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Sample records for feeding practices cd4

  1. A microfluidic device for practical label-free CD4(+) T cell counting of HIV-infected subjects.

    PubMed

    Cheng, Xuanhong; Irimia, Daniel; Dixon, Meredith; Sekine, Kazuhiko; Demirci, Utkan; Zamir, Lee; Tompkins, Ronald G; Rodriguez, William; Toner, Mehmet

    2007-02-01

    Practical HIV diagnostics are urgently needed in resource-limited settings. While HIV infection can be diagnosed using simple, rapid, lateral flow immunoassays, HIV disease staging and treatment monitoring require accurate counting of a particular white blood cell subset, the CD4(+) T lymphocyte. To address the limitations of current expensive, technically demanding and/or time-consuming approaches, we have developed a simple CD4 counting microfluidic device. This device uses cell affinity chromatography operated under differential shear flow to specifically isolate CD4(+) T lymphocytes with high efficiency directly from 10 microliters of unprocessed, unlabeled whole blood. CD4 counts are obtained under an optical microscope in a rapid, simple and label-free fashion. CD4 counts determined in our device matched measurements by conventional flow cytometry among HIV-positive subjects over a wide range of absolute CD4 counts (R(2) = 0.93). This CD4 counting microdevice can be used for simple, rapid and affordable CD4 counting in point-of-care and resource-limited settings. PMID:17268618

  2. Infant feeding practices in Malaysia.

    PubMed

    Chen, S T

    1978-12-01

    Retrospective nutritional data on 100 children, aged 6 months to 2 1/2 years, who were admitted to the University Hospital in Kuala Lumpur, Malaysia, was obtained by interviewing the mothers of the children. Analysis of the data revealed that 1) only 49% of the children were breast-fed as infants; 2) 50% of the mothers who did breast-feed discontinued breast-feeding before the children were 3 months old; and 3) the weaning diet of at least 1/3 of the children was inadequate. 18% of the children were Malays, 49% were Chinese, and 33% were Indian. The proportion of breast-fed children was highest among the Malays and lowest among the Chinese. Mothers with higher incomes tended to stop breast-feeding earlier than mothers with lower incomes. 67% of the women said they stopped breast-feeding due to inadequate lactation. Most of the children received supplementary foods at relatively early ages. 50% of the infants received starchy foods by the time they were 3 1/2 months old, and 50% received fruit or fruit juice by the time they were 3 1/2 months old. Vegetable products, meat, fish, and eggs were not added to the diet until the children were considerably older. Recommendations, based on the study findings, were 1) hospitals should discontinue the practice of deferring breast-feeding initiation for 24 hours after delivery; 2) mothers should be encouraged to breast-feed fully; and 3) health personnel should discourage the widespread use of costly precooked cereals for supplementary feeding. Tables depicted 1) the frequency distribution of the 100 children by income and by milk feeding patterns according to ethnic affiliation and 2) the cost of serving precooked cereals as compared to the cost of serving home cooked meals. PMID:755160

  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. Infant feeding practices and obesity.

    PubMed

    Himes, J H

    1979-08-01

    Selected assumptions regarding associations between artificial feeding and infantile obesity are examined. Although some artificial baby foods (desserts, meats, egg yolks) have considerably greater caloric density than breast milk, a large class of baby foods and most milks and formulas are comparable to breast milk in caloric density. The intake of infant foods seems to be related more to caloric density than volume. Modern day artificial feeding in developed countries tends to produce larger weight gains than breast feeding, although no good data exist to evaluate the composition of these weight gains. Many more data from well planned studies are needed to fully elucidate possible mechanisms of infantile obesity. PMID:458075

  5. 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…

  6. Parental feeding practices and children's weight.

    PubMed

    Wardle, Jane; Carnell, Susan

    2007-04-01

    Global increases in childhood obesity rates demand that we tackle the problem from many directions. One promising avenue is to explore the impact of parental feeding practices, particularly those related to parental control over children's intake. In this paper, we review studies of parent feeding and child adiposity covering a range of research methodologies (case-control studies, high risk studies, cross-sectional community studies and longitudinal cohort studies). We also present results from a cross-sectional community study of pre-schoolers (n = 439) and a longitudinal study of twins from ages of 4 to 7 years (n = 3175 pairs). We conclude that parents are more likely to encourage leaner than heavier children to eat, but relationships between adiposity and other parental feeding strategies are unclear. We suggest that future research should: (i) explore the impact of a comprehensive range of authoritative and authoritarian parental feeding behaviours, preferably using the same validated scales consistently across studies; (ii) test the generalisation of existing findings to diverse socio-economic and ethnic groups and (iii) utilise experimental, prospective and genetic methodologies to explore the causal relationships between parental feeding and child weight. We describe current projects in our own group that are designed to take forward these recommendations.

  7. Infant feeding practices in rural Bangladesh.

    PubMed

    Das, D K; Talukder, M Q; Sella, G E

    1992-01-01

    A longitudinal study was done on the infant feeding practices in a rural area. One hundred and ten infants were followed up from birth to 1 year of age by alternate day home visits, to inquire about the type of food, and frequency of consuming it. It was found that 100% mothers breast-fed their infants from birth to 1 year, almost every day. But, bottles containing various kinds of milk and starchy food were added to 60% of infants diets by 3 months, and 80% by 5 months of age. This additional food was given mostly in diluted form, which was more so in case of tinned milk. Family food such as rice and vegetables were given in 30% and 40% child days respectively from 6 months to 1 year. Rural people withhold protein food and fruits during infancy. It is concluded, that infant feeding practices in our population is improper and mothers should, therefore, be trained and motivated on weaning practices for timely and adequate supplementation to ameliorate the presently observed dietary deficiency and early malnutrition in rural Bangladesh. PMID:1459679

  8. Impact of sepsis on CD4 T cell immunity

    PubMed Central

    Cabrera-Perez, Javier; Condotta, Stephanie A.; Badovinac, Vladimir P.; Griffith, Thomas S.

    2014-01-01

    Sepsis remains the primary cause of death from infection in hospital patients, despite improvements in antibiotics and intensive-care practices. Patients who survive severe sepsis can display suppressed immune function, often manifested as an increased susceptibility to (and mortality from) nosocomial infections. Not only is there a significant reduction in the number of various immune cell populations during sepsis, but there is also decreased function in the remaining lymphocytes. Within the immune system, CD4 T cells are important players in the proper development of numerous cellular and humoral immune responses. Despite sufficient clinical evidence of CD4 T cell loss in septic patients of all ages, the impact of sepsis on CD4 T cell responses is not well understood. Recent findings suggest that CD4 T cell impairment is a multipronged problem that results from initial sepsis-induced cell loss. However, the subsequent lymphopenia-induced numerical recovery of the CD4 T cell compartment leads to intrinsic alterations in phenotype and effector function, reduced repertoire diversity, changes in the composition of naive antigen-specific CD4 T cell pools, and changes in the representation of different CD4 T cell subpopulations (e.g., increases in Treg frequency). This review focuses on sepsis-induced alterations within the CD4 T cell compartment that influence the ability of the immune system to control secondary heterologous infections. The understanding of how sepsis affects CD4 T cells through their numerical loss and recovery, as well as function, is important in the development of future treatments designed to restore CD4 T cells to their presepsis state. PMID:24791959

  9. 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;…

  10. 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…

  11. HIV exceptionalism, CD4+ cell testing, and conscientious subversion

    PubMed Central

    Jansen, L

    2005-01-01

    In recent years, many states in the United States have passed legislation requiring laboratories to report the names of patients with low CD4 cell counts to their state Departments of Health. This name reporting is an integral part of the growing number of "HIV Reporting and Partner Notification Laws" which have emerged in response to recently revised guidelines suggested by the National Centers for Disease Control (CDC). Name reporting for patients with low CD4 cell counts allows for a more accurate tracking of the natural history of HIV disease. However, given that this test is now considered to be an "indicator" of HIV, should it be subject to the same strict consent required for HIV testing? While the CDC has recommended that each state develop its own consent requirements for CD4 cell testing, most states have continued to rely on the presumed consent standards for CD4 cell testing that were in place before the passage of name reporting statutes. This allows physicians who treat patients who refuse HIV testing to order a CD4 cell blood analysis to gather information that is indicative of their patient's HIV status. This paper examines the ethical and legal issues associated with the practice of "conscientious subversion" as it arises when clinicians use CD4 cell counts as a surrogate for HIV testing. PMID:15923478

  12. 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. PMID:20872057

  13. Maternal correlates of maternal child feeding practices: a systematic review.

    PubMed

    McPhie, Skye; Skouteris, Helen; Daniels, Lynne; Jansen, Elena

    2014-01-01

    Establishing healthy eating habits early in life is one important strategy to combat childhood obesity. Given that early maternal child feeding practices have been linked to child food intake and weight, identifying the maternal correlates of maternal child feeding practices is important in order to understand the determinants of childhood obesity; this was the overall aim of the current review. Academic databases were searched for studies examining the relationship between maternal child feeding practices and parenting, personal characteristics and psychopathology of mothers with preschoolers. Papers were limited to those published in English, between January 2000 and June 2012. Only studies with mothers of normally developing children between the ages of 2 and 6 years were included. There were no restrictions regarding the inclusion of maternal nationality or socioeconomic status (SES). Seventeen eligible studies were sourced. Information on the aim, sample, measures and findings of these was summarised into tables. The findings of this review support a relationship between maternal controlling parenting, general and eating psychopathology, and SES and maternal child feeding practices. The main methodological issues of the studies reviewed included inconsistency in measures of maternal variables across studies and cross-sectional designs. We conclude that the maternal correlates associated with maternal child feeding practices are complex, and the pathways by which maternal correlates impact these feeding practices require further investigation.

  14. 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. PMID:25064278

  15. CD4 (T-Cell) Tests

    MedlinePlus

    ... 3 to 6 months when starting antiretroviral therapy (ART, see fact sheet 403 ). Once treatment has increased ... Fact Sheet 514 ) Monitoring treatment success: With successful ART, CD4 counts rise. Sometimes they rise quickly. Other ...

  16. Predicting AIDS-related events using CD4 percentage or CD4 absolute counts

    PubMed Central

    Pirzada, Yasmin; Khuder, Sadik; Donabedian, Haig

    2006-01-01

    Background The extent of immunosuppression and the probability of developing an AIDS-related complication in HIV-infected people is usually measured by the absolute number of CD4 positive T-cells. The percentage of CD4 positive cells is a more easily measured and less variable number. We analyzed sequential CD4 and CD8 numbers, percentages and ratios in 218 of our HIV infected patients to determine the most reliable predictor of an AIDS-related event. Results The CD4 percentage was an unsurpassed predictor of the occurrence of AIDS-related events when all subsets of patients are considered. The CD4 absolute count was the next most reliable, followed by the ratio of CD4/CD8 percentages. The value of CD4 percentage over the CD4 absolute count was seen even after the introduction of highly effective HIV therapy. Conclusion The CD4 percentage is unsurpassed as a parameter for predicting the onset of HIV-related diseases. The extra time and expense of measuring the CD4 absolute count may be unnecessary. PMID:16916461

  17. [Breast feeding practice in a region of Beirut].

    PubMed

    Chacar Rabay, H; Sokhn, M; Azar, M

    1997-01-01

    The practice of breast-feeding was reviewed in an inquiry carried on by the nursing students in Beirut and suburbs. 170 mothers answered the questionary concerning their experience in feeding their 170 babies as well as their previous 263 children of whom 249 were breast-fed. 31.17% of these mothers were breast-feeding for the first time. 11% of the newborns were fed in the first hour of life. 29% of the newborns received breast milk as the first food. Breast milk remained exclusive for the first month of life in 37.54% of these newborns. Breast-feeding mothers changed their feeding habit in half of the cases. They increased the quantity but the quality of nutriments was still deficient. This misunderstanding of breast-feeding is due primarily to the insufficiently informed mothers and to the inadequate habits of nursery. It is important to ameliorate the quality of information for the breast-feeding mothers and their household for the success of any policy encouraging breast-feeding in Lebanon. PMID:9289505

  18. A survey of breast feeding practices in infants seen in general practice.

    PubMed

    Chia, S F

    1992-06-01

    This is a study of infant feeding practices of 126 mothers. Seventy-seven mothers or 61.1% practised breast feeding. The typical breast feeding mother was more likely to be a Malay, with lower family income and residing in the rural area. The educational status of the mother was not an important factor in influencing her to breast feed. Health education on breast feeding should be intensified in schools to reinforce the implementation of the Malaysian Code of Ethics for Infant Formula Products. PMID:1494334

  19. A survey of breast feeding practices in infants seen in general practice.

    PubMed

    Chia, S F

    1992-06-01

    This is a study of infant feeding practices of 126 mothers. Seventy-seven mothers or 61.1% practised breast feeding. The typical breast feeding mother was more likely to be a Malay, with lower family income and residing in the rural area. The educational status of the mother was not an important factor in influencing her to breast feed. Health education on breast feeding should be intensified in schools to reinforce the implementation of the Malaysian Code of Ethics for Infant Formula Products.

  20. CD4 immunophenotyping in HIV infection

    PubMed Central

    Barnett, David; Walker, Brooke; Landay, Alan; Denny, Thomas N.

    2009-01-01

    The ability to rapidly identify immune cell subsets such as CD4 cells, which became possible around the same time as the onset of the HIV/AIDS pandemic, was one of the greatest advances in clinical and diagnostic immunology. The evolution of this global pandemic and the subsequent development of treatment strategies to prolong the life of infected individuals mean that it is now more crucial than ever that we develop affordable, reliable and accurate methods for the enumeration of CD4 cells. Here, we provide an overview of the historical developments in CD4 enumeration technologies that are related to HIV infection, and summarize the current technological challenges that must be overcome to meet the needs of those living with HIV infection. PMID:18923413

  1. Cd4As2Br3

    PubMed Central

    Kars, Mohammed; Roisnel, Thierry; Dorcet, Vincent; Rebbah, Allaoua; Otero-Diáz, L. Carlos

    2014-01-01

    Single crystals of Cd4As2Br3 (tetra­cadmium biarsenide tri­bromide) were grown by a chemical transport reaction. The structure is isotypic with the members of the cadmium and mercury pnictidohalides family with general formula M 4 A 2 X 3 (M = Cd, Hg; A = P, As, Sb; X = Cl, Br, I) and contains two independent As atoms on special positions with site symmetry -3 and two independent Cd atoms, of which one is on a special position with site symmetry -3. The Cd4As2Br3 structure consists of AsCd4 tetra­hedra sharing vertices with isolated As2Cd6 octa­hedra that contain As–As dumbbells in the centre of the octahedron. The Br atoms are located in the voids of this three-dimensional arrangement and bridge the different polyhedra through Cd⋯Br contacts. PMID:24764933

  2. 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

  3. Idiopathic CD4 lymphocytopenia with sensorimotor polyneuropathy.

    PubMed

    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

  4. 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...

  5. 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,…

  6. 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.

  7. 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. PMID:25700629

  8. Identification of a CD4 variant in Microminipigs not detectable with available anti-CD4 monoclonal antibodies.

    PubMed

    Matsubara, Tatsuya; Nishii, Naohito; Takashima, Satoshi; Takasu, Masaki; Imaeda, Noriaki; Aiki-Oshimo, Kayo; Yamazoe, Kazuaki; Kametani, Yoshie; Ando, Asako; Kitagawa, Hitoshi

    2015-12-15

    The Microminipig is an extra-small sized novel miniature pig developed in Japan. In the process of peripheral blood mononuclear cells analysis by flow cytometry, CD4+ cells could not be detected in some pigs with an anti-pig CD4 antibody (clone 74-12-4), or in some pigs with two other antibodies from different clones (MIL17 and PT90A). In a herd of 178 Microminipigs, 87 pigs (48.9%) were reactive with the anti-CD4 antibody (designated as CD4.A), and 91 pigs (51.1%) were non-reactive (designated as CD4.B). The CD4 types of piglets delivered from parents with CD4.A were CD4.A or CD4.B, and piglets delivered from parents with CD4.B were only CD4.B. This implies that the CD4.A pigs were homozygous for CD4.A or heterozygous for CD4.A and CD4.B, and the CD4.B pigs were homozygous for CD4.B. The CD4.B trait might be recessive. Significant differences could not be found in the percentage of CD3+ and CD8+ cells in whole lymphocytes between CD4.A and CD4.B animals. In the profile of CD4.B pigs, CD4+CD8+ T cells appeared to be detected in the CD4-CD8+ T cell region because the CD8 dull T cell population was observed. Thus, we considered that the CD4 molecules may be expressed on helper T cells, but the CD4 expressing cells could not be detected with the three anti-pig CD4 antibodies. Clinical abnormalities have not been observed in CD4.B pigs. Significant differences were not observed in immunoglobulin concentrations between CD4.A and CD4.B, though lower tendency was observed in plasma IgM concentrations from CD4.B pigs >36-months-old. These results imply that the CD4.B does not affect basic humoral immunity in vivo.

  9. Infant feeding practices in an urban squatter community.

    PubMed

    Khor Geok Lin

    1989-06-01

    The pattern of infant feeding practice was studied among Malay mothers in Kg. Sentosa, a squatter community in Kuala Lumpur. Breastmilk only was provided by most mothers up to the 4th week, after which it was increasingly replaced by cow's milk. 95% of the working mothers and 54% of the full-time housewives had introduced bottle-feeding supplemented with precooked cereal and porridge by 2 months of age. Factors related to maternal employment, household income and occurrence of illness in child affect significantly the duration of exclusive breastfeeding. Variability in the timing of commencement and completion of weaning could be attributed partially only (42.1% and 26.8% respectively) to the household, maternal and child variables taken together. This seems to imply that personal reasons largely govern decisions related to feeding infants. (Author's). PMID:12342397

  10. Critical practicalities in sampling for mycotoxins in feed.

    PubMed

    Wagner, Claas

    2015-01-01

    The presence of mycotoxins, in particular aflatoxin B1 , can cause significant health problems as well as severe economic loss, and are therefore regulated with respect to maximum acceptable concentration for various feed- and foodstuffs. International regulatory authorities have recognized the importance of representative sampling, and sampling guidelines that only partly comply with the Theory of Sampling have been formulated. Practical guidance regarding sampling, including correct design and operation of sampling devices and explanations on how to develop sufficient sampling protocols are lacking in current guidelines. These are critical practicalities of main importance, especially when dealing with trace concentrations and/or concentrations that are irregularly distributed, as for mycotoxins. Heterogeneity characterization, which is necessary to be able develop valid sampling protocols or validation assessments of existing sampling operations, is currently not mentioned in the existing guidelines. This paper explains all critical practicalities with respect to sampling of mycotoxins for 1-D and 3-0 feed decision units. Correct design and use of sampling and mass reduction devices, as well as structural guidelines for correctly designing experimental heterogeneity characterizations are presented, allowing evaluation of sampling representativeness and determination of optimal number of increments per composite sample. Practical examples are given on how to extract information from variographic analysis and replication experiments, based on an extensive field trials performed to determine aflatoxin levels in various feed components.

  11. 'These are modern times': infant feeding practice in Peninsular Malaysia.

    PubMed

    Manderson, L

    1984-01-01

    Traditionally, Malaysian women (Malay, Indian and Chinese) breastfed their infants as a matter of course and for an extended period of time; only elite Chinese women might have resorted to a wet-nurse. But the introduction of condensed and dehydrated milk in colonial Malaya from the late nineteenth century, and the later marketing also of commercially manufactured baby foods, led to some variation in traditional practice. Structural changes, industrialiZation and urbanisation affected social as well as economic life, and again these broad changes had an impact on infant feeding. Today, few women remain unfamiliar with the wide range of infant food products sold in the most isolated provision shops. This paper focuses on key sociological factors that might predict the frequency and duration of breastfeeding and weaning patterns. The data analysed below, collected during semi-structured interviews with 278 women presenting at Maternal and Child Health Clinics in Peninsular Malaysia, are in part confusing. They suggest that the women most likely to bottle feed only or to breast feed for a short period, and to use commercial baby foods, are young, with one child only, who reside in urban or peri-urban areas and have a reasonable household income. Higher educated women, and women whose husbands are in non-traditional occupations, are also less likely to breast feed or to do so for an extended period. But the profile of infant feeding practices is by no means clear. One of the shortcomings of the study relates to the method of collection of data, and highlights the need for detailed ethnographic studies to better explore the variability and complexity of the patterns of infant feeding. PMID:6695200

  12. 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.

  13. 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.

  14. 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. PMID:18023502

  15. 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. PMID:23962403

  16. 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.

  17. Home enteral feeding: part 2 current issues in community practice.

    PubMed

    Fogg, Louisa

    2007-07-01

    Part 1 provided an overview of enteral tube feeding and management in the community. Due to the limited evidence base there are many aspects of the practical management of patients on home enteral tube feeding (HETF) that has as yet not been standardized, particularly around issues such as the type of syringes and water that should be used in HETF. There are also some areas where the guidelines are clear but difficult to apply in the community (such as with maximum feed 'hanging times') or where further guidance is required (such as for confirming the position of nasogastric tubes in patients on acid-reducing therapy). Finally, as NHS trusts look at further ways to save money, enteral feeding is being increasingly scrutinised and needs to be carefully managed, with the involvement of healthcare professionals who understand patient needs and the commercial HETF market. This article is based on personal views and local discussions about the issues in question and, until further research and national standards are available, are subject to local interpretation. PMID:17851308

  18. Historical Overview of Transitional Feeding Recommendations and Vegetable Feeding Practices for Infants and Young Children

    PubMed Central

    Kleinman, Ronald E.; Coletta, Frances A.

    2016-01-01

    Although recommendations for introducing solid foods to infants and young children have changed significantly since the beginning of the 20th century, vegetable consumption recommendations have always been an important part of the child-feeding repertoire. In 1958, the first report of the American Academy of Pediatrics (AAP) Committee on Nutrition stated that developmental maturity of the gut and neuromuscular system, growth rate, and activity level were good indicators for determining when to introduce solid foods to infants than age. All 7 editions of the AAP Pediatric Nutrition Handbook use an evidence-based model for recommendations concerning the complementary feeding of infants and young children. The model includes developmental readiness principles, feeding practices, and age-appropriate nutrient requirements. Dietary patterns and nutrient consumption among infants and young children have been analyzed using data from the 2002 and 2008 Feeding Infants and Toddlers Study (FITS). The 2008 FITS also collected information concerning participation in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). Since 1972, WIC has been a cost-effective means of improving the diets and health of infants and young children from low-income families. Data from the 2008 FITS showed that many young children did not consume recommended amounts of fiber or potassium, and vegetable and fruit intakes continued to be lower than recommended. Low vegetable consumption and limited variety were also seen among WIC participants and nonparticipants aged 6 months to 4 years prior to changes in the WIC food package. Increasing children’s consumption of all vegetables should continue to be a focus going forward. PMID:27003950

  19. Low inhibitory control and restrictive feeding practices predict weight outcomes

    PubMed Central

    Anzman, Stephanie L.; Birch, Leann L.

    2009-01-01

    Objective A priority for research is to identify individuals early in development who are particularly susceptible to weight gain in the current, obesogenic environment. This longitudinal study investigated whether early individual differences in inhibitory control, an aspect of temperament, predicted weight outcomes and whether parents’ restrictive feeding practices moderated this relation. Study design Participants included 197 non-Hispanic White girls and their parents; families were assessed when girls were 5, 7, 9, 11, 13, and 15 years old. Measures included mothers’ reports of girls’ inhibitory control levels, girls’ reports of parental restriction in feeding, girls’ body mass indexes (BMIs), and parents’ BMIs, education, and income. Results Girls with lower inhibitory control at age 7 had higher concurrent BMIs, greater weight gain, higher BMIs at all subsequent time points, and were 1.95 times more likely to be overweight at age 15. Girls who perceived higher parental restriction exhibited the strongest inverse relation between inhibitory control and weight status. Conclusion Variability in inhibitory control could help identify individuals who are predisposed to obesity risk; the current findings also highlight the importance of parenting practices as potentially modifiable factors which exacerbate or attenuate this risk. PMID:19595373

  20. 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.

  1. 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.

  2. 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. PMID:27352882

  3. Complementary feeding practices in South Asia: analyses of recent national survey data by the South Asia Infant Feeding Research Network.

    PubMed

    Senarath, Upul; Dibley, Michael J

    2012-01-01

    South Asian region has the highest global burden of child undernutrition, with almost 41% of children stunted, 16% wasted and 33% underweight. Improved feeding of children less than 2 years of age is particularly important because they experience rapid growth and development, and are vulnerable to illnesses such as acute respiratory infections and diarrhoeal diseases. The present supplement aimed to describe complementary feeding practices in five South Asian countries - Bangladesh, India, Nepal, Pakistan and Sri Lanka - using the new and updated global complementary feeding indicators and to identify determinants of inappropriate complementary feeding practices. The South Asia Infant Feeding Research Network held a series of workshops to study and discuss the operational guidelines for the new complementary feeding indicators in consultation with regional and international experts. The latest Demographic and Health Surveys for Bangladesh, Nepal, Pakistan and Sri Lanka, and the National Family Health Survey of India were used as data sources. Four key indicators were calculated: introduction of solid, semisolid or soft foods in 6-8 months aged, minimum dietary diversity, minimum meal frequency and minimum acceptable diet in 6-23-month-aged children. Univariate and multivariate logistic regression analyses were performed to identify determinants of poor complementary feeding practices. The papers in this supplement present results of these analyses for each individual country and a comparison between countries. The results have important implications for policies, programmes and research on infant and young child feeding in the region, especially for targeting groups at high risk for suboptimal practices.

  4. Marketing Breastfeeding—Reversing Corporate Influence on Infant Feeding Practices

    PubMed Central

    Graff, Kristina M.

    2008-01-01

    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 (~85%), a minority of infants is breastfed exclusively at 8 weeks postpartum (~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. PMID:18463985

  5. Breast-feeding in preterm twins: Development of feeding behavior and milk intake during hospital stay and related caregiving practices.

    PubMed

    Nyqvist, Kerstin Hedberg

    2002-08-01

    In a prospective study of 13 preterm twins still in the hospital, 85% were breast-fed, of which 46% were breast-fed exclusively. Most mothers preferred simultaneous breast-feeding, using the football hold. Observations and maternal descriptions showed differences between the twins in their development of breast-feeding behavior, especially in sucking. The mothers' suggestions regarding special support for the breast-feeding mothers of preterm twins involved synchronizing feeding with the twins' behavioral states; twin cobedding; appropriate armchairs and breast-feeding pillows; experimenting with breast-feeding positions; information about breast milk production; nurses' spontaneous practical assistance, encouragement, and emotional support; the provision of privacy; the availability of parent rooms; and opportunities for fathers' presence in the hospital. PMID:12219324

  6. 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

  7. 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.

  8. CRTAM determines the CD4+ cytotoxic T lymphocyte lineage.

    PubMed

    Takeuchi, Arata; Badr, Mohamed El Sherif Gadelhaq; Miyauchi, Kosuke; Ishihara, Chitose; Onishi, Reiko; Guo, Zijin; Sasaki, Yoshiteru; Ike, Hiroshi; Takumi, Akiko; Tsuji, Noriko M; Murakami, Yoshinori; Katakai, Tomoya; Kubo, Masato; Saito, Takashi

    2016-01-11

    Naive T cells differentiate into various effector T cells, including CD4(+) helper T cell subsets and CD8(+) cytotoxic T cells (CTL). Although cytotoxic CD4(+) T cells (CD4 +: CTL) also develop from naive T cells, the mechanism of development is elusive. We found that a small fraction of CD4(+) T cells that express class I-restricted T cell-associated molecule (CRTAM) upon activation possesses the characteristics of both CD4(+) and CD8(+) T cells. CRTAM(+) CD4(+) T cells secrete IFN-γ, express CTL-related genes, such as eomesodermin (Eomes), Granzyme B, and perforin, after cultivation, and exhibit cytotoxic function, suggesting that CRTAM(+) T cells are the precursor of CD4(+)CTL. Indeed, ectopic expression of CRTAM in T cells induced the production of IFN-γ, expression of CTL-related genes, and cytotoxic activity. The induction of CD4(+)CTL and IFN-γ production requires CRTAM-mediated intracellular signaling. CRTAM(+) T cells traffic to mucosal tissues and inflammatory sites and developed into CD4(+)CTL, which are involved in mediating protection against infection as well as inducing inflammatory response, depending on the circumstances, through IFN-γ secretion and cytotoxic activity. These results reveal that CRTAM is critical to instruct the differentiation of CD4(+)CTL through the induction of Eomes and CTL-related gene.

  9. CRTAM determines the CD4+ cytotoxic T lymphocyte lineage

    PubMed Central

    Takeuchi, Arata; Badr, Mohamed El Sherif Gadelhaq; Miyauchi, Kosuke; Ishihara, Chitose; Onishi, Reiko; Guo, Zijin; Sasaki, Yoshiteru; Ike, Hiroshi; Takumi, Akiko; Tsuji, Noriko M.; Murakami, Yoshinori; Katakai, Tomoya; Kubo, Masato

    2016-01-01

    Naive T cells differentiate into various effector T cells, including CD4+ helper T cell subsets and CD8+ cytotoxic T cells (CTL). Although cytotoxic CD4+ T cells (CD4+CTL) also develop from naive T cells, the mechanism of development is elusive. We found that a small fraction of CD4+ T cells that express class I–restricted T cell–associated molecule (CRTAM) upon activation possesses the characteristics of both CD4+ and CD8+ T cells. CRTAM+ CD4+ T cells secrete IFN-γ, express CTL-related genes, such as eomesodermin (Eomes), Granzyme B, and perforin, after cultivation, and exhibit cytotoxic function, suggesting that CRTAM+ T cells are the precursor of CD4+CTL. Indeed, ectopic expression of CRTAM in T cells induced the production of IFN-γ, expression of CTL-related genes, and cytotoxic activity. The induction of CD4+CTL and IFN-γ production requires CRTAM-mediated intracellular signaling. CRTAM+ T cells traffic to mucosal tissues and inflammatory sites and developed into CD4+CTL, which are involved in mediating protection against infection as well as inducing inflammatory response, depending on the circumstances, through IFN-γ secretion and cytotoxic activity. These results reveal that CRTAM is critical to instruct the differentiation of CD4+CTL through the induction of Eomes and CTL-related gene. PMID:26694968

  10. Differential endocytosis of CD4 in lymphocytic and nonlymphocytic cells

    PubMed Central

    1991-01-01

    The endocytosis of the T cell differentiation antigen CD4 has been investigated in CD4-transfected HeLa cells, the promyelocytic HL-60 cell line, and in a number of leukemia- or lymphoma-derived T cell lines. CD4 internalization was followed using radioiodinated antibodies in an acid-elution endocytosis assay, or by covalently modifying cell surface proteins with biotin and analyzing CD4 distributions by immunoprecipitation; both approaches gave equivalent results. The assays demonstrated that in transfected HeLa cells and in HL-60 cells CD4 was constitutively internalized and recycled in the absence of ligand. Immunogold labeling and electron microscopy demonstrated that CD4 enters cells through coated pits. In contrast to the nonlymphocytic cells, T cell lines showed very little endocytosis of CD4. Measurements of fluid phase endocytosis and morphometric analysis of the endosome compartment indicated that the endocytic capacities of HeLa and lymphoid cells are equivalent and suggested that the low level of CD4 uptake in lymphocytic cells is due to exclusion of CD4 from coated pits. This conclusion was supported by experiments using truncated CD4 molecules, lacking the bulk of the cytoplasmic domain, which were internalized equally efficiently in both transfected lymphocytes and HeLa cells. Together, these results indicate that the cytoplasmic domain of CD4 mediates the different interactions with the endocytic apparatus in lymphoid and nonlymphoid cells. We suggest that the CD4- associated lymphocyte-specific protein tyrosine kinase p56lck may be involved in preventing CD4 endocytosis in T cells. PMID:1900077

  11. 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

  12. 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

  13. Milk distribution and feeding practice data for the PATHWAY model

    SciTech Connect

    Ward, G.M.; Whicker, F.W. )

    1990-11-01

    Milk is a major source for ingestion of several radionuclides, particularly when it is produced from fresh forage. Estimation of radionuclide ingestion via milk from Nevada Test Site fallout events in the 1950s required information on the sources of milk, feeding practices for cows, and elapsed time between milking and consumption for various geographic areas. These data were essential input to the food-chain model, PATHWAY. A data base was compiled from personal interviews. Milk sources included private cows, local dairies, and regional plants that collected from and distributed to wide geographic areas. Estimates of the contribution of each source were made for communities in a nine-state area. Pasture seasons varied from 3 to 6 mo. Pasture use varied from zero to 80% of the cows' diet. Pasture use declined during the 1950s, as did the number of family cows and local dairy plants. Regional distributors captured a larger portion of the market, and improved technologies increased the shelf life of milk. These factors tended to reduce the human intake of fallout radionuclides from milk in the latter part of the 1950s.

  14. Exclusive Transduction of Human CD4+ T Cells upon Systemic Delivery of CD4-Targeted Lentiviral Vectors.

    PubMed

    Zhou, Qi; Uhlig, Katharina M; Muth, Anke; Kimpel, Janine; Lévy, Camille; Münch, Robert C; Seifried, Janna; Pfeiffer, Anett; Trkola, Alexandra; Coulibaly, Cheick; von Laer, Dorothee; Wels, Winfried S; Hartwig, Udo F; Verhoeyen, Els; Buchholz, Christian J

    2015-09-01

    Playing a central role in both innate and adaptive immunity, CD4(+) T cells are a key target for genetic modifications in basic research and immunotherapy. In this article, we describe novel lentiviral vectors (CD4-LV) that have been rendered selective for human or simian CD4(+) cells by surface engineering. When applied to PBMCs, CD4-LV transduced CD4(+) but not CD4(-) cells. Notably, also unstimulated T cells were stably genetically modified. Upon systemic or intrasplenic administration into mice reconstituted with human PBMCs or hematopoietic stem cells, reporter gene expression was predominantly detected in lymphoid organs. Evaluation of GFP expression in organ-derived cells and blood by flow cytometry demonstrated exclusive gene transfer into CD4(+) human lymphocytes. In bone marrow and spleen, memory T cells were preferentially hit. Toward therapeutic applications, we also show that CD4-LV can be used for HIV gene therapy, as well as for tumor therapy, by delivering chimeric Ag receptors. The potential for in vivo delivery of the FOXP3 gene was also demonstrated, making CD4-LV a powerful tool for inducible regulatory T cell generation. In summary, our work demonstrates the exclusive gene transfer into a T cell subset upon systemic vector administration opening an avenue toward novel strategies in immunotherapy.

  15. Rate of CD4 Decline and Factors Associated with Rapid CD4 Decline in Asymptomatic HIV-Infected Patients.

    PubMed

    Chaiyasin, Natdanai; Sungkanuparph, Somnuek

    2016-01-01

    The accurate marker to assess the risk of disease progression in HIV disease is CD4 count. CD4 decline to <200 cells/mm3 prompts the patients to have risk of opportunistic infections. A retrospective cohort study was conducted in asymptomatic HIV-infected patients who had CD4 count>200 cell/mm3, were antiretroviral naive, and had ≥1-year follow-up. Eighty patients, with mean age of 36.4 (standard deviation [SD]=9.1) years and 58.8% females, were analyzed. The mean (SD) baseline CD4 count was 423 (119) cells/mm3. During the median (IQR) time of 29.0 (14.1-49.6) months, 26.3% had CD4 declined to <200 cells/mm3. From Cox proportional hazard model, only baseline CD4 count<350 cells/mm3 was significantly associated with rapid decline in CD4 count (HR 4.208; 95%CI, 1.428-12.397; P=.009). Age, gender, comorbid disease, risk of HIV infection, duration of HIV diagnosis, and body weight were not associated with rapid CD4 decline. This indicates that asymptomatic patients with CD4 count<350 cells/mm3 are at priority for antiretroviral therapy in resource-limited settings.

  16. 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…

  17. 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...

  18. Sialylation regulates peripheral tolerance in CD4+ T cells.

    PubMed

    Brennan, Patrick J; Saouaf, Sandra J; Van Dyken, Steve; Marth, Jamey D; Li, Bin; Bhandoola, Avinash; Greene, Mark I

    2006-05-01

    Decreased binding by the 6C10 auto-antibody serves as a unique marker for CD4+ T cell unresponsiveness after the induction of T cell tolerance in Vbeta8.1 TCR transgenic mice. We further define the nature of the epitope recognized by the 6C10 antibody to be a subset of Thy-1 bearing incompletely sialylated N-linked glycans, and furthermore, we demonstrate that tolerant CD4+ T cells have an increased degree of cell-surface sialylation. To test the significance of the altered glycosylation state identified by the 6C10 auto-antibody in the tolerant CD4+ T cell population, surface sialic acid was cleaved enzymatically. Treatment of purified peripheral CD4+ T cells with Vibrio cholerae sialidase (VCS) leads to increased 6C10 binding, significantly enhances proliferation in the tolerant CD4+ population and corrects defects in phosphotyrosine signaling observed in the tolerant CD4+ T cell. Furthermore, in vivo administration of VCS enhances proliferation in both tolerant and naive CD4+ T cell subsets. These studies suggest that sialylation of glycoproteins on the surface of the CD4+ T cell contributes to the regulation of T cell responsiveness in the tolerant state. PMID:16291658

  19. 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…

  20. Factors associated with parental use of restrictive feeding practices to control their children's food intake.

    PubMed

    Gray, Wendy N; Janicke, David M; Wistedt, Kristin M; Dumont-Driscoll, Marilyn C

    2010-10-01

    There is a critical need to identify risk factors that make parents more likely to restrict their child's food intake. Child weight and ethnicity, parent weight, parent body dissatisfaction, and parent concern of child weight were examined as correlates of parent use of restrictive feeding practices in a diverse sample of 191 youth (ages 7-17). Participants attending a pediatric outpatient visit completed the Child Feeding Questionnaire (parent feeding practices and beliefs), the Figure Rating Scale (body dissatisfaction) and a demographic form. Parent BMI and child degree of overweight were calculated. Parent use of restrictive feeding practices was positively associated with parent BMI and was moderated by parent body dissatisfaction. Parent concern of child weight mediated the relationship between increasing child degree of overweight and parent use of restrictive feeding practices. There were no differences by child gender or ethnicity in parent use of restrictive feeding practices. These preliminary findings highlight the importance of assessing for underlying parent motivations for utilizing restrictive feeding practices and may help to identify and intervene with families at-risk for engaging in counterproductive weight control strategies. Continued identification of correlates of parent use of restrictive feeding practices is needed across child development and among individuals from diverse backgrounds. PMID:20633586

  1. 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

  2. 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

  3. 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.

  4. Breast-feeding and infant feeding practices in selected rural and semi-urban communities in Kemaman, Terengganu.

    PubMed

    Manan, W A

    1995-03-01

    A survey was carried out in the district of Kemaman, Terengganu, Malaysia to study infant feeding practices in rural and semi-urban communities. A total of 593 mothers were interviewed and their socio-demographic information recorded. Data on infant feeding practices were collected from mothers who had children up to 15 months of age. Among breast-feeding mothers (n =157), 42.0 % fed their babies for less than 3 months and 58.0% bottle fed for more than 6 months. Sixteen children were found to be fed on sweetened condensed milk with 62.5% of them for the first 3 months. Among those who breast fed their babies, 40.1% were found to have bottle fed at one time or another. The majority of breast feeding mothers belonged to the groups having incomplete primary schooling or completed primary education only and household income below RM600 per month. A substantial number of breast fed babies were given weaning foods in the form of porridge mixture (rice + egg, rice + vegetables, rice + meat, rice+ fish and cereals) between the age of 0 - 3 months. The findings of this study concluded that although breast-feeding is widely practiced, however, their duration has dwindled, and early introduction of solid foods is widespread. PMID:22692014

  5. Regulated expression of human CD4 rescues helper T cell development in mice lacking expression of endogenous CD4.

    PubMed Central

    Killeen, N; Sawada, S; Littman, D R

    1993-01-01

    During T cell development, precursor thymocytes that co-express the CD4 and CD8 glycoproteins give rise to mature progeny expressing one of these molecules to the exclusion of the other. Continued expression of only CD4 is the hallmark of mature helper T cells, whereas cytotoxic T cells express CD8 and extinguish CD4. The differentiation program that generates the two T cell subsets is likely to be intimately tied to regulation of expression of these cell surface molecules. We now describe the use of a murine CD4 enhancer in the generation of transgenic mice expressing physiologic levels of human CD4. The transgene is appropriately regulated during T cell development and includes the necessary cis-acting sequences for extinguishing expression in the CD8 lineage. Furthermore, in mice whose endogenous CD4 gene is inactivated, the transgenic human CD4 mediates rescue of the CD4 lineage and restoration of normal helper cell functions. The generation of these mice exemplifies a general approach for developing reliable animal models for the human immune system. Images PMID:8467804

  6. 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

  7. 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. PMID:3492511

  8. 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

  9. 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.

  10. 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. PMID:25555536

  11. Isolation and Characterization of Salmonid CD4+ T Cells.

    PubMed

    Maisey, Kevin; Montero, Ruth; Corripio-Miyar, Yolanda; Toro-Ascuy, Daniela; Valenzuela, Beatriz; Reyes-Cerpa, Sebastián; Sandino, Ana María; Zou, Jun; Wang, Tiehui; Secombes, Christopher J; Imarai, Mónica

    2016-05-15

    This study reports the isolation and functional characterization of rainbow trout (Oncorhynchus mykiss) CD4-1(+) T cells and the establishment of an IL-15-dependent CD4-1(+) T cell line. By using Abs specific for CD4-1 and CD3ε it was possible to isolate the double-positive T cells in spleen and head kidney. The morphology and the presence of transcripts for T cell markers in the sorted CD4-1(+)CD3ε(+) cells were studied next. Cells were found to express TCRα, TCRβ, CD152 (CTLA-4), CD154 (CD40L), T-bet, GATA-3, and STAT-1. The sorted CD4-1(+) T cells also had a distinctive functional attribute of mammalian T lymphocytes, namely they could undergo Ag-specific proliferation, using OVA as a model Ag. The OVA-stimulated cells showed increased expression of several cytokines, including IFN-γ1, IL-4/13A, IL-15, IL-17D, IL-10, and TGF-β1, perhaps indicating that T cell proliferation led to differentiation into distinct effector phenotypes. Using IL-15 as a growth factor, we have selected a lymphoid cell line derived from rainbow trout head kidney cells. The morphology, cell surface expression of CD4-1, and the presence of transcripts of T cell cytokines and transcription factors indicated that this is a CD4-1(+) T cell line. To our knowledge, this is the first demonstration of the presence of CD4-1(+)CD3ε(+) T cells in salmonids. As in mammals, CD4-1(+) T cells may be the master regulators of immune responses in fish, and therefore these findings and the new model T cell line developed will contribute to a greater understanding of T cell function and immune responses in teleost fish. PMID:27053758

  12. 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

  13. 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

  14. 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. PMID:26364791

  15. 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.

  16. 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.…

  17. 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.

  18. 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.

  19. 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

  20. 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. PMID:15980096

  1. 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

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

    PubMed Central

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

    2015-01-01

    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. PMID:26478664

  3. Trends and Predictors of Prelacteal Feeding Practices in Nigeria (2003–2013)

    PubMed Central

    Agho, Kingsley E.; Ogeleka, Pascal; Ogbo, Felix A.; Ezeh, Osita K.; Eastwood, John; Page, Andrew

    2016-01-01

    Prelacteal feeding practices are associated with an increased risk of diarrhoea and many early-life diseases. This paper examined trends and predictors of prelacteal feeding practices in Nigeria. A sample of 6416 infants aged 0–6 months from the Nigeria Demographic and Health Survey data for the period (2003–2013) was used. Trends and multilevel logistic regression analyses were used to determine the predictors. The trends of prelacteal feeding rates fluctuated between 55% and 66% over the study period and were significantly lower among mothers with secondary or higher levels of education (13.1%, 95% confidence interval (CI): 0.54–25.9, p-value = 0.041), delivered at the health facility (13.7%, CI: 1.39–25.9, p-value = 0.029), from more affluent households (18.7%, CI: 1.53–35.9, p-value = 0.033), and lived in urban areas (26.9%, CI: 18.3–35.5, p-value < 0.001). Multivariable analyses revealed that mothers with no schooling, younger mothers (aged 15–24 years), mothers who delivered at home, and delivered by caesarean section were more likely to introduce prelacteal feeds. Many mothers still engage in prelacteal feeding practices in Nigeria, with prelacteal feeding more prevalent in young mothers, mothers with no schooling, and mothers who delivered at home. Interventions involving community health volunteers are needed to improve feeding practices in Nigeria. PMID:27483309

  4. Trends and Predictors of Prelacteal Feeding Practices in Nigeria (2003-2013).

    PubMed

    Agho, Kingsley E; Ogeleka, Pascal; Ogbo, Felix A; Ezeh, Osita K; Eastwood, John; Page, Andrew

    2016-01-01

    Prelacteal feeding practices are associated with an increased risk of diarrhoea and many early-life diseases. This paper examined trends and predictors of prelacteal feeding practices in Nigeria. A sample of 6416 infants aged 0-6 months from the Nigeria Demographic and Health Survey data for the period (2003-2013) was used. Trends and multilevel logistic regression analyses were used to determine the predictors. The trends of prelacteal feeding rates fluctuated between 55% and 66% over the study period and were significantly lower among mothers with secondary or higher levels of education (13.1%, 95% confidence interval (CI): 0.54-25.9, p-value = 0.041), delivered at the health facility (13.7%, CI: 1.39-25.9, p-value = 0.029), from more affluent households (18.7%, CI: 1.53-35.9, p-value = 0.033), and lived in urban areas (26.9%, CI: 18.3-35.5, p-value < 0.001). Multivariable analyses revealed that mothers with no schooling, younger mothers (aged 15-24 years), mothers who delivered at home, and delivered by caesarean section were more likely to introduce prelacteal feeds. Many mothers still engage in prelacteal feeding practices in Nigeria, with prelacteal feeding more prevalent in young mothers, mothers with no schooling, and mothers who delivered at home. Interventions involving community health volunteers are needed to improve feeding practices in Nigeria. PMID:27483309

  5. 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

  6. Functional and Phenotypic Plasticity of CD4+ T Cell Subsets

    PubMed Central

    Caza, Tiffany; Landas, Steve

    2015-01-01

    The remarkable plasticity of CD4+ T cells allows individuals to respond to environmental stimuli in a context-dependent manner. A balance of CD4+ T cell subsets is critical to mount responses against pathogen challenges to prevent inappropriate activation, to maintain tolerance, and to participate in antitumor immune responses. Specification of subsets is a process beginning in intrathymic development and continuing within the circulation. It is highly flexible to adapt to differences in nutrient availability and the tissue microenvironment. CD4+ T cell subsets have significant cross talk, with the ability to “dedifferentiate” given appropriate environmental signals. This ability is dependent on the metabolic status of the cell, with mTOR acting as the rheostat. Autoimmune and antitumor immune responses are regulated by the balance between regulatory T cells and Th17 cells. When a homeostatic balance of subsets is not maintained, immunopathology can result. CD4+ T cells carry complex roles within tumor microenvironments, with context-dependent immune responses influenced by oncogenic drivers and the presence of inflammation. Here, we examine the signals involved in CD4+ T cell specification towards each subset, interconnectedness of cytokine networks, impact of mTOR signaling, and cellular metabolism in lineage specification and provide a supplement describing techniques to study these processes. PMID:26583116

  7. Feeding beliefs and practices of Chinese immigrant mothers. Validation of a modified version of the child feeding questionnaire.

    PubMed

    Liu, Wei-Hong; Mallan, Kimberley M; Mihrshahi, Seema; Daniels, Lynne A

    2014-09-01

    The Child Feeding Questionnaire (CFQ) developed by Birch et al. (2001) is a widely used tool for measuring parental feeding beliefs, attitudes and practices. However, the appropriateness of the CFQ for use with Chinese populations is unknown. This study tested the construct validity of a novel Chinese version of the CFQ using confirmatory factor analysis (CFA). Participants included a convenience sample of 254 Chinese-Australian mothers of children aged 1-4 years. Prior to testing, the questionnaire was translated into Chinese using a translation-back-translation method, one item was reworded to be culturally appropriate, a new item was added (monitoring), and five items that were not age-appropriate for the sample were removed. Based on previous literature, both a seven-factor and an eight-factor model were assessed via CFA. Results showed that the eight-factor model, which separated restriction and use of food rewards, improved the conceptual clarity of the constructs and provided a good fit to the data. Internal consistency of all eight factors was acceptable (Cronbach's α: .60-.93). This modified eight-factor CFQ appears to be a linguistically and culturally appropriate instrument for assessing feeding beliefs and practices in Chinese-Australian mothers of young children.

  8. Infant feeding in the first year. 2: feeding practices from 6-12 months of life.

    PubMed

    Meyer, Rosan

    2009-01-01

    The mainstay of nutrition in infants below six months of age is breast and/or formula milk. Infants aged between six and 12 months require additional sources of nutrition and numerous oral and developmental milestones have to be achieved to support normal development of feeding skills. Requirements increase during this period for protein, vitamin D, thiamin, niacin, vitamin B6, vitamin B12, zinc, iron and magnesium. This increased demand is met through weaning foods and breast-feeding, and, if breast milk is not available, through a suitable milk formula. The choice of milk formula above the age of six months is very much dependent on the individual infant and the stage of weaning. One of the principal factors in choosing a suitable formula at this age is the depleting iron stores. Infant formulae suitable from birth along with age-appropriate weaning foods will provide adequate iron for the majority of infants. However, iron-fortified formula may be useful to reduce iron deficiency in some vulnerable infants. Weaning should be commenced by six months of age, but not earlier than 17 weeks. Delaying wheat, egg, soy, fish and dairy beyond six months of age does not prevent the development of allergies and these foods contribute significantly to nutrients required for growth and development. It is important that parents receive evidence-based guidance on what constitutes optimal nutrition during this period of increased requirements and rapid development. PMID:19517945

  9. Infant feeding in the first year. 2: feeding practices from 6-12 months of life.

    PubMed

    Meyer, Rosan

    2009-01-01

    The mainstay of nutrition in infants below six months of age is breast and/or formula milk. Infants aged between six and 12 months require additional sources of nutrition and numerous oral and developmental milestones have to be achieved to support normal development of feeding skills. Requirements increase during this period for protein, vitamin D, thiamin, niacin, vitamin B6, vitamin B12, zinc, iron and magnesium. This increased demand is met through weaning foods and breast-feeding, and, if breast milk is not available, through a suitable milk formula. The choice of milk formula above the age of six months is very much dependent on the individual infant and the stage of weaning. One of the principal factors in choosing a suitable formula at this age is the depleting iron stores. Infant formulae suitable from birth along with age-appropriate weaning foods will provide adequate iron for the majority of infants. However, iron-fortified formula may be useful to reduce iron deficiency in some vulnerable infants. Weaning should be commenced by six months of age, but not earlier than 17 weeks. Delaying wheat, egg, soy, fish and dairy beyond six months of age does not prevent the development of allergies and these foods contribute significantly to nutrients required for growth and development. It is important that parents receive evidence-based guidance on what constitutes optimal nutrition during this period of increased requirements and rapid development.

  10. Oral vaccination with lipid-formulated BCG induces a long-lived, multifunctional CD4(+) T cell memory immune response.

    PubMed

    Ancelet, Lindsay R; Aldwell, Frank E; Rich, Fenella J; Kirman, Joanna R

    2012-01-01

    Oral delivery of BCG in a lipid formulation (Liporale™-BCG) targets delivery of viable bacilli to the mesenteric lymph nodes and confers protection against an aerosol Mycobacterium tuberculosis challenge. The magnitude, quality and duration of the effector and memory immune response induced by Liporale™-BCG vaccination is unknown. Therefore, we compared the effector and memory CD4(+) T cell response in the spleen and lungs of mice vaccinated with Liporale™-BCG to the response induced by subcutaneous BCG vaccination. Liporale™-BCG vaccination induced a long-lived CD4(+) T cell response, evident by the detection of effector CD4(+) T cells in the lungs and a significant increase in the number of Ag85B tetramer-specific CD4(+) T cells in the spleen up to 30 weeks post vaccination. Moreover, following polyclonal stimulation, Liporale™-BCG vaccination, but not s.c. BCG vaccination, induced a significant increase in both the percentage of CD4(+) T cells in the lungs capable of producing IFNγ and the number of multifunctional CD4(+) T cells in the lungs at 30 weeks post vaccination. These results demonstrate that orally delivered Liporale™-BCG vaccine induces a long-lived multifunctional immune response, and could therefore represent a practical and effective means of delivering novel BCG-based TB vaccines. PMID:23049885

  11. 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.

  12. 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. PMID:24275668

  13. 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. PMID:21495181

  14. Analysis of CD4-positive T cell subpopulation in sarcoidosis.

    PubMed Central

    Gerli, R; Darwish, S; Broccucci, L; Minotti, V; Spinozzi, F; Cernetti, C; Bertotto, A; Rambotti, P

    1988-01-01

    Double-labelling immunofluorescence analysis within the CD4+ cell subset was carried out in 27 bronchoalveolar lavage fluids and 11 peripheral blood samples of sarcoidosis patients with anti-TQ1, anti-2H4 and anti-4B4 monoclonal antibodies. Helper/inducer CD4+TQ1-/4B4+ cells were strongly increased in the lung and slightly, but significantly, decreased in the blood of sarcoidosis patients with respect to normal controls. No differences were found in the number of both lung and blood CD4+2H4+ cells between sarcoidosis patients and controls. The findings are further evidence for a compartmentalization of T cell subsets in sarcoidosis. PMID:3263230

  15. 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

  16. 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.

  17. 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. PMID:24269508

  18. 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. PMID:24780349

  19. 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.

  20. 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.

  1. Feeding of Young Children during Diarrhea: Caregivers' Intended Practices and Perceptions

    PubMed Central

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

    2014-01-01

    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. PMID:25092824

  2. Child feeding knowledge and practices among women participating in growth monitoring and promotion in Accra, Ghana

    PubMed Central

    2014-01-01

    Background Child undernutrition and poor feeding practices remain a concern in Ghana. The Growth Monitoring and Promotion (GMP) programme seeks to empower mothers to provide appropriate child care. Although the program has been implemented in Ghana for over four decades, little is known about its impact on child feeding outcomes. The current study assessed the association between GMP exposure and mothers' child feeding knowledge and practices in the Accra Metropolitan Area (AMA), Ghana. Methods A cross-sectional survey of 199 mother-child pairs accessing child welfare services in six public health facilities in the AMA was conducted. A structured questionnaire was used to collect data on respondent characteristics and child feeding knowledge; a 24-hour dietary recall tool was used to record child feeding practices. Linear regression analysis was used to determine the association between mothers' exposure to GMP and their knowledge and practices on child feeding. Results Seventy four percent of mothers had not missed any scheduled child welfare clinic sessions. Over 60% of mothers knew the appropriate age of introduction of foods; 86% also gave correct response regarding minimum number of times their child should be fed daily. About 81% of children less than 6 months were exclusively breastfed in the preceding 24 hours, although 36% had received water since birth. Forty two percent of children 6–23 months received dietary diverse meals while 64% were fed the required number of times in a day. Overall, only 32% of children 6–23 months received a minimum acceptable diet in the preceding 24 hours. A higher GMP exposure was positively associated with feeding knowledge scores among mothers with children below 6 months (p < 0.05). Conclusion Although most mothers were knowledgeable about recommendations, feeding practices were suboptimal, especially complementary feeding. GMP exposure was associated with feeding knowledge only among mothers with children less

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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. ...

  9. 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

  10. 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

  11. Mechanism of human immunodeficiency virus type 1 localization in CD4-negative thymocytes: differentiation from a CD4-positive precursor allows productive infection.

    PubMed Central

    Kitchen, S G; Uittenbogaart, C H; Zack, J A

    1997-01-01

    Human immunodeficiency virus (HIV) infection of the thymus could have profound effects on development of the immune response, particularly in children. We and others have established that in addition to infecting and depleting CD4-bearing thymocytes, functional HIV proviruses are found in thymocytes lacking surface CD4 expression. Using in vitro thymocyte cultures, we show that neither HIV-mediated down regulation of CD4 nor CD4-independent infection contributes to the localization of HIV in cells lacking the primary virus receptor. Rather, infection of a CD4-positive precursor cell (CD4 positive/CD8 positive) with subsequent differentiation into a mature CD4-negative phenotype results in productively infected CD4-negative cells. This novel mechanism may contribute to pathogenesis by distributing viral sequences into functional subsets of T cells typically refractory to HIV infection and could account for the presence of viral DNA in CD8-positive lymphocytes recently observed in patients. PMID:9223457

  12. Latina Mothers’ Beliefs and Practices Related to Weight Status, Feeding and the Development of Child Overweight

    PubMed Central

    2010-01-01

    Objective To examine maternal beliefs and practices related to weight status, child feeding, and child overweight in the Latino culture that may contribute to the rising rates of overweight among preschool Latino children in the U.S. Design and sample This two-phase qualitative study relies on data obtained in 6 focus groups with a total of 31 primarily Spanish-speaking, low income mothers, followed by 20 individual, in-depth interviews with women participating in a health promotion educational program. Measures Child-feeding beliefs, practices and weight status perceptions were elicited. Results Findings indicated that most respondents reported personal struggles with weight gain, particularly during and after pregnancy, and were concerned that their children would become obese. Although subjects understood the health and social consequences related to overweight, many discussed the pressures of familial and cultural influences endorsing a “chubby child.” Conclusions Education and interventions that incorporate “culturally mediated” pathways to address mothers’ feeding practices are essential for prevention and control of childhood overweight among low-income Latinos. Nurses should be aware of social and cultural influences on Latina mothers’ beliefs and practices related to weight status and feeding practices and address these in their education approaches to prevent childhood overweight and obesity with this population group. PMID:21442018

  13. An Assessment of the Breastfeeding Practices and Infant Feeding Pattern among Mothers in Mauritius

    PubMed Central

    Motee, Ashmika; Ramasawmy, Deerajen; Pugo-Gunsam, Prity; Jeewon, Rajesh

    2013-01-01

    Proper breastfeeding practices are effective ways for reducing childhood morbidity and mortality. While many mothers understand the importance of breastfeeding, others are less knowledgeable on the benefits of breastfeeding and weaning. The aim in here is to assess breastfeeding pattern, infant formula feeding pattern, and weaning introduction in Mauritius and to investigate the factors that influence infant nutrition. 500 mothers were interviewed using a questionnaire which was designed to elicit information on infant feeding practices. Statistical analyses were done using SPSS (version 13.0), whereby chi-square tests were used to evaluate relationships between different selected variables. The prevalence of breastfeeding practice in Mauritius has risen from 72% in 1991 to 93.4% as found in this study, while only 17.9% breastfed their children exclusively for the first 6 months, and the mean duration of EBF (exclusive breastfeeding) is 2.10 months. Complementary feeding was more commonly initiated around 4–6 months (75.2%). Despite the fact that 60.6% of mothers initiate breastfeeding and 26.1% of mothers are found to breastfeed up to 2 years, the practice of EBF for the first 6 months is low (17.9%). Factors found to influence infant feeding practices are type of delivery, parity, alcohol consumption, occupation, education, and breast problems. PMID:23864943

  14. 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.

  15. Decline of breast-feeding among New York urban poor linked to sources of information on infant feeding practices: a lesson for African countries.

    PubMed

    Isenalumhe, T E

    1984-01-01

    Using a structured interview schedule, the relationship between infant feeding practices and sources of information on infant feeding was evaluated. Subjects of the study were 2 matched groups of breast feeding and non-breast feeding mothers of low socioeconomic status in New York City. It was found that non-breast feeding mothers received significantly more information (p 0.01) from the baby food industry, physicians, and nurses than breast feeding mothers. By contrast, breast feeders received significantly more information (p 0.03) from relatives, friends, and organizations that promote breast feeding than did the non-breast feeders. Over 80% of educational materials on infant feeding, supplied freely to mothers attending ante- and postnatal clinics, were produced by different infant food industries compared with only 17% of such materials produced by the professionals; the materials produced by infant food industries were essentially promotional of the respective company's products with a high potential for discouraging breast feeding. It is suggested that health workers in developing countries should produce and utilize educational materials on infant feeding practices relevant to their respective communities instead of relying on the supply of these materials by baby food manufactures.

  16. Child-feeding Practices among Chinese-American and Non-Hispanic White Caregivers

    PubMed Central

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

    2012-01-01

    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 ages 2 to 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 to 5 and 6 to 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 to 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 to 5 year-olds. These results suggest that differences in child-feeding practices exist between Chinese-American and non-Hispanic white caregivers. PMID:22343192

  17. Predictors of caregiver feeding practices differentiating persistently obese from persistently non-overweight adolescents ✩

    PubMed Central

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

    2015-01-01

    Understanding the contribution of caregiver feeding practices to adolescent diet and weight is important to refining caregiver roles within the context of adolescent obesity prevention and treatment. This secondary data analysis examined whether feeding practices of female caregivers differentiated persistently non-overweight (n = 29) from persistently obese (n = 47) adolescents. Families who previously participated in a cross-sectional study on correlates of obesity were recruited for this follow-up study. At the time of the follow-up study, anthropometric measures were taken for all female caregivers and adolescents, and caregivers completed the Child Feeding Questionnaire-Adolescent version. Socioeconomic, demographic, female caregiver anthropometric, and psychological (caregiver perceived self-weight and concern for adolescent overweight) variables were examined as predictors of feeding practices found to differentiate the two groups. Female caregivers of persistently obese adolescents reported significantly greater use of restriction and monitoring compared to female caregivers of persistently non-overweight adolescents. Restriction was predicted by female caregiver age and concern for adolescent overweight whereas monitoring was predicted by concern for adolescent overweight only. Caregiver feeding strategies may be an important target for adolescent obesity prevention and intervention efforts particularly among those with heightened concern about their teen’s weight status. PMID:25246031

  18. Stabilization of HIV-1 envelope in the CD4-bound conformation through specific cross-linking of a CD4 mimetic.

    PubMed

    Martin, Grégoire; Burke, Brian; Thaï, Robert; Dey, Antu K; Combes, Olivier; Ramos, Oscar H P; Heyd, Bernadette; Geonnotti, Anthony R; Montefiori, David C; Kan, Elaine; Lian, Ying; Sun, Yide; Abache, Toufik; Ulmer, Jeffrey B; Madaoui, Hocine; Guérois, Raphaël; Barnett, Susan W; Srivastava, Indresh K; Kessler, Pascal; Martin, Loïc

    2011-06-17

    CD4 binding on gp120 leads to the exposure of highly conserved regions recognized by the HIV co-receptor CCR5 and by CD4-induced (CD4i) antibodies. A covalent gp120-CD4 complex was shown to elicit CD4i antibody responses in monkeys, which was correlated with control of the HIV virus infection (DeVico, A., Fouts, T., Lewis, G. K., Gallo, R. C., Godfrey, K., Charurat, M., Harris, I., Galmin, L., and Pal, R. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 17477-17482). Because the inclusion of CD4 in a vaccine formulation should be avoided, due to potential autoimmune reactions, we engineered small sized CD4 mimetics (miniCD4s) that are poorly immunogenic and do not induce anti-CD4 antibodies. We made covalent complexes between such an engineered miniCD4 and gp120 or gp140, through a site-directed coupling reaction. These complexes were recognized by CD4i antibodies as well as by the HIV co-receptor CCR5. In addition, they elicit CD4i antibody responses in rabbits and therefore represent potential vaccine candidates that mimic an important HIV fusion intermediate, without autoimmune hazard.

  19. Requirement for CD4 T Cell Help in Generating Functional CD8 T Cell Memory

    NASA Astrophysics Data System (ADS)

    Shedlock, Devon J.; Shen, Hao

    2003-04-01

    Although primary CD8 responses to acute infections are independent of CD4 help, it is unknown whether a similar situation applies to secondary responses. We show that depletion of CD4 cells during the recall response has minimal effect, whereas depletion during the priming phase leads to reduced responses by memory CD8 cells to reinfection. Memory CD8 cells generated in CD4+/+ mice responded normally when transferred into CD4-/- hosts, whereas memory CD8 cells generated in CD4-/- mice mounted defective recall responses in CD4+/+ adoptive hosts. These results demonstrate a previously undescribed role for CD4 help in the development of functional CD8 memory.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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. PMID:25703866

  5. Comparison of the complementary feeding practices between mothers with twins and mothers with singletons

    PubMed Central

    Bentil, Helena Joycelyn; Steiner-Asiedu, Matilda; Lartey, Anna

    2016-01-01

    Introduction Several studies have been done on infant feeding practices but few have focused on twins. The aim of this study was to compare the complementary feeding practices between mothers with twins and mothers with singletons. Methods Mother-infant pairs (50 mother-twin pairs and 50 mother-singleton pairs) with children aged 6 to 23 months were recruited from two public health clinics and communities in Tema and Ashaiman. Information was collected on the background characteristics of the mothers. Recumbent length and weight of the children were measured. Dietary information on the infants was collected using 24 hour recall. The differences between two groups were tested using independent t-student test for continuous variables and chi-square test for categorical variables. Results The minimum dietary diversity (4+ food groups) was met by only 32% of the twins and 40% of the singletons, and 28% of the twins and 38% of the singletons met the requirement for minimum acceptable diet (minimum dietary diversity and the minimum meal frequency). Minimum meal frequency was met by 78% of the twins and 76% of the singletons. There were no significant differences between the two groups of infants. Prevalence of undernutrition was not significantly different among the two groups (twins versus singletons: underweight-26% versus 24%, stunting-20% versus 24% and wasting-14% versus 10%. Conclusion Complementary feeding practices were suboptimal in both groups of mothers requiring interventions to improve infant feeding practices. PMID:27642393

  6. Comparison of the complementary feeding practices between mothers with twins and mothers with singletons

    PubMed Central

    Bentil, Helena Joycelyn; Steiner-Asiedu, Matilda; Lartey, Anna

    2016-01-01

    Introduction Several studies have been done on infant feeding practices but few have focused on twins. The aim of this study was to compare the complementary feeding practices between mothers with twins and mothers with singletons. Methods Mother-infant pairs (50 mother-twin pairs and 50 mother-singleton pairs) with children aged 6 to 23 months were recruited from two public health clinics and communities in Tema and Ashaiman. Information was collected on the background characteristics of the mothers. Recumbent length and weight of the children were measured. Dietary information on the infants was collected using 24 hour recall. The differences between two groups were tested using independent t-student test for continuous variables and chi-square test for categorical variables. Results The minimum dietary diversity (4+ food groups) was met by only 32% of the twins and 40% of the singletons, and 28% of the twins and 38% of the singletons met the requirement for minimum acceptable diet (minimum dietary diversity and the minimum meal frequency). Minimum meal frequency was met by 78% of the twins and 76% of the singletons. There were no significant differences between the two groups of infants. Prevalence of undernutrition was not significantly different among the two groups (twins versus singletons: underweight-26% versus 24%, stunting-20% versus 24% and wasting-14% versus 10%. Conclusion Complementary feeding practices were suboptimal in both groups of mothers requiring interventions to improve infant feeding practices.

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

    PubMed

    Cross, Matthew B; Hallett, Allen M; Ledoux, Tracey A; O'Connor, Daniel P; Hughes, Sheryl O

    2014-10-01

    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 were 299 low-income African American and Hispanic parents and their preschool-aged children who participated in Head Start. Parents completed questionnaires about controlling feeding practices (pressure to eat, restriction) and children's appetitive characteristics (enjoyment of food, food responsiveness, satiety responsiveness). Path analyses were used to determine whether children's self-regulation of eating mediated the relationship between feeding practices and child weight. Greater satiety responsiveness in African American preschool-age children partially mediated the inverse association between pressure to eat and children's weight, B (SE) = -0.073 (0.036), P < .05. Enjoyment of food and food responsiveness did not mediate the relationship between pressure to eat and weight in the African American sample, ps > .05, nor did appetitive characteristics mediate the relationship between restriction and child weight, ps > .05. Appetitive characteristics did not mediate the relationship between controlling feeding practices and child weight in the Hispanic sample, ps > .05. Implications include the need for culturally sensitive self-report measures and for researchers to account for the possible effects of racial/ethnic differences when designing interventions. PMID:24930598

  8. 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...

  9. 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…

  10. 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...

  11. Human Immunodeficiency Virus Type 1 Attachment to HeLa CD4 Cells Is CD4 Independent and gp120 Dependent and Requires Cell Surface Heparans

    PubMed Central

    Mondor, Isabelle; Ugolini, Sophie; Sattentau, Quentin J.

    1998-01-01

    The binding of human immunodeficiency virus type 1 (HIV-1) (Hx10) virions to two different cell lines was analyzed by using a novel assay based on the detection, by anti-HLA-DR-specific antibodies, of HLA-DR+ virus binding to HLA-DR− cells. Virion attachment to the CD4+-T-cell line A3.01 was highly CD4 dependent in that it was potently inhibited by CD4 monoclonal antibodies (MAbs), and little virus binding to the CD4− sister A2.01 line was observed. By contrast, virion binding to HeLa cells expressing moderate or high levels of CD4 was equivalent to, or lower than, binding to wild-type CD4− HeLa cells. Moreover, several CD4 MAbs did not reduce, but enhanced, HIV-1 attachment to HeLa-CD4 cells. CD4 was required for infection of HeLa cells, however, demonstrating a postattachment role for this receptor. MAbs specific for the V2 and V3 loops and the CD4i epitope of gp120 strongly inhibited virion binding to HeLa-CD4 cells, whereas MAbs specific for the CD4bs and the 2G12 epitopes enhanced attachment. Despite this, all gp120- and gp41-specific MAbs tested neutralized infectivity on HeLa-CD4 cells. HIV-1 attachment to HeLa cells was only partially inhibited by MAbs specific for adhesion molecules present on the virus or target cells but was completely blocked by polyanions such as heparin, dextran sulfate, and pentosan sulfate. Treatment of HeLa-CD4 cells with heparinases completely eliminated HIV attachment and infection, strongly implicating cell surface heparans in the attachment process. CD4 dependence for HIV-1 attachment to target cells is thus highly cell line specific and may be replaced by other ligand-receptor interactions. PMID:9557643

  12. 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.

  13. Energetics of the HIV gp120-CD4 binding reaction.

    PubMed

    Myszka, D G; Sweet, R W; Hensley, P; Brigham-Burke, M; Kwong, P D; Hendrickson, W A; Wyatt, R; Sodroski, J; Doyle, M L

    2000-08-01

    HIV infection is initiated by the selective interaction between the cellular receptor CD4 and gp120, the external envelope glycoprotein of the virus. We used analytical ultracentrifugation, titration calorimetry, and surface plasmon resonance biosensor analysis to characterize the assembly state, thermodynamics, and kinetics of the CD4-gp120 interaction. The binding thermodynamics were of unexpected magnitude; changes in enthalpy, entropy, and heat capacity greatly exceeded those described for typical protein-protein interactions. These unusual thermodynamic properties were observed with both intact gp120 and a deglycosylated and truncated form of gp120 protein that lacked hypervariable loops V1, V2, and V3 and segments of its N and C termini. Together with previous crystallographic studies, the large changes in heat capacity and entropy reveal that extensive structural rearrangements occur within the core of gp120 upon CD4 binding. CD spectral studies and slow kinetics of binding support this conclusion. These results indicate considerable conformational flexibility within gp120, which may relate to viral mechanisms for triggering infection and disguising conserved receptor-binding sites from the immune system.

  14. Jacalin: a lectin mitogenic for human CD4 T lymphocytes.

    PubMed Central

    Pineau, N; Aucouturier, P; Brugier, J C; Preud'homme, J L

    1990-01-01

    The major protein component of seeds from jackfruit is the lectin jacalin. Jackfruit crude extracts are known to stimulate human lymphocytes, but the mitogenic properties of purified jacalin have not been studied in detail so far. Study of the proliferative response of cell populations from normal human peripheral blood to purified jacalin showed it to be mitogenic through an interaction with lymphocytes by its lectin-binding site, as shown by inhibition by IgA. Jacalin failed to stimulate B cells to proliferate and to undergo plasma cell maturation. It induced a proliferation of CD4 (and not CD8) lymphocytes, as shown by phenotypic analysis of cells recovered after culture and by studies of the response of isolated T cell subpopulations. The proliferative response to jacalin was autologous monocyte-dependent. The kinetics of jacalin-induced DNA synthesis, expression of CD25 and interleukin-2 secretion was shifted by comparison with that induced by phytohaemagglutinin. The reason for the restricted responsiveness of CD4 T cells is presently unclear; jacalin bound to all blood cells and did not significantly co-cap with CD1, CD2, CD3, CD4, CD8 and CD38, and jacalin response was neither enhanced nor inhibited by antibodies to these surface antigens. PMID:2372991

  15. 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

  16. 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

    2016-01-01

    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

  17. 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

  18. 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.

  19. 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

  20. Transporters for Antiretroviral Drugs in Colorectal CD4+ T Cells and Circulating α4β7 Integrin CD4+ T Cells: Implications for HIV Microbicides.

    PubMed

    Mukhopadhya, Indrani; Murray, Graeme I; Duncan, Linda; Yuecel, Raif; Shattock, Robin; Kelly, Charles; Iannelli, Francesco; Pozzi, Gianni; El-Omar, Emad M; Hold, Georgina L; Hijazi, Karolin

    2016-09-01

    CD4+ T lymphocytes in the colorectal mucosa are key in HIV-1 transmission and dissemination. As such they are also the primary target for antiretroviral (ARV)-based rectal microbicides for pre-exposure prophylaxis. Drug transporters expressed in mucosal CD4+ T cells determine ARV distribution across the cell membrane and, most likely, efficacy of microbicides. We describe transporters for antiretroviral drugs in colorectal mucosal CD4+ T lymphocytes and compare gene expression with circulating α4β7+CD4+ T cells, which traffic to the intestine and have been shown to be preferentially infected by HIV-1. Purified total CD4+ T cells were obtained from colorectal tissue and blood samples by magnetic separation. CD4+ T cells expressing α4β7 integrin were isolated by fluorescence-activated cell sorting from peripheral blood mononuclear cells of healthy volunteers. Expressions of 15 efflux and uptake drug transporter genes were quantified using Taqman qPCR assays. Expression of efflux transporters MRP3, MRP5, and BCRP and uptake transporter CNT2 were significantly higher in colorectal CD4+ T cells compared to circulating CD4+ T cells (p = 0.01-0.03). Conversely, circulating α4β7+CD4+ T cells demonstrated significantly higher expression of OATPD compared to colorectal CD4+ T cells (p = 0.001). To the best of our knowledge this is the first report of drug transporter gene expression in colorectal CD4+ and peripheral α4β7+CD4+ T cells. The qualitative and quantitative differences in drug transporter gene expression profiles between α4β7+CD4+ T cells and total mucosal CD4+ T cells may have significant implications for the efficacy of rectally delivered ARV-microbicides. Most notably, we have identified efflux drug transporters that could be targeted by selective inhibitors or beneficial drug-drug interactions to enhance intracellular accumulation of antiretroviral drugs.

  1. HIVgp120 activates autoreactive CD4-specific T cell responses by unveiling of hidden CD4 peptides during processing

    PubMed Central

    1995-01-01

    T cells are made tolerant only to those self-peptides that are presented in sufficient amounts by antigen-presenting cells. They ignore cryptic self-determinants, such as either those not generated by processing machinery or generated in insufficient amounts. It is anticipated that mechanisms that either change antigen processing or increase the yield of previously "invisible" peptides may be capable of inducing T cell priming and, if they are self-maintained, may sustain autoimmune diseases. Herein, we demonstrate for the first time a mechanism by which the gp120 human immunodeficiency virus-I, by downregulating plasma membrane CD4 and increasing its processing, unveils hidden CD4 epitopes, inducing an autoimmune-specific T cell response. PMID:7760011

  2. 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

  3. Links between maternal feeding practices and children's eating difficulties. Validation of French tools.

    PubMed

    Rigal, Natalie; Chabanet, Claire; Issanchou, Sylvie; Monnery-Patris, Sandrine

    2012-04-01

    The main objectives of the present study were to validate measures of young children's eating difficulties and maternal feeding practices in a French sample, as well as to assess the links between these practices and children's eating difficulties. Mothers (n=502) of French children aged 20-36 months completed four questionnaires that were validated using a Structural Equation Modelling approach. Links between children and maternal components were investigated using a PLS regression. The Children's Eating Difficulties Questionnaire yielded a 4-dimension solution: Neophobia, Pickiness, Low Appetite and Low Enjoyment in food. The Feeding Style Questionnaire assessed three dimensions: Authoritarian, Authoritative and Permissive Styles. The Feeding Strategy Questionnaire, designed to evaluate strategies used by mothers to make their child taste rejected foods, resulted in four factors: Coercion, Explanation, Contingency and Preference. The Questionnaire relating to Parental Motivations when buying food for children presented a 6-dimension solution: Convenience, Weight-control, Natural, Health-concern, Preference and Price. The factors associated positively with the four dimensions of the Children's Eating Difficulties Questionnaire were on the one hand Permissive Style and Practices to fulfil child's desires, and on the other hand Authoritarian Style, Contingent and Coercive Practices aimed at forcing children to taste rejected foods.

  4. 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.

  5. 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. PMID:25666300

  6. Associations between Infant Feeding Practices and Length, Weight, and Disease in Developing Countries.

    PubMed

    Yarnoff, Benjamin O; Allaire, Benjamin T; Detzel, Patrick

    2013-01-01

    The health benefits of exclusive breastfeeding are well-known, but the relative detrimental impacts of other foods on infant health are unknown. Because infants in developing countries are fed a wide range of food, quantifying the burden of these diverse feeding practices on infant health is essential for public health policy. We used data from the Demographic Health Survey from 20 developing countries over multiple years to examine the independent association of six different types of food (exclusive breastfeeding, non-exclusive breastfeeding, infant formula, milk liquids, non-milk liquids, and solid foods) with five measures of infant health (length, weight, diarrhea, fever, and cough). We estimated associations with regression analysis, controlling for confounding factors with infant, mother, and household factors and community-year fixed effects. We used these estimates in a simulation model to quantify the burden of different combinations of food on infant health. We show that for an infant younger than 6 months old, following current guidelines and exclusively breastfeeding instead of giving the infant solid foods may increase length by 0.75 cm and weight by 0.25 kg and decrease diarrhea, fever, and cough prevalence by 8, 12, and 11%, respectively. We found that the burden on infant health of some feeding practices is less than others. Although all other feeding practices are associated with worse health outcomes than exclusive breastfeeding, breastfeeding supplemented with liquids has a lower burden on infant health than solid foods and infant formula has a lower burden than milk or non-milk liquids as measured by four of five health metrics. Providing specific quantified burden estimates of these practices can help inform public health policy related to infant feeding practices. PMID:24400267

  7. 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.

  8. Associations between Infant Feeding Practices and Length, Weight, and Disease in Developing Countries.

    PubMed

    Yarnoff, Benjamin O; Allaire, Benjamin T; Detzel, Patrick

    2013-01-01

    The health benefits of exclusive breastfeeding are well-known, but the relative detrimental impacts of other foods on infant health are unknown. Because infants in developing countries are fed a wide range of food, quantifying the burden of these diverse feeding practices on infant health is essential for public health policy. We used data from the Demographic Health Survey from 20 developing countries over multiple years to examine the independent association of six different types of food (exclusive breastfeeding, non-exclusive breastfeeding, infant formula, milk liquids, non-milk liquids, and solid foods) with five measures of infant health (length, weight, diarrhea, fever, and cough). We estimated associations with regression analysis, controlling for confounding factors with infant, mother, and household factors and community-year fixed effects. We used these estimates in a simulation model to quantify the burden of different combinations of food on infant health. We show that for an infant younger than 6 months old, following current guidelines and exclusively breastfeeding instead of giving the infant solid foods may increase length by 0.75 cm and weight by 0.25 kg and decrease diarrhea, fever, and cough prevalence by 8, 12, and 11%, respectively. We found that the burden on infant health of some feeding practices is less than others. Although all other feeding practices are associated with worse health outcomes than exclusive breastfeeding, breastfeeding supplemented with liquids has a lower burden on infant health than solid foods and infant formula has a lower burden than milk or non-milk liquids as measured by four of five health metrics. Providing specific quantified burden estimates of these practices can help inform public health policy related to infant feeding practices.

  9. Progressive CD4+ central–memory T cell decline results in CD4+ effector–memory insufficiency and overt disease in chronic SIV infection

    PubMed Central

    Okoye, Afam; Meier-Schellersheim, Martin; Brenchley, Jason M.; Hagen, Shoko I.; Walker, Joshua M.; Rohankhedkar, Mukta; Lum, Richard; Edgar, John B.; Planer, Shannon L.; Legasse, Alfred; Sylwester, Andrew W.; Piatak, Michael; Lifson, Jeffrey D.; Maino, Vernon C.; Sodora, Donald L.; Douek, Daniel C.; Axthelm, Michael K.; Grossman, Zvi; Picker, Louis J.

    2007-01-01

    Primary simian immunodeficiency virus (SIV) infections of rhesus macaques result in the dramatic depletion of CD4+ CCR5+ effector–memory T (TEM) cells from extra-lymphoid effector sites, but in most infections, an increased rate of CD4+ memory T cell proliferation appears to prevent collapse of effector site CD4+ TEM cell populations and acute-phase AIDS. Eventually, persistent SIV replication results in chronic-phase AIDS, but the responsible mechanisms remain controversial. Here, we demonstrate that in the chronic phase of progressive SIV infection, effector site CD4+ TEM cell populations manifest a slow, continuous decline, and that the degree of this depletion remains a highly significant correlate of late-onset AIDS. We further show that due to persistent immune activation, effector site CD4+ TEM cells are predominantly short-lived, and that their homeostasis is strikingly dependent on the production of new CD4+ TEM cells from central–memory T (TCM) cell precursors. The instability of effector site CD4+ TEM cell populations over time was not explained by increasing destruction of these cells, but rather was attributable to progressive reduction in their production, secondary to decreasing numbers of CCR5− CD4+ TCM cells. These data suggest that although CD4+ TEM cell depletion is a proximate mechanism of immunodeficiency, the tempo of this depletion and the timing of disease onset are largely determined by destruction, failing production, and gradual decline of CD4+ TCM cells. PMID:17724130

  10. Intimate partner violence and infant feeding practices in India: a cross-sectional study.

    PubMed

    Zureick-Brown, Sarah; Lavilla, Kayla; Yount, Kathryn M

    2015-10-01

    Intimate partner violence (IPV) is widespread; yet research is thin and equivocal regarding its potential adverse effects on infant feeding practices. With a national sample of 3552 mothers and infants aged 180 days or younger from the 2005-2006 National Family Health Survey for India, we used logistic regression to estimate the unadjusted and adjusted associations of maternal reported lifetime exposure to any IPV and to physical or sexual IPV with feeding practices at birth and in the prior 24 h. Compared with their unexposed counterparts, mothers exposed to any IPV and to any physical or sexual IPV had higher adjusted odds of giving their infant liquids [aOR 1.32, 95% confidence interval (CI) 1.04-1.66; aOR 1.37, 95% CI 1.08-1.75, respectively], and thus lower adjusted odds of exclusively breastfeeding their infant in the prior 24 h (aOR 0.78, 95% CI 0.62-0.98; aOR 0.74, 95% CI 0.58-0.95). Mothers exposed to physical or sexual IPV also had higher adjusted odds of feeding their infant solids in the prior 24 h (aOR 1.50, 95% CI 1.01-2.23). Exposure to IPV was not significantly associated with breastfeeding immediately after birth or with bottle feeding in the prior 24 h. Perinatal screening for IPV, and addressing IPV and feeding practices in exposed mothers, may improve maternal health and infant nutrition in similar settings.

  11. 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.

  12. 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. PMID:11732077

  13. 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.

  14. AP-2 Is the Crucial Clathrin Adaptor Protein for CD4 Downmodulation by HIV-1 Nef in Infected Primary CD4+ T Cells.

    PubMed

    Gondim, Marcos Vinicius; Wiltzer-Bach, Linda; Maurer, Brigitte; Banning, Carina; Arganaraz, Enrique; Schindler, Michael

    2015-12-01

    HIV-1 Nef-mediated CD4 downmodulation involves various host factors. We investigated the importance of AP-1, AP-2, AP-3, V1H-ATPase, β-COP, and ACOT8 for CD4 downmodulation in HIV-1-infected short hairpin RNA (shRNA)-expressing CD4(+) T cells and characterized direct interaction with Nef by Förster resonance energy transfer (FRET). Binding of lentiviral Nefs to CD4 and AP-2 was conserved, and only AP-2 knockdown impaired Nef-mediated CD4 downmodulation from primary T cells. Altogether, among the factors tested, AP-2 is the most important player for Nef-mediated CD4 downmodulation.

  15. 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.

  16. 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. PMID:22265752

  17. 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. PMID:26952561

  18. 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.

  19. Macrophages overexpressing Aire induce CD4+Foxp3+ T cells.

    PubMed

    Sun, Jitong; Fu, Haiying; Wu, Jing; Zhu, Wufei; Li, Yi; Yang, Wei

    2013-01-01

    Aire plays an important role in central immune tolerance by regulating the transcription of thousands of genes. However, the role of Aire in the peripheral immune system is poorly understood. Regulatory T (Treg) cells are considered essential for the maintenance of peripheral tolerance, but the effect of Aire on Treg cells in the peripheral immune system is currently unknown. In this study, we investigated the effects of macrophages overexpressing Aire on CD4+Foxp3+ Treg cells by co-culturing Aire-overexpressing RAW264.7 cells or their supernatant with splenocytes. The results show that macrophages overexpressing Aire enhanced the expression of Foxp3 mRNA and induced different subsets of Treg cells in splenocytes through cell-cell contact or a co-culture supernatants. TGF-β is a key molecule in the increases of CD4+CD45RA+Foxp3hi T cell and activating Treg (aTreg) levels observed following cell‑supernatant co-culturing. Subsets of Treg cells were induced by Aire-overexpressing macrophages, and the manipulation of Treg cells by the targeting of Aire may provide a method for the treatment of inflammatory or autoimmune diseases.

  20. 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

  1. 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. PMID:24951434

  2. 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

  3. Depletion of the surface CD4 molecule by the envelope protein of human immunodeficiency virus expressed in a human CD4 sup + monocytoid cell line

    SciTech Connect

    Kawamura, Ikuo; Koga, Yasuhiro; Oh-Hori, Nobuhira; Kimura, Genki; Nomoto, Kikuo ); Onodera, Kazukiyo )

    1989-09-01

    A CD4{sup +} human monocytoid cell line, U937, was transfected with a constructed plasmid which has the envelope gene of human immunodeficiency virus under the transcriptional control of the human metallothionein IIA promoter and was cloned thereafter. These cloned cell lines (EH and EL cells) expressed the viral gp160 in the cytoplasm. The expression of surface CD4 antigen examined by Leu3a and OKT4 monoclonal antibodies, however, disappeared completely in EH cells, which produce a larger amount of gp160, while diminishing only partly in EL cells, which produce a smaller amount of gp160. These results indicate that the level of expression of surface CD4 antigen correlates inversely with the amount of intracellular gp160. Moreover, immunoprecipitation studies using lysate from EH cells showed that OKT4 monoclonal antibody precipitated a significant number of CD4 molecules even after surface CD4 disappeared. However, Leu3a monoclonal antibody, which recognizes the binding site for envelope protein, could not precipitate any CD4 molecules in the same cell lysate. Taken together, these results suggested that CD4 molecules are still synthesized normally after the augmented production of gp160 in the cells but form a complex with the envelope protein in the cytoplasm and become unable to be transported to the cell surface, resulting in the observed depletion of surface CD4 antigen. This mechanism may explain the decrease or absence of surface CD4 antigens in human lymphocytes infected with human immunodeficiency virus.

  4. 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.

  5. 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.

  6. [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. PMID:27392058

  7. 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.

  8. 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. PMID:24816322

  9. 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.

  10. Induction of CD4 suppressor T cells with anti-Leu-8 antibody

    SciTech Connect

    Kanof, M.E.; Strober, W.; James, S.P.

    1987-07-01

    To characterize the conditions under which CD4 T cells suppress polyclonal immunoglobulin synthesis, we investigated the capacity of CD4 T cells that coexpress the surface antigen recognized by the monoclonal antibody anti-Leu-8 to mediate suppression. In an in vitro system devoid of CD8 T cells, CD4, Leu-8+ T cells suppressed pokeweed mitogen-induced immunoglobulin synthesis. Similarly, suppressor function was induced in unfractionated CD4 T cell populations after incubation with anti-Leu-8 antibody under cross-linking conditions. This induction of suppressor function by anti-Leu-8 antibody was not due to expansion of the CD4, Leu-8+ T cell population because CD4 T cells did not proliferate in response to anti-Leu-8 antibody. However, CD4, Leu-8+ T cell-mediated suppression was radiosensitive. Finally, CD4, Leu-8+ T cells do not inhibit immunoglobulin synthesis when T cell lymphokines were used in place of helper CD4 T cells (CD4, Leu-8- T cells), suggesting that CD4 T cell-mediated suppression occurs at the T cell level. We conclude that CD4 T cells can be induced to suppress immunoglobulin synthesis by modulation of the membrane antigen recognized by anti-Leu-8 antibody.

  11. The role of CD4 on mechanical properties of live cell membrane.

    PubMed

    Bui, Van-Chien; Nguyen, Thi-Huong

    2016-01-01

    Although much progress has been made in the characterization and identification of CD4 functions, its role in mechanical properties of cell membrane remains largely unknown. Here an atomic force microscopy (AFM) was used to investigate the roles of CD4 in the elasticity of the leukemic human Jurkat (clone E6-1) cell membranes. Analysis of the approach force curves with Hertz model for a completely elastic soft sample measured on the selected CD4+ and CD4- cells showed that CD4+ cell membrane was softer than CD4- one. To confirm that CD4 plays a role in altering cell elasticity, human embryonic kidney 293T cells were transiently transfected with wild type (wt) CD4 plasmid before being used in AFM nanoindentation experiments. The results also demonstrated CD4- membrane was stiffer than CD4+ one suggesting that CD4 integrated into plasma membrane and altered its mechanical properties. The study gives insights into the role of CD4 on cell membrane mechanical characteristics and might be helpful for development of cell biology and medicine. PMID:26362701

  12. The role of CD4 on mechanical properties of live cell membrane.

    PubMed

    Bui, Van-Chien; Nguyen, Thi-Huong

    2016-01-01

    Although much progress has been made in the characterization and identification of CD4 functions, its role in mechanical properties of cell membrane remains largely unknown. Here an atomic force microscopy (AFM) was used to investigate the roles of CD4 in the elasticity of the leukemic human Jurkat (clone E6-1) cell membranes. Analysis of the approach force curves with Hertz model for a completely elastic soft sample measured on the selected CD4+ and CD4- cells showed that CD4+ cell membrane was softer than CD4- one. To confirm that CD4 plays a role in altering cell elasticity, human embryonic kidney 293T cells were transiently transfected with wild type (wt) CD4 plasmid before being used in AFM nanoindentation experiments. The results also demonstrated CD4- membrane was stiffer than CD4+ one suggesting that CD4 integrated into plasma membrane and altered its mechanical properties. The study gives insights into the role of CD4 on cell membrane mechanical characteristics and might be helpful for development of cell biology and medicine.

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

    PubMed Central

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

    2009-01-01

    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. PMID:19721784

  14. Child feeding practices are associated with child nutritional status in Latin America: innovative uses of the demographic and health surveys.

    PubMed

    Ruel, Marie T; Menon, Purnima

    2002-06-01

    Data from the Demographic and Health Surveys (DHS) for 5 Latin American countries (7 data sets) were used to explore the feasibility of creating a composite feeding index and to examine the association between feeding practices and child height-for-age Z-scores (HAZ). The variables used for the index were as follows: current breast-feeding, use of complementary foods and liquids in the past 24 h, frequency of use over the past week and feeding frequency. The index was made age specific for 6- to 9-, 9- to 12- and 12- to 36-mo-old age groups, and age-specific feeding terciles were created. Bivariate analyses showed that feeding practices were strongly and significantly associated with child HAZ in all 7 data sets, especially after 12 mo of age. Differences in HAZ between child feeding terciles remained significant after controlling for potentially confounding influences, for all countries except Bolivia. Multiple regression analyses also revealed that better feeding practices were more important for children of lower, compared with higher socioeconomic status (in Colombia 1995 and Nicaragua 1998); among children of Ladino (Spanish speaking) compared with indigenous origin (in Guatemala 1995); and among children whose mothers had primary schooling compared with mothers with no schooling, or mothers with higher than primary school level (Peru 1996). The data available in DHS data sets can thus be used effectively to create a composite child feeding index and to identify vulnerable groups that could be targeted by nutrition education and behavior change interventions.

  15. 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…

  16. Beta-catenin signaling mediates CD4 expression on mature CD8+ T cells.

    PubMed

    Schenkel, Jason M; Zloza, Andrew; Li, Wei; Narasipura, Srinivas D; Al-Harthi, Lena

    2010-08-15

    Upon activation, a subset of mature human CD8(+) T cells re-expresses CD4 dimly. This CD4(dim)CD8(bright) T cell population is genuine and enriched in antiviral CD8(+) T cell responses. The signaling pathway that leads to CD4 re-expression on mature CD8(+) T cells is not clear. Given that Wnt/beta-catenin signaling plays a critical role in the transition of CD4(-)CD8(-) to CD4(+)CD8(+) thymocytes, we determined whether beta-catenin mediates CD4 expression on mature CD8(+) T cells. We demonstrate that active beta-catenin expression is 20-fold higher on CD4(dim)CD8(bright) than CD4(-)CD8(+) T cells. Activation of beta-catenin signaling, through LiCl or transfection with a constitutively active construct of beta-catenin, induced CD4 on CD8(+) T cells by approximately 10-fold. Conversely, inhibition of beta-catenin signaling through transfection with a dominant-negative construct for T cell factor-4, a downstream effector of beta-catenin signaling, diminished CD4 expression on CD8(+) T cells by 50% in response to T cell activation. Beta-catenin-mediated induction of CD4 on CD8(+) T cells is transcriptionally regulated, as it induced CD4 mRNA, and T cell factor/lymphoid enhancer factor sites were identified within the human CD4 promoter. Further, beta-catenin expression induced the antiapoptotic factor BcL-xL, suggesting that beta-catenin may mediate protection against activation-induced cell death. Collectively, these data demonstrate that beta-catenin is critical in inducing CD4 expression on mature CD8(+) T cells, suggesting that it is a common pathway for CD4 upregulation among thymocytes and mature CD8(+) T cells. PMID:20631314

  17. Modulation of CD4 lateral mobility in intact cells by an intracellularly applied antibody.

    PubMed Central

    Grebenkämper, K; Tosi, P F; Lazarte, J E; Sneed, L; Brüggemann, U; Kubitscheck, U; Nicolau, C; Peters, R

    1995-01-01

    This study shows that the lateral mobility of CD4, an important plasma-membrane immune receptor, can be modulated by intracellular application of an anti-CD4 antibody. For this purpose, (i) full-length CD4 and a truncated CD4 mutant, lacking a 32-residue-long C-terminal intracellularly exposed domain, were expressed in Spodoptera frugiperda (Sf9) insect cells, (ii) a monoclonal antibody, C6, with specificity for the C-terminal domain was generated, and (iii) a versatile apparatus for fluorescence microphotolysis (FM) studies was constructed. By these means it was found that the commercial anti-CD4 antibody Leu3a-PE, in contrast with several other anti-CD4 antibodies, could be used as a fluorescent label of CD4 without interfering greatly with CD4 mobility. Labelled by Leu3a-PE, full-length CD4 had a lateral diffusion coefficient of D = (4.7 +/- 1.9) x 10(-10) cm2/s and a mobile fraction of fm = 80 +/- 16% (room temperature). Within experimental accuracy the truncated CD4 had the same mobility as full-length CD4. Introduction of the C6 antibody into Sf9 cells by microinjection or by fusion with C6-loaded liposomes decreased the mobility of full-length CD4 (fm = 40%) but not of truncated CD4 (fm = 80%). Treatment of Sf9 cells with phorbol ester also reduced the mobility of full-length CD4 (fm = 50%) but not truncated CD4 (fm = 90%). A calmodulin inhibitor but not a protein kinase C (PKC) inhibitor abolished the phorbol ester effect. Images Figure 1 Figure 2 Figure 4 PMID:7492321

  18. Infant-feeding practices and American Indian infants' gut microbiome: Rationale of the pilot study.

    PubMed

    Zamora-Kapoor, Anna; Sinclair, Ka'imi

    2016-03-01

    This study aims to examine the relationship between infant-feeding practices and American Indian infants' gut microbiome--laying the foundation of a research program aimed at identifying potential aetiologies of childhood obesity in this population. Previous studies have emphasised the high prevalence of obesity in American Indian infants, but its underlying causes remain unclear. We received funding from the University of Washington to examine attitudes towards breastfeeding and formula feeding in American Indian mothers, their dietary and physical activity habits and the yield, quality and diversity of their infants' gut microbiome. Our study combines the strengths of qualitative and quantitative data with DNA sequencing. Results will be used to propose a larger study aimed at clarifying aetiologies of childhood obesity in this population and to identify prevention strategies. This protocol describes the theoretical basis of the study, rationale for the target population, study design, participant recruitment and data analysis plan.

  19. Infant-feeding practices and American Indian infants' gut microbiome: Rationale of the pilot study.

    PubMed

    Zamora-Kapoor, Anna; Sinclair, Ka'imi

    2016-03-01

    This study aims to examine the relationship between infant-feeding practices and American Indian infants' gut microbiome--laying the foundation of a research program aimed at identifying potential aetiologies of childhood obesity in this population. Previous studies have emphasised the high prevalence of obesity in American Indian infants, but its underlying causes remain unclear. We received funding from the University of Washington to examine attitudes towards breastfeeding and formula feeding in American Indian mothers, their dietary and physical activity habits and the yield, quality and diversity of their infants' gut microbiome. Our study combines the strengths of qualitative and quantitative data with DNA sequencing. Results will be used to propose a larger study aimed at clarifying aetiologies of childhood obesity in this population and to identify prevention strategies. This protocol describes the theoretical basis of the study, rationale for the target population, study design, participant recruitment and data analysis plan. PMID:27188076

  20. Household food security is associated with infant feeding practices in rural Bangladesh.

    PubMed

    Saha, Kuntal K; Frongillo, Edward A; Alam, Dewan S; Arifeen, Shams E; Persson, Lars Ake; Rasmussen, Kathleen M

    2008-07-01

    Although household food security (HHFS) has been shown to affect diet, nutrition, and health of adults and also learning in children, no study has examined associations with infant feeding practices (IFP). We studied 1343 infants born between May 2002 and December 2003 in the Maternal and Infant Nutrition Intervention in Matlab study to investigate the effect of HHFS on IFP in rural Bangladesh. We measured HHFS using a previously developed 11-item scale. Cumulative and current infant feeding scales were created from monthly infant feeding data for the age groups of 1-3, 1-6, 1-9, and 1-12 mo based on comparison to infant feeding recommendations. We used lagged, dynamic, and difference longitudinal regression models adjusting for various infant and maternal variables to examine the association between HHFS and changes in IFP, and Cox proportional hazards models to examine the influence of HHFS on the duration of breast-feeding and the time of introduction of complementary foods. Better HHFS status was associated with poor IFP during 3-6 mo but was associated with better IFP during 6-9 and 9-12 mo of age. Although better HHFS was not associated with the time of introduction of complementary foods, it was associated with the type of complementary foods given to the infants. Intervention programs to support proper IFP should target mothers in food-secure households when their babies are 3-6 mo old and also mothers in food-insecure households during the 2nd half of infancy. Our results provide strong evidence that HHFS influences IFP in rural Bangladesh.

  1. 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.

  2. Late adolescents' perceptions of their caregiver's feeding styles and practices and those they will use with their own children.

    PubMed

    Fletcher, J; Branen, L J; Lawrence, A

    1997-01-01

    The purpose of this study was to examine the perceptions of late adolescents regarding their caregivers' feeding styles and practices and their perceptions of those they plan to use with their children. The 546 subjects were from a randomly selected sample of 1,000, nonparenting, 18 to 23-year old college students who responded to a questionnaire. Two distinct feeding styles emerged: adult-controlled and cooperative. The adult-controlled style reflects a perception of control which the adult decides what and how much a child will eat. The cooperative style reflects shared control where the adult decides what food will be presented and the child decides how much and whether to eat. Chi-square analysis of the relationship between subjects' perceptions of their caregivers' feeding styles and their perceptions of the styles they believe they will use with their children, resulted in a positive association. To examine perceived past and future feeding practices, a Pearson's r was computed on subscales from a factor analysis. Results indicated positive correlations between subjects' perceived past and future feeding practices. These results suggest generational transmission of feeding styles and practices. A recommendation is made for parent and nutrition educators to focus on both parenting styles and feeding practices.

  3. 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

  4. 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

  5. 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

  6. CD4+ T-cell deficiency in HIV patients responding to antiretroviral therapy is associated with increased expression of interferon-stimulated genes in CD4+ T cells.

    PubMed

    Fernandez, Sonia; Tanaskovic, Sara; Helbig, Karla; Rajasuriar, Reena; Kramski, Marit; Murray, John M; Beard, Michael; Purcell, Damian; Lewin, Sharon R; Price, Patricia; French, Martyn A

    2011-12-15

    Most patients with human immunodeficiency virus (HIV) who remain CD4(+) T-cell deficient on antiretroviral therapy (ART) exhibit marked immune activation. As CD4(+) T-cell activation may be mediated by microbial translocation or interferon-alpha (IFN-α), we examined these factors in HIV patients with good or poor CD4(+) T-cell recovery on long-term ART. Messenger RNA levels for 3 interferon-stimulated genes were increased in CD4(+) T cells of patients with poor CD4(+) T-cell recovery, whereas levels in patients with good recovery did not differ from those in healthy controls. Poor CD4(+) T-cell recovery was also associated with CD4(+) T-cell expression of markers of activation, senescence, and apoptosis, and with increased serum levels of the lipopolysaccharide receptor and soluble CD14, but these were not significantly correlated with expression of the interferon-stimulated genes. Therefore, CD4(+) T-cell recovery may be adversely affected by the effects of IFN-α, which may be amenable to therapeutic intervention.

  7. CD4+CD25hiFOXP3+ Cells in Cord Blood of Neonates Born from Filaria Infected Mother Are Negatively Associated with CD4+Tbet+ and CD4+RORγt+ T Cells

    PubMed Central

    Zettlmeissl, Eva; van der Vlugt, Luciën E. P. M.; de Jong, Sanne; Matsiegui, Pierre-Blaise; Ramharter, Michael; Kremsner, Peter G.; Yazdanbakhsh, Maria; Adegnika, Ayola Akim

    2014-01-01

    Background Children who have been exposed in utero to maternal filarial infection are immunologically less responsive to filarial antigens, have less pathology, and are more susceptible to acquire infection than offspring of uninfected mothers. Moreover children from filaria infected mothers have been shown to be less responsive to vaccination as a consequence of an impairment of their immune response. However, it is not well known how in utero exposure to parasite antigens affects cellular immune responses. Methodology Here, 30 pregnant women were examined for the presence of microfilaria of Loa loa and Mansonella perstans in peripheral blood. At delivery, cord blood mononuclear cells (CBMC) were obtained and the CD4+T cells were phenotyped by expression of the transcription factors Tbet, RORγt, and FOXP3. Results No significant difference was observed between newborns from infected versus uninfected mothers in the frequencies of total CD4+T cells and CD4+T cells subsets including CD4+Tbet+, CD4+RORγt+ T and CD4+CD25hiFOXP3+ T cells. However, there was a negative association between CD4+CD25hiFOXP3+T cells and CD4+Tbet+ as well as CD4+RORγt+ T cells in the infected group only (B = −0.242, P = 0.002; B = −0.178, P = 0.013 respectively). Conclusion Our results suggest that filarial infection during pregnancy leads to an expansion of functionally active regulatory T cells that keep TH1 and TH17 in check. PMID:25531674

  8. 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

    2004-09-01

    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

  9. CD4 T-Cell Enumeration in a Field Setting: Evaluation of CyFlow Counter Using the CD4 Easy Count Kit-Dry and Pima CD4 Systems

    PubMed Central

    Wade, Djibril; Diaw, Papa Alassane; Daneau, Géraldine; Camara, Makhtar; Dieye, Tandakha Ndiaye; Mboup, Souleymane; Kestens, Luc

    2013-01-01

    Background Flow Cytometry (FCM) is still considered to be the method of choice for accurate CD4 enumeration. However, the use of FCM in developing countries is problematic due to their cost and complexity. Lower-cost technologies have been introduced. We evaluated CyFlow Counter together with its lyophilized reagents, and Pima CD4 in high-temperature area, using FACSCount as reference. Materials and Methods Whole blood samples were consecutively collected by venipuncture from 111 HIV+ patients and 17 HIV-negative donors. CD4 T-cell enumeration was performed on CyFlow Counter, Pima CD4 and FACSCount. Results CyFlow Counter and Pima CD4 systems showed good correlation with FACSCount (slope of 0.82 and 0.90, and concordance ρc of 0.94 and 0.98, respectively). CyFlow Counter showed absolute or relative biases (LOA) of −63 cells/mm3 (−245 to 120) or −9.8% (−38.1 to 18.4) respectively, and Pima CD4 showed biases (LOA) of −30 cells/mm3 (−160 to 101) or −3.5% (−41.0 to 33.9%). CyFlow Counter and Pima CD4 showed respectively 106.7% and 105.9% of similarity with FACSCount. According to WHO-2010 ART initiation threshold of 350 cells/mm3, CyFlow Counter and Pima CD4 showed respectively sensibility of 100% and 97%, and specificity of 91% and 93%. CyFlow Counter and Pima CD4 were strongly correlated (slope of 1.09 and ρc of 0.95). These alternative systems showed good agreement with bias of 33 cells/mm3 (−132 to 203) or 6.3% (−31.2 to 43.8), and similarity of 104.3%. Conclusion CyFlow Counter using CD4 easy count kit-dry and Pima CD4 systems can accurately provide CD4 T-cell counts with acceptable agreement to those of FACSCount. PMID:24066184

  10. 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.

  11. 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.

  12. Burn-injury affects gut-associated lymphoid tissues derived CD4+ T cells☆

    PubMed Central

    Fazal, Nadeem; Shelip, Alla; Alzahrani, Alhusain J.

    2013-01-01

    After scald burn-injury, the intestinal immune system responds to maintain immune balance. In this regard CD4+T cells in Gut-Associated Lymphoid Tissues (GALT), like mesenteric lymph nodes (MLN) and Peyer's patches (PP) respond to avoid immune suppression following major injury such as burn. Therefore, we hypothesized that the gut CD4+T cells become dysfunctional and turn the immune homeostasis towards depression of CD4+ T cell-mediated adaptive immune responses. In the current study we show down regulation of mucosal CD4+ T cell proliferation, IL-2 production and cell surface marker expression of mucosal CD4+ T cells moving towards suppressive-type. Acute burn-injury lead to up-regulation of regulatory marker (CD25+), down regulation of adhesion (CD62L, CD11a) and homing receptor (CD49d) expression, and up-regulation of negative co-stimulatory (CTLA-4) molecule. Moreover, CD4+CD25+ T cells of intestinal origin showed resistance to spontaneous as well as induced apoptosis that may contribute to suppression of effector CD4+ T cells. Furthermore, gut CD4+CD25+ T cells obtained from burn-injured animals were able to down-regulate naïve CD4+ T cell proliferation following adoptive transfer of burn-injured CD4+CD25+ T cells into sham control animals, without any significant effect on cell surface activation markers. Together, these data demonstrate that the intestinal CD4+ T cells evolve a strategy to promote suppressive CD4+ T cell effector responses, as evidenced by enhanced CD4+CD25+ T cells, up-regulated CTLA-4 expression, reduced IL-2 production, tendency towards diminished apoptosis of suppressive CD4+ T cells, and thus lose their natural ability to regulate immune homeostasis following acute burn-injury and prevent immune paralysis. PMID:24600563

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

    PubMed

    Ma, Cindy S; 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

    2016-07-25

    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

  14. MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency

    PubMed Central

    2012-01-01

    Background Binding of the viral envelope protein (Env), and particularly of its gp120 subunit, to the cellular CD4 receptor is the first essential step of the HIV-1 entry process. The CD4 binding site (CD4bs) of gp120, and especially a recessed cavity occupied by the CD4 Phe43 residue, are known to be highly conserved among the different circulating subtypes and therefore constitute particularly interesting targets for vaccine and drug design. The miniCD4 proteins are a promising class of CD4bs inhibitors. Studying virus evolution under pressure of CD4bs inhibitors could provide insight on the gp120-CD4 interaction and viral entry. Results The present study reports on the resistance induction of two subtype B HIV-1 against the most active miniCD4, M48U1, and its ancestor, M48, and how these mutated positions affect CD4bs recognition, entry efficiency, and sensitivity to other CD4bs inhibitors. Resistance against M48U1 was always associated with S375R/N substitution in both BaL and SF162; M48 resistance was associated with D474N substitution in SF162 and with H105Y substitution in BaL. In addition, some other mutations at position V255 and G471 were of importance for SF162 resistant viruses. Except for 474, all of these mutated positions are conserved, and introducing them into an SF162 Env expressing infectious molecular clone (pBRNL4.3 SF162) resulted in decreased entry efficiency. Furthermore, resistant mutants showed at least some cross-resistance towards other CD4bs inhibitors, the V3 monoclonal antibody 447-52D and some even against the monoclonal antibody 17b, of which the epitope overlaps the co-receptor binding site. Conclusions The mutations H105Y, V255M, S375R/N, G471R/E, and D474N are found to be involved in resistance towards M48 and M48U1. All mutated positions are part of, or in close proximity to, the CD4bs; most are highly conserved, and all have an impact on the entry efficiency, suggesting their importance for optimal virus infectivity. PMID

  15. The effects of an anti-CD4 monoclonal antibody, keliximab, on peripheral blood CD4+ T-cells in asthma.

    PubMed

    Kon, O M; Sihra, B S; Loh, L C; Barkans, J; Compton, C H; Barnes, N C; Larché, M; Kay, A B

    2001-07-01

    CD4+ T-cells are likely to be involved as a source of pro-inflammatory cytokines in asthma. This study assessed the effects of an infusion of keliximab (IDEC CE9.1), an anti-CD4+ monoclonal antibody, on peripheral blood CD4+ T-cells in corticosteroid-dependent asthmatics. Three cohorts of patients (termed C0.5: n=6, C1.5: n=5, and C3.0: n=5) received a single infusion of 0.5, 1.5 or 3.0 mg x kg(-1), respectively, with a fourth receiving placebo (Cpl: n=6), and were followed-up for 4 weeks. By flow cytometry in peripheral blood, pre- and postinfusion assessment was made of: a) CD4 and CD8 counts and mean fluorescence; b) CD25, human leukocyte antigen-DR (HLA-DR), CD45RO and CD45RA expression on CD4+ T-cells; and c) interferon (IFN)-gamma, interleukin (IL)-4 and IL-5 expression in CD4+ T-cells. Keliximab's in vitro effects on allergen-specific peripheral blood mononuclear cells (PBMC) proliferation in atopic asthmatics were also evaluated. There was a significant increase in lung function (peak expiratory flow rate) in the C3.0 group. Following infusion in C0.5, C1.5 and C3.0 but not Cpl: 1) the CD4, but not CD8 count was significantly decreased; 2) there was total loss of Leu3a staining; 3) there were significant reductions in the mean fluorescence of OKT4 binding; and 4) there were significant reductions in the numbers of CD25, HLA-DR, CD45RO and CD45RA/CD4+ cells. There were no changes in CD4+ cell expression of IFN-gamma, IL-4 or IL-5. Keliximab caused a significant reduction in T-cell proliferation as compared to a control monoclonal antibody. Keliximab, as an anti-CD4 monoclonal antibody, leads to a transient reduction in the number of CD4+ T-cells and modulation of CD4+ receptor expression in severe asthmatics. The effects of keliximab may be mediated through a decrease in CD4+ surface expression and T-lymphocyte numbers, in addition to a reduction in allergen-induced proliferation.

  16. 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.

  17. 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. PMID:7269553

  18. 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.

  19. Micronutrient powder use and infant and young child feeding practices in an integrated program.

    PubMed

    Mirkovic, Kelsey R; Perrine, Cria G; Subedi, Giri Raj; Mebrahtu, Saba; Dahal, Pradiumna; Jefferds, Maria Elena D

    2016-01-01

    Integrated infant and young child feeding (IYCF)/micronutrient powder (MNP) programs are increasingly used to address poor IYCF practices and micronutrient deficiencies in low-income settings; however, little is known about how MNP use may affect IYCF practices. We describe how MNP use was associated with IYCF practices in a pilot program in select districts of Nepal where free MNP for children 6-23 months were added to an existing IYCF platform. Representative cross-sectional surveys were conducted in pilot districts with mothers of eligible children at 3 months (plains ecozone, n=1054) or 15 months (hill ecozone, rural only, n=654) after implementation of an integrated MNP/IYCF program. We used logistic regression to assess how IYCF practices varied by MNP use (none, 1-30, 30-60 sachets). At both time points, consuming 30-60 MNP sachets vs. none was associated with achieving minimum dietary diversity and minimum acceptable diet. In the 3 month survey consuming 30- 60 MNP sachets vs none was also associated with achieving minimum meal frequency and continued breastfeeding at 2 years. In this setting, addition of MNP to an existing platform of IYCF messaging did not appear detrimental to IYCF practices. PMID:27222419

  20. Pharmacy Refill Adherence Compared with CD4 Count Changes for Monitoring HIV-Infected Adults on Antiretroviral Therapy

    PubMed Central

    Bisson, Gregory P; Gross, Robert; Bellamy, Scarlett; Chittams, Jesse; Hislop, Michael; Regensberg, Leon; Frank, Ian; Maartens, Gary; Nachega, Jean B

    2008-01-01

    Background World Health Organization (WHO) guidelines for monitoring HIV-infected individuals taking combination antiretroviral therapy (cART) in resource-limited settings recommend using CD4+ T cell (CD4) count changes to monitor treatment effectiveness. In practice, however, falling CD4 counts are a consequence, rather than a cause, of virologic failure. Adherence lapses precede virologic failure and, unlike CD4 counts, data on adherence are immediately available to all clinics dispensing cART. However, the accuracy of adherence assessments for predicting future or detecting current virologic failure has not been determined. The goal of this study therefore was to determine the accuracy of adherence assessments for predicting and detecting virologic failure and to compare the accuracy of adherence-based monitoring approaches with approaches monitoring CD4 count changes. Methodology and Findings We conducted an observational cohort study among 1,982 of 4,984 (40%) HIV-infected adults initiating non-nucleoside reverse transcriptase inhibitor-based cART in the Aid for AIDS Disease Management Program, which serves nine countries in southern Africa. Pharmacy refill adherence was calculated as the number of months of cART claims submitted divided by the number of complete months between cART initiation and the last refill prior to the endpoint of interest, expressed as a percentage. The main outcome measure was virologic failure defined as a viral load > 1,000 copies/ml (1) at an initial assessment either 6 or 12 mo after cART initiation and (2) after a previous undetectable (i.e., < 400 copies/ml) viral load (breakthrough viremia). Adherence levels outperformed CD4 count changes when used to detect current virologic failure in the first year after cART initiation (area under the receiver operating characteristic [ROC] curves [AUC] were 0.79 and 0.68 [difference = 0.11; 95% CI 0.06 to 0.16; χ2 = 20.1] respectively at 6 mo, and 0.85 and 0.75 [difference = 0.10; 95% CI

  1. 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

  2. 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

  3. 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

  4. Crystal Structure of HIV-1 Primary Receptor CD4 i Complex with a Potent Antiviral Antibody

    SciTech Connect

    Freeman, M.M.; Hong, X.; Seaman, M.S.; Rits-Vollock, S.p Kao, C.Y.; Ho, D.D.; Chen, B.

    2010-06-18

    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 {angstrom} resolution. Ibalizumab grips CD4 primarily by the BC-loop (residues 121125) 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.

  5. Tissue-specific expression of human CD4 in transgenic mice.

    PubMed

    Gillespie, F P; Doros, L; Vitale, J; Blackwell, C; Gosselin, J; Snyder, B W; Wadsworth, S C

    1993-05-01

    The gene for the human CD4 glycoprotein, which serves as the receptor for human immunodeficiency virus type 1, along with approximately 23 kb of sequence upstream of the translational start site, was cloned. The ability of 5' flanking sequences to direct tissue-specific expression was tested in cell culture and in transgenic mice. A 5' flanking region of 6 kb was able to direct transcription of the CD4 gene in NIH 3T3 cells but did not result in detectable expression in the murine T-cell line EL4 or in four lines of transgenic mice. A larger 5' flanking region of approximately 23 kb directed high-level CD4 transcription in the murine T-cell line EL4 and in three independent lines of transgenic mice. Human CD4 expression in all tissues analyzed was tightly correlated with murine CD4 expression; the highest levels of human CD4 RNA expression were found in the thymus and spleen, with relatively low levels detected in other tissues. Expression of human CD4 protein in peripheral blood mononuclear cells was examined by flow cytometry in these transgenic animals and found to be restricted to the murine CD4+ subset of lymphocytes. Human CD4 protein, detected with an anti-human CD4 monoclonal antibody, was present on the surface of 45 to 50% of the peripheral blood mononuclear cells from all transgenic lines. PMID:8474453

  6. CD4-Specific Designed Ankyrin Repeat Proteins Are Novel Potent HIV Entry Inhibitors with Unique Characteristics

    PubMed Central

    Schweizer, Andreas; Rusert, Peter; Berlinger, Livia; Ruprecht, Claudia R.; Mann, Axel; Corthésy, Stéphanie; Turville, Stuart G.; Aravantinou, Meropi; Fischer, Marek; Robbiani, Melissa; Amstutz, Patrick; Trkola, Alexandra

    2008-01-01

    Here, we describe the generation of a novel type of HIV entry inhibitor using the recently developed Designed Ankyrin Repeat Protein (DARPin) technology. DARPin proteins specific for human CD4 were selected from a DARPin DNA library using ribosome display. Selected pool members interacted specifically with CD4 and competed with gp120 for binding to CD4. DARPin proteins derived in the initial selection series inhibited HIV in a dose-dependent manner, but showed a relatively high variability in their capacity to block replication of patient isolates on primary CD4 T cells. In consequence, a second series of CD4-specific DARPins with improved affinity for CD4 was generated. These 2nd series DARPins potently inhibit infection of genetically divergent (subtype B and C) HIV isolates in the low nanomolar range, independent of coreceptor usage. Importantly, the actions of the CD4 binding DARPins were highly specific: no effect on cell viability or activation, CD4 memory cell function, or interference with CD4-independent virus entry was observed. These novel CD4 targeting molecules described here combine the unique characteristics of DARPins—high physical stability, specificity and low production costs—with the capacity to potently block HIV entry, rendering them promising candidates for microbicide development. PMID:18654624

  7. Small CD4 Mimetics Prevent HIV-1 Uninfected Bystander CD4 + T Cell Killing Mediated by Antibody-dependent Cell-mediated Cytotoxicity

    PubMed Central

    Richard, Jonathan; Veillette, Maxime; Ding, Shilei; Zoubchenok, Daria; Alsahafi, Nirmin; Coutu, Mathieu; Brassard, Nathalie; Park, Jongwoo; Courter, Joel R.; Melillo, Bruno; Smith, Amos B.; Shaw, George M.; Hahn, Beatrice H.; Sodroski, Joseph; Kaufmann, Daniel E.; Finzi, Andrés

    2015-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection causes a progressive depletion of CD4 + T cells. Despite its importance for HIV-1 pathogenesis, the precise mechanisms underlying CD4 + T-cell depletion remain incompletely understood. Here we make the surprising observation that antibody-dependent cell-mediated cytotoxicity (ADCC) mediates the death of uninfected bystander CD4 + T cells in cultures of HIV-1-infected cells. While HIV-1-infected cells are protected from ADCC by the action of the viral Vpu and Nef proteins, uninfected bystander CD4 + T cells bind gp120 shed from productively infected cells and are efficiently recognized by ADCC-mediating antibodies. Thus, gp120 shedding represents a viral mechanism to divert ADCC responses towards uninfected bystander CD4 + T cells. Importantly, CD4-mimetic molecules redirect ADCC responses from uninfected bystander cells to HIV-1-infected cells; therefore, CD4-mimetic compounds might have therapeutic utility in new strategies aimed at specifically eliminating HIV-1-infected cells. PMID:26870823

  8. Small CD4 Mimetics Prevent HIV-1 Uninfected Bystander CD4 + T Cell Killing Mediated by Antibody-dependent Cell-mediated Cytotoxicity.

    PubMed

    Richard, Jonathan; Veillette, Maxime; Ding, Shilei; Zoubchenok, Daria; Alsahafi, Nirmin; Coutu, Mathieu; Brassard, Nathalie; Park, Jongwoo; Courter, Joel R; Melillo, Bruno; Smith, Amos B; Shaw, George M; Hahn, Beatrice H; Sodroski, Joseph; Kaufmann, Daniel E; Finzi, Andrés

    2016-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection causes a progressive depletion of CD4 + T cells. Despite its importance for HIV-1 pathogenesis, the precise mechanisms underlying CD4 + T-cell depletion remain incompletely understood. Here we make the surprising observation that antibody-dependent cell-mediated cytotoxicity (ADCC) mediates the death of uninfected bystander CD4 + T cells in cultures of HIV-1-infected cells. While HIV-1-infected cells are protected from ADCC by the action of the viral Vpu and Nef proteins, uninfected bystander CD4 + T cells bind gp120 shed from productively infected cells and are efficiently recognized by ADCC-mediating antibodies. Thus, gp120 shedding represents a viral mechanism to divert ADCC responses towards uninfected bystander CD4 + T cells. Importantly, CD4-mimetic molecules redirect ADCC responses from uninfected bystander cells to HIV-1-infected cells; therefore, CD4-mimetic compounds might have therapeutic utility in new strategies aimed at specifically eliminating HIV-1-infected cells.

  9. 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.

  10. Mice Transgenic for CD4-Specific Human CD4, CCR5 and Cyclin T1 Expression: A New Model for Investigating HIV-1 Transmission and Treatment Efficacy

    PubMed Central

    Zheng, Jian Hua; Zhang, Cong; Chen, Ken; Dutta, Monica; Deneroff, Kathryn; Ochsenbauer, Christina; Kappes, John C.; Littman, Dan R.; Goldstein, Harris

    2013-01-01

    Mice cannot be used to evaluate HIV-1 therapeutics and vaccines because they are not infectible by HIV-1 due to structural differences between several human and mouse proteins required for HIV-1 entry and replication including CD4, CCR5 and cyclin T1. We overcame this limitation by constructing mice with CD4 enhancer/promoter-regulated human CD4, CCR5 and cyclin T1 genes integrated as tightly linked transgenes (hCD4/R5/cT1 mice) promoting their efficient co-transmission and enabling the murine CD4-expressing cells to support HIV-1 entry and Tat-mediated LTR transcription. All of the hCD4/R5/cT1 mice developed disseminated infection of tissues that included the spleen, small intestine, lymph nodes and lungs after intravenous injection with an HIV-1 infectious molecular clone (HIV-IMC) expressing Renilla reniformis luciferase (LucR). Furthermore, localized infection of cervical-vaginal mucosal leukocytes developed after intravaginal inoculation of hCD4/R5/cT1 mice with the LucR-expressing HIV-IMC. hCD4/R5/cT1 mice reproducibly developed in vivo infection after inoculation with LucR-expressing HIV-IMC which could be bioluminescently quantified and visualized with a high sensitivity and specificity which enabled them to be used to evaluate the efficacy of HIV-1 therapeutics. Treatment with highly active anti-retroviral therapy or one dose of VRC01, a broadly neutralizing anti-HIV-1 antibody, almost completed inhibited acute systemic HIV-1 infection of the hCD4/R5/cT1 mice. hCD4/R5/cT1 mice could also be used to evaluate the capacity of therapies delivered by gene therapy to inhibit in vivo HIV infection. VRC01 secreted in vivo by primary B cells transduced with a VRC01-encoding lentivirus transplanted into hCD4/R5/cT1 mice markedly inhibited infection after intravenous challenge with LucR-expressing HIV-IMC. The reproducible infection of CD4/R5/cT1 mice with LucR-expressing HIV-IMC after intravenous or mucosal inoculation combined with the availability of Luc

  11. 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…

  12. Lack of permissivity of human monoclonal CD4+ lymphocytes to HIV.

    PubMed

    Chapel, A; Bourges, J F; Bensussan, A; d'Auriol, L; Vilmer, E; Dormont, D

    1990-01-01

    Although knowledge has accumulated about GP110-CD4 interaction, viral penetration into human CD4+ lymphocytes remains unclear, in spite of the fact that all studies on HIV infection were performed on cell-transformed lineages, or on human polyclonal CD4+ cells. In order to investigate this viral entrance into susceptible cells, we studied the permissivity of 13 human monoclonal CD4+ lymphocytes by means of reverse transcriptase (RT) assay and immunocapture. We demonstrated a differential susceptibility to HIV of these CD4+ clones. In a second experiment, HIV infection was studied: (1) sequentially by RT assay and P24 immunocapture on several clones; (2) by cocultivation of infected clones with umbilical cord lymphocytes. These experiments suggested existence of permissive and "nonpermissive" CD4+ monoclonal lymphocytes. Slot blot, then PCR, revealed that proviral DNA sequences were detectable in all clones, but were present at lower levels in nonpermissive clones.

  13. Blocking of HIV-1 Infectivity by a Soluble, Secreted Form of the CD4 Antigen

    NASA Astrophysics Data System (ADS)

    Smith, Douglas H.; Byrn, Randal A.; Marsters, Scot A.; Gregory, Timothy; Groopman, Jerome E.; Capon, Daniel J.

    1987-12-01

    The initial event in the infection of human T lymphocytes, macrophages, and other cells by human immunodeficiency virus (HIV-1) is the attachment of the HIV-1 envelope glycoprotein gp120 to its cellular receptor, CD4. As a step toward designing antagonists of this binding event, soluble, secreted forms of CD4 were produced by transfection of mammalian cells with vectors encoding versions of CD4 lacking its transmembrane and cytoplasmic domains. The soluble CD4 so produced binds gp120 with an affinity and specificity comparable to intact CD4 and is capable of neutralizing the infectivity of HIV-1. These studies reveal that the high-affinity CD4-gp120 interaction does not require other cell or viral components and may establish a novel basis for therapeutic intervention in the acquired immune deficiency syndrome (AIDS).

  14. 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.

  15. Antibodies to CD4 in individuals infected with human immunodeficiency virus type 1.

    PubMed Central

    Kowalski, M; Ardman, B; Basiripour, L; Lu, Y C; Blohm, D; Haseltine, W; Sodroski, J

    1989-01-01

    The attachment of human immunodeficiency virus type 1 (HIV-1) to target cells is mediated by a specific interaction between the viral envelope glycoprotein (gp120) and the CD4 receptor. Here we report that approximately 10% of HIV-1-infected individuals produce antibodies that recognize the extracellular portion of the CD4 molecule. Carboxyl-terminal deletions of CD4 that do not affect HIV-1 gp120 binding eliminate recognition of CD4 by patient antisera. In contrast, mutations in the amino-terminal domain of CD4 that attenuate HIV-1 gp120 binding do not diminish CD4 recognition by patient antisera. These results suggest that HIV-1 infection can generate antibodies directed against a region of the viral receptor distinct from the virus-binding domain. Images PMID:2541442

  16. 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

  17. Increased competition for antigen during priming negatively impacts the generation of memory CD4 T cells

    PubMed Central

    Blair, David A.; Lefrançois, Leo

    2007-01-01

    The factors involved in the differentiation of memory CD4 T cells from naïve precursors are poorly understood. We developed a system to examine the effect of increased competition for antigen by CD4 T cells on the generation of memory in response to infection with a recombinant vesicular stomatitis virus. Competition was initially regulated by increasing the precursor frequency of adoptively transferred naïve T cell antigen receptor transgenic CD4 T cells. Despite robust proliferation at high precursor frequencies, memory CD4 T cells did not develop, whereas decreasing the input number of naïve CD4 T cells promoted memory development after infection. The lack of memory development was linked to reduced blastogenesis and poor effector cell induction, but not to initial recruitment or proliferation of antigen-specific CD4 T cells. To prove that availability of antigen alone could regulate memory CD4 T cell development, we used treatment with an mAb specific for the epitope recognized by the transferred CD4 T cells. At high doses, this mAb effectively inhibited the antigen-specific CD4 T cell response. However, at a very low dose of mAb, primary CD4 T cell expansion was unaffected, although memory development was dramatically reduced. Moreover, the induction of effector function was concomitantly inhibited. Thus, competition for antigen during CD4 T cell priming is a major contributing factor to the development of the memory CD4 T cell pool. PMID:17827281

  18. CD4+ invariant natural killer T cells protect from murine GVHD lethality through expansion of donor CD4+CD25+FoxP3+ regulatory T cells.

    PubMed

    Schneidawind, Dominik; Pierini, Antonio; Alvarez, Maite; Pan, Yuqiong; Baker, Jeanette; Buechele, Corina; Luong, Richard H; Meyer, Everett H; Negrin, Robert S

    2014-11-20

    Dysregulated donor T cells lead to destruction of host tissues resulting in graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). We investigated the impact of highly purified (>95%) donor CD4(+) invariant natural killer T (iNKT) cells on GVHD in a murine model of allogeneic HCT. We found that low doses of adoptively transferred donor CD4(+) iNKT cells protect from GVHD morbidity and mortality through an expansion of donor CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs). These Tregs express high levels of the Ikaros transcription factor Helios and expand from the Treg pool of the donor graft. Furthermore, CD4(+) iNKT cells preserve T-cell-mediated graft-versus-tumor effects. Our studies reveal new aspects of the cellular interplay between iNKT cells and Tregs in the context of tolerance induction after allogeneic HCT and set the stage for clinical translation. PMID:25293774

  19. 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. PMID:26025758

  20. Applying Rank Sum Ratio (RSR) to the Evaluation of Feeding Practices Behaviors, and Its Associations with Infant Health Risk in Rural Lhasa, Tibet.

    PubMed

    Wang, Zhenjie; Dang, Shaonong; Xing, Yuan; Li, Qiang; Yan, Hong

    2015-12-01

    To evaluate the status of feeding practices and analyze the association between feeding practice and health status among Tibetan infants, a cross-sectional survey of 386 women with children aged under 24 months was conducted in rural areas surrounding Lhasa, Tibet. All participants were selected using simple random sampling and were interviewed face-to-face by trained interviewers. Mothers were interviewed to collect information on their feeding practices. A feeding practices index was created using the rank sum ratio method. Most of the infants had been or were being breastfed at the time of the interview. The feeding practices index was significantly and inversely associated with the prevalence of acute upper respiratory infection, and the odds ratio for the qualified feeding practices index vs. the non-qualified feeding practices index was 0.43 (95% confidence interval: 0.20-0.94). There were no measurable associations observed between acute upper respiratory infection, diarrhea, and the feeding practices index after controlling for selected factors. The method of rank sum ratio provides a flexible way to evaluate feeding practices and is easy to understand. Furthermore, appropriate infant feeding practices might play a protective role in Tibetan infants' health.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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. PMID:25014743

  6. The Influence of Early Infant-Feeding Practices on the Intestinal Microbiome and Body Composition in Infants.

    PubMed

    O'Sullivan, Aifric; Farver, Marie; Smilowitz, Jennifer T

    2015-01-01

    Despite many years of widespread international recommendations to support exclusive breastfeeding for the first six months of life, common hospital feeding and birthing practices do not coincide with the necessary steps to support exclusive breastfeeding. These common hospital practices can lead to the infant receiving formula in the first weeks of life despite mothers' dedication to exclusively breastfeed. Consequently, these practices play a role in the alarmingly high rate of formula-feeding worldwide. Formula-feeding has been shown to alter the infant gut microbiome in favor of proinflammatory taxa and increase gut permeability and bacterial load. Furthermore, several studies have found that formula-feeding increases the risk of obesity in later childhood. While research has demonstrated differences in the intestinal microbiome and body growth between exclusively breast versus formula-fed infants, very little is known about the effects of introducing formula to breastfed infants either briefly or long term on these outcomes. Understanding the relationships between mixed-feeding practices and infant health outcomes is complicated by the lack of clarity in the definition of mixed-feeding as well as the terminology used to describe this type of feeding in the literature. In this commentary, we highlight the need for hospitals to embrace the 10 steps of the Baby Friendly Hospital Initiative developed by UNICEF and the WHO for successful breastfeeding. We present a paucity of studies that have focused on the effects of introducing formula to breastfed infants on the gut microbiome, gut health, growth, and body composition. We make the case for the need to conduct well-designed studies on mixed-feeding before we can truly answer the question: how does brief or long-term use of formula influence the health benefits of exclusive breastfeeding?

  7. The Influence of Early Infant-Feeding Practices on the Intestinal Microbiome and Body Composition in Infants

    PubMed Central

    O’Sullivan, Aifric; Farver, Marie; Smilowitz, Jennifer T.

    2015-01-01

    Despite many years of widespread international recommendations to support exclusive breastfeeding for the first six months of life, common hospital feeding and birthing practices do not coincide with the necessary steps to support exclusive breastfeeding. These common hospital practices can lead to the infant receiving formula in the first weeks of life despite mothers’ dedication to exclusively breastfeed. Consequently, these practices play a role in the alarmingly high rate of formula-feeding worldwide. Formula-feeding has been shown to alter the infant gut microbiome in favor of proinflammatory taxa and increase gut permeability and bacterial load. Furthermore, several studies have found that formula-feeding increases the risk of obesity in later childhood. While research has demonstrated differences in the intestinal microbiome and body growth between exclusively breast versus formula-fed infants, very little is known about the effects of introducing formula to breastfed infants either briefly or long term on these outcomes. Understanding the relationships between mixed-feeding practices and infant health outcomes is complicated by the lack of clarity in the definition of mixed-feeding as well as the terminology used to describe this type of feeding in the literature. In this commentary, we highlight the need for hospitals to embrace the 10 steps of the Baby Friendly Hospital Initiative developed by UNICEF and the WHO for successful breastfeeding. We present a paucity of studies that have focused on the effects of introducing formula to breastfed infants on the gut microbiome, gut health, growth, and body composition. We make the case for the need to conduct well-designed studies on mixed-feeding before we can truly answer the question: how does brief or long-term use of formula influence the health benefits of exclusive breastfeeding? PMID:26715853

  8. Infant and Young Child Feeding Behaviors among Working Mothers in India: Implications for Global Health Policy and Practice

    PubMed Central

    Kumar, Vinay; Arora, Gunjan; Midha, Ish Kumar; Gupta, Yogender Pal

    2015-01-01

    Background: The National Guidelines on Infant and Young Child Feeding introduced in 2006 recommended the initiation of breastfeeding immediately after birth, preferably within one hour; exclusive breastfeeding for the first six months; appropriate and adequate complementary feeding from six months of age while continuing breastfeeding; and continued breastfeeding up to the age of two years or beyond. Working women in India constitute a dominant and expanding pool of mothers. There is paucity of research focused on feeding behavior within this group. Method: One hundred and fifty working women answered a structured questionnaire about their demographics, birth history, levels of awareness and practice of feeding guidelines, and perceptions about breastfeeding and counseling. Data analysis was carried out using Microsoft Excel and the Statistical Package for the Social Sciences. Results: Majority of participants belonged to 21-39 years age group, had nuclear families, received college education, and delivered in institutional setups. Gaps were observed between the mother’s levels of awareness and practice for different tenets of national guidelines. Higher education, longer maternity leave, higher income, and utilization of counseling services facilitated adoption of optimal feeding behavior. Most women perceived breast milk to be superior to any alternative and favored provision of counseling during last trimester. Conclusions and Global Health Implications: Counseling women on optimal feeding behavior is a potential intervention to convert its awareness into actual practice. The lessons learned from this study can help refine both national and global Mother and Child Health policies and programs.

  9. 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.

  10. 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

  11. Peripheral canine CD4(+)CD8(+) double-positive T cells - unique amongst others.

    PubMed

    von Buttlar, Heiner; Bismarck, Doris; Alber, Gottfried

    2015-12-15

    T lymphocytes co-expressing CD4 and CD8 ("double-positive T cells") are commonly associated with a thymic developmental stage of T cells. Their first description in humans and pigs as extrathymic T cells with a memory phenotype almost 30 years ago came as a surprise. Meanwhile peripheral double-positive T cells have been described in a growing number of different species. In this review we highlight novel data from our very recent studies on canine peripheral double-positive T cells which point to unique features of double-positive T cells in the dog. In contrast to porcine CD4(+)CD8(+) T cells forming a homogenous cellular population based on their expression of CD4 and CD8α, canine CD4(+)CD8(+) T cells can be divided into three different cellular subsets with distinct expression levels of CD4 and CD8α. Double-positive T cells expressing CD8β are present in humans and dogs but absent in swine. Moreover, canine CD4(+)CD8(+) T cells can not only develop from CD4(+) single-positive T cells but also from CD8(+) single-positive T cells. Together, this places canine CD4(+)CD8(+) T cells closer to their human than porcine counterparts since human double-positive T cells also appear to be heterogeneous in their CD4 and CD8α expression and have both CD4(+) and CD8(+) T cells as progenitor cells. However, CD4(+) single-positive T cells are the more potent progenitors for canine double-positive T cells, whereas CD8(+) single-positive T cells are more potent progenitors for human double-positive T cells. Canine double-positive T cells have an activated phenotype and may have as yet unrecognized roles in vivo in immunity to infection or in inflammatory diseases such as chronic infection, autoimmunity, allergy, or cancer.

  12. Evaluation of the FACSPresto, a New Point of Care Device for the Enumeration of CD4% and Absolute CD4+ T Cell Counts in HIV Infection

    PubMed Central

    Makadzange, Azure Tariro; Bogezi, Carola; Boyd, Kathryn; Gumbo, Anesu; Mukura, Dorinda; Matubu, Allen; Ndhlovu, Chiratidzo Ellen

    2016-01-01

    Introduction Enumeration of CD4+ T lymphocytes is important for pre-ART disease staging and screening for opportunistic infections, however access to CD4 testing in resource limited settings is poor. Point of care (POC) technologies can facilitate improved access to CD4 testing. We evaluated the analytical performance of a novel POC device the FACSPresto compared to the FACSCalibur as a reference standard and to the PIMA, a POC device in widespread use in sub-Saharan Africa. Method Specimens were obtained from 253 HIV infected adults. Venous blood samples were analyzed on the FACSPresto and the FACSCalibur, in a subset of 41 samples additional analysis was done on the PIMA. Results The absolute CD4 count results obtained on the FACSPresto were comparable to those on the FACSCalibur with low absolute (9.5cells/μl) and relative bias (3.2%). Bias in CD4% values was also low (1.06%) with a relative bias of 4.9%. The sensitivity was lower at a CD4 count threshold of ≤350cells/μl compared with ≤500cells/μl (84.9% vs. 92.8%) resulting in a high upward misclassification rate at low CD4 counts. Specificity at thresholds of ≤350cells/μl and ≤500cells/μl were 96.6% and 96.8% respectively. The PIMA had a high absolute (-68.6cells/μl) and relative bias (-10.5%) when compared with the FACSCalibur. At thresholds of ≤350cells/μl and ≤500cells/μl the sensitivity was 100% and 95.5% respectively; specificity was 85.7% and 84.2% respectively. The coefficients of repeatability were 4.13%, 5.29% and 9.8% respectively. Discussion The analytic performance of the FACSPresto against the reference standard was very good with better agreement and precision than the PIMA. The FACSPresto had comparable sensitivity at a threshold of 500 cells/μl and better specificity than the PIMA. However the FACSPresto showed reduced sensitivity at low CD4 count thresholds. Conclusion The FACSPresto can be reliably used as a POC device for enumerating absolute CD4 count and CD4% values

  13. PIMA Point of Care CD4+ Cell Count Machines in Remote MNCH Settings: Lessons Learned from Seven Districts in Zimbabwe

    PubMed Central

    Mtapuri-Zinyowera, Sekesai; Chiyaka, Edward T.; Mushayi, Wellington; Musuka, Godfrey; Naluyinda-Kitabire, Florence; Mushavi, Angella; Chikwasha, Vasco

    2013-01-01

    An evaluation was commissioned to generate evidence on the impact of PIMA point-of-care CD4+ count machines in maternal and new-born child health settings in Zimbabwe; document best practices, lessons learned, challenges, and recommendations related to scale up of this new technology. A mixed methodology approach that included 31 in-depth interviews with stakeholders involved in procurement, distribution, and use of the POC machines was employed. Additionally, data was also abstracted from 207 patient records from 35 sites with the PIMA POC CD4+ count machines and 10 other comparative sites without the machine. A clearer training strategy was found to be necessary. The average time taken to initiate clients on antiretroviral treatment (ART) was substantially less, 15 days (IQR-1-149) for sites with a PIMA POC machine as compared to 32.7 days (IQR-1-192) at sites with no PIMA POC machine. There was general satisfaction because of the presence of the PIMA POC CD4+ count machine at sites that also initiated ART. PMID:24847177

  14. 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

  15. 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

  16. AFM force measurements of the gp120-sCD4 and gp120 or CD4 antigen-antibody interactions

    SciTech Connect

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

    2011-04-08

    Highlights: {yields} The unbinding force of sCD4-gp120 interaction was 25.45 {+-} 20.46 pN. {yields} The unbinding force of CD4 antigen-antibody interaction was 51.22 {+-} 34.64 pN. {yields} The unbinding force of gp120 antigen-antibody interaction was 89.87 {+-} 44.63 pN. {yields} The interaction forces between various HIV inhibitors and the target molecules are significantly different. {yields} Functionalizing on AFM tip or substrate of an interaction pair caused different results. -- Abstract: 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, 51.22 {+-} 34.64, 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.

  17. 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. PMID:25655255

  18. Use of MHC class II tetramers to investigate CD4+ T cell responses: problems and solutions.

    PubMed

    Cecconi, Virginia; Moro, Monica; Del Mare, Sara; Dellabona, Paolo; Casorati, Giulia

    2008-11-01

    MHC-class I tetramers technology enabled the characterization of peptide-specific T cells at the single cell level in a variety of studies. Several laboratories have also developed MHC-class II multimers to characterize Ag-specific CD4+ T cells. However, the generation and use of MHC-class II multimers seems more problematic than that of MHC-I multimers. We have generated HLA-DR*1101 tetramers in a versatile empty form, which can be loaded after purification with peptides of interest. We discuss the impact of critical biological and structural parameters for the optimal staining of Ag-specific CD4+ T cells using HLA-DR*1101 tetramers, such as: (i) activation state of CD4+ T cells; (ii) membrane trafficking in the target CD4+ T cells; (iii) binding characteristics of the loaded CD4 epitope. Our data indicate that reorganization of TCR on the plasma membrane upon CD4+ T cell activation, as well as an homogenous binding frame of the CD4 epitopes to the soluble HLA-DR monomer, are critical for a stable TCR/MHC-class II tetramer interaction. These factors, together with the low frequencies and affinities of specific CD4+ T cells, explain the need for in vitro expansion or ex vivo enrichment of specific T cells for the optimal visualization with MHC-class II tetramers. PMID:18612991

  19. 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 ...

  20. 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...

  1. 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

  2. Electrochemical magneto-actuated biosensor for CD4 count in AIDS diagnosis and monitoring.

    PubMed

    Carinelli, S; Xufré Ballesteros, C; Martí, M; Alegret, S; Pividori, M I

    2015-12-15

    The counting of CD4(+) T lymphocytes is a clinical parameter used for AIDS diagnosis and follow-up. As this disease is particularly prevalent in developing countries, simple and affordable CD4 cell counting methods are urgently needed in resource-limited settings. This paper describes an electrochemical magneto-actuated biosensor for CD4 count in whole blood. The CD4(+) T lymphocytes were isolated, preconcentrated and labeled from 100 μL of whole blood by immunomagnetic separation with magnetic particles modified with antiCD3 antibodies. The captured cells were labeled with a biotinylated antiCD4 antibody, followed by the reaction with the electrochemical reporter streptavidin-peroxidase conjugate. The limit of detection for the CD4 counting magneto-actuated biosensor in whole blood was as low as 44 cells μL(-1) while the logistic range was found to be from 89 to 912 cells μL(-1), which spans the whole medical interest range for CD4 counts in AIDS patients. The electrochemical detection together with the immunomagnetic separation confers high sensitivity, resulting in a rapid, inexpensive, robust, user-friendly method for CD4 counting. This approach is a promising alternative for the costly standard flow cytometry and suitable as diagnostic tool at decentralized practitioner sites in low resource settings, especially in less developed countries.

  3. CD4+CD25+ cells in multiple myeloma related renal impairment

    PubMed Central

    Huang, Hongdong; Luo, Yang; Liang, Yumei; Long, Xi-Dai; Peng, Youming; Liu, Zhihua; Wen, Xiaojun; Jia, Meng; Tian, Ru; Bai, Chengli; Li, Cui; Dong, Xiaoqun

    2015-01-01

    CD4+CD25+ cells are critical regulators in almost all of the animal models of human organ-specific autoimmune diseases, transplant rejection and allergic diseases. We aimed to explore the role of CD4+CD25+ cells in the pathogenesis of multiple myeloma (MM) related renal impairment (RI). Thirty patients with MM related RI and 30 healthy volunteers were studied. The number of CD4+CD25+ cells was examined by flow cytometry. Clinical and laboratory data were collected from each subject. Glomerular injury was assessed by histopathology. Serum IL-2, IL-4 and IL-6 were analyzed by ELISA. CD4+CD25+ cells significantly decreased in MM related RI patients compared to the controls (P<0.05). CD4+CD25+ cell number was negatively associated with blood urea nitrogen (BUN), supernatant IL-4, serum IL-6, monoclonal immunoglobulin and β2-microglobulin, as well as bone marrow plasma cell percentage and proteinuria; whereas positively associated with estimated glomerular filtration rate (eGFR) (all P < 0.05). CD4+CD25+ cells gradually decreased as the Clinic Stage increased. The number of CD4+CD25+ cells reduced in MM related RI patients, and was correlated with disease severity. CD4+CD25+ cells may play an important role in the pathogenesis of MM related RI. PMID:26564056

  4. Electrochemical magneto-actuated biosensor for CD4 count in AIDS diagnosis and monitoring.

    PubMed

    Carinelli, S; Xufré Ballesteros, C; Martí, M; Alegret, S; Pividori, M I

    2015-12-15

    The counting of CD4(+) T lymphocytes is a clinical parameter used for AIDS diagnosis and follow-up. As this disease is particularly prevalent in developing countries, simple and affordable CD4 cell counting methods are urgently needed in resource-limited settings. This paper describes an electrochemical magneto-actuated biosensor for CD4 count in whole blood. The CD4(+) T lymphocytes were isolated, preconcentrated and labeled from 100 μL of whole blood by immunomagnetic separation with magnetic particles modified with antiCD3 antibodies. The captured cells were labeled with a biotinylated antiCD4 antibody, followed by the reaction with the electrochemical reporter streptavidin-peroxidase conjugate. The limit of detection for the CD4 counting magneto-actuated biosensor in whole blood was as low as 44 cells μL(-1) while the logistic range was found to be from 89 to 912 cells μL(-1), which spans the whole medical interest range for CD4 counts in AIDS patients. The electrochemical detection together with the immunomagnetic separation confers high sensitivity, resulting in a rapid, inexpensive, robust, user-friendly method for CD4 counting. This approach is a promising alternative for the costly standard flow cytometry and suitable as diagnostic tool at decentralized practitioner sites in low resource settings, especially in less developed countries. PMID:26264263

  5. Polyfunctional CD4 T cells in the 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. However, the a...

  6. 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...

  7. Simple and rapid CD4 testing based on large-field imaging system composed of microcavity array and two-dimensional photosensor.

    PubMed

    Saeki, Tatsuya; Sugamura, Yuriko; Hosokawa, Masahito; Yoshino, Tomoko; Lim, Tae-Kyu; Harada, Manabu; Matsunaga, Tadashi; Tanaka, Tsuyoshi

    2015-05-15

    This study presents a novel method for CD4 testing based on one-shot large-field imaging. The large-field imaging system was fabricated by a microcavity array and a two-dimensional (2D) photosensor within the desk-top-sized instrument. The microcavity array was employed to separate leukocytes from whole blood based on differences in the size of leukocytes and other blood cells. The large-field imaging system with lower side irradiation enabled acquisition of cell signatures with high signal-to-noise ratio, because the metallic substrate of the microcavity array obstructed excessive excitation light. In this setting, dual-color imaging of CD4(+) and CD8(+) T cells was achieved within the entire image area (64 mm(2)) in 2s. The practical performance of the large-field imaging system was demonstrated by determining the CD4/CD8 ratio in a few microliter of control whole blood as small as those obtained by a finger prick. The CD4/CD8 ratios measured using the large-field imaging system correlated well with those measured by microscopic analysis. These results indicate that our proposed system provides a simple and rapid CD4 testing for the application of HIV/AIDS treatment.

  8. 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.

  9. 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. PMID:26194743

  10. The Interplay Between Monocytes/Macrophages and CD4+ T Cell Subsets in Rheumatoid Arthritis

    PubMed Central

    Roberts, Ceri A.; Dickinson, Abigail K.; Taams, Leonie S.

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by inflammation of the synovial lining (synovitis). The inflammation in the RA joint is associated with and driven by immune cell infiltration, synovial hyperproliferation, and excessive production of proinflammatory mediators, such as tumor necrosis factor α (TNFα), interferon γ (IFNγ), interleukin (IL)-1β, IL-6, and IL-17, eventually resulting in damage to the cartilage and underlying bone. The RA joint harbors a wide range of immune cell types, including monocytes, macrophages, and CD4+ T cells (both proinflammatory and regulatory). The interplay between CD14+ myeloid cells and CD4+ T cells can significantly influence CD4+ T cell function, and conversely, effector vs. regulatory CD4+ T cell subsets can exert profound effects on monocyte/macrophage function. In this review, we will discuss how the interplay between CD4+ T cells and monocytes/macrophages may contribute to the immunopathology of RA. PMID:26635790

  11. Production of erythrocyte autoantibodies in NZB mice is inhibited by CD4 antibodies.

    PubMed Central

    Oliveira, G G; Hutchings, P R; Roitt, I M; Lydyard, P M

    1994-01-01

    NZB mice spontaneously develop haemolytic anaemia as the result of production of erythrocyte autoantibodies. The mechanisms leading to breakdown in tolerance to erythrocyte autoantigens are unknown. Antibodies to CD4 have been successfully used to treat several murine models of autoimmune disease. In this study we injected NZB mice with non-depleting CD4 antibodies and were able to prevent and abrogate erythrocyte autoantibody production in young (Coombs' negative) and old (Coombs' positive) mice, respectively. Our data indicate the dependency of autoantibody production on CD4+ T cells. However, withdrawal of anti-CD4 antibodies resulted in the appearance of erythrocyte autoantibodies, showing that under these conditions we were unable to re-establish tolerance to autoantigens on erythrocytes using anti-CD4 treatment. PMID:8187337

  12. T lymphocytes in rat germinal centres belong to an ER3+ subpopulation of CD4+ cells.

    PubMed Central

    Vonderheide, R H; Hunt, S V

    1990-01-01

    Two-colour immunofluorescence histochemistry showed directly that greater than 90% of CD4+ germinal centre T cells in rat spleen or lymph node examined 7 days after immunization bear the antigen recognized by the monoclonal antibody (mAb) ER3. By contrast, only 30-40% of all thoracic duct or lymph node CD4+ cells were ER3+, as determined by two-colour flow cytometry. CD8+ cells were ER3+, but nearly all B cells were ER3-. Thus, germinal centre T cells belong to a subpopulation of CD4+ cells. Because only 25-30% of CD4+ cells that lack higher molecular weight forms of CD45 (i.e. mAb MRC OX32 cells, equivalent to MRC OX22 cells) express ER3, the CD4+ subpopulations defined by ER3 are neither identical nor complementary to the subsets defined by restricted expression of CD45 epitopes. Images Figure 1 PMID:1970805

  13. CD4-Blockade Can Induce Protection from Peanut-Induced Anaphylaxis

    PubMed Central

    Duarte, Joana; Caridade, Marta; Graca, Luis

    2011-01-01

    Monoclonal antibodies (mAb) have been shown effective in inducing immune tolerance in a range of animal models of autoimmunity, allergy, and transplantation. We investigated whether CD4-blockade, effective in inducing transplantation tolerance, could prevent systemic immune responses leading to anaphylaxis. We found that treatment with a non-depleting anti-CD4 mAb could prevent peanut-induced anaphylaxis following subsequent systemic exposure to crude peanut extract (CPE). Furthermore, the effect of CD4-blockade did not interfere with overall immune competence, as anti-CD4 treated mice remained fully competent to respond to unrelated antigens. Protection from anaphylaxis correlated with increased frequency of Foxp3+ regulatory T cells (Treg), and was abrogated following Treg depletion. Taken together our data suggest that activation of T cells by CPE in presence of CD4-blockade leads to Treg expansion that can prevent peanut-induced anaphylaxis. PMID:22566846

  14. Targeting of liposomes to HIV-1-infected cells by peptides derived from the CD4 receptor.

    PubMed

    Slepushkin, V A; Salem, I I; Andreev, S M; Dazin, P; Düzgüneş, N

    1996-10-23

    Liposomes can be targeted to HIV-infected cells by either reconstituting transmembrane CD4 in the membrane or covalently coupling soluble CD4 to modified lipids. We investigated whether synthetic peptides could be used as ligands for targeting liposomes. A synthetic peptide from the complementarity determining region 2 (CDR-2)-like domain of CD4 could bind specifically to HIV-infected cells and mediate the binding of peptide-coupled liposomes to these cells. A peptide from the CDR-3-like domain of CD4 inhibited HIV-induced syncytia formation, but failed to target liposomes to infected cells. This apparent discrepancy may be due to the requirement for a conformational change in the CD4 receptor for the CDR-3 region to interact with the HIV envelope protein. Our results demonstrate the feasibility of using synthetic peptides to target liposomes containing antiviral drugs to HIV-infected cells.

  15. 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.

  16. 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

  17. 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

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

    PubMed

    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

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

    PubMed

    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.

  20. 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

  1. Effects of CD4 monitoring frequency on clinical endpoints in clinically stable HIV-infected patients with viral suppression

    PubMed Central

    Ahn, Jin Young; Boettiger, David; Law, Matthew; Kumarasamy, Nagalingeswaran; Yunihastuti, Evy; Chaiwarith, Romanee; Lee, Man Po; Sim, Benedict LH; Oka, Shinichi; Wong, Wingwai; Kamarulzaman, Adeeba; Kantipong, Pacharee; Phanuphak, Praphan; Ng, Oon Tek; Kiertiburanakul, Sasisopin; Zhang, Fujie; Pujari, Sanjay; Ditangco, Rossana; Ratanasuwan, Winai; Merati, Tuti Parwati; Saphonn, Vonthanak; Sohn, Annette H.; Choi, Jun Yong

    2015-01-01

    Background Current treatment guidelines for HIV infection recommend routine CD4+ lymphocyte (CD4) count monitoring in patients with viral suppression. This may have a limited impact on influencing care as clinically meaningful CD4 decline rarely occurs during viral suppression. Methods In a regional HIV observational cohort in the Asia-Pacific, patients with viral suppression (2 consecutive viral loads <400 copies/mL) and a CD4 count ≥200 cells/μL who had CD4 testing 6 monthly were analyzed. Main study endpoints were occurrence of one CD4 count <200 cells/μL (single CD4<200) and two CD4 counts <200 cells/μL within a 6-month period (confirmed CD4<200). A comparison of time to single and confirmed CD4<200 with biannual or annual CD4 assessment was performed by generating a hypothetical group comprised of the same patients with annual CD4 testing by removing every second CD4 count. Results Among 1538 patients, the rate of single CD4<200 was 3.45/100 patient-years, and of confirmed CD4<200 was 0.77/100 patient-years. During 5 years of viral suppression, patients with baseline CD4 200-249 cells/μL were significantly more likely to experience confirmed CD4<200 compared with patients with higher baseline CD4 (hazard ratio 55.47 [95% confidence interval 7.36–418.20], p<0.001 versus baseline CD4 ≥500 cells/μL). Cumulative probabilities of confirmed CD4<200 was also higher in patients with baseline CD4 200-249 cells/μL compared with patients with higher baseline CD4. There was no significant difference in time to confirmed CD4<200 between biannual and annual CD4 measurement (p=0.336). Conclusions Annual CD4 monitoring in virally suppressed HIV patients with a baseline CD4 ≥250 cells/μL may be sufficient for clinical management. PMID:25850606

  2. 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.

  3. 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

  4. 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

    2016-01-01

    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

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

    PubMed

    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

  6. 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

  7. 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…

  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. Preventative lipid-based nutrient supplements (LNS) and young child feeding practices: findings from qualitative research in Haiti.

    PubMed

    Lesorogol, Carolyn; Jean-Louis, Sherlie; Green, Jamie; Iannotti, Lora

    2015-12-01

    To prevent undernutrition in an urban slum in Haiti, a lipid-based nutrient supplement (LNS) was introduced through a randomised control trial. Food supplementation for young child nutrition has a long history in Haiti, but there is little empirical information regarding the effects of supplementation on young child feeding practices. One of the concerns raised by supplementation is that it may disrupt other positive feeding practices such as breastfeeding and use of other complementary foods, with negative consequences for child nutrition. We conducted 29 in-depth interviews with mother-baby pairs from the three comparison groups: control, 3-month LNS supplementation and 6-month LNS supplementation. Findings from those in the LNS groups indicated high acceptance and satisfaction with LNS and perceptions that it positively affects child health and development. LNS was integrated into and enhanced ongoing complementary feeding practices. The effects of LNS use on duration and perceived quantity of breastfeeding were variable, but generally, breastfeeding was maintained during and after the intervention. Interviews generated insights into beliefs regarding infant and young child feeding practices such as introduction and use of complementary foods, and breastfeeding duration, exclusivity and cessation. Implications for the use of LNS in public health nutrition programmes are discussed.

  10. 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.

  11. 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...

  12. Regulation of T cell receptor expression in immature CD4+CD8+ thymocytes by p56lck tyrosine kinase: basis for differential signaling by CD4 and CD8 in immature thymocytes expressing both coreceptor molecules

    PubMed Central

    1993-01-01

    Signals transduced through the T cell antigen receptor (TCR) are modulated by the src family tyrosine kinase p56lck (lck), which associates in mature T cells with the coreceptor molecules CD4 and CD8. Here we describe a novel function of lck in immature CD4+CD8+ thymocytes, that of regulating TCR expression. Activation of lck in immature CD4+CD8+ thymocytes by intrathymic engagement of CD4 maintains low TCR expression by causing most TCR components to be retained and degraded within the endoplasmic reticulum. Importantly, activation of lck in immature CD4+CD8+ thymocytes results from engagement of surface CD4 molecules, but not surface CD8 molecules, despite the nearly fourfold greater surface expression of CD8 than CD4. The competence of CD4 to activate lck in CD4+CD8+ thymocytes relates to the fact that a relatively large fraction of surface CD4 molecules (25-50%) are associated with intracellular lck molecules, whereas only 2% of surface CD8 molecules are associated with lck. The amount of lck associated with CD4 in CD4+CD8+ thymocytes is diminished by chronic CD4 engagement in the thymus, as activated lck molecules subsequently dissociate from CD4. Indeed, the amount of lck associated with CD4 in CD4+CD8+ thymocytes is markedly increased in major histocompatibility complex (MHC) class II- mice that lack the intrathymic ligand for CD4 and in which surface CD4 molecules are consequently not engaged. Thus, the present study demonstrates that (a) activation of lck in CD4+CD8+ thymocytes regulates distribution and expression of TCR components; (b) unlike CD4 molecules, CD8 molecules on CD4+CD8+ thymocytes cannot efficiently activate lck despite their significantly greater surface expression; and (c) the amount of lck associated with CD4 in the CD4+CD8+ thymocytes is inversely related to the extent of CD4 engagement by MHC class II molecules in the thymus. PMID:8228817

  13. 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.

  14. Impaired CD4 T Cell Memory Response to Streptococcus pneumoniae Precedes CD4 T Cell Depletion in HIV-Infected Malawian Adults

    PubMed Central

    Mzinza, David; Harawa, Visopo; Miles, David J. C.; Jambo, Kondwani C.; Gordon, Stephen B.; Williams, Neil A.; Heyderman, Robert S.

    2011-01-01

    Objective Invasive pneumococcal disease (IPD) is a leading cause of morbidity and mortality in HIV-infected African adults. CD4 T cell depletion may partially explain this high disease burden but those with relatively preserved T cell numbers are still at increased risk of IPD. This study evaluated the extent of pneumococcal-specific T cell memory dysfunction in asymptomatic HIV infection early on in the evolution of the disease. Methods Peripheral blood mononuclear cells were isolated from asymptomatic HIV-infected and HIV-uninfected Malawian adults and stained to characterize the underlying degree of CD4 T cell immune activation, senescence and regulation. Pneumococcal-specific T cell proliferation, IFN-γ, IL-17 production and CD154 expression was assessed using flow cytometry and ELISpot. Results We find that in asymptomatic HIV-infected Malawian adults, there is considerable immune disruption with an increase in activated and senescent CD4+CD38+PD-1+ and CD4+CD25highFoxp3+ Treg cells. In the context of high pneumococcal exposure and therefore immune stimulation, show a failure in pneumococcal-specific memory T cell proliferation, skewing of T cell cytokine production with preservation of interleukin-17 but decreased interferon-gamma responses, and failure of activated T cells to express the co-stimulatory molecule CD154. Conclusion Asymptomatic HIV-infected Malawian adults show early signs of pneumococcal- specific immune dysregulation with a shift in the balance of CD4 memory, T helper 17 cells and Treg. Together these data offer a mechanistic understanding of how antigen-specific T cell dysfunction occurs prior to T cell depletion and may explain the early susceptibility to IPD in those with relatively preserved CD4 T cell numbers. PMID:21980502

  15. 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

  16. SAMHD1 restricts HIV-1 reverse transcription in quiescent CD4+ T-cells

    PubMed Central

    2012-01-01

    Background Quiescent CD4+ T lymphocytes are highly refractory to HIV-1 infection due to a block at reverse transcription. Results Examination of SAMHD1 expression in peripheral blood lymphocytes shows that SAMHD1 is expressed in both CD4+ and CD8+ T cells at levels comparable to those found in myeloid cells. Treatment of CD4+ T cells with Virus-Like Particles (VLP) containing Vpx results in the loss of SAMHD1 expression that correlates with an increased permissiveness to HIV-1 infection and accumulation of reverse transcribed viral DNA without promoting transcription from the viral LTR. Importantly, CD4+ T-cells from patients with Aicardi-Goutières Syndrome harboring mutation in the SAMHD1 gene display an increased susceptibility to HIV-1 infection that is not further enhanced by VLP-Vpx-treatment. Conclusion Here, we identified SAMHD1 as the restriction factor preventing efficient viral DNA synthesis in non-cycling resting CD4+ T-cells. These results highlight the crucial role of SAMHD1 in mediating restriction of HIV-1 infection in quiescent CD4+ T-cells and could impact our understanding of HIV-1 mediated CD4+ T-cell depletion and establishment of the viral reservoir, two of the HIV/AIDS hallmarks. PMID:23092122

  17. CD4+ T cells mediate mucosal and systemic immune responses to experimental hookworm infection

    PubMed Central

    DONDJI, B.; SUN, T.; BUNGIRO, R. D.; VERMEIRE, J. J.; HARRISON, L. M.; BIFULCO, C.; CAPPELLO, M.

    2011-01-01

    SUMMARY Hookworm infection is associated with anaemia and malnutrition in many resource-limited countries. Ancylostoma hookworms have previously been shown to modulate host cellular immune responses through multiple mechanisms, including reduced mitogen-mediated lymphocyte proliferation, impaired antigen presentation/processing, and relative reductions in CD4+ T cells in the spleen and mesenteric lymph nodes. Syrian hamsters were depleted of CD4+ for up to 9 days following intraperitoneal injection (200 μg) of a murine anti-mouse CD4 monoclonal IgG (clone GK1·5). CD4+ T-cell-depleted hamsters infected with the hookworm Ancylostoma ceylanicum exhibited a threefold higher mean intestinal worm burden and more severe anaemia than animals that received isotype control IgG. In addition, depletion of CD4+ T cells was associated with impaired cellular and humoral (serum and mucosal) immune responses to hookworm antigens. These data demonstrate an effector role for CD4+ T cells in hookworm immunity and disease pathogenesis. Ultimately, these studies may yield important insights into the relationship between intestinal nematode infections and diseases that are associated with CD4+ T-cell depletion, including HIV. PMID:20500671

  18. Transmission of survival signals through Delta-like 1 on activated CD4+ T cells

    PubMed Central

    Furukawa, Takahiro; Ishifune, Chieko; Tsukumo, Shin-ichi; Hozumi, Katsuto; Maekawa, Yoichi; Matsui, Naoko; Kaji, Ryuji; Yasutomo, Koji

    2016-01-01

    Notch expressed on CD4+ T cells transduces signals that mediate their effector functions and survival. Although Notch signaling is known to be cis-inhibited by Notch ligands expressed on the same cells, the role of Notch ligands on T cells remains unclear. In this report we demonstrate that the CD4+ T cell Notch ligand Dll1 transduces signals required for their survival. Co-transfer of CD4+ T cells from Dll1−/− and control mice into recipient mice followed by immunization revealed a rapid decline of CD4+ T cells from Dll1−/− mice compared with control cells. Dll1−/− mice exhibited lower clinical scores of experimental autoimmune encephalitis than control mice. The expression of Notch target genes in CD4+ T cells from Dll1−/− mice was not affected, suggesting that Dll1 deficiency in T cells does not affect cis Notch signaling. Overexpression of the intracellular domain of Dll1 in Dll1-deficient CD4+ T cells partially rescued impaired survival. Our data demonstrate that Dll1 is an independent regulator of Notch-signaling important for the survival of activated CD4+ T cells, and provide new insight into the physiological roles of Notch ligands as well as a regulatory mechanism important for maintaining adaptive immune responses. PMID:27659682

  19. CD4+CD25+ T Cells in primary malignant hypertension related kidney injury

    PubMed Central

    Huang, Hongdong; Luo, Yang; Liang, Yumei; Long, Xidai; Peng, Youming; Liu, Zhihua; Wen, Xiaojun; Jia, Meng; Tian, Ru; Bai, Chengli; Li, Cui; He, Fuliang; Lin, Qiushi; Wang, Xueyan; Dong, Xiaoqun

    2016-01-01

    CD4+CD25+ T cells are critical for maintenance of immunologic self-tolerance. We measured the number of CD4+CD25+ cells in the patients with primary malignant hypertension related kidney injury, to explore the molecular pathogenesis of this disease. We selected 30 patients with primary malignant hypertension related kidney injury and 30 healthy volunteers. Information on clinical characteristics and laboratory tests was obtained from each subject. The number of CD4+CD25+ cells and glomerular injury were assessed by flow cytometry and histopathology, respectively. Both serum IL-2, IL-4, and IL-6 and endothelial cell markers were analyzed by ELISA. ADAMTS13 antibody was detected by Western blotting. CD4+CD25+ cells were significantly reduced in patients with primary malignant hypertension related kidney injury compared to controls (P < 0.05). The number of CD4+CD25+ cells was negatively related to blood urea nitrogen, serum uric acid, proteinuria, and supernatant IL-4; whereas positively associated with estimated glomerular filtration rate in patients. Gradually decreasing CD4+CD25+ cells were also found as increasing renal injury. Additionally, patients exhibited increasing supernatant IL-4, serum IL-2 and IL-6, endothelial cell markers, and anti-ADAMTS13 antibody compared with controls (all P < 0.05). CD4+CD25+ cells may play a key role in the pathogenesis of primary malignant hypertension related kidney injury. PMID:27278520

  20. 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

  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. Distribution of CD4 Lymphocyte Cells Among Apparently Healthy HIV Seropositive and Seronegative Populations

    PubMed Central

    Abubakar, Abdulazeez A

    2012-01-01

    Background: CD4 lymphocyte cells are often used as prognostic markers for monitoring the progression of immunosupression such as HIV infection. Aim: This study was conducted to assess the distribution of CD4 lymphocytes among apparently healthy human immunodeficiency virus (HIV) seronegative and seropositive populations in a Nigerian state. Materials and Methods: A total of 1520 apparently healthy subjects aged 18–64 years, composed of 800 males and 720 females attending some selected health institutions in the state, participated in the study. Ten milliliters of blood was collected from each subject; 5 ml of this was used for HIV antibodies sero-typing while the remaining 5 ml was anticoagulated and used for CD4 lymphocytes level determination. Only samples tested positive both with Capillus and Determine HIV test kits were further differentiated into sero-types with a standard diagnostic HIV test kit. The CD4 lymphocyte levels of all the sample were determined; mean CD4 levels of 205.1±0.09 and 287.4±0.3 cells/μl were recorded among females seropositives and seronagatives respectively. Statistical analysis by the Student t-test showed a significant difference in the mean CD4 lymphocyte count by gender. Results: Findings showed a mean CD4 level of 311.7±1.2 cells/μl among seropositive males while 399.3±0.6 cells/μl was recorded among seronegatives (t=5.86). The study also recorded a CD4 lymphocyte range of 232–464 cells/μl among apparently healthy seronegative population in this locality. Conclusion: The findings showed a significantly higher mean CD4 lymphocyte count among adult male HIV seronegatives (χ2=9.22) and seropositives (χ2=15.07) than their female counterparts. Further research work using the automation technique is suggested to confirm this new range for monitoring HIV subjects on antiretroviral therapy. PMID:22454823

  3. Granzyme B mediated function of Parvovirus B19-specific CD4+ T cells

    PubMed Central

    Kumar, Arun; Perdomo, Maria F; Kantele, Anu; Hedman, Lea; Hedman, Klaus; Franssila, Rauli

    2015-01-01

    A novel conception of CD4+ T cells with cytolytic potential (CD4+ CTL) is emerging. These cells appear to have a part in controlling malignancies and chronic infections. Human parvovirus B19 can cause a persistent infection, yet no data exist on the presence of B19-specific CD4+ CTLs. Such cells could have a role in the pathogenesis of some autoimmune disorders reported to be associated with B19. We explored the cytolytic potential of human parvovirus B19-specific T cells by stimulating peripheral blood mononuclear cell (PBMC) with recombinant B19-VP2 virus-like particles. The cytolytic potential was determined by enzyme immunoassay-based quantitation of granzyme B (GrB) and perforin from the tissue culture supernatants, by intracellular cytokine staining (ICS) and by detecting direct cytotoxicity. GrB and perforin responses with the B19 antigen were readily detectable in B19-seropositive individuals. T-cell depletion, HLA blocking and ICS experiments showed GrB and perforin to be secreted by CD4+ T cells. CD4+ T cells with strong GrB responses were found to exhibit direct cytotoxicity. As anticipated, ICS of B19-specific CD4+ T cells showed expected co-expression of GrB, perforin and interferon gamma (IFN-γ). Unexpectedly, also a strong co-expression of GrB and interleukin 17 (IL-17) was detected. These cells expressed natural killer (NK) cell surface marker CD56, together with the CD4 surface marker. To our knowledge, this is the first report on virus-specific CD4+ CTLs co-expressing CD56 antigen. Our results suggest a role for CD4+ CTL in B19 immunity. Such cells could function within both immune regulation and triggering of autoimmune phenomena such as systemic lupus erythematosus (SLE) or rheumatoid arthritis. PMID:26246896

  4. Low-cost CD4 enumeration in HIV-infected patients in Thailand.

    PubMed

    Pattanapanyasat, Kovit; Lerdwana, Surada; Shain, Hla; Noulsri, Egarit; Thepthai, Charin; Prasertsilpa, Varipin; Eksaengsri, Achara; Kraisintu, Krisana

    2003-06-01

    In Thailand, over one million people have been infected with HIV since the beginning of the epidemic. This has created a great burden on the country's limited health care budget. Monitoring CD4+ T-lymphocytes is important to determine the success of any antiretroviral therapy as well as HIV vaccine trials. However, the high cost of CD4 counts makes monitoring of every HIV-infected patient impossible in Thailand. Therefore, the development of affordable strategies is necessary in order to allow more HIV infected persons to access CD4 testing to control the disease. The current standard methods for enumeration of CD4+ T-lymphocytes are performed on whole blood by flow cytometric immunophenotyping using the 6-tube 2-color and 3-tube 3-color panels recommended by the Centers for Diseases Control (CDC). In this study, percentage CD4+ T-lymphocyte values (from 142 HIV-seropositive patients and 26 anti-HIV negative adult blood donors) generated by the use of just 2 reagents (CD45/CD4) in a 1-tube 2-color panel employing side scatter/CD45 morphospectral gating were compared to those obtained by state of the art methods. We also compared the use of generic monoclonal antibody reagents with commercial reagents and found the results to be comparable with an overall correlation coefficient (r) of more than 0.95 for both CD4+ and CD8+ T-lymphocytes. Bland-Altman analysis of the mean CD4 values plotted against the difference in values between the generic reagents and the commercial reagents showed no bias. The 1-tube 2-color method using generic monoclonal antibody reagents potentially permits more affordable but reliable CD4 testing and therefore could increase access for more HIV-infected patients in resource-poor countries.

  5. Zinc is essential for binding of p56(lck) to CD4 and CD8alpha.

    PubMed

    Lin, R S; Rodriguez, C; Veillette, A; Lodish, H F

    1998-12-01

    Binding of the protein tyrosine kinase p56(lck) to T-cell co-receptors CD4 and CD8alpha is necessary for T-lymphocyte development and activation. Association of p56(lck) with CD4 requires two conserved cysteine residues in the cytosolic domain of CD4 and two in the amino terminus of p56(lck), consistent with the notion that these four residues coordinate a single metal atom (1-5). Here we demonstrate that Zn2+ is essential for complex formation. In an in vitro binding reaction, Zn2+ mediates p56(lck) association with a glutathione S-transferase (GST) fusion protein containing the cytosolic domains of CD4 or CD8alpha; no other metals tested support binding. Treatment of preformed GST-CD4.p56(lck) dimers with the Zn2+ chelators 1,10-O-phenanthroline or 8-hydroxyquinoline-5-sulfonic acid results in dissociation of GST-CD4 from p56(lck), consistent with the finding of Huse et al. (5) that Zn2+ is contained within similar complexes. Furthermore, we show that, within live cells, CD4.p56(lck) and CD8alpha.p56(lck) interactions occur in a zinc-dependent fashion. Specifically, pretreatment of the human Jurkat T-cell line with membrane permeable zinc chelators disrupts CD4.p56(lck) complexes, and treatment of COS cells co-expressing CD8alpha and p56(lck) with such chelators likewise leads to dissociation of CD8alpha.p56(lck) complexes. CD4. p56(lck) and CD8alpha.p56(lck) represent the first examples of intracellular proteins that require zinc as a bridge for heterodimerization.

  6. 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

  7. IL-7 signaling imparts polyfunctionality and stemness potential to CD4(+) T cells.

    PubMed

    Ding, Zhi-Chun; Liu, Chufeng; Cao, Yang; Habtetsion, Tsadik; Kuczma, Michal; Pi, Wenhu; Kong, Heng; Cacan, Ercan; Greer, Susanna F; Cui, Yan; Blazar, Bruce R; Munn, David H; Zhou, Gang

    2016-06-01

    The functional status of CD4(+) T cells is a critical determinant of antitumor immunity. Polyfunctional CD4(+) T cells possess the ability to concomitantly produce multiple Th1-type cytokines, exhibiting a functional attribute desirable for cancer immunotherapy. However, the mechanisms by which these cells are induced are neither defined nor it is clear if these cells can be used therapeutically to treat cancer. Here, we report that CD4(+) T cells exposed to exogenous IL-7 during antigenic stimulation can acquire a polyfunctional phenotype, characterized by their ability to simultaneously express IFNγ, IL-2, TNFα and granzyme B. This IL-7-driven polyfunctional phenotype was associated with increased histone acetylation in the promoters of the effector genes, indicative of increased chromatin accessibility. Moreover, forced expression of a constitutively active (CA) form of STAT5 recapitulated IL-7 in inducing CD4(+) T-cell polyfunctionality. Conversely, the expression of a dominant negative (DN) form of STAT5 abolished the ability of IL-7 to induce polyfunctional CD4(+) T cells. These in-vitro-generated polyfunctional CD4(+) T cells can traffic to tumor and expand intratumorally in response to immunization. Importantly, adoptive transfer of polyfunctional CD4(+) T cells following lymphodepletive chemotherapy was able to eradicate large established tumors. This beneficial outcome was associated with the occurrence of antigen epitope spreading, activation of the endogenous CD8(+) T cells and persistence of donor CD4(+) T cells exhibiting memory stem cell attributes. These findings indicate that IL-7 signaling can impart polyfunctionality and stemness potential to CD4(+) T cells, revealing a previously unknown property of IL-7 that can be exploited in adoptive T-cell immunotherapy.

  8. Human CD4 Metastability Is a Function of the Allosteric Disulfide Bond in Domain 2.

    PubMed

    Owen, Gavin R; Channell, Jennifer A; Forsyth, V Trevor; Haertlein, Michael; Mitchell, Edward P; Capovilla, Alexio; Papathanasopoulos, Maria; Cerutti, Nichole M

    2016-04-19

    CD4 is expressed on the surface of specific leukocytes where it plays a key role in the activation of immunostimulatory T-cells and acts as a primary receptor for HIV-1 entry. CD4 has four ecto-domains (D1-D4) of which D1, D2, and D4 contain disulfide bonds. Although disulfide bonds commonly serve structural or catalytic functions, a rare class of disulfide bonds possessing unusually high dihedral strain energy and a relative ease of reduction can impact protein function by shuffling their redox state. D2 of CD4 possesses one such "allosteric" disulfide. While it is becoming accepted that redox exchange of the D2 allosteric disulfide plays an essential role in regulating CD4 activity, the biophysical consequences of its reduction remain incompletely understood. By analyzing the hydrodynamic volume, secondary structure, and thermal stability of the reduced and nonreduced forms of the single D1 and D2 domains, as well as the various redox isomers of two domain CD4, we have shown that ablation of the allosteric disulfide bond in domain 2 results in both a favorable structural collapse and an increase in the stability of CD4. Conversely, ablating the structural disulfide of D1 results in destabilizing structural rearrangements in CD4. These findings expand our understanding of the mechanisms by which oxidoreduction of the D2 allosteric disulfide regulates CD4 function; they reveal the intrinsic disulfide-dependent metastability of D2 and illustrate that redox shuffling of the allosteric disulfide results in previously undescribed conformational changes in CD4 that are likely important for its interaction with its protein partners. PMID:27009680

  9. Infection of brain microglial cells by human immunodeficiency virus type 1 is CD4 dependent.

    PubMed Central

    Jordan, C A; Watkins, B A; Kufta, C; Dubois-Dalcq, M

    1991-01-01

    In the central nervous system of AIDS patients, human immunodeficiency virus (HIV) infects primarily microglia, a cell type of bone marrow origin. Moreover, microglial cells isolated from adult human brain support the replication of macrophage-adapted strains of HIV type 1 (HIV-1) (B.A. Watkins, H.H. Dorn, W.B. Kelly, R.C. Armstrong, B. Potts, F. Michaels, C.V. Kufta, and M. Dubois-Dalcq, Science 249:549-553, 1990). To determine whether the CD4 receptor, which is expressed in brain, mediates the entry of HIV-1 in microglial cells, we analyzed CD4 transcript expression in cultured microglia using highly sensitive polymerase chain reaction detection of cDNAs synthesized from RNA. With this method, CD4 transcripts could be detected in cultured microglia--as well as in various human brain regions and cultured macrophages used as positive controls--along with transcripts for the LDL and Fc receptors which are characteristic of cells of the macrophage lineage. We then attempted to block viral entry into microglial cells using anti-CD4 antibodies or soluble CD4 (sCD4), which recognize binding sites on CD4 and HIV-1 glycoprotein gp120, respectively. Cultures were pretreated with blocking antibodies (Leu-3a, OKT4A) or virus was preincubated with sCD4 prior to infection with HIV-1 strain AD87(M) or BaL. With either viral strain, these treatments resulted in the prevention of infection or significant and dose-dependent reduction in the number of infected cells and in the levels of reverse transcriptase or p24 antigen released in the medium. Thus, brain-derived microglial cells, which are the primary target of HIV-1 infection in the brain, express the CD4 receptor and this receptor is effectively used for viral entry in vitro. Images PMID:1702842

  10. Identification of Owl Monkey CD4 Receptors Broadly Compatible with Early-Stage HIV-1 Isolates

    PubMed Central

    Meyerson, Nicholas R.; Sharma, Amit; Wilkerson, Gregory K.

    2015-01-01

    ABSTRACT Most HIV-1 variants isolated from early-stage human infections do not use nonhuman primate versions of the CD4 receptor for cellular entry, or they do so poorly. We and others have previously shown that CD4 has experienced strong natural selection over the course of primate speciation, but it is unclear whether this selection has influenced the functional characteristics of CD4 as an HIV-1 receptor. Surprisingly, we find that selection on CD4 has been most intense in the New World monkeys, animals that have never been found to harbor lentiviruses related to HIV-1. Based on this, we sampled CD4 genetic diversity within populations of individuals from seven different species, including five species of New World monkeys. We found that some, but not all, CD4 alleles found in Spix's owl monkeys (Aotus vociferans) encode functional receptors for early-stage human HIV-1 isolates representing all of the major group M clades (A, B, C, and D). However, only some isolates of HIV-1 subtype C can use the CD4 receptor encoded by permissive Spix's owl monkey alleles. We characterized the prevalence of functional CD4 alleles in a colony of captive Spix's owl monkeys and found that 88% of surveyed individuals are homozygous for permissive CD4 alleles, which encode an asparagine at position 39 of the receptor. We found that the CD4 receptors encoded by two other species of owl monkeys (Aotus azarae and Aotus nancymaae) also serve as functional entry receptors for early-stage isolates of HIV-1. IMPORTANCE Nonhuman primates, particularly macaques, are used for preclinical evaluation of HIV-1 vaccine candidates. However, a significant limitation of the macaque model is the fact that most circulating HIV-1 variants cannot use the macaque CD4 receptor to enter cells and have to be adapted to these species. This is particularly true for viral variants from early stages of infection, which represent the most relevant vaccine targets. In this study, we found that some individuals

  11. Sequestration from Immune CD4^+ T Cells of Mycobacteria Growing in Human Macrophages

    NASA Astrophysics Data System (ADS)

    Pancholi, Preeti; Mirza, Asra; Bhardwaj, Nina; Steinman, Ralph M.

    1993-05-01

    CD4^+ helper T cells mediate resistance to tuberculosis, presumably by enhancing the antimicrobial activity of macrophages within which the Mycobacterium tuberculosis organism grows. A first step in resistance should be the presentation of mycobacterial antigens by macrophages to CD4^+ T cells. However, when the antigenic stimulus is limited to organisms growing in human monocytes, the organisms become sequestered from immune CD4^+ T cells. This block in presentation is selective for growing mycobacteria and not for other stimuli. Sequestration would allow replicating organisms to persist in infected individuals and may contribute to virulence.

  12. 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. PMID:23382748

  13. Associations of parenting styles, parental feeding practices and child characteristics with young children's fruit and vegetable consumption.

    PubMed

    Vereecken, Carine; Rovner, Alisha; Maes, Lea

    2010-12-01

    The purpose of this study was to investigate the role of parent and child characteristics in explaining children's fruit and vegetable intakes. In 2008, parents of preschoolers (mean age 3.5 years) from 56 schools in Belgium-Flanders completed questionnaires including a parent and child fruit and vegetable food frequency questionnaire, general parenting styles (laxness, overreactivity and positive interactions), specific food parenting practices (child-centered and parent-centered feeding practices) and children's characteristics (children's shyness, emotionality, stubbornness, activity, sociability, and negative reactions to food). Multiple linear regression analyses (n = 755) indicated a significant positive association between children's fruit and vegetable intake and parent's intake and a negative association with children's negative reactions to food. No general parenting style dimension or child personality characteristic explained differences in children's fruit and vegetable intakes. Child-centered feeding practices were positively related to children's fruit and vegetable intakes, while parent-centered feeding practices were negatively related to children's vegetable intakes. In order to try to increase children's fruit and vegetable consumption, parents should be guided to improve their own diet and to use child-centered parenting practices and strategies known to decrease negative reactions to food.

  14. 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.

  15. A complementary method to CD4 counting: measurement of CD4+/CD8+ T lymphocyte ratio in a tandem affinity microfluidic system.

    PubMed

    Li, Wenjie; Gao, Yan; Pappas, Dimitri

    2015-12-01

    We describe a tandem affinity microfluidic separation that measures the ratio of CD4+/CD8+ T lymphocytes from blood samples. It is performed by injecting 2 μL of lysed blood samples at 1800-2700 cells μL(-1) into a microfluidic device containing two serially linked affinity regions, followed with a stop flow incubation that captures CD4+/CD8+ T lymphocytes on the corresponding affinity regions. Fluorophore conjugated antibodies are then injected at a controlled shear stress of 1.7 dyn cm(-2) to label target cells while eluting non-specific cells; and at last the CD4/CD8 ratio is calculated after the cell enumeration. The ratio of CD4+/CD8+ T lymphocytes achieved by our tandem affinity microfluidic system was in close agreement with that performed using conventional flow cytometry (R (2)  = 0.97) over a wide range (0.4-2.5) that covered the reference values from immune deficient patients to healthy people. This approach may represent an inexpensive and powerful tool in diagnosis of immunodeficiency disorders including HIV or mycobacterium tuberculosis.

  16. Decline in CD4+ cell numbers in cats with naturally acquired feline immunodeficiency virus infection.

    PubMed

    Hoffmann-Fezer, G; Thum, J; Ackley, C; Herbold, M; Mysliwietz, J; Thefeld, S; Hartmann, K; Kraft, W

    1992-03-01

    T-cell subsets were studied by fluorescence-activated cell sorter analysis in 57 feline immunodeficiency virus (FIV)-seropositive cats with naturally acquired FIV infection to see whether CD4(+)-CD8+ alterations were comparable to those observed in human immunodeficiency virus-infected patients. CD4+ values were decreased and CD8+ values were increased. The CD4+/CD8+ ratio was reduced to 1.6, compared with 3.3 in 33 FIV-seronegative control cats. Variance analysis of data showed a significant influence of FIV seropositivity, sex, and spaying of female cats on CD4+ values. CD8+ values were significantly influenced by FIV seropositivity, age, and breed. These findings indicate a similarity between FIV and human immunodeficiency virus infections, as far as alterations of T-cell subsets are concerned. PMID:1310760

  17. Tapping CD4 T cells for cancer immunotherapy: the choice of personalized genomics.

    PubMed

    Zanetti, Maurizio

    2015-03-01

    Cellular immune responses that protect against tumors typically have been attributed to CD8 T cells. However, CD4 T cells also play a central role. It was shown recently that, in a patient with metastatic cholangiocarcinoma, CD4 T cells specific for a peptide from a mutated region of ERBB2IP could arrest tumor progression. This and other recent findings highlight new opportunities for CD4 T cells in cancer immunotherapy. In this article, I discuss the role and regulation of CD4 T cells in response to tumor Ags. Emphasis is placed on the types of Ags and mechanisms that elicit tumor-protective responses. I discuss the advantages and drawbacks of cancer immunotherapy through personalized genomics. These considerations should help to guide the design of next-generation therapeutic cancer vaccines.

  18. 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. PMID:26858442

  19. 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

  20. Defective CD8 T Cell Memory Following Acute Infection Without CD4 T Cell Help

    NASA Astrophysics Data System (ADS)

    Sun, Joseph C.; Bevan, Michael J.

    2003-04-01

    The CD8+ cytotoxic T cell response to pathogens is thought to be CD4+ helper T cell independent because infectious agents provide their own inflammatory signals. Mice that lack CD4+ T cells mount a primary CD8 response to Listeria monocytogenes equal to that of wild-type mice and rapidly clear the infection. However, protective memory to a challenge is gradually lost in the former animals. Memory CD8+ T cells from normal mice can respond rapidly, but memory CD8+ T cells that are generated without CD4 help are defective in their ability to respond to secondary encounters with antigen. The results highlight a previously undescribed role for CD4 help in promoting protective CD8 memory development.

  1. 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.

  2. 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.…

  3. 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

  4. Inflammation Enhances IL-2 Driven Differentiation of Cytolytic CD4 T Cells

    PubMed Central

    Workman, Aspen M.; Jacobs, Ashley K.; Vogel, Alexander J.; Condon, Shirley; Brown, Deborah M.

    2014-01-01

    Cytolytic CD4 T cells (CD4 CTL) have been identified in vivo in response to viral infections; however, the factors necessary for driving the cytolytic phenotype have not been fully elucidated. Our previously published work suggests IL-2 may be the master regulator of perforin-mediated cytotoxicity in CD4 effectors. To further dissect the role of IL-2 in CD4 CTL generation, T cell receptor transgenic mice deficient in the ability to produce IL-2 or the high affinity IL-2 receptor (IL-2Rα, CD25) were used. Increasing concentrations of IL-2 were necessary to drive perforin (Prf) expression and maximal cytotoxicity. Granzyme B (GrB) expression and killing correlated with STAT5 activation and CD25 expression in vitro, suggesting that signaling through the high affinity IL-2R is critical for full cytotoxicity. IL-2 signaling was also necessary in vivo for inducing the Th1 phenotype and IFN-γ expression in CD4 T cells during influenza A (IAV) infection. In addition, GrB expression, as measured by mean fluorescent intensity, was decreased in CD25 deficient cells; however, the frequency of CD4 cells expressing GrB was unchanged. Similarly, analysis of cytolytic markers such as CD107a/b and Eomesodermin indicate high IL-2Rα expression is not necessary to drive the CD4 CTL phenotype during IAV infection. Thus, inflammatory signals induced by viral infection may overcome the need for strong IL-2 signals in driving cytotoxicity in CD4 cells. PMID:24586481

  5. The SPL7013 dendrimer destabilizes the HIV-1 gp120-CD4 complex.

    PubMed

    Nandy, Bidisha; Saurabh, Suman; Sahoo, Anil Kumar; Dixit, Narendra M; Maiti, Prabal K

    2015-11-28

    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. PMID:26495445

  6. CD4 ligands inhibit the formation of multifunctional transduction complexes involved in T cell activation.

    PubMed

    Jabado, N; Pallier, A; Le Deist, F; Bernard, F; Fischer, A; Hivroz, C

    1997-01-01

    Ligands binding to the CD4 molecule can inhibit TCR-mediated T cell activation. We have previously reported that transcription factors regulating the expression of the IL-2 gene, NF-AT, NF-kappaB, and AP-1, are targets of this inhibitory effect in an in vitro model using peripheral human CD4+ T cells activated by a CD3 mAb. Two T cell activation pathways involved in the regulation of these transcription factors, calcium flux and the p21ras pathway, were investigated as potential targets. Binding of HIV envelope glycoprotein gp160/gp120 or a CD4 mAb to the CD4+ T cells, prior to TCR/CD3 activation, inhibited the intracellular calcium elevation. This event strongly suggested an inhibition of PLCgamma1 activity. Tyrosine phosphorylation of PLCgamma1, induced by CD3 activation, was not affected, but its association with tyrosine-phosphorylated proteins, including a 62-kDa protein, was disrupted. This PLCgamma1-associated p62 was found to be immunoreactive to p62-Sam68 Abs. The activation-induced phosphorylation of two p21ras effectors, Raf-1 and Erk2, was inhibited by the CD4 ligands, indirectly pointing to inhibition of the p21ras activation pathway. In addition, we demonstrate that TCR activation of normal CD4+ T cells induced the formation of p120GAP and PLCgamma1-containing complexes. These complexes also contain other unidentified proteins. CD4 ligand binding induced a defective formation of these transduction complexes. This may result in inefficient signaling, partially accounting for the inhibitory effects of the CD4 ligands on both p21ras and calcium-activation pathways.

  7. Methionine enkephalin is hydrolyzed by aminopeptidase N on CD4+ and CD8+ spleen T cells.

    PubMed

    Miller, B C; Thiele, D L; Hersh, L B; Cottam, G L

    1994-05-15

    Exogenous methionine enkephalin incubated with CD4+ or CD8+ T cells purified from murine spleen is metabolized primarily, if not exclusively, by aminopeptidase N (aminopeptidase M, EC 3.4.11.2), a membrane-anchored ectopeptidase. The enzyme activity is identified by its substrate specificity, sensitivity to inhibition by amastatin, and immunoreactivity with antibody to rat kidney aminopeptidase N. Activation of CD4+ T cells results in a small increase per cell in aminopeptidase N activity.

  8. Nuclear Retention of Multiply Spliced HIV-1 RNA in Resting CD4+ T Cells

    PubMed Central

    Lassen, Kara G; Ramyar, Kasra X; Bailey, Justin R; Zhou, Yan; Siliciano, Robert F

    2006-01-01

    HIV-1 latency in resting CD4+ T cells represents a major barrier to virus eradication in patients on highly active antiretroviral therapy (HAART). We describe here a novel post-transcriptional block in HIV-1 gene expression in resting CD4+ T cells from patients on HAART. This block involves the aberrant localization of multiply spliced (MS) HIV-1 RNAs encoding the critical positive regulators Tat and Rev. Although these RNAs had no previously described export defect, we show that they exhibit strict nuclear localization in resting CD4+ T cells from patients on HAART. Overexpression of the transcriptional activator Tat from non-HIV vectors allowed virus production in these cells. Thus, the nuclear retention of MS HIV-1 RNA interrupts a positive feedback loop and contributes to the non-productive nature of infection of resting CD4+ T cells. To define the mechanism of nuclear retention, proteomic analysis was used to identify proteins that bind MS HIV-1 RNA. Polypyrimidine tract binding protein (PTB) was identified as an HIV-1 RNA-binding protein differentially expressed in resting and activated CD4+ T cells. Overexpression of PTB in resting CD4+ T cells from patients on HAART allowed cytoplasmic accumulation of HIV-1 RNAs. PTB overexpression also induced virus production by resting CD4+ T cells. Virus culture experiments showed that overexpression of PTB in resting CD4+ T cells from patients on HAART allowed release of replication-competent virus, while preserving a resting cellular phenotype. Whether through effects on RNA export or another mechanism, the ability of PTB to reverse latency without inducing cellular activation is a result with therapeutic implications. PMID:16839202

  9. 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

  10. Quantification of cells with specific phenotypes II: determination of CD4 expression level on reconstituted lyophilized human PBMC labelled with anti-CD4 FITC antibody.

    PubMed

    Wang, L; Stebbings, R; Gaigalas, A K; Sutherland, J; Kammel, M; John, M; Roemer, B; Kuhne, M; Schneider, R J; Braun, M; Engel, A; Dikshit, D; Abbasi, F; Marti, G E; Sassi, M; Revel, L; Kim, S K; Baradez, M; Lekishvili, T; Marshall, D; Whitby, L; Jing, W; Ost, V; Vonsky, M; Neukammer, J

    2015-03-01

    This report focuses on the characterization of CD4 expression level in terms of equivalent number of reference fluorophores (ERF). Twelve different flow cytometer platforms across sixteen laboratories were utilized in this study. As a first step the participants were asked to calibrate the fluorescein isothiocyanate (FITC) channel of each flow cytometer using commercially available calibration standard consisting of five populations of microspheres. Each population had an assigned value of equivalent fluorescein fluorophores (EFF denotes a special case of the generic term ERF with FITC as the reference fluorophore). The EFF values were assigned at the National Institute of Standards and Technology (NIST). A surface-labelled lyophilized cell preparation was provided by the National Institute of Biological Standards and Control (NIBSC), using human peripheral blood mononuclear cells (PBMC) pre-labeled with a FITC conjugated anti-CD4 monoclonal antibody. Three PBMC sample vials, provided to each participant, were used for the CD4 expression analysis. The PBMC are purported to have a fixed number of surface CD4 receptors. On the basis of the microsphere calibration, the EFF value of the PBMC samples was measured to characterize the population average CD4 expression level of the PBMC preparations. Both the results of data analysis performed by each participant and the results of centralized analysis of all participants' raw data are reported. Centralized analysis gave a mean EFF value of 22,300 and an uncertainty of 750, corresponding to 3.3% (level of confidence 68%) of the mean EFF value. The next step will entail the measurement of the ERF values of the lyophilized PBMC stained with labels for other fluorescence channels. The ultimate goal is to show that lyophilized PBMC is a suitable biological reference cell material for multicolor flow cytometry and that it can be used to present multicolor flow cytometry measurements in terms of ABC (antibodies bound per cell

  11. 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. PMID:24618036

  12. CD4 T cells in murine acquired immunodeficiency syndrome: polyclonal progression to anergy

    PubMed Central

    1992-01-01

    We have examined the kinetics of changes that occur in the helper T cell subset during murine acquired immunodeficiency syndrome, which occurs after infection with the mix of viruses known as BM5. We find that there is expansion of the CD4 T cells by 2 wk, 50% of the CD4 T cells become large as the disease progresses, and the CD4 T cell population is increasingly comprised of cells with a memory/activated phenotype. These effects are apparent by 2 wk postinfection, and the change is nearly complete by 6-8 wk. The phenotypic shift is paralleled by the loss of the ability of the CD4 T cells to proliferate or to produce interleukin 2 (IL-2), IL-3, IL-4, and interferon gamma in response to stimulation with mitogens, superantigen, or anti-CD3. There is no obvious expansion or deletion of CD4 T cells expressing particular V beta genes, as might be expected if a conventional superantigen were driving the changes. The results suggest, however, that the total CD4 population has been driven to anergy by some potent polyclonal stimulus directly associated with viral infection. PMID:1588283

  13. 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.

  14. Involvement of claudin-7 in HIV infection of CD4(-) cells

    PubMed Central

    Zheng, Junying; Xie, Yiming; Campbell, Richard; Song, Jun; Massachi, Samira; Razi, Miriam; Chiu, Robert; Berenson, James; Yang, Otto O; Chen, Irvin SY; Pang, Shen

    2005-01-01

    Background Human immunodeficiency virus (HIV) infection of CD4(-) cells has been demonstrated, and this may be an important mechanism for HIV transmission. Results We demonstrated that a membrane protein, claudin-7 (CLDN-7), is involved in HIV infection of CD4(-) cells. A significant increase in HIV susceptibility (2- to 100-fold) was demonstrated when CLDN-7 was transfected into a CD4(-) cell line, 293T. In addition, antibodies against CLDN-7 significantly decreased HIV infection of CD4(-) cells. Furthermore, HIV virions expressing CLDN-7 on their envelopes had a much higher infectivity for 293T CD4(-) cells than the parental HIV with no CLDN-7. RT-PCR results demonstrated that CLDN-7 is expressed in both macrophages and stimulated peripheral blood leukocytes, suggesting that most HIV virions generated in infected individuals have CLDN-7 on their envelopes. We also found that CLDN-7 is highly expressed in urogenital and gastrointestinal tissues. Conclusion Together these results suggest that CLDN-7 may play an important role in HIV infection of CD4(-) cells. PMID:16368003

  15. Methodologies for the Analysis of HCV-Specific CD4+ T Cells

    PubMed Central

    Lokhande, Megha U.; Thimme, Robert; Klenerman, Paul; Semmo, Nasser

    2015-01-01

    Virus-specific CD4+ T cells play a major role in viral infections, such as hepatitis C virus (HCV). Viral clearance is associated with vigorous and multi-specific CD4+ T-cell responses, while chronic infection has been shown to be associated with weak or absent T-cell responses. Most of these studies have used functional assays to analyze virus-specific CD4+ T-cell responses; however, these and other detection methods have various limitations. Therefore, the important question of whether virus-specific CD4+ T cells are completely absent or primarily impaired in specific effector functions during chronic infection, has yet to be analyzed in detail. A novel assay, in which virus-specific CD4+ T-cell frequencies can be determined by de novo CD154 (CD40 ligand) expression in response to viral antigens, can help to overcome some of the limitations of functional assays and restrictions of multimer-based methods. This and other current established methods for the detection of HCV-specific CD4+ T cells will be discussed in this review. PMID:25767470

  16. Notch Signaling Regulates Antigen Sensitivity of Naive CD4+ T Cells by Tuning Co-stimulation

    PubMed Central

    Laky, Karen; Evans, Sharron; Perez-Diez, Ainhoa

    2015-01-01

    SUMMARY Adaptive immune responses begin when naive CD4+ T cells engage peptide+major histocompatibility complex class II and co-stimulatory molecules on antigen-presenting cells (APCs). Notch signaling can influence effector functions in differentiated CD4+ T helper and T regulatory cells. Whether and how ligand-induced Notch signaling influences the initial priming of CD4+ T cells has not been addressed. We have found that Delta Like Ligand 4 (DLL4)-induced Notch signaling potentiates phosphatidylinositol 3-OH kinase (PI3K)-dependent signaling downstream of the T cell receptor+CD28, allowing naive CD4+ T cells to respond to lower doses of antigen. In vitro, DLL4-deficient APCs were less efficient stimulators of CD4+ T cell activation, metabolism, proliferation, and cytokine secretion. With deletion of DLL4 from CD11c+ APCs in vivo, these deficits translated to an impaired ability to mount an effective CD4+-dependent anti-tumor response. These data implicate Notch signaling as an important regulator of adaptive immune responses. PMID:25607460

  17. Indoleamine 2,3-dioxygenase (IDO) downregulates the cell surface expression of the CD4 molecule.

    PubMed

    Huang, Guanyou; Zeng, Yaoying; Liang, Peiyan; Zhou, Congrong; Zhao, Shuyun; Huang, Xiuyan; Wu, Lingfei; He, Xianhui

    2012-01-01

    Indoleamine 2,3-dioxygenase (IDO) has been implicated in preventing the fetus from undergoing maternal T cell-mediated immune responses, yet the mechanism underlying these kinds of IDO-mediated immune responses has not been fully elucidated. Since the CD4 molecule plays a central role in the onset and regulation of antigen-specific immune responses, and T cell is sensitive in the absence of tryptophan, we hypothesize that IDO may reduce cell surface CD4 expression. To test this hypothesis, an adenoviral vector-based construct IDO-EGFP was generated and the effect of IDO-EGFP on CD4 expression was determined on recombinant adenoviral infected C8166 and MT-2 cells, by flow cytometry and/or Western blot analysis. The results revealed a significant downregulation of cell membrane CD4 in pAd-IDOEGFP infected cells when compared to that of mock-infected cells or infection with empty vector pAd-EGFP. Further experiments disclosed that either an addition of tryptophan or IDO inhibitor could partly restore CD4 expression in pAd-IDOEGFP infected C8166 cells. Our findings suggest that downregulation of CD4 by IDO might be one of the mechanisms through which IDO regulates T cell-mediated immune responses.

  18. 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.

  19. CD4(+) lymphoid tissue-inducer cells promote innate immunity in the gut.

    PubMed

    Sonnenberg, Gregory F; Monticelli, Laurel A; Elloso, M Merle; Fouser, Lynette A; Artis, David

    2011-01-28

    Fetal CD4(+) lymphoid tissue inducer (LTi) cells play a critical role in the development of lymphoid tissues. Recent studies identified that LTi cells persist in adults and are related to a heterogeneous population of innate lymphoid cells that have been implicated in inflammatory responses. However, whether LTi cells contribute to protective immunity remains poorly defined. We demonstrate that after infection with Citrobacter rodentium, CD4(+) LTi cells were a dominant source of interleukin-22 (IL-22) early during infection. Infection-induced CD4(+) LTi cell responses were IL-23 dependent, and ablation of IL-23 impaired innate immunity. Further, depletion of CD4(+) LTi cells abrogated infection-induced expression of IL-22 and antimicrobial peptides, resulting in exacerbated host mortality. LTi cells were also found to be essential for host protective immunity in lymphocyte-replete hosts. Collectively these data demonstrate that adult CD4(+) LTi cells are a critical source of IL-22 and identify a previously unrecognized function for CD4(+) LTi cells in promoting innate immunity in the intestine.

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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. PMID:21400312

  5. Major histocompatibility complex class I-restricted alloreactive CD4+ T cells.

    PubMed

    Boyle, Louise H; Goodall, Jane C; Gaston, J S Hill

    2004-05-01

    Although it is well established that CD4+ T cells generally recognize major histocompatibility complex (MHC) class II molecules, MHC class I-reactive CD4+ T cells have occasionally been reported. Here we describe the isolation and characterization of six MHC class I-reactive CD4+ T-cell lines, obtained by co-culture of CD4+ peripheral blood T cells with the MHC class II-negative, transporter associated with antigen processing (TAP)-negative cell line, T2, transfected with human leucocyte antigen (HLA)-B27. Responses were inhibited by the MHC class I-specific monoclonal antibody (mAb), W6/32, demonstrating the direct recognition of MHC class I molecules. In four cases, the restriction element was positively identified as HLA-A2, as responses by these clones were completely inhibited by MA2.1, an HLA-A2-specific mAb. Interestingly, three of the CD4+ T-cell lines only responded to cells expressing HLA-B27, irrespective of their restricting allele, implicating HLA-B27 as a possible source of peptides presented by the stimulatory MHC class I alleles. In addition, these CD4+ MHC class I alloreactive T-cell lines could recognize TAP-deficient cells and therefore may have particular clinical relevance to situations where the expression of TAP molecules is decreased, such as viral infection and transformation of cells. PMID:15096184

  6. 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.

  7. The story of CD4+ CD28- T cells revisited: solved or still ongoing?

    PubMed

    Maly, Kathrin; Schirmer, Michael

    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

  8. 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.

  9. Myeloid dendritic cells induce HIV-1 latency in non-proliferating CD4+ T cells.

    PubMed

    Evans, Vanessa A; Kumar, Nitasha; Filali, Ali; Procopio, Francesco A; Yegorov, Oleg; Goulet, Jean-Philippe; Saleh, Suha; Haddad, Elias K; da Fonseca Pereira, Candida; Ellenberg, Paula C; Sekaly, Rafick-Pierre; Cameron, Paul U; Lewin, Sharon R

    2013-01-01

    Latently infected resting CD4(+) T cells are a major barrier to HIV cure. Understanding how latency is established, maintained and reversed is critical to identifying novel strategies to eliminate latently infected cells. We demonstrate here that co-culture of resting CD4(+) T cells and syngeneic myeloid dendritic cells (mDC) can dramatically increase the frequency of HIV DNA integration and latent HIV infection in non-proliferating memory, but not naïve, CD4(+) T cells. Latency was eliminated when cell-to-cell contact was prevented in the mDC-T cell co-cultures and reduced when clustering was minimised in the mDC-T cell co-cultures. Supernatants from infected mDC-T cell co-cultures did not facilitate the establishment of latency, consistent with cell-cell contact and not a soluble factor being critical for mediating latent infection of resting CD4(+) T cells. Gene expression in non-proliferating CD4(+) T cells, enriched for latent infection, showed significant changes in the expression of genes involved in cellular activation and interferon regulated pathways, including the down-regulation of genes controlling both NF-κB and cell cycle. We conclude that mDC play a key role in the establishment of HIV latency in resting memory CD4(+) T cells, which is predominantly mediated through signalling during DC-T cell contact.

  10. HLA Class-II Associated HIV Polymorphisms Predict Escape from CD4+ T Cell Responses

    PubMed Central

    Erdmann, Nathan; Du, Victor Y.; Carlson, Jonathan; Schaefer, Malinda; Jureka, Alexander; Sterrett, Sarah; Yue, Ling; Dilernia, Dario; Lakhi, Shabir; Tang, Jianming; Sidney, John; Gilmour, Jill; Allen, Susan; Hunter, Eric; Heath, Sonya; Bansal, Anju; Goepfert, Paul A.

    2015-01-01

    Antiretroviral therapy, antibody and CD8+ T cell-mediated responses targeting human immunodeficiency virus-1 (HIV-1) exert selection pressure on the virus necessitating escape; however, the ability of CD4+ T cells to exert selective pressure remains unclear. Using a computational approach on HIV gag/pol/nef sequences and HLA-II allelic data, we identified 29 HLA-II associated HIV sequence polymorphisms or adaptations (HLA-AP) in an African cohort of chronically HIV-infected individuals. Epitopes encompassing the predicted adaptation (AE) or its non-adapted (NAE) version were evaluated for immunogenicity. Using a CD8-depleted IFN-γ ELISpot assay, we determined that the magnitude of CD4+ T cell responses to the predicted epitopes in controllers was higher compared to non-controllers (p<0.0001). However, regardless of the group, the magnitude of responses to AE was lower as compared to NAE (p<0.0001). CD4+ T cell responses in patients with acute HIV infection (AHI) demonstrated poor immunogenicity towards AE as compared to NAE encoded by their transmitted founder virus. Longitudinal data in AHI off antiretroviral therapy demonstrated sequence changes that were biologically confirmed to represent CD4+ escape mutations. These data demonstrate an innovative application of HLA-associated polymorphisms to identify biologically relevant CD4+ epitopes and suggests CD4+ T cells are active participants in driving HIV evolution. PMID:26302050

  11. 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

  12. Lectin-activated CD4+CD45RA+ T-lymphocytes have no ability to kill monocytes.

    PubMed

    Pryjma, J; Baran, J; Zembala, M

    1996-01-01

    Monocytes are eliminated from cell culture by antigen or mitogen activated cytotoxic CD4+ T-lymphocytes. In this report we asked the question whether CD4+CD45RA+ and CD4+CD45RO+ subpopulations differ in the ability to kill monocytes in pokeweed mitogen (PWM)-activated cultures. Data are presented that although CD4+CD45RA+ vigorously proliferate in the presence of PWM, they do not kill monocytes or secrete IFN gamma.

  13. Associations between maternal sense of coherence and controlling feeding practices: The importance of resilience and support in families of preschoolers.

    PubMed

    Eli, Karin; Sorjonen, Kimmo; Mokoena, Lincoln; Pietrobelli, Angelo; Flodmark, Carl-Erik; Faith, Myles S; Nowicka, Paulina

    2016-10-01

    Sense of Coherence (SOC) measures an individual's positive, or salutogenic, orientation toward her/his capacities, environment, future, and life. SOC comprises three factors: comprehensibility (the sense of one's own life as ordered and understandable); manageability (the perception of available resources and skills to manage stressors); and meaningfulness (the overall sense that life is filled with meaning and purpose). In numerous studies, SOC has been associated with resilience to stress. However, associations between parental SOC and controlling feeding practices have yet to be studied. This study examines the validity of the SOC 13-item, 3-factor questionnaire, associations between SOC and maternal and child characteristics, and associations between SOC and use of pressuring or restrictive feeding, among mothers of 4-year-olds. 565 mothers (23.5% of foreign origin, 30.3% with overweight/obesity) recruited via the Swedish population registry (response rate: 65%), completed the SOC-13, the Child Feeding Questionnaire (CFQ), and a background questionnaire. The validity of SOC-13 was examined using confirmatory factor analysis; associations with background characteristics and feeding practices were tested with structural equation modeling. SOC-13 validity testing showed acceptable fit (TLI = 0.93, CFI = 0.94, RMSEA = 0.06, SRMR = 0.04) after allowing one pair of error terms to correlate. The Cronbach's alpha for meaningfulness was 0.73, comprehensibility 0.76, and manageability 0.75. SOC increased with mothers' Swedish background and education, and decreased with higher BMI. Child gender, age, and BMI, were not associated with SOC. Lower SOC was associated with controlling practices and with concern about child weight and eating. The associations between SOC and feeding suggest that SOC-related parameters could inform childhood obesity research, and that prevention should address the socioeconomic barriers that parents face in building resilience to stress.

  14. Factors associated with maternal dietary intake, feeding and weaning practices, and the development of food hypersensitivity in the infant.

    PubMed

    Venter, Carina; Pereira, Brett; Voigt, Kerstin; Grundy, Jane; Clayton, C Bernie; Higgins, Bernie; Arshad, S Hasan; Dean, Taraneh

    2009-06-01

    Maternal diet during pregnancy and breastfeeding, as well as infant feeding and weaning practices, may play a role in the development of sensitization to food and food hypersensitivity (FHS) and need further investigation. Pregnant women were recruited at 12 wk pregnancy. Information regarding family history of allergy was obtained by means of a questionnaire. A food frequency questionnaire was completed at 36 wk gestation. Information regarding feeding practices and reported symptoms of atopy was obtained during the infants' first 3 yr of life. Children were also skin-prick tested at 1, 2 and 3 yr to a pre-defined panel of food allergens. Food challenges were conducted where possible. Maternal dietary intake during pregnancy, and breast-feeding duration did not influence the development of sensitization to food allergens or FHS, but weaning age (>or=16 wk) did for sensitization at 1 yr (p = 0.03), FHS by 1 yr (p = 0.02), sensitization at 3 yr (p = 0.01) and FHS by 3 yr (p = 0.02). In contrast, children who were not exposed to a certain food allergen before the age of 3-6 months were less likely to become sensitized or develop FHS. Women with a family history of allergic disease were more likely to breastfeed exclusively at 3 months (p = 0.008) and avoid peanuts from the infant's diet at 6 months (p = 0.03). Maternal dietary intake during pregnancy, and breast-feeding duration did not appear to influence the development of sensitization to food allergens or FHS. Weaning age may affect sensitization to foods and development of FHS. A history of allergic disease has very little impact on maternal dietary, feeding, and weaning practices.

  15. Associations between maternal sense of coherence and controlling feeding practices: The importance of resilience and support in families of preschoolers.

    PubMed

    Eli, Karin; Sorjonen, Kimmo; Mokoena, Lincoln; Pietrobelli, Angelo; Flodmark, Carl-Erik; Faith, Myles S; Nowicka, Paulina

    2016-10-01

    Sense of Coherence (SOC) measures an individual's positive, or salutogenic, orientation toward her/his capacities, environment, future, and life. SOC comprises three factors: comprehensibility (the sense of one's own life as ordered and understandable); manageability (the perception of available resources and skills to manage stressors); and meaningfulness (the overall sense that life is filled with meaning and purpose). In numerous studies, SOC has been associated with resilience to stress. However, associations between parental SOC and controlling feeding practices have yet to be studied. This study examines the validity of the SOC 13-item, 3-factor questionnaire, associations between SOC and maternal and child characteristics, and associations between SOC and use of pressuring or restrictive feeding, among mothers of 4-year-olds. 565 mothers (23.5% of foreign origin, 30.3% with overweight/obesity) recruited via the Swedish population registry (response rate: 65%), completed the SOC-13, the Child Feeding Questionnaire (CFQ), and a background questionnaire. The validity of SOC-13 was examined using confirmatory factor analysis; associations with background characteristics and feeding practices were tested with structural equation modeling. SOC-13 validity testing showed acceptable fit (TLI = 0.93, CFI = 0.94, RMSEA = 0.06, SRMR = 0.04) after allowing one pair of error terms to correlate. The Cronbach's alpha for meaningfulness was 0.73, comprehensibility 0.76, and manageability 0.75. SOC increased with mothers' Swedish background and education, and decreased with higher BMI. Child gender, age, and BMI, were not associated with SOC. Lower SOC was associated with controlling practices and with concern about child weight and eating. The associations between SOC and feeding suggest that SOC-related parameters could inform childhood obesity research, and that prevention should address the socioeconomic barriers that parents face in building resilience to stress

  16. 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

  17. Infant feeding practices in Kenya, Mexico and Malaysia. The rarity of the exclusively breast-fed infant.

    PubMed

    Dimond, H J; Ashworth, A

    1987-02-01

    Infant feeding practices of 6149 mothers in Kenya, Mexico and Malaysia are reported. A high proportion of mothers initiated breast-feeding in each country regardless of social class. Most Kenyan mothers continued to breast-feed for at least 12 months. In Mexico and Malaysia, however, breast-feeding was discontinued relatively early, especially among urban mothers. Early supplementation of breast-fed infants with milk and/or other food was a common practice in each of the three countries. Among breast-fed infants below 4 months of age, the percentages who were exclusively breast-fed in the urban elite, urban poor and rural groups respectively were 6, 14 and 21 per cent in Kenya, 8, 19 and 31 per cent in Mexico, and 11, 9 and 11 per cent in Malaysia. Supplementation of breast-fed infants in the first two months of life was more likely to be with infant formula than with any other milk or food. At three months of age, however, nonmilk foods were the most common supplements in all population groups with the exception of those in urban Kenya. The policy implications are discussed.

  18. Determinants of suboptimal complementary feeding practices among children aged 6-23 months in seven francophone 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 play a crucial role in the health and development of children. The objective of this research paper was to identify factors associated with suboptimal complementary feeding practices among children aged 6-23 months in seven francophone West African countries, namely, Benin, Burkina Faso, Cote d'Ivoire, Guinea, Mali, Niger and Senegal. This study covered 22 376 children aged 6-23 months from the seven countries surveyed (Benin: 3732 children; Burkina Faso: 4205 children; Cote d'Ivoire: 2109 children, Guinea: 1944 children, Mali: 3798 children, Niger: 3451 children and Senegal: 3137 children). The most recent Demographic and Health Survey datasets of the various countries were used as data sources. A set of individual-, household- and community-level factors were used to examine the four complementary feeding indicators. Multivariate analysis revealed that the youngest age bracket (6-11 months) of children, administrative/geographical region, mother's limited or non-access to the mass media, mothers' lack of contact with a health facility, rural residence, poor households and non-working mothers were the main factors associated with suboptimal complementary feeding in the countries surveyed. Our findings highlight the need to consider broader social, cultural and economic factors when designing child nutritional interventions. PMID:26364790

  19. Determinants of suboptimal complementary feeding practices among children aged 6-23 months in seven francophone 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 play a crucial role in the health and development of children. The objective of this research paper was to identify factors associated with suboptimal complementary feeding practices among children aged 6-23 months in seven francophone West African countries, namely, Benin, Burkina Faso, Cote d'Ivoire, Guinea, Mali, Niger and Senegal. This study covered 22 376 children aged 6-23 months from the seven countries surveyed (Benin: 3732 children; Burkina Faso: 4205 children; Cote d'Ivoire: 2109 children, Guinea: 1944 children, Mali: 3798 children, Niger: 3451 children and Senegal: 3137 children). The most recent Demographic and Health Survey datasets of the various countries were used as data sources. A set of individual-, household- and community-level factors were used to examine the four complementary feeding indicators. Multivariate analysis revealed that the youngest age bracket (6-11 months) of children, administrative/geographical region, mother's limited or non-access to the mass media, mothers' lack of contact with a health facility, rural residence, poor households and non-working mothers were the main factors associated with suboptimal complementary feeding in the countries surveyed. Our findings highlight the need to consider broader social, cultural and economic factors when designing child nutritional interventions.

  20. Role of CD4 epitopes outside the gp120-binding site during entry of human immunodeficiency virus type 1.

    PubMed Central

    Simon, J H; Stumbles, P; Signoret, N; Somoza, C; Puklavec, M; Sattentau, Q J; Barclay, A N; James, W

    1997-01-01

    CD4 is the primary receptor for human immunodeficiency virus (HIV). The binding site for the surface glycoprotein of HIV type 1 (HIV-1), gp120, has been mapped to the C'-C" region of domain 1 of CD4. Previously, we have shown that a mutant of rat CD4, in which this region was exchanged for that of human CD4, is able to mediate infection of human cells by HIV-1, suggesting that essential interactions between HIV and CD4 are confined to this region. Our observations appeared to conflict with mutagenesis and antibody studies which implicate regions of CD4 outside the gp120-binding site in postbinding events during viral entry. In order to resolve this issue, we have utilized a panel of anti-rat CD4 monoclonal antibodies in conjunction with the rat-human chimeric CD4 to distinguish sequence-specific from steric effects. We find that several antibodies to rat CD4 inhibit HIV infection in cells expressing the chimeric CD4 and that this is probably due to steric hinderance. In addition, we demonstrate that replacement of the rat CDR3-like region with its human homolog does not increase the affinity of the rat-human chimeric CD4 for gp120 or affect the exposure of gp41 following binding to CD4, providing further evidence that this region does not play a crucial role during entry of virus. PMID:8995673

  1. 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.

  2. 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

  3. Brazilian mothers' beliefs, attitudes and practices related to child weight status and early feeding within the context of nutrition transition.

    PubMed

    Lindsay, Ana Cristina; Machado, Marcia Tavares; Sussner, Katarina M; Hardwick, Cary K; Kerr, Ligia Regina Franco Sansigolo; Peterson, Karen E

    2009-01-01

    With the rapid pace of the nutrition transition worldwide, understanding influences of child feeding practices within a context characterized by the co-existence of overweight and undernutrition in the same population has increasing importance. This qualitative study describes Brazilian mothers' child feeding practices and their perceptions of their association with child weight status and explores the role of socioeconomic, cultural and organizational factors on these relationships. Forty-one women enrolled in the Family Health/Community Health Workers Programme were selected from rural, urban, coastal and indigenous areas in Ceara State, north-east Brazil, to participate in four focus group discussions. Content analysis identified fourteen emergent themes showing mothers' child feeding practices in this setting were influenced by economic resources, mothers' immediate social support networks (e.g. neighbours and family members) and participation in nutrition assistance programmes. Child malnutrition was the most common nutritional concern; nevertheless, mothers were aware of the negative health consequences of obesity but misunderstood its causes (e.g. foods filled with fat would make a person fat; others thought that birth control pills and stimulants given to children were causes of obesity); several reported their own struggles with overweight. Food assistance programmes emerged as an important influence on children's dietary adequacy, especially among mothers describing dire economic situations. The findings have implications for targeting food assistance as well as health and nutrition education strategies in low-income families undergoing the nutrition transition in north-east Brazil.

  4. Confirmatory Factor Analysis of the Malay Version Comprehensive Feeding Practices Questionnaire Tested among Mothers of Primary School Children in Malaysia

    PubMed Central

    Shohaimi, Shamarina; Yoke Wei, Wong; Mohd Shariff, Zalilah

    2014-01-01

    Comprehensive feeding practices questionnaire (CFPQ) is an instrument specifically developed to evaluate parental feeding practices. It has been confirmed among children in America and applied to populations in France, Norway, and New Zealand. In order to extend the application of CFPQ, we conducted a factor structure validation of the translated version of CFPQ (CFPQ-M) using confirmatory factor analysis among mothers of primary school children (N = 397) in Malaysia. Several items were modified for cultural adaptation. Of 49 items, 39 items with loading factors >0.40 were retained in the final model. The confirmatory factor analysis revealed that the final model (twelve-factor model with 39 items and 2 error covariances) displayed the best fit for our sample (Chi-square = 1147; df = 634; P < 0.05; CFI = 0.900; RMSEA = 0.045; SRMR = 0.0058). The instrument with some modifications was confirmed among mothers of school children in Malaysia. The present study extends the usability of the CFPQ and enables researchers and parents to better understand the relationships between parental feeding practices and related problems such as childhood obesity. PMID:25538958

  5. Maternal feeding practices predict fruit and vegetable consumption in young children. Results of a 12-month longitudinal study.

    PubMed

    Gregory, Jane E; Paxton, Susan J; Brozovic, Anna M

    2011-08-01

    This study aimed to explore the prospective relationship between maternal feeding practices and young children's frequency of consumption of fruits, vegetables and sweets, and also child weight-for-height z-scores. Participants were 60 mothers who completed questionnaires when their children were 1 year old and again when their children were 2 years old. Regression analyses were performed. After controlling for availability and prior child consumption of the target food, maternal use of pressure to eat at 1 year predicted lower child frequency of fruit consumption at 2 years and approached significance for lower vegetable consumption. Maternal modelling of healthy eating at 1 year predicted higher child frequency of vegetable consumption at 2 years. Restriction did not significantly predict child frequency of consumption of fruits, vegetables or sweets over time. Child weight-for-height scores at 2 years were predicted by weight-for-height at 1 year but not by feeding practices. The findings suggest that maternal feeding practices can influence child eating at a very young age. Interventions should focus on encouraging parents to model healthy eating to promote healthy eating in children. PMID:21569809

  6. Confirmatory factor analysis of the Malay version comprehensive feeding practices questionnaire tested among mothers of primary school children in Malaysia.

    PubMed

    Shohaimi, Shamarina; Wei, Wong Yoke; Shariff, Zalilah Mohd

    2014-01-01

    Comprehensive feeding practices questionnaire (CFPQ) is an instrument specifically developed to evaluate parental feeding practices. It has been confirmed among children in America and applied to populations in France, Norway, and New Zealand. In order to extend the application of CFPQ, we conducted a factor structure validation of the translated version of CFPQ (CFPQ-M) using confirmatory factor analysis among mothers of primary school children (N = 397) in Malaysia. Several items were modified for cultural adaptation. Of 49 items, 39 items with loading factors >0.40 were retained in the final model. The confirmatory factor analysis revealed that the final model (twelve-factor model with 39 items and 2 error covariances) displayed the best fit for our sample (Chi-square = 1147; df = 634; P < 0.05; CFI = 0.900; RMSEA = 0.045; SRMR = 0.0058). The instrument with some modifications was confirmed among mothers of school children in Malaysia. The present study extends the usability of the CFPQ and enables researchers and parents to better understand the relationships between parental feeding practices and related problems such as childhood obesity. PMID:25538958

  7. 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

  8. 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.

  9. Bronchoalveolar CD4+ T cell responses to respiratory antigens are impaired in HIV-infected adults

    PubMed Central

    Sepako, Enoch; Fullerton, Duncan G; Mzinza, David; Glennie, Sarah; Wright, Adam K; Heyderman, Robert S; Gordon, Stephen B

    2011-01-01

    Rationale HIV-infected adults are at an increased risk of lower respiratory tract infections. HIV infection impairs systemic acquired immunity, but there is limited information in humans on HIV-related cell-mediated immune defects in the lung. Objective To investigate antigen-specific CD4+ T cell responses to influenza virus, Streptococcus pneumoniae and Mycobacterium tuberculosis antigens in bronchoalveolar lavage (BAL) and peripheral blood between HIV-infected individuals and HIV-uninfected Malawian adults. Methods We obtained BAL fluid and blood from HIV-infected individuals (n=21) and HIV-uninfected adults (n=24). We determined the proportion of T cell subsets including naive, memory and regulatory T cells using flow cytometry, and used intracellular cytokine staining to identify CD4+ T cells recognising influenza virus-, S pneumoniae- and M tuberculosis-antigens. Main results CD4+ T cells in BAL were predominantly of effector memory phenotype compared to blood, irrespective of HIV status (p<0.001). There was immune compartmentalisation with a higher frequency of antigen-specific CD4+ T cells against influenza virus, S pneumoniae and M tuberculosis retained in BAL compared to blood in HIV-uninfected adults (p<0.001 in each case). Influenza virus- and M tuberculosis-specific CD4+ T cell responses in BAL were impaired in HIV-infected individuals: proportions of total antigen-specific CD4+ T cells and of polyfunctional IFN-γ and TNF-α-secreting cells were lower in HIV-infected individuals than in HIV-uninfected adults (p<0.05 in each case). Conclusions BAL antigen-specific CD4+ T cell responses against important viral and bacterial respiratory pathogens are impaired in HIV-infected adults. This might contribute to the susceptibility of HIV-infected adults to lower respiratory tract infections such as pneumonia and tuberculosis. PMID:21357587

  10. 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.

  11. Multiple CD4+ T cell subsets produce immunomodulatory interleukin-10 during respiratory syncytial virus infection

    PubMed Central

    Weiss, Kayla A.; Christiaansen, Allison F.; Fulton, Ross B.; Meyerholz, David K.; Varga, Steven M.

    2011-01-01

    The host immune response is believed to contribute to the severity of pulmonary disease induced by acute respiratory syncytial virus (RSV) infection. Because RSV-induced pulmonary disease is associated with immunopathology, we evaluated the role of IL-10 in modulating the RSV-specific immune response. We found that IL-10 protein levels in the lung were increased following acute RSV infection with maximum production corresponding to the peak of the virus-specific T cell response. The majority of IL-10 producing cells in the lung during acute RSV infection were CD4+ T cells. The IL-10-producing CD4+ T cells included Foxp3+Tregs, Foxp3− CD4+ T cells that co-produce IFN-γ, and Foxp3− CD4+ T cells that do not co-produce IFN-γ. RSV infection of IL-10-deficient mice resulted in more severe disease, as measured by increased weight loss and airway resistance, as compared to control mice. We also observed an increase in the magnitude of the RSV-induced CD8+ and CD4+ T cell response that correlated with increased disease severity in the absence of IL-10 or following IL-10R blockade. Interestingly, IL-10R blockade during acute RSV infection altered CD4+ T cell subset distribution, resulting in a significant increase in IL-17A-producing CD4+ T cells and a concomitant decrease in Foxp3+ regulatory T cells. These results demonstrate that IL-10 plays a critical role in modulating the adaptive immune response to RSV by limiting T-cell-mediated pulmonary inflammation and injury. PMID:21844390

  12. TNFAIP3 promotes survival of CD4 T cells by restricting MTOR and promoting autophagy

    PubMed Central

    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. PMID:26043155

  13. Third-party CD4+ invariant natural killer T cells protect from murine GVHD lethality.

    PubMed

    Schneidawind, Dominik; Baker, Jeanette; Pierini, Antonio; Buechele, Corina; Luong, Richard H; Meyer, Everett H; Negrin, Robert S

    2015-05-28

    Graft-versus-host disease (GVHD) is driven by extensive activation and proliferation of alloreactive donor T cells causing significant morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). Invariant natural killer T (iNKT) cells are a potent immunoregulatory T-cell subset in both humans and mice. Here, we explored the role of adoptively transferred third-party CD4(+) iNKT cells for protection from lethal GVHD in a murine model of allogeneic HCT across major histocompatibility barriers. We found that low numbers of CD4(+) iNKT cells from third-party mice resulted in a significant survival benefit with retained graft-versus-tumor effects. In vivo expansion of alloreactive T cells was diminished while displaying a T helper cell 2-biased phenotype. Notably, CD4(+) iNKT cells from third-party mice were as protective as CD4(+) iNKT cells from donor mice although third-party CD4(+) iNKT cells were rejected early after allogeneic HCT. Adoptive transfer of third-party CD4(+) iNKT cells resulted in a robust expansion of donor CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) that were required for protection from lethal GVHD. However, in vivo depletion of myeloid-derived suppressor cells abrogated both Treg expansion and protection from lethal GVHD. Despite the fact that iNKT cells are a rare cell population, the almost unlimited third-party availability and feasibility of in vitro expansion provide the basis for clinical translation.

  14. 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

  15. Effect of community level intervention on nutritional status and feeding practices of under five children in Ile Ife, Nigeria

    PubMed Central

    Ogundele, Olorunfemi Akinbode; Ogundele, Tolulope

    2015-01-01

    Introduction Childhood malnutrition remains a widespread problem in developing world like Nigeria. The country ranks second among the ten countries contributing to sixty percent of the world's wasted under-five children. Community Integrated Management of Childhood illness (CIMCI) is a programme that employs the use of community based counsellors to address child health and nutritional challenges of the under-five and has the potential to reduce the morbidity and mortality resulting from poor nutritional and feeding practices. The study assessed the effect of community level intervention on nutritional status and feeding practices of children in Ile-Ife, Nigeria. Methods A cross-sectional comparative study that employed the use of multi stage cluster sampling techniques in selecting 722 mothers of index under five children. The study was done in two Local Government Areas of Osun State, Nigeria. Quantitative techniques were used in data collection. Data analysis was done using SPSS version 20.0. Descriptive and bivariate analyses was performed. Results The two Local Government Area (LGA) did not differ significantly in their wealth index (p = 0.344). However, more children in the non-implementing LGA (16.1%) had low weight for age compared with 3.6% in the CIMCI implementing LGA (p = 0.000). A statistically significant difference exist in the MUAC measurement of children 12-23 months between the CIMCI implementing and non-implementing communities (p = 0.007). A higher percentage of caregivers (19.3%) introduced complementary feeding earlier than 6 months in the non-implementing area (p < 0.001). Conclusion Using community level nutritional counseling can greatly improve nutritional status and feeding practices of under five children. PMID:26958118

  16. Preclinical targeting of human T-cell malignancies using CD4-specific chimeric antigen receptor (CAR)-engineered T cells.

    PubMed

    Pinz, K; Liu, H; Golightly, M; Jares, A; Lan, F; Zieve, G W; Hagag, N; Schuster, M; Firor, A E; Jiang, X; Ma, Y

    2016-03-01

    Peripheral T-cell lymphomas (PTCLs) are aggressive lymphomas with no effective upfront standard treatment and ineffective options in relapsed disease, resulting in poorer clinical outcomes as compared with B-cell lymphomas. The adoptive transfer of T cells engineered to express chimeric antigen receptors (CARs) is a promising new approach for treatment of hematological malignancies. However, preclinical reports of targeting T-cell lymphoma with CARs are almost non-existent. Here we have designed a CAR, CD4CAR, which redirects the antigen specificity of CD8+ cytotoxic T cells to CD4-expressing cells. CD4CAR T cells derived from human peripheral blood mononuclear cells and cord blood effectively redirected T-cell specificity against CD4+ cells in vitro. CD4CAR T cells efficiently eliminated a CD4+ leukemic cell line and primary CD4+ PTCL patient samples in co-culture assays. Notably, CD4CAR T cells maintained a central memory stem cell-like phenotype (CD8+CD45RO+CD62L+) under standard culture conditions. Furthermore, in aggressive orthotropic T-cell lymphoma models, CD4CAR T cells efficiently suppressed the growth of lymphoma cells while also significantly prolonging mouse survival. Combined, these studies demonstrate that CD4CAR-expressing CD8+ T cells are efficacious in ablating malignant CD4+ populations, with potential use as a bridge to transplant or stand-alone therapy for the treatment of PTCLs.

  17. Preclinical targeting of human T-cell malignancies using CD4-specific chimeric antigen receptor (CAR)-engineered T cells.

    PubMed

    Pinz, K; Liu, H; Golightly, M; Jares, A; Lan, F; Zieve, G W; Hagag, N; Schuster, M; Firor, A E; Jiang, X; Ma, Y

    2016-03-01

    Peripheral T-cell lymphomas (PTCLs) are aggressive lymphomas with no effective upfront standard treatment and ineffective options in relapsed disease, resulting in poorer clinical outcomes as compared with B-cell lymphomas. The adoptive transfer of T cells engineered to express chimeric antigen receptors (CARs) is a promising new approach for treatment of hematological malignancies. However, preclinical reports of targeting T-cell lymphoma with CARs are almost non-existent. Here we have designed a CAR, CD4CAR, which redirects the antigen specificity of CD8+ cytotoxic T cells to CD4-expressing cells. CD4CAR T cells derived from human peripheral blood mononuclear cells and cord blood effectively redirected T-cell specificity against CD4+ cells in vitro. CD4CAR T cells efficiently eliminated a CD4+ leukemic cell line and primary CD4+ PTCL patient samples in co-culture assays. Notably, CD4CAR T cells maintained a central memory stem cell-like phenotype (CD8+CD45RO+CD62L+) under standard culture conditions. Furthermore, in aggressive orthotropic T-cell lymphoma models, CD4CAR T cells efficiently suppressed the growth of lymphoma cells while also significantly prolonging mouse survival. Combined, these studies demonstrate that CD4CAR-expressing CD8+ T cells are efficacious in ablating malignant CD4+ populations, with potential use as a bridge to transplant or stand-alone therapy for the treatment of PTCLs. PMID:26526988

  18. Selective Loss of Innate CD4+ Vα24 Natural Killer T Cells in Human Immunodeficiency Virus Infection

    PubMed Central

    Sandberg, Johan K.; Fast, Noam M.; Palacios, Emil H.; Fennelly, Glenn; Dobroszycki, Joanna; Palumbo, Paul; Wiznia, Andrew; Grant, Robert M.; Bhardwaj, Nina; Rosenberg, Michael G.; Nixon, Douglas F.

    2002-01-01

    Vα24 natural killer T (NKT) cells are innate immune cells involved in regulation of immune tolerance, autoimmunity, and tumor immunity. However, the effect of human immunodeficiency virus type 1 (HIV-1) infection on these cells is unknown. Here, we report that the Vα24 NKT cells can be subdivided into CD4+ or CD4− subsets that differ in their expression of the homing receptors CD62L and CD11a. Furthermore, both CD4+ and CD4− NKT cells frequently express both CXCR4 and CCR5 HIV coreceptors. We find that the numbers of NKT cells are reduced in HIV-infected subjects with uncontrolled viremia and marked CD4+ T-cell depletion. The number of CD4+ NKT cells is inversely correlated with HIV load, indicating depletion of this subset. In contrast, CD4− NKT-cell numbers are unaffected in subjects with high viral loads. HIV infection experiments in vitro show preferential depletion of CD4+ NKT cells relative to regular CD4+ T cells, in particular with virus that uses the CCR5 coreceptor. Thus, HIV infection causes a selective loss of CD4+ lymph node homing (CD62L+) NKT cells, with consequent skewing of the NKT-cell compartment to a predominantly CD4− CD62L− phenotype. These data indicate that the key immunoregulatory NKT-cell compartment is compromised in HIV-1-infected patients. PMID:12097565

  19. Activation requirements and responses to TLR ligands in human CD4+ T cells: comparison of two T cell isolation techniques.

    PubMed

    Lancioni, Christina L; Thomas, Jeremy J; Rojas, Roxana E

    2009-05-15

    Direct regulation of T cell function by microbial ligands through Toll-like receptors (TLR) is an emerging area of T cell biology. Currently either immunomagnetic cell sorting (IMACS) or fluorescence-activated cell sorting (FACS), are utilized to isolate T-cell subsets for such studies. However, it is unknown to what extent differences in T cell purity between these isolation techniques influence T cell functional assays. We compared the purity, response to mitogen, activation requirements, and response to TLR ligands between human CD4(+) T cells isolated either by IMACS (IMACS-CD4(+)) or by IMACS followed by FACS (IMACS/FACS-CD4(+)). As expected, IMACS-CD4(+) were less pure than IMACS/FACS-CD4(+) (92.5%+/-1.4% versus 99.7%+/-0.2%, respectively). Consequently, IMACS-CD4(+) proliferated and produced cytokines in response to mitogen alone and had lower activation requirements compared to IMACS/FACS-CD4(+). In addition IMACS-CD4(+) but not IMACS/FACS-CD4(+) responses were upregulated by the TLR-4 ligand lipopolysaccharide (LPS). On the other hand, TLR-2 and TLR-5 engagement induced costimulation in both IMACS-CD4(+) and highly purified IMACS-/FACS-CD4(+). Altogether these results indicate that small differences in cell purity can significantly alter T cell responses to TLR ligands. This study stresses the importance of a stringent purification method when investigating the role of microbial ligands in T cell function. PMID:19272393

  20. 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

  1. 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

  2. Blood-Derived CD4 T Cells Naturally Resist Pyroptosis During Abortive HIV-1 Infection

    PubMed Central

    Muñoz-Arias, Isa; Doitsh, Gilad; Yang, Zhiyuan; Sowinski, Stefanie; Ruelas, Debbie; Greene, Warner C.

    2015-01-01

    Summary Progression to AIDS is driven by CD4 T-cell depletion, mostly involving pyroptosis elicited by abortive HIV infection of CD4 T cells in lymphoid tissues. Inefficient reverse transcription in these cells leads to cytoplasmic accumulation of viral DNAs that are detected by the DNA sensor IFI16, resulting in inflammasome assembly, caspase-1 activation, and pyroptosis. Unexpectedly, we found that peripheral blood-derived CD4 T cells naturally resist pyroptosis. This resistance is partly due to their deeper resting state, resulting in fewer HIV-1 reverse transcripts and lower IFI16 expression. However, when co-cultured with lymphoid-derived cells, blood-derived CD4 T cells become sensitized to pyroptosis, likely recapitulating interactions occurring within lymphoid tissues. Sensitization correlates with higher levels of activated NF-κB, IFI16 expression, and reverse transcription. Blood-derived lymphocytes re-purified from co-cultures lose sensitivity to pyroptosis. These differences highlight how the lymphoid tissue microenvironment encountered by trafficking CD4 T lymphocytes dynamically shapes their biological response to HIV. PMID:26468749

  3. Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody.

    PubMed

    Bonsignori, Mattia; Zhou, Tongqing; Sheng, Zizhang; Chen, Lei; Gao, Feng; Joyce, M Gordon; Ozorowski, Gabriel; Chuang, Gwo-Yu; Schramm, Chaim A; Wiehe, Kevin; Alam, S Munir; Bradley, Todd; Gladden, Morgan A; Hwang, Kwan-Ki; Iyengar, Sheelah; Kumar, Amit; Lu, Xiaozhi; Luo, Kan; Mangiapani, Michael C; Parks, Robert J; Song, Hongshuo; Acharya, Priyamvada; Bailer, Robert T; Cao, Allen; Druz, Aliaksandr; Georgiev, Ivelin S; Kwon, Young D; Louder, Mark K; Zhang, Baoshan; Zheng, Anqi; Hill, Brenna J; Kong, Rui; Soto, Cinque; Mullikin, James C; Douek, Daniel C; Montefiori, David C; Moody, Michael A; Shaw, George M; Hahn, Beatrice H; Kelsoe, Garnett; Hraber, Peter T; Korber, Bette T; Boyd, Scott D; Fire, Andrew Z; Kepler, Thomas B; Shapiro, Lawrence; Ward, Andrew B; Mascola, John R; Liao, Hua-Xin; Kwong, Peter D; Haynes, Barton F

    2016-04-01

    Antibodies with ontogenies from VH1-2 or VH1-46-germline genes dominate the broadly neutralizing response against the CD4-binding site (CD4bs) on HIV-1. Here, we define with longitudinal sampling from time-of-infection the development of a VH1-46-derived antibody lineage that matured to neutralize 90% of HIV-1 isolates. Structures of lineage antibodies CH235 (week 41 from time-of-infection, 18% breadth), CH235.9 (week 152, 77%), and CH235.12 (week 323, 90%) demonstrated the maturing epitope to focus on the conformationally invariant portion of the CD4bs. Similarities between CH235 lineage and five unrelated CD4bs lineages in epitope focusing, length-of-time to develop breadth, and extraordinary level of somatic hypermutation suggested commonalities in maturation among all CD4bs antibodies. Fortunately, the required CH235-lineage hypermutation appeared substantially guided by the intrinsic mutability of the VH1-46 gene, which closely resembled VH1-2. We integrated our CH235-lineage findings with a second broadly neutralizing lineage and HIV-1 co-evolution to suggest a vaccination strategy for inducing both lineages.

  4. Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation.

    PubMed

    Gerriets, Valerie A; Kishton, Rigel J; Nichols, Amanda G; Macintyre, Andrew N; Inoue, Makoto; Ilkayeva, Olga; Winter, Peter S; Liu, Xiaojing; Priyadharshini, Bhavana; Slawinska, Marta E; Haeberli, Lea; Huck, Catherine; Turka, Laurence A; Wood, Kris C; Hale, Laura P; Smith, Paul A; Schneider, Martin A; MacIver, Nancie J; Locasale, Jason W; Newgard, Christopher B; Shinohara, Mari L; Rathmell, Jeffrey C

    2015-01-01

    Activation of CD4+ T cells results in rapid proliferation and differentiation into effector and regulatory subsets. CD4+ effector T cell (Teff) (Th1 and Th17) and Treg subsets are metabolically distinct, yet the specific metabolic differences that modify T cell populations are uncertain. Here, we evaluated CD4+ T cell populations in murine models and determined that inflammatory Teffs maintain high expression of glycolytic genes and rely on high glycolytic rates, while Tregs are oxidative and require mitochondrial electron transport to proliferate, differentiate, and survive. Metabolic profiling revealed that pyruvate dehydrogenase (PDH) is a key bifurcation point between T cell glycolytic and oxidative metabolism. PDH function is inhibited by PDH kinases (PDHKs). PDHK1 was expressed in Th17 cells, but not Th1 cells, and at low levels in Tregs, and inhibition or knockdown of PDHK1 selectively suppressed Th17 cells and increased Tregs. This alteration in the CD4+ T cell populations was mediated in part through ROS, as N-acetyl cysteine (NAC) treatment restored Th17 cell generation. Moreover, inhibition of PDHK1 modulated immunity and protected animals against experimental autoimmune encephalomyelitis, decreasing Th17 cells and increasing Tregs. Together, these data show that CD4+ subsets utilize and require distinct metabolic programs that can be targeted to control specific T cell populations in autoimmune and inflammatory diseases.

  5. Role of miRNAs in CD4 T cell plasticity during inflammation and tolerance

    PubMed Central

    Sethi, Apoorva; Kulkarni, Neeraja; Sonar, Sandip; Lal, Girdhari

    2013-01-01

    Gene expression is tightly regulated in a tuneable, cell-specific and time-dependent manner. Recent advancement in epigenetics and non-coding RNA (ncRNA) revolutionized the concept of gene regulation. In order to regulate the transcription, ncRNA can promptly response to the extracellular signals as compared to transcription factors present in the cells. microRNAs (miRNAs) are ncRNA (~22 bp) encoded in the genome, and present as intergenic or oriented antisense to neighboring genes. The strategic location of miRNA in coding genes helps in the coupled regulation of its expression with host genes. miRNA together with complex machinery called RNA-induced silencing complex (RISC) interacts with target mRNA and degrade the mRNA or inhibits the translation. CD4 T cells play an important role in the generation and maintenance of inflammation and tolerance. Cytokines and chemokines present in the inflamed microenvironment controls the differentiation and function of various subsets of CD4 T cells [Th1, Th2, Th17, and regulatory CD4 T cells (Tregs)]. Recent studies suggest that miRNAs play an important role in the development and function of all subsets of CD4 T cells. In current review, we focused on how various miRNAs are regulated by cell's extrinsic and intrinsic signaling, and how miRNAs affect the transdifferentiation of subsets of CD4 T cell and controls their plasticity during inflammation and tolerance. PMID:23386861

  6. IL-15 induces CD4+ effector memory T cell production and tissue emigration in nonhuman primates

    PubMed Central

    Picker, Louis J.; Reed-Inderbitzin, Edward F.; Hagen, Shoko I.; Edgar, John B.; Hansen, Scott G.; Legasse, Alfred; Planer, Shannon; Piatak, Michael; Lifson, Jeffrey D.; Maino, Vernon C.; Axthelm, Michael K.; Villinger, Francois

    2006-01-01

    HIV infection selectively targets CD4+ effector memory T (TEM) cells, resulting in dramatic depletion of CD4+ T cells in mucosal effector sites in early infection. Regeneration of the TEM cell compartment is slow and incomplete, even when viral replication is controlled by antiretroviral therapy (ART). Here, we demonstrate that IL-15 dramatically increases in vivo proliferation of rhesus macaque (RM) CD4+ and CD8+ TEM cells with little effect on the naive or central memory T (TCM) cell subsets, a response pattern that is quite distinct from that of either IL-2 or IL-7. TEM cells produced in response to IL-15 did not accumulate in blood. Rather, 5-bromo-2′-deoxyuridine (BrdU) labeling studies suggest that many of these cells rapidly disperse to extralymphoid effector sites, where they manifest (slow) decay kinetics indistinguishable from that of untreated controls. In RMs with uncontrolled SIV infection and highly activated immune systems, IL-15 did not significantly increase CD4+ TEM cell proliferation, but with virologic control and concomitant reduction in immune activation by ART, IL-15 responsiveness was again observed. These data suggest that therapeutic use of IL-15 in the setting of ART might facilitate specific restoration of the CD4+ T cell compartment that is the primary target of HIV with less risk of exhausting precursor T cell compartments or generating potentially deleterious regulatory subsets. PMID:16691294

  7. Role of distinct CD4(+) T helper subset in pathogenesis of oral lichen planus.

    PubMed

    Wang, Hui; Zhang, Dunfang; Han, Qi; Zhao, Xin; Zeng, Xin; Xu, Yi; Sun, Zheng; Chen, Qianming

    2016-07-01

    Oral lichen planus (OLP) is one of the most common chronic inflammatory oral mucosal diseases with T-cell-mediated immune pathogenesis. In subepithelial and lamina propria of OLP local lesions, the presence of CD4(+) T helper (CD4(+) Th) cells appeared as the major lymphocytes. These CD4(+) T lymphocytes can differentiate into distinct Th cell types such as Th1, Th2, Treg, Th17, Th22, Th9, and Tfh within the context of certain cytokines environment. Growing evidence indicated that Th1/Th2 imbalance may greatly participate into the cytokine network of OLP immunopathology. In addition, Th1/Th2 imbalance can be regulated by the Treg subset and also greatly influenced by the emerging novel CD4(+) Th subset Th17. Furthermore, the presence of novel subsets Th22, Th9 and Tfh in OLP patients is yet to be clarified. All these Th subsets and their specific cytokines may play a critical role in determining the character, extent and duration of immune responses in OLP pathogenesis. Therefore, we review the roles of distinct CD4(+) Th subsets and their signature cytokines in determining disease severity and susceptibility of OLP and also reveal the novel therapeutic strategies based on T lymphocytes subsets in OLP treatment. PMID:26693958

  8. CD4-positive diffuse large B-cell lymphoma: A variant with aggressive clinical potential

    PubMed Central

    Hussaini, Mohammad O; Kreisel, Friederike H; Hassan, Anjum; Nguyen, TuDung T; Frater, John L

    2016-01-01

    CD4 expression is rare in diffuse large B-cell lymphoma (DLBCL), with 4 previously reported cases. Its significance is uncertain. We report five patients with CD4+ DLBCL and one CD4+ primary mediastinal large B-cell lymphoma. Cases were identified by searching the electronic database of the department; each was reviewed. Average age was 56 years. Neoplastic cells expressed CD20 (5/6 tested cases). BCL2/BCL6 expression were seen in 3/3 tested cases, suggesting a germinal center origin. Additionally, expression of T-cell antigens CD2 and CD5 was noted in 2/2 and CD7 in 1/1 tested case. CD3 was negative in all. Lymph nodes were commonly involved (67%). Patients received chemotherapy +/- radiation (6/6) and bone marrow transplant (2/6). Average survival was 44.2 mo. CD4 expression in DLBCL raises questions of lineage commitment. CD4+ DLBCL is rare; care should be exercised not to diagnose these as T-cell lymphomas. A subset behaves aggressively. PMID:27679780

  9. CD4 quantification based on magneto ELISA for AIDS diagnosis in low resource settings.

    PubMed

    Carinelli, S; Xufré, C; Alegret, S; Martí, M; Pividori, M I

    2016-11-01

    The Acquired Immune Deficiency Syndrome (AIDS) affects the life of millions of people around the world. Although rapid and low cost screening tests are widely available for the diagnosis of HIV infection, the count of CD4+ T lymphocytes remains a drawback in the areas mostly affected by the HIV, being this control imperative for assessing the deterioration of the immunological system and the progression towards AIDS, when the counting of cells falls down 200cellsμL(-1). This paper describes a high-throughput, simple and rapid method for CD4+ T lymphocytes quantification, directly in whole blood, based on a magneto ELISA. The CD4 cells are separated and preconcentrated from whole blood in magnetic particles, and labeled with an enzyme for the optical readout performed with a standard microplate reader. The magneto ELISA is able to reach the whole CD4 counting range of medical interest, being the limit of detection as low as 50 CD4+ cells per μL of whole blood, without any pretreatment. This method is a highly suitable alternative diagnostic tool for the expensive flow cytometry at the community and primary care level, providing a sensitive method but by using instrumentation widely available in low-resource settings laboratories and requiring low-maintenance, as is the case of a microplate reader operated by filters.

  10. p24 antigenaemia, CD4 lymphocyte counts and the development of AIDS.

    PubMed

    Phillips, A N; Lee, C A; Elford, J; Webster, A; Janossy, G; Griffiths, P D; Kernoff, P B

    1991-10-01

    A cohort of 111 HIV-infected haemophiliacs has been followed for up to 11 years, during which time 33 patients have been diagnosed with AIDS. Twenty-seven of the cohort developed detectable p24 antigenaemia while remaining free of AIDS. These patients experienced an increased risk of progression to AIDS compared with those patients who were persistently p24-negative (relative risk 7.24; P less than 0.0001, Cox proportional hazards model). The relative risk was reduced to 5.42 (P less than 0.0001) after adjustment for age and cytomegalovirus seropositivity. After adjustment for the patients' declining CD4 lymphocyte count during follow-up, the relative risk fell dramatically to 1.97 and became non-significant (P = 0.2). p24-antigenaemic patients tended to develop AIDS at levels of similar CD4 lymphocyte counts to those who were persistently p24-antigen-negative (median CD4 lymphocyte counts, 70 and 50 x 10(6)/l, respectively). These results suggests that the association between p24 antigenaemia and the rate of progression to AIDS can be explained largely by a more rapid decline in CD4 lymphocyte count among patients with p24 antigenaemia than in those without. The major pathological effects of increased plasma viral load, as detected by the presence or absence of p24 antigenaemia, appear to act via progressive CD4 lymphocyte depletion.

  11. Interleukin-27-Producing CD4(+) T Cells Regulate Protective Immunity during Malaria Parasite Infection.

    PubMed

    Kimura, Daisuke; Miyakoda, Mana; Kimura, Kazumi; Honma, Kiri; Hara, Hiromitsu; Yoshida, Hiroki; Yui, Katsuyuki

    2016-03-15

    Interleukin-27 (IL-27) is a heterodimeric regulatory cytokine of the IL-12 family, which is produced by macrophages, dendritic cells, and B cells upon stimulation through innate immune receptors. Here, we described regulatory CD4(+) T cells that produce IL-27 in response to T cell receptor stimulation during malaria infection, inhibiting IL-2 production and clonal expansion of other T cells in an IL-27-dependent manner. IL-27-producing CD4(+) T cells were Foxp3(-)CD11a(+)CD49d(+) malaria antigen-specific CD4(+) T cells and were distinct from interferon-γ (IFN-γ) producing Th1 or IL-10 producing Tr1 cells. In mice lacking IL-27 in T cells, IL-2 production was restored and clonal expansion and IFN-γ production by specific CD4(+) T cells were improved, culminating in reduced parasite burden. This study highlights a unique population of IL-27 producing regulatory CD4(+) T cells and their critical role in the regulation of the protective immune response against malaria parasites.

  12. The Fc and not CD4 Receptor Mediates Antibody Enhancement of HIV Infection in Human Cells

    NASA Astrophysics Data System (ADS)

    Homsy, Jacques; Meyer, Mia; Tateno, Masatoshi; Clarkson, Sarah; Levy, Jay A.

    1989-06-01

    Antibodies that enhance human immunodeficiency virus (HIV) infectivity have been found in the blood of infected individuals and in infected or immunized animals. These findings raise serious concern for the development of a safe vaccine against acquired immunodeficiency syndrome. To address the in vivo relevance and mechanism of this phenomenon, antibody-dependent enhancement of HIV infectivity in peripheral blood macrophages, lymphocytes, and human fibroblastoid cells was studied. Neither Leu3a, a monoclonal antibody directed against the CD4 receptor, nor soluble recombinant CD4 even at high concentrations prevented this enhancement. The addition of monoclonal antibody to the Fc receptor III (anti-FcRIII), but not of antibodies that react with FcRI or FcRII, inhibited HIV type 1 and HIV type 2 enhancement in peripheral blood macrophages. Although enhancement of HIV infection in CD4+ lymphocytes could not be blocked by anti-FcRIII, it was inhibited by the addition of human immunoglobulin G aggregates. The results indicate that the FcRIII receptor on human macrophages and possibly another Fc receptor on human CD4+ lymphocytes mediate antibody-dependent enhancement of HIV infectivity and that this phenomenon proceeds through a mechanism independent of the CD4 protein.

  13. CD4-positive diffuse large B-cell lymphoma: A variant with aggressive clinical potential.

    PubMed

    Hussaini, Mohammad O; Kreisel, Friederike H; Hassan, Anjum; Nguyen, TuDung T; Frater, John L

    2016-09-26

    CD4 expression is rare in diffuse large B-cell lymphoma (DLBCL), with 4 previously reported cases. Its significance is uncertain. We report five patients with CD4(+) DLBCL and one CD4(+) primary mediastinal large B-cell lymphoma. Cases were identified by searching the electronic database of the department; each was reviewed. Average age was 56 years. Neoplastic cells expressed CD20 (5/6 tested cases). BCL2/BCL6 expression were seen in 3/3 tested cases, suggesting a germinal center origin. Additionally, expression of T-cell antigens CD2 and CD5 was noted in 2/2 and CD7 in 1/1 tested case. CD3 was negative in all. Lymph nodes were commonly involved (67%). Patients received chemotherapy +/- radiation (6/6) and bone marrow transplant (2/6). Average survival was 44.2 mo. CD4 expression in DLBCL raises questions of lineage commitment. CD4(+) DLBCL is rare; care should be exercised not to diagnose these as T-cell lymphomas. A subset behaves aggressively. PMID:27679780

  14. Specific interaction of aurintricarboxylic acid with the human immunodeficiency virus/CD4 cell receptor

    SciTech Connect

    Schols, D.; Baba, M.; Pauwels, R.; Desmyter, J.; De Clercq, E. )

    1989-05-01

    The triphenylmethane derivative aurintricarboxylic acid (ATA), but not aurin, selectively prevented the binding of OKT4A/Leu-3a monoclonal antibody (mAb) and, to a lesser extent, OKT4 mAb to the CD4 cell receptor for human immunodeficiency virus type 1 (HIV-1). The effect was seen within 1 min at an ATA concentration of 10 {mu}M in various T4{sup +} cells (MT-4, U-937, peripheral blood lymphocytes, and monocytes). It was dose-dependent and reversible. ATA prevented the attachment of radiolabeled HIV-1 particles to MT-4 cells, which could be expected as the result of its specific binding to the HIV/CD4 receptor. Other HIV inhibitors such as suramin, fuchsin acid, azidothymidine, dextran sulfate, heparin, and pentosan polysulfate did not affect OKT4A/Leu-3a mAb binding to the CD4 receptor, although the sulfated polysaccharides suppressed HIV-1 adsorption to the cells at concentrations required for complete protection against HIV-1 cytopathogenicity. Thus, ATA is a selective marker molecule for the CD4 receptor. ATA also interfered with the staining of membrane-associated HIV-1 glycoprotein gp120 by a mAb against it. These unusual properties of a small molecule of nonimmunological origin may have important implications for the study of CD4/HIV/AIDS pathogenesis and possibly treatment.

  15. [Human chronic chagasic myocarditis: quantitative study of CD4+ and CD8+ lymphocytes in inflammatory exudates].

    PubMed

    Tostes Júnior, S; Lopes, E R; Pereira, F E; Chapadeiro, E

    1994-01-01

    Myocardial exsudate CD4+ and CD8+ lymphocytes were counted in transmural left ventricular free wall frozen sections taken from 10 necropsied chronic cardiac chagasic patients. The cells were labeled with monoclonal antibodies using a streptavidin-biotin technique. We counted: 1) lymphocytes in the total exsudate (LTE) and, separately, 2) the lymphocytes touching or very near to myocells (LTVNM). Lymphocytes were considered very near whenever their own nuclear shortest nuclear diameter was larger than their distance from myocells. CD8+ lymphocytes were more numerous than CD4+ lymphocytes, especially among the LTVNM. The LTE CD4/CD8 ratio was 0.37 +/- 0.20, but the LTVNM CD4/CD8 ratio was smaller (0.23 +/- 0.11). Among the LTE, 34 +/- 11% of CD8+ (against 24 +/- 12% of CD4+) were LTVNM. All these differences were statistically significant. Both subtypes of T-lymphocytes were found to have an intimate relationship with both ruptured and unruptured myocells, and parasites were not seen. These findings are in accordance with the idea that the myocardial cell lesions in the cardiac form of human Chagas' disease are mediated mainly by T-cytotoxic lymphocytes.

  16. Immune activation induces immortalization of HTLV-1 LTR-Tax transgenic CD4+ T cells.

    PubMed

    Swaims, Alison Y; Khani, Francesca; Zhang, Yingyu; Roberts, Arthur I; Devadas, Satish; Shi, Yufang; Rabson, Arnold B

    2010-10-21

    Infection with the human T-cell leukemia virus-1 (HTLV-1) results in a variety of diseases including adult T-cell leukemia/lymphoma (ATL). Although the pathogenesis of these disorders is poorly understood, it involves complex interactions with the host immune system. Activation of infected T cells may play an important role in disease pathogenesis through induction of the oncogenic HTLV-1 Tax transactivator protein. To test this hypothesis, we employed transgenic mice in which Tax is regulated by the HTLV-1 LTR. T-cell receptor stimulation of LTR-Tax CD4(+) T cells induced Tax expression, hyper-proliferation, and immortalization in culture. The transition to cellular immortalization was accompanied by markedly increased expression of the antiapoptotic gene, mcl-1, previously implicated as important in T-cell survival. Immortalized cells exhibited a CD4(+)CD25(+)CD3(-) phenotype commonly observed in ATL. Engraftment of activated LTR-Tax CD4(+) T cells into NOD/Shi-scid/IL-2Rγ null mice resulted in a leukemia-like phenotype with expansion and tissue infiltration of Tax(+), CD4(+) lymphocytes. We suggest that immune activation of infected CD4(+) T cells plays an important role in the induction of Tax expression, T-cell proliferation, and pathogenesis of ATL in HTLV-1-infected individuals. PMID:20634377

  17. Probing the Effect of Force on HIV-1 Receptor CD4

    PubMed Central

    2015-01-01

    Cell-surface proteins are central for the interaction of cells with their surroundings and are also associated with numerous diseases. These molecules are exposed to mechanical forces, but the exact relation between force and the functions and pathologies associated with cell-surface proteins is unclear. An important cell-surface protein is CD4, the primary receptor of HIV-1. Here we show that mechanical force activates conformational and chemical changes on CD4 that may be important during viral attachment. We have used single-molecule force spectroscopy and analysis on HIV-1 infectivity to demonstrate that the mechanical extension of CD4 occurs in a time-dependent manner and correlates with HIV-1 infectivity. We show that Ibalizumab, a monoclonal antibody that blocks HIV-1, prevents the mechanical extension of CD4 domains 1 and 2. Furthermore, we demonstrate that thiol/disulfide exchange in CD4 requires force for exposure of cryptic disulfide bonds. This mechanical perspective provides unprecedented information that can change our understanding on how viruses interact with their hosts. PMID:25299596

  18. Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody.

    PubMed

    Bonsignori, Mattia; Zhou, Tongqing; Sheng, Zizhang; Chen, Lei; Gao, Feng; Joyce, M Gordon; Ozorowski, Gabriel; Chuang, Gwo-Yu; Schramm, Chaim A; Wiehe, Kevin; Alam, S Munir; Bradley, Todd; Gladden, Morgan A; Hwang, Kwan-Ki; Iyengar, Sheelah; Kumar, Amit; Lu, Xiaozhi; Luo, Kan; Mangiapani, Michael C; Parks, Robert J; Song, Hongshuo; Acharya, Priyamvada; Bailer, Robert T; Cao, Allen; Druz, Aliaksandr; Georgiev, Ivelin S; Kwon, Young D; Louder, Mark K; Zhang, Baoshan; Zheng, Anqi; Hill, Brenna J; Kong, Rui; Soto, Cinque; Mullikin, James C; Douek, Daniel C; Montefiori, David C; Moody, Michael A; Shaw, George M; Hahn, Beatrice H; Kelsoe, Garnett; Hraber, Peter T; Korber, Bette T; Boyd, Scott D; Fire, Andrew Z; Kepler, Thomas B; Shapiro, Lawrence; Ward, Andrew B; Mascola, John R; Liao, Hua-Xin; Kwong, Peter D; Haynes, Barton F

    2016-04-01

    Antibodies with ontogenies from VH1-2 or VH1-46-germline genes dominate the broadly neutralizing response against the CD4-binding site (CD4bs) on HIV-1. Here, we define with longitudinal sampling from time-of-infection the development of a VH1-46-derived antibody lineage that matured to neutralize 90% of HIV-1 isolates. Structures of lineage antibodies CH235 (week 41 from time-of-infection, 18% breadth), CH235.9 (week 152, 77%), and CH235.12 (week 323, 90%) demonstrated the maturing epitope to focus on the conformationally invariant portion of the CD4bs. Similarities between CH235 lineage and five unrelated CD4bs lineages in epitope focusing, length-of-time to develop breadth, and extraordinary level of somatic hypermutation suggested commonalities in maturation among all CD4bs antibodies. Fortunately, the required CH235-lineage hypermutation appeared substantially guided by the intrinsic mutability of the VH1-46 gene, which closely resembled VH1-2. We integrated our CH235-lineage findings with a second broadly neutralizing lineage and HIV-1 co-evolution to suggest a vaccination strategy for inducing both lineages. PMID:26949186

  19. CD4 quantification based on magneto ELISA for AIDS diagnosis in low resource settings.

    PubMed

    Carinelli, S; Xufré, C; Alegret, S; Martí, M; Pividori, M I

    2016-11-01

    The Acquired Immune Deficiency Syndrome (AIDS) affects the life of millions of people around the world. Although rapid and low cost screening tests are widely available for the diagnosis of HIV infection, the count of CD4+ T lymphocytes remains a drawback in the areas mostly affected by the HIV, being this control imperative for assessing the deterioration of the immunological system and the progression towards AIDS, when the counting of cells falls down 200cellsμL(-1). This paper describes a high-throughput, simple and rapid method for CD4+ T lymphocytes quantification, directly in whole blood, based on a magneto ELISA. The CD4 cells are separated and preconcentrated from whole blood in magnetic particles, and labeled with an enzyme for the optical readout performed with a standard microplate reader. The magneto ELISA is able to reach the whole CD4 counting range of medical interest, being the limit of detection as low as 50 CD4+ cells per μL of whole blood, without any pretreatment. This method is a highly suitable alternative diagnostic tool for the expensive flow cytometry at the community and primary care level, providing a sensitive method but by using instrumentation widely available in low-resource settings laboratories and requiring low-maintenance, as is the case of a microplate reader operated by filters. PMID:27591585

  20. CD4-positive diffuse large B-cell lymphoma: A variant with aggressive clinical potential

    PubMed Central

    Hussaini, Mohammad O; Kreisel, Friederike H; Hassan, Anjum; Nguyen, TuDung T; Frater, John L

    2016-01-01

    CD4 expression is rare in diffuse large B-cell lymphoma (DLBCL), with 4 previously reported cases. Its significance is uncertain. We report five patients with CD4+ DLBCL and one CD4+ primary mediastinal large B-cell lymphoma. Cases were identified by searching the electronic database of the department; each was reviewed. Average age was 56 years. Neoplastic cells expressed CD20 (5/6 tested cases). BCL2/BCL6 expression were seen in 3/3 tested cases, suggesting a germinal center origin. Additionally, expression of T-cell antigens CD2 and CD5 was noted in 2/2 and CD7 in 1/1 tested case. CD3 was negative in all. Lymph nodes were commonly involved (67%). Patients received chemotherapy +/- radiation (6/6) and bone marrow transplant (2/6). Average survival was 44.2 mo. CD4 expression in DLBCL raises questions of lineage commitment. CD4+ DLBCL is rare; care should be exercised not to diagnose these as T-cell lymphomas. A subset behaves aggressively.

  1. Coinhibitory receptor PD-1H preferentially suppresses CD4+ T cell–mediated immunity

    PubMed Central

    Flies, Dallas B.; Han, Xue; Higuchi, Tomoe; Zheng, Linghua; Sun, Jingwei; Ye, Jessica Jane; Chen, Lieping

    2014-01-01

    T cell activation is regulated by the interactions of surface receptors with stimulatory and inhibitory ligands. Programmed death-1 homolog (PD-1H, also called VISTA) is a member of the CD28 family of proteins and has been shown to act as a coinhibitory ligand on APCs that suppress T cell responses. Here, we determined that PD-1H functions as a coinhibitory receptor for CD4+ T cells. CD4+ T cells in mice lacking PD-1H exhibited a dramatically increased response to antigen stimulation. Furthermore, delivery of a PD-1H–specific agonist mAb directly inhibited CD4+ T cell activation both in vitro and in vivo, validating a coinhibitory function of PD-1H. In a murine model of acute hepatitis, administration of a PD-1H agonist mAb suppressed CD4+ T cell–mediated acute inflammation. PD-1H–deficient animals were highly resistant to tumor induction in a murine brain glioma model, and depletion of CD4+ T cells, but not CD8+ T cells, promoted tumor formation. Together, our findings suggest that PD-1H has potential as a target of immune modulation in the treatment of human inflammation and malignancies. PMID:24743150

  2. Role of miRNAs in CD4 T cell plasticity during inflammation and tolerance.

    PubMed

    Sethi, Apoorva; Kulkarni, Neeraja; Sonar, Sandip; Lal, Girdhari

    2013-01-01

    Gene expression is tightly regulated in a tuneable, cell-specific and time-dependent manner. Recent advancement in epigenetics and non-coding RNA (ncRNA) revolutionized the concept of gene regulation. In order to regulate the transcription, ncRNA can promptly response to the extracellular signals as compared to transcription factors present in the cells. microRNAs (miRNAs) are ncRNA (~22 bp) encoded in the genome, and present as intergenic or oriented antisense to neighboring genes. The strategic location of miRNA in coding genes helps in the coupled regulation of its expression with host genes. miRNA together with complex machinery called RNA-induced silencing complex (RISC) interacts with target mRNA and degrade the mRNA or inhibits the translation. CD4 T cells play an important role in the generation and maintenance of inflammation and tolerance. Cytokines and chemokines present in the inflamed microenvironment controls the differentiation and function of various subsets of CD4 T cells [Th1, Th2, Th17, and regulatory CD4 T cells (Tregs)]. Recent studies suggest that miRNAs play an important role in the development and function of all subsets of CD4 T cells. In current review, we focused on how various miRNAs are regulated by cell's extrinsic and intrinsic signaling, and how miRNAs affect the transdifferentiation of subsets of CD4 T cell and controls their plasticity during inflammation and tolerance.

  3. Access of protective antiviral antibody to neuronal tissues requires CD4 T-cell help.

    PubMed

    Iijima, Norifumi; Iwasaki, Akiko

    2016-05-26

    Circulating antibodies can access most tissues to mediate surveillance and elimination of invading pathogens. Immunoprivileged tissues such as the brain and the peripheral nervous system are shielded from plasma proteins by the blood-brain barrier and blood-nerve barrier, respectively. Yet, circulating antibodies must somehow gain access to these tissues to mediate their antimicrobial functions. Here we examine the mechanism by which antibodies gain access to neuronal tissues to control infection. Using a mouse model of genital herpes infection, we demonstrate that both antibodies and CD4 T cells are required to protect the host after immunization at a distal site. We show that memory CD4 T cells migrate to the dorsal root ganglia and spinal cord in response to infection with herpes simplex virus type 2. Once inside these neuronal tissues, CD4 T cells secrete interferon-γ and mediate local increase in vascular permeability, enabling antibody access for viral control. A similar requirement for CD4 T cells for antibody access to the brain is observed after intranasal challenge with vesicular stomatitis virus. Our results reveal a previously unappreciated role of CD4 T cells in mobilizing antibodies to the peripheral sites of infection where they help to limit viral spread. PMID:27225131

  4. Prevalence of human herpesvirus-8 salivary shedding in HIV increases with CD4 count.

    PubMed

    Gandhi, M; Koelle, D M; Ameli, N; Bacchetti, P; Greenspan, J S; Navazesh, M; Anastos, K; Greenblatt, R M

    2004-08-01

    Human herpesvirus-8 (HHV-8) is the etiologic agent of Kaposi's sarcoma (KS), which occurs in epidemic form in human immunodeficiency virus(HIV)-infected individuals. Saliva is the only mucosal fluid in which infectious HHV-8 has been identified, although factors associated with HHV-8 salivary shedding remain unclear. Our study performed PCR analysis for HHV-8 DNA in saliva (and other body fluids) in 66 HIV- and HHV-8-co-infected women without KS so that we could examine predictors for HHV-8 DNA detection. CD4 count was the most significant predictor of HHV-8 salivary shedding, with increased prevalence of HHV-8 salivary DNA at higher CD4 counts. The odds of salivary HHV8 shedding at CD4 counts > = 350 cells/microL was 63 times the odds of shedding at CD4 < 350 (95%CI, 1.3-3078), with an increase in effect size when the analysis was restricted to those with a CD4 nadir > 200. Analysis of these data suggests an increased potential for HHV-8 transmission early in HIV infection, with implications for HHV-8 prevention.

  5. Protein kinase D regulates positive selection of CD4+ thymocytes through phosphorylation of SHP-1

    PubMed Central

    Ishikawa, Eri; Kosako, Hidetaka; Yasuda, Tomoharu; Ohmuraya, Masaki; Araki, Kimi; Kurosaki, Tomohiro; Saito, Takashi; Yamasaki, Sho

    2016-01-01

    Thymic selection shapes an appropriate T cell antigen receptor (TCR) repertoire during T cell development. Here, we show that a serine/threonine kinase, protein kinase D (PKD), is crucial for thymocyte positive selection. In T cell-specific PKD-deficient (PKD2/PKD3 double-deficient) mice, the generation of CD4 single positive thymocytes is abrogated. This defect is likely caused by attenuated TCR signalling during positive selection and incomplete CD4 lineage specification in PKD-deficient thymocytes; however, TCR-proximal tyrosine phosphorylation is not affected. PKD is activated in CD4+CD8+ double positive (DP) thymocytes on stimulation with positively selecting peptides. By phosphoproteomic analysis, we identify SH2-containing protein tyrosine phosphatase-1 (SHP-1) as a direct substrate of PKD. Substitution of wild-type SHP-1 by phosphorylation-defective mutant (SHP-1S557A) impairs generation of CD4+ thymocytes. These results suggest that the PKD–SHP-1 axis positively regulates TCR signalling to promote CD4+ T cell development. PMID:27670070

  6. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection

    NASA Astrophysics Data System (ADS)

    Doitsh, Gilad; Galloway, Nicole L. K.; Geng, Xin; Yang, Zhiyuan; Monroe, Kathryn M.; Zepeda, Orlando; Hunt, Peter W.; Hatano, Hiroyu; Sowinski, Stefanie; Muñoz-Arias, Isa; Greene, Warner C.

    2014-01-01

    The pathway causing CD4 T-cell death in HIV-infected hosts remains poorly understood although apoptosis has been proposed as a key mechanism. We now show that caspase-3-mediated apoptosis accounts for the death of only a small fraction of CD4 T cells corresponding to those that are both activated and productively infected. The remaining over 95% of quiescent lymphoid CD4 T cells die by caspase-1-mediated pyroptosis triggered by abortive viral infection. Pyroptosis corresponds to an intensely inflammatory form of programmed cell death in which cytoplasmic contents and pro-inflammatory cytokines, including IL-1β, are released. This death pathway thus links the two signature events in HIV infection--CD4 T-cell depletion and chronic inflammation--and creates a pathogenic vicious cycle in which dying CD4 T cells release inflammatory signals that attract more cells to die. This cycle can be broken by caspase 1 inhibitors shown to be safe in humans, raising the possibility of a new class of `anti-AIDS' therapeutics targeting the host rather than the virus.

  7. Memory CD4+ T cells do not induce graft-versus-host disease.

    PubMed

    Anderson, Britt E; McNiff, Jennifer; Yan, Jun; Doyle, Hester; Mamula, Mark; Shlomchik, Mark J; Shlomchik, Warren D

    2003-07-01

    Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic stem cell transplantation (alloSCT). Donor T cells that accompany stem cell grafts cause GVHD by attacking recipient tissues; therefore, all patients receive GVHD prophylaxis by depletion of T cells from the allograft or through immunosuppressant drugs. In addition to providing a graft-versus-leukemia effect, donor T cells are critical for reconstituting T cell-mediated immunity. Ideally, immunity to infectious agents would be transferred from donor to host without GVHD. Most donors have been exposed to common pathogens and have an increased precursor frequency of memory T cells against pathogenic antigens. We therefore asked whether memory CD62L-CD44+ CD4+ T cells would induce less GVHD than unfractionated or naive CD4+ T cells. Strikingly, we found that memory CD4 cells induced neither clinical nor histologic GVHD. This effect was not due to the increased number of CD4+CD25+ regulatory T cells found in the CD62L-CD44+ fraction because memory T cells depletion of these cells did not cause GVHD. Memory CD4 cells engrafted and responded to antigen both in vivo and in vitro. If these murine results are applicable to human alloSCT, selective administration of memory T cells could greatly improve post-transplant immune reconstitution.

  8. Access of protective antiviral antibody to neuronal tissues requires CD4 T-cell help.

    PubMed

    Iijima, Norifumi; Iwasaki, Akiko

    2016-05-26

    Circulating antibodies can access most tissues to mediate surveillance and elimination of invading pathogens. Immunoprivileged tissues such as the brain and the peripheral nervous system are shielded from plasma proteins by the blood-brain barrier and blood-nerve barrier, respectively. Yet, circulating antibodies must somehow gain access to these tissues to mediate their antimicrobial functions. Here we examine the mechanism by which antibodies gain access to neuronal tissues to control infection. Using a mouse model of genital herpes infection, we demonstrate that both antibodies and CD4 T cells are required to protect the host after immunization at a distal site. We show that memory CD4 T cells migrate to the dorsal root ganglia and spinal cord in response to infection with herpes simplex virus type 2. Once inside these neuronal tissues, CD4 T cells secrete interferon-γ and mediate local increase in vascular permeability, enabling antibody access for viral control. A similar requirement for CD4 T cells for antibody access to the brain is observed after intranasal challenge with vesicular stomatitis virus. Our results reveal a previously unappreciated role of CD4 T cells in mobilizing antibodies to the peripheral sites of infection where they help to limit viral spread.

  9. Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody

    DOE PAGESBeta

    Bonsignori, Mattia; Zhou, Tongqing; Sheng, Zizhang; Chen, Lei; Gao, Feng; Joyce, M.  Gordon; Ozorowski, Gabriel; Chuang, Gwo-Yu; Schramm, Chaim A.; Wiehe, Kevin; et al

    2016-04-01

    Here, we report that antibodies with ontogenies from VH1-2 or VH1-46-germline genes dominate the broadly neutralizing response against the CD4-binding site (CD4bs) on HIV-1. We define with longitudinal sampling from time-of-infection the development of a VH1-46-derived antibody lineage that matured to neutralize 90% of HIV-1 isolates. Structures of lineage antibodies CH235 (week 41 from time-of-infection, 18% breadth), CH235.9 (week 152, 77%), and CH235.12 (week 323, 90%) demonstrated the maturing epitope to focus on the conformationally invariant portion of the CD4bs. Similarities between CH235 lineage and five unrelated CD4bs lineages in epitope focusing, length-of-time to develop breadth, and extraordinary level ofmore » somatic hypermutation suggested commonalities in maturation among all CD4bs antibodies. Fortunately, the required CH235-lineage hypermutation appeared substantially guided by the intrinsic mutability of the VH1-46 gene, which closely resembled VH1-2. Lastly, we integrated our CH235-lineage findings with a second broadly neutralizing lineage and HIV-1 co-evolution to suggest a vaccination strategy for inducing both lineages.« less

  10. Computational modeling of heterogeneity and function of CD4+ T cells

    PubMed Central

    Carbo, Adria; Hontecillas, Raquel; Andrew, Tricity; Eden, Kristin; Mei, Yongguo; Hoops, Stefan; Bassaganya-Riera, Josep

    2014-01-01

    The immune system is composed of many different cell types and hundreds of intersecting molecular pathways and signals. This large biological complexity requires coordination between distinct pro-inflammatory and regulatory cell subsets to respond to infection while maintaining tissue homeostasis. CD4+ T cells play a central role in orchestrating immune responses and in maintaining a balance between pro- and anti- inflammatory responses. This tight balance between regulatory and effector reactions depends on the ability of CD4+ T cells to modulate distinct pathways within large molecular networks, since dysregulated CD4+ T cell responses may result in chronic inflammatory and autoimmune diseases. The CD4+ T cell differentiation process comprises an intricate interplay between cytokines, their receptors, adaptor molecules, signaling cascades and transcription factors that help delineate cell fate and function. Computational modeling can help to describe, simulate, analyze, and predict some of the behaviors in this complicated differentiation network. This review provides a comprehensive overview of existing computational immunology methods as well as novel strategies used to model immune responses with a particular focus on CD4+ T cell differentiation. PMID:25364738

  11. Reconstitution of CD4 T Cells in Bronchoalveolar Lavage Fluid after Initiation of Highly Active Antiretroviral Therapy▿

    PubMed Central

    Knox, Kenneth S.; Vinton, Carol; Hage, Chadi A.; Kohli, Lisa M.; Twigg, Homer L.; Klatt, Nichole R.; Zwickl, Beth; Waltz, Jeffrey; Goldman, Mitchell; Douek, Daniel C.; Brenchley, Jason M.

    2010-01-01

    The massive depletion of gastrointestinal-tract CD4 T cells is a hallmark of the acute phase of HIV infection. In contrast, the depletion of the lower-respiratory-tract mucosal CD4 T cells as measured in bronchoalveolar lavage (BAL) fluid is more moderate and similar to the depletion of CD4 T cells observed in peripheral blood (PB). To understand better the dynamics of disease pathogenesis and the potential for the reconstitution of CD4 T cells in the lung and PB following the administration of effective antiretroviral therapy, we studied cell-associated viral loads, CD4 T-cell frequencies, and phenotypic and functional profiles of antigen-specific CD4 T cells from BAL fluid and blood before and after the initiation of highly active antiretroviral therapy (HAART). The major findings to emerge were the following: (i) BAL CD4 T cells are not massively depleted or preferentially infected by HIV compared to levels for PB; (ii) BAL CD4 T cells reconstitute after the initiation of HAART, and their infection frequencies decrease; (iii) BAL CD4 T-cell reconstitution appears to occur via the local proliferation of resident BAL CD4 T cells rather than redistribution; and (iv) BAL CD4 T cells are more polyfunctional than CD4 T cells in blood, and their functional profile is relatively unchanged after the initiation of HAART. Taken together, these data suggest mechanisms for mucosal CD4 T-cell depletion and interventions that might aid in the reconstitution of mucosal CD4 T cells. PMID:20610726

  12. 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.

  13. Species specificity and augmentation of responses to class II major histocompatibility complex molecules in human CD4 transgenic mice

    PubMed Central

    1992-01-01

    Murine T cell responses to human class II major histocompatibility complex (MHC) molecules were shown to be a minimum of 20-70-fold lower than responses to allogeneic molecules. Transgenic mice expressing slightly below normal (75-95%) or very high (250-380%) cell surface levels of human CD4 were utilized to determine whether this was due to a species-specific interaction between murine CD4 and class II molecules. Human CD4 was shown to function in signal transduction events in murine T cells based on the ability of anti-human CD4 antibody to synergize with suboptimal doses of anti-murine CD3 antibody in stimulating T cell proliferation. In mice expressing lower levels of human CD4, T cell responses to human class II molecules were enhanced up to threefold, whereas allogeneic responses were unaltered. In mice expressing high levels of human CD4, responses to human class II molecules were enhanced at least 10-fold, whereas allogeneic responses were between one and three times the level of normal responses. The relatively greater enhancement of the response to human class II molecules in both lines argues for a preferential interaction between human CD4 and human class II molecules. In mice expressing lower levels of human CD4, responses to human class II molecules were blocked by antibodies to CD4 of either species, indicating participation by both molecules. In mice expressing high levels of human CD4, responses to both human and murine class II molecules were almost completely blocked with anti-human CD4 antibody, whereas anti-murine CD4 antibody had no effect. However, anti-murine CD4 continued to synergize with anti-CD3 in stimulating T cell proliferation in these mice. Thus, overexpression of human CD4 selectively impaired the ability of murine CD4 to assist in the process of antigen recognition. The ability of human CD4 to support a strong allogeneic response under these conditions indicates that this molecule can interact with murine class II molecules to a

  14. Knowledge, attitude and practice related to infant feeding among women in rural Papua New Guinea: a descriptive, mixed method study

    PubMed Central

    2013-01-01

    Background Despite the well-recognized effectiveness of exclusive breastfeeding for the first six months of an infant life for reducing infant mortality, adherence to this practice is not widespread in the developing world. Although several studies on infant nutrition practices have been conducted in urban settings of Papua New Guinea (PNG), there is only scant information on infant feeding practices in rural settings. Therefore, this study aimed to investigate knowledge, attitude and practice associated with exclusive breastfeeding in various locations in rural PNG. Methods A mixed method study using interviews based on a semi-structured questionnaire (n = 140) and Focus Group Discussions (FGDs) was conducted among mothers in rural PNG between August and September 2012. Participants were selected using convenience sampling. Included in the study were both primiparous and multiparous mothers with a child below the age of two years. Content analysis was used for qualitative data and descriptive statistics were used for quantitative data. Results Whereas most women indicated breastfeeding as a better way to feed babies, knowledge of the reasons for its superiority over infant formula was generally poor. Only 17% of mothers practiced exclusive breastfeeding for the first six months postpartum. Our study showed that the size of the gap between exclusive breastfeeding practice and global recommendations was striking. Taking into account the low educational profile of the participants, the disparity may be explained by the fact that most of the mothers in this study had no formal education on infant feeding. Conclusions This study showed a lack of understanding of the importance of and poor adherence to exclusive breastfeeding for the first six months postpartum among rural mothers. As exclusive breastfeeding promotion has been proved to be one of most effective ways to improve infant survival, more attention should be given to it, especially targeting the large

  15. Influence of the availability of commercial infant foods on feeding practices in Jamaica.

    PubMed

    De Morales, A; Larkin, F A

    1972-03-01

    A study was conducted into infant feeding regimens among 150 Jamaican women. The target population was limited to women living in the Kingston-St. Andrews Corporate area and attending hospitals or clinics where nutrition education was offered. Subjects were questioned as to obstetric history, socio-economic status, sources of information, and infant feeding habits. Nearly all infants in the study were weaned by 1 year of age with a nearly equal number being weaned in the 1st 6 months and the 2nd 6 months. Mothers who never breast fed their infants or weaned early did so for unavoidable reasons, e.g., maternal illness, infant prematurity or hospitalization, or insufficient milk. Most weaning due to these reasons occurred within the 1st 6 months of life. More than 1/2 of the women did not have clearly defined physiological reasons for discontinuing breast feeding. Income and place of residence were not related to the decision to cease breast feeding. Women attending private clinics and receiving information on infant nutrition from health personnel tended to breast feed for a longer time. 18 commercial infant food products were available. 15 of these were a form of processed cow's milk requiring a measure of skill in preparing. The rest were goat's milk, cow's milk, or gruel. 40% of the women in the study used more than 1 of these commercial preparations, indicating a general preference for formulas rather than for a particular brand name. There is a question as to whether the wide availability of these products actually influenced women's decisions to discontinue breast feeding.

  16. 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. PMID:25624022

  17. 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.

  18. The ion channel TRPV1 regulates the activation and proinflammatory properties of CD4+ T cells

    PubMed Central

    Bertin, Samuel; Aoki-Nonaka, Yukari; de Jong, Petrus Rudolf; Stanwood, Shawna R.; Srikanth, Sonal; Lee, Jihyung; To, Keith; Abramson, Lior; Yu, Timothy; Han, Tiffany; Touma, Ranim; Li, Xiangli; González-Navajas, José M.; Herdman, Scott; Corr, Maripat; Fu, Guo; Dong, Hui; Gwack, Yousang; Franco, Alessandra; Jefferies, Wilfred A.; Raz, Eyal

    2016-01-01

    TRPV1 is a Ca2+-permeable channel mostly studied as a pain receptor in sensory neurons. However, its role in other cell types is poorly understood. Here, we demonstrate that TRPV1 is functionally expressed in CD4+ T cells where it acts as a non-store-operated Ca2+ channel and contributes to T cell receptor (TCR)-induced Ca2+ influx, TCR signaling and T cell activation. In models of T cell-mediated colitis, TRPV1 promotes colitogenic T cell responses and intestinal inflammation. Furthermore, genetic and pharmacological inhibition of TRPV1 in human CD4+ T cells recapitulates the phenotype of murine Trpv1−/− CD4+ T cells. These findings suggest that TRPV1 inhibition could represent a new therapeutic strategy to restrain proinflammatory T cell responses. PMID:25282159

  19. CCL2 Increases X4-tropic HIV-1 Entry into Resting CD4+ T Cells*

    PubMed Central

    Campbell, Grant R.; Spector, Stephen A.

    2008-01-01

    During human immunodeficiency virus type 1 (HIV-1) infection, there is a strong positive correlation between CCL2 levels and HIV viral load. To determine whether CCL2 alters HIV-1 infection of resting CD4+ T cells, we infected purified resting CD4+ T cells after incubation with CCL2. We show that CCL2 up-regulates CXCR4 on resting CD4+ T cells in a CCR2-dependent mechanism, and that this augmentation of CXCR4 expression by CCL2 increases the ability of these cells to be chemoattracted to CXCR4 using gp120 and renders them more permissive to X4-tropic HIV-1 infection. Thus, CCL2 has the capacity to render a large population of lymphocytes more susceptible to HIV-1 late in the course of infection. PMID:18784079

  20. CD1-restricted CD4+ T cells in major histocompatibility complex class II-deficient mice

    PubMed Central

    1995-01-01

    Rather unexpectedly, major histocompatibility complex class II- deficient mice have a significant population of peripheral CD4+ T lymphocytes. We have investigated these cells at the population and clonal levels. CD4+ T lymphocytes from class II-deficient animals are thymically derived, appear early in ontogeny, exhibit the phenotype of resting memory cells, are potentially functional by several criteria, and have a diverse T cell receptor repertoire. They do not include substantially elevated numbers of NK1.1+ cells. Hybridomas derived after polyclonal stimulation of the CD4+ lymphocytes from class II- deficient animals include a subset with an unusual reactivity pattern, responding to splenocytes from many mouse strains including the strain of origin. Most members of this subset recognize the major histocompatibility complex class Ib molecule CD1; their heterogeneous reactivities and T cell receptor usage further suggest the involvement of peptides and/or highly variable posttranslational modifications. PMID:7561702

  1. CD4+ T cell anergy prevents autoimmunity and generates regulatory T cell precursors

    PubMed Central

    Kalekar, Lokesh A.; Schmiel, Shirdi E.; Nandiwada, Sarada L.; Lam, Wing Y.; Barsness, Laura O.; Zhang, Na; Stritesky, Gretta L.; Malhotra, Deepali; Pauken, Kristen E.; Linehan, Jonathan L.; O’Sullivan, M. Gerard; Fife, Brian T.; Hogquist, Kristin A.; Jenkins, Marc K.; Mueller, Daniel L.

    2015-01-01

    The role that anergy, an acquired state of T cell functional unresponsiveness, plays in natural peripheral tolerance remains unclear. In this study, we demonstrate that anergy is selectively induced in fetal antigen-specific maternal CD4+ T cells during pregnancy. A naturally occurring subpopulation of anergic polyclonal CD4+ T cells, enriched in self antigen-specific T cell receptors, is also observed in healthy hosts. Neuropilin-1 expression in anergic conventional CD4+ T cells is associated with thymic regulatory T cell (Treg cell)-related gene hypomethylation, and this correlates with their capacity to differentiate into Foxp3+ Treg cells that suppress immunopathology. Thus, our data suggest that not only is anergy induction important in preventing autoimmunity, but it also generates the precursors for peripheral Treg cell differentiation. PMID:26829766

  2. Antigens for CD4 and CD8 T Cells in Tuberculosis

    PubMed Central

    Lindestam Arlehamn, Cecilia S.; Lewinsohn, David; Sette, Alessandro; Lewinsohn, Deborah

    2014-01-01

    Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis (MTB), represents an important cause of morbidity and mortality worldwide for which an improved vaccine and immunodiagnostics are urgently needed. CD4+ and CD8+ T cells play an important role in host defense to TB. Definition of the antigens recognized by these T cells is critical for improved understanding of the immunobiology of TB and for development of vaccines and diagnostics. Herein, the antigens and epitopes recognized by classically HLA class I– and II–restricted CD4+ and CD8+ T cells in humans infected with MTB are reviewed. Immunodominant antigens and epitopes have been defined using approaches targeting particular TB proteins or classes of proteins and by genome-wide discovery approaches. Antigens and epitopes recognized by classically restricted CD4+ and CD8+ T cells show extensive breadth and diversity in MTB-infected humans. PMID:24852051

  3. Thymic Atrophy and Apoptosis of CD4+CD8+ Thymocytes in the Cuprizone Model of Multiple Sclerosis

    PubMed Central

    Talaber, Gergely; Veto, Sara; Acs, Peter; Gallyas, Ferenc; Illes, Zsolt; Fekete, Katalin; Zalan, Petra; Szanto, Arpad; Bognar, Zita

    2015-01-01

    Previous studies on the degenerative animal model of multiple sclerosis suggested that the copper-chelator cuprizone might directly suppress T-cell functions. Peripheral T-cell function in the cuprizone model has already been explored; therefore, in the present study, we investigated, for the first time, how cuprizone feeding affects the thymus, the organ of T-cell maturation and selection. We found that even one week of cuprizone treatment induced significant thymic atrophy, affecting the cortex over the medulla. Fluorescent microscopy and flow-cytometric analyses of thymi from cuprizone- and vehicle-treated mice indicated that eradication of the cluster of the differentiation-4 (CD4)-CD8 double-positive T-cell subset was behind the substantial cell loss. This result was confirmed with CD3-CD4-CD8 triple-staining experiments. Ultrastructurally, we observed degraded as well as enlarged mitochondria, myelin-bodies, large lipid droplets, and large lysosomes in the thymi of cuprizone-treated mice. Some of these features were similar to those in physiological and steroid-induced accelerated aging. According to our results, apoptosis was mainly of mitochondrial origin mediated by both caspase-3- and apoptosis inducing factor-mediated mechanisms. Additionally, mitogen activated protein kinase activation and increased pro-apoptotic B cell lymphoma-2 family protein expression were the major underlying processes. Our results do not indicate a functional relationship between cuprizone-induced thymus involution and the absence of inflammatory responses or the selective demyelination observed in the cuprizone model. On the other hand, due to the reversible nature of cuprizone’s deleterious effects, the cuprizone model could be valuable in studying thymus regeneration as well as remyelination processes. PMID:26053248

  4. Characterizing the dynamics of CD4+ T cell priming within a lymph node1

    PubMed Central

    Linderman, Jennifer J.; Riggs, Thomas; Pande, Manjusha; Miller, Mark; Marino, Simeone; Kirschner, Denise E.

    2011-01-01

    Generating adaptive immunity after infection or immunization requires physical interaction within a lymph node (LN) T-zone between antigen-bearing dendritic cells (DCs) and rare cognate T cells. Many fundamental questions remain regarding the dynamics of DC-CD4+ T cell interactions leading to priming. For example, it is not known how the production of primed CD4+ T cells relates to the numbers of cognate T cells, antigen-bearing DCs, or peptide-MHCII level on the DC. To address these questions, we developed an agent-based model of a LN to examine the relationships among cognate T cell frequency, DC density, parameters characterizing DC-T interactions and the output of primed T cells. We found that the output of primed CD4+ T cells is linearly related to cognate frequency, but non-linearly related to the number of antigen-bearing DCs present during infection. This addresses the applicability of two photon microscopy studies to understanding actual infection dynamics, as these types of experiments increase the cognate frequency by orders of magnitude as compared to physiologic levels. We found a trade-off between the quantity of peptide-MHCII on the surface of individual DCs and number of antigen-bearing DCs present in the LN in contributing to the production of primed CD4+ T cells. Interestingly, pMHCII half-life plays a minor, although still significant, role in determining CD4+ T cell priming, unlike the primary role that has been suggested for CD8+ T cell priming. Finally, we identify several pathogen-targeted mechanisms that, if altered in their efficiency, can significantly effect the generation of primed CD4+ T cells. PMID:20154206

  5. CD4-Mimetic Small Molecules Sensitize Human Immunodeficiency Virus to Vaccine-Elicited Antibodies

    PubMed Central

    Madani, Navid; Princiotto, Amy M.; Schön, Arne; LaLonde, Judith; Feng, Yu; Freire, Ernesto; Park, Jongwoo; Courter, Joel R.; Jones, David M.; Robinson, James; Liao, Hua-Xin; Moody, M. Anthony; Permar, Sallie; Haynes, Barton; Smith, Amos B.; Wyatt, Richard

    2014-01-01

    ABSTRACT Approaches to prevent human immunodeficiency virus (HIV-1) transmission are urgently needed. Difficulties in eliciting antibodies that bind conserved epitopes exposed on the unliganded conformation of the HIV-1 envelope glycoprotein (Env) trimer represent barriers to vaccine development. During HIV-1 entry, binding of the gp120 Env to the initial receptor, CD4, triggers conformational changes in Env that result in the formation and exposure of the highly conserved gp120 site for interaction with the coreceptors, CCR5 and CXCR4. The DMJ compounds (+)-DMJ-I-228 and (+)-DMJ-II-121 bind gp120 within the conserved Phe 43 cavity near the CD4-binding site, block CD4 binding, and inhibit HIV-1 infection. Here we show that the DMJ compounds sensitize primary HIV-1, including transmitted/founder viruses, to neutralization by monoclonal antibodies directed against CD4-induced (CD4i) epitopes and the V3 region, two gp120 elements involved in coreceptor binding. Importantly, the DMJ compounds rendered primary HIV-1 sensitive to neutralization by antisera elicited by immunization of rabbits with HIV-1 gp120 cores engineered to assume the CD4-bound state. Thus, small molecules like the DMJ compounds may be useful as microbicides to inhibit HIV-1 infection directly and to sensitize primary HIV-1 to neutralization by readily elicited antibodies. IMPORTANCE Preventing HIV-1 transmission is a priority for global health. Eliciting antibodies that can neutralize many different strains of HIV-1 is difficult, creating problems for the development of a vaccine. We found that certain small-molecule compounds can sensitize HIV-1 to particular antibodies. These antibodies can be elicited in rabbits. These results suggest an approach to prevent HIV-1 sexual transmission in which a virus-sensitizing microbicide is combined with a vaccine. PMID:24696475

  6. Pattern of CD4 T-lymphocyte Values in Cancer Patients on Cytotoxic Therapy

    PubMed Central

    Madu, AJ; Ocheni, S; Ibegbulam, OG; Aguwa, EN; Madu, KA

    2013-01-01

    Background: Assessment of patients prior to cytotoxic chemotherapy usually includes absolute neutrophils count. Other cellular markers of susceptibility to infection as well as immunocompetence include the T Helper lymphocyte count. In cancer patients, decrease in these lymphocytes has been observed to be associated with decreased overall survival. Aim: To assess the degree of CD4 lymphopenia encountered during cytotoxic chemotherapeutic treatment for cancer and evaluate the differences observed for the various drug combinations. Subjects and Methods: Eighty patients with various histologically diagnosed malignancies had their CD4 lymphocyte counts carried out at days 0 and 12 of the first cycle of their various chemotherapeutic regimens. They were adult patients who had been diagnosed with breast cancer 36/80 cases (45%), non-Hodgkin's lymphoma 8/80 cases (10%), Hodgkin's lymphoma 13/80 cases (16.3%), multiple myeloma 7/80 cases (8.8%), colorectal carcinoma 6/80 cases (7.5%), and other malignancies 10/80 cases (12.5%). CD4 lymphocyte count was done using the Partec Cyflow® 2000 CD4 cell counter, and their socio-demographic data of the patients were assessed using a questionnaire. Results: The mean (sd) CD4 lymphocyte count pre- and post-chemotherapy was observed to be 567 (341) cells/μLand 349 (207) cells/μL while the median values were 454 cells/μLand 349 cells/μL respectively. There were significant differences in CD4 lymphocyte counts after chemotherapy compared to the pre-chemotherapy values. Conclusion: Epirubicin combinations used in breast cancer patients as well as (Adriamycin, Bleomycin, Vinblastine, Dacarbazine) ABVD regimen used in treatment of Hodgkin's lymphoma were found to be significantly less lymphotoxic than other chemotherapeutic combinations. These drugs or their combinations may be less immunotoxic than other known regimen used for these malignancies. PMID:24379998

  7. Differential role of CD4+ cells in the sensitization and effector phases of accelerated graft rejection.

    PubMed

    Sablinski, T; Sayegh, M H; Hancock, W W; Kut, J P; Kwok, C A; Milford, E L; Tilney, N L; Kupiec-Weglinski, J W

    1991-01-01

    Although CD4-targeted therapy markedly prolongs survival of organ allografts in naive rodents, its effects in primed hosts have not been studied. In our model of accelerated rejection (ACCR) of cardiac Tx in rats, treatment with BWH-4, a CD4 mAb (IgG2a), in the sensitization (between skin and heart Tx) but not in the effector (after cardiac Tx) phase, abrogated fulminant less than 36 hr rejection response and prolonged Tx survival to ca. 11 days. This effect correlated with decreased frequency of circulating CD4+ cells, but it did not depend upon their total depletion. It was also related to BWH-4 mAb-mediated elimination/depression of strong anti-donor humoral responses and cellular responses as determined by lymphocyte-mediated cytotoxicity and mixed lymphocyte reaction and mounted otherwise at the time of engraftment by untreated sensitized hosts. Immunoperoxidase studies of cardiac Tx from BWH-4-conditioned recipients revealed reduced T and B cell activities, reflected in abolition/reduction in deposition of humoral mediators, infiltrating cells, intra-Tx elaboration of interleukin-2 and interferon-gamma, and cell activation. This first report of the successful use of CD4 mAb in sensitized recipients of vascularized organ Tx, stresses the role of CD4+ cells as potential targets for immunosuppression in the sensitization phase of accelerated Tx injury. The beneficial therapeutic effect, probably due to both depletion and functional inhibition of CD4+ T cells, has been achieved by using relatively low doses of BWH-4 mAb. PMID:1824805

  8. CD4+ CD31+ recent thymic emigrants in CHD7 haploinsufficiency (CHARGE syndrome): a case.

    PubMed

    Assing, Kristian; Nielsen, Christian; Kirchhoff, Maria; Madsen, Hans O; Ryder, Lars P; Fisker, Niels

    2013-09-01

    Lymphocyte counts <2000 cells/μL are associated with early death in infants with CHARGE (Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies/deafness) syndrome and CHD7 haploinsufficiency. Absence of recent thymic emigrants is also accompanied by an Omenn-like syndrome and infant death in CHD7 haploinsufficiency. Studies positively identifying recent thymic emigrants, in relation to CHD7 haploinsufficiency, are non-existent. Thirty two months of flow-cytometric work-up of an athymic (evaluated by four chest X-rays) infant, with a novel CHD7 deletion, demonstrated sparse (<50 cells/mm(3)) but continuous egress of recent thymic emigrants (CD3(+) CD4(+) CD45RA(+) CD45RO(-) CD31(+)) and homeostatic lymphocyte expansion. Infectious or autoimmune episodes (e.g., Omenn-like syndrome) were not detected (despite lymphocyte counts <2000 cells/μL) and excellent vaccination (tetanus, Haemophilus influenzae type B and pneumococcal conjugate vaccines) and proliferation (anti-CD3 and anti-CD28 stimulated) responses were recorded. Her CD4(+) T cells displayed Gaussian distributed TCR (CDR3) spectratypes (22 functional Vβ families). Her CD4(+) T cell profile was also characterized by a slightly increased proportion CD4(+) CD25(+) FoxP3(+) T cells. Since CD3(+) CD4(+) CD45RA(+) CD45RO(-) CD31(+) RTE are reported to be TCR diverse and to contain regulatory T cells, we found it important to report that continuously reduced numbers of CD3(+) CD4(+) CD45RA(+) CD45RO(-) CD31(+) RTE, in the context of CHD7 haploinsufficiency and despite severe lymphopenia, is consistent with an uneventful clinical outcome.

  9. New Insights into the Generation of CD4 Memory May Shape Future Vaccine Strategies for Influenza

    PubMed Central

    Devarajan, Priyadharshini; Bautista, Bianca; Vong, Allen M.; McKinstry, Karl Kai; Strutt, Tara M.; Swain, Susan L.

    2016-01-01

    Influenza viral evolution presents a formidable challenge to vaccination due to the virus’ ability to rapidly mutate to evade immune responses. Live influenza infections generate large and diverse CD4 effector T cell responses that yield highly protective, long-lasting CD4 T cell memory that can target conserved viral epitopes. We review advances in our understanding of mechanisms involved in generating CD4 T cell responses against the influenza A virus (IAV), focusing on specialized follicular helper (TFH) and CD4 cytotoxic (ThCTL) effector subsets and on CD4 T cell memory. We also discuss two recent findings in context of enhancing vaccine responses. First, helper T cells require priming with APC secreting high levels of IL-6. Second, the transition of IAV-generated effectors to memory depends on IL-2, costimulation and antigen signals, just before effectors reach peak numbers, defined as the “memory checkpoint.” The need for these signals during the checkpoint could explain why many current influenza vaccines are poorly effective and elicit poor cellular immunity. We suggest that CD4 memory generation can be enhanced by re-vaccinating at this time. Our best hope lies in a universal vaccine that will not need to be formulated yearly against seasonal antigenically novel influenza strains and will also be protective against a pandemic strain. We suggest a vaccine approach that elicits a powerful T cell response, by initially inducing high levels of APC activation and later providing antigen at the memory checkpoint, may take us a step closer to such a universal influenza vaccine. PMID:27148257

  10. Aire-Overexpressing Dendritic Cells Induce Peripheral CD4⁺ T Cell Tolerance.

    PubMed

    Li, Dongbei; Li, Haijun; Fu, Haiying; Niu, Kunwei; Guo, Yantong; Guo, Chuan; Sun, Jitong; Li, Yi; Yang, Wei

    2015-12-29

    Autoimmune regulator (Aire) can promote the ectopic expression of peripheral tissue-restricted antigens (TRAs) in thymic medullary epithelial cells (mTECs), which leads to the deletion of autoreactive T cells and consequently prevents autoimmune diseases. However, the functions of Aire in the periphery, such as in dendritic cells (DCs), remain unclear. This study's aim was to investigate the effect of Aire-overexpressing DCs (Aire cells) on the functions of CD4⁺ T cells and the treatment of type 1 diabetes (T1D). We demonstrated that Aire cells upregulated the mRNA levels of the tolerance-related molecules CD73, Lag3, and FR4 and the apoptosis of CD4⁺ T cells in STZ-T1D mouse-derived splenocytes. Furthermore, following insulin stimulation, Aire cells decreased the number of CD4⁺ IFN-γ⁺ T cells in both STZ-T1D and WT mouse-derived splenocytes and reduced the expression levels of TCR signaling molecules (Ca(2+) and p-ERK) in CD4⁺ T cells. We observed that Aire cells-induced CD4⁺ T cells could delay the development of T1D. In summary, Aire-expressing DCs inhibited TCR signaling pathways and decreased the quantity of CD4⁺IFN-γ⁺ autoreactive T cells. These data suggest a mechanism for Aire in the maintenance of peripheral immune tolerance and provide a potential method to control autoimmunity by targeting Aire.

  11. A quartz nanopillar hemocytometer for high-yield separation and counting of CD4+ T lymphocytes

    NASA Astrophysics Data System (ADS)

    Kim, Dong-Joo; Seol, Jin-Kyeong; Wu, Yu; Ji, Seungmuk; Kim, Gil-Sung; Hyung, Jung-Hwan; Lee, Seung-Yong; Lim, Hyuneui; Fan, Rong; Lee, Sang-Kwon

    2012-03-01

    We report the development of a novel quartz nanopillar (QNP) array cell separation system capable of selectively capturing and isolating a single cell population including primary CD4+ T lymphocytes from the whole pool of splenocytes. Integrated with a photolithographically patterned hemocytometer structure, the streptavidin (STR)-functionalized-QNP (STR-QNP) arrays allow for direct quantitation of captured cells using high content imaging. This technology exhibits an excellent separation yield (efficiency) of ~95.3 +/- 1.1% for the CD4+ T lymphocytes from the mouse splenocyte suspensions and good linear response for quantitating captured CD4+ T-lymphoblasts, which is comparable to flow cytometry and outperforms any non-nanostructured surface capture techniques, i.e. cell panning. This nanopillar hemocytometer represents a simple, yet efficient cell capture and counting technology and may find immediate applications for diagnosis and immune monitoring in the point-of-care setting.We report the development of a novel quartz nanopillar (QNP) array cell separation system capable of selectively capturing and isolating a single cell population including primary CD4+ T lymphocytes from the whole pool of splenocytes. Integrated with a photolithographically patterned hemocytometer structure, the streptavidin (STR)-functionalized-QNP (STR-QNP) arrays allow for direct quantitation of captured cells using high content imaging. This technology exhibits an excellent separation yield (efficiency) of ~95.3 +/- 1.1% for the CD4+ T lymphocytes from the mouse splenocyte suspensions and good linear response for quantitating captured CD4+ T-lymphoblasts, which is comparable to flow cytometry and outperforms any non-nanostructured surface capture techniques, i.e. cell panning. This nanopillar hemocytometer represents a simple, yet efficient cell capture and counting technology and may find immediate applications for diagnosis and immune monitoring in the point-of-care setting

  12. Maternal practices of baby feeding and hygiene in the city of Ludhiana, Punjab, India.

    PubMed

    Hubbard, C

    1978-10-01

    66 mothers with children aged between 12-24 months were interviewed with a questionnaire in the industrial city of Lubhiana. The average age of the mothers ranged from 18-45 years. 66% were between 21-30; 39% had only 1 living child. 41% of the children were well nourished; were third degree malnourished. 91% were breast fed from birth. 30% mothers gave milk top feeds from birth; the additional milk was fresh buffalo (84%). The milk was boiled in 100% of cases and the water diluting the feeds was boiled in 46% cases. The water was added before the milk was boiled. 5% of mothers washed the bottle with water alone; 30% washed with an abrasive such as sand or ash. 49% never boiled the feeding bottle; 33% boiled the bottle once a day, and 18% boiled it before each feed. 23% claimed no incident or vomiting or diarrhoea, 26% admitted 1-2 incidents of vomiting or diarrhoea; 21% less than monthly bouts; 12% more than monthly bouts; and 18% admitted to weekly or more incidents of diarrhoea and vomiting. Deaths in rural India in the under age 5 group are attributed to malnutrition in 5% of cases.

  13. 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.

  14. Assessment of knowledge, attitudes and practices of infant feeding in the context of HIV: a case study from western Kenya.

    PubMed

    Wachira, J; Otieno-Nyunya, B; Ballidawa, J; Braitstein, P

    2009-11-01

    Guidelines for infant feeding options among HIV-positive mothers are changing with informative research. Cultural factors, socialisation processes, gender dimensions and socio-economic status within communities should be considered in recommending feasible and sustainable options. The objective of this study was to assess the knowledge, attitudes and practices with regards to infant feeding in the context of HIV. A cross-sectional study was conducted between November 2003 and January 2004. The study was carried out in Kosirai Division, Nandi-North District, in western Kenya. The target population was community members aged 18 - 45 years and key informants aged 18 years and above. Structured questionnaires and in-depth interviews were used to collect data. Multistage and snowball sampling methods were used to identify study participants. Quantitative data were analysed using the SPSS statistical package for social scientists (Version 12). Cross-tabulations were calculated and Pearson's chi-square test used to test significance of relationships between categorical variables. Recorded qualitative data were transcribed and coded. Themes were developed and integrated. A generation of concepts was used to organise the presentation into summaries, interpretations and text. A total of 385 individuals participated in the survey, 50% of whom were women. There were 30 key informants. Farming was the main source of income but half of the women (49.7% ) had no income. Most of the respondents (85.5% ) knew of breastfeeding as a route of HIV transmission with sex (p=0.003) and age (p=0.000) being highly associated with this knowledge. Breastfeeding was the norm although exclusive breastfeeding was not practised. Cow's milk, the main breast milk substitute, was reported as being given to infants as early as two weeks. It was the most popular (93.5% ) infant feeding option in the context of HIV/AIDS. Heating expressed milk, wet nursing and milk banks were least preferred. Thus, the

  15. Differential human immunodeficiency virus expression in CD4+ cloned lymphocytes: from viral latency to replication.

    PubMed Central

    Chapel, A; Bensussan, A; Vilmer, E; Dormont, D

    1992-01-01

    By using cloning methodology, 13 CD4+, CD8-, CD45RO+, and CD29+ clones, isolated from human immunodeficiency virus (HIV)-negative donors, have been characterized and tested regarding their susceptibility to two strains of HIV type 1 (HIV-1). Infected clones possess integrated provirus. Only six are able to replicate HIV-1, while seven may normally grow without cytopathic effect and without viral replication. These results argue that all CD4+ lymphocyte clones may be infectable but that a heterogeneity exists regarding their abilities to replicate HIV-1. Images PMID:1374814

  16. Differential human immunodeficiency virus expression in CD4+ cloned lymphocytes: from viral latency to replication.

    PubMed

    Chapel, A; Bensussan, A; Vilmer, E; Dormont, D

    1992-06-01

    By using cloning methodology, 13 CD4+, CD8-, CD45RO+, and CD29+ clones, isolated from human immunodeficiency virus (HIV)-negative donors, have been characterized and tested regarding their susceptibility to two strains of HIV type 1 (HIV-1). Infected clones possess integrated provirus. Only six are able to replicate HIV-1, while seven may normally grow without cytopathic effect and without viral replication. These results argue that all CD4+ lymphocyte clones may be infectable but that a heterogeneity exists regarding their abilities to replicate HIV-1.

  17. Implementation and Operational Research: CD4 Count Monitoring Frequency and Risk of CD4 Count Dropping Below 200 Cells Per Cubic Millimeter Among Stable HIV-Infected Patients in New York City, 2007–2013

    PubMed Central

    Xia, Qiang; Torian, Lucia V.; Irvine, Mary; Harriman, Graham; Sepkowitz, Kent A.; Shepard, Colin W.

    2016-01-01

    Introduction: The evidence has begun to mount for diminishing the frequency of CD4 count testing. To determine whether these observations were applicable to an urban US population, we used New York City (NYC) surveillance data to explore CD4 testing among stable patients in NYC, 2007–2013. Methods: We constructed a population-based retrospective open cohort analysis of NYC HIV surveillance data. HIV+ patients aged ≥13 years with stable viral suppression (≥1 viral load the previous year; all <400 copies per milliliter) and immune status (≥1 CD4 the previous year; all ≥200 cells per cubic millimeter) entered the cohort the following year beginning January 1, 2007. Each subsequent year, eligible patients not previously included entered the cohort on January 1. Outcomes were annual frequency of CD4 monitoring and probability of maintaining CD4 ≥200 cells per cubic millimeter. A multivariable Cox model identified factors associated with maintaining CD4 ≥200 cells per cubic millimeter. Results: During 1.9 years of observation (median), 62,039 patients entered the cohort. The mean annual number of CD4 measurements among stable patients was 2.8 and varied little by year or characteristic. Two years after entering, 93.4% and 97.8% of those with initial CD4 350–499 and CD4 ≥500 cells per cubic millimeter, respectively, maintained CD4 ≥200 cells per cubic millimeter. Compared to those with initial CD4 ≥500 cells per cubic millimeter, those with CD4 200–349 cells per cubic millimeter and CD4 350–499 cells per cubic millimeter were more likely to have a CD4 <200 cells per cubic millimeter, controlling for sex, race, age, HIV risk group, and diagnosis year. Conclusions: In a population-based US cohort with well-controlled HIV, the probability of maintaining CD4 ≥200 cells per cubic millimeter for ≥2 years was >90% among those with initial CD4 ≥350 cells per cubic millimeter, suggesting that limited CD4 monitoring in these patients is appropriate

  18. Crystal structure of a complete ternary complex of T-cell receptor, peptide-MHC, and CD4

    SciTech Connect

    Yin, Yiyuan; Wang, Xin Xiang; Mariuzza, Roy A

    2012-07-11

    Adaptive immunity depends on specific recognition by a T-cell receptor (TCR) of an antigenic peptide bound to a major histocompatibility complex (pMHC) molecule on an antigen-presenting cell (APC). In addition, T-cell activation generally requires binding of this same pMHC to a CD4 or CD8 coreceptor. Here, we report the structure of a complete TCR-pMHC-CD4 ternary complex involving a human autoimmune TCR, a myelin-derived self-peptide bound to HLA-DR4, and CD4. The complex resembles a pointed arch in which TCR and CD4 are each tilted ~65° relative to the T-cell membrane. By precluding direct contacts between TCR and CD4, the structure explains how TCR and CD4 on the T cell can simultaneously, yet independently, engage the same pMHC on the APC. The structure, in conjunction with previous mutagenesis data, places TCR-associated CD3εγ and CD3εδ subunits, which transmit activation signals to the T cell, inside the TCR-pMHC-CD4 arch, facing CD4. By establishing anchor points for TCR and CD4 on the T-cell membrane, the complex provides a basis for understanding how the CD4 coreceptor focuses TCR on MHC to guide TCR docking on pMHC during thymic T-cell selection.

  19. Immunization of simian immunodeficiency virus-infected rhesus monkeys with soluble human CD4 elicits an antiviral response.

    PubMed Central

    Watanabe, M; Levine, C G; Shen, L; Fisher, R A; Letvin, N L

    1991-01-01

    Since the CD4 molecule is a high-affinity cell-surface receptor for the human immunodeficiency virus (HIV), it has been suggested that a soluble truncated form of CD4 may compete with cell-surface CD4 for HIV binding and thus be of use in the therapy of AIDS. We have utilized the simian immunodeficiency virus of macaques (SIVmac)-infected rhesus monkeys to explore another possible therapeutic application of CD4 in AIDS--the use of recombinant soluble CD4 (rsCD4) as an immunogen. SIVmac-infected rhesus monkeys immunized with human rsCD4 developed not only an anti-human CD4 but also an anti-rhesus monkey CD4 antibody response. Coincident with the generation of this antibody response, SIVmac could not be isolated easily from peripheral blood lymphocytes and bone marrow macrophages of these animals. Furthermore, the decreased number of both granulocyte/macrophage and erythrocyte colonies grown from the bone marrow of these immunized monkeys rose to normal levels. These findings suggest that a modified human CD4 molecule serving as an immunogen might elicit an antibody response in man that could induce a beneficial therapeutic response in HIV-infected individuals. PMID:2052546

  20. Impaired CD4+CD25+ regulatory T cell activity in the peripheral blood of patients with autoimmune sensorineural hearing loss.

    PubMed

    Xia, Ming; Zhang, Han Bing; Liu, Fang; Yin, Hai Ying; Xu, An Ting

    2008-09-01

    CD4+CD25+ regulatory T cells exert an immune regulatory function and thus play an important role in the control of self-reactivity in the pathogenesis of autoimmune inflammatory conditions. The aim of the study presented here is to perform a quantitative and functional analyses of these cells in patients with autoimmune sensorineural hearing loss (ASNHL). T cell subsets (CD4+CD25+, CD4+CD25(high), CD4+, and CD8+) from the peripheral blood of 17 patients with ASNHL, 16 patients with noise induced hearing loss (NHL), and 100 normal controls were analyzed by flow cytometry. The CD4/CD8 ratio was also analyzed. In addition, the suppressive capability of CD4+CD25+ T cells was tested in vitro by measuring their ability to suppress the proliferation and IFN-gamma secretion of CD4+CD25- T cells. No significant difference was found in the T cell subsets of ASNHL patients compared to normal controls or NHL patients, except that the proportion of CD4+ T cells was elevated in ASNHL patients. However, we did observe defective regulatory function of CD4+CD25+ T cells in patients with ASNHL. Our data supported the idea that CD4+CD25+ regulatory T cells played an immunosuppressive function in the periphery. The impaired suppressive activity of these cells may be an important factor in the pathogenesis of ASNHL.

  1. Antiretroviral therapy suppressed participants with low CD4+ T-cell counts segregate according to opposite immunological phenotypes

    PubMed Central

    Pérez-Santiago, Josué; Ouchi, Dan; Urrea, Victor; Carrillo, Jorge; Cabrera, Cecilia; Villà-Freixa, Jordi; Puig, Jordi; Paredes, Roger; Negredo, Eugènia; Clotet, Bonaventura; Massanella, Marta; Blanco, Julià

    2016-01-01

    Background: The failure to increase CD4+ T-cell counts in some antiretroviral therapy suppressed participants (immunodiscordance) has been related to perturbed CD4+ T-cell homeostasis and impacts clinical evolution. Methods: We evaluated different definitions of immunodiscordance based on CD4+ T-cell counts (cutoff) or CD4+ T-cell increases from nadir value (ΔCD4) using supervised random forest classification of 74 immunological and clinical variables from 196 antiretroviral therapy suppressed individuals. Unsupervised clustering was performed using relevant variables identified in the supervised approach from 191 individuals. Results: Cutoff definition of CD4+ cell count 400 cells/μl performed better than any other definition in segregating immunoconcordant and immunodiscordant individuals (85% accuracy), using markers of activation, nadir and death of CD4+ T cells. Unsupervised clustering of relevant variables using this definition revealed large heterogeneity between immunodiscordant individuals and segregated participants into three distinct subgroups with distinct production, programmed cell-death protein-1 (PD-1) expression, activation and death of T cells. Surprisingly, a nonnegligible number of immunodiscordant participants (22%) showed high frequency of recent thymic emigrants and low CD4+ T-cell activation and death, very similar to immunoconcordant participants. Notably, human leukocyte antigen - antigen D related (HLA-DR) PD-1 and CD45RA expression in CD4+ T cells allowed reproducing subgroup segregation (81.4% accuracy). Despite sharp immunological differences, similar and persistently low CD4+ values were maintained in these participants over time. Conclusion: A cutoff value of CD4+ T-cell count 400 cells/μl classified better immunodiscordant and immunoconcordant individuals than any ΔCD4 classification. Immunodiscordance may present several, even opposite, immunological patterns that are identified by a simple immunological follow-up. Subgroup

  2. Long-term increase in CD4+ T-cell counts during combination antiretroviral therapy for HIV-1 infection

    PubMed Central

    Lok, Judith J; Bosch, Ronald J; Benson, Constance A; Collier, Ann C; Robbins, Gregory K; Shafer, Robert W; Hughes, Michael D

    2010-01-01

    Objective To inform guidelines concerning when to initiate combination antiretroviral therapy (ART), we investigated whether CD4+ T-cell counts (CD4 counts) continue to increase over long periods of time on ART. Losses-to-follow-up and some patients discontinuing ART at higher CD4 counts hamper such evaluation, but novel statistical methods can help address these issues. We estimated the long-term CD4 count trajectory accounting for losses-to-follow-up and treatment discontinuations. Design The study population included 898 U.S. patients first initiating ART in a randomized trial (ACTG 384); 575 were subsequently prospectively followed in an observational study (ALLRT). Methods Inverse probability of censoring weighting statistical methods were used to estimate the CD4 count trajectory accounting for losses-to-follow-up and ART-discontinuations, overall and for pre-treatment CD4 count categories ≤ 200, 201–350, 351–500, and >500 cells/mm3. Results Median CD4 count increased from 270 cells/mm3 pre-ART to an estimated 556 at three and 532 cells/mm3 at seven years after starting ART in analyses ignoring treatment discontinuations; and to 570 and 640 cells/mm3, respectively, had all patients continued ART. However, even had ART been continued, an estimated 25%, 9%, 3% and 2% of patients with pre-treatment CD4 counts of ≤ 200, 201–350, 351–500, and >500 cells/mm3 would have had CD4 counts ≤350 cells/mm3 after seven years. Conclusions If patients remain on ART, CD4 counts increase in most patients for at least seven years. However, the substantial percentage of patients starting therapy at low CD4 counts who still had low CD4 counts after seven years provides support for ART initiation at higher CD4 counts. PMID:20467286

  3. 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.

  4. 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

  5. Assessment of health and nutritional status of infants in relation to breast feeding practices in Karmouz area, Alexandria.

    PubMed

    Deghedi, B; Mahdy, N H; Abd, el-A H

    1999-01-01

    Infants are most precious part of nation's life. Infant health is a reflection of the health of the mother and it gives an indication of the health of the adult population of the future. The present work was designed to study the health and nutritional status of infants in Karmouz area in Alexandria as well as the effect of breast feeding practices on the health status of infants. Accordingly, a house to house survey was conducted through cluster sampling technique. The total sample amounted to 396 mothers and 409 infants. Data were collected about infants health status and their feeding practices. Weight and length were measured for all infants. Stool samples were collected and