tbuckley/cabot-search huggingface dataset:
Neutrophil extracellular traps induce endothelial dysfunction in systemic lupus erythematosus through the activation of matrix metalloproteinase-2
Authors: Carmelo Carmona-Rivera, Wenpu Zhao, Srilakshmi Yalavarthi, Mariana J Kaplan
Journal: Annals of the Rheumatic Diseases (2014)

Rationale The structural and functional integrity of the endothelium is crucial in maintaining vascular homeostasis and preventing atherosclerosis. Patients with systemic lupus erythematosus (SLE) have an increased risk of developing endothelial dysfunction and premature cardiovascular disease. Neutrophil extracellular trap (NET) formation is increased in SLE and has been proposed to contribute to endothelial damage, but the mechanism remains unclear. Objective To determine the mechanism by which enhanced NET formation by low-density granulocytes (LDGs) in SLE contributes to endothelial damage and disrupts the endothelium. Results The putative role of NET-externalised matrix metalloproteinases (MMPs) in altering the functional integrity of the endothelium was examined. MMP-9 externalised by lupus LDGs during NET formation specifically impaired murine aortic endothelium-dependent vasorelaxation and induced endothelial cell apoptosis. Endothelial dysfunction correlated with the activation of endothelial MMP-2 by MMP-9 present in NETs, while inhibition of MMP-2 activation restored endothelium-dependent function and decreased NET-induced vascular cytotoxicity. Moreover, immunogenic complexes composed of MMP-9 and anti-MMP-9 were identified in SLE sera. These complexes, as well as anti-MMP-9 autoantibodies, induced NETosis and enhanced MMP-9 activity. Conclusions These observations implicate activation of endothelial MMP-2 by MMP-9 contained in NETs as an important player in endothelial dysfunction, and MMP-9 as a novel self-antigen in SLE. These results further support that aberrant NET formation plays pathogenic roles in SLE.
Abstract 822: KRAS and BRAF mutation analysis using formalin fixed and paraffin embedded colorectal tissue and fine needle aspiration biopsies from thyroid
Authors: Sibele Inacio Meireles, Fabio E. Nakano, Luciane Choppa do Valle Consolin, Mônica Maria Ágata Stiepcich, Ana O. Hoff, Rosa Paula Mello Biscolla, Renata Almeida Coudry
Journal: Cancer Research (2010)

Abstract Point mutations in codons 12, 13 and 61 of the KRAS gene and in codon 600 of the BRAF gene can be identified in neoplastic tissue from many different organs. KRAS mutations are present in approximately 40% of sporadic colorectal adenocarcinoma and this analysis is important to determine response to anti-EGFR targeted therapies. BRAF mutations are present in approximately 40% of the papillary thyroid carcinoma and 10% sporadic colorectal adenocarcinoma. BRAF mutation V600E is associated with more aggressive thyroid tumors and its detection is important for thyroid cancer prognosis. Detection of BRAF mutation in colorectal cancer is also useful for characterizing sporadic tumors. A method developed in-house to identify mutations in KRAS (codos 12 and 13) was validated using formalin-fixed paraffin-embeded tissue (FFPE) from 31 surgical specimens diagnosed with metastatic colorrectal cancer. Similarly, a method for BRAF mutation analysis (codon 600) was developed and validaded using 39 smears from fine needle aspiration biopsies (FNAB) of the thyroid. Cytology analysis was performed to confirm the presence of neoplastic or suspected lesions. DNA was extract from 1-4 slides containing the FFPE tissue sections or smears from the FNAB. Mutation analyses were performed by Sanger sequencing and results were compared with pyrosequencing. Automatic analysis of nucleotide sequences using the SeqScape software (Applied Biosystems) was also implemented. There was 85.7% and 100% concordance between Sanger sequencing and pyrosequencing for KRAS and BRAF mutation analysis, respectively. Precision intra- and inter-assay analysis were concordant, with the exception of one sample with KRAS mutation. Sensitivity was evaluated using pools containing different proportions of mutated and non-mutated DNA from cell lines. Data analysis by visual inspection resulted in the detection of the mutant allele in samples with at least 10% of mutated DNA. However, KRAS and BRAF mutations analysis using SeqScape software detected the mutant allele in pools containing at least 30% and 25% of mutated DNA, respectively. This is in accordance with the overall sensitivity observed by standard sequencing analysis. In conclusion, KRAS and BRAF mutation analysis can be successfully performed using small amount of tissue sections from FFPE specimens and smears from FNAB. This material has the advantage of requiring small amounts of sample and also allows cytology review of the tissue content prior to molecular analysis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 822.
The Malady of Toulouse-Lautrec
Authors: Pierre Maroteaux
Journal: JAMA (1965)

Although infirmity and physical suffering have profoundly affected the work of many artists, few lives have been so extensively influenced by illness as that of Henri de Toulouse-Lautrec. Very early, skeletal disorders prevented him from riding, a traditional pastime in his family, and led him towards painting. From then on his physical disgrace constantly directed his life and his artistic efforts. Many doctors have directed their attention to the very mysterious disease whose victim has given us "Au Moulin Rouge," "Jane Avril," "La Goulue," and so many other masterpieces, but making a retrospective diagnosis in bone pathology is a difficult and extremely risky undertaking when no radiological documents are available. This explains the many theories which have so far been produced on Toulouse-Lautrec's disease. However, as we shall show by brief comments, none of the previous diagnoses is satisfactory. Among the more distinct episodes in Toulouse-Lautrec's disease, the two fractures
THE TUBERCULOSIS PROBLEM IN LOS ANGELES.
Authors: GEORGE H. KRESS
Journal: JAMA (1905)

The mortality statistics for pulmonary tuberculosis for the city of Los Angeles, when analyzed, suggest some rather interesting questions, not only for the physicians and citizens of Los Angeles, but for our professional brethren east of the Rocky Mountains, since it is these latter gentlemen who are largely responsible for the fact that Los Angeles has a tuberculosis problem. It is the purpose of this paper to consider various phases of these statistics, to draw some conclusions therefrom and to suggest some measures whereby such danger as exists for the public health from an unusually high mortality rate from pulmonary tuberculosis may be minimized or entirely prevented. Tn order that the task may be accomplished with some degree of completeness, most of the etiologic factors that are known to influence the morbidity and mortality rates of the great white plague will be considered in turn. <h3>FACTORS INFLUENCING MORBIDITY AND MORTALITY</h3>
Nearly 2000 amendments are not enough to save health bill, says BMA
Authors: Z. Kmietowicz
Journal: BMJ (2012)

The BMA has said that the government needs to go back to the drawing board with its plans for the NHS if care of patients and efficiency are to improve.

Last week the Department of Health announced a further 137 amendments to the Health and Social Care Bill in addition to the 1800 already tabled ( BMJ 2012;344:e859, doi:10.1136/bmj.e859). But these have done little to tackle the problems underlying the bill, which remains fundamentally flawed and should be withdrawn, says the BMA in a briefing paper to peers ahead of the report stage in the House of Lords, which starts on 8 February.

Nearly all BMJ readers who responded to an online poll last …
Glycemic Treatment
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2004)

This is the first of three articles dealing with the International Diabetes Federation meeting, which was held in Paris, 24–29 August 2003. Michael Stumvoll (Tubigen, Germany) gave the Minkowski lecture, discussing aspects of the control of glycemia, illustrating the “hyperbolic law of glucose control,” depicting the inverse relationship between insulin secretion and insulin sensitivity. If one adds the 2-h glucose in a three-dimensional plot, however, as insulin resistance worsens there is a progressive increase in the 2-h glucose, so that one cannot consider insulin secretion to perfectly balance the degree of insulin resistance (1). Stumvoll gave an overview of the fascinating science involved in understanding glycemia, describing the products of six genes involved in glucose homeostasis. Adiponectin is a protein released by fat cells to an extent inversely related to total body fat mass. Treatment of insulin-resistant diabetic mice with adiponectin decreases glucose levels, and in humans there is an inverse relationship between the degree of insulin resistance and the adiponectin level. Stearoyl-CoA desaturase regulates tissue lipid synthesis and is involved in the metabolism of stearate to oleate. In liver, inhibition of this enzyme prevents hepatic steatosis in leptin-deficient animals, and the oleate-to-stearate ratio on liver biopsy is inversely related to the insulin sensitivity. The insulin receptor (IR) substrate (IRS)1 modulates insulin secretion, with β-cell overexpression of normal IRS1 increasing insulin secretion, whereas overexpression of an abnormal IRS1 decreases insulin secretion by these cells. In humans, those with the Gly972Arg IRS1 polymorphism have shown a decrease in both the first- and second-phase insulin secretory response to intravenous glucose (2). CEACAM1 (CEA-related cell adhesion molecule 1) regulates a pathway responsible for IR internalization, and abnormality causes diabetes. CEACAM1 causes receptor-mediated hepatic insulin endocytosis and degradation in a phosphorylation-dependent manner (3). The liver clears approximately half of the insulin molecules …
Medical Complications During Pregnancy
Authors: Stephen R. Carr
Journal: JAMA (1995)

Who is qualified to care for pregnant women with coexisting medical disease? If you were to ask an obstetrician, the most likely answer would be those who practice maternal-fetal medicine, a subspecialty of obstetrics-gynecology that deals with maternal and fetal abnormalities during pregnancy. If you were to ask an internist, the most likely answer would be an internist, or perhaps an obstetrical internist—a new subspecialty of internal medicine. (The only two fellowships in obstetrical medicine in North America are at Brown University in Providence, RI, and McMaster University in Toronto, Canada.) In reality, the two disciplines complement each other; the maternal-fetal medicine specialists bring their understanding of the normal physiologic changes of pregnancy and the impact of maternal disease on fetal well-being to the discussion, and the internists bring their deeper understanding of the pathophysiology of chronic disease. Maximal patient benefit accrues when the patient finds herself in that area
Pseudomonas exotoxin shock. A preliminary report of studies in dogs
Authors: M. Atik
Journal: JAMA (1968)

A study of shock following infusion of a newly described exotoxin from Pseudomonas aeruginosa (strain P-A-103) in the dog demonstrated two types of reactions: an immediate anaphylactoid reaction from which the dogs usually recovered, and a late hypotensive reaction which persisted and slowly progressed to death in 24 hours in all six of the untreated dogs. The circulatory and certain biochemical changes studied with this exotoxin shock were similar to those observed with endotoxin shock. Pretreatment with saline in five dogs and with nonimmune serum in eight dogs offered no significant protection. Pretreatment with dextran 40 minimized the anaphylactoid reaction but did not provide significant protection against ultimate death. Pretreatment with specific immune serum resulted in survival of all six dogs infused with the exotoxin but did not reduce the severity of transient anaphylactoid reaction.
Whence Interferon? Variety in the Production of Interferon in Response to Viral Infection
Authors: David E. Levy
Journal: The Journal of Experimental Medicine (2002)

The type I IFNs (IFN-α and IFN-β) were first characterized as cytokines capable of inducing an antiviral state in sensitive target cells ([1][1]). They were originally classified as leukocyte IFN and fibroblast IFN, respectively, to designate their distinct presumptive cellular origins. This
Utility of hepatitis C virus RNA determinations in hepatic tissue as an end point for interferon treatment of chronic hepatitis C
Authors: A GURAKAR
Journal: Hepatology (1995)

A total of 41 patients with chronic hepatitis C virus (HCV) defined as abnormal liver injury test results for 6 months or more and HCV RNA positivity in plasma were studied to determine if the liver might not be the only focus of HCV infection in individuals treated with interferon alfa (IFN-alpha). All patients were examined for the presence of confounding liver disease and tested negatively for such findings. All tested positively for HCV RNA and had an abnormal hepatic histology. All were treated with IFN for 6 months at a dosage of 5 million units daily. After 6 months of therapy, 29 (71%) had normal alanine transaminase (ALT) values, and 25 (61%) tested negatively for HCV RNA. After 6 months of follow-up, without IFN therapy, 17 (41%) still had normal ALT values, and 16 (39%) still tested negatively for HCV RNA in serum. Patients who continued to test negatively for HCV RNA in serum after 6 months of follow-up also tested negatively for HCV RNA in the liver at the end of IFN therapy. Only 2 subjects who tested negatively for HCV RNA in the liver at the end of treatment relapsed after discontinuing IFN therapy. In contrast, patients who tested positively for HCV RNA in the liver after 6 months of therapy relapsed and tested positively for HCV RNA in serum during the 6 months of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)
“Abnormal” movements: What are they reflections of?
Authors: C. C. A. M. Gielen
Journal: Behavioral and Brain Sciences (1996)

Abstract We agree with Latash &amp; Anson that therapeutic approaches should be directed toward solving the underlying problem, not toward adapting the abnormal to normal behaviour. The fundamental obstacle, however, is that doing so requires a solution of the “equivalence problem” in movement control.
932 POLYMORPHISMA OF MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN GENE AND PHOSPHATIDYLETHANOLAMINE N-METHYLTRANSFERASE GENE IN ALCOHOLIC AND NON ALCOHOLIC FATTY LIVER DISEASE IN KOREANS
Authors: D.W. Jun, J.H. Han, E.C. Jang, Sang H. Kim, J.D. Chae, M.H. Song, Sung H. Kim, Y.J. Jo, Y.S. Park
Journal: Journal of Hepatology (2008)
Effect of Escitalopram on Mental Stress–Induced Myocardial Ischemia
Authors: Wei Jiang, Eric J. Velazquez, Maragatha Kuchibhatla, Zainab Samad, Stephen H. Boyle, Cynthia Kuhn, Richard C. Becker, Thomas L. Ortel, Redford B. Williams, Joseph G. Rogers, Christopher O’Connor
Journal: JAMA (2013)

<h3>Importance</h3>Mental stress can induce myocardial ischemia and also has been implicated in triggering cardiac events. However, pharmacological interventions aimed at reducing mental stress–induced myocardial ischemia (MSIMI) have not been well studied.<h3>Objective</h3>To examine the effects of 6 weeks of escitalopram treatment vs placebo on MSIMI and other psychological stress–related biophysiological and emotional parameters.<h3>Design, Setting, and Participants</h3>The REMIT (Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment) study, a randomized, double-blind, placebo-controlled trial of patients with clinically stable coronary heart disease and laboratory-diagnosed MSIMI. Enrollment occurred from July 24, 2007, through August 24, 2011, at a tertiary medical center.<h3>Interventions</h3>Eligible participants were randomized 1:1 to receive escitalopram (dose began at 5 mg/d, with titration to 20 mg/d in 3 weeks) or placebo over 6 weeks.<h3>Main Outcomes and Measures</h3>Occurrence of MSIMI, defined as development or worsening of regional wall motion abnormality; left ventricular ejection fraction reduction of 8% or more; and/or horizontal or down-sloping ST-segment depression of 1 mm or more in 2 or more leads, lasting for 3 or more consecutive beats, during 1 or more of 3 mental stressor tasks.<h3>Results</h3>Of 127 participants randomized to receive escitalopram (n = 64) or placebo (n = 63), 112 (88.2%) completed end point assessments (n = 56 in each group). At the end of 6 weeks, more patients taking escitalopram (34.2% [95% CI, 25.4%-43.0%]) had absence of MSIMI during the 3 mental stressor tasks compared with patients taking placebo (17.5% [95% CI, 10.4%-24.5%]), based on the unadjusted multiple imputation model for intention-to-treat analysis. A significant difference favoring escitalopram was observed (odds ratio, 2.62 [95% CI, 1.06-6.44]). Rates of exercise-induced ischemia were slightly lower at 6 weeks in the escitalopram group (45.8% [95% CI, 36.6%-55.0%]) than in patients receiving placebo (52.5% [95% CI, 43.3%-61.8%]), but this difference was not statistically significant (adjusted odds ratio; 1.24 [95% CI, 0.60-2.58]; P = .56).<h3>Conclusions and Relevance</h3>Among patients with stable coronary heart disease and baseline MSIMI, 6 weeks of escitalopram, compared with placebo, resulted in a lower rate of MSIMI. There was no statistically significant difference in exercise-induced ischemia. Replication of these results in multicenter settings and investigations of other medications for reducing MSIMI are needed.<h3>Trial Registration</h3>clinicaltrials.gov Identifier: NCT00574847 .
Does reference value of “Normal Liver Stiffness” using fibroscan have a regional variation?
Authors: Ramesh Kumar, Manoj Kumar Sharma, Shiv Kumar Sarin
Journal: Hepatology (2012)

We read with interest the recently published article by Das et al.,1 where the investigators have reported a U-shaped distribution of liver stiffness measure (LSM) among healthy subjects categorized as per body mass index (BMI), and proposed 8.5 KPa as the upper limit of normal (ULN) of LSM in healthy Indian subjects. Such observations can have significant implications in clinical practice. This is a well-conducted study; however, the investigators' interpretation about U-shaped distribution of LSM is not supported by strong data. The mean LSM was similar over a broad range of BMI (18-29.9 kg/m2), and higher values of LSM at one extreme were based on data of obese persons, which were only 4 (<1%) in number. Furthermore, as per the Asian standard of BMI categories, the distribution pattern of LSM would not have been U-shaped. Although underweight subjects had significantly higher LSM values than healthy and preobese subjects, the mean difference in absolute value was only 0.5 KPa, suggesting that the body-size effect is not perceptible using the current FibroScan machines. The ULN of LSM has been reported to vary from 5.3 to 7.0 KPa in various studies,2, 3 including one study based on histopathology.2 Thus, 8.5 kPa as the ULN of LSM seems too high for a healthy liver in any given population across the world. Such a high cutoff may erroneously cause the exclusion of healthy subjects or patients who would require further evaluation. Though this value corresponded to the 95th percentile, the dispersion of data (mean, 95% confidence interval) revealed that 414 of 418 healthy subjects actually had LSM values within 6.5 KPa, as shown in Fig. 2 of the Das et al. study.1 Notably, sufficient investigations were not done to exclude potential underlying liver disease in healthy subjects with high LSM. Also, approximately 16% of LSM results are known to be unreliable. In our experience, in a cohort of 445 healthy adult subjects, the mean LSM value was 5.1 ± 1.1 KPa, and the 95th percentile value was 7.07 KPa. LSM values increased with increasing BMI categories (4.1 ± 0.7, 5.08 ± 0.6, and 6.08 ± 1.2 KPa in healthy BMI, overweight, and obese subjects, respectively).3 None of our patients belonged to the underweight category; hence, the distribution of LSM cannot be compared with the present study. To conclude, the present study results seem to have limited external validity. However, the background population and properly validated regional data are important while interpreting LSM using FibroScan. Ramesh Kumar M.D., D.M.*, Manoj Kumar Sharma M.D., D.M.*, Shiv Kumar Sarin M.D., D.M.*, * Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
Dynamic similarities in action systems
Authors: Allen W. Burton
Journal: Behavioral and Brain Sciences (1996)

Abstract Latash &amp; Anson's contention that movement patterns that are different from those typically observed in persons without impairments should not be considered abnormal and usually should not be corrected is consistent with Davis &amp; Burton's Ecological Task Analysis (ETA). Extending from the ETA concept of performer-scaled performance measures, the use of Froude numbers may offer insight into the global dynamics of a person's action system.
The sleep of elite athletes at sea level and high altitude: a comparison of sea-level natives and high-altitude natives (ISA3600)
Authors: Gregory D Roach, Walter F Schmidt, Robert J Aughey, Pitre C Bourdon, Rudy Soria, Jesus C Jimenez Claros, Laura A Garvican-Lewis, Martin Buchheit, Ben M Simpson, Kristal Hammond, Marlen Kley, Nadine Wachsmuth, Christopher J Gore, Charli Sargent
Journal: British Journal of Sports Medicine (2013)

Background Altitude exposure causes acute sleep disruption in non-athletes, but little is known about its effects in elite athletes. The aim of this study was to examine the effects of altitude on two groups of elite athletes, that is, sea-level natives and high-altitude natives. Methods Sea-level natives were members of the Australian under-17 soccer team (n=14). High-altitude natives were members of a Bolivian under-20 club team (n=12). Teams participated in an 18-day (19 nights) training camp in Bolivia, with 6 nights at near sea level in Santa Cruz (430 m) and 13 nights at high altitude in La Paz (3600 m). Sleep was assessed on every day/night using activity monitors. Results The Australians’ sleep was shorter, and of poorer quality, on the first night at altitude compared with sea level. Sleep quality returned to normal by the end of the first week at altitude, but sleep quantity had still not stabilised at its normal level after 2 weeks. The quantity and quality of sleep obtained by the Bolivians was similar, or greater, on all nights at altitude compared with sea level. The Australians tended to obtain more sleep than the Bolivians at sea level and altitude, but the quality of the Bolivians’ sleep tended to be better than that of the Australians at altitude. Conclusions Exposure to high altitude causes acute and chronic disruption to the sleep of elite athletes who are sea-level natives, but it does not affect the sleep of elite athletes who are high-altitude natives.