tbuckley/cabot-search huggingface dataset:
Case–Control Study of Lung Function in World Trade Center Health Registry Area Residents and Workers
Authors: Stephen M. Friedman, Carey B. Maslow, Joan Reibman, Parul S. Pillai, Roberta M. Goldring, Mark R. Farfel, Steven D. Stellman, Kenneth I. Berger
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: Residents and area workers who inhaled dust and fumes from the World Trade Center disaster reported lower respiratory symptoms in two World Trade Center Health Registry surveys (2003–2004 and 2006–2007), but lung function data were lacking.Objectives: To examine the relationship between persistent respiratory symptoms and pulmonary function in a nested case–control study of exposed adult residents and area workers 7–8 years after September 11, 2001.Methods: Registrants reporting post September 11th onset of a lower respiratory symptom in the first survey and the same symptom in the second survey were solicited as potential cases. Registrants without lower respiratory symptoms in either Registry survey were solicited as potential control subjects. Final case–control status was determined by lower respiratory symptoms at a third interview (the study), when spirometry and impulse oscillometry were also performed.Measurements and Main Results: We identified 180 cases and 473 control subjects. Cases were more likely than control subjects to have abnormal spirometry (19% vs. 11%; P < 0.05), and impulse oscillometry measurements of elevated airway resistance (R5; 68% vs. 27%; P < 0.0001) and frequency dependence of resistance (R5–20; 36% vs. 7%; P < 0.0001). When spirometry was normal, cases were more likely than control subjects to have elevated R5 and R5–20 (62% vs. 25% and 27% vs. 6%, respectively; both P < 0.0001). Associations between symptoms and oscillometry held when factors significant in bivariate comparisons (body mass index, spirometry, and exposures) were analyzed using logistic regression.Conclusions: This study links persistent respiratory symptoms and oscillometric abnormalities in World Trade Center–exposed residents and area workers. Elevated R5 and R5–20 in cases despite normal spirometry suggested distal airway dysfunction as a mechanism for symptoms.
Scaling Up Programmatic Management of Drug-Resistant Tuberculosis: A Prioritized Research Agenda
Authors: Frank G. J Cobelens, Einar Heldal, Michael E Kimerling, Carole D Mitnick, Laura J Podewils, Rajeswari Ramachandran, Hans L Rieder, Karin Weyer, Matteo Zignol
Journal: PLoS Medicine (2008)

Guidelines and
Genetic and Biochemical Evidence That Haploinsufficiency of the <i>Nf1</i> Tumor Suppressor Gene Modulates Melanocyte and Mast Cell Fates in Vivo
Authors: David A. Ingram, Feng-Chun Yang, Jeffrey B. Travers, Mary Jo Wenning, Kelly Hiatt, Sheryl New, Antoinette Hood, Kevin Shannon, David A. Williams, D. Wade Clapp
Journal: The Journal of Experimental Medicine (2000)

Neurofibromatosis type 1 (NF1) is a common autosomal-dominant disorder characterized by cutaneous neurofibromas infiltrated with large numbers of mast cells, melanocyte hyperplasia, and a predisposition to develop malignant neoplasms. NF1 encodes a GTPase activating protein (GAP) for Ras. Consistent with Knudson's “two hit” model of tumor suppressor genes, leukemias and malignant solid tumors in NF1 patients frequently demonstrate somatic loss of the normal NF1 allele. However, the phenotypic and biochemical consequences of heterozygous inactivation of Nf1 are largely unknown. Recently neurofibromin, the protein encoded by NF1, was shown to negatively regulate Ras activity in Nf1−/− murine myeloid hematopoietic cells in vitro through the c-kit receptor tyrosine kinase (dominant white spotting, W). Since the W and Nf1 locus appear to function along a common developmental pathway, we generated mice with mutations at both loci to examine potential interactions in vivo. Here, we show that haploinsufficiency at Nf1 perturbs cell fates in mast cells in vivo, and partially rescues coat color and mast cell defects in W41 mice. Haploinsufficiency at Nf1 also increased mast cell proliferation, survival, and colony formation in response to Steel factor, the ligand for c-kit. Furthermore, haploinsufficiency was associated with enhanced Ras–mitogen-activated protein kinase activity, a major downstream effector of Ras, via wild-type and mutant (W41) c-kit receptors. These observations identify a novel interaction between c-kit and neurofibromin in vivo, and offer experimental evidence that haploinsufficiency of Nf1 alters both cellular and biochemical phenotypes in two cell lineages that are affected in individuals with NF1. Collectively, these data support the emerging concept that heterozygous inactivation of tumor suppressor genes may have profound biological effects in multiple cell types.
The Contribution of the Autonomic Nervous System to Changes of Glucagon and Insulin Secretion during Hypoglycemic Stress*
Authors: PETER J. HAVEL, GERALD J. TABORSKY
Journal: Endocrine Reviews (1989)

DURING hypoglycemic stress, glucagon secretion increases and insulin secretion decreases. The traditional view is that these changes are due to the effect of low circulating glucose levels acting directly on the pancreatic islet. In contrast, a number of studies suggest that these responses are due to activation of autonomic nervous system that accompanies hypoglycemia in vivo, a view that we favor. Although central nervous system and autonomic neural control of the endocrine pancreashas been reviewed before (1–4), this review will focus specifically on the autonomic activation produced by glucopenic stress and its potential contribution to the accompanying changes of glucagon and insulin secretion. The goal of this review is not to negate the traditional view that hypoglycemia has direct actions on the islet, but rather to suggest that the autonomic contribution may have been underestimated in a whole class of experiments because of unrecognized redundancy in the autonomic input to the islet. The first section will review the supporting evidence that each of three autonomic inputs to the pancreas is activated during this stress. The three inputs are: 1) pancreatic parasympathetic nerves, 2) adrenal medullary epinephrine, and 3) pancreatic sympathetic nerves. The various techniques for measuring these autonomic inputs to the pancreas will be discussed, and the factors which influence the magnitude of the autonomic activation will be outlined.
Pseudomonas aeruginosa diversity in distinct paediatric patient groups
Authors: G.A. Tramper-Stranders, C.K. van der Ent, T.F.W. Wolfs, J.L.L. Kimpen, A Fleer, U Johansen, H.K. Johansen, N. Høiby
Journal: Clinical Microbiology and Infection (2008)
Response to Letter Regarding Article, “Acetaminophen Increases Blood Pressure in Patients With Coronary Artery Disease”
Authors: Isabella Sudano, Andreas J. Flammer, Daniel Périat, Frank Enseleit, Matthias Hermann, Mathias Wolfrum, Astrid Hirt, Priska Kaiser, David Hurlimann, Johannes Holzmeister, Ulf Landmesser, Roberto Corti, Thomas F. Lüscher, Georg Noll, Frank Ruschitzka, Pavani Mocharla, Sarah R. Haile, Michel Neidhart, Steffen Gay, Juerg Nussberger, Paul M. Vanhoutte
Journal: Circulation (2011)
VALUE AND LIMITATIONS OF SPINAL PUNCTURE IN CEREBRAL HEMORRHAGE OF THE NEW-BORN
Authors: ABRAHAM LEVINSON
Journal: JAMA (1935)

During the past few years, numerous investigators have studied the value of spinal puncture in the diagnosis and treatment of cerebral hemorrhage in the new-born. Sharpe concludes that bloody fluid is an indication of cerebral hemorrhage, that clear fluid practically excludes such a diagnosis, and that whenever the cerebrospinal fluid is bloody, repeated punctures should be done. In a recent report he<sup>1</sup>says: If free blood is present in the cerebrospinal fluid, repeated lumbar punctures of spinal drainage are immediately instituted, just as in adults and children with head injuries, in order to permit the free blood to escape and thus avoid the great danger not only of death but in some cases the even more tragic result of spasticity and retarded mentality. If the diagnostic lumbar puncture reveals clear cerebrospinal fluid, the physician knows almost certainly that no intracranial hemorrhage has occurred and that the signs were most
Reduced -defensin expression is associated with inflammation and not NOD2 mutation status in ileal Crohn's disease
Authors: L A Simms, J D Doecke, M D Walsh, N Huang, E V Fowler, G L Radford-Smith
Journal: Gut (2008)

<h3>Abstract</h3> <h3>Objective</h3> To compare prenatal care providers’ perceived self-efficacy in starting discussions about gestational weight gain with pregnant women under a variety of conditions of gradated difficulty, when weight gain has been in excess of current guidelines. <h3>Design</h3> A 42-item online questionnaire related to the known barriers to and facilitators of having discussions about gestational weight gain. <h3>Setting</h3> Canada. <h3>Participants</h3> Prenatal care providers were contacted through the Family Medicine Maternity Care list server of the College of Family Physicians of Canada. <h3>Main outcome measures</h3> The 42 items were clustered into categories representing patient factors, interpersonal factors, and system factors. Participants scored their self-efficacy on a scale from 0 (“cannot do at all”) to 5 (“moderately certain can do”) to 10 (“highly certain can do”). The significance level was set at α = .05. <h3>Results</h3> Overall, clinicians rated their self-efficacy to be high, ranging from a low mean (SD) score of 5.14 (3.24) if the clinic was running late, to a high mean score of 8.97 (1.34) if the clinician could externalize the reason for undertaking the discussion. There were significant differences in self-efficacy scores within categories depending on the degree of difficulty proposed by the items in those categories. <h3>Conclusion</h3> The results were inconsistent with previous studies that have demonstrated that prenatal care providers do not frequently raise the subject of excess gestational weight gain. On the one hand providers rate their self-efficacy in having these discussions to be high, but on the other hand they do not undertake the behaviour, at least according to their patients. Future research should explore this discrepancy with a view to informing interventions to help providers and patients in their efforts to address excess gestational weight gain, which is increasingly an important contributor to the obesity epidemic.
Wheezing Disorders in the Preschool Child
Authors: J Grigg
Journal: Thorax (2004)

Martinez F D, Godfrey S. London: Martin Dunitz, 2003, £40.00, ISBN 1 84184 155 2

In this monograph Martinez and Godfrey have set out to inform clinicians about preschool wheeze—a condition that has as many labels (for example, wheezy bronchitis, infant asthma, …
Inhaled Corticosteroids and Hip Fracture
Authors: Richard B. Hubbard, Chris J. P. Smith, Liam Smeeth, Tim W. Harrison, Anne E. Tattersfield
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

There is accumulating evidence that the use of inhaled corticosteroids is associated with a dose-related reduction in bone mineral density. Whether this translates to an increase in fracture is unclear. We have used the General Practice Research Database to perform a case-control analysis, including 16,341 cases of hip fracture (mean age of 79 years, 79% female, median period prescribing data 2.7 years) and 29,889 control subjects, individually matched by age, sex, and general practice. Data for all prescriptions for corticosteroids and for potential confounders, including other drug use and comorbid illnesses, were extracted, and the impact of inhaled corticosteroid exposure was analyzed using conditional logistic regression. The risk of hip fracture was associated with exposure to inhaled corticosteroids with an odds ratio of 1.26 (95% confidence interval, 1.17 to 1.36). This odds ratio was reduced after adjusting the model for annual courses of oral corticosteroids, the only confounder of note (OR 1.19; 95% CI, 1.10 to 1.28). There was a dose-response relationship between inhaled corticosteroid use and hip fracture even after adjusting for the annual number of courses of oral corticosteroids (p trend = 0.007). In older subjects, the recent use of inhaled corticosteroids is associated with a dose-related increase in hip fracture.
Studies on the composition of the mononuclear cell infiltrates in liver from patients with chronic active delta hepatitis
Authors: Chia-Ming Chu, Yun-Fan Liaw
Journal: Hepatology (1989)

To evaluate the immune process involved in the pathogenesis of liver cell damage in chronic hepatitis delta virus infection, a panel of monoclonal antibodies against pan T cells (Leu 4), inducer/helper T cells (Leu 3a+3b), suppressor/cytotoxic T cells (Lue 2a), B cell (Leu 12), monocyts/macrophages (Leu M3) and NK/K cells (Leu 7) was used to characterize the subsets of the mononuclear cell infiltrates in livers from 12 patients with chronic type D hepatitis, with special emphasis on the areas of periportal piecemeal necrosis and intralobular necrosis. A control group of 12 patients with chronic type B hepatitis was also studied for comparison. The results revealed that the livers from patients with chronic type D hepatitis showed a prominent mononuclear cell infiltration in portal/periportal and intralobular areas. Furthermore, the vast majority of the mononuclear cell infiltrates in liver were T cells, which constituted more than 80% of the cells in the areas of periportal piecemeal necrosis and intralobular necrosis and about 60% of the cells in the portal tract, whereas B cells, monocytes/macrophages and NK/K cells were relatively uncommon. Among T cell populations, the inducer/helper T cells were predominant in the portal tract, and, by contrast, the suppressor/cytotoxic T cells were predominant in the areas of piecemeal necrosis and intralobular necrosis. The distribution of the mononuclear cell subsets in relation to the different topographical areas of the liver in patients with chronic type B hepatitis was essentially the same as that observed in chronic type D hepatitis. Our findings therefore suggest that T cell–mediated immunity might play a role in the pathogenesis of chronic type D hepatitis, similar to that suggested for chronic type B hepatitis.
Family history of heart attack: a modifiable risk factor?
Authors: K T Khaw, E Barrett-Connor
Journal: Circulation (1986)

A family history of heart attack is reported to be an independent predictor of cardiovascular death in men. In a 9 year follow-up of 4014 adults from 40 to 79 years old in the Rancho Bernardo Study, men under 60 years of age with a family history of heart attack were at fivefold increased risk. In this study, we sought to determine whether modifiable risk factors, i.e., blood pressure, plasma cholesterol, obesity, and cigarette smoking, have a differential effect on cardiovascular risk in those with and without a family history of heart attack. For both sexes, cigarette smoking was a stronger predictor of cardiovascular disease in those with a family history of heart attack (relative risk of smokers vs nonsmokers was 2.5 for men and 4.0 for women) than in those with no such family history (relative risk of smokers vs nonsmokers was 1.1 for men and 1.7 for women). Conversely, an increased risk of cardiovascular mortality in men with a family history of heart attack was present predominantly in smokers (relative risk related to positive family history was 1.2 in nonsmokers, and 3.3 in smokers). An estimated 68% of the excess deaths in men with a family history of heart attack were attributable solely to the interaction of family history with smoking habit and were therefore potentially avoidable. The risk of cardiovascular disease associated with an apparently inherited predisposition appears to be profoundly affected by modifiable behavior.
Induction of T-Cell Apoptosis in Rats by Genetically Engineered Glioma Cells Expressing Granulocyte-Macrophage Colony-Stimulating Factor and B7.1
Authors: Sheng-Hong Tseng, Yun Chen, Chun-Jung Chang, Kuo-Feng Tai, Swei-Ming Lin, Lih-Hwa Hwang
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To evaluate antitumor effects on intracerebral gliomas of genetically engineered tumor vaccines expressing granulocyte-macrophage colony-timulating factor (GM-CSF), B7.1, or both (combination). Experimental Design: A rat glioma cell line, RT-2, was engineered with a retroviral vector to express GM-CSF, B7.1, or combination. Tumorigenicity of engineered cells and therapeutic effects of s.c. given irradiated or live tumor vaccines on parental intracerebral gliomas were studied. Immune cell infiltration induced at vaccine and tumor sites was examined by histologic and immunohistochemical staining. Apoptosis of T cells from vaccine sites was analyzed with fluorescence-activated cell sorting. Results: Engineered RT-2 cells exhibited reduced s.c. tumorigenicity in rats with reduced tumor growth and prolonged animal survival time compared with control rats. Rats with intracerebral gliomas s.c. treated with irradiated or live GM-CSF-expressing vaccines had 60% and 100% survival rates, respectively, significantly better than the control groups (P &amp;lt; 0.05). In contrast, rats treated with vaccines expressing B7.1 or the combination had no or mild therapeutic effects. Studies revealed less T-cell infiltration at both vaccine and tumor sites in rats treated with vaccines expressing B7.1 or the combination than in rats treated with a vaccine expressing GM-CSF. Cell sorting analyses revealed higher proportions of apoptotic T cells at vaccine sites of rats treated with the combination than those treated with vaccine expressing GM-CSF. Conclusions: Combination of GM-CSF- and B7.1-expressing tumor vaccines exerted no synergistic, or even worse, therapeutic effects on gliomas compared with single GM-CSF-secreting tumor vaccine. The worse therapeutic effects of the GM-B7.1-expressing tumor vaccine than the GM-CSF-expressing tumor vaccine were related to the reduced T-cell amount and increased T-cell apoptosis in the former.
Exploitation of conserved eukaryotic host cell farnesylation machinery by an F-box effector of <i>Legionella pneumophila</i>
Authors: Christopher T.D. Price, Tasneem Al-Quadan, Marina Santic, Snake C. Jones, Yousef Abu Kwaik
Journal: The Journal of Experimental Medicine (2010)

Farnesylation involves covalent linkage of eukaryotic proteins to a lipid moiety to anchor them into membranes, which is essential for the biological function of Ras and other proteins. A large cadre of bacterial effectors is injected into host cells by intravacuolar pathogens through elaborate type III–VII translocation machineries, and many of these effectors are incorporated into the pathogen-containing vacuolar membrane by unknown mechanisms. The Dot/Icm type IV secretion system of Legionella pneumophila injects into host cells the F-box effector Ankyrin B (AnkB), which functions as platforms for the docking of polyubiquitinated proteins to the Legionella-containing vacuole (LCV) to enable intravacuolar proliferation in macrophages and amoeba. We show that farnesylation of AnkB is indispensable for its anchoring to the cytosolic face of the LCV membrane, for its biological function within macrophages and Dictyostelium discoideum, and for intrapulmonary proliferation in mice. Remarkably, the protein farnesyltransferase, RCE-1 (Ras-converting enzyme-1), and isoprenyl cysteine carboxyl methyltransferase host farnesylation enzymes are recruited to the LCV in a Dot/Icm-dependent manner and are essential for the biological function of AnkB. In conclusion, this study shows novel localized recruitment of the host farnesylation machinery and its anchoring of an F-box effector to the LCV membrane, and this is essential for biological function in vitro and in vivo.
Headache in sport
Authors: P McCrory
Journal: British Journal of Sports Medicine (2001)

Warm upA whiV of the future I was intrigued to read in the press recently, a story based on a new study published by de Boer in the journal, Geology, that in Ancient Greece, the oracle at Delphi was probably in a state of a drug induced trance when advising supplicants.Plutarch, the historian, who was also the high priest at the temple of Apollo in Delphi, describes how the high priestess who spoke the oracles inhaled "sweet smelling vapours" in her chasm under the temple.De Boer and his coworkers discovered that the walls of this chasm or adytum contain volatile gases from the bituminous limestone that lies beneath the temple.The most common of these gases was ethylene, which smells sweet and moreover breathing it often induces a state of euphoria.Sometimes people have a more violent reaction.They become delirious and thrash around-a state that Plutarch also recorded.The high priestess, it seems, was as much a glue sniVer as a guru.It is interesting how attitudes change.What was seen in Ancient Greece as prophecy would today be seen as a social problem.Glue sniYng and other illicit drug use are banes of urban society.In sport, drug use is widespread.Both recreational drugs as well as performance enhancing or ergogenic agents are a commonplace feature of elite competition.We are no longer shocked when athletes are sent home from competition, stripped of their records or medals or stopped
Defective Mismatch Repair, Microsatellite Mutation Bias, and Variability in Clinical Cancer Phenotypes
Authors: Sandeep N. Shah, Suzanne E. Hile, Kristin A. Eckert
Journal: Cancer Research (2010)

Abstract Microsatellite instability is associated with 10% to 15% of colorectal, endometrial, ovarian, and gastric cancers, and has long been used as a diagnostic tool for hereditary nonpolyposis colorectal carcinoma–related cancers. Tumor-specific length alterations within microsatellites are generally accepted to be a consequence of strand slippage events during DNA replication, which are uncorrected due to a defective postreplication mismatch repair (MMR) system. Mutations arising within microsatellites associated with critical target genes are believed to play a causative role in the evolution of MMR-defective tumors. In this review, we summarize current evidence of mutational biases within microsatellites arising as a consequence of intrinsic DNA sequence effects as well as variation in MMR efficiency. Microsatellite mutational biases are generally not considered during clinical testing; however, we suggest that such biases may be clinically significant as a factor contributing to phenotypic variation among microsatellite instability–positive tumors. Cancer Res; 70(2); 431–5
Treatment of canine permeability pulmonary edema: short-term effects of dobutamine, furosemide, and hydralazine.
Authors: W D Molloy, K Y Lee, L Girling, R M Prewitt
Journal: Circulation (1985)

The effects of treatment of oleic acid pulmonary edema with dobutamine, furosemide, and hydralazine on cardiopulmonary function in 24 dogs were investigated. Pulmonary capillary wedge pressure (PCWP) was adjusted to approximately 7 mm Hg; 45 min after oleic acid (0.08 ml/kg), dogs were randomly divided into a control group, in which PCWP was maintained at approximately 7 mm Hg, and into treatment groups as described above. Mean time-averaged PCWP was 2.3 mm Hg in dogs treated with dobutamine, 4.1 mm Hg with furosemide, and 4.4 mm Hg with hydralazine. Four hours of treatment with dobutamine and furosemide significantly (p less than .01) reduced accumulation of lung water compared with the control and hydralazine groups. Qs/Qt was lower (p less than .05) with dobutamine and furosemide compared with the other groups. In dogs given hydralazine, cardiac output (CO) and systemic vascular resistance (SVR) remained constant over the 4 hr treatment interval. In contrast, in all other groups, SVR increased and CO decreased (both p less than .05). The short-term pulmonary effects of the above drugs are probably explained by differences in PCWP and/or by regional pulmonary vascular effects.