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Sample records for feeding practices cd4

  1. Mortality during the first 24 months after delivery in relation to CD4 T-lymphocyte levels and viral load in a cohort of breast-feeding HIV-1-infected women in Dar es Salaam, Tanzania.

    PubMed

    Kilewo, Charles; Karlsson, Katarina; Swai, Andrew; Massawe, Augustine; Lyamuya, Eligius; Mhalu, Fred; Biberfeld, Gunnel

    2005-04-15

    The objective of this study was to analyze the mortality during the first 24 months after delivery in relation to CD4 T-lymphocyte levels and viral load at enrollment (36 weeks of gestation) in a cohort of HIV-1-seropositive breast-feeding women at the Dar es Salaam site of the multicenter Petra trial (a mother-to-child HIV-1 transmission intervention trial using antiretroviral therapy). Antiretroviral treatment was not available in this setting apart from the short treatment given within the trial around delivery to prevent mother-to-child transmission of HIV. T-lymphocyte subsets were determined by flow cytometry. Plasma HIV-1 RNA was quantified by the Amplicor HIV-1 RNA Monitor v 1.5 assay. Mortality after delivery was analyzed using the life-table technique and Cox regression. The analysis included 266 mothers. The CD4 cell counts at enrollment were <200 cells/mm in 14.5% of the mothers. The viral load at enrollment was >100,000 RNA copies/mL in 33.6% of the mothers. The mortality 24 months after delivery was 6.7% (95% CI = 3.1-10.1%). The mortality 24 months after delivery was 29.9% (95% CI = 13.1-46.9%) for mothers with <200 CD4 cells/mm at enrollment, 3.3% (95% CI = 0-6.6%) for mothers with 200-499 CD4 cells/mm, 2.9% (95% CI = 0-7.1%) for mothers with >500 CD4 cells/mm (P = 0.0000), 15.0% (95% CI = 6.6-23.4%) for mothers with viral load >100,000 copies/mL at enrollment, and 2.8% (95% CI = 0-5.6%) for mothers with viral load <100,000 copies/mL (P = 0.0000). In the multivariate analysis CD4 cell counts and viral load were both independent risk factors for mortality (P < 0.001 and P = 0.004, respectively). In conclusion, the mortality was high among women with severe immunosuppression or high viral load at enrollment, but not in the rest of the women. CD4 lymphocyte count in late pregnancy was a better predictor of death within 2 years than was viral load. The results support the World Health Organization recommendation to initiate antiretroviral treatment in

  2. Prenatal office practices regarding infant feeding choices.

    PubMed

    Dusdieker, Lois B; Dungy, Claibourne I; Losch, Mary E

    2006-11-01

    The objective of this study was to determine the obstetric care providers' roles in breast-feeding promotion during prenatal care. A questionnaire addressing breast-feeding issues was sent to family practitioners (FP), obstetric-gynecologists (OB/GYN), and nurse midwives (NM) in Iowa, USA. All NM, 97% of FP, and 85% of OB/GYN reported asking infant feeding preference-usually only at the first prenatal visit. NM (73%) were most likely to provide extensive breast-feeding counseling. OB/GYN (68%) and FP physicians (90%) reported doing their own breast-feeding counseling. Breast examinations targeting future breast-feeding problems were done in 82% to 84% of patients. NM practices shared more information supportive of breast-feeding. Nearly all providers offered prenatal classes, but only 41% of FP offered breast-feeding classes. Free formula samples were available in 73% of FP, 54% of OB/GYN, and 36% NM offices. Pamphlets on formula feeding and also breast-feeding were readily available. Overall NM (64%) reported being strong breast-feeding advocates compared to only 13% of FP and 7% of OB/GYN. In conclusion, little promotion of breast-feeding occurs in most prenatal practice settings.

  3. Idiopathic CD4 Lymphocytopenia

    PubMed Central

    Régent, Alexis; Autran, Brigitte; Carcelain, Guislaine; Cheynier, Rémi; Terrier, Benjamin; Charmeteau-De Muylder, Bénédicte; Krivitzky, Alain; Oksenhendler, Eric; Costedoat-Chalumeau, Nathalie; Hubert, Pascale; Lortholary, Olivier; Dupin, Nicolas; Debré, Patrice; Guillevin, Loïc; Mouthon, Luc

    2014-01-01

    Abstract Idiopathic CD4 T lymphocytopenia (ICL) is a rare and severe condition with limited available data. We conducted a French multicenter study to analyze the clinical and immunologic characteristics of a cohort of patients with ICL according to the Centers for Disease Control criteria. We recruited 40 patients (24 female) of mean age 44.2 ± 12.2 (19–70) years. Patients underwent T-lymphocyte phenotyping and lymphoproliferation assay at diagnosis, and experiments related to thymic function and interferon (IFN)-γ release by natural killer (NK) cell were performed. Mean follow-up was 6.9 ± 6.7 (0.14–24.3) years. Infectious, autoimmune, and neoplastic events were recorded, as were outcomes of interleukin 2 therapy. In all, 25 patients had opportunistic infections (12 with human papillomavirus infection), 14 had autoimmune symptoms, 5 had malignancies, and 8 had mild or no symptoms. At the time of diagnosis, the mean cell counts were as follows: mean CD4 cell count: 127/mm3 (range, 4–294); mean CD8: 236/mm3 (range, 1–1293); mean CD19: 113/mm3 (range, 3–547); and mean NK cell count: 122/mm3 (range, 5–416). Most patients had deficiency in CD8, CD19, and/or NK cells. Cytotoxic function of NK cells was normal, and patients with infections had a significantly lower NK cell count than those without (p = 0.01). Patients with autoimmune manifestations had increased CD8 T-cell count. Proliferation of thymic precursors, as assessed by T-cell rearrangement excision circles, was increased. Six patients died (15%). CD4 T-cell count <150/mm3 and NK cell count <100/mm3 were predictors of death. In conclusion, ICL is a heterogeneous disorder often associated with deficiencies in CD8, CD19, and/or NK cells. Long-term prognosis may be related to initial CD4 and NK cell deficiency. PMID:24646462

  4. College Students' Attitudes regarding Infant Feeding Practices

    ERIC Educational Resources Information Center

    Bomba, Anne K.; Chang, Yunhee; Knight, Kathy B.; Tidwell, Diane K.; Wachter, Kathy; Endo, Seiji; West, Charles K.

    2009-01-01

    This study investigated the attitudes of college students toward various infant feeding practices using a questionnaire created by the authors on the basis of a review of the literature. Five hundred ten students enrolled at the University of Mississippi took part in the study. Findings indicated that respondents believed both high school and…

  5. Feeding Students in School: Providing Guidelines and Information on Safe Feeding Practices for Special Students.

    ERIC Educational Resources Information Center

    Hall, Sandra; And Others

    This manual provides guidelines for safe feeding practices for students with disabilities in Oregon schools. Stressed is the importance of distinguishing between feeding for the maintenance of health and feeding for the acquisition of skills. Individual sections cover: definitions of feeding programs; the school district responsibility; risks;…

  6. Fathers' child feeding practices: a review of the evidence.

    PubMed

    Khandpur, Neha; Blaine, Rachel E; Fisher, Jennifer Orlet; Davison, Kirsten K

    2014-07-01

    Despite their expanding role in child rearing, fathers are underrepresented in child feeding research. To address this knowledge gap and encourage father-focused research, this review compiles child feeding research that has included fathers and (i) documents characteristics of studies assessing fathers' feeding practices including study design, setting, recruitment strategies, participant characteristics, theoretical models utilized and measures of child feeding, (ii) outlines general patterns in fathers' feeding practices along with similarities and differences in mothers' and fathers' feeding practices, (iii) summarizes evidence on child and parent correlates of fathers' feeding practices and (iv) generates future research recommendations. A literature review of relevant articles published up to February 2014 was conducted. Studies were eligible for inclusion if they: (i) included fathers, or primary male caregivers, of children 2-18 years of age, (ii) measured fathers' child feeding practices or perceived role in child feeding through objective (e.g., meal observations) or subjective (i.e., fathers' self-report) methods, (iii) analyzed and presented data on fathers separately from mothers and (iv) were published in a peer reviewed journal in the English language. Twenty studies met eligibility criteria. Few studies included an operational definition of "father". Samples were generally small and focused on white, well-educated fathers, cohabiting with the child's mother. Most studies utilized self-report measures of child feeding practices that have not been validated specifically for use with fathers. Pressuring children to eat was a common feeding strategy adopted by fathers. Some differences were noted in mothers' and fathers' feeding practices; fathers were generally less likely to monitor children's food intake and to limit access to food compared with mothers. Child adiposity and a range of child and parent characteristics were associated with fathers

  7. Infant Feeding Practices in Central Anatolia, Turkey

    ERIC Educational Resources Information Center

    Sanlier, Nevin; Unusan, Nurhan

    2009-01-01

    Infant feeding decisions are some of the most important choices parents make. Breast milk or formula is the first decision made in infant feeding. Complementary feeding is common among very young children in Turkey. Therefore, the aim of this research is to focus on the introduction of solid foods, and to determine the relationship between…

  8. Breast Feeding Practice among Medical Women in Nigeria.

    PubMed

    Sadoh, A E; Sadoh, W E; Oniyelu, P

    2011-01-01

    BACKGROUND: Health care workers are important in the promotion, protection and support of breast feeding. Their ability to do this may be influenced by their knowledge, personal experiences and work. PATIENTS AND METHOD: The breast feeding experience of 36 female medical doctors who had babies within the preceding two years and had resumed work was evaluated using a semi-structured self administered questionnaire. RESULT: All respondents knew that babies should be exclusively breast fed for the first six months of life but only 60% knew that breast feeding should continue until two years. The exclusive breast feeding rate for the studied doctors was 11.1%. Before their babies were six months old, about 75% of respondents had resumed work whilst over 50% had started taking calls. Most could not breast feed during working or call hours. Alternative feeds during working or call hours included expressed breast milk in 34.4% and infant formula in 21.9%. Feeding bottle was the major method (77.4%) for feeding these alternatives. Work schedule was rearranged to allow breast feeding in only 27.3% of respondents. CONCLUSION: Failure to carry out exclusive breast feeding, the use of infant formula and feeding bottles (rather than cup feeding) are practices that may be inimical to the practice of breast feeding in society in general. The suboptimal breast feeding experience in these doctors and the identified knowledge deficits may limit their effectiveness in promoting and supporting breast feeding among their patients and communities. Female medical personnel should be empowered to carry out optimal feeding of their own infants.

  9. Maternal feeding practices and feeding behaviors of Australian children aged 12-36 months.

    PubMed

    Chan, L; Magarey, A M; Daniels, L A

    2011-11-01

    To explore parents' perceptions of the eating behaviors and related feeding practices of their young children. Mothers (N=740) of children aged 12-36 months and born in South Australia were randomly selected by birth date in four 6-month age bands from a centralized statewide database and invited to complete a postal questionnaire. Valid completed questionnaires were returned for 374 children (51% response rate; 54% female). Although mothers generally reported being confident and happy in feeding their children, 23% often worried that they gave their child the right amount of food. Based on a checklist of 36 specified items, 15% of children consumed no vegetables in the previous 24 h, 11% no fruit and for a further 8% juice was the only fruit. Of 12 specified high fat/sugar foods and drinks, 11% of children consumed none, 20% one, 26% two, and 43% three or more. Six of eight child-feeding practices that promote healthy eating behaviors were undertaken by 75% parents 'often' or 'all of the time'. However, 8 of 11 practices that do not promote healthy eating were undertaken by a third of mothers at least 'sometimes'. In this representative sample, dietary quality issues emerge early and inappropriate feeding practices are prevalent thus identifying the need for very early interventions that promote healthy food preferences and positive feeding practices. Such programs should focus not just on the 'what', but also the 'how' of early feeding, including the feeding relationship and processes appropriate to developmental stage.

  10. Nutrition: safe practice in adult enteral tube feeding.

    PubMed

    Fletcher, Jane

    The use of enteral feeding tubes, such as nasogastric and gastrostomy tubes, to support a patient's nutritional intake is generally considered to be safe and effective. However, recent alerts and recommendations from the National Patient Safety Agency (NPSA) regarding enteral feeding have led health professionals to review their practice and guidelines. This article explores safe practice in enteral tube feeding in the light of three NPSA alerts: Promoting safer measurement and administration of liquid medicines via oral and other enteral routes (2007), Early detection of complications after gastrostomy (2010) and Reducing the harm caused by misplaced nasogastric tubes in adults and children (2011).

  11. Predicting children's fussiness with vegetables: The role of feeding practices.

    PubMed

    Holley, Clare E; Haycraft, Emma; Farrow, Claire

    2017-03-01

    Vegetables are commonly rejected by children, making it is important to consider factors that are associated with children's fussiness with vegetables. The current study aimed to investigate whether fussiness with vegetables is associated with a number of factors including caregiver and child vegetable consumption; caregivers' general feeding practices; and caregivers' vegetable-specific feeding practices. Caregivers (N = 297) of preschool children completed questionnaire measures of their child's fussiness with vegetables, as well as several caregiver and child factors hypothesised to be associated with children's fussiness with vegetables. Findings indicate that children who are fussier with vegetables consume a smaller quantity of vegetables and that almost all have caregivers who eat a smaller quantity of vegetables. Children's fussiness with vegetables was not significantly related to any general feeding practices used by caregivers. However, children's fussiness with vegetables was significantly associated with the use of several vegetable specific feeding practices. Caregivers of fussier children used more encouragement/pressure to eat with vegetables (r = 0.14, p = .01), hid vegetables within other foods more often (r = 0.30, p = <.01), used more food rewards for vegetable consumption (r = 0.19, p <.01), more other rewards for vegetable consumption (r = 0.21, p < .01), and compromised more when feeding vegetables (r = 0.14, p = .01). These findings suggest that rather than caregivers' general feeding practices being related to children's fussiness with vegetables, the specific feeding practices used when vegetables are rejected are more significant. It may therefore be helpful to develop advice for caregivers about which feeding practices to avoid when faced with a child who is fussy about eating vegetables.

  12. The emotional and practical experiences of formula-feeding mothers.

    PubMed

    Fallon, Victoria; Komninou, Sophia; Bennett, Kate M; Halford, Jason C G; Harrold, Joanne A

    2016-11-14

    The majority of infant-feeding research is focused on identifying mother's reasons for the cessation of breastfeeding. The experience of mothers who choose to use formula is largely overlooked in quantitative designs. This study aimed to describe the emotional and practical experiences of mothers who formula feed in any quantity, and examine whether these experiences would vary among different cohorts of formula-feeding mothers according to prenatal feeding intention and postnatal feeding method. A total of 890 mothers of infants up to 26 weeks of age, who were currently formula feeding in any quantity, were recruited through relevant international social media sites via advertisements providing a link to an online survey. Predictors of emotional experiences included guilt, stigma, satisfaction, and defense as a result of their infant feeding choices. Practical predictor variables included support received from health professionals, respect displayed by their everyday environment, and main sources of infant feeding information. Descriptive findings from the overall sample highlighted a worryingly high percentage of mother's experienced negative emotions as a result of their decision to use formula. Multinomial logit models revealed that negative emotions such as guilt, dissatisfaction, and stigma were directly associated with feeding intention and method. The evidence suggests that the current approach to infant-feeding promotion and support may be paradoxically related to significant issues with emotional well-being. These findings support criticisms of how infant-feeding recommendations are framed by health care professionals and policy makers, and highlight a need to address formula feeding in a more balanced, woman-centered manner.

  13. A comparison between the feeding practices of parents and grandparents.

    PubMed

    Farrow, Claire

    2014-08-01

    Grandparents play a valuable role in the socialisation of young children, and as many as 36% of British parents use grandparents as their main form of childcare. Research has begun to explore how grandparents impact the social and cognitive development of children, but very little research has evaluated their contribution to child feeding. The present study explores whether there are differences between parents and grandparents in terms of their feeding practices, and whether grandparents' feeding practices are related to the number of hours that they spend caring for grandchildren. Results indicate that grandparents reported using significantly more maladaptive feeding practices such as using food to regulate emotions and restricting food, but more positive practices such as providing a healthy food environment. The more hours that grandparents spent caring for children the more their feeding practices resembled those broadly reported by parents. Results suggest that grandparents can have a measurable impact on child feeding behaviour which in turn is likely to predict the eating behaviours of their grandchildren.

  14. Cloning, expression, and characterization of fugu CD4, the first ectothermic animal CD4.

    PubMed

    Suetake, Hiroaki; Araki, Kyosuke; Suzuki, Yuzuru

    2004-08-01

    We have cloned and sequenced the first ectothermic animal CD4 gene from fugu, Takifugu rubripes, using a public database of the third draft sequence of the fugu genome. The fugu CD4 gene encodes a predicted protein of 463 amino acids containing four extracellular immunoglobulin (Ig)-like domains, a transmembrane region, and a cytoplasmic tail. Fugu CD4 shares low identity of about 15-20% with avian and mammalian CD4 proteins. Unlike avian and mammalian CD4, fugu CD4 lacks the Cys pair of the first Ig-like domain, but has a unique possible disulfide bond in the third domain. These differences suggest that fugu CD4 may have a different structure that could affect binding of major histocompatibility complex class II molecules and subsequent T-cell activation. In the putative fugu cytoplasmic region, the protein tyrosine kinase p56lck binding motif is conserved. The predicted fugu CD4 gene is composed of 12 exons, differing from other CD4 genes, but showing conserved synteny and many conserved sequence motifs in the promoter region. RT-PCR analysis demonstrated that the fugu CD4 gene is expressed predominantly in lymphoid tissues. We also show that fugu CD4 can be expressed on the surface of cells via transfection. Molecular characterization of CD4 in fish provides insights into the evolution of both the CD4 molecule and the immune system.

  15. Variation in Feeding Practices Following the Norwood Procedure

    PubMed Central

    Lambert, Linda M.; Pike, Nancy A.; Medoff-Cooper, Barbara; Zak, Victor; Pemberton, Victoria L.; Young-Borkowski, Lisa; Clabby, Martha L.; Nelson, Kathryn N.; Ohye, Richard G.; Trainor, Bethany; Uzark, Karen; Rudd, Nancy; Bannister, Louise; Korsin, Rosalind; Cooper, David S.; Pizarro, Christian; Zyblewski, Sinai C.; Bartle, Bronwyn H.; Williams, Richard V.

    2013-01-01

    Objectives To assess variation in feeding practice at Norwood discharge, factors associated with tube feeding, and associations between site, feeding mode, and growth prior to stage II. Study design From May 2005 to July 2008, 555 subjects from 15 centers were enrolled in the Pediatric Heart Network Single Ventricle Reconstruction Trial; 432 survivors with Norwood discharge feeding data were analyzed. Results Demographic and clinical variables were compared among 4 feeding modes: oral only (n=140), oral/tube (n=195), nasogastric tube (N-tube) only (n=40), and gastrostomy tube (G-tube) only (n=57). There was significant variation in feeding mode among sites (oral only 0–81% and G-tube only 0–56%, p<0.01). After adjusting for site, multivariable modeling showed G-tube feeding at discharge was associated with longer hospitalization, and N-tube feeding was associated with greater number of discharge medications (R2=0.65, p<0.01). After adjusting for site, mean pre-stage II weight-for-age z-score (WAZ) was significantly higher in the oral only group (−1.4) vs. the N-tube only (−2.2) and G-tube only (−2.1) groups (p=0.04 and 0.02, respectively). Conclusions Feeding mode at Norwood discharge varied among sites. Prolonged hospitalization and greater number of medications at the time of Norwood discharge were associated with tube feeding. Infants exclusively fed orally had a higher WAZ pre-stage II than those fed exclusively by tube. Exploring strategies to prevent morbidities and promote oral feeding in this highest risk population is warranted. PMID:24210923

  16. Enteral tube feeding: using good practice to prevent infection.

    PubMed

    Malhi, Hardip

    2017-01-12

    Enteral tube feeding is the delivery of nutritionally complete feed via a tube into the gut. It is used for patients who are unable to meet their nutritional needs orally. Enteral feeding can be given through a variety of different tubes that access the gastrointestinal tract either via the stomach or the small bowel. The contamination of enteral feed can often be overlooked as a source of bacterial infection. Enteral feeds can become contaminated in a variety of different ways. Most often infections result in extended lengths of stay in hospital and patients also need additional therapies and treatments in order to resolve these infections. Healthcare-associated infections not only affect the patients who acquire them but also have an impact on the staff involved in their care. Each acute trust will have its own local policies and guidelines regarding enteral feeding and infection control and prevention. These local documents will be based on national initiatives and guidelines. It is important for nurses to refer to their local policies and guidelines before they start a patient on enteral feeding to ensure that they are doing so in the safest manner possible. Nurses' practice is key to preventing bacterial contamination in such patients.

  17. Expression of CD4 by human megakaryocytes.

    PubMed Central

    Basch, R S; Kouri, Y H; Karpatkin, S

    1990-01-01

    The CD4 antigen, which serves as the receptor for human immunodeficiency virus type 1 (HIV-1) on T cells, has been detected on human megakaryocytes. Recent evidence of impaired thrombopoiesis in HIV-1-related thrombocytopenia suggested that these cells could be directly infected by the virus and prompted a search for a receptor on megakaryocytes of normal subjects that could permit entry of HIV-1. Bone marrow specimens from uninfected normal control subjects were centrifuged over Ficoll-Hypaque (1.077 g/ml) and analyzed by three-color analysis with a flow cytometer utilizing monoclonal antibodies against CD4 and a glycoprotein present on the surface of megakaryocytes and platelets (GPIIb/IIIa; CD41), as well as 7-aminoactinomycin D, a stain for DNA. Cells presumed to be megakaryocytes were identified by having a DNA content greater than tetraploid and staining brightly with anti-CD41. Approximately 0.4% of the nucleated cells of the marrow met these criteria. Twenty-five percent of these megakaryocytes stained as brightly as CD4+ T cells. Several clones of antibody recognizing different epitopes of the CD4 molecule gave similar results. Platelets were CD4-. Staining of megakaryocytes with anti-CD4 was confirmed by direct microscopic examination of Percoll-gradient-enriched megakaryocytes employing two-color (CD4-phycoerythrin and CD41-fluorescein) immunofluorescence analysis and phase-contrast microscopy. The proportion of double-labeled cells among 112 phase-contrast-identifiable megakaryocytes from five bone marrow specimens varied between 20% and 26% with a mean and SD of 22% +/- 2.5%. Thus some human megakaryocytes express CD4 on their surface that should be capable of binding the HIV-1 gp120 envelope protein. This could serve as a portal of entry for HIV-1. Images PMID:2236021

  18. Feeding practices correlated with authoritative parenting style and responsive feeding style scores

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Study objective was to identify correlations of authoritative parenting and responsive feeding styles with parental practices and child behaviors previously found to protect children from or increase risk of child obesity. Participants were 144 low-income mothers of 3- to 5-year-old children (71 gir...

  19. Mothers Who Formula Feed: Their Practices, Support Needs and Factors Influencing Their Infant Feeding Decision

    ERIC Educational Resources Information Center

    Tarrant, Roslyn C.; Sheridan-Pereira, Margaret; McCarthy, Roberta A.; Younger, Katherine M.; Kearney, John M.

    2013-01-01

    The majority of mothers in Ireland provide formula milk to their infants during the initial weeks postpartum; however, data are lacking on their formula feeding practices and support needs. This prospective Dublin-based observational study, which included 450 eligible mother-term infant pairs recruited and followed up to six months postpartum,…

  20. CD4 CTL, a Cytotoxic Subset of CD4+ T Cells, Their Differentiation and Function

    PubMed Central

    Takeuchi, Arata; Saito, Takashi

    2017-01-01

    CD4+ T cells with cytotoxic activity (CD4 CTL) have been observed in various immune responses. These cells are characterized by their ability to secrete granzyme B and perforin and to kill the target cells in an MHC class II-restricted fashion. Although CD4 CTLs were once thought to be an in vitro artifact associated with long-term culturing, they have since been identified in vivo and shown to play important roles in antiviral and antitumor immunity, as well as in inflammation. Functional characterization of CD4 CTL suggests their potential significance for therapeutic purposes. However, in order to develop effective CD4 CTL therapy it is necessary to understand the differentiation and generation of these cells. Although the mechanisms regulating development of various CD4+ Th subsets have been clarified in terms of the cytokine and transcription factor requirement, the CD4 CTL differentiation mechanism remains elusive. These cells are thought to be most closely related to Th1 cells secreting IFNγ and regulated by eomesodermin and/or T-bet transcription factors for their differentiation. However, our studies and those of others have identified CD4 CTLs within other CD4+ T cell subsets, including naïve T cells. We have identified class I-restricted T cell-associated molecule as a marker of CD4 CTL and, by using this marker, we detected a subset of naïve T cells that have the potential to differentiate into CD4 CTL. CD4 CTL develops at sites of infections as well as inflammation. In this review, we summarize recent findings about the generation of CD4 CTL and propose a model with several differentiation pathways. PMID:28280496

  1. Impact of infant feeding practices on childhood obesity.

    PubMed

    Butte, Nancy F

    2009-02-01

    Childhood obesity is a complex disease influenced by genetic and environmental factors and their interactions. The current surge in childhood obesity in the United States is attributable to an interaction between a genetic predisposition toward obesity and a permissive environment. Several recent systematic reviews and meta-analyses have been published on the association between breast-feeding and childhood obesity. In these analyses, adjustment for confounding factors attenuated or nullified the protective effect of breast-feeding on later obesity. The Viva La Familia Study was designed to identify genetic and environmental factors affecting obesity and its comorbidities in 1030 Hispanic children from 319 families. Odds ratios for potential risk factors associated with childhood overweight were computed using binary logistic regression for panel data. Early infant-feeding practices were not significant. Salient independent risk factors for childhood obesity in this cohort of Hispanic children were age, birth weight, maternal obesity, paternal obesity, number of children in the family, and the percentage of awake time spent in sedentary activity. Breast-feeding may have a small protective effect against childhood obesity, although residual confounding may exist. Human milk is exquisitely fitted for optimal infant growth and development and may uniquely modulate neuroendocrine and immunologic pathways involved in the regulation of body weight. Nevertheless, other genetic and environmental determinants such as socioeconomic status, parental obesity, smoking, birth weight, and rapid infancy weight gain far supersede infant-feeding practices as risk factors for childhood obesity.

  2. Feeding infants and young children. From guidelines to practice.

    PubMed

    Hetherington, Marion M; Cecil, Joanne E; Jackson, Diane M; Schwartz, Camille

    2011-12-01

    Following a workshop on infant feeding held at the Rowett Institute of Nutrition and Health, University of Aberdeen on March 17, 2010 experts were invited to exchange ideas and to review evidence on both pre and post natal dietary environments in shaping children's eating habits. A central theme during the workshop was the idea of "sensitive periods" during infancy for learning about foods and a particular focus was developed around acceptance and intake of fruits and vegetables. Presentations covered the guidelines provided by various governments on how to feed infants during weaning; the importance of the in utero experience; the impact of varying the sensory experience at weaning; the effect of parenting styles and practices on children's eating habits; the use of visual experience in promoting intake of vegetables; and reports from mothers regarding their decisions about weaning and the introduction of vegetables. This collection of papers seeks to review guidance from governments on feeding infants and to consider current evidence on parental feeding practices with the aim of enhancing insight into best practice in establishing healthy eating in children.

  3. Association of fathers' feeding practices and feeding style on preschool age children's diet quality, eating behavior and body mass index.

    PubMed

    Vollmer, Rachel L; Adamsons, Kari; Foster, Jaime S; Mobley, Amy R

    2015-06-01

    The associations of parental feeding practices and feeding style with childhood obesity have gained more attention in the literature recently; however, fathers are rarely included within these studies. The aim of this research was to determine the relationship of paternal feeding practices on child diet quality, weight status, and eating behavior, and the moderating effect of paternal feeding style on these relationships in preschool age children. This study included a one-time, one-on-one interview with biological fathers of preschoolers (n = 150) to assess feeding practices (Child Feeding Questionnaire), feeding style (Caregiver Feeding Style Questionnaire), child eating behaviors (Child Eating Behavior Questionnaire), and diet quality (24 hour recall, Healthy Eating Index). Height and weight for each father and child were also measured and Body Mass Index (BMI) or BMI z-score calculated. Linear regression was used to test the relationship between paternal feeding practices, style and child diet quality and/or body weight. Overall, the findings revealed that a father's feeding practices and feeding style are not associated with children's diet quality or weight status. However, child eating behaviors are associated with child BMI z-score and these relationships are moderated by paternal feeding practices. For example, child satiety responsiveness is inversely (β = -.421, p = 0.031) associated with child BMI z-score only if paternal restriction scores are high. This relationship is not significant when paternal restriction scores are low (β = -.200, p = 0.448). These results suggest that some child appetitive traits may be related to child weight status when exposed to certain paternal feeding practices. Future studies should consider the inclusion of fathers as their feeding practices and feeding style may be related to a child's eating behavior.

  4. Complementary feeding in the MENA region: practices and challenges.

    PubMed

    Nasreddine, L; Zeidan, M N; Naja, F; Hwalla, N

    2012-10-01

    Suboptimal feeding patterns during the first two years of life are key determinants of malnutrition in children and constitute an important predictor of health in later years. Early-childhood nutritional factors, stunting, and obesity have been highlighted as prominent core underlying factors of Non-Communicable Disease (NCD) development whereas the improvement of complementary feeding practices has been cited as one of the most effective preventive strategies for reducing malnutrition and adult NCDs. In the MENA region NCD prevalence shows very high rates and the limited available studies show that current practices fall behind global recommendations. Common to all countries of this region are practices of mixed breast and bottle-feeding as early as the first month, as well as the premature introduction of complementary foods. Early introduction of non-milk fluids, such as sweetened water and herbal teas, has been described as a common practice in the region and the premature introduction of complementary foods has been reported in as high as 80% of infants in several of the countries. Thus, enhancing infant/young child health can significantly reduce morbidities and mortalities, as well as adult-onset diseases, ultimately decreasing the region's overall burden of disease.

  5. Idiopathic CD4 lymphocytopenia with sensorimotor polyneuropathy

    PubMed Central

    Puri, Vinod; Duggal, Ashish Kumar; Chaudhry, Neera

    2016-01-01

    A, 21-years-old, male, presented with acute onset, gradually progressive, predominantly distal, symmetrical weakness of both upper and lower limbs with arreflexia. He had impaired sensations in glove and stocking distribution with distal gradient. He was found to have absolute CD4 + cell count of 188 cells/μL, absolute CD8 cell count, 532 cells/μL and CD4: CD8 ratio of 0.35. Electrophysiology revealed reduced to absent CMAP amplitude as well as SNAPs in various nerves of upper and lower limbs, along with normal conduction velocity and normal F wave latencies. Pattern evoked visual potentials were prolonged, on both sides, P100 being 130 ms, on right and 108 ms, on left side. In the follow up of 2 years, he showed spontaneous but gradual clinical improvement but his electrophysiological parameters as well as CD 4+ cells count did not show any significant improvement. PMID:27570393

  6. Are parenting style and controlling feeding practices related?

    PubMed

    Blissett, J; Haycraft, E

    2008-01-01

    This study examined the relationships between parenting styles, feeding practices and BMI in a non-clinical sample of mothers and fathers of UK preschool children. Ninety-six cohabiting parents of 48 children (19 male, 29 female, mean age 42 months) completed a series of self-report questionnaires assessing parenting style, feeding practices, eating psychopathology and a range of demographic information. There were no relationships between authoritarian parenting and controlling feeding practices. In both mothers and fathers, permissive parenting style was related to lower monitoring of children's unhealthy food intake. Permissive parenting was also associated with increased use of restriction by mothers and pressure to eat by fathers. Authoritative parenting style was also related to lower use of pressure to eat by fathers only. Parenting styles were not related to child BMI in this sample. Higher child BMI was best predicted by lower paternal application of pressure to eat and greater paternal reports of drive for thinness. Parenting style may not have a direct impact on child BMI until child food selection and consumption becomes more autonomous.

  7. A practical guide to successful breast-feeding management.

    PubMed

    Freed, G L; Landers, S; Schanler, R J

    1991-08-01

    It is often difficult for new mothers to know whom to approach for the necessary guidance and practical problem solving required for successful long-term lactation. Although obstetricians are familiar with the care of the breast, they may not maintain the degree of postpartum follow-up necessary to ensure its proper function nor is it their responsibility to ensure that the infant receives proper nourishment. Pediatricians are expected to offer advice and information regarding not only the advantages and disadvantages of breastfeeding but also practical management of this art. We provide a guide for practitioners who wish to assist breast-feeding mothers and their infants.

  8. Relation of parenting styles, feeding styles and feeding practices to child overweight and obesity. Direct and moderated effects.

    PubMed

    Hubbs-Tait, Laura; Dickin, Katherine L; Sigman-Grant, Madeleine; Jahns, Lisa; Mobley, Amy R

    2013-12-01

    The purpose of this study was to evaluate the direct and interacting relations of parenting styles, feeding styles, and feeding practices to child overweight and obesity. Participants were 144 mothers and children under 6 years of age. Mothers completed questionnaires about parenting and feeding styles and feeding practices. Researchers weighed and measured mothers and children or obtained measurements from a recent health report. Feeding practices were not directly related to child weight status. Compared to the uninvolved feeding style, authoritative and authoritarian feeding style categories were linked to lower odds of overweight. Feeding practices interacted with authoritative and authoritarian parenting styles to predict obesity: (1) healthful modeling was associated with 61% (OR = 0.39) reduced odds of obesity in children of authoritative mothers but with 55% (OR = 1.55) increased odds in children of non-authoritative mothers and (2) covert control was linked to 156% (OR = 2.56) increased odds of obesity in children of authoritarian mothers but with 51% (OR = 0.49) decreased odds in children of non-authoritarian mothers. Healthful modeling interacted with feeding style demandingness to predict overweight and with responsiveness to predict obesity. Findings suggest the need for research and interventions on mechanisms mediating between feeding practices and obesity in families characterized by non-authoritative parenting styles.

  9. Modulation of CD4 by suramin.

    PubMed Central

    Allen, P D; Johnston, D H; Macey, M G; Williams, N S; Newland, A C

    1993-01-01

    Suramin is a polysulphonated compound which can selectively bind to, and inhibit the activity of, a wide range of growth factors. There has been renewed interest recently in suramin as an anti-cancer agent and therefore we have studied its effects on lymphocyte subset populations and recombinant human IL-2 (rhIL-2) activation on lymphocytes in vitro. In the presence of rhIL-2 (1000 U/ml), suramin (200 micrograms/ml) caused a decrease in percentage of cells expressing the predominantly T cell antigen CD3; no change in percentage of cells expressing the T suppressor/cytotoxic subset antigen, CD8; a small rise in those expressing the natural killer cell antigen, CD56; and a large significant fall in those expressing the T helper subset antigen CD4 (48.51% versus 27.97%; P < 0.001). CD4 modulation by suramin was also found on the CD4+ cell lines CEM and MOLT-4. The effect of suramin on rhIL-2-induced activation antigen expression remains equivocal, since a small rise in CD25 expression and small falls in CD71 and HLA-Dr expression were recorded. The modulatory effect of suramin on CD4 expression was not reversible over a 96-h culture period in its continued presence. However, on removal of suramin by extensive washing, recovery of CD4 expression was detected within 24 h. Suramin-induced modulation, but not PMA-induced modulation, could be partially inhibited by preincubation with tyrphostin (12 microM), a tyrosine kinase inhibitor. PMID:8419075

  10. Marketing breastfeeding--reversing corporate influence on infant feeding practices.

    PubMed

    Kaplan, Deborah L; Graff, Kristina M

    2008-07-01

    Breast milk is the gold standard for infant nutrition and the only necessary food for the first 6 months of an infant's life. Infant formula is deficient and inferior to breast milk in meeting infants' nutritional needs. The infant formula industry has contributed to low rates of breastfeeding through various methods of marketing and advertising infant formula. Today, in New York City, although the majority of mothers initiate breastfeeding (approximately 85%), a minority of infants is breastfed exclusively at 8 weeks postpartum (approximately 25%). The article reviews the practices of the formula industry and the impact of these practices. It then presents the strategic approach taken by the NYC Department of Health and Mental Hygiene and its partners to change hospital practices and educate health care providers and the public on the benefits of breast milk, and provides lessons learned from these efforts to make breastfeeding the normative and usual method of infant feeding in New York City.

  11. Fusion proteins of HIV-1 envelope glycoprotein gp120 with CD4-induced antibodies showed enhanced binding to CD4 and CD4 binding site antibodies

    SciTech Connect

    Chen, Weizao; Feng, Yang; Wang, Yanping; Zhu, Zhongyu; Dimitrov, Dimiter S.

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer Some recombinant HIV-1 gp120s do not preserve their conformations on gp140s. Black-Right-Pointing-Pointer We hypothesize that CD4i antibodies could induce conformational changes in gp120. Black-Right-Pointing-Pointer CD4i antibodies enhance binding of CD4 and CD4bs antibodies to gp120. Black-Right-Pointing-Pointer CD4i antibody-gp120 fusion proteins could have potential as vaccine immunogens. -- Abstract: Development of successful AIDS vaccine immunogens continues to be a major challenge. One of the mechanisms by which HIV-1 evades antibody-mediated neutralizing responses is the remarkable conformational flexibility of its envelope glycoprotein (Env) gp120. Some recombinant gp120s do not preserve their conformations on gp140s and functional viral spikes, and exhibit decreased recognition by CD4 and neutralizing antibodies. CD4 binding induces conformational changes in gp120 leading to exposure of the coreceptor-binding site (CoRbs). In this study, we test our hypothesis that CD4-induced (CD4i) antibodies, which target the CoRbs, could also induce conformational changes in gp120 leading to better exposed conserved neutralizing antibody epitopes including the CD4-binding site (CD4bs). We found that a mixture of CD4i antibodies with gp120 only weakly enhanced CD4 binding. However, such interactions in single-chain fusion proteins resulted in gp120 conformations which bound to CD4 and CD4bs antibodies better than the original or mutagenically stabilized gp120s. Moreover, the two molecules in the fusion proteins synergized with each other in neutralizing HIV-1. Therefore, fusion proteins of gp120 with CD4i antibodies could have potential as components of HIV-1 vaccines and inhibitors of HIV-1 entry, and could be used as reagents to explore the conformational flexibility of gp120 and mechanisms of entry and immune evasion.

  12. Apoptotic depletion of CD4+ T cells in idiopathic CD4+ T lymphocytopenia.

    PubMed Central

    Laurence, J; Mitra, D; Steiner, M; Lynch, D H; Siegal, F P; Staiano-Coico, L

    1996-01-01

    Progressive loss of CD4+ T lymphocytes, accompanied by opportunistic infections characteristic of the acquired immune deficiency syndrome, ahs been reported in the absence of any known etiology. The pathogenesis of this syndrome, a subset of idiopathic CD4+ T lymphocytopenia (ICL), is uncertain. We report that CD4+ T cells from seven of eight ICL patients underwent accelerated programmed cell death, a process facilitated by T cell receptor cross-linking. Apoptosis was associated with enhanced expression of Fas and Fas ligand in unstimulated cell populations, and partially inhibited by soluble anti-Fas mAb. In addition, apoptosis was suppressed by aurintricarboxylic acid, an inhibitor of calcium-dependent endonucleases and proteases, in cells from four of seven patients, The in vivo significance of these findings was supported by three factors: the absence of accelerated apoptosis in persons with stable, physiologic CD4 lymphopenia without clinical immune deficiency; detection of serum antihistone H2B autoantibodies, one consequence of DNA fragmentation, in some patients; and its selectivity, with apoptosis limited to the CD4 population in some, and occurring among CD8+ T cells predominantly in those individuals with marked depletion of both CD4+ T lymphocytes linked to clinical immune suppression have evidence for accelerated T cell apoptosis in vitro that may be pathophysiologic and amenable to therapy with apoptosis inhibitors. PMID:8609222

  13. Infant feeding practices in a poor district of Santo Domingo.

    PubMed

    Mclennan, J D; Spady, D W

    1994-01-01

    During August-December 1989, in the Dominican Republic, local health promoters interviewed 103 primary caretakers and took anthropometric measurements from 103 children aged 3 years and under during home visits in three poor neighborhoods of Los Alcarrizos (Alto de Chavon, Barrio Landia, and Pueblo Nuevo) to examine infant feeding practices. 95% of the mothers had started breast feeding. The median duration of breast feeding was 7.5 months. Almost 33% had quit breast feeding by 3 months. Perception of insufficient milk was the leading reason for early discontinuation of exclusive breast feeding. The local pharmacies in all three communities offered powdered milk. About 25% of mothers began using breast milk substitutes within the first week. A non-infant formula milk powder was the most commonly used breast milk substitute. 30% of mothers stored prepared milk for later feeds, as long as half a day. Only 13% of households had a refrigerator. The most frequently used first weaning foods were orange juice, lime juice, and beans. 76% of mothers had used or were currently using baby bottles. 95% of them reported washing the bottle in boiling water. The median age of introducing the baby bottle was 3 days. Only 44% of mother covered prepared food during storage. The most commonly eaten foods among children aged at least 1 year were milk, beans, rice, and citrus fruits. Yet the children did not eat all these foods daily. 18% of 1-2 year olds and 13% of 2-3 year olds did not eat meats and alternatives regularly. 7% of 1-2 year olds and 10% of 2-3 year olds did not eat fruits and vegetables regularly. 4% of 1-2 year olds and 3% of 2-3 year olds did not eat breads and cereals regularly. About 14% of all children were not consuming any milk at the time of the survey. These findings will be used to refine nutrition education programs in the district to make them more effective.

  14. CD4-Induced Antibodies Promote Association of the HIV-1 Envelope Glycoprotein with CD4-Binding Site Antibodies

    PubMed Central

    Fellinger, Christoph H.; Prasad, Neha R.; Zhou, Amber S.; Kondur, Hema R.; Joshi, Vinita R.; Quinlan, Brian D.; Farzan, Michael

    2016-01-01

    ABSTRACT The HIV-1 envelope glycoprotein (Env) is a trimer of gp120/gp41 heterodimers that mediates viral entry. Env binds cellular CD4, an association which stabilizes a conformation favorable to its subsequent association with a coreceptor, typically CCR5 or CXCR4. The CD4- and coreceptor-binding sites serve as epitopes for two classes of HIV-1-neutralizing antibodies: CD4-binding site (CD4bs) and CD4-induced (CD4i) antibodies, respectively. Here we observed that, at a fixed total concentration, mixtures of the CD4i antibodies (E51 or 412d) and the CD4bs antibody VRC01 neutralized the HIV-1 isolates 89.6, ADA, SG3, and SA32 more efficiently than either antibody alone. We found that E51, and to a lesser extent 412d and 17b, promoted association of four CD4bs antibodies to the Env trimer but not to monomeric gp120. We further demonstrated that the binding of the sulfotyrosine-binding pocket by CCR5mim2-Ig was sufficient for promoting CD4bs antibody binding to Env. Interestingly, the relationship is not reciprocal: CD4bs antibodies were not as efficient as CD4-Ig at promoting E51 or 412d binding to Env trimer. Consistent with these observations, CD4-Ig, but none of the CD4bs antibodies tested, substantially increased HIV-1 infection of a CD4-negative, CCR5-positive cell line. We conclude that the ability of CD4i antibodies to promote VRC01 association with Env trimers accounts for the increase potency of VRC01 and CD4i antibody mixtures. Our data further suggest that potent CD4bs antibodies avoid inducing Env conformations that bind CD4i antibodies or CCR5. IMPORTANCE Potent HIV-1-neutralizing antibodies can prevent viral transmission and suppress an ongoing infection. Here we show that CD4-induced (CD4i) antibodies, which recognize the conserved coreceptor-binding site of the HIV-1 envelope glycoprotein (Env), can increase the association of Env with potent broadly neutralizing antibodies that recognize the CD4-binding site (CD4bs antibodies). We further show that

  15. Relationships between parenting style, feeding style and feeding practices and fruit and vegetable consumption in early childhood.

    PubMed

    Blissett, Jackie

    2011-12-01

    Despite substantial evidence suggesting that a diet high in fruit and vegetables (FV) is associated with reduced risk of cancer, only 21% of children in the UK consume the recommended 5 portions of fruit or vegetables a day. This review examines the role of parenting style, feeding style and feeding practices in FV consumption in early childhood. Whilst inconsistencies in concepts and terminology cloud this literature, overall the evidence suggests that the context of an authoritative parenting and feeding style is associated with better FV consumption in the childhood years. This context is typified by emotional warmth but high expectations for children's dietary adequacy and behaviour, accompanied by specific feeding practices such as modeling consumption of FV, making FV available within the home, covertly restricting unhealthy alternative snack foods, and encouraging children to try FV. Further longitudinal and intervention studies are required to determine the efficacy of modification of parenting style and feeding practice on children's FV intake.

  16. Mothers' perceptions of the influences on their child feeding practices - A qualitative study.

    PubMed

    Spence, Alison C; Hesketh, Kylie D; Crawford, David A; Campbell, Karen J

    2016-10-01

    Children's diets are important determinants of their health, but typically do not meet recommendations. Parents' feeding practices, such as pressure or restriction, are important influences on child diets, but reasons why parents use particular feeding practices, and malleability of such practices, are not well understood. This qualitative study aimed to explore mothers' perceptions of influences on their feeding practices, and assess whether an intervention promoting recommended feeding practices was perceived as influential. The Melbourne Infant Feeding, Activity and Nutrition Trial (InFANT) Program was a cluster-randomised controlled trial involving 542 families aiming to improve child diets. Following the trial, when children were two years old, 81 intervention arm mothers were invited to participate in qualitative interviews, and 26 accepted (32%). Thematic analysis of interview transcripts used a tabular thematic framework. Eight major themes were identified regarding perceived influences on child feeding practices. Broadly these encompassed: practical considerations, family setting, formal information sources, parents' own upbringing, learning from friends and family, learning from child and experiences, and parents' beliefs about food and feeding. Additionally, the Melbourne InFANT Program was perceived by most respondents as influential. In particular, many mothers reported being previously unaware of some recommended feeding practices, and that learning and adopting those practices made child feeding easier. These findings suggest that a variety of influences impact mothers' child feeding practices. Health practitioners should consider these factors in providing feeding advice to parents, and researchers should consider these factors in planning interventions.

  17. Immune memory in CD4+ CD45RA+ T cells.

    PubMed Central

    Richards, D; Chapman, M D; Sasama, J; Lee, T H; Kemeny, D M

    1997-01-01

    This study addresses the question of whether human peripheral CD4+ CD45RA+ T cells possess antigen-specific immune memory. CD4+ CD45RA+ T cells were isolated by a combination of positive and negative selection. Putative CD4+ CD45RA+ cells expressed CD45RA (98.9%) and contained < 0.1% CD4+ CD45RO+ and < 0.5% CD4+ CD45RA+ CD45RO+ cells. Putative CD45RO+ cells expressed CD45RO (90%) and contained 9% CD45RA+ CD45RO+ and < 0.1% CD4+ CD45RA+ cells. The responder frequency of Dermatophagoides pteronyssinus-stimulated CD4+ CD45RA+ and CD4+ CD45RO+ T cells was determined in two atopic donors and found to be 1:11,314 and 1:8031 for CD4+ CD45RA+ and 1:1463 and 1:1408 for CD4+ CD45RO+ T cells. The responder frequencies of CD4+ CD45RA+ and CD4+ CD45RO+ T cells from two non-atopic, but exposed, donors were 1:78031 and 1:176,903 for CD4+ CD45RA+ and 1:9136 and 1:13,136 for CD4+ CD45RO+ T cells. T cells specific for D. pteronyssinus were cloned at limiting dilution following 10 days of bulk culture with D. pteronyssinus antigen. Sixty-eight clones were obtained from CD4+ CD45RO+ and 24 from CD4+ CD45RA+ T cells. All clones were CD3+ CD4+ CD45RO+ and proliferated in response to D. pteronyssinus antigens. Of 40 clones tested, none responded to Tubercule bacillus purified protein derivative (PPD). No difference was seen in the pattern of interleukin-4 (IL-4) or interferon-gamma (IFN-gamma) producing clones derived from CD4+ CD45RA+ and CD4+ CD45RO+ precursors, although freshly isolated and polyclonally activated CD4+ CD45RA+ T cells produced 20-30-fold lower levels of IL-4 and IFN-gamma than their CD4+ CD45RO+ counterparts. Sixty per cent of the clones used the same pool of V beta genes. These data support the hypothesis that immune memory resides in CD4+ CD45RA+ as well as CD4+ CD45RO+ T cells during the chronic immune response to inhaled antigen. PMID:9301520

  18. Interaction between the cytoplasmic domains of HIV-1 Vpu and CD4: role of Vpu residues involved in CD4 interaction and in vitro CD4 degradation.

    PubMed

    Margottin, F; Benichou, S; Durand, H; Richard, V; Liu, L X; Gomas, E; Benarous, R

    1996-09-15

    The Vpu and CD4 cytoplasmic domains were found, by using a two-hybrid assay in yeast, to interact in the absence of their membrane anchor domains. Studies on several deletion and point mutants revealed that the overall structure of the Vpu cytoplasmic domain is required for this interaction. The Vpu amino acid residues involved in the interaction with CD4 were identified. Deletion of the C-terminal residues of Vpu, required for CD4 degradation, as well as the double mutation on the casein kinase II phosphorylation sites S52N-S56N, also involved in CD4 degradation, resulted in the loss of interaction with CD4 and in the inability to induce CD4 degradation. These results suggest that the ability of Vpu to mediate the degradation of CD4 is linked to its capacity to physically interact with CD4. However, additional mutagenesis on the S52 site revealed that the interaction between the cytoplasmic domains of Vpu and CD4 is not sufficient for in vitro Vpu-mediated CD4 degradation.

  19. A qualitative systematic review of maternal infant feeding practices in transitioning from milk feeds to family foods.

    PubMed

    Harrison, Michelle; Brodribb, Wendy; Hepworth, Julie

    2016-10-03

    Evidence supports the establishment of healthy feeding practices early in life to promote lifelong healthy eating patterns protective against chronic disease such as obesity. Current early childhood obesity prevention interventions are built on extant understandings of how feeding practices relate to infant's cues of hunger and satiety. Further insights regarding factors that influence feeding behaviors in early life may improve program designs and outcomes. Four electronic databases were searched for peer-reviewed qualitative studies published between 2000 to 2014 with transitional infant feeding practice rationale from developed countries. Reporting transparency and potential bias was assessed using the Consolidated Criteria for Reporting Qualitative Research quality checklist. Thematic synthesis of 23 manuscripts identified three themes (and six sub-themes): Theme 1. Infant (physical cues and behavioural cues) focuses on the perceived signs of readiness to start solids and the feeding to influence growth and "health happiness." Theme 2. Mother (coping strategies and knowledge and skills) focuses on the early survival of the infant and the family and the feeding to satisfy hunger and influence infant contentment, and sleep. Theme 3. Community (pressure and inconsistent advice) highlights the importance of generational feeding and how conflicting feeding advice led many mothers to adopt valued familial or culturally established practices. Overall, mothers were pivotal to feeding decisions. Satisfying infant's needs to reach "good mothering" status as measured by societal expectations was highly valued but lacked consideration of nutrition, obesity, and long term health. Maternal interpretation of healthy infant feeding and successful parenting need attention when developing strategies to support new families.

  20. Infant feeding practices and breastfeeding duration in Japan: A review

    PubMed Central

    2012-01-01

    The Japanese health system places great emphasis on healthy development. However, the prevalence of Exclusive Breastfeeding at one month postpartum between 1980 and 2005 has remained unchanged, fluctuating between 42% and 49%. At the same time, the Any Breastfeeding prevalence has gradually increased from about 80% to 95%. In 2010, the latest national breastfeeding report showed that ‘exclusive’ and ‘any’ breastfeeding rates have improved. However, as the World Health Organization (WHO) definition of breastfeeding practices was not used in this study or in other national surveys, it is difficult to interpret these latest results. While the Japanese government has launched several promotion projects, there have been few studies and reviews of risk factors that influence breastfeeding duration. The objectives of this review were to summarise the factors that have influenced the duration of breastfeeding in Japan to provide information relevant to breastfeeding promotion programs. A search of electronic databases in Japanese and English was undertaken up to 2011. The inclusion criteria for this review were studies that focused on infant feeding practices and targeted Japanese mothers, fathers, or health professionals, but excluded mothers’ friends and peer groups. In total, 12 articles were selected for the final analysis. Smoking status, low birth weight of infants and maternal perceptions of insufficient breast milk supply were negative influences on breastfeeding duration, while support from husbands/partners is associated with continued breastfeeding. Some factors that have been found to be associated with breastfeeding in other countries, including maternal age, family income, maternal educational levels, and living with grandparents of infants have not been confirmed in Japan. While the national breastfeeding rates were higher than other countries of similar health status, inconsistent knowledge of breastfeeding benefits and inappropriate hospital

  1. Antibody raised against soluble CD4-rgp120 complex recognizes the CD4 moiety and blocks membrane fusion without inhibiting CD4-gp120 binding

    PubMed Central

    1990-01-01

    We studied the humoral response of mice immunized with soluble CD4- rgp120 complex, testing polyclonal and monoclonal antibodies (mAbs) with the aim of identifying molecular changes that take place after the first interaction between human immunodeficiency virus and the cell surface. The antisera had a paradoxically high syncytia-blocking titer associated with anti-CD4 specificity, while their capacity to inhibit CD4-gp120 binding was relatively modest. One of the mAbs produced from these responders blocks syncytia formation but does not inhibit CD4 interaction with gp120. Apparently, this mAb interacts with the CD4 moiety of CD4-gp120 complex and prevents a post-binding event necessary for membrane fusion and viral infection. PMID:2212945

  2. Enteral feeding in prostaglandin-dependent neonates: is it a safe practice?

    PubMed

    Willis, Lisa; Thureen, Patti; Kaufman, Jonathan; Wymore, Erica; Skillman, Heather; da Cruz, Eduardo

    2008-12-01

    In many centers presurgical term neonates with prostaglandin-dependent cardiac lesions experience nutritional deficiency because of postponed enteral feeds. We recently adopted early enteral feeding in these infants. This retrospective study demonstrates feeding tolerance in 33 of 34 neonates fed enterally while receiving prostaglandin, suggesting the safety of this practice.

  3. Influence of maternal feeding goals and practices on children's eating behaviors.

    PubMed

    Hoffmann, Debra A; Marx, Jenna M; Kiefner-Burmeister, Allison; Musher-Eizenman, Dara R

    2016-12-01

    Parents are highly influential in shaping their children's dietary habits. This study examined whether negative feeding practices mediated the relationship between feeding goals (health and convenience) and children's eating behaviors. One hundred ninety-two mothers (mean age = 34.2; mean BMI = 27.0) of 7-11 year old children participated via Amazon's Mechanical Turk. Results showed that negative feeding practices fully mediated the relationship between convenience feeding goals and children's eating behaviors (goals to healthy/unhealthy eating behaviors: β = -0.08/.09, n.s.; goals to feeding practices: β = 0.27, p < 0.01; feeding practices to healthy/unhealthy eating behaviors: β = -0.57/.48, p < 0.05). On the other hand, negative feeding practices did not fully mediate the relationship between health feeding goals and children's eating behaviors (goals to healthy/unhealthy eating behaviors: β = 0.66/-0.29, p < 0.01; goals to feeding practices: β = -0.28, p < 0.001; feeding practices to healthy/unhealthy eating behaviors: β = -0.26/.44, p < 0.05). In other words, children whose mothers emphasized health goals consumed more healthy food and less unhealthy food, above and beyond the use of negative feeding practices. Because parents are on the front lines of shaping children's eating habits, understanding the best point of intervention for parents (e.g., shaping parents' goals, changing parents' feeding practices) might be especially fruitful, considering that childhood obesity has become a global public health crisis and energy intake is one of the key factors contributing to this problem.

  4. A rapid manual method for CD4+ T-cell quantitation for use in developing countries.

    PubMed

    Landay, A; Ho, J L; Hom, D; Russell, T; Zwerner, R; Minuty, J G; Kataaha, P; Mmiro, F; Jackson, B

    1993-12-01

    Clinicians took blood samples from 294 HIV-1 seropositive patients and 88 HIV-1 seronegative patients at Cornell University Medical College and The New York Hospital in New York City, Rush-Presbyterian-St. Luke's Medical Center in Chicago, and Makerere University Medical school in Kampala, Uganda, to assess a manual method's (Cytosphere) ability to accurately determine the CD4+ T-cell count. The Cytosphere assay uses latex beads coated with CD4 antibody which are combined with anticoagulated whole blood followed by red cell lysis. A hemacytometer then counts the bead-coated cells. The average technologist only needs 1-3 days of training (20 CD4 practice assays/days) in the Cytosphere assay. The minimal equipment required for the assay are a pipette, a hemacytometer, and a light microscope. The lysing agent inactivates HIV-1. The overall correlation between the standard flow cytometry method and the Cytosphere assay stood at 0.912 and was significant (p .001). When the researchers stratified the samples based on CD4+ T-cell counts defined by flow cytometry, the predictive values of the Cytosphere assay for correctly identifying patients with CD4 T-cell counts greater or less than 200 x 1 million/1 were 96% and 92%, respectively. These findings suggested that the Cytosphere assay has the potential to quantify CD4 cells in the limited laboratories in developing countries. Larger longitudinal studies of HIV seropositive people in developing countries are needed to test the reliability and reproducibility of the assay.

  5. Child feeding practices and overweight status among Mexican immigrant families.

    PubMed

    Vera-Becerra, Luz Elvia; Lopez, Martha L; Kaiser, Lucia L

    2015-04-01

    The purpose was to compare maternal perceptions, feeding practices, and overweight status of children in immigrant households in California (US) with a cohort in Guanajuato, Mexico (MX). In 2006, staff interviewed mothers and weighed and measured their children, 1-6 years (US: n = 95 and MX: n = 200). Prevalence of overweight [body mass index z-score (BMIZ) >1.0 and <1.65] and obesity (BMIZ > 1.65) was 21.1 and 28.4% in the US respectively, compared to 11.5 and 12.9% in MX (p < 0.001). No differences were observed in maternal ability to identify correctly the child's weight status or ever being told the child was overweight. US children ate away from home more often (p < 0.0001), had fewer family meals (p < 0.0001), and played outdoors less often than MX children (p < 0.0002). Further analyses should examine how differences in eating and activity patterns explain the disparity in childhood obesity across the countries.

  6. CD4-binding site alterations in CCR5-using HIV-1 envelopes influencing gp120-CD4 interactions and fusogenicity

    SciTech Connect

    Sterjovski, Jasminka; Churchill, Melissa J.; Roche, Michael; Ellett, Anne; Farrugia, William; Wesselingh, Steven L.; Cunningham, Anthony L.; Ramsland, Paul A.; Gorry, Paul R.

    2011-02-20

    CD4-binding site (CD4bs) alterations in gp120 contribute to different pathophysiological phenotypes of CCR5-using (R5) HIV-1 strains, but the potential structural basis is unknown. Here, we characterized functionally diverse R5 envelope (Env) clones (n = 16) to elucidate potential structural alterations within the gp120 CD4bs that influence Env function. Initially, we showed that the magnitude of gp120-CD4-binding correlates with increased fusogenicity and reduced CD4 dependence. Analysis of three-dimensional gp120 structural models revealed two CD4bs variants, D279 and N362, that were associated with reduced CD4 dependence. Further structural analysis showed that a wider aperture of the predicted CD4bs cavity, as constrained by the inner-most atoms at the gp120 V1V2 stem and the V5 loop, was associated with amino acid alterations within V5 and correlated with increased gp120-CD4 binding and increased fusogenicity. Our results provide evidence that the gp120 V5 loop may alter CD4bs conformation and contribute to increased gp120-CD4 interactions and Env fusogenicity.

  7. CD4 aptamer-RORγt shRNA chimera inhibits IL-17 synthesis by human CD4(+) T cells.

    PubMed

    Song, Pingfang; Chou, Yuan K; Zhang, Xiaowei; Meza-Romero, Roberto; Yomogida, Kentaro; Benedek, Gil; Chu, Cong-Qiu

    2014-10-03

    Cell type specific delivery of RNAi to T cells has remained to be a challenge. Here we describe an aptamer mediated delivery of shRNA to CD4(+) T cells targeting RORγt to suppress Th17 cells. A cDNA encoding CD4 aptamer and RORγt shRNA was constructed and the chimeric CD4 aptamer-RORγt shRNA (CD4-AshR-RORγt) was generated using in vitro T7 RNA transcription. 2'-F-dCTP and 2'-F-dUTP were incorporated into CD4-AshR-RORγt for RNase resistance. CD4-AshR-RORγt was specifically uptaken by CD4(+) Karpas 299 cells and primary human CD4(+) T cells. The RORγt shRNA moiety of CD4-AshR-RORγt chimera was cleaved and released by Dicer. Furthermore, CD4-AshR-RORγt suppressed RORγt gene expression in Karpas 299 cells and CD4(+) T cells and consequently inhibited Th17 cell differentiation and IL-17 production. These results demonstrate that aptamer-facilitated cell specific delivery of shRNA represents a novel approach for efficient RNAi delivery and is potentially to be developed for therapeutics targeting specific T cells subtypes.

  8. Parental feeding practices in Mexican American families: Initial test of an expanded measure

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although obesity rates are high among Latino children, relatively few studies of parental feeding practices have examined Latino families as a separate group. Culturally-based approaches to measurement development can begin to identify parental feeding practices in specific cultural groups. This stu...

  9. Retrospective reports of child feeding practices, current eating behaviors, and BMI in college students.

    PubMed

    Galloway, Amy T; Farrow, Claire V; Martz, Denise M

    2010-07-01

    Research concerning child feeding practices has focused on children and adolescents, and little is known about how feeding practices used in childhood relate to eating behaviors and weight status in early adulthood. We assessed college students' and their parents' retrospective reports of child feeding practices used when the students were in middle childhood. We also assessed the college students' current reports of their eating behaviors using the Dutch Eating Behavior Questionnaire (DEBQ) and the Intuitive Eating Scale (IES), and measured their current BMI. Results showed that college students' and their parents' reports about previous parental use of child feeding practices were not correlated. Parent reports of their own use of child feeding practices were more related to students' eating behaviors and BMI than were students' recollections about feeding practices used by their parents. An analysis of gender effects showed that there were positive correlations between parental child feeding practices, BMI, and emotional eating for female students. These relationships did not exist for male students. The results suggest that child feeding practices recollected by parents are linked to the development of emotional eating and weight status of women in early adulthood.

  10. Feeding practices of low-income mothers: How do they compare to current recommendations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Despite a growing consensus on the feeding practices associated with healthy eating patterns, few observational studies of maternal feeding practices with young children have been conducted, especially in low-income populations. The aim of this study was to provide such data on a low income sample t...

  11. Recommended Feeding and Dietary Practices To Improve Infant and Maternal Nutrition.

    ERIC Educational Resources Information Center

    Academy for Educational Development, Washington, DC.

    The LINKAGES Project is intended to improve breastfeeding and related complementary feeding and maternal dietary practices. The project, in consultation with technical experts and program managers, identified a set of recommended feeding and dietary practices intended to break the cycle of poor health and nutrition that passes from generation to…

  12. Virions of primary human immunodeficiency virus type 1 isolates resistant to soluble CD4 (sCD4) neutralization differ in sCD4 binding and glycoprotein gp120 retention from sCD4-sensitive isolates.

    PubMed Central

    Moore, J P; McKeating, J A; Huang, Y X; Ashkenazi, A; Ho, D D

    1992-01-01

    Primary isolates of human immunodeficiency virus type 1 (HIV-1) are much less sensitive to neutralization by soluble CD4 (sCD4) and sCD4-immunoglobulin (Ig) chimeras (CD4-IgG) than are HIV-1 strains adapted to growth in cell culture. We demonstrated that there are significant reductions (10- to 30-fold) in the binding of sCD4 and CD4-IgG to intact virions of five primary isolates compared with sCD4-sensitive, cell culture-adapted isolates RF and IIIB. However, soluble envelope glycoproteins (gp120) derived from the primary isolate virions, directly by detergent solubilization or indirectly by recombinant DNA technology, differed in affinity from RF and IIIB gp120 by only one- to threefold. The reduced binding of sCD4 to these primary isolate virions must therefore be a consequence of the tertiary or quaternary structure of the envelope glycoproteins in their native, oligomeric form on the viral surface. In addition, the rate and extent of sCD4-induced gp120 shedding from these primary isolates was lower than that from RF. We suggest that reduced sCD4 binding and increased gp120 retention together account for the relative resistance of these primary isolates to neutralization by sCD4 and CD4-IgG and that virions of different HIV-1 isolates vary both in the mechanism of sCD4 binding and in subsequent conformational changes in their envelope glycoproteins. PMID:1727487

  13. Feeding Challenges in Young Children: Toward a Best Practices Model

    ERIC Educational Resources Information Center

    Bruns, Deborah A.; Thompson, Stacy D.

    2010-01-01

    Young children often encounter feeding challenges, such as food refusal, an inability to meet nutritional needs, and limited skills to self-feed. Further, overall development can be adversely affected when an infant or a toddler has difficulties with intake of fluid and solid foods. A variety of strategies are available to address these challenges…

  14. Feeding of young children during diarrhea: caregivers' intended practices and perceptions.

    PubMed

    Pantenburg, Birte; Ochoa, Theresa J; Ecker, Lucie; Ruiz, Joaquim

    2014-09-01

    Childhood diarrhea is an important cause of malnutrition, which can be worsened when caretakers limit nutritional support. We queried 390 caregivers and their children in a peri-urban community in Lima, Peru regarding general perceptions of feeding and feeding practices during diarrhea. Overall, 22.1% of caregivers perceived feeding during diarrhea to be harmful. At baseline, 71.9% of caregivers would discontinue normal feeding or give less food. Most would withhold milk, eggs, and meats. Approximately 40% of caregivers would withhold vegetables and fruits. A pilot educational intervention was performed to improve feeding during diarrhea. At follow-up survey 3 months later, none of the caregivers would recommend withholding food. Only 23.2% would recommend discontinuing normal feeding and 1.8% perceived food to be damaging. Misperceptions of the role of feeding during diarrhea pose a significant health risk for children, but a simple educational intervention might have a major impact on these perceptions and practices.

  15. Food avoidance in children. The influence of maternal feeding practices and behaviours.

    PubMed

    Powell, Faye C; Farrow, Claire V; Meyer, Caroline

    2011-12-01

    The aim of this study was to examine the contribution of a broad range of maternal feeding practices in predicting parental reports of food avoidance eating behaviours in young children, after controlling for child temperament, and maternal dietary restraint which have previously been associated with feeding problems. One hundred and four mothers of children aged between 3 and 6 years completed self report measures of their child's eating behaviour and temperament, maternal dietary restraint and child feeding practices. Maternal reports of food avoidance eating behaviours were associated with an emotional child temperament, high levels of maternal feeding control, using food for behaviour regulation and low encouragement of a balanced and varied food intake. Maternal feeding practices, predominantly pressure to eat, significantly predicted food avoidance eating behaviours after controlling for child emotionality and maternal dietary restraint. The significant contribution of maternal feeding practices, which are potentially modifiable behaviours, suggests that the feeding interactions of parents and their children should be targeted for intervention and the prevention of feeding difficulties during early childhood. Future research should continue to explore how a broader range of feeding practices, particular those that may be more adaptive, might influence child eating behaviour.

  16. Obstetric and infant feeding practices in Punjab: effect of educational intervention.

    PubMed

    Gupta, A; Gupta, R

    1992-03-01

    A survey of obstetric and infant feeding practices in 100 mothers showed that only 17% infants were exclusively breast fed. Antenatal advice regarding breast feeding was given to only 13%. Sixty eight per cent infants were put to breast 24 hours after delivery. Campaign against bottle feeding was then launched. Fifteen months later, a survey on another 100 mothers showed that 44% infants were exclusively breast-fed, antenatal advice was given to 11% mothers and 60% mothers got active postnatal advice regarding disadvantages of bottle feeds. Incidence of exclusive breast feeding was more in infants who were roomed-in with the mother early, started on breast feeding earlier and whose mothers received antenatal advice. It was concluded that even if the percentage of antenatal advice did not improve, active postnatal campaign directed towards dangers of bottle feeding could increase the prevalence of exclusive breast feeding.

  17. Making the literature palatable at the bedside: Reference poster promotes oral feeding best practice.

    PubMed

    Lasby, Karen; Dressler-Mund, Donna

    2011-02-01

    Neonatal nurses often draw upon prior experiences and intuition to feed neonates. Such experience and skill vary from nurse to nurse and may not be based on recent research, nor tailored to each neonate's feeding skill. An evidence-based neonatal oral feeding guideline was produced to improve oral feeding practices among nurses and parents. The implementation was initially less than ideal, resulting in poor compliance. A bedside reference poster was designed to serve as a visual succinct reminder of the oral feeding guideline.

  18. Range of CD4-Bound Conformations of HIV-1 gp120, as Defined Using Conditional CD4-Induced Antibodies

    PubMed Central

    Kaplan, Gilad; Roitburd-Berman, Anna; Lewis, George K.

    2016-01-01

    ABSTRACT The HIV envelope binds cellular CD4 and undergoes a range of conformational changes that lead to membrane fusion and delivery of the viral nucleocapsid into the cellular cytoplasm. This binding to CD4 reveals cryptic and highly conserved epitopes, the molecular nature of which is still not fully understood. The atomic structures of CD4 complexed with gp120 core molecules (a form of gp120 in which the V1, V2, and V3 loops and N and C termini have been truncated) have indicated that a hallmark feature of the CD4-bound conformation is the bridging sheet minidomain. Variations in the orientation of the bridging sheet hairpins have been revealed when CD4-liganded gp120 was compared to CD4-unliganded trimeric envelope structures. Hence, there appears to be a number of conformational transitions possible in HIV-1 monomeric gp120 that are affected by CD4 binding. The spectrum of CD4-bound conformations has been interrogated in this study by using a well-characterized panel of conditional, CD4-induced (CD4i) monoclonal antibodies (MAbs) that bind HIV-1 gp120 and its mutations under various conditions. Two distinct CD4i epitopes of the outer domain were studied: the first comprises the bridging sheet, while the second contains elements of the V2 loop. Furthermore, we show that the unliganded extended monomeric core of gp120 (coree) assumes an intermediate CD4i conformation in solution that further undergoes detectable rearrangements upon association with CD4. These discoveries impact both accepted paradigms concerning gp120 structure and the field of HIV immunogen design. IMPORTANCE Elucidation of the conformational transitions that the HIV-1 envelope protein undergoes during the course of entry into CD4+ cells is fundamental to our understanding of HIV biology. The binding of CD4 triggers a range of gp120 structural rearrangements that could present targets for future drug design and development of preventive vaccines. Here we have systematically interrogated and

  19. Intergenerational impact of maternal obesity and postnatal feeding practices on pediatric obesity

    PubMed Central

    Thompson, Amanda L.

    2014-01-01

    The postnatal feeding practices of obese and overweight mothers may place their children at particular risk for the development of obesity through shared biology and family environments. This paper reviews the feeding practices of obese mothers, describes potential mechanisms linking maternal feeding behaviors to child obesity risk, and highlights potential avenues for intervention. This review documents that supporting breastfeeding, improving the food choices of obese women, and encouraging the development of feeding styles that are responsive to hunger and satiety cues are important for improving the quality of the eating environment and preventing the intergenerational transmission of obesity. PMID:24147925

  20. Associations between herd-level feeding management practices, feed sorting, and milk production in freestall dairy farms.

    PubMed

    Sova, A D; LeBlanc, S J; McBride, B W; DeVries, T J

    2013-07-01

    The challenges associated with group-housed dairy cows include within-herd variability in nutrient consumption and milk production, which may be related to feeding management. The objective of this observational study was to examine the association of herd-level feeding management factors, feed sorting, and milk production. Twenty-two freestall herds with an average lactating herd size of 162±118 cows, feeding total mixed rations, were each studied for 7 consecutive days in summer and winter. In cases of multiple feeding groups within a herd, the highest producing group of cows with an even distribution of days in milk and parity was selected for this study. The average group size studied was 83±31 cows. The average study group consisted of cows 187±47 days in milk, with a parity of 2.3±0.6, consuming 24.3±2.6kg of dry matter, with an average group-level yield of 34.3±6kg of milk/d, 3.7±0.3% milk fat, and 3.2±0.18% milk protein. Milk production parameters, including yield, fat, and protein, were recorded through regular Dairy Herd Improvement milk testing. A survey of feeding management practices and barn characteristics was administered on each farm. The amounts of feed offered and refused were recorded and sampled daily to assess dry matter intake (DMI) and particle size distribution. Feeding twice per day compared with once per day was associated with an average increase of 1.42kg of DMI, 2.0kg of milk yield, and less sorting against long ration particles (>19mm). Every 2% group-level selective refusal (sorting) of long particles was associated with 1kg/d of reduction in milk yield. A 10cm/cow increase in feed bunk space was associated with a 0.06-percentage-point increase in group-average milk fat and a 13% decrease in group-average somatic cell count. These results support that herd-level management practices to promote feed access, such as increased feeding frequency and bunk space, may improve DMI and promote more balanced nutrient intake and greater

  1. Administration of interleukin-7 increases CD4 T cells in idiopathic CD4 lymphocytopenia

    PubMed Central

    Porter, Brian O.; DerSimonian, Rebecca; Kovacs, Stephen B.; Thompson, William L.; Perez-Diez, Ainhoa; Freeman, Alexandra F.; Roby, Gregg; Mican, JoAnn; Pau, Alice; Rupert, Adam; Adelsberger, Joseph; Higgins, Jeanette; Bourgeois, Jeffrey S.; Jensen, Stig M. R.; Morcock, David R.; Burbelo, Peter D.; Osnos, Leah; Maric, Irina; Natarajan, Ven; Croughs, Therese; Yao, Michael D.; Estes, Jacob D.; Sereti, Irini

    2016-01-01

    Idiopathic CD4 lymphopenia (ICL) is a rare syndrome defined by low CD4 T-cell counts (<300/µL) without evidence of HIV infection or other known cause of immunodeficiency. ICL confers an increased risk of opportunistic infections and has no established treatment. Interleukin-7 (IL-7) is fundamental for thymopoiesis, T-cell homeostasis, and survival of mature T cells, which provides a rationale for its potential use as an immunotherapeutic agent for ICL. We performed an open-label phase 1/2A dose-escalation trial of 3 subcutaneous doses of recombinant human IL-7 (rhIL-7) per week in patients with ICL who were at risk of disease progression. The primary objectives of the study were to assess safety and the immunomodulatory effects of rhIL-7 in ICL patients. Injection site reactions were the most frequently reported adverse events. One patient experienced a hypersensitivity reaction and developed non-neutralizing anti-IL-7 antibodies. Patients with autoimmune diseases that required systemic therapy at screening were excluded from the study; however, 1 participant developed systemic lupus erythematosus while on study and was excluded from further rhIL-7 dosing. Quantitatively, rhIL-7 led to an increase in the number of circulating CD4 and CD8 T cells and tissue-resident CD3 T cells in the gut mucosa and bone marrow. Functionally, these T cells were capable of producing cytokines after mitogenic stimulation. rhIL-7 was well tolerated at biologically active doses and may represent a promising therapeutic intervention in ICL. This trial was registered at www.clinicaltrials.gov as #NCT00839436. PMID:26675348

  2. A Cultural Understanding of Chinese Immigrant Mothers’ Feeding Practices: A Qualitative Study

    PubMed Central

    Zhou, Nan; Cheah, Charissa S. L.; Van Hook, Jennifer; Thompson, Darcy A.; Jones, Shelby S.

    2015-01-01

    Differences in parental feeding practices revealed across and within different ethnic/ cultural groups indicate that cultural examinations of feeding practices in understudied non-European-American populations require urgent attention. China ranks as the second largest source country for children in foreign-born U.S. households. Contrary to the stereotype of slender Asians, Chinese-American young children are at high risk for obesity but have not received sufficient attention from researchers and practitioners dealing with parental feeding practices and childhood obesity. The present study aimed to understand food-related parenting practices among Chinese immigrants in the U.S. using qualitative focus groups. Twenty-two mothers with preschool aged children participated in a discussion regarding parent-child food-related interactions and feeding practices. A thematic approach was adopted to analyze the focus group data following five stages of framework analysis. Thirteen key themes of feeding practices were identified, including 9 that are in existing feeding measures (pre-exiting practices) and 4 practices that have not been documented or emphasized in previous feeding measures (culturally-emphasized practices), including regulating healthy routines and food energy, spoon-feeding, using social comparison to pressure the child to eat, and making an effort to prepare/cook specific foods. Through the use of an emic approach and meaning-centered evidence, the complexities of parent-child interactions and unique nuances of parental feeding in this understudied population were revealed. Our findings can guide future development of culturally-appropriate measurement and inform intervention programs to promote the healthy development of Chinese-American children. PMID:25555536

  3. A cultural understanding of Chinese immigrant mothers' feeding practices. A qualitative study.

    PubMed

    Zhou, Nan; Cheah, Charissa S L; Van Hook, Jennifer; Thompson, Darcy A; Jones, Shelby S

    2015-04-01

    Differences in parental feeding practices revealed across and within different ethnic/cultural groups indicate that cultural examinations of feeding practices in understudied non-European-American populations require urgent attention. China ranks as the second largest source country for children in foreign-born U.S. households. Contrary to the stereotype of slender Asians, Chinese-American young children are at high risk for obesity but have not received sufficient attention from researchers and practitioners dealing with parental feeding practices and childhood obesity. The present study aimed to understand food-related parenting practices among Chinese immigrants in the U.S. using qualitative focus groups. Twenty-two mothers with preschool aged children participated in a discussion regarding parent-child food-related interactions and feeding practices. A thematic approach was adopted to analyze the focus group data following five stages of framework analysis. Thirteen key themes of feeding practices were identified, including 9 that are in existing feeding measures (pre-exiting practices) and 4 practices that have not been documented or emphasized in previous feeding measures (culturally-emphasized practices), including regulating healthy routines and food energy, spoon-feeding, using social comparison to pressure the child to eat, and making an effort to prepare/cook specific foods. Through the use of an emic approach and meaning-centered evidence, the complexities of parent-child interactions and unique nuances of parental feeding in this understudied population were revealed. Our findings can guide future development of culturally-appropriate measurement and inform intervention programs to promote the healthy development of Chinese-American children.

  4. Assessment of feed resources, feeding practices and coping strategies to feed scarcity by smallholder urban dairy producers in Jimma town, Ethiopia.

    PubMed

    Duguma, Belay; Janssens, Geert Paul Jules

    2016-01-01

    Smallholder dairy production is increasingly becoming popular in Jimma town. However, feed shortage is a major constraint to dairy production. The objectives of this study was to assess feed resources, feeding practices and farmers' perceived causes of feed shortage and coping strategies to feed scarcity in smallholder dairy producers in Jimma town, Oromia Regional State, Ethiopia. A total of 54 randomly selected dairy farmers were interviewed using a pre-tested structured questionnaire and through direct observations. Twenty major feed types used by dairy farmers were identified and categorized into five classes: natural pasture grazing, green feeds, hay, concentrate (commercial mix and agro-industrial by-products) and non-conventional feed resources. Green feeds-fresh or succulent grasses and legumes (mean rank = 0.361), concentrate (0.256), hay (0.198), non-conventional feeds (0.115) and natural pasture grazing (0.070) were ranked as the main feed resources in that order of importance. Green feed (94.4 % of the respondents) was found to be the main basal diet of dairy cattle. Overall, wheat bran (85.2 % of the respondents), commercial concentrate (55.6 %), noug (Guizotia abyssinica) cake (20.4 %), cotton seed cake (7.4 %) and molasses (7.4 %) were the main concentrate supplements used (P > 0.05). Local brew waste (attela) (77.8 % of the respondents), bean and pea hulls (42.6 %) enset (Ensete ventricosum) leaf and pseudo-stem (37 %), sugarcane tops (33.3 %), banana leaf and stem/stover (16.7 %) and papaya stem (16.7 %) were the dominant non-conventional feed resources in the surveyed area (P > 0.05). About 79.6, 7.4, 1.9 and 11.1 % of the farmers used zero-, semi-zero-, and the combination of zero- and semi-zero- and free-grazing systems, respectively. Most farmers (90.7 %) offered concentrate supplements to milking cows. However, supplementation did not consider milk yield, physiological status and condition of cows. All the farmers (100

  5. Pattern and determinants of breast feeding and contraceptive practices among mothers within six months postpartum.

    PubMed

    Kunwar, Shipra; Faridi, Mohammad M A; Singh, Shivani; Zahra, Fatima; Alizaidi, Zeashan

    2010-08-01

    The present study aims to determine the patterns of breast feeding, return of menstruation, and contraceptive practices in the first six months postpartum in women visiting the outpatient department at a teaching hospital in Lucknow, Northern India. Mothers of infants between six to eight months of age visiting the outpatient department of Era's Lucknow Medical College were interviewed regarding breast feeding practices, return of menstruation, sexual activity, and contraceptive practices within the first six months postpartum using a structured questionnaire. Of all women interviewed only 75.8% practiced exclusive breast feeding with the mean duration of exclusive breast feeding (EBF) being 3.5 months with only 41% practicing EBF for six months, 28% were sexually active within six weeks postpartum, 64.5% women had a return of menstruation within six months. Contraception was practiced by only 54.4% women with a barrier method such as a condom, being the most common. Better education was the only factor significantly affecting EBF (p < 0.004) and use of contraception (p < 0.027). There were a total of 10 pregnancies within six months postpartum. In conclusion, optimal breast feeding practices are poor in this part of the country and lactational amenorrhoea cannot be effectively and reliably used as a method of contraception. Therefore, optimal breast feeding practices, timely introduction of contraception and institutional delivery need to be encouraged.

  6. The problem of suboptimal complementary feeding practices in West Africa: what is the way forward?

    PubMed

    Issaka, Abukari I; Agho, Kingsley E; Page, Andrew N; Burns, Penelope L; Stevens, Garry J; Dibley, Michael J

    2015-10-01

    The objective of this paper was to review the policy implications of inadequate complementary feeding among children aged 6-23 months in West Africa. The review was undertaken from the initial results and findings from a series of studies on the comparison of complementary feeding indicators among children aged 6-23 months in four anglophone and seven francophone West African countries. It also examined a study of the determinants of suboptimal complementary feeding practices among children aged 6-23 months in those countries. Among the four complementary feeding indicators, it was only the introduction of solid, semi-solid or soft foods that was adequate among children in all the West African countries surveyed. The rates of the other complementary feeding indicators were found to be inadequate in all countries surveyed, although relatively better among children in the anglophone countries. Alarmingly, low rates of minimum acceptable diet were reported among children from both the anglophone and the francophone countries. Infants 6-11 months of age, children living in poor households, administrative/geographical regional differences and mothers' access to the media were some of the common risk factors for optimal complementary feeding practices in these countries. Assessing complementary feeding indicators and determinants of suboptimal complementary feeding practices in these West African countries is crucial to improving infant and young child feeding practices. It is recommended that governments and stakeholders of the West African countries studied make greater efforts to improve these critical practices in order to reduce child morbidity and mortality in the West Africa sub-region. Intervention studies on complementary feeding should target those socio-demographic factors that pose risks to optimal complementary feeding.

  7. Primary Human Mammary Epithelial Cells Endocytose HIV-1 and Facilitate Viral Infection of CD4+ T Lymphocytes ▿

    PubMed Central

    Dorosko, Stephanie M.; Connor, Ruth I.

    2010-01-01

    The contribution of mammary epithelial cells (MEC) to human immunodeficiency virus type 1 (HIV-1) in breast milk remains largely unknown. While breast milk contains CD4+ cells throughout the breast-feeding period, it is not known whether MEC directly support HIV-1 infection or facilitate infection of CD4+ cells in the breast compartment. This study evaluated primary human MEC for direct infection with HIV-1 and for indirect transfer of infection to CD4+ target cells. Primary human MEC were isolated and assessed for expression of HIV-1 receptors. MEC were exposed to CCR5-, CXCR4- and dual-tropic strains of HIV-1 and evaluated for viral reverse transcription and integration and productive viral infection. MEC were also tested for the ability to transfer HIV to CD4+ target cells and to activate resting CD4+ T cells. Our results demonstrate that MEC express HIV-1 receptor proteins CD4, CCR5, CXCR4, and galactosyl ceramide (GalCer). While no evidence for direct infection of MEC was found, HIV-1 virions were observed in MEC endosomal compartments. Coculture of HIV-exposed MEC resulted in productive infection of activated CD4+ T cells. In addition, MEC secretions increased HIV-1 replication and proliferation of infected target cells. Overall, our results indicate that MEC are capable of endosomal uptake of HIV-1 and can facilitate virus infection and replication in CD4+ target cells. These findings suggest that MEC may serve as a viral reservoir for HIV-1 and may enhance infection of CD4+ T lymphocytes in vivo. PMID:20702626

  8. CD4 cell count and CD4/CD8 ratio increase during rituximab maintenance in granulomatosis with polyangiitis patients

    PubMed Central

    Nossent, Johannes C.

    2016-01-01

    Introduction Rituximab (RTX) is a B cell-depleting agent approved for the treatment of granulomatosis with polyangiitis (GPA). RTX reduces antibody producing precursor plasma cells and inhibits B and T cells interaction. Infections related to T cell immunodeficiency are not infrequent during RTX treatment. Our study investigated CD4 cell count and CD4/CD8 ratio in GPA patients during the first two years of long-term RTX treatment. Methods A single centre cohort study of 35 patients who received median total cumulative dose of cyclophosphamide (CYC) of 15 g and were treated with RTX 2 g followed by retreatment with either 2 g once annually or 1 g biannually. Serum levels of total immunoglobulin (Ig) and lymphocytes subsets were recorded at RTX initiation and at 3, 6, 12, 18 and 24 months. Low CD4 count and inverted CD4/CD8 ratio were defined as CD4 < 0.3 × 109/l and ratio < 1. Results The CD4 cell count and CD4/CD8 ratio decreased slightly following the initial RTX treatment and then increased gradually during maintenance treatment. While the proportion of patients with low CD4 cell count decreased from 43% at baseline to 18% at 24 months, the ratio remained inverted in 40%. Oral daily prednisolone dose at baseline, CYC exposure and the maintenance regimen did not influence the CD4 cell count and ratio. Being older (p = 0.012) and having a higher CRP (p = 0.044) and ESR (p = 0.024) at baseline significantly increased the risk of inverted CD4/CD8 ratio at 24 months. Inverted ratio at baseline associated with lower total Ig levels during the study. Conclusions Overall, the CD4 and CD4/CD8 ratio increased during maintenance RTX therapy in GPA with no discernible impact of other immunosuppressive therapy. However the increase in CD4 was not followed by an increase in the CD4/CD8 ratio, especially in older patients. Inverted CD4/CD8 ratio associated with lower Ig levels, suggesting a more profound B cell depleting effect of RTX with a relative increase in CD8

  9. Infant Feeding Practices: Perceptions of Native American Mothers and Health Paraprofessionals

    ERIC Educational Resources Information Center

    Horodynski, Mildred A; Calcatera, Mary; Carpenter, Amanda

    2012-01-01

    Objective: To ascertain infant feeding practices and to explore the feasibility of an in-home feeding intervention with Native American Indian (NAI) mothers in six Native American communities in the United States (US). Design: Qualitative focus group study. Setting: Six Native American communities in the Midwest region of the United States.…

  10. Parental child feeding practices: how do perceptions of mother, father, sibling, and self vary?

    PubMed

    Pulley, Carol; Galloway, Amy T; Webb, Rose Mary; Payne, Lucinda O

    2014-09-01

    Mothers are important contributors to the development of eating behavior in children, but less is known about the influence of fathers. The purpose of this study was to investigate family perceptions of parental child feeding practices. Seventy two-parent American families including a mother, father, and two biologically related children participated in the study. Participants completed parent and child versions of the Child Feeding Questionnaire that assessed perceptions of parental control in child feeding. Most family member reports were positively correlated, indicating agreement about the use of the examined parental feeding practices; however, some salient differences between the reported behaviors of mothers and fathers were uncovered. Mothers reported using higher levels of monitoring and responsibility than fathers. In addition, fathers and children reported higher levels of paternal pressure related to feeding compared with mothers. Mothers and fathers used more pressure and felt more responsible for feeding younger children compared with older children. One interaction revealed that older male siblings reported the highest level of pressure from fathers. Reported differences in parents' use of child feeding practices suggest that mothers and fathers may have distinct interactions with their children regarding food. Paternal feeding practices are likely to have unique implications for understanding the development of children's eating behavior.

  11. Persistently Obese Youth: Interactions Between Parenting Styles and Feeding Practices With Child Temperament

    PubMed Central

    Boles, Richard E.; Reiter-Purtill, Jennifer; Zeller, Meg H.

    2013-01-01

    Objective To assess the interaction of parent and child characteristics with feeding practices and mealtime functioning. Design Longitudinal, predictive study comparing baseline characteristics with follow-up assessments. Participants The caregivers of 52 persistently obese youth and 32 nonoverweight comparison youth completed measurements of child temperament, parental feeding practices, parenting styles, and interactions during mealtimes. Results Adolescents with persistent obesity were significantly more likely to be parented using problematic feeding practices when parents also reported difficult child temperaments. Additionally, adolescents with persistent obesity and difficult temperaments were significantly more likely to have lower levels of positive mealtime interactions. Conclusion Persistently obese youth are at increased risk for problematic parental feeding practices and mealtime functioning, particularly when youth are described as having difficult temperaments. These results indicate that further investigations are needed to better understand the mechanisms linking parent and child characteristics with health-related behaviors for adolescents with obesity. PMID:23884967

  12. Feed-in Tariffs: Good Practices and Design Considerations

    SciTech Connect

    Cox, Sadie; Esterly, Sean

    2016-01-02

    In recent years, feed-in tariff (FIT) activity has focused primarily on revisions to current policies, underscoring the need for stable and predictable, yet flexible, policy environments. This policy brief provides a primer on key FIT design elements, lessons from country experience, and support resources to enable more detailed and country-specific FIT policy design.

  13. Complementary Feeding: Review of Recommendations, Feeding Practices, and Adequacy of Homemade Complementary Food Preparations in Developing Countries - Lessons from Ethiopia.

    PubMed

    Abeshu, Motuma Adimasu; Lelisa, Azeb; Geleta, Bekesho

    2016-01-01

    Breastfeeding provides the ideal food during the first 6 months of life. Complementary feeding starts when breast milk is no longer sufficient by itself, where the target age is for 6-23 months. The gap between nutritional requirement and amount obtained from breast milk increases with age. For energy, 200, 300, and 550 kcal per day is expected to be covered by complementary foods at 6-8, 9-11, and 12-23 months, respectively. In addition, the complementary foods must provide relatively large proportions of micronutrients such as iron, zinc, phosphorus, magnesium, calcium, and vitamin B6. In several parts of the developing world, complementary feeding continues as a challenge to good nutrition in children. In Ethiopia, only 4.2% of breastfed children of 6-23 months of age have a minimum acceptable diet. The gaps are mostly attributed to either poor dietary quality or poor feeding practices, if not both. Commercial fortified foods are often beyond the reach of the poor. Thus, homemade complementary foods remain commonly used. Even when based on an improved recipe, however, unfortified plant-based complementary foods provide insufficient key micronutrients (especially, iron, zinc, and calcium) during the age of 6-23 months. Thus, this review assessed complementary feeding practice and recommendation and reviewed the level of adequacy of homemade complementary foods.

  14. Infant-feeding practices among African American women: social-ecological analysis and implications for practice.

    PubMed

    Reeves, Elizabeth A; Woods-Giscombé, Cheryl L

    2015-05-01

    Despite extensive evidence supporting the health benefits of breastfeeding, significant disparities exist between rates of breastfeeding among African American women and women of other races. Increasing rates of breastfeeding among African American women can contribute to the improved health of the African American population by decreasing rates of infant mortality and disease and by enhancing cognitive development. Additionally, higher rates of breastfeeding among African American women could foster maternal-child bonding and could contribute to stronger families, healthier relationships, and emotionally healthier adults. The purpose of this article is twofold: (a) to use the social-ecological model to explore the personal, socioeconomic, psychosocial, and cultural factors that affect the infant feeding decision-making processes of African American women and (b) to discuss the implications of these findings for clinical practice and research to eliminate current disparities in rates of breastfeeding.

  15. Maternal self-efficacy and feeding practices in children aged 3-6 years

    PubMed Central

    Doaei, Saeid; Gholamalizadeh, Maryam; Entezari, Mohammad Hassan

    2015-01-01

    Objective: Nutrition in childhood has an important role in current and adulthood health. Recent studies have shown that the mother’s lifestyle has an important role in the methods used by mother to feed child. This paper aimed to investigate the association between mother’s weight efficacy lifestyle with feeding practices in children aged 3- 6 years. Materials and Methods: In this cross-sectional study which was carried out in 30 primary schools of Rasht (Iran) in 2012, 165 mothers with children aged 3-6 years were participated. Mothers reported their own and their child’s demographics. Aspects of mother’s weight efficacy lifestyle and mother’s control practices were assessed using Weight Efficacy Lifestyle (WEL) questionnaire and Comprehensive Feeding Practices questionnaire (CFPQ) respectively. Height and weight of mothers participated in the study were measured. The role of mother’s weight efficacy in predicting child’s feeding practices was assessed using linear regression. Results: Results showed that mother’s weight efficacy was related to child feeding practices. The mothers with similar weight efficacy lifestyle applied similar methods in child nutrition. Mothers with better weight efficacy used more encourage balance and variety, environmental control, child involvement and less emotion regulation using foods. Conclusion: ‎ ‏ ‏‎ The result of the ‎study showed that maternal ‎lifestyle was associated with ‎child feeding practices.‎ PMID:27006673

  16. CD4+ T cell activation in multiple sclerosis.

    PubMed

    Verselis, S J; Goust, J M

    1987-02-01

    Interleukin-2 (IL-2) production by CD4-enriched T cells from multiple sclerosis (MS) patients and normal individuals stimulated with concanavalin A (conA) and/or autologous and allogeneic B lymphoid cell lines (B-LCL) was evaluated 24, 48 and 96 h after stimulation. ConA-stimulated CD4+ cells from MS patients did not produce significantly more IL-2 than normal CD4+ cells. In contrast, autologous B-LCL-induced IL-2 production by MS CD4+ cells significantly (P = 0.026) exceeded that produced by normal CD4+ cells identically stimulated after 24 h in culture. Differences in IL-2 production by CD4+ cells from MS patients reached highest significance using allogeneic B-LCL, whose stimulatory capacity was similar, whether established from normal individuals or MS patients. This increased IL-2 production in response to B-LCL may represent a supranormal response of CD4+ cells from MS patients to class II major histocompatibility (MHC)-associated stimuli. It suggests that the deficiency of suppressor T cell functions postulated to play a role in MS does not arise from a lack of IL-2 induction and might indicate that bursts of IL-2 production could play a role in MS.

  17. Characterization of a polymorphism of CD4 in miniature swine.

    PubMed

    Sundt, T M; LeGuern, C; Germana, S; Smith, C V; Nakajima, K; Lunney, J K; Sachs, D H

    1992-05-15

    A polymorphism of CD4 in miniature swine has been identified by failure of cells from some animals to react with mAb 74-12-4. The phenotypic, molecular genetic, and functional characteristics of these animals have been defined. Cells from heterozygous animals bear approximately 50% the number of 74-12-4-reactive molecules on their surface as do cells from animals homozygous for the wild type. Animals of both phenotypes demonstrate similar flow cytometric profiles for CD8+ T cells. Northern blot analysis confirms the presence of mRNA for CD4 among PBL of animals failing to stain with 74-12-4. CD4 allelism is confirmed by Southern blot analysis, revealing RFLP. Function of the CD4 subset in vivo, as demonstrated by antibody production against a T cell-dependent Ag, is similar between animals of both phenotypes. Proliferative responses to PHA and alloantigen stimulation by a full haplotype mismatch or a class II mismatch alone are equivalent for animals of both phenotypes. These data suggest that the allelic form of CD4, designated CD4.2 in contrast to the wild-type CD4.1, is capable of performing normally as an accessory molecule in the generation of immune responses. Furthermore, antixenogeneic responses to C57B10.BR were equivalent, suggesting that both CD4 molecular types may be capable of interacting with xenogeneic class II molecules. Although the polymorphism includes differences in exons 3 and 4, regions thought to encode portions of the molecule interacting with MHC class II, these results imply that this naturally occurring CD4 polymorphism does not affect the interaction with class II molecules.

  18. Isolated cutaneous cryptococcosis in clinically unsuspected idiopathic CD4 lymphocytopenia

    PubMed Central

    Sharma, Divya; Singh, Neha; Kaushal, Seema; Jain, Shyama

    2014-01-01

    Idiopathic CD4 lymphocytopenia first defined in 1992 by the U.S. Centers for Disease Control and Prevention, as the repeated presence of a CD4+ T-lymphocyte count of fewer than 300 cells/cumm or of <20% of total T-cells with no evidence of human immunodeficiency virus (HIV) infection and therapy that might cause depressed CD4 T-cells. Most of the cases present with systemic opportunistic infections. We report a case without risk factors or laboratory evidence of HIV infection, presenting with cutaneous cryptococcal infection, diagnosed on cytology. PMID:25745296

  19. Maternal and paternal controlling feeding practices with male and female children.

    PubMed

    Blissett, Jacqueline; Meyer, Caroline; Haycraft, Emma

    2006-09-01

    This study aimed to compare maternal and paternal feeding practices with male and female children and examine the influence of the gender of both the parent and child on the relationship between parental unhealthy eating attitudes and controlling feeding practices. One hundred and eighty-eight participants (94 co-habiting mother-father dyads, mean age 36.4 years, SD=4.9), who were the parents of 46 male and 48 female children (mean age 37.7 months, SD=12.7) completed measures of unhealthy eating attitudes and feeding practices. Mothers and fathers differed significantly in their reports of unhealthy eating attitudes but not in their restrictive or pressurising feeding practices. Mothers reported greater perceived feeding responsibility and greater monitoring of their children's food intake than fathers. Bulimia scores were correlated with controlling feeding practices in mothers of girls but not boys. Fathers' body dissatisfaction was correlated with monitoring of sons' but not daughters' food intake. These findings suggest that parental extrapolation of weight concerns may be more likely to occur within mother-daughter and father-son relationships.

  20. Myeloma-like cast nephropathy caused by human recombinant soluble CD4 (sCD4) in monkeys.

    PubMed Central

    Bugelski, P. J.; Solleveld, H. A.; Fong, K. L.; Klinkner, A. M.; Hart, T. K.; Morgan, D. G.

    1992-01-01

    CD4 is the receptor for human immunodeficiency virus (HIV) on lymphocytes and macrophages. Soluble CD4 (sCD4), a recombinant truncated form of CD4, has been shown to inhibit HIV-1 in vitro and is being tested as a therapy for AIDS. Preclinical studies in cynomolgus monkeys revealed a protein cast nephropathy after four daily intravenous doses of 100 mg/kg/day. Renal lesions were not found in monkeys that received 10 mg/kg/day. The renal lesions consisted of proteinaceous tubular casts associated with multinucleate giant cells and neutrophils located in the tubules of the distal nephron. The affected tubules were surrounded by an interstitial mixed inflammatory cell infiltrate. By electron microscopy, the casts were composed of moderately electron dense, paracrystalline material. Immunostaining demonstrated that the casts contained sCD4-derived material and Tamm-Horsfall protein. Moreover, biochemical analysis of urine showed that a portion of sCD4 was excreted as intact protein. Because infection with HIV-1 can be associated with clinically significant nephropathy, these data suggest that renal function should be closely monitored in patients receiving soluble forms of CD4. Images Figure 1 Figure 2 Figure 3 PMID:1546739

  1. Interleukin-2 Therapy Induces CD4 Downregulation, Which Decreases Circulating CD4 T Cell Counts, in African Green Monkeys

    PubMed Central

    Mudd, Joseph C.; Perkins, Molly R.; DiNapoli, Sarah R.; Hirsch, Vanessa M.

    2016-01-01

    ABSTRACT African green monkeys (AGMs) are natural hosts of simian immunodeficiency virus (SIVAGM). Because these animals do not develop simian AIDS despite maintaining high viral loads, there is considerable interest in determining how these animals have evolved to avoid SIV disease progression. Unlike nonnatural hosts of SIV, adult AGMs maintain low levels of CD4+ T cells at steady states and also have a large population of virus-resistant CD8αα T cells that lack CD4 expression despite maintaining T helper cell functionalities. In recent work, we have shown that homeostatic cytokines can induce CD4 downregulation in AGM T cells in vitro. Through administering therapeutic doses of recombinant human interleukin-2 (IL-2) to AGMs, we show here that this mechanism is operative in vivo. IL-2 therapy induced transient yet robust proliferation in all major T cell subsets. Within the CD4+ T cell population, those that were induced into cycle by IL-2 exhibited characteristics of CD4-to-CD8αα conversion. In all animals receiving IL-2, circulating CD4+ T cell counts and proportions tended to be lower and CD4− CD8αα+ T cell counts tended to be higher. Despite reductions in circulating target cells, the viral load was unaffected over the course of study. IMPORTANCE The data in this study identify that homeostatic cytokines can downregulate CD4 in vivo and, when given therapeutically, can induce AGMs to sustain very low levels of circulating CD4+ T cells without showing signs of immunodeficiency. PMID:27053558

  2. A rationally designed CD4 analogue inhibits experimental allergic encephalomyelitis

    NASA Astrophysics Data System (ADS)

    Jameson, Bradford A.; McDonnell, James M.; Marini, Joseph C.; Korngold, Robert

    1994-04-01

    EXPERIMENTAL allergic encephalomyelitis (EAE) is an acute inflammatory autoimmune disease of the central nervous system that can be elicited in rodents and is the major animal model for the study of multiple sclerosis (MS)1,2. The pathogenesis of both EAE and MS directly involves the CD4+ helper T-cell subset3-5. Anti-CD4 monoclonal antibodies inhibit the development of EAE in rodents6-9, and are currently being used in human clinical trials for MS. We report here that similar therapeutic effects can be achieved in mice using a small (rationally designed) synthetic analogue of the CD4 protein surface. It greatly inhibits both clinical incidence and severity of EAE with a single injection, but does so without depletion of the CD4+ subset and without the inherent immunogenicity of an antibody. Furthermore, this analogue is capable of exerting its effects on disease even after the onset of symptoms.

  3. Feeding infants and young children. From guidelines to practice-conclusions and future directions.

    PubMed

    Vereijken, C M J L; Weenen, H; Hetherington, M M

    2011-12-01

    Infant feeding is a challenging and intricate process. Food intake is shaped by prior experience of flavours derived from the maternal diet in utero and via human milk, by ongoing experience of foods eaten during the first years of life including the variety, types and frequency of foods offered. The ways in which parents interact with their children including the way foods are presented, the emotional context they cultivate and the feeding practices they use can influence their children's eating habits, either positively or negatively. There is a mismatch between what government guidelines advise parents in relation to the "when, what and how" to feed children including during the weaning period and what parents actually do. Acquisition of food preferences and the establishment of eating habits in the early years form part of an ongoing, complex developmental process, however there is a gap between experimental evidence on best practice in infant feeding and what parents receive as advice about feeding. It is timely, therefore, to translate these findings into solutions for parents. Practical support for infant feeding should be evidence based, parent-focused and contingent on the needs of the developing child since infant feeding sets the foundation of healthy eating habits for life.

  4. Daily enteral feeding practice on the ICU: attainment of goals and interfering factors

    PubMed Central

    Binnekade, JM; Tepaske, R; Bruynzeel, P; Mathus-Vliegen, EMH; de Hann, RJ

    2005-01-01

    Background The purpose of this study was to evaluate the daily feeding practice of enterally fed patients in an intensive care unit (ICU) and to study the impact of preset factors in reaching predefined optimal nutritional goals. Methods The feeding practice of all ICU patients receiving enteral nutrition for at least 48 hours was recorded during a 1-year period. Actual intake was expressed as the percentage of the prescribed volume of formula (a success is defined as 90% or more). Prescribed volume (optimal intake) was guided by protocol but adjusted to individual patient conditions by the intensivist. The potential barriers to the success of feeding were assessed by multivariate analysis. Results Four-hundred-and-three eligible patients had a total of 3,526 records of feeding days. The desired intake was successful in 52% (1,842 of 3,526) of feeding days. The percentage of successful feeding days increased from 39% (124 of 316) on day 1 to 51% (112 of 218) on day 5. Average ideal protein intake was 54% (95% confidence interval (CI) 52 to 55), energy intake was 66% (95% CI 65 to 68) and volume 75% (95% CI 74 to 76). Factors impeding successful nutrition were the use of the feeding tube to deliver contrast, the need for prokinetic drugs, a high Therapeutic Intervention Score System category and elective admissions. Conclusion The records revealed an unsatisfactory feeding process. A better use of relative successful volume intake, namely increasing the energy and protein density, could enhance the nutritional yield. Factors such as an improper use of tubes and feeding intolerance were related to failure. Meticulous recording of intake and interfering factors helps to uncover inadequacies in ICU feeding practice. PMID:15987393

  5. Dysregulation of CD4(+) T Cell Subsets in Intracranial Aneurysm.

    PubMed

    Zhang, Hai-Feng; Zhao, Ming-Guang; Liang, Guo-Biao; Yu, Chun-Yong; He, Wenxiu; Li, Zhi-Qing; Gao, Xu

    2016-02-01

    Intracranial aneurysms (IAs) and potential IA rupture are one of the direct causes of permanent brain damage and mortality. Interestingly, the major risk factors of IA development, including hemodynamic stress, hypertension, smoking, and genetic predispositions, are closely associated with a proinflammatory immune status. Therefore, we examined the roles of CD4(+) T cells in IA pathogenesis. IA patients exhibited peripheral CD4(+) T-cell imbalance, with overrepresented T helper 1 (Th1) and Th17 activities and underrepresented Th2 and regulatory T (Treg) activities, including increased IFN-γ, TNF-α, and IL-17 production and decreased IL-10 production from total CD4(+) T cells. Chemokine receptors CXCR3 and CCR6 were used to identify Th1, Th2, and Th17 cell subsets, and CD4(+)CD25(hi) was used to identify Treg cells. Based on these markers, the data then showed altered cytokine production by each cell type and shifted subpopulation frequency. Moreover, this shift in frequency was directly correlated with IA severity. To examine the underlying mechanism of CD4(+) T cell skewing, we cocultured CD4(+) T cells with autologous monocytes and found that coculture with monocytes could significantly increase IFN-γ and IL-17 production through contact-independent mechanisms, demonstrating that monocytes could potentially contribute to the altered CD4(+) T cell composition in IA. Analyzing mRNA transcripts revealed significantly upregulated IL-1β and TNF-α expression by monocytes from IA patients. We found a loss of CD4(+) T cell subset balance that was likely to promote a higher state of inflammation in IA, which may exacerbate the disease through a positive feedback loop.

  6. Late Adolescents' Perceptions of Their Caregiver's Feeding Styles and Practices and Those They Will Use with Their Own Children.

    ERIC Educational Resources Information Center

    Fletcher, Janice; Branen, Laurel J.; Lawrence, Adair

    1997-01-01

    Examines the perceptions of late adolescents regarding their caregivers' feeding styles and practices. Results, based on 546 subjects (ages 18 to 23 years), revealed two types of feeding styles: adult-controlled and cooperative. Positive correlations emerged between subjects' perceived past and future feeding practices, suggesting the generational…

  7. Cyclotriazadisulfonamides: promising new CD4-targeted anti-HIV drugs.

    PubMed

    Vermeire, Kurt; Schols, Dominique

    2005-08-01

    It is imperative to continue efforts to identify novel effective therapies that can assist in containing the spread of HIV. Recently acquired knowledge about the HIV entry process points to new strategies to block viral entry. For most HIV strains, the successful infection of their target cells is mainly dependent on the presence of the CD4 surface molecule, which serves as the primary virus receptor. The attachment of the viral envelope to this cellular CD4 receptor can be considered as an ideal target with multiple windows of opportunity for therapeutic intervention. Therefore, drugs that interfere with the CD4 receptor, and thus inhibit viral entry, may be promising agents for the treatment of AIDS. The CD4-targeted HIV entry inhibitors cyclotriazadisulfonamides represent a novel class of small molecule antiviral agents with a unique mode of action. The lead compound, CADA, specifically interacts with the cellular CD4 receptor and is active against a wide variety of HIV strains at submicromolar levels when evaluated in different cell-types such as T cells, monocytes and dendritic cells. Moreover, a strict correlation has been demonstrated between anti-HIV activity and CD4 interaction of about 20 different CADA analogues. In addition, CADA acted synergistically in combination with all other FDA-approved anti-HIV drugs as well as with compounds that target the main HIV co-receptors. In this article, the characteristics of cyclotriazadisulfonamide compounds are presented and the possible application of CADA as a microbicide is also discussed.

  8. Food consumption by young children: a function of parental feeding goals and practices.

    PubMed

    Kiefner-Burmeister, Allison E; Hoffmann, Debra A; Meers, Molly R; Koball, Afton M; Musher-Eizenman, Dara R

    2014-03-01

    Staggering health implications are associated with poor child diet. Given the importance of parents in impacting children's eating outcomes, the current study examined a theoretical framework in which both parental feeding goals and practices impact specific healthy and unhealthy child eating behaviors. Participants were 171 mothers of 3-6year old children who were diverse both socioeconomically and with regard to BMI. Mothers completed questionnaires via Mechanical Turk, an online workforce through Amazon.com. Structural Equation Modeling showed an adequate model fit in which Negative Feeding Practices (e.g., using food as a reward) mediated the relationship between Health-Related Feeding Goals (i.e., feeding children with health-oriented goals in mind) and Negative Eating Behaviors (e.g., consumption of candy and snacks). However, Negative Feeding Practices did not mediate the relationship between Health-Related Feeding Goals and Positive Eating Behaviors (i.e., fruits and vegetables). These findings suggest the important role of habitual food parenting practices in children's eating and have implications for parental health education programs.

  9. A Study of Breast Feeding Practices Among Families of Armed Forces Personnel in a Large Cantonment.

    PubMed

    Singh, Pmp; Bhalwar, R

    2002-10-01

    A cross sectional epidemiological study design was undertaken on a randomly selected sample of 175 families of Armed Forces personnel staying in a large cantonment and having at least one child in the age group 3 to 24 months. The mean duration of lactational amenorrhoea was found to be 6.24 months (SD ± 3.25 months) and that of breast feeding was found to be 11.14 months (SD ± 6.37 month). The present study observed positive association between the duration of exclusive breast feeding and the duration of lactational amenorrhoea, as well as between the lack of practice of exclusive breast feeding and number of spells of upper respiratory tract infection and acute gastroenteritis. Based on the findings of the study, certain measures to promote the practice of exclusive breast feeding for the first 4-6 months of life have been suggested.

  10. Alternatives to restrictive feeding practices to promote self-regulation in childhood: a developmental perspective.

    PubMed

    Rollins, B Y; Savage, J S; Fisher, J O; Birch, L L

    2016-10-01

    Intake of energy-dense snack foods is high among US children. Although the use of restrictive feeding practices has been shown to be counterproductive, there is very limited evidence for effective alternatives to restriction that help children moderate their intake of these foods and that facilitate the development of self-regulation in childhood. The developmental literature on parenting and child outcomes may provide insights into alternatives to restrictive feeding practices. This review paper uses a model of parental control from the child development and parenting literatures to (i) operationally define restrictive feeding practices; (ii) summarize current evidence for antecedents and effects of parental restriction use on children's eating behaviours and weight status, and (iii) highlight alternative feeding practices that may facilitate the development of children's self-regulation and moderate children's intake of palatable snack foods. We also discuss recent empirical evidence highlighting the role of child temperament and food motivation related behaviours as factors that prompt parents to use restrictive feeding practices and, yet, may increase children's dysregulated intake of forbidden foods.

  11. Controlling parental feeding practices and child body composition in ethnically and economically diverse preschool children.

    PubMed

    Wehrly, Sarah E; Bonilla, Chantal; Perez, Marisol; Liew, Jeffrey

    2014-02-01

    Controlling parental feeding practices may be associated with childhood overweight, because coercive or intrusive feeding practices may negatively impact children's development of self-regulation of eating. This study examined pressuring or forcing a child (healthy or unhealthy foods) and restricting child from unhealthy or snack foods as two types of controlling feeding practices that explain unique variances in measures of child body composition (BMI, percent body fat, and parental perception of child weight). In an ethnically and economically diverse sample of 243 children aged 4-6years old and their biological parents (89% biological mothers, 8% biological fathers, and 3% step or grand-parent), descriptive statistics indicate ethnic and family income differences in measures of feeding practices and child body composition. Additionally, the two "objective" indices of body composition (BMI and percent body fat) were related to low pressure to eat, whereas the "subjective" index (perceived child weight) was related to restriction. Regression analyses accounting for ethnic and family income influences indicate that pressure to eat and restriction both explained unique variances in the two "objective" indices of body composition, whereas only restriction explained variance in perceived child weight. Findings have implications for helping parents learn about feeding practices that promote children's self-regulation of eating that simultaneously serves as an obesity prevention strategy.

  12. Associations between child emotional eating and general parenting style, feeding practices, and parent psychopathology.

    PubMed

    Braden, Abby; Rhee, Kyung; Peterson, Carol B; Rydell, Sarah A; Zucker, Nancy; Boutelle, Kerri

    2014-09-01

    Emotional eating is the tendency to eat in response to negative emotions. Prior research has identified a relationship between parenting style and child emotional eating, but this has not been examined in clinical samples. Furthermore, the relationship between specific parenting practices (e.g., parent feeding practices) and child emotional eating has not yet been investigated. The current study examined relationships between child emotional eating and both general and specific parenting constructs as well as maternal symptoms of depression and binge eating among a treatment-seeking sample of overweight children. Participants included 106 mother-child dyads who attended a baseline assessment for enrollment in a behavioral intervention for overeating. Ages of children ranged from 8 to 12  years old. Mothers completed self-report measures of their child's emotional eating behavior, their own feeding practices, and symptoms of depression and binge eating. Children completed a self-report measure of their mothers' general parenting style. A stepwise regression analysis was conducted to identify the parent variable that was most strongly related to child emotional eating, controlling for child age and gender. Emotional feeding behavior (i.e., a tendency to offer food to soothe a child's negative emotions) was the parent factor most significantly related to child emotional eating. Findings suggest that emotional feeding practices in parents may be related to emotional eating in children. Treatment with overweight children who engage in emotional eating may be improved by targeting parent feeding practices.

  13. Complementary feeding practices and associated factors among HIV positive mothers in Southern Ethiopia.

    PubMed

    Haile, Demewoz; Belachew, Tefera; Berhanu, Getenesh; Setegn, Tesfaye; Biadgilign, Sibhatu

    2015-05-01

    The objective of this study was to assess complementary feeding practices and associated factors among HIV exposed infants in Sidama Zone, Southern Ethiopia. An institutional based cross-sectional study with cluster random sampling technique was employed and all HIV exposed infants aged 6-17 months found in randomly selected health institutions in Sidama zone, Southern Ethiopia were included. A 24-hour dietary recall and 7-day quasi-food group frequency was used to assess complementary feeding practices. The prevalence of timely initiation of complementary feeding (6-8 months) was 42% [95% CI: (30-54%)]. Of all the HIV exposed infants aged 6-17 months, 40.7% had practiced bottle-feeding. About 65.6% and 53.3% of HIV exposed infants did not receive the recommended number of food groups and frequency of complementary feeding in the last 24 hours respectively. Pulse (plant protein) was consumed by only 22.5% of the infants while only 9.9% of the infants consumed animal source food in the last 24 hours. Presence of infant food prohibition (β = -0.342, P = 0.001) and age of the infant (β = 0.311, P = 0.001) were found to be an independent predictors of dietary diversity. Presence of infant food prohibition (β = -0.181, P = 0.02) and age of infant (β = 0.388, P < 0.001) were also the predictors of 24 hour meal frequency. Having lower educational status [AOR = (0.21, 95% CI (0.062-0.71)] was an independent negative predictor of bottle-feeding practice. Many of the complementary feeding practices like meal frequency; dietary diversity and bottle-feeding were sub-optimal. Nutrition education should be designed for improving complementary feeding practices of HIV exposed infants in Sidama Zone, Southern Ethiopia. Mothers with higher educational status should be also targeted for nutrition education especially on bottle feeding practice.

  14. Parent feeding interactions and practices during childhood cancer treatment. A qualitative investigation.

    PubMed

    Fleming, Catharine A K; Cohen, Jennifer; Murphy, Alexia; Wakefield, Claire E; Cohn, Richard J; Naumann, Fiona L

    2015-06-01

    In the general population it is evident that parent feeding practices can directly shape a child's life long dietary intake. Young children undergoing childhood cancer treatment may experience feeding difficulties and limited food intake, due to the inherent side effects of their anti-cancer treatment. What is not clear is how these treatment side effects are influencing the parent-child feeding relationship during anti-cancer treatment. This retrospective qualitative study collected telephone based interview data from 38 parents of childhood cancer patients who had recently completed cancer treatment (child's mean age: 6.98 years). Parents described a range of treatment side effects that impacted on their child's ability to eat, often resulting in weight loss. Sixty-one percent of parents (n = 23) reported high levels of stress in regard to their child's eating and weight loss during treatment. Parents reported stress, feelings of helplessness, and conflict and/or tension between parent and the child during feeding/eating interactions. Parents described using both positive and negative feeding practices, such as: pressuring their child to eat, threatening the insertion of a nasogastric feeding tube, encouraging the child to eat and providing home cooked meals in hospital. Results indicated that parent stress may lead to the use of coping strategies such as positive or negative feeding practices to entice their child to eat during cancer treatment. Future research is recommended to determine the implication of parent feeding practice on the long term diet quality and food preferences of childhood cancer survivors.

  15. Loss of CD4 membrane expression and CD4 mRNA during acute human immunodeficiency virus replication

    PubMed Central

    1988-01-01

    Using mAbs and genomic probe to the CD4 molecule, the HIV receptor, we demonstrated that HIV replication induces the disappearance of its functional receptor from the cell surface by two distinct mechanisms. First, after being expressed onto the cell surface, HIV envelope gp110 will complex CD4, efficiently masking the CD4 epitope used by the virus to bind its receptor. This phenomenon occurs on the surface of each infected cell and is not due to the release of soluble gp110; infection with recombinant HIV/vaccinia viruses expressing a mutated HIV env gene designed to prevent gp110 release from the cell surface induces a similar gp/CD4 complexes formation. Second, virus replication induces a dramatic and rapid loss of CD4 mRNA transcripts, preventing new CD4 molecules from being synthesized. These two mechanisms of receptor modulation could have been developed to avoid reinfection of cells replicating the virus as well as to produce more infectious particles. These results suggest that the classical virus interference documented for other retroviruses might not only be due to receptor/envelope interaction, but might also depend on receptor gene expression. PMID:3264318

  16. The practice and attitudes of gypsy and traveller women towards early infant feeding.

    PubMed

    Pinkney, Kate

    2012-07-01

    This research explores the early infant feeding practice of gypsy and traveller women and their attitudes towards breast and formula feeding in one primary care trust. This research was undertaken using a quantitative research approach. Two structured questionnaires were administered. The first questionnaire was completed by all health visitors employed by the trust. This questionnaire established that most gypsy and traveller women choose to formula feed their infants and the breastfeeding rate in this community is very low. The second questionnaire was completed by 50% of the gypsy and traveller community who met the inclusion criteria. The Iowa Infant Feeding Attitude Scale (IIFAS) was completed as part of this questionnaire. This questionnaire showed that gypsy and traveller women had a more neutral attitude towards early infant feeding than was expected. This is significant as previous research suggests that women with neutral attitude scores are not fixed in their early infant feeding intentions. This therefore implies that the infant feeding practice of these women could potentially be influenced. This study, therefore, concludes that implementing focused interventions aimed at promoting breastfeeding could potentially increase the breastfeeding initiation rate in this community.

  17. [Breastfeeding, complimentary feeding practices and childhood malnutrition in the Bolivian Andes].

    PubMed

    Cruz Agudo, Yesmina; Jones, Andrew D; Berti, Peter R; Larrea Macías, Sergio

    2010-03-01

    Northern Potosi is one of the poorest parts of Bolivia with the highest indicators of rural poverty, malnutrition and food insecurity in the Bolivian Andes. The objective of this research was to characterize the levels of malnutrition and describe infant feeding practices in Potosi, Bolivia and use this information to develop an effective, gender sensitive and culturally relevant intervention encouraging good infant feeding practices. Standard methods were used to collect anthropometric data. Weight and height data were collected for 400 children under five years of age from 30 communities. In six of these communities, interviews and focus group discussions were conducted with 33 mothers and other families in addition to household observational data that were collected to describe infant feeding practices. Nearly 20% of children were underweight; stunting was widespread as well. 38% of mothers initiated breastfeeding 12 hours or more after birth. 39% of mothers initiated complementary feeding in the first three months following birth. The type of complementary food given to children was usually inadequate. With this research we could see that nutritional deficiencies often begin when the mother starts breastfeeding and when first introduced complementary feeding. Interventions aimed at improving maternal and child nutrition will require changes in parents' behavior, greater recognition and community support of the importance of child feeding, and the inclusion of strategies to reach young people, involve men, and make high quality nutrition promotion more widely available in the communities.

  18. Parenting Styles, Feeding Styles, Feeding Practices, and Weight Status in 4–12 Year-Old Children: A Systematic Review of the Literature

    PubMed Central

    Shloim, Netalie; Edelson, Lisa R.; Martin, Nathalie; Hetherington, Marion M.

    2015-01-01

    Childhood is a critical period in the development of obesity. Eating patterns established early in life track into later life. Therefore, parental approaches to feeding in their general parenting style, feeding styles, and specific feeding practices will have a profound impact on how children eat and grow. A systematic research review following PRISMA guidelines was conducted to identify, discuss and integrate recent research investigating the relationship between parenting styles, feeding styles, feeding practices, and body mass index (BMI) in children. Medline (Ovid), PsycINFO, Web of Science, and Food Science and Technology Abstracts were systematically searched using sensitive search strategies. Studies were limited to papers published in English between 2010 and February 2015 with participants aged 4–12 years old with outcomes including obesity, change in weight, or BMI. The search yielded 31 relevant quantitative peer-reviewed papers meeting all inclusion criteria: seven longitudinal, 23 cross-sectional, one randomized control trial. Associations between parenting style and child BMI were strongest and most consistent within the longitudinal studies. Uninvolved, indulgent or highly protective parenting was associated with higher child BMI, whereas authoritative parenting was associated with a healthy BMI. Similarly for feeding styles, indulgent feeding was consistently associated with risk of obesity within cross-sectional studies. Specific feeding practices such as restriction and pressure to eat were linked to BMI, especially within cross-sectional studies. Where child traits were measured, the feeding practice appeared to be responsive to the child, therefore restriction was applied to children with a high BMI and pressure to eat applied to children with a lower BMI. Behaviors and styles that are specific to the feeding context are consistently associated with child BMI. However, since obesity emerges over time, it is through longitudinal, carefully

  19. Parenting Styles, Feeding Styles, Feeding Practices, and Weight Status in 4-12 Year-Old Children: A Systematic Review of the Literature.

    PubMed

    Shloim, Netalie; Edelson, Lisa R; Martin, Nathalie; Hetherington, Marion M

    2015-01-01

    Childhood is a critical period in the development of obesity. Eating patterns established early in life track into later life. Therefore, parental approaches to feeding in their general parenting style, feeding styles, and specific feeding practices will have a profound impact on how children eat and grow. A systematic research review following PRISMA guidelines was conducted to identify, discuss and integrate recent research investigating the relationship between parenting styles, feeding styles, feeding practices, and body mass index (BMI) in children. Medline (Ovid), PsycINFO, Web of Science, and Food Science and Technology Abstracts were systematically searched using sensitive search strategies. Studies were limited to papers published in English between 2010 and February 2015 with participants aged 4-12 years old with outcomes including obesity, change in weight, or BMI. The search yielded 31 relevant quantitative peer-reviewed papers meeting all inclusion criteria: seven longitudinal, 23 cross-sectional, one randomized control trial. Associations between parenting style and child BMI were strongest and most consistent within the longitudinal studies. Uninvolved, indulgent or highly protective parenting was associated with higher child BMI, whereas authoritative parenting was associated with a healthy BMI. Similarly for feeding styles, indulgent feeding was consistently associated with risk of obesity within cross-sectional studies. Specific feeding practices such as restriction and pressure to eat were linked to BMI, especially within cross-sectional studies. Where child traits were measured, the feeding practice appeared to be responsive to the child, therefore restriction was applied to children with a high BMI and pressure to eat applied to children with a lower BMI. Behaviors and styles that are specific to the feeding context are consistently associated with child BMI. However, since obesity emerges over time, it is through longitudinal, carefully

  20. Household Food Insecurity, Mother's Feeding Practices, and the Early Childhood's Iron Status

    PubMed Central

    Salarkia, Nahid; Neyestani, Tirang R.; Omidvar, Nasrin; Zayeri, Farid

    2015-01-01

    Background: Health consequences of food insecurity among infants and toddlers have not been fully examined. The purpose of this study was to assess the relationship between household food insecurity, mother's infant feeding practices and iron status of 6–24 months children. Methods: In this cross-sectional study, 423 mother-child pairs were randomly selected by multistage sampling method. Children blood samples were analyzed for hemoglobin and serum ferritin concentrations. Household food security was evaluated using a validated Household Food Insecurity Access Scale. The mother's feeding practices were evaluated using Infant and Young Child Feeding practice variables including: The duration of breastfeeding and the time of introducing of complementary feeding. Results: Based on the results, of the studied households only 47.7% were food secure. Mild and moderate-severe household food insecurity was 39.5% and 12.8%, respectively. Anemia, iron deficiency (ID), and iron deficiency anemia were seen in 29.1%, 12.2%, and 4.8% of children, respectively. There was no significant association between household food insecurity; mother's feeding practices and child ID with or without anemia. Conclusions: We found no association between household food insecurity and the occurrence of anemia in the 6–24 months children. However, these findings do not rule out the possibility of other micronutrient deficiencies among the food-insecure household children. PMID:26445633

  1. Breast-, complementary and bottle-feeding practices in Kenya: stagnant trends were experienced from 1998 to 2009.

    PubMed

    Matanda, Dennis J; Mittelmark, Maurice B; Kigaru, Dorcus Mbithe D

    2014-06-01

    The pattern of infant and young child feeding that provides the most benefit includes being put to the breast within an hour of birth, exclusive breastfeeding for 6 months, continued breastfeeding along with complementary foods up to 2 years of age or beyond, and avoidance of any bottle-feeding. However, since there are no published data from Kenya regarding trends in these feeding practices, this research undertook time trend estimation of these feeding practices using the 1998, 2003, and 2008-2009 Kenya Demographic and Health Survey and also examined the multivariate relationships between sociodemographic factors and feeding practices with data from 2008 to 2009. Logistic regression was used to test the significance of trends and to analyze sociodemographic characteristics associated with feeding practices. There was a significant decline in early initiation of breastfeeding among children in Central and Western provinces and those residing in urban areas. Trends in exclusive breastfeeding showed significant improvement in most sociodemographic segments, whereas trends in complementary feeding and breastfeeding remained stable. Bottle-feeding significantly decreased among children aged 12 to 23 months, as well as those living in Coast, Eastern, and Rift Valley provinces. In the multivariate analysis, the province was significantly associated with feeding practices, after controlling for child's size, birth order, and parity. The stagnant (and in some cases worsening) trends in early initiation of breastfeeding and complementary feeding with breastfeeding paint a worrisome picture of breastfeeding practices in Kenya; therefore, efforts to promote the most beneficial feeding practices should be intensified.

  2. Controlling maternal feeding practices associated with decreased dieting behavior in sixth-grade children.

    PubMed

    Rhee, Kyung E; Appugliese, Danielle P; Prisco, Alicia; Kaciroti, Niko A; Corwyn, Robert F; Bradley, Robert H; Lumeng, Julie C

    2010-04-01

    Controlling maternal feeding practices have been linked to increased caloric intake, disinhibited eating, and obesity in children. Its relationship to child dieting behavior, however, is unknown. Using the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development, this study examined whether controlling feeding practices are associated with increased or decreased dieting behavior in children. Controlling maternal feeding practices were assessed in third grade with the question, "Do you let your child eat what he/she feels like eating?" Answers ranged from 1 to 4; higher scores were reverse-coded to indicate greater control. Child dieting behavior was assessed in sixth grade and dichotomized into "any dieting behaviors" vs "none." Multiple logistic regression was used to investigate the relationship between controlling maternal feeding practices and dieting behavior and included the covariates of sex, race, maternal education, maternal weight status, child weight status in third grade, and change in body mass index z score between third and sixth grade. In sixth grade (n=776), 41.5% of children engaged in dieting behavior. In the multivariate analysis, greater maternal control over child eating predicted lower odds of child dieting in sixth grade (odds ratio=0.79; 95% confidence interval: 0.64 to 0.97). There was no interaction between controlling maternal feeding practices and child's sex or baseline obesity status. Exerting more control over what a child eats in third grade may protect against future dieting behavior in children, independent of child's weight status or rate of weight gain. Further work is needed to better define which controlling feeding practices are beneficial for the child.

  3. Feeding practices and nutritional status of infants in Morogoro Municipality, Tanzania.

    PubMed

    Safari, John G; Kimambo, Stella C; Lwelamira, James E

    2013-07-01

    Breast feeding practice especially exclusive breast feeding (EBF) is a major determinant of child growth and development. In Tanzania, most women breastfeed their infants for long periods, but many introduce alternative feeding too early in life. The objective of this study was to determine factors affecting EBF and the relationship between feeding practices and the nutritional status of infants. This cross-sectional survey, using a semi-structured questionnaire, was conducted in Morogoro Municipality in Tanzania. The study involved lactating women recruited from five randomly selected health facilities. Demographic, clinical, knowledge and practices related to infant feeding as well as infant anthropometric information were collected. Infant nutritional status was assessed based on weight-for-age, height-for-age and weight- for- height. There were wide variations in knowledge and practice of breastfeeding among women. Majority (92%) of the respondents gave colostrums to infants although more than 50% did not know its benefits. Eight percent of the respondents discarded colostrums on the account that it is not good for their neonates. Only 23.1% of the respondents thought that infants should be breastfed exclusively during the first six months of infancy. Ninety-eight percent of infants < 1 month of age received breast milk only, compared with 28.5% of infants aged 2-3 months and 22.3% among those who were above 3 months of age. No child in the ≥ 4 months old was exclusively breastfed. Over 80% of the infants had normal weights, 13% were stunted and 8% wasted. EBF was associated with higher scores for height- for- age Z (P < 0.05) and weight- for- height Z (P < 0.01). Age, education level and occupation of respondents were important predictors of EBF. Overall, breast feeding practices in the study population were largely suboptimal. As a result, considerable proportions of children had poor health indicators. Thus, correct breastfeeding practices should be

  4. Identification and characterization of a second CD4-like gene in teleost fish.

    PubMed

    Dijkstra, Johannes Martinus; Somamoto, Tomonori; Moore, Lindsey; Hordvik, Ivar; Ototake, Mitsuru; Fischer, Uwe

    2006-02-01

    In fish, T cell subdivision is not well studied, although CD8 and CD4 homologues have been reported. This study describes a second teleost CD4-like gene, CD4-like 2 (CD4L-2). Two rainbow trout copies of this gene were found, -2a and -2b, encoding molecules sharing 81% aa identity. The 2a/2b duplication may be related to tetraploid ancestry of salmonid fishes. In the Fugu genome CD4L-2 lies head to tail with an earlier reported, very different CD4-like gene [Suetake, H., Araki, K., Suzuki, Y., 2004. Cloning, expression, and characterization of fugu CD4, the first ectothermic animal CD4. Immunogenetics 56, 368-374], which was designated CD4L-1 in the present article. The flanking genes of the Fugu CD4L-1 and CD4L-2 are reminiscent of the genes surrounding CD4 and LAG-3 in mammals. However, neither synteny nor phylogenetic analysis could decide between CD4 and LAG-3 identity for the fish CD4L genes. CD4L-1 and CD4L-2 share a tyrosine protein kinase p56(lck) binding motif in the cytoplasmic tail with CD4 but not with LAG-3. Trout CD4L-2 expression is highest in the thymus, similar to mammalian and chicken CD4, whereas Fugu CD4L-1 expression was highest in the spleen. However, CD4L-2 encodes only two IG-like domains, whereas CD4L-1, CD4 and LAG-3 encode four. The CD4-like genes 1 and 2 in fish apparently went through an evolution different from that of LAG-3 and CD4 in higher vertebrates.

  5. Normalization of CD4+ T Cell Metabolism Reverses Lupus

    PubMed Central

    Yin, Yiming; Choi, Seung-Chul; Xu, Zhiwei; Perry, Daniel J.; Seay, Howard; Croker, Byron P.; Sobel, Eric S.; Brusko, Todd M.; Morel, Laurence

    2015-01-01

    Systemic Lupus Erythematosus (SLE) is an autoimmune disease in which autoreactive CD4+ T cells play an essential role. CD4+ T cells rely on glycolysis for inflammatory effector functions, but recent studies have shown that mitochondrial metabolism supports their chronic activation. How these processes contribute to lupus is unclear. Here, we show that both glycolysis and mitochondrial oxidative metabolism are elevated in CD4+ T cells from lupus-prone B6.Sle1.Sle2.Sle3 (TC) mice as compared to non-autoimmune controls. In vitro, both the mitochondrial metabolism inhibitor metformin and the glucose metabolism inhibitor 2-Deoxy-D-glucose (2DG) reduced IFNγ production, although at different stages of activation. Metformin also restored the defective IL-2 production by TC CD4+ T cells. In vivo, treatment of TC mice and other lupus models with a combination of metformin and 2DG normalized T cell metabolism and reversed disease biomarkers. Further, CD4+ T cells from SLE patients also exhibited enhanced glycolysis and mitochondrial metabolism that correlated with their activation status, and their excessive IFNγ production was significantly reduced by metformin in vitro. These results suggest that normalization of T cell metabolism through the dual inhibition of glycolysis and mitochondrial metabolism is a promising therapeutic venue for SLE. PMID:25673763

  6. Idiopathic CD4+ lymphocytopenia: natural history and prognostic factors

    PubMed Central

    Falloon, Judith; Bennett, John E.; Shaw, Pamela A.; Chaitt, Doreen; Baseler, Michael W.; Adelsberger, Joseph W.; Metcalf, Julia A.; Polis, Michael A.; Kovacs, Stephen J.; Kovacs, Joseph A.; Davey, Richard T.; Lane, H. Clifford; Masur, Henry

    2008-01-01

    Idiopathic CD4+ lymphocytopenia (ICL) is a rare non–HIV-related syndrome with unclear natural history and prognosis. This prospective natural history cohort study describes the clinical course, CD4 T lymphocyte kinetics, outcome, and prognostic factors of ICL. Thirty-nine patients (17 men, 22 women) 25 to 85 years old with ICL were evaluated between 1992 and 2006, and 36 were followed for a median of 49.5 months. Cryptococcal and nontuberculous mycobacterial infections were the major presenting opportunistic infections. Seven patients presented with no infection. In 32, CD4 T-cell counts remained less than 300/mm3 throughout the study period and in 7 normalized after an average of 31 months. Overall, 15 (41.6%) developed an opportunistic infection in follow-up, 5 (13.8%) of which were “AIDS-defining clinical conditions,” and 4 (11.1%) developed autoimmune diseases. Seven patients died, 4 from ICL-related opportunistic infections, within 42 months after diagnosis. Immunologic analyses revealed increased activation and turnover in CD4 but not CD8 T lymphocytes. CD8 T lymphocytopenia (< 180/mm3) and the degree of CD4 T cell activation (measured by HLA-DR expression) at presentation were associated with adverse outcome (opportunistic infection-related death; P = .003 and .02, respectively). This trial is registered at http://clinicaltrials.gov as #NCT00001319. PMID:18456875

  7. Small ruminant feed systems: perceptions and practices in the transitional zone of Ghana

    PubMed Central

    2010-01-01

    into major feeds, the creation of non-cropping zones around village fringes and studies on labour demands of different feed systems are proposed. The insight gained in this study on farmers' perceptions and practices relating to small ruminant feeds could guide in the selection and introduction of feed innovations that fit into current feed systems to enhance adoption. PMID:20298617

  8. Development of promyelocytic leukemia zinc finger-expressing innate CD4 T cells requires stronger T-cell receptor signals than conventional CD4 T cells.

    PubMed

    Qiao, Yu; Zhu, Lingqiao; Sofi, Hanief; Lapinski, Philip E; Horai, Reiko; Mueller, Kristen; Stritesky, Gretta L; He, Xi; Teh, Hung-Sia; Wiest, David L; Kappes, Dietmar J; King, Philip D; Hogquist, Kristin A; Schwartzberg, Pamela L; Sant'Angelo, Derek B; Chang, Cheong-Hee

    2012-10-02

    MHC class II-expressing thymocytes and thymic epithelial cells can mediate CD4 T-cell selection resulting in functionally distinct thymocyte-selected CD4 (T-CD4) and epithelial-selected CD4 (E-CD4) T cells, respectively. However, little is known about how T-cell receptor (TCR) signaling influences the development of these two CD4 T-cell subsets. To study TCR signaling for T-CD4 T-cell development, we used a GFP reporter system of Nur77 in which GFP intensity directly correlates with TCR signaling strength. T-CD4 T cells expressed higher levels of GFP than E-CD4 T cells, suggesting that T-CD4 T cells received stronger TCR signaling than E-CD4 T cells during selection. Elimination of Ras GTPase-activating protein enhanced E-CD4 but decreased T-CD4 T-cell selection efficiency, suggesting a shift to negative selection. Conversely, the absence of IL-2-inducible T-cell kinase that causes poor E-CD4 T-cell selection due to insufficient TCR signaling improved T-CD4 T-cell generation, consistent with rescue from negative selection. Strong TCR signaling during T-CD4 T-cell development correlates with the expression of the transcription factor promyelocytic leukemia zinc finger protein. However, although modulation of the signaling strength affected the efficiency of T-CD4 T-cell development during positive and negative selection, the signaling strength is not as important for the effector function of T-CD4 T cells. These findings indicate that innate T-CD4 T cells, together with invariant natural killer T cells and γδ T cells, receive strong TCR signals during their development and that signaling requirements for the development and the effector functions are distinct.

  9. Selective inhibition of immature CD4-CD8+ thymocyte proliferation, but not differentiation, by the thymus atrophy-inducing compound di-n-butyltin dichloride.

    PubMed Central

    Pieters, R H; Bol, M; Ariëns, T; Punt, P; Seinen, W; Bloksma, N; Penninks, A H

    1994-01-01

    Effects of the thymus atrophy-inducing organotin compound di-n-butyltin dichloride (DBTC) on the differentiation and proliferation of immature rat thymocyte subsets were studied in vivo and in vitro. Incubation of freshly isolated CD4-CD8- or immature CD4-CD8+ (characterized as CD4-CD53-) thymocytes with 10(-7) M DBTC for 18 hr did not affect cell recovery or their ability to differentiate to CD4-CD8+ cells and CD4+CD8+ or to CD4+CD8+ cells, respectively. The same treatment decreased the spontaneous as well as the phytohaemagglutinin (PHA)-induced proliferation in both subsets. However, the inhibition of proliferation by DBTC of immature CD4-CD8+, but not of CD4-CD8- thymocytes, appeared to increase with their growth rate. Data show that differentiation of immature thymocytes can proceed independently of proliferation and that DBTC causes thymus atrophy by selectively inhibiting the proliferation of immature CD4-CD8+ thymocytes. Administration to rats of DBTC via the diet for 14 days resulted in an initial decrease of thymoblast number by day 2, followed by a decrease in the total number of thymocytes by day 4. Total thymocyte numbers were lowest on day 7 and did not significantly change thereafter. CD4/CD8 thymocyte subset distributions were similar to controls on day 4, but on day 7 of feeding a marked reduction of the percentage of CD4+CD8+ thymocytes and consequently an increase of the percentages of the three other CD4/CD8 subsets were found. Thereafter, the CD4/CD8 subset distribution recovered, reaching near control values on day 14, despite the very low numbers of thymoblasts and of total thymocytes at that time. Data together indicate that DBTC reduces the production of CD4+CD8+ and mature single-positive thymocytes by selectively inhibiting immature CD4-CD8+ thymocyte proliferation but without affecting the differentiation capacity of these cells. This suggests that thymocyte proliferation and differentiation are separately regulated processes. PMID

  10. The relationship between controlling feeding practices and boys' and girls' eating in the absence of hunger.

    PubMed

    Harris, Holly; Mallan, Kimberley M; Nambiar, Smita; Daniels, Lynne A

    2014-12-01

    Parental controlling feeding practices have been directly associated with maladaptive child eating behaviors, such as eating in the absence of hunger (EAH). The aims of this study were to examine EAH in very young children (3-4years old) and to investigate the association between maternal controlling feeding practices and energy intake from a standardized selection of snacks consumed 'in the absence of hunger'. Thirty-seven mother-child dyads enrolled in the NOURISH RCT participated in a modified EAH protocol conducted in the child's home. All children displayed EAH, despite 80% reporting to be full or very full following completion of lunch 15min earlier. The relationships between maternal and child covariates and controlling feeding practices and EAH were examined using non-parametric tests, and were stratified by child gender. For boys only, pressure to eat was positively associated with EAH. Neither restriction nor monitoring practices were associated with EAH in either boys or girls. Overall, the present findings suggest that gender differences in the relationship between maternal feeding practices and children's eating behaviors emerge early and should be considered in future research and intervention design.

  11. Decentralization of CD4 testing in resource-limited settings: 7 years of experience in six African countries.

    PubMed

    Marinucci, F; Medina-Moreno, S; Paterniti, A D; Wattleworth, M; Redfield, R R

    2011-05-01

    Improving access to CD4 testing in resource-limited settings can be achieved through both centralized and decentralized testing networks. Decentralized testing models are more suitable for countries where the HIV epidemic affects a large portion of rural populations. Timely access to accurate CD4 results is crucial at the primary level of the health system. For the past 7 years, the Institute of Human Virology of the University of Maryland School of Medicine has implemented a flexible and sustainable three-phase model: (1) site assessment and improvement, (2) appropriate technology selection with capacity building through practical training and laboratory mentoring, and (3) quality management system strengthening and monitoring, to support accessibility to reliable CD4 counting at the point of service. CD4 testing capacity was established in 122 of 229 (53%) laboratories supported in Nigeria, Uganda, Kenya, Zambia, Tanzania, and Rwanda. Among those in rural settings, 46% (69/151) had CD4 testing available at site level, with a functioning flow cytometer installed at 28% (8/29) and 50% (61/122) of level 1 and level 2 sites, respectively. To strengthen local capacity, a total of 1,152 laboratory technicians were trained through 188 training sessions provided both on-site and at central locations. The overall quality of CD4 total testing procedure was assessed at 76% (92/121) of the laboratories, with 25% (23/92), 34% (31/92), and 33% (30/92) of them reporting excellent, good, and satisfactory performance. Balancing country-specific factors with the location of the clinic, number of patients, and the expected workload, was crucial in adapting this flexible model for decentralizing CD4 testing. The close collaboration with local governments and private vendors was key to successfully expanding access to CD4 testing within the framework of HIV care and treatment programs and for the sustainability of medical laboratories in resource-limited settings.

  12. Child-feeding practices among Chinese-American and non-Hispanic white caregivers.

    PubMed

    Huang, Shirley H; Parks, Elizabeth P; Kumanyika, Shiriki K; Grier, Sonya A; Shults, Justine; Stallings, Virginia A; Stettler, Nicolas

    2012-06-01

    This study compared child-feeding and related practices with child weight status between Chinese-American and non-Hispanic white caregivers who attended three community health centers. Study participants were caregivers of 50 Chinese-American and 108 non-Hispanic white children aged 2-12 years who completed a short version of the child feeding questionnaire in English or Chinese. The feeding behaviors assessed were concern, pressure, restriction, and monitoring. Child body mass index (BMI) z-scores were calculated from child weight and height measured in clinic by clinicians trained in anthropometrics. The sample was stratified into 2-5 and 6-12 years age groups to account for developmental differences. Internal consistency (Cronbach's alpha) was moderate to high and similar by ethnicity for all four behaviors for Chinese-Americans and non-Hispanic whites. In models adjusted for confounding variables, Chinese-American caregivers had higher mean scores than non-Hispanic white caregivers for concern and restriction in all age groups and monitoring in 2-5 year-olds. No feeding practices were associated with child BMI in Chinese-Americans; concern and restriction were associated with child BMI in non-Hispanic whites in 2-5 year-olds. These results suggest that differences in child-feeding practices exist between Chinese-American and non-Hispanic white caregivers.

  13. Retrospective reports of parental feeding practices and emotional eating in adulthood: The role of food preoccupation.

    PubMed

    Tan, Cin Cin; Ruhl, Holly; Chow, Chong Man; Ellis, Lillian

    2016-10-01

    The current study examined the role of food preoccupation as a potential mediator of the associations between parental feeding behaviors during childhood (i.e., restriction for weight, restriction for health, emotion regulation) and emotional eating in adulthood. Participants (N = 97, Mage = 20.3 years) recalled their parents' feeding behaviors during early and middle childhood and reported on current experiences of food preoccupation and emotional eating. Findings revealed that recalled parental feeding behaviors (restriction for weight, restriction for health, emotion regulation) and food preoccupation were positively associated with later emotional eating (correlations ranged from 0.21 to 0.55). In addition, recalled restriction for weight and emotion regulation feeding were positively associated with food preoccupation, r = 0.23 and 0.38, respectively. Further, food preoccupation mediated the association between emotion regulation feeding and later emotional eating (CI95% = 0.10 to 0.44). These findings indicate that parental feeding practices in childhood are related to food preoccupation, and that food preoccupation mediates the association between emotion regulation feeding in childhood and emotional eating in adulthood.

  14. A novel differentiation pathway from CD4+ T cells to CD4− T cells for maintaining immune system homeostasis

    PubMed Central

    Zhao, X; Sun, G; Sun, X; Tian, D; Liu, K; Liu, T; Cong, M; Xu, H; Li, X; Shi, W; Tian, Y; Yao, J; Guo, H; Zhang, D

    2016-01-01

    CD4+ T lymphocytes are key players in the adaptive immune system and can differentiate into a variety of effector and regulatory T cells. Here, we provide evidence that a novel differentiation pathway of CD4+ T cells shifts the balance from a destructive T-cell response to one that favors regulation in an immune-mediated liver injury model. Peripheral CD4−CD8−NK1.1− double-negative T cells (DNT) was increased following Concanavalin A administration in mice. Adoptive transfer of DNT led to significant protection from hepatocyte necrosis by direct inhibition on the activation of lymphocytes, a process that occurred primarily through the perforin-granzyme B route. These DNT converted from CD4+ rather than CD8+ T cells, a process primarily regulated by OX40. DNT migrated to the liver through the CXCR3-CXCL9/CXCL10 interaction. In conclusion, we elucidated a novel differentiation pathway from activated CD4+ T cells to regulatory DNT cells for maintaining homeostasis of the immune system in vivo, and provided key evidence that utilizing this novel differentiation pathway has potential application in the prevention and treatment of autoimmune diseases. PMID:27077809

  15. Idiopathic CD4 lymphocytopenia presenting as refractory cryptococcal meningitis.

    PubMed

    Sharma, A; Lal, V; Modi, M; Khurana, D; Bal, S; Prabhakar, S

    2010-04-01

    Idiopathic CD4 T-lymphocytopenia (ICL) is a syndrome characterized by depletion of CD4 T-cells without evidence of human immunodeficiency virus (HIV) infection. There are a few reported cases of ICL associated with different diseases and clinical conditions, most commonly the opportunistic infections like Tuberculosis, fungal and parasitic diseases which are also seen in HIV-positive patients. We report a case without risk factors or laboratory evidence of HIV infection who presented with refractory cryptococcal meningitis and was found to have ICL.

  16. A focused ethnographic assessment of Middle Eastern mothers' infant feeding practices in Canada.

    PubMed

    Jessri, Mahsa; Farmer, Anna P; Olson, Karin

    2015-10-01

    The aim of this study was to examine the barriers to following complementary feeding guidelines among Middle Eastern mothers and the cultural considerations of practitioners from an emic perspective. This is a two-phase focused ethnographic assessment of infant feeding among 22 Middle Eastern mothers in Western Canada who had healthy infants aged <1 year. Data were collected through four focus groups conducted in Arabic/Farsi, and were further complemented by comprehensive survey data collected in the second phase of study. Mothers' main criterion for choosing infant foods was whether or not foods were Halal, while food allergens were not causes for concern. Vitamin D supplements were not fed to 18/22 of infants, and mashed dates (Halawi), rice pudding (Muhallabia/Ferni) and sugared water/tea were the first complementary foods commonly consumed. Through constant comparison of qualitative data, three layers of influence emerged, which described mothers' process of infant feeding: socio-cultural, health care system and personal factors. Culture was an umbrella theme influencing all aspects of infant feeding decisions. Mothers cited health care professionals' lack of cultural considerations and lack of relevance and practicality of infant feeding guidelines as the main reasons for ignoring infant feeding recommendations. Early introduction of pre-lacteal feeds and inappropriate types of foods fed to infants among immigrant/refugee Middle Eastern mothers in Canada is cause of concern. Involving trained language interpreters in health teams and educating health care staff on cultural competency may potentially increase maternal trust in the health care system and eventually lead to increased awareness of and adherence to best practices with infant feeding recommendations.

  17. Relationship between Parental Feeding Practices and Neural Responses to Food Cues in Adolescents.

    PubMed

    Allen, Harriet A; Chambers, Alison; Blissett, Jacqueline; Chechlacz, Magdalena; Barrett, Timothy; Higgs, Suzanne; Nouwen, Arie

    2016-01-01

    Social context, specifically within the family, influences adolescent eating behaviours and thus their health. Little is known about the specific mechanisms underlying the effects of parental feeding practices on eating. We explored relationships between parental feeding practices and adolescent eating habits and brain activity in response to viewing food images. Fifty- seven adolescents (15 with type 2 diabetes mellitus, 21 obese and 21 healthy weight controls) underwent fMRI scanning whilst viewing images of food or matched control images. Participants completed the Kids Child Feeding Questionnaire, the Childrens' Dutch Eating Behaviour Questionnaire (DEBQ) and took part in an observed meal. Parents completed the Comprehensive Feeding Practices Questionniare and the DEBQ. We were particularly interested in brain activity in response to food cues that was modulated by different feeding and eating styles. Healthy-weight participants increased activation (compared to the other groups) to food in proportion to the level of parental restriction in visual areas of the brain such as right lateral occipital cortex (LOC), right temporal occipital cortex, left occipital fusiform gyrus, left lateral and superior LOC. Adolescents with type 2 diabetes mellitus had higher activation (compared to the other groups) with increased parental restrictive feeding in areas relating to emotional control, attention and decision-making, such as posterior cingulate, precuneus, frontal operculum and right middle frontal gyrus. Participants with type 2 diabetes mellitus also showed higher activation (compared to the other groups) in the left anterior intraparietal sulcus and angular gyrus when they also reported higher self restraint. Parental restriction did not modulate food responses in obese participants, but there was increased activity in visual (visual cortex, left LOC, left occipital fusiform gyrus) and reward related brain areas (thalamus and parietal operculum) in response to

  18. Relationship between Parental Feeding Practices and Neural Responses to Food Cues in Adolescents

    PubMed Central

    Chambers, Alison; Blissett, Jacqueline; Chechlacz, Magdalena; Barrett, Timothy; Higgs, Suzanne; Nouwen, Arie

    2016-01-01

    Social context, specifically within the family, influences adolescent eating behaviours and thus their health. Little is known about the specific mechanisms underlying the effects of parental feeding practices on eating. We explored relationships between parental feeding practices and adolescent eating habits and brain activity in response to viewing food images. Fifty- seven adolescents (15 with type 2 diabetes mellitus, 21 obese and 21 healthy weight controls) underwent fMRI scanning whilst viewing images of food or matched control images. Participants completed the Kids Child Feeding Questionnaire, the Childrens’ Dutch Eating Behaviour Questionnaire (DEBQ) and took part in an observed meal. Parents completed the Comprehensive Feeding Practices Questionniare and the DEBQ. We were particularly interested in brain activity in response to food cues that was modulated by different feeding and eating styles. Healthy-weight participants increased activation (compared to the other groups) to food in proportion to the level of parental restriction in visual areas of the brain such as right lateral occipital cortex (LOC), right temporal occipital cortex, left occipital fusiform gyrus, left lateral and superior LOC. Adolescents with type 2 diabetes mellitus had higher activation (compared to the other groups) with increased parental restrictive feeding in areas relating to emotional control, attention and decision-making, such as posterior cingulate, precuneus, frontal operculum and right middle frontal gyrus. Participants with type 2 diabetes mellitus also showed higher activation (compared to the other groups) in the left anterior intraparietal sulcus and angular gyrus when they also reported higher self restraint. Parental restriction did not modulate food responses in obese participants, but there was increased activity in visual (visual cortex, left LOC, left occipital fusiform gyrus) and reward related brain areas (thalamus and parietal operculum) in response to

  19. Breast feeding a sick child; can social media influence practice?

    PubMed

    Mylod, Dominique

    2015-06-01

    Breast milk represents optimum infant nutrition. The World Health Organization's recommendation that babies should be exclusively breastfed for a minimum of 6 months (Kramer & Kakuma, 2001) remains unchanged in its second decade (Kramer & Kakuma, 2014), which is acknowledged in industrialized countries by successive policies and guidelines for the promotion and care of breastfeeding in children's wards and departments. The known protective influence of breast milk in preventing the onset of disease in later life is of particular import for any sick infant, but the user voice as represented by Helen Calvert's Twitter campaign @heartmummy#hospitalbreastfeeding has united service user and professional voices to call for improved breastfeeding support in pediatric care. Although breastfeeding rates in industrialized countries drop markedly in the first 6 weeks, breastfed babies with cardiac conditions benefit from better oxygen saturations, faster weight gain, and shorter hospital stays. Unwell babies are most in need of the benefits of breast milk. However, families and staff overcome physical barriers to the initiation and maintenance of breastfeeding, including lack of space, privacy, and separation of the maternal-infant dyad. Many women are motivated to breastfeed or express milk but are reluctant to approach health professionals for help and advice. Despite robust evidence and sound guidelines and policies, breastfeeding knowledge and experience amongst Child Health professionals is often inadequate and leaves them unable to support families. While @heartmummy#hospitalbreastfeeding highlights the issue, Child Health strategy needs investment in young people's long term health by increasing staff skills and focusing on breastfeeding as a core therapeutic intervention. Lactation Consultants could offer training, disseminate good practice, and address the needs of breastfeeding families.

  20. Breast-feeding problems after epidural analgesia for labour: a retrospective cohort study of pain, obstetrical procedures and breast-feeding practices.

    PubMed

    Volmanen, P; Valanne, J; Alahuhta, S

    2004-01-01

    Various clinical practices have been found to be associated with breast-feeding problems. However, little is known about the effect of pain, obstetrical procedures and analgesia on breast-feeding behaviour. We designed a retrospective study with a questionnaire concerning pain, obstetrical procedures and breast-feeding practices mailed to 164 primiparae in Lapland. Altogether 99 mothers (60%) returned completed questionnaires that could be included in the analysis, which was carried out in two steps. Firstly, all accepted questionnaires were grouped according to the success or failure to breast-feed fully during the first 12 weeks of life. Secondly, an ad hoc cohort study was performed on the sub-sample of 64 mothers delivered vaginally. As many as 44% of the 99 mothers reported partial breast feeding or formula feeding during the first 12 weeks. Older age of the mother, use of epidural analgesia and the problem of "not having enough milk" were associated with the failure to breast-feed fully. Caesarean section, other methods of labour analgesia and other breast-feeding problems were not associated with partial breast feeding or formula feeding. In the sub-sample, 67% of the mothers who had laboured with epidural analgesia and 29% of the mothers who laboured without epidural analgesia reported partial breast feeding or formula feeding (P = 0.003). The problem of "not having enough milk" was more often reported by those who had had epidural analgesia. Further studies conducted prospectively are needed to establish whether a causal relationship exists between epidural analgesia and breast-feeding problems.

  1. Predictors of Paternal and Maternal Controlling Feeding Practices with 2- to 5-Year-Old Children

    ERIC Educational Resources Information Center

    Haycraft, Emma; Blissett, Jackie

    2012-01-01

    Objective: This study aimed to identify predictors of controlling feeding practices in both mothers and fathers of young children. Design: Cross-sectional, questionnaire design. Setting: Nursery schools within the United Kingdom recruited participants. Participants: Ninety-six mothers and fathers comprising 48 mother-father pairs of male and…

  2. Parental feeding practices and child weight status in Mexican American families: A longitudinal analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Parental feeding practices are thought to influence children's weight status, through children's eating behavior and nutritional intake. However, because most studies have been cross-sectional, the direction of influence is unclear. Moreover, although obesity rates are high among Latino children, fe...

  3. Effects of children's self-regulation of eating on parental feeding practices and child weight

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of this study was to determine whether self-regulation of eating in minority preschool-aged children mediates the relationship between parent feeding practices and child weight. Participants low-income African American and Hispanic parents and their preschool-aged children who participat...

  4. Effect of CD4 gene expression on adenovirus replication.

    PubMed Central

    Hotta, J; Shi, L; Ginsberg, H S

    1994-01-01

    The gene encoding the CD4 receptor was introduced into KB cells to establish the KBT4 cell line, a cell line susceptible to infection with human immunodeficiency virus type 1. Adenovirus replication was found to be significantly less in these cells than in the parental KB cells. Similar decreased adenovirus type 5 (Ad5) replication occurred in HeLaT4 cells compared with the original HeLa cells. The presence of CD4 did not alter the cell surface population of KB cell adenovirus receptors, since viral adsorption was similar in the two cell lines. Moreover, addition of soluble CD4 did not reduce viral replication in either KB or KBT4 infected cells. Uncoating of viral DNA was also unchanged in KBT4 cells compared with the parental KB cells. In contrast, migration to or entrance of viral DNA into nuclei and synthesis of early viral RNAs was delayed and reduced in KBT4 cells. These effects were more pronounced for Ad7 than for Ad5. The yields of infectious viruses were the same in both cell lines, however, after transfection of naked viral DNAs to initiate infection. These results imply that the expression of the CD4 gene in KBT4 cells interfered with passage of uncoated virus across endosomal vesicles and/or transfer of uncoated core viral DNA into the nucleus. Images PMID:7933112

  5. Effect of CD4 gene expression on adenovirus replication.

    PubMed

    Hotta, J; Shi, L; Ginsberg, H S

    1994-11-01

    The gene encoding the CD4 receptor was introduced into KB cells to establish the KBT4 cell line, a cell line susceptible to infection with human immunodeficiency virus type 1. Adenovirus replication was found to be significantly less in these cells than in the parental KB cells. Similar decreased adenovirus type 5 (Ad5) replication occurred in HeLaT4 cells compared with the original HeLa cells. The presence of CD4 did not alter the cell surface population of KB cell adenovirus receptors, since viral adsorption was similar in the two cell lines. Moreover, addition of soluble CD4 did not reduce viral replication in either KB or KBT4 infected cells. Uncoating of viral DNA was also unchanged in KBT4 cells compared with the parental KB cells. In contrast, migration to or entrance of viral DNA into nuclei and synthesis of early viral RNAs was delayed and reduced in KBT4 cells. These effects were more pronounced for Ad7 than for Ad5. The yields of infectious viruses were the same in both cell lines, however, after transfection of naked viral DNAs to initiate infection. These results imply that the expression of the CD4 gene in KBT4 cells interfered with passage of uncoated virus across endosomal vesicles and/or transfer of uncoated core viral DNA into the nucleus.

  6. CD4+ T Cells: guardians of the phagosome.

    PubMed

    Tubo, Noah J; Jenkins, Marc K

    2014-04-01

    CD4(+) T cells are key cells of the adaptive immune system that use T cell antigen receptors to recognize peptides that are generated in endosomes or phagosomes and displayed on the host cell surface bound to major histocompatibility complex molecules. These T cells participate in immune responses that protect hosts from microbes such as Mycobacterium tuberculosis, Cryptococcus neoformans, Leishmania major, and Salmonella enterica, which have evolved to live in the phagosomes of macrophages and dendritic cells. Here, we review studies indicating that CD4(+) T cells control phagosomal infections asymptomatically in most individuals by secreting cytokines that activate the microbicidal activities of infected phagocytes but in a way that inhibits the pathogen but does not eliminate it. Indeed, we make the case that localized, controlled, persistent infection is necessary to maintain large numbers of CD4(+) effector T cells in a state of activation needed to eradicate systemic and more pathogenic forms of the infection. Finally, we posit that current vaccines for phagosomal infections fail because they do not produce this "periodic reminder" form of CD4(+) T cell-mediated immune control.

  7. Cellular Plasticity of CD4+ T Cells in the Intestine

    PubMed Central

    Brucklacher-Waldert, Verena; Carr, Edward J.; Linterman, Michelle A.; Veldhoen, Marc

    2014-01-01

    Barrier sites such as the gastrointestinal tract are in constant contact with the environment, which contains both beneficial and harmful components. The immune system at the epithelia must make the distinction between these components to balance tolerance, protection, and immunopathology. This is achieved via multifaceted immune recognition, highly organized lymphoid structures, and the interaction of many types of immune cells. The adaptive immune response in the gut is orchestrated by CD4+ helper T (Th) cells, which are integral to gut immunity. In recent years, it has become apparent that the functional identity of these Th cells is not as fixed as initially thought. Plasticity in differentiated T cell subsets has now been firmly established, in both health and disease. The gut, in particular, utilizes CD4+ T cell plasticity to mold CD4+ T cell phenotypes to maintain its finely poised balance of tolerance and inflammation and to encourage biodiversity within the enteric microbiome. In this review, we will discuss intestinal helper T cell plasticity and our current understanding of its mechanisms, including our growing knowledge of an evolutionarily ancient symbiosis between microbiota and malleable CD4+ T cell effectors. PMID:25339956

  8. CD4 immunodiagnostics for HIV in the developing world.

    PubMed

    Redd, Andrew D; Quinn, Thomas C

    2008-11-01

    This supplement on evaluating CD4 diagnostics for HIV is the fourth in a series of user-friendly operational guides explaining how to conduct evaluations of diagnostic tests for infectious diseases that are of public health importance in the developing world. Here, Andrew Redd and Thomas Quinn introduce the supplement.

  9. Biomarkers of CD4+ CTL cell Mediated Immunity to Tuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The immune responses mediated by interactions between T-lymphocyte subsets and mycobacteria-infected macrophages are critical for control of tuberculosis. In these studies, the bovine model was used to characterize the cytolytic and mycobactericidal CD4+ T cell response induced by BCG vaccination. ...

  10. STAT5 and CD4 + T Cell Immunity

    PubMed Central

    Owen, David L.; Farrar, Michael A.

    2017-01-01

    STAT5 plays a critical role in the development and function of many cell types. Here, we review the role of STAT5 in the development of T lymphocytes in the thymus and its subsequent role in the differentiation of distinct CD4 + helper and regulatory T-cell subsets. PMID:28163905

  11. Resistance of primary isolates of human immunodeficiency virus type 1 to soluble CD4 is independent of CD4-rgp120 binding affinity.

    PubMed Central

    Ashkenazi, A; Smith, D H; Marsters, S A; Riddle, L; Gregory, T J; Ho, D D; Capon, D J

    1991-01-01

    The infection of human cells by laboratory strains of human immunodeficiency virus type 1 (HIV-1) can be blocked readily in vitro by recombinant soluble CD4 and CD4-immunoglobulin hybrid molecules. In contrast, infection by primary isolates of HIV-1 is much less sensitive to blocking in vitro by soluble CD4-based molecules. To investigate the molecular basis for this difference between HIV-1 strains, we isolated the gp120-encoding genes from several CD4-resistant and CD4-sensitive HIV-1 strains and characterized the CD4-binding properties of their recombinant gp120 (rgp120) products. Extensive amino acid sequence variation was found between the gp120 genes of CD4-resistant and CD4-sensitive HIV-1 isolates. However, the CD4-binding affinities of rgp120 from strains with markedly different CD4 sensitivities were essentially the same, and only small differences were observed in the kinetics of CD4 binding. These results suggest that the lower sensitivity of primary HIV-1 isolates to neutralization by CD4-based molecules is not due to lower binding affinity between soluble CD4 and free gp120. PMID:1871120

  12. Plasticity of Human CD4 T Cell Subsets

    PubMed Central

    Geginat, Jens; Paroni, Moira; Maglie, Stefano; Alfen, Johanna Sophie; Kastirr, Ilko; Gruarin, Paola; De Simone, Marco; Pagani, Massimiliano; Abrignani, Sergio

    2014-01-01

    Human beings are exposed to a variety of different pathogens, which induce tailored immune responses and consequently generate highly diverse populations of pathogen-specific T cells. CD4+ T cells have a central role in adaptive immunity, since they provide essential help for both cytotoxic T cell- and antibody-mediated responses. In addition, CD4+ regulatory T cells are required to maintain self-tolerance and to inhibit immune responses that could damage the host. Initially, two subsets of CD4+ helper T cells were identified that secrete characteristic effector cytokines and mediate responses against different types of pathogens, i.e., IFN-γ secreting Th1 cells that fight intracellular pathogens, and IL-4 producing Th2 cells that target extracellular parasites. It is now well established that this dichotomy is insufficient to describe the complexity of CD4+ T cell differentiation, and in particular the human CD4 compartment contains a myriad of T cell subsets with characteristic capacities to produce cytokines and to home to involved tissues. Moreover, it has become increasingly clear that these T cell subsets are not all terminally differentiated cells, but that the majority is plastic and that in particular central memory T cells can acquire different properties and functions in secondary immune responses. In addition, there is compelling evidence that helper T cells can acquire regulatory functions upon chronic stimulation in inflamed tissues. The plasticity of antigen-experienced human T cell subsets is highly relevant for translational medicine, since it opens new perspectives for immune-modulatory therapies for chronic infections, autoimmune diseases, and cancer. PMID:25566245

  13. Infant Feeding Practices in a Multi-Ethnic Asian Cohort: The GUSTO Study.

    PubMed

    Toh, Jia Ying; Yip, Grace; Han, Wee Meng; Fok, Doris; Low, Yen-Ling; Lee, Yung Seng; Rebello, Salome A; Saw, Seang-Mei; Kwek, Kenneth; Godfrey, Keith M; Chong, Yap-Seng; Chong, Mary Foong-Fong

    2016-05-13

    The optimal introduction of complementary foods provides infants with nutritionally balanced diets and establishes healthy eating habits. The documentation of infant feeding practices in multi-ethnic Asian populations is limited. In a Singapore cohort study (GUSTO), 842 mother-infant dyads were interviewed regarding their feeding practices when the infants were aged 9 and 12 months. In the first year, 20.5% of infants were given dietary supplements, while 5.7% took probiotics and 15.7% homeopathic preparations. At age 9 months, 45.8% of infants had seasonings added to their foods, increasing to 56.3% at 12 months. At age 12 months, 32.7% of infants were given blended food, although 92.3% had begun some form of self-feeding. Additionally, 87.4% of infants were fed milk via a bottle, while a third of them had food items added into their bottles. At both time points, more than a third of infants were provided sweetened drinks via the bottle. Infants of Indian ethnicity were more likely to be given dietary supplements, have oil and seasonings added to their foods and consumed sweetened drinks from the bottle (p < 0.001). These findings provide a better understanding of variations in infant feeding practices, so that healthcare professionals can offer more targeted and culturally-appropriate advice.

  14. Infant Feeding Practices in a Multi-Ethnic Asian Cohort: The GUSTO Study

    PubMed Central

    Toh, Jia Ying; Yip, Grace; Han, Wee Meng; Fok, Doris; Low, Yen-Ling; Lee, Yung Seng; Rebello, Salome A.; Saw, Seang-Mei; Kwek, Kenneth; Godfrey, Keith M.; Chong, Yap-Seng; Chong, Mary Foong-Fong

    2016-01-01

    The optimal introduction of complementary foods provides infants with nutritionally balanced diets and establishes healthy eating habits. The documentation of infant feeding practices in multi-ethnic Asian populations is limited. In a Singapore cohort study (GUSTO), 842 mother-infant dyads were interviewed regarding their feeding practices when the infants were aged 9 and 12 months. In the first year, 20.5% of infants were given dietary supplements, while 5.7% took probiotics and 15.7% homeopathic preparations. At age 9 months, 45.8% of infants had seasonings added to their foods, increasing to 56.3% at 12 months. At age 12 months, 32.7% of infants were given blended food, although 92.3% had begun some form of self-feeding. Additionally, 87.4% of infants were fed milk via a bottle, while a third of them had food items added into their bottles. At both time points, more than a third of infants were provided sweetened drinks via the bottle. Infants of Indian ethnicity were more likely to be given dietary supplements, have oil and seasonings added to their foods and consumed sweetened drinks from the bottle (p < 0.001). These findings provide a better understanding of variations in infant feeding practices, so that healthcare professionals can offer more targeted and culturally-appropriate advice. PMID:27187461

  15. Evolution of the CD4 family: teleost fish possess two divergent forms of CD4 in addition to lymphocyte activation gene-3

    USGS Publications Warehouse

    Laing, K.J.; Zou, J.J.; Purcell, M.K.; Phillips, R.; Secombes, C.J.; Hansen, J.D.

    2006-01-01

    The T cell coreceptor CD4 is a transmembrane glycoprotein belonging to the Ig superfamily and is essential for cell-mediated immunity. Two different genes were identified in rainbow trout that resemble mammalian CD4. One (trout CD4) encodes four extracellular Ig domains reminiscent off mammalian CD4, whereas the other (CD4REL) codes for two Ig domains. Structural motifs within the amino acid sequences suggest that the two Ig domains of CD4REL duplicated to generate the four-domain molecule of CD4 and the related gene, lymphocyte activation gene-3. Here we present evidence that both of these molecules in trout are homologous to mammalian CD4 and that teleosts encode an additional CD4 family member, lymphocyte activation gene-3, which is a marker for activated T cells. The syntenic relationships of similar genes in other teleost and non-fish genomes provide evidence for the likely evolution of CD4-related molecules in vertebrates, with CD4REL likely representing the primordial form in fish. Expression of both CD4 genes is highest in the thymus and spleen, and mRNA expression of these genes is limited to surface IgM- lymphocytes, consistent with a role for T cell functionality. Finally, the intracellular regions of both CD4 and CD4REL possess the canonical CXC motif involved in the interaction off CD4 with p56LCK, implying that similar mechanisms for CD4 + T cell activation are present in all vertebrates. Our results therefore raise new questions about T cell development and functionality in lower vertebrates that cannot be answered by current mammalian models and, thus, is of fundamental importance for understanding the evolution of cell-mediated immunity in gnathosomes. Copyright ?? 2006 by The American Association of Immunologists, Inc.

  16. Delineating CD4 dependency of HIV-1: Adaptation to infect low level CD4 expressing target cells widens cellular tropism but severely impacts on envelope functionality

    PubMed Central

    Beauparlant, David; Rusert, Peter; Magnus, Carsten; Weber, Jacqueline; Uhr, Therese; Clapham, Paul R.; Metzner, Karin J.

    2017-01-01

    A hallmark of HIV-1 infection is the continuously declining number of the virus’ predominant target cells, activated CD4+ T cells. With diminishing CD4+ T cell levels, the capacity to utilize alternate cell types and receptors, including cells that express low CD4 receptor levels such as macrophages, thus becomes crucial. To explore evolutionary paths that allow HIV-1 to acquire a wider host cell range by infecting cells with lower CD4 levels, we dissected the evolution of the envelope-CD4 interaction under in vitro culture conditions that mimicked the decline of CD4high target cells, using a prototypic subtype B, R5-tropic strain. Adaptation to CD4low targets proved to severely alter envelope functions including trimer opening as indicated by a higher affinity to CD4 and loss in shielding against neutralizing antibodies. We observed a strikingly decreased infectivity on CD4high target cells, but sustained infectivity on CD4low targets, including macrophages. Intriguingly, the adaptation to CD4low targets altered the kinetic of the entry process, leading to rapid CD4 engagement and an extended transition time between CD4 and CCR5 binding during entry. This phenotype was also observed for certain central nervous system (CNS) derived macrophage-tropic viruses, highlighting that the functional perturbation we defined upon in vitro adaptation to CD4low targets occurs in vivo. Collectively, our findings suggest that CD4low adapted envelopes may exhibit severe deficiencies in entry fitness and shielding early in their evolution. Considering this, adaptation to CD4low targets may preferentially occur in a sheltered and immune-privileged environment such as the CNS to allow fitness restoring compensatory mutations to occur. PMID:28264054

  17. TCRαβ+/CD4+ Large Granular Lymphocytosis

    PubMed Central

    Lima, Margarida; Almeida, Julia; dos Anjos Teixeira, Maria; Alguero, Maria del Carmen; Santos, Ana Helena; Balanzategui, Ana; Queirós, Maria Luís; Bárcena, Paloma; Izarra, Antonio; Fonseca, Sónia; Bueno, Clara; Justiça, Benvindo; Gonzalez, Marcos; San Miguel, Jesús F.; Orfao, Alberto

    2003-01-01

    Large granular lymphocyte (LGL) leukemia is a well-recognized disease of mature T-CD8+ or less frequently natural killer cells; in contrast, monoclonal expansions of CD4+ T-LGL have only been sporadically reported in the literature. In the present article we have explored throughout a period of 56 months the incidence of monoclonal expansions of CD4+ T-LGL in a population of 2.2 million inhabitants and analyzed the immunophenotype and the pattern of cytokine production of clonal CD4+ T cells of a series of 34 consecutive cases. Like CD8+ T-LGL leukemias, CD4+ T-LGL leukemia patients have an indolent disease; however, in contrast to CD8+ T-LGL leukemias, they do not show cytopenias and autoimmune phenomena and they frequently have associated neoplasias, which is usually determining the clinical course of the disease. Monoclonal CD4+ T-LGLshowed expression of TCRαβ, variable levels of CD8 (CD8−/+dim) and a homogeneous typical cytotoxic (granzyme B+, CD56+, CD57+, CD11b+/−) and activated/memory T cell (CD2+bright, CD7−/+dim, CD11a+bright, CD28−, CD62L− HLA-DR+) immunophenotype. In addition, they exhibited a Th1 pattern of cytokine production [interferon-γ++, tumor necrosis factor-α++, interleukin (IL-2)−/+, IL-4−, IL-10−, IL-13−]. Phenotypic analysis of the TCR-Vβ repertoire revealed large monoclonal TCR-Vβ expansions; only a restricted number of TCR-Vβ families were represented in the 34 cases analyzed. These findings suggest that monoclonal TCRαβ+/CD4+/NKa+/CD8−/+dim T-LGL represent a subgroup of monoclonal LGL lymphoproliferative disorders different from both CD8+ T-LGL and natural killer cell-type LGL leukemias. Longer follow-up periods are necessary to determine the exact significance of this clonal disorder. PMID:12875995

  18. The role of family communication and parents' feeding practices in children's food preferences.

    PubMed

    Alm, Siril; Olsen, Svein Ottar; Honkanen, Pirjo

    2015-06-01

    This study used Family Communication Patterns Theory (FCPT) to explore how family-dinner-related communication takes place and how parents' feeding practices may be associated with children's preferences for dinner meals. The sample consisted of 12 dyads with seven- and eight-year-old Norwegian children and their parents. In-depth photo interviews were used for collecting data. Interview transcripts and photographs were examined through content analysis. Results indicated that most families were conversation oriented, and communication tended to shift from consensual during weekdays to pluralistic at weekends. On weekdays, the dinner menu was often a compromise between children's preferences and parents' intentions to provide quick, healthy dinner options for the family. To a greater extent at weekends, children were allowed to choose dinner alternatives for the entire family. Restriction of unhealthy dinner alternatives was the practice most used to control children's diets and, in fact, might explain children's high preferences for unhealthy dinner alternatives. Results underline the importance of giving children control of what they eat and being responsive to children's preferences while guiding them towards healthy dinner alternatives rather than using force and restriction. From a more theoretical perspective, this study explored how FCPT could be combined with theories about parents' feeding practices to understand meal preferences and choices among young children and their families, and how time and situation (context) influence families' communication patterns and feeding practices in their homes.

  19. Association between Australian-Indian mothers' controlling feeding practices and children's appetite traits.

    PubMed

    Jani, Rati; Mallan, Kimberley M; Daniels, Lynne

    2015-01-01

    This cross-sectional study examined the association between controlling feeding practices and children's appetite traits. The secondary aim studied the relationship between controlling feeding practices and two proxy indicators of diet quality. Participants were 203 Australian-Indian mothers with children aged 1-5 years. Controlling feeding practices (pressure to eat, restriction, monitoring) and children's appetite traits (food approach traits: food responsiveness, enjoyment of food, desire to drink, emotional overeating; food avoidance traits: satiety responsiveness, slowness in eating, fussiness and emotional undereating) were measured using self-reported, previously validated scales/questionnaires. Children's daily frequency of consumption of core and non-core foods was estimated using a 49-item list of foods eaten (yes/no) in the previous 24 hours as an indicator of diet quality. Higher pressure to eat was associated with higher scores for satiety responsiveness, slowness in eating, fussiness and lower score for enjoyment of food. Higher restriction was related to higher scores for food responsiveness and emotional overeating. Higher monitoring was inversely associated with fussiness, slowness in eating, food responsiveness and emotional overeating and positively associated with enjoyment of food. Pressure to eat and monitoring were related to lower number of core and non-core foods consumed in the previous 24 hours, respectively. All associations remained significant after adjusting for maternal and child covariates (n = 152 due to missing data). In conclusion, pressure to eat was associated with higher food avoidance traits and lower consumption of core foods. Restrictive feeding practices were associated with higher food approach traits. In contrast, monitoring practices were related to lower food avoidance and food approach traits and lower non-core food consumption.

  20. Early childhood feeding: assessing knowledge, attitude, and practices of multi-ethnic child-care providers.

    PubMed

    Freedman, Marjorie R; Alvarez, Karina P

    2010-03-01

    Early childhood is a critical period for shaping and influencing feeding and lifestyle behaviors that have implications for future weight and health. With more women in the workforce, families have become reliant on child care. Thus, the child-feeding relationship has become a shared responsibility between the parent and child-care provider. Little is known about the impact of child-care providers on development of early childhood feeding behaviors and subsequent risk for obesity, especially in the Hispanic ethnic group. This research examined child-feeding attitudes, practices, and knowledge of multi-ethnic home-based and center-based child-care providers. Questionnaires were completed by a convenience sample of 72 providers, 50 of whom completed a pre- and post-test on child-feeding knowledge after receiving a 90-minute class based on Satter's division of responsibility feeding model during the spring of 2008. Results indicate many providers had practices consistent with this model. However, substantial differences were reported by Hispanic providers, who were statistically more likely to encourage children to finish meals before dessert, prepare foods they perceived as well-liked by children, coach children to eat foods perceived as appropriate, and not eat with children during meals. A substantial increase in knowledge from 73% correct at pretest to 82% at post-test was noted, with a substantial increase in knowledge on five of 13 questions. However, knowledge was not always congruent with behavior. This study points to differences among providers based on ethnicity, and strongly recommends recruiting Hispanic child-care providers to participate in educational programs and community efforts to prevent obesity.

  1. Complementary Feeding Practices of Mothers and Their Perceived Impacts on Young Children: Findings from KEEA District of Ghana.

    PubMed

    Egyir, Bridget K; Ramsay, Samantha A; Bilderback, Barry; Safaii, SeAnne

    2016-09-01

    Objective Appropriate and timely complementary feeding practices are fundamental to a child's growth, health, and development during the first 2 years of life. This study aimed to understand (1) Ghanaian mother's complementary feeding practices, and (2) their perceived and observed impacts of complementary feeding on their children. Methods Ghanaian mothers with children 4-24 months of age were recruited from four communities in the Komenda Edina Eguafo Abrem district in the Central Region of Ghana (n = 99). A qualitative methodological approach with focus group interview discussions was used. Eleven focus group interviews were conducted, and were audio recorded and transcribed. The audio transcriptions were coded and analyzed into pertinent themes, meta-themes, and theoretical concepts. Results Over 80 % (85) of mothers reported poor knowledge about the effects of complementary feeding on their children and 45 % (45) of the children were undernourished, indicating inappropriate complementary feeding practices. Some mothers held misconceptions about the effect of food on children's health. Four overarching themes were identified: (1) mothers' background knowledge about food, child health and growth outcomes, (2) mothers' motivation in feeding their children, (3) barriers to feeding, (4) foods mothers offered their children. Conclusion for Practice Nutrition education on complementary feeding is needed for Ghanaian mothers. Health facilities and community outreach programs could be a venue to provide education to mothers regarding infant and young child feeding practices in Ghana.

  2. Infant feeding practices in a South African birth cohort-A longitudinal study.

    PubMed

    Budree, Shrish; Goddard, Elizabeth; Brittain, Kirsty; Cader, Shihaam; Myer, Landon; Zar, Heather J

    2016-10-02

    Childhood malnutrition is highly prevalent in low- and middle-income countries. The choices of complementary foods, which are important in infant nutrition, are poorly described in this setting. We investigated infant feeding practices in a South African birth cohort, the Drakenstein Child Health Study. Longitudinal feeding data were collected from March 2012 to March 2015. Feeding practices at birth, 6-10 and 14 weeks and 6, 9, and 12 months, were investigated using food frequency questionnaires. Anthropometry was measured at birth and 12 months. The quality of the diet was analyzed using the World Health Organization infant and young child feeding indicators. Regression models were used to explore associations between feeding and growth outcomes at 1 year. Exclusive breastfeeding for 6 months was low (13%), and 19% of infants were introduced to solid foods before 4 months. There was high daily consumption of processed meat (56%) and inappropriate foods such as fruit juice (82%), soft drinks (54%), and refined sugary foods (51%) at 1 year. Dietary diversity and consumption of iron rich foods were low at 6 months (5% and 3%, respectively) but higher by 12 months (75% and 78%). Longer duration of exclusive breastfeeding was associated with a lower height-for-age z-score at 1 year. Several dietary deficits and a rising trend in the consumption of inappropriate nutritionally poor foods were identified. These findings raise concern about poor dietary practices and the impact on child and long-term health.

  3. Feeding practices and nutritional status of children under two years of age.

    PubMed

    Khan, M I; Hoque, M A; Mollah, A H; Islam, M N; Latif, S A; Hossain, M A

    2011-10-01

    A descriptive cross sectional study was done in the department of Pediatrics Mymensingh Medical College Hospital. The purpose of the study was to assess breast feeding pattern, complementary feeding pattern, types of complementary foods and also to assess the nutritional status and to detect any relationship with the nutritional status and the feeding practices. Mothers with their children aged less than 2 years were included and very sick children, mother less children, handicapped children were excluded. Four hundred (400) consecutive children were enrolled from eight upazillas of Mymensingh district who were selected randomly. Out of 400 children, 214 children (53.5%) were male and 186 children (47.5%) were female and M:F was 1.2:1. Exclusive breastfeeding rate was 41.5%. Pre-lacteal feeding rate were 30.7% and most common pre-lacteal foods were honey and sugar water. Colostrum was given in 69.3% children. Breast feeding continued at the time of interview was 58.1%. Complementary feeding started in time in 35.8%, early weaning in 44.5% children. Type of complementary food was mainly luta (rice powder mixed with boiled water and sugar only) in 38.8% and khichuri (rice, pulses, soybean oil) in 19.5%. Bottle feeding rate was 31.30%. Around 43% children were underweight and 10.25% children were severely underweight and common in between 12 to 23 months of age group. Around 29% children were stunted among 11.25% were severely stunted. About 13.5% children were wasted and among them 2.5% were severely wasted. Stunting prevalent over the age of 9 months and wasting started after 6 months of age. Malnutrition was common in partially breast fed and early weaning with carbohydrate rich food.

  4. A study of marketing and its effect on infant feeding practices.

    PubMed

    Suleiman, A

    2001-09-01

    A baby milk market was created in the late nineteenth and early twentieth centuries and was conceived through the mutual attraction of the manufacturers and doctors. This has partly attributed to the change from breast to artificial feeding. This study was conducted to determine whether marketing had any effect on infant feeding practices. Fifty Malay mothers whose last child was aged less than five years were asked, by questionnaire and by interview, to identify whether several marketing methods influenced their decision on the selection of infant feeding practice. It was found that these mothers felt milk advertisements on television were attractive (72%), were influenced by others to buy a particular brand of formula (38.4%), were influenced by free milk samples to buy a particular brand of milk formula (65.2%) and were not influenced by their doctors on the chosen method of feeding (68%). More studies should be conducted on a bigger sample in other settings and targeting other methods of marketing to substantiate the above results. Further, similar studies among Chinese and Indian mothers are also required.

  5. Does maternal history of eating disorders predict mothers' feeding practices and preschoolers' emotional eating?

    PubMed

    de Barse, Lisanne M; Tharner, Anne; Micali, Nadia; Jaddoe, Vincent V W; Hofman, Albert; Verhulst, Frank C; Franco, Oscar H; Tiemeier, Henning; Jansen, Pauline W

    2015-02-01

    We aimed to examine whether a maternal history of eating disorders predicted mothers' feeding practices and preschoolers' emotional eating patterns. Data were available from 4851 mothers and their children, who participated in a Dutch population-based cohort study (the Generation R Study). Maternal history of lifetime eating disorders was assessed during pregnancy using a self-report questionnaire. Mothers filled out the Child Feeding Questionnaire and the Child Eating Behaviour Questionnaire when children were four years old. Linear regression analyses were performed, adjusting for potential confounders. Of all mothers, 8.6% had a history of an eating disorder (2.5% anorexia nervosa (AN); 3.9% bulimia nervosa (BN); 2.2% both AN and BN). Compared to mothers without a history of eating disorders, mothers with a history of eating disorders, in particular AN, used less pressuring feeding strategies (standardized B = -0.30; 95% CI: -0.49, -0.11). Children of mothers with a history of AN had relatively high levels of emotional overeating (standardized B = 0.19; 95% CI: 0.00, 0.39). Maternal history of BN was not related to mothers' feeding practices or children's emotional eating. Overall, the levels of emotional overeating among children of mothers with a history of eating disorders are noteworthy, particularly considering the young age (4 years) of participating children. This finding may reflect an effect of maternal eating disorders on the development of disordered eating patterns, but could also be subject to mothers' perception.

  6. Infant feeding practices among mildly wasted children: a retrospective study on Nias Island, Indonesia

    PubMed Central

    2012-01-01

    Background This study investigated the infant feeding practices of participating mothers who were recruited into a research project aimed at improving the nutritional status of mildly wasted children (< -1.0 to ≥ -1.5 Weight-for-Height Z-scores) aged ≥ 6 to < 60 months on Nias Island, Indonesia. Methods Cross-sectional, questionnaire-based interview of mothers of the index children (n = 215) who were admitted to the community program for mildly wasted children in the study area. Four focus groups and twenty in-depth interviews were conducted to explore further information on infant feeding practices in the study area. Results Retrospective results indicated that 6% of the mothers never breastfed. Fifty two percent of mothers initiated breastfeeding within six hours of birth, but 17% discarded colostrum. Exclusive breastfeeding until 6 months of age was practiced by 12%. Seventy-four percent of the mothers offered supplementary liquids besides breast milk within the first 7 days of life, and 14% of infants received these supplementary liquids from 7 days onwards until 6 months of age. Moreover, 79% of the infants were given complementary foods (solid, semi-solid, or soft foods) before 6 months of age. About 9% of the children were breastfed at least two years. Less than one in five of the mildly wasted children (19%) were breastfed on admission to the community program. Qualitative assessments found that inappropriate infant feeding practices were strongly influenced by traditional beliefs of the mothers and paternal grandmothers in the study areas. Conclusion Generally, suboptimal infant feeding was widely practiced among mothers of mildly wasted children in the study area on Nias Island, Indonesia. To promote breastfeeding practices among mothers on Nias Island, appropriate nutrition training for community workers and health-nutrition officers is needed to improve relevant counseling skills. In addition, encouraging public nutrition education that promotes

  7. CD4 T-cell memory generation and maintenance.

    PubMed

    Gasper, David J; Tejera, Melba Marie; Suresh, M

    2014-01-01

    Immunologic memory is the adaptive immune system's powerful ability to remember a previous antigen encounter and react with accelerated vigor upon antigen re-exposure. It provides durable protection against reinfection with pathogens and is the foundation for vaccine-induced immunity. Unlike the relatively restricted immunologic purview of memory B cells and CD8 T cells, the field of CD4 T-cell memory must account for multiple distinct lineages with diverse effector functions, the issue of lineage commitment and plasticity, and the variable distribution of memory cells within each lineage. Here, we discuss the evidence for lineage-specific CD4 T-cell memory and summarize the known factors contributing to memory-cell generation, plasticity, and long-term maintenance.

  8. Circumvention of regulatory CD4(+) T cell activity during cross-priming strongly enhances T cell-mediated immunity.

    PubMed

    Heit, Antje; Gebhardt, Friedemann; Lahl, Katharina; Neuenhahn, Michael; Schmitz, Frank; Anderl, Florian; Wagner, Hermann; Sparwasser, Tim; Busch, Dirk H; Kastenmüller, Kathrin

    2008-06-01

    Immunization with purified antigens is a safe and practical vaccination strategy but is generally unable to induce sustained CD8(+) T cell-mediated protection against intracellular pathogens. Most efforts to improve the CD8(+) T cell immunogenicity of these vaccines have focused on co-administration of adjuvant to support cross-presentation and dendritic cell maturation. In addition, it has been shown that CD4(+) T cell help during the priming phase contributes to the generation of protective CD8(+) memory T cells. In this report we demonstrate that the depletion of CD4(+) T cells paradoxically enhances long-lasting CD8-mediated protective immunity upon protein vaccination. Functional and genetic in vivo inactivation experiments attribute this enhancement primarily to MHC class II-restricted CD4(+) regulatory T cells (Treg), which appear to physiologically suppress the differentiation process towards long-living effector memory T cells. Since, in functional terms, this suppression by Treg largely exceeds the positive effects of conventional CD4(+) T cell help, even the absence of all CD4(+) T cells or lack of MHC class II-mediated interactions on priming dendritic cells result in enhanced CD8(+) T cell immunogenicity. These findings have important implications for the improvement of vaccines against intracellular pathogens or tumors, especially in patients with highly active Treg.

  9. Tyrosine kinase activity of CD4-associated p56lck may not be required for CD4-dependent T-cell activation.

    PubMed Central

    Collins, T L; Burakoff, S J

    1993-01-01

    The lymphoid-specific tyrosine kinase p56lck (Lck) is critical for the development and activation of T lymphocytes, and Lck kinase activity has been implicated in both T-cell antigen receptor/CD3- and CD4-mediated signaling. CD4-dependent T-cell activation has been demonstrated to be dependent upon the association of CD4 with Lck. To examine the role of the kinase activity of Lck in CD4-dependent T-cell activation, we have generated several kinase-deficient mutants of Lck. When transfected into CD4+ murine T-cell hybridoma cells, these mutants cause approximately 90% diminution in CD4-associated Lck kinase activity. Specifically, upon CD4 crosslinking there is decreased Lck autophosphorylation and decreased phosphorylation of an exogenous substrate. When CD4 is crosslinked to the T-cell antigen receptor-CD3 complex, decreased phosphorylation of associated substrates is also observed. In spite of this striking inhibition of Lck kinase function, cells expressing the kinase-deficient mutants demonstrate normal or enhanced CD4-dependent antigen responsiveness. These data demonstrate that the level of Lck kinase activity does not correlate with its CD4-associated function and suggest that the kinase activity of Lck may not be required for CD4-mediated signaling. Images Fig. 1 Fig. 2 Fig. 3 PMID:7505449

  10. Comparative evaluation of the CD4+CD8+ and CD4+CD8- lymphocytes in the immune response to porcine rubulavirus.

    PubMed

    Hernández, J; Garfias, Y; Nieto, A; Mercado, C; Montaño, L F; Zenteno, E

    2001-05-30

    The porcine immune system is unique in the expression of CD4+CD8+ (double-positive, DP) lymphocytes. These cells have been associated with immunological memory due to their gradual increase with age, the expression of memory phenotype and their ability to respond to recall viral antigen. This work analyzes the biological function of CD4+CD8- and CD4+CD8+ lymphocytes in the immune response to porcine rubulavirus (PRv). CD4+CD8- cells isolated from pigs 3 weeks after infection with porcine rubulavirus proliferated in response to homologous virus and generated lymphoblasts which were predominantly of the CD4+CD8+ phenotype, whereas stimulation with mitogen induced proliferation but did not switch the phenotype. CD4+CD8- lymphocytes isolated after 10 weeks of infection proliferated in response to phytohemagglutinin (PHA) but did not proliferate in response to homologous virus and did not change their phenotype, whereas CD4+CD8+ lymphocytes proliferated in response to PHA and to viral antigen. The cytokine profile of both lymphocyte populations showed the presence of IL-2 and IL-10 transcripts, quantitation demonstrated that CD4+CD8+ cells expressed mainly IL-10, whereas CD4+CD8- lymphocytes expressed primarily IL-2. Our results show that CD4+CD8- lymphocytes in the early phase of porcine rubulavirus infection can be converted to double-positive cells expressing IL-10 in an antigen-dependent manner, and that CD4+CD8- T-cells late in infection do not acquire CD8.

  11. Child feeding practices, food habits, anthropometric indicators and cognitive performance among preschoolers in Peninsular Malaysia.

    PubMed

    Mohd Nasir, Mohd Taib; Norimah, Abdul Karim; Hazizi, Abu Saad; Nurliyana, Abdul Razak; Loh, Siow Hon; Suraya, Ibrahim

    2012-04-01

    This study aimed to determine the relationship between child feeding practices, food habits, and anthropometric indicators with cognitive performance of preschoolers aged 4-6 years in Peninsular Malaysia (n=1933). Parents were interviewed on socio-demographic background, nutrition knowledge, child feeding practices and food habits. Height and weight of the preschoolers were measured; BMI-for-age, weight-for-age and height-for-age were determined. Cognitive performance was assessed using Raven's Colored Progressive Matrices. The mean monthly household income was RM3610 and 59.6% of parents attained secondary education. Thirty-three percent of parents had good knowledge on nutrition, 39% satisfactory and 28% poor. For child feeding practices, perceived responsibility had the highest mean score (M=3.99, SD=0.72), while perceived child weight had the lowest (M=2.94, SD=0.38). The prevalence of possible risk of overweight, being overweight, and obesity were 3.9%, 7.9% and 8.1%, respectively, whereas the prevalence of underweight and stunting were 8.0% and 8.4%, respectively. Breakfast was the second most frequently skipped meal (16.8%) after dinner (18.1%). The mean cognitive score was 103.5 (SD=14.4). Height-for-age and consumption of dinner were found to contribute significantly towards cognitive performance after controlling for socio-demographic background and parent's nutrition knowledge.

  12. Correlates of parental feeding practices with pre-schoolers: Parental body image and eating knowledge, attitudes, and behaviours.

    PubMed

    Damiano, Stephanie R; Hart, Laura M; Paxton, Susan J

    2016-06-01

    Parental feeding practices have been linked to eating and weight status in young children; however, more research is needed to understand what influences these feeding practices. The aim of this study was to examine how parental feeding practices that are linked to unhealthy eating patterns in young children, are related to parental body image and eating knowledge, attitudes, and behaviours . Participants were 330 mothers of a 2- to 6-year-old child. Mothers completed measures of knowledge of child body image and eating patterns, overvaluation of weight and shape, internalization of general media and athletic ideals, dieting, and parental feeding practices. Higher maternal knowledge of strategies to promote positive child body image and eating patterns predicted lower weight restriction, instrumental, emotional, and pushing to eat feeding practices. Overvaluation of weight and shape predicted use of fat restriction. Maternal internalization of the athletic ideal predicted instrumental and pushing to eat feeding practices. As these feeding practices have been associated with long-term risk of children's weight gain and/or disordered eating, these findings highlight the need for prevention interventions to target knowledge, attitudes, and behaviours of parents of pre-schoolers.

  13. CD4 Variability in Malawi: Implications for Use of a CD4 Threshold of 500 Cells/mm3 Versus Universal Eligibility for Antiretroviral Therapy

    PubMed Central

    Schooley, Alan L.; Kamudumuli, Pocha Samuel; Vangala, Sitaram; Tseng, Chi-hong; Soko, Chifundo; Parent, Julie; Phiri, Khumbo; Jahn, Andreas; Namarika, Dan; Hoffman, Risa M.

    2016-01-01

    Background. Given the uncertainty about the ability of a single CD4 count to accurately classify a patient as antiretroviral therapy (ART) eligible, we sought to understand the extent to which CD4 variability results in misclassification at a CD4 threshold of 500 cells/mm3. Methods. We performed a prospective study of CD4 variability in Malawian human immunodeficiency virus-infected, ART-naive, World Health Organization (WHO) stage 1 or 2, nonpregnant adults. CD4 counts were performed daily for 8 days. We fit a Bayesian linear mixed-effects model of log-transformed CD4 cell counts to the data. We used Monte Carlo approximations to estimate misclassification rates for different observed values of CD4. The misclassification rate was calculated based on the conditional probability of true CD4 given the geometric mean of observed CD4 measurements. Results. Fifty patients were enrolled from 2 sites. The median age was 33.5 years (interquartile range, 27.5–40.0) and 34 (68%) were female. Misclassification rates were <1% when the observed CD4 counts were ≤250 or ≥750 cells/mm3. Rates of misclassification were high at observed CD4 counts between 350 and 650 cells/mm3, particularly when a single measurement was used (up to 46.7%). Conclusions. Our data show that ART eligibility based on a single CD4 count results in highest risk of misclassification when observed CD4 counts are in the range of 350–650 cells/mm3. Given the benefits of early ART, countries should weigh the costs and complexity of CD4 testing using a 500 cell/mm3 threshold against the cost savings and public health benefits of universal eligibility. PMID:27704028

  14. Breast-feeding, self-exam, and exercise practices before and after reduction mammoplasty.

    PubMed

    Brown, Jennifer R; Holton, Luther H; Chung, Thomas L; Slezak, Sheri

    2008-10-01

    The current indications for reduction mammoplasty include the relief of painful physical symptoms of macromastia. Numerous studies have demonstrated not only improvement in physical symptoms following reduction mammoplasty, but postoperative psychological benefits as well, including increased ability to participate in physical activity as a result of pain relief and decreased breast mass. Reduction mammoplasty may have additional effects on the patient's ability to breast-feed and perform breast self-exam. The present study is a retrospective study of the effects of reduction mammoplasty on breast-feeding, breast self-exam, physical symptoms, and physical activity. One-hundred and forty-one patients who underwent reduction mammoplasty at our institution between the years 1996-2005 agreed to participate in the study. Each was asked a series of questions in order to assess changes in symptoms and behaviors including breast-feeding and breast self-exam practices before and after the surgery. Patients were also asked questions regarding their pain symptoms and physical activity profiles. Ninety-seven percent of the participants claimed to have back, neck, and/or shoulder pain that was either significantly improved or completely resolved. Moreover, 100% of patients report that physical activity such as exercise was easier following reduction mammoplasty. Ninety-three percent of participants reported that performing breast self-exam following surgery was either the same (68%) or easier (25%) as a result of having less breast tissue. Eighty-nine percent of participants had no children following surgery, therefore effects on breast-feeding practices following reduction mammoplasty were not statistically significant. However, we suggest that when patients are seen in consultation or in the perioperative period, there is an opportunity to teach patients about the benefits of breast-feeding, and to assure patients that a pedicle flap reduction will likely allow breastfeeding

  15. Feeding practices for infants and young children during and after common illness. Evidence from South Asia

    PubMed Central

    Aguayo, Víctor M.

    2016-01-01

    Abstract Global evidence shows that children's growth deteriorates rapidly during/after illness if foods and feeding practices do not meet the additional nutrient requirements associated with illness/convalescence. To inform policies and programmes, we conducted a review of the literature published from 1990 to 2014 to document how children 0–23 months old are fed during/after common childhood illnesses. The review indicates that infant and young child feeding (IYCF) during common childhood illnesses is far from optimal. When sick, most children continue to be breastfed, but few are breastfed more frequently, as recommended. Restriction/withdrawal of complementary foods during illness is frequent because of children's anorexia (perceived/real), poor awareness of caregivers' about the feeding needs of sick children, traditional beliefs/behaviours and/or suboptimal counselling and support by health workers. As a result, many children are fed lower quantities of complementary foods and/or are fed less frequently when they are sick. Mothers/caregivers often turn to family/community elders and traditional/non‐qualified practitioners to seek advice on how to feed their sick children. Thus, traditional beliefs and behaviours guide the use of ‘special’ feeding practices, foods and diets for sick children. A significant proportion of mothers/caregivers turn to the primary health care system for support but receive little or no advice. Building the knowledge, skills and capacity of community health workers and primary health care practitioners to provide mothers/caregivers with accurate and timely information, counselling and support on IYCF during and after common childhood illnesses, combined with large‐scale communication programmes to address traditional beliefs and norms that may be harmful, is an urgent priority to reduce the high burden of child stunting in South Asia. PMID:26840205

  16. The relationship between maternal feeding beliefs and practices and perceptions of infant eating behaviours at 4 months.

    PubMed

    Mallan, Kimberley M; Sullivan, Serena E; de Jersey, Susan J; Daniels, Lynne A

    2016-10-01

    Parental feeding practices and children's eating behaviours are inter-related and both have been implicated in the development of childhood obesity. However, research on the parent-child feeding relationship during the first few months of life is limited. The aim of this study was to examine the cross-sectional relationship between maternal feeding beliefs and practices and infant eating behaviours in a community sample. Mothers (N = 413) of 4 month old infants recruited during pregnancy for the New Beginnings: Healthy Mothers and Babies study self-reported feeding beliefs/practices and eating behaviours of their infants on established tools. Data on a comprehensive range of maternal and infant characteristics were also collected. Multivariable regression models were used to assess the associations between five feeding beliefs and practices and four eating behaviours, adjusting for key maternal and infant covariates. Mothers concerned about their infant becoming underweight rated the infant higher on satiety responsiveness and lower on enjoyment of food. Higher awareness of infant feeding cues was associated with higher infant enjoyment of food. Mothers concerned about their infant becoming overweight and those who used food to calm their baby rated the infant as higher on food responsiveness. Feeding to a schedule (vs on demand) was not associated with any of the infant eating behaviours. A relationship between maternal feeding beliefs and practices and infant eating behaviours is apparent early in life, therefore longitudinal investigation to establish the directions of this relationship is warranted.

  17. Knowledge, attitudes, and beliefs that can influence infant feeding practices in American Indian mothers.

    PubMed

    Eckhardt, Cara L; Lutz, Tam; Karanja, Njeri; Jobe, Jared B; Maupomé, Gerardo; Ritenbaugh, Cheryl

    2014-10-01

    The promotion of healthy infant feeding is increasingly recognized as an important obesity-prevention strategy. This is relevant for American Indian populations that exhibit high levels of obesity and low compliance with infant feeding guidelines. The literature examining the knowledge, attitudes, and beliefs surrounding infant feeding within the American Indian population is sparse and focuses primarily on breastfeeding, with limited information on the introduction of solid foods and related practices that can be important in an obesity-prevention context. This research presents descriptive findings from a baseline knowledge, attitudes, and beliefs questionnaire on infant feeding and related behaviors administered to mothers (n=438) from five Northwest American Indian tribes that participated in the Prevention of Toddler Overweight and Teeth Health Study (PTOTS). Enrollment occurred during pregnancy or up to 6 months postpartum. The knowledge, attitudes, and beliefs questionnaire focused on themes of breastfeeding/formula feeding and introducing solid foods, with supplemental questions on physical activity. Knowledge questions were multiple choice or true/false. Attitudes and beliefs were assessed on Likert scales. Descriptive statistics included frequencies and percents and means and standard deviations. Most women knew basic breastfeeding recommendations and facts, but fewer recognized the broader health benefits of breastfeeding (eg, reducing diabetes risk) or knew when to introduce solid foods. Women believed breastfeeding to be healthy and perceived their social networks to agree. Attitudes and beliefs about formula feeding and social support were more ambivalent. This work suggests opportunities to increase the perceived value of breastfeeding to include broader health benefits, increase knowledge about solid foods, and strengthen social support.

  18. Knowledge, Attitudes and Beliefs That May Influence Infant Feeding Practices in American Indian Mothers

    PubMed Central

    Eckhardt, Cara L.; Lutz, Tam; Karanja, Njeri; Jobe, Jared B.; Maupomé, Gerardo; Ritenbaugh, Cheryl

    2014-01-01

    The promotion of healthy infant feeding is increasingly recognized as an important obesity prevention strategy. This is relevant for American Indian (AI) populations, who exhibit high levels of obesity and low compliance with infant feeding guidelines. The literature examining the knowledge, attitudes and beliefs (KAB) surrounding infant feeding within the AI population is sparse and focuses primarily on breastfeeding, with limited information on the introduction of solid foods and related practices that may be important in an obesity prevention context. This research presents descriptive findings from a baseline KAB questionnaire on infant feeding and related behaviors, administered to mothers (n=438) from five Northwest AI tribes that participated in the Prevention of Toddler Overweight and Teeth Health Study (PTOTS). Enrollment occurred during pregnancy or up to 6 months postpartum. The KAB questionnaire focused on themes of Breastfeeding/Formula Feeding and Introducing Solid Foods, with supplemental questions on Physical Activity. Knowledge questions were multiple-choice or true/false. Attitudes and beliefs were assessed on Likert scales. Descriptive statistics included frequencies and percents, and means and standard deviations. Most women knew basic breastfeeding recommendations and facts, but fewer recognized the broader health benefits of breastfeeding (e.g., reducing diabetes risk), or knew when to introduce solid foods. Women believed breastfeeding to be healthy and perceived their social networks to agree. Attitudes and beliefs about formula feeding and social support were more ambivalent. This work suggests opportunities to increase the perceived value of breastfeeding to include broader health benefits, increase knowledge about solid foods, and strengthen social support. PMID:24951434

  19. Research on improving infant feeding practices to prevent diarrhoea or reduce its severity: memorandum from a JHU/WHO meeting.

    PubMed Central

    1989-01-01

    In developing countries the highest incidence of diarrhoea occurs among infants who are given fluids or foods to supplement or replace breast-feeding, and numerous studies have been conducted to examine the relationship between feeding practices during the weaning period and the risk of diarrhoea and malnutrition. This Memorandum summarizes current knowledge about the potential impact of improved infant feeding practices on diarrhoeal morbidity and mortality and describes experiences gained with interventions to promote improved practices. Further research activities to examine the role of improved infant feeding practices in the control of diarrhoeal diseases and to identify more effective approaches to the promotion of such practices in the context of a public health programme are also proposed. Finally, methodological issues concerning the design, implementation, and analysis of intervention studies are reviewed. PMID:2706725

  20. Feeding practice and influence on selected blood parameters in show jumping horses competing in Switzerland.

    PubMed

    Brunner, J; Liesegang, A; Weiss, S; Wichert, B

    2015-08-01

    The aim of this study was to compare the nutritional management of show jumping horses in practice with recommendations from the literature. Additionally, the effects of these feeding practices on several blood metabolic parameters before and after exercise were studied. Blood samples were collected in the field from 27 different horses at 71 trials on the level M1 to S2 show jumping competitions in Switzerland and questionnaires on feeding practice of the studied horses were evaluated. The questionnaires revealed that during training and on tournament days horses received on average 3.1 kg of concentrate per day (min. 2.0 kg, max. 6.6 kg) divided into two to three meals. The horses were fed on average 6.9 kg of roughage per day (min. 4.0 kg, max. 13.0 kg). Additionally, it was observed that the horses received the last meal on average 6 h 10 min (min. 1 h 50 min, max. 12 h 30 min) before the start of the first show jumping turn, respectively, 7 h 30 min (min 1 h 50 min, max. 13 h 0 min) before the second turn. Seven horses (35%) had access to hay waiting in the trailer between two turns. The statistical analysis revealed no significant influence of the concentrate feeding time point on lactate, triglyceride and insulin levels, but a significant influence on free fatty acids (FFA) and blood glucose concentrations. Roughage feeding of the show jumping horses 2-4 h prior to exercise revealed the most remarkable changes in blood parameters during the show jumping course. These results received under field conditions should be approved in future under standardized conditions.

  1. [Infant feeding practices in Nouakchott: between medical guidelines and grandmothers’ instructions].

    PubMed

    Diagana, Moussa Salatou; Kane, Hélène

    2016-01-01

    The World Health Organization recommends exclusive breastfeeding up to the age of six months and continuation of partial breastfeeding up to the age of two years, in addition to nutritionally adequate and safe food. In Mauritania, despite some progress, most mothers do not comply with these recommendations. The aim of this study, conducted in Nouakchott, was to evaluate breastfeeding and feeding practices, and measure factors associated with achievement of the optimal duration of exclusive breastfeeding. The methodology combined quantitative and qualitative approaches. A descriptive cross-sectional study was conducted by questionnaires among 330 mothers from different departments of the capital. Twenty semi-structured interviews were then conducted with Mauritanian grandmothers in order to understand their roles and perceptions about infant feeding. Before the age of 6 months, the exclusive breastfeeding rate was 18.4%, the predominant breastfeeding rate was 44.3% and the partial breastfeeding with milk rate was 28.1%. In addition, 9.2% of infants received supplementary feeding. We found that 50.5% of mothers were aware of the optimal duration of exclusive breastfeeding, but only 14.2% complied with this recommendation. The factors significantly associated with compliance with the optimal duration of exclusive breastfeeding were maternal age over 35 years and multiparity. Interviews revealed that grandmothers knew about some of the nutritional recommendations, but denied their relevance based on their experience. Their advice contradicted certain medical recommendations. Our study revealed inadequacies concerning the mother’s knowledge and more frequently their practices in terms of infant feeding. The gap between knowledge and practice can be essentially explained by the relative importance attributed to recommendations by the mothers, as well as the confrontation between medical recommendations and grandmothers’ traditional knowledge.

  2. Parental perceptions, feeding practices, feeding styles, and level of acculturation of Chinese Americans in relation to their school-age child's weight status.

    PubMed

    Pai, Hsiao-Liang; Contento, Isobel

    2014-09-01

    Parents influence their child's eating behavior and attitudes directly as food providers and indirectly through their parental feeding styles and feeding concerns and practices. Chinese American parents' practices are likely influenced by culture. The objective of this study was to explore the relationships between parental perceptions, feeding practices, feeding styles, level of parental acculturation (LPA), and child weight status via a self-administered questionnaire. This survey study involved a convenience sample of 712 individuals who were parents of 5- to 10-year old children attending Chinese language after-school programs. The prevalence of overweight was 11.5% and obesity was 11.1%. LPA was not directly predictive of child overweight in multiple regression but from categorical data, Chinese American parents tended to use indulgent (33.2%) and authoritarian (27.9%) feeding styles, with the former increasing with acculturation and the latter decreasing. Indulgent parents had more than expected overweight and obese children, and authoritarian and authoritative parents, fewer. LPA was negatively predictive of pressure to eat healthy foods (p < .01), which was negatively correlated with child weight status (p < .01). LPA was also independently positively correlated to responsiveness to child needs (p < .01), monitoring of child intake (p < .01), and perceived responsibility for child feeding. Parental perceptions and concerns about child weight were predictors of child weight. Consequently, parental concerns and responsiveness to child needs without also encouragement (demandingness) to eat healthy foods (indulgent feeding style) may promote overweight. The authoritative parental feeding style may contribute to children having healthy weights and therefore healthy lives.

  3. Developing a Co-Regulated, Cue-Based Feeding Practice: The Critical Role of Assessment and Reflection.

    PubMed

    Thoyre, Suzanne; Park, Jinhee; Pados, Britt; Hubbard, Carol

    2013-08-01

    Assessment of early feeding skills of vulnerable infants is common practice in neonatal care centers. However, assessment is often merely an identification of feeding outcomes, rather than a description of the infant's capacities and methods of adapting to the feeding challenge. Descriptive assessment of the feeding process takes into account the dynamic nature of feeding and notes changes that occur as the infant matures and gains feeding experience. Assessment of the variability that occurs during the feeding as the challenge changes, due to fatigue or physiologic instability, are critical to understanding the infant's feeding skills. As individual components of the feeding are assessed, such as sucking, swallowing and breathing, a reflective process builds understanding of the patterns of coordination of system components in relation to one another. Taking the whole into account and considering the dynamics of the process is necessary if we are going to select appropriate interventions targeted to the individual infant's feeding skills. Using a very preterm infant case, this paper will illustrate assessment of early feeding skills and demonstrate how reflection on and integration of the components of the assessment identifies potential targets for co-regulated, cue-based feeding.

  4. Do maternal perceptions of child eating and feeding help to explain the disconnect between reported and observed feeding practices?: A follow-up study.

    PubMed

    Bergmeier, Heidi J; Skouteris, Helen; Hetherington, Marion M; Rodgers, Rachel F; Campbell, Karen J; Cox, Rachael

    2017-02-08

    Research demonstrates a mismatch between reported and observed maternal feeding practices. This mismatch may be explained by maternal cognitions, attitudes, and motivations relating to dyadic parent-child feeding interactions. These complex constructs may not be apparent during observations nor evidenced in self-report questionnaire. Therefore, the aim of this study was to use a qualitative approach to gain a more nuanced and contextualized understanding of (a) maternal perceptions of children's food intake control; (b) how parent-child mealtime interactions influence maternal feeding practices; and (c) ways in which mothers may promote healthy child eating and weight outcomes. Semistructured telephone interviews were conducted with 23 mothers (M = 38.4 ± 3.7 years of age) of preschool-aged children (M = 3.8 ± 0.6 years of age, 19 were normal weight, 14 were girls), who had previously completed child feeding questionnaire and participated in two home-based mealtime observations, 12 months apart. Interviews were recorded, transcribed, and themes extracted to create the database. Four major themes emerged: (a) Maternal confidence in children's ability to regulate food intake is variable; (b) Implementing strategies for nurturing healthy relationships with food beyond the dining table; (c) Fostering positive mealtime interactions is valued above the content of what children eat; and (d) Situation-specific practices and inconsistencies. Findings indicate that maternal feeding practices are shaped by both parent and child influences, and child feeding is mostly guided by controlling the family food environment, rather than by directly pressuring or restricting their child's eating. Results also highlighted the need for research to consider both parent and child influences on child feeding.

  5. Feeding practices and patent ductus arteriosus ligation preferences-are they related?

    PubMed

    Jhaveri, Nami; Soll, Roger F; Clyman, Ronald I

    2010-09-01

    We hypothesized that there is a significant relationship between a neonatologist's belief that feedings must be stopped in the presence of a patent ductus arteriosus (PDA) and his or her willingness to ligate a PDA. We administered the same survey questionnaire to two separate populations of neonatologists to assess their beliefs regarding PDA treatment practices. Although >90% of U.S. and non-U.S. neonatologists reported that they would ligate a PDA when infants with birth weights <900 g required mechanical ventilation (and indomethacin was contraindicated or had failed to close the PDA), U.S. neonatologists reported that they were significantly more likely to ligate a PDA when less respiratory support was required. U.S. neonatologists were also more likely to stop feedings when a PDA was present. The reported likelihood that a neonatologist would ligate a PDA in infants who did not require mechanical ventilation was significantly increased if the neonatologist believed that feedings had to be stopped because of the PDA. After controlling for the belief that "feedings must be stopped in the presence of a PDA," the significant difference between U.S. and non-U.S. neonatologists, in their reported desire to ligate infants who did not require mechanical ventilation, was no longer present.

  6. Perceptions, practices, and consequences associated with foodborne pathogens and the feeding of raw meat to dogs.

    PubMed

    Lenz, Jennifer; Joffe, Daniel; Kauffman, Michael; Zhang, Yifan; LeJeune, Jeffery

    2009-06-01

    This study explored the impact of feeding raw meat to dogs on the fecal prevalence of several enteric bacterial zoonotic pathogens. Campylobacter jejuni was isolated from 1/42 (2.6%) raw meat-fed dogs. Salmonella enterica was isolated from 2/40 (5%) of the raw meat feeds, 6/42 (14%) raw meat-fed dog feces, none of the dogs that did not receive raw meat (P = 0.001), 4/38 (10.5%) of the vacuum cleaner waste samples from households where raw meat was fed, and 2/44 (4.5%) of vacuum cleaner waste samples from households where raw meat was not fed to dogs (P = 0.41). Responses to a questionnaire probing practices and beliefs regarding raw meat feeding that was administered to dog owners demonstrated that dog owners may either not be aware or refuse to acknowledge the risks associated with raw meat-feeding; thus, they may neglect to conduct adequate intervention strategies to prevent zoonoses among themselves and their families.

  7. Putative alpha-helical structures in the human immunodeficiency virus type 1 Vpu protein and CD4 are involved in binding and degradation of the CD4 molecule.

    PubMed Central

    Tiganos, E; Yao, X J; Friborg, J; Daniel, N; Cohen, E A

    1997-01-01

    The human immunodeficiency virus type 1 (HIV-1) vpu gene encodes a 16-kDa class I integral membrane phosphoprotein with an N-terminal membrane-spanning region and a C-terminal cytoplasmic domain. In the cytoplasmic domain, two amphipathic alpha-helices joined by a flexible turn containing two phosphoacceptor sites have been predicted. Previous studies have shown that Vpu downregulates CD4 molecules by inducing their specific degradation in the endoplasmic reticulum. Phosphorylation of serine residues 52 and 56, present within the cytoplasmic domain of the Vpu protein, has been shown to be essential to this Vpu function. However, the contribution of these two phosphoacceptor sites in the mechanism of CD4 degradation remains undefined. Interestingly, a specific interaction between Vpu and CD4 was recently demonstrated in coimmunoprecipitation experiments. Binding of Vpu was shown to be necessary but not sufficient to mediate CD4 degradation, indicating that interaction between Vpu and CD4 represents an early step critical in triggering a process leading to CD4 degradation. To delineate the sequence(s) and/or structural determinant(s) involved in this Vpu-CD4 interaction and in the Vpu-mediated CD4 degradation, we performed a mutational analysis of the cytoplasmic domain of CD4 and Vpu. Coimmunoprecipitation experiments reveal that disruption of the putative alpha-helical structure in the membrane-proximal cytoplasmic domain of CD4 affects the binding to Vpu, suggesting that this structure may act as an interface for the CD4-Vpu interaction that mediates CD4 degradation. Vpu proteins containing mutations in either or both of the phosphoacceptor sites (Ser52 or/and Ser56) were inactive in regard to CD4 degradation yet retained the capacity to interact with the cytoplasmic domain of CD4. In an attempt to define the minimal region responsible for this interaction, we tested a panel of mutations which were designed to affect the integrity of the putative alpha

  8. Variations in Eastern bongo (Tragelaphus eurycerus isaaci) feeding practices in UK zoological collections.

    PubMed

    Wright, D J; Omed, H M; Bishop, C M; Fidgett, A L

    2011-01-01

    The feeding strategy of the Eastern bongo in the wild is unusual, poorly understood, and few captive feeding recommendations are currently available to zoos. To assess the current state of nutritional husbandry of this rare antelope, eight UK zoos were surveyed. A nutritional husbandry questionnaire was completed and bongos at each zoo were visually assessed by body condition scoring (BCS). Representative samples of the forage and browse consumed by bongos at each zoo were analyzed for nutrient composition using standard agricultural techniques. Significant differences in bongo body condition were found, indicating that zoo husbandry practices are sufficiently varied to have identifiable impacts on the physical condition of the animals. The results highlight a disparity in feeding regimes and diet quality, with significant differences found in forage and browse nutrient compositions and in vitro digestibility. Most forage samples were of a low nutritional quality. Browse provision was found to be largely opportunistic and limited in most zoos. The provision of energy-rich produce was also found to be unnecessary in maintaining a bongo herd at an ideal mean BCS. This survey provides baseline data which may be useful in establishing "good practice" standards for Eastern bongo captive nutrition and highlights several areas requiring further research.

  9. Food addiction in children: Associations with obesity, parental food addiction and feeding practices.

    PubMed

    Burrows, T; Skinner, J; Joyner, M A; Palmieri, J; Vaughan, K; Gearhardt, A N

    2017-02-16

    Food addiction research in children is limited, and to date addictive-like eating behaviors within families have not been investigated. The aim of this study is to understand factors associated with addictive-like eating in children. The association between food addiction in children with obesity, parental food addiction, and parental feeding practices (i.e., restriction, pressure to eat, monitoring) was investigated. Parents/primary caregivers (aged≥18years) of children aged 5-12years, recruited and completed an online cross-sectional survey including demographics, the Yale Food Addiction Scale (YFAS), and the Child Feeding Questionnaire (CFQ). Parents, reporting on themselves and one of their children, were given a food addiction diagnosis and symptom score according to the YFAS predefined criteria. The total sample consisted of 150 parents/primary caregivers (48% male) and 150 children (51% male). Food addiction was found to be 12.0% in parents and 22.7% in children. In children, food addiction was significantly associated with higher child BMI z-scores. Children with higher food addiction symptoms had parents with higher food addiction scores. Parents of FA children reported significantly higher levels of Restriction and Pressure to eat feeding practices, but not Monitoring. Children with elevated YFAS-C scores may be at greater risk for eating-related issues.

  10. Affinity maturation of human CD4 by yeast surface display and crystal structure of a CD4–HLA-DR1 complex

    PubMed Central

    Wang, Xin Xiang; Li, Yili; Yin, Yiyuan; Mo, Min; Wang, Qian; Gao, Wei; Wang, Lili; Mariuzza, Roy A.

    2011-01-01

    Helper T-cell activation generally requires the coreceptor CD4, which binds MHC class II molecules. A remarkable feature of the CD4–MHC class II interaction is its exceptionally low affinity, which ranges from KD = ∼200 μM to >2 mM. Investigating the biological role of the much lower affinity of this interaction than those of other cell–cell recognition molecules will require CD4 mutants with enhanced binding to MHC class II for testing in models of T-cell development. To this end, we used in vitro-directed evolution to increase the affinity of human CD4 for HLA-DR1. A mutant CD4 library was displayed on the surface of yeast and selected using HLA-DR1 tetramers or monomers, resulting in isolation of a CD4 clone containing 11 mutations. Reversion mutagenesis showed that most of the affinity increase derived from just two substitutions, Gln40Tyr and Thr45Trp. A CD4 variant bearing these mutations bound HLA-DR1 with KD = 8.8 μM, compared with >400 μM for wild-type CD4. To understand the basis for improved affinity, we determined the structure of this CD4 variant in complex with HLA-DR1 to 2.4 Å resolution. The structure provides an atomic-level description of the CD4-binding site on MHC class II and reveals how CD4 recognizes highly polymorphic HLA-DR, -DP, and -DQ molecules by targeting invariant residues in their α2 and β2 domains. In addition, the CD4 mutants reported here constitute unique tools for probing the influence of CD4 affinity on T-cell activation and development. PMID:21900604

  11. Feeding Practices and Expectations among Middle-Class Anglo and Puerto Rican Mothers of 12-Month-Old Infants.

    ERIC Educational Resources Information Center

    Schulze, Pamela A.; Harwood, Robin L.; Schoelmerich, Axel

    2001-01-01

    Investigated differences in beliefs and practices about infant feeding among middle class Anglo and Puerto Rican mothers. Interviews and observations indicated that Anglo mothers reported earlier attainment of self-feeding and more emphasis on child rearing goals related to self-maximization. Puerto Rican mothers reported later attainment of…

  12. A survey of practice for clinicians working with children with autism spectrum disorders and feeding difficulties.

    PubMed

    Marshall, Jeanne; Hill, Rebecca J; Dodrill, Pamela

    2013-06-01

    The aim of this study was to document information from allied health clinicians about children on their caseload with autism spectrum disorders and feeding difficulties. An electronic survey was disseminated to clinicians working with this group around Australia, where 150 responses were returned and 96 were able to be analysed. Variability in responses was observed for service delivery models, frequency of input, referral reasons, and intervention choices. The majority of respondents identified limited-to-average knowledge of feeding therapy options for this population. Clinician confidence was significantly correlated with perceived therapy success. Results of the survey suggest a need for clinical guidelines in the area to direct practice. Low levels of clinician confidence and perceived therapy success also highlight a need for ongoing research and training.

  13. Maternal symptoms of depression are related to observations of controlling feeding practices in mothers of young children.

    PubMed

    Haycraft, Emma; Farrow, Claire; Blissett, Jackie

    2013-02-01

    Maternal depression can impair parenting practices and has been linked with less sensitive feeding interactions with children, but existing research is based on self-reports of feeding practices. This study examined relationships between maternal self-reported symptoms of depression with observations of mothers' child feeding practices during a mealtime. Fifty-eight mothers of 3- and 4-year-old children were video recorded eating a standardized lunch. The recording was then coded for instances of maternal controlling feeding practices and maternal vocalizations using the Family Mealtime Coding System. Mothers also provided information on current symptoms of depression and anxiety. Mothers who reported greater symptoms of depression were observed to use more verbal and physical pressure for their child to eat and to offer more incentives or conditions in exchange for their child eating. Mothers also used more vocalizations with their child about food during the observed mealtime when they had greater symptoms of depression. There was no link between symptoms of depression and observations of maternal use of restriction. Symptoms of depression are linked with observations of mothers implementing a more controlling, less sensitive feeding style with their child. Health professionals working with families in which mothers have symptoms of depression may benefit from receiving training about the possible impact of maternal depression on child-feeding practices, and mothers with symptoms of depression may benefit from guidance regarding its potential impact on their child-feeding interactions.

  14. Infant feeding practices and diarrhoea in sub-Saharan African countries with high diarrhoea mortality

    PubMed Central

    Ogbo, Felix A.; Agho, Kingsley; Ogeleka, Pascal; Woolfenden, Sue; Page, Andrew; Eastwood, John

    2017-01-01

    Background The impacts of optimal infant feeding practices on diarrhoea have been documented in some developing countries, but not in countries with high diarrhoea mortality as reported by the World Health Organisation/United Nations Children’s Fund. We aimed to investigate the association between infant feeding practices and diarrhoea in sub-Saharan African countries with high diarrhoea mortality. Method The study used the most recent Demographic and Health Survey datasets collected in nine sub-Saharan African countries with high diarrhoea mortality, namely: Burkina Faso (2010, N = 9,733); Demographic Republic of Congo (2013; N = 10,458); Ethiopia (2013, N = 7,251); Kenya (2014, N = 14,034); Mali (2013, N = 6,365); Niger (2013, N = 7,235); Nigeria (2013, N = 18,539); Tanzania (2010, N = 5,013); and Uganda (2010, N = 4,472). Multilevel logistic regression models that adjusted for cluster and sampling weights were used to investigate the association between infant feeding practices and diarrhoea in these nine African countries. Results Diarrhoea prevalence was lower among children whose mothers practiced early initiation of breastfeeding, exclusive and predominant breastfeeding. Early initiation of breastfeeding and exclusive breastfeeding were significantly associated with lower risk of diarrhoea (OR = 0.81; 95% confidence interval (CI): 0.77–0.85, P<0.001 and OR = 0.50; 95%CI: 0.43–0.57, respectively). In contrast, introduction of complementary foods (OR = 1.31; 95%CI: 1.14–1.50) and continued breastfeeding at one year (OR = 1.27; 95%CI: 1.05–1.55) were significantly associated with a higher risk of diarrhoea. Conclusion Early initiation of breastfeeding and exclusive breastfeeding are protective of diarrhoea in sub-Saharan African countries with high diarrhoea mortality. To reduce diarrhoea mortality and also achieve the health-related sustainable development goals in sub-Saharan African, an integrated, multi-agency strategic partnership within each

  15. Livestock feed resources utilization practices in Tanqua-Abergelle district of Tigray, Northern Ethiopia.

    PubMed

    Gebremariam, Tikabo; Belay, Shumuye

    2016-08-01

    A study was carried out with the objective to assess the utilization practices of local feed resources. It was implemented in Tanqua-Abergelle district of the Tigray region, Northern Ethiopia. Lemlem and Gera peasant associations (PAs) were selected purposively based on their potentiality in livestock resources and road access for household (HH) interview purpose. Likewise, Sheka-Tekli and Hadinet PAs were chosen for the purpose of focus group discussion (FGD). A total of 60 HHs (30 from each PA) were selected randomly for interview using semi-structured questionnaire. About 16 % of the respondents were female HHs. Two FGDs were held with key informants. The collected data were analyzed using SPSS (2013, version 21) statistical software procedures. The study area is characterized by mixed crop-livestock farming system with high interaction between crop and livestock. Livestock are the mainstay for the farm community with many benefits as sources of draught, meat, milk, income, and manures. Cattle are kept primarily for the purpose of draught power with meat and milk as secondary products, whereas shoats are kept mainly for cash income, manure, meat, and milk. The land holding size per HH was 1.44 ha while the herd size was 4.93 tropical livestock unit (TLU). Almost all the land holding (97 %) is allocated for crop cultivation with lesser for forage production (<1 %) indicating poor attention for fodder harvesting. The cattle herd is composed of local breeds (99 %) with less exotic/crossbred (1 %), indicating that the livestock rearing is practiced using local breed. Crop residues, natural pastures, stubble grazing, hay, and browsing are the main feed resources for animals. The availability and contribution of each feed vary with season and areas. Sorghum stover is the main feed source in the area and followed by maize stover, Eragrostis tef straw, and pulse straws. Crop residues are fed as basal diet with no or less supplementation using local concentrates

  16. Chimpanzees Immunized with Recombinant Soluble CD4 Develop Anti-Self CD4 Antibody Responses with Anti-Human Immunodeficiency Virus Activity

    NASA Astrophysics Data System (ADS)

    Watanabe, Mamoru; Boyson, Jonathan E.; Lord, Carol I.; Letvin, Norman L.

    1992-06-01

    In view of the efficiency with which human immunodeficiency virus replication can be blocked in vitro with anti-CD4 antibodies, the elicitation of an anti-CD4 antibody response through active immunization might represent a useful therapeutic strategy for AIDS. Here we demonstrate that immunization of chimpanzees with recombinant soluble human CD4 elicited an anti-CD4 antibody response. The elicited antibody bound self CD4 on digitonin-treated but not freshly isolated lymphocytes. Nevertheless, this antibody blocked human immunodeficiency virus replication in chimpanzee and human lymphocytes. These observations suggest that immunization with recombinant soluble CD4 from human immunodeficiency virus-infected humans may be feasible and therapeutically beneficial.

  17. Epidemiology of Trichinella infection in the horse: the risk from animal product feeding practices.

    PubMed

    Murrell, K D; Djordjevic, M; Cuperlovic, K; Sofronic, Lj; Savic, M; Djordjevic, M; Damjanovic, S

    2004-09-02

    A discovery in 2002 of a Trichinella spiralis-infected horse in Serbia offered an opportunity to conduct needed epidemiological studies on how horses, considered herbivores, acquire a meat-borne parasite. This enigma has persisted since the first human outbreaks from infected horse meat occurred in then 1970s. The trace back of the infected horse to a farm owner was carried out. Interviews and investigations on the farm led to the conclusion that the owner had fed the horse food waste in order to condition the horse prior to sale. Further investigations were then carried out to determine the frequency of such practices among horse owners. Based on interviews of horse producers at local horse markets, it was revealed that the feeding of animal products to horses was a common practice. Further, it was alleged that many horses, particularly those in poor nutritional condition would readily consume meat. A subsequent series of trials involving the experimental feeding of 219 horses demonstrated that 32% would consume meat patties. To confirm that horses would eat infected meat under normal farm conditions, three horses were offered infected ground pork balls containing 1100 larvae. All three became infected, and at necropsy at 32 weeks later, were still positive by indirect IFA testing, but not by ELISA using an excretory-secretory (ES) antigen. This result indicates that further study is needed on the nature of the antigen(s) used for potential serological monitoring and surveillance of horse trichinellosis, especially the importance of antigenic diversity. The experimentally-infected horses also had very low infection levels (larvae per gram of muscle) at 32 weeks of infection, and although the public health consequences are unknown, the question of whether current recommended inspection procedures based on pepsin digestion of selected muscle samples require sufficient quantities of muscle should be addressed. It is concluded that horses are more willing to consume

  18. Functional aortic stiffness: role of CD4(+) T lymphocytes.

    PubMed

    Majeed, Beenish A; Eberson, Lance S; Tawinwung, Supannikar; Larmonier, Nicolas; Secomb, Timothy W; Larson, Douglas F

    2015-01-01

    The immune system is suggested to be essential in vascular remodeling and stiffening. To study the dependence upon lymphocytes in vascular stiffening, we compared an angiotensin II-model of vascular stiffening in normal C57BL/6J mice with lymphocyte-deficient RAG 1(-/-) mice and additionally characterized the component of vascular stiffness due to vasoconstriction vs. vascular remodeling. Chronic angiotensin II increased aortic pulse wave velocity, effective wall stiffness, and effective Young's modulus in C57BL/6J mice by three-fold but caused no change in the RAG 1(-/-) mice. These functional measurements were supported by aortic morphometric analysis. Adoptive transfer of CD4(+) T helper lymphocytes restored the angiotensin II-mediated aortic stiffening in the RAG 1(-/-) mice. In order to account for the hydraulic vs. material effects of angiotensin II on pulse wave velocity, subcutaneous osmotic pumps were removed after 21 days of angiotensin II-infusion in the WT mice to achieve normotensive values. The pulse wave velocity (PWV) decreased from three- to two-fold above baseline values up to 7 days following pump removal. This study supports the pivotal role of the CD4(+) T-lymphocytes in angiotensin II-mediated vascular stiffening and that angiotensin II-mediated aortic stiffening is due to the additive effect of active vascular smooth muscle vasoconstriction and vascular remodeling.

  19. Human immunodeficiency virus type 1 Nef-induced down-modulation of CD4 is due to rapid internalization and degradation of surface CD4.

    PubMed Central

    Rhee, S S; Marsh, J W

    1994-01-01

    Human immunodeficiency virus type 1 (HIV-1) Nef is a myristylated protein with a relative molecular mass of 27 kDa, is localized to the cytoplasmic surfaces of cellular membranes, and has been reported to down-modulate CD4 in human T cells. To understand the mechanism of HIV-1 Nef-mediated down-modulation of cell surface CD4, we expressed Nef protein in human T-cell line VB. Expression of HIV-1 Nef protein down-modulated surface CD4 molecules. In pulse-chase experiments, CD4 molecules in Nef-expressing cells were synthesized at normal levels. However, the bulk of newly synthesized CD4 protein was degraded with a half-life of approximately 6 h, compared with the 24-h half-life in control cells. This Nef-induced acceleration of CD4 turnover was inhibited by lysosomotropic agents NH4Cl and chloroquine as well as by the protease inhibitor leupeptin. Surface CD4 biotinylation experiments demonstrated that CD4 molecules in Nef-expressing T cells are transported to the plasma membrane with normal kinetics but are then rapidly internalized. Therefore, HIV-1 Nef-induced down-modulation of CD4 is due to rapid internalization of surface CD4 and subsequent degradation by an acid-dependent process, potentially lysosomal. Additionally, in a Nef-expressing cell, we find accelerated dissociation of the T-cell tyrosine kinase p56lck and CD4 but only after the complex reaches the plasma membrane. This implies that HIV-1 Nef protein might play a role in triggering a series of T-cell activation-like events, which contribute to p56lck dissociation and internalization of surface CD4 molecules. Images PMID:8035515

  20. Associations of infant feeding practices and picky eating behaviors of preschool children.

    PubMed

    Shim, Jae Eun; Kim, Juhee; Mathai, Rose Ann

    2011-09-01

    Picky eating behaviors are prevalent during childhood and are often linked to nutritional problems. However, information on the determinants of picky eating behaviors during infancy, when food acceptance patterns develop, is scarce. This study was conducted to evaluate the impact of infant feeding practices on the development of picky eating behaviors during preschool years. Baseline survey data from the Synergistic Theory and Research on Obesity and Nutrition Group Kids (STRONG Kids) program were used for this retrospective data analysis. Primary caregiver-child dyads were recruited from child-care centers in Eastern Illinois between February and July of 2009. A total of 129 self-reported responses from mothers of preschool-aged children were analyzed. Logistic regression was used to evaluate the association between infant feeding practices and picky eating behaviors. Children who were introduced to complementary foods before 6 months of age had 2.5 times higher odds of developing food neophobia and limited variety of foods (95% confidence interval [CI]: 1.01 to 5.93 and 1.06 to 5.73, respectively). Children who were breastfed exclusively for 6 months had lower odds of developing a preference for specific food-preparation methods by 78% (95% CI: 19% to 94%), food rejection by 81% (95% CI: 31% to 94%), and food neophobia by 75% (95% CI: 11% to 93%). Breastfeeding and introduction of complementary foods after 6 months of age reduced the odds of picky eating during early childhood. This study documents an association between infant-feeding practices and the development of picky eating behaviors in early childhood.

  1. Comparison of CD4 cell count by a simple enzyme-linked immunosorbent assay using the TRAx CD4 test kit and by flow cytometry and hematology.

    PubMed Central

    Paxton, H; Pins, M; Denton, G; McGonigle, A D; Meisner, P S; Phair, J P

    1995-01-01

    Measurement of CD4 T-lymphocyte levels is clinically useful in monitoring immune status in a number of conditions, including human immunodeficiency virus (HIV) infection, in which the absolute CD4 count is used to guide therapy. The absolute CD4 count is obtained by multiplying the results of the leukocyte count and the differential with a hematology cell counter and the percentage of CD4+ T lymphocytes determined by flow cytometry. These techniques require expensive, complex instrumentation, and interlaboratory results are difficult to standardize and reproduce. The rapid growth of HIV infection worldwide has increased the need for more-reproducible and cost-effective methods for CD4 T-cell monitoring. The TRAx CD4 test kit is based on a novel adaptation of conventional enzyme-linked immunosorbent assay (ELISA) and permits the simple quantitation of total CD4 protein from whole-blood lysates. In this study, the relationship between total CD4 protein measured in units per milliliter (TRAx) and in cells per microliter (flow cytometry and hematology) was defined in a multisite clinical study using linear regression analysis. Data from 230 HIV-seronegative and 321 HIV-seropositive specimens were used to calibrate the TRAx assay recombinant CD4 standards and controls in equivalent CD4 T lymphocytes per microliter (cells per microliter). The calibration of the TRAx CD4 assay in cells per microliter was validated with a second group of specimens from 17 healthy volunteers and 20 HIV-seropositive patients which were collected and tested under strictly controlled conditions intended to minimize the effects of specimen aging on the results of the reference method. These data were also used to estimate the variability of absolute CD4 count by cytometric methods as well as the precision of the TRAx CD4 result after it was calibrated in cells per microliter. Overall, correlations between the two methods ranged from 0.87 to 0.95. Additional studies demonstrated that the

  2. Inhibition of Nef- and phorbol ester-induced CD4 degradation by macrolide antibiotics.

    PubMed Central

    Luo, T; Anderson, S J; Garcia, J V

    1996-01-01

    Human immunodeficiency virus type 1 (HIV-1) is the causative agent of AIDS. The simian immunodeficiency virus (SIV) causes a similar syndrome in macaques. The product of the nef gene of SIV has been shown to be important for virus replication and disease progression in vivo. In vitro, both SIV and HIV Nef downregulate surface expression of CD4 and accelerate total CD4 turnover. The mechanism by which Nef downregulates CD4 has not been established. A current model suggests that Nef enhances cell surface CD4 endocytosis and degradation in lysosomes. However, this was recently challenged when CD4 was found to accumulate in early endosomes of cells expressing Nef. Because inhibition of Nef function might halt virus replication and disease progression, we tested two macrolide antibiotics for their ability to inhibit Nef function. Concanamycin B (ConB) and bafilomycin A1 (BFLA1) are specific inhibitors of acidification of cell endosomes and lysosomes and, unlike other inhibitors, do not affect transport. Although ConB (25 nM) and BFLA1 (100 nM) blocked phorbol myristate acetate- and Nef-induced CD4 degradation in human monocyte U937 cells, CD4 surface expression was not recovered. Instead, CD4 accumulated in lysosomes. To determine if Nef is directly responsible for CD4 degradation or if they bind to each other in a manner similar to Vpu, transcripts of human CD4 and HIV-1 nef were cotranslated in vitro. Our results indicate that under our experimental conditions, Nef does not affect CD4 stability and does not associate with CD4 in this in vitro system. Our data suggest that (i) CD4 downregulation by Nef results in degradation of CD4 in lysosomes, (ii) inhibition of CD4 degradation by macrolide antibiotics does not restore surface expression, and (iii) the inhibition of CD4 expression by Nef appears to be indirect and is likely to involve cellular factors. PMID:8627671

  3. Obesity Risk in Children: The Role of Acculturation in the Feeding Practices and Styles of Low-Income Hispanic Families

    PubMed Central

    Power, Thomas G.; O'Connor, Teresia M.; Orlet Fisher, Jennifer

    2015-01-01

    Abstract Background: Parent feeding has been associated with child overweight/obesity in low-income families. Because acculturation to the United States has been associated with increased adult obesity, our study aim was to determine whether acculturation was associated with feeding in these populations. Methods: Low-income Hispanic mothers of preschoolers were recruited to participate in a longitudinal study examining child eating behaviors. At baseline, mothers completed questionnaires on feeding styles, feeding practices, and acculturation. Regression analyses compared feeding styles and food parenting practices of first-generation, immigrant mothers born outside the United States (n = 138) and mothers born in the United States (n = 31). The correlates of acculturation with these same constructs were also examined. Results: Immigrant mothers reported using highly directive food parenting practices more often than mothers born in the United States, including pressuring their child to consume more food, using food as a reward, and controlling child food intake by limiting less-healthy foods. First-generation mothers were more likely to show authoritarian, and less likely to show indulgent, feeding styles. Greater maternal acculturation was associated with less restriction of food for weight reasons. Conclusions: Although first-generation, immigrant mothers reported using highly controlling food parenting practices with their children, those born in the United States were more indulgent with their children in the feeding context. Mechanisms that promote greater indulgence in more-acculturated mothers need to be identified. PMID:26584157

  4. CD4 Lymphocyte Decline and Survival in Human Immunodeficiency Virus Infection

    DTIC Science & Technology

    1992-01-01

    assess the association of CD4 cell decline (half-life), race, age, gender, initial CD4-cell count, and treatment (anti- Pneumocystis carinii pneumonia ...with a median interval of 2.65 mo between tests. (AZT), anti-Pneumnocystis cariniI pneumonia (PCP) prophy- The decline of CD4 cell count over time for

  5. Quaternary contact in the initial interaction of CD4 with the HIV-1 envelope trimer.

    PubMed

    Liu, Qingbo; Acharya, Priyamvada; Dolan, Michael A; Zhang, Peng; Guzzo, Christina; Lu, Jacky; Kwon, Alice; Gururani, Deepali; Miao, Huiyi; Bylund, Tatsiana; Chuang, Gwo-Yu; Druz, Aliaksandr; Zhou, Tongqing; Rice, William J; Wigge, Christoph; Carragher, Bridget; Potter, Clinton S; Kwong, Peter D; Lusso, Paolo

    2017-04-01

    Binding of the gp120 envelope (Env) glycoprotein to the CD4 receptor is the first step in the HIV-1 infectious cycle. Although the CD4-binding site has been extensively characterized, the initial receptor interaction has been difficult to study because of major CD4-induced structural rearrangements. Here we used cryogenic electron microscopy (cryo-EM) to visualize the initial contact of CD4 with the HIV-1 Env trimer at 6.8-Å resolution. A single CD4 molecule is embraced by a quaternary HIV-1-Env surface formed by coalescence of the previously defined CD4-contact region with a second CD4-binding site (CD4-BS2) in the inner domain of a neighboring gp120 protomer. Disruption of CD4-BS2 destabilized CD4-trimer interaction and abrogated HIV-1 infectivity by preventing the acquisition of coreceptor-binding competence. A corresponding reduction in HIV-1 infectivity occurred after the mutation of CD4 residues that interact with CD4-BS2. Our results document the critical role of quaternary interactions in the initial HIV-Env-receptor contact, with implications for treatment and vaccine design.

  6. Divergent CD4+ T memory stem cell dynamics in pathogenic and nonpathogenic simian immunodeficiency virus infections.

    PubMed

    Cartwright, Emily K; McGary, Colleen S; Cervasi, Barbara; Micci, Luca; Lawson, Benton; Elliott, Sarah T C; Collman, Ronald G; Bosinger, Steven E; Paiardini, Mirko; Vanderford, Thomas H; Chahroudi, Ann; Silvestri, Guido

    2014-05-15

    Recent studies have identified a subset of memory T cells with stem cell-like properties (T(SCM)) that include increased longevity and proliferative potential. In this study, we examined the dynamics of CD4(+) T(SCM) during pathogenic SIV infection of rhesus macaques (RM) and nonpathogenic SIV infection of sooty mangabeys (SM). Whereas SIV-infected RM show selective numeric preservation of CD4(+) T(SCM), SIV infection induced a complex perturbation of these cells defined by depletion of CD4(+)CCR5(+) T(SCM), increased rates of CD4(+) T(SCM) proliferation, and high levels of direct virus infection. The increased rates of CD4(+) T(SCM) proliferation in SIV-infected RM correlated inversely with the levels of central memory CD4(+) T cells. In contrast, nonpathogenic SIV infection of SM evidenced preservation of both CD4(+) T(SCM) and CD4(+) central memory T cells, with normal levels of CD4(+) T(SCM) proliferation, and lack of selective depletion of CD4(+)CCR5(+) T(SCM). Importantly, SIV DNA was below the detectable limit in CD4(+) T(SCM) from 8 of 10 SIV-infected SM. We propose that increased proliferation and infection of CD4(+) T(SCM) may contribute to the pathogenesis of SIV infection in RM.

  7. Inhibition of HIV replication by pokeweed antiviral protein targeted to CD4+ cells by monoclonal antibodies

    NASA Astrophysics Data System (ADS)

    Zarling, Joyce M.; Moran, Patricia A.; Haffar, Omar; Sias, Joan; Richman, Douglas D.; Spina, Celsa A.; Myers, Dorothea E.; Kuebelbeck, Virginia; Ledbetter, Jeffrey A.; Uckun, Fatih M.

    1990-09-01

    FUNCTIONAL impairment and selective depletion of CD4+ T cells, the hallmark of AIDS, are at least partly caused by human immunodeficiency virus (HIV-1) type 1 binding to the CD4 molecule and infecting CD4+ cells1,2. It may, therefore, be of therapeutic value to target an antiviral agent to CD4+ cells to prevent infection and to inhibit HIV-1 production in patients' CD4+ cells which contain proviral DNA3,4. We report here that HIV-1 replication in normal primary CD4+ T cells can be inhibited by pokeweed antiviral protein, a plant protein of relative molecular mass 30,000 (ref. 5), which inhibits replication of certain plant RNA viruses6-8, and of herpes simplex virus, poliovirus and influenza virus9-11. Targeting pokeweed antiviral protein to CD4+ T cells by conjugating it to monoclonal antibodies reactive with CDS, CD7 or CD4 expressed on CD4+ cells, increased its anti-HIV potency up to 1,000-fold. HIV-1 replication is inhibited at picomolar concentrations of conjugates of pokeweed antiviral protein and monoclonal antibodies, which do not inhibit proliferation of normal CD4+ T cells or CD4-dependent responses. These conjugates inhibit HIV-1 protein synthesis and also strongly inhibit HIV-1 production in activated CD4+ T cells from infected patients.

  8. A comparison of infant and toddler feeding practices of mothers with and without histories of eating disorders.

    PubMed

    Hoffman, Elizabeth R; Bentley, Margaret E; Hamer, Robert M; Hodges, Eric A; Ward, Dianne S; Bulik, Cynthia M

    2014-07-01

    This preliminary study surveyed the feeding practices of mothers with eating disorder histories through evaluation of mothers' reported feeding styles, child diet composition and restrictive special approaches to feeding. For this non-randomised cohort study, 25 mothers with eating disorder histories and 25 mothers with no history of an eating disorder with children ages 6-36 months were selected such that the groups were similar based on child age group and child sex. Mothers were compared on self-reported feeding style using the Infant Feeding Styles Questionnaire and on child diet composition and special feeding approaches using a modified version of the Toddler Diet Questionnaire from the Women, Infants, and Children program. Mothers with eating disorder histories scored lower on the restrictive feeding style subscale than controls. No significant differences were detected between groups in child diet including the percentage of mothers who breastfed, duration of breastfeeding, age at solid food introduction, daily number of meals or snacks or daily frequency of consumption of fruits, vegetables or protein foods. Mothers with eating disorder histories were more likely to report taking a restrictive special approach to feeding such as limiting processed foods or feeding organic foods only. Although mothers with eating disorder histories may not differ greatly from control mothers in terms of child diet composition (smaller effects may not have been detected due to limited sample size), they may be more likely to take restrictive special approaches to feeding which mirror dietary rules common in individuals with eating disorders.

  9. Infant feeding practices in St. Vincent and factors which affect them.

    PubMed

    Greiner, T; Latham, M C

    1981-03-01

    A survey was conducted in the summer of 1975 in 2 towns in St. Vincent--Layou and Georgetown--in the effort to obtain information regarding infant feeding practices and some of the factors which may influence them. Mothers of children from 1-2 years of age were interviewed in their homes. Complete data sets were obtained on 192 of the 216 eligible children in the 2 towns. For most children the period of exclusive breastfeeding (no other milk product given) was very short. About 1/2 of the children had received milk by 2 weeks of age, and 75% by 1 month. This was followed by a much longer period of "mixed" feeding--both breast and bottle--until breastfeeding was stopped at a median age of 6.8 months. Many types of milk were used for infant feeding. For 73% of the infants, infant formula was the 1st type of milk given. This was commonly replaced by a "heavier" full cream powdered milk at a few months of age. Prelacteal feeds were very common, predominantly glucose water. "Tonics," often consisting of vitamin preparations, were another common supplement during the early months of life. Among solid foods, arrowroot, "custard," and commercial infant cereals were the first to be introduced. Relatively inexpensive locally bagged staple foods and milk powders were available in both towns, but most mothers relied heavily on packaged brand name products for infant feeding even though the cost was 2-10 times higher. It was not possible to pinpoint the exact causes for the high levels of bottle feeding, nor for the possible recent decline in breastfeeding, but several important factors were identified. Part of the problem appeared to be due to poor health and nutritional status of the mothers. In addition, in several cases the mothers reported that they had wanted to continue breastfeeding but had received no support from health professionals, and in a few instances had been ordered to stop for seemingly trivial medical reasons.

  10. Complementary feeding practices among mothers in selected slums of Dhaka city: a descriptive study.

    PubMed

    Saleh, Farzana; Ara, Ferdous; Hoque, Md Asirul; Alam, Md Safiul

    2014-03-01

    Improper complementary feeding (CF) practice is one of the main reasons for malnutrition among Bangladeshi children aged less than two years. In this context, using the guidelines of the World Health Organization (WHO), this study assessed the CF practices among mothers in four selected slums (Tejgoan, Rayerbazar, Beribadh, and Jafrabad) of Dhaka city. This descriptive study, conducted during January-June 2010, included 120 mother-child pairs from the selected slums. Samples were selected conveniently, and the sociodemographic profiles of mothers in the four slums were similar. The mean (standard deviation) age of the children was 14.68 +/- 5.55 months. A questionnaire, developed following the guidelines of WHO for CF practices, was used for collecting data. Twenty-seven (23%) mothers were exclusively breastfeeding (EBF) their children. Among non-EBF mothers, 15 (16%) started CF after the recommended time. At 6-8 months of age, 2 (40%) of the EBF and 12 (67%) of the non-EBF mothers gave complementary foods twice a day to their children. In both the groups--9-11 months of age--about 70% mothers gave complementary foods twice a day to their children. The frequency of CF was acceptable (3 times a day) in 13 (81%) of the EBF and 32 (56%) of the non-EBF children at 12-23 months of age. Complementary foods given by 24 (89%) of the EBF and 86 (93%) of the non-EBF mothers to their children were not adequate in energy contents. Two (7%) EBF and 16 (17%) non-EBF mothers did not wash their hands after defaecation. Three (11%) EBF and 24 (26%) non-EBF mothers did not properly clean their hands and utensils before feeding. Nine (33%) EBF mothers did not wash their children's hands. Fifty (54%) non-EBF mothers also did not do this. Feeding with psychosocial care practices was not perfect in either of the groups. The findings showed that, according to the WHO guidelines, the CF practices among mothers of children aged less than two years were very poor in the selected slums of

  11. Decreased percentage of CD4+Foxp3+TGF-β+ and increased percentage of CD4+IL-17+ cells in bronchoalveolar lavage of asthmatics

    PubMed Central

    2014-01-01

    Background Asthma is a chronic inflammatory disorder of the airways with the proven role of Th2 cells in its pathogenesis. The role and characteristic of different subsets of CD4+ cells is much less known. Aim The aim of the study was to analyze the incidence of different subsets of CD4+ T cells, in particular different subsets of CD4+ cells with the co-expression of different cytokines. Methods Twenty five stable asthmatic and twelve age-matched control subjects were recruited to the study. Bronchoscopy and bronchoalveolar lavage (BAL) were performed in all study subjects. CD4+ T cells were isolated from BAL fluid by positive magnetic selection. After stimulation simultaneous expression of TGF-β, FoxP3, CD25, IFN-γ, IL-4, TNF-α (set 1); IL-10, FoxP3, CD25, IFN-γ, IL-4, MIP-1β (set 2); IL-17A, IL-8, IFN-γ, IL-4, MIP-1β (set 3) were measured by flow cytometry. Results The percentage of CD4+ cells co-expressing Foxp3 and TGF-β (CD4+Foxp3+TGF-β+ cells) was significantly lower (P = 0.03), whereas the percentage of CD4+IL-17+ cells (P = 0.008), CD4+IL-17+ IFN-γ+ cells (P = 0.047) and CD4+IL-4+ cells (P = 0.01) were significantly increased in asthmatics compared with that seen in healthy subjects. A significantly higher percentage of CD4+Foxp3+ cells from asthma patients expressed IFN-γ (P = 0.01), IL-4 (P = 0.004) and CD25 (P = 0.04), whereas the percentage of CD4+IL-10+ cells expressing Foxp3 was significantly decreased in asthmatics (P = 0.03). FEV1% predicted correlated negatively with the percentage of CD4+IL-17+ cells (r = -0.33; P = 0.046) and positively with CD4+Foxp3+TGF-β+ cells (r = 0.43; P = 0.01). Conclusions Our results suggest that in the airways of chronic asthma patients there is an imbalance between increased numbers of CD4+IL-17+ cells and Th2 cells and decreased number of CD4+Foxp3+TGF-β+. PMID:25132806

  12. WIC Infant and Toddler Feeding Practices Study: protocol design and implementation.

    PubMed

    Harrison, Gail G; Hirschman, Jay D; Owens, Tameka A; McNutt, Suzanne W; Sallack, Linnea E

    2014-03-01

    The federal Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), which began in the 1970s, has undergone revisions in the past several years, including revision to contents of the supplemental food "packages" in 2009 based on recommendations provided by an Institute of Medicine (IOM) committee of The National Academies. In 2010, the IOM held a workshop to examine and recommend research priorities for the program. The overall purpose of the current (ie, second) WIC Infant and Toddler Feeding Practices Study (ITFPS-2) is to conduct a nationally representative, longitudinal study of contemporary WIC infant and toddler feeding practices. This study will update earlier studies and collect information on variations in WIC program components. The study will also assess ways in which WIC may address obesity in early childhood and examine changes in feeding practices that may stem from the 2009 food package revisions. The sample is drawn from the universe of WIC sites nationally, excluding only those with an insufficient volume of eligible participants. Eligibility for the study includes the ability to be interviewed in English or Spanish. Approximately 8000 women and infants are being sampled, and ∼ 4000 are expected to participate. Eligible women are invited to participate during their WIC enrollment visit, and informed consent is sought. The design includes a core sample to be followed until the infant reaches age 2 y and a supplemental sample to be used in some cross-sectional analyses to ensure adequate representation of groups that might be underrepresented in the core sample. Participants will complete up to 11 interviews (core sample) or 4 interviews (supplemental sample) each except for the prenatal interview, which includes a quantitative 24-h recall of food intake for the infant. Eighty sites have been sampled across 26 states and 1 territory. Instruments have been developed and pretested in both English and Spanish, and interviewers

  13. Restoring homeostasis of CD4⁺ T cells in hepatitis-B-virus-related liver fibrosis.

    PubMed

    Cheng, Li-Sha; Liu, Yun; Jiang, Wei

    2015-10-14

    Immune-mediated liver injury is widely seen during hepatitis B virus (HBV) infection. Unsuccessful immune clearance of HBV results in chronic hepatitis and increases the risk of liver cirrhosis and hepatocellular carcinoma. HBV-related liver fibrosis (HBVLF), occurring as a result of HBV-induced chronic hepatitis, is a reversible, intermediate stage of chronic hepatitis B (CHB) and liver cirrhosis. Therefore, defining the pathogenesis of HBVLF is of practical significance for achieving better clinical outcomes. Recently, the homeostasis of CD4(+) T cells was considered to be pivotal in the process of HBVLF. To better uncover the underlying mechanisms, in this review, we systematically retrospect the impacts of different CD4(+) T-cell subsets on CHB and HBVLF. We emphasize CD4(+) T-cell homeostasis and the important balance between regulatory T (Treg) and T helper 17 (Th17) cells. We discuss some cytokines associated with Treg and Th17 cells such as interleukin (IL)-17, IL-22, IL-21, IL-23, IL-10, IL-35 and IL-33, as well as surface molecules such as programmed cell death protein 1, cytotoxic T lymphocyte-associated antigen 4, T cell immunoglobulin domain and mucin domain-containing molecule 3 and cannabinoid receptor 2 that have potential therapeutic implications for the homeostasis of CD4(+) T cells in CHB and HBVLF.

  14. Child feeding practices and household food insecurity among low-income mothers in Buenos Aires, Argentina.

    PubMed

    Lindsay, Ana Cristina; Ferarro, Mabel; Franchello, Alejandra; Barrera, Raul de La; Machado, Marcia Maria Tavares; Pfeiffer, Martha Erin; Peterson, Karen Eileen

    2012-03-01

    This qualitative study of low-income mothers in Buenos Aires, Argentina, examines the influence of socio-economic conditions, organizational structures, family relationships, and food insecurity on child feeding practices and weight status. Thirty-eight mothers of preschool children living in urban Buenos Aires participated in four focus group discussions. The results indicated that many mothers were aware that obesity may be detrimental to the child's health, but most of them are unclear about the specific consequences. Maternal employment, family pressures, food insecurity and financial worries seem to influence child feeding practices. These findings have important implications for developing strategies for nutritional assistance that could benefit the health of children and provide opportunities for educational programs that are directed to nutritional awareness in Buenos Aires, Argentina. The right to eat regularly and properly is an obligation of the State and must be implemented taking into account the notion of food sovereignty and respecting the importance of preserving the culture and eating habits of a country and its diverse population groups.

  15. Control of inflammatory heart disease by CD4+ T cells.

    PubMed

    Barin, Jobert G; Čiháková, Daniela

    2013-05-01

    This review focuses on autoimmune myocarditis and its sequela, inflammatory dilated cardiomyopathy (DCMI), and the inflammatory and immune mechanisms underlying the pathogenesis of these diseases. Several mouse models of myocarditis and DCMI have improved our knowledge of the pathogenesis of these diseases, informing more general problems of cardiac remodeling and heart failure. CD4(+) T cells are critical in driving the pathogenesis of myocarditis. We discuss in detail the role of T helper cell subtypes in the pathogenesis of myocarditis, the biology of T cell-derived effector cytokines, and the participation of other leukocytic effectors in mediating disease pathophysiology. We discuss interactions between these subsets in both suppressive and collaborative fashions. These findings indicate that cardiac inflammatory disease, and autoimmunity in general, may be more diverse in divergent effector mechanisms than has previously been appreciated.

  16. Structural Basis for Species Selectivity in the HIV-1 gp120-CD4 Interaction: Restoring Affinity to gp120 in Murine CD4 Mimetic Peptides

    PubMed Central

    Kassler, Kristin; Meier, Julia; Eichler, Jutta; Sticht, Heinrich

    2011-01-01

    The first step of HIV-1 infection involves interaction between the viral glycoprotein gp120 and the human cellular receptor CD4. Inhibition of the gp120-CD4 interaction represents an attractive strategy to block HIV-1 infection. In an attempt to explore the known lack of affinity of murine CD4 to gp120, we have investigated peptides presenting the putative gp120-binding site of murine CD4 (mCD4). Molecular modeling indicates that mCD4 protein cannot bind gp120 due to steric clashes, while the larger conformational flexibility of mCD4 peptides allows an interaction. This finding is confirmed by experimental binding assays, which also evidenced specificity of the peptide-gp120 interaction. Molecular dynamics simulations indicate that the mCD4-peptide stably interacts with gp120 via an intermolecular β-sheet, while an important salt-bridge formed by a C-terminal lysine is lost. Fixation of the C-terminus by introducing a disulfide bridge between the N- and C-termini of the peptide significantly enhanced the affinity to gp120. PMID:22312332

  17. Investigation of Food Acceptability and Feeding Practices for Lipid Nutrient Supplements and Blended Flours Used to Treat Moderate Malnutrition

    ERIC Educational Resources Information Center

    Wang, Richard J.; Trehan, Indi; LaGrone, Lacey N.; Weisz, Ariana J.; Thakwalakwa, Chrissie M.; Maleta, Kenneth M.; Manary, Mark J.

    2013-01-01

    Objective: To examine acceptability and feeding practices associated with different supplementary food items and identify practices associated with weight gain. Methods: Caregivers (n = 409) whose children had been enrolled in a trial comparing a fortified corn-soy blended flour (CSB++), soy ready-to-use supplementary food (RUSF), and soy/whey…

  18. Investigation of food acceptability and feeding practices for lipid nutrient supplements and blended flours used to treat moderate malnutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The study objectives were to examine acceptability and feeding practices associated with different supplementary food items and to identify practices associated with weight gain. Caregivers (n = 409) whose children had been enrolled in a trial comparing a fortified corn-soy blended flour (CSB++), so...

  19. Analysis of recombinant human tumour necrosis factor-alpha-induced CD4 expression on human eosinophils.

    PubMed Central

    Hossain, M; Okubo, Y; Horie, S; Sekiguchi, M

    1996-01-01

    We examined the hypothesis that one of the pro-inflammatory cytokines, tumour necrosis factor-alpha (TNF-alpha), could induce expression of the adhesion molecule CD4 on human eosinophils. We further examined the effector function of CD4 and the mechanisms regulating CD4 expression. Human eosinophils were cultured with various concentrations of recombinant human TNF-alpha (rhTNF-alpha) with or without various drugs for 24 hr. After culture, eosinophils were stained for CD4 using a monoclonal antibody and then analysed by flow cytometry. Eosinophil-derived neurotoxin (EDN) release as eosinophil degranulation was examined by cross-linking of CD4 on eosinophils. The rhTNF-alpha induced CD4 expression on human eosinophils in a dose- and time-dependent fashion; rhTNF-alpha-induced CD4 expression was significantly inhibited by 10(-6) M cycloheximide, 10(-8) M dexamethasone, or 10(-6) M herbimycin A. Recombinant human interferon-gamma inhibited rhTNF-alpha-induced CD4 expression in a dose-dependent manner. However, cross-linking of CD4 on eosinophils did not evoke EDN release, suggesting that newly expressed CD4 molecules on human eosinophils do not play any role in triggering degranulation. Our data indicate that TNF-alpha-induced CD4 expression on human eosinophils is dependent on protein synthesis and may be dependent on tyrosine kinase activity. PMID:8690465

  20. Molecular cloning and characterization of CD4 in an aquatic mammal, the white whale Delphinapterus leucas.

    PubMed

    Romano, T A; Ridgway, S H; Felten, D L; Quaranta, V

    1999-05-01

    Given the importance of the cell surface recognition protein, CD4, in immune function, the cloning and characterization of CD4 at the molecular level from an odontocete cetacean, the white whale (Delphinapterus leucas), was carried out. Whale CD4 cDNA contains 2662 base pairs and translates into a protein containing 455 amino acids. Whale CD4 shares 64% and 51% identity with the human and mouse CD4 protein, respectively, and is organized in a similar manner. Unlike human and mouse, however, the cytoplasmic domain, which is highly conserved, contains amino acid substitutions unique to whale. Moreover, only one of the seven potential N-linked glycosylation sites present in whale is shared with human and mouse. Evolutionarily, the whale CD4 sequence is most similar to pig and structurally similar to dog and cat, in that all lack the cysteine pair in the V2 domain. These differences suggest that CD4 may have a different secondary structure in these species, which may affect binding of class II and subsequent T-cell activation, as well as binding of viral pathogens. Interestingly, as a group, species with these CD4 characteristics all have high constitutive expression of class II molecules on T lymphocytes, suggesting potential uniqueness in the interaction of CD4, class II molecules, and the immune response. Molecular characterization of CD4 in an aquatic mammal provides information on the CD4 molecule itself and may provide insight into adaptive evolutionary changes of the immune system.

  1. Disappearance of CD4 lymphocyte circadian cycles after autologous bone marrow transplantation.

    PubMed

    Martini, E; Gorin, N C; Gastal, C; Doinel, C; Roquin, H; Najman, A; Salmon, C

    1988-01-01

    Circadian variations are observed in CD4 lymphocyte count in healthy people. Samples taken of the basal value occurring around 08.00 hr and peak value at midnight made it possible to define the range of cyclic variations. Movement of lymphocytes seems important in accounting for the observed circadian variations. CD4 circadian cycle amplitudes were investigated in 12 patients with autologous bone marrow transplantation. Cycle abnormalities were observed in 7 patients. Two of them had a normal CD4 lymphocyte count. It was therefore possible for functional abnormalities in CD4 lymphocytes to be detected in patients with a normal CD4 count. Because of these results, we are of the opinion that the evaluation of CD4 lymphocyte cycle might be a more sensitive test than the absolute CD4 count itself.

  2. Expression of the CD4 gene requires a Myb transcription factor.

    PubMed Central

    Siu, G; Wurster, A L; Lipsick, J S; Hedrick, S M

    1992-01-01

    We have analyzed the control of developmental expression of the CD4 gene, which encodes an important recognition molecule and differentiation antigen on T cells. We have determined that the CD4 promoter alone functions at high levels in the CD4+ CD8- mature T cell but not at the early CD4+ CD8+ stage of T-cell development. In addition, the CD4 promoter functions only in T lymphocytes; thus, the stage and tissue specificity of the CD4 gene is mediated in part by its promoter. We have determined that a Myb transcription factor binds to the CD4 promoter and is critical for full promoter function. Thus, Myb plays an important role in the expression of T-cell-specific developmentally regulated genes. Images PMID:1347906

  3. Infant and young child feeding practices and stunting in two highland provinces in Ecuador.

    PubMed

    Roche, Marion L; Gyorkos, Theresa W; Blouin, Brittany; Marquis, Grace S; Sarsoza, Julieta; Kuhnlein, Harriet V

    2017-04-01

    The first two years of life are critical for growth and development. Little is known about infant and young child feeding (IYCF) practices in the Ecuadorian highlands and how they contribute to stunting. With the objective of understanding nutritional status and the influencing factors to design an intervention, we assessed the nutritional status of 293 infants and children between 0 and 24 months of age, living in 14 communities in the provinces of Tungurahua and Chimborazo using a cross-sectional study design. We used the WHO IYCF indicators to assess feeding practices; estimated dietary intake with 24-h recalls; and identified nutritious local foods by food frequency questionnaires. Multiple regression modelling was performed to identify correlates of nutritional status. Stunting was found in 56.2% of children. Mean protein, vitamin A and vitamin C intakes were above recommendations for all ages. Only infants 6.0 to 8.9 months of age and non-breastfed children 12-23.9 months of age consumed energy intakes below recommendations. Younger age groups had below recommended intakes for iron and calcium. While mean complementary food densities met recommendations for protein, vitamin A, vitamin C and energy, those for zinc, iron and calcium were lower than recommended. Older age, respiratory infections and being male were predictors of lower HAZ, whereas early initiation of breastfeeding, higher socioeconomic status, consumption of iron-rich foods and higher dietary protein density were protective. Interventions that promote and support optimal breastfeeding practices and enable increased consumption of nutritious local foods have potential to contribute to reducing stunting in this vulnerable population. © 2016 John Wiley & Sons Ltd.

  4. Risk factors, CD4 long-term evolution and mortality of HIV-infected patients who persistently maintain low CD4 counts, despite virological response to HAART.

    PubMed

    Pacheco, Yolanda M; Jarrín, Inmaculada; Del Amo, Julia; Moreno, Santiago; Iribarren, José A; Viciana, Pompeyo; Parra, Jorge; Gomez-Sirvent, Juan L; Gutierrez, Félix; Blanco, José R; Vidal, Francesc; Leal, Manuel

    2009-11-01

    A proportion of HIV-patients does not normally restore their CD4 counts despite virological response to HAART. Those whose CD4 counts persistently remain closed to the critical threshold for opportunistic infections deserve special interest. To study the risk factors, the long-term CD4 counts evolution, and the risk of death of patients who persistently maintain low CD4 counts, despite virological response to HAART, within a multicenter, hospital-based cohort study. A total of 147 patients were selected from CoRIS-MD and classified into a "Low-Group" or a "High-Group", depending on their CD4 counts after two-years of effective HAART (threshold 250 cells/microL). Associated risk factors were analysed by logistic regression, the CD4 dynamics were evaluated over a total period of 7.70 years (IQR, 6.70-9.00), and mortality was estimated by Cox proportional hazard. A total of 40 patients (27%) were classified into the "Low-Group". The odds ratio for this group increased with age, being 4.56 (2.23-9.33) for over 40, and was also higher among IDU, 3.63 (1.04-12.68). Six years thereafter, among these patients, only a 30% exceeded 350 CD4 cells/microL and a 12% exceeded 500 CD4 cells/microL. Furthermore, the "Low-Group" had a death rate of 2.42 per 100 persons/year (95%CI, 1.01-5.81), although once adjusted by age the estimates were no longer significant [4.14 (0.87-19.72)]. Our results suggest that those HIV patients who have not overcome the critical threshold of 250 CD4 cells/microL after a two years period of virologically effective HAART do persist with the aforementioned failure of CD4 restoration for a much longer time.

  5. Complementary Feeding: Review of Recommendations, Feeding Practices, and Adequacy of Homemade Complementary Food Preparations in Developing Countries – Lessons from Ethiopia

    PubMed Central

    Abeshu, Motuma Adimasu; Lelisa, Azeb; Geleta, Bekesho

    2016-01-01

    Breastfeeding provides the ideal food during the first 6 months of life. Complementary feeding starts when breast milk is no longer sufficient by itself, where the target age is for 6–23 months. The gap between nutritional requirement and amount obtained from breast milk increases with age. For energy, 200, 300, and 550 kcal per day is expected to be covered by complementary foods at 6–8, 9–11, and 12–23 months, respectively. In addition, the complementary foods must provide relatively large proportions of micronutrients such as iron, zinc, phosphorus, magnesium, calcium, and vitamin B6. In several parts of the developing world, complementary feeding continues as a challenge to good nutrition in children. In Ethiopia, only 4.2% of breastfed children of 6–23 months of age have a minimum acceptable diet. The gaps are mostly attributed to either poor dietary quality or poor feeding practices, if not both. Commercial fortified foods are often beyond the reach of the poor. Thus, homemade complementary foods remain commonly used. Even when based on an improved recipe, however, unfortified plant-based complementary foods provide insufficient key micronutrients (especially, iron, zinc, and calcium) during the age of 6–23 months. Thus, this review assessed complementary feeding practice and recommendation and reviewed the level of adequacy of homemade complementary foods. PMID:27800479

  6. Unique and shared signaling pathways cooperate to regulate the differentiation of human CD4+ T cells into distinct effector subsets

    PubMed Central

    Wong, Natalie; Rao, Geetha; Nguyen, Akira; Avery, Danielle T.; Payne, Kathryn; Torpy, James; O’Young, Patrick; Deenick, Elissa; Bustamante, Jacinta; Puel, Anne; Okada, Satoshi; Kobayashi, Masao; Martinez-Barricarte, Ruben; Elliott, Michael; Sebnem Kilic, Sara; El Baghdadi, Jamila; Minegishi, Yoshiyuki; Bousfiha, Aziz; Robertson, Nic; Hambleton, Sophie; Arkwright, Peter D.; French, Martyn; Blincoe, Annaliesse K.; Hsu, Peter; Campbell, Dianne E.; Stormon, Michael O.; Wong, Melanie; Adelstein, Stephen; Fulcher, David A.; Cook, Matthew C.; Stepensky, Polina; Boztug, Kaan; Beier, Rita; Ikincioğullari, Aydan; Ziegler, John B.; Gray, Paul; Picard, Capucine; Boisson-Dupuis, Stéphanie; Phan, Tri Giang; Grimbacher, Bodo; Warnatz, Klaus; Holland, Steven M.; Uzel, Gulbu; Casanova, Jean-Laurent; Tangye, Stuart G.

    2016-01-01

    Naive CD4+ T cells differentiate into specific effector subsets—Th1, Th2, Th17, and T follicular helper (Tfh)—that provide immunity against pathogen infection. The signaling pathways involved in generating these effector cells are partially known. However, the effects of mutations underlying human primary immunodeficiencies on these processes, and how they compromise specific immune responses, remain unresolved. By studying individuals with mutations in key signaling pathways, we identified nonredundant pathways regulating human CD4+ T cell differentiation in vitro. IL12Rβ1/TYK2 and IFN-γR/STAT1 function in a feed-forward loop to induce Th1 cells, whereas IL-21/IL-21R/STAT3 signaling is required for Th17, Tfh, and IL-10–secreting cells. IL12Rβ1/TYK2 and NEMO are also required for Th17 induction. Strikingly, gain-of-function STAT1 mutations recapitulated the impact of dominant-negative STAT3 mutations on Tfh and Th17 cells, revealing a putative inhibitory effect of hypermorphic STAT1 over STAT3. These findings provide mechanistic insight into the requirements for human T cell effector function, and explain clinical manifestations of these immunodeficient conditions. Furthermore, they identify molecules that could be targeted to modulate CD4+ T cell effector function in the settings of infection, vaccination, or immune dysregulation. PMID:27401342

  7. Use of Thickened Liquids to Manage Feeding Difficulties in Infants: A Pilot Survey of Practice Patterns in Canadian Pediatric Centers.

    PubMed

    Dion, Stephanie; Duivestein, Janice A; St Pierre, Astrid; Harris, Susan R

    2015-08-01

    Improved survival rates of sick or preterm infants have resulted in an increase of observed feeding difficulties. One common method for managing feeding difficulties in infants is to manipulate liquid viscosity by adding thickening agents to formula or expressed breast milk. Concerns regarding the lack of clinical practice guidelines for the use of this strategy have been raised in the literature and in clinical settings for several years. This study aimed to survey feeding clinicians working in major Canadian pediatric centers to identify current practice patterns for use of thickened liquids in managing feeding difficulties of infants and to justify the need for standardization of this practice. A web-based pilot survey was developed using Fluidsurveys software. The questionnaire contained 37 questions targeting the process of prescribing thickeners, choice of thickener, awareness of issues, and inconsistencies raised in the literature about thickener use and how to address them. A total of 69 questionnaire responses were analyzed using descriptive statistics and inductive thematic analysis methods. Our study results indicate that thickened liquids continue to be broadly used to manage feeding difficulties in Canadian infants, despite numerous areas of concern related to their use raised by our respondents. While clear practice patterns for assessment and management were observed among the respondents, some areas of practice did not reflect recent published research or experts' opinion. Further research to develop a systematic approach for assessment, intervention, and follow-up is warranted to guide clinicians in this complex decision-making process.

  8. Eating Behaviours of Preadolescent Children over Time: Stability, Continuity and the Moderating Role of Perceived Parental Feeding Practices.

    PubMed

    Houldcroft, Laura; Farrow, Claire; Haycraft, Emma

    2016-04-20

    The links between childhood eating behaviours and parental feeding practices are well-established in younger children, but there is a lack of research examining these variables in a preadolescent age group, particularly from the child's perspective, and longitudinally. This study firstly aimed to examine the continuity and stability of preadolescent perceptions of their parents' controlling feeding practices (pressure to eat and restriction) over a 12 month period. The second aim was to explore if perceptions of parental feeding practices moderated the relationship between preadolescents' eating behaviours longitudinally. Two hundred and twenty nine preadolescents (mean age at recruitment 8.73 years) completed questionnaires assessing their eating behaviours and their perceptions of parental feeding practices at two time points, 12 months apart (T1 and T2). Preadolescents' perceptions of their parental feeding practices remained stable. Perceptions of restriction and pressure to eat were continuous. Perceptions of parental pressure to eat and restriction significantly moderated the relationships between eating behaviours at T1 and T2. The findings from this study suggest that in a preadolescent population, perceptions of parental pressure to eat and restriction of food may exacerbate the development of problematic eating behaviours.

  9. Eating Behaviours of Preadolescent Children over Time: Stability, Continuity and the Moderating Role of Perceived Parental Feeding Practices

    PubMed Central

    Houldcroft, Laura; Farrow, Claire; Haycraft, Emma

    2016-01-01

    The links between childhood eating behaviours and parental feeding practices are well-established in younger children, but there is a lack of research examining these variables in a preadolescent age group, particularly from the child’s perspective, and longitudinally. This study firstly aimed to examine the continuity and stability of preadolescent perceptions of their parents’ controlling feeding practices (pressure to eat and restriction) over a 12 month period. The second aim was to explore if perceptions of parental feeding practices moderated the relationship between preadolescents’ eating behaviours longitudinally. Two hundred and twenty nine preadolescents (mean age at recruitment 8.73 years) completed questionnaires assessing their eating behaviours and their perceptions of parental feeding practices at two time points, 12 months apart (T1 and T2). Preadolescents’ perceptions of their parental feeding practices remained stable. Perceptions of restriction and pressure to eat were continuous. Perceptions of parental pressure to eat and restriction significantly moderated the relationships between eating behaviours at T1 and T2. The findings from this study suggest that in a preadolescent population, perceptions of parental pressure to eat and restriction of food may exacerbate the development of problematic eating behaviours. PMID:27104552

  10. Parental feeding practices and socioeconomic status are associated with child adiposity in a multi-ethnic sample of children.

    PubMed

    Cardel, Michelle; Willig, Amanda L; Dulin-Keita, Akilah; Casazza, Krista; Beasley, T Mark; Fernández, José R

    2012-02-01

    Parental feeding practices have been associated with children's weight status, but results have been inconsistent across populations. Research is needed to elucidate the relationship between parental feeding practices and adiposity in diverse populations. The present study tested if: (1) parental feeding practices differed by race/ethnicity, (2) parental pressure to eat and parental restriction were associated with adiposity levels, and (3) to investigate the relationship between parental feeding practices and/or child adiposity with socioeconomic status (SES). Structural equations modeling was conducted to test the model in 267 children aged 7-12 years self-identified as African American (AA), European American (EA), or Hispanic American (HA) from economically diverse backgrounds. Dual energy X-ray absorptiometry and computed tomography scanning were used to determine body composition and abdominal fat distribution, respectively. Parental restriction was a significant predictor of child adiposity while parental pressure to eat had an inverse relationship with child adiposity. HA parents reported significantly higher levels of restriction and pressure to eat, whereas EA parents reported the lowest. SES was positively associated with child adiposity and inversely related to parental restriction and pressure to eat. Thus, parental feeding practices differ across racial/ethnic groups and SES and may contribute to population differences in child adiposity.

  11. Maternal child-feeding practices and dietary inadequacy of 4-year-old children.

    PubMed

    Durão, Catarina; Andreozzi, Valeska; Oliveira, Andreia; Moreira, Pedro; Guerra, António; Barros, Henrique; Lopes, Carla

    2015-09-01

    This study aimed to evaluate the association between maternal perceived responsibility and child-feeding practices and dietary inadequacy of 4-year-old children. We studied 4122 mothers and children enrolled in the population-based birth cohort - Generation XXI (Porto, Portugal). Mothers self-completed the Child Feeding Questionnaire and a scale on covert and overt control, and answered to a food frequency questionnaire in face-to-face interviews. Using dietary guidelines for preschool children, adequacy intervals were defined: fruit and vegetables (F&V) 4-7 times/day; dairy 3-5 times/day; meat and eggs 5-10 times/week; fish 2-4 times/week. Inadequacy was considered as below or above these cut-points. For energy-dense micronutrient-poor foods and beverages (EDF), a tolerable limit was defined (<6 times/week). Associations between maternal perceived responsibility and child-feeding practices (restriction, monitoring, pressure to eat, overt and covert control) and children's diet were examined by logistic regression models. After adjustment for maternal BMI, education, and diet, and children's characteristics (sex, BMI z-scores), restriction, monitoring, overt and covert control were associated with 11-18% lower odds of F&V consumption below the interval defined as adequate. Overt control was also associated with 24% higher odds of their consumption above it. Higher perceived responsibility was associated with higher odds of children consuming F&V and dairy above recommendations. Pressure to eat was positively associated with consumption of dairy above the adequate interval. Except for pressure to eat, maternal practices were associated with 14-27% lower odds of inadequate consumption of EDF. In conclusion, children whose mothers had higher levels of covert control, monitoring, and restriction were less likely to consume F&V below recommendations and EDF above tolerable limits. Higher overt control and pressure to eat were associated, respectively, with higher

  12. The influence of maternal infant feeding practices and beliefs on the expression of food neophobia in toddlers.

    PubMed

    Cassells, Erin L; Magarey, Anthea M; Daniels, Lynne A; Mallan, Kimberley M

    2014-11-01

    Food neophobia is a highly heritable trait characterized by the rejection of foods that are novel or unknown and potentially limits dietary variety, with lower intake and preference particularly for fruits and vegetables. Understanding non-genetic (environmental) factors that may influence the expression of food neophobia is essential to improving children's consumption of fruits and vegetables and encouraging the adoption of healthier diets. The aim of this study was to examine whether maternal infant feeding beliefs (at 4 months) were associated with the expression of food neophobia in toddlers and whether controlling feeding practices mediated this relationship. Participants were 244 first-time mothers (M=30.4, SD=5.1 years) allocated to the control group of the NOURISH randomized controlled trial. The relationships between infant feeding beliefs (Infant Feeding Questionnaire) at 4 months and controlling child feeding practices (Child Feeding Questionnaire) and food neophobia (Child Food Neophobia Scale) at 24 months were tested using correlational and multiple linear regression models (adjusted for significant covariates). Higher maternal Concern about infant under-eating and becoming underweight at 4 months was associated with higher child food neophobia at 2 years. Similarly, lower Awareness of infant hunger and satiety cues was associated with higher child food neophobia. Both associations were significantly mediated by mothers' use of Pressure to eat. Intervening early to promote positive feeding practices to mothers may help reduce the use of controlling practices as children develop. Further research that can further elucidate the bi-directional nature of the mother-child feeding relationship is still required.

  13. Parental feeding practices and associations with child weight status. Swedish validation of the Child Feeding Questionnaire finds parents of 4-year-olds less restrictive.

    PubMed

    Nowicka, Paulina; Sorjonen, Kimmo; Pietrobelli, Angelo; Flodmark, Carl-Erik; Faith, Myles S

    2014-10-01

    The Child Feeding Questionnaire (CFQ) assesses parental feeding attitudes, beliefs and practices concerned with child feeding and obesity proneness. The questionnaire has been developed in the U.S., and validation studies in other countries are limited. The aim of this study was to examine the psychometric properties of the CFQ in Sweden and the associations between parenting practices and children's weight status. Based on records from the Swedish population register, all mothers of 4-year-olds (n = 3007) from the third largest city in Sweden, Malmö, were contacted by mail. Those who returned the CFQ together with a background questionnaire (n = 876) received the CFQ again to enable test-retest evaluation; 564 mothers completed the CFQ twice. We used confirmatory factor analysis to test whether the original 7-factor model was supported. Good fit (CFI = 0.94, TLI = 0.95, RMSEA = 0.04, SRMR = 0.05) was obtained after minor modifications such as dropping 2 items on restriction and adding 3 error covariances. The internal reliability and the 2-week test-retest reliability were good. The scores on restriction were the lowest ever reported. When the influence of parenting practices on child BMI (dependent variable) was examined in a structural equation model (SEM), child BMI had a positive association with restriction and a negative association with pressure to eat. Restriction was positively influenced by concern about child weight. The second SEM treated parenting practices as dependent variables. Parental foreign origin and child BMI had direct effects on restriction, while pressure to eat was also influenced by parental education. While the results of the study support the usefulness of the CFQ in Sweden, carefully designed cross-cultural comparisons are needed to explain why the levels of restrictive feeding in Swedish families are the lowest reported.

  14. The Feeding Practices and Structure Questionnaire (FPSQ-28): A parsimonious version validated for longitudinal use from 2 to 5 years.

    PubMed

    Jansen, Elena; Williams, Kate E; Mallan, Kimberley M; Nicholson, Jan M; Daniels, Lynne A

    2016-05-01

    Prospective studies and intervention evaluations that examine change over time assume that measurement tools measure the same construct at each occasion. In the area of parent-child feeding practices, longitudinal measurement properties of the questionnaires used are rarely verified. To ascertain that measured change in feeding practices reflects true change rather than change in the assessment, structure, or conceptualisation of the constructs over time, this study examined longitudinal measurement invariance of the Feeding Practices and Structure Questionnaire (FPSQ) subscales (9 constructs; 40 items) across 3 time points. Mothers participating in the NOURISH trial reported their feeding practices when children were aged 2, 3.7, and 5 years (N = 404). Confirmatory Factor Analysis (CFA) within a structural equation modelling framework was used. Comparisons of initial cross-sectional models followed by longitudinal modelling of subscales, resulted in the removal of 12 items, including two redundant or poorly performing subscales. The resulting 28-item FPSQ-28 comprised 7 multi-item subscales: Reward for Behaviour, Reward for Eating, Persuasive Feeding, Overt Restriction, Covert Restriction, Structured Meal Setting and Structured Meal Timing. All subscales showed good fit over 3 time points and each displayed at least partial scalar (thresholds equal) longitudinal measurement invariance. We recommend the use of a separate single item indicator to assess the family meal setting. This is the first study to examine longitudinal measurement invariance in a feeding practices questionnaire. Invariance was established, indicating that the subscales of the shortened FPSQ-28 can be used with mothers to validly assess change in 7 feeding constructs in samples of children aged 2-5 years of age.

  15. Mother's feeding practices for children 3-10 years of age and their associations with child demographics.

    PubMed

    Hendy, Helen M; Williams, Keith E

    2012-04-01

    The present study examined relationships between mothers' feeding practices and child demographics such as gender, age, weight status, and family income. This cross-sectional analysis was conducted using data from 2259 children between 3 and 10 years of age who were sampled for the development of the Parent Mealtime Action Scale. No child gender differences were found in mothers' feeding practices. Older children received more Fat Reduction and Many Food Choices, but less Positive Persuasion, Use of Rewards, Insistence on Eating, and Special Meals, with differences in these feeding practices being most notable from before to after school age. Overweight children received less Insistence on Eating and more Fat Reduction than underweight or normal weight children. Children with the lowest family incomes received less Fat Reduction, less Daily FV Availability, more Use of Rewards. Results suggest that mothers respond to changing conditions, possibly including feedback from school nurses, increases in children's weight status, and availability of financial resources.

  16. TGF-β receptor maintains CD4 T helper cell identity during chronic viral infections

    PubMed Central

    Lewis, Gavin M.; Wehrens, Ellen J.; Labarta-Bajo, Lara; Streeck, Hendrik; Zuniga, Elina I.

    2016-01-01

    Suppression of CD8 and CD4 T cells is a hallmark in chronic viral infections, including hepatitis C and HIV. While multiple pathways are known to inhibit CD8 T cells, the host molecules that restrict CD4 T cell responses are less understood. Here, we used inducible and CD4 T cell–specific deletion of the gene encoding the TGF-β receptor during chronic lymphocytic choriomeningitis virus infection in mice, and determined that TGF-β signaling restricted proliferation and terminal differentiation of antiviral CD4 T cells. TGF-β signaling also inhibited a cytotoxic program that includes granzymes and perforin expression at both early and late stages of infection in vivo and repressed the transcription factor eomesodermin. Overexpression of eomesodermin was sufficient to recapitulate in great part the phenotype of TGF-β receptor–deficient CD4 T cells, while SMAD4 was necessary for CD4 T cell accumulation and differentiation. TGF-β signaling also restricted accumulation and differentiation of CD4 T cells and reduced the expression of cytotoxic molecules in mice and humans infected with other persistent viruses. These data uncovered an eomesodermin-driven CD4 T cell program that is continuously suppressed by TGF-β signaling. During chronic viral infection, this program limits CD4 T cell responses while maintaining CD4 T helper cell identity. PMID:27599295

  17. Crystal structure of HIV-1 primary receptor CD4 in complex with a potent antiviral antibody.

    PubMed

    Freeman, Michael M; Seaman, Michael S; Rits-Volloch, Sophia; Hong, Xinguo; Kao, Chia-Ying; Ho, David D; Chen, Bing

    2010-12-08

    Ibalizumab is a humanized, anti-CD4 monoclonal antibody. It potently blocks HIV-1 infection and targets an epitope in the second domain of CD4 without interfering with immune functions mediated by interaction of CD4 with major histocompatibility complex (MHC) class II molecules. We report here the crystal structure of ibalizumab Fab fragment in complex with the first two domains (D1-D2) of CD4 at 2.2 Å resolution. Ibalizumab grips CD4 primarily by the BC-loop (residues 121-125) of D2, sitting on the opposite side of gp120 and MHC-II binding sites. No major conformational change in CD4 accompanies binding to ibalizumab. Both monovalent and bivalent forms of ibalizumab effectively block viral infection, suggesting that it does not need to crosslink CD4 to exert antiviral activity. While gp120-induced structural rearrangements in CD4 are probably minimal, CD4 structural rigidity is dispensable for ibalizumab inhibition. These results could guide CD4-based immunogen design and lead to a better understanding of HIV-1 entry.

  18. Crystal structure of HIV-1 primary receptor CD4 in complex with a potent antiviral antibody

    PubMed Central

    Freeman, Michael M.; Seaman, Michael S.; Rits-Volloch, Sophia; Hong, Xinguo; Kao, Chia-Ying; Ho, David D.; Chen, Bing

    2010-01-01

    Summary Ibalizumab is a humanized, anti-CD4 monoclonal antibody. It potently blocks HIV-1 infection and targets an epitope in the second domain of CD4 without interfering with immune functions mediated by interaction of CD4 with major histocompatibility complex (MHC) class II molecules. We report here the crystal structure of ibalizumab Fab fragment in complex with the first two domains (D1-D2) of CD4 at 2.2 Å resolution. Ibalizumab grips CD4 primarily by the BC-loop (residues 121-125) of D2, sitting on the opposite side of gp120 and MHC-II binding sites. No major conformational change in CD4 accompanies binding to ibalizumab. Both monovalent and bivalent forms of ibalizumab effectively block viral infection, suggesting that it does not need to crosslink CD4 to exert antiviral activity. While gp120-induced structural rearrangements in CD4 are probably minimal, CD4 structural rigidity is dispensable for ibalizumab inhibition. These results could guide CD4-based immunogen design and lead to a better understanding of HIV-1 entry. PMID:21134642

  19. Serum iron, Folate, Ferritin and CD4 Count in HIV Seropositive Women.

    PubMed

    Kharb, Simmi; Kumawat, Manjulata; Lallar, Meenakshi; Ghalaut, P S; Nanda, Smiti

    2017-03-01

    HIV infects cluster of differentiation 4 (CD4) T-lymphocytes, monocytes and macrophages resulting in decreased number and function of CD4 cells, changes that affect both cell mediated and humoral immunity. Hematological abnormalities are a common complication of human immune virus (HIV) infection and these abnormalities increase as the disease advances. Anemia is the most common haematological abnormality in HIV seropositive patients and its incidence is strongly associated with the progression of the disease. The aim of present study was to assess the haematological profile of HIV seropositive women and compare them with CD4 count. Two hundred seropositive females (age 18-25 years) attending antiretroviral therapy clinic were selected. Routine gynaecological and haematological investigations were carried out, study samples were drawn and serum iron, folate and ferritin were analysed by chemiluminiscence and CD4 count was determined by using flow-cytometry. Anemia was prevalent in seropositive women especially in those with low CD4 levels. Serum folate and ferritin levels were significantly lower in females with lower CD4 levels. Serum iron levels were higher at low CD4 levels. The mean CD4 count in HIV seropositive anaemic women were lower as compared to non anaemics suggesting that anaemia improves with higher CD4 cell counts. Plasma folate and ferritin levels are sensitive predictor of anaemia in early HIV infections and these patients should have a regular monitoring of their folate and ferritin levels especially with lower CD4 levels.

  20. DC-SIGN Increases the Affinity of HIV-1 Envelope Glycoprotein Interaction with CD4

    PubMed Central

    Hijazi, Karolin; Wang, Yufei; Scala, Carlo; Jeffs, Simon; Longstaff, Colin; Stieh, Daniel; Haggarty, Beth; Vanham, Guido; Schols, Dominique; Balzarini, Jan; Jones, Ian M.; Hoxie, James; Shattock, Robin; Kelly, Charles G.

    2011-01-01

    Mannose-binding C-type lectin receptors, expressed on Langerhans cells and subepithelial dendritic cells (DCs) of cervico-vaginal tissues, play an important role in HIV-1 capture and subsequent dissemination to lymph nodes. DC-SIGN has been implicated in both productive infection of DCs and the DC-mediated trans infection of CD4+ T cells that occurs in the absence of replication. However, the molecular events that underlie this efficient transmission have not been fully defined. In this study, we have examined the effect of the extracellular domains of DC-SIGN and Langerin on the stability of the interaction of the HIV-1 envelope glycoprotein with CD4 and also on replication in permissive cells. Surface plasmon resonance analysis showed that DC-SIGN increases the binding affinity of trimeric gp140 envelope glycoproteins to CD4. In contrast, Langerin had no effect on the stability of the gp140:CD4 complex. In vitro infection experiments to compare DC-SIGN enhancement of CD4-dependent and CD4-independent strains demonstrated significantly lower enhancement of the CD4-independent strain. In addition DC-SIGN increased the relative rate of infection of the CD4-dependent strain but had no effect on the CD4-independent strain. DC-SIGN binding to the HIV envelope protein effectively increases exposure of the CD4 binding site, which in turn contributes to enhancement of infection. PMID:22163292

  1. Factors associated with CD4 lymphocyte counts in HIV-negative Senegalese individuals

    PubMed Central

    Mair, C; Hawes, S E; Agne, H D; Sow, P S; N'doye, I; Manhart, L E; Fu, P L; Gottlieb, G S; Kiviat, N B

    2008-01-01

    CD4+ lymphocytes are a primary target of the human immunodeficiency virus (HIV), and CD4 counts are one of the factors used to measure disease progression in HIV-positive individuals. CD4 counts vary in uninfected individuals and across populations due to a variety of demographic, environmental, immunological and genetic factors that probably persist throughout the course of HIV infection. This study sought to determine reference levels and identify factors that influence lymphocyte counts in 681 HIV-uninfected adults in Senegal, where residents are exposed to a variety of infectious diseases and other conditions that may affect CD4 counts. Lymphocyte counts were assessed in commercial sex workers, symptomatic men and women presenting to the University of Dakar infectious disease clinic for out-patient care and women seeking family planning services. CD4 and CD3 lymphocyte counts differed between the four study groups (P < 0·01). Men had the lowest mean CD4 count (711·6 cells/μl), while commercial sex workers had the highest levels (966·0 cells/μl). After adjustment for age and other behavioural and clinical factors, the difference in CD4 counts between the three groups of women did not remain. However, both gender and smoking were associated independently with CD4 counts, as men maintained lower mean CD4 counts (β = −156·4 cells/μl, P < 0·01) and smokers had higher mean CD4 counts (β = 124·0 cells/μl, P < 0·01) than non-smokers in multivariable analyses. This study is the first to explore factors that may influence CD4 levels in Senegal and to estimate baseline CD4 levels among HIV-negatives, information that may guide clinicians in interpreting CD4 counts. PMID:18190600

  2. Stabilization of HIV-1 gp120-CD4 Receptor Complex through Targeted Interchain Disulfide Exchange*

    PubMed Central

    Cerutti, Nichole; Mendelow, Barry V.; Napier, Grant B.; Papathanasopoulos, Maria A.; Killick, Mark; Khati, Makobetsa; Stevens, Wendy; Capovilla, Alexio

    2010-01-01

    HIV-1 enters cells via interaction between the trimeric envelope (Env) glycoprotein gp120/gp41 and the host cell surface receptor molecule CD4. The requirement of CD4 for viral entry has rationalized the development of recombinant CD4-based proteins as competitive viral attachment inhibitors and immunotherapeutic agents. In this study, we describe a novel recombinant CD4 protein designed to bind gp120 through a targeted disulfide-exchange mechanism. According to structural models of the gp120-CD4 receptor complex, substitution of Ser60 on the CD4 domain 1 α-helix with Cys positions a thiol in proximity of the gp120 V1/V2 loop disulfide (Cys126–Cys196), satisfying the stereochemical and geometric conditions for redox exchange between CD4 Cys60 and gp120 Cys126, and the consequent formation of an interchain disulfide bond. In this study, we provide experimental evidence for this effect by describing the expression, purification, refolding, receptor binding and antiviral activity analysis of a recombinant two-domain CD4 variant containing the S60C mutation (2dCD4-S60C). We show that 2dCD4-S60C binds HIV-1 gp120 with a significantly higher affinity than wild-type protein under conditions that facilitate disulfide exchange and that this translates into a corresponding increase in the efficacy of CD4-mediated viral entry inhibition. We propose that targeted redox exchange between conserved gp120 disulfides and nucleophilic moieties positioned strategically on CD4 (or CD4-like scaffolds) conceptualizes a new strategy in the development of high affinity HIV-1 Env ligands, with important implications for therapy and vaccine development. More generally, this chalcogen substitution approach provides a general means of stabilizing receptor-ligand complexes where the structural and biophysical conditions for disulfide exchange are satisfied. PMID:20538591

  3. Conformational Rearrangement Within the Soluble Domains of the CD4 Receptor is Ligand-Specific

    SciTech Connect

    Ashish,F.; Juncadella, I.; Garg, R.; Boone, C.; Anguita, J.; Krueger, J.

    2008-01-01

    Ligand binding induces shape changes within the four modular ectodomains (D1-D4) of the CD4 receptor, an important receptor in immune signaling. Small angle x-ray scattering (SAXS) on both a two-domain and a four-domain construct of the soluble CD4 (sCD4) is consistent with known crystal structures demonstrating a bilobal and a semi-extended tetralobal Z conformation in solution, respectively. Detection of conformational changes within sCD4 as a result of ligand binding was followed by SAXS on sCD4 bound to two different glycoprotein ligands: the tick saliva immunosuppressor Salp15 and the HIV-1 envelope protein gp120. Ab initio modeling of these data showed that both Salp15 and gp120 bind to the D1 domain of sCD4 and yet induce drastically different structural rearrangements. Upon binding, Salp15 primarily distorts the characteristic lobal architecture of the sCD4 without significantly altering the semi-extended shape of the sCD4 receptor. In sharp contrast, the interaction of gp120 with sCD4 induces a shape change within sCD4 that can be described as a Z-to-U bi-fold closure of the four domains across its flexible D2-D3 linker. Placement of known crystal structures within the boundaries of the SAXS-derived models suggests that the ligand-induced shape changes could be a result of conformational changes within this D2-D3 linker. Functionally, the observed shape changes in CD4 receptor causes dissociation of lymphocyte kinase from the cytoplasmic domain of Salp15-bound CD4 and facilitates an interaction between the exposed V3 loops of CD4-bound gp120 molecule to the extracellular loops of its co-receptor, a step essential for HIV-1 viral entry.

  4. Sociocultural and Environmental Influences on Brazilian Immigrant Mothers' Beliefs and Practices Related to Child Feeding and Weight Status.

    PubMed

    Lindsay, Ana Cristina; Wallington, Sherrie F; Greaney, Mary L; Hasselman, Maria H; Machado, Marcia M T; Mezzavilla, Raquel S; Detro, Barbara M

    2016-12-28

    Background Length of residence in the United States (US), changes in dietary and physical activity behaviors, and economic and social barriers contribute to high childhood obesity rates among children from immigrant families in the US. Brazilians comprise a fast-growing immigrant population group in the US, yet little research has focused on health issues affecting Brazilian children in immigrant families. Understanding sociocultural and environmental influences on parents' beliefs and practices related to child feeding and weight status is essential to altering obesity trends in this group. Methods Qualitative study consisting of five focus groups with a convenience sample of 29 Brazilian immigrant mothers. Results Analyses revealed that the sociocultural and environment transitions faced by Brazilian immigrant mothers' influence their beliefs and practices related to child feeding and weight status. Additionally, acculturation emerged as a factor affecting mothers' feeding practices and their children's eating habits, with mothers preferring Brazilian food environments and that their children preferring American food environments. Mothers viewed themselves as being responsible for promoting and maintaining their children's healthy eating and feeding behaviors, but changes in their social and cultural environments due to immigration and the pressures and demands of raising a family in a new country make this difficult. Conclusions Health promotion interventions to improve healthful eating and feeding practices of Brazilian children in immigrant families must account for social and cultural changes and daily life demands due to immigration as well as potential variation in the levels of acculturation between mothers and their children.

  5. Human CD4+ central and effector memory T cells produce IL-21: effect on cytokine-driven proliferation of CD4+ T cell subsets.

    PubMed

    Onoda, Tadashi; Rahman, Mizanur; Nara, Hidetoshi; Araki, Akemi; Makabe, Koki; Tsumoto, Kouhei; Kumagai, Izumi; Kudo, Toshio; Ishii, Naoto; Tanaka, Nobuyuki; Sugamura, Kazuo; Hayasaka, Kiyoshi; Asao, Hironobu

    2007-10-01

    IL-21 regulates certain functions of T cells, B cells, NK cells and dendritic cells. Although activated CD4(+) T cells produce IL-21, data identifying the specific CD4(+) T cell subsets that produce IL-21 are conflicting. In a previous study, mouse IL-21 message was detected in T(H)2, whereas human IL-21 (hIL-21) message was found in both T(H)1 and follicular helper T cells. To identify the IL-21-secreting cell populations in human, we established a hybridoma cell line producing an anti-hIL-21 mAb. Intracellular hIL-21-staining experiments showed that hIL-21 was mainly expressed in activated CD4(+) central memory T cells and in activated CD4(+) effector memory T cells, but not in activated CD4(+) naive T cells. Moreover, IL-21 was produced upon activation by some IFN-gamma-producing T(H)1-polarized cells and some IL-17-producing T(H)17-polarized cells, but not by IL-4-producing T(H)2-polarized cells. These results suggest that specific CD4(+) T cell populations produce IL-21. In the functional analysis, we found that IL-21 significantly enhanced the cytokine-driven proliferation of CD4(+) helper T cells synergistically with IL-7 and IL-15 without T cell activation stimuli. Taken together, IL-21 produced from CD4(+) memory T cells may have a supportive role in the maintenance of CD4(+) T cell subsets.

  6. Chromosomal localisation of the CD4cre transgene in B6·Cg-Tg(Cd4-cre)1Cwi mice.

    PubMed

    Westendorf, Kerstin; Durek, Pawel; Ayew, Samia; Mashreghi, Mir-Farzin; Radbruch, Andreas

    2016-09-01

    The B6·Cg-Tg(Cd4-cre)1Cwi line expresses CRE recombinase under the control of the promoter and regulatory elements of the Cd4 gene. Here we show that CRE recombinase expression reduces the number and frequencies of CD4 positive subsets in a dose-dependent manner and localize the integration site of the transgenic construct to position 60335693-60341285 (qD) of chromosome 3. The insert contains at least 15 complete sequential copies of the transgenic construct. Based on this information we describe a novel PCR assay for genetic typing of transgenic mice.

  7. Feeding intervention in cleft lip and palate babies: a practical approach to feeding efficiency and weight gain.

    PubMed

    Ize-Iyamu, I N; Saheeb, B D

    2011-09-01

    Using a disposable syringe to feed 1-14-week-old babies with cleft lip and palate (CLP) was studied. 57 CLP babies were randomly divided into: syringe-fed (intervention) and cup-and-spoon-fed groups and compared with 55 normal breast- or bottle-fed babies. Differences in weight gained from birth to 6, 10 and 14 weeks were compared. Syringe-fed CLP babies fed breast milk had a significant difference in weight gain (0.7 and 0.8 kg) compared with cup-and-spoon-fed babies (0.4 kg), at 10 and 14 weeks, respectively. Normal breast-fed babies gained 0.6 and 0.7 kg. Cup-and-spoon-fed CLP babies fed artificial and breast milk gained 0.5 and 0.6 kg; syringe-fed CLP babies gained 0.6 and 1.2 kg. Normal babies gained 1.0 and 1.7 kg for the same age and food. Average feeding times were 10 ml/1.25 min for syringe-fed and 10 ml/2.08 min for cup-and-spoon-fed CLP babies at 6 weeks. 19 (100%) cup-and-spoon-fed babies exhibited spill and regurgitation at 6 weeks compared with 30 (79%) CLP syringe-fed babies (P<0.05). In both groups spill and regurgitation decreased with age. CLP babies fed with the modified method had a faster feeding time, less spill and regurgitation and gained the same weight as normal babies at 10 and 14 weeks.

  8. Bystander CD4+ T lymphocytes survive in HIV-infected human lymphoid tissue

    NASA Technical Reports Server (NTRS)

    Grivel, Jean-Charles; Biancotto, Angelique; Ito, Yoshinori; Lima, Rosangela G.; Margolis, Leonid B.

    2003-01-01

    HIV infection is associated with depletion of CD4(+) T cells. The mechanisms of this phenomenon remain to be understood. In particular, it remains controversial whether and to what extent uninfected ("bystander") CD4(+) T cells die in HIV-infected individuals. We address this question using a system of human lymphoid tissue ex vivo. Tissue blocks were inoculated with HIV-1. After productive infection was established, they were treated with the reverse transcriptase inhibitor nevirapine to protect from infection those CD4(+) T cells that had not yet been infected. These CD4(+) T cells residing in HIV-infected tissue are by definition bystanders. Our results demonstrate that after nevirapine application the number of bystander CD4(+) T cells is conserved. Thus, in the context of HIV-infected human lymphoid tissue, productive HIV infection kills infected cells but is not sufficient to cause the death of a significant number of uninfected CD4(+) T cells.

  9. Infant feeding practices and maternal dietary intake among Latino immigrants in California.

    PubMed

    Guendelman, Sylvia; Siega-Riz, Anna Maria

    2002-07-01

    Mothers of 8-16-month-old infants were surveyed to examine infant feeding practices and maternal dietary intake associated with increased years of residency by Mexican immigrant families (n = 1093 mother-infant pairs). Mothers were recruited from San Diego and Contra Costa counties in California during 1992-93. Twenty-nine percent of Mexican mothers living in the United States for <6 years breastfed their infants exclusively for at least 16 weeks; only 20% of mothers living in the United States between 6 and 15 years and 17% of mothers residing in the United States for over 15 years engaged in exclusive breastfeeding. Neither breastfeeding duration nor the introduction of solids differed by years of residency. In contrast, maternal dietary intake varied markedly. Second generation mothers and those living in the United States the longest had significantly higher intakes of vegetables, low fat milk, salty snacks, animal protein, and cereals. Beyond early caregiving practices, the influence of years of residency on the diets of toddlers is less than that of the mothers.

  10. Nutritional status and feeding practices of under-five children in Simanjiro District, Tanzania.

    PubMed

    Nyaruhucha, C N M; Msuya, J M; Mamiro, P S; Kerengi, A J

    2006-09-01

    This study was undertaken to assess the nutritional status and feeding practices of < 5 year children among the pastoral communities of Simanjiro district, northern Tanzania. Face-to-face interviews with the sampled mothers were conducted using a semi-structured questionnaire. Anthropometric measurements using weight-for-age criterion were employed to assess the nutritional status. The study showed that 31% of the children were undernourished, some (6%) of them severely. Children 2 - 3 years old were the most affected. Breastfeeding duration of more than one year was common among the mothers. Fifty-four percent of the mothers weaned their children as early as two months after birth. The most common type of weaning food was maize porridge (gruel) mixed with cow's milk (46%). Generally, 87% of households were facing some degree of food insecurity where some of them either experienced food shortage for 3-4 months (40%) or reported to eat less than three meals per day (75%). An educated mother was less likely to have an undernourished child, while a child from a teenage mother was more likely to be undernourished. Small size of a household was in favour of nutrition status. There is a great need to undertake interventions through community education to rescue the situation in Simanjiro district. Efforts should also be undertaken to mobilize the community members to adopt practices that favour good nutrition of children.

  11. Perspectives and reflections on the practice of behaviour change communication for infant and young child feeding.

    PubMed

    Pelto, Gretel H; Martin, Stephanie L; van Liere, Marti J; Fabrizio, Cecilia S

    2016-04-01

    Behaviour change communication (BCC) is a critical component of infant and young child feeding (IYCF) interventions. In this study we asked BCC practitioners working in low- and middle-income countries to participate in an examination of BCC practice. We focus here on results of their personal reflections related to larger issues of practice. We used a combination of iterative triangulation and snowball sampling procedures to obtain a sample of 29 BCC professionals. Major themes include (1) participants using tools and guidelines to structure their work, and many consider their organisation's tools to be their most important contribution to the field; (2) they value research to facilitate programme design and implementation; (3) half felt research needed to increase; (4) they have a strong commitment to respecting cultural beliefs and culturally appropriate programming; (5) they are concerned about lack of a strong theoretical foundation for their work. Based on participants' perspectives and the authors' reflections, we identified the following needs: (1) conducting a systematic examination of the alternative theoretical structures that are available for nutrition BCC, followed by a review of the evidence base and suggestions for future programmatic research to fill the gaps in knowledge; (2) developing a checklist of common patterns to facilitate efficiency in formative research; (3) developing an analytic compendium of current IYCF BCC guidelines and tools; (4) developing tools and guidelines that cover the full programme process, including use of innovative channels to support 'scaling up nutrition'; and (5) continued support for programmes of proven effectiveness.

  12. In Vivo Binding and Retention of CD4-Specific DARPin 57.2 in Macaques

    PubMed Central

    Pugach, Pavel; Krarup, Anders; Gettie, Agegnehu; Kuroda, Marcelo; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D.; Trkola, Alexandra; Robbiani, Melissa

    2010-01-01

    Background The recently described Designed Ankyrin Repeat Protein (DARPin) technology can produce highly selective ligands to a variety of biological targets at a low production cost. Methodology/Principal Findings To investigate the in vivo use of DARPins for future application to novel anti-HIV strategies, we identified potent CD4-specific DARPins that recognize rhesus CD4 and followed the fate of intravenously injected CD4-specific DARPin 57.2 in rhesus macaques. The human CD4-specific DARPin 57.2 bound macaque CD4+ cells and exhibited potent inhibitory activity against SIV infection in vitro. DARPin 57.2 or the control E3_5 DARPin was injected into rhesus macaques and the fate of cell-free and cell-bound CD4-specific DARPin was evaluated. DARPin-bound CD4+ cells were detected in the peripheral blood as early as 30 minutes after the injection, decreasing within 6 hours and being almost undetectable within 24 hours. The amount of DARPin bound was dependent on the amount of DARPin injected. CD4-specific DARPin was also detected on CD4+ cells in the lymph nodes within 30 minutes, which persisted with similar kinetics to blood. More extensive analysis using blood revealed that DARPin 57.2 bound to all CD4+ cell types (T cells, monocytes, dendritic cells) in vivo and in vitro with the amount of binding directly proportional to the amount of CD4 on the cell surface. Cell-free DARPins were also detected in the plasma, but were rapidly cleared from circulation. Conclusions/Significance We demonstrated that the CD4-specific DARPin can rapidly and selectively bind its target cells in vivo, warranting further studies on possible clinical use of the DARPin technology. PMID:20805996

  13. Expression of CD8alpha identifies a distinct subset of effector memory CD4+ T lymphocytes.

    PubMed

    Macchia, Iole; Gauduin, Marie-Claire; Kaur, Amitinder; Johnson, R Paul

    2006-10-01

    Circulating CD4+ CD8+ T lymphocytes have been described in the peripheral blood of humans and several animal species. However, the origin and functional properties of these cells remain poorly understood. In the present study, we evaluated the frequency, phenotype and function of peripheral CD4+ CD8+ T cells in rhesus macaques. Two distinct populations of CD4+ CD8+ T cells were identified: the dominant one was CD4hi CD8lo and expressed the CD8alphaalpha homodimer, while the minor population was CD4lo CD8hi and expressed the CD8alphabeta heterodimer. The majority of CD4hi CD8alphalo T cells exhibited an activated effector/memory phenotype (CCR5lo CD7- CD28- HLA-DR+) and expressed relatively high levels of granzyme B. Intracellular cytokine staining assays demonstrated that the frequency of cytomegalovirus-specific T cells was enriched five-fold in CD4hi CD8alphalo T cells compared to single-positive CD4+ T cells, whereas no consistent enrichment was observed for simian immunodeficiency virus (SIV)-specific T cells. Cross-sectional studies of SIV-infected animals demonstrated that the frequency of CD4hi CD8alphalo T cells was lower in wild-type SIV-infected animals compared to uninfected controls, although prospective studies of SIV-infected animals demonstrated depletion of CD4hi CD8alphalo lymphocytes only in a subset of animals. Taken together, these data suggest that CD4+ T cells expressing CD8alpha represent an effector/memory subset of CD4+ T cells and that this cell population can be depleted during the course of SIV infection.

  14. Determinants of suboptimal complementary feeding practices among children aged 6-23 months in four anglophone West African countries.

    PubMed

    Issaka, Abukari I; Agho, Kingsley E; Page, Andrew N; Burns, Penelope L; Stevens, Garry J; Dibley, Michael J

    2015-10-01

    Suboptimal complementary feeding practices have a detrimental impact on a child's growth, health and development in the first two years of life. They lead to child malnutrition, which contributes to the high prevalence of stunting (38%) and underweight (28%) reported for children <5 years of age in Sub-Saharan Africa. This study analysed complementary feeding practices in four anglophone West African countries (Ghana, Liberia, Nigeria and Sierra Leone) using the most recent Demographic and Health Surveys. The study covered 12 623 children aged 6-23 months from four anglophone West African countries (Ghana: 822 children: Liberia: 1458 children, Nigeria: 8786 children and Sierra Leone: 1557 children). Four complementary feeding indicators were examined against a set of individual-, household- and community-level factors, using multiple regression analysis. Multivariate analyses found that lack of post-natal contacts with health workers, maternal illiteracy and geographical region were common determinants of delayed introduction of solid, semi-solid or soft foods across all four countries. Predictors for minimum dietary diversity, minimum meal frequency and minimum acceptable diet included children aged 6-11 months, administrative/geographical region, poorer household income and limited access to media. The authors recommend that the four anglophone West African countries studied should prioritise efforts to improve complementary feeding practices in order to reduce child morbidity and mortality. Interventional studies on complementary feeding should target those from poor and illiterate households.

  15. H + CD4 abstraction reaction dynamics: product energy partitioning.

    PubMed

    Hu, Wenfang; Lendvay, György; Troya, Diego; Schatz, George C; Camden, Jon P; Bechtel, Hans A; Brown, Davida J A; Martin, Marion R; Zare, Richard N

    2006-03-09

    This paper presents experimental and theoretical studies of the product energy partitioning associated with the H + CD4 (nu = 0) --> HD + CD3 reaction for the collision energy range 0.5-3.0 eV. The theoretical results are based on quasiclassical trajectories from (1) first principles direct dynamics calculations (B3LYP/6-31G), (2) an empirical surface developed by Espinosa-García [J. Chem. Phys. 2002, 116, 10664] (EG), and (3) two semiempirical surfaces (MSINDO and reparametrized MSINDO). We find that most of the energy appears in product translation at energies just above the reactive threshold; however, HD vibration and rotation become quite important at energies above 1 eV, each accounting for over 20% of the available energy above 1.5 eV, according to the B3LYP calculations. The barrier on the B3LYP surface, though being later than that on EG, predicts significantly higher HD vibrational excitation than EG. This deviation is contradictory to what would be expected on the basis of the Polanyi rules and derives from modest differences in the potential energy surfaces. The CD3 internal energy is generally quite low, and we present detailed rotational state distributions which show that the CD3 rotational distribution is largely independent of collision energy in the 0.75-1.95 eV range. The most populated rotational levels are N = 5 and 6 on B3LYP, with most of that excitation being associated with motion about the C2 axes, rather than C3 axis, of the CD3 product, in good agreement with the experimental results. Through our extensive studies in this and previous work concerning the scattering dynamics, we conclude that B3LYP/6-31G provides the best available description of the overall dynamics for the title reaction at relatively high collision energies.

  16. TNF-α blockade induces IL-10 expression in human CD4+ T cells

    NASA Astrophysics Data System (ADS)

    Evans, Hayley G.; Roostalu, Urmas; Walter, Gina J.; Gullick, Nicola J.; Frederiksen, Klaus S.; Roberts, Ceri A.; Sumner, Jonathan; Baeten, Dominique L.; Gerwien, Jens G.; Cope, Andrew P.; Geissmann, Frederic; Kirkham, Bruce W.; Taams, Leonie S.

    2014-02-01

    IL-17+ CD4+ T (Th17) cells contribute to the pathogenesis of several human inflammatory diseases. Here we demonstrate that TNF inhibitor (TNFi) drugs induce the anti-inflammatory cytokine IL-10 in CD4+ T cells including IL-17+ CD4+ T cells. TNFi-mediated induction of IL-10 in IL-17+ CD4+ T cells is Treg-/Foxp3-independent, requires IL-10 and is overcome by IL-1β. TNFi-exposed IL-17+ CD4+ T cells are molecularly and functionally distinct, with a unique gene signature characterized by expression of IL10 and IKZF3 (encoding Aiolos). We show that Aiolos binds conserved regions in the IL10 locus in IL-17+ CD4+ T cells. Furthermore, IKZF3 and IL10 expression levels correlate in primary CD4+ T cells and Aiolos overexpression is sufficient to drive IL10 in these cells. Our data demonstrate that TNF-α blockade induces IL-10 in CD4+ T cells including Th17 cells and suggest a role for the transcription factor Aiolos in the regulation of IL-10 in CD4+ T cells.

  17. ESTABLISHING MEAN CD4+ T CELL VALUES AMONG HEALTHY JAVANESE ADULTS IN INDONESIA.

    PubMed

    Prasetyo, Afiono Agung; Zaini, Khilyat Ulin Nur

    2015-07-01

    The objective of this study was to establish mean CD4+ T cell values among healthy Javanese adults in Indonesia. Two hundred forty-one healthy adults (119 women and 122 men), aged 18-65 years, were enrolled in the study. CD4+ T cells were analyzed by immunophenotyping. The mean absolute CD4+ T cell count was 753.3 ± 270.3 cells/µl (median = 725.0 cells/µl) and the mean CD4+ T cell percentage was 32.6 ± 7.7%, (median = 31.0%). Women had a slightly higher mean absolute CD4+ T cell count and CD4+ T cell percentage (779.1 ± 271.0 cells/ µl; 33.4 ± 8.2%) than men (728.2 ± 268.3 cells/µl; 31.8 ± 7.1%), but the differences were not statistically significant (p = 0.126, p = 0.216, respectively). The mean absolute CD4+ T cell varied significantly by age group (p = 0.002). Sixty-one point seven percent of men studied (37/60) had a CD4+ T cell count less than 500 cells/µl (OR 1.8; 95% CI = 1.001-3.300). Absolute CD4+ T cell counts among Javanese Indonesians varied significantly by age.

  18. Clinical Evaluation of the BD FACSPresto™ Near-Patient CD4 Counter in Kenya

    PubMed Central

    Angira, Francis; Akoth, Benta; Omolo, Paul; Opollo, Valarie; Bornheimer, Scott; Judge, Kevin; Tilahun, Henok; Lu, Beverly; Omana-Zapata, Imelda; Zeh, Clement

    2016-01-01

    Background The BD FACSPresto™ Near-Patient CD4 Counter was developed to expand HIV/AIDS management in resource-limited settings. It measures absolute CD4 counts (AbsCD4), percent CD4 (%CD4), and hemoglobin (Hb) from a single drop of capillary or venous blood in approximately 23 minutes, with throughput of 10 samples per hour. We assessed the performance of the BD FACSPresto system, evaluating accuracy, stability, linearity, precision, and reference intervals using capillary and venous blood at KEMRI/CDC HIV-research laboratory, Kisumu, Kenya, and precision and linearity at BD Biosciences, California, USA. Methods For accuracy, venous samples were tested using the BD FACSCalibur™ instrument with BD Tritest™ CD3/CD4/CD45 reagent, BD Trucount™ tubes, and BD Multiset™ software for AbsCD4 and %CD4, and the Sysmex™ KX-21N for Hb. Stability studies evaluated duration of staining (18–120-minute incubation), and effects of venous blood storage <6–24 hours post-draw. A normal cohort was tested for reference intervals. Precision covered multiple days, operators, and instruments. Linearity required mixing two pools of samples, to obtain evenly spaced concentrations for AbsCD4, total lymphocytes, and Hb. Results AbsCD4 and %CD4 venous/capillary (N = 189/ N = 162) accuracy results gave Deming regression slopes within 0.97–1.03 and R2 ≥0.96. For Hb, Deming regression results were R2 ≥0.94 and slope ≥0.94 for both venous and capillary samples. Stability varied within 10% 2 hours after staining and for venous blood stored less than 24 hours. Reference intervals results showed that gender—but not age—differences were statistically significant (p<0.05). Precision results had <3.5% coefficient of variation for AbsCD4, %CD4, and Hb, except for low AbsCD4 samples (<6.8%). Linearity was 42–4,897 cells/μL for AbsCD4, 182–11,704 cells/μL for total lymphocytes, and 2–24 g/dL for Hb. Conclusions The BD FACSPresto system provides accurate, precise clinical

  19. Enhanced HIV-1 neutralization by a CD4-VH3-IgG1 fusion protein

    SciTech Connect

    Meyuhas, Ronit; Noy, Hava; Fishman, Sigal; Margalit, Alon; Montefiori, David C.; Gross, Gideon

    2009-08-21

    HIV-1 gp120 is an alleged B cell superantigen, binding certain VH3+ human antibodies. We reasoned that a CD4-VH3 fusion protein could possess higher affinity for gp120 and improved HIV-1 inhibitory capacity. To test this we produced several human IgG1 immunoligands harboring VH3. Unlike VH3-IgG1 or VH3-CD4-IgG1, CD4-VH3-IgG1 bound gp120 considerably stronger than CD4-IgG1. CD4-VH3-IgG1 exhibited {approx}1.5-2.5-fold increase in neutralization of two T-cell laboratory-adapted strains when compared to CD4-IgG1. CD4-VH3-IgG1 improved neutralization of 7/10 clade B primary isolates or pseudoviruses, exceeding 20-fold for JR-FL and 13-fold for Ba-L. It enhanced neutralization of 4/8 clade C viruses, and had negligible effect on 1/4 clade A pseudoviruses. We attribute this improvement to possible pairing of VH3 with CD4 D1 and stabilization of an Ig Fv-like structure, rather than to superantigen interactions. These novel findings support the current notion that CD4 fusion proteins can act as better HIV-1 entry inhibitors with potential clinical implications.

  20. Protection conferred by heterologous vaccination against tuberculosis is dependent on the ratio of CD4(+) /CD4(+)  Foxp3(+) cells.

    PubMed

    Fedatto, Paola Fernanda; Sérgio, Cássia Alves; Paula, Marina Oliveira e; Gembre, Ana Flávia; Franco, Luís Henrique; Wowk, Pryscilla Fanini; Ramos, Simone Gusmão; Horn, Cynthia; Marchal, Gilles; Turato, Walter Miguel; Silva, Célio Lopes; da Fonseca, Denise Morais; Bonato, Vânia Luiza Deperon

    2012-11-01

    CD4(+) Foxp3(+) regulatory T cells inhibit the production of interferon-γ, which is the major mediator of protection against Mycobacterium tuberculosis infection. In this study, we evaluated whether the protection conferred by three different vaccines against tuberculosis was associated with the number of spleen and lung regulatory T cells. We observed that after homologous immunization with the 65 000 molecular weight heat-shock protein (hsp 65) DNA vaccine, there was a significantly higher number of spleen CD4(+) Foxp3(+) cells compared with non-immunized mice. Heterologous immunization using bacillus Calmette-Guérin (BCG) to prime and DNA-hsp 65 to boost (BCG/DNA-hsp 65) or BCG to prime and culture filtrate proteins (CFP)-CpG to boost (BCG/CFP-CpG) induced a significantly higher ratio of spleen CD4(+) /CD4(+) Foxp3(+) cells compared with non-immunized mice. In addition, the protection conferred by either the BCG/DNA-hsp 65 or the BCG/CFP-CpG vaccines was significant compared with the DNA-hsp 65 vaccine. Despite the higher ratio of spleen CD4(+) /CD4(+) Foxp3(+) cells found in BCG/DNA-hsp 65-immunized or BCG/CFP-CpG-immunized mice, the lungs of both groups of mice were better preserved than those of DNA-hsp 65-immunized mice. These results confirm the protective efficacy of BCG/DNA-hsp 65 and BCG/CFP-CpG heterologous prime-boost vaccines and the DNA-hsp 65 homologous vaccine. Additionally, the prime-boost regimens assayed here represent a promising strategy for the development of new vaccines to protect against tuberculosis because they probably induce a proper ratio of CD4(+) and regulatory (CD4(+) Foxp3(+) ) cells during the immunization regimen. In this study, this ratio was associated with a reduced number of regulatory cells and no injury to the lungs.

  1. CD4+ primary T cells expressing HCV-core protein upregulate Foxp3 and IL-10, suppressing CD4 and CD8 T cells.

    PubMed

    Fernandez-Ponce, Cecilia; Dominguez-Villar, Margarita; Aguado, Enrique; Garcia-Cozar, Francisco

    2014-01-01

    Adaptive T cell responses are critical for controlling HCV infection. While there is clinical evidence of a relevant role for regulatory T cells in chronic HCV-infected patients, based on their increased number and function; mechanisms underlying such a phenomena are still poorly understood. Accumulating evidence suggests that proteins from Hepatitis C virus can suppress host immune responses. We and others have shown that HCV is present in CD4+ lymphocytes from chronically infected patients and that HCV-core protein induces a state of unresponsiveness in the CD4+ tumor cell line Jurkat. Here we show that CD4+ primary T cells lentivirally transduced with HCV-core, not only acquire an anergic phenotype but also inhibit IL-2 production and proliferation of bystander CD4+ or CD8+ T cells in response to anti-CD3 plus anti-CD28 stimulation. Core-transduced CD4+ T cells show a phenotype characterized by an increased basal secretion of the regulatory cytokine IL-10, a decreased IFN-γ production upon stimulation, as well as expression of regulatory T cell markers, CTLA-4, and Foxp3. A significant induction of CD4+CD25+CD127(low)PD-1(high)TIM-3(high) regulatory T cells with an exhausted phenotype was also observed. Moreover, CCR7 expression decreased in HCV-core expressing CD4+ T cells explaining their sequestration in inflamed tissues such as the infected liver. This work provides a new perspective on de novo generation of regulatory CD4+ T cells in the periphery, induced by the expression of a single viral protein.

  2. Early Infant Feeding Practices May Influence the Onset of Symptomatic Celiac Disease

    PubMed Central

    Sharma, Shiv Dayal; Gupta, Rajkumar; Goyal, Alok; Sharma, Aakash

    2016-01-01

    Purpose To study whether breastfeeding and breastfeeding status during gluten introduction influences the age at diagnosis of celiac disease (CD). In addition to study, whether the timing of gluten introduction influences the age at diagnosis of CD. Methods It was a hospital based observational study. Total 198 patients diagnosed with CD as per modified European Society of Pediatric Gastroenterology, Hepatology and Nutrition (2012) criteria, aged between 6 months to 6 years were included. Detail history taken with special emphasis on breastfeeding and age of gluten introduction. Standard statistical methods used to analyze the data. Results Mean±standard deviation age of onset and diagnosis of CD in breastfed cases was 2.81±1.42 years and 3.68 ±1.55 years respectively as compared to 1.84±1.36 years and 2.70±1.65 years respectively in not breastfed cases (p<0.05). Those who had continued breastfeeding during gluten introduction and of longer duration had significantly delayed onset of disease. The age at onset of CD was under one year in 40.42% of the cases, who had started gluten before 6 months of age compared to only 12.58% of those who had started gluten later (p<0.001). The proposed statistical model showed that two variables, i.e., breast feeding status during gluten introduction and age at gluten introduction positively influencing the age at diagnosis of CD. Conclusion Delayed gluten introduction to infant's diet along with continuing breastfeeding, delays symptomatic CD. However, it is not clear from our study that these infant feeding practices provide permanent protection against the disease or merely delays the symptoms. PMID:28090467

  3. Popularizing right food and feeding practices in Spain (1847-1950). The handbooks of domestic economy.

    PubMed

    Perdiguero-Gil, Enrique; Castejón-Bolea, Ramón

    2010-01-01

    The aim of this paper is to analyze a sample of domestic economy handbooks in order to assess the popularization of correct food and feeding practices in Spain between 1847 and 1950. With this contribution, we wish to evaluate another factor that would influence the Spanish food transition. We are aware that this is a very indirect source, given the high levels of illiteracy among women in Spain during the last third of the 19th century and the beginning of the 20th century. A further factor to be considered is the low proportion of girls attending school. We have analyzed the handbooks published in three periods. The first ranges from the last third of the 19th century to the first decade of the 20th. These handbooks are considered in order to provide background for a comparison with the works published from 1900 onwards. The second period focuses on the 1920s and the 1930s. The last period covers the handbooks published after the Civil War under the monopoly of the Sección Femenina (women's section of the Falange). Over the years under consideration, recommendations underwent a progressive modification from the very simple leaflets used in the 19th century to the introduction of scientific factors into the teaching of domestic economy.The work of Rosa Sensat represented the beginnings of this trend. A further modernizing factor was the appearance of vitamins in some of the handbooks. After the war, the number of handbooks decreased and they were, in general, very poor. If we consider the content on vitamins, there was a lack or shortage of information in comparison with some of the books published in the same period outside the monopoly of the Sección Femenina. In conclusion, we can state that the repetition of recommendations on good feeding habits and the increase in girls attending school would exert a positive influence on the food transition of the Spanish population.

  4. Nutritional Deficiencies, the Absence of Information and Caregiver Shortcomings: A Qualitative Analysis of Infant Feeding Practices in Rural China

    PubMed Central

    Yue, Ai; Marsh, Lauren; Medina, Alexis; Luo, Renfu; Shi, Yaojiang; Zhang, Linxiu; Kenny, Kaleigh; Rozelle, Scott

    2016-01-01

    Background and Objectives Development during the first two years of life is critical and has a lasting impact on a child’s health. Poor infant and child nutrition can lead to deficiencies in essential micronutrients, which may cause a weakened immune system and lasting effects on children's growth and development. Recent studies in rural Shaanxi Province found an anemia prevalence of 54.3% among rural children aged six to twelve months. While new large-scale, quantitative research has begun to catalogue the extent of child malnutrition and anemia, no effort has yet been made to look more closely at the potential reasons for rural children’s nutritional deficiencies through qualitative analysis. This study aims to elucidate some of the fundamental causes of poor complementary feeding practices that may lead to anemia among children in rural Shaanxi Province, China. Methodology We interviewed sixty caregivers participating in a large survey on child health and nutrition. We conducted three waves of interviews with children’s primary caregivers in seventeen rural villages within four nationally-designated poverty counties in the southern part of Shaanxi Province. Results The qualitative analysis reveals that poor complementary feeding practices are common across our sample. Information gathered from our interviews suggests that complementary feeding practices are impeded by two constraints: absence of understanding topics related to infant health and nutrition under caregivers, as well as inadequate sources of information on these topics. Poverty does not appear to constrain child feeding practices. Conclusion Our results uncover lack of proper knowledge on infant and child nutrition among rural caregivers in China. This situation causes them to fail incorporating micronutrient rich foods in their children's diet. Age-appropriate complementary feeding can stimulate children’s physical and cognitive development, but in its absence it leads to iron

  5. Feeding style differences in food parenting practices associated with fruit and vegetable intake in children fromlow-income families

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to examine the moderating effects of feeding styles on the relationship between food parenting practices and fruit and vegetable intake in low-income families with preschool-aged children. Focus group meetings with Head Start parents were conducted by using the nomina...

  6. Feeding Practices and Styles Used by a Diverse Sample of Low-Income Parents of Preschool-age Children

    ERIC Educational Resources Information Center

    Ventura, Alison K.; Gromis, Judy C.; Lohse, Barbara

    2010-01-01

    Objective: To describe the feeding practices and styles used by a diverse sample of low-income parents of preschool-age children. Design: Thirty- to 60-minute meetings involving a semistructured interview and 2 questionnaires administered by the interviewer. Setting: Low-income communities in Philadelphia, PA. Participants: Thirty-two parents of…

  7. A call for research exploring social media influences on mothers' child feeding practices and childhood obesity risk.

    PubMed

    Doub, Allison E; Small, Meg; Birch, Leann L

    2016-04-01

    There is increasing interest in leveraging social media to prevent childhood obesity, however, the evidence base for how social media currently influences related behaviors and how interventions could be developed for these platforms is lacking. This commentary calls for research on the extent to which mothers use social media to learn about child feeding practices and the mechanisms through which social media influences their child feeding practices. Such formative research could be applied to the development and dissemination of evidence-based childhood obesity prevention programs that utilize social media. Mothers are identified as a uniquely important target audience for social media-based interventions because of their proximal influence on children's eating behavior and their high engagement with social media platforms. Understanding mothers' current behaviors, interests, and needs as they relate to their social media use and child feeding practices is an integral first step in the development of interventions that aim to engage mothers for obesity prevention. This commentary highlights the importance of mothers for childhood obesity prevention; discusses theoretical and analytic frameworks that can inform research on social media and mothers' child feeding practices; provides evidence that social media is an emerging context for social influences on mothers' attitudes and behaviors in which food is a salient topic; and suggests directions for future research.

  8. The Use of Inappropriate Feeding Practices by Rural Parents and Their Effect on Preschoolers' Fruit and Vegetable Preferences and Intake

    ERIC Educational Resources Information Center

    Bante, Holly; Elliott, Michael; Harrod, Amanda; Haire-Joshu, Debra

    2008-01-01

    Objective: To describe the frequency of inappropriate feeding practices used by parents of preschoolers and the impact on a child's preference for and intake of fruits and vegetables (FV). Design: Cross-sectional analysis of baseline data from a telephone interview. Setting: A community-based program in rural southeastern Missouri. Participants:…

  9. Breast versus bottle: correlates of adolescent mothers' infant-feeding practices.

    PubMed

    Joffe, A; Radius, S M

    1987-05-01

    Since the 1970s, breast-feeding as the preferred method of infant feeding has increased in overall popularity. However, certain populations, particularly poor, young, black, and less-educated women, have been slow to adopt this method. This prospective study was undertaken to identify factors relating to the choice of infant-feeding method among inner-city adolescents. Two hundred fifty-four pregnant adolescents completed a questionnaire supplying information regarding attitudes toward and knowledge about breast-feeding, social support, personal experience, and other variables hypothesized to correlate with their choice of infant-feeding method. Of the total sample, 17% said they were "probably" or "definitely" going to breast-feed their babies. Analyses revealed adolescents most likely to intend to breast-feed were those who perceived more benefits to breast-feeding, who desired more knowledge about it, who were themselves breast-fed, who reported supportive social environments, and who perceived relatively fewer barriers to breast-feeding their infants. Specific interventions based upon these findings are proposed. We conclude that adolescent mothers are interested in breast-feeding their babies and that interventions are feasible to increase breast-feeding within this population.

  10. Early feeding practices and family structure: associations with overweight in children.

    PubMed

    Hunsberger, Monica

    2014-02-01

    The aim of this review is to examine two factors that may be associated with development of childhood overweight: early feeding, namely exclusive breastfeeding practices; family structure. Findings from the Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS (IDEFICS) study are presented in the context of the literature. IDEFICS is a multi-centre European study exploring the risks for overweight and obesity in children, which recruited 16,224 children aged 2-9 years from September 2007 to June 2008 at survey centres in Italy, Estonia, Cyprus, Belgium, Sweden, Hungary, Germany and Spain. Among the IDEFICS sample, after controlling for confounders, exclusive breastfeeding for 4-6 months was protective of overweight (including obesity) when compared with children never exclusively breastfed (OR 0·73, 95% CI 0·63, 0·85). Family structure and number of siblings may also be associated with overweight. IDEFICS children without siblings were more likely (OR 1·52, 95% CI 1·34, 1·72) to be overweight than their peers with siblings when controlling for factors related to childhood overweight such as country, parental education, parental weight, maternal age, child's age, birth weight and gender. Both early feeding practices and family structure play a role in the future development of obesity. The impact of breastfeeding on future development of overweight is dependent upon the dose. Exclusive breastfeeding for the recommended 6 months appears to be protective of overweight. Family structure is also an important component and emerging research suggests only children are at increased risk for overweight in comparison with those with siblings. In European countries, approximately 22 million children are overweight. Early dietary exposures, genetic, environmental and social factors have all been proposed as potential causal factors. Two such factors include exclusive breastfeeding and the impact of being an only child. We

  11. Self-reported breast feeding practices and the Baby Friendly Hospital Initiative in Riyadh, Saudi Arabia: prospective cohort study

    PubMed Central

    Sarkar, Abdullah; Hashem, Alaa AbouBakr; Hamadah, Reem E; Alhoulan, Asma; AlMakadma, Yosra A; Khan, Tehreem A; Al-Hamdani, Abdurahman K; Senok, Abiola

    2016-01-01

    Background The Baby Friendly Hospital Initiative (BFHI) is a practice guideline for healthcare providers to promote breastfeeding and increase breastfeeding rates. Objective This study aimed to examine reported experiences and views on breastfeeding of women using prenatal and postnatal services, and opinions of staff, in the context of the BFHI programme in Riyadh, Saudi Arabia. Design Prospective cohort study. Setting This prospective, longitudinal study was conducted from December 2013 to September 2015 at two healthcare facilities (BFHI and non-BFHI) in Riyadh Saudi Arabia. Methods Women 36–40 weeks gestation receiving antenatal care at the hospitals were enrolled. Questionnaires were administered prenatally, at 1, 3 and 6 months postnatal and to the administrator and maternity staff. Results We recruited 277 women with an estimated 80% response rate. 156 (BFHI=78/139, non-BFHI=78/138, 56%) participants completed all questionnaires. Most BFHI-hospital participants (77.9%, n=8 for this question) acknowledged seeing the breast feeding policy compared to 23.5% (n=23) at the non-BFHI-hospital (p<0.01). Breast feeding education and encouragement was higher at the BFHI-hospital (93.3%) compared to the non-BFHI-hospital (48.2%; p<0.01). At postpartum discharge, 51% (n=53) of mothers in the BFHI-hospital were breast feeding exclusively versus 29.6% (n=29) at the non-BFHI-hospital. Where formula feed was introduced, women in the BFHI-hospital more often practiced mixed feeding rather than exclusive formula feeding with some switching from mixed feeding to exclusive breast feeding between 3 and 6 months postpartum. Exclusive breast feeding rates declined in both hospitals at 3 and 6 months postpartum with lack of community services for lactation being a major reason. Although BFHI-hospital staff (n=9) were more conversant with BFHI principles, defects in adherence to the BFHI 10 Steps were identified. Conclusions This is the first study assessing the

  12. Differential T cell receptor-mediated signaling in naive and memory CD4 T cells.

    PubMed

    Farber, D L; Acuto, O; Bottomly, K

    1997-08-01

    Naive and memory CD4 T cells differ in cell surface phenotype, function, activation requirements, and modes of regulation. To investigate the molecular bases for the dichotomies between naive and memory CD4 T cells and to understand how the T cell receptor (TCR) directs diverse functional outcomes, we investigated proximal signaling events triggered through the TCR/CD3 complex in naive and memory CD4 T cell subsets isolated on the basis of CD45 isoform expression. Naive CD4 T cells signal through TCR/CD3 similar to unseparated CD4 T cells, producing multiple tyrosine-phosphorylated protein species overall and phosphorylating the T cell-specific ZAP-70 tyrosine kinase which is recruited to the CD3zeta subunit of the TCR. Memory CD4 T cells, however, exhibit a unique pattern of signaling through TCR/CD3. Following stimulation through TCR/CD3, memory CD4 T cells produce fewer species of tyrosine-phosphorylated substrates and fail to phosphorylate ZAP-70, yet unphosphorylated ZAP-70 can associate with the TCR/CD3 complex. Moreover, a 26/28-kDa phosphorylated doublet is associated with CD3zeta in resting and activated memory but not in naive CD4 T cells. Despite these differences in the phosphorylation of ZAP-70 and CD3-associated proteins, the ZAP-70-related kinase, p72syk, exhibits similar phosphorylation in naive and memory T cell subsets, suggesting that this kinase could function in place of ZAP-70 in memory CD4 T cells. These results indicate that proximal signals are differentially coupled to the TCR in naive versus memory CD4 T cells, potentially leading to distinct downstream signaling events and ultimately to the diverse functions elicited by these two CD4 T cell subsets.

  13. Association of p56lck with the cytoplasmic domain of CD4 modulates HIV-1 expression.

    PubMed Central

    Tremblay, M; Meloche, S; Gratton, S; Wainberg, M A; Sékaly, R P

    1994-01-01

    To investigate the role played by the cytoplasmic domain of the CD4 glycoprotein in the process of HIV infection, we have transfected two CD4-negative human T cell lines with cDNAs encoding the full-length CD4 and a truncated form of the molecule, lacking most of the cytoplasmic domain. Levels of viral replication were significantly higher in cells carrying the truncated version of CD4, in comparison with cells expressing the full-length CD4, as measured by the percentage of cells expressing viral p24 protein and the number of infectious particles released into culture supernatants. The extent of viral entry and reverse transcription was similar in each case, as monitored by an enzymatic test and quantitative PCR. Quantitative differences at RNA and protein levels were responsible for changes in viral production. To further characterize the mechanisms responsible for decreased rates of HIV replication in CD4-expressing cells we have treated the different cell lines, very early after HIV infection, with azidothymidine and soluble CD4, two antiviral agents that inhibit replication of HIV at different stages in the virus replicative cycle. Results from these experiments indicate that a cellular signal is mediated by the CD4 molecule, which negatively regulates the expression of viral DNA already present in such cells. This signal would be initiated following oligomerization of the CD4 molecule by the virus itself. Results from experiments with a CD4 construct containing mutations of the cysteine residues which are responsible for association of CD4 with p56lck demonstrate that p56lck is implicated in the transduction of the signal negatively regulating HIV replication. Images PMID:8112293

  14. Soluble CD4 antigen reactivity in intravenous immunoglobulin preparations: is it specific?

    PubMed Central

    Perosa, F; Rizzi, R; Pulpito, V; Dammacco, F

    1995-01-01

    Soluble CD4 antigen (sCD4) was measured in seven commercially available intravenous immunoglobulin preparations (IVIg) by means of a double determinant immunoassay (DDIA), whereby two MoAbs recognizing two distinct and spatially distant epitopes on CD4 were used to capture and detect the antigen, respectively. Preincubation of six out of seven IVIg, which were found to be apparently positive for sCD4, with mouse- and bovine-derived serum or purified immunoglobulins completely neutralized DDIA reactivity for sCD4. The inhibition was specific since it was not or only partially observed when IVIg were mixed with whole serum or purified IgG from rabbit. Extensive absorption of six IVIg on insolubilized mouse IgG (mIgG) resulted in a complete loss of reactivity. Eluted human anti-mouse antibodies (HAMA) from any of the IVIg displayed a dose-dependent binding in a DDIA, though its extent varied from one preparation to another. Western blot analysis showed that HAMA from all IVIg contained no component with a molecular weight identical with or close to that of recombinant CD4. Purified mIgG markedly influenced the sCD4 reactivity of two IVIg (Sandoglobulin and Globuman I.V.) when sCD4 was measured with a purchased 'CD4-specific Test Kit', thus suggesting that HAMA can exceed the absorbing capacity of the sample diluent. Taken as a whole, these data indicate that sCD4-based DDIA signal is mostly, if not completely, generated by the presence of human immunoglobulin with anti-mouse immunoglobulin reactivity, thus casting doubts on the actual occurrence of sCD4 in IVIg. Images Fig. 4 PMID:7813106

  15. Immunological predictors of CD4+ T cell decline in antiretroviral treatment interruptions

    PubMed Central

    Seoane, Elena; Resino, Salvador; Moreno, Santiago; de Quiros, Juan Carlos Lopez Bernaldo; Moreno, Ana; Rubio, Rafael; Gonzalez-García, Juan; Arribas, José Ramón; Pulido, Federico; Muñoz-Fernández, Ma Ángeles

    2008-01-01

    Background The common response to stopping anti-HIV treatment is an increase of HIV-RNA load and decrease in CD4+, but not all the patients have similar responses to this therapeutic strategy. The aim was to identify predictive markers of CD4+ cell count declines to < 350/μL in CD4-guided antiretroviral treatment interruptions. Methods 27 HIV-infected patients participated in a prospective multicenter study in with a 24 month follow-up. Patients on stable highly active antiretroviral therapy (HAART), with CD4+ count > 600/μL, and HIV-RNA < 50 copies/ml for at least 6 months were offered the option to discontinue antiretroviral therapy. The main outcome was a decline in CD4+ cell count to < 350/μL. Results After 24 months of follow-up, 16 of 27 (59%) patients (who discontinued therapy) experienced declines in CD4+ cell count to < 350/μL. Patients with a CD4+ nadir of < 200 cells/μL had a greater risk of restarting therapy during the follow-up (RR (CI95%): 3.37 (1.07; 10.36)). Interestingly, lymphoproliferative responses to Mycobacterium tuberculosis purified protein derivative (PPD) below 10000 c.p.m. at baseline (4.77 (1.07; 21.12)), IL-4 production above 100 pg/mL at baseline (5.95 (1.76; 20.07)) in PBMC cultured with PPD, and increased IL-4 production of PBMC with p24 antigen at baseline (1.25 (1.01; 1.55)) were associated to declines in CD4+ cell count to < 350/μL. Conclusion Both the number (CD4+ nadir) and the functional activity of CD4+ (lymphoproliferative response to PPD) predict the CD4+ decrease associated with discontinuation of ART in patients with controlled viremia. PMID:18302775

  16. A Low Peripheral Blood CD4/CD8 Ratio Is Associated with Pulmonary Emphysema in HIV

    PubMed Central

    Attia, Engi F.; Akgün, Kathleen M.; Soo Hoo, Guy W.; Freiberg, Matthew S.; Butt, Adeel A.; Wongtrakool, Cherry; Goetz, Matthew Bidwell; Brown, Sheldon T.; Graber, Christopher J.; Huang, Laurence; Crothers, Kristina

    2017-01-01

    Objectives The prevalence of emphysema is higher among HIV-infected (HIV+) individuals compared to HIV-uninfected persons. While greater tobacco use contributes, HIV-related effects on immunity likely confer additional risk. Low peripheral blood CD4+ to CD8+ T-lymphocyte (CD4/CD8) ratio may reflect chronic inflammation in HIV and may be a marker of chronic lung disease in this population. Therefore, we sought to determine whether the CD4/CD8 ratio was associated with chronic obstructive pulmonary disease (COPD), particularly the emphysema subtype, in a cohort of HIV+ subjects. Methods We performed a cross-sectional analysis of 190 HIV+ subjects enrolled in the Examinations of HIV Associated Lung Emphysema (EXHALE) study. Subjects underwent baseline laboratory assessments, pulmonary function testing and chest computed tomography (CT) analyzed for emphysema severity and distribution. We determined the association between CD4/CD8 ratio and emphysema, and the association between CD4/CD8 ratio and pulmonary function markers of COPD. Results Mild or greater emphysema (>10% lung involvement) was present in 31% of subjects. Low CD4/CD8 ratio was associated with >10% emphysema in multivariable models, adjusting for risk factors including smoking, current and nadir CD4 count and HIV RNA level. Those with CD4/CD8 ratio <0.4 had 6.3 (1.1–39) times the odds of >10% emphysema compared to those with a ratio >1.0 in fully adjusted models. A low CD4/CD8 ratio was also associated with reduced diffusion capacity (DLCO). Conclusions A low CD4/CD8 ratio was associated with emphysema and low DLCO in HIV+ subjects, independent of other risk factors and clinical markers of HIV. The CD4/CD8 ratio may be a useful, clinically available, marker for risk of emphysema in HIV+ subjects in the antiretroviral therapy (ART) era. PMID:28122034

  17. The Transcription Factor Hobit Identifies Human Cytotoxic CD4+ T Cells

    PubMed Central

    Oja, Anna E.; Vieira Braga, Felipe A.; Remmerswaal, Ester B. M.; Kragten, Natasja A. M.; Hertoghs, Kirsten M. L.; Zuo, Jianmin; Moss, Paul A.; van Lier, René A. W.; van Gisbergen, Klaas P. J. M.; Hombrink, Pleun

    2017-01-01

    The T cell lineage is commonly divided into CD4-expressing helper T cells that polarize immune responses through cytokine secretion and CD8-expressing cytotoxic T cells that eliminate infected target cells by virtue of the release of cytotoxic molecules. Recently, a population of CD4+ T cells that conforms to the phenotype of cytotoxic CD8+ T cells has received increased recognition. These cytotoxic CD4+ T cells display constitutive expression of granzyme B and perforin at the protein level and mediate HLA class II-dependent killing of target cells. In humans, this cytotoxic profile is found within the human cytomegalovirus (hCMV)-specific, but not within the influenza- or Epstein–Barr virus-specific CD4+ T cell populations, suggesting that, in particular, hCMV infection induces the formation of cytotoxic CD4+ T cells. We have previously described that the transcription factor Homolog of Blimp-1 in T cells (Hobit) is specifically upregulated in CD45RA+ effector CD8+ T cells that arise after hCMV infection. Here, we describe the expression pattern of Hobit in human CD4+ T cells. We found Hobit expression in cytotoxic CD4+ T cells and accumulation of Hobit+ CD4+ T cells after primary hCMV infection. The Hobit+ CD4+ T cells displayed highly overlapping characteristics with Hobit+ CD8+ T cells, including the expression of cytotoxic molecules, T-bet, and CX3CR1. Interestingly, γδ+ T cells that arise after hCMV infection also upregulate Hobit expression and display a similar effector phenotype as cytotoxic CD4+ and CD8+ T cells. These findings suggest a shared differentiation pathway in CD4+, CD8+, and γδ+ T cells that may involve Hobit-driven acquisition of long-lived cytotoxic effector function. PMID:28392788

  18. Effect of Peer Counselling by Mother Support Groups on Infant and Young Child Feeding Practices: The Lalitpur Experience

    PubMed Central

    Kushwaha, Komal P.; Sankar, Jhuma; Sankar, M. Jeeva; Gupta, Arun; Dadhich, J. P.; Gupta, Y. P.; Bhatt, Girish C.; Ansari, Dilshad A.; Sharma, B.

    2014-01-01

    Objective Our primary objective was to evaluate the effect of peer counselling by mother support groups (MSG's) in improving the infant and young child feeding (IYCF) practices in the community. Methods We conducted this repeated-measure before and after study in the Lalitpur district of Uttar Pradesh, India between 2006 and 2011. We assessed the IYCF practices before and after creating MSG's within the community. The feeding practices were reassessed at two time points–2 (T1) and 5 years (T2) after the intervention and compared with that of the pre-intervention phase (T0). Results The total population covered by the project from the time of its initiation was 105000. A total of 425 (T0), 480 (T1) and 521 (T2) mother infant pairs were selected from this population. There was significant improvement in the following IYCF practices in the community (represented as %; adjOR (95% CI, p) such as initiation of breast feeding within 1 hour at both T1 (71% vs. 11%); 19.6 (13.6, 28.2, p = <0.0001)and T2 (62% vs. 11%); 13.3 (9.4, 18.9, p = <0.0001); use of prelacteal feeds at both T1 (67% vs. 15%); 12.6 (CI: 9.0, 17.6, p<0.0001) and T2 (67% vs. 5%); 44.4 (28.8, 68.4, p = <0.0001); rates of exclusive breast feeding for 6 months at both T1 (50% vs. 7%); 13.6 (7.6, 25.0, p = <0.0001) and T2 (60% vs. 7%); 20.5 (11.3, 37.2, p = <0.0001); initiation of complementary feeding at T1 (85% vs. 54%); 5.6 (3.6, 8.7, p = <0.0001) and T2 (96% vs. 54%); 22.9 (11.8, 44.1, p = <0.0001) and complementary feeding along with continued breast feeding at both T1 (36% vs. 4.5%); 6 (1.15, 31.4, p = 0.033) and T2 (42% vs. 4.5%); 8.06 (1.96, 49.1, p = 0.005) as compared to pre-intervention period (T0) after adjusting for important social and demographic variables. Conclusions Peer counseling by MSG's improved the IYCF practices in the district and could be sustained. PMID:25369452

  19. Heavy agricultural workloads and low crop diversity are strong barriers to improving child feeding practices in the Bolivian Andes.

    PubMed

    Jones, Andrew D; Cruz Agudo, Yesmina; Galway, Lindsay; Bentley, Jeffery; Pinstrup-Andersen, Per

    2012-11-01

    Most nutrition initiatives to date aimed at improving infant and young child feeding (IYCF) have emphasized addressing knowledge gaps through behavior change messaging with less focus on addressing the underlying environmental barriers that may shape these behaviors. This research integrates an analysis of longitudinal dietary data with qualitative data on barriers to improved child feeding to identify the nature and extent of the barriers caregivers face to improving IYCF practices in a farming region of the Bolivian Andes, and to determine the relative influence of these barriers on caregivers' abilities to improve IYCF practices. Sixty-nine caregivers were selected from a sample of 331 households that participated in a longitudinal survey assessing changes in IYCF practices among caregivers with children aged 0-36 months from March 2009 to March 2010. Forty-nine barriers within 12 categories of barriers were identified through semi-structured interviews with the 69 caregivers. The most frequently reported barriers were those related to women's time dedicated to agricultural labor, the limited diversity of household agricultural production, and lack of support for child feeding from spouses and mothers-in-law. In multivariate analyses controlling for several variables that could potentially influence IYCF practices, these barriers were negatively associated with changes to the diversity of child diets, child dietary energy intake, and child meal frequency. While knowledge gaps and individual-level influences affected IYCF practices, physical and social caregiving environments in this region of Bolivia were even more important. Behavior change communication alone will likely not address the social and environmental barriers to improved child feeding that often prevent translation of improved knowledge into action. Particularly in rural regions, agriculture may strongly influence child feeding, not only indirectly through household food security, but also directly

  20. Heavy agricultural workloads and low crop diversity are strong barriers to improving child feeding practices in the Bolivian Andes

    PubMed Central

    Jones, Andrew D; Agudo, Yesmina Cruz; Galway, Lindsay; Bentley, Jeffery; Pinstrup-Andersen, Per

    2012-01-01

    Most nutrition initiatives to date aimed at improving infant and young child feeding (IYCF) have emphasized addressing knowledge gaps through behavior change messaging with less focus on addressing the underlying environmental barriers that may shape these behaviors. This research integrates an analysis of longitudinal dietary data with qualitative data on barriers to improved child feeding to identify the nature and extent of the barriers caregivers face to improving IYCF practices in a farming region of the Bolivian Andes, and to determine the relative influence of these barriers on caregivers’ abilities to improve IYCF practices. Sixty-nine caregivers were selected from a sample of 331 households that participated in a longitudinal survey assessing changes in IYCF practices among caregivers with children aged 0–36 months from March 2009 to March 2010. Forty-nine barriers within 12 categories of barriers were identified through semi-structured interviews with the 69 caregivers. The most frequently reported barriers were those related to women’s time dedicated to agricultural labor, the limited diversity of household agricultural production, and lack of support for child feeding from spouses and mothers-in-law. In multivariate analyses controlling for several variables that could potentially influence IYCF practices, these barriers were negatively associated with changes to the diversity of child diets, child dietary energy intake, and child meal frequency. While knowledge gaps and individual-level influences affected IYCF practices, physical and social caregiving environments in this region of Bolivia were even more important. Behavior change communication alone will likely not address the social and environmental barriers to improved child feeding that often prevent translation of improved knowledge into action. Particularly in rural regions, agriculture may strongly influence child feeding, not only indirectly through household food security, but also

  1. Maternal representations of their children in relation to feeding beliefs and practices among low-income mothers of young children.

    PubMed

    Leung, Christy Y Y; Miller, Alison L; Lumeng, Julie C; Kaciroti, Niko A; Rosenblum, Katherine L

    2015-12-01

    Identifying maternal characteristics in relation to child feeding is important for addressing the current childhood obesity epidemic. The present study examines whether maternal representations of their children are associated with feeding beliefs and practices. Maternal representations refer to mothers' affective and cognitive perspectives regarding their children and their subjective experiences of their relationships with their children. This key maternal characteristic has not been examined in association with maternal feeding. Thus the purpose of the current study was to examine whether maternal representations of their children, reflected by Working Model of the Child Interview typologies (Balanced, Disengaged, or Distorted), were associated with maternal feeding beliefs (Authority, Confidence, and Investment) and practices (Pressure to Eat, Restriction, and Monitoring) among low-income mothers of young children, with maternal education examined as a covariate. Results showed that Balanced mothers were most likely to demonstrate high authority, Distorted mothers were least likely to demonstrate confidence, and Disengaged mothers were least likely to demonstrate investment in child feeding. Moreover, Balanced mothers were least likely to pressure their children to eat. Findings are discussed with regard to implications for the study of childhood obesity and for applied preventions.

  2. Smartphone Versus Pen-and-Paper Data Collection of Infant Feeding Practices in Rural China

    PubMed Central

    Zhang, Shuyi; Wu, Qiong; van Velthoven, Michelle HMMT; Chen, Li; Car, Josip; Rudan, Igor; Li, Ye; Scherpbier, Robert W

    2012-01-01

    Background Maternal, Newborn, and Child Health (MNCH) household survey data are collected mainly with pen-and-paper. Smartphone data collection may have advantages over pen-and-paper, but little evidence exists on how they compare. Objective To compare smartphone data collection versus the use of pen-and-paper for infant feeding practices of the MNCH household survey. We compared the two data collection methods for differences in data quality (data recording, data entry, open-ended answers, and interrater reliability), time consumption, costs, interviewers’ perceptions, and problems encountered. Methods We recruited mothers of infants aged 0 to 23 months in four village clinics in Zhaozhou Township, Zhao County, Hebei Province, China. We randomly assigned mothers to a smartphone or a pen-and-paper questionnaire group. A pair of interviewers simultaneously questioned mothers on infant feeding practices, each using the same method (either smartphone or pen-and-paper). Results We enrolled 120 mothers, and all completed the study. Data recording errors were prevented in the smartphone questionnaire. In the 120 pen-and-paper questionnaires (60 mothers), we found 192 data recording errors in 55 questionnaires. There was no significant difference in recording variation between the groups for the questionnaire pairs (P = .32) or variables (P = .45). The smartphone questionnaires were automatically uploaded and no data entry errors occurred. We found that even after double data entry of the pen-and-paper questionnaires, 65.0% (78/120) of the questionnaires did not match and needed to be checked. The mean duration of an interview was 10.22 (SD 2.17) minutes for the smartphone method and 10.83 (SD 2.94) minutes for the pen-and-paper method, which was not significantly different between the methods (P = .19). The mean costs per questionnaire were higher for the smartphone questionnaire (¥143, equal to US $23 at the exchange rate on April 24, 2012) than for the pen

  3. Infant feeding practice and associated factors among HIV positive mothers in Debre Markos Referral Hospital East Gojam zone, North West Ethiopia

    PubMed Central

    Wakwoya, Elias Bekele; Zewudie, Tatek Abate; Gebresilasie, Kahsay Zenebe

    2016-01-01

    Introduction The dilemma posed between lifesaving benefit and risk of transmission through breast feeding complicates infant feedings among communities grossly affected by HIV/AIDS. According to the world health organization’s guideline which was revised in 2010, exclusive breast feeding and exclusive replacement feeding are the recommended infant feeding practices for HIV positive mothers. The aim of this study was to assess infant feeding practice and associated factors among HIV positive mothers in Debre Markos Referral Hospital, North West Ethiopia. Methods An institutional based cross sectional study was conducted from May to September 2013. A Randomly selected 260 HIV positive mothers were included. The data were collected by using a pretested and structured questionnaire. Bivariate and multivariate analysis were performed to check association and to control confounders. Results From a total of 260 HIV positive mothers, 85.8% of them were feeding their children based on the recommended feeding way of infant feeding practice with the remaining percentage 14.2% were practicing mixed feeding. In multivariate analysis mothers attending high school and above AOR = 5.3 [95% CI = 1.25-22.1], having antenatal care follow up AOR = 5.5 [95% CI = 1.5-20.16], being on anti-retro viral therapy AOR = 6.5 [95% CI = 1.88-22.51] and disclosure of HIV status AOR = 7.1 [95% CI = 1.26-39.76] were found to be independently associated with infant feeding practice. Conclusion This study revealed that large proportion of HIV positive mothers had followed the recommended infant feeding practice and significantly high number of mothers had practiced mixed feeding. Educating mothers, increasing ANC utilization, counseling mothers to start ART, encouraging and supporting mothers to disclose their HIV status were recommended. PMID:28154655

  4. Quantification of cells with specific phenotypes I: determination of CD4+ cell count per microliter in reconstituted lyophilized human PBMC prelabeled with anti-CD4 FITC antibody.

    PubMed

    Stebbings, Richard; Wang, Lili; Sutherland, Janet; Kammel, Martin; Gaigalas, Adolfas K; John, Manuela; Roemer, Bodo; Kuhne, Maren; Schneider, Rudolf J; Braun, Michael; Engel, Andrea; Dikshit, Dinesh K; Abbasi, Fatima; Marti, Gerald E; Sassi, Maria Paola; Revel, Laura; Kim, Sook-Kyung; Baradez, Marc-Olivier; Lekishvili, Tamara; Marshall, Damian; Whitby, Liam; Jing, Wang; Ost, Volker; Vonsky, Maxim; Neukammer, Jörg

    2015-03-01

    A surface-labeled lyophilized lymphocyte (sLL) preparation has been developed using human peripheral blood mononuclear cells prelabeled with a fluorescein isothiocyanate conjugated anti-CD4 monoclonal antibody. The sLL preparation is intended to be used as a reference material for CD4+ cell counting including the development of higher order reference measurement procedures and has been evaluated in the pilot study CCQM-P102. This study was conducted across 16 laboratories from eight countries to assess the ability of participants to quantify the CD4+ cell count of this reference material and to document cross-laboratory variability plus associated measurement uncertainties. Twelve different flow cytometer platforms were evaluated using a standard protocol that included calibration beads used to obtain quantitative measurements of CD4+ T cell counts. There was good overall cross-platform and counting method agreement with a grand mean of the laboratory calculated means of (301.7 ± 4.9) μL(-1) CD4+ cells. Excluding outliers, greater than 90% of participant data agreed within ±15%. A major contribution to variation of sLL CD4+ cell counts was tube to tube variation of the calibration beads, amounting to an uncertainty of 3.6%. Variation due to preparative steps equated to an uncertainty of 2.6%. There was no reduction in variability when data files were centrally reanalyzed. Remaining variation was attributed to instrument specific differences. CD4+ cell counts obtained in CCQM-P102 are in excellent agreement and show the robustness of both the measurements and the data analysis and hence the suitability of sLL as a reference material for interlaboratory comparisons and external quality assessment.

  5. Quantification of Cells with Specific Phenotypes I: Determination of CD4+ Cell Count Per Microliter in Reconstituted Lyophilized Human PBMC Prelabeled with Anti-CD4 FITC Antibody

    PubMed Central

    Stebbings, Richard; Wang, Lili; Sutherland, Janet; Kammel, Martin; Gaigalas, Adolfas K; John, Manuela; Roemer, Bodo; Kuhne, Maren; Schneider, Rudolf J; Braun, Michael; Engel, Andrea; Dikshit, Dinesh K; Abbasi, Fatima; Marti, Gerald E; Paola Sassi, Maria; Revel, Laura; Kim, Sook-Kyung; Baradez, Marc-Olivier; Lekishvili, Tamara; Marshall, Damian; Whitby, Liam; Jing, Wang; Ost, Volker; Vonsky, Maxim; Neukammer, Jörg

    2015-01-01

    A surface-labeled lyophilized lymphocyte (sLL) preparation has been developed using human peripheral blood mononuclear cells prelabeled with a fluorescein isothiocyanate conjugated anti-CD4 monoclonal antibody. The sLL preparation is intended to be used as a reference material for CD4+ cell counting including the development of higher order reference measurement procedures and has been evaluated in the pilot study CCQM-P102. This study was conducted across 16 laboratories from eight countries to assess the ability of participants to quantify the CD4+ cell count of this reference material and to document cross-laboratory variability plus associated measurement uncertainties. Twelve different flow cytometer platforms were evaluated using a standard protocol that included calibration beads used to obtain quantitative measurements of CD4+ T cell counts. There was good overall cross-platform and counting method agreement with a grand mean of the laboratory calculated means of (301.7 ± 4.9) μL−1 CD4+ cells. Excluding outliers, greater than 90% of participant data agreed within ±15%. A major contribution to variation of sLL CD4+ cell counts was tube to tube variation of the calibration beads, amounting to an uncertainty of 3.6%. Variation due to preparative steps equated to an uncertainty of 2.6%. There was no reduction in variability when data files were centrally reanalyzed. Remaining variation was attributed to instrument specific differences. CD4+ cell counts obtained in CCQM-P102 are in excellent agreement and show the robustness of both the measurements and the data analysis and hence the suitability of sLL as a reference material for interlaboratory comparisons and external quality assessment. © 2015 The Authors. Published by Wiley Periodicals, Inc. PMID:25655255

  6. CD4/CD8 ratio and CD8 counts predict CD4 response in HIV-1-infected drug naive and in patients on cART

    PubMed Central

    Sauter, Rafael; Huang, Ruizhu; Ledergerber, Bruno; Battegay, Manuel; Bernasconi, Enos; Cavassini, Matthias; Furrer, Hansjakob; Hoffmann, Matthias; Rougemont, Mathieu; Günthard, Huldrych F; Held, Leonhard

    2016-01-01

    Abstract Plasma HIV viral load is related to declining CD4 lymphocytes. The extent to which CD8 cells, in addition to RNA viral load, predict the depletion of CD4 cells is not well characterized so far. We examine if CD8 cell count is a prognostic factor for CD4 cell counts during an HIV infection. A longitudinal analysis is conducted using data from the Swiss HIV cohort study collected between January 2000 and October 2014. Linear mixed regression models were applied to observations from HIV-1-infected treatment naive patients (NAIVE) and cART-treated patients to predict the short-term evolution of CD4 cell counts. For each subgroup, it was quantified to which extent CD8 cell counts or CD4/CD8 ratios are prognostic factors for disease progression. In both subgroups, 2500 NAIVE and 8902 cART patients, past CD4 cells are positively (P < 0.0001) and past viral load is negatively (P < 0.0001) associated with the outcome. Including additionally past CD8 cell counts improves the fit significantly (P < 0.0001) and increases the marginal explained variation 31.7% to 40.7% for the NAIVE and from 44.1% to 50.7% for the cART group. The past CD4/CD8 ratio (instead of the past CD8 level) is positively associated with the outcome, increasing the explained variation further to 41.8% for NAIVE and 51.9% for cART. PMID:27759638

  7. Polyfunctional cytokine responses by central memory CD4+T cells in response to bovine tuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    CD4 T cells are crucial in immunity to tuberculosis (TB). Polyfunctional CD4 T cells simultaneously produce interferon-gamma (IFN-gamma), interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) and play relevant roles in several chronic infections, including human TB and HIV. Mycobacterium ...

  8. Polyfunctional cytokine responses by central memory CD4*T cells in response to bovine tuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    CD4 T cells are crucial in immunity to tuberculosis (TB). Polyfunctional CD4 T cells simultaneously produce interferon-gamma (IFN-gamma), interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) and play relevant roles in several chronic infections, including human TB. Mycobacterium bovis in...

  9. Chronic exposure to trichloroethylene increases DNA methylation of the Ifng promoter in CD4(+) T cells.

    PubMed

    Gilbert, Kathleen M; Blossom, Sarah J; Erickson, Stephen W; Broadfoot, Brannon; West, Kirk; Bai, Shasha; Li, Jingyun; Cooney, Craig A

    2016-10-17

    CD4(+) T cells in female MRL+/+ mice exposed to solvent and water pollutant trichloroethylene (TCE) skew toward effector/memory CD4(+) T cells, and demonstrate seemingly non-monotonic alterations in IFN-γ production. In the current study we examined the mechanism for this immunotoxicity using effector/memory and naïve CD4(+) T cells isolated every 6 weeks during a 40 week exposure to TCE (0.5mg/ml in drinking water). A time-dependent effect of TCE exposure on both Ifng gene expression and IFN-γ protein production was observed in effector/memory CD4(+) T cells, with an increase after 22 weeks of exposure and a decrease after 40 weeks of exposure. No such effect of TCE was observed in naïve CD4(+) T cells. A cumulative increase in DNA methylation in the CpG sites of the promoter of the Ifng gene was observed in effector/memory, but not naïve, CD4(+) T cells over time. Also unique to the Ifng promoter was an increase in methylation variance in effector/memory compared to naïve CD4(+) T cells. Taken together, the CpG sites of the Ifng promoter in effector/memory CD4(+) T cells were especially sensitive to the effects of TCE exposure, which may help explain the regulatory effect of the chemical on this gene.

  10. Selective culling of high avidity antigen-specific CD4+ T cells after virulent Salmonella infection.

    PubMed

    Ertelt, James M; Johanns, Tanner M; Mysz, Margaret A; Nanton, Minelva R; Rowe, Jared H; Aguilera, Marijo N; Way, Sing Sing

    2011-12-01

    Typhoid fever is a persistent infection caused by host-adapted Salmonella strains adept at circumventing immune-mediated host defences. Given the importance of T cells in protection, the culling of activated CD4+ T cells after primary infection has been proposed as a potential immune evasion strategy used by this pathogen. We demonstrate that the purging of activated antigen-specific CD4+ T cells after virulent Salmonella infection requires SPI-2 encoded virulence determinants, and is not restricted only to cells with specificity to Salmonella-expressed antigens, but extends to CD4+ T cells primed to expand by co-infection with recombinant Listeria monocytogenes. Unexpectedly, however, the loss of activated CD4+ T cells during Salmonella infection demonstrated using a monoclonal population of adoptively transferred CD4+ T cells was not reproduced among the endogenous repertoire of antigen-specific CD4+ T cells identified with MHC class II tetramer. Analysis of T-cell receptor variable segment usage revealed the selective loss and reciprocal enrichment of defined CD4+ T-cell subsets after Salmonella co-infection that is associated with the purging of antigen-specific cells with the highest intensity of tetramer staining. Hence, virulent Salmonella triggers the selective culling of high avidity activated CD4+ T-cell subsets, which re-shapes the repertoire of antigen-specific T cells that persist later after infection.

  11. The differentiation and protective function of cytolytic CD4 T cells in influenza infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    CD4 T cells that recognize peptide antigen in the context of Class II MHC can differentiate into various subsets that are characterized by their helper functions. However, increasing evidence indicates that CD4 cells with direct cytolytic activity play a role in chronic, as well as, acute infections...

  12. Genetic determinism in the relationship between human CD4+ and CD8+ T lymphocyte populations?

    PubMed

    Ahmadi, K R; Hall, M A; Norman, P; Vaughan, R W; Snieder, H; Spector, T D; Lanchbury, J S

    2001-11-01

    The adaptive immune system in mammals acts in a coordinated manner to eliminate environmentally derived pathogens. Humans, mice and rats show within species variation in the levels and ratios of their peripheral CD4+ and CD8+ T cells and to a significant degree this variation is under the control of polymorphic genes. Whether genes act separately to specify CD4+ and CD8+ subpopulation levels or whether CD8+ variation is controlled through gene and environmental action on CD4+ cells or vice versa, is not known. We use a quantitative modelling approach in identical and non-identical female human twins to delineate the lines of control which act upon and between CD4+ and CD8+ subsets. The major findings of the study are: (1) genetic variation controls CD8+ T cell levels through two major routes-the first is via an effect on CD4+ T cells which accounts for the observed co-variation between CD4+ and CD8+ T cells, the second is through direct action on CD8+ T cell levels. (2) No evidence of a gene effect from CD8+ T cells on CD4+ cells is observed. Our findings have implications for the evolution of the complex defence system of which CD4+ and CD8+ T cells are a crucial part and encourage further work towards locating common pleiotropic quantitative trait loci responsible for variation in numbers of T cells.

  13. Itk Signals Promote Neuroinflammation by Regulating CD4+ T-Cell Activation and Trafficking

    PubMed Central

    Kannan, Arun K.; Kim, Do-Geun

    2015-01-01

    Here we demonstrate that interleukin-2-inducible T-cell kinase (Itk) signaling in cluster of differentiation 4-positive (CD4+) T cells promotes experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). We show that Itk−/− mice exhibit reduced disease severity, and transfer of Itk−/− CD4+ T cells into T cell-deficient recipients results in lower disease severity. We observed a significant reduction of CD4+ T cells in the CNS of Itk−/− mice or recipients of Itk−/− CD4+ T cells during EAE, which is consistent with attenuated disease. Itk−/− CD4+ T cells exhibit defective response to myelin antigen stimulation attributable to displacement of filamentous actin from the CD4+ coreceptor. This results in inadequate transmigration of Itk−/− CD4+ T cells into the CNS and across brain endothelial barriers in vitro. Finally, Itk−/− CD4+ T cells show significant reduction in production of T-helper 1 (Th1) and Th17 cytokines and exhibit skewed T effector/T regulatory cell ratios. These results indicate that signaling by Itk promotes autoimmunity and CNS inflammation, suggesting that it may be a viable target for treatment of MS. PMID:25568116

  14. Human CD4−8− T cells are a distinctive immunoregulatory subset

    PubMed Central

    Huang, Mei-Chuan; Patel, Kalpesh; Taub, Dennis D.; Longo, Dan L.; Goetzl, Edward J.

    2010-01-01

    Human CD4−8− T cells are a minor subset quantitatively but potentially important in immunity because they are predominantly distributed at body surfaces, and their number and activities increase in autoimmune diseases and decrease with aging. Distinguishing characteristics of CD4−8− T cells are found to include a unique profile of cytokines, including Serpin E1, which is not generated by other T cells, MIF, and TGF-β. At 2–5% of the total in mixtures with CD4 + CD8 T cells, CD4−8− T cells enhance the generation of IFN-γ and IL-17 by up to 12- and 5-fold, respectively, without contributing either cytokine or affecting cytokine production by NK/NKT cells. CD4−8− T cell-derived MIF is their major enhancer and TGFβ their principal inhibitor of CD4 and CD8 T cell cytokine production. Decreases in CD4−8− T cell effects may diminish protective immunity in aging, whereas increases may augment the severity of autoimmune diseases.—Huang, M.-C., Patel, K., Taub, D. D., Longo, D. L., Goetzl, E. J. Human CD4−8− T cells are a distinctive immunoregulatory subset. PMID:20154266

  15. Key role for CD4 T cells during mixed antibody mediated rejection of renal allografts

    PubMed Central

    Gaughan, A.; Wang, J.; Pelletier, R.P.; Nadasdy, T.; Brodsky, S.; Roy, S.; Lodder, M.; Bobek, D.; Mofatt-Bruce, S.; Fairchild, R.L.; Henry, M.L.; Hadley, G.A.

    2014-01-01

    We utilized mouse models to elucidate the immunologic mechanisms of functional graft loss during mixed antibody mediated rejection of renal allografts (mixed AMR), in which humoral and cellular responses to the graft occur concomitantly. Although the majority of T cells in the graft at the time of rejection were CD8 T cells with only a minor population of CD4 T cells, depletion of CD4 but not CD8 cells prevented acute graft loss during mixed AMR. CD4 depletion eliminated anti-donor alloantibodies and conferred protection from destruction of renal allografts. ELISPOT revealed that CD4 T effectors responded to donor alloantigens by both the direct and indirect pathways of allorecognition. In transfer studies, CD4 T effectors primed to donor alloantigens were highly effective at promoting acute graft dysfunction, and exhibited the attributes of effector T cells. Laser capture microdissection and confirmatory immunostaining studies revealed that CD4 T cells infiltrating the graft produced effector molecules with graft destructive potential. Bioluminescent imaging confirmed that CD4 T effectors traffic to the graft site in immune replete hosts. These data document that host CD4 T cells can promote acute dysfunction of renal allografts by directly mediating graft injury in addition to facilitating anti-donor alloantibody responses. PMID:24410909

  16. Role of LAP+CD4+ T cells in the tumor microenvironment of colorectal cancer

    PubMed Central

    Zhong, Wu; Jiang, Zhi-Yuan; Zhang, Lei; Huang, Jia-Hao; Wang, Shi-Jun; Liao, Cun; Cai, Bin; Chen, Li-Sheng; Zhang, Sen; Guo, Yun; Cao, Yun-Fei; Gao, Feng

    2017-01-01

    AIM To investigate the abundance and potential functions of LAP+CD4+ T cells in colorectal cancer (CRC). METHODS Proportions of LAP+CD4+ T cells were examined in peripheral blood and tumor/paratumor tissues of CRC patients and healthy controls using flow cytometry. Expression of phenotypic markers such as forkhead box (Fox)p3, cytotoxic T-lymphocyte-associated protein (CTLA)-4, chemokine CC receptor (CCR)4 and CCR5 was measured using flow cytometry. LAP-CD4+ and LAP+CD4+ T cells were isolated using a magnetic cell-sorting system and cell purity was analyzed by flow cytometry. Real-time quantitative polymerase chain reaction was used to measure expression of cytokines interleukin (IL)-10 and transforming growth factor (TGF)-β. RESULTS The proportion of LAP+CD4+ T cells was significantly higher in peripheral blood from patients (9.44% ± 3.18%) than healthy controls (1.49% ± 1.00%, P < 0.001). Among patients, the proportion of LAP+CD4+ T cells was significantly higher in tumor tissues (11.76% ± 3.74%) compared with paratumor tissues (3.87% ± 1.64%, P < 0.001). We also observed positive correlations between the proportion of LAP+CD4+ T cells and TNM stage (P < 0.001), distant metastasis (P < 0.001) and serum level of carcinoembryonic antigen (P < 0.05). Magnetic-activated cell sorting gave an overall enrichment of LAP+CD4+ T cells (95.02% ± 2.87%), which was similar for LAP-CD4+ T cells (94.75% ± 2.76%). In contrast to LAP-CD4+ T cells, LAP+CD4+ T cells showed lower Foxp3 expression but significantly higher levels of CTLA-4, CCR4 and CCR5 (P < 0.01). LAP+CD4+ T cells expressed significantly larger amounts of IL-10 and TGF-β but lower levels of IL-2, IL-4, IL-17 and interferon-γ, compared with LAP-CD4+ T cells. CONCLUSION LAP+CD4+ T cells accumulated in the tumor microenvironment of CRC patients and were involved in immune evasion mediated by IL-10 and TGF-β. PMID:28210081

  17. Intimate Partner Violence Against HIV-Positive Women is Associated with Sub-Optimal Infant Feeding Practices in Lusaka, Zambia.

    PubMed

    Hampanda, Karen

    2016-12-01

    Objectives The aim of this study is to determine how intimate partner violence against HIV-positive women affects safe infant feeding practices in Lusaka, Zambia. Methods A cross-sectional face-to-face survey was conducted with 320 married postpartum women at a large public health center in Lusaka, Zambia, in 2014. Variables were measured using previously validated instruments from the Demographic and Health Survey. Data were analyzed using simple and multivariate logistic regression in Stata 12. Results Thirty-seven percent of women report early mixed infant feeding prior to six months. Women who experienced intimate partner violence have 2.8 higher adjusted odds of early mixed infant feeding (p < 0.001). Women who experienced emotional violence, specifically, have 1.9 higher adjusted odds of early mixed infant feeding (p < 0.05), while women who experienced sexual violence have 2.3 higher adjusted odds (p < 0.01). There is also a dose-response relationship between IPV and early mixed infant feeding (p < 0.05). Lastly, disclosing one's HIV-positive status to the husband is associated with at least 67 % lower adjusted odds of early mixed feeding (p < 0.05). Conclusions Intimate partner violence against HIV-positive women, in particular emotional and sexual violence, increases the likelihood of early mixed infant feeding, putting infants at greater risk for both mother-to-child transmission of HIV and other infant morbidities. Intimate partner violence should thus be given increased attention within the context of infant feeding and HIV in sub-Saharan Africa.

  18. HIV-1 Vpu targets cell surface markers CD4 and BST-2 through distinct mechanisms

    PubMed Central

    Andrew, Amy; Strebel, Klaus

    2010-01-01

    Vpu is a small integral membrane protein encoded by HIV-1 and some SIV isolates. The protein is known to induce degradation of the viral receptor molecule CD4 and to enhance the release of newly formed virions from the cell surface. Vpu accomplishes these two functions through two distinct mechanisms. In the case of CD4, Vpu acts as a molecular adaptor to connect CD4 to an E3 ubiquitin ligase complex resulting in CD4 degradation by cellular proteasomes. This requires signals located in Vpu's cytoplasmic domain. Enhancement of virus release on the other hand involves the neutralization of a cellular host factor, BST-2 (also known as CD317, HM1.24, or tetherin) and requires Vpu's TM domain. The current review discusses recent advances on the role of Vpu in controlling degradation of CD4 and in regulating virus release. PMID:20858517

  19. Emerging technologies for point-of-care CD4 T-lymphocyte counting

    PubMed Central

    Boyle, David S.; Hawkins, Kenneth R.; Steele, Matthew S.; Singhal, Mitra; Cheng, Xuanhong

    2012-01-01

    A CD4 T-lymphocyte count determines eligibility for antiretroviral therapy (ART) with patients recently diagnosed with HIV and also monitors the efficacy of ART treatment thereafter. ART slows the progression of HIV to AIDS. In the developing world, CD4 tests are often performed in centralized laboratories, typically in urban areas. The expansion of ART programs into rural areas has created a need for rapid CD4 counting as logistical barriers can delay the timely dissemination of test results and affect patient care through delay in intervention or loss of follow-up care. CD4 measurement at the point-of-care (POC) in rural areas could help facilitating ART and monitoring of treatment. This review highlights recent technology developments with applications towards determining CD4 counts at the POC. PMID:21798607

  20. Immunogold detection of CD3 and CD4 antigens in patients with Mycosis fungoides.

    PubMed

    Grzanka, A A; Placek, W; Grzanka, A

    2006-01-01

    In this study, we analyzed the distribution of CD3 and CD4 antigens at the ultrastructural level in tissue samples from mycosis fungoides patients using double-immunogold labeling. We observed clusters composed of CD3 and CD4 antigens on the plasma membrane and intracellular. There were also clusters only of one type of the antigen and we could observe more often CD4 than CD3. Labeling of CD3 and CD4 was not found in control cells incubated with non-immune serum. In conclusion, our ultrastructural studies not only visualized pattern distribution and relationship between CD3 and CD4 antigens but might also suggest that the type and form of distribution provides new clues to their possible translocation in mycosis fungoides cells.

  1. Tissue adaptation of regulatory and intraepithelial CD4+ T cells controls gut inflammation

    PubMed Central

    Sujino, Tomohisa; London, Mariya; Hoytema van Konijnenburg, David P.; Rendon, Tomiko; Buch, Thorsten; Silva, Hernandez M.; Lafaille, Juan J.; Reis, Bernardo S.; Mucida, Daniel

    2016-01-01

    Foxp3+ regulatory T cells in peripheral tissues (pTregs) are instrumental in limiting inflammatory responses to non-self antigens. Within the intestine, pTregs are located primarily in the lamina propria, while intraepithelial CD4+ T cells (CD4IELs), which also exhibit anti-inflammatory properties and depend on similar environmental cues, reside in the epithelium. Using intravital microscopy, we show distinct cell dynamics of intestinal Tregs and CD4IELs. Upon migration to the epithelium, Tregs lose Foxp3 and convert to CD4IELs in a microbiota-dependent fashion, an effect attributed to the loss of the transcription factor ThPOK. Finally, we demonstrate that pTregs and CD4IELs perform complementary roles in the regulation of intestinal inflammation. These results reveal intra-tissue specialization of anti-inflammatory T cells shaped by discrete niches of the intestine. PMID:27256884

  2. The risks and benefits of infant feeding practices for women and their children.

    PubMed

    Stuebe, A M; Schwarz, E B

    2010-03-01

    Infant feeding decisions affect maternal and child health outcomes, worldwide. Even in settings with clean water and good sanitation, infants who are not breast-fed face an increased risk of infectious, as well as non-infectious morbidity and mortality. The decision not to breast-feed can also adversely affect mothers' health by increasing the risk of pre-menopausal breast cancer, ovarian cancer, type II diabetes, hypertension, hyperlipidemia and cardiovascular disease. Clinicians who counsel mothers about the health impact of infant feeding and provide evidence-based care to maximize successful breast-feeding, can improve the short and long-term health of both mothers and infants.

  3. Consumption of highly processed snacks, sugar-sweetened beverages and child feeding practices in a rural area of Nicaragua.

    PubMed

    Contreras, Mariela; Zelaya Blandón, Elmer; Persson, Lars-Åke; Ekström, Eva-Charlotte

    2016-01-01

    Appropriate feeding behaviours are important for child growth and development. In societies undergoing nutrition transition, new food items are introduced that may be unfavourable for child health. Set in rural Nicaragua, the aim of this study was to describe the infant and young child feeding (IYCF) practices as well as the consumption of highly processed snack foods (HP snacks) and sugar-sweetened beverages (SSBs). All households with at least one child 0- to 35-month-old (n = 1371) were visited to collect information on current IYCF practices in the youngest child as well as consumption of SSBs and HP snacks. Breastfeeding was dominant (98%) among 0- to 1-month-olds and continued to be prevalent (60%) in the second year, while only 34% of the 0- to 5-month-olds were exclusively breastfed. Complementary feeding practices were deemed acceptable for only 59% of the 6- to 11-month-old infants, with low dietary diversity reported for 50% and inadequate meal frequency reported for 30%. Consumption of HP snacks and SSBs was frequent and started early; among 6- to 8-month-olds, 42% and 32% had consumed HP snacks and SSBs, respectively. The difference between the observed IYCF behaviours and World Health Organization recommendations raises concern of increased risk of infections and insufficient intake of micronutrients that may impair linear growth. The concurrent high consumption of SSBs and HP snacks may increase the risk of displacing the recommended feeding behaviours. To promote immediate and long-term health, growth and development, there is a need to both promote recommended IYCF practices as well as discourage unfavourable feeding behaviours.

  4. Low-dose IL-2 selectively activates subsets of CD4+ Tregs and NK cells

    PubMed Central

    Hirakawa, Masahiro; Matos, Tiago; Liu, Hongye; Koreth, John; Kim, Haesook T.; Paul, Nicole E.; Murase, Kazuyuki; Whangbo, Jennifer; Alho, Ana C.; Nikiforow, Sarah; Cutler, Corey; Ho, Vincent T.; Armand, Philippe; Alyea, Edwin P.; Antin, Joseph H.; Blazar, Bruce R.; Lacerda, Joao F.; Soiffer, Robert J.

    2016-01-01

    CD4+ regulatory T cells (CD4Tregs) play a critical role in the maintenance of immune tolerance and prevention of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. IL-2 supports the proliferation and survival of CD4Tregs and previous studies have demonstrated that IL-2 induces selective expansion of CD4Tregs and improves clinical manifestations of chronic GVHD. However, mechanisms for selective activation of CD4Tregs and the effects of low-dose IL-2 on other immune cells are not well understood. Using mass cytometry, we demonstrate that low concentrations of IL-2 selectively induce STAT5 phosphorylation in Helios+ CD4Tregs and CD56brightCD16– NK cells in vitro. Preferential activation and expansion of Helios+ CD4Tregs and CD56brightCD16– NK cells was also demonstrated in patients with chronic GVHD receiving low-dose IL-2. With prolonged IL-2 treatment for 48 weeks, phenotypic changes were also observed in Helios– CD4Tregs. The effects of low-dose IL-2 therapy on conventional CD4+ T cells and CD8+ T cells were limited to increased expression of PD-1 on effector memory T cells. These studies reveal the selective effects of low-dose IL-2 therapy on Helios+ CD4Tregs and CD56bright NK cells that constitutively express high-affinity IL-2 receptors as well as the indirect effects of prolonged exposure to low concentrations of IL-2 in vivo. PMID:27812545

  5. Using CD4 Percentage and Age to Optimize Pediatric Antiretroviral Therapy Initiation

    PubMed Central

    Warshaw, Meredith G.; Miller, William C.; Castro, Hannah; Fiscus, Susan A.; Harper, Lynda M.; Harrison, Linda J.; Klein, Nigel J.; Lewis, Joanna; Melvin, Ann J.; Tudor-Williams, Gareth; McKinney, Ross E.

    2014-01-01

    BACKGROUND: Quantifying pediatric immunologic recovery by highly active antiretroviral therapy (HAART) initiation at different CD4 percentage (CD4%) and age thresholds may inform decisions about timing of treatment initiation. METHODS: HIV-1-infected, HAART-naive children in Europe and the Americas were followed from 2002 through 2009 in PENPACT-1. Data from 162 vertically infected children, with at least World Health Organization “mild” immunosuppression and CD4% <10th percentile, were analyzed for improvement to a normal CD4% (≥10th percentile) within 4 years after HAART initiation. Data from 209 vertically infected children, regardless of immune status, were analyzed for CD4% outcomes at 4 years and viral failure within 4 years. RESULTS: Seventy-two percent of baseline immunosuppressed children recovered to normal within 4 years. Compared with “severe” immunosuppression, more children with “mild” immunosuppression (difference 36%, 95% confidence interval [CI]: 22% to 49%) or “advanced” immunosuppression (difference 20.8%, 95% CI: 5.8% to 35.9%) recovered a normal CD4%. For each 5-year increase in baseline age, the proportion of children achieving a normal CD4% declined by 19% (95% CI: 11% to 27%). Combining baseline CD4% and age effects resulted in >90% recovery when initiating HAART with “mild” immunosuppression at any age or “advanced” immunosuppression at age <3 years. Baseline CD4% effects became greater with increasing age (P = .02). At 4 years, most immunologic benefits were still significant but diminished. Viral failure was highest in infancy (56%) and adolescence (63%). CONCLUSIONS: Initiating HAART at higher CD4% and younger ages maximizes potential for immunologic recovery. Guidelines should weigh immunologic benefits against long-term risks. PMID:25266426

  6. Upregulation of peripheral CD4+CXCR5+ T cells in osteosarcoma.

    PubMed

    Xiao, Hong; Luo, Gang; Son, Haihang; Zhou, Yue; Zheng, Wenjie

    2014-06-01

    Immune dysregulation plays a key role in the development of osteosarcoma (OS). Peripheral blood CD4+CXCR5+ T cells can induce B-cell activation and produce various cytokines and therefore may play critical roles in tumorigenesis. The purpose of the study was to investigate changes of peripheral CD4+CXCR5+ T cells in OS. Peripheral CD4+CXCR5+ T cells and its subtypes were determined by measuring CD3, CD4, CXCR5, CXCR3, and CCR6 in 38 OS patients and 42 healthy controls using flow cytometry. Data demonstrated that percentage of peripheral CD4+CXCR5+ T cells was significantly increased in OS patients (13.9 %) than in controls (8.6 %, p<0.001). Further analysis identified a profound skewing of peripheral CD4+CXCR5+ T cell subsets toward Th2 and Th17 cells in OS patients. Investigating clinical status of the patients showed that prevalence of peripheral CD4+CXCR5+ T cells was significantly elevated in cases with metastasis (17.4 %) than those without metastasis (12.7 %). Similarly, patients with high tumor grade revealed increased percentage of CD4+CXCR5+ T cells compared to those with low tumor grade (15.3 versus 11.0 %). Interestingly, the upregulation of peripheral CD4+CXCR5+ T cells in patients with metastasis or high tumor grade was contributed by Th1 and Th17 subtypes. This study suggests the involvement of peripheral CD4+CXCR5+ T cells in the pathogenesis and progression of OS and provides novel knowledge for understanding this disease.

  7. The Differentiation and Protective Function of Cytolytic CD4 T Cells in Influenza Infection

    PubMed Central

    Brown, Deborah M.; Lampe, Anna T.; Workman, Aspen M.

    2016-01-01

    CD4 T cells that recognize peptide antigen in the context of class II MHC can differentiate into various subsets that are characterized by their helper functions. However, increasing evidence indicates that CD4 cells with direct cytolytic activity (CD4 CTL) play a role in chronic as well as acute infections, such as influenza A virus (IAV) infection. In the last couple of decades, techniques to measure the frequency and activity of these cytolytic cells has demonstrated their abundance in infections, such as human immunodeficiency virus, mouse pox, murine gamma herpes virus, cytomegalovirus, Epstein–Barr virus, and influenza among others. We now appreciate a greater role for CD4 CTL as direct effectors in viral infections and antitumor immunity through their ability to acquire perforin-mediated cytolytic activity and contribution to lysis of virally infected targets or tumors. As early as the 1980s, CD4 T cell clones with cytolytic potential were identified after influenza virus infection, yet much of this early work was dependent on in vitro culture and little was known about the physiological relevance of CD4 CTL. Here, we discuss the direct role CD4 CTL play in protection against lethal IAV infection and the factors that drive the generation of perforin-mediated lytic activity in CD4 cells in vivo during IAV infection. While focusing on CD4 CTL generated during IAV infection, we pull comparisons from the literature in other antiviral and antitumor systems. Further, we highlight what is currently known about CD4 CTL secondary and memory responses, as well as vaccination strategies to induce these potent killer cells that provide an extra layer of cell-mediated immune protection against heterosubtypic IAV infection. PMID:27014272

  8. A novel differentiation pathway from CD4⁺ T cells to CD4⁻ T cells for maintaining immune system homeostasis.

    PubMed

    Zhao, X; Sun, G; Sun, X; Tian, D; Liu, K; Liu, T; Cong, M; Xu, H; Li, X; Shi, W; Tian, Y; Yao, J; Guo, H; Zhang, D

    2016-04-14

    CD4(+) T lymphocytes are key players in the adaptive immune system and can differentiate into a variety of effector and regulatory T cells. Here, we provide evidence that a novel differentiation pathway of CD4(+) T cells shifts the balance from a destructive T-cell response to one that favors regulation in an immune-mediated liver injury model. Peripheral CD4(-)CD8(-)NK1.1(-) double-negative T cells (DNT) was increased following Concanavalin A administration in mice. Adoptive transfer of DNT led to significant protection from hepatocyte necrosis by direct inhibition on the activation of lymphocytes, a process that occurred primarily through the perforin-granzyme B route. These DNT converted from CD4(+) rather than CD8(+) T cells, a process primarily regulated by OX40. DNT migrated to the liver through the CXCR3-CXCL9/CXCL10 interaction. In conclusion, we elucidated a novel differentiation pathway from activated CD4(+) T cells to regulatory DNT cells for maintaining homeostasis of the immune system in vivo, and provided key evidence that utilizing this novel differentiation pathway has potential application in the prevention and treatment of autoimmune diseases.

  9. Electronic structure and properties of Cd4As2Br3 and Cd4Sb2I3, analogues of CdSe and CdTe

    NASA Astrophysics Data System (ADS)

    Roy, Anand; Suchitra; Manjunath, K.; Ahmad, Tokeer; Waghmare, Umesh V.; Rao, C. N. R.

    2017-04-01

    Substitution of aliovalent anions in metal oxides and chalcogenides significantly affects the electronic structure and properties of the materials. Thus, substitution of P3- and Cl- in CdS decreases the band gap and favorably influences the photocatalytic activity. Complete substitution of a trivalent (A3-) and a monovalent (B-) anions in a cadmium chalcogenides, CdX, should give rise to a material of the composition Cd A0.5B0.5 or Cd2AB, but a compound with the composition Cd4P2Cl3 (or Cd2PCl1.5) is obtained in the case of CdS. We have investigated the analogous compounds, Cd4As2Br3 and Cd4Sb2I3, wherein the anions in CdSe and CdTe are substituted by As, Br and Sb, I respectively. These compounds are direct band gap semiconductors with a band gap of 1.8-1.9 eV and a photoluminescence band in the visible region. First-principles calculations show both Cd4As2Br3 and Cd4Sb2I3 to be direct band gap semiconductors. The arsenic bromide is predicted to be photochemically more active for HER than the antimony iodide.

  10. AFM Force measurements of the gp120-sCD4 and gp120 or CD4 antigen-antibody interactions

    PubMed Central

    Chen, Yong; Zeng, Gucheng; Chen, Sherry Shiyi; Feng, Qian; Chen, Zheng Wei

    2011-01-01

    Soluble CD4 (sCD4), anti-CD4 antibody, and anti-gp120 antibody have long been regarded as entry inhibitors in human immunodeficiency virus (HIV) therapy. However, the interactions between these HIV entry inhibitors and corresponding target molecules are still poorly understood. In this study, atomic force microscopy (AFM) was utilized to investigate the interaction forces among them. We found that the unbinding forces of sCD4-gp120 interaction, CD4 antigen-antibody interaction, and gp120 antigen-antibody interaction were 25.45 ± 20.46 pN, 51.22 ± 34.64 pN, and 89.87 ± 44.63 pN, respectively, which may provide important mechanical information for understanding the effects of viral entry inhibitors on HIV infection. Moreover, we found that the functionalization of an interaction pair on AFM tip or substrate significantly influenced the results, implying that we must perform AFM force measurement and analyze the data with more caution. PMID:21382342

  11. The CD4+ T cell methylome contributes to a distinct CD4+ T cell transcriptional signature in Mycobacterium bovis-infected cattle

    PubMed Central

    Doherty, Rachael; Whiston, Ronan; Cormican, Paul; Finlay, Emma K.; Couldrey, Christine; Brady, Colm; O’Farrelly, Cliona; Meade, Kieran G.

    2016-01-01

    We hypothesised that epigenetic regulation of CD4+ T lymphocytes contributes to a shift toward a dysfunctional T cell phenotype which may impact on their ability to clear mycobacterial infection. Combined RNA-seq transcriptomic profiling and Reduced Representation Bisulfite Sequencing identified 193 significantly differentially expressed genes and 760 differentially methylated regions (DMRs), between CD4+ T cells from M. bovis infected and healthy cattle. 196 DMRs were located within 10 kb of annotated genes, including GATA3 and RORC, both of which encode transcription factors that promote TH2 and TH17 T helper cell subsets respectively. Gene-specific DNA methylation and gene expression levels for the TNFRSF4 and Interferon-γ genes were significantly negatively correlated suggesting a regulatory relationship. Pathway analysis of DMRs identified enrichment of genes involved in the anti-proliferative TGF-β signaling pathway and TGFB1 expression was significantly increased in peripheral blood leukocytes from TB-infected cattle. This first analysis of the bovine CD4+ T cell methylome suggests that DNA methylation directly contributes to a distinct gene expression signature in CD4+ T cells from cattle infected with M. bovis. Specific methylation changes proximal to key inflammatory gene loci may be critical to the emergence of a non-protective CD4+ T cell response during mycobacterial infection in cattle. PMID:27507428

  12. Exploratory assessment of CD4+ T lymphocytes in brown hares (Lepus europeus) using a cross-reactive anti-rabbit CD4 antibody.

    PubMed

    Rütgen, Barbara C; Gerner, Wilhelm; Beiglböck, Christoph; Schaschl, Helmut; Saalmüller, Armin; Suchentrunk, Franz; Essler, Sabine E

    2014-09-15

    In lagomorphs, lymphocyte subset distributions and the importance of CD4(+) T cell levels has so far only been considered in the frame of rabbit disease models. In this study, the first assessment of CD4(+) T lymphocytes in peripheral blood cells in brown hares (Lepus europaeus L., 1758), a further leporid species using a cross-reactive rabbit anti-CD4 antibody in flow cytometry, is presented. In addition, the entire coding region of the hare CD4 gene (1380 bp) coding for a polypeptide of 459 amino acids has been sequenced. Using generalized least squares fitting by maximum likelihood (GLS) test, significantly (p=0.0095) higher CD4(+) T cell frequencies in males than in females and significantly (p=0.0001) higher frequencies for leverets (younger than 2 months of age) than for subadult and adult (older than 7 months of age) individuals were detected. No significant age influence, however, was found for subadult and adult hares. The study is particularly meant to provide a first step in establishing a toolbox for the assessment of the immune response in this leporid species.

  13. Maternal obesity and breast-feeding practices among white and black women.

    PubMed

    Liu, Jihong; Smith, Michael G; Dobre, Mirela A; Ferguson, James E

    2010-01-01

    Despite the increase in obesity among women of reproductive ages, few studies have considered maternal obesity as a risk factor for breast-feeding success. We tested the hypothesis that women who are obese (BMI = 30-34.9) and very obese (BMI >or=35) before pregnancy are less likely to initiate and maintain breast-feeding than are their normal-weight counterparts (BMI = 18.5-24.9) among white and black women. Data from 2000 to 2005 South Carolina Pregnancy Risk Assessment Monitoring System (PRAMS) were used. The overall response rate was 71.0%; there were 3,517 white and 2,846 black respondents. Black women were less likely to initiate breast-feeding and breast-fed their babies for a shorter duration than white women. Compared to normal-weight white women, very obese white women were less likely to initiate breast-feeding (odds ratio: 0.63; 95% confidence interval (CI) = 0.42, 0.94) and more likely to discontinue breast-feeding within the first 6 months (hazard ratio (HR) = 1.89; 95% CI: 1.39, 2.58). Among black women, prepregnancy BMI was neither associated with breast-feeding initiation nor with breast-feeding continuation within the first 6 months. Because very obese white women are less likely to initiate or continue breast-feeding than other white women, health professionals should be aware that very obese white women need additional breast-feeding support. Lower rates of breast-feeding among black women suggest that they should continue to be the focus of the programs and policies aimed at breast-feeding promotion in the United States.

  14. Feeding Practices of Mothers from Varied Income and Racial/Ethnic Groups

    ERIC Educational Resources Information Center

    Worobey, John; Borrelli, Amanda; Espinosa, Carolina; Worobey, Harriet S.

    2013-01-01

    Objective: Relatively few investigators have explored the role of maternal control in describing the feeding behaviour of nonwhite parents of preschool-age children. The present study was conducted to examine if controlling feeding behaviours (i.e. restriction and pressuring) varied by income (middle vs. low) and race/ethnicity (white vs.…

  15. Feeding practices and early childhood caries: a cross-sectional study of preschool children in kanpur district, India.

    PubMed

    Prakasha Shrutha, Santhebachalli; Vinit, Grandim Balarama Gupta; Giri, Kolli Yada; Alam, Sarwar

    2013-01-01

    Background. Early childhood caries (ECC) is a public health problem due to its impact on children's health, development, and wellbeing. The objective of this study was to assess the caries experience in 3-5-year-old children and to evaluate the relationship with their mothers' practices regarding feeding and oral hygiene habits in Kanpur. Method. A cross-sectional survey was undertaken on 2000 (974 boys and 1026 girls) children aged 3-5 years from a random sample of preschools in Kanpur district, India. Dental caries experience was recorded using WHO criteria. A pretested questionnaire with 9 questions was used for collecting information regarding mothers' practices regarding feeding and oral hygiene practices. Chi-square test (χ (2)) and Student's t-test were used for statistical analysis. Results. The prevalence of ECC was 48% with mean dmft of 2.03 ± 2.99. Boys (57%) were affected more than girls (43%) which was found to be statistically significant (P < 0.05). Caries prevalence was high and statistically significant (P < 0.05) among those who were breast fed for longer duration, during nighttime, those falling asleep with bottle, and those fed with additional sugar in milk. Conclusion. Determining the role of feeding practices on early childhood caries can help in the development of appropriate oral health promotion strategies.

  16. Laboratory control values for CD4 and CD8 T lymphocytes. Implications for HIV-1 diagnosis.

    PubMed Central

    Bofill, M; Janossy, G; Lee, C A; MacDonald-Burns, D; Phillips, A N; Sabin, C; Timms, A; Johnson, M A; Kernoff, P B

    1992-01-01

    With the advent of standard flow cytometric methods using two-colour fluorescence on samples of whole blood, it is possible to establish the ranges of CD3, CD4 and CD8 T lymphocyte subsets in the routine laboratory, and also to assist the definition of HIV-1-related deviations from these normal values. In 676 HIV-1-seronegative individuals the lymphocyte subset percentages and absolute counts were determined. The samples taken mostly in the morning. The groups included heterosexual controls, people with various clotting disorders but without lymphocyte abnormalities as well as seronegative homosexual men as the appropriate controls for the HIV-1-infected groups. The stability of CD4% and CD8% values was demonstrated throughout life, and in children CD4 values less than 25% could be regarded as abnormal. The absolute counts of all T cell subsets decreased from birth until the age of 10 years. In adolescents and adults the absolute numbers (mean +/- s.d.) of lymphocytes, CD3, CD4 and CD8 cells were 1.90 +/- 0.55, 1.45 +/- 0.46, 0.83 +/- 0.29 and 0.56 +/- 0.23 x 10(9)/l, respectively. In patients with haemophilia A and B the mean values did not differ significantly. In homosexual men higher CD8 levels were seen compared with heterosexual men and 27% had an inverted CD4/CD8 ratio but mostly without CD4 lymphopenia (CD4 less than 0.4 x 10(9)/l). However, some healthy uninfected people were 'physiologically' lymphopenic without having inverted CD4/CD8 ratios. When the variations 'within persons' were studied longitudinally over a 5-year period, the absolute CD4 counts tended to be fixed at different levels. As a marked contrast, over 60% of asymptomatic HIV-1+ patients exhibited low CD4 counts less than 0.4 x 10(9)/l together with inverted CD4/CD8 ratios. Such combined changes among the heterosexual and HIV-1-seronegative homosexual groups were as rare as 1.4% and 3%, respectively. For this reason, when the lymphocyte tests show less than 0.4 x 10(9)/l CD4 count and a CD

  17. Predictors of head start and child-care providers' healthful and controlling feeding practices with children aged 2 to 5 years.

    PubMed

    Dev, Dipti A; McBride, Brent A; Speirs, Katherine E; Donovan, Sharon M; Cho, Hyun Keun

    2014-09-01

    Few child-care providers meet the national recommendations for healthful feeding practices. Effective strategies are needed to address this disparity, but research examining influences on child-care providers' feeding practices is limited. The purpose of this study was to identify determinants of child-care providers' healthful and controlling feeding practices for children aged 2 to 5 years. In this cross-sectional study, child-care providers (n=118) from 24 center-based programs (six Head Start [HS], 11 Child and Adult Care Food Program [CACFP] funded, and seven non-CACFP) completed self-administered surveys during 2011-2012. Multilevel multivariate linear regression models were used to predict seven feeding practices. Working in an HS center predicted teaching children about nutrition and modeling healthy eating; that may be attributed to the HS performance standards that require HS providers to practice healthful feeding. Providers who reported being concerned about children's weight, being responsible for feeding children, and had an authoritarian feeding style were more likely to pressure children to eat, restrict intake, and control food intake to decrease or maintain children's weight. Providers with nonwhite race, who were trying to lose weight, who perceived nutrition as important in their own diet, and who had a greater number of nutrition training opportunities were more likely to use restrictive feeding practices. These findings suggest that individual- and child-care-level factors, particularly provider race, education, training, feeding attitudes and styles, and the child-care context may influence providers' feeding practices with young children. Considering these factors when developing interventions for providers to meet feeding practice recommendations may add to the efficacy of childhood obesity prevention programs.

  18. Blockade of Human Immunodeficiency Virus Type 1 Production in CD4^+ T Cells by an Intracellular CD4 Expressed Under Control of the Viral Long Terminal Repeat

    NASA Astrophysics Data System (ADS)

    Buonocore, Linda; Rose, John K.

    1993-04-01

    A retroviral vector was constructed in which a gene encoding a mutated soluble CD4 protein that is retained in the endoplasmic reticulum (sCD4-KDEL) is expressed under control of human immunodeficiency virus type 1 (HIV-1) regulatory elements. HIV-1 infection of a human T-cell line transduced with this vector led to induction of sCD4-KDEL synthesis and a block in transport of the HIV envelope protein to the cell surface. There was a complete block to maturation of infectious HIV-1 in the transduced cells, no viral spread, and little or no syncytium formation. Infected cells gradually disappeared from the culture over a period of 2 months. This intracellular trap for HIV has potential application in gene therapy for AIDS.

  19. [Effects of infant feeding practice on eczema during early childhood in Shanghai, Hohhot, and Fuzhou].

    PubMed

    Zheng, X Q; Zhu, G W; Zheng, Z Q; Yang, Y; Gong, C D; Deng, S S; Wu, Q L; Peng, Y M

    2016-12-02

    Objective: To estimate the prevalence of eczema in early childhood and effect of infant feeding practice on eczema by different regions of China with diverse climate and dietary patterns. Method: A questionnaire survey was conducted from June 2012 to October 2012 in Shanghai, Hohhot, and Fuzhou. The parent or guardian of the children aged between 2.5 to 3.5 years attending routine health visit in the chosen communities were invited to complete a modified questionnaire of the International Study of Asthma and Allergy in Childhood (ISAAC). Logistic regression model was used to analyze of the family history of allergy, duration of breastfeeding, timing of introduction of complementary foods and other potential confounders. Result: A total of 2 242 children were interviewed, 750 from Shanghai, 716 from Hohhot, and 776 from Fuzhou. The prevalence of eczema in early childhood was significantly different among Shanghai (16.9%, 95%CI 16.87-16.93), Hohhot (34.5%, 95%CI 34.46-34.54)and Fuzhou (44.3%, 95%CI 44.26-44.34). The difference was statistically significant between 3 groups (χ(2)=72.05, P<0.05). Introducing complementary food after the age of 6 months was associated with a decreased risk for eczema when compared to introduction between 4 to 6 months(odds ratio (OR) 0.58, 95%CI 0.41-0.81) in Fuzhou, while there was no significant association between timing of introduction of complementary foods and eczema in Shanghai and Hohhot. Conclusion: The prevalence of eczema during early childhood is various among three cities. The relationship between timing of introduction of complementary foods and eczema in Fuzhou is different from that in Shanghai and Hohhot. The role of climate and dietary patterns on prevalence of eczema needs further studies.

  20. Anaemia in infancy in rural Bangladesh: contribution of iron deficiency, infections and poor feeding practices.

    PubMed

    Rawat, Rahul; Saha, Kuntal Kumar; Kennedy, Andrew; Rohner, Fabian; Ruel, Marie; Menon, Purnima

    2014-01-14

    Few data exist on the aetiology of anaemia and Fe deficiency (ID) during early infancy in South Asia. The present study aimed to determine the contribution of ID, infections and feeding practices to anaemia in Bangladeshi infants aged 6-11 months. Baseline data from 1600 infants recruited into a cluster-randomised trial testing the effectiveness of micronutrient powder sales by frontline health workers on the prevalence of anaemia were used. Multivariate logistic regression was used to identify risk factors for anaemia and ID, and population attributable fractions (PAF) were computed to estimate the proportion of anaemia that might be prevented by the elimination of individual risk factors. It was found that 68 % of the infants were anaemic, 56 % were Fe deficient, and one-third had evidence of subclinical infections. The prevalence of anaemia and ID increased rapidly, until 8-9 months of age, while that of subclinical infections was constant. ID (adjusted OR (AOR) 2·6-5·0; P< 0·001) and subclinical infections (AOR 1·4-1·5; P< 0·01) were major risk factors for anaemia, in addition to age and male sex. Similarly, subclinical infections, age and male sex were significant risk factors for ID. Previous-day consumption of Fe-rich foods was very low and not associated with anaemia or ID. The PAF of anaemia attributable to ID was 67 % (95 % CI 62, 71) and that of subclinical infections was 16 % (95 % CI 11, 20). These results suggest that a multipronged strategy that combines improvements in dietary Fe intake alongside infection control strategies is needed to prevent anaemia during infancy in Bangladesh.

  1. Faecal eosinophil cationic protein and serum immunoglobulin E in relation to infant feeding practices.

    PubMed

    Hua, Man-Chin; Chen, Chien-Chang; Liao, Sui-Ling; Yao, Tsung-Chieh; Tsai, Ming-Han; Lai, Shen-Hao; Chiu, Chih-Yung; Yeh, Kuo-Wei; Huang, Jing-Long

    2017-03-01

    Background To date, the effects of exclusive breastfeeding duration and timing of solid food introduction on allergy prevention are unclear. The aim of this study was to determine the effect of variable feeding practices on intestinal inflammation in infants using faecal eosinophil cationic protein as a surrogate marker and to assess whether faecal eosinophil cationic protein is associated with serum immunoglobulin E. Methods Subjects ( n = 206) were enrolled from the Prediction of Allergies in Taiwanese CHildren (PATCH) birth cohort study. Stool samples were collected at 6 and 12 months for determining eosinophil cationic protein, and blood was collected for determining total and allergen-specific immunoglobulin E at 12 months. We compared these biomarkers between infants with variable exclusive breastfeeding duration and infants introduced to solid foods at various periods. The association between faecal eosinophil cationic protein, total serum immunoglobulin E and specific immunoglobulin E was also analysed. Results Faecal eosinophil cationic protein was significantly higher in exclusively breastfed infants compared with formula-fed infants and infants who were not exclusively breastfed at 6 months of age ( P < 0.05). At 12 months, infants who were introduced to solid foods at 5-6 months had the lowest faecal eosinophil cationic protein compared with those who were introduced at earlier and later periods. There was no significant association between faecal eosinophil cationic protein and serum immunoglobulin E. Conclusion We found that breastfeeding exclusively for >6 months did not reduce serum immunoglobulin E, but rather increased intestinal inflammation. Faecal eosinophil cationic protein was not associated with total serum immunoglobulin E and specific immunoglobulin E and might not be a useful indictor of immunoglobulin E sensitization in infancy.

  2. Carbon footprint and land requirement for dairy herd rations: impacts of feed production practices and regional climate variations.

    PubMed

    Henriksson, M; Cederberg, C; Swensson, C

    2014-08-01

    Feed production is a significant source of greenhouse gas (GHG) emissions from dairy production and demands large arable and pasture acreage. This study analysed how regional conditions influence GHG emissions of dairy feed rations in a life cycle perspective, that is the carbon footprint (CF) and the land area required. Factors assessed included regional climate variations, grass/clover silage nutrient quality, feedstuff availability, crop yield and feed losses. Using the Nordic feed evaluation model NorFor, rations were optimised for different phases of lactation, dry and growing periods for older cows, first calvers and heifers by regional feed advisors and combined to annual herd rations. Feed production data at farm level were based on national statistics and studies. CF estimates followed standards for life cycle assessment and used emissions factors provided by IPCC. The functional unit was 'feed consumption to produce 1 kg energy corrected milk (ECM) from a cow with annual milk yield of 9 900 kg ECM including replacement animals and feed losses'. Feed ration CF varied from 417 to 531 g CO2 e/kg ECM. Grass/clover silage contributed more than 50% of total GHG emissions. Use of higher quality silage increased ration CF by up to 5% as a result of an additional cut and increased rates of synthetic N-fertiliser. Domestically produced horse bean (Vicia faba), by-products from the sugar industry and maize silage were included in the rations with the lowest CF, but horse bean significantly increased ration land requirement. Rations required between 1.4 to 2 m2 cropland and 0.1 to 0.2 m2/kg semi-natural grassland per kg ECM and year. Higher yield levels reduced ration total CF. Inclusion of GHG emissions from land use change associated with Brazilian soya feed significantly increased ration CF. Ration CF and land use depended on ration composition, which was highly influenced by the regional availability and production of feedstuffs. The impact of individual

  3. CD4+ T cell–independent DNA vaccination against opportunistic infections

    PubMed Central

    Zheng, Mingquan; Ramsay, Alistair J.; Robichaux, Myles B.; Norris, Karen A.; Kliment, Corrine; Crowe, Christopher; Rapaka, Rekha R.; Steele, Chad; McAllister, Florencia; Shellito, Judd E.; Marrero, Luis; Schwarzenberger, Paul; Zhong, Qiu; Kolls, Jay K.

    2005-01-01

    Depletion or dysfunction of CD4+ T lymphocytes profoundly perturbs host defenses and impairs immunogenicity of vaccines. Here, we show that plasmid DNA vaccination with a cassette encoding antigen (OVA) and a second cassette encoding full-length CD40 ligand (CD40L), a molecule expressed on activated CD4+ T lymphocytes and critical for T cell helper function, can elicit significant titers of antigen-specific immunoglobulins in serum and Tc1 CD8+ T cell responses in CD4-deficient mice. To investigate whether this approach leads to CD4+ T cell–independent vaccine protection against a prototypic AIDS-defining infection, Pneumocystis (PC) pneumonia, we used serum from mice vaccinated with PC-pulsed, CD40L-modifed DCs to immunoprecipitate PC antigens. Kexin, a PC antigen identified by this approach, was used in a similar DNA vaccine strategy with or without CD40L. CD4-deficient mice receiving DNA vaccines encoding Kexin and CD40L showed significantly higher anti-PC IgG titers as well as opsonic killing of PC compared with those vaccinated with Kexin alone. Moreover, CD4-depleted, Kexin-vaccinated mice showed a 3-log greater protection in a PC challenge model. Adoptive transfer of CD19+ cells or IgG to SCID mice conferred protection against PC challenge, indicating a role of humoral immunity in the protection. The results of these studies show promise for CD4-independent vaccination against HIV-related or other opportunistic pathogens. PMID:16308571

  4. In situ depletion of CD4+ T cells in human skin by Zanolimumab.

    PubMed

    Villadsen, L S; Skov, L; Dam, T N; Dagnaes-Hansen, F; Rygaard, J; Schuurman, J; Parren, P W H I; van de Winkel, J G J; Baadsgaard, O

    2007-02-01

    CD4(+) T cells, in activated or malignant form, are involved in a number of diseases including inflammatory skin diseases such as psoriasis, and T cell lymphomas such as the majority of cutaneous T cell lymphomas (CTCL). Targeting CD4 with an antibody that inhibits and/or eliminates disease-driving T cells in situ may therefore be a useful approach in the treatment of inflammatory and malignant skin diseases. Depletion of CD4(+) T cells in intact inflamed human skin tissue by Zanolimumab, a fully human therapeutic monoclonal antibody (IgG1, kappa) against CD4, was studied in a human psoriasis xenograft mouse model. Zanolimumab treatment was shown to induce a significant reduction in the numbers of inflammatory mononuclear cells in upper dermis. This reduction in inflammatory mononuclear cells in situ was primarily due to a significant reduction in the numbers of skin-infiltrating CD4(+), but not CD8(+) CD3(+) T cells. The capacity of Zanolimumab to deplete the CD4(+) T cells in the skin may be of importance in diseases where CD4(+) T cells play a central role. Indeed, in a phase II clinical trial Zanolimumab has shown a dose-dependent clinical response in patients with CTCL and the antibody is currently in a phase III clinical trial for CTCL, a disease for which there is no safe and effective treatment available today.

  5. Human CD4- 8- T cells are a distinctive immunoregulatory subset.

    PubMed

    Huang, Mei-Chuan; Patel, Kalpesh; Taub, Dennis D; Longo, Dan L; Goetzl, Edward J

    2010-07-01

    Human CD4(-)8(-) T cells are a minor subset quantitatively but potentially important in immunity because they are predominantly distributed at body surfaces, and their number and activities increase in autoimmune diseases and decrease with aging. Distinguishing characteristics of CD4(-)8(-) T cells are found to include a unique profile of cytokines, including Serpin E1, which is not generated by other T cells, MIF, and TGF-beta. At 2-5% of the total in mixtures with CD4 + CD8 T cells, CD4(-)8(-) T cells enhance the generation of IFN-gamma and IL-17 by up to 12- and 5-fold, respectively, without contributing either cytokine or affecting cytokine production by NK/NKT cells. CD4(-)8(-) T cell-derived MIF is their major enhancer and TGFbeta their principal inhibitor of CD4 and CD8 T cell cytokine production. Decreases in CD4(-)8(-) T cell effects may diminish protective immunity in aging, whereas increases may augment the severity of autoimmune diseases.

  6. Characterization of a promoter within the first intron of the human CD4 gene.

    PubMed

    Rushton, J J; Zorich, G P; Stolc, V; Neudorf, S M

    1997-05-01

    The CD4 molecule is subject to complex regulation during T cell differentiation and activation. The elements regulating CD4 gene expression have only partially been defined. In this report, we identified a promoter element located in the first intron of the CD4 gene. This promoter preferentially functions in T cell lines and is preferentially active in CD4+, CD8+ cells. These findings are similar to other systems in which multiple promoters define tissue- and developmental-specific patterns of expression. Through a series of deletions, electrophoretic mobility shift assays and exonuclease III protection assays, we localized the basal promoter element to a 32-bp fragment. This element lacks potential binding domains for myb and ets, both of which have previously been shown to be involved in the function of the 5' murine and human CD4 promoter, and this suggests the presence of a novel, T-cell-specific transcription factor. These results also suggest that the CD4 expression requires the use of multiple regulatory elements located throughout the CD4 gene.

  7. Frequency of CD4+CD161+ T Cell and Interleukin-10 Expression in Inflammatory Bowel Diseases

    PubMed Central

    Tsuchiya, Kazuyo; Ikeda, Takuto; Batmunkh, Baatarsuren; Choijookhuu, Narantsog; Ishizaki, Hidenobu; Hotokezaka, Masayuki; Hishikawa, Yoshitaka; Nanashima, Atsushi

    2017-01-01

    Mucosal immune dysregulation associated with T cells plays a critical role in the development of inflammatory bowel diseases (IBD). However, the definite significances of these cells in IBD still remain unclear. Therefore, we investigated the population and expression of CD4+CD161+ T cells in the colonic lamina propria mononuclear cells (LPMCs) in patients with IBD by analyses using flow cytometry and immunohistochemistry. Interleukin-10 (IL-10) mRNA levels in both LPMCs and CD4+ T cells in lamina propria (LP-CD4+ T cells) were measured using a real-time quantitative reverse transcription-polymerase chain reaction. IL-10 production was investigated with immunohistochemistry. The results revealed that the population of CD4+CD161+ T cells was significantly decreased in active ulcerative colitis (UC) compared with inactive UC (P < 0.05). The CD4+CD161+ T cell population was inversely correlated with disease activity in patients with UC (r = −0.6326, P = 0.0055), but there was no significant correlation in those with Crohn’s disease. Over-expression of IL-10 mRNA in both LPMCs and LP-CD4+ T cells were detected in active UC. Immunohistochemistry revealed decreased frequency of CD161+ cells and increased IL-10 positive cells in active UC. The frequency of CD4+CD161+ T cells and IL-10 expression was supposed to be associated with the pathological status of mucosal immunoregulation in IBD. PMID:28386147

  8. Interleukin-37 Enhances the Suppressive Activity of Naturally Occurring CD4+CD25+ Regulatory T Cells

    PubMed Central

    Wang, Da-Wei; Dong, Ning; Wu, Yao; Zhu, Xiao-Mei; Wang, Chun-Ting; Yao, Yong-Ming

    2016-01-01

    Naturally occurring CD4+CD25+ regulatory T cells (Tregs) are essential for the suppression of autoimmunity and can control the immune-mediated pathology during the early phase of sepsis. Our previous data showed that silencing interleukin-37 (IL-37) in human CD4+CD25+ Tregs obviously reduced the suppressive activity of CD4+CD25+ Tregs. Here, we found that rhIL-37 stimulation markedly enhanced the suppressive activity of CD4+CD25+ Tregs isolated from naive C57BL/6 J mice in the absence or presence of lipopolysaccharide (LPS). Treatment with rhIL-37 could significantly upregulate the expression of cytotoxic T-lymphocyte-associated antigen (CTLA)-4 and forkhead/winged helix transcription factor p3 (Foxp3) on CD4+CD25+ Tregs. Also, rhIL-37 stimulation promoted the production of transforming growth factor-β1 (TGF-β1) but not IL-10 in the supernatants of cultured CD4+CD25+ Tregs. Pretreated CD4+CD25+ Tregs with rhIL-37 in the presence or absence of LPS were cocultured with CD4+CD25− T cells, ratio of IL-4/interferon-γ in the supernatants obviously increased in IL-37-stimulated groups. In addition, early administration of IL-37 significantly improved the survival rate of septic mice induced by cecal ligation and puncture. Taken together, we concluded that rhIL-37 enhances the suppressive activity of CD4+CD25+ Tregs and might be a potential immunomodulator for the treatment of septic complications. PMID:27941849

  9. DJ-1/Park7 Sensitive Na(+) /H(+) Exchanger 1 (NHE1) in CD4(+) T Cells.

    PubMed

    Zhou, Yuetao; Shi, Xiaolong; Chen, Hong; Zhang, Shaqiu; Salker, Madhuri S; Mack, Andreas F; Föller, Michael; Mak, Tak W; Singh, Yogesh; Lang, Florian

    2016-08-10

    DJ-1/Park7 is a redox-sensitive chaperone protein counteracting oxidation and presumably contributing to the control of oxidative stress responses and thus inflammation. DJ-1 gene deletion exacerbates the progression of Parkinson's disease presumably by augmenting oxidative stress. Formation of reactive oxygen species (ROS) is paralleled by activation of the Na(+) /H(+) exchanger 1 (NHE1). ROS formation in CD4(+) T cells plays a decisive role in regulating inflammatory responses. In the present study we explored whether DJ-1 is expressed in CD4(+) T cells and affects ROS production as well as NHE1 in those cells. To this end, DJ-1 and NHE1 transcript and protein levels were quantified by qRT-PCR and Western blotting respectively, intracellular pH (pHi) utilizing bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) fluorescence, NHE activity from realkalinization after an ammonium pulse, and ROS production utilizing 2',7' -dichlorofluorescin diacetate (DCFDA) fluorescence. As a result DJ-1 was expressed in CD4(+) T cells. ROS formation, NHE1 transcript levels, NHE1 protein, and NHE activity were higher in CD4(+) T cells from DJ-1 deficient mice than in CD4(+) T cells from wild type mice. Antioxidant N-acetyl-cysteine (NAC) and protein tyrosine kinase (PTK) inhibitor staurosporine decreased the NHE activity in DJ-1 deficient CD4(+) T cells, and blunted the difference between DJ-1(-/-) and DJ-1(+/+) CD4(+) T cells, an observation pointing to a role of ROS in the up-regulation of NHE1 in DJ-1(-/-) CD4(+) T cells. In conclusion, DJ-1 is a powerful regulator of ROS production as well as NHE1 expression and activity in CD4(+) T cells. This article is protected by copyright. All rights reserved.

  10. Daily subcutaneous injections of peptide induce CD4+ CD25+ T regulatory cells

    PubMed Central

    Dahlberg, P E; Schartner, J M; Timmel, A; Seroogy, C M

    2007-01-01

    Peptide immunotherapy is being explored to modulate varied disease states; however, the mechanism of action remains poorly understood. In this study, we investigated the ability of a subcutaneous peptide immunization schedule to induce of CD4+ CD25+ T regulatory cells. DO11·10 T cell receptor (TCR) transgenic mice on a Rag 2–/– background were injected subcutaneously with varied doses of purified ovalbumin (OVA323−339) peptide daily for 16 days. While these mice have no CD4+ CD25+ T regulatory cells, following this injection schedule up to 30% of the CD4+ cells were found to express CD25. Real-time quantitative polymerase chain reaction (QPCR) analysis of the induced CD4+ CD25+ T cells revealed increased expression of forkhead box P3 (FoxP3), suggesting that these cells may have a regulatory function. Proliferation and suppression assays in vitro utilizing the induced CD4+ CD25+ T cells revealed a profound anergic phenotype in addition to potent suppressive capability. Importantly, co-injection of the induced CD4+ CD25+ T cells with 5,6-carboxy-succinimidyl-fluorescence-ester (CFSE)-labelled naive CD4+ T cells (responder cells) into BALB/c recipient mice reduced proliferation and differentiation of the responder cells in response to challenge with OVA323−339 peptide plus adjuvant. We conclude that repeated subcutaneous exposure to low-dose peptide leads to de novo induction of CD4+ CD25+ FoxP3+ T regulatory cells with potent in vitro and in vivo suppressive capability, thereby suggesting that one mechanism of peptide immunotherapy appears to be induction of CD4+ CD25+ Foxp3+ T regulatory cells. PMID:17490400

  11. CD4 Enumeration Technologies: A Systematic Review of Test Performance for Determining Eligibility for Antiretroviral Therapy

    PubMed Central

    Peeling, Rosanna W.; Sollis, Kimberly A.; Glover, Sarah; Crowe, Suzanne M.; Landay, Alan L.; Cheng, Ben; Barnett, David; Denny, Thomas N.; Spira, Thomas J.; Stevens, Wendy S.; Crowley, Siobhan; Essajee, Shaffiq; Vitoria, Marco; Ford, Nathan

    2015-01-01

    Background Measurement of CD4+ T-lymphocytes (CD4) is a crucial parameter in the management of HIV patients, particularly in determining eligibility to initiate antiretroviral treatment (ART). A number of technologies exist for CD4 enumeration, with considerable variation in cost, complexity, and operational requirements. We conducted a systematic review of the performance of technologies for CD4 enumeration. Methods and Findings Studies were identified by searching electronic databases MEDLINE and EMBASE using a pre-defined search strategy. Data on test accuracy and precision included bias and limits of agreement with a reference standard, and misclassification probabilities around CD4 thresholds of 200 and 350 cells/μl over a clinically relevant range. The secondary outcome measure was test imprecision, expressed as % coefficient of variation. Thirty-two studies evaluating 15 CD4 technologies were included, of which less than half presented data on bias and misclassification compared to the same reference technology. At CD4 counts <350 cells/μl, bias ranged from -35.2 to +13.1 cells/μl while at counts >350 cells/μl, bias ranged from -70.7 to +47 cells/μl, compared to the BD FACSCount as a reference technology. Misclassification around the threshold of 350 cells/μl ranged from 1-29% for upward classification, resulting in under-treatment, and 7-68% for downward classification resulting in overtreatment. Less than half of these studies reported within laboratory precision or reproducibility of the CD4 values obtained. Conclusions A wide range of bias and percent misclassification around treatment thresholds were reported on the CD4 enumeration technologies included in this review, with few studies reporting assay precision. The lack of standardised methodology on test evaluation, including the use of different reference standards, is a barrier to assessing relative assay performance and could hinder the introduction of new point-of-care assays in countries

  12. A CD4 homologue in sea bass (Dicentrarchus labrax): molecular characterization and structural analysis.

    PubMed

    Buonocore, Francesco; Randelli, Elisa; Casani, Daniela; Guerra, Laura; Picchietti, Simona; Costantini, Susan; Facchiano, Angelo M; Zou, Jun; Secombes, Chris J; Scapigliati, Giuseppe

    2008-06-01

    CD4 is a transmembrane glycoprotein fundamental for cell-mediated immunity. Its action as a T cell co-receptor increases the avidity of association between a T cell and an antigen-presenting cell by interacting with portions of the complex between MHC class II and TR molecules. In this paper we report the cDNA cloning, expression and structural analysis of a CD4 homologue from sea bass (Dicentrarchus labrax). The sea bass CD4 cDNA consists of 2071 bp that translates in one reading frame to give the entire molecule containing 480 amino acids. The analysis of the sequence shows the presence of four putative Ig-like domains and that some fundamental structural features, like a disulphide bond in domain D2 and the CXC signalling motif in the cytoplasmic tail, are conserved from sea bass to mammals. Real-time PCR analysis showed that very high levels of CD4 mRNA transcripts are present in thymus, followed by gut and gills. In vitro stimulation of head kidney leukocytes with LPS and PHA-L gave an increase of CD4 mRNA levels after 4h and a decrease after 24h. Homology modelling has been applied to create a 3D model of sea bass CD4 and to investigate its interaction with sea bass MHC-II. The analysis of the 3D complex between sea bass CD4 and sea bass MHC-II suggests that the absence of a disulfide bond in the CD4 D1 domain could make this molecule more flexible, inducing a different conformation and affecting the binding and the way of interaction between CD4 and MHC-II. Our results will add new insights into the sea bass T cell immune responses and will help in the identification of T cell subsets in teleost fishes to better understand the evolution of cell-mediated immunity from fish to mammals.

  13. Daily subcutaneous injections of peptide induce CD4+ CD25+ T regulatory cells.

    PubMed

    Dahlberg, P E; Schartner, J M; Timmel, A; Seroogy, C M

    2007-08-01

    Peptide immunotherapy is being explored to modulate varied disease states; however, the mechanism of action remains poorly understood. In this study, we investigated the ability of a subcutaneous peptide immunization schedule to induce of CD4(+) CD25(+) T regulatory cells. DO11.10 T cell receptor (TCR) transgenic mice on a Rag 2(-/-) background were injected subcutaneously with varied doses of purified ovalbumin (OVA(323-339)) peptide daily for 16 days. While these mice have no CD4(+) CD25(+) T regulatory cells, following this injection schedule up to 30% of the CD4(+) cells were found to express CD25. Real-time quantitative polymerase chain reaction (QPCR) analysis of the induced CD4(+) CD25(+) T cells revealed increased expression of forkhead box P3 (FoxP3), suggesting that these cells may have a regulatory function. Proliferation and suppression assays in vitro utilizing the induced CD4(+) CD25(+) T cells revealed a profound anergic phenotype in addition to potent suppressive capability. Importantly, co-injection of the induced CD4(+) CD25(+) T cells with 5,6-carboxy-succinimidyl-fluorescence-ester (CFSE)-labelled naive CD4(+) T cells (responder cells) into BALB/c recipient mice reduced proliferation and differentiation of the responder cells in response to challenge with OVA(323-339) peptide plus adjuvant. We conclude that repeated subcutaneous exposure to low-dose peptide leads to de novo induction of CD4(+) CD25(+) FoxP3(+) T regulatory cells with potent in vitro and in vivo suppressive capability, thereby suggesting that one mechanism of peptide immunotherapy appears to be induction of CD4(+) CD25(+) Foxp3(+) T regulatory cells.

  14. Complementary feeding practices and child growth outcomes in Haiti: an analysis of data from Demographic and Health Surveys.

    PubMed

    Heidkamp, Rebecca A; Ayoya, Mohamed Ag; Teta, Ismael Ngnie; Stoltzfus, Rebecca J; Marhone, Joseline Pierre

    2015-10-01

    The Haitian National Nutrition Policy identifies the promotion of optimal complementary feeding (CF) practices as a priority action to prevent childhood malnutrition. We analysed data from the nationally representative 2005-2006 Haiti Demographic Health Survey using the World Health Organization 2008 infant and young child feeding indicators to describe feeding practices among children aged 6-23 months and thus inform policy and programme planning. Multivariate regression analyses were used to identify the determinants of CF practices and to examine their association with child growth outcomes. Overall, 87.3% of 6-8-month-olds received soft, solid or semi-solid foods in the previous 24 h. Minimum dietary diversity (MDD), minimum meal frequency (MMF) and minimum acceptable diet (MAD) were achieved in 29.2%, 45.3% and 17.1% of children aged 6-23 months, respectively. Non-breastfed children were more likely to achieve MDD than breastfed children of the same age (37.3% vs. 25.8%; P < 0.001). The proportion of children achieving MMF varied significantly by age (P < 0.001). Children with overweight mothers were more likely to achieve MDD, MMF and MAD [odds ratio (OR) 2.08, P = 0.012; OR 1.81, P = 0.02; and OR 2.4, P = 0.01, respectively] than children of normal weight mothers. Odds of achieving MDD and MMF increased with household wealth. Among mothers with secondary or more education, achieving MDD or MAD was significantly associated with lower mean weight-for-age z-score and height-for-age z-score (P-value <0.05 for infants and young child feeding indicator × maternal education interaction). CF practices were mostly inadequate and contributed to growth faltering among Haitian children 6-23 months old.

  15. CD4 T-Cell Subsets in Malaria: TH1/TH2 Revisited

    PubMed Central

    Perez-Mazliah, Damian; Langhorne, Jean

    2015-01-01

    CD4+ T-cells have been shown to play a central role in immune control of infection with Plasmodium parasites. At the erythrocytic stage of infection, IFN-γ production by CD4+ T-cells and CD4+ T-cell help for the B-cell response are required for control and elimination of infected red blood cells. CD4+ T-cells are also important for controlling Plasmodium pre-erythrocytic stages through the activation of parasite-specific CD8+ T-cells. However, excessive inflammatory responses triggered by the infection have been shown to drive pathology. Early classical experiments demonstrated a biphasic CD4+ T-cell response against erythrocytic stages in mice, in which T helper (Th)1 and antibody-helper CD4+ T-cells appear sequentially during a primary infection. While IFN-γ-producing Th1 cells do play a role in controlling acute infections, and they contribute to acute erythrocytic-stage pathology, it became apparent that a classical Th2 response producing IL-4 is not a critical feature of the CD4+ T-cell response during the chronic phase of infection. Rather, effective CD4+ T-cell help for B-cells, which can occur in the absence of IL-4, is required to control chronic parasitemia. IL-10, important to counterbalance inflammation and associated with protection from inflammatory-mediated severe malaria in both humans and experimental models, was originally considered be produced by CD4+ Th2 cells during infection. We review the interpretations of CD4+ T-cell responses during Plasmodium infection, proposed under the original Th1/Th2 paradigm, in light of more recent advances, including the identification of multifunctional T-cells such as Th1 cells co-expressing IFN-γ and IL-10, the identification of follicular helper T-cells (Tfh) as the predominant CD4+ T helper subset for B-cells, and the recognition of inherent plasticity in the fates of different CD4+ T-cells. PMID:25628621

  16. Profound reduction of CD4+ lymphocytes without HIV infection: two cases from the horn of Africa.

    PubMed

    Ollé-Goig, J E; Ramírez, J; Cervera, C; Miró, J M

    2012-09-01

    Idiopathic CD4+ lymphocytopenia is a disorder associated with low CD4+ T cell count and opportunistic infections resembling AIDS. Most cases are described in developed countries. We report two HIV-negative patients with idiopathic CD4+ lymphocytopenia and AIDS-defining events diagnosed in Djibouti. The first patient developed lesions of Kaposi's sarcoma and the second one presented with pulmonary tuberculosis. Both patients died with severe immunodepression. In poor resource-areas where HIV testing may not be available it is important to bear in mind that severe immunodepression and a clinical presentation compatible with AIDS do not necessary carry the diagnosis of AIDS.

  17. Patterns and determinants of breastfeeding and complementary feeding practices of Emirati Mothers in the United Arab Emirates

    PubMed Central

    2013-01-01

    Background Breastfeeding is the preferred method of feeding for the infant. The present study aimed at investigating the different infant feeding practices and the influencing factors in the United Arab Emirates (UAE). Methods A convenient sample of 593 Emirati mothers who had infants up to 2 years of age was interviewed. The interviews included a detailed questionnaire and conducted in the Maternal and Child Health Centers (MCH) and Primary Health Centers (PHC) in three cities. Results Almost all the mothers in the study had initiated breastfeeding (98%). The mean duration of breastfeeding was 8.6 months. The initiation and duration of breastfeeding rates were influenced by mother’s age (P<0.034)and education(P<0.01), parity(OR=2.13; P<0.001), rooming in(OR=21.70; P<0.001), nipple problem(P<0.010) and use of contraception(P<0.034). As for the feeding patterns, the results of the multiple logistic analyses revealed that rooming in (OR=4.48; P<0.001), feeding on demand (OR=2.29; P<0.005) and feeding more frequently at night (P<0.001) emerged as significant factors associated with exclusive or predominantly breastfeeding practices. Among the 593 infants in the study, 24.1% had complementary feeding, 25% of the infants were exclusively breastfed, and 49.4% were predominantly breastfed since birth. About 30% of the infants were given nonmilk fluids such as: Anis seed drink (Yansun), grippe water and tea before 3 months of age. The majority of the infants (83.5%) in the three areas received solid food before the age of 6 months. A variety of reasons were reported as perceived by mothers for terminating breastfeeding. The most common reasons were: new pregnancy (32.5%), insufficient milk supply (24.4%) and infant weaned itself (24.4%). Conclusions In conclusion, infant and young child feeding practices in this study were suboptimal. There is a need for a national community-based breastfeeding intervention programme and for the promotion of exclusive breastfeeding as

  18. Stability and continuity of parentally reported child eating behaviours and feeding practices from 2 to 5 years of age.

    PubMed

    Farrow, C; Blissett, J

    2012-02-01

    Previous research suggests that many eating behaviours are stable in children but that obesigenic eating behaviours tend to increase with age. This research explores the stability (consistency in individual levels over time) and continuity (consistency in group levels over time) of child eating behaviours and parental feeding practices in children between 2 and 5 years of age. Thirty one participants completed measures of child eating behaviours, parental feeding practices and child weight at 2 and 5 years of age. Child eating behaviours and parental feeding practices remained stable between 2 and 5 years of age. There was also good continuity in measures of parental restriction and monitoring of food intake, as well as in mean levels of children's eating behaviours and BMI over time. Mean levels of maternal pressure to eat significantly increased, whilst mean levels of desire to drink significantly decreased, between 2 and 5 years of age. These findings suggest that children's eating behaviours are stable and continuous in the period prior to 5 years of age. Further research is necessary to replicate these findings and to explore why later developmental increases are seen in children's obesigenic eating behaviours.

  19. Novel CD28 antagonist mPEG PV1-Fab’ mitigates experimental autoimmune uveitis by suppressing CD4+ T lymphocyte activation and IFN-γ production

    PubMed Central

    Papotto, Pedro Henrique; Marengo, Eliana Blini; Sardinha, Luiz Roberto; Carvalho, Karina Inácio; de Carvalho, Ana Eduarda Zulim; Castillo-Mendez, Sheyla; Jank, Carina Calixto; Vanhove, Bernard; Goldberg, Anna Carla; Rizzo, Luiz Vicente

    2017-01-01

    Autoimmune Uveitis is an important chronic inflammatory disease and a leading cause of impaired vision and blindness. This ocular autoimmune disorder is mainly mediated by T CD4+ lymphocytes poising a TH1 phenotype. Costimulatory molecules are known to play an important role on T cell activation and therefore represent interesting therapeutical targets for autoimmune disorders. CD28 is the prototypical costimulatory molecule for T lymphocytes, and plays a crucial role in the initiation, and maintenance of immune responses. However, previous attempts to use this molecule in clinical practice achieved no success. Thus, we evaluated the efficacy of mPEG PV1-Fab’ (PV1), a novel selective CD28 antagonist monovalent Fab fragment in the treatment of Experimental Autoimmune Uveitis (EAU). Here, we showed that PV1 treatment decreases both average disease score and incidence of EAU. A decrease in the activation profile of both T CD4+ and T CD8+ eye-infiltrating lymphocytes was evidenced. In the periphery, T CD4+ cells from PV1-treated mice also showed a decrease in their activation status, with reduced expression of CD69, CD25, and PD-1 molecules. This suppression was not dependent on Treg cells, as both their frequency and absolute number were lower in PV1-treated mice. In addition, frequency of CD4+IFN-γ+ T cells was significantly lower in PV1-treated group, but not of IL-17-producing T cells. Moreover, after specific restimulation, PV1 blockade selectively blocked IFN-γ production by CD4+ lymphocytes Taken together, our data suggest that mPEG PV1-Fab’ acts mainly on IFN-γ-producing CD4+ T cells and emphasize that this specific CD28 blockade strategy is a potential specific and alternative tool for the treatment of autoimmune disorders in the eye. PMID:28248972

  20. Breastfeeding, bottle feeding practices and malocclusion in the primary dentition: a systematic review of cohort studies.

    PubMed

    Hermont, Ana Paula; Martins, Carolina C; Zina, Lívia G; Auad, Sheyla M; Paiva, Saul M; Pordeus, Isabela A

    2015-03-16

    The World Health Organization recommends exclusive breast feeding for at least six months. However, there is no scientific evidence of the benefits of breast feeding for oral health in children under primary dentition. This study aimed to search for scientific evidence regarding the following question: is bottle feeding associated with malocclusion in the primary dentition compared to children that are breastfed? An electronic search was performed in seven databases. The systematic review included 10 cohort studies. It was not possible to conduct meta-analysis; therefore a qualitative analysis was assessed. The majority of studies evaluated feeding habits by means of questionnaires and conducted a single examination. Three studies observed that bottle feeding was significantly associated with overjet and posterior crossbite. Studies reported several cut-off times for breastfeeding (varying from 1 month up to 3 years of age) and several types of malocclusion. Controlling for non-nutritive sucking habits was reported for only half of the studies and this may have led to biased results. The scientific evidence could not confirm a specific type of malocclusion associated with the feeding habits or an adequate time of breastfeeding to benefit the children against malocclusion. Further cohort studies are needed to confirm this evidence.

  1. Breastfeeding, Bottle Feeding Practices and Malocclusion in the Primary Dentition: A Systematic Review of Cohort Studies

    PubMed Central

    Hermont, Ana Paula; Martins, Carolina C.; Zina, Lívia G.; Auad, Sheyla M.; Paiva, Saul M.; Pordeus, Isabela A.

    2015-01-01

    The World Health Organization recommends exclusive breast feeding for at least six months. However, there is no scientific evidence of the benefits of breast feeding for oral health in children under primary dentition. This study aimed to search for scientific evidence regarding the following question: is bottle feeding associated with malocclusion in the primary dentition compared to children that are breastfed? An electronic search was performed in seven databases. The systematic review included 10 cohort studies. It was not possible to conduct meta-analysis; therefore a qualitative analysis was assessed. The majority of studies evaluated feeding habits by means of questionnaires and conducted a single examination. Three studies observed that bottle feeding was significantly associated with overjet and posterior crossbite. Studies reported several cut-off times for breastfeeding (varying from 1 month up to 3 years of age) and several types of malocclusion. Controlling for non-nutritive sucking habits was reported for only half of the studies and this may have led to biased results. The scientific evidence could not confirm a specific type of malocclusion associated with the feeding habits or an adequate time of breastfeeding to benefit the children against malocclusion. Further cohort studies are needed to confirm this evidence. PMID:25785498

  2. Platelets modulate the immune response following trauma by interaction with CD4+ T regulatory cells in a mouse model.

    PubMed

    Bergmann, Christian B; Hefele, Friederike; Unger, Marina; Huber-Wagner, Stefan; Biberthaler, Peter; van Griensven, Martijn; Hanschen, Marc

    2016-04-01

    CD4+ T regulatory cells (Tregs) play a pivotal role in the anti-inflammatory immune response following trauma. The mechanisms of CD4+ Treg activation are mostly unknown. Here, we hypothesize that platelets regulate CD4+ Treg activation following trauma. In a murine burn injury model (male C57Bl/6N mice), depletion of platelets or CD4+ Tregs was conducted. Draining lymph nodes, blood and spleen were harvested 2 h and 7 days after trauma. CD4+ Treg activation was measured using phospho- and conventional flow cytometry. Platelet activation was analyzed using thromboelastometry and flow cytometry. Trauma differentially activates CD4+ T cells, early after trauma only CD4+ Tregs are activated. Following burn injury, platelets augment the activation of CD4+ Tregs. This effect could only be seen early after trauma. While CD4+ Tregs influence hemostasis early following trauma, platelet activation markers were unchanged. Beyond their role in hemostasis, platelets are able to modulate the immunologic host response to trauma-induced injury by augmenting the activation of CD4+ Tregs. CD4+ Treg activation following trauma is considered protective. In addition, CD4+ Tregs are capable of modulating the hemostatic function of platelets. For the first time, we could show reciprocal activation of platelets and CD4+ Tregs as part of the protective immune response following trauma.

  3. Characterization of circulating CD4(+) CD8(+) double positive and CD4(-) CD8(-) double negative T-lymphocyte in children with β-thalassemia major.

    PubMed

    Zahran, Asmaa M; Saad, Khaled; Elsayh, Khalid I; Alblihed, Mohamd A

    2017-03-01

    Infectious complications represent the second most common cause of mortality and a major cause of morbidity in β-thalassemia major (BTM), with a prevalence of 12-13%. The data on unconventional T-lymphocyte subsets in BTM children are limited. The aim of the present study was to investigate and evaluate phenotypic alterations in CD4(+)CD8(+) double positive (DP), CD4(-) CD8(-) double negative (DN), and natural killer T-lymphocytes (NKT) in BTM children in comparison to healthy controls. Our case control study included 80 children with BTM and 40 healthy children as controls. Assessment of unconventional T-lymphocyte populations was done using sensitive four-color flow cytometry (FACSCalibur). Our analysis of the data showed a significantly higher frequency CD4(+) CD8(+) (double-positive) T cells, CD4(-) CD8(-) (double negative) T cells, and natural killer T cells in the peripheral blood of both BTM groups (splenectomized and non-splenectomized) as compared to healthy controls, suggesting that these cells may play a role in the clinical course of BTM. The relationship of the unconventional T-lymphocytes to immune disorders in BTM children remains to be determined. Further longitudinal study with a larger sample size is warranted to elucidate the role these cells in BTM.

  4. Role of Social Support in Improving Infant Feeding Practices in Western Kenya: A Quasi-Experimental Study

    PubMed Central

    Mukuria, Altrena G; Martin, Stephanie L; Egondi, Thaddeus; Bingham, Allison; Thuita, Faith M

    2016-01-01

    ABSTRACT Background: We designed and tested an intervention that used dialogue-based groups to engage infants’ fathers and grandmothers to support optimal infant feeding practices. The study’s aim was to test the effectiveness of increased social support by key household influencers on improving mothers’ complementary feeding practices. Methods: Using a quasi-experimental design, we enrolled mothers, fathers, and grandmothers from households with infants 6–9 months old in 3 rural communities (1 intervention arm with fathers, 1 intervention arm with grandmothers, and 1 comparison arm) in western Kenya. We engaged 79 grandmothers and 85 fathers in separate dialogue groups for 6 months from January to July 2012. They received information on health and nutrition and were encouraged to provide social support to mothers (defined as specific physical actions in the past 2 weeks or material support actions in the past month). We conducted a baseline household survey in December 2011 in the 3 communities and returned to the same households in July 2012 for an endline survey. We used a difference-in-difference (DiD) approach and logistic regression to evaluate the intervention. Results: We surveyed 554 people at baseline (258 mothers, 165 grandmothers, and 131 fathers) and 509 participants at endline. The percentage of mothers who reported receiving 5 or more social support actions (of a possible 12) ranged from 58% to 66% at baseline in the 3 groups. By endline, the percentage had increased by 25.8 percentage points (P=.002) and 32.7 percentage points (P=.001) more in the father and the grandmother intervention group, respectively, than in the comparison group. As the number of social support actions increased in the 3 groups, the likelihood of a mother reporting that she had fed her infant the minimum number of meals in the past 24 hours also increased between baseline and endline (odds ratio [OR], 1.14; confidence interval [CI], 1.00 to 1.30; P=.047). When taking

  5. Association Between Maternal Stress, Work Status, Concern About Child Weight, and Restrictive Feeding Practices in Preschool Children.

    PubMed

    Swyden, Katheryn; Sisson, Susan B; Morris, Amanda S; Lora, Karina; Weedn, Ashley E; Copeland, Kristen A; DeGrace, Beth

    2017-01-30

    Objectives To examine the relationship between maternal stress, work status, concern about child weight, and the use of restrictive feeding practices among mothers of preschool children. Methods 285 mothers of 2-to-5-year-old children completed an on-line survey. Questions included demographics, items from the Depression Anxiety Stress Scale, and the Child Feeding Questionnaire. Linear regression and ANOVA examined the relationship between maternal stress, work hours, concern about child weight, and the use of restrictive practices for one 2-to-5-year-old child living within the home. Results Mothers were 32.6 ± 5.2 years of age and spent 39.7 ± 12.0 h/week at work. Seventy-one percent worked full time. Children were 3.4 ± 1.0 years of age and 51% male. Stress (3.41 ± 0.77, p ≤ 0.001) and concern about child weight (3.41 ± 0.77, p ≤ 0.00) were associated with the use of restrictive feeding practices. Mothers with severe/extremely severe stress used restriction more than mothers with normal stress, respectively (3.63 ± 0.80, 3.30 ± 0.81, p = 0.03). No difference was found among mothers with mild/moderate stress (3.50 ± 0.63, p = 0.06). There was no association between work hours (p = 0.50) or work status (p = 0.91) and the use of restrictive feeding practices. Conclusions Maternal stress and concern about child weight were associated with the use of restrictive feeding practices. Considering the current rates of childhood obesity in the United States, understanding factors that influence a child's food environment is advantageous and can help improve maternal and child health.

  6. IL-21 induces IL-22 production in CD4+ T cells.

    PubMed

    Yeste, Ada; Mascanfroni, Ivan D; Nadeau, Meghan; Burns, Evan J; Tukpah, Ann-Marcia; Santiago, Andrezza; Wu, Chuan; Patel, Bonny; Kumar, Deepak; Quintana, Francisco J

    2014-05-06

    Interleukin (IL)-22 produced by innate lymphoid cells (ILCs) and CD4+ T cells plays an important role in host defence and mucosal homeostasis, thus it is important to investigate the mechanisms that regulate IL-22 production. We investigated the regulation IL-22 production by CD4+ T cells. Here we show that IL-21 triggers IL-22, but not IL-17 production by CD4+ T cells. STAT3, activated by IL-21, controls the epigenetic status of the il22 promoter and its interaction with the aryl hydrocarbon receptor (AhR). Moreover, IL-21 and AhR signalling in T cells control IL-22 production and the development of dextran sodium sulphate-induced colitis in ILC-deficient mice. Thus, we have identified IL-21 as an inducer of IL-22 production in CD4+ T cells in vitro and in vivo.

  7. Quantifying CD4/CCR5 Usage Efficiency of HIV-1 Env Using the Affinofile System.

    PubMed

    Webb, Nicholas E; Lee, Benhur

    2016-01-01

    Entry of HIV-1 into target cells involves the interaction of the HIV envelope (Env) with both a primary receptor (CD4) and a coreceptor (CXCR4 or CCR5). The relative efficiency with which a particular Env uses these receptors is a major component of cellular tropism in the context of entry and is related to a variety of pathological Env phenotypes (Chikere et al. Virology 435:81-91, 2013). The protocols outlined in this chapter describe the use of the Affinofile system, a 293-based dual-inducible cell line that expresses up to 25 distinct combinations of CD4 and CCR5, as well as the associated Viral Entry Receptor Sensitivity Assay (VERSA) metrics used to summarize the CD4/CCR5-dependent infectivity results. This system allows for high-resolution profiling of CD4 and CCR5 usage efficiency in the context of unique viral phenotypes.

  8. Polyfunctional and IFN-γ monofunctional human CD4+ T cell populations are molecularly distinct

    PubMed Central

    Burel, Julie G.; Apte, Simon H.; Groves, Penny L.; McCarthy, James S.; Doolan, Denise L.

    2017-01-01

    Pathogen-specific polyfunctional T cell responses have been associated with favorable clinical outcomes, but it is not known whether molecular differences exist between polyfunctional and monofunctional cytokine-producing T cells. Here, we report that polyfunctional CD4+ T cells induced during Plasmodium falciparum (P. falciparum) blood-stage infection in humans have a unique transcriptomic profile compared with IFN-γ monofunctional CD4+ T cells and, thus, are molecularly distinct. The 14-gene signature revealed in P. falciparum–reactive polyfunctional T cells is associated with cytokine signaling and lymphocyte chemotaxis, and systems biology analysis identified IL-27 as an upstream regulator of the polyfunctional gene signature. Importantly, the polyfunctional gene signature is largely conserved in Influenza-reactive polyfunctional CD4+ T cells, suggesting that polyfunctional T cells have core characteristics independent of pathogen specificity. This study provides the first evidence to our knowledge that consistent molecular differences exist between polyfunctional and monofunctional CD4+ T cells. PMID:28194431

  9. Development of a device for selective removal of CD4+ T cells.

    PubMed

    Onodera, Hirokazu; Ninomiya, Kasumi; Yoshida, Makoto; Matsuo, Hidenori; Shibuya, Noritoshi

    2003-06-01

    To control antigen (Ag)-specific immune cells is important in the treatment of autoimmune diseases. In particular, controlling the immune response of autoimmune T cells is effective in the treatment of these diseases. The development of a device that can remove CD4+ T cells specifically by extracorporeal circulation is now in progress, with the aim to deplete autoimmune T cells. We developed a removal material made of polypropylene non-woven fabrics with anti human CD4 monoclonal antibody immobilized on the surface. Using a column packed with the removal material, we succeeded in removing CD4+ T cells specifically from peripheral whole blood by direct perfusion. Moreover, CD4+ T cells can be specifically removed even from blood with lower surface antigen density by in vitro activation.

  10. The SPL7013 dendrimer destabilizes the HIV-1 gp120-CD4 complex

    NASA Astrophysics Data System (ADS)

    Nandy, Bidisha; Saurabh, Suman; Sahoo, Anil Kumar; Dixit, Narendra M.; Maiti, Prabal K.

    2015-11-01

    The poly (l-lysine)-based SPL7013 dendrimer with naphthalene disulphonate surface groups blocks the entry of HIV-1 into target cells and is in clinical trials for development as a topical microbicide. Its mechanism of action against R5 HIV-1, the HIV-1 variant implicated in transmission across individuals, remains poorly understood. Using docking and fully atomistic MD simulations, we find that SPL7013 binds tightly to R5 gp120 in the gp120-CD4 complex but weakly to gp120 alone. Further, the binding, although to multiple regions of gp120, does not occlude the CD4 binding site on gp120, suggesting that SPL7013 does not prevent the binding of R5 gp120 to CD4. Using MD simulations to compute binding energies of several docked structures, we find that SPL7013 binding to gp120 significantly weakens the gp120-CD4 complex. Finally, we use steered molecular dynamics (SMD) to study the kinetics of the dissociation of the gp120-CD4 complex in the absence of the dendrimer and with the dendrimer bound in each of the several stable configurations to gp120. We find that SPL7013 significantly lowers the force required to rupture the gp120-CD4 complex and accelerates its dissociation. Taken together, our findings suggest that SPL7013 compromises the stability of the R5 gp120-CD4 complex, potentially preventing the accrual of the requisite number of gp120-CD4 complexes across the virus-cell interface, thereby blocking virus entry.The poly (l-lysine)-based SPL7013 dendrimer with naphthalene disulphonate surface groups blocks the entry of HIV-1 into target cells and is in clinical trials for development as a topical microbicide. Its mechanism of action against R5 HIV-1, the HIV-1 variant implicated in transmission across individuals, remains poorly understood. Using docking and fully atomistic MD simulations, we find that SPL7013 binds tightly to R5 gp120 in the gp120-CD4 complex but weakly to gp120 alone. Further, the binding, although to multiple regions of gp120, does not occlude

  11. Fighting Viral Infections and Virus-Driven Tumors with Cytotoxic CD4+ T Cells

    PubMed Central

    Muraro, Elena; Merlo, Anna; Martorelli, Debora; Cangemi, Michela; Dalla Santa, Silvia; Dolcetti, Riccardo; Rosato, Antonio

    2017-01-01

    CD4+ T cells have been and are still largely regarded as the orchestrators of immune responses, being able to differentiate into distinct T helper cell populations based on differentiation signals, transcription factor expression, cytokine secretion, and specific functions. Nonetheless, a growing body of evidence indicates that CD4+ T cells can also exert a direct effector activity, which depends on intrinsic cytotoxic properties acquired and carried out along with the evolution of several pathogenic infections. The relevant role of CD4+ T cell lytic features in the control of such infectious conditions also leads to their exploitation as a new immunotherapeutic approach. This review aims at summarizing currently available data about functional and therapeutic relevance of cytotoxic CD4+ T cells in the context of viral infections and virus-driven tumors. PMID:28289418

  12. Fast sorting of CD4+ T cells from whole blood using glass microbubbles.

    PubMed

    Hsu, Chia-Hsien; Chen, Chihchen; Irimia, Daniel; Toner, Mehmet

    2015-03-01

    The isolation of CD4 positive T lymphocyte (CD4+) from peripheral blood is important for monitoring patients after HIV infection. Here, we demonstrate a fast isolation strategy for CD4+ cells that involves mixing blood and glass microbubbles. After the specific binding of target cells to the microbubbles carrying specific antibodies on their surface, target cells will spontaneously float to the top of the blood vial and can be quickly separated. Using this strategy, we demonstrate that the isolation of CD4+ cells in less than 5 minutes and with better than 90% efficiency. This strategy for cell isolation based on buoyancy and glass microbubbles is quick and inexpensive, minimizes blood handling, does not require magnetic fields, or centrifugation equipment, and could lead to new, efficient strategies for AIDS diagnosis in resource-limited areas.

  13. Clonally expanded CD4+ T cells can produce infectious HIV-1 in vivo.

    PubMed

    Simonetti, Francesco R; Sobolewski, Michele D; Fyne, Elizabeth; Shao, Wei; Spindler, Jonathan; Hattori, Junko; Anderson, Elizabeth M; Watters, Sarah A; Hill, Shawn; Wu, Xiaolin; Wells, David; Su, Li; Luke, Brian T; Halvas, Elias K; Besson, Guillaume; Penrose, Kerri J; Yang, Zhiming; Kwan, Richard W; Van Waes, Carter; Uldrick, Thomas; Citrin, Deborah E; Kovacs, Joseph; Polis, Michael A; Rehm, Catherine A; Gorelick, Robert; Piatak, Michael; Keele, Brandon F; Kearney, Mary F; Coffin, John M; Hughes, Stephen H; Mellors, John W; Maldarelli, Frank

    2016-02-16

    Reservoirs of infectious HIV-1 persist despite years of combination antiretroviral therapy and make curing HIV-1 infections a major challenge. Most of the proviral DNA resides in CD4(+)T cells. Some of these CD4(+)T cells are clonally expanded; most of the proviruses are defective. It is not known if any of the clonally expanded cells carry replication-competent proviruses. We report that a highly expanded CD4(+) T-cell clone contains an intact provirus. The highly expanded clone produced infectious virus that was detected as persistent plasma viremia during cART in an HIV-1-infected patient who had squamous cell cancer. Cells containing the intact provirus were widely distributed and significantly enriched in cancer metastases. These results show that clonally expanded CD4(+)T cells can be a reservoir of infectious HIV-1.

  14. Interleukin-7 is required for CD4+ T cell activation and autoimmune neuroinflammation

    PubMed Central

    Lawson, Brian R.; Gonzalez-Quintial, Rosana; Eleftheriadis, Theodoros; Farrar, Michael A.; Miller, Stephen D.; Sauer, Karsten; McGavern, Dorian B.; Kono, Dwight H.; Baccala, Roberto; Theofilopoulos, Argyrios N.

    2015-01-01

    IL-7 is known to be vital for T cell homeostasis but has previously been presumed to be dispensable for TCR-induced activation. Here, we show that IL-7 is critical for the initial activation of CD4+ T cells in that it provides some of the necessary early signaling components, such as activated STAT5 and Akt. Accordingly, short-term in vivo IL-7Rα blockade inhibited the activation and expansion of autoantigen-specific CD4+ T cells and, when used to treat experimental autoimmune encephalomyelitis (EAE), prevented and ameliorated disease. Our studies demonstrate that IL-7 signaling is a prerequisite for optimal CD4+ T cell activation and that IL-7R antagonism may be effective in treating CD4+ T cell-mediated neuroinflammation and other autoimmune inflammatory conditions. PMID:26319414

  15. Persistent expansion of CD4+ effector memory T cells in Wegener's granulomatosis.

    PubMed

    Abdulahad, W H; van der Geld, Y M; Stegeman, C A; Kallenberg, C G M

    2006-09-01

    In order to test the hypothesis that Wegener's granulomatosis (WG) is associated with an ongoing immune effector response, even in remission, we examined the distribution of peripheral naive and memory T-lymphocytes in this disease, and analyzed the function-related phenotypes of the memory T-cell population. Peripheral blood mononuclear cells (PBMCs) were freshly isolated from WG-patients in remission (R-WG, n=40), active WG-patients (A-WG, n=17), and age-matched healthy controls (HCs, n=21). Expression of CD4, CD8, CD45RO, CCR7, interleukin (IL)-18Ralpha, ST2L, and FoxP3 were determined by four-color flow cytometric analysis. CD45RO and CCR7 were used for distinction between naive and memory T cells, IL-18Ralpha, ST2L, and FoxP3 for the assessment of Type1, Type2, and regulatory T-cells, respectively. In R-WG, the CD4+CD45RO+CCR7- effector memory T-cell subpopulation (TEM) was relatively increased, whereas the CD4+CD45RO-CCR7+ naive T-cell population (TNaive) was decreased as compared to HC. The distribution of naive and memory CD8+T cells did not differ between R-WG, A-WG, and HC, nor did CD4+CD45RO+CCR7+ central memory T cells (TCM). In contrast to HC, the percentage of CD4+TNaive cells in R-WG correlated negatively with age, whereas CD4+TEM cells showed a positive correlation. In R-WG, a skewing towards Type2 T cells was observed in CD4+TEM cells. No differences were detected in FoxP3+CD4+TEM cells between R-WG and A-WG, whereas the FoxP3-CD4+TEM cells were increased in R-WG and decreased in A-WG as compared to HC. Collectively, peripheral blood homeostasis of CD4+T cells is disturbed in R-WG with the persistent expansion of non-regulatory CD4+TEM cells. These cells might be involved in relapse and may constitute a target for therapy.

  16. CD4 T cell activation by B cells in human Leishmania (Viannia) infection

    PubMed Central

    2014-01-01

    Background An effective adaptive immune response requires activation of specific CD4 T cells. The capacity of B cells to activate CD4 T cells in human cutaneous leishmaniasis caused by Leishmania (Viannia) has not been evaluated. Methods CD4 T cell activation by B cells of cutaneous leishmaniasis patients was evaluated by culture of PBMCs or purified B cells and CD4 T cells with Leishmania panamensis antigens. CD4 T cell and B cell activation markers were evaluated by flow cytometry and 13 cytokines were measured in supernatants with a bead-based capture assay. The effect of Leishmania antigens on BCR-mediated endocytosis of ovalbumin was evaluated in the Ramos human B cell line by targeting the antigen with anti-IgM-biotin and anti-biotin-ovalbumin-FITC. Results Culture of PBMCs from cutaneous leishmaniasis patients with Leishmania antigens resulted in upregulation of the activation markers CD25 and CD69 as well as increased frequency of CD25hiCD127- cells among CD4 T cells. Concomitantly, B cells upregulated the costimulatory molecule CD86. These changes were not observed in PBMCs from healthy subjects, indicating participation of Leishmania-specific lymphocytes expanded in vivo. Purified B cells from these patients, when interacting with purified CD4 T cells and Leishmania antigens, were capable of inducing significant increases in CD25 and CD69 expression and CD25hiCD127- frequency in CD4 T cells. These changes were associated with upregulation of CD86 in B cells. Comparison of changes in CD4 T cell activation parameters between PBMC and B cell/CD4 T cell cultures showed no statistically significant differences; further, significant secretion of IFN-γ, TNF-α, IL-6 and IL-13 was induced in both types of cultures. Additionally, culture with Leishmania antigens enhanced BCR-mediated endocytosis of ovalbumin in Ramos human B cells. Conclusions The capacity of B cells specific for Leishmania antigens in peripheral blood of cutaneous leishmaniasis patients to

  17. Barriers to Infant and Child-feeding Practices: A Qualitative Study of Primary Caregivers in Rural Uganda

    PubMed Central

    Nankumbi, Joyce

    2015-01-01

    ABSTRACT The purpose of this study was to explore the barriers to the use of appropriate infant and young child-feeding practices by primary caregivers living in a rural Ugandan district. A community-based qualitative design and focus group discussions were used for collecting data from primary caregivers of children aged 0 to 24 month(s). On an average, each of the four focus group discussions had 11 participants. The focus group discussions were conducted using a structured interview guide and were tape-recorded. The recorded data were later transcribed and analyzed using qualitative thematic analysis techniques. All the participants were females, and the majority had low levels of education and at least one child in the age-group of 0-24 month(s) in their household. The findings show that the main barriers to the use of appropriate infant and young child-feeding practices fall under four themes: caregiver's knowledge about breastfeeding, caregiver's knowledge about complimentary feeding, influence of culture custodians on the caregivers, and patterns and burden of other responsibilities the caregivers have in the household. The four categories of barriers imply that there are various missed opportunities to implement hospital and community-based interventions to improve infant and young child-feeding practices, which is one way of preventing malnutrition. Therefore, in rural areas of Uganda, the major factors responsible for the high prevalence of malnutrition among infants and children are still those related to knowledge, culture, and social status of the primary caregivers. PMID:25995727

  18. Suppression of CD4+ Effector Responses by Naturally Occurring CD4+ CD25+ Foxp3+ Regulatory T Cells Contributes to Experimental Cerebral Malaria

    PubMed Central

    Blanc, Anne-Laurence; Keswani, Tarun; Gorgette, Olivier; Bandeira, Antonio; Malissen, Bernard; Cazenave, Pierre-André

    2015-01-01

    The role of naturally occurring CD4+ CD25+ Foxp3+ regulatory T cells (nTreg) in the pathogenesis of cerebral malaria (CM), which involves both pathogenic T cell responses and parasite sequestration in the brain, is still unclear. To assess the contribution and dynamics of nTreg during the neuropathogenesis, we unbalanced the ratio between nTreg and naive CD4+ T cells in an attenuated model of Plasmodium berghei ANKA-induced experimental CM (ECM) by using a selective cell enrichment strategy. We found that nTreg adoptive transfer accelerated the onset and increased the severity of CM in syngeneic C57BL/6 (B6) P. berghei ANKA-infected mice without affecting the level of parasitemia. In contrast, naive CD4+ T cell enrichment prevented CM and promoted parasite clearance. Furthermore, early during the infection nTreg expanded in the spleen but did not efficiently migrate to the site of neuroinflammation, suggesting that nTreg exert their pathogenic action early in the spleen by suppressing the protective naive CD4+ T cell response to P. berghei ANKA infection in vivo in both CM-susceptible (B6) and CM-resistant (B6-CD4−/−) mice. However, their sole transfer was not sufficient to restore CM susceptibility in two CM-resistant congenic strains tested. Altogether, these results demonstrate that nTreg are activated and functional during P. berghei ANKA infection and that they contribute to the pathogenesis of CM. They further suggest that nTreg may represent an early target for the modulation of the immune response to malaria. PMID:26553468

  19. Tracking Virus-Specific CD4+ T Cells during and after Acute Hepatitis C Virus Infection

    PubMed Central

    Pfafferot, Katja; Heeg, Malte H.J.; Gaudieri, Silvana; Grüner, Norbert; Rauch, Andri; Gerlach, J. Tilman; Jung, Maria-Christina; Zachoval, Reinhart; Pape, Gerd R.; Schraut, Winfried; Santantonio, Teresa; Nitschko, Hans; Obermeier, Martin; Phillips, Rodney; Scriba, Thomas J.; Semmo, Nasser; Day, Cheryl; Weber, Jonathan N.; Fidler, Sarah; Thimme, Robert; Haberstroh, Anita; Baumert, Thomas F.; Klenerman, Paul; Diepolder, Helmut M.

    2007-01-01

    Background CD4+ T cell help is critical in maintaining antiviral immune responses and such help has been shown to be sustained in acute resolving hepatitis C. In contrast, in evolving chronic hepatitis C CD4+ T cell helper responses appear to be absent or short-lived, using functional assays. Methodology/Principal Findings Here we used a novel HLA-DR1 tetramer containing a highly targeted CD4+ T cell epitope from the hepatitis C virus non-structural protein 4 to track number and phenotype of hepatitis C virus specific CD4+ T cells in a cohort of seven HLA-DR1 positive patients with acute hepatitis C in comparison to patients with chronic or resolved hepatitis C. We observed peptide-specific T cells in all seven patients with acute hepatitis C regardless of outcome at frequencies up to 0.65% of CD4+ T cells. Among patients who transiently controlled virus replication we observed loss of function, and/or physical deletion of tetramer+ CD4+ T cells before viral recrudescence. In some patients with chronic hepatitis C very low numbers of tetramer+ cells were detectable in peripheral blood, compared to robust responses detected in spontaneous resolvers. Importantly we did not observe escape mutations in this key CD4+ T cell epitope in patients with evolving chronic hepatitis C. Conclusions/Significance During acute hepatitis C a CD4+ T cell response against this epitope is readily induced in most, if not all, HLA-DR1+ patients. This antiviral T cell population becomes functionally impaired or is deleted early in the course of disease in those where viremia persists. PMID:17653276

  20. Remarkably low affinity of CD4/peptide-major histocompatibility complex class II protein interactions

    PubMed Central

    Jönsson, Peter; Southcombe, Jennifer H.; Santos, Ana Mafalda; Huo, Jiandong; Fernandes, Ricardo A.; McColl, James; Lever, Melissa; Evans, Edward J.; Hudson, Alexander; Chang, Veronica T.; Hanke, Tomáš; Godkin, Andrew; Dunne, Paul D.; Horrocks, Mathew H.; Palayret, Matthieu; Screaton, Gavin R.; Petersen, Jan; Rossjohn, Jamie; Fugger, Lars; Dushek, Omer; Xu, Xiao-Ning; Davis, Simon J.; Klenerman, David

    2016-01-01

    The αβ T-cell coreceptor CD4 enhances immune responses more than 1 million-fold in some assays, and yet the affinity of CD4 for its ligand, peptide-major histocompatibility class II (pMHC II) on antigen-presenting cells, is so weak that it was previously unquantifiable. Here, we report that a soluble form of CD4 failed to bind detectably to pMHC II in surface plasmon resonance-based assays, establishing a new upper limit for the solution affinity at 2.5 mM. However, when presented multivalently on magnetic beads, soluble CD4 bound pMHC II-expressing B cells, confirming that it is active and allowing mapping of the native coreceptor binding site on pMHC II. Whereas binding was undetectable in solution, the affinity of the CD4/pMHC II interaction could be measured in 2D using CD4- and adhesion molecule-functionalized, supported lipid bilayers, yielding a 2D Kd of ∼5,000 molecules/μm2. This value is two to three orders of magnitude higher than previously measured 2D Kd values for interacting leukocyte surface proteins. Calculations indicated, however, that CD4/pMHC II binding would increase rates of T-cell receptor (TCR) complex phosphorylation by threefold via the recruitment of Lck, with only a small, 2–20% increase in the effective affinity of the TCR for pMHC II. The affinity of CD4/pMHC II therefore seems to be set at a value that increases T-cell sensitivity by enhancing phosphorylation, without compromising ligand discrimination. PMID:27114505

  1. A simple theoretical framework for understanding heterogeneous differentiation of CD4+ T cells

    PubMed Central

    2012-01-01

    Background CD4+ T cells have several subsets of functional phenotypes, which play critical yet diverse roles in the immune system. Pathogen-driven differentiation of these subsets of cells is often heterogeneous in terms of the induced phenotypic diversity. In vitro recapitulation of heterogeneous differentiation under homogeneous experimental conditions indicates some highly regulated mechanisms by which multiple phenotypes of CD4+ T cells can be generated from a single population of naïve CD4+ T cells. Therefore, conceptual understanding of induced heterogeneous differentiation will shed light on the mechanisms controlling the response of populations of CD4+ T cells under physiological conditions. Results We present a simple theoretical framework to show how heterogeneous differentiation in a two-master-regulator paradigm can be governed by a signaling network motif common to all subsets of CD4+ T cells. With this motif, a population of naïve CD4+ T cells can integrate the signals from their environment to generate a functionally diverse population with robust commitment of individual cells. Notably, two positive feedback loops in this network motif govern three bistable switches, which in turn, give rise to three types of heterogeneous differentiated states, depending upon particular combinations of input signals. We provide three prototype models illustrating how to use this framework to explain experimental observations and make specific testable predictions. Conclusions The process in which several types of T helper cells are generated simultaneously to mount complex immune responses upon pathogenic challenges can be highly regulated, and a simple signaling network motif can be responsible for generating all possible types of heterogeneous populations with respect to a pair of master regulators controlling CD4+ T cell differentiation. The framework provides a mathematical basis for understanding the decision-making mechanisms of CD4+ T cells, and it can be

  2. The transcriptome of HIV-1 infected intestinal CD4+ T cells exposed to enteric bacteria

    PubMed Central

    Dillon, Stephanie M.; Phang, Tzu; Lee, Eric J.; Helm, Karen; Kappes, John C.; McCarter, Martin D.

    2017-01-01

    Global transcriptome studies can help pinpoint key cellular pathways exploited by viruses to replicate and cause pathogenesis. Previous data showed that laboratory-adapted HIV-1 triggers significant gene expression changes in CD4+ T cell lines and mitogen-activated CD4+ T cells from peripheral blood. However, HIV-1 primarily targets mucosal compartments during acute infection in vivo. Moreover, early HIV-1 infection causes extensive depletion of CD4+ T cells in the gastrointestinal tract that herald persistent inflammation due to the translocation of enteric microbes to the systemic circulation. Here, we profiled the transcriptome of primary intestinal CD4+ T cells infected ex vivo with transmitted/founder (TF) HIV-1. Infections were performed in the presence or absence of Prevotella stercorea, a gut microbe enriched in the mucosa of HIV-1-infected individuals that enhanced both TF HIV-1 replication and CD4+ T cell death ex vivo. In the absence of bacteria, HIV-1 triggered a cellular shutdown response involving the downregulation of HIV-1 reactome genes, while perturbing genes linked to OX40, PPAR and FOXO3 signaling. However, in the presence of bacteria, HIV-1 did not perturb these gene sets or pathways. Instead, HIV-1 enhanced granzyme expression and Th17 cell function, inhibited G1/S cell cycle checkpoint genes and triggered downstream cell death pathways in microbe-exposed gut CD4+ T cells. To gain insights on these differential effects, we profiled the gene expression landscape of HIV-1-uninfected gut CD4+ T cells exposed to bacteria. Microbial exposure upregulated genes involved in cellular proliferation, MAPK activation, Th17 cell differentiation and type I interferon signaling. Our findings reveal that microbial exposure influenced how HIV-1 altered the gut CD4+ T cell transcriptome, with potential consequences for HIV-1 susceptibility, cell survival and inflammation. The HIV-1- and microbe-altered pathways unraveled here may serve as a molecular blueprint

  3. AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges.

    PubMed

    Gardner, Matthew R; Kattenhorn, Lisa M; Kondur, Hema R; von Schaewen, Markus; Dorfman, Tatyana; Chiang, Jessica J; Haworth, Kevin G; Decker, Julie M; Alpert, Michael D; Bailey, Charles C; Neale, Ernest S; Fellinger, Christoph H; Joshi, Vinita R; Fuchs, Sebastian P; Martinez-Navio, Jose M; Quinlan, Brian D; Yao, Annie Y; Mouquet, Hugo; Gorman, Jason; Zhang, Baoshan; Poignard, Pascal; Nussenzweig, Michel C; Burton, Dennis R; Kwong, Peter D; Piatak, Michael; Lifson, Jeffrey D; Gao, Guangping; Desrosiers, Ronald C; Evans, David T; Hahn, Beatrice H; Ploss, Alexander; Cannon, Paula M; Seaman, Michael S; Farzan, Michael

    2015-03-05

    Long-term in vivo expression of a broad and potent entry inhibitor could circumvent the need for a conventional vaccine for HIV-1. Adeno-associated virus (AAV) vectors can stably express HIV-1 broadly neutralizing antibodies (bNAbs). However, even the best bNAbs neutralize 10-50% of HIV-1 isolates inefficiently (80% inhibitory concentration (IC80) > 5 μg ml(-1)), suggesting that high concentrations of these antibodies would be necessary to achieve general protection. Here we show that eCD4-Ig, a fusion of CD4-Ig with a small CCR5-mimetic sulfopeptide, binds avidly and cooperatively to the HIV-1 envelope glycoprotein (Env) and is more potent than the best bNAbs (geometric mean half-maximum inhibitory concentration (IC50) < 0.05 μg ml(-1)). Because eCD4-Ig binds only conserved regions of Env, it is also much broader than any bNAb. For example, eCD4-Ig efficiently neutralized 100% of a diverse panel of neutralization-resistant HIV-1, HIV-2 and simian immunodeficiency virus isolates, including a comprehensive set of isolates resistant to the CD4-binding site bNAbs VRC01, NIH45-46 and 3BNC117. Rhesus macaques inoculated with an AAV vector stably expressed 17-77 μg ml(-1) of fully functional rhesus eCD4-Ig for more than 40 weeks, and these macaques were protected from several infectious challenges with SHIV-AD8. Rhesus eCD4-Ig was also markedly less immunogenic than rhesus forms of four well-characterized bNAbs. Our data suggest that AAV-delivered eCD4-Ig can function like an effective HIV-1 vaccine.

  4. AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges

    PubMed Central

    Gardner, Matthew R.; Kattenhorn, Lisa M.; Kondur, Hema R.; von Schaewen, Markus; Dorfman, Tatyana; Chiang, Jessica J.; Haworth, Kevin G.; Decker, Julie M.; Alpert, Michael D.; Bailey, Charles C.; Neale, Ernest S.; Fellinger, Christoph H.; Joshi, Vinita R.; Fuchs, Sebastian P.; Martinez-Navio, Jose M.; Quinlan, Brian D.; Yao, Annie Y.; Mouquet, Hugo; Gorman, Jason; Zhang, Baoshan; Poignard, Pascal; Nussenzweig, Michel C.; Burton, Dennis R.; Kwong, Peter D.; Piatak, Michael; Lifson, Jeffrey D.; Gao, Guangping; Desrosiers, Ronald C.; Evans, David T.; Hahn, Beatrice H.; Ploss, Alexander; Cannon, Paula M.; Seaman, Michael S.; Farzan, Michael

    2015-01-01

    Long-term in vivo expression of a broad and potent entry inhibitor could circumvent the need for a conventional vaccine for HIV-1. Adeno-associated virus (AAV) vectors can stably express HIV-1 broadly neutralizing antibodies (bNAbs)1,2. However even the best bNAbs neutralize 10–50% of HIV-1 isolates inefficiently (IC80 > 5 μg/ml), suggesting that high concentrations of these antibodies would be necessary to achieve general protection3–6. Here we show that eCD4-Ig, a fusion of CD4-Ig with a small CCR5-mimetic sulfopeptide, binds avidly and cooperatively to the HIV-1 envelope glycoprotein (Env) and is more potent than the best bNAbs (geometric mean IC50 < 0.05 μg/ml). Because eCD4-Ig binds only conserved regions of Env, it is also much broader than any bNAb. For example, eCD4-Ig efficiently neutralized 100% of a diverse panel of neutralization-resistant HIV-1, HIV-2, and SIV isolates, including a comprehensive set of isolates resistant to the CD4-binding site bNAbs VRC01, NIH45-46, and 3BNC117. Rhesus macaques inoculated with an AAV vector stably expressed 17 to 77 μg/ml of fully functional rhesus eCD4-Ig for 40 weeks, and these macaques were protected from multiple infectious challenges with SHIV-AD8. Rhesus eCD4-Ig was also markedly less immunogenic than rhesus forms of four well characterized bNAbs. Our data suggest that AAV-delivered eCD4-Ig can function like an effective HIV-1 vaccine. PMID:25707797

  5. HIV-specific cytolytic CD4 T cell responses during acute HIV infection predict disease outcome

    PubMed Central

    Soghoian, Damien Z.; Jessen, Heiko; Flanders, Michael; Sierra-Davidson, Kailan; Cutler, Sam; Pertel, Thomas; Ranasinghe, Srinika; Lindqvist, Madelene; Davis, Isaiah; Lane, Kimberly; Rychert, Jenna; Rosenberg, Eric S.; Piechocka-Trocha, Alicja; Brass, Abraham L.; Brenchley, Jason M.; Walker, Bruce D.; Streeck, Hendrik

    2013-01-01

    Early immunological events during acute HIV infection are thought to fundamentally influence long-term disease outcome. Whereas the contribution of HIV-specific CD8 T cell responses to early viral control is well established, the role of HIV-specific CD4 T cell responses in the control of viral replication following acute infection is unknown. A growing body of evidence suggests that CD4 T cells - besides their helper function - have the capacity to directly recognize and kill virally infected cells. In a longitudinal study of a cohort of individuals acutely infected with HIV, we observed that subjects able to spontaneously control HIV replication in the absence of antiretroviral therapy showed a significant expansion of HIV-specific CD4 T cell responses—but not CD8 T cell responses–compared to subjects who progressed to a high viral set point (p=0.038). Strikingly, this expansion occurred prior to differences in viral load or CD4 T cell count and was characterized by robust cytolytic activity and expression of a distinct profile of perforin and granzymes at the earliest time point. Kaplan-Meier analysis revealed that the emergence of Granzyme A+ HIV-specific CD4 T cell responses at baseline was highly predictive of slower disease progression and clinical outcome (average days to CD4 T cell count <350/μl was 575 versus 306, p=0.001). These data demonstrate that HIV-specific CD4 T cell responses can be used during the earliest phase of HIV infection as an immunological predictor of subsequent viral set point and disease outcome. Moreover, these data suggest that expansion of Granzyme A+ HIV-specific cytolytic CD4 T cell responses early during acute HIV infection contributes substantially to the control of viral replication. PMID:22378925

  6. Human Plasmacytoid Dendritic Cells Efficiently Capture HIV-1 Envelope Glycoproteins via CD4 for Antigen Presentation

    PubMed Central

    Sandgren, Kerrie J; Smed-Sörensen, Anna; Forsell, Mattias N; Soldemo, Martina; Adams, William C; Liang, Frank; Perbeck, Leif; Koup, Richard A; Wyatt, Richard T; Hedestam, Gunilla B Karlsson; Loré, Karin

    2013-01-01

    Advances in HIV-1 vaccine clinical trials and preclinical research indicate that the virus envelope glycoproteins (Env) are likely to be an essential component of a prophylactic vaccine. Efficient antigen uptake and presentation by dendritic cells (DCs) is important for strong CD4+ T helper cell responses and the development of effective humoral immune responses. Here, we examined the capacity of distinct primary human DC subsets to internalise and present recombinant Env to CD4+ T cells. Consistent with their specific receptor expression, skin DCs bound and internalised Env via C-type lectin receptors (CLRs) while blood DC subsets, including CD1c+ myeloid DCs (MDCs), CD123+ plasmacytoid DCs (PDCs) and CD141+ DCs exhibited a restricted repertoire of CLRs and relied on CD4 for uptake of Env. Despite a generally poor capacity for antigen uptake compared to MDCs, the high expression of CD4 on PDCs allowed them to bind and internalise Env very efficiently. CD4-mediated uptake delivered Env to EEA1+ endosomes that progressed to Lamp1+ and MHC class II+ lysosomes where internalised Env was degraded rapidly. Finally, all three blood DC subsets were able to internalise an Env-CMV pp65 fusion protein via CD4 and stimulate pp65-specific CD4+ T cells. Thus, in the in vitro systems described here, CD4-mediated uptake of Env is a functional pathway leading to antigen presentation and this may therefore be a mechanism utilised by blood DCs, including PDCs, for generating immune responses to Env-based vaccines. PMID:23729440

  7. Farming practices in Sweden related to feeding milk and colostrum from cows treated with antimicrobials to dairy calves

    PubMed Central

    2013-01-01

    Background Milk produced by cows in receipt of antimicrobial therapy may contain antimicrobial residues. Such antimicrobial-containing waste milk must be withdrawn from human consumption and is therefore sometimes used as calf feed. Unfortunately, this approach might promote selection of antimicrobial resistant bacteria in the calves’ intestinal microbiota. The objectives of this study were therefore to obtain an overview of waste milk feeding practices on Swedish dairy farms and to investigate if these practices were associated with certain farm characteristics. A representative group of 457 Swedish dairy farmers participated in a web-based survey with questions about the use of colostrum and milk from cows treated with antimicrobials at dry off or during lactation, respectively, as calf feed. Results Colostrum (milk from the first milking after calving) and transition milk (milk from the second milking to the fourth day after calving) from cows treated with antimicrobials at dry off was fed to calves on 89% and 85% of the farms in the study, respectively. When antimicrobial therapy was given to cows during lactation, 56% of the farms fed milk that was produced during the course of treatment to calves, whereas milk that was produced during the subsequent withdrawal period was fed to calves on 79% of the farms. Surveyed farmers were less prone to feed such milk if the antimicrobial therapy was due to mastitis than other infections. In Sweden, a majority of antimicrobial treatments during lactation are systemic administration of benzylpenicillin and thus, the bulk of waste milk in Sweden is likely to contain residues of this drug. Feeding waste milk to calves was more common on non-organic farms, and on farms located in Southern Sweden, and was less common on farms with cows housed in cold free stalls barns. Conclusions Waste milk that may contain antimicrobial residues is, at least occasionally, used as feed for calves on a majority of surveyed Swedish dairy

  8. Human Immunodeficiency Virus Type 1 Nef-Induced CD4 Cell Surface Downregulation Is Inhibited by Ikarugamycin

    PubMed Central

    Luo, Tianci; Fredericksen, Brenda L.; Hasumi, Keiji; Endo, Akira; Garcia, J. Victor

    2001-01-01

    One well-characterized in vitro function of Nef is its ability to remove CD4, the human immunodeficiency virus (HIV) receptor, from the cell surface. Nef accomplishes this by accelerating the internalization and degradation of CD4. Current models propose that Nef promotes CD4 internalization via an increased association of CD4 with clathrin-coated pits (CCP). Here, we investigated the effect of a naturally occurring antiprotozoan antibiotic, ikarugamycin (IKA), on CD4 cell surface expression in human monocytic cells stably expressing HIV type 1 SF2 Nef. IKA was able to efficiently restore CD4 cell surface expression in Nef-expressing cells without affecting either CD4 synthesis or Nef expression. In addition, we demonstrate that IKA is also capable of efficiently blocking CD4 down-modulation in response to phorbol myristate acetate. Our data suggest that IKA may be an efficient and useful inhibitor of CCP-dependent endocytosis. PMID:11160755

  9. Association between breast-feeding practices and sucking habits: a cross-sectional study of children in their first year of life.

    PubMed

    Moimaz, Suzely A S; Zina, Lívia G; Saliba, Nemre A; Saliba, Orlando

    2008-09-01

    In addition to providing nutrition and immunological protection, breast-feeding has positive effects on the development of the infant's oral cavity. The aim of the present study is to assess breast-feeding patterns and to analyze the influence of breast-feeding practices and maternal sociodemographic variables on the prevalence of non-nutritive sucking habits in a sample of Brazilian infants. This cross-sectional study was carried out in Southern Brazil. A random sample of 100 mothers of infants up to 12 months of age was interviewed during the National Vaccination Campaign Day. The prevalence and median duration of breast-feeding were assessed. Breast-feeding practice, the exposure factor, was categorized as exclusive breast-feeding, predominant breast-feeding, complementary breast-feeding, or weaning. Maternal sociodemographic variables included age, race, marital status, educational level, profession, and family income. The outcome investigated was the prevalence of sucking habits (pacifier use and thumb sucking). We used two-sample tests, the chi-square test and FISHER'S EXACT TEST for statistical analyses of the data. The study revealed that 75% of infants were being breast-fed. Pacifier use and thumb sucking were common in 55%. Bottle-feeding was prevalent in 74% of infants. Breast-feeding was negatively correlated with pacifier use and thumb sucking (OR=0.11; 95% CI: 0.03 to 0.4). Bottle-feeding was strongly associated with weaning (p=0.0003). Among the sociodemographic variables, only marital status showed a statistical association with sucking habits (p=0.04). These findings suggest that breast-feeding can prevent the occurrence of sucking habits. Although we could not evaluate causality assessment, malocclusion prevention seems to be yet one more reason for promoting breast-feeding practices.

  10. Operational challenges in delivering CD4 diagnostics in sub-Saharan Africa.

    PubMed

    Thairu, L; Katzenstein, D; Israelski, D

    2011-07-01

    Access to reliable and low cost CD4 T-cell enumeration to stage illness and monitor anti-retroviral therapy remains elusive in resource-limited settings. We report challenges in delivering CD4 testing using the microcapillary Fluorescence-Activated Cell Sorter (FACS) methodology (Guava EasyCD4 instrument Guava Technologies, Hayward) in Burkina Faso and Zimbabwe. Resources, instruments, reagents, and training were provided to local laboratories within the existing infrastructure and data on CD4 were collected from routine laboratory testing. Challenges encountered included frequent instrument breakdown; poor manufacturer maintenance; difficulties in managing reagent stocks; high technician turnover; reliance on antiquated data management systems; redundant service provision; and lack of repeat testing in male HIV+ patients and in patients with higher CD4 counts after initial staging. While adopting newer, less expensive technologies such as fluorescent platforms and point of care tests can facilitate access to lower cost CD4 testing, our experience suggests that supply chain, corporate commitment to implementation, and community factors also require consideration.

  11. Cocaine Enhances HIV-1–Induced CD4+ T-Cell Apoptosis

    PubMed Central

    Pandhare, Jui; Addai, Amma B.; Mantri, Chinmay K.; Hager, Cynthia; Smith, Rita M.; Barnett, Louis; Villalta, Fernando; Kalams, Spyros A.; Dash, Chandravanu

    2015-01-01

    Substance abuse is a major barrier in eradication of the HIV epidemic because it serves as a powerful cofactor for viral transmission, disease progression, and AIDS-related mortality. Cocaine, one of the commonly abused drugs among HIV-1 patients, has been suggested to accelerate HIV disease progression. However, the underlying mechanism remains largely unknown. Therefore, we tested whether cocaine augments HIV-1–associated CD4+ T-cell decline, a predictor of HIV disease progression. We examined apoptosis of resting CD4+ T cells from HIV-1–negative and HIV-1–positive donors in our study, because decline of uninfected cells plays a major role in HIV-1 disease progression. Treatment of resting CD4+ T cells with cocaine (up to 100 μmol/L concentrations) did not induce apoptosis, but 200 to 1000 μmol/L cocaine induced apoptosis in a dose-dependent manner. Notably, treatment of CD4+ T cells isolated from healthy donors with both HIV-1 virions and cocaine significantly increased apoptosis compared with the apoptosis induced by cocaine or virions alone. Most important, our biochemical data suggest that cocaine induces CD4+ T-cell apoptosis by increasing intracellular reactive oxygen species levels and inducing mitochondrial depolarization. Collectively, our results provide evidence of a synergy between cocaine and HIV-1 on CD4+ T-cell apoptosis that may, in part, explain the accelerated disease observed in HIV-1–infected drug abusers. PMID:24486327

  12. Stephanthraniline A suppressed CD4(+) T cell-mediated immunological hepatitis through impairing PKCθ function.

    PubMed

    Chen, Feng-Yang; Zhou, Li-Fei; Li, Xiao-Yu; Zhao, Jia-Wen; Xu, Shi-Fang; Huang, Wen-Hai; Gao, Li-Juan; Hao, Shu-Juan; Ye, Yi-Ping; Sun, Hong-Xiang

    2016-10-15

    Stephanthraniline A (STA), a C21 steroid isolated from Stephanotis mucronata (Blanco) Merr., was previously shown to inhibit T cells activation and proliferation in vitro and in vivo. The purpose of this study was to further evaluate the in vivo immunosuppressive activity of STA and to elucidate its potential mechanisms. The results showed that pretreatment with STA significantly attenuated concanavalin A (Con A)-induced hepatitis and reduced CD4(+) T cells activation and aggregation in hepatic tissue in mice. STA directly suppressed the activation and proliferation of Con A-induced CD4(+) T cells, and inhibited NFAT, NFκB and MAPK signaling cascades in activated CD4(+) T cells in vitro. Moreover, it was proved that STA inhibited T cells activation and proliferation through proximal T cell-receptor (TCR) signaling- and Ca(2+) signaling-independent way. The molecular docking studies predicted that STA could tight bind to PKCθ via five hydrogen. The further findings indicated STA directly inhibited PKCθ kinase activity, and its phosphorylation in activated CD4(+) T cells in vitro. Collectively, the present study indicated that STA could protect against CD4(+) T cell-mediated immunological hepatitis in mice through PKCθ and its downstream NFAT, NFκB and MAPK signaling cascades. These results highlight the potential of STA as an effective leading compound for use in the treatment of CD4(+) T cell-mediated inflammatory and autoimmune diseases.

  13. A colitogenic memory CD4+ T cell population mediates gastrointestinal graft-versus-host disease

    PubMed Central

    Zhou, Vivian; Agle, Kimberle; Chen, Xiao; Beres, Amy; Komorowski, Richard; Belle, Ludovic; Taylor, Carolyn; Zhu, Fenlu; Haribhai, Dipica; Williams, Calvin B.; Verbsky, James; Blumenschein, Wendy; Sadekova, Svetlana; Bowman, Eddie; Ballantyne, Christie; Weaver, Casey; Serody, David A.; Vincent, Benjamin; Serody, Jonathan; Cua, Daniel J.; Drobyski, William R.

    2016-01-01

    Damage to the gastrointestinal tract is a major cause of morbidity and mortality in graft-versus-host disease (GVHD) and is attributable to T cell–mediated inflammation. In this work, we identified a unique CD4+ T cell population that constitutively expresses the β2 integrin CD11c and displays a biased central memory phenotype and memory T cell transcriptional profile, innate-like properties, and increased expression of the gut-homing molecules α4β7 and CCR9. Using several complementary murine GVHD models, we determined that adoptive transfer and early accumulation of β2 integrin–expressing CD4+ T cells in the gastrointestinal tract initiated Th1-mediated proinflammatory cytokine production, augmented pathological damage in the colon, and increased mortality. The pathogenic effect of this CD4+ T cell population critically depended on coexpression of the IL-23 receptor, which was required for maximal inflammatory effects. Non–Foxp3-expressing CD4+ T cells produced IL-10, which regulated colonic inflammation and attenuated lethality in the absence of functional CD4+Foxp3+ T cells. Thus, the coordinate expression of CD11c and the IL-23 receptor defines an IL-10–regulated, colitogenic memory CD4+ T cell subset that is poised to initiate inflammation when there is loss of tolerance and breakdown of mucosal barriers. PMID:27500496

  14. CD4⁺ follicular helper T cell infiltration predicts breast cancer survival.

    PubMed

    Gu-Trantien, Chunyan; Loi, Sherene; Garaud, Soizic; Equeter, Carole; Libin, Myriam; de Wind, Alexandre; Ravoet, Marie; Le Buanec, Hélène; Sibille, Catherine; Manfouo-Foutsop, Germain; Veys, Isabelle; Haibe-Kains, Benjamin; Singhal, Sandeep K; Michiels, Stefan; Rothé, Françoise; Salgado, Roberto; Duvillier, Hugues; Ignatiadis, Michail; Desmedt, Christine; Bron, Dominique; Larsimont, Denis; Piccart, Martine; Sotiriou, Christos; Willard-Gallo, Karen

    2013-07-01

    CD4⁺ T cells are critical regulators of immune responses, but their functional role in human breast cancer is relatively unknown. The goal of this study was to produce an image of CD4⁺ T cells infiltrating breast tumors using limited ex vivo manipulation to better understand the in vivo differences associated with patient prognosis. We performed comprehensive molecular profiling of infiltrating CD4⁺ T cells isolated from untreated invasive primary tumors and found that the infiltrating T cell subpopulations included follicular helper T (Tfh) cells, which have not previously been found in solid tumors, as well as Th1, Th2, and Th17 effector memory cells and Tregs. T cell signaling pathway alterations included a mixture of activation and suppression characterized by restricted cytokine/chemokine production, which inversely paralleled lymphoid infiltration levels and could be reproduced in activated donor CD4⁺ T cells treated with primary tumor supernatant. A comparison of extensively versus minimally infiltrated tumors showed that CXCL13-producing CD4⁺ Tfh cells distinguish extensive immune infiltrates, principally located in tertiary lymphoid structure germinal centers. An 8-gene Tfh signature, signifying organized antitumor immunity, robustly predicted survival or preoperative response to chemotherapy. Our identification of CD4⁺ Tfh cells in breast cancer suggests that they are an important immune element whose presence in the tumor is a prognostic factor.

  15. CD4+ follicular helper T cell infiltration predicts breast cancer survival

    PubMed Central

    Gu-Trantien, Chunyan; Loi, Sherene; Garaud, Soizic; Equeter, Carole; Libin, Myriam; de Wind, Alexandre; Ravoet, Marie; Le Buanec, Hélène; Sibille, Catherine; Manfouo-Foutsop, Germain; Veys, Isabelle; Haibe-Kains, Benjamin; Singhal, Sandeep K.; Michiels, Stefan; Rothé, Françoise; Salgado, Roberto; Duvillier, Hugues; Ignatiadis, Michail; Desmedt, Christine; Bron, Dominique; Larsimont, Denis; Piccart, Martine; Sotiriou, Christos; Willard-Gallo, Karen

    2013-01-01

    CD4+ T cells are critical regulators of immune responses, but their functional role in human breast cancer is relatively unknown. The goal of this study was to produce an image of CD4+ T cells infiltrating breast tumors using limited ex vivo manipulation to better understand the in vivo differences associated with patient prognosis. We performed comprehensive molecular profiling of infiltrating CD4+ T cells isolated from untreated invasive primary tumors and found that the infiltrating T cell subpopulations included follicular helper T (Tfh) cells, which have not previously been found in solid tumors, as well as Th1, Th2, and Th17 effector memory cells and Tregs. T cell signaling pathway alterations included a mixture of activation and suppression characterized by restricted cytokine/chemokine production, which inversely paralleled lymphoid infiltration levels and could be reproduced in activated donor CD4+ T cells treated with primary tumor supernatant. A comparison of extensively versus minimally infiltrated tumors showed that CXCL13-producing CD4+ Tfh cells distinguish extensive immune infiltrates, principally located in tertiary lymphoid structure germinal centers. An 8-gene Tfh signature, signifying organized antitumor immunity, robustly predicted survival or preoperative response to chemotherapy. Our identification of CD4+ Tfh cells in breast cancer suggests that they are an important immune element whose presence in the tumor is a prognostic factor. PMID:23778140

  16. Foxp3-dependent Transformation of Human Primary CD4+ T Lymphocytes by the Retroviral Protein Tax

    PubMed Central

    Chen, Li; Liu, Dan; Zhang, Yang; Zhang, Huan; Cheng, Hua

    2015-01-01

    The retroviral Tax proteins of human T cell leukemia virus type 1 and 2 (HTLV-1 and -2) are highly homologous viral transactivators. Both viral proteins can immortalize human primary CD4+ memory T cells, but when expressed alone they rarely transform T cells. In the present study, we found that the Tax proteins displayed a differential ability to immortalize human CD4+Foxp3+ T cells with characteristic expression of CTLA-4 and GITR. Because epidermal growth factor receptor (EGFR) was reportedly expressed and activated in a subset of CD4+Foxp3+ T cells, we introduced an activated EGFR into Tax-immortalized CD4+Foxp3+ T cells. We observed that these modified cells were grown independently of exogenous IL-2, correlating with a T cell transformation phenotype. In Tax-immortalized CD4+Foxp3- T cells, ectopic expression of Foxp3 was a prerequisite for Tax transformation of T cells. Accordingly, treatment of the transformed T cells with erlotinib, a selective inhibitor of EGFR, induced degradation of EGFR in lysosome, consequently causing T cell growth inhibition. Further, we identified autophagy as a crucial cellular survival pathway for the transformed T cells. Silencing key autophagy molecules including Beclin1, Atg5 and PI3 kinase class III (PI3KC3) resulted in drastic impairment of T cell growth. Our data, therefore, unveiled a previously unidentified role of Foxp3 in T cell transformation, providing a molecular basis for HTLV-1 transformation of CD4+Foxp3+ T cells. PMID:26381169

  17. Correlation between total lymphocyte count, hemoglobin, hematocrit and CD4 count in HIV patients in Nigeria.

    PubMed

    Emuchay, Charles Iheanyichi; Okeniyi, Shemaiah Olufemi; Okeniyi, Joshua Olusegun

    2014-04-01

    The expensive and technology limited setting of CD4 count testing is a major setback to the initiation of HAART in a resource limited country like Nigeria. Simple and inexpensive tools such as Hemoglobin (Hb) measurement and Total Lymphocyte Count (TLC) are recommended as substitute marker. In order to assess the correlations of these parameters with CD4 count, 100 "apparently healthy" male volunteers tested HIV positive aged ≥ 20 years but ≤ 40 years were recruited and from whom Hb, Hct, TLC and CD4 count were obtained. The correlation coefficients, R, the Nash-Sutcliffe Coefficient of Efficiency (CoE) and the p-values of the ANOVA model of Hb, Hct and TLC with CD4 count were assessed. The assessments show that there is no significant relationship of any of these parameters with CD4 count and the correlation coefficients are very weak. This study shows that Hb, Hct and TLC cannot be substitute for CD4 count as this might lead to certain individuals' deprivation of required treatment.

  18. CD4 binding site broadly neutralizing antibody selection of HIV-1 escape mutants.

    PubMed

    Dreja, Hanna; Pade, Corinna; Chen, Lei; McKnight, Áine

    2015-07-01

    All human immunodeficiency virus type-1 (HIV-1) viruses use CD4 to enter cells. Consequently, the viral envelope CD4-binding site (CD4bs) is relatively conserved, making it a logical neutralizing antibody target. It is important to understand how CD4-binding site variation allows for escape from neutralizing antibodies. Alanine scanning mutagenesis identifies residues in antigenic sites, whereas escape mutant selection identifies viable mutants. We selected HIV-1 to escape CD4bs neutralizing mAbs b12, A12 and HJ16. Viruses that escape from A12 and b12 remained susceptible to HJ16, VRC01 and J3, whilst six different viruses that escape HJ16 remained sensitive to A12, b12 and J3. In contrast, their sensitivity to VRC01 was variable. Triple HJ16/A12/b12-resistant virus proved that HIV-1 could escape multiple broadly neutralizing monoclonal antibodies, but still retain sensitivity to VRC01 and the llama-derived J3 nanobody. This antigenic variability may reflect that occurring in circulating viruses, so studies like this can predict immunologically relevant antigenic forms of the CD4bs for inclusion in HIV-1 vaccines.

  19. Abdominal visceral adiposity influences CD4+ T cell cytokine production in pregnancy.

    PubMed

    Ozias, Marlies K; Li, Shengqi; Hull, Holly R; Brooks, William M; Petroff, Margaret G; Carlson, Susan E

    2015-02-01

    Women with pre-gravid obesity are at risk for pregnancy complications. While the macrophage response of obese pregnant women categorized by body mass index (BMI) has been documented, the relationship between the peripheral CD4(+) T cell cytokine profile and body fat compartments during pregnancy is unknown. In this study, third trimester peripheral CD4(+) T cell cytokine profiles were measured in healthy pregnant women [n=35; pre-pregnancy BMI: 18.5-40]. CD4(+) T cells were isolated from peripheral blood mononuclear cells and stimulated to examine their capacity to generate cytokines. Between 1 and 3weeks postpartum, total body fat was determined by dual-energy X-ray absorptiometry and abdominal subcutaneous and visceral fat masses were determined by magnetic resonance imaging. Pearson's correlation was performed to assess relationships between cytokines and fat mass. Results showed that greater abdominal visceral fat mass was associated with a decrease in stimulated CD4(+) T cell cytokine expression. IFN-gamma, TNF-alpha, IL-12p70, IL-10 and IL-17A were inversely related to visceral fat mass. Chemokines CCL3 and IL-8 and growth factors G-CSF and FLT-3L were also inversely correlated. Additionally, total body fat mass was inversely correlated with FGF-2 while abdominal subcutaneous fat mass and BMI were unrelated to any CD4(+) T cell cytokine. In conclusion, lower responsiveness of CD4(+) T cell cytokines associated with abdominal visceral fat mass is a novel finding late in gestation.

  20. Altered Intracellular ATP Production by Activated CD4+ T-Cells in Very Preterm Infants

    PubMed Central

    Corvaglia, Luigi; Gabrielli, Liliana; Chiereghin, Angela; Lazzarotto, Tiziana

    2016-01-01

    Background. The neonatal immune system is not fully developed at birth; newborns have adequate lymphocytes counts but these cells lack function. Objective. To assess the activity of T-cells and the influence of the main perinatal factors in very preterm infants (birth weight < 1500 g). Design. Blood samples from 59 preterm infants (21/59 were dizygotic twins) were collected at birth and at 30 days of life to measure CD4+ T-cell activity using the ImmuKnow™ assay. Fifteen healthy adults were included as a control group. Results. CD4+ T-cell activity was lower in VLBW infants compared with adults (p < 0.001). Twins showed lower immune activity compared to singletons (p = 0.005). Infants born vaginally showed higher CD4+ T-cell activity compared to those born by C-section (p = 0.031); infants born after prolonged Premature Rupture of Membranes (pPROM) showed higher CD4+ T-cell activity at birth (p = 0.002) compared to infants born without pPROM. Low CD4+ T-cell activity at birth is associated with necrotizing enterocolitis (NEC) in the first week of life (p = 0.049). Conclusions. Preterm infants show a lack in CD4+ T-cell activity at birth. Perinatal factors such as intrauterine inflammation, mode of delivery, and zygosity can influence the adaptive immune activation capacity at birth and can contribute to exposing these infants to serious complications such as NEC. PMID:28070527

  1. Interleukin 4-producing CD4+ T cells in the skin of cats with allergic dermatitis.

    PubMed

    Roosje, P J; Dean, G A; Willemse, T; Rutten, V P M G; Thepen, T

    2002-03-01

    Lesional skin of cats with allergic dermatitis has a cellular infiltrate and a CD4/CD8 ratio comparable to that in humans with atopic dermatitis. CD4+ helper T cells and in particular cells belonging to the Th2 subset play an important role in disease pathogenesis in humans. We investigated the cytokine pattern of CD4+ T cells in situ, with special emphasis on the putative presence of cells producing interleukin 4 (IL4), in cats with allergic dermatitis. Immunohistochemical procedures were used to determine that CD4+ T cells in lesional and nonlesional skin of cats with allergic dermatitis can produce IL4, as occurs in humans. Lesional and nonlesional skin of cats with allergic dermatitis had significantly more IL4+ T cells (P = 0.001) than did skin of healthy control cats. Double staining indicated that all IL4+ cells were positive for pan-T or CD4 markers. Double labeling for mast cell chymase and IL4 stained primarily different cells. Western blotting demonstrated cross-reactivity between the antibody against human IL4 and a feline recombinant IL4. These results indicate that IL4 is primarily produced by CD4+ T cells and is also present in clinically uninvolved skin, indicating a role in the pathogenesis of allergic dermatitis in cats.

  2. Foxp3-dependent transformation of human primary CD4+ T lymphocytes by the retroviral protein tax.

    PubMed

    Chen, Li; Liu, Dan; Zhang, Yang; Zhang, Huan; Cheng, Hua

    2015-10-23

    The retroviral Tax proteins of human T cell leukemia virus type 1 and 2 (HTLV-1 and -2) are highly homologous viral transactivators. Both viral proteins can immortalize human primary CD4+ memory T cells, but when expressed alone they rarely transform T cells. In the present study, we found that the Tax proteins displayed a differential ability to immortalize human CD4+Foxp3+ T cells with characteristic expression of CTLA-4 and GITR. Because epidermal growth factor receptor (EGFR) was reportedly expressed and activated in a subset of CD4+Foxp3+ T cells, we introduced an activated EGFR into Tax-immortalized CD4+Foxp3+ T cells. We observed that these modified cells were grown independently of exogenous IL-2, correlating with a T cell transformation phenotype. In Tax-immortalized CD4+Foxp3- T cells, ectopic expression of Foxp3 was a prerequisite for Tax transformation of T cells. Accordingly, treatment of the transformed T cells with erlotinib, a selective inhibitor of EGFR, induced degradation of EGFR in lysosome, consequently causing T cell growth inhibition. Further, we identified autophagy as a crucial cellular survival pathway for the transformed T cells. Silencing key autophagy molecules including Beclin1, Atg5 and PI3 kinase class III (PI3KC3) resulted in drastic impairment of T cell growth. Our data, therefore, unveiled a previously unidentified role of Foxp3 in T cell transformation, providing a molecular basis for HTLV-1 transformation of CD4+Foxp3+ T cells.

  3. The effect of probiotics on CD4 counts among people living with HIV: a systematic review.

    PubMed

    Miller, H; Ferris, R; Phelps, B R

    2016-06-01

    Probiotics are defined by the WHO as 'live microorganisms which when administered in adequate amounts confer a health benefit on the host'. Ongoing research has shown probiotics provide benefits to humans, including protection and restoration of the gastrointestinal and other mucosal tracts. As human immunodeficiency virus (HIV) activates gut-associated lymphoid tissue (GALT), several studies have investigated the effect of probiotics on CD4 cell count and related outcomes among those living with HIV. These studies are summarised here. Manuscripts were identified using the search terms 'probiotics', 'synbiotics', 'HIV', and 'CD4', and were reviewed for relevance and inclusion of CD4 count as an immunologic endpoint. Bibliographies of relevant manuscripts were also reviewed for additional studies matching inclusion and exclusion criteria. The search yielded 91 results; 13 included relevant outcomes. Seven of these studies produced beneficial CD4 outcomes, while the remaining 6 reported on insignificant beneficial or negative CD4 outcomes. The studies summarised here collectively suggest that daily consumption of probiotics over a prolonged period of time may improve CD4 count in people living with HIV.

  4. A novel role for CD4+ T cells in the control of cachexia.

    PubMed

    Wang, Zhuangzhi; Zhao, Chunfang; Moya, Rosa; Davies, Joanna D

    2008-10-01

    Cachexia is the dramatic weight loss and muscle atrophy seen in chronic disease states, including autoimmunity, cancer, and infection, and is often associated with lymphopenia. We have previously shown that CD4(+) T cells that express the lowest density of CD44 (CD4(+)CD44(v.low)) are significantly reduced in diabetic NOD mice that are cachexic compared with diabetic mice that are not cachexic. Using this model, and a model of cancer cachexia, we test the hypothesis that CD4(+)CD44(v.low) cells play an active role in protecting the host from cachexia. CD4(+)CD44(v.low) cells, but not CD4(+) cells depleted of CD44(v.low) cells, delay the onset of wasting when infused into either diabetic or prediabetic NOD recipients. However, no significant effect on the severity of diabetes was detected. In a model of cancer cachexia, they significantly reduce muscle atrophy, and inhibit muscle protein loss and DNA loss, even when given after the onset of cachexia. Protection from wasting and muscle atrophy by CD4(+)CD44(v.low) cells is associated with protection from lymphopenia. These data suggest, for the first time, a role for an immune cell subset in protection from cachexia, and further suggest that the mechanism of protection is independent of protection from autoimmunity.

  5. CD4+CD25+ Treg cells in patients with toenail onychomycosis.

    PubMed

    Kaya, Tamer Irfan; Eskandari, Gulcin; Guvenc, Ulas; Gunes, Gulcan; Tursen, Umit; Burak Cimen, M Y; Ikizoglu, Guliz

    2009-10-01

    The essential role played by CD25+CD4+ regulatory T (Treg) cells in the control of immunity against some pathogens such as Helicobacter pylori is now well established. But their role in cutaneous fungal infections is still unknown. Onychomycosis is the chronic fungal infection of the nails, which is very common. The aim of this study was to evaluate possible relationship of CD4+CD25+ Treg cells and onychomycosis. Peripheral blood samples were investigated for CD4+CD25+ Treg cells using flow cytometry analysis in 43 toenail onychomycosis patients and in 30 healthy controls. We have found that onychomycosis patients had a higher expression of CD25+CD4+ Treg cells than controls, with values of 8.45 +/- 4.47% versus 4.64 +/- 1.59%, respectively (P = 0.001). The results of this study suggests that increased numbers of CD4+CD25+ Treg cells may play a role in failure of clearance of dermatophytes from skin by preventing the protective inflammation which is leading to development of onychomycosis. Accordingly, we address the possibility that CD4+CD25+ Treg cells may play a role in immune pathogenesis of other superficial fungal infections.

  6. CD4+ and CD8+ T cells have opposing roles in breast cancer progression and outcome

    PubMed Central

    Zhang, Qunyuan; Ye, Jian; Wang, Fang; Zhang, Yanping; Hunborg, Pamela; Varvares, Mark A.; Hoft, Daniel F.; Hsueh, Eddy C.; Peng, Guangyong

    2015-01-01

    The Cancer Immunoediting concept has provided critical insights suggesting dual functions of immune system during the cancer initiation and development. However, the dynamics and roles of CD4+ and CD8+ T cells in the pathogenesis of breast cancer remain unclear. Here we utilized two murine breast cancer models (4T1 and E0771) and demonstrated that both CD4+ and CD8+ T cells were increased and involved in immune responses, but with distinct dynamic trends in breast cancer development. In addition to cell number increases, CD4+ T cells changed their dominant subsets from Th1 in the early stages to Treg and Th17 cells in the late stages of the cancer progression. We also analyzed CD4+ and CD8+ T cell infiltration in primary breast cancer tissues from cancer patients. We observed that CD8+ T cells are the key effector cell population mediating effective anti-tumor immunity resulting in better clinical outcomes. In contrast, intra-tumoral CD4+ T cells have negative prognostic effects on breast cancer patient outcomes. These studies indicate that CD4+ and CD8+ T cells have opposing roles in breast cancer progression and outcomes, which provides new insights relevant for the development of effective cancer immunotherapeutic approaches. PMID:25968569

  7. Impact of nicotine on the interplay between human periodontal ligament cells and CD4+ T cells.

    PubMed

    Ge, Xin; Liu, Ying-Feng; Wong, Yong; Wu, Li-Zheng; Tan, Ling; Liu, Fen; Wang, Xiao-Jing

    2016-09-01

    Periodontitis is a common infectious disease associated with destruction of periodontal ligaments and alveolar bones. CD4(+) T cell-mediated immune response is involved in the progression of periodontitis. Tobacco consumption increases the risk of periodontal disease. However, the impact of nicotine on the interaction between human periodontal ligament (PDL) cells and CD4(+) T cells remains unrevealed. Our study aims to investigate the effect of nicotine on PDL cells and the cocultured CD4(+) T cells. The PDL cell cultures were established by explants from healthy individuals, exposed to nicotine or α-bungarotoxin (α-BTX), and incubated solely or in combination with CD4(+) T cells. Afterwards, cell viability, secreted cytokines, and matrix metalloproteinases (MMPs) were evaluated. In monoculture of PDL cells, nicotine dramatically repressed cell viability and increased apoptosis. Meanwhile, α-BTX largely reversed the nicotine-induced apoptosis and increased viability of PDL cells. Compared with the monoculture, MMP-1, MMP-3, interleukin (IL)-1β, IL-6, IL-17, and IL-21 in supernatant of cocultures were markedly elevated after treatment with nicotine. Moreover, α-BTX significantly attenuated nicotine-triggered production of these components either in mono- or co-cultures. In addition, PDL cell-derived CXCL12 following nicotine treatment recruited CD4(+) T cells. Above all, nicotine deteriorated periodontitis partially by promoting PDL cell-CD4(+) T cell-mediated inflammatory response and matrix degradation.

  8. Expression of fas protein on CD4+T cells irradiated by low level He-Ne

    NASA Astrophysics Data System (ADS)

    Nie, Fan; Zhu, Jing; Zhang, Hui-Guo

    2005-07-01

    Objective: To investigate the influence on the Expression of Fas protein on CD4+ T cells irradiated by low level He-Ne laser in the cases of psoriasis. Methods:the expression of CD4+ T Fas protein was determined in the casee of psoriasis(n=5) pre and post-low level laser irradiation(30 min、60min and 120min)by flow cytometry as compared withthe control(n=5). Results:In the cases of psoriasis,the expression of CD4+T FAS protein 21.4+/-3.1% was increased significantly than that of control group 16.8+/-2.1% pre-irradiation, p<0.05in the control,there is no difference between pre and post- irradiation,p>0.05in the cases , the expression of CD4+T Fas protein wae positively corelated to the irradiation times, when the energy density arrived to 22.92J/cm2(60 minutes)and 45.84J/cm2(120minutes), the expression of CD4+ T Fas protein was increased significantly as compared with pre-irradiation,p<0.05.Conclusion: The expression of CD4+T Fas protein may be increased by low level He-Ne laser irradiation ,the uncontrolled status of apoptosis could be corrected.

  9. The generation and antigen-specificity of CD4+CD25+ regulatory T cells.

    PubMed

    Taams, Leonie S; Curnow, S John; Vukmanovic-Stejic, M; Akbar, Arne N

    2006-09-01

    CD4+CD25+ regulatory T cells are essential components of the immune system. They help to maintain immune tolerance by exerting suppressive effects on cells of the adaptive and innate immune system. In the last few years there has been an abundance of papers addressing the suppressive effects of CD4+CD25+ regulatory T cells and their putative role in various experimental disease models and human diseases. Despite the enormous amounts of data on these cells a number of controversial issues still exists. CD4+CD25+ regulatory T cells were originally described as thymus-derived anergic/suppressive T cells. Recent papers however indicate that these cells might also be generated in the periphery. Due to the thymic development of CD4+CD25+ regulatory T cells it was thought that these cells were specific for self-antigens. Indeed it was shown that CD4+CD25+ regulatory T cells could be positively selected upon high affinity interaction with self-antigens. However, evidence is accumulating that these cells might also interact with non-self antigens. Finally, in the literature there is conflicting evidence regarding the role of soluble factors versus cell-contact in the mechanism of suppression. The aim of this review is to summarize the evidence supporting these opposing viewpoints and to combine them into a general model for the origin, function and antigen-specificity of CD4+CD25+ regulatory T cells.

  10. Interfacial cavity filling to optimize CD4-mimetic miniprotein interactions with the HIV-1 surface protein

    PubMed Central

    Morellato-Castillo, Laurence; Acharya, Priyamvada; Combes, Olivier; Michiels, Johan; Descours, Anne; Ramos, Oscar H. P.; Yang, Yongping; Vanham, Guido; Ariën, Kevin K.; Kwong, Peter D.; Martin, Loïc; Kessler, Pascal

    2013-01-01

    Ligand affinities can be optimized by interfacial cavity filling. A hollow (Phe43 cavity) between HIV-1 surface protein (gp120) and cluster of differentiation 4 (CD4) receptor, extends beyond residue phenylalanine 43 of CD4 and cannot be fully accessed by natural amino acids. To increase HIV-1 gp120 affinity for a family of CD4-mimetic miniproteins (miniCD4s), we targeted the gp120 Phe43 cavity with eleven non-natural phenylalanine derivatives, introduced into a miniCD4 named M48 (1). The best derivative named M48U12 (13) binds HIV-1 YU2 gp120 with 8 pM affinity, and shows potent HIV-1 neutralization. It contained a methylcyclohexyl derivative of 4-aminophenylalanine and its co-crystal structure with gp120 revealed the cyclohexane ring buried within the gp120 hydrophobic core but able to assume multiple orientations in the binding pocket, and an aniline nitrogen potentially providing a focus for further improvement. Altogether, the results provide a framework for filling the interfacial Phe43 cavity to enhance miniCD4 affinity. PMID:23710622

  11. Interfacial Cavity Filling To Optimize CD4-Mimetic Miniprotein Interactions with HIV-1 Surface Glycoprotein

    SciTech Connect

    Morellato-Castillo, Laurence; Acharya, Priyamvada; Combes, Olivier; Michiels, Johan; Descours, Anne; Ramos, Oscar H.P.; Yang, Yongping; Vanham, Guido; Ariën, Kevin K.; Kwong, Peter D.; Martin, Loïc; Kessler, Pascal

    2013-08-05

    Ligand affinities can be optimized by interfacial cavity filling. A hollow (Phe43 cavity) between HIV-1 surface glycoprotein (gp120) and cluster of differentiation 4 (CD4) receptor extends beyond residue phenylalanine 43 of CD4 and cannot be fully accessed by natural amino acids. To increase HIV-1 gp120 affinity for a family of CD4-mimetic miniproteins (miniCD4s), we targeted the gp120 Phe43 cavity with 11 non-natural phenylalanine derivatives, introduced into a miniCD4 named M48 (1). The best derivative, named M48U12 (13), bound HIV-1 YU2 gp120 with 8 pM affinity and showed potent HIV-1 neutralization. It contained a methylcyclohexyl derivative of 4-aminophenylalanine, and its cocrystal structure with gp120 revealed the cyclohexane ring buried within the gp120 hydrophobic core but able to assume multiple orientations in the binding pocket, and the aniline nitrogen potentially providing a focus for further improvement. Altogether, the results provide a framework for filling the interfacial Phe43 cavity to enhance miniCD4 affinity.

  12. IL-21 is required for CD4 memory formation in response to viral infection

    PubMed Central

    Yuan, Yuqing; Huang, Xiaopei

    2017-01-01

    IL-21 has been shown to play an important role in the CD8 T cell response during acute and chronic viral infections. However, the role of IL-21 signaling in the CD4 T cell response to viral infection remains incompletely defined. In a model of infection with vaccinia virus, we show that intrinsic IL-21 signaling on CD4 T cells was critical for the formation of memory CD4 T cells in vivo. We further reveal that IL-21 promoted CD4 T cell survival in a mechanism dependent on activation of the STAT1 and STAT3 signaling pathways. In addition, the activation of Akt is also required for IL-21–dependent survival of CD4 T cells in vivo. These results identify a critical role for intrinsic IL-21 signaling in CD4 T cell survival and memory formation in response to viral infection in vivo and may provide insights into the design of effective vaccine strategies.

  13. Structural repertoire of HIV-1-neutralizing antibodies targeting the CD4 supersite in 14 donors

    PubMed Central

    Zhou, Tongqing; Lynch, Rebecca M.; Chen, Lei; Acharya, Priyamvada; Wu, Xueling; Doria-Rose, Nicole A.; Joyce, M. Gordon; Lingwood, Daniel; Soto, Cinque; Bailer, Robert T.; Ernandes, Michael J.; Kong, Rui; Longo, Nancy S.; Louder, Mark K.; McKee, Krisha; O’Dell, Sijy; Schmidt, Stephen D.; Tran, Lillian; Yang, Zhongjia; Druz, Aliaksandr; Luongo, Timothy S.; Moquin, Stephanie; Srivatsan, Sanjay; Yang, Yongping; Zhang, Baoshan; Zheng, Anqi; Pancera, Marie; Kirys, Tatsiana; Georgiev, Ivelin S.; Gindin, Tatyana; Peng, Hung-Pin; Yang, An-Suei; Mullikin, James C.; Gray, Matthew D.; Stamatatos, Leonidas; Burton, Dennis R.; Koff, Wayne C.; Cohen, Myron S.; Haynes, Barton F.; Casazza, Joseph P.; Connors, Mark; Corti, Davide; Lanzavecchia, Antonio; Sattentau, Quentin J.; Weiss, Robin A.; West, Anthony P.; Bjorkman, Pamela J.; Scheid, Johannes F.; Nussenzweig, Michel C.; Shapiro, Lawrence; Mascola, John R.; Kwong, Peter D.

    2015-01-01

    The site on the HIV-1 gp120 glycoprotein that binds the CD4 receptor is recognized by broadly reactive antibodies, several of which neutralize over 90% of HIV-1 strains. To understand how antibodies achieve such neutralization, we isolated CD4-binding-site (CD4bs) antibodies and analyzed 16 co-crystal structures –8 determined here– of CD4bs antibodies from 14 donors. The 16 antibodies segregated by recognition mode and developmental ontogeny into two types: CDR H3-dominated and VH-gene-restricted. Both could achieve greater than 80% neutralization breadth, and both could develop in the same donor. Although paratope chemistries differed, all 16 gp120-CD4bs antibody complexes showed geometric similarity, with antibody-neutralization breadth correlating with antibody-angle of approach relative to the most effective antibody of each type. The repertoire for effective recognition of the CD4 supersite thus comprises antibodies with distinct paratopes arrayed about two optimal geometric orientations, one achieved by CDR H3 ontogenies and the other achieved by VH-gene-restricted ontogenies. PMID:26004070

  14. Definition of target antigens for naturally occurring CD4(+) CD25(+) regulatory T cells.

    PubMed

    Nishikawa, Hiroyoshi; Kato, Takuma; Tawara, Isao; Saito, Kanako; Ikeda, Hiroaki; Kuribayashi, Kagemasa; Allen, Paul M; Schreiber, Robert D; Sakaguchi, Shimon; Old, Lloyd J; Shiku, Hiroshi

    2005-03-07

    The antigenic targets recognized by naturally occurring CD4(+) CD25(+) regulatory T cells (T reg cells) have been elusive. We have serologically defined a series of broadly expressed self-antigens derived from chemically induced mouse sarcomas by serological identification of antigens by recombinant expression cloning (SEREX). CD4(+) CD25(+) T cells from mice immunized with SEREX-defined self-antigens had strong suppressive activity on peptide-specific proliferation of CD4(+) CD25(-) T cells and CD8(+) T cells. The suppressive effect was observed without in vitro T cell stimulation. Foxp3 expression in these CD4(+) CD25(+) T cells from immunized mice was 5-10 times greater than CD4(+) CD25(+) T cells derived from naive mice. The suppressive effect required cellular contact and was blocked by anti-glucocorticoid-induced tumor necrosis factor receptor family-related gene antibody. In vitro suppressive activity essentially disappeared 8 wk after the last immunization. However, it was regained by in vitro restimulation with cognate self-antigen protein but not with control protein. We propose that SEREX-defined self-antigens such as those used in this study represent self-antigens that elicit naturally occurring CD4(+) CD25(+) T reg cells.

  15. The Story of CD4+CD28− T Cells Revisited: Solved or Still Ongoing?

    PubMed Central

    Maly, Kathrin

    2015-01-01

    CD4+CD28− T cells are a unique type of proinflammatory T cells characterised by blockade of costimulatory CD28 receptor expression at the transcriptional level, which is still reversible by IL-12. In healthy individuals older than 65 years, these cells may accumulate to up to 50% of total CD4+ T lymphocytes as in many immune-mediated diseases, immunodeficiency, and specific infectious diseases. Here we focus on CD4+CD28− T cells in chronic immune-mediated diseases, summarizing various phenotypic and functional characteristics, which vary depending on the underlying disease, disease activity, and concurrent treatment. CD4+CD28− T cells present as effector/memory cells with increased replicative history and oligoclonality but reduced apoptosis. As an alternative costimulatory signal instead of CD28, not only natural killer cell receptors and Toll-like receptors, but also CD47, CTLA-4, OX40, and 4-1BB have to be considered. The proinflammatory and cytotoxic capacities of these cells indicate an involvement in progression and maintenance of chronic immune-mediated disease. So far it has been shown that treatment with TNF-α blockers, abatacept, statins, and polyclonal antilymphocyte globulins (ATG) mediates reduction of the CD4+CD28− T cell level. The clinical relevance of targeting CD4+CD28− T cells as a therapeutic option has not been examined so far. PMID:25834833

  16. Innate-like CD4 T cells selected by thymocytes suppress adaptive immune responses against bacterial infections

    PubMed Central

    Qiao, Yu; Gray, Brian M.; Sofi, Mohammed H.; Bauler, Laura D.; Eaton, Kathryn A.; O'Riordan, Mary X. D.; Chang, Cheong-Hee

    2012-01-01

    We have reported a new innate-like CD4 T cell population that expresses cell surface makers of effector/memory cells and produce Th1 and Th2 cytokines immediately upon activation. Unlike conventional CD4 T cells that are selected by thymic epithelial cells, these CD4 T cells, named T-CD4 T cells, are selected by MHC class II expressing thymocytes. Previously, we showed that the presence of T-CD4 T cells protected mice from airway inflammation suggesting an immune regulatory role of T-CD4 T cells. To further understand the function of T-CD4 T cells, we investigated immune responses mediated by T-CD4 T cells during bacterial infection because the generation of antigen specific CD4 T cells contributes to clearance of infection and for the development of immune memory. The current study shows a suppressive effect of T-CD4 T cells on both CD8 and CD4 T cell-mediated immune responses during Listeria and Helicobacter infections. In the mouse model of Listeria monocytogenes infection, T-CD4 T cells resulted in decreasedfrequency of Listeria-specific CD8 T cells and the killing activity of them. Furthermore, mice with T-CD4 T cells developed poor immune memory, demonstrated by reduced expansion of antigen-specific T cells and high bacterial burden upon re-infection. Similarly, the presence of T-CD4 T cells suppressed the generation of antigen-specific CD4 T cells in Helicobacter pylori infected mice. Thus, our studies reveal a novel function of T-CD4 T cells in suppressing anti-bacterial immunity. PMID:23264931

  17. Practice paper of the Academy of Nutrition and Dietetics abstract: ethical and legal issues of feeding and hydration.

    PubMed

    Schwartz, Denise Baird; Posthauer, Mary Ellen; O'Sullivan Maillet, Julie

    2013-07-01

    It is the position of the Academy of Nutrition and Dietetics that individuals have the right to request or refuse nutrition and hydration as medical treatment. Registered dietitians should work collaboratively as part of an interprofessional team to make recommendations on providing, withdrawing, or withholding nutrition and hydration in individual cases and serve as active members of institutional ethics committees. This practice paper provides a proactive, integrated, systematic process to implement the Academy's position. The position and practice papers should be used together to address the history and supporting information of ethical and legal issues of feeding and hydration identified by the Academy. Elements of collaborative ethical deliberation are provided for pediatrics and adults and in different conditions. The process of ethical deliberation is presented with the roles and responsibilities of the registered dietitian and the dietetic technician, registered. Understanding the importance and applying concepts dealing with cultural values and religious diversity is necessary to integrate clinical ethics into nutrition care. Incorporating screening for quality-of-life goals is essential before implementing the Nutrition Care Process and improving health literacy with individual interactions. Developing institution-specific policies and procedures is necessary to accelerate the practice change with artificial nutrition, clinical ethics, and quality improvement projects to determine best practice. This paper supports the "Position of the Academy of Nutrition and Dietetics: Ethical and Legal Issues of Feeding and Hydration" published in the June 2013 issue of the Journal of the Academy of Nutrition and Dietetics.

  18. Child gender and weight status moderate the relation of maternal feeding practices to body esteem in 1st grade children.

    PubMed

    Shriver, Lenka H; Hubbs-Tait, Laura; Harrist, Amanda W; Topham, Glade; Page, Melanie

    2015-06-01

    Prevention of body dissatisfaction development is critical for minimizing adverse effects of poor body esteem on eating behaviors, self-esteem, and overall health. Research has examined body esteem and its correlates largely in pre-adolescents and adolescents; however, important questions remain about factors influencing body esteem of younger children. The main purpose of this study was to test moderation by children's gender and weight status of the relation of maternal controlling feeding practices to 1st graders' body esteem. The Body Esteem Scale (BES) and anthropometric measurements were completed during one-on-one child interviews at school. Mothers completed the Child Feeding Questionnaire (restriction, monitoring, concern, self-assessed maternal weight). A total of 410 mother/child dyads (202 girls) participated. Percent of children classified as overweight (BMI-for-age ≥85th) was: girls - 29%; boys - 27%. Gender moderated the relation between restriction and body esteem (β = -.140, p = .05), with maternal restriction predicting body esteem in girls but not boys. The hypothesized three-way interaction among gender, child weight status, and monitoring was confirmed. Monitoring was significantly inversely related to body esteem only for overweight/obese girls (b = -1.630). The moderating influence of gender or gender and weight status on the link between maternal feeding practices and body esteem suggests the importance of body esteem interventions for girls as early as first grade.

  19. Early childhood feeding practices and dental caries in preschool children: a multi-centre birth cohort study

    PubMed Central

    2011-01-01

    Background Dental caries (decay) is an international public health challenge, especially amongst young children. Early Childhood Caries is a rapidly progressing disease leading to severe pain, anxiety, sepsis and sleep loss, and is a major health problem particularly for disadvantaged populations. There is currently a lack of research exploring the interactions between risk and protective factors in the development of early childhood caries, in particular the effects of infant feeding practises. Methods/Design This is an observational cohort study and involves the recruitment of a birth cohort from disadvantaged communities in South Western Sydney. Mothers will be invited to join the study soon after the birth of their child at the time of the first home visit by Child and Family Health Nurses. Data on feeding practices and dental health behaviours will be gathered utilizing a telephone interview at 4, 8 and 12 months, and thereafter at 6 monthly intervals until the child is aged 5 years. Information collected will include a) initiation and duration of breastfeeding, b) introduction of solid food, c) intake of cariogenic and non-cariogenic foods, d) fluoride exposure, and e) oral hygiene practices. Children will have a dental and anthropometric examination at 2 and 5 years of age and the main outcome measures will be oral health quality of life, caries prevalence and caries incidence. Discussion This study will provide evidence of the association of early childhood feeding practices and the oral health of preschool children. In addition, information will be collected on breastfeeding practices and the oral health concerns of mothers living in disadvantaged areas in South Western Sydney. PMID:21223601

  20. The organotin-induced thymus atrophy, characterized by depletion of CD4+ CD8+ thymocytes, is preceded by a reduction of the immature CD4- CD8+ TcR alpha beta-/low CD2high thymoblast subset.

    PubMed Central

    Pieters, R H; Bol, M; Lam, B W; Seinen, W; Penninks, A H

    1992-01-01

    Thymic changes in the rat induced by the thymus atrophy-inducing organotin compound di-n-butyltin dichloride (DBTC) were examined using FACS analyses. The number of CD4+CD8+ thymocytes was reduced by DBTC treatment from Day 2 onwards and reached minimum level on Days 4 and 5 after dosing. On these days the CD4-CD8- and both the CD4-CD8+ and CD4+CD8- subsets were not affected. On Day 2 we observed a reduced proportion of transferrin receptor (CD71)-positive CD4-OX44- cells, representing the cycling immature CD4-CD8+ cells, and of CD71+OX44- cells, representing the cycling CD4+CD8+ cells, but not of CD71+CD4-CD8- cells. When compared to controls, the FSChigh cell population of DBTC-treated rats contained less CD4-OX44- and OX44- cells, which were further characterized as CD2high and T-cell receptor (TcR)alpha beta- low. Moreover, fewer TcR alpha beta high cells were detected in the OX44- thymoblast subset of DBTC-treated rats. The number of CD4-CD8- thymoblasts appeared marginally decreased while the numbers of CD4+OX44+ cells, representing mature CD4+ cells, were not affected. These data indicate that DBTC causes a preferential initial depletion of immature CD4-CD8+CD2high TcR alpha beta-low thymoblasts. This initial event may result in a decreased formation of CD4+CD8+ thymoblasts and of small CD4+CD8+ thymocytes. These characteristics of the initially depleted subset indicate a specific anti-proliferative effect of DBTC and may give clues for the mechanism involved in the induction of thymus atrophy. PMID:1353062

  1. Empiric Deworming and CD4 Count Recovery in HIV-Infected Ugandans Initiating Antiretroviral Therapy

    PubMed Central

    Lankowski, Alexander J.; Tsai, Alexander C.; Kanyesigye, Michael; Bwana, Mwebesa; Haberer, Jessica E.; Wenger, Megan; Martin, Jeffrey N.; Bangsberg, David R.; Hunt, Peter W.; Siedner, Mark J.

    2014-01-01

    Background There is conflicting evidence on the immunologic benefit of treating helminth co-infections (“deworming”) in HIV-infected individuals. Several studies have documented reduced viral load and increased CD4 count in antiretroviral therapy (ART) naïve individuals after deworming. However, there are a lack of data on the effect of deworming therapy on CD4 count recovery among HIV-infected persons taking ART. Methodology/Principal Findings To estimate the association between empiric deworming therapy and CD4 count after ART initiation, we performed a retrospective observational study among HIV-infected adults on ART at a publicly operated HIV clinic in southwestern Uganda. Subjects were assigned as having received deworming if prescribed an anti-helminthic agent between 7 and 90 days before a CD4 test. To estimate the association between deworming and CD4 count, we fit multivariable regression models and analyzed predictors of CD4 count, using a time-by-interaction term with receipt or non-receipt of deworming. From 1998 to 2009, 5,379 subjects on ART attended 21,933 clinic visits at which a CD4 count was measured. Subjects received deworming prior to 668 (3%) visits. Overall, deworming was not associated with a significant difference in CD4 count in either the first year on ART (β = 42.8; 95% CI, −2.1 to 87.7) or after the first year of ART (β = −9.9; 95% CI, −24.1 to 4.4). However, in a sub-analysis by gender, during the first year of ART deworming was associated with a significantly greater rise in CD4 count (β = 63.0; 95% CI, 6.0 to 120.1) in females. Conclusions/Significance Empiric deworming of HIV-infected individuals on ART conferred no significant generalized benefit on subsequent CD4 count recovery. A significant association was observed exclusively in females and during the initial year on ART. Our findings are consistent with recent studies that failed to demonstrate an immunologic advantage to empirically deworming ART

  2. An HIV gp120-CD4 Immunogen Does Not Elicit Autoimmune Antibody Responses in Cynomolgus Macaques.

    PubMed

    Schwartz, Jennifer A; Prado, Ilia; Misamore, Johnathan; Weiss, Deborah; Francis, Jesse; Pal, Ranajit; Huaman, Maria; Cristillo, Anthony; Lewis, George K; Gallo, Robert C; DeVico, Anthony L; Fouts, Timothy R

    2016-07-01

    A promising concept for human immunodeficiency virus (HIV) vaccines focuses immunity on the highly conserved transition state structures and epitopes that appear when the HIV glycoprotein gp120 binds to its receptor, CD4. We are developing chimeric antigens (full-length single chain, or FLSC) in which gp120 and CD4 sequences are flexibly linked to allow stable intrachain complex formation between the two moieties (A. DeVico et al., Proc Natl Acad Sci U S A 104:17477-17482, 2007, doi:10.1073/pnas.0707399104; T. R. Fouts et al., J Virol 74:11427-11436, 2000, doi:10.1128/JVI.74.24.11427-11436.2000). Proof of concept studies with nonhuman primates show that FLSC elicited heterologous protection against simian-human immunodeficiency virus (SHIV)/simian immunodeficiency virus (SIV) (T. R. Fouts et al., Proc Natl Acad Sci U S A 112:E992-E999, 2016, doi:10.1073/pnas.1423669112), which correlated with antibodies against transition state gp120 epitopes. Nevertheless, advancement of any vaccine that comprises gp120-CD4 complexes must consider whether the CD4 component breaks tolerance and becomes immunogenic in the autologous host. To address this, we performed an immunotoxicology study with cynomolgus macaques vaccinated with either FLSC or a rhesus variant of FLSC containing macaque CD4 sequences (rhFLSC). Enzyme-linked immunosorbent assay (ELISA) binding titers, primary CD3(+) T cell staining, and temporal trends in T cell subset frequencies served to assess whether anti-CD4 autoantibody responses were elicited by vaccination. We find that immunization with multiple high doses of rhFLSC did not elicit detectable antibody titers despite robust responses to rhFLSC. In accordance with these findings, immunized animals had no changes in circulating CD4(+) T cell counts or evidence of autoantibody reactivity with cell surface CD4 on primary naive macaque T cells. Collectively, these studies show that antigens using CD4 sequences to stabilize transition state gp120 structures

  3. An HIV gp120-CD4 Immunogen Does Not Elicit Autoimmune Antibody Responses in Cynomolgus Macaques

    PubMed Central

    Schwartz, Jennifer A.; Prado, Ilia; Misamore, Johnathan; Weiss, Deborah; Francis, Jesse; Pal, Ranajit; Huaman, Maria; Cristillo, Anthony; Lewis, George K.; Gallo, Robert C.; DeVico, Anthony L.

    2016-01-01

    A promising concept for human immunodeficiency virus (HIV) vaccines focuses immunity on the highly conserved transition state structures and epitopes that appear when the HIV glycoprotein gp120 binds to its receptor, CD4. We are developing chimeric antigens (full-length single chain, or FLSC) in which gp120 and CD4 sequences are flexibly linked to allow stable intrachain complex formation between the two moieties (A. DeVico et al., Proc Natl Acad Sci U S A 104:17477–17482, 2007, doi:10.1073/pnas.0707399104; T. R. Fouts et al., J Virol 74:11427–11436, 2000, doi:10.1128/JVI.74.24.11427-11436.2000). Proof of concept studies with nonhuman primates show that FLSC elicited heterologous protection against simian-human immunodeficiency virus (SHIV)/simian immunodeficiency virus (SIV) (T. R. Fouts et al., Proc Natl Acad Sci U S A 112:E992–E999, 2016, doi:10.1073/pnas.1423669112), which correlated with antibodies against transition state gp120 epitopes. Nevertheless, advancement of any vaccine that comprises gp120-CD4 complexes must consider whether the CD4 component breaks tolerance and becomes immunogenic in the autologous host. To address this, we performed an immunotoxicology study with cynomolgus macaques vaccinated with either FLSC or a rhesus variant of FLSC containing macaque CD4 sequences (rhFLSC). Enzyme-linked immunosorbent assay (ELISA) binding titers, primary CD3+ T cell staining, and temporal trends in T cell subset frequencies served to assess whether anti-CD4 autoantibody responses were elicited by vaccination. We find that immunization with multiple high doses of rhFLSC did not elicit detectable antibody titers despite robust responses to rhFLSC. In accordance with these findings, immunized animals had no changes in circulating CD4+ T cell counts or evidence of autoantibody reactivity with cell surface CD4 on primary naive macaque T cells. Collectively, these studies show that antigens using CD4 sequences to stabilize transition state gp120 structures

  4. BST-2 Expression Modulates Small CD4 Mimetic Sensitization of HIV-1-infected cells to ADCC.

    PubMed

    Richard, Jonathan; Prévost, Jérémie; von Bredow, Benjamin; Ding, Shilei; Brassard, Nathalie; Medjahed, Halima; Coutu, Mathieu; Melillo, Bruno; Bibollet-Ruche, Frédéric; Hahn, Beatrice H; Kaufmann, Daniel E; Smith, Amos B; Sodroski, Joseph; Sauter, Daniel; Kirchhoff, Frank; Gee, Katrina; Neil, Stuart J; Evans, David T; Finzi, Andrés

    2017-03-22

    Antibodies recognizing conserved CD4-induced (CD4i) epitopes on HIV-1 Env and able to mediate antibody-dependent cellular cytotoxicity (ADCC) have been shown to be present in sera from most HIV-1-infected individuals. These antibodies preferentially recognize Env in its CD4-bound conformation. CD4 downregulation by Nef and Vpu dramatically reduces exposure of CD4i HIV-1 Env epitopes and therefore reduce the susceptibility of HIV-1-infected cells to ADCC mediated by HIV+ sera. Importantly, this mechanism of immune evasion can be circumvented with small-molecule CD4-mimetics (CD4mc) which are able to transition Env into the CD4-bound conformation and sensitize HIV-1-infected cells to ADCC mediated by HIV+ sera. However, HIV-1 developed additional mechanisms to avoid ADCC including Vpu-mediated BST-2 antagonism, which decreases the overall amount of Env present at the cell surface. Accordingly, BST-2 up-regulation in response to IFN-α was shown to increase the susceptibility of HIV-1-infected cells to ADCC despite the activity of Vpu. Here we show that BST-2 upregulation by IFN-β and IL-27 also increases the surface expression of Env and thus boosts the ability of CD4mc to sensitize HIV-1-infected cells to ADCC by sera from HIV-1-infected individuals.IMPORTANCE HIV-1 evolved sophisticated strategies to conceal Env epitopes from ADCC-mediating antibodies present in HIV+ sera. Vpu-mediated BST-2 downregulation was shown to decrease ADCC responses by limiting the amount of Env present at the cell surface. This effect of Vpu was shown to be attenuated by IFN-α treatment. Here we show that in addition to IFN-α, IFN-β and IL-27 also affect Vpu-mediated BST-2 downregulation and greatly enhance ADCC responses against HIV-1-infected cells in the presence of CD4mc. These findings may inform strategies aimed at HIV prevention and eradication.

  5. Comparison of effects of breast-feeding practices on birth-spacing in three societies: nomadic Turkana, Gainj, and Quechua.

    PubMed

    Gray, S J

    1994-01-01

    Variation in the duration and pattern of breast-feeding contributes significantly to inter-population differences in fertility. In this paper, measures of suckling frequency and intensity are used to compare the effects of breast-feeding practices on the duration of lactational amenorrhoea, and on the length of the birth interval in three prospective studies undertaken during the 1980s, among Quechua Indians of Peru, Turkana nomads of Kenya, and Gainj of Papua New Guinea. In all three societies, lactation is prolonged well into the second year postpartum, and frequent, on-demand breast-feeding is the norm. However, the duration of lactational amenorrhoea and the length of birth intervals vary considerably. Breast-feeding patterns among Gainj and Turkana are similar, but Turkana women resume menses some 3 months earlier than do the Gainj. The average birth interval among the Gainj exceeds that of nomadic Turkana by over 15 months. Suckling activity decreases significantly with increasing age of nurslings among both Gainj and Quechua, but not among Turkana. Earlier resumption of menses among Turkana women may be linked to the unpredictable demands of the pastoral system, which increase day-to-day variation in the number of periods of on-demand breast-feeding, although not in suckling patterns. This effect is independent of the age of infants. The short birth intervals of Turkana women, relative to those of the Gainj, may be related to early supplementation of Turkana nurslings with butterfat and animals' milk, which reduces energetic demands on lactating women at risk of negative energy balance.

  6. Feed Intake Regulation for the Female Broiler Breeder: In Theory and in Practice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The modern commercial broiler is the product of intensive genetic selection for rapid and efficient growth. An unintended consequence of this selective breeding has been the loss of the ability for self-regulation of feed intake to closely match the requirements for maintenance, growth and reproduc...

  7. Analysis of postpartum lactational amenorrhoea in relation to breast-feeding: some methodological and practical aspects.

    PubMed

    Le Strat, Y; Thalabard, J C

    2001-10-01

    A large multicentre epidemiological study was carried out by WHO between 1991 and 1995 to analyse the duration of lactational amenorrhoea in relation to breast-feeding. The main results of this analysis, which used classical statistical modelling, have been already published. However, some specific aspects of the postpartum fertility amenorrhoea and breast-feeding covariates, and more specifically the observed progressive exhaustion of the breast-feeding inhibitory effect on the reproductive axis, may justify a closer look at the validity of the statistical tools. Indeed, as has already been emphasized, analysis of large longitudinal data sets in reproduction often faces three difficulties: (i) the precise determination of the event of interest, (ii) the way to handle the time evolution of both the studied variables and their effect on the event of interest and (iii) the often discrete nature of the data and the associated problem of tied events. The first objective of the present work was to give additional insights into the estimation and quantification of the dynamics of the effect of breast-feeding over time, considering this covariate either as fixed or time-dependent. The second objective was to show how to perform the analyses using corresponding adapted procedures in widely available statistical packages, without the need for acquiring particular programming skills.

  8. Utilization of leukapheresis and CD4 positive selection in Treg isolation and the ex-vivo expansion for a clinical application in transplantation and autoimmune disorders

    PubMed Central

    Gołąb, Karolina; Grose, Randall; Trzonkowski, Piotr; Wickrema, Amittha; Tibudan, Martin; Marek-Trzonkowska, Natalia; Matosz, Sabrina; Solomina, Julia; Ostrega, Diane; Millis, J. Michael; Witkowski, Piotr

    2016-01-01

    Adoptive transfer of T regulatory cells (Tregs) is of great interest as a novel immunosuppressive therapy in autoimmune disorders and transplantation. Obtaining a sufficient number of stable and functional Tregs generated according to current Good Manufacturing Practice (cGMP) requirements has been a major challenge in introducing Tregs as a clinical therapy. Here, we present a protocol involving leukapheresis and CD4+ cell pre-enrichment prior to Treg sorting, which allows a sufficient number of Tregs for a clinical application to be obtained. With this method there is a decreased requirement for ex-vivo expansion. The protocol was validated in cGMP conditions. Our final Treg product passed all release criteria set for clinical applications. Moreover, during expansion Tregs presented their stable phenotype: percentage of CD4+CD25hiCD127− and CD4+FoxP3+ Tregs was > 95% and > 80%, respectively, and Tregs maintained proper immune suppressive function in vitro. Our results suggest that utilization of leukapheresis and CD4 positive selection during Treg isolation improves the likelihood of obtaining a sufficient number of high quality Treg cells during subsequent ex-vivo expansion and they can be applied clinically. PMID:27821811

  9. Effect of Integrated Yoga (IY) on psychological states and CD4 counts of HIV-1 infected patients: A randomized controlled pilot study

    PubMed Central

    Naoroibam, Rosy; Metri, Kashinath G; Bhargav, Hemant; Nagaratna, R; Nagendra, HR

    2016-01-01

    Background: Human immunodeficiency virus (HIV) infected individuals frequently suffer from anxiety and depression. Depression has been associated with rapid decline in CD4 counts and worsened treatment outcomes in HIV-infected patients. Yoga has been used to reduce psychopathology and improve immunity. Aim: To study the effect of 1-month integrated yoga (IY) intervention on anxiety, depression, and CD4 counts in patients suffering from HIV-1 infection. Methods: Forty four HIV-1 infected individuals from two HIV rehabilitation centers of Manipur State of India were randomized into two groups: Yoga (n = 22; 12 males) and control (n = 22; 14 males). Yoga group received IY intervention, which included physical postures (asanas), breathing practices (pranayama), relaxation techniques, and meditation. IY sessions were given 60 min/day, 6 days a week for 1 month. Control group followed daily routine during this period. All patients were on anti-retroviral therapy (ART) and dosages were kept stable during the study. There was no significant difference in age, gender, education, CD4 counts, and ART status between the two groups. Hospital anxiety and depression scale was used to assess anxiety and depression, CD4 counts were measured by flow cytometry before and after intervention. Analysis of variance – repeated measures was applied to analyze the data using SPSS version 10. Results: Within group comparison showed a significant reduction in depression scores (F [1, 21] =4.19, P < 0.05) and non-significant reduction in anxiety scores along with non significant increment in CD4 counts in the yoga group. In the control group, there was a non-significant increase in anxiety and depression scores and reduction in CD4 counts. Between-group comparison revealed a significant reduction in depression scores (F [1, 21] =5.64, P < 0.05) and significant increase in CD4 counts (F [1, 21] =5.35, P < 0.05) in the yoga group as compared to the control. Conclusion: One month practice of IY

  10. Correlations Among Parental and Neonatal Anthropometric Parameters, Feeding Practices and Infant Obesity

    PubMed Central

    SABAU, DANIEL; STAMATIN, MARIA; STOICESCU, SILVIA; FILIP, VALERIA; CUCEREA, MANUELA; OGNEAN, LIVIA; BLAGA, LIGIA; AVASILOAIEI, ANDREEA; SIMIONESCU, BIANCA; MIU, NICOLAE

    2014-01-01

    Background and aims Infant and adult obesity is becoming a real public health concern in Romania, similar to other countries of the European Union. Maternal obesity and excessive weight gain during pregnancy are proven risk factors for the obesity of the child. The protective role of the breastfeeding against obesity has also been demonstrated. The most important issue is whether the choice of a milk formula with the right protein composition could or not protect the newborn from becoming a future obese infant and child. Our study aims to describe the characteristics of a group of macrosomic newborns, in relation to the mothers’ weight gain during pregnancy, mode of delivery, birth weight, complications at birth, time of first feeding and type of feeding during maternity stay. Patients and methods We conducted a retrospective study on 179 newborns with birth weights >4000 grams, born over a period of three months (March–May) in 6 large maternity hospitals in Romania. Results the newborns had a mean gestational age of 39.5 weeks and a mean birth weight of 4195 grams. Male newborns were prevalent (74%). More than half were born by Cesarian section and had Apgar scores with a median of 9. Macrosomes are prone to complications at birth and in our study those were mainly hypoglycemia and birth trauma. Time at first feeding was 95 minutes (mean), with a high percentage of formula/mixed feeding (68%). Conclusion Macrosomia itself attracts the risk of birth by cesarean section (54% of study group), birth trauma and a low rate of exclusive breast milk feeding (32% of study group) at discharge. PMID:26528018

  11. Establishment of mouse leukemia cell lines expressing human CD4/CCR5 using lentiviral vectors.

    PubMed

    Li, Ya-Jing; ZhuGe, Fu-Yan; Zeng, Chang-Chun; He, Jin-Yang; Tan, Ning; Liang, Juan

    2017-04-01

    A low-cost rodent model of HIV infection and which presents high application value is an effective tool to investigate HIV infection and pathogenesis. However, development of such a small animal model has been hampered by the unsuitability of rodent cells for HIV-1 replication given that the retrovirus HIV-1 has high selectivity to its host cell. Our study used the mouse leukemia cell lines L615 and L1210 that were induced by murine leukemia virus and transfected with hCD4/CCR5 loaded-lentiviral vector. Lentiviral vectors containing the genes hCD4/CCR5 under the transcriptional control of cytomegalovirus promoter were designed. Transfection efficiencies of human CD4 and CCR5 in L615 and L1210 cells were analyzed by quantitative real-time polymerase chain reaction (RT-PCR) and Western blot assay. Results showed that hCD4 and CCR5 proteins were expressed on the cell surface, demonstrating that the L615 and L1210 cells were humanized and that they possess the characteristics necessary for HIV infection of human host cells. Moreover, the sensitivity of human CD4/CCR5 transgenic mouse cells to HIV infection was confirmed by RT-PCR and ELISA. Mouse leukemia cell lines that could express hCD4 and CCR5 were thus established to facilitate normal entry of HIV-1 so that a human CD4/CCR5 transgenic mice cell model can be used to investigate the transmission and pathogenesis of HIV/AIDS and potential antiviral drugs against this disease.

  12. Cytotoxic activity of CD4+ T cells against autologous tumor cells.

    PubMed

    Konomi, Y; Sekine, T; Takayama, T; Fuji, M; Tanaka, T

    1995-09-01

    The 51Cr-release assay is mostly applied to detecting the cytotoxic activity of CD8+ T cells, and little is known about the activity of CD4+ T cells. Therefore, the correlation between the cytotoxic activity of CD4+ or CD8+ T cells and the incubation period with autologous tumor cells was analyzed by two methods. The incubation periods were 4 and 20 h (4 h and 20 h assay) for the 51Cr-release assay. Eight pairs of tumor cells and T cells were assayed. T cells were fractionated into CD4+ and CD8+ T cells by using magnetic beads and panning methods, and those cells were activated by culture with recombinant interleukin-2 and immobilized anti-CD3 monoclonal antibody. In 6 out of 8 cases, no cytotoxic activity of CD4+ T cells was detected by the 4 h assay, whereas cytotoxic activity was detected in all cases in the 20 h assay. The cytotoxic activities in 20 h assay of CD4+ T cells were increased 67-fold in comparison with the activities in 4 h assay (range: 5-197). In the case of CD8+ T cells, cytotoxic activities were detected in 6 out of 8 cases in the 4 h assay. The lytic unit ratio of CD4+ and CD8+ T cells was calculated as 1.5 in the 20 h assay (range: 0.2- > 7.2) versus 0.4 in the 4 h assay (range: < 0.1-1.3). Cytotoxic activities in colorimetric assay using Crystal Violet with a 24 h incubation were similar to those in the 20 h 51Cr-release assay in all eight cases. These results indicate that CD4+ T cells have cytotoxic activity as strong as that of CD8+ T cells towards autologous tumor cells.

  13. TNFAIP3 promotes survival of CD4 T cells by restricting MTOR and promoting autophagy.

    PubMed

    Matsuzawa, Yu; Oshima, Shigeru; Takahara, Masahiro; Maeyashiki, Chiaki; Nemoto, Yasuhiro; Kobayashi, Masanori; Nibe, Yoichi; Nozaki, Kengo; Nagaishi, Takashi; Okamoto, Ryuichi; Tsuchiya, Kiichiro; Nakamura, Tetsuya; Ma, Averil; Watanabe, Mamoru

    2015-01-01

    Autophagy plays important roles in metabolism, differentiation, and survival in T cells. TNFAIP3/A20 is a ubiquitin-editing enzyme that is thought to be a negative regulator of autophagy in cell lines. However, the role of TNFAIP3 in autophagy remains unclear. To determine whether TNFAIP3 regulates autophagy in CD4 T cells, we first analyzed Tnfaip3-deficient naïve CD4 T cells in vitro. We demonstrated that Tnfaip3-deficient CD4 T cells exhibited reduced MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) puncta formation, increased mitochondrial content, and exaggerated reactive oxygen species (ROS) production. These results indicate that TNFAIP3 promotes autophagy after T cell receptor (TCR) stimulation in CD4 T cells. We then investigated the mechanism by which TNFAIP3 promotes autophagy signaling. We found that TNFAIP3 bound to the MTOR (mechanistic target of rapamycin) complex and that Tnfaip3-deficient cells displayed enhanced ubiquitination of the MTOR complex and MTOR activity. To confirm the effects of enhanced MTOR activity in Tnfaip3-deficient cells, we analyzed cell survival following treatment with Torin1, an MTOR inhibitor. Tnfaip3-deficient CD4 T cells exhibited fewer cell numbers than the control cells in vitro and in vivo. In addition, the impaired survival of Tnfaip3-deficient cells was ameliorated with Torin1 treatment in vitro and in vivo. The effect of Torin1 was abolished by Atg5 deficiency. Thus, enhanced MTOR activity regulates the survival of Tnfaip3-deficient CD4 T cells. Taken together, our findings illustrate that TNFAIP3 restricts MTOR signaling and promotes autophagy, providing new insight into the manner in which MTOR and autophagy regulate survival in CD4 T cells.

  14. Quorum-Sensing in CD4+ T Cell Homeostasis: A Hypothesis and a Model

    PubMed Central

    Almeida, Afonso R. M.; Amado, Inês F.; Reynolds, Joseph; Berges, Julien; Lythe, Grant; Molina-París, Carmen; Freitas, Antonio A.

    2012-01-01

    Homeostasis of lymphocyte numbers is believed to be due to competition between cellular populations for a common niche of restricted size, defined by the combination of interactions and trophic factors required for cell survival. Here we propose a new mechanism: homeostasis of lymphocyte numbers could also be achieved by the ability of lymphocytes to perceive the density of their own populations. Such a mechanism would be reminiscent of the primordial quorum-sensing systems used by bacteria, in which some bacteria sense the accumulation of bacterial metabolites secreted by other elements of the population, allowing them to “count” the number of cells present and adapt their growth accordingly. We propose that homeostasis of CD4+ T cell numbers may occur via a quorum-sensing-like mechanism, where IL-2 is produced by activated CD4+ T cells and sensed by a population of CD4+ Treg cells that expresses the high-affinity IL-2Rα-chain and can regulate the number of activated IL-2-producing CD4+ T cells and the total CD4+ T cell population. In other words, CD4+ T cell populations can restrain their growth by monitoring the number of activated cells, thus preventing uncontrolled lymphocyte proliferation during immune responses. We hypothesize that malfunction of this quorum-sensing mechanism may lead to uncontrolled T cell activation and autoimmunity. Finally, we present a mathematical model that describes the key role of IL-2 and quorum-sensing mechanisms in CD4+ T cell homeostasis during an immune response. PMID:22654881

  15. Influence of Cultural Beliefs on Infant Feeding, Postpartum and Childcare Practices among Chinese-American Mothers in New York City.

    PubMed

    Lee, Adele; Brann, Lynn

    2015-06-01

    As one of the fastest growing communities in the United States, Chinese-Americans receive relatively little research attention on their rates of breastfeeding versus formula feeding, and what factors influence that choice. This research aims to examine the influence of elders and cultural beliefs on postpartum, infant feeding, and childcare practices. Semi-structured interviews with 22 recently postpartum mothers who met the recruiting criteria were conducted between July 2012 and February 2013. The traditional postpartum practice, zuo yuezi, presented negative physical and emotional outcomes and maternal reporting of delay in lactation. Early introduction of solids for traditional reasons was reported. The support from husbands and elders were necessary for breastfeeding success, while some mothers had to first negotiate with elders for breastfeeding. The practice of sending infants back to China to be taken care of by extended families presented cultural implications related to grandparents' involvement in raising grandchildren. With the respect and appreciation for elders and traditions, it is likely that Chinese mothers negotiate between cultural traditions and societal expectation in the western home.

  16. Associations between infant feeding practice prior to six months and body mass index at six years of age.

    PubMed

    Imai, Cindy Mari; Gunnarsdottir, Ingibjorg; Thorisdottir, Birna; Halldorsson, Thorhallur Ingi; Thorsdottir, Inga

    2014-04-17

    Rapid growth during infancy is associated with increased risk of overweight and obesity and differences in weight gain are at least partly explained by means of infant feeding. The aim was to assess the associations between infant feeding practice in early infancy and body mass index (BMI) at 6 years of age. Icelandic infants (n = 154) were prospectively followed from birth to 12 months and again at age 6 years. Birth weight and length were gathered from maternity wards, and healthcare centers provided the measurements made during infancy up to 18 months of age. Information on breastfeeding practices was documented 0-12 months and a 24-h dietary record was collected at 5 months. Changes in infant weight gain were calculated from birth to 18 months. Linear regression analyses were performed to examine associations between infant feeding practice at 5 months and body mass index (BMI) at 6 years. Infants who were formula-fed at 5 months of age grew faster, particularly between 2 and 6 months, compared to exclusively breastfed infants. At age 6 years, BMI was on average 1.1 kg/m2 (95% CI 0.2, 2.0) higher among infants who were formula fed and also receiving solid foods at 5 months of age compared to those exclusively breastfed. In a high-income country such as Iceland, early introduction of solid foods seems to further increase the risk of high childhood BMI among formula fed infants compared with exclusively breastfed infants, although further studies with greater power are needed.

  17. Associations between Infant Feeding Practice Prior to Six Months and Body Mass Index at Six Years of Age

    PubMed Central

    Imai, Cindy Mari; Gunnarsdottir, Ingibjorg; Thorisdottir, Birna; Halldorsson, Thorhallur Ingi; Thorsdottir, Inga

    2014-01-01

    Rapid growth during infancy is associated with increased risk of overweight and obesity and differences in weight gain are at least partly explained by means of infant feeding. The aim was to assess the associations between infant feeding practice in early infancy and body mass index (BMI) at 6 years of age. Icelandic infants (n = 154) were prospectively followed from birth to 12 months and again at age 6 years. Birth weight and length were gathered from maternity wards, and healthcare centers provided the measurements made during infancy up to 18 months of age. Information on breastfeeding practices was documented 0–12 months and a 24-h dietary record was collected at 5 months. Changes in infant weight gain were calculated from birth to 18 months. Linear regression analyses were performed to examine associations between infant feeding practice at 5 months and body mass index (BMI) at 6 years. Infants who were formula-fed at 5 months of age grew faster, particularly between 2 and 6 months, compared to exclusively breastfed infants. At age 6 years, BMI was on average 1.1 kg/m2 (95% CI 0.2, 2.0) higher among infants who were formula fed and also receiving solid foods at 5 months of age compared to those exclusively breastfed. In a high-income country such as Iceland, early introduction of solid foods seems to further increase the risk of high childhood BMI among formula fed infants compared with exclusively breastfed infants, although further studies with greater power are needed. PMID:24747694

  18. Mothers’ Child-Feeding Practices Are Associated with Children’s Sugar-Sweetened Beverage Intake1234

    PubMed Central

    Park, Sohyun; Li, Ruowei; Birch, Leann

    2015-01-01

    Background: Sugar-sweetened beverage (SSB) intake is a substantial source of energy in the diet of US children. Objective: We examined the associations between mothers’ child-feeding practices and SSB intake among 6-y-old children. Methods: We analyzed data from the Year 6 Follow-up of the Infant Feeding Practices Study II in 1350 US children aged 6 y. The outcome variable was child’s SSB intake. The exposure variables were 4 child-feeding practices of mothers: setting limits on sweets or junk foods, regulating their child’s favorite food intake to prevent overconsumption, pressuring their child to eat enough, and pressuring their child to “clean the plate.” We used multinomial logistic regression and controlled for child and maternal characteristics. Analyses were stratified on child weight status. Results: The consumption of SSBs ≥1 time/d was observed among 17.1% of underweight/normal-weight children and in 23.2% of overweight/obese children. Adjusted ORs (aORs) of consuming SSBs ≥1 time/d (vs. no SSB consumption) were significantly lower in children whose mothers reported setting limits on sweets/junk foods (aOR: 0.29; 95% CI: 0.15, 0.58 for underweight/normal-weight children; aOR: 0.16; 95% CI: 0.03, 0.79 for overweight/obese children). SSB intake was higher among underweight/normal-weight children whose mothers reported trying to keep the child from eating too much of their favorite foods (aOR: 2.03; 95% CI: 1.25, 3.29). Mothers’ tendency to pressure their children to consume more food or to “clean the plate” was not associated with child’s SSB intake. Conclusions: SSBs were commonly consumed by young children. The odds of daily SSB intake were lower among children whose mothers set limits on sweets/junk foods regardless of child’s weight but were higher among underweight/normal-weight children whose mothers restricted the child’s favorite food intake. Future studies can investigate the impact of alternatives to restrictive feeding

  19. Understanding care and feeding practices: building blocks for a sustainable intervention in India and Pakistan.

    PubMed

    Lingam, Raghu; Gupta, Pallavi; Zafar, Shamsa; Hill, Zelee; Yousafzai, Aisha; Iyengar, Sharad; Sikander, Siham; Haq, Zaeem ul; Mehta, Shilpa; Skordis-Worrel, Jolene; Rahman, Atif; Kirkwood, Betty

    2014-01-01

    Undernutrition and inadequate stimulation both negatively influence child health and development and have a long-term impact on school attainment and income. This paper reports data from India and Pakistan looking at how families interact, play with, and feed children; their expectations of growth and development; and the perceived benefits, consequences, opportunities, and barriers of adopting recommended feeding and developmental behaviors. These data were collected as part of formative research for the Sustainable Program Incorporating Nutrition and Games (SPRING) trial. This trial aims to deliver an innovative, feasible, affordable, and sustainable intervention that can achieve delivery at a scale of known effective interventions that maximize child development, growth, and survival and improve maternal psychosocial well-being in rural India and Pakistan.

  20. Baseline CD4 Cell Counts of Newly Diagnosed HIV Cases in China: 2006–2012

    PubMed Central

    Tang, Houlin; Mao, Yurong; Shi, Cynthia X.; Han, Jing; Wang, Liyan; Xu, Juan; Qin, Qianqian; Detels, Roger; Wu, Zunyou

    2014-01-01

    Background Late diagnosis of HIV infection is common. We aim to assess the proportion of newly diagnosed HIV cases receiving timely baseline CD4 count testing and the associated factors in China. Methods Data were extracted from the Chinese HIV/AIDS Comprehensive Response Information Management System. Adult patients over 15 years old who had been newly diagnosed with HIV infection in China between 2006 and 2012 were identified. The study cohort comprised individuals who had a measured baseline CD4 count. Results Among 388,496 newly identified HIV cases, the median baseline CD4 count was 294 cells/µl (IQR: 130–454), and over half (N = 130,442, 58.8%) were less than 350 cells/µl. The median baseline CD4 count increased from 221 (IQR: 63–410) in 2006 to 314 (IQR: 159–460) in 2012. A slight majority of patients (N = 221,980, 57.1%) received baseline CD4 count testing within 6 months of diagnosis. The proportion of individuals who received timely baseline CD4 count testing increased significantly from 20.0% in 2006 to 76.9% in 2012. Factors associated with failing to receiving timely CD4 count testing were: being male (OR: 1.17, 95% CI: 1.15–1.19), age 55 years or older (OR:1.03, 95% CI: 1.00–1.06), educational attainment of primary school education or below (OR: 1.30, 95% CI: 1.28–1.32), infection with HIV through injection drug use (OR: 2.07, 95% CI: 2.02–2.12) or sexual contact and injection drug use (OR: 1.87, 95% CI: 1.76–1.99), diagnosis in a hospital (OR: 1.91, 95% CI: 1.88–1.95) or in a detention center (OR: 1.75, 95% CI: 1.70–1.80), and employment as a migrant worker (OR:1.55, 95% CI:1.53–1.58). Conclusion The proportion of newly identified HIV patients receiving timely baseline CD4 testing has increased significantly in China from 2006–2012. Continued effort is needed for further promotion of early HIV diagnosis and timely baseline CD4 cell count testing. PMID:24901790

  1. Access to CD4 Testing for Rural HIV Patients: Findings from a Cohort Study in Zimbabwe

    PubMed Central

    Vogt, Florian; Tayler-Smith, Katie; Bernasconi, Andrea; Makondo, Eliphas; Taziwa, Fabian; Moyo, Buhlebenkosi; Havazvidi, Liberty; Satyanarayana, Srinath; Manzi, Marcel; Khogali, Mohammed; Reid, Anthony

    2015-01-01

    Background CD4 cell count measurement remains an important diagnostic tool for HIV care in developing countries. Insufficient laboratory capacity in rural Sub-Saharan Africa is frequently mentioned but data on the impact at an individual patient level are lacking. Urban-rural discrepancies in CD4 testing have not been quantified to date. Such evidence is crucial for public health planning and to justify new yet more expensive diagnostic procedures that could circumvent access constraints in rural areas. Objective To compare CD4 testing among rural and urban HIV patients during the first year of treatment. Methods Records from 2,145 HIV positive adult patients from a Médecins sans Frontières (Doctors without Borders) HIV project in Beitbridge, Zimbabwe, during 2011 and 2012 were used for a retrospective cohort analysis. Covariate-adjusted risk ratios were calculated to estimate the effects of area of residence on CD4 testing at treatment initiation, six and 12 months among rural and urban patients. Findings While the proportion of HIV patients returning for medical consultations at six and 12 months decreased at a similar rate in both patient groups, CD4 testing during consultations dropped to 21% and 8% for urban, and 2% and 1% for rural patients at six and 12 months, respectively. Risk ratios for missing CD4 testing were 0.8 (95% CI 0.7-0.9), 9.2 (95% CI 5.5-15.3), and 7.6 (95% 3.7-17.1) comparing rural versus urban patients at treatment initiation, six and 12 months, respectively. Conclusions CD4 testing was low overall, and particularly poor in rural patients. Difficulties with specimen transportation were probably a major factor underlying this difference and requires new diagnostic approaches. Our findings point to severe health system constraints in providing CD4 testing overall that need to be addressed if effective monitoring of HIV patients is to be achieved, whether by alternative CD4 diagnostics or newly-recommended routine viral load testing. PMID

  2. The effect of CD4 receptor downregulation and its downstream signaling molecules on HIV-1 latency

    SciTech Connect

    Kim, Kyung-Chang; Kim, Hyeon Guk; Roh, Tae-Young; Park, Jihwan; Jung, Kyung-Min; Lee, Joo-Shil; Choi, Sang-Yun; Kim, Sung Soon; Choi, Byeong-Sun

    2011-01-14

    Research highlights: {yields} CD4 receptors were downregulated on the surface of HIV-1 latently infected cells. {yields} CD4 downstream signaling molecules were suppressed in HIV-1 latently infected cells. {yields} HIV-1 progeny can be reactivated by induction of T-cell activation signal molecules. {yields} H3K4me3 and H3K9ac were highly enriched in CD4 downstream signaling molecules. {yields} HIV-1 latency can be maintained by the reduction of downstream signaling molecules. -- Abstract: HIV-1 can establish a latent infection in memory CD4 + T cells to evade the host immune response. CD4 molecules can act not only as the HIV-1 receptor for entry but also as the trigger in an intracellular signaling cascade for T-cell activation and proliferation via protein tyrosine kinases. Novel chronic HIV-1-infected A3.01-derived (NCHA) cells were used to examine the involvement of CD4 downstream signaling in HIV-1 latency. CD4 receptors in NCHA cells were dramatically downregulated on its surface but were slightly decreased in whole-cell lysates. The expression levels of CD4 downstream signaling molecules, including P56{sup Lck}, ZAP-70, LAT, and c-Jun, were sharply decreased in NCHA cells. The lowered histone modifications of H3K4me3 and H3K9ac correlated with the downregulation of P56{sup Lck}, ZAP-70, and LAT in NCHA cells. AP-1 binding activity was also reduced in NCHA cells. LAT and c-Jun suppressed in NCHA cells were highly induced after PMA treatment. In epigenetic analysis, other signal transduction molecules which are associated with active and/or latent HIV-1 infection showed normal states in HIV-1 latently infected cells compared to A3.01 cells. In conclusion, we demonstrated that the HIV-1 latent state is sustained by the reduction of downstream signaling molecules via the downregulation of CD4 and the attenuated activity of transcription factor as AP-1. The HIV-1 latency model via T-cell deactivation may provide some clues for the development of the new

  3. Primary brain tumors treated with steroids and radiotherapy: Low CD4 counts and risk of infection

    SciTech Connect

    Hughes, Michael A.; Parisi, Michele; Grossman, Stuart; Kleinberg, Lawrence . E-mail: kleinla@jhmi.edu

    2005-08-01

    Purpose: Patients with primary brain tumors are often treated with high doses of corticosteroids for prolonged periods to reduce intracranial swelling and alleviate symptoms such as headaches. This treatment may lead to immunosuppression, placing the patient at risk of life-threatening opportunistic infections, such as Pneumocystis carinii pneumonia. The risk of contracting some types of infection may be reduced with prophylactic antibiotics. The purpose of this study was to determine the occurrence of low CD4 counts and whether monitoring CD4 counts during and after radiotherapy (RT) is warranted. Methods and Materials: CD4 counts were measured during RT in 70 of 76 consecutive patients with newly diagnosed Grade III and IV astrocytoma and anaplastic oligodendroglioma treated with corticosteroids and seen at the Johns Hopkins Hospital. Weekly CD4 measurements were taken in the most recent 25 patients. Prophylactic trimethoprim-sulfamethoxazole (160 mg/800 mg p.o. every Monday, Wednesday, and Friday) or dapsone (100 mg p.o. daily) in those with sulfa allergy was prescribed only if patients developed a low CD4 count. Carmustine chemotherapy wafers were placed at surgery in 23% of patients, evenly distributed between the groups. No patient received any other chemotherapy concurrent with RT. Results: CD4 counts decreased to <200/mm{sup 3} in 17 (24%) of 70 patients. For the 25 patients with weekly CD4 counts, all CD4 counts were >450/mm{sup 3} before RT, but 6 (24%) of 25 fell to <200/mm{sup 3} during RT. Patients with counts <200/mm{sup 3} were significantly more likely to be hospitalized (41% vs. 9%, p <0.01) and be hospitalized for infection (23% vs. 4%, p <0.05) during RT. Overall survival was not significantly different between the groups. All patients with low CD4 counts were treated with prophylactic antibiotics, and no patient developed Pneumocystis carinii pneumonia. No patients developed a serious adverse reaction to antibiotic therapy. The mean dose of

  4. High CD4+ T cell density is associated with poor prognosis in patients with non-muscle-invasive bladder cancer

    PubMed Central

    Zhang, Qinglei; Hao, Chongli; Cheng, Guangzhou; Wang, Lei; Wang, Xiang; Li, Chang; Qiu, Juhui; Ding, Kejia

    2015-01-01

    Purpose: The aim of this study was to investigate the clinical significance of CD4+ T cells in non-muscle-invasive bladder cancer (NMIBC) tissues in situ. Methods: Immunohistochemistry was used to examine the distribution of CD4+ T cells in 131 NMIBC tissues. Kaplan-Meier analysis and Cox proportional hazards regression models were applied to estimate overall survival (OS) and recurrence-free survival (RFS). Results: NMIBC patients were divided into two groups based on the median frequency of CD4+ T cells (median, 1/×400 high resolution). On univariate analysis, CD4+ T cell density was inversely associated with overall survival (P = 0.01). In those patients with high CD4+ T density, 5-year OS rates was only 77%, compared with 86% in those with low density, respectively. Although CD4+ T cell density showed no prognostic significance for RFS (P = 0.36), 5-year RFS rates of patients with high CD4+ T density (58%) was lower than those of patients with low CD4+ T density (65%, respectively). By multivariate analysis, tumor infiltrating CD4+ T cell density emerged as an independent prognostic factor for OS (HR, 2.75; P = 0.004). In addition, no association was found between CD4+ T cell density and any clinicopathological variables (P > 0.05). Conclusion: Our findings suggest that CD4+ T cells could potentially serve as a poor prognostic marker for patients with NMIBC. PMID:26617883

  5. Bispecific antibodies directed to CD4 domain 2 and HIV envelope exhibit exceptional breadth and picomolar potency against HIV-1

    PubMed Central

    Pace, Craig S.; Song, Ruijiang; Ochsenbauer, Christina; Andrews, Chasity D.; Franco, David; Yu, Jian; Oren, Deena A.; Seaman, Michael S.; Ho, David D.

    2013-01-01

    In the absence of an effective HIV-1 vaccine, passive immunization using broadly neutralizing Abs or Ab-like molecules could provide an alternative to the daily administration of oral antiretroviral agents that has recently shown promise as preexposure prophylaxis. Currently, no single broadly neutralizing Ab (bNAb) or combination of bNAbs neutralizes all HIV-1 strains at practically achievable concentrations in vivo. To address this problem, we created bispecific Abs that combine the HIV-1 inhibitory activity of ibalizumab (iMab), a humanized mAb directed to domain 2 of human CD4, with that of anti-gp120 bNAbs. These bispecific bNAbs (BibNAbs) exploit iMab’s potent anti–HIV-1 activity and demonstrated clinical efficacy and safety to anchor and thereby concentrate a second broadly neutralizing agent at the site of viral entry. Two BibNabs, PG9-iMab and PG16-iMab, exhibit exceptional breadth and potency, neutralizing 100% of the 118 viruses tested at low picomolar concentrations, including viruses resistant to both parental mAbs. The enhanced potency of these BibNAbs was entirely dependent on CD4 anchoring, not on membrane anchoring per se, and required optimal Ab geometry and linker length. We propose that iMab-based BibNAbs, such as PG9-iMab and PG16-iMab, are promising candidates for passive immunization to prevent HIV-1 infection. PMID:23878231

  6. Bispecific antibodies directed to CD4 domain 2 and HIV envelope exhibit exceptional breadth and picomolar potency against HIV-1.

    PubMed

    Pace, Craig S; Song, Ruijiang; Ochsenbauer, Christina; Andrews, Chasity D; Franco, David; Yu, Jian; Oren, Deena A; Seaman, Michael S; Ho, David D

    2013-08-13

    In the absence of an effective HIV-1 vaccine, passive immunization using broadly neutralizing Abs or Ab-like molecules could provide an alternative to the daily administration of oral antiretroviral agents that has recently shown promise as preexposure prophylaxis. Currently, no single broadly neutralizing Ab (bNAb) or combination of bNAbs neutralizes all HIV-1 strains at practically achievable concentrations in vivo. To address this problem, we created bispecific Abs that combine the HIV-1 inhibitory activity of ibalizumab (iMab), a humanized mAb directed to domain 2 of human <