tbuckley/cabot-search huggingface dataset:
Resistin-like molecule- is a human airway remodelling mediator
Authors: C. Fang, Q. Meng, H. Wu, G. Eid, G. Zhang, X. Zhang, S. Yang, K. Huang, T.H. Lee, C.J. Corrigan, S. Ying
Journal: European Respiratory Journal (2011)

Though implicated in vascular remodelling, a role for the resistin-like molecule (RELM)-β in human airway remodelling remains unexplored. We hypothesised that RELM-β expression is increased in the airways of asthmatics and regulates airways epithelial cell function. Expression of RELM-β in the bronchial mucosa and its concentrations in bronchoalveolar lavage (BAL) fluid from asthmatics and controls were measured by immunohistochemistry and ELISA, respectively. Proliferation assays, Western blotting, ELISA and real-time PCR were employed to detect effects of RELM-β on airways epithelial cells. RELM-β expression was increased in the bronchial mucosa and BAL fluid of asthmatics compared with controls. In the asthmatics, the numbers of mucosal RELM-β+ cells correlated inversely with forced expiratory volume in 1 s (r=-0.531, p=0.016), while the numbers of epithelial RELM-β+ cells correlated positively with those of mucin (MUC)5AC+ cells. In vitro , interleukin-13 enhanced RELM-β expression by primary human airways epithelial cells, while RELM-β itself acted on these cells to induce proliferation, expression of MUC5AC, extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK)-phosphatidylinositol 3-kinase (PI3K)/Akt phosphorylation and elevated expression of transforming growth factor-β2, epidermal growth factor and vascular endothelial growth factor. RELM-β has the potential to contribute to airway remodelling in diseases such as asthma by acting on epithelial cells to increase proliferation, mucin and growth factor production, at least partly via ERK/MAPK-PI3K/Akt signalling pathways.
Lead Absorption by Children of Battery Workers
Authors: Lorcan A. O'Tuama, John F. Rogers, Walter Rogan
Journal: JAMA (1979)

<h3>To the Editor.—</h3> The recent discovery of unexpected increased lead absorption in children of female battery workers strikingly reflects the impact on clinical practice of the increased participation by women in the work force. This experience illustrates other epidemiologic principles that we believe need wider appreciation. We have detailed these points to pediatricians<sup>1</sup>and wish now to reiterate them for a more general medical audience. <h3>Report of a Case.—</h3> A 24-year-old woman had intermittent headache, dizziness, and amnesia. Results of neurological evaluation were normal, but anemia with basophilic stippling was found. Her work involved burning lead battery terminals, but the importance of this information was not appreciated until her 20-month-old son showed a high blood lead level on routine screening. Subsequently, increased lead absorption was disclosed in the woman, and chelation therapy produced clinical and biochemical improvement. Three of her children, and children in the families of five other
Anti-transforming growth factor (TGF)-beta antibodies inhibit breast cancer cell tumorigenicity and increase mouse spleen natural killer cell activity. Implications for a possible role of tumor cell/host TGF-beta interactions in human breast cancer progression.
Authors: C L Arteaga, S D Hurd, A R Winnier, M D Johnson, B M Fendly, J T Forbes
Journal: Journal of Clinical Investigation (1993)

TGF-beta effects on angiogenesis, stroma formation, and immune function suggest its possible involvement in tumor progression. This hypothesis was tested using the 2G7 IgG2b, which neutralizes TGF-beta 1, -beta 2, and -beta 3, and the MDA-231 human breast cancer cell line. Inoculation of these cells in athymic mice decreases mouse spleen natural killer (NK) cell activity. Intraperitoneal injections of 2G7 starting 1 d after intraperitoneal inoculation of tumor cells suppressed intraabdominal tumor and lung metastases, whereas the nonneutralizing anti-TGF-beta 12H5 IgG2a had no effect. 2G7 transiently inhibited growth of established MDA-231 subcutaneous tumors. Histologically, both 2G7-treated and control tumors were identical. Intraperitoneal administration of 2G7 resulted in a marked increase in mouse spleen NK cell activity. 2G7 did not inhibit MDA-231 primary tumor or metastases formation, nor did it stimulate NK cell-mediated cytotoxicity in beige NK-deficient nude mice. Finally, serum-free conditioned medium from MDA-231 cells inhibited the NK cell activity of human blood lymphocytes. This inhibition was blocked by the neutralizing anti-TGF-beta 2G7 antibody but not by a nonspecific IgG2. These data support a possible role for tumor cell TGF-beta in the progression of mammary carcinomas by suppressing host immune surveillance.
Significance of sputum purulence to guide antibiotic therapy in exacerbations of COPD
Authors: Deepak Aggarwal, Prasanta R. Mohapatra, Phiza Aggarwal
Journal: European Respiratory Journal (2012)

Significance of sputum purulence to guide antibiotic therapy in exacerbations of COPDTo the Editor:We read with interest the study by SOLER et al.[1] evaluating role of sputum purulence as a guide for antibiotic use in hospitalised patients with exacerbations of chronic obstructive pulmonary disease (COPD).Besides bacteria, viruses and air pollution can also lead to exacerbations of COPD.These episodes are characterised by recruitment of leukocytes (neutrophils, eosinophils, etc.), which leads to sputum purulence.The sputum colour/purulence is strongly correlated with markers of bronchial inflammation, like myeloperoxidase (green coloured) and leukocyte elastase present within these inflammatory cells [2], and may not mandate the bacterial presence.Moreover, isolation of bacteria from sputum may represent bronchial colonisation, especially in conditions with co-existent architectural distortion like bronchiectasis.
Evidence in managing traumatic anterior shoulder instability: a scoping review
Authors: A Paul Monk, Patrick Garfjeld Roberts, Kartik Logishetty, Andrew J Price, Rohit Kulkarni, Amar Rangan, Jonathan L Rees
Journal: British Journal of Sports Medicine (2013)

Background Traumatic anterior shoulder instability (TASI) accounts for 95% of glenohumeral dislocations and is associated with soft tissue and bony pathoanatomies. Non-operative treatments include slings, bracing and physiotherapy. Operative treatment is common, including bony and soft-tissue reconstructions performed through open or arthroscopic approaches. There is management variation in patient pathways for TASI including when to refer and when to operate. Methods A scoping review of systematic reviews, randomised controlled trials, comparing operative with non-operative treatments and different operative treatments were the methods followed. Search was conducted for online bibliographic databases and reference lists of relevant articles from 2002 to 2012. Systematic reviews were appraised using AMSTAR (assessment of multiple systematic reviews) criteria. Controlled trials were appraised using the CONSORT (consolidation of standards of reporting trials) tool. Results Analysis of the reviews did not offer strong evidence for a best treatment option for TASI. No studies directly compare open, arthroscopic and structured rehabilitation programmes. Evaluation of arthroscopic studies and comparison to open procedures was difficult, as many of the arthroscopic techniques included are no longer used. Recurrence rate was generally considered the best measure of operative success, but was poorly documented throughout all studies. There was conflicting evidence on the optimal timing of intervention and no consensus on any scoring system or outcome measure. Conclusions There is no agreement about which validated outcome tool should be used for assessing shoulder instability in patients. There is limited evidence regarding the comparative effectiveness of surgical and non-surgical treatment of TASI, including a lack of evidence regarding the optimal timing of such treatments. There is a need for a well-structured randomised control trial to assess the efficacy of surgical and non-surgical interventions for this common type of shoulder instability.
Risk Prediction of Cardiovascular Disease in Type 2 Diabetes
Authors: Jan Cederholm, Katarina Eeg-Olofsson, Björn Eliasson, Björn Zethelius, Peter M. Nilsson, Soffia Gudbjörnsdottir
Journal: Diabetes Care (2008)

OBJECTIVE—Risk prediction models obtained in samples from the general population do not perform well in type 2 diabetic patients. Recently, 5-year risk estimates were proposed as being more accurate than 10-year risk estimates. This study presents a diabetes-specific equation for estimation of the absolute 5-year risk of first incident fatal/nonfatal cardiovascular disease (CVD) in type 2 diabetic patients with use of A1C and clinical characteristics. RESEARCH DESIGN AND METHODS—The study was based on 11,646 female and male patients, aged 18–70 years, from the Swedish National Diabetes Register with 1,482 first incident CVD events based on 58,342 person-years with mean follow-up of 5.64 years. RESULTS—This risk equation incorporates A1C, as in the UK Prospective Diabetes Study risk engine, and several clinical characteristics: onset age of diabetes, diabetes duration, sex, BMI, smoking, systolic blood pressure, and antihypertensive and lipid-reducing drugs. All predictors included were associated with the outcome (P &amp;lt; 0.0001, except for BMI P = 0.0016) with Cox regression analysis. Calibration was excellent when assessed by comparing observed and predicted risk. Discrimination was sufficient, with a receiver operator curve statistic of 0.70. Mean 5-year risk of CVD in all patients was 12.0 ± 7.5%, whereas 54% of the patients had a 5-year risk ≥10%. CONCLUSIONS—This more simplified risk equation enables 5-year risk prediction of CVD based on easily available nonlaboratory predictors in clinical practice and A1C and was elaborated in a large observational study obtained from the normal patient population aged up to 70 years.
Positive and Negative Selection on Noncoding DNA Close to Protein-Coding Genes in Wild House Mice
Authors: Athanasios Kousathanas, Fiona Oliver, Daniel L. Halligan, Peter D. Keightley
Journal: Molecular Biology and Evolution (2010)

During the past two decades, evidence has accumulated of adaptive evolution within protein-coding genes in a variety of species. However, with the exception of Drosophila and humans, little is known about the extent of adaptive evolution in noncoding DNA. Here, we study regions upstream and downstream of protein-coding genes in the house mouse Mus musculus castaneus, a species that has a much larger effective population size (Ne) than humans. We analyze polymorphism data for 78 genes from 15 wild-caught M. m. castaneus individuals and divergence to a closely related species, Mus famulus. We find high levels of nucleotide diversity and moderate levels of selective constraint in upstream and downstream regions compared with nonsynonymous sites of protein-coding genes. From the polymorphism data, we estimate the distribution of fitness effects (DFE) of new mutations and infer that most new mutations in upstream and downstream regions behave as effectively neutral and that only a small fraction is strongly negatively selected. We also estimate the fraction of substitutions that have been driven to fixation by positive selection (α) and the ratio of adaptive to neutral divergence (ωα). We find that α for upstream and downstream regions (∼10%) is much lower than α for nonsynonymous sites (∼50%). However, ωα estimates are very similar for nonsynonymous sites (∼10%) and upstream and downstream regions (∼5%). We conclude that negative selection operating in upstream and downstream regions of M. m. castaneus is weak and that the low values of α for upstream and downstream regions relative to nonsynonymous sites are most likely due to the presence of a higher proportion of neutrally evolving sites and not due to lower absolute rates of adaptive substitution.
The Man Who Mistook his Wife for a Hat and Other Clinical Tales
Authors: David Warriner
Journal: BMJ (2008)

Oliver Sacks describes himself as a “physician and naturalist,” and as he has written on matters as disparate as ferns, the periodic table, and encephalitis lethargica I am inclined to agree. It is this collection of case reports, however, that I consider to be his finest work.

The book is divided into four thematic parts: “Losses,” “Excesses,” “Transports,” and “The world of the simple.” I discovered it in the sixth form, and it inspired me to study medicine and to practise—like Sacks—in the manner of James Purdon Martin, in which “patient and physician were co-equals . . . learning from and helping the other . . . …
The Cell Fate Determination Factor Dachshund Inhibits Androgen Receptor Signaling and Prostate Cancer Cellular Growth
Authors: Kongming Wu, Sanjay Katiyar, Agnes Witkiewicz, Anping Li, Peter McCue, Liang-Nian Song, Lifeng Tian, Ming Jin, Richard G. Pestell
Journal: Cancer Research (2009)

Initially isolated as the dominant suppressor of the mutant epidermal growth factor receptor (ellipse), the Dachshund gene plays a key role in metazoan development regulating the Retinal Determination Gene Network. Herein, the DACH1 gene was expressed in normal prostate epithelial cells with reduced expression in human prostate cancer. DACH1 inhibited prostate cancer cellular DNA synthesis, growth in colony forming assays, and blocked contact-independent growth in soft agar assays. DACH1 inhibited androgen receptor (AR) activity, requiring a conserved DS Domain (Dachshund domain conserved with Ski/Sno) that bound NCoR/HDAC and was recruited to an androgen-responsive gene promoter. DACH1 inhibited ligand-dependent activity of AR mutations identified in patients with androgen-insensitive prostate cancer. The DS domain was sufficient for repression of the AR wild-type but failed to repress an AR acetylation site point mutant. These studies show a role for the Retinal Determination Gene Network in regulating cellular growth and signaling in prostate cancer.
CENPA overexpression promotes genome instability in pRb-depleted human cells
Authors: Angela Amato, Tiziana Schillaci, Laura Lentini, Aldo Di Leonardo
Journal: Molecular Cancer (2009)

Abstract Background Aneuploidy is a hallmark of most human cancers that arises as a consequence of chromosomal instability and it is frequently associated with centrosome amplification. Functional inactivation of the Retinoblastoma protein (pRb) has been indicated as a cause promoting chromosomal instability as well centrosome amplification. However, the underlying molecular mechanism still remains to be clarified. Results Here we show that pRb depletion both in wild type and p53 knockout HCT116 cells was associated with the presence of multipolar spindles, anaphase bridges, lagging chromosomes and micronuclei harbouring whole chromosomes. In addition aneuploidy caused by pRb acute loss was not affected by p53 loss. Quantitative real-time RT-PCR showed that pRB depletion altered expression of genes involved in centrosome duplication, kinetochore assembly and in the Spindle Assembly Checkpoint (SAC). However, despite MAD2 up-regulation pRb-depleted cells seemed to have a functional SAC since they arrested in mitosis after treatments with mitotic poisons. Moreover pRb-depleted HCT116 cells showed BRCA1 overexpression that seemed responsible for MAD2 up-regulation. Post-transcriptional silencing of CENPA by RNA interference, resulting in CENP-A protein levels similar to those present in control cells greatly reduced aneuploid cell numbers in pRb-depleted cells. Conclusion Altogether our findings indicate a novel aspect of pRb acute loss that promotes aneuploidy mainly by inducing CENPA overexpression that in turn might induce micronuclei by affecting the correct attachment of spindle microtubules to kinetochores.
Primary psoas abscess
Authors: T THONGNGARM
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background:</h3> Proximal interphalangeal joint (PIPJ) hyperextension injuries are common in children. There is a range of opinion on management but little evidence to suggest best practice. <h3>Aims:</h3> To determine from a convenient sample size, the overall and significant fracture rate. Whether significant injuries can be differentiated from the insignificant clinically and whether children get complications. <h3>Methods:</h3> Data were collected on all PIPJ hyperextension injuries (thumb excluded) presenting to a children’s emergency department between October and December 2006. Staff were trained to perform standardised assessment and documentation and all injuries were <i>x</i> rayed. The diagnosis was cross-referenced with <i>x</i> ray reports. All notes were reviewed for 4 months. Management, complications and unscheduled returns were noted. <h3>Results:</h3> From the population of 134 patients, there was a fracture rate of 55% (74/134). Of those, 57% (42/74) were defined as significant. Others included buckle (9/74), flake (14/74) and avulsion (9/74) fractures. Obvious deformity and inability to touch pulp to palm were significantly associated with a fracture. Except for those with clinical deformity requiring manipulation, all injuries were treated conservatively. There were no unscheduled returns with any complications 4 months post-injury. <h3>Conclusions:</h3> There is a significant risk of a fracture in children sustaining hyperextension injuries to the PIPJ. These results show that, except in those with an obvious deformity, it is difficult to differentiate clinically between those with a sprain, minor or significant fracture. Even those with a significant fracture were managed conservatively. Children appear not to have the complications seen in the adult population with similar injuries.
Detection of Coronary Artery Stenoses by Contrast-Enhanced, Retrospectively Electrocardiographically-Gated, Multislice Spiral Computed Tomography
Authors: Stephan Achenbach, Tom Giesler, Dieter Ropers, Stefan Ulzheimer, Hans Derlien, Christoph Schulte, Evelyn Wenkel, Werner Moshage, Werner Bautz, Werner G. Daniel, Willi A. Kalender, Ulrich Baum
Journal: Circulation (2001)

Multislice spiral computed tomography (MSCT) with retrospectively ECG-gated image reconstruction permits coronary artery visualization. We investigated the method's ability to identify high-grade coronary artery stenoses and occlusions.A total of 64 consecutive patients were studied by MSCT (4x1 mm cross-sections, 500-ms rotation, table feed 1.5 mm/rotation, intravenous contrast agent, retrospectively ECG-gated image reconstruction). All coronary arteries and side branches with a luminal diameter >/=2.0 mm were assessed concerning evaluability and the presence of high-grade stenoses (>70% diameter stenosis) or occlusions. Results were compared with quantitative coronary angiography. Of 256 coronary arteries (left main, left anterior descending, left circumflex and right coronary artery, including their respective side branches), 174 could be evaluated (68%). In 19 patients (30%), all arteries were evaluable. Artifacts caused by coronary motion were the most frequent reason for unevaluable arteries. Overall, 32 of 58 high-grade stenoses and occlusions were detected by MSCT (58%). In evaluable arteries, 32 of 35 lesions were detected, and the absence of stenosis was correctly identified in 117 of 139 arteries (sensitivity, 91%; specificity, 84%). If analysis was extended to all stenoses with >50% diameter reduction, sensitivity was 85% (40 of 47) and specificity was 76% (96 of 127).MSCT with retrospective ECG gating permits the detection of coronary artery stenoses with high accuracy if image quality is sufficient, but its clinical use may presently be limited due to degraded image quality in a substantial number of cases, mainly due to rapid coronary motion.
Paradigm shifts in lung cancer as defined in the new IASLC/ATS/ERS lung adenocarcinoma classification
Authors: W.D. Travis, E. Brambilla, P. Van Schil, G.V. Scagliotti, R.M. Huber, J-P. Sculier, J. Vansteenkiste, A.G. Nicholson
Journal: European Respiratory Journal (2011)

The new international multidisciplinary lung adenocarcinoma classification is sponsored by the European Respiratory Society (ERS), as well as the International Association for the Study of Lung Cancer (IASLC) and the American Thoracic Society (ATS) [1]. This classification is now published in the Journal of Thoracic Oncology , the official journal of the IASLC. Under the scientific oversight of the ATS and ERS, the classification project involved a systematic review to provide an evidence-based foundation with specific recommendations.

For decades, the field of lung cancer has been relatively static with few major advances. However, in the past 5–6 yrs this has changed to a rapidly evolving field. At the heart of this change is the impact of the molecular discovery that the activating mutations in the epidermal growth factor receptor ( EGFR ) are a marker for response and improved progression-free survival with tyrosine kinase inhibitor (TKI) therapy compared to conventional chemotherapy in advanced lung adenocarcinoma patients [2–5].

In this editorial, we summarise a series of major paradigm shifts that are outlined in this classification that will result in major changes in the approach to diagnosis of lung cancer compared to those outlined in previous World Health Organization (WHO) classifications. While this classification is primarily focused on lung adenocarcinoma, many of the recommendations will impact on how all histologic types of lung cancer are diagnosed in the future. This classification is divided into two major components: classification based on resection specimens (table 1) and on small biopsies and cytology (table 2).

View this table:

Table 1– 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification of lung adenocarcinoma in resection specimens 

View this table:

Table 2– Proposed International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification for small biopsies/cytology 

Historically, tumour classification has been primarily been performed by the WHO with panels primarily consisting of pathologists [6–9]. Due to the many major advances that have occurred at each level (pathology, molecular biology, radiology, respiratory medicine, oncology and surgery) this current …
Effects of sample storage time, temperature and syringe type on blood gas tensions in samples with high oxygen partial pressures.
Authors: J J Pretto, P D Rochford
Journal: Thorax (1994)

BACKGROUND--Although plastic arterial sampling syringes are now commonly used, the effects of sample storage time and temperature on blood gas tensions are poorly described for samples with a high oxygen partial pressure (PaO2) taken with these high density polypropylene syringes. METHODS--Two ml samples of tonometered whole blood (PaO2 86.7 kPa, PaCO2 4.27 kPa) were placed in glass syringes and in three brands of plastic blood gas syringes. The syringes were placed either at room temperature or in iced water and blood gas analysis was performed at baseline and after 5, 10, 20, 40, 60, 90, and 120 minutes. RESULTS--In the first 10 minutes measured PaO2 in plastic syringes at room temperature fell by an average of 1.21 kPa/min; placing the sample on ice reduced the rate of PaO2 decline to 0.19 kPa/min. The rate of fall of PaO2 in glass at room temperature was 0.49 kPa/min. The changes in PaCO2 were less dramatic and at room temperature averaged increases of 0.47 kPa for plastic syringes and 0.71 kPa for glass syringes over the entire two hour period. These changes in gas tension for plastic syringes would lead to an overestimation of pulmonary shunt measured by the 100% oxygen technique of 0.6% for each minute left at room temperature before analysis. CONCLUSIONS--Glass syringes are superior to plastic syringes in preserving samples with a high PaO2, and prompt and adequate cooling of such samples is essential for accurate blood gas analysis.