tbuckley/cabot-search huggingface dataset:
Is the increase in childhood asthma coming to an end? Findings from three surveys of schoolchildren in Rome, Italy
Authors: R. Ronchetti, M.P. Villa, M. Barreto, R. Rota, J. Pagani, S. Martella, C. Falasca, B. Paggi, F. Guglielmi, G. Ciofetta
Journal: European Respiratory Journal (2001)

Time trends in the prevalence of asthma, family history of asthma and atopy in Roman schoolchildren were assessed. The study population consisted of all children (aged 6–14 yrs) attending two primary schools in Rome, situated in urban areas that differed markedly in socioeconomic conditions and environmental pollution. Three questionnaire-based surveys were conducted in 1974, 1992 and 1998 in 2,259, 1,229 and 1,139 children. The prevalence of asthma in males and females increased significantly during 1974–1992 and remained stable from 1992–1998. In age groups born in the subsequent 4-yr periods it increased almost linearly, for children born from 1962–1965 to 1982–1985 (4.4%–12.5%), and remained remarkably stable in children born after 1985. Because the prevalence of asthma had a steeper trend in males than in females (approximately 0.55%·yr −1 versus 0.25%·yr −1 ), the male:female asthma ratio increased (1:38 in 1974; 1:84 in 1992 and 1:62 in 1998). No single environmental factor, including area of residence, seemed to influence the prevalence of asthma. Family history of asthma and atopy also increased steadily (0.72%·yr −1 and 0.30%·yr −1 respectively) more than doubling during the 24-yr study period. The strong relationship between asthma and a family history of atopy not only persisted but also strengthened over time (23.3% of asthmatic children belonged to families with atopic illnesses in 1974 but 44.2% in 1998). The environmental factors that might explain the almost three-fold rise in childhood asthma between 1974 and 1992 remain unknown but the genetic background of the disease has presumably remained unchanged since the early 1970s. The fact that the prevalence of asthma increased no further during the past 6 yrs suggests that the progressive induction of asthma symptoms in genetically predisposed subjects is a self-limiting process that has probably come to an end in the authors' study area.
Patients with Small-Cell Lung Cancer Treated with Combination Chemotherapy with or without Irradiation
Authors: BRUCE E. JOHNSON
Journal: Annals of Internal Medicine (1985)

We assessed the outcome in 252 patients with small-cell lung cancer 5 to 11 years after treatment with combination chemotherapy, with or without chest and cranial irradiation, in National Cancer Institute therapeutic trials from 1973 through 1978. Twenty-eight patients (11%) survived free of cancer for 30 months or more. Fourteen patients remain alive without evidence of cancer beyond 5 years (range, 6.4 to 11.3 years), and 7 patients have returned to a lifestyle similar to that before diagnosis. The other 14 patients who were cancer-free at 30 months have developed cancer or died; 6 patients had a relapse, 4 developed or died from non-small-cell lung cancer, and 4 died of unrelated causes. A few patients with small-cell lung cancer (5.6%) may be cured. Thirty-month, cancer-free survival is insufficient to show a cure. Although late toxicities are troublesome, they do not outweigh the benefits of prolonged survival and potential for cure with modern aggressive therapy in small-cell lung cancer.
Effects of belimumab, a B lymphocyte stimulator-specific inhibitor, on disease activity across multiple organ domains in patients with systemic lupus erythematosus: combined results from two phase III trials
Authors: Susan Manzi, Jorge Sánchez-Guerrero, Joan T Merrill, Richard Furie, Dafna Gladman, Sandra V Navarra, Ellen M Ginzler, David P D'Cruz, Andrea Doria, Simon Cooper, Z John Zhong, Douglas Hough, William Freimuth, Michelle A Petri
Journal: Annals of the Rheumatic Diseases (2012)

To evaluate the effects of belimumab versus placebo, plus standard systemic lupus erythematosus (SLE) therapy, on organ domain-specific SLE disease activity.Data obtained after 52 weeks of treatment from two phase III trials (BLISS-52 and BLISS-76) comparing belimumab 1 and 10 mg/kg versus placebo, plus standard therapy, in 1684 autoantibody-positive patients were analysed post hoc for changes in British Isles Lupus Assessment Group (BILAG) and Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) organ domain scores.At baseline, the domains involved in the majority of patients were musculoskeletal and mucocutaneous by both BILAG and SELENA-SLEDAI, and immunological by SELENA-SLEDAI. At 52 weeks, significantly more patients treated with belimumab versus placebo had improvement in BILAG musculoskeletal and mucocutaneous domains (1 and 10 mg/kg), and in SELENA-SLEDAI mucocutaneous (10 mg/kg), musculoskeletal (1 mg/kg) and immunological (1 and 10 mg/kg) domains. Improvement was also observed in other organ systems with a low prevalence (≤16%) at baseline, including the SELENA-SLEDAI vasculitis and central nervous system domains. Significantly fewer patients treated with belimumab versus placebo had worsening in the BILAG haematological domain (1 mg/kg) and in the SELENA-SLEDAI immunological (10 mg/kg), haematological (10 mg/kg) and renal (1 mg/kg) domains.Belimumab treatment improved overall SLE disease activity in the most common musculoskeletal and mucocutaneous organ domains. Less worsening occurred in the haematological, immunological and renal domains.
Electrocardiogram in the Normal Rat and Its Alteration with Experimental Coronary Occlusion
Authors: SIGURD J. NORMANN, ROBERT E. PRIEST, EARL P. BENDITT
Journal: Circulation Research (1961)

A reliable and reprodueible method of recording rat electrocardiograms is described, including the use of precordial electrodes This system was utilized in studying 44 nor mal animals and in recording the electrical abnormalities associated with the ligation of the left coronary artery in 10 rats. The char acteristics of the normal electrocardiogram of the rat arc described. Following apical and anterior infarction, Q waves in associatioii with transitory R-wavc augmentation ap peared, with prolongation of the Q-T interval, electrical axis deviation, and inversion of the T wave. No abnormal conduction patterns were noted. The pathological lesions are described, and attention is called to the absence of mural intraventrienlar thrombosis despite transmnral infarction.
Contrasting Cholesterol Management Guidelines for Adults with CKD
Authors: Lisandro D. Colantonio, Usman Baber, Maciej Banach, Rikki M. Tanner, David G. Warnock, Orlando M. Gutiérrez, Monika M. Safford, Christoph Wanner, George Howard, Paul Muntner
Journal: Journal of the American Society of Nephrology (2014)

The Kidney Disease Improving Global Outcomes Lipid Work Group recommends statins for adults ≥50 years old with CKD. The American College of Cardiology/American Heart Association endorses statins for adults with atherosclerotic cardiovascular disease, adults with LDL cholesterol≥190 mg/dl, and adults 40–79 years old with LDL cholesterol=70–189 mg/dl and diabetes or a 10-year predicted risk for atherosclerotic cardiovascular disease ≥7.5% estimated using the Pooled Cohort risk equations. Using data from the Reasons for Geographic and Racial Differences in Stroke Study, we calculated the agreement for statin treatment between these two guidelines for adults 50–79 years old with CKD (eGFR<60 ml/min per 1.73 m2 or albuminuria≥30 mg/g) not on dialysis. We assessed the validity of the Pooled Cohort risk equations in individuals with CKD. Study participants were enrolled between 2003 and 2007, and we report incident cardiovascular disease events (stroke and coronary heart disease) through December of 2010. Among 4726 participants with CKD, 2366 (50%) were taking statins, and 1984 (42%) were recommended statins by the American College of Cardiology/American Heart Association guideline but not taking them. Overall, 376 (8%) participants did not meet the American College of Cardiology/American Heart Association criteria for initiating statin treatment. Cardiovascular disease incidence was low (3.0/1000 person-years; 95% confidence interval, 0.1 to 5.9) among these participants. The Pooled Cohort risk equations were well calibrated (Hosmer–Lemeshow chi-squared=2.7, P=0.45) with moderately good discrimination (C index, 0.71; 95% confidence interval, 0.65 to 0.77). In conclusion, these guidelines show high concordance for statin treatment for adults with CKD.
UT-A Urea Transporter Protein Expressed in Liver
Authors: JANET D. KLEIN, RICHARD T. TIMMER, PATRICIA ROUILLARD, JAMES L. BAILEY, JEFF M. SANDS
Journal: Journal of the American Society of Nephrology (1999)

Abstract. In perfused rat liver, there is phloretin-inhibitable urea efflux, but whether it is mediated by the kidney UT-A urea transporter family is unknown. To determine whether cultured HepG2 cells transport urea, thiourea influx was measured. HepG2 cells had a thiourea influx rate of 1739 ± 156 nmol/g protein per min; influx was inhibited 46% by phloretin and 32% by thionicotinamide. Western analysis of HepG2 cell lysate using an antibody to UT-A1, UT-A2, and UT-A4 revealed two protein bands: 49 and 36 kD. The same bands were detected in cultured rat hepatocytes, freshly isolated rat hepatocytes, and in liver from rat, mouse, and chimpanzee. Both bands were present when analyzed by native gel electrophoresis, and deglycosylation of rat liver lysate had no effect on either band. Differential centrifugation of rat liver lysate showed that the 49-kD protein is in the membrane fraction and the 36-kD protein is in the cytoplasm. To determine whether the abundance of these UT-A proteins varies in vivo, rats were made uremic by 5/6 nephrectomy. The 49-kD protein was significantly increased 5.5-fold in livers from uremic rats compared to pair-fed control rats. It is concluded that phloretininhibitable urea flux in liver may occur via a 49-kD protein that is specifically detected by a UT-A antibody. Uremia increases the abundance of this 49-kD UT-A protein in rat liver in vivo.
Induction of monocyte procoagulant activity by murine hepatitis virus type 3 parallels disease susceptibility in mice.
Authors: G A Levy, J L Leibowitz, T S Edgington
Journal: The Journal of Experimental Medicine (1981)

The in vitro induction of procoagulant activity (PCA) in murine peripheral blood mononuclear cells (PBM) by murine hepatitis virus type 3 (MHV-3) correlates with the disease susceptibility in three strains of mice. PBM from BALB/c mice, a strain in which MHV-3 infection results in fatal acute fulminant hepatitis, responds to the virus with a robust PCA response, whereas PBM from C3H/St mice, a strain which develops mild acute hepatitis followed by chronic hepatitis, only exhibit a modest PCA response. In contrast, PBM from A/J mice, a strain fully resistant to MHV-3, generate no increase in PCA above control levels. The induction phase of MHV-3 PCA is rapid, with an increase within 1-1.5 h, with maximum activity at 18h, and it precedes MHV-3 replication in either 17 CL1 cells, a fully permissive cell line, or in monocytes from these strains of mice. The PCA response of BALB/c PBM exceeds the response to any other known stimulus. No induction occurs upon direct stimulation of monocytes by MHV-3, but in the presence of lymphocyte collaboration, the PCA response is observed first at a lymphocyte:monocyte ratio of 2:1 and reaches a maximum as the lymphocyte:monocyte ratio approaches 4:1. This response appears to provide a functional marker for susceptibility to MHV-3 infection in inbred strains of mice and could be important in the pathogenesis of MHV-3-induced disease.
THE SEROLOGICAL DIAGNOSIS OF RELAPSING FEVER
Authors: George J. Stein
Journal: The Journal of Experimental Medicine (1944)

1. Spirochetes of relapsing fever have been separated from the blood of heavily infected mice and rats by hemolysing with saponin, followed by repeated washing of the spirochetal suspension with physiological saline. 2. Spirochetes obtained in this manner appear to have broad antigenic specificity. Antigens of this type fixed complement in the presence of serum obtained from man or animals infected with one or other of the recognized strains or "species" of relapsing fever spirochetes. Macroscopic agglutination of the antigens likewise was observed with sera from the same sources. 3. Positive serological reactions were not observed with convalescent sera obtained following infection with other diseases, for example, typhus fever, malaria, Rocky Mountain spotted fever, Weil's disease, syphilis, and typhoid fever. Hyperimmune sera prepared against other pathogens also failed to react with the relapsing fever antigens. 4. No apparent change in the antigen occurred following storage in the ice box for as long as 4 months. 5. The results indicate that treatment of the spirochetes of relapsing fever with saponin yields a relatively stable antigenic preparation which may prove useful in the serological diagnosis of this disease.
Cutaneous lesions of disseminated histoplasmosis in human immunodeficiency virus-infected patients
Authors: Philip R. Cohen, David E. Bank, David N. Silvers, Marc E. Grossman
Journal: Journal of the American Academy of Dermatology (1990)

Disseminated histoplasmosis is being diagnosed more frequently in persons infected with the human immunodeficiency virus and is often the initial manifestation of the acquired immunodeficiency syndrome (AIDS). Disease-related cutaneous features of HIV-associated disseminated histoplasmosis are defined as mucocutaneous lesions from which fungal organisms were either cultured or demonstrated histopathologically. We report four HIV-seropositive patients with disseminated histoplasmosis who had culture-positive skin or oral lesions of histoplasmosis and review the specific cutaneous manifestations of HIV-associated disseminated histoplasmosis. Including our patients, disease-related skin and/or mucosal lesions were present in 11% of patients (26% of 239) with HIV-associated disseminated histoplasmosis. The possibility of disseminated histoplasmosis should be considered in all HIV-infected persons and in persons with AIDS risk factors who have fever, weight loss, hepatosplenomegaly, and new cutaneous lesions. An early skin or mucosal biopsy specimen for crushed tissue preparation, histologic evaluation, and fungal culture is a simple, rapid diagnostic procedure.
Chloride Transport in Nasal Ciliated Cells of Cystic Fibrosis Heterozygotes
Authors: Isabelle Sermet-Gaudelus, Michèle Déchaux, Benoît Vallée, Anne Fajac, Emanuelle Girodon, Thao Nguyen-Khoa, Rémi Marianovski, Ilse Hurbain, Jean Louis Bresson, Gérard Lenoir, Aleksander Edelman
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Studying subjects heterozygous for mutations of the cystic fibrosis (CF) gene may help clarify the impact on disease onset of CF transmembrane conductance regulator protein (CFTR-)-dependent chloride secretion. CFTR-mediated chloride transport was evaluated in 52 heterozygous subjects, 32 healthy control subjects, and 77 patients with CF with class I or II mutations. We measured the change in nasal potential difference in response to chloride-free isoproterenol solution for each subject and used a video-imaging fluorescent dye assay to assess the percentage of nasal ciliated cells with cAMP-dependent anion conductance. Our findings did not confirm the standard assumption that heterozygosity implies 50% of normal CFTR function. Half the heterozygous subjects had CFTR-mediated chloride transport levels below 50% of the normal range, and one-third had levels similar to those of the patients with CF. This reduced CFTR function was not associated with an elevated prevalence of CF-like symptoms in heterozygous subjects but was highly related to respiratory status in the patients with CF. These data suggest that CFTR-dependent chloride conductance does not directly modulate disease severity but may be part of a more global defect in patients with CF involving other CFTR functions or currently unknown modulatory factors.
Conformational Control Inhibition of the BCR-ABL1 Tyrosine Kinase, Including the Gatekeeper T315I Mutant, by the Switch-Control Inhibitor DCC-2036
Authors: Wayne W. Chan, Scott C. Wise, Michael D. Kaufman, Yu Mi Ahn, Carol L. Ensinger, Torsten Haack, Molly M. Hood, Jennifer Jones, John W. Lord, Wei Ping Lu, David Miller, William C. Patt, Bryan D. Smith, Peter A. Petillo, Thomas J. Rutkoski, Hanumaiah Telikepalli, Lakshminarayana Vogeti, Tony Yao, Lawrence Chun, Robin Clark, Peter Evangelista, L. Cristina Gavrilescu, Katherine Lazarides, Virginia M. Zaleskas, Lance J. Stewart, Richard A. Van Etten, Daniel L. Flynn
Journal: Cancer Cell (2011)
Laser Accelerated Radiotherapy: Is It On Its Way to the Clinic?
Authors: M. Martin
Journal: JNCI Journal of the National Cancer Institute (2009)

radiation. Loma Linda (Calif.) University Medical Center oncologists are using protons to treat early stage lung cancers, pituitary adenomas, pediatric orbital and ocular tumors, acoustic neuromas, benign meningiomas, and prostate cancer. To target therapy and minimize tissue damage, radiation oncologists exploit a proton beam characteristic called the Bragg peak. A Bragg curve plots how ionizing radiation loses energy as it travels through matter, in this case, tissue. For accelerated protons, the energy curve peaks sharply as the particle stops, releasing its power like a well-placed punch. This so-called Bragg peak effect provides “normal tissue sparing superior to other radiotherapies,” said Albert Einstein’s Kalnicki.
Reduced nicotinamide adenine dinucleotide phosphate oxidase mediates fibrotic and inflammatory effects of leptin on hepatic stellate cells
Authors: Samuele De Minicis, Ekihiro Seki, Christoph Oesterreicher, Bernd Schnabl, Robert F. Schwabe, David A. Brenner
Journal: Hepatology (2008)

Although leptin induces fibrotic activity in hepatic stellate cells (HSCs), the mechanisms are not entirely understood. To investigate the potential role of reduced nicotinamide adenine dinucleotide phosphate oxidase (NADPH) and reactive oxygen species (ROS) in leptin signaling in HSCs, we analyzed leptin-induced intracellular signaling pathways in primary wild-type (WT), p47(phox(-/-) ), and signal transducer and activator of transcription protein 3 (STAT3)-deleted HSCs. Leptin-stimulated ROS production was attenuated in human and mouse HSCs by the NADPH oxidase inhibitor diphenylene-iodonium (DPI) and in HSCs lacking the NADPH component p47(phox). Leptin-induced phosphorylation of extracellular signal-regulated kinase (ERK) and AKT, but not of STAT3, was blocked by NADPH oxidase inhibition. Moreover, leptin-induced ROS production was inhibited by the Janus kinase (JAK) inhibitor, AG490, but normal ROS production was observed in STAT3-deleted HSCs. Pharmacologic or genetic inhibition of NADPH in HSCs not only resulted in a reduction of leptin-mediated HSC proliferation but also reduced the leptin-mediated up-regulation of the fibrogenic markers collagen alpha1(I) and alpha-smooth muscle actin and of the inflammatory mediators monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein 1 (MIP-1), and macrophage inflammatory protein 2 (MIP-2). In vivo, leptin enhanced chemokine expression induced by chemokine (C-C motif) ligand 4 (CCl(4)) in WT mice, but a blunted response was observed in p47(phox-/-) mice. In conclusion, NADPH oxidase is a crucial mediator of proliferative, fibrogenic, and inflammatory actions of leptin. Leptin-induced NADPH oxidase acts downstream of JAK activation but is independent of STAT3. Our results, in conjunction with previous studies on angiotensin II and platelet-derived growth factor (PDGF), place NADPH in the center of the fibrogenic signaling response in HSCs and demonstrate its potential role as a pharmacological target for antifibrotic therapies.
On the Origins and Admixture of Malagasy: New Evidence from High-Resolution Analyses of Paternal and Maternal Lineages
Authors: S. Tofanelli, S. Bertoncini, L. Castri, D. Luiselli, F. Calafell, G. Donati, G. Paoli
Journal: Molecular Biology and Evolution (2009)

The Malagasy have been shown to be a genetically admixed population combining parental lineages with African and South East Asian ancestry. In the present paper, we fit the Malagasy admixture history in a highly resolved phylogeographic framework by typing a large set of mitochondrial DNA and Y DNA markers in unrelated individuals from inland (Merina) and coastal (Antandroy, Antanosy, and Antaisaka) ethnic groups. This allowed performance of a multilevel analysis in which the diversity among main ethnic divisions, lineage ancestries, and modes of inheritance could be concurrently evaluated. Admixture was confirmed to result from the encounter of African and Southeast Asian people with minor recent male contributions from Europe. However, new scenarios are depicted about Malagasy admixture history. The distribution of ancestral components was ethnic and sex biased, with the Asian ancestry appearing more conserved in the female than in the male gene pool and in inland than in coastal groups. A statistic based on haplotype sharing (DHS), showing low sampling error and time linearity over the last 200 generations, was introduced here for the first time and helped to integrate our results with linguistic and archeological data. The focus about the origin of Malagasy lineages was enlarged in space and pushed back in time. Homelands could not be pinpointed but appeared to comprise two vast areas containing different populations from sub-Saharan Africa and South East Asia. The pattern of diffusion of uniparental lineages was compatible with at least two events: a primary admixture of proto-Malay people with Bantu speakers bearing a western-like pool of haplotypes, followed by a secondary flow of Southeastern Bantu speakers unpaired for gender (mainly male driven) and geography (mainly coastal).
Excess incidence of asthma among Finnish cleaners employed in different industries
Authors: A. Karjalainen, R. Martikainen, J. Karjalainen, T. Klaukka, K. Kurppa
Journal: European Respiratory Journal (2002)

The incidence and risk of asthma among female cleaners employed in different industries was explored. An increased risk of asthma has been associated with the cleaning profession, in some but not all studies. All Finnish females employed as cleaners and all those employed in administrative work were followed for asthma incidence through a record linkage in 1986–1998. An individual was defined as an “incident case of asthma” if they received rights for special reimbursement of asthma medication from the national health insurance or were recognized as having occupational asthma. Age-adjusted relative risks (RR) were estimated for cleaners in comparison with those employed in administrative work. There were 2,414 and 5,235 cases of asthma among the cleaners and administrative workers, respectively. The RR was 1.50 (95% confidence interval (CI) 1.43–1.57) in cleaners. The risk was increased in cleaners working in nearly all major sectors of economic activity, but cleaners employed by companies concerned with the manufacture of basic metals (RR 2.47; 95% CI 1.68–3.64) and food products (RR 2.19; 95% CI 1.69–2.85) had the highest risk. Only 25 of the “cases of asthma” among cleaners had been recognized as being occupational asthma. It could be concluded that cleaners have an increased risk of persistent adult-onset asthma. Factors inherent to the environment where cleaning is performed or differences in the cleaning agents used may explain the observed differences between industries.