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Biomedical subjects

F D Martinez

Publications and source records attributed to F D Martinez.

At least 19 recordsLinked to original sources
PubMed2002

Effect of a zwitterionic surfactant (HPS) on the conformation and hemolytic activity of St I and St II, two isotoxins purified from Stichodactyla helianthus.

N-hexadecyl-N-N'-dimethyl-3-ammonio-1-propane-sulfonate (BPS) is a zwitterionic surfactant that readily binds to sticholysins I and II, two sea toxins isolated from Stichodactyla helianthus. The binding constants, evaluated from changes in fluorescence intensities elicited by the surfactant, are approximately 0.5-0.7 microM(-1). The binding of the surfactant changes the conformation of the tertiary protein, without significant changes in its secondary structure, as reported from far-ultraviolet circular dichroism spectra. The changes elicited by HPS lead to loss of the native conformation (as reported from near-ultraviolet circular dichroism spectra) and to a shift of the intrinsic protein fluorescence toward longer wavelengths, an increase in fluorescence intensities and lifetimes, and a faster quenching by acrylamide. All these changes are indicative of a more expanded tertiary conformation. Despite this, the toxins fully retain their hemolytic activities, indicating that spectroscopic changes can be poor predictors of toxin activity.

Animals↗
PubMed2002

The association between persistent eosinophilia and asthma in childhood is independent of atopic status.

BACKGROUND: Although peripheral blood eosinophilia is associated with risk of asthma, the relation with atopy has not been established. OBJECTIVE: To assess the relationship between eosinophils and chronic asthma in childhood, and to determine the factors associated with eosinophil levels over time. METHODS: Percent eosinophils/300 white blood cell (WBC) count ('eos') was measured at 9 months, 6 years and 11 years in subjects participating in the prospective Tucson Children's Respiratory Study. Children were classified based on the number of measurements in which they had low (< or = 2%) or high (>5%) eosinophils, as follows: (1) Persistently low eos (n = 130); (2) Low eos (intermittently low or consistently moderate, but never high, n = 317); (3) Intermittently high eos (n = 192); and (4) Persistently high eos (n = 17). Only children with > or = 2 eos measurements were included in the analysis. Chronic asthma was defined as medical doctor (MD)-diagnosed asthma with reports of wheezing during the previous year, on > or = 3 questionnaires completed between 2 and 13 years of age. Children with at least one positive skin prick test (SPT; > or = 3 mm) at age 6 or 11 were considered 'atopic'. RESULTS: Chronic asthma was linearly related to longitudinally ascertained eosinophils (trend chi2 P<0.001) with prevalence ranging from 5.8% among children with persistently low eos to 37.5% among children with persistently high eos. This relation was independent of atopy. Parental history of asthma was associated with both chronic asthma (P <0.001) and with longitudinal eosinophil status (P < 0.001). After adjusting for atopy and gender, there was a 70% increase in asthma risk with each increase in longitudinal eosinophil level. This stepwise increase was reduced to 48% when parental asthma was added to the model. CONCLUSION: Longitudinal eosinophil levels are linearly associated with chronic asthma in childhood, independent of atopy. The strong association between parental asthma and eosinophil status suggests that genetic background may be an important determinant of eosinophilic response.

Asthma↗
PubMed2001

A common single nucleotide polymorphism in the CD14 promoter decreases the affinity of Sp protein binding and enhances transcriptional activity.

CD14 is a pattern recognition receptor that plays a central role in innate immunity through recognition of bacterial lipoglycans, primarily LPS. Recently, our group has identified a common single nucleotide polymorphism, -159C-->T, in the CD14 proximal promoter. Homozygous carriers of the T allele have a significant increase in soluble CD14, but a decreased total serum IgE. This epidemiologic evidence led us to investigate the molecular basis for the effects of CD14/-159C-->T on CD14 regulation in monocytes and hepatocytes, the two major cell types known to express this gene in vivo. EMSA analysis showed that the T allele results in decreased affinity of DNA/protein interactions at a GC box that contains a binding site for Sp1, Sp2, and Sp3 transcription factors. In reporter assays, the transcriptional activity of the T allele was increased in monocytic Mono Mac 6 cells, which express low levels of Sp3, a member of the Sp family with inhibitory potential relative to activating Sp1 and Sp2. By contrast, both alleles were transcribed equivalently in Sp3-rich hepatocytic HepG2 cells. Our data indicate that the interplay between CD14 promoter affinity and the [Sp3]:[Sp1 + Sp2] ratio plays a critical mechanistic role in regulating transcription of the two CD14 alleles. Variation in a key gene of innate immunity may be important for the pathogenesis of allergy and inflammatory disease through gene-by-gene and/or gene-by-environment interactions.

Base Sequence↗
PubMed2001

Familial correlation in the decline of forced expiratory volume in one second.

Studies have shown evidence of significant parent-offspring and sibling correlation in FEV1, but familial aggregation of decline of FEV1 over time has not been reported. Our study population comprised 392 families enrolled in the Tucson Epidemiological Study of Airway Obstructive Diseases. Subjects were older than 18 yr of age and performed at least 3 pulmonary function tests over 5 to 20 yr. The slope of FEV1 was calculated for each subject using simple linear regression. Multiple regression models were used to compute standardized residual slope values adjusted for possible confounders. Familial correlation analysis on residual slope values demonstrated no evidence of spousal or parent-offspring correlation. However, sibling pairs were highly correlated (r = 0.256, p < 0.001, n = 166), especially smoking-concordant pairs (r = 0.483, p < 0.01 for ever-smokers, and r = 0.280, p < 0.05 for never-smokers). The residual slopes of smoking-discordant siblings were not significantly correlated (r = 0.031, p < 0.77). Genetic susceptibility to an accelerated rate of decline associated with smoking may be evidenced in the increased correlation among smoking sibling pairs, and in the lack of correlation among smoking-discordant sibling pairs. High sibling correlation in the absence of parent-offspring correlation is compatible with a recessive model of inheritance.

Adult↗
PubMed2001

The coming-of-age of the hygiene hypothesis.

The hygiene hypothesis, as originally proposed, postulated an inverse relation between the incidence of infectious diseases in early life and the subsequent development of allergies and asthma. New evidence from epidemiological, biological and genetic studies has significantly enlarged the scope of the hypothesis. It now appears probable that environmental 'danger' signals regulate the pattern of immune responses in early life. Microbial burden in general, and not any single acute infectious illness, is the main source of these signals. The latter interact with a sensitive and complex receptor system, and genetic variations in this receptor system may be an important determinant of inherited susceptibility to asthma and allergies.

Child, Preschool↗
PubMed2001

Differences in proliferation of the hematopoietic cell line TF-1 and cytokine production by peripheral blood leukocytes induced by 2 naturally occurring forms of human IL-3.

BACKGROUND: A naturally occurring polymorphism in the coding region of the human IL3 gene leads to a change in amino acid residue 8 from proline to serine. OBJECTIVE: We sought to determine whether the 2 different forms of IL-3 varied in function. These different forms are available as recombinant proteins (recombinant human IL-3/proline 8 [rhIL-3/P8] and recombinant human IL-3/serine 8 [rhIL-3/S8]). METHODS: The erythroleukemic cell line TF-1 was incubated with varying concentrations of rhIL-3/P8 or rhIL-3/S8 to determine the capacity of each type of IL-3 to induce proliferation. Human leukocytes were primed with rhIL-3/P8 or rhIL-3/S8 for up to 24 hours and then stimulated with anti-IgE and assessed for leukotrienes (LTs), IL-4, and TNF-alpha. RESULTS: Proliferation of TF-1 cells was induced by both forms of IL-3 at 48 and 72 hours but to a greater degree by rhIL-3/P8. In contrast, the mean fold increase over control values of LT and IL-4 production was higher after priming the cells with rhIL-3/S8 versus rhIL-3/P8. Additionally, TNF-alpha production was greater (and reached significance only) for rhIL-3/S8. This activity was independent of IgE and thus directly stimulated by IL-3. Studies with basophil-enriched and basophil-depleted cell preparations revealed that LT production was evident only from the former and TNF-alpha only from the latter. CONCLUSION: We conclude that the 2 naturally occurring forms of human IL-3 have similar spectra of activities on cells with IL-3 receptors, but the 2 forms have reversed relative efficacies for promoting proliferation (rhIL-3/P8 > rhIL-3/S8) compared with priming or inducing mediator secretion (rhIL-3/S8 > rhIL-3/P8).

Cell Line↗
PubMed2001

Links between pediatric and adult asthma.

Connections between events occurring in early life with adult asthma suggest that both the altered regulation of airway caliber and tone and the changes in airway structure present in many asthma cases may have their roots in developmental patterns established during infancy and childhood. The Melbourne epidemiologic study, the British 1958 birth cohort, and the Tasmanian asthma survey all provide important information on the outcomes of childhood asthma in later life. Among the findings, these studies showed that in a large proportion of asthmatic children, asthma remits in early adulthood, and the severity of asthma tracks significantly with age. Newer longitudinal studies have measured lung function shortly after birth, before any respiratory symptoms have occurred. Several lines of evidence suggest that those children who will go on to have more severe and persistent asthma symptoms already have immune responses skewed toward the T-helper type 2 (TH2) at the time of the very first episodes of airway obstruction in infancy. In most children whose asthma is triggered mainly by respiratory infections, asthma symptoms appear to remit by the adolescent years. Congenital and acquired deficits in lung function, however, may lead to recurrence of these symptoms during adult life and after long periods of remission, especially among active smokers.

Adult↗
PubMed2001

Dog exposure in infancy decreases the subsequent risk of frequent wheeze but not of atopy.

BACKGROUND: Influence of household pets in the development of childhood asthma or atopy has been controversial. OBJECTIVE: The purpose of this study was to investigate whether pet exposure in early life decreases the subsequent risk of frequent wheezing and/or allergic sensitization. METHODS: This was a prospective observational birth cohort study. The setting was a large health maintenance organization in Tucson, Ariz; the subjects were a population sample of 1246 newborns enrolled at birth and followed prospectively to age 13 years. The main outcome measures were as follows: time to first report of frequent wheezing (>3 episodes in the past year), skin prick test reactivity at 6 years and 11 years of age, and total serum IgE at 9 months, 6 years, and 11 years of age. RESULTS: Children living in households with > or =1 indoor dogs at birth were less likely to develop frequent wheeze than those not having indoor dogs (P =.004). This inverse association was confined to children without parental asthma (hazard ratio = 0.47; P <.001 [Cox regression]) and was not evident for children with parental asthma (hazard ratio = 0.96; P =.87). Adjustment by potential confounders did not change the results. Indoor cat exposure was not significantly associated with the risk of frequent wheezing. Neither cat exposure in early life nor dog exposure in early life was associated with skin prick test reactivity or total serum IgE at any age. CONCLUSION: Dog exposure in early life might prevent the development of asthma-like symptoms, at least in low-risk children with no family history of asthma. Nevertheless, early pet exposure does not seem to significantly influence the development of allergic sensitization.

Adolescent↗
PubMed2001

Factor analysis of asthma and atopy traits shows 2 major components, one of which is linked to markers on chromosome 5q.

BACKGROUND: A variety of definitions of asthma and atopy traits have been used in genetic studies. The variables used may be correlated, increasing the likelihood of type I error. OBJECTIVE: We sought to clarify and quantify phenotypes that may be characterized by related traits. Principal components and factor analysis were applied to the correlation matrix of asthma and atopy traits before linkage analysis. METHODS: Factor analysis was performed on 468 Hispanic and non-Hispanic white children enrolled in the Tucson Children's Respiratory Study, with complete information on 24 items, including skin test response to 7 allergens, total serum IgE levels, presence or absence of asthma attacks, wheezing episodes, hay fever, and cough. Factor score coefficients were then applied to all siblings (n = 877), and quantitative factor scores were derived. Single-point and multipoint nonparametric sib-pair analyses were performed to assess linkage to markers on chromosome 5q31-33. Analyses were also performed for individual items. RESULTS: Two main factors were identified: Factor I had high loadings on atopic items, including skin test responses, IgE, and hay fever, and Factor II had high loadings that included asthma diagnosis, wheezing, cough, and Alternaria species skin test response. Factors I and II were correlated at an r value of 0.19. For the quantitative factor scores, significant single-point linkage (P < .0001) was demonstrated only for atopic Factor I, and a peak multipoint LOD score of 2.7 was seen for marker D5S479. Multipoint LOD scores for individual items were 1.1 or less. CONCLUSION: These analyses suggest evidence for a locus or loci mapping to chromosome 5q31-33 associated with this composite atopic phenotype.

Asthma↗
PubMed2001

Factors influencing the relation of infant feeding to asthma and recurrent wheeze in childhood.

BACKGROUND: The relationship between infant feeding and childhood asthma is controversial. This study tested the hypothesis that the relation between breast feeding and childhood asthma is altered by the presence of maternal asthma. METHODS: Healthy non-selected newborn infants (n = 1246) were enrolled at birth. Asthma was defined as a physician diagnosis of asthma plus asthma symptoms reported on > or = 2 questionnaires at 6, 9, 11 or 13 years. Recurrent wheeze (> or = 4 episodes in the past year) was reported by questionnaire at seven ages in the first 13 years of life. Duration of exclusive breast feeding was based on prospective physician reports or parental questionnaires completed at 18 months. Atopy was assessed by skin test responses at the age of 6 years. RESULTS: The relationship between breast feeding, asthma, and wheeze differed with the presence or absence of maternal asthma and atopy in the child. After adjusting for confounders, children with asthmatic mothers were significantly more likely to have asthma if they had been exclusively breast fed (OR 8.7, 95% CI 3.4 to 22.2). This relationship was only evident for atopic children and persisted after adjusting for confounders. In contrast, the relation between recurrent wheeze and breast feeding was age dependent. In the first 2 years of life exclusive breast feeding was associated with significantly lower rates of recurrent wheeze (OR 0.45, 95% CI 0.2 to 0.9), regardless of the presence or absence of maternal asthma or atopy in the child. Beginning at the age of 6 years, exclusive breast feeding was unrelated to prevalence of recurrent wheeze, except for children with asthmatic mothers in whom it was associated with a higher odds ratio for wheeze (OR 5.7, 95% CI 2.3 to 14.1), especially if the child was atopic. CONCLUSION: The relationship between breast feeding and asthma or recurrent wheeze varies with the age of the child and the presence or absence of maternal asthma and atopy in the child. While associated with protection against recurrent wheeze early in life, breast feeding is associated with an increased risk of asthma and recurrent wheeze beginning at the age of 6 years, but only for atopic children with asthmatic mothers.

Adolescent↗
PubMed2001

Increased incidence of asthmalike symptoms in girls who become overweight or obese during the school years.

The possibility of a causal relationship is suggested by recent concomitant increases in the prevalence of obesity and asthma. In a general population sample, prevalence and incidence of asthma symptoms, skin tests, and body mass index (BMI) were ascertained at mean ages of 6.3 (n = 688) and 10.9 (n = 600) yr. Lung function, bronchodilator responsiveness, and daily peak flow variability were measured at 11 yr of age. There was no association between BMI at age 6 and wheezing prevalence at any age. Females, but not males, who were overweight or obese at 11 yr of age were more likely to have current wheezing at ages 11 and 13 but not at ages 6 or 8. This effect was strongest among females beginning puberty before the age of 11. Females who became overweight or obese between 6 and 11 yr of age were 7 times more likely to develop new asthma symptoms at age 11 or 13 (p = 0.0002); at age 11 their peak flow variability and bronchodilator responsiveness were significantly more likely to be increased. In females, becoming overweight or obese between 6 and 11 yr of age increases the risk of developing new asthma symptoms and increased bronchial responsiveness during the early adolescent period.

Age Distribution↗
PubMed2001

Relation of two different subtypes of croup before age three to wheezing, atopy, and pulmonary function during childhood: a prospective study.

OBJECTIVE: Some retrospective evidence suggests that children with a history of croup may be at increased risk of subsequently developing asthma, atopy, and diminished pulmonary function. The objective of this study was to determine the long-term outcome of croup (as diagnosed by a physician) in early life. METHODS: Lower respiratory illnesses (LRIs) in the first 3 years of life were assessed in 884 children who were enrolled in a large longitudinal study of airway diseases at birth. Pulmonary function tests, markers of atopy, and wheezing episodes were studied at different ages between birth and 13 years. RESULTS: Ten percent of children had croup with wheeze (Croup/Wheeze), 5% had croup without wheeze (Croup/No Wheeze), 36% had another LRI (Other LRI), and 48% had no LRI. Respiratory syncytial virus was more frequently isolated in children with Croup/Wheeze and Other LRI than in those with Croup/No Wheeze. There was no association between croup in early life and markers of atopy measured during the school years. Only children with Croup/Wheeze and with Other LRI had a significant risk of subsequent persistent wheeze later in life. Significantly lower levels of indices of intrapulmonary airway function were observed at ages <1 (before any LRI), 6, and 11 years in children with Croup/Wheeze and Other LRI compared with children with No LRI. Conversely, inspiratory resistance before any LRI episode was significantly higher in infants who later developed Croup/No Wheeze than in the other 3 groups. CONCLUSIONS: We distinguish 2 manifestations of croup with and without wheezing. Children who present with croup may or may not be at increased risk of subsequent recurrent lower airway obstruction, depending on the initial lower airway involvement, and preillness and postillness abnormalities in lung function associated with this condition.

Asthma↗
PubMed2001

Relation between infantile colic and asthma/atopy: a prospective study in an unselected population.

OBJECTIVE: To assess whether children with history of infantile colic may be at increased risk of subsequently developing asthma and/or atopy. METHODS: We used data collected in a large, prospective study from an unselected population. Infantile colic and concurrent feeding method were determined from the 2-month well-infant visit form completed by the physician for 983 children who were enrolled at birth. Markers of atopy (total serum immunoglobulin E and allergy skin prick test), allergic rhinitis, asthma, wheezing, and peak flow variability were the main outcome measures studied at different ages between infancy and 11 years. RESULTS: Ninety (9.2%) children had infantile colic. Prevalence of colic was similar among children fed either breast milk or formula. There was no association between infantile colic and markers of atopy, asthma, allergic rhinitis, wheezing, or peak flow variability at any age. CONCLUSION: Our data cannot support the hypothesis that infantile colic provides increased risk for subsequent allergic disease or atopy.

Asthma↗
PubMed2000

Siblings, day-care attendance, and the risk of asthma and wheezing during childhood.

BACKGROUND: Young children with older siblings and those who attend day care are at increased risk for infections, which in turn may protect against the development of allergic diseases, including asthma. However, the results of studies examining the relation between exposure to other children and the subsequent development of asthma have been conflicting. METHODS: In a study involving 1035 children followed since birth as part of the Tucson Children's Respiratory Study, we determined the incidence of asthma (defined as at least one episode of asthma diagnosed by a physician when the child was 6 to 13 years old) and the prevalence of frequent wheezing (more than three wheezing episodes during the preceding year) in relation to the number of siblings at home and in relation to attendance at day care during infancy. RESULTS: The presence of one or more older siblings at home protected against the development of asthma (adjusted relative risk for each additional older sibling, 0.8; 95 percent confidence interval, 0.7 to 1.0; P=0.04), as did attendance at day care during the first six months of life (adjusted relative risk, 0.4; 95 percent confidence interval, 0.2 to 1.0; P=0.04). Children with more exposure to other children at home or at day care were more likely to have frequent wheezing at the age of 2 years than children with little or no exposure (adjusted relative risk, 1.4; 95 percent confidence interval, 1.1 to 1.8; P=0.01) but were less likely to have frequent wheezing from the age of 6 (adjusted relative risk, 0.8; 95 percent confidence interval, 0.6 to 1.0; P=0.03) through the age of 13 (adjusted relative risk, 0.3; 95 percent confidence interval, 0.2 to 0.5; P<0.001). CONCLUSIONS: Exposure of young children to older children at home or to other children at day care protects against the development of asthma and frequent wheezing later in childhood.

Adolescent↗
PubMed2000

A cluster of seven tightly linked polymorphisms in the IL-13 gene is associated with total serum IgE levels in three populations of white children.

BACKGROUND: Increased levels of total serum IgE are a strong risk factor for the development of asthma. IgE is also involved in host defenses against parasites and fungi. Linkage of total serum IgE with markers located close to the 3 Mb cluster of cytokine genes in chromosome 5q31 has been reported. IL-4 or IL-13 are regarded as essential for IgE synthesis. OBJECTIVE: We tested whether polymorphisms in the IL-13 gene might explain the linkage between chromosome 5q31 and total serum IgE levels. METHODS: We used denaturing HPLC to detect polymorphisms in overlapping PCR fragments of the IL-13 gene including promoter and 3' untranslated regions. After sequencing was performed to identify the locations of the polymorphisms, PCR and primer-induced restriction site assays were used to genotype subjects in 3 unselected populations. RESULTS: We report here 7 polymorphisms (6 novel) in IL-13. Four of these polymorphisms are tightly linked to a variant in the terminal portion of the coding region of the gene that results in a predicted amino acid change in residue 130 (Arg130Gln). The Gln form is strongly associated (P =.000002) with increased serum IgE levels in 3 different populations comprising a total of 1399 children. Two additional polymorphisms in the promoter region of IL-13 are more loosely linked to Arg130Gln and are also less significantly associated with total serum IgE levels. CONCLUSION: These data suggest that the Arg130Gln polymorphism in IL-13, or others in close linkage with it, is associated with the development of the elevated serum IgE phenotype.

Asthma↗