. J.; Hedgecock, D.

    1997-01-01

    The effect that inbreeding has on the fixation and segregation of genes has rarely been confirmed by direct observation. Here, fixation, segregation, and linkage of allozymes is investigated in the progeny of self-fertilized hermaphrodites of the normally outcrossing Pacific oyster Crassostrea gigas. The estimate of fixation pooled over loci, individuals, and families, F = 0.462, is significantly lower than the expected value of 0.5. Log-likelihood ratios reveal significant heterogeneity in fixation among individuals, among families, and among loci. In addition, the grand pooled segregation ratio, 127:243:54, deviates significantly from 1:2:1, with a bias against homozygotes for alleles of lesser frequency in the natural population. Segregation ratios for 11 of 14 loci are significantly heterogeneous among families, and exact tests for segregation within families reveal 16 significant results out of 51 tests. Thus, fixation and segregation of allozyme markers in inbred oyster families deviates from the expectations of neutral inbreeding theory. Di-genic disequilibria are significant for four of 74 di-locus pairs revealing two linkage groups. Strong viability selection is apparently conditional on the genotype of the hermaphrodite-founders and is largely focused on these two linkage groups. These genetic effects are explained by interaction between cis-linked factors and polymorphic regulatory backgrounds. PMID:9136021

  3. Lagerstroemia L. from the middle Miocene Siwalik deposits, northern India: Implication for Cenozoic range shifts of the genus and the family Lythraceae

    NASA Astrophysics Data System (ADS)

    Srivastava, Gaurav; Gaur, Rajan; Mehrotra, R. C.

    2015-02-01

    Fossil leaves of Lagerstroemia (Lythraceae) are described from the Siwalik deposits (middle Miocene) of Kathgodam, Uttarakhand, India. The fossil records of the Lythraceae indicate its worldwide distribution in the Cenozoic. The family had its widest distribution during the Miocene but became less widespread during the Pliocene, followed by range expansion during the Quaternary. The present leaf fossil, along with the previous fossil records of Lagerstroemia, indicates that the genus followed the same pattern of expansion and retraction as the entire family Lythraceae suggesting that both the genus and the family adapted in similar ways. The fossil plant assemblage from the Lower Siwalik deposits indicates warm and humid climate with plenty of rainfall in the region during the depositional period.

  4. Work, Welfare, and Family Well-Being.

    ERIC Educational Resources Information Center

    Sing, Merrile; Hill, Heather; Mendenko, Linda

    As more families move from welfare to work, little is known about the implications of employment for family well-being. This survey and case study examined the effects of employment on the economic, social, and emotional well-being of parents, children, and families. Survey respondents received assistance through Iowa's Family Investment Program…

  5. Understanding the contribution of family history to colorectal cancer risk and its clinical implications: A state-of-the-science review.

    PubMed

    Lowery, Jan T; Ahnen, Dennis J; Schroy, Paul C; Hampel, Heather; Baxter, Nancy; Boland, C Richard; Burt, Randall W; Butterly, Lynn; Doerr, Megan; Doroshenk, Mary; Feero, W Gregory; Henrikson, Nora; Ladabaum, Uri; Lieberman, David; McFarland, Elizabeth G; Peterson, Susan K; Raymond, Martha; Samadder, N Jewel; Syngal, Sapna; Weber, Thomas K; Zauber, Ann G; Smith, Robert

    2016-09-01

    Persons with a family history (FH) of colorectal cancer (CRC) or adenomas that are not due to known hereditary syndromes have an increased risk for CRC. An understanding of these risks, screening recommendations, and screening behaviors can inform strategies for reducing the CRC burden in these families. A comprehensive review of the literature published within the past 10 years has been performed to assess what is known about cancer risk, screening guidelines, adherence and barriers to screening, and effective interventions in persons with an FH of CRC and to identify FH tools used to identify these individuals and inform care. Existing data show that having 1 affected first-degree relative (FDR) increases the CRC risk 2-fold, and the risk increases with multiple affected FDRs and a younger age at diagnosis. There is variability in screening recommendations across consensus guidelines. Screening adherence is <50% and is lower in persons under the age of 50 years. A provider's recommendation, multiple affected relatives, and family encouragement facilitate screening; insufficient collection of FH, low knowledge of guidelines, and poor family communication are important barriers. Effective interventions incorporate strategies for overcoming barriers, but these have not been broadly tested in clinical settings. Four strategies for reducing CRC in persons with familial risk are suggested: 1) improving the collection and utilization of the FH of cancer, 2) establishing a consensus for screening guidelines by FH, 3) enhancing provider-patient knowledge of guidelines and communication about CRC risk, and 4) encouraging survivors to promote screening within their families and partnering with existing screening programs to expand their reach to high-risk groups. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2633-2645. © 2016 American Cancer Society. PMID:27258162

  6. How pediatricians can respond to the psychosocial implications of disasters. American Academy of Pediatrics. Committee on Psychosocial Aspects of Child and Family Health, 1998-1999.

    PubMed

    Wolraich, M L; Aceves, J; Feldman, H M; Hagan, J F; Howard, B J; Navarro, A; Richtsmeier, A J; Tolmas, H C

    1999-02-01

    Natural and human-caused disasters, violence with weapons, and terrorist acts have touched directly the lives of thousands of families with children in the United States.1 Media coverage of disasters has brought images of floods, hurricanes, and airplane crashes into the living rooms of most American families, with limited censorship for vulnerable young children. Therefore, children may be exposed to disastrous events in ways that previous generations never or rarely experienced. Pediatricians should serve as important resources to the community in preparing for disasters, as well as acting in its behalf during and after such events. PMID:9925857

  7. Implications for observant Jewish families in the provision of mother's own and donor milk for their very low birth weight infant.

    PubMed

    Kassierer, Moshe Yair; O'Connor, Deborah L; Rutherford, Eva; Rolnitzky, Asaph; Unger, Sharon

    2014-11-01

    Jewish law recognizes the importance of breast milk, and breastfeeding rates are high among religious mothers. Infants born at very low birth weight are medically fragile, and breast milk is of critical importance for their health protection and optimal growth and development. For observant Jewish infants and their families, there may be scenarios for special consideration in their health care. This report reviews briefly the relevant Jewish laws related to breast milk provision, both mother's own milk and donor milk, in the neonatal intensive care unit with background information for counseling such families. PMID:25092199

  8. A genetic contribution to circulating cytokines and obesity in children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cytokines are considered to be involved in obesity-related metabolic diseases. Study objectives are to determine the heritability of circulating cytokine levels, to investigate pleiotropy between cytokines and obesity traits, and to present genome scan results for cytokines in 1030 Hispanic children...

  9. Cytokine Regulation of Microenvironmental Cells in Myeloproliferative Neoplasms

    PubMed Central

    Hoermann, Gregor; Greiner, Georg; Valent, Peter

    2015-01-01

    The term myeloproliferative neoplasms (MPN) refers to a heterogeneous group of diseases including not only polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), but also chronic myeloid leukemia (CML), and systemic mastocytosis (SM). Despite the clinical and biological differences between these diseases, common pathophysiological mechanisms have been identified in MPN. First, aberrant tyrosine kinase signaling due to somatic mutations in certain driver genes is common to these MPN. Second, alterations of the bone marrow microenvironment are found in all MPN types and have been implicated in the pathogenesis of the diseases. Finally, elevated levels of proinflammatory and microenvironment-regulating cytokines are commonly found in all MPN-variants. In this paper, we review the effects of MPN-related oncogenes on cytokine expression and release and describe common as well as distinct pathogenetic mechanisms underlying microenvironmental changes in various MPN. Furthermore, targeting of the microenvironment in MPN is discussed. Such novel therapies may enhance the efficacy and may overcome resistance to established tyrosine kinase inhibitor treatment in these patients. Nevertheless, additional basic studies on the complex interplay of neoplastic and stromal cells are required in order to optimize targeting strategies and to translate these concepts into clinical application. PMID:26543328

  10. C-reactive protein, cytokines and inflammation in cardiovascular diseases.

    PubMed

    Bucova, M; Bernadic, M; Buckingham, T

    2008-01-01

    Inflammation of vascular cell wall is the key problem and proinflammatory cytokines and chemokines play a great role in it. These molecules, togheter with C-reactive protein (CRP) can predict risk of coronary events. It is questionable to what extend are CRP and pro-inflammatory cytokines purely acute phase markers and to what extend are they active inflammatory participants. Besides inflammation, other prominent mechanism in the pathogenesis of atherosclerosis and atherothrombosis--underlying causes of coronary events, is genetics. Gene polymorphisms including polymorphisms of inflammatory markers are studied and one of them, polymorphism of monocyte chemoattractant protein (MCP-1/CCL2) and its receptor CCR2 (key components of atherosclerosis) belong to most studied one. MCP-1/CCL2 and CCR2 polymorphisms have been implicated as susceptibility factors for chronic stable angina pectoris and myocardial infarction by several independent investigators. It seems that CCL2/CCR2 axis plays an important role both in post-ischemic and post-reperfusion inflammation and could become a new therapeutic goal in selected cardiovascular diseases as well as in stroke in future. Inhibition of this axis disrupts ischemic-reperfusion injury by decreasing edema, leucocyte infiltration and expression of inflammatory mediators. One can suppose that identifying genes influencing inflammatory biomarkers might improve understanding of genetic determinants of cardiovascular disease our management and prevention (Tab. 2, Fig. 1, Ref. 105). Full Text (Free, PDF) www.bmj.sk. PMID:18837239

  11. Suppressors of Cytokine Signaling in Sickness and in Health of Pancreatic β-Cells

    PubMed Central

    Ye, Cheng; Driver, John P.

    2016-01-01

    Suppressors of cytokine signaling (SOCS) are a family of eight proteins that negatively regulate Janus kinase and signal transducers and activators of transcription signaling in cells that utilize this pathway to respond to extracellular stimuli. SOCS are best known for attenuating cytokine signaling in the immune system. However, they are also expressed in many other cell types, including pancreatic β-cells, where there is considerable interest in harnessing SOCS molecules to prevent cytokine-mediated apoptosis during diabetes and allogeneic transplantation. Apart from their potential as therapeutic targets, SOCS molecules play a central role for regulating important functions in β-cells, including growth, glucose sensing, and insulin secretion. This review will discuss SOCS proteins as central regulators for diverse cellular processes important for normal β-cell function as well as their protective anti-apoptotic effects during β-cell stress. PMID:27242781

  12. Proinflammatory Cytokines Induce Endocrine Differentiation in Pancreatic Ductal Cells via STAT3-Dependent NGN3 Activation.

    PubMed

    Valdez, Ivan Achel; Dirice, Ercument; Gupta, Manoj K; Shirakawa, Jun; Teo, Adrian Kee Keong; Kulkarni, Rohit N

    2016-04-19

    A major goal of diabetes research is to develop strategies that replenish pancreatic insulin-producing beta cells. One emerging strategy is to harness pancreatic plasticity-the ability of pancreatic cells to undergo cellular interconversions-a phenomenon implicated in physiological stress and pancreatic injury. Here, we investigate the effects of inflammatory cytokine stress on the differentiation potential of ductal cells in a human cell line, in mouse ductal cells by pancreatic intraductal injection, and during the progression of autoimmune diabetes in the non-obese diabetic (NOD) mouse model. We find that inflammatory cytokine insults stimulate epithelial-to-mesenchymal transition (EMT) as well as the endocrine program in human pancreatic ductal cells via STAT3-dependent NGN3 activation. Furthermore, we show that inflammatory cytokines activate ductal-to-endocrine cell reprogramming in vivo independent of hyperglycemic stress. Together, our findings provide evidence that inflammatory cytokines direct ductal-to-endocrine cell differentiation, with implications for beta cell regeneration. PMID:27068459

  13. International Symposium on Services for Young Disabled Children, Their Parents, and Families. Proceedings: Discussions and Implications for Future Activities (Washington, D.C., December 6-11, 1981).

    ERIC Educational Resources Information Center

    Research Assessment Management, Inc., Silver Spring, MD.

    The document reports on a symposium, sponsored by UNESCO (United Nations Educational, Cultural and Scientific Organization), designed to develop strategies for improving educational, health, and social service to handicapped children and their families, particularly in developing nations. Section 1 is an overview of the background and organization…

  14. Individuals with a family history of ESRD are a high-risk population for CKD: implications for targeted surveillance and intervention activities.

    PubMed

    McClellan, William M; Satko, Scott G; Gladstone, Elisa; Krisher, Jenna O; Narva, Andrew S; Freedman, Barry I

    2009-03-01

    Activities intended to improve the detection, treatment, and control of chronic kidney disease (CKD) should be incorporated into existing health care systems and targeted to high-risk populations to avoid redundancy and waste of resources. One high-risk population consists of first- or second-degree family members of patients with end-stage renal disease (ESRD), who are 2 to 3 times as likely to have incident ESRD, have high rates of impaired kidney function and undetected and uncontrolled high blood pressure, and are more likely to be obese. These individuals usually are unaware of their underlying CKD and may discount their own risk of ESRD. The ESRD Network 6 Family History Project shows that the ESRD Networks, which constitute a national CKD surveillance system for patients with stage 5 CKD, may be an existing resource that can be used to identify relatives of incident patients with ESRD and provide these families with information about CKD. Nationally available resources have been developed by the National Kidney Disease Education Program for use with these at-risk families. Individuals interested in population-based CKD control activities should be aware of and use these resources. PMID:19231753

  15. The New Welfare Law and Vulnerable Families: Implications for Child Welfare/Child Protection Systems. Children and Welfare Reform Issue Brief 3.

    ERIC Educational Resources Information Center

    Knitzer, Jane; Bernard, Stanley

    This report examines the potential impact of federal welfare legislation, Public Law 104-193, The Personal Responsibility and Work Opportunity Reconciliation Act, on vulnerable families already in or at risk of entering the child welfare/child protection systems. The report includes an overview of the challenges states face; questions for state…

  16. An Exploratory Study of the Relationship of Family Support and Coping with Adjustment: Implications for College Students with a Chronic Illness

    ERIC Educational Resources Information Center

    Wodka, Ericka L.; Barakat, Lamia P.

    2007-01-01

    To examine the role of family support and coping in the adjustment of adolescents with chronic illness (CI) transitioning into college, college freshmen and sophomores (N[subscript chronic illness] = 32, N[subscript primarily negative life event] = 53, N[subscript primarily positive life event] = 16) were administered standard measures. CI group…

  17. Visual Impairment in Young Children: A Review of the Literature with Implications for Working with Families of Diverse Cultural and Linguistic Backgrounds. Technical Report.

    ERIC Educational Resources Information Center

    Chen, Deborah

    This report identifies key issues for providing early childhood special education services to young children who are visually impaired and for working with families of culturally and linguistically diverse backgrounds. First, it discusses the incidence of visual impairment and associated disabilities among young children, the process of early…

  18. Fathers' and Mothers' Home Literacy Involvement and Children's Cognitive and Social Emotional Development: Implications for Family Literacy Programs

    ERIC Educational Resources Information Center

    Baker, Claire E.

    2013-01-01

    The relations between fathers' and mothers' home literacy involvement at 24 months and children's cognitive and social emotional development in preschool were examined using a large sample of African American and Caucasian families ("N" = 5190) from the Early Childhood Longitudinal Study-Birth Cohort (ECLS-B). Hierarchical…

  19. Child Abuse Screening: Implications of the Limited Predictive Power of Abuse Discriminants from a Controlled Family Study of Pediatric Social Illness.

    ERIC Educational Resources Information Center

    Daniel, Jessica H.; And Others

    The predictive value of a child abuse screening instrument on unselected populations is illustrated for varying hypothesized levels of child abuse prevalence to demonstrate outcome of a hypothetical national screening program. At any level of application, the prediction of false positives (nonabusing families labeled as abusing or potentially…

  20. Proteomic-Based Approaches for the Study of Cytokines in Lung Cancer

    PubMed Central

    Marrugal, Ángela; Ojeda, Laura; Paz-Ares, Luis

    2016-01-01

    Proteomic techniques are currently used to understand the biology of different human diseases, including studies of the cell signaling pathways implicated in cancer progression, which is important in knowing the roles of different proteins in tumor development. Due to its poor prognosis, proteomic approaches are focused on the identification of new biomarkers for the early diagnosis, prognosis, and targeted treatment of lung cancer. Cytokines are proteins involved in inflammatory processes and have been proposed as lung cancer biomarkers and therapeutic targets because it has been reported that some cytokines play important roles in tumor development, invasion, and metastasis. In this review, we aim to summarize the different proteomic techniques used to discover new lung cancer biomarkers and therapeutic targets. Several cytokines have been identified as important players in lung cancer using these techniques. We underline the most important cytokines that are useful as biomarkers and therapeutic targets. We also summarize some of the therapeutic strategies targeted for these cytokines in lung cancer. PMID:27445423

  1. Proinflammatory cytokines and HIV-1 synergistically enhance CXCL10 expression in human astrocytes.

    PubMed

    Williams, Rachel; Dhillon, Navneet K; Hegde, Sonia T; Yao, Honghong; Peng, Fuwang; Callen, Shannon; Chebloune, Yahia; Davis, Randall L; Buch, Shilpa J

    2009-05-01

    HIV encephalitis (HIVE), the pathologic correlate of HIV-associated dementia (HAD) is characterized by astrogliosis, cytokine/chemokine dysregulation, and neuronal degeneration. Increasing evidence suggests that inflammation is actively involved in the pathogenesis of HAD. In fact, the severity of HAD/HIVE correlates more closely with the presence of activated glial cells than with the presence and amount of HIV-infected cells in the brain. Astrocytes, the most numerous cell type within the brain, provide an important reservoir for the generation of inflammatory mediators, including interferon-gamma inducible peptide-10 (CXCL10), a neurotoxin and a chemoattractant, implicated in the pathophysiology of HAD. Additionally, the proinflammatory cytokines, IFN-gamma and TNF-alpha, are also markedly increased in CNS tissues during HIV-1 infection. In this study, we hypothesized that the interplay of host cytokines and HIV-1 could lead to enhanced expression of the toxic chemokine, CXCL10. Our findings demonstrate a synergistic induction of CXCL10 mRNA and protein in human astrocytes exposed to HIV-1 and the proinflammatory cytokines. Signaling molecules, including JAK, STATs, MAPK (via activation of Erk1/2, AKT, and p38), and NF-kappaB were identified as instrumental in the synergistic induction of CXCL10. Understanding the mechanisms involved in HIV-1 and cytokine-mediated up-regulation of CXCL10 could aid in the development of therapeutic modalities for HAD. PMID:18985732

  2. Expression patterns of Brassica napus genes implicate IPT, CKX, sucrose transporter, cell wall invertase, and amino acid permease gene family members in leaf, flower, silique, and seed development.

    PubMed

    Song, Jiancheng; Jiang, Lijun; Jameson, Paula Elizabeth

    2015-08-01

    Forage brassica (Brassica napus cv. Greenland) is bred for vegetative growth and biomass production, while its seed yield remains to be improved for seed producers without affecting forage yield and quality. Cytokinins affect seed yield by influencing flower, silique and seed number, and seed size. To identify specific cytokinin gene family members as targets for breeding, as well as genes associated with yield and/or quality, a B. napus transcriptome was obtained from a mixed sample including leaves, flower buds and siliques of various stages. Gene families for cytokinin biosynthesis (BnIPT1, 2, 3, 5, 7, 8 and 9), cytokinin degradation (BnCKX1 to BnCKX7), cell wall invertase (BnCWINV1 to BnCWINV6), sugar transporter (BnSUT1 to BnSUT6) and amino acid permease (BnAAP1 to BnAAP8) were identified. As B. napus is tetraploid, homoeologues of each gene family member were sought. Using multiple alignments and phylogenetic analysis, the parental genomes of the two B. napus homoeologues could be differentiated. RT-qPCR was then used to determine the expression of gene family members and their homoeologues in leaves, flowers, siliques and seeds of different developmental stages. The expression analysis showed both temporal and organ-specific expression profiles among members of these multi-gene families. Several pairs of homoeologues showed differential expression, both in terms of level of expression and differences in temporal or organ-specificity. BnCKX2 and 4 were identified as targets for TILLING, EcoTILLING and MAS. PMID:25873685

  3. Longitudinal Study of Cytokine Expression, Lipid Profile and Neuronal Growth Factors in Human Breast Milk from Term and Preterm Deliveries

    PubMed Central

    Collado, Maria Carmen; Santaella, Marina; Mira-Pascual, Laia; Martínez-Arias, Elena; Khodayar-Pardo, Parisá; Ros, Gaspar; Martínez-Costa, Cecilia

    2015-01-01

    Breast milk (BM) is considered as a reference for infant nutrition. The role of bioactive components, such as cytokines, hormones, growth factors (GFs) and fatty acids (FAs) is poorly known, but they might be implicated in immune response development. The aim of this study was to identify the lipid profile and the spectrum of cytokines and neuronal GF in BM samples and analyse the influence of gestational age and lactation time on these components. This study used a longitudinal prospective method for the characterization of cytokines, FAs and GFs global profiles in 120 BM samples from 40 healthy mothers (20 preterm and 20 term) collected as colostrum, transitional and mature milk. The cytokines were analysed by protein array (Ray Bio® Human Cytokine Array G6. Ray Biotech, Inc. Norcross, GA, USA) and the FAs were analysed by gas chromatography. The FA profile was similar between the term and the preterm BM samples. Omega-3-α-linoleic and docosahexaenoic acid (DHA) and omega-6-linoleic acid were the most abundant in the term and preterm samples during lactation. Omega-3 ETA and omega-3 EPA we observed exclusively in the preterm samples. The cytokine profile showed a different trend based on gestational age. A significantly higher expression of neurotrophic factors was found in the mature preterm milk samples as compared to the mature term samples. Our study is the first to identify the influence and interactions of perinatal factors on cytokine, GFs and FAs in human milk. PMID:26492267

  4. Longitudinal Study of Cytokine Expression, Lipid Profile and Neuronal Growth Factors in Human Breast Milk from Term and Preterm Deliveries.

    PubMed

    Collado, Maria Carmen; Santaella, Marina; Mira-Pascual, Laia; Martínez-Arias, Elena; Khodayar-Pardo, Parisá; Ros, Gaspar; Martínez-Costa, Cecilia

    2015-10-01

    Breast milk (BM) is considered as a reference for infant nutrition. The role of bioactive components, such as cytokines, hormones, growth factors (GFs) and fatty acids (FAs) is poorly known, but they might be implicated in immune response development. The aim of this study was to identify the lipid profile and the spectrum of cytokines and neuronal GF in BM samples and analyse the influence of gestational age and lactation time on these components. This study used a longitudinal prospective method for the characterization of cytokines, FAs and GFs global profiles in 120 BM samples from 40 healthy mothers (20 preterm and 20 term) collected as colostrum, transitional and mature milk. The cytokines were analysed by protein array (Ray Bio® Human Cytokine Array G6. Ray Biotech, Inc. Norcross, GA, USA) and the FAs were analysed by gas chromatography. The FA profile was similar between the term and the preterm BM samples. Omega-3-α-linoleic and docosahexaenoic acid (DHA) and omega-6-linoleic acid were the most abundant in the term and preterm samples during lactation. Omega-3 ETA and omega-3 EPA we observed exclusively in the preterm samples. The cytokine profile showed a different trend based on gestational age. A significantly higher expression of neurotrophic factors was found in the mature preterm milk samples as compared to the mature term samples. Our study is the first to identify the influence and interactions of perinatal factors on cytokine, GFs and FAs in human milk. PMID:26492267

  5. ANTIBODY-CYTOKINE FUSION PROTEINS FOR TREATMENT OF CANCER: ENGINEERING CYTOKINES FOR IMPROVED EFFICACY AND SAFETY

    PubMed Central

    Young, Patricia A.; Morrison, Sherie L.; Timmerman, John M.

    2014-01-01

    The true potential of cytokine therapies in cancer treatment is limited by the inability to deliver optimal concentrations into tumor sites due to dose-limiting systemic toxicities. To maximize the efficacy of cytokine therapy, recombinant antibody-cytokine fusion proteins have been constructed by a number of groups to harness the tumor-targeting ability of monoclonal antibodies. The aim is to guide cytokines specifically to tumor sites where they might stimulate more optimal anti-tumor immune responses while avoiding the systemic toxicities of free cytokine therapy. Antibody-cytokine fusion proteins containing IL-2, IL-12, IL-21, TNFα, and interferons α, β and γ have been constructed and have shown anti-tumor activity in pre-clinical and early phase clinical studies. Future priorities for development of this technology include optimization of tumor targeting, bioactivity of the fused cytokine, and choice of appropriate agents for combination therapies. This review is intended to serve as a framework for engineering an ideal antibody-cytokine fusion protein, focusing on previously developed constructs and their clinical trial results. PMID:25440607

  6. Inmate family functioning.

    PubMed

    Klein, Shirley R; Bartholomew, Geannina S; Hibbert, Jeff

    2002-02-01

    Two-hundred-nine noninmates and 169 inmates completed questionnaires that assessed retrospective perceptions of 12 dimensions of family life and one overall assessment of quality of family life. Between the inmates and noninmates, means for all dependent variables differed significantly except for self-reliance; however, meaningful eta-squares were found only for dimensions of bridging, disengagement, and quality of life. Among the independent-samples t tests for gender, eta-squares were not meaningful. Implications for family life interventions in correctional facilities are suggested. PMID:12112992

  7. HMGB1: The Central Cytokine for All Lymphoid Cells

    PubMed Central

    Li, Guanqiao; Liang, Xiaoyan; Lotze, Michael T.

    2013-01-01

    High-mobility group box 1 (HMGB1) is a leaderless cytokine, like the IL-1 and FGF family members, that has primary roles within the nucleus and the cytosol. Within the nucleus, it serves as another guardian of the genome, protecting it from oxidant injury and promoting access to transcriptional complexes such as nuclear hormone/nuclear hormone receptors and p53/p73 complexes. Within the cytosol it promotes autophagy and recruitment of the myddosome to Toll-like receptor (TLR) 9 vesicular compartments. Outside of the cell, it can either bind to specific receptors itself, or with high affinity to DNA, nucleosomes, IL-1β, lipopolysaccharide, and lipoteichoic acid to mediate responses in specific physiological or pathological conditions. Currently identified receptors include TLR2, TLR4, the receptor for advanced glycation end products, CD24-Siglec G/10, chemokine CXC receptor 4, and TIM-3. In terms of its effects or functions within lymphoid cells, HMGB1 is principally secreted from mature dendritic cells (DCs) to promote T-cell and B-cell reactivity and expansion and from activated natural killer cells to promote DC maturation during the afferent immune response. Some studies suggest that its primary role in the setting of chronic inflammation is to promote immunosuppression. As such, HMGB1 is a central cytokine for all lymphoid cells playing a role complementary to its better studied role in myeloid cells. PMID:23519706

  8. Interleukin-18 Increases TLR4 and Mannose Receptor Expression and Modulates Cytokine Production in Human Monocytes

    PubMed Central

    Dias-Melicio, Luciane Alarcão; Fernandes, Reginaldo Keller; Rodrigues, Daniela Ramos; Golim, Marjorie Assis; Soares, Angela Maria Victoriano Campos

    2015-01-01

    Interleukin-18 is a proinflammatory cytokine belonging to the interleukin-1 family of cytokines. This cytokine exerts many unique biological and immunological effects. To explore the role of IL-18 in inflammatory innate immune responses, we investigated its impact on expression of two toll-like receptors (TLR2 and TLR4) and mannose receptor (MR) by human peripheral blood monocytes and its effect on TNF-α, IL-12, IL-15, and IL-10 production. Monocytes from healthy donors were stimulated or not with IL-18 for 18 h, and then the TLR2, TLR4, and MR expression and intracellular TNF-α, IL-12, and IL-10 production were assessed by flow cytometry and the levels of TNF-α, IL-12, IL-15, and IL-10 in culture supernatants were measured by ELISA. IL-18 treatment was able to increase TLR4 and MR expression by monocytes. The production of TNF-α and IL-10 was also increased by cytokine treatment. However, IL-18 was unable to induce neither IL-12 nor IL-15 production by these cells. Taken together, these results show an important role of IL-18 on the early phase of inflammatory response by promoting the expression of some pattern recognition receptors (PRRs) that are important during the microbe recognition phase and by inducing some important cytokines such as TNF-α and IL-10. PMID:25873755

  9. Discovering Family Concerns, Priorities, and Resources: Sensitive Family Information Gathering.

    ERIC Educational Resources Information Center

    Banks, Ronald A.; Santos, Rosa Milagros; Roof, Virginia

    2003-01-01

    This article provides an overview of the family information gathering process in early intervention and the effect of cultural and linguistic diversity on family information gathering. Practical strategies that early intervention providers can use in interviews, surveys, and observations are discussed, as well as implications for personnel…

  10. Treatment of Cancer Pain by Targeting Cytokines

    PubMed Central

    Vendrell, I.; Macedo, D.; Alho, I.; Dionísio, M. R.; Costa, L.

    2015-01-01

    Inflammation is one of the most important causes of the majority of cancer symptoms, including pain, fatigue, cachexia, and anorexia. Cancer pain affects 17 million people worldwide and can be caused by different mediators which act in primary efferent neurons directly or indirectly. Cytokines can be aberrantly produced by cancer and immune system cells and are of particular relevance in pain. Currently, there are very few strategies to control the release of cytokines that seems to be related to cancer pain. Nevertheless, in some cases, targeted drugs are available and in use for other diseases. In this paper, we aim to review the importance of cytokines in cancer pain and targeted strategies that can have an impact on controlling this symptom. PMID:26538839

  11. The family and schizophrenia.

    PubMed

    Wuerker, A K

    2000-01-01

    There has been controversy about the role of family in the etiology and course of schizophrenia for almost 70 years. Psychoanalysts and family therapists have proposed theories about the development of schizophrenia that overtly blamed parents, and recently, expressed emotion (EE) research has been criticized as implicating families once again. However, the study of schizophrenia as a brain disorder has resulted in new understandings of the influence of the family. This article reviews recent research revealing a unique vulnerability to stress in persons with schizophrenia and suggesting that communication difficulties may be due to a shared genetic heritage. Advanced practice mental health nurses who have a solid foundation in neurobiology are ideally suited to help the person with schizophrenia and his or her family. Knowledge about the neurobiological basis of schizophrenia has become very sophisticated and complex, but that knowledge is nevertheless essential to understand the otherwise puzzling patterns of behavior shown by persons with schizophrenia. PMID:10839056

  12. Transition from the Lactational Amenorrhea Method to other modern family planning methods in rural Bangladesh: barrier analysis and implications for behavior change communication program intervention design.

    PubMed

    Kouyaté, Robin Anthony; Ahmed, Salahuddin; Haver, Jaime; McKaig, Catharine; Akter, Nargis; Nash-Mercado, Angela; Baqui, Abdullah

    2015-06-01

    The timely transition from Lactational Amenorrhea Method (LAM)(2) to another modern family planning method contributes to healthy spacing of pregnancies by increasing the adoption of family planning during the first year postpartum. Yet, literature suggests challenges in completing a timely LAM transition. To guide program implementation in Bangladesh, this study identified factors influencing women's transition decisions. Eighty postpartum women, comprising 40 who transitioned from LAM(3) and 40 who did not,(4) participated. Half of each group participated in in-depth interviews to explore the decision-making process. All participants responded to a "Barrier Analysis" questionnaire to identify differences in eight behavioral determinants. More than half of transitioners switched to another modern method before or within the same month that LAM ended. Of the 18 transitioners who delayed,(5) 15 waited for menses to return. For non-transitioners, key barriers included waiting for menses to return, misconceptions on return to fertility, and perceived lack of familial support. The LAM transition can help women prevent unintended pregnancy during the first year postpartum. Increased emphasis on counseling women about the risk of pregnancy, and misconceptions about personal fertility patterns are critical for facilitating the transition. Strategies should also include interventions that train health workers and improve social support. PMID:25710895

  13. Health Insurance Coverage and Use of Family Planning Services among Current and Former Foster Youth: Implications of the Health Care Reform Law

    PubMed Central

    Dworsky, Amy; Ahrens, Kym; Courtney, Mark

    2013-01-01

    This research uses data from a longitudinal study to examine how two provisions in the Patient Protection and Affordable Care Act could affect health insurance coverage among young women who have aged out of foster care. It also explores how allowing young people to remain in foster care until age twenty-one affects their health insurance coverage, use of family planning services, and information about birth control. We find that young women are more likely to have health insurance if they remain in foster care until their twenty-first birthday and that having health insurance is associated with an increase in the likelihood of receiving family planning services. Our results also suggest that many young women who would otherwise lack health insurance after aging out of foster care will be eligible for Medicaid under the health care reform law. Because having health insurance is associated with use of family planning services, this increase in Medicaid eligibility may result in fewer unintended pregnancies among this high-risk population. PMID:23262773

  14. Health insurance coverage and use of family planning services among current and former foster youth: implications of the health care reform law.

    PubMed

    Dworsky, Amy; Ahrens, Kym; Courtney, Mark

    2013-04-01

    This research uses data from a longitudinal study to examine how two provisions in the Patient Protection and Affordable Care Act could affect health insurance coverage among young women who have aged out of foster care. It also explores how allowing young people to remain in foster care until age twenty-one affects their health insurance coverage, use of family planning services, and information about birth control. We find that young women are more likely to have health insurance if they remain in foster care until their twenty-first birthday and that having health insurance is associated with an increase in the likelihood of receiving family planning services. Our results also suggest that many young women who would otherwise lack health insurance after aging out of foster care will be eligible for Medicaid under the health care reform law. Because having health insurance is associated with use of family planning services, this increase in Medicaid eligibility may result in fewer unintended pregnancies among this high-risk population. PMID:23262773

  15. Cytokine-induced tumor suppressors: a GRIM story

    PubMed Central

    Kalvakolanu, Dhan V; Nallar, Shreeram C; Kalakonda, Sudhakar

    2010-01-01

    Cytokines belonging to the IFN family are potent growth suppressors. In a number of clinical and preclinical studies, vitamin A and its derivatives like retinoic acid (RA) have been shown to exert synergistic growth-suppressive effects on several tumor cells. We have employed a genome-wide expression-knockout approach to identify the genes critical for IFN/RA-induced growth suppression. A number of novel Genes associated with Retinoid-Interferon-induced Mortality (GRIM) were isolated. In this review, we will describe the molecular mechanisms of actions of one GRIM-19 which participates in multiple pathways for exerting growth control and/or cell death. This protein is emerging as a new tumor suppressor. In addition, GRIM-19 appears to participate in innate immune responses as its activity is modulated by several viruses and bacteria. Thus, GRIMs seem to couple with multiple biological responses by acting at critical nodes. PMID:20382543

  16. Germ-line transmission of trisomy 21: Data from 80 families suggest an implication of grandmaternal age and a high frequency of female-specific trisomy rescue

    PubMed Central

    2010-01-01

    Background Trisomy of chromosome 21 (T21; Down syndrome, DS) is the most common aneuploidy in live births. Though its etiology has been intensively studied for a half of century, there are surprisingly many problems awaiting their elucidation. Some of the open questions are related directly to germ line mosaicism for T21, other problems include the prevalence of males with non-mosaic trisomy over females (skewed sex ratio, SR), the genetic predisposition to non-disjunction, etc. Studies in families of gonadal mosaicism (GM) carriers might help resolving some of these problems. Results 80 families of carriers of GM, in which the sex of the offspring had been specified, were identified in the literature and in logbooks of two local genetic units. Mothers in these families were relatively young: only 8% of mothers were 35 years old and older at the time of delivery of their first affected offspring while the proportion of grandmothers on the GM carrier's side aged 35 years old and older was significantly higher (39%). Postzygotic rescue of T21 due to error in the meiosis I had been proposed as a mechanism of parental GM formation in 78% of the families with known origin of the T21. For the other 22%, rescue of errors in the meiosis II or postzygotic mitotic non-disjunction was assumed. Mosaicism for T21 in successive generations was reported in at least 12 families. The proportion of mosaics among affected female offspring (14%) is significantly higher compared to that among affected male offspring (0%). Male preponderance (SR = 1.5) is found in non mosaic liveborn offspring with either maternally- or paternally transmitted T21. Among unaffected offspring of male carriers of GM there is a notable excess of females (SR = 0.27). Conclusion Both direct (results of cytogenetic and molecular study of the origin of trisomic line) and indirect (advanced grandmaternal age on the side of GM carrier) evidences allow to assume that significant proportion of the mosaic parents

  17. Cytokine Reduction in the Treatment of Joint Conditions

    PubMed Central

    Martel-Pelletier, J.; Otterness, I. G.; Pelletier, J.-P.

    1994-01-01

    The destruction of joints caused by rheumatoid arthritis and osteoarthritis is characterized by an imbalance of enzyme catalysed cartilage breakdown and regeneration. A complex cytokine network perpetuates joint conditions by direct regulation of metalloproteases, by indirect recruitment of cells that secrete degradative enzymes, and by inhibition of reparative processes. The destructive action of cytokines such as interleukin-1, interleukin-6 and tumour necrosis factor-α can be modulated at multiple points associated either with cytokine production or with cytokine action. Potential agents for cytokine reduction include selective anti-cytokine antibodies, anticytokine receptor antibodies, cytokine receptor antagonist proteins, and soluble and chimeric cytokine receptor molecules. Pharmacologic regulation of IL-1 and TNFα remain primary targets for treatment of arthritis, and results of early clinical trials are promising. However, the results of long-term clinical trials will be required to support the value of anti-cytokine therapy in treatment of arthritis. PMID:18472950

  18. Time budgets of Snow Geese Chen caerulescens and Ross's Geese Chen rossii in mixed flocks: Implications of body size, ambient temperature and family associations

    USGS Publications Warehouse

    Jonsson, J.E.; Afton, A.D.

    2009-01-01

    Body size affects foraging and forage intake rates directly via energetic processes and indirectly through interactions with social status and social behaviour. Ambient temperature has a relatively greater effect on the energetics of smaller species, which also generally are more vulnerable to predator attacks than are larger species. We examined variability in an index of intake rates and an index of alertness in Lesser Snow Geese Chen caerulescens caerulescens and Ross's Geese Chen rossii wintering in southwest Louisiana. Specifically we examined variation in these response variables that could be attributed to species, age, family size and ambient temperature. We hypothesized that the smaller Ross's Geese would spend relatively more time feeding, exhibit relatively higher peck rates, spend more time alert or raise their heads up from feeding more frequently, and would respond to declining temperatures by increasing their proportion of time spent feeding. As predicted, we found that Ross's Geese spent more time feeding than did Snow Geese and had slightly higher peck rates than Snow Geese in one of two winters. Ross's Geese spent more time alert than did Snow Geese in one winter, but alert rates differed by family size, independent of species, in contrast to our prediction. In one winter, time spent foraging and walking was inversely related to average daily temperature, but both varied independently of species. Effects of age and family size on time budgets were generally independent of species and in accordance with previous studies. We conclude that body size is a key variable influencing time spent feeding in Ross's Geese, which may require a high time spent feeding at the expense of other activities. ?? 2008 The Authors.

  19. Extremely low penetrance of deafness associated with the mitochondrial 12S rRNA mutation in 16 Chinese families: Implication for early detection and prevention of deafness

    SciTech Connect

    Dai Pu; Liu Xin; Han Dongyi . E-mail: hdy301@263.net; Qian Yaping; Huang Deliang; Yuan Huijun; Li Weiming; Yu Fei; Zhang Ruining; Lin Hongyan; He Yong; Yu Youjun; Sun Quanzhu; Qin Huaiyi; Li Ronghua; Zhang Xin; Kang Dongyang; Cao Juyang; Young Wieyen . E-mail: ywy301@163.net; Guan Minxin |. E-mail: min-xin.guan@cchmc.org

    2006-02-03

    Mutations in mitochondrial DNA (mtDNA) have been found to be associated with sensorineural hearing loss. We report here the clinical, genetic, and molecular characterization of 16 Chinese pedigrees (a total of 246 matrilineal relatives) with aminoglycoside-induced impairment. Clinical evaluation revealed the variable phenotype of hearing impairment including audiometric configuration in these subjects, although these subjects share some common features: being bilateral and sensorineural hearing impairment. Strikingly, these Chinese pedigrees exhibited extremely low penetrance of hearing loss, ranging from 4% to 18%, with an average of 8%. In particular, nineteen of 246 matrilineal relatives in these pedigrees had aminoglycoside-induced hearing loss. Mutational analysis of the mtDNA in these pedigrees showed the presence of homoplasmic 12S rRNA A1555G mutation, which has been associated with hearing impairment in many families worldwide. The extremely low penetrance of hearing loss in these Chinese families carrying the A1555G mutation strongly supports the notion that the A1555G mutation itself is not sufficient to produce the clinical phenotype. Children carrying the A1555G mutation are susceptible to the exposure of aminoglycosides, thereby inducing or worsening hearing impairment, as in the case of these Chinese families. Using those genetic and molecular approaches, we are able to diagnose whether children carry the ototoxic mtDNA mutation. Therefore, these data have been providing valuable information and technology to predict which individuals are at risk for ototoxicity, to improve the safety of aminoglycoside therapy, and eventually to decrease the incidence of deafness.

  20. Sequencing of candidate genes in Dominican families implicates both rare exonic and common non-exonic variants for carotid intima-media thickness at bifurcation.

    PubMed

    Wang, Liyong; Beecham, Ashley; Dueker, Nicole; Blanton, Susan H; Rundek, Tatjana; Sacco, Ralph L

    2015-10-01

    Through linkage and tagSNP-based association studies in 100 Dominican Republic (DR) families, we previously identified ANLN and AOAH (7p14.3) as candidate genes for carotid intima-media thickness at bifurcation (bIMT). Introns, exons, and flanking regions of ANLN and AOAH were re-sequenced in 151 individuals from nine families with evidence for linkage at 7p14.3. For common variants [CV, minor allele frequency (MAF) ≥5 %], single variant-based analysis was performed. For rare variants (RV, MAF < 5 %), gene-based analysis aggregating all RVs within a gene was performed. CV analysis revealed the strongest signal at rs3815483 (P = 0.0003) in ANLN and rs60023210 (P = 0.00005) in AOAH. In ANLN, RV analysis found suggestive evidence for association with exonic RVs (P = 0.08), and in particular non-synonymous RVs (P = 0.04) but not with all RVs (P = 0.15). The variant alleles of all non-synonymous RVs segregated with the major allele of rs3815483 and were associated with lower bIMT while a novel synonymous RV segregated with the minor allele of rs3815483 and was associated with greater bIMT. Additional analysis in 561 DR individuals found suggestive evidence for association with all ANLN non-synonymous RVs (P = 0.08). In AOAH, no evidence for association with RVs was detected. Instead, conditional analysis revealed that multiple independent intronic CVs are associated with bIMT in addition to rs60023210. We demonstrate the utility of using family-based studies to evaluate the contribution of RVs. Our data suggest two modes of genetic architecture underlying the linkage and association at ANLN (multiple exonic RVs) and AOAH (multiple intronic CVs with uncharacterized functions). PMID:26319989

  1. Toward an assessment of the social role of rural midwives and its implication for the family planning program: an Iranian case study.

    PubMed

    Beeman, W O; Bhattacharyya, A K

    1978-01-01

    An axiom of family planning programming is the importance of culturally-appropriate communicators and motivators. Traditional midwives seem ideal for this task but few studies have been done to verify this assumption by analyzing the midwife's social role as perceived by the community. 325 married women and 81 unmarried girls from a "model village" near Shiraz were interviewed by female undergraduates. 82.5% of the women are of childbearing age; 66% married before 14 years; 33% use contraception, mostly the pill, but most want large families because they expect high child mortality rates. Most of the older women are able to assist in childbirth but none, except the village's one recognized midwife, who is considered to have divine backing, will do so except in an emergency. The midwife's activities cause her to be held in low esteem by the community because 1) she has contact with a woman's sexual parts and this fact is public; 2) she has contact with vaginal excretia which are, in Islam, polluting; and 3) she is paid for her services, which labels her as a woman "without shame". The midwife is, however, widely used since women and their husbands fear the trip to the hospital and treatment by a male doctor much more than a midwife-supervised birth. The midwife in the study village had been there only 2 years and feels that she is not fully trusted. She is not consulted on birth control at all, because women expect the pill to be dispensed by doctors and consider other methods as a matter strictly between husband and wife. The midwife's role seems to complement that of the government health authorities rather than compete. The midwife's low status and circumscribed sphere of activity, the weak respect in which her advice is held and the pattern of having only 1 recognized midwife in a village at a time make the midwife a poor agent for family planning services. Her effectiveness as an agent of social change could be improved by training her in hygienic practices of

  2. Th1, Th2 and Treg/T17 cytokines in two types of proliferative glomerulonephritis.

    PubMed

    Stangou, M; Bantis, C; Skoularopoulou, M; Korelidou, L; Kouloukouriotou, D; Scina, M; Labropoulou, I T; Kouri, N M; Papagianni, A; Efstratiadis, G

    2016-01-01

    IgA nephropathy (IgAN) and focal segmental necrotizing glomerulonephritis (FSNGN) are characterized by proliferation of native glomerular cells and infiltration by inflammatory cells. Several cytokines act as mediators of kidney damage in both diseases. The aim of the present study was to investigate the role of Th1, Th2 and Treg/T17 cytokines in these types of proliferative glomerulonephritis. Simultaneous measurement of Th1 interleukin (IL-2, IL-12, tumor necrosis factor-alpha [TNF-α], interferon-gamma [INF-γ]), Th2 (IL-4, IL-5, IL-6, IL-10, IL-13), Treg/T17 transforming growth factor-beta 1 (TGF-β1, granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-17) cytokines and C-C chemokines Monocyte chemoattractant protein-1 (MCP-1, macrophage inflammatory protein-1 [MIP-1] β) was performed in first-morning urine samples, at the day of renal biopsy, using a multiplex cytokine assay. Cytokine concentrations were correlated with histological findings and renal function outcome. Urinary excretion of Th1, Th2 and Treg/Th17 cytokines were significantly higher in FSNGN compared to IgAN patients. In IgAN patients (n = 50, M/F: 36/14, M age: 40.7 [17-67] years), Th1, Th2 and T17 cytokines correlated significantly with the presence of endocapillary proliferation, while in FSNGN patients (n = 40, M/F: 24/16, M age: 56.5 [25-80] years), MCP-1 and TGF-β1 had a positive correlation with severe extracapillary proliferation (P = 0.001 and P = 0.002, respectively). Urinary IL-17 was the only independent parameter associated with endocapillary proliferation in IgAN and with MCP-1 urinary excretion in FSNGN. Response to treatment was mainly predicted by IL-6 in IgAN, and by Th2 (IL-4, IL-6), Treg (GM-CSF) cytokines and MIP-1 β in FSNGN. Th1, Th2 and T17 cytokines were directly implicated in renal pathology in IgAN and possibly through MCP-1 production in FSNGN. IL-17 and IL-6 seem to have a central role in inflammation and progression of kidney injury. PMID:27194829

  3. Th1, Th2 and Treg/T17 cytokines in two types of proliferative glomerulonephritis

    PubMed Central

    Stangou, M.; Bantis, C.; Skoularopoulou, M.; Korelidou, L.; Kouloukouriotou, D.; Scina, M.; Labropoulou, I. T.; Kouri, N. M.; Papagianni, A.; Efstratiadis, G.

    2016-01-01

    IgA nephropathy (IgAN) and focal segmental necrotizing glomerulonephritis (FSNGN) are characterized by proliferation of native glomerular cells and infiltration by inflammatory cells. Several cytokines act as mediators of kidney damage in both diseases. The aim of the present study was to investigate the role of Th1, Th2 and Treg/T17 cytokines in these types of proliferative glomerulonephritis. Simultaneous measurement of Th1 interleukin (IL-2, IL-12, tumor necrosis factor-alpha [TNF-α], interferon-gamma [INF-γ]), Th2 (IL-4, IL-5, IL-6, IL-10, IL-13), Treg/T17 transforming growth factor-beta 1 (TGF-β1, granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-17) cytokines and C-C chemokines Monocyte chemoattractant protein-1 (MCP-1, macrophage inflammatory protein-1 [MIP-1] β) was performed in first-morning urine samples, at the day of renal biopsy, using a multiplex cytokine assay. Cytokine concentrations were correlated with histological findings and renal function outcome. Urinary excretion of Th1, Th2 and Treg/Th17 cytokines were significantly higher in FSNGN compared to IgAN patients. In IgAN patients (n = 50, M/F: 36/14, M age: 40.7 [17–67] years), Th1, Th2 and T17 cytokines correlated significantly with the presence of endocapillary proliferation, while in FSNGN patients (n = 40, M/F: 24/16, M age: 56.5 [25–80] years), MCP-1 and TGF-β1 had a positive correlation with severe extracapillary proliferation (P = 0.001 and P = 0.002, respectively). Urinary IL-17 was the only independent parameter associated with endocapillary proliferation in IgAN and with MCP-1 urinary excretion in FSNGN. Response to treatment was mainly predicted by IL-6 in IgAN, and by Th2 (IL-4, IL-6), Treg (GM-CSF) cytokines and MIP-1 β in FSNGN. Th1, Th2 and T17 cytokines were directly implicated in renal pathology in IgAN and possibly through MCP-1 production in FSNGN. IL-17 and IL-6 seem to have a central role in inflammation and progression of kidney injury. PMID:27194829

  4. Ndfip-mediated degradation of Jak1 tunes cytokine signalling to limit expansion of CD4+ effector T cells

    PubMed Central

    O'Leary, Claire E.; Riling, Christopher R.; Spruce, Lynn A.; Ding, Hua; Kumar, Suresh; Deng, Guoping; Liu, Yuhong; Seeholzer, Steven H.; Oliver, Paula M.

    2016-01-01

    Nedd4 family E3 ubiquitin ligases have been shown to restrict T-cell function and impact T-cell differentiation. We show here that Ndfip1 and Ndfip2, activators of Nedd4 family ligases, together limit accumulation and function of effector CD4+ T cells. Using a three-part proteomics approach in primary T cells, we identify stabilization of Jak1 in Ndfip1/2-deficient T cells stimulated through the TCR. Jak1 degradation is aborted in activated T cells that lack Ndfips. In wild-type cells, Jak1 degradation lessens CD4+ cell sensitivity to cytokines during TCR stimulation, while in Ndfip-deficient cells cytokine responsiveness persists, promoting increased expansion and survival of pathogenic effector T cells. Thus, Ndfip1/Ndfip2 regulate the cross talk between the T-cell receptor and cytokine signalling pathways to limit inappropriate T-cell responses. PMID:27088444

  5. In vitro cytokine responses of peripheral blood mononuclear cells from healthy dogs to distemper virus, Malassezia and Toxocara.

    PubMed

    Valli, J L; Williamson, A; Sharif, S; Rice, J; Shewen, P E

    2010-04-15

    Naïve CD4+ T cells may differentiate into a number of subsets including T helper 1 (Th1) Th2, Th3, Th17 and T regulatory (Treg) cells depending on the type of antigen they encounter. These CD4+ families have been defined based on the array of cytokines they produce and the effects they have on adaptive immune responses. CD4+ subsets are cross regulatory and at times cooperative. The study of these adaptive immune modulators has revealed the important role that cytokines play in mounting effective as well as detrimental immune responses to pathogens. Examining the cytokine responses of lymphocytes in culture can provide important understanding of how immune responses to pathogens are orchestrated. For this purpose the in vitro cytokine production of peripheral blood mononuclear cells (PBMC) from healthy dogs was examined in response to stimulation with antigens from a common canine virus (canine distemper virus, CDV), a commensal skin yeast of dogs (Malassezia pachydermatis) and a common canine helminth (Toxocara canis (T. canis)). Cell culture supernatants were removed from antigen stimulated and unstimulated control PBMC after 4, 24, 48 and 72 h and the concentration of Th1 type cytokines (IL-2, IFN-gamma, TNF-alpha) and Th2 type cytokines (IL-4, IL-5, IL-10) was determined using sandwich ELISA assays. CDV induced low levels of cytokine production initially with a predominance of IL-10 at 24h and a balanced response at 48 h of incubation. Malassezia antigen stimulated an early type 2 cytokine response with dramatic production of IL-4 at 24h of incubation compared to the other stimulants examined. By 48 h of incubation, however, the cytokine mix in response to Malassezia had also moved toward a Th1 type response. T. canis induced early production of Th2 type cytokines with IL-5 predominating; however, with longer incubation (48-72 h) there was a switch to a balanced Th1/Th2 response. In conclusion, the cytokines produced in vitro by canine PBMC in response to

  6. Mechanisms of Cytokine-Induced Behavioral Changes: Psychoneuroimmunology at the Translational Interface Norman Cousins Lecture

    PubMed Central

    Timmie, William P.

    2009-01-01

    Work in our laboratory has focused on the mechanisms by which cytokines can influence the brain and behavior in humans and non-human primates. Using administration of interferon (IFN)-alpha as a tool to unravel these mechanisms, we have expanded upon findings from the basic science literature implicating cytokine-induced changes in monoamine metabolism as a primary pathway to depression. More specifically, a role for serotonin metabolism has been supported by the clinical efficacy of serotonin reuptake inhibitors in blocking the development of IFN-alpha-induced depression, and the capacity of IFN-alpha to activate metabolic enzymes (indolamine 2,3 dioxygenase) and cytokine signaling pathways (p38 mitogen activated protein kinase) that can influence the synthesis and reuptake of serotonin. Our data also support a role for dopamine depletion as reflected by IFN-alpha-induced changes in behavior (psychomotor slowing and fatigue) and regional brain activity, which implicate the involvement of the basal ganglia, as well as the association of IFN-alpha-induced depressive-like behavior in rhesus monkeys with decreased cerebrospinal fluid concentrations of the dopamine metabolite, homovanillic acid. Neuroimaging data in IFN-alpha-treated patients also suggest that activation of neural circuits (dorsal anterior cingulate cortex) associated with anxiety and alarm may contribute to cytokine-induced behavioral changes. Taken together, these effects of cytokines on the brain and behavior appear to subserve competing evolutionary survival priorities that promote reduced activity to allow healing, and hypervigilance to protect against future attack. Depending on the relative balance between these behavioral accoutrements of an activated innate immune response, clinical presentations may be distinct and warrant individualized therapeutic approaches. PMID:18793712

  7. [Cytokines in the treatment of blood diseases].

    PubMed

    Robak, T

    1995-01-01

    Cytokines are a class of signal peptides which represent a major communication network in living organism. Over the last decade, the discovery, cloning and purification of hematopoietic cytokines (interleukins, hematopoietic growth factors) has increased our understanding of the regulation, proliferation, differentiation and function of hematopoietic cells. More recently, the large scale production of the recombinant forms of these molecules has enabled to treat the patients with pharmacologic doses of cytokines. The therapeutic activity of interferon-alpha (IFN-alpha) has been demonstrated in patients with chronic myeloid leukaemia and other chronic myeloproliferative syndromes. IFN-gamma is useful in the prevention of infections in patients with chronic granulomatous disease. Erythropoietin (EPO) was the first hematopoietic growth factor available for clinical use, initially to treat anaemia in renal failure patients. The next cytokines introduced into the clinic were granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF). They are used successfully in haematological malignant disorders to stimulate granulopoiesis after chemotherapy or bone marrow transplantation and to help mobilise marrow stem cells for peripheral blood stem cell transplantation. Interleukin (IL)-1, -2, -3, -4, -6 and -11 have been tested in clinical trials. However, the value of these agents remains to be established. PMID:7544526

  8. Cytokine therapeutics: lessons from interferon alpha.

    PubMed Central

    Gutterman, J U

    1994-01-01

    Cytokines are soluble proteins that allow for communication between cells and the external environment. Interferon (IFN) alpha, the first cytokine to be produced by recombinant DNA technology, has emerged as an important regulator of growth and differentiation, affecting cellular communication and signal transduction pathways as well as immunological control. This review focuses on the biological and clinical activities of the cytokine. Originally discovered as an antiviral substance, the efficacy of IFN-alpha in malignant, viral, immunological, angiogenic, inflammatory, and fibrotic diseases suggests a spectrum of interrelated pathophysiologies. The principles learned from in vivo studies will be discussed, particularly hairy cell leukemia, chronic myelogenous leukemia, certain angiogenic diseases, and hepatitis. After the surprising discovery of activity in a rare B-cell neoplasm, IFN-alpha emerged as a prototypic tumor suppressor protein that represses the clinical tumorigenic phenotype in some malignancies capable of differentiation. Regulatory agencies throughout the world have approved IFN-alpha for treatment of 13 malignant and viral disorders. The principles established with this cytokine serve as a paradigm for future development of natural proteins for human disease. PMID:8108387

  9. Cytokines as biomarkers of nanoparticle immunotoxicity

    PubMed Central

    Elsabahy, Mahmoud; Wooley, Karen L.

    2013-01-01

    Nanoscale objects, whether of biologic origin or synthetically created, are being developed into devices for a variety of bionanotechnology diagnostic and pharmaceutical applications. However, the potential immunotoxicity of these nanomaterials and mechanisms by which they may induce adverse reactions have not received sufficient attention. Nanomaterials, depending on their characteristics and compositions, can interact with the immune system in several ways and either enhance or suppress immune system function. Cytokines perform pleiotropic functions to mediate and regulate the immune response and are generally recognized as biomarkers of immunotoxicity. While the specificity and validity of certain cytokines as markers of adverse immune response has been established for chemicals, small and macromolecular drugs, research on their applicability for predicting and monitoring the immunotoxicity of engineered nanomaterials is still ongoing. The goal of this review is to provide guidelines as to important cytokines that can be utilized for evaluating the immunotoxicity of nanomaterials and to highlight the role of those cytokines in mediating adverse reactions, which is of particular importance for the clinical development of nanopharmaceuticals and other nanotechnology-based products. Importantly, the rational design of nanomaterials of low immunotoxicity will be discussed, focusing on synthetic nanodevices, with emphasis on both the nanoparticle-forming materials and the embedded cargoes. PMID:23549679

  10. CYTOKINE PROFILING FOR CHEMICAL RESPIRATORY SENSITIZERS

    EPA Science Inventory

    CYTOKINE PROFILING FOR CHEMICAL RESPIRATORY SENSITIZERS. LM Plitnick1, SE Loveless2, GS Ladics2, MP Holsapple3, MJ Selgrade4, DM Sailstad4 & RJ Smialowicz4. 1UNC, Chapel Hill, NC; 2DuPont Co., Haskell Laboratory, Newark, DE; 3Dow Chemical, Midland, MI & 4USEPA, NHEERL, RTP, NC.

  11. Cytokine levels as biomarkers for leptospirosis patients.

    PubMed

    Chirathaworn, C; Supputtamongkol, Y; Lertmaharit, S; Poovorawan, Y

    2016-09-01

    Inflammatory mediators were suggested to be biomarkers for prediction of disease severity. In this study, we investigated the levels of IL-6, IL-8, IL-10 and TNF-α in leptospirosis patients with mild or severe illnesses. Sera samples were divided into two groups. The OI group and NOI groups included sera from patients with and without organ involvement, respectively. Each group consisted of 20 pairs of sera. Twenty-five sera from healthy individuals were included as controls. Cytokine levels were compared. Although IL-6, IL-8 and IL-10 levels in acute sera from the OI group were significantly higher than NOI group, only IL-8 level was significantly higher in the OI group when cytokine levels in convalescent sera were compared. TNF-α, an inflammatory cytokine widely studied in leptospirosis was not significantly different between two groups of patients. Our data suggested that IL-6, IL-8 and IL-10 were involved in disease severity. However, time of specimen collection could affect the significant levels of cytokines especially as biomarkers for monitoring disease severity. PMID:27295614

  12. Family Meals

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Family Meals KidsHealth > For Parents > Family Meals Print A ... even more important as kids get older. Making Family Meals Happen It can be a big challenge ...

  13. Family History

    MedlinePlus

    Your family history includes health information about you and your close relatives. Families have many factors in common, including their genes, ... as heart disease, stroke, and cancer. Having a family member with a disease raises your risk, but ...

  14. Family Arguments

    MedlinePlus

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Life Listen Español Text Size Email Print Share Family Arguments Page Content Article Body We seem to ...

  15. Family History

    MedlinePlus

    ... CDC Cancel Submit Search The CDC Family Health History Note: Javascript is disabled or is not supported ... visit this page: About CDC.gov . Family Health History The Basics Family Health History & Chronic Disease Planning ...

  16. Family Folklore

    ERIC Educational Resources Information Center

    Kotkin, Amy J.; Baker, Holly C.

    1977-01-01

    Discusses the Family Folklore Program of the Smithsonian Institution's annual Festival of American Folklife, in which the whole family can be involved in tracing family history through story telling, photographs, etc. (MS)

  17. Acidosis Sensing Receptor GPR65 Correlates with Anti-Apoptotic Bcl-2 Family Member Expression in CLL Cells: Potential Implications for the CLL Microenvironment

    PubMed Central

    Rosko, Ashley E; McColl, Karen S; Zhong, Fei; Ryder, Christopher B; Chang, Ming-Jin; Sattar, Abdus; Caimi, Paolo F; Hill, Brian T; Al-Harbi, Sayer; Almasan, Alexandru; Distelhorst, Clark W

    2015-01-01

    The tumor microenvironment is generally an acidic environment, yet the effect of extracellular acidosis on chronic lymphocytic leukemia (CLL) is not well established. Here we are the first to report that the extracellular acid sensing G-protein coupled receptor, GPR65, is expressed in primary CLL cells where its level correlate strongly with anti-apoptotic Bcl-2 family member levels. GPR65 expression is found normally within the lymphoid lineage and has not been previously reported in CLL. We demonstrate a wide range of GPR65 mRNA expression among CLL 87 patient samples. The correlation between GPR65 mRNA levels and Bcl-2 mRNA levels is particularly strong (r=0.8063, p= <0.001). The correlation extends to other anti-apoptotic Bcl-2 family members, Mcl-1 (r=0.4847, p=0.0010) and Bcl-xl (r=0.3411, p=0.0252), although at lower levels of significance. No correlation is detected between GPR65 and levels of the pro-apoptotic proteins BIM, PUMA or NOXA. GPR65 expression also correlates with the favorable prognostic marker of 13q deletion. The present findings suggest the acid sensing receptor GPR65 may be of significance to allow CLL tolerance of extracellular acidosis. The correlation of GPR65 with Bcl-2 suggests a novel cytoprotective mechanism that enables CLL cell adaptation to acidic extracellular conditions. These findings suggest the potential value of targeting GPR65 therapeutically. PMID:25984552

  18. Structural Conservation Despite Huge Sequence Diversity Allows EPCR Binding by the PfEMP1 Family Implicated in Severe Childhood Malaria

    PubMed Central

    Lau, Clinton K.Y.; Turner, Louise; Jespersen, Jakob S.; Lowe, Edward D.; Petersen, Bent; Wang, Christian W.; Petersen, Jens E.V.; Lusingu, John; Theander, Thor G.; Lavstsen, Thomas; Higgins, Matthew K.

    2015-01-01

    Summary The PfEMP1 family of surface proteins is central for Plasmodium falciparum virulence and must retain the ability to bind to host receptors while also diversifying to aid immune evasion. The interaction between CIDRα1 domains of PfEMP1 and endothelial protein C receptor (EPCR) is associated with severe childhood malaria. We combine crystal structures of CIDRα1:EPCR complexes with analysis of 885 CIDRα1 sequences, showing that the EPCR-binding surfaces of CIDRα1 domains are conserved in shape and bonding potential, despite dramatic sequence diversity. Additionally, these domains mimic features of the natural EPCR ligand and can block this ligand interaction. Using peptides corresponding to the EPCR-binding region, antibodies can be purified from individuals in malaria-endemic regions that block EPCR binding of diverse CIDRα1 variants. This highlights the extent to which such a surface protein family can diversify while maintaining ligand-binding capacity and identifies features that should be mimicked in immunogens to prevent EPCR binding. PMID:25482433

  19. The 1.3-Å resolution structure of Nitrosomonas europaea Rh50 and mechanistic implications for NH3 transport by Rhesus family proteins

    PubMed Central

    Lupo, Domenico; Li, Xiao-Dan; Durand, Anne; Tomizaki, Takashi; Cherif-Zahar, Baya; Matassi, Giorgio; Merrick, Mike; Winkler, Fritz K.

    2007-01-01

    The Rhesus (Rh) proteins are a family of integral membrane proteins found throughout the animal kingdom that also occur in a number of lower eukaryotes. The significance of Rh proteins derives from their presence in the human red blood cell membrane, where they constitute the second most important group of antigens used in transfusion medicine after the ABO group. Rh proteins are related to the ammonium transport (Amt) protein family and there is considerable evidence that, like Amt proteins, they function as ammonia channels. We have now solved the structure of a rare bacterial homologue (from Nitrosomonas europaea) of human Rh50 proteins at a resolution of 1.3 Å. The protein is a trimer, and analysis of its subunit interface strongly argues that all Rh proteins are likely to be homotrimers and that the human erythrocyte proteins RhAG and RhCE/D are unlikely to form heterooligomers as previously proposed. When compared with structures of bacterial Amt proteins, NeRh50 shows several distinctive features of the substrate conduction pathway that support the concept that Rh proteins have much lower ammonium affinities than Amt proteins and might potentially function bidirectionally. PMID:18032606

  20. Growth of Chitinophaga pinensis on Plant Cell Wall Glycans and Characterisation of a Glycoside Hydrolase Family 27 β-l-Arabinopyranosidase Implicated in Arabinogalactan Utilisation

    PubMed Central

    McKee, Lauren S.; Brumer, Harry

    2015-01-01

    The genome of the soil bacterium Chitinophaga pinensis encodes a diverse array of carbohydrate active enzymes, including nearly 200 representatives from over 50 glycoside hydrolase (GH) families, the enzymology of which is essentially unexplored. In light of this genetic potential, we reveal that C. pinensis has a broader saprophytic capacity to thrive on plant cell wall polysaccharides than previously reported, and specifically that secretion of β-l-arabinopyranosidase activity is induced during growth on arabinogalactan. We subsequently correlated this activity with the product of the Cpin_5740 gene, which encodes the sole member of glycoside hydrolase family 27 (GH27) in C. pinensis, CpArap27. Historically, GH27 is most commonly associated with α-d-galactopyranosidase and α-d-N-acetylgalactosaminidase activity. A new phylogenetic analysis of GH27 highlighted the likely importance of several conserved secondary structural features in determining substrate specificity and provides a predictive framework for identifying enzymes with the less common β-l-arabinopyranosidase activity. PMID:26448175