tbuckley/cabot-search huggingface dataset:
Treatment of COPD by clinical phenotypes: putting old evidence into clinical practice
Authors: Marc Miravitlles, Juan José Soler-Cataluña, Myriam Calle, Joan B. Soriano
Journal: European Respiratory Journal (2012)

The new Global Initiative for Chronic Obstructive Lung Disease update has moved the principles of treatment of stable chronic obstructive pulmonary disease (COPD) forward by including the concepts of symptoms and risks into the decision of therapy. However, no mention of the concept of clinical phenotypes is included. It is recognised that COPD is a very heterogeneous disease and not all patients respond to all drugs available for treatment. The identification of responders to therapies is crucial in chronic diseases to provide the most appropriate treatment and avoid unnecessary medications. The classically defined phenotypes of chronic bronchitis and emphysema, together with the newly described phenotypes of overlap COPD-asthma and frequent exacerbator, allow a simple classification of patients that share clinical characteristics and outcomes and, more importantly, similar responses to existing treatments. These clinical phenotypes can help clinicians identify patients that respond to specific pharmacological interventions. For example, frequent exacerbators are the only subjects with an indication for anti-inflammatory treatment in COPD. Among them, those with chronic bronchitis are the only candidates to receive phosphodiesterase-4 inhibitors. Patients with overlap COPD-asthma phenotype show an enhanced response to inhaled corticosteroids and infrequent exacerbators should only receive bronchodilators. These well-defined clinical phenotypes could potentially be incorporated into treatment guidelines.
The novel<i>GJB3</i>mutation p.Thr202Asn in the M4 transmembrane domain underlies erythrokeratodermia variabilis
Authors: K. Sugiura, M. Arima, K. Matsunaga, M. Akiyama
Journal: British Journal of Dermatology (2014)

Journal Article The novel GJB3 mutation p.Thr202Asn in the M4 transmembrane domain underlies erythrokeratodermia variabilis Get access K. Sugiura, K. Sugiura Department of Dermatology Nagoya University Graduate School of Medicine 65 Tsurumai‐cho, Showa‐ku Nagoya Aichi 466‐8550 Japan Search for other works by this author on: Oxford Academic Google Scholar M. Arima, M. Arima Department of Dermatology Fujita Health University School of Medicine 1‐98 Dengakugakubo, Kutsukake‐cho Toyoake Aichi 470‐1192 Japan Search for other works by this author on: Oxford Academic Google Scholar K. Matsunaga, K. Matsunaga Department of Dermatology Fujita Health University School of Medicine 1‐98 Dengakugakubo, Kutsukake‐cho Toyoake Aichi 470‐1192 Japan Search for other works by this author on: Oxford Academic Google Scholar M. Akiyama M. Akiyama Department of Dermatology Nagoya University Graduate School of Medicine 65 Tsurumai‐cho, Showa‐ku Nagoya Aichi 466‐8550 Japan Correspondence: Masashi Akiyama. E‐mail: makiyama@med.nagoya-u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 1, 1 July 2015, Pages 309–311, https://doi.org/10.1111/bjd.13641 Published: 01 July 2015
Assessment of the relationship between signal intensities and transcript concentration for Affymetrix GeneChip®arrays
Authors: Eugene Chudin, Randal Walker, Alan Kosaka, Sue X Wu, Douglas Rabert, Thomas K Chang, Dirk E Kreder
Journal: Genome biology (2001)

Affymetrix microarrays have become increasingly popular in gene-expression studies; however, limitations of the technology have not been well established for commercially available arrays. The hybridization signal has been shown to be proportional to actual transcript concentration for specialized arrays containing hundreds of distinct probe pairs per gene. Additionally, the technology has been described as capable of distinguishing concentration levels within a factor of 2, and of detecting transcript frequencies as low as 1 in 2,000,000. Using commercially available arrays, we assessed these representations directly through a series of 'spike-in' hybridizations involving four prokaryotic transcripts in the absence and presence of fixed eukaryotic background. The contribution of probe-target interactions to the mismatch signal was quantified under various analyte concentrations.A linear relationship between transcript abundance and signal was consistently observed between 1 pM and 10 pM transcripts. The signal ceased to be linear above the 10 pM level and commenced saturating around the 100 pM level. The 0.1 pM transcripts were virtually undetectable in the presence of eukaryotic background. Our measurements show that preponderance of the signal for mismatch probes derives from interactions with the target transcripts.Landmark studies outlining an observed linear relationship between signal and transcript concentration were carried out under highly specialized conditions and may not extend to commercially available arrays under routine operating conditions. Additionally, alternative metrics that are not based on the difference in the signal of members of a probe pair may further improve the quantitative utility of the Affymetrix GeneChip array.
P168 THE EPOXYEICOSATRIENOIC ACIDS PLAY AN ANTI-INFLAMMATORY ROLE IN THE METHIONINE-CHOLINE-DEFICIENT-DIET INDUCED STEATOHEPATITIS IN MICE BY INHIBITING THE EFFECTS OF KUPFFER CELLS
Authors: X. Wang, L. Li, H. Wang, J. Luo, F. Xiao, T. Harris, K.S.S. Lee, B. Hammock, X. Luo, Q. Ning
Journal: Journal of Hepatology (2014)
HER2 and Breast Cancer Stem Cells: More than Meets the Eye
Authors: Hasan Korkaya, Max S. Wicha
Journal: Cancer Research (2013)

Abstract The development of HER2 targeting agents has dramatically altered the natural history of HER2-positive breast cancer and is often cited as a prime example of the effectiveness of molecularly targeted therapy. Emerging data suggest that the remarkable clinical efficacy of these agents may be related to their ability to target the breast cancer stem cell (CSC) population. A new study suggests that the regulation of BCSCs by HER2 may extend to breast cancers that do not display HER2 gene amplification. In these tumors, HER2 is selectively expressed in the CSC population, and this expression is regulated by the tumor microenvironment. In mouse models, trastuzumab blocked growth of these HER2-negative tumors when administered in the adjuvant setting but had no effect on established tumors. These studies provide a potential biologic explanation for retrospective analysis of clinical trials, which surprisingly suggest that the clinical benefits of adjuvant trastuzumab may extend to women currently classified as HER2-negative. In addition to having significant implications for breast cancer therapy, these studies suggest the need to reevaluate the role of HER2 in regulating CSCs in other tumor types. Furthermore, these studies suggest that effective adjuvant therapies may need to target the CSC population. Cancer Res; 73(12); 3489–93. ©2013 AACR.
Importance of Atrial Compliance in Cardiac Performance
Authors: HIROYUKI SUGA
Journal: Circulation Research (1974)

Effects of changes in atrial compliance on cardiac performance were analyzed using a circulatory analog model. The atrium was assumed to be a noncontracting chamber with a constant compliance. It connected the venous return system, which was represented by mean circulatory filling pressure and a venous return resistance in accordance with Guyton's concept, with the ventricle, which was characterized by a time-varying elasticity. Atrial compliance was increased from near zero to a value at which atrial volume was twice ventricular stroke volume, while the parameters of ventricular contractility were kept unchanged. Cardiac output increased from 2,400 to 3,240 ml/min with increases in atrial compliance from 0.1 to 20 ml/mm Hg (venous return resistance 0.1 mm Hg sec/ml), whereas mean atrial pressure simultaneously decreased from 3.0 to 2.2 mm Hg. This result indicates that cardiac performance in terms of the cardiac output-mean atrial pressure relationship was markedly improved by increases in atrial compliance in spite of constant ventricular contractility. The analysis of the model strongly suggests that natural atrial compliance in situ, by pooling venous return flow during systole and supplying it to the ventricle during diastole, facilitates the transformation of the continuous venous return flow into the intermittent ventricular filling flow.
Increased Risk for Fetal Loss in Carriers of the Factor V Leiden Mutation
Authors: Johan R. Meinardi
Journal: Annals of Internal Medicine (1999)

Background: An increased risk for fetal loss caused by placental thrombosis is probable in carriers of the factor V Leiden mutation but has not been demonstrated consistently in previous studies. Objective: To determine the overall risk for fetal loss and the separate risks for miscarriage and stillbirth in carriers of the factor V Leiden mutation. Design: Retrospective cohort study. Setting: Three university hospitals. Participants: 228 carriers of the factor V Leiden mutation (77 propositi, 151 relatives) and 121 noncarrier relatives (controls). All participants had been pregnant at least once. Measurements: Risks for fetal loss, miscarriage (defined as fetal loss within 20 weeks of gestation), and stillbirth (defined as fetal loss after >20 weeks of gestation) in women and in pregnancies were estimated and compared in carriers and noncarriers. Adjusted odds ratios were calculated by using multiple regression analysis. A random-effects model was used for comparisons of pregnancies. Results: Fetal loss occurred in 31.6% of carriers and 22.3% of noncarriers, miscarriage occurred in 29.4% of carriers and 17.4% of noncarriers, and stillbirth occurred in 5.7% of carriers and 5.0% of noncarriers. Fetal loss recurred in 10.1% of carriers and 4.1% of noncarriers (odds ratio, 2.60 [95% CI, 0.96 to 7.03]). Adjusted odds ratios were 2.12 (CI, 1.35 to 3.33) for fetal loss, 2.08 (CI, 1.33 to 3.25) for miscarriage, and 1.60 (CI, 0.58 to 4.43) for stillbirth when pregnancies in carriers and noncarriers were compared. Homozygous carriers had a greater risk for fetal loss (odds ratio, 2.01 [CI, 0.94 to 4.32]) and stillbirth (odds ratio, 4.85 [CI, 0.82 to 25.58]) than heterozygous carriers. Conclusions: Carriers of the factor V Leiden mutation have a greater risk for fetal loss (particularly miscarriage) than noncarriers. These data further suggest a greater risk for recurrence of fetal loss in carriers than in noncarriers and a greater risk for fetal loss and stillbirth in homozygous carriers than in heterozygous carriers.
Myocardial Protection by Insulin at Reperfusion Requires Early Administration and Is Mediated via Akt and p70s6 Kinase Cell-Survival Signaling
Authors: Anne K. Jonassen, Michael N. Sack, Ole D. Mjøs, Derek M. Yellon
Journal: Circulation Research (2001)

The “metabolic cocktail” comprising glucose-insulin-potassium administrated at reperfusion reduces infarct size in the in vivo rat heart. We propose that insulin is the major component mediating this protection and acts via Akt prosurvival signaling. This hypothesis was studied in isolated perfused rat hearts (measuring infarct size to area of risk [%]) subjected to 35 minutes regional myocardial ischemia and 2 hours reperfusion. Insulin administered at the onset of reperfusion attenuated infarct size by ≥45% versus control hearts ( P &lt;0.001). Insulin-mediated cardioprotection was found to be independent of the presence of glucose at reperfusion. Moreover, the cell survival benefit of insulin is temporally dependent, in that insulin administration from the onset of reperfusion and maintained for either 15 minutes or for the duration of reperfusion reduced infarct size. In contrast, protection was abrogated if insulin administration was delayed until 15 minutes into reperfusion. Pharmacological inhibition of both upstream and downstream signals in the Akt prosurvival pathway abolished the cardioprotective effects of insulin. Here coadministration of insulin with the tyrosine kinase inhibitor lavendustin A, the phosphatidylinositol3-kinase (PI3-kinase) inhibitor wortmannin, and mTOR/p70s6 kinase inhibitor rapamycin abolished cardioprotection. Steady-state levels of activated/phosphorylated Akt correlated with insulin administration. Finally, downstream prosurvival targets of Akt including p70s6 kinase and BAD were modulated by insulin. In conclusion, insulin administration at reperfusion reduces myocardial infarction, is dependent on early administration during reperfusion, and is mediated via Akt and p70s6 kinase dependent signaling pathway. Moreover, BAD is maintained in its inert phosphorylated state in response to insulin therapy.
The Question Is, My Dear Watson, Why Did the Dog Not Bark?
Authors: Aaron Vinik
Journal: Diabetes Care (2011)

The Joslin Gold Medalists comprise 351 U.S. residents who have survived with type 1 diabetes for >50 years. A high proportion of Medalists remain free from proliferative diabetic retinopathy (PDR) (42.6%), nephropathy (86.9%), neuropathy (39.4%), or cardiovascular disease (51.5%). Current and longitudinal (the past 15 years) glycemic control were unrelated to complications. Advanced glycation end product (AGE) concentrations include carboxyethyl-lysine (CEL), an AGE derived from methylglyoxal; pentosidine, a glycoxidation ascorbate product; and carboxymethyl-lysine (CML), a glycoxidation and advanced lipoxidation product. Fructose-lysine CML and CEL were significantly elevated in the Medalists as compared with nondiabetic, age-matched control subjects ( N = 23, mean age 67.7 years). Subjects with both CEL >5.3 μmol/mol lysine and pentosidine (>1.0 pmol/mg protein) were the most likely to have any complication (7.2 times more likely) ( P = 0.001), or suffer from nephropathy (3.1 times more likely) ( P = 0.007), neuropathy (2.5 times more likely) ( P = 0.005), or cardiovascular disease (2.3 times more likely) ( P = 0.002). These data are the first to suggest that specific AGEs may decrease risk for diabetes complications because high current CML and fructose-lysine concentrations were negatively correlated with PDR development. Previous reports indicated that AGEs and their precursors may be important in the pathogenesis of diabetes complications; however, it is unexpected that lower current levels of CML and fructose-lysine are inversely related to PDR development in light of reports indicating an association between elevations of these AGEs measured in other tissues and retinopathy. The Medalist population is likely enriched for protective factors against complications. The question is, what are the protective factors?

### Metabolic memory in diabetes

The notion of good metabolic memory has been applied to the beneficial effects of an initial period of good glycemic, lipid, and blood pressure control resulting in effects going beyond that of the period of near euglycemia and followed …
Effect of chronic Pseudomonas aeruginosa infection on the development of atherosclerosis in a rat model
Authors: C. Turkay, R. Saba, N. Pahin, H. Altunbap, Ö. Özbudak, B. Akkaya, G. Özbilim, Ý. Gölbapý, M. Turkay, D. Ögünç, Ö. Bayezid
Journal: Clinical Microbiology and Infection (2004)
Congenital rubella syndrome and left pulmonary artery sling
Authors: E. Martinez-Quintana, F. Rodriguez-Gonzalez, P. Junquera-Rionda
Journal: European Respiratory Journal (2012)

To the Editors:

The classic rubella syndrome is characterised by the combination of cardiac, ocular and hearing defects, although infection and damage can occur in every organ system. Since the advent of effective vaccination, the number of new cases of congenital rubella has plummeted.

The cardiac abnormality most frequently found in rubella syndrome is a combination of branch pulmonary artery stenosis and patent ductus arteriosus, though isolated branch pulmonary artery stenosis is twice as common as isolated patent ductus arteriosus [1]. However, a wide variety of cardiac malformations may be produced, such as ventricular and atrial septal defects, stenosis of the pulmonary and aortic valves, Fallot's tetralogy, coarctation of the aorta, tricuspid atresia and transposition of the great vessels. Localised pulmonary arterial stenosis may appear in one of three main forms. First, there may be …
Sputum biomarkers in COPD exacerbations
Authors: Szabolcs Soter, Imre Barta, Balazs Antus
Journal: European Respiratory Journal (2011)

Sputum analysis may provide valuable information about inflammatory processes in COPD. In this longitudinal study we assessed the pattern of inflammatory cells and the levels of some putative biomarkers in the sputum of patients with COPD exacerbations.  Spontaneous sputum collection, fractional exhaled nitric oxide (FENO), lung function and blood gas measurements were performed in 22 ex-smoking COPD patients (mean age: 70.1±2.3 years, 12 males, 10 females) at hospital admission due to an exacerbation of the disease, and at discharge following treatment.  In most patients the sputum inflammatory cell profile at admission and discharge was similar (p>0.05). However, in patients with sputum eosinophilia (n=6) there was a significant decrease in the number of eosinophils by the end of the treatment (13.7±5.8 vs. 1.6±0.9, p 0.05). By contrast, prostaglandin E2 metabolite concentration was significantly reduced in samples obtained at discharge (36.1±9.6 vs. 22.4±6.5 pg/ml, p  Our data suggest that some patients with COPD exacerbations show sputum eosinophilia that is diminished during hospital treatment without an effect on sputum biomarkers investigated in this study.
Effect of Mediterranean diet<i>versus</i>prudent diet combined with physical activity on OSAS: a randomised trial
Authors: Christopher Papandreou, Sophia E. Schiza, Izolde Bouloukaki, Christos M. Hatzis, Anthony G. Kafatos, Nikolaos M. Siafakas, Nikolaos E. Tzanakis
Journal: European Respiratory Journal (2011)

We aimed to evaluate the effect of the Mediterranean diet (MD) compared with a prudent diet (PD) combined with physical activity on obese obstructive sleep apnoea syndrome (OSAS) patients who were treated with continuous positive airway pressure. 900 patients were evaluated and 40 obese patients (body mass index ≥30.0 kg·m −2 ) who met the inclusion criteria, with moderate-to-severe OSAS (apnoea–hypopnoea index (AHI) &gt;15 events·h −1 and Epworth Sleepiness Scale score &gt;10) based on overnight attended polysomnography, were included in the study. After randomisation, 20 patients followed the MD and 20 a PD for a 6-month period. All patients were counselled to increase their physical activity. Concerning sleep parameters, only AHI during rapid eye movement (REM) sleep was reduced to a statistically significant degree, by mean± sd 18.4±17.6 events·h −1 in the MD group and by 2.6±23.7 events·h −1 in the PD group (p&lt;0.05). The MD group also showed a greater reduction in waist circumference (WC) (-8.7±3.6 cm), WC/height ratio (-0.04±0.02 cm·m −1 ) and WC/hip ratio (-0.04±0.03 cm·cm −1 ), compared with the other group (-2.6±1.7 events·h −1 , -5.7±3.8 cm, -0.03±0.02 cm·m −1 and 0.02±0.02 cm·cm −1 , respectively; p&lt;0.05). Our results showed that the MD combined with physical activity for a 6-month period was effective in reducing the AHI during REM sleep without any statistically significant effect in the other sleep parameters, compared with a PD in obese adults with moderate-to-severe OSAS.
Localization of eosinophil granule major basic protein in human basophils.
Authors: S J Ackerman, G M Kephart, T M Habermann, P R Greipp, G J Gleich
Journal: The Journal of Experimental Medicine (1983)

In experiments using an immunofluorescent method to localize human eosinophil granule major basic protein (MBP) in cells and tissues, a small number of cells stained for MBP that subsequently could not be identified as eosinophils. Because the Charcot-Leyden crystal protein, another eosinophil protein, was recently identified in basophils, we tested whether MBP might also be a constituent of blood basophils. Highly purified, eosinophil-free basophil suspensions were prepared using the fluorescence-activated cell sorter (FACS) to sort basophil-containing mononuclear cell preparations stained with fluorescein-conjugated sheep IgG anti-human IgE antibody. Using these FACS-purified basophils, we found that: (a) enrichment for surface IgE-positive cells (greater than 95% basophils) by FACS also enriched for cells staining for MBP by immunofluorescence; (b) MBP appeared to be localized in the histamine-, heparin-containing granules; (c) significant quantities of MBP were measurable by radioimmunoassay (RIA) in freeze-thaw detergent extracts of purified basophils; and (d) RIA dose-response curves for extracts of purified eosinophils and basophils had identical slopes. The MBP content of basophils from normal individuals averaged 140 ng/10(6) cells, whereas purified eosinophils from normal donors and patients with the hyper-eosinophilic syndrome averaged 4,979 and 824 ng/10(6) cells, respectively. MBP was also detected by immunofluorescence and RIA in cells obtained from a patient with basophil leukemia, although the MBP content for basophil leukemia cells was lower than that for normal basophils. We conclude that basophils contain a protein that is immunochemically indistinguishable from eosinophil granule MBP.
Prognosis in familial non-polyposis colorectal cancer.
Authors: F Kee, B J Collins, C C Patterson
Journal: Gut (1991)

Familial cases of non-polyposis colorectal cancer have attracted much interest but little is known of their natural history. Using a population based study we have determined whether a positive family history of bowel cancer is an independent prognostic factor. All patients under 55 years with histologically confirmed colorectal cancer in Northern Ireland during the period 1976-8 were studied. The family history was validated in 95% of all nonpolyposis cases (n = 205). Medical history or cause of death were verified for 98% of 1811 first degree relatives. The strength of the family history was assessed using a score that compares the mortality from bowel cancer in the family against the average population mortality, taking account of family size and age structure. The family history score was not predictive of survival neither in univariate analysis or in a Cox9s proportional hazards multivariate analysis controlling for age, sex, stage, site, and duration of symptoms. In conclusion, a positive family history does not independently influence prognosis in patients with bowel cancer.
Costs of liver transplantation: Primum non obfuscare
Authors: Laurence F. McMahon
Journal: Hepatology (1986)

The costs and benefits of liver transplantation in adult patients at the University of Pittsburgh were reviewed for the period from 1981 through 1984. Indirect costs such as those to support the surgical and hepatology programs, the operating rooms and the clinical pathology department were ignored, and only those costs generated by the liver transplant program were considered in this analysis. Benefits to the patients are survival itself. Over 8.5% of those who leave the hospital return to full-time employment or other useful activity, including normal, albeit complicated, pregnancies. Most deaths occur during the first 3 months, after which there is a slow decline during the first year. Costs to the patient and/or the third party payers are enormous, and include evaluation as a transplant candidate, procurement of the donor liver, the transplantation itself and lifelong medical-surgical follow-up and immunosuppression plus the management of the undesirable consequences of the whole procedure. Laboratory tests alone average over $52,000 per patient. The consumption of blood and blood products is great and averages 30 units per patient. Duration of hospital admissions averaged about 55 days per patient, of which about 10 were in intensive care units. Total dollar costs were not calculated, however. The benefits to medicine are considerable in the acquisition of new knowledge and skills applicable to other disorders and other patients. The authors conclude that with further experience, the costs will decrease and the benefits will increase.