tbuckley/cabot-search huggingface dataset:
Salicylate induces an antibiotic efflux pump in Burkholderia cepacia complex genomovar III (B. cenocepacia)
Authors: Bindu M. Nair, K-John Cheung, Adam Griffith, Jane L. Burns
Journal: Journal of Clinical Investigation (2004)

An antibiotic efflux gene cluster that confers resistance to chloramphenicol, trimethoprim, and ciprofloxacin has been identified in Burkholderia cenocepacia (genomovar III), an important cystic fibrosis pathogen. Five open reading frames have been identified in the cluster. There is apparently a single transcriptional unit, with llpE encoding a lipase-like protein, ceoA encoding a putative periplasmic linker protein, ceoB encoding a putative cytoplasmic membrane protein, and opcM encoding a previously described outer membrane protein. A putative LysR-type transcriptional regulatory gene, ceoR, is divergently transcribed upstream of the structural gene cluster. Experiments using radiolabeled chloramphenicol and salicylate demonstrated active efflux of both compounds in the presence of the gene cluster. Salicylate is an important siderophore produced by B. cepacia complex isolates, and both extrinsic salicylate and iron starvation appear to upregulate ceoR promoter activity, as does chloramphenicol. These results suggest that salicylate is a natural substrate for the efflux pump in B. cenocepacia and imply that the environment of low iron concentration in the cystic fibrosis lung can induce efflux-mediated resistance, even in the absence of antibiotic selective pressure.
A successful conservative approach to managing lower leg pain in a university sports injury clinic: a two patient case study
Authors: A Cunningham, I R Spears
Journal: British Journal of Sports Medicine (2004)

There is a lack of information on the conservative treatment of lower leg pain induced by running. In this study, non-invasive treatment based on a change of footwear was applied to two patients, and, on the basis of pain scale questionnaires, deemed successful.
Interleukin-6 Modulates the Expression of the Bone Morphogenic Protein Receptor Type II Through a Novel STAT3–microRNA Cluster 17/92 Pathway
Authors: Matthias Brock, Michelle Trenkmann, Renate E. Gay, Beat A. Michel, Steffen Gay, Manuel Fischler, Silvia Ulrich, Rudolf Speich, Lars C. Huber
Journal: Circulation Research (2009)

Dysregulated expression of bone morphogenetic protein receptor type II (BMPR2) is a pathogenetic hallmark of pulmonary hypertension. Downregulation of BMPR2 protein but not mRNA has been observed in multiple animal models mimicking the disease, indicating a posttranscriptional mechanism of regulation. Because microRNAs (miRNAs) regulate gene expression mainly through inhibition of target gene translation, we hypothesized that miRNAs may play a role in the modulation of BMPR2. Performing a computational algorithm on the BMPR2 gene, several miRNAs encoded by the miRNA cluster 17/92 (miR-17/92) were retrieved as potential regulators. Ectopic overexpression of miR-17/92 resulted in a strong reduction of the BMPR2 protein, and a reporter gene system showed that BMPR2 is directly targeted by miR-17-5p and miR-20a. By stimulation experiments, we found that the miR-17/92 cluster is modulated by interleukin (IL)-6, a cytokine involved in the pathogenesis of pulmonary hypertension. Because IL-6 signaling is mainly mediated by STAT3 (signal transducer and activator of transcription 3), the expression of STAT3 was knocked down by small interfering RNA, which abolished the IL-6–mediated expression of miR-17/92. Consistent with these data, we found a highly conserved STAT3-binding site in the promoter region of the miR-17/92 gene (C13orf25). Promoter studies confirmed that IL-6 enhances transcription of C13orf25 through this distinct region. Finally, we showed that persistent activation of STAT3 leads to repressed protein expression of BMPR2. Taken together, we describe here a novel STAT3–miR-17/92—BMPR2 pathway, thus providing a mechanistic explanation for the loss of BMPR2 in the development of pulmonary hypertension.
Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Disease Risk in Adults: Synopsis of the 2013 American College of Cardiology/American Heart Association Cholesterol Guideline
Authors: Neil J. Stone, Jennifer G. Robinson, Alice H. Lichtenstein, David C. Goff, Donald M. Lloyd-Jones, Sidney C. Smith, Conrad Blum, J. Sanford Schwartz
Journal: Annals of Internal Medicine (2014)

In November 2013, the American College of Cardiology and American Heart Association (ACC/AHA) released a clinical practice guideline on the treatment of blood cholesterol to reduce cardiovascular risk in adults. This synopsis summarizes the major recommendations.In 2008, the National Heart, Lung, and Blood Institute convened the Adult Treatment Panel (ATP) IV to update the 2001 ATP-III cholesterol guidelines using a rigorous process to systematically review randomized, controlled trials (RCTs) and meta-analyses of RCTs that examined cardiovascular outcomes. The panel commissioned independent systematic evidence reviews on low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol goals in secondary and primary prevention and the effect of lipid drugs on atherosclerotic cardiovascular disease events and adverse effects. In September 2013, the panel's draft recommendations were transitioned to the ACC/AHA.This synopsis summarizes key features of the guidelines in 8 areas: lifestyle, groups shown to benefit from statins, statin safety, decision making, estimation of cardiovascular disease risk, intensity of statin therapy, treatment targets, and monitoring of statin therapy.
ELECTRICAL TREATMENT OF NEURITIS AND WRITER'S CRAMP
Authors: W. B. Jones
Journal: BMJ (1931)

TMEHDBRISLOURAL 5-~~~~~~~~~[EIA ORA quite well until March 14th, 1931, when he was brought up to the casualty department in a marked hypoglycaemic attack (produced by an unusual amount of exercise) in which he almost lost consciousness.IHe responded quickly to glucose treatment, and, feeling fit, discharged himself on Monday, March 16th.His bowels, which were usually quite regular,
The acid pocket and its relevance to reflux disease
Authors: R. H Holloway, D. A Sifrim
Journal: Gut (2008)

Gastric pH is one of the primary determinants of gastro-oesophageal reflux disease (GORD). The severity of both oesophageal mucosal damage and symptoms is directly related to the pH of the refluxate and thereby intragastric pH. The proximal stomach is particularly relevant as it is the most immediate source of the refluxate, particularly in patients with hiatus hernia. An important characteristic of gastro-oesophageal reflux is the postprandial increase in reflux episodes. Indeed, the majority of reflux episodes in most patients occur in the postprandial period. However, meals lead to transient buffering of gastric acid, particularly in the proximal stomach,1 2 yet, early in the postprandial period, acid and weakly acidic reflux episodes are often interspersed.3 Conventional intragastric pH monitoring 5 cm below the lower oesophageal sphincter (LOS) often reveals discrepancies between gastric pH and that of the refluxate in the oesophagus, with a lower pH in the oesophagus than in the stomach during reflux episodes.

Important insights into this apparent discrepancy between gastric and oesophageal pH during reflux were obtained by Fletcher and colleagues.4 Using a stepwise pull-through of a pH electrode from the proximal stomach across the gastro-oesophageal junction, they were able to demonstrate that 15 min after a meal, there was a short zone of apparently unbuffered highly acidic gastric juice extending 2 cm below the LOS that they termed the “acid pocket”. The median pH in this zone was 1.6 compared with 4.4 in the meal-buffered region below. Subsequent studies have confirmed these findings.2 5–7 Concurrent pH monitoring in the gastric cardia and distal oesophagus during reflux episodes has also shown the pH in the cardia to be consistently lower than that in the distal oesophagus.6 Thus, reflux from this acid pocket provided a plausible explanation for acid reflux in the …
Blood mRNA Expression Profiling Predicts Survival in Patients Treated with Tremelimumab
Authors: Yvonne Saenger, Jay Magidson, Bobby Liaw, Ellen de Moll, Sara Harcharik, Yichun Fu, Karl Wassmann, David Fisher, John Kirkwood, William K. Oh, Philip Friedlander
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Tremelimumab (ticilimumab, Pfizer), is a monoclonal antibody (mAb) targeting cytotoxic T lymphocyte–associated antigen-4 (CTLA-4). Ipilimumab (Yervoy, BMS), another anti-CTLA-4 antibody, is approved by the U.S. Federal Drug Administration (FDA). Biomarkers are needed to identify the subset of patients who will achieve tumor control with CTLA-4 blockade. Experimental Design: Pretreatment peripheral blood samples from 218 patients with melanoma who were refractory to prior therapy and receiving tremelimumab in a multicenter phase II study were measured for 169 mRNA transcripts using reverse transcription polymerase chain reaction (RT-PCR). A two-class latent model yielded a risk score based on four genes that were highly predictive of survival (P &amp;lt; 0.001). This signature was validated in an independent population of 260 treatment-naïve patients with melanoma enrolled in a multicenter phase III study of tremelimumab. Results: Median follow-up was 297 days for the training population and 386 days for the test population. Expression levels of the 169 genes were closely correlated across the two populations (r = 0.9939). A four-gene model, including cathepsin D (CTSD), phopholipase A2 group VII (PLA2G7), thioredoxin reductase 1 (TXNRD1), and interleukin 1 receptor–associated kinase 3 (IRAK3), predicted survival in the test population (P = 0.001 by log-rank test). This four-gene model added to the predictive value of clinical predictors (P &amp;lt; 0.0001). Conclusions: Expression levels of CTSD, PLA2G7, TXNRD1, and IRAK3 in peripheral blood are predictive of survival in patients with melanoma treated with tremelimumab. Blood mRNA signatures should be further explored to define patient subsets likely to benefit from immunotherapy. Clin Cancer Res; 20(12); 3310–8. ©2014 AACR.
Microalterations of Inherently Unstable Genomic Regions in Rat Mammary Carcinomas as Revealed by Long Oligonucleotide Array-Based Comparative Genomic Hybridization
Authors: Tatjana Adamovic, Donna McAllister, Victor Guryev, Xujing Wang, Jaime Wendt Andrae, Edwin Cuppen, Howard J. Jacob, Sonia L. Sugg
Journal: Cancer Research (2009)

The presence of copy number variants in normal genomes poses a challenge to identify small genuine somatic copy number changes in high-resolution cancer genome profiling studies due to the use of unpaired reference DNA. Another problem is the well-known rearrangements of immunoglobulin and T-cell receptor genes in lymphocytes (a commonly used reference), which may misdirect the researcher to a locus with no relevance in tumorigenesis. We here show real gains of the IgG heavy chain V gene region in carcinogen-induced rat mammary tumor samples after normalization to paired mammary gland, a tissue without lymphocyte infiltration. We further show that the segmental duplication region encompassing the IgG heavy chain V genes is a copy number variant between the susceptible (SS) and the resistant (BN) to mammary tumor development inbred rat strains. Our data suggest that the already inherently unstable genomic region is a convenient target for additional structural rearrangements (gains) at the somatic level when exposed to a carcinogen (7,12-dimethylbenz[a]anthracene), which subsequently seem to benefit tumor development in the mammary gland of the susceptible strain. Thus, the selection of an appropriate reference DNA enabled us to identify immunoglobulin genes as novel cancer targets playing a role in mammary tumor development. We conclude that control DNA in array-based comparative genomic hybridization experiments should be selected with care, and DNA from pooled spleen (contains immature lymphocytes and is used as reference in animal studies) or blood may not be the ideal control in the study of primary tumors.
Ischemic preconditioning prevents ischemia/reperfusion-induced activation of protease CPP32 and cleavage of poly(ADP-ribose) polymerase in rat hearts in vivo
Authors: C.A. Plot, J.-F. Martini, S.K. Bui, R.I. Weiner, C.L. Wolfe
Journal: Journal of the American College of Cardiology (1998)
Prevention of coronary artery disease is a pediatric problem
Authors: L. Van Horn
Journal: JAMA (1997)

The report by Bao et al 1 underscores the importance of primary prevention of coronary artery disease (CAD) beginning in childhood. Specifically, their findings suggest that the most effective strategy for prevention of CAD in adulthood may be prevention of obesity in childhood. Data from the Bogalusa Heart Study show consistently increased incidence of overweight children whose parents have early CAD. These individuals were identified as being overweight in childhood and developed an adverse cardiovascular risk profile in adulthood that was predictive of premature CAD. Data from the National Health and Nutrition Examination Survey III (NHANES III) compared with previous NHANES data document an increasing obesity epidemic in this country, especially in children. 2 Given the universally acknowledged failure of most weight-loss treatment programs, obese children are likely to become obese adults, thereby increasing their risks of hypertension, diabetes, hyperlipidemia, and chronic diseases, including coronary heart disease. 3 On a
Acceptance and long-term compliance with nCPAP in patients with obstructive sleep apnoea syndrome
Authors: T Pieters, P Collard, G Aubert, M Dury, P Delguste, DO Rodenstein
Journal: European Respiratory Journal (1996)

Previous studies have generally shown poor effective long-term compliance with nasal continuous positive airway pressure (nCPAP) in patients with obstructive sleep apnoea syndrome (OSAS). We performed a retrospective study of patients treated with nCPAP for more than one year. Compliance was defined as the average number of hours of nCPAP use per day, where hours of use were obtained from the built-in time counter of the nCPAP device, after deduction of the 10% difference between effective use and time counters previously shown by others. We present data on the first 95 patients for whom results were available. The follow-up period was 784 +/- 366 (mean +/- SD) days for the whole group. Compliance was 5 +/- 1.8 h. For a subgroup of 36 patients, we had data on two consecutive follow-up periods (673 +/- 235 and 390 +/- 147 days for the first and second period, respectively). Compliance remained stable (5.2 +/- 1.5 and 5 +/- 2.3 h, respectively). For the whole group, a significant correlation was found between compliance and sleep fragmentation expressed as the movement arousal index (r = 0.226). During a similar 3 year period, 155 patients with a confirmed diagnosis of OSAS were offered a nCPAP trial. CPAP was actually delivered for home use to 117 patients (76%). During this same 3 year period, only 21 patients out of a total of 192 followed-up in our institution quit treatment, mainly due to intolerance or cure. These results indicate that in a nonselected group of obstructive sleep apnoea syndrome patients a high and stable compliance with nasal continuous positive pressure can be achieved, contradicting recent results of other series.
ABC of psychological medicine: Functional somatic symptoms and syndromes
Authors: R. Mayou
Journal: BMJ (2002)

Concern about symptoms is a major reason for patients to seek medical help. Many of the somatic symptoms that they present with—such as pain, weakness, and fatigue—remain unexplained by identifiable disease even after extensive medical assessment. Several general terms have been used to describe this problem—somatisation, somatoform, abnormal illness behaviour, medically unexplained symptoms, and functional symptoms. We will use the term functional symptoms, which does not assume psychogenesis but only a disturbance in bodily functioning.

### Some common functional symptoms and syndromes

Most functional symptoms are transient, but a sizeable minority become persistent. Persistent symptoms are often multiple and disabling and may be described as functional syndromes. Although different medical and psychiatric classifications of functional syndromes exist, these are simply alternative ways of describing the same conditions.



Rene Descartes, who formulated the philosophical principle of separation of brain and mind. This has led to continuing dualism—separation of body and mind—in Western medicine and difficulty in accepting the interaction of physical and psychological factors in aetiology



Medical syndromes (such as fibromyalgia and chronic fatigue, chronic pain, and irritable bowel syndromes) highlight patterns of somatic symptoms, often in relation to particular bodily systems. Although they are useful in everyday medical practice, recent studies show there is substantial overlap between them.

Psychiatric syndromes (such as anxiety, depression, and somatoform disorders) highlight psychological processes and the number of somatic symptoms irrespective of the bodily system to which they refer. Depression and anxiety often present with somatic symptoms that may resolve with effective treatment of these disorders. In other cases the appropriate psychiatric diagnostic category is a somatoform disorder.

The existence of parallel classificatory systems is confusing. Both have merits, and both are imperfect. For …
Effect of Pregnancy on Survival in Women With Cutaneous Malignant Melanoma
Authors: Marko B. Lens, Inger Rosdahl, Anders Ahlbom, Bahman Y. Farahmand, Ingrid Synnerstad, Bernt Boeryd, Julia A. Newton Bishop
Journal: Journal of Clinical Oncology (2004)

Purpose An adverse influence of pregnancy on the risk of death in women with cutaneous melanoma was suggested historically by anecdotal reports. Previous studies included small numbers of women observed for short periods. Methods Using data from the Swedish National and Regional Registries, we performed a retrospective cohort study of all Swedish women who were diagnosed with cutaneous melanoma during their reproductive period, from January 1, 1958, to December 31, 1999. The relationship between pregnancy status at the diagnosis of melanoma and overall survival was examined in multivariable proportional-hazards models. Results The cohort comprised 185 women (3.3%) diagnosed with melanoma during pregnancy and 5,348 (96.7%) women of the same childbearing age diagnosed with melanoma while not pregnant. There was no statistically significant difference in overall survival between pregnant and nonpregnant groups (log-rank χ 2 1[r] = 0.84, P = .361). Pregnancy status at the time of diagnosis of melanoma was not related to survival in a multivariable Cox model in the 2,101 women (hazard ratio for death in the pregnant group was 1.08; 95% CI, 0.60 to 1.93). In the multivariable analysis, pregnancy status after diagnosis of melanoma was not a significant predictor of survival (hazard ratio for death in women who had pregnancy subsequent to the diagnosis of melanoma was 0.58; 95% CI, 0.32 to 1.05). Conclusion The survival of pregnant women with melanoma is not worse than the survival of nonpregnant women with melanoma. Pregnancy subsequent to the diagnosis of primary melanoma was not associated with an increased risk of death.
T-cell responses to the components of pyruvate dehydrogenase complex in primary biliary cirrhosis
Authors: David E. J. Jones, Jeremy M. Palmer, Oliver F. W. James, Stephen J. Yeaman, Margaret F. Bassendine, Austin G. Diamond
Journal: Hepatology (1995)

Primary biliary cirrhosis (PBC) is an autoimmune condition that results in destruction of the intrahepatic biliary epithelial cells and is characterized by autoantibodies to pyruvate dehydrogenase complex (PDC). The portal tract T-cell infiltrate and up-regulation of HLA class I, HLA class II, and cell adhesion molecules such as intercellular adhesion molecule-1 on the biliary epithelial cells suggest that T cells play a significant role in mediating this damage. The authors have characterized the peripheral blood T-cell proliferative responses of 24 PBC patients and 48 controls (20 normal, 28 non-PBC chronic liver disease) to the dominant autoantigen PDC, and its constituent components E1, E2 and protein X (which co-purify), and E3. A significant proportion of both PBC patients and controls showed T-cell responses to whole PDC (12 of 24 vs. 24 of 48 SI > 2.5 P = NS) and E1 (15 of 24 vs. 25 of 48 P = NS). Responses to PDC and E1 are thus seen in normal individuals and are not limited to PBC patients. T-cell responses to E2/X were seen in most PBC patients (14 of 24), but in only a small number of controls (6 of 48, P < .0001), responses to E2/X being significantly more frequent in pre-cirrhotic PBC patients (stages I to III, 12 of 15) than cirrhotic (stage IV, 2 of 9 P < .05). Peripheral blood T-cell responses to E2/X are thus strongly associated with early PBC. Responses to E3 were low in both PBC patients and controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Relationship of the 37,000- and 40,000-M(r) tryptic fragments of islet antigens in insulin-dependent diabetes to the protein tyrosine phosphatase-like molecule IA-2 (ICA512).
Authors: M A Payton, C J Hawkes, M R Christie
Journal: Journal of Clinical Investigation (1995)

Sera from patients with insulin-dependent diabetes immunoprecipitate 64,000-M(r) proteins, distinct from glutamate decarboxylase, that are cleaved to 37,000- and 40,000-M(r) fragments by trypsin. We investigated possible relationships between 37,000- or 40,000-M(r) fragments of antigen and the tyrosine phosphatase-like protein, IA-2 (ICA512). Antibodies from nondiabetic relatives bound differentially to 37,000- and 40,000-M(r) fragments indicating presence of distinct epitopes. Precursors of these fragments could be separated on immobilized lectins, suggesting different carbohydrate content. Levels of antibodies to 40,000-M(r) fragments were strongly associated with those to the intracellular domain of IA-2. Recombinant intracellular domain of IA-2 blocked binding of antibodies to 40,000-M(r) fragments expressed by insulinoma cells and partially blocked binding to 37,000-M(r) fragments. Furthermore, trypsinization of recombinant intracellular domain of IA-2 generated proteolytic fragments of identical M(r) to the 40,000-M(r) fragments of insulinoma antigen; 37,000-M(r) fragments were not generated. Thus, 40,000-M(r) fragments of islet autoantigen are derived from a protein similar or identical to the tyrosine phosphatase-like molecule, IA-2. The 37,000-M(r) fragments are derived from a different, although related, protein.
Unpredictable Location of Central Catheter
Authors: Sandra R. DiBrito, R. Scott Stephens
Journal: JAMA Surgery (2014)

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