tbuckley/cabot-search huggingface dataset:
Respiratory Symptoms, Pulmonary Function, and Markers of Inflammation Among Bar Workers Before and After a Legislative Ban on Smoking in Public Places
Authors: Daniel Menzies, Arun Nair, Peter A. Williamson, Stuart Schembri, Mudher Z. H. Al-Khairalla, Martyn Barnes, Tom C. Fardon, Lesley McFarlane, Gareth J. Magee, Brian J. Lipworth
Journal: JAMA (2006)

Scotland prohibited smoking in confined public places on March 26, 2006.To investigate the association of smoke-free legislation with symptoms, pulmonary function, and markers of inflammation of bar workers.This prospective observational study was conducted in Tayside, Scotland from February-June 2006. One hundred five nonasthmatic and asthmatic nonsmoking bar workers were initially enrolled, of whom 77 completed the study per protocol.Respiratory and sensory symptoms, spirometry measurements, serum cotinine levels, peripheral inflammatory cell count, asthma quality-of-life scores, and exhaled nitric oxide levels were evaluated before and after introduction of the smoking ban.For the per-protocol analysis, the percentage of bar workers with respiratory and sensory symptoms decreased from 79.2% (n = 61) before the smoke-free policy to 53.2% (n = 41) (total change, -26%; 95% confidence interval [CI], -13.8% to -38.1%; P<.001) and 46.8% (n = 38) (-32.5%; 95% CI, -19.8% to -45.2%; P<.001) 1 and 2 months afterward. Forced expiratory volume in the first second increased from 96.6% predicted to 104.8% (change, 8.2%; 95% CI, 3.9% to 12.4%; P<.001) and then 101.7% (change, 5.1%; 95% CI, 2.1% to 8.0%; P = .002), and serum cotinine levels decreased from 5.15 ng/mL to 3.22 ng/mL (change, -1.93 ng/mL; 95% CI, -2.83 to -1.03 ng/mL; P<.001) and then 2.93 ng/mL (-2.22 ng/mL; 95% CI, -3.10 to -1.34 ng/mL; P<.001). The total white blood cell and neutrophil count was reduced from 7610 to 6980 cells/microL at 2 months (-630 cells/muL; 95% CI, -1010 to -260 cells/microL; P = .002) and from 4440 to 4030 cells/microL (-410 cells/microL; 95% CI, -740 to -90 cells/microL; P = .03), respectively. Asthmatic bar workers also had less airway inflammation, with a reduction in exhaled nitric oxide from 34.3 parts per billion (ppb) to 27.4 ppb 1 month after the ban (0.8-fold change; 95% CI, 0.67 to 0.96 ppb; P = .04), and Juniper quality-of-life scores increased from 80.2 to 87.5 points (7.3 points; 95% CI, 0.1 to 14.6 points; P = .049).Smoke-free legislation was associated with significant early improvements in symptoms, spirometry measurements, and systemic inflammation of bar workers. Asthmatic bar workers also had reduced airway inflammation and improved quality of life.
Turbulent blood flow in the ascending aorta of humans with normal and diseased aortic valves.
Authors: P D Stein, H N Sabbah
Journal: Circulation Research (1976)

Turbulent blood flow may contribute to a variety of pathophysiological effects. Because of its postulated importance, this study was undertaken to determine whether turbulent flow does in fact occur in the human body. In 15 persons (seven normal, seven aortic valvular disease, one prosthetic aortic valve), point velocity was measured in the ascending aorta with a hot-film anemometer probe. In one normal individual with a high cardiac output, turbulent flow occurred above the aortic valve during peak flow which corresponded to a peak Reynolds number of 10,000. In the other six normal subjects (peak Reynolds numbers of 5,700-8,900), flow was highly disturbed during peak ejection. Each of the subjects with aortic valvular disease and the subject with a prosthetic aortic valve showed turbulent flow during nearly the entire period of ejection, with Fourier components of velocity of significant magnitude up to 320 Hz (the maximum frequency we could evaluate with the equipment available). The turbulence energy density was higher in subjects with abnormal valves (3.2-14.6 ergs/cm3), than in normal subjects (0.6-2.9 ergs/cm3). In subjects with aortic stenosis, turbulence was observed throughout the ascending aorta and in the innominate artery. In others, the turbulence dissipated more proximally. The results of this study indicate that turbulent flow can occur in the ascending aorta of subjects with normal cardiac function; and it occurs consistently in the ascending aorta of individuals with abnormal aortic valves.
Exit from Arsenite-Induced Mitotic Arrest Is p53 Dependent
Authors: Samuel C. McNeely, Xiaogiang Xu, B. Frazier Taylor, Wolfgang Zacharias, Michael J. McCabe, J. Christopher States
Journal: Environmental Health Perspectives (2006)

BackgroundArsenic is both a human carcinogen and a chemotherapeutic agent, but the mechanism of neither arsenic-induced carcinogenesis nor tumor selective cytotoxicity is clear. Using a model cell line in which p53 expression is regulated exogenously in a tetracycline-off system (TR9-7 cells), our laboratory has shown that arsenite disrupts mitosis and that p53-deficient cells [p53(−)], in contrast to p53-expressing cells [p53(+)], display greater sensitivity to arsenite-induced mitotic arrest and apoptosis.ObjectiveOur goal was to examine the role p53 plays in protecting cells from arsenite-induced mitotic arrest.Methodsp53(+) and p53(−) cells were synchronized in G2 phase using Hoechst 33342 and released from synchrony in the presence or absence of 5 μM sodium arsenite.ResultsMitotic index analysis demonstrated that arsenite treatment delayed exit from G2 in p53(+) and p53(−) cells. Arsenite-treated p53(+) cells exited mitosis normally, whereas p53(−) cells exited mitosis with delayed kinetics. Microarray analysis performed on mRNAs of cells exposed to arsenite for 0 and 3 hr after release from G2 phase synchrony showed that arsenite induced inhibitor of DNA binding-1 (ID1) differentially in p53(+)and p53(−) cells. Immunoblotting con-firmed that ID1 induction was more extensive and sustained in p53(+) cells.Conclusionsp53 promotes mitotic exit and leads to more extensive ID1 induction by arsenite. ID1 is a dominant negative inhibitor of transcription that represses cell cycle regulatory genes and is elevated in many tumors. ID1 may play a role in the survival of arsenite-treated p53(+) cells and contribute to arsenic carcinogenicity.
A role for quorum sensing in regulating innate immune responses mediated by<i>Vibrio cholerae</i>outer membrane vesicles (OMVs)
Authors: Harald Bielig, Mitesh Dongre, Birte Zurek, Sun N. Wai, Thomas A. Kufer
Journal: Gut Microbes (2011)

Outer membrane vesicles (OMVs) are released from many Gram-negative bacteria. OMVs interact with and are taken up by human cells. We and others have now showed that OMVs contain peptidoglycan, which is sensed mainly by the pattern-recognition receptor NOD1 in the cytoplasm of host cells. Vibrio cholerae is clinically important as one of the causative agents of severe dehydrating diarrhea in humans. We showed that non-O1 non-O139 V. cholerae (NOVC) strains of V. cholera produce OMVs. Of note, we revealed that NOVC can evade NOD1-mediated immune surveillance by the quorum sensing machinery. Here we review these recent findings and discuss the relevance for our understanding of bacterial infections and innate immune responses.
The Role of the Akt/mTOR Pathway in Tobacco Carcinogen–Induced Lung Tumorigenesis
Authors: Regan M. Memmott, Phillip A. Dennis
Journal: Clinical Cancer Research (2009)

Lung cancer is the leading cause of cancer-related death in the United States, and 85 to 90% of lung cancer cases are associated with tobacco use. Tobacco components promote lung tumorigenesis through genotoxic effects, as well as through biochemical modulation of signaling pathways such as the Akt/mammalian target of rapamycin (mTOR) pathway that regulates cell proliferation and survival. This review will describe cell surface receptors and other upstream components required for tobacco carcinogen-induced activation of Akt and mTOR. Preclinical studies show that inhibitors of the Akt/mTOR pathway inhibit tumor formation in mouse models of carcinogen-induced lung tumorigenesis. Some of these inhibitors will be highlighted, and their clinical potential for the treatment and prevention of lung cancer will be discussed.
The effect of race and ethnicity on patch test results
Authors: Vincent A. DeLeo, Susan C. Taylor, Donald V. Belsito, Joseph F. Fowler, Anthony F. Fransway, Howard I. Maibach, James G. Marks, C.G.Toby Mathias, James R. Nethercott, Melanie D. Pratt, Robert R. Reitschel, Elizabeth F. Sherertz, Frances J. Storrs, James S. Taylor
Journal: Journal of the American Academy of Dermatology (2002)
Association of Hyperapobetalipoproteinemia with Endogenous Hypertriglyceridemia and Atherosclerosis
Authors: ALLAN D. SNIDERMAN
Journal: Annals of Internal Medicine (1982)

Researchers disagree on whether plasma triglyceride levels are an independent risk factor for atherosclerotic coronary artery disease. We hypothesized that patients with endogenous hypertriglyceridemia would differ: Some would have normal values of plasma low-density lipoprotein (LDL) B protein; others, despite their normal level of LDL cholesterol, would have increased levels of LDL B protein. We believed the latter patients—those with hyperapobetalipoproteinemia—would be the ones at risk for atherosclerosis. We studied two populations. Group 1, consisting of 162 patients with type IV lipoprotein patterns, was divided into two groups. One subgroup (A), which included 38 patients with elevated plasma LDL B protein levels, had a significantly higher prevalence of atherosclerotic disease than the other subgroup (B) of 36 patients with normal levels of plasma LDL B protein (10 patients versus two, p < 0.02). Group 2 consisted of 100 patients who had had myocardial infarction. Eighty-one percent of the 47 hypertriglyceridemic and 70% of the 53 normotriglyceridemic patients had elevated plasma LDL B protein levels (129 mg/dL or greater)—a proportion significantly higher than that in Group 1 (p < 0.001). Thus, an elevated plasma level of LDL B protein not only identifies subgroups of patients with type IV lipoprotein patterns, but also may be an important marker for atherosclerotic disease.
Preconditioning the human myocardium by simulated ischemia: studies on the early and delayed protection
Authors: S Ghosh
Journal: Cardiovascular Research (2000)

Background: There are data supporting the existence of ischemic preconditioning in man. This study investigated the most effective preconditioning protocol for the human myocardium and whether the second window of ischemic preconditioning (24 h) is as protective as the first window (≤2 h). Methods and results: Right atrial appendages (n=6/group) obtained during coronary bypass surgery were prepared and superfused with normoxic and normothermic Krebs–Henseleit solution. After 30 min stabilisation, muscles were subjected to various preconditioning protocols followed by 90 min ischemia and 120 min reperfusion. At the end of each protocol, the leakage of creatinine kinase (CK, U/g wet wt) and the reduction of MTT to insoluble formazan dye (OD/mg wet wt), an index of cell viability, were measured. In study 1, preconditioning was induced by 2, 3, 5 and 10 min of ischemia followed by 5 min reperfusion. In study 2, 1–4 cycles of 2 or 5 min ischemia–5 min reperfusion were applied. In study 3, preconditioning was induced by 5 min ischemia–5 min reperfusion followed by 1, 2, 3 or 4 h reperfusion before the subsequent 90 min ischemia. In study 4, preconditioning with 5 min ischemia followed by 5 min reperfusion either immediately preceded 30 or 90 min ischemia/120 min reperfusion or was applied 24 h before. In study 1 and 2, optimal protection was achieved with 5 min or two cycles of 2 min preconditioning ischemia (CK=3.06±0.31 and 2.89±0.02; MTT=0.56±0.05 and 0.47±0.09, respectively vs. CK=5.56±0.52 and MTT=0.18±0.04 in ischemia alone group; P<0.05). In study 3, protection was observed 2 h after preconditioning (CK=3.43±0.22 and MTT=0.46±0.09; P<0.01 vs. ischemia alone group) but it was lost beyond 2 h (CK=6.30±0.56 and MTT=0.16±0.02 after 3 h; P=NS vs. ischemia alone group). In study 4, protection was observed 24 h following preconditioning when the atrial specimens were exposed to 30 min ischemia (CK=2.96±0.38 and MTT=0.61±0.01 vs. CK=4.56±0.26 and MTT=0.43±0.02 in ischemia alone group, P<0.05); however, when the period of ischemia was extended to 90 min the beneficial effect of preconditioning was lost (CK=10.28±0.5 and MTT=0.11±0.05 vs. CK=9.56±0.62 and MTT=0.104±0.05 in ischemia alone group, P=NS). Conclusions: In the isolated human myocardium maximal protection induced by preconditioning is achieved by a total 4–5 min ischemic stimulus, an effect that is lost beyond 2 h of its application. Two windows of protection were identified, the first (≤2 h) being more potent than the second (24 h).
Infestation by Dermatobia hominis
Authors: Donald A. Person
Journal: JAMA (1976)

To the Editor.—  Iannini et al made several important points and, although I do not wishto detract from those points, I am compelled to comment on their reference to the use of fat over the lesions in the treatment of cutaneous myiasis. 1   While serving with the US Army in the Panama Canal Zone, I had occasion to accompany an air force medical team on a trip to visit Antonio, a Choco Indian, and his clan living in the tropical rain forest adjoining Gatun Lake, specifically to attend to their medical needs. Antonio played an integral part in the Air Force Jungle Survival School, and his involvement with the training of our astronauts was highlighted in a feature article in the National Geographic magazine that was published in early 1965. 2   One of the members of his family, an infant of 6 to 8 months of age, was brought to
Genetically Diverse Rhinoviruses and History of Wheezing/Asthma Among Hospitalized Children: a Two-Year Surveillance Study
Authors: E MILLER, Y ZHU, M GRIFFIN, L HEIL, G WEINBERG, C HALL, P SZILAGYI, X LU, M IWANE, K EDWARDS
Journal: Journal of Allergy and Clinical Immunology (2008)
Does animal experimentation inform human healthcare? Observations from a systematic review of international animal experiments on fluid resuscitation
Authors: I. Roberts
Journal: BMJ (2002)

Animal models are often used to test the effectiveness of a drug or procedure before proceeding to clinical trials. One reason for use of animal models is that they allow researchers to focus on particular pathological processes without the confounding effects of other injuries and treatments. However, it is essential that their results are valid and precise. Biased or imprecise results from animal experiments may result in clinical trials of biologically inert or even harmful substances, thus exposing patients to unnecessary risk and wasting scarce research resources. Moreover, if animal experiments fail to inform medical research then the animals suffer unnecessarily.

The Italian pathologist Pietro Croce criticised vivisection on scientific grounds. He argued that results from animal experiments cannot be applied to humans because of the biological differences between animals and humans and because the results of animal experiments are too dependent on the type of animal model used.1 Croce's arguments were based on insights into zoology and pathophysiology. In this paper, we make some methodological observations on animal experiments. Our observations were made in the context of a systematic review of all available randomised controlled trials of fluid resuscitation in animal models of uncontrolled bleeding. We conducted this review because we wanted to assess the scientific basis for fluid resuscitation. A previous systematic review of randomised trials of fluid resuscitation in bleeding trauma patients had provided no evidence that fluid resuscitation improved outcome.2

#### Summary points

New drugs and procedures are usually tested in animals before conducting clinical trials

Validity of animal experiments is essential for human health care and fundamental to animal welfare

A systematic review of animal experiments on fluid resuscitation found that most studies were underpowered and provided little information on possible bias

Systematic reviews of animal experiments allow a more objective appraisal of the evidence and …
Neuropsychological Correlates of Hippocampal Volumes in Patients Experiencing a First Episode of Schizophrenia
Authors: Philip R. Szeszko, Rael D. Strous, Robert S. Goldman, Manzar Ashtari, Kevin H. Knuth, Jeffrey A. Lieberman, Robert M. Bilder
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Despite evidence for hippocampal structural abnormalities in patients with schizophrenia, their functional correlates remain largely unknown. This study investigated the neuropsychological correlates of hippocampal volume in 43 men and 32 women experiencing a first episode of schizophrenia. METHOD: Posterior and anterior hippocampal volumes were computed from contiguous 3.1-mm magnetic resonance images and examined in relationship to six domains of neuropsychological functioning. Significant structure-function associations were investigated by examining the correlations between functioning and individual hippocampal slice volumes across the long axis of the hippocampus after interpolation to 10 equally spaced slice positions. RESULTS: Among men, worse executive and motor functioning correlated significantly with smaller anterior, but not posterior, hippocampal volume. The relationship between executive and motor functioning and hippocampal volume was not linear, however, when examined across the long axis of the hippocampus. Anterior hippocampal volume was more strongly correlated with both executive and motor functioning than with either memory or language functioning in men. None of the correlations between either posterior or anterior hippocampal volumes and the neuropsychological domains was significant among women. Anterior hippocampal volume was more strongly correlated with motor functioning in men than in women. CONCLUSIONS: Anterior hippocampal abnormalities associated with deficits on tests considered sensitive to frontal lobe functions implicate a defect in the integrated system linking frontal and mesiotemporal lobe regions. These findings further suggest that there are sex differences in structure-function relations in schizophrenia such that men may have more pronounced frontolimbic system abnormalities.
Interrelationships of human interferon-gamma with lymphotoxin and monocyte cytotoxin.
Authors: D S Stone-Wolff, Y K Yip, H C Kelker, J Le, D Henriksen-Destefano, B Y Rubin, E Rinderknecht, B B Aggarwal, J Vilcek
Journal: The Journal of Experimental Medicine (1984)

Crude preparations of interferon (IFN)-gamma derived from human peripheral blood leukocyte (PBL) cultures induced with 12-O-tetra-decanoylphorbol-13-acetate (TPA) and phytohemagglutinin (PHA) were more cytotoxic to HeLa cells than partially purified nautral or highly purified recombinant human IFN-gamma preparations. Conditioned media from PBL cultures contained, in addition to IFN-gamma, a mixture of cytotoxins, including classic lymphocyte-derived lymphotoxin (LT), and a TPA-induced cytotoxic activity produced by the adherent cell population (presumably monocytes). These two types of cytotoxins, indistinguishable in the mouse L929 cell LT assay, could be differentiated by an antiserum prepared against LT derived from the B lymphoblastoid cell line RPMI 1788. This antiserum neutralized lymphocyte-derived classic LT but failed to neutralize the activity of the monocyte-derived cytotoxin. Processing of conditioned media by sequential chromatography on silicic acid, Con A-Sepharose, and DEAE-Sephacel failed to separate IFN-gamma from the LT activity. However, this procedure did remove the monocyte-derived cytotoxic activity present in the original starting material, leaving predominantly classic LT. This LT showed a slightly basic isoelectric point (pI 7.6) which partially overlapped the more basic pI range of IFN-gamma. The two lymphokine activities also could not be completely separated by fast protein liquid chromatography or molecular sieve chromatography. LT in these partially purified preparations was associated with a protein having an apparent molecular weight of 58,000 on gel filtration. This form dissociated partially into a 20,000 mol wt species after denaturation with 0.1% NaDodSO4. IFN-gamma could be selectively removed from preparations containing both IFN-gamma and LT with the aid of monoclonal antibody to IFN-gamma. The addition of purified LT to purified E. coli-derived recombinant human IFN-gamma resulted in a marked synergistic enhancement of cytotoxicity for HeLa cells.
PHYLOGENETIC ORIGINS OF ANTIBODY STRUCTURE
Authors: J. Marchalonis, G. M. Edelman
Journal: The Journal of Experimental Medicine (1965)

The elasmobranch Mustelus canis has been shown to produce antibodies to Limulus hemocyanin. The serum of both normal and immunized M. canis contains immunoglobulins having sedimentation coefficients of approximately 7S and 17S. Antibody activity was found in the 17S immunoglobulin which may be dissociated to 7S components with concomitant loss of activity. Both 17S and 7S serum, immunoglobulins were antigenically identical. They consisted of light and heavy chains present in amounts comparable to those of higher vertebrates. Peptide maps indicated that the light chains had an entirely different primary structure than the heavy chains, but that the corresponding chains of 7S and 17S dogfish serum immunoglobulins were similar in primary structure. The heavy chains appeared to resemble the n chains of immunoglobulins of higher vertebrates in their starch gel electrophoretic behavior. It is suggested that the elasmobranch M. canis may have only one major class of immunoglobulins resembling that of macroglobulins (gammaM-immunoglobulins) seen in higher vertebrates. The results indicate that the multichain structure of antibodies is an ancient evolutionary development.
Evolution of phototransduction, vertebrate photoreceptors and retina
Authors: Trevor D. Lamb
Journal: Progress in Retinal and Eye Research (2013)

Evidence is reviewed from a wide range of studies relevant to the evolution of vertebrate photoreceptors and phototransduction, in order to permit the synthesis of a scenario for the major steps that occurred during the evolution of cones, rods and the vertebrate retina. The ancestral opsin originated more than 700 Mya (million years ago) and duplicated to form three branches before cnidarians diverged from our own lineage. During chordate evolution, ciliary opsins (C-opsins) underwent multiple stages of improvement, giving rise to the 'bleaching' opsins that characterise cones and rods. Prior to the '2R' rounds of whole genome duplication near the base of the vertebrate lineage, 'cone' photoreceptors already existed; they possessed a transduction cascade essentially the same as in modern cones, along with two classes of opsin: SWS and LWS (short- and long-wave-sensitive). These cones appear to have made synaptic contact directly onto ganglion cells, in a two-layered retina that resembled the pineal organ of extant non-mammalian vertebrates. Interestingly, those ganglion cells appear to be descendants of microvillar photoreceptor cells. No lens was associated with this two-layered retina, and it is likely to have mediated circadian timing rather than spatial vision. Subsequently, retinal bipolar cells evolved, as variants of ciliary photoreceptors, and greatly increased the computational power of the retina. With the advent of a lens and extraocular muscles, spatial imaging information became available for central processing, and gave rise to vision in vertebrates more than 500 Mya. The '2R' genome duplications permitted the refinement of cascade components suitable for both rods and cones, and also led to the emergence of five visual opsins. The exact timing of the emergence of 'true rods' is not yet clear, but it may not have occurred until after the divergence of jawed and jawless vertebrates.