The aim of this study is to investigate the association between birth defects (BDs), prematurity and small-for-gestational age (SGA) in a population-based sample.
Participants were singleton live ...births enrolled in the National Birth Defects Prevention Study, including 18 737 case infants with one or more BD and 7999 controls. Logistic regression models to evaluate associations between BDs, prematurity and fetal growth were computed while adjusting for covariates.
Cases were significantly more likely to be born prematurely than controls, particularly at 24 to 28 weeks of gestation. The highest odds ratios for preterm birth were found for intestinal atresia, anencephaly, gastroschisis and esophageal atresia. Infants with BDs were also significantly more likely to be SGA than controls (17.2 and 7.8%).
Infants with BDs are more likely than controls to be born prematurely and SGA. Findings from this study present additional evidence demonstrating a complex interaction between the development of BDs, prematurity and intrauterine growth.
Rates of neural tube defects have decreased since folic acid fortification of the food supply in the United States. The authors’ objective was to evaluate the associations between neural tube defects ...and maternal folic acid intake among pregnancies conceived after fortification. This is a multicenter, case-control study that uses data from the National Birth Defects Prevention Study, 1998–2003. Logistic regression was used to compute crude and adjusted odds ratios between cases and controls assessing maternal periconceptional use of folic acid and intake of dietary folic acid. Among 180 anencephalic cases, 385 spina bifida cases, and 3, 963 controls, 21.1%, 25.2%, and 26.1%, respectively, reported periconceptional use of folic acid supplements. Periconceptional supplement use did not reduce the risk of having a pregnancy affected by a neural tube defect. Maternal intake of dietary folate was not significantly associated with neural tube defects. In this study conducted among pregnancies conceived after mandatory folic acid fortification, the authors found little evidence of an association between neural tube defects and maternal folic acid intake. A possible explanation is that folic acid fortification reduced the occurrence of folic acid-sensitive neural tube defects. Further investigation is warranted to possibly identify women who remain at increased risk of preventable neural tube defects.
Background: The use of chlorine for water disinfection results in the formation of numerous contaminants called disinfection by-products (DBPs), which may be associated with birth defects, including ...urinary tract defects. Methods: We used Arkansas birth records (1998–2002) to conduct a population-based case-control study investigating the relationship between hypospadias and two classes of DBPs, trihalomethanes (THM) and haloacetic acids (HAA). We utilised monitoring data, spline regression and geographical information systems (GIS) to link daily concentrations of these DBPs from 263 water utilities to 320 cases and 614 controls. We calculated ORs for hypospadias and exposure to DBPs between 6 and 16 weeks’ gestation, and conducted subset analyses for exposure from ingestion, and metrics incorporating consumption, showering and bathing. Results: We found no increase in risk when women in the highest tertiles of exposure were compared to those in the lowest for any DBP. When ingestion alone was used to assess exposure among a subset of 40 cases and 243 controls, the intermediate tertiles of exposure to total THM and the five most common HAA had ORs of 2.11 (95 CI 0.89 to 5.00) and 2.45 (95 CI 1.06 to 5.67), respectively, compared to women with no exposure. When exposure to total THM from consumption, showering and bathing exposures was evaluated, we found an OR of 1.96 (95 CI 0.65 to 6.42) for the highest tertile of exposure and weak evidence of a dose–response relationship. Conclusions: Our results provide little evidence for a positive relationship between DBP exposure during gestation and an increased risk of hypospadias but emphasise the necessity of including individual-level data when assessing exposure to DBPs.
The PM
2.5
standard proposed by the U.S. Environmental Protection Agency (EPA) has stimulated research on the relationships between particulate matter concentrations and the exposures and subsequent ...health responses of sensitive subpopulations, such as the elderly. Since individuals in these subpopulations may spend more than 90% of their time indoors, understanding the relationship between outdoor particle concentrations and those found in indoor microenvironments is critical. This research resulted in a time-dependent indoor air quality model incorporating all potential particle sources and loss mechanisms. Monte Carlo simulations of the model identified the mechanisms, such as particle loss during penetration through the building envelope, that modify the outdoor particle size distribution during transport into the interior of a building, calculated indoor-to-outdoor (I/O) concentration ratios, and estimated penetration factors as a function of particle size. Indoor particle generation and transport of outdoor particles through the HVAC system were the most important contributors to the indoor concentration in residential and commercial buildings, respectively. The most significant removal mechanisms included ventilation through and particle removal by the HVAC filter if an HVAC system was present, or particle deposition on indoor surfaces if an HVAC system was not present. The modeled I/O concentration ratios varied between 0.05 and 0.5, depending on particle size and type of ventilation system, and agreed well with published experimental results. Penetration factors less than unity were calculated for particles with aerodynamic diameters larger than 0.2 θ m if the air exchange rate and steady-state I/O concentration ratio were correlated during the simulations. An additional correlation between the air exchange rate and particle deposition velocity is required if penetration factors less than unity are to be modeled for particles with aerodynamic diameters smaller than 0.2 θ m. These results
The prostate cancer detection rate from screening by digital rectal examination and tactilely guided prostate biopsy is approximately 1.7%. Among 1,807 men a detection rate of 14.6% was achieved in a ...clinical urological practice by physician-conducted prostate ultrasonography, digital rectal examination and determination of serum prostate specific antigen. Results are presented in 5-year increments as well as for the group as a whole. The possible benefit to be derived from an improved detection rate is undetermined. Recommendations are made regarding the clinical use of these diagnostic modalities.
cDNA clones corresponding to an Mr approximately 80,000 receptor (type I receptor) for interleukin‐1 (IL‐1) have been isolated previously by mammalian expression. Here, we report the use of an ...improved expression cloning method to isolate human and murine cDNA clones encoding a second type (Mr approximately 60,000) of IL‐1 receptor (type II receptor). The mature type II IL‐1 receptor consists of (i) a ligand binding portion comprised of three immunoglobulin‐like domains; (ii) a single transmembrane region; and (iii) a short cytoplasmic domain of 29 amino acids. This last contrasts with the approximately 215 amino acid cytoplasmic domain of the type I receptor, and suggests that the two IL‐1 receptors may interact with different signal transduction pathways. The type II receptor is expressed in a number of different tissues, including both B and T lymphocytes, and can be induced in several cell types by treatment with phorbol ester. Both IL‐1 receptors appear to be well conserved in evolution, and map to the same chromosomal location. Like the type I receptor, the human type II IL‐1 receptor can bind all three forms of IL‐1 (IL‐1 alpha, IL‐1 beta and IL‐1ra). Vaccinia virus contains an open reading frame bearing strong resemblance to the type II IL‐1 receptor.
Receptors for interleukin-4 (IL-4) are expressed at low levels on a wide variety of primary cells and cultured cell lines. Fluorescence-activated sorting of CTLL-2 cells resulted in the isolation of ...a subclone, CTLL 19.4, which expressed 10(6) IL-4 receptors per cell. These cells were used for the purification of IL-4 receptor protein and to prepare a hybrid-subtracted cDNA probe for isolation of cDNA clones. Three classes of IL-4 receptor cDNA were identified. The first encoded a 140 kd membrane bound IL-4 receptor containing extracellular, transmembrane, and cytoplasmic domains. The second class lacked the cytoplasmic region, and the third encoded a secreted form of the receptor. All cDNA clones expressed in COS-7 cells had IL-4 binding properties comparable to the native IL-4 receptor. The soluble form of the IL-4 receptor blocked the ability of IL-4 to induce CTLL cell proliferation and may represent a regulatory molecule specific for IL-4-dependent immune responses.
Ciliary neurotrophic factor (CNTF) has been described as a neuro-active cytokine that shares functional similarities with
the leukemia inhibitory factor (LIF). We demonstrate here that, like LIF, ...CNTF stimulates expression of acute phase plasma
proteins in rat H-35 hepatoma cells. Transfection of the LIF receptor into Hep3B hepatoma cells reconstituted LIF and oncostatin
M regulation of acute phase plasma protein genes. Co-expression of the LIF receptor and the CNTF receptor, but not expression
of either subunit alone, generated CNTF responsiveness in Hep3B cells, suggesting cooperativity of these receptor subunits.
Evidence is presented for direct interaction of the LIF receptor with the intracellular signal transduction machinery.
IL-4, a pleiotropic cytokine produced by T lymphocytes, plays an important role in immune responsiveness by regulating proliferation and differentiation of a variety of lymphoid and myeloid cells via ...binding to high affinity receptors. In this report we describe the isolation and functional expression of a human IL-4-R cDNA. When transfected into COS-7 cells, the cDNA encodes a 140-kD cell-surface protein. After transfection into a murine T cell line, the cDNA encodes a protein that binds human IL-4 with high affinity and can confer responsiveness to human IL-4. The predicted extracellular domain of the IL-4-R exhibits significant amino acid sequence homology with the beta subunit of the IL-2-R (p75), and the receptors for IL-6, erythropoietin, and prolactin. These receptors comprise a novel superfamily with extracellular domains characterized by four conserved cysteine residues and a double tryptophan-serine (WSXWS) motif located proximal to the transmembrane region.
Specific low-affinity receptors for leukemia inhibitory factor (LIF), oncostatin M (OSM; gp130), and ciliary neurotrophic factor (CNTF; receptor α, CNTFRα) may be utilized in various combinations to ...generate high-affinity binding sites and signal transduction. We have tested the ability of combinations of these receptors to transduce a proliferative signal in BAF-B03 cells. Coexpression of the LIF receptor and gp130 in these cells conferred high-affinity LIF and OSM binding and responsiveness to LIF and OSM. These cells also responded to CNTF in the absence of detectable binding. The further addition of CNTFRα conferred high-affinity CNTF binding and enhanced responsiveness to CNTF but did not modify responses to LIF or OSM. Coexpression of LIF receptor and CNTFRα resulted in a nonfunctional high-affinity binding site. These data are consistent with a role for the CNTFRα in enhancing CNTF action but the CNTFRα is not absolutely required for CNTF action and suggest a wider range of targets for CNTF.
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