tbuckley/cabot-search huggingface dataset:
Remarks on the Effects of the Trades of Sheffield: On the Workmen Employed in Them: With Special Reference to Inhaled Irritants
Authors: J. C. Hall
Journal: BMJ (1876)

AT the repeated request of the President, Dr. Chadwick, I have consented to introduce to the members of the British Medical Association the all- important subject of the effects produced by inhaled irritants.I did not refuse at first to comply from any wish not to take a fair share in the discussion of a subject which, for more than a quarter of a century, I have made a special study.But, having given evidence before a Royal Commission and occupied many pages of a Blue Book of the House of Commons-after having spoken often, and again and again published the results of my gleanings on the diseases of the grinders and other workmen following like trades-nothing seemed left but to repeat myself.This subject, affecting as it does thousands of the working classes of this and other countries, is surely well worthy the careful investigation of an Association leariied and powerful as this; and, I venture to think, even our amiable critic, dating from the " sad sea waves", will hardly venture to apply to investigations such as we are engaged in this morning his proverbial "cui bono ?"If we cannot altogether prevent these diseases of our industrious artisans, let us, at any rate, endeavour if possible to render them less deadly.If a man spend a considerable portion of his time, day after day, in a room the atmosphere of which is constantly loaded with small dust- like atoms of coal, cotton, flour (millers') dust, and fine particles of foreign hair and dust, and if the most perfect and efficient means be not taken to carry off this dust, the serious effects of the mechanical irritation soon exhibit themselves.The girls employed in hair seating, workmen in leather and flax, chaff-cutters, stone-masons, metal-miners, quarrymen, the machine-filers of Leeds, potters, needle-grinders, razor- grinders, scissor-grinders, fork-grinders, sheep-shears grinders, and, during some part of the process, table-blade grinders, all suffer more or less.
Duodenal-Ulcer Disease Associated with Elevated Serum Pepsinogen I
Authors: Rotter Ji, Sones Jq, Samloff Im, Richardson Ct, Gursky Jm, Walsh Jh, Rimoin Dl
Journal: New England Journal of Medicine (1979)

To delineate genetic factors involved in the pathogenesis of duodenal ulcer, serum pepsinogen I levels were determined by radioimmunoassay in two large kindreds with multiple members affected with duodenal ulcer. An elevated serum immunoreactive pepsinogen I concentration (greater than 100 ng per milliliter) segregated as an autosomal dominant trait in these families. Furthermore, 10 of 11 patients with clinical ulcer disease in these families had hyperpepsinogenemia. An elevated serum pepsinogen I concentration appears to be a subclinical marker of the ulcer diathesis in families with this autosomal dominant form of peptic-ulcer disease.
Editorial: Defusing the two-wheeled menace
Authors: L. N. Hames
Journal: JAMA (1975)

Physicians who work with children and teen-agers in their daily practice are in a good position to help to reduce the severity of what is rapidly turning into an epidemic. On page 55 of this issue ofThe Journal, Speca and Cowell discuss the trauma resulting from the use by youngsters of minibikes, bicycles, go-carts, and motorcycles. They suggest that if the incidence for the entire country is similar to that of Wilmington, Del, approximately 10,000 operators of these vehicles end up in an emergency room each summer. We hold no brief one way or another as to whether 10,000 such cases constitute an epidemic, but there should be no argument that 10,000 injuries, many resulting in permanent impairment, including paraplegia and amputations, constitute a serious problem. Hardly any area in the practice of preventive medicine provides physicians with as great an opportunity for satisfaction as an attempt to reduce
Mumps and the UK epidemic 2005
Authors: Ravindra K Gupta, Jennifer Best, Eithne MacMahon
Journal: BMJ (2005)

The United Kingdom is in the grip of a nationwide mumps epidemic with almost 5000 notifications in the first month of 2005 alone. 1Most patients are aged between 19 and 23, and there is now the threat of outbreaks among under-immunised children.As a result of the measles, mumps, and rubella (MMR) vaccine, which was introduced in 1988, the current generation of practising doctors have little experience of mumps infection.Mumps may have permanent sequelae, and not all cases can be diagnosed clinically.Here we explain the basis of the current epidemic and review the epidemiology, clinical presentation, complications, laboratory confirmation, and treatment of mumps. MethodsWe searched Medline for evidence based information on the internet, using a range of search terms.Other internet based resources included the websites of the Health Protection Agency (HPA), the World Health Organization (WHO), and the US Centers for Disease Control (CDC).We also used various formal texts.
Influence of anti-TNF patient warning regarding avoidance of high risk foods on rates of listeria and salmonella infections in the UK
Authors: Rebecca Davies, William G Dixon, Kath D Watson, Mark Lunt, Deborah P M Symmons, Kimme L Hyrich
Journal: Annals of the Rheumatic Diseases (2012)

Tumour necrosis factor (TNF) plays a pivotal role in the control of bacterial intracellular infection.1 The introduction of anti-TNF therapy to treat rheumatoid arthritis (RA) prompted the investigation of infection rates within these patients.2 Following an early signal of an increased risk of tuberculosis in anti-TNF treated patients,3 there have been many reports suggesting an increased risk of other intracellular bacterial infections, including listeria and salmonella.4 ,5 Indeed, the BSR Biologics Register (BSRBR) has reported an increase of such infections within anti-TNF treated patients compared with patients treated with non-biologic disease-modifying antirheumatic drugs.6 In response to these findings, patient information leaflets for anti-TNF agents (etanercept (ETN), infliximab (INF), adalimumab (ADA)) were modified in the UK in January 2006 advising patients to avoid high risk foods, such as raw eggs and poultry, which are associated with an increased risk of these infections.7–9 Given the addition of this advice, we investigated the rate of bacterial intracellular infection, before and after these guidelines were introduced, in RA patients treated with anti-TNF therapy within the BSRBR.10 

A total of 11 723 patients with RA starting their first anti-TNF on enrolment in the BSRBR were included. This comprised 9376 patients starting therapy …
Dioxin in Vietnam: fighting a legacy of war.
Authors: S M Booker
Journal: Environmental Health Perspectives (2001)

Singapore was the site of an East-West convergence over the week of 27 November-1 December 2000. At the behest of their respective governments, scientists from the United States and Vietnam came together for what promises to be the first of many meetings. Their mission: to explore the possibility of launching a joint research program to study the human and environmental health effects resulting from spraying Agent Orange and other herbicides during the Vietnam War.
Purinergic modulation of adult guinea pig cardiomyocytes in long term cultures and co-cultures with extracardiac or intrinsic cardiac neurones
Authors: M Horackova, M H Huang, J A Armour
Journal: Cardiovascular Research (1994)

Objective: To determine the capacity of ATP to modify cardiomyocytes directly or indirectly via peripheral autonomic neurones, the effects of various purinergic agents were studied on long term cultures of adult guinea pig ventricular myocytes and their co-cultures with extracardiac (stellate ganglion) or intrinsic cardiac neurones. Methods: Ventricular myocytes and cardiac neurones were enzymatically dissociated and plated together or alone (myocytes only). Myocyte cultures were used for experiments after three to six weeks. The electrical and contractile properties of cultured myocytes and myocyte-neuronal networks were investigated. Results: The spontaneous beating frequency of ventricular myocytes co-cultured with stellate ganglion neurones increased by ∼140% (p<0.001) following supervision with 10−5 M ATP. This effect was not modified significantly by tetrodotoxin or by β adrenoceptor blockade (10−5 M timolol), but was eliminated following application of the P2 antagonist suramin (10−5 M). Basal spontaneous contractile rate was reduced by ∼86% (p<0.001) in the presence of suramin, indicating the existence of tonically active purinergic synaptic mechanisms in stellate ganglion neurone-myocyte cocultures. Suramin did not significantly affect non-innervated myocyte cultures. ATP increased myocyte contractile rate in intrinsic cardiac neurone-myocyte co-cultures by ∼40% (p<0.01) under control conditions, but when β adrenergic receptors of tetrodotoxin sensitive neural responses were blocked, ATP induced greater augmentation (>100%). In contrast, ATP induced much smaller effects in non- innervated myocyte cultures (∼26%, p<0.01). Analogues of ATP showed the following order of potency: ATP > UTP > MSATP > βγ ATP > αβ ATP. Adenosine (10−4 M) attenuated the beating frequency of myocytes in both types of co-culture, while not significantly affecting non-innervated myocyte cultures. Conclusions: The experimental model used in this study showed that extrinsic and intrinsic cardiac neurones which possess P2receptors can greatly enhance cardiac myocyte contractile rate when activated by ATP. Since adenosine reduced contractile rate in both types of co-cultures while not affecting non-innervated myocytes, it is concluded that some of these neurones possess P1 receptors. Cardiovascular Research 1994;28:673-679
201 COMBINED THERAPY WITH LOW DOSE HEPATITIS B IMMUNOGLOBULIN (HBIG) AND LAMIVUDINE (LAM) IN PATIENTS TRANSPLANTED FOR HBV CHRONIC LIVER DISEASE: LONG TERM EFFICACY AND COSTS
Authors: M. Giusto, F. Gentili, I. Loria, S. Grieco, M. Rossi, G. Novelli, P. Berloco, G. Ferretti, S. Ginanni Corradini, A.F. Attili, M. Merli
Journal: Journal of Hepatology (2008)
Genesis of Heart Sounds-Reply
Authors: Jonathan Abrams
Journal: JAMA (1978)

Dr Prakash has nicely underlined the current focus of controversy regarding the genesis of the so-called tricuspid component of SI and the disagreement regarding the onset of A2 with respect to the timing of actual aortic valve leaflet coaptation. His investigations are consistent with the most recent studies in this area, and it is my judgment that he is probably correct. I deliberately avoided a comprehensive review of these controversial areas because of the space limitations of a brief review article.
Abstract LB-246: Recurrent inactivating mutations in SPOP define a molecular subset of prostate cancer
Authors: Christopher E. Barbieri, Francesca Demichelis, Catherine Grasso, Terry Vuong, Theresa MacDonald, Gunther Boysen, Samprit Banerjee, Naoki Kitabayashi, Michael F. Berger, Ashutosh K. Tewari, Levi A. Garraway, Arul M. Chinnaiyan, Mark A. Rubin
Journal: Cancer Research (2011)

Abstract Considerable evidence exists that prostate cancer is driven by cardinal genetic alterations that activate oncogenes and inactivate tumor suppressors. Recently, recurrent fusions involving members of the ETS transcription factor family have been implicated in the majority of prostate cancer. In addition, several studies have shown that prostate cancers can be classified by genome-wide analysis of somatic copy-number aberration, or transcriptome-wide analysis of gene expression profiles. These discoveries raise the possibility that prostate cancer may soon transition from a poorly understood, clinically heterogeneous disease to a collection of homogenous subtypes identifiable by molecular criteria. However, the limited number of known driver alterations in prostate cancer currently limits this effort. Here, we report the presence of recurrent mutations in human prostate cancer in SPOP, the substrate-recognition component of an E3-ubiquitin ligase. Recurrent missense mutations in SPOP were discovered by whole genome DNA sequencing (DNA-seq) and whole transcription RNA sequencing (RNA-seq). SPOP mutations were found in approximately 10% of prostate cancers in multiple independent patient cohorts. All mutations were heterozygous, and were found exclusively in the structurally-defined substrate-binding cleft of SPOP. Structural analysis suggests that these mutations inactivate SPOP function by disrupting SPOP-substrate interaction, and loss of SPOP function in prostate cell lines resulted in increased invasion. Prostate cancers harboring SPOP mutations displayed characteristic somatic genomic aberrations. However, all tumors with SPOP mutations lacked both ERG rearrangement and deletion of PTEN, two of the most common genetic alterations in human prostate cancer. We conclude from these results that recurrent mutations in SPOP define a distinct molecular subclass of prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-246. doi:10.1158/1538-7445.AM2011-LB-246
Molecular targeted therapies in hepatocellular carcinoma
Authors: Josep M. Llovet, Jordi Bruix
Journal: Hepatology (2008)

Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor with several genomic alterations. There is evidence of aberrant activation of several signaling cascades such as epidermal growth factor receptor (EGFR), Ras/extracellular signal-regulated kinase, phosphoinositol 3-kinase/mammalian target of rapamycin (mTOR), hepatocyte growth factor/mesenchymal-epithelial transition factor, Wnt, Hedgehog, and apoptotic signaling. Recently a multikinase inhibitor, sorafenib, has shown survival benefits in patients with advanced HCC. This advancement represents a breakthrough in the treatment of this complex disease and proves that molecular therapies can be effective in HCC. It is becoming apparent, however, that to overcome the complexity of genomic aberrations in HCC, combination therapies will be critical. Phase II studies have tested drugs blocking EGFR, vascular endothelial growth factor/platelet-derived growth factor receptor, and mTOR signaling. No relevant data has been produced so far in combination therapies. Future research is expected to identify new compounds to block important undruggable pathways, such as Wnt signaling, and to identify new oncogenes as targets for therapies through novel high-throughput technologies. Recent guidelines have established a new frame for the design of clinical trials in HCC. Randomized phase II trials with a time-to-progression endpoint are proposed as pivotal for capturing benefits from novel drugs. Survival remains the main endpoint to measure effectiveness in phase III studies. Patients assigned to the control arm should receive standard-of-care therapy, that is, chemoembolization for patients with intermediate-stage disease and sorafenib for patients with advanced-stage disease. Biomarkers and molecular imaging should be part of the trials, in order to optimize the enrichment of study populations and identify drug responders. Ultimately, a molecular classification of HCC based on genome-wide investigations and identification of patient subclasses according to drug responsiveness will lead to a more personalized medicine. (HEPATOLOGY 2008;48:1312–1327.)
PIM2 inhibition as a rational therapeutic approach in B-cell lymphoma
Authors: Cristina Gómez-Abad, Helena Pisonero, Carmen Blanco-Aparicio, Giovanna Roncador, Alberto González-Menchén, Jose A. Martinez-Climent, Eva Mata, María Elena Rodríguez, Guillermo Muñoz-González, Margarita Sánchez-Beato, Juan F. Leal, James R. Bischoff, Miguel A. Piris
Journal: Blood (2011)
Essential role of peripheral node addressin in lymphocyte homing to nasal-associated lymphoid tissues and allergic immune responses
Authors: Yukari Ohmichi, Jotaro Hirakawa, Yasuyuki Imai, Minoru Fukuda, Hiroto Kawashima
Journal: The Journal of Experimental Medicine (2011)

Nasal-associated lymphoid tissue (NALT) is a mucosal immune tissue that provides immune responses against inhaled antigens. Lymphocyte homing to NALT is mediated by specific interactions between lymphocytes and high endothelial venules (HEVs) in NALT. In contrast to HEVs in other mucosal lymphoid tissues, NALT HEVs strongly express peripheral node addressins (PNAds) that bear sulfated glycans recognized by the monoclonal antibody MECA-79. We investigated the role of PNAd in lymphocyte homing to NALT using sulfotransferase N-acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST) 1 and GlcNAc6ST-2 double knockout (DKO) mice. The expression of PNAd in NALT HEVs was eliminated in DKO mice. Short-term homing assays indicated that lymphocyte homing to NALT was diminished by 90% in DKO mice. Production of antigen-specific IgE and the number of sneezes in response to nasally administered ovalbumin were also substantially diminished. Consistently, the NALT of DKO mice showed reduced production of IL-4 and increased production of IL-10 together with an increase in CD4+CD25+ regulatory T cells (Treg cells). Compared with the homing of CD4+CD25− conventional T cells, the homing of CD4+CD25+ Treg cells to NALT was less dependent on the L-selectin–PNAd interaction but was partially dependent on PSGL-1 (P-selectin glycoprotein ligand 1) and CD44. These results demonstrate that PNAd is essential for lymphocyte homing to NALT and nasal allergic responses.
S42 Early Identification of Mycobacterium tuberculosis (M.tb) and Mycobacterium other than tuberculosis (MOTT) by "cord formation" evaluation in liquid culture
Authors: A. Elsaghir, S. Abdullah, F. Sundram, D. D. Creer
Journal: Thorax (2011)

The identification of <i>M.tb</i> in smear negative samples has the inherent TB culture delays. These delays potentially affect treatment choices and contact tracing decisions particularly where TB prevalence is low and isolation of MOTT common. Faster molecular techniques are expensive and not universally available. The identification of cord formation1 in positive cultures gives an early indication of the likely TB culture result before the final reference laboratory identification (local audit data: <i>M.tb</i> 12.3±5.9 d, MOTT 13.7±11.6 d). We evaluated the presence of cord formation in AFB smears prepared from MGIT tubes and stained by auramine-phenol staining from positive liquid culture (BACTEC MGIT growth supplement medium) for the presumptive identification of <i>M.tb</i>. We prospectively evaluated 612 positive mycobacterial culture specimens from 316 patients over 3 years. All specimens were sent to our local reference laboratory for species identification. The identification of <i>M.tb</i> by the presence of cord formation was compared with the subsequent reference laboratory report. 420/426 samples showing cording by smear microscopy were confirmed by the reference laboratory as <i>M.tb</i> (PPV: 98.6%). 182/186 non-cording culture positive specimens were confirmed as MOTT (NPV: 97.9%). The 6/612 (0.9%) MOTT misidentified as <i>M.tb</i> by cording were <i>M kansasii</i> as previously described.1 The 4/612 (0.7%) <i>M.tb</i> misidentified as MOTT by the absence of cording were all 3+ sputum smear positive samples as previously described.2 The presumptive identification of <i>M.tb</i> and MOTT by the presence or absence of cording formation in liquid culture is both sensitive and specific. This technique has a potentially significant impact on treatment timing and contact tracing decisions.
Length of training, hostility and the martial arts: a comparison with other sporting groups.
Authors: K Daniels, E Thornton
Journal: British Journal of Sports Medicine (1992)

Previous research has indicated that training in the martial arts leads to a reduction in levels of hostility. However, such research has only compared hostility within martial arts groups. The present research compares two martial arts groups and two other sporting groups on levels of assaultive, verbal and indirect hostility. Moderated multiple regression analyses revealed a significant interaction between length of training in the respondent's stated sport and whether that sport was a martial art in predicting assaultive and verbal hostility. The form of the interaction suggests that participation in the martial arts is associated, over time, with decreased feelings of assaultive and verbal hostility.
The mitogen-activated protein kinase pathway can mediate growth inhibition and proliferation in smooth muscle cells. Dependence on the availability of downstream targets.
Authors: K E Bornfeldt, J S Campbell, H Koyama, G M Argast, C C Leslie, E W Raines, E G Krebs, R Ross
Journal: Journal of Clinical Investigation (1997)

Activation of the classical mitogen-activated protein kinase (MAPK) pathway leads to proliferation of many cell types. Accordingly, an inhibitor of MAPK kinase, PD 098059, inhibits PDGF-induced proliferation of human arterial smooth muscle cells (SMCs) that do not secrete growth-inhibitory PGs such as PGE2. In striking contrast, in SMCs that express the inducible form of cyclooxygenase (COX-2), activation of MAPK serves as a negative regulator of proliferation. In these cells, PDGF-induced MAPK activation leads to cytosolic phospholipase A2 activation, PGE2 release, and subsequent activation of the cAMP-dependent protein kinase (PKA), which acts as a strong inhibitor of SMC proliferation. Inhibition of either MAPK kinase signaling or of COX-2 in these cells releases them from the influence of the growth-inhibitory PGs and results in the subsequent cell cycle traverse and proliferation. Thus, the MAPK pathway mediates either proliferation or growth inhibition in human arterial SMCs depending on the availability of specific downstream enzyme targets.
Rodent models of cardiopulmonary disease: their potential applicability in studies of air pollutant susceptibility.
Authors: U P Kodavanti, D L Costa, P A Bromberg
Journal: Environmental Health Perspectives (1998)

The mechanisms by which increased mortality and morbidity occur in individuals with preexistent cardiopulmonary disease following acute episodes of air pollution are unknown. Studies involving air pollution effects on animal models of human cardiopulmonary diseases are both infrequent and difficult to interpret. Such models are, however, extensively used in studies of disease pathogenesis. Primarily they comprise those developed by genetic, pharmacologic, or surgical manipulations of the cardiopulmonary system. This review attempts a comprehensive description of rodent cardiopulmonary disease models in the context of their potential application to susceptibility studies of air pollutants regardless of whether the models have been previously used for such studies. The pulmonary disease models include bronchitis, emphysema, asthma/allergy, chronic obstructive pulmonary disease, interstitial fibrosis, and infection. The models of systemic hypertension and congestive heart failure include: those derived by genetics (spontaneously hypertensive, Dahl S. renin transgenic, and other rodent models); congestive heart failure models derived by surgical manipulations; viral myocarditis; and cardiomyopathy induced by adriamycin. The characteristic pathogenic features critical to understanding the susceptibility to inhaled toxicants are described. It is anticipated that this review will provide a ready reference for the selection of appropriate rodent models of cardiopulmonary diseases and identify not only their pathobiologic similarities and/or differences to humans but also their potential usefulness in susceptibility studies.