Whole-exome sequencing of a pedigree segregating asthma.

Background: Despite the success of genome-wide association studies for asthma, few, if any, definitively causal variants have been identified and there is still a substantial portion of the heritability of the disease yet to be discovered. Some of this "missing heritability" may be accounted for by family-specific coding variants found to be segregating with asthma.

Methods: To identify family-specific variants segregating with asthma, we recruited one family from a previous study of asthma as reporting multiple asthmatic and non-asthmatic children.

Histophilus somni causes extracellular trap formation by bovine neutrophils and macrophages.

Histophilus somni (formerly Haemophilus somnus) is a Gram-negative pleomorphic coccobacillus that causes respiratory, reproductive, cardiac and neuronal diseases in cattle. H. somni is a member of the bovine respiratory disease complex that causes severe bronchopneumonia in cattle.

Mannheimia haemolytica and its leukotoxin cause macrophage extracellular trap formation by bovine macrophages.

Human and bovine neutrophils release neutrophil extracellular traps (NETs), which are protein-studded DNA matrices capable of extracellular trapping and killing of pathogens. Recently, we reported that bovine neutrophils release NETs in response to the important respiratory pathogen Mannheimia haemolytica and its leukotoxin (LKT). Here, we demonstrate macrophage extracellular trap (MET) formation by bovine monocyte-derived macrophages exposed to M.

Mannheimia haemolytica leukotoxin binds cyclophilin D on bovine neutrophil mitochondria.

Mannheimia haemolytica is an important member of the bovine respiratory disease (BRD) complex that causes fibrinous and necrotizing pleuropneumonia in cattle. BRD is characterized by abundant neutrophil infiltration into the alveoli and fibrin deposition. The most important virulence factor of M.

Mannheimia haemolytica and its leukotoxin cause neutrophil extracellular trap formation by bovine neutrophils.

Mannheimia haemolytica is an important member of the bovine respiratory disease complex, which is characterized by abundant neutrophil infiltration into the alveoli and fibrin deposition. Recently several authors have reported that human neutrophils release neutrophil extracellular traps (NETs), which are protein-studded DNA matrices capable of trapping and killing pathogens. Here, we demonstrate that the leukotoxin (LKT) of M.

Effects of lipopolysaccharide and Mannheimia haemolytica leukotoxin on bovine lung microvascular endothelial cells and alveolar epithelial cells.

Bovine respiratory disease resulting from infection with Mannheimia haemolytica commonly results in extensive vascular leakage into the alveoli. M. haemolytica produces two substances, lipopolysaccharide (LPS) and leukotoxin (LKT), that are known to be important in inducing some of the pathological changes.

Association of maternal caffeine consumption with decrements in fetal growth.

Whether caffeine consumption during pregnancy represents a fetal hazard remains uncertain. The authors report on a large prospective study designed to examine this question. In 1996-2000, 2,291 mothers with singleton livebirths in Connecticut and Massachusetts were evaluated after their first prenatal visit and were questioned about caffeine consumption and important confounding factors.

Heterogeneity in assessing self-reports of caffeine exposure: implications for studies of health effects.

Background: Coffee and its metabolite caffeine are widely studied for their health effects but with inconclusive results. Caffeine is particularly difficult to assess, and therefore we explore heterogeneity of caffeine exposure.

Methods: We categorized caffeine exposure among 2,478 pregnant women in southern New England during 1996-2000 by the traditional laboratory-based methods of M.

Environmental tobacco smoke exposure and small-for-gestational-age birth.

The aim of this analysis was to examine the effect of environmental tobacco smoke exposure on the risk of small-for-gestational-age (SGA) birth. The study population included 2,283 nonsmokers from a nested cohort study undertaken in southern Connecticut from 1988 to 1992. The duration and intensity of exposures incurred at multiple locations during the third trimester of pregnancy were measured by postpartum interview.

Correlates of residential wiring code used in studies of health effects of residential electromagnetic fields.

The home wiring code is the most widely used metric for studies of residential electromagnetic field (EMF) exposure and health effects. Despite the fact that wiring code often shows stronger correlations with disease outcome than more direct EMF home assessments, little is known about potential confounders of the wiring code association. In a study carried out in southern Connecticut in 1988-1991, the authors used strict and widely used criteria to assess the wiring codes of 3,259 homes in which respondents lived.

Spontaneous abortion and exposure to electric blankets and heated water beds.

We conducted a prospective study (N = 2,967) to evaluate the relation of spontaneous abortion with use of electrically heated beds (electric blankets and heated water beds) during pregnancy. At interview, 61.5% of women were at less than 12 weeks gestation, and 38.

Maternal caffeine consumption and spontaneous abortion: a prospective cohort study.

We investigated the relation between caffeine beverage consumption and spontaneous abortion in 2,967 pregnant women planning to deliver at Yale-New Haven Hospital in 1988-1992. We evaluated coffee, tea, and soda drinking in the first month of pregnancy in interviews before the end of the sixteenth week of gestation. We obtained information on 98.

Exposure to electromagnetic fields during pregnancy with emphasis on electrically heated beds: association with birthweight and intrauterine growth retardation.

Several animal and human studies indicate that fetal growth may be retarded following exposure to electromagnetic fields (EMF). We conducted a prospective study (N = 2,967) to evaluate the relation of birthweight and fetal growth retardation with use of electrically heated beds (electric blankets and heated water beds) during pregnancy. A "nested" study design allowed monitoring of exposure at different stages of pregnancy using both direct and indirect methods.

Association of cocaine use with sperm concentration, motility, and morphology.

Use of cocaine within 2 years of their first semen analysis has been found to be twice as common among men with sperm counts less than 20 X 10(6) mL (odds ratio [OR] = 2.1, 95% confidence interval [CI] 1.0, 4.

Conception delay after oral contraceptive use: the effect of estrogen dose.

A significant delay was observed in conception among 248 former oral contraceptive (OC) users compared with women discontinuing other methods of contraception (n = 1,365). The mean time to conception was 5.88 cycles (95% confidence interval [CI] 5.

Effect of maternal work activity on preterm birth and low birth weight.

The association of the prolonged standing required by certain jobs with the rate of preterm births and low birth weight deliveries was examined in New Haven, Connecticut, between 1980 and 1982. In a sample of 1,206 women, the rate of preterm births (births occurring less than 37 weeks from the last menstrual period) was higher among women with jobs requiring prolonged standing (7.7%) compared with those with sedentary (4.

Proportional weight gain and complications of pregnancy, labor, and delivery in healthy women of normal prepregnant stature.

Detailed reproductive information was obtained through interview at early prenatal visits to hospital clinics, private medical groups, or health maintenance organizations for 4186 women delivered at Yale-New Haven Hospital. From these women, 1,396 were selected who had no preexisting chronic disease, were within their normal prepregnant weight for height as determined by Quetelet's Index (weight2/height2), and were delivered of single infants with no major congenital malformations between 37 and 42 weeks. These women were divided into four quartiles according to their proportional weight gain (weight gain/prepregnant weight): quartile 1 = gains less than or equal to 15%; quartile 2 = gains 16% to 25%; quartile 3 = gains 26% to 35%; quartile 4 = gains greater than 35%.

Low birth weight in pregnancies following induced abortion: no evidence for an association.

Compared with women delivering a first pregnancy, those delivering a second pregnancy after aborting the first have similar rates of low (less than 2,500 g) birth weight newborns (relative risk (RR) G2A1/G1 = 0.86, 95% confidence interval (CI) = 0.49-1.

Methylprednisolone and neurological function 1 year after spinal cord injury. Results of the National Acute Spinal Cord Injury Study.

A multi-center double-blind randomized clinical trial was conducted by the National Acute Spinal Cord Injury Study Group to examine the efficacy of high-dose methylprednisolone (1000-mg bolus and 1000 mg daily thereafter for 10 days) compared with that of a standard dose (100-mg bolus and 100 mg daily for 10 days). No significant difference was observed in neurological recovery of motor function, pinprick response, or touch sensation 1 year after injury between the two treatment groups, after adjustment for other potentially confounding factors. Analyses that specifically took into account the patients' total steroid dose and relative weight confirmed the lack of a steroid treatment effect.

Changes in the prevalence distribution of hypertension: Connecticut adults 1978-79 to 1982.

In the Spring and Summer of 1982 the Second Connecticut Blood Pressure Survey (CBPS-II) was completed. This survey is independent of, but essentially identical in design and implementation to the First Connecticut Blood Pressure Survey reported on by Freeman et al. [1].

Efficacy of methylprednisolone in acute spinal cord injury.

A multicenter double-blind randomized trial was conducted to examine the efficacy of a high dose of methylprednisolone (1,000-mg bolus and daily thereafter for ten days) compared with a standard dose (100-mg bolus and daily thereafter for ten days) in 330 patients with acute spinal cord injury. No difference in neurological recovery of motor function or pinprick and light touch sensation was observed between the two treatment groups six weeks and six months after injury. The lack of a treatment effect was independent of the severity of the initial lesion or the time from injury to starting treatment.

Dietary salt intake and blood pressure.

With an index for dietary salt use designed to provide a semiquantitative estimate of salt intake, we have found that in a sample representative of the 2.1 million adults in Connecticut, the mean BP of those at the 90th percentile or higher of salt intake differs by a quantitatively insignificant amount from the mean BP of those at the tenth percentile or lower of salt intake. When we examined the obese (body mass index, 90th percentile or higher) separately, similar results were obtained.

The prevalence distribution of hypertension: Connecticut adults 1978-1979.

The results of the first Connecticut Blood Pressure Survey are reported. It was found that sharp differences exist in the prevalence of hypertension by age and sex but that race differences are much less than previously reported for United States populations. Differences were also found between men and women with respect to the patterns of treatment and control.