Editorial: pulsatile hormone patterns governing transcription factor function. Physiology of episodic GH secretion.
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Animals↗
Biomedical subjects
J Schwartz
Publications and source records attributed to J Schwartz.
The concentration-response relation between air pollution and daily deaths.
Studies on three continents have reported associations between various measures of airborne particles and daily deaths. Sulfur dioxide has also been associated with daily deaths, particularly in Europe. Questions remain about the shape of those associations, particularly whether there are thresholds at low levels. We examined the association of daily concentrations of black smoke and SO(2) with daily deaths in eight Spanish cities (Barcelona, Bilbao, Castellón, Gijón, Oviedo, Valencia, Vitoria, and Zaragoza) with different climates and different environmental and social characteristics. We used nonparametric smoothing to estimate the shape of the concentration-response curve in each city and combined those results using a metasmoothing technique developed by Schwartz and Zanobetti. We extended their method to incorporate random variance components. Black smoke had a nearly linear association with daily deaths, with no evidence of a threshold. A 10 microg/m(3) increase in black smoke was associated with a 0.88% increase in daily deaths (95% confidence interval, 0.56%-1.20%). SO(2) had a less plausible association: Daily deaths increased at very low concentrations, but leveled off and then decreased at higher concentrations. These findings held in both one- and two-pollutant models and held whether we optimized our weather and seasonal model in each city or used the same smoothing parameters in each city. We conclude that the association with particle levels is more convincing than for SO(2), and without a threshold. Linear models provide an adequate estimation of the effect of particulate air pollution on mortality at low to moderate concentrations.
Adolescent↗
Gaseous pollutants in particulate matter epidemiology: confounders or surrogates?
Air pollution epidemiologic studies use ambient pollutant concentrations as surrogates of personal exposure. Strong correlations among numerous ambient pollutant concentrations, however, have made it difficult to determine the relative contribution of each pollutant to a given health outcome and have led to criticism that health effect estimates for particulate matter may be biased due to confounding. In the current study we used data collected from a multipollutant exposure study conducted in Baltimore, Maryland, during both the summer and winter to address the potential for confounding further. Twenty-four-hour personal exposures and corresponding ambient concentrations to fine particulate matter (PM(2.5)), ozone, nitrogen dioxide, sulfur dioxide, and carbon monoxide were measured for 56 subjects. Results from correlation and regression analyses showed that personal PM(2.5) and gaseous air pollutant exposures were generally not correlated, as only 9 of the 178 individual-specific pairwise correlations were significant. Similarly, ambient concentrations were not associated with their corresponding personal exposures for any of the pollutants, except for PM(2.5), which had significant associations during both seasons (p < 0.0001). Ambient gaseous concentrations were, however, strongly associated with personal PM(2.5) exposures. The strongest associations were shown between ambient O(3) and personal PM(2.5) (p < 0.0001 during both seasons). These results indicate that ambient PM(2.5) concentrations are suitable surrogates for personal PM(2.5) exposures and that ambient gaseous concentrations are surrogates, as opposed to confounders, of PM(2.5). These findings suggest that the use of multiple pollutant models in epidemiologic studies of PM(2.5) may not be suitable and that health effects attributed to the ambient gases may actually be a result of exposures to PM(2.5).
Adolescent↗
Investigating regional differences in short-term effects of air pollution on daily mortality in the APHEA project: a sensitivity analysis for controlling long-term trends and seasonality.
Short-term effects of air pollution on daily mortality in eight western and five central-eastern European countries have been reported previously, as part of the APHEA project. One intriguing finding was that the effects were lower in central-eastern European cities. The analysis used sinusoidal terms for seasonal control and polynomial terms for meteorologic variables, but this is a more rigid approach than the currently accepted method, which uses generalized additive models (GAM). We therefore reanalyzed the original data to examine the sensitivity of the results to the statistical model. The data were identical to those used in the earlier analyses. The outcome was the daily total number of deaths, and the pollutants analyzed were black smoke (BS) and sulfur dioxide (SO(2)). The analyses were restricted to days with pollutant concentration < 200 microg/m(3) and < 150 microg/m(3) alternately. We used Poisson regression in a GAM model, and combined individual city regression coefficients using fixed and random-effect models. An increase in BS by 50 microg/m(3) was associated with a 2.2% and 3.1% increase in mortality when analysis was restricted to days < 200 microg/m(3) and < 150 microg/m(3), respectively. The corresponding figures were 5.0% and 5.6% for a similar increase in SO(2). These estimates are larger than the ones published previously: by 69% for BS and 55% for SO(2). The increase occurred only in central-eastern European cities. The ratio of western to central-eastern cities for estimates was reduced to 1.3 for BS (previously 4.8) and 2.6 for SO(2) (previously 4.4). We conclude that part of the heterogeneity in the estimates of air pollution effects between western and central-eastern cities reported in previous publications was caused by the statistical approach used and the inclusion of days with pollutant levels above 150 microg/m(3). However, these results must be investigated further.
Adolescent↗
Interrelations of lead levels in bone, venous blood, and umbilical cord blood with exogenous lead exposure through maternal plasma lead in peripartum women.
Recent research has raised the possibility that fetal lead exposure is not estimated adequately by measuring lead content in maternal whole blood lead because of the variable partitioning of lead in whole blood between plasma and red blood cells. Lead in maternal plasma may derive in large part from maternal bone lead stores. In this study we aimed to estimate the contribution of maternal whole blood lead, maternal bone lead levels, and environmental lead to umbilical cord blood lead levels (as a measure of fetal lead exposure). In the model, we assumed that lead from all of these sources reaches the fetus through the maternal plasma lead pathway. In 1994-1995, we recruited 615 pregnant women for a study of lead exposure and reproductive outcomes in Mexico City. We gathered maternal and umbilical cord blood samples within 12 hr of each infant's delivery and measured maternal lead levels in cortical bone and trabecular bone by a K-X-ray fluorescence (K-XRF) instrument within 1 month after delivery. We administered a questionnaire to assess use of lead-glazed ceramics (LGC) to cook food and we obtained data on regional air lead levels during the 2 months before delivery. We used structural equation models (SEMs) to estimate plasma lead as the unmeasured (latent) variable and to quantify the interrelations of plasma lead, the other lead biomarkers, and environmental lead exposure. In the SEM analysis, a model that allowed plasma lead to vary freely from whole blood lead explained the variance of cord blood lead (as reflected by a total model R(2); R(2) = 0.79) better than did a model without plasma lead (r(2) = 0.67). Cortical bone lead, trabecular bone lead, use of LGC, and mean air lead level contributed significantly to plasma lead. The exchange of lead between plasma and red blood cells was mostly in the direction of plasma to cells. According to the final model, an increase in trabecular bone lead and cortical bone lead was associated with increases in cord blood lead of 0.65 and 0.25 microg/dL, respectively. An increase of 0.1 microg/m(3) in air lead was associated with an increase in the mean level of fetal cord blood lead by 0.67 microg/dL. With one additional day of LCG use per week in the peripartum period, the mean fetal blood lead level increased by 0.27 microg/dL. Our analyses suggested that maternal plasma lead varies independently from maternal whole blood lead and that the greatest influences on maternal plasma lead are maternal bone lead stores, air lead exposures, and recent cooking with LGC. The contributions from endogenous (bone) and exogenous (environmental) sources were relatively equal. Measurement of plasma and bone lead may be important in accurately assessing fetal lead exposure and its major sources, particularly if exogenous exposures decline.
Air Pollutants↗
Influence of bone resorption on the mobilization of lead from bone among middle-aged and elderly men: the Normative Aging Study.
Bone stores of lead accrued from environmental exposures and found in most of the general population have recently been linked to the development of hypertension, cognitive decrements, and adverse reproductive outcomes. The skeleton is the major endogenous source of lead in circulating blood, particularly under conditions of accelerated bone turnover and mineral loss, such as during pregnancy and in postmenopausal osteoporosis. We studied the influence of bone resorption rate on the release of lead from bone in 333 men, predominantly white, middle-aged and elderly (mostly retired) from the Boston area. We evaluated bone resorption by measuring cross-linked N-telopeptides of type I collagen (NTx) in 24-hr urine samples with an enzyme-linked immunosorbent assay. We used K-X-ray fluorescence to measure lead content in cortical (tibia) and trabecular (patella) bone; we used graphite furnace atomic absorption spectroscopy and inductively coupled plasma mass spectroscopy to measure lead in blood and urine, respectively. After adjustment for age and creatinine clearance, the positive relation of patella lead to urinary lead was stronger among subjects in the upper two NTx tertiles (beta for patella lead > or =0.015) than in the lowest NTx tertile (beta for patella lead = 0.008; overall p-value for interactions = 0.06). In contrast, we found no statistically significant influence of NTx tertile on the relationship of blood lead to urinary lead. As expected, the magnitude of the relationship of bone lead to urinary lead diminished after adjustment for blood lead. Nevertheless, the pattern of the relationships of bone lead to urinary lead across NTx tertiles remained unchanged. Furthermore, after adjustment for age, the relation of patella lead to blood lead was significantly stronger in the upper two NTx tertiles (beta for patella lead > or =0.125) than in the lowest NTx tertile (beta for patella lead = 0.072). The results provide evidence that bone resorption influences the release of bone lead stores (particularly patella lead) into the circulation.
Adult↗
Air pollution and blood markers of cardiovascular risk.
Recent studies have linked air pollution to tens of thousands of premature cardiovascular deaths per year. The mechanisms of such associations remain unclear. In this study we examine the association between blood markers of cardiovascular risk and air pollution in a national sample of the U.S. population. Air pollution concentrations were merged to subjects in the Third National Health and Nutrition Examination Survey (NHANES III) in the United States, and the association with fibrinogen levels and counts of platelets and white blood cells were examined. The subjects in NHANES III are a representative sample of the U.S. population. Regressions controlled for age, race, sex, body mass index, current smoking, and number of cigarettes per day. The complex survey design was dealt with using mixed models with a random sampling site effect. In single-pollutant models, PM(10) (particulate matter with a mass median aerodynamic diameter less than 10 microm) was associated with all three outcomes (p< 0.05): Sulfur dioxide (SO(2)) was significantly associated only with white cell counts, nitrogen dioxide (NO(2)) with platelet counts and fibrinogen, and ozone with none of the outcomes. In two-pollutant models, PM(10) remained a significant predictor of white cell counts controlling for SO(2) but not vice versa. PM(10) was marginally significant in a model for platelet counts with NO(2), and the sign of the NO(2) coefficient was reversed. These results were stable with control for indoor exposures (wood stoves, environmental tobacco smoke, gas stoves, fireplaces), dietary risk factors (saturated fat, alcohol, caffeine intake, n-3 fatty acids), and serum cholesterol. The magnitude of the effects are modest [e.g., 13 microg/dL fibrinogen for an interquartile range (IQR) change in PM(subscript)10(/subscript), 95% confidence interval (CI) 4.6-22.1 mg/dL]. However, the odds ratio of being in the top 10% of fibrinogen for the same IQR change was 1.77 (95% CI 1.26-2.49). These effects provide considerable biologic plausibility to the mortality studies. PM(10), but not gaseous air pollutants, is associated with blood markers of cardiovascular risk, and this may explain epidemiologic associations with early deaths.
Adult↗
Prepro-thyrotropin-releasing hormone 178-199 increases sensitivity of AtT-20 cells to dexamethasone.
The prepro-thyrotropin-releasing hormone (ppTRH)-derived peptide, ppTRH178-199, has been proposed to inhibit ACTH release at the level of the pituitary and attenuate prolactin and behavioral responses to stress as well. The objective of this study was to elucidate a possible link between the effects of ppTRH178-199 and glucocorticoids on the inhibition of ACTH release in corticotrophs. Compared with mock-transfected cells, AtT-20 cells that were stably transfected with full-length ppTRH cDNA showed significantly increased sensitivity to dexamethasone, as measured by inhibition of ACTH release. In a group of control cells, expressing a mutated form of ppTRH cDNA lacking the ppTRH178-199 region, sensitivity to dexamethasone was not different from mock-transfected controls. Exogenous ppTRH178-199 also increased the inhibitory effect of dexamethasone in wild-type AtT-20 cells. The combined effect of dexamethasone and ppTRH cDNA in cells that express the latter was not due to increased endogenous secretion of ppTRH178-199 in response to dexamethasone, as dexamethasone was independently found to inhibit secretion of ppTRH178-199. Taken together, these data suggest that ppTRH178-199 can interact with the glucocorticoid negative feedback inhibition to regulate ACTH secretion.
Adrenocorticotropic Hormone↗
Calculating percent stenosis.
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Cerebrovascular Disorders↗
Credo for a care manager. Use of clinical principles can improve relations with providers.
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Case Management↗
Characterization of urocortin in human pregnancy.
OBJECTIVE: To examine whether urocortin is produced locally to regulate utero-placental vascular tone during pregnancy. METHODS: We examined the distribution of urocortin in human placenta, fetal membranes and uterine tissue at term in the presence and absence of labor using a urocortin antibody produced in our laboratory and the immunoperoxidase staining method. Subsequently, we tested urocortin secretion from chorio-decidual cells in vitro using an immunoblot technique. Then, we tested whether urocortin is present in maternal plasma throughout gestation using a radioimmunoassay. A Sephadex G-50 column was used to examine whether immunoreactive urocortin (IR-urocortin) in maternal plasma is the same as synthetic urocortin. RESULTS: IR-urocortin was observed in vascular smooth muscle of myometrium decidual stromal cells, syncytiotrophoblast and amnion epithelium. No differences in staining intensity for urocortin were detected between tissues obtained in the absence or presence of labor. Staining intensity for IR-urocortin was greatest in the decidua, suggesting this may be the main site of urocortin production. Positive staining for urocortin was observed in 40% of chorio-decidual cells with 34% of these cells secreting urocortin under basal conditions. Urocortin was detectable in maternal plasma from 16 weeks gestation and concentrations did not change as gestation progressed. IR-urocortin in the maternal plasma eluted from a Sephadex G-50 column at the same site as synthetic urocortin and had a calculated retention co-efficient of 0.44. CONCLUSION: This study indicates that urocortin is produced by the decidua during human pregnancy and is detectable in maternal plasma. These data are consistent with the hypothesis that urocortin is produced locally by the decidua and may act to regulate utero-placental blood flow.
Animals↗
Association between psychosocial work characteristics and health functioning in American women: prospective study.
OBJECTIVE: To examine prospectively the relation between psychosocial work characteristics and changes in health related quality of life over four years in a cohort of working women in the United States. DESIGN: Longitudinal cohort study. SETTING: United States. PARTICIPANTS: 21 290 female registered nurses who completed the Karasek's job content questionnaire and a modified version of the short form 36 questionnaire (SF-36) as used for a survey of health status by the medical outcomes study. MAIN OUTCOME MEASURES: Seven dimensions of health status: physical functioning, role limitations due to physical health problems, bodily pain, vitality, social functioning, role limitations due to emotional problems, and mental health. RESULTS: Examined separately low job control, high job demands, and low work related social support were associated with poor health status at baseline as well as greater functional declines over the four year follow up period. Examined in combination, women with low job control, high job demands, and low work related social support ("iso-strain" jobs) had the greatest functional declines. These associations could not be explained by age, body mass index, comorbid disease status, alcohol consumption, smoking status, education level, exercise level, employment status, marital status, or presence of a confidant. CONCLUSIONS: Adverse psychosocial work conditions are important predictors of poor functional status and its decline over time.
Adult↗
The role of STAT proteins in growth hormone signaling.
Growth hormone (GH) has long been known to be the body's primary regulator of body growth and a regulator of metabolism, yet the mechanisms by which GH regulates the transcription of specific genes required for these processes are just now being delineated. GH binding to its receptor recruits and activates the receptor-associated JAK2 that in turn phosphorylates tyrosines within itself and the GH receptor. These tyrosines form binding sites for a number of signaling proteins, including members of the family of signal transducers and activators of transcription (STAT). Among the known signaling molecules for GH, STAT proteins play a particularly prominent role in the regulation of gene transcription. This paper will review what is currently understood about which STAT proteins are regulated by GH, how they are regulated by GH, the GH-dependent genes they regulate, and discuss current theories about how GH-activated STAT signaling is regulated. Particular attention will be given to the novel role that STAT5 plays in sexually dimorphic gene expression in the liver as determined by the secretory pattern of GH and the role of STAT5 in body growth. Oncogene (2000).
Adaptor Proteins, Signal Transducing↗
Evidence for collective oblate rotation in N = Z 68Se
A gamma-ray spectroscopic measurement of the N = Z nucleus 68Se has been made following the 12C(58Ni,2n) reaction at 185 and 220 MeV using Gammasphere and the Argonne Fragment Mass Analyzer. Despite a very low production cross section of 200(50) &mgr;b, two distinct rotational bands were found; the ground state band consistent with oblate collective rotation, and an excited band consistent with prolate rotation. These observations support long-standing predictions that nuclear ground states with substantial oblate (beta(2) approximately -0.3) deformation should exist in this region.
Journal Article↗
Ambient pollution and heart rate variability.
BACKGROUND: We investigated associations between ambient pollution levels and cardiovascular function in a repeated measures study including 163 observations on twenty-one 53- to 87-year-old active Boston residents observed up to 12 times from June to September 1997. Particles with aerodynamic diameter </=2.5 microm (PM(2.5)) were measured continuously using a tapered element oscillating microbalance. METHODS AND RESULTS: The protocol involved 25 minutes per week of continuous Holter ECG monitoring, including 5 minutes of rest, 5 minutes of standing, 5 minutes of exercise outdoors, 5 minutes of recovery, and 20 cycles of slow breathing. Heart rate variability (HRV) was assessed through time domain variables: the standard deviation of normal RR intervals (SDNN) and the square root of the mean of the squared differences between adjacent normal RR intervals (r-MSSD). Mean 4-hour PM(2.5) levels ranged from 3 to 49 microg/m(3); 1-hour ozone levels ranged from 1 to 77 ppb. In multivariate analyses, significantly less HRV (SDNN and r-MSSD) was associated with elevated PM(2.5). During slow breathing, a reduction in r-MSSD of 6.1 ms was associated with an interquartile (14.3 microg/m(3)) increase in PM(2.5) during the hour of and the 3 hours previous to the Holter session (P=0.006). During slow breathing, a multiple pollution model was associated with a reduction in r-MSSD of 5.4 ms (P=0.02) and 5.5 ms (P=0.03) for interquartile changes in PM(2.5) and ozone, respectively, resulting in a combined effect equivalent to a 33% reduction in the mean r-MSSD. CONCLUSIONS: Particle and ozone exposure may decrease vagal tone, resulting in reduced HRV.
Aged↗
Harvesting and long term exposure effects in the relation between air pollution and mortality.
While time series analyses have demonstrated that airborne particles are associated with early death, they have not clarified how much the deaths are advanced. If all of the pollution-related deaths were advanced by only a few days, one would expect little association between weekly averages of air pollution and daily deaths. The author used the STL algorithm to classify data on air pollution, daily deaths, and weather from Boston, Massachusetts (1979-1986) into three time series: one reflecting seasonal and longer fluctuations, one reflecting short term fluctuations, and one reflecting intermediate patterns. By varying the cutoff point between short term and intermediate term, it was possible to examine harvesting on different time scales. For chronic obstructive pulmonary disease, there was evidence that most of the mortality was displaced by only a few months. For pneumonia, heart attacks, and all-cause mortality, the effect size increased with longer time scales. The percentage increase in all deaths associated with a 10-microg/m3 increase in PM2.5 rose from 2.1% (95% confidence interval: 1.5, 4.3) to 3.75% (95% confidence interval: 3.2, 4.3) as the focus moved from daily patterns to monthly patterns. This is consistent with the larger effect seen in prospective cohort studies, rather than harvesting's playing a major role.
Air Pollutants↗
Patients with chronic obstructive pulmonary disease are at increased risk of death associated with urban particle air pollution: a case-crossover analysis.
The authors assessed the acute association between particulate air pollution and mortality among subjects suffering from chronic obstructive pulmonary disease by using a case-crossover analysis. This design avoided the common concerns about the methods used to assess the acute effects of air pollution. The 1,845 men and the 460 women included were residents of Barcelona, Spain, who were over age 35 years, had died during the period 1990-1995, and had visited emergency rooms because of a chronic obstructive pulmonary disease exacerbation during the period 1985-1989. Particle levels (measured as black smoke at the city monitoring stations) were associated with mortality for all causes (odds ratio (OR) for an increase of 20 microg/m3, the interquartile change, adjusted for temperature, humidity, and influenza = 1.112, 95 percent confidence interval (CI): 1.017, 1.215). The association was stronger for respiratory causes (OR = 1.182, 95 percent CI: 1.025, 1.365), but was not significant for cardiovascular causes (OR = 1.077, 95 percent CI: 0.917, 1.264). Older women, patients admitted to intensive care units, and patients with a higher rate of emergency room visits were at greater risk of dying associated with black smoke. The results reinforced the deleterious role of urban pollution and provided information on factors possibly conferring susceptibility to the acute role of air pollution.
Adult↗
Laparoscopic splenectomies for idiopathic thrombocytopenic purpura: experience of sixty cases.
We performed a laparoscopic splenectomy (LS) in 60 patients (age 9-83, 45 females) with idiopathic thrombocytopenic purpura (ITP) who did not achieve sustained remission on steroid therapy. Using a modified procedure, the mean duration of LS was 78 min (range 25-240 min) and surgery was associated with only 5% major and 5% minor complications. Ten patients had a platelet count less than 50 x 10(9)/l during surgery despite the administration of immune globulin (0.4 g/kg x 3-5 days) or pulsed oral dexamethasone (40 mg/day x 4 days). Three patients were refractory to these therapies and underwent LS with a platelet count less than 5 x 10(9)/l. Bleeding complications during or after surgery were rare (5%). Accessory spleens were removed in eight patients. Convalescence was rapid and the mean hospital stay was 2.3 days (range 1-7 days). The patients were followed for a mean of 16 months (range 1-36 months), and 49 patients (84%) are in complete remission. Seven patients (12.5%) relapsed despite an initial good response in 6 of them. Two patients underwent laparoscopic removal of accessory spleens with excellent response. We conclude that LS for ITP is safe and effective and associated with low morbidity and fast recovery. Thus, LS may be considered earlier in the course of ITP.
Adolescent↗