tbuckley/cabot-search huggingface dataset:
The Effect of Air Pollution on Lung Development from 10 to 18 Years of Age
Authors: W. James Gauderman, Edward Avol, Frank Gilliland, Hita Vora, Duncan Thomas, Kiros Berhane, Rob McConnell, Nino Kuenzli, Fred Lurmann, Edward Rappaport, Helene Margolis, David Bates, John Peters
Journal: New England Journal of Medicine (2004)

Whether exposure to air pollution adversely affects the growth of lung function during the period of rapid lung development that occurs between the ages of 10 and 18 years is unknown.In this prospective study, we recruited 1759 children (average age, 10 years) from schools in 12 southern California communities and measured lung function annually for eight years. The rate of attrition was approximately 10 percent per year. The communities represented a wide range of ambient exposures to ozone, acid vapor, nitrogen dioxide, and particulate matter. Linear regression was used to examine the relationship of air pollution to the forced expiratory volume in one second (FEV(1)) and other spirometric measures.Over the eight-year period, deficits in the growth of FEV(1) were associated with exposure to nitrogen dioxide (P=0.005), acid vapor (P=0.004), particulate matter with an aerodynamic diameter of less than 2.5 microm (PM(2.5)) (P=0.04), and elemental carbon (P=0.007), even after adjustment for several potential confounders and effect modifiers. Associations were also observed for other spirometric measures. Exposure to pollutants was associated with clinically and statistically significant deficits in the FEV(1) attained at the age of 18 years. For example, the estimated proportion of 18-year-old subjects with a low FEV(1) (defined as a ratio of observed to expected FEV(1) of less than 80 percent) was 4.9 times as great at the highest level of exposure to PM(2.5) as at the lowest level of exposure (7.9 percent vs. 1.6 percent, P=0.002).The results of this study indicate that current levels of air pollution have chronic, adverse effects on lung development in children from the age of 10 to 18 years, leading to clinically significant deficits in attained FEV(1) as children reach adulthood.
How Experience Gets Under the Skin to Create Gradients in Developmental Health
Authors: Clyde Hertzman, Tom Boyce
Journal: Annual Review of Public Health (2010)

Social environments and experiences get under the skin early in life in ways that affect the course of human development. Because most factors associated with early child development are a function of socio-economic status, differences in early child development form a socio-economic gradient. We are now learning how, when, and by what means early experiences influence key biological systems over the long term to produce gradients: a process known as biological embedding. Opportunities for biological embedding are tethered closely to sensitive periods in the development of neural circuitry. Epigenetic regulation is the best example of operating principles relevant to biological embedding. We are now in a position to ask how early childhood environments work together with genetic variation and epigenetic regulation to generate socially partitioned developmental trajectories with impact on health across the life course.
Traffic-related Air Pollution and the Development of Asthma and Allergies during the First 8 Years of Life
Authors: Ulrike Gehring, Alet H. Wijga, Michael Brauer, Paul Fischer, Johan C. de Jongste, Marjan Kerkhof, Marieke Oldenwening, Henriette A. Smit, Bert Brunekreef
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

The role of air pollution exposure in the development of asthma, allergies, and related symptoms remains unclear, due in part to the limited number of prospective cohort studies with sufficiently long follow-ups addressing this problem.We studied the association between traffic-related air pollution and the development of asthma, allergy, and related symptoms in a prospective birth cohort study with a unique 8-year follow-up.Annual questionnaire reports of asthma, hay fever, and related symptoms during the first 8 years of life were analyzed for 3,863 children. At age 8, measurements of allergic sensitization and bronchial hyperresponsiveness were performed for subpopulations (n = 1,700 and 936, respectively). Individual exposures to nitrogen dioxide (NO(2)), particulate matter (PM(2.5)), and soot at the birth address were estimated by land-use regression models. Associations between exposure to traffic-related air pollution and repeated measures of health outcomes were assessed by repeated-measures logistic regression analysis. Effects are presented for an interquartile range increase in exposure after adjusting for covariates.Annual prevalence was 3 to 6% for asthma and 12 to 23% for asthma symptoms. Annual incidence of asthma was 6% at age 1, and 1 to 2% at later ages. PM(2.5) levels were associated with a significant increase in incidence of asthma (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.10-1.49), prevalence of asthma (OR, 1.26; 95% CI, 1.04-1.51), and prevalence of asthma symptoms (OR, 1.15; 95% CI, 1.02-1.28). Findings were similar for NO(2) and soot. Associations were stronger for children who had not moved since birth. Positive associations with hay fever were found in nonmovers only. No associations were found with atopic eczema, allergic sensitization, and bronchial hyperresponsiveness.Exposure to traffic-related air pollution may cause asthma in children.
Lifetime Risk of Cardiovascular Disease Among Individuals With and Without Diabetes Stratified by Obesity Status in the Framingham Heart Study
Authors: Caroline S. Fox, Michael J. Pencina, Peter W.F. Wilson, Nina P. Paynter, Ramachandran S. Vasan, Ralph B. D’Agostino
Journal: Diabetes Care (2008)

We assessed the lifetime risk of cardiovascular disease (CVD) among individuals with and without obesity and diabetes.Participants were drawn from the original and offspring cohorts of the Framingham Heart Study. Lifetime (30-year) risk of CVD was assessed using a modified Kaplan-Meier approach adjusting for the competing risk of death, beginning from age 50 years.Over 30 years, the lifetime risk of CVD among women with diabetes was 54.8% among normal-weight women and 78.8% among obese women. Among normal-weight men with diabetes, the lifetime risk of CVD was 78.6%, whereas it was 86.9% among obese men.The lifetime risk of CVD among individuals with diabetes is high, and this relationship is further accentuated with increasing adiposity.
Effect of prolonged nitrate therapy on left ventricular remodeling after canine acute myocardial infarction.
Authors: B I Jugdutt, M I Khan
Journal: Circulation (1994)

BACKGROUND Prolonged nitrate therapy during healing between 2 days and 6 weeks after anterior myocardial infarction has the potential for limiting further left ventricular remodeling (or changes in topography) and preserving function. Longterm therapy throughout healing over 6 weeks might be more beneficial than short-term therapy over the first 2 weeks after infarction. METHODS AND RESULTS The effect of prolonged nitrate therapy between 2 days and 6 weeks during healing after infarction on serial parameters of ventricular remodeling (scar expansion, scar thinning, ventricular dilation, and hypertrophy) and function (asynergy or akinesis plus dyskinesis and ejection fraction) by serial two-dimensional echocardiography, hemodynamics, postmortem topography (computerized planimetry, geometric maps, and radiographs), and collagen content (hydroxyproline) was studied in 64 instrumented dogs randomized 2 days after left anterior descending coronary artery ligation to various nitrate regimens (n = 32) over the first 2 weeks (subgroup 1: 2% transdermal nitroglycerin at 8 AM and 4 PM, n = 6; subgroup 2: 2% transdermal nitroglycerin plus 2.6 mg of sustained-release oral nitroglycerin at 8 AM, 3 PM, and 10 PM, n = 5; subgroup 3: oral isosorbide dinitrate, 30 mg at 8 AM and 4 PM, n = 11) or 6 weeks (subgroup 4: isosorbide dinitrate, n = 10) and in matching controls (n = 32). Nitrate therapy reduced left atrial pressure, mean arterial pressure, and the rate-pressure product compared with controls over the 6 weeks. Postmortem scar mass and hydroxyproline were similar in control and nitrate groups. However, scar stretching and thinning, cavity dilation, noninfarct wall hypertrophy, and apical bulging were less with nitrates, especially in the long-term subgroup 4. In vivo remodeling parameters between 2 days and 6 weeks after ligation showed that, compared with controls, nitrate therapy prevented further stretching of the asynergic segment, decreased the expansion index, decreased further scar thinning, prevented the increase in ventricular volumes, reduced the frequency of ventricular aneurysm, prevented the increase in ventricular mass, reduced the extent of asynergy, and improved ejection fraction. Although the beneficial effect on topography and function was seen in all nitrate subgroups, the overall benefit was greater with long-term therapy over 6 weeks (subgroup 4) than short-term therapy confined to the first 2 weeks (subgroups 1, 2, and 3). CONCLUSIONS Prolonged nitrate therapy, in various regimens during healing after infarction, effectively reduced left ventricular loading and prevented infarct thinning, further infarct expansion, progressive ventricular dilation, and the increase in mass. These effects were associated with decreased asynergy and improved ejection fraction. The beneficial effects were greater with long-term therapy over 6 weeks than short-term therapy over the first 2 weeks.
Metastatic Growth from Dormant Cells Induced by a Col-I–Enriched Fibrotic Environment
Authors: Dalit Barkan, Lara H. El Touny, Aleksandra M. Michalowski, Jane Ann Smith, Isabel Chu, Anne Sally Davis, Joshua D. Webster, Shelley Hoover, R. Mark Simpson, Jack Gauldie, Jeffrey E. Green
Journal: Cancer Research (2010)

Breast cancer that recurs as metastatic disease many years after primary tumor resection and adjuvant therapy seems to arise from tumor cells that disseminated early in the course of disease but did not develop into clinically apparent lesions. These long-term surviving, disseminated tumor cells maintain a state of dormancy, but may be triggered to proliferate through largely unknown factors. We now show that the induction of fibrosis, associated with deposition of type I collagen (Col-I) in the in vivo metastatic microenvironment, induces dormant D2.0R cells to form proliferative metastatic lesions through beta1-integrin signaling. In vitro studies using a three-dimensional culture system modeling dormancy showed that Col-I induces quiescent D2.0R cells to proliferate through beta1-integrin activation of SRC and focal adhesion kinase, leading to extracellular signal-regulated kinase (ERK)-dependent myosin light chain phosphorylation by myosin light chain kinase and actin stress fiber formation. Blocking beta1-integrin, Src, ERK, or myosin light chain kinase by short hairpin RNA or pharmacologic approaches inhibited Col-I-induced activation of this signaling cascade, cytoskeletal reorganization, and proliferation. These findings show that fibrosis with Col-I enrichment at the metastatic site may be a critical determinant of cytoskeletal reorganization in dormant tumor cells, leading to their transition from dormancy to metastatic growth. Thus, inhibiting Col-I production, its interaction with beta1-integrin, and downstream signaling of beta1-integrin may be important strategies for preventing or treating recurrent metastatic disease.
Aldose reductase and myo-inositol transporter mRNA are independently regulated in rat renal medulla.
Authors: T Nakanishi, A Yamauchi, M Sugita, Y Takamitsu
Journal: Journal of the American Society of Nephrology (1996)

During antidiuresis, renal papillary cells accumulate organic osmolytes preferentially over inorganic ions. It has been previously demonstrated that sodium infusion increased all of these organic osmolytes except myo-inositol (1). Conversely, urea infusion increased only glycerophosphorylcholine significantly. In addition to sodium and urea, potassium localized in tissue and urine influenced the composition of organic osmolytes. The goal of this study was to clarify how the level of mRNA of osmoregulatory protein is regulated by the extracellular solutes and how it affects the accumulation of organic osmolytes. To clarify the relationship between intra- or extracellular solutes and the regulation of Na/myo-inositol cotransporter and aldose reductase, mRNA of these osmo-regulatory proteins were determined in water-deprived sodium chloride-, potassium chloride-, and urea-loaded rats. Medullary content of sorbitol and myo-inositol, and aldose-reductase enzymatic activity were measured simultaneously in these animals. In water-deprived, sodium-loaded, and potassium-loaded rats, the inner medullary sorbitol content increased significantly in accordance with the rise in the enzymatic activity and the level of aldose reductase mRNA. In urea-loaded rats, both the sorbitol content and the level of aldose reductase mRNA were equal to that in hydrated rats. In the outer and inner medullary tissues, the level of myo-inositol transporter mRNA was increased in all hyperosmolality protocols, including urea infusion, which corresponded with the rise in myo-inositol content. In conclusion, potassium chloride infusion is as effective as water deprivation and sodium chloride infusion in raising the level of aldose reductase and myo-inositol transporter mRNA, whereas urea influenced only myo-inositol transporter. Although aldose reductase and myo-inositol transporter are osmoregulatory proteins in the renal medulla, the levels of aldose reductase and sodium-dependent myo-inositol transporter mRNA are regulated independently.
THE VALUE OF LABORATORY TESTS IN DISEASES OF THE LIVER AND PANCREAS
Authors: W. L. Brown
Journal: BMJ (1923)

IT is clear that in the time at my disposal nothing more than a very general review of this large subject can be attempted.Thle liver and pancreas are both developed as outgrowths of the alimentary tract, and their ducts are innervated in the same general -way as the canal from which they develop.Their close co-operation is further slhown in the way they pour their secretions into the alimentary tract at the same point, in their complementary r6les in the utilization of fat and in carbolhydrate metabolism, as well as by the circulatory conditions which ensure that any-internal secretion from the pancreas slhall pass straiglht to the liver.Situated on the path by wlhiclh all the blood from the digestive organs enters the svstemic circulation, it is not surprising to find that the liver helps to prepare all tlhree foodstuffs for utilization by
Antinuclear antibodies are common in an infectious environment but do not predict systemic lupus erythematosus
Authors: F Cainelli
Journal: Annals of the Rheumatic Diseases (2004)

The reasons underlying the appearance of autoantibodies are poorly understood. The recent proposal that childhood infections prevent both autoantibody formation and occurrence of autoimmune diseases1,2 led to the suggestion that widespread vaccination against infectious diseases might favour the development of autoimmune diseases.2

To verify whether repeated infections from childhood prevent autoantibody formation we compared the prevalence of antinuclear antibodies (ANA), autoantibodies of infrequent occurrence in healthy controls from Western Europe and associated with systemic lupus erythematosus (SLE) and other autoimmune diseases, in populations with different prevalence of infections throughout the course of life—namely, African immigrants to Italy and Italians.

We obtained written informed consent from 137 Ghanaian or Nigerian apparently healthy immigrants to Italy and living in Verona (northeastern Italy), unrelated to patients with SLE or …
Certificate of Need Regulation and Cardiac Catheterization Appropriateness After Acute Myocardial Infarction
Authors: Joseph S. Ross, Vivian Ho, Yongfei Wang, Stephen S. Cha, Andrew J. Epstein, Frederick A. Masoudi, Brahmajee K. Nallamothu, Harlan M. Krumholz
Journal: Circulation (2007)

Certificate of need (CON) regulation was introduced to control healthcare costs and improve quality of care in part by limiting the number of facilities providing complex medical care. Our objective was to examine whether rates of appropriate cardiac catheterization after admission for acute myocardial infarction varied between states with and without CON regulation of cardiac catheterization.We performed a retrospective analysis of chart-abstracted data for 137,279 Medicare patients admitted for acute myocardial infarction between 1994 and 1996 at 4179 US acute-care hospitals. Using 3-level hierarchical generalized linear modeling adjusted for patient sociodemographic and clinical characteristics and physician and hospital characteristics, we compared catheterization rates within 60 days of admission for states (and the District of Columbia) with (n=32) and without (n=19) CON regulation in the full cohort and stratified by catheterization appropriateness. Appropriateness was categorized as strongly, equivocally, or weakly indicated. We found CON regulation was associated with a borderline-significant lower rate of catheterization overall (45.8% versus 46.5%; adjusted risk ratio [RR] 0.91, 95% confidence interval 0.82 to 1.00, P=0.06). After stratification by appropriateness, CON regulation was not associated with a significantly lower rate of catheterization among 63,823 patients with strong indications (49.9% versus 50.3%; adjusted RR 0.94, 95% confidence interval 0.86 to 1.02, P=0.17). However, CON regulation was associated with significantly lower rates of catheterization among 65,077 patients with equivocal indication (45.0% versus 46.0%; adjusted RR 0.88, 95% confidence interval 0.78 to 1.00, P=0.05) and among 8379 patients with weak indications (19.8% versus 21.8%; adjusted RR 0.84, 95% confidence interval 0.71 to 0.98, P=0.04). Associations were weakened substantially after adjustment for hospital coronary artery bypass graft surgery or cardiac catheterization capability.CON regulation was associated with modestly lower rates of equivocally and weakly indicated cardiac catheterization after admission for acute myocardial infarction, but no significant differences existed in rates of strongly indicated catheterization.
Treatment of respiratory failure: introduction
Authors: M. Decramer, C. Roussos
Journal: European Respiratory Journal (2003)

The present supplement of the European Respiratory Journal contains a number of reviews concerning Treatment of Respiratory Failure . Important progress has been made in this area since the early 1990s. This supplement is the result of a symposium held in Barcelona on January 18, 2003. The symposium was organised by the European Institute of Healthcare, set up by AstraZeneca. It was the fifth symposium of its kind. The goals of the Institute have been discussed extensively in previous supplements 1–4.

As previously, the programme of the present symposium was put together by an independent programme committee. The core of this committee was the two editors of the present supplement. Other members were: K.F. Chung (London, UK), R. Dekhuijzen (Nijmegen, the …
Randomized Phase II Trial of Three Schedules of Pemetrexed and Gemcitabine As Front-Line Therapy for Advanced Non–Small-Cell Lung Cancer
Authors: Cynthia X. Ma, Suresh Nair, Sachdev Thomas, Sumithra J. Mandrekar, Daniel A. Nikcevich, Kendrith M. Rowland, Tom R. Fitch, Harold E. Windschitl, Shauna L. Hillman, Steven E. Schild, James R. Jett, Coleman Obasaju, Alex A. Adjei
Journal: Journal of Clinical Oncology (2005)

A randomized three-arm phase II study was undertaken to evaluate the optimum administration schedule of pemetrexed and gemcitabine in chemotherapy-naïve patients with non-small-cell lung cancer.Patients were randomly assigned to three schedules of pemetrexed 500 mg/m2 plus gemcitabine 1,250 mg/m2, separated by a 90-minute interval, on a 21-day cycle as follows: schedule A, pemetrexed followed by gemcitabine on day 1 and gemcitabine on day 8; schedule B, gemcitabine followed by pemetrexed on day 1 and gemcitabine on day 8; and schedule C, gemcitabine on day 1 and pemetrexed followed by gemcitabine on day 8.One hundred fifty-two eligible patients (schedule A, n = 59; schedule B, n = 31, and schedule C, n = 62) received a median of five (schedule A), two (schedule B), and four (schedule C) treatment cycles. Overall, 66% of patients experienced grade 3 or 4 neutropenia. Common grade 3 and 4 nonhematologic toxicities were dyspnea (11%), fatigue (16%), and transaminase elevation (9%). Schedule A seemed less toxic compared with schedule C (grade 3 or 4 events: 86% v 94%, respectively; P = .19; grade 4 events: 39% v 48%, respectively; P = .30). Schedule B was closed at interim analysis for inferior efficacy. Schedule A, with a confirmed response rate of 31% (95% CI, 20% to 45%), met the protocol-defined efficacy criteria, whereas schedule C, with a confirmed response rate of 16.1% (95% CI, 11% to 34%), did not. Median survival time and time to progression were 11.4 and 4.4 months, respectively, with no observable difference between the arms.Pemetrexed and gemcitabine administered as outlined for schedule A met the protocol-defined efficacy criteria, was less toxic compared with the other treatment schedules, and should be further evaluated.
β2-Microglobulin Induces Epithelial to Mesenchymal Transition and Confers Cancer Lethality and Bone Metastasis in Human Cancer Cells
Authors: Sajni Josson, Takeo Nomura, Jen-Tai Lin, Wen-Chin Huang, Daqing Wu, Haiyen E. Zhau, Majd Zayzafoon, M. Neale Weizmann, Murali Gururajan, Leland W. K. Chung
Journal: Cancer Research (2011)

Bone metastasis is one of the predominant causes of cancer lethality. This study demonstrates for the first time how β2-microglobulin (β2-M) supports lethal metastasis in vivo in human prostate, breast, lung, and renal cancer cells. β2-M mediates this process by activating epithelial to mesenchymal transition (EMT) to promote lethal bone and soft tissue metastases in host mice. β2-M interacts with its receptor, hemochromatosis (HFE) protein, to modulate iron responsive pathways in cancer cells. Inhibition of either β2-M or HFE results in reversion of EMT. These results demonstrate the role of β2-M in cancer metastasis and lethality. Thus, β2-M and its downstream signaling pathways are promising prognostic markers of cancer metastases and novel therapeutic targets for cancer therapy.