RESUMO
BACKGROUND/OBJECTIVES: Growing evidence suggests that antibiotic use is associated with childhood body mass index (BMI), potentially via mechanisms mediated by gut microbiome alterations. Less is known on the potential role of prenatal antimicrobial use in offspring obesity risk. We examined whether prenatal antibiotic or antifungal use was associated with BMI at the age of 2 years in 527 birth cohort participants. METHODS/SUBJECTS: Antimicrobial use was obtained from the prenatal medical record. Height and weight were measured at the age of 2 years. Overweight/obesity was defined as a BMI ⩾85th percentile. RESULTS: A total of 303 (57.5%) women used antibiotics and 101 (19.2%) used antifungals during pregnancy. Prenatal antifungal use was not associated with child BMI at the age of 2 years. In the fully adjusted model, prenatal antibiotic use was associated with a 0.20±0.10 (P=0.046) higher mean BMI Z-score at the age of 2 years. Associations between prenatal antibiotic use and childhood BMI varied by trimester of exposure, with first or second-trimester exposure more strongly associated with larger BMI at the age of 2 years for both BMI Z-score (interaction P=0.032) and overweight/obesity (interaction P=0.098) after covariate adjustment. CONCLUSIONS: Prenatal antibiotic, but not antifungal, use is associated with larger BMI at the age of 2 years; associations were stronger for antibiotic exposures in earlier trimesters. Future studies examining whether these associations are due to alterations in the maternal and/or infant microbiome are necessary. Children who are overweight at the age of 2 years are at higher risk for being overweight as they age; prenatal antibiotic use is a potentially modifiable exposure that could reduce childhood obesity.
Assuntos
Antibacterianos , Índice de Massa Corporal , Sobrepeso/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Cuidado Pré-Natal , Fatores de RiscoRESUMO
Research has largely reported that dog exposure is associated with reduced allergic disease risk. Responsible mechanism(s) are not understood. The goal was to investigate whether introducing a dog into the home changes the home dust microbiota. Families without dogs or cats planning to adopt a dog and those who were not were recruited. Dust samples were collected from the homes at recruitment and 12 months later. Microbiota composition and taxa (V4 region of the 16S rRNA gene) were compared between homes that did and did not adopt a dog. A total of 91 dust samples from 54 families (27 each, dog and no dog; 17 dog and 20 no dog homes with paired samples) were analyzed. A significant dog effect was seen across time in both unweighted UniFrac and Canberra metrics (both P = .008), indicating dog introduction may result in rapid establishment of rarer and phylogenetically related taxa. A significant dog-time interaction was seen in both weighted UniFrac (P < .001) and Bray-Curtis (P = .002) metrics, suggesting that while there may not initially be large relative abundance shifts following dog introduction, differences can be seen within a year. Therefore, dog introduction into the home has both immediate effects and effects that emerge over time.
Assuntos
Microbiologia do Ar , Poluição do Ar em Ambientes Fechados/análise , Cães/microbiologia , Poeira/análise , Microbiota , Animais , Monitoramento Ambiental , Habitação , Humanos , Hipersensibilidade/etiologia , Hipersensibilidade/microbiologiaRESUMO
BACKGROUND: The effect of dog exposure on the risk of children developing allergic disease remains controversial. Many analyses have not considered that associations may vary within population subgroups. OBJECTIVE: To examine whether associations between living with a dog in the first year of life and allergic outcomes vary within subgroups selected a priori (race, gender and delivery mode). METHODS: Black (n = 496) and White (n = 196) children enrolled in the WHEALS birth cohort study had a clinical examination at age 2 years to assess eczema and allergen-specific IgE (sIgE) and perform skin prick testing (SPT). Whether the child lived with an indoor dog in the first year of life was assessed through interview, as was doctor diagnosis of asthma at ages 3-6 years. RESULTS: Living with a dog was associated with decreased odds of having ≥ 1 positive SPT (OR = 0.56, 95% CI: 0.34, 0.91) and having eczema (OR = 0.34, 95% CI: 0.20, 0.60). The association with SPT was stronger in those children born via caesarean section (c-section) vs. vaginally (OR = 0.29, 95% CI: 0.12, 0.74 vs. OR = 0.76, 95% CI: 0.43, 1.37, respectively, interaction P = 0.087) and in those who were firstborn vs. not (OR = 0.27, 95% CI: 0.11, 0.67 vs. OR = 0.82, 95% CI: 0.45, 1.47, respectively, interaction P = 0.044). The association with eczema was stronger in children born vaginally compared with those born via caesarean section (OR = 0.17, 95% CI: 0.06, 0.43 vs. OR = 0.65, 95% CI: 0.31, 1.35, respectively, interaction P = 0.025) and was stronger in Black vs. White children (OR = 0.30, 95% CI: 0.15, 0.61 vs. OR = 0.78, 95% CI: 0.29, 2.11, respectively, interaction P = 0.12). Dog keeping was not significantly inversely associated with having ≥ 1 elevated sIgE and only approached statistical significance with asthma. CONCLUSIONS AND CLINICAL RELEVANCE: Results likely vary between studies due to variability of specific exposure-outcome associations in subgroups defined by other factors as well as the relative distributions of those subgroups. Important allergic disorder associations will be missed without subgroup analyses.
Assuntos
Exposição Ambiental , Hipersensibilidade/epidemiologia , Hipersensibilidade/imunologia , Animais de Estimação/imunologia , Adulto , Fatores Etários , Alérgenos/imunologia , Animais , Cães , Feminino , Humanos , Hipersensibilidade/diagnóstico , Imunoglobulina E/imunologia , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Razão de Chances , Gravidez , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: There is emerging evidence suggesting the role of peripheral blood leukocytes in the pathogenesis of obesity and related diseases. However, few studies have taken a genome-wide approach to investigating gene expression profiles in peripheral leukocytes between obese and lean individuals with the consideration of obesity-related shifts in leukocyte types. METHOD: We conducted this study in 95 African Americans (AAs) of both genders (age 14-20 years, 46 lean and 49 obese). Complete blood count with differential test (CBC) was performed in whole blood. Genome-wide gene expression analysis was obtained using the Illumina HumanHT-12 V4 Beadchip with RNA extracted from peripheral leukocytes. Out of the 95 participants, 64 had neutrophils stored. The validation study was based on real-time PCR with RNA extracted from purified neutrophils. RESULTS: CBC test suggested that, in males, obesity was associated with increased neutrophil percentage (P=0.03). Genome-wide gene expression analysis showed that, in males, the majority of the most differentially expressed genes were related to neutrophil activation. Validation of the gene expression levels of ELANE (neutrophil elastase) and MPO (myeloperoxidase) in purified neutrophils demonstrated that the expression of these two genes--important biomarkers of neutrophils activation--were significantly elevated in obese males (P=0.01 and P=0.02, respectively). CONCLUSION: The identification of increased neutrophil percentage and activation in obese AA males suggests that neutrophils have an essential role in the pathogenesis of obesity-related disease. Further functional and mechanistic studies on neutrophils may contribute to the development of novel intervention strategies reducing the burden associated with obesity-related health problems.
Assuntos
Negro ou Afro-Americano , Inflamação/epidemiologia , Ativação de Neutrófilo/genética , Obesidade/epidemiologia , Adolescente , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Imunidade Inata/genética , Inflamação/genética , Inflamação/imunologia , Masculino , Neutrófilos/imunologia , Obesidade/genética , Obesidade/imunologia , Reação em Cadeia da Polimerase em Tempo Real , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Separately, prenatal antibiotics and Caesarian delivery have been found to be associated with increased risk of allergic diseases. It is not clear whether these factors may modify the effect of each other. OBJECTIVE: To assess whether the associations between delivery types and eczema, sensitization and total IgE at age 2 years were modified by maternal use of prenatal medications. METHODS: Prenatal charts of women enrolled in the WHEALS birth cohort were reviewed for delivery mode and medications prescribed and administered throughout their entire pregnancy, including systemic antibiotics and vaginally applied antifungal medications. The associations between the delivery mode and select medications and, eczema, sensitization (≥ 1 of 10 allergen-specific IgE ≥ 0.35 IU/mL) and total IgE at age 2 years were assessed. RESULTS: There was a lower risk of eczema among vaginally vs. c-section born children (relative risk adjusted for race = aRR = 0.77, 95% CI 0.56, 1.05). Although not statistically significantly different, this association was stronger among the subset of children born vaginally to a mother who did not use systemic antibiotics or vaginal antifungal medications (aRR = 0.69, 95% CI 0.44, 1.08) compared to those born vaginally to mothers who used systemic antibiotics or vaginal antifungals (aRR = 0.81, 95% CI 0.57, 1.14). A protective association between vaginal birth and sensitization (aRR = 0.86, 95% CI 0.72, 1.03) was similar for those children born vaginally to a mother who did not (aRR = 0.87, 95% CI 0.69, 1.10) and who did (RR = 0.85, 95% CI 0.70, 1.04) use systemic antibiotics or vaginal antifungal medications. There were no associations with total IgE. CONCLUSIONS: Children born vaginally had lower risk of eczema and sensitization compared with those born via c-section; however, the protective association with eczema may be slightly weakened when mothers took systemic antibiotics or vaginally applied medications during pregnancy.
Assuntos
Parto Obstétrico , Eczema/epidemiologia , Eczema/etiologia , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Adulto , Fatores Etários , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/efeitos adversos , Cesárea/efeitos adversos , Pré-Escolar , Parto Obstétrico/métodos , Feminino , Humanos , Imunoglobulina E/imunologia , Masculino , Michigan/epidemiologia , Razão de Chances , Gravidez , Risco , Streptococcus agalactiae/imunologiaRESUMO
UNLABELLED: Previous studies have suggested that exposure to cats and dogs during early childhood reduces the risk of allergic disease, possibly by increasing home endotoxin exposure. This study asked the question of whether cats and dogs are the dominant influence on dust endotoxin concentrations in homes after considering other variables reportedly associated with endotoxin. The presence of cats or dogs in homes, household and home characteristics, and dust endotoxin concentrations from 5 locations were assessed in 966 urban and suburban homes. Whether considered together as pets or as cats and dogs separately, the presence of cats and dogs significantly contributed to living room and bedroom floor endotoxin concentrations, but not to bed endotoxin concentrations. However, the two variables consistently related to endotoxin in all home sites were the home occupant density (occupants/room) and cleanliness of the home. Our data suggest that reducing occupant density and improving home cleanliness would reduce home endotoxin concentrations more than removing pet cats or dogs from the home. PRACTICAL IMPLICATIONS: Many studies have shown that early childhood exposure to indoor cats or dogs is associated with a reduced risk of later allergic disease and asthma. An important question is whether alteration in allergic risk associated with cat and dog exposure results from increased endotoxin exposure or from some other associated exposure. Our findings show that cats and dogs are not the dominant source of endotoxin in homes; rather, the density of human occupation and poor cleaning contribute more consistently to higher home endotoxin concentrations especially in the beds.
Assuntos
Gatos , Cães , Poeira/análise , Endotoxinas/análise , Habitação/estatística & dados numéricos , Animais , Humanos , Michigan , Análise Multivariada , Animais de EstimaçãoRESUMO
BACKGROUND: Racial disparities in allergic disease outcomes have been reported with African Americans suffering disproportionately compared to White individuals. OBJECTIVE: To examine whether or not racial disparities are present as early as age 2 years in a racially diverse birth cohort in the Detroit metropolitan area. METHODS: All children who were participants in a birth cohort study in the Detroit metropolitan area were invited for a standardized physician exam with skin prick testing and parental interview at age 2 years. Physicians made inquiries regarding wheezing and allergy symptoms and inspected for and graded any atopic dermatitis (AD). Skin testing was performed for Alternaria, cat, cockroach, dog, Dermatophagoides farinae (Der F), Short Ragweed, Timothy grass, egg, milk and peanut. Specific IgE was measured for these same allergens and total IgE was determined. RESULTS: African American children (n = 466) were more likely than White children (n = 223) to have experienced any of the outcomes examined: at least 1 positive skin prick test from the panel of 10 allergens (21.7% vs. 11.0%, P = 0.001); at least one specific IgE ≥ 0.35 IU/mL (out of a panel of 10 allergens) (54.0% vs. 42.9%, P = 0.02); had AD (27.0% vs. 13.5%, Chi-square P < 0.001); and to ever have wheezed (44.9% vs. 36.0%, P = 0.03). African American children also tended to have higher total IgE (geometric means 23.4 IU/mL (95%CI 20.8, 27.6) vs. 16.7 IU/mL (95%CI 13.6, 20.6 IU/mL), Wilcoxon Rank Sum P = 0.004). With the exception of wheezing, the associations did not vary after adjusting for common social economic status variables (e.g. household income), environmental variables (endotoxin; dog, cat and cockroach allergen in house dust) or variables that differed between the racial groups (e.g. breastfeeding). After adjustment, the wheeze difference was ameliorated. CONCLUSIONS: With disparities emerging as early as age 2 years, investigations into sources of the disparities should include the prenatal period and early life.
Assuntos
Negro ou Afro-Americano , Hipersensibilidade/etnologia , Alérgenos/imunologia , Animais , Gatos , Estudos de Coortes , Dermatite Atópica/imunologia , Cães , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Gravidez , Sons Respiratórios/imunologia , Testes Cutâneos , População BrancaRESUMO
BACKGROUND: Prior research about whether keeping a dog or cat at home causes allergies to that pet has been limited to outcomes in early childhood. OBJECTIVE: Evaluate the association between lifetime dog and cat exposure and allergic sensitization to the specific animal at 18 years of age. METHODS: Participants enrolled in the Detroit Childhood Allergy Study birth cohort during 1987-1989 were contacted at the age 18 years. Sensitization to dog or cat was defined as animal-specific IgE ≥ 0.35 kU/L. Annual interview data from childhood and follow-up interviews at age 18 years were used to determine lifetime indoor dog and cat exposure (indoor was defined when the animal spent >50% of their time inside the house). Exposure was considered in various ways: first year, age groups and cumulative lifetime. Analyses were conducted separately for dogs and cats. RESULTS: Among males, those with an indoor dog during the first year of life had half the risk [relative risk (RR)=0.50, 95% confidence interval (CI) 0.27, 0.92] of being sensitized to dogs at age 18 compared with those who did not have an indoor dog in the first year. This was also true for males and females born via c-section (RR=0.33, 95% CI 0.07, 0.97). Overall, teens with an indoor cat in the first year of life had a decreased risk (RR=0.52, 95% CI 0.31, 0.90) of being sensitized to cats. Neither cumulative exposure nor exposure at any other particular age was associated with either outcome. CONCLUSIONS AND CLINICAL RELEVANCE: The first year of life is the critical period during childhood when indoor exposure to dogs or cats influences sensitization to these animals.
Assuntos
Alérgenos/imunologia , Gatos/imunologia , Cães/imunologia , Exposição Ambiental , Hipersensibilidade Imediata/epidemiologia , Hipersensibilidade Imediata/imunologia , Adolescente , Poluição do Ar em Ambientes Fechados/efeitos adversos , Animais , Animais Domésticos/imunologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Humanos , Hipersensibilidade Imediata/etiologia , Imunoglobulina E/sangue , Lactente , Masculino , Fatores de Risco , Testes Cutâneos , Adulto JovemRESUMO
BACKGROUND: The ability to identify potentially resistant participants early in the course of an intervention could inform development of strategies for behavior change and improve program effectiveness. OBJECTIVE: The objective of this analysis was to identify factors related to nonresponse (i.e., lack of behavior change) to an asthma management intervention for urban teenagers. The intervention targeted several behaviors, including medication adherence, having a rescue inhaler nearby, and smoking. METHODS: A discriminate analysis was conducted using data from a randomized trial of the intervention. Included in this analysis are participants who reported a physician diagnosis of asthma, completed a baseline questionnaire, were randomized to the treatment group, completed >or=2 of 4 educational sessions, and completed >or=2 of 3 follow-up questionnaires. Ninety students met criteria for inclusion in this subgroup analysis. RESULTS: In logistic regression models for medication adherence, nonresponse was related to low baseline asthma self-regulation, odds ratio = 3.6 (95% confidence interval = 1.3-9.5). In models for having an inhaler nearby, nonresponse was related to low baseline self-regulation and to rebelliousness, OR = 4.7 (1.6-13.2) and 5.6 (1.7-18.0), respectively. Nonresponse to smoking messages was related to rebelliousness, low emotional support, and low religiosity, ORs = 7.6 (1.8-32.3), 9.5 (1.4-63.5), and 6.6 (1.5-29.8) respectively. CONCLUSIONS: Certain variables had the ability to discriminate the likelihood of response from that of nonresponse to an asthma program for urban, African American adolescents with asthma. These variables can be used to identify resistant subgroups early in the intervention, allowing the application of specialized strategies through tailoring. These types of analyses can inform behavioral interventions.
Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Terapia Comportamental/métodos , Modelos Psicológicos , Adolescente , Negro ou Afro-Americano , Asma/psicologia , Terapia Comportamental/educação , Feminino , Humanos , Modelos Logísticos , Masculino , Michigan , Cooperação do Paciente , Educação de Pacientes como Assunto , Fumar , Software , População UrbanaRESUMO
Asthma and obesity disproportionately affect US African-American youth. Among youth with asthma, obesity has been associated with poor control. The impact of gender on this association is unclear. We examined these relationships in a sample of urban, African-American adolescents with asthma. Questionnaires were used to identify high school students with asthma, and to examine the association of body mass index (BMI) to asthma morbidity, by gender. Of 5967 students completing questionnaires, 599 (10%) met criteria for asthma and 507 had data sufficient for inclusion in further analyses (46% male, mean age = 15.1 yr). Univariately, BMI > 85th percentile was significantly related only to reported emergency department visits (ED) and school days missed for any reason, Odds Ratio (95%Confidence Interval) = 1.7(1.1-2.7), p = 0.01 and 1.8(1.1-3.0), p = 0.01, respectively. A significant gender-BMI interaction (p < 0.05) was observed in multivariate models for ED visits, hospitalizations and school days missed for asthma. In gender-specific models, adjusted Risk Ratios for BMI > 85th and ED visits, hospitalizations, and school days missed because of asthma were 1.7(0.9-3.2), 6.6(3.1-14.6) and 3.6(1.8-7.2) in males. These associations were not observed in females. Gender modifies the association between BMI and asthma-related morbidity among adolescents with asthma. Results have implications for clinical management as well as future research.
Assuntos
Asma/epidemiologia , Sobrepeso/epidemiologia , Adolescente , Índice de Massa Corporal , Feminino , Humanos , Masculino , Análise Multivariada , Fatores de Risco , Fatores Sexuais , Inquéritos e Questionários , Estados Unidos/epidemiologia , População Urbana/estatística & dados numéricosRESUMO
BACKGROUND: Early life pet exposure may protect against allergic sensitization during childhood. Few studies have evaluated the effect of prenatal pet exposure on potential neonatal markers of allergic risk. OBJECTIVE: The aim of this study was to investigate whether maternal exposure to pets affects cord blood IgE levels in a population-based, general risk, ethnically mixed birth cohort. METHODS: Pet keeping during pregnancy was ascertained from women residing in a defined area of Wayne County Michigan and recruited from five staff model obstetric clinics. Maternal venous blood was analysed for total and allergen-specific IgE along with cord blood total IgE from 1049 infants. RESULTS: Compared with infants from households with no cats or dogs kept indoors during pregnancy, infants whose homes had either cats or dogs had significantly reduced mean cord IgE levels [0.34 IU/mL (95% CI 0.30-0.38) vs. 0.24 IU/mL (0.20-0.27), P=0.025]. Similar effects were apparent in cat-only households [0.21 IU/mL (0.16-0.27), P=0.020] and dog-only households [0.24 IU/mL (0.19-0.29), P=0.045]. There was no effect on results when excluding mothers who reported avoiding pets due to allergy-related concerns. CONCLUSION: Mothers with either cats or dogs in their home during pregnancy deliver children with lower cord blood IgE levels compared with mothers who do not live with these pets, supporting the hypothesis that pet exposure influences immune development in a manner that is protective for atopy and is operant even before birth.
Assuntos
Animais Domésticos/imunologia , Sangue Fetal/imunologia , Feto/imunologia , Imunoglobulina E/sangue , Exposição Materna , Adulto , Animais , Gatos , Cães , Feminino , Humanos , Hipersensibilidade Imediata/etiologia , Pessoa de Meia-Idade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/imunologia , Adulto JovemRESUMO
The cytotoxic nucleoside 2'-deoxyadenosine is excreted in excessive amounts by individuals with genetic deficiency of adenosine deaminase, and may be in part responsible for the severe combined immune dysfunction from which they suffer. Earlier studies from this laboratory showed that 2'-deoxyadenosine causes the irreversible inactivation of the enzyme S-adenosylhomocysteine hydrolase by an active site-directed, "suicide-like" process. In this communication we have demonstrated similar inactivation of S-adenosylhomocysteine hydrolase in hemolysate and in intact erythrocytes, as well as a striking deficiency of S-adenosylhomocysteine hydrolase activity in the erythrocytes of three adenosine deaminase-deficient patients. In vivo suicide-like inactivation of S-adenosylhomocysteine hydrolase by 2'-deoxyadenosine may contribute to the cytotoxicity of 2'-deoxyadenosine and to the immune dysfunction in adenosine deaminase deficiency.
Assuntos
Adenosina Desaminase/deficiência , Desoxiadenosinas/farmacologia , Eritrócitos/enzimologia , Hidrolases/sangue , Nucleosídeo Desaminases/deficiência , Adenosina Desaminase/sangue , Adulto , Feminino , Humanos , Hidrolases/antagonistas & inibidores , Cinética , Masculino , S-Adenosil-HomocisteínaRESUMO
Regulation of respiratory mucosal immunity by microbial-derived metabolites has been a proposed mechanism that may provide airway protection. Here we examine the effect of oral Lactobacillus johnsonii supplementation on metabolic and immune response dynamics during respiratory syncytial virus (RSV) infection. L. johnsonii supplementation reduced airway T helper type 2 cytokines and dendritic cell (DC) function, increased regulatory T cells, and was associated with a reprogrammed circulating metabolic environment, including docosahexanoic acid (DHA) enrichment. RSV-infected bone marrow-derived DCs (BMDCs) from L. johnsonii-supplemented mice had altered cytokine secretion, reduced expression of co-stimulatory molecules, and modified CD4+ T-cell cytokines. This was replicated upon co-incubation of wild-type BMDCs with either plasma from L. johnsonii-supplemented mice or DHA. Finally, airway transfer of BMDCs from L. johnsonii-supplemented mice or with wild-type derived BMDCs pretreated with plasma from L. johnsonii-supplemented mice reduced airway pathological responses to infection in recipient animals. Thus L. johnsonii supplementation mediates airway mucosal protection via immunomodulatory metabolites and altered immune function.
Assuntos
Células da Medula Óssea/imunologia , Células Dendríticas/imunologia , Lactobacillus johnsonii/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sinciciais Respiratórios/imunologia , Linfócitos T Reguladores/metabolismo , Células Th2/metabolismo , Animais , Células da Medula Óssea/virologia , Linhagem Celular , Microambiente Celular , Reprogramação Celular , Citocinas/metabolismo , Células Dendríticas/virologia , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/metabolismo , Imunomodulação , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Linfócitos T Reguladores/imunologia , Células Th2/imunologiaRESUMO
Serum concentrations of IgG, IgA, IgM, IgE, and allergen-specific IgE were measured in presurgical serum samples from 400 women admitted to a multidisciplinary study of primary breast cancer. The relationships between the serum immunoglobulins and patient survival were analyzed with the use of a Cox proportional hazards linear model. After adjustment for TNM stage, tumor histopathologic grade, and estrogen receptor (E2R) status, lower IgM concentrations were associated with longer survival. Lower IgE concentrations were also associated with longer survival, but only in patients whose tumors were E2R positive. IgG and IgA were not related to survival. Serum IgM and IgE concentrations, allergen-specific IgE scores, and the tumor E2R status were combined to construct a three-level risk classification that was more prognostic than any of the individual components. Cox model analysis demonstrated that this combination of immunologic and hormonal variables provided significant new information beyond that obtained from TNM staging and histopathologic grading of the tumors (P = .01). This new information may be useful to physicians in advising patients with primary, operable breast cancer about the relative risks and benefits of adjuvant therapy and in designing clinical trials of adjuvant therapy.
Assuntos
Neoplasias da Mama/mortalidade , Imunoglobulinas/análise , Neoplasias da Mama/imunologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Estadiamento de Neoplasias , Prognóstico , Receptores de Estrogênio/análise , RiscoRESUMO
Early patterns of gut colonization may predispose children to adult disease. Exposures in utero and during delivery are associated with the infant gut microbiome. Although ~35% of women carry group B strep (GBS; Streptococcus agalactiae) during pregnancy, it is unknown if GBS presence influences the infant gut microbiome. As part of a population-based, general risk birth cohort, stool specimens were collected from infant's diapers at research visits conducted at ~1 and 6 months of age. Using the Illumina MiSeq (San Diego, CA) platform, the V4 region of the bacterial 16S rRNA gene was sequenced. Infant gut bacterial community compositional differences by maternal GBS status were evaluated using permutational multivariate analysis of variance. Individual operational taxonomic units (OTUs) were tested using a zero-inflated negative binomial model. Data on maternal GBS and infant gut microbiota from either 1 (n=112) or 6-month-old stool (n=150) specimens was available on 262 maternal-child pairs. Eighty women (30.5%) were GBS+, of who 58 (72.5%) were given intrapartum antibiotics. After adjusting for maternal race, prenatal antifungal use and intrapartum antibiotics, maternal GBS status was statistically significantly associated with gut bacterial composition in the 6 month visit specimen (Canberra R 2=0.008, P=0.008; Unweighted UniFrac R 2=0.010, P=0.011). Individual OTU tests revealed that infants of GBS+ mothers were significantly enriched for specific members of the Clostridiaceae, Ruminococcoceae, and Enterococcaceae in the 6 month specimens compared with infants of GBS- mothers. Whether these taxonomic differences in infant gut microbiota at 6 months lead to differential predisposition for adult disease requires additional study.
Assuntos
Microbioma Gastrointestinal , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae , Adulto , Antibacterianos/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Pessoa de Meia-Idade , Gravidez , Infecções Estreptocócicas/tratamento farmacológico , Adulto JovemRESUMO
An improved technique for separating rosetted from non-rosetted lymphocytes is described. The major advantage of this new technique is the elimination of the need to mechanically resuspend the cell pellet resulting from the rosette formation step before using a density gradient to separate the rosetted from the non-rosetted cells. Instead the rosette containing cell pellet is directly overlayed with Percoll at a density of 1.078 g/ml and during a subsequent centrifugation the non-rosetted cells float to the surface of the Percoll while the rosetted cells remain in the cell pellet. The utility of this technique is illustrated by separating human T lymphocytes forming rosettes with neuraminidase treated sheep erythrocytes (En) from other mononuclear cells obtained by Ficoll-Hypaque separation of whole blood. Using several markers the resulting T cells were contaminated with less than 0.3% monocytes and 2% B cells. The non-T cell population contained less than 3% T cells. This method offers a rapid and easily reproducible means for obtaining highly purified cell populations.
Assuntos
Separação Celular/métodos , Formação de Roseta/métodos , Linfócitos T , Anticorpos Monoclonais/imunologia , Concanavalina A/farmacologia , Humanos , Ativação Linfocitária , Fito-Hemaglutininas/farmacologia , Linfócitos T/imunologiaRESUMO
OBJECTIVE: To determine the stability of immunoglobulin E levels in obstetric sera. METHODS: AlaSTAT(R) and AlaTOP(R) (Diagnostic Products) were used to assay total and specific IgE levels in obstetric sera collected in Memphis, TN and Portland, OR. The samples were collected from the Collaborative Perinatal Project (CPP) between 1959 and 1965 and stored at -20 degrees C. The assay results were compared with IgE levels found in sera collected at the same locations for the Calcium for Pre-eclampsia Prevention Study (CPEP) and stored since 1992 at -70 degrees C. The samples were also assayed for cockroach (CR) and mouse urine specific IgE using the AlaSTAT(R) assay (Diagnostic Products). RESULTS: Total IgE and specific IgE to CR and mouse urine were detectable in older and recent samples. The median total IgE for the recent and older Portland samples was 26 IU/ml and 65 IU/ml, respectively. The median total IgE was identical (40 IU/ml) in the recent and older Memphis samples. CONCLUSION: Long-term storage does not diminish the ability to measure serum IgE. Levels of IgE in sera stored 32-37 years were equal to or greater than levels in sera stored for 5 years. reserved.
Assuntos
Imunoglobulina E/sangue , Animais , Feminino , Humanos , Camundongos , Sódio/sangueRESUMO
Exposure to environmental tobacco smoke is an important variable in many pediatric epidemiologic studies. We measured urinary cotinine, a specific metabolite of nicotine, in a population-based cohort of children every other month from birth through two years of age. Extensive data regarding exposure to smokers (people in the home, in home and away from home day care, home visitors, visits to smokers) were collected monthly by way of home interviews. We evaluated, with multiple cotinine measurements as the gold standard, other measures of exposure that are more feasible to obtain in large-scale studies. Comparing one cotinine to the average of multiple measurements, we found that 33.7% were in error in excess of 100 ng/mg, but 84% of the infants could be correctly classified into categories of low versus high. Parental smoking patterns had the highest predictive accuracy (fathers 67.0% and mothers 64.1%). Combining selected smoker categories (either parent, other home residents outside day care workers) resulted in improved accuracy of 79.3%.
Assuntos
Cotinina/urina , Creatinina/urina , Inquéritos e Questionários , Poluição por Fumaça de Tabaco , Pai , Humanos , Lactente , Recém-Nascido , Mães , Valor Preditivo dos Testes , Fumar/efeitos adversosRESUMO
A patient with occupational asthma in the beet sugar processing industry is described. Symptomatology, skin testing, immunologic testing, and specific bronchoprovocation testing indicate exposure to moldy sugar beet pulp was the cause of the patient's occupational asthma. Cooperation between the treating physician and public health authorities is encouraged.