tbuckley/cabot-search huggingface dataset:
Chromosome typing in lymphangioleiomyomatosis of the lung with and without tuberous sclerosis
Authors: HH Popper, R Gamperl, MG Pongratz, P Kullnig, FM Juttner-Smolle, R Pfragner
Journal: European Respiratory Journal (1993)

Two cases of lymphangioleiomyomatosis (LLM) of the lungs are compared, one with tuberous sclerosis and the other representing an isolated lung involvement. An increased frequency of complex chromosomal rearrangements was found in peripheral lymphocytes of the patient with tuberous sclerosis, in comparison to the patient with isolated lymphangioleiomyomatosis. Telomeric associations were found in cultured pulmonary smooth muscle cells from the patient with isolated LLM.
The scholar's tale
Authors: L. Farrell
Journal: BMJ (2009)

Many of the skills of general practice lie beyond the remit of mere medical science, though I am always circumspect about giving non-medical advice. “Never criticise a brave until you have walked a mile in his moccasins,” goes the proverb, to which I might add: “Especially if it’s uphill on a hot day, the brave sweats a lot, he has a fungal foot infection and doubtful personal hygiene, and his moccasins are made out of recycled rubber tyres.”

But sometimes we have no choice. …
The Role of Glutamatergic Neurotransmission in the Pathophysiology of Alcoholism
Authors: Guochuan Tsai, Joseph T. Coyle
Journal: Annual Review of Medicine (1998)

Recent evidence suggests that ethanol abuse produces its diverse effects on the brain to a substantial degree by disrupting the function of the major excitatory neurotransmitter, glutamate. Ethanol, at concentrations associated with behavioral effects in humans, inhibits the N-methyl-d-aspartate (NMDA) receptor, which mediates the post-synaptic excitatory effects of glutamate. Tolerance to ethanol results in up-regulation of the NMDA receptor so that abrupt withdrawal produces a hyperexcitable state that leads to seizures, delerium tremens, and excitotoxic neuronal death. Ethanol's inhibition of the NMDA receptor in the fetal brain likely contributes to the CNS manifestations of fetal alcohol syndrome. Therapeutic strategies aimed at correcting glutamatergic dysregulation in alcoholism need to be explored.
Akt1 and Akt3 Exert Opposing Roles in the Regulation of Vascular Tumor Growth
Authors: Thuy L. Phung, Wa Du, Qi Xue, Sriram Ayyaswamy, Damien Gerald, Zeus Antonello, Sokha Nhek, Carole A. Perruzzi, Isabel Acevedo, Rajesh Ramanna-Valmiki, Paul Rodriguez-Waitkus, Ladan Enayati, Marcelo L. Hochman, Dina Lev, Sandaruwan Geeganage, Laura E. Benjamin
Journal: Cancer Research (2014)

Abstract Vascular tumors are endothelial cell neoplasms whose mechanisms of tumorigenesis are poorly understood. Moreover, current therapies, particularly those for malignant lesions, have little beneficial effect on clinical outcomes. In this study, we show that endothelial activation of the Akt1 kinase is sufficient to drive de novo tumor formation. Mechanistic investigations uncovered opposing functions for different Akt isoforms in this regulation, where Akt1 promotes and Akt3 inhibits vascular tumor growth. Akt3 exerted negative effects on tumor endothelial cell growth and migration by inhibiting activation of the translation regulatory kinase S6-Kinase (S6K) through modulation of Rictor expression. S6K in turn acted through a negative feedback loop to restrain Akt3 expression. Conversely, S6K signaling was increased in vascular tumor cells where Akt3 was silenced, and the growth of these tumor cells was inhibited by a novel S6K inhibitor. Overall, our findings offer a preclinical proof of concept for the therapeutic utility of treating vascular tumors, such as angiosarcomas, with S6K inhibitors. Cancer Res; 75(1); 40–50. ©2014 AACR.
CHARACTERIZATION OF THE RENIN-ANTIRENIN SYSTEM
Authors: Bert Warren, Arthur G. Johnson, S. W. Hoobler
Journal: The Journal of Experimental Medicine (1966)

Rabbit antibody capable of neutralizing the pressor activity of the enzyme renin, derived from hog kidneys, was characterized with respect to type and capacity to react serologically. Three antirenin antibodies were detected, both a precipitating and nonprecipitating, neutralizing antibody as well as a neutralizing antibody capable of being absorbed by inactivated renin. The precipitating, neutralizing antibody was purified and used successfully in an assay for hog renin by means of a hemagglutination inhibition test. By immunofluorescent methods utilizing the purified antiserum, renin was found to be localized in the macula densa of the distal convoluted tubules and the juxtaglomerular cells of the afferent arteriole in both hog and dog kidneys.
Set-back versus buried vertical mattress suturing: Results of a randomized blinded trial
Authors: Audrey S. Wang, Rebecca Kleinerman, April W. Armstrong, Sarah Fitzmaurice, Anabella Pascucci, Smita Awasthi, Mondhipa Ratnarathorn, Raja Sivamani, Thomas H. King, Daniel B. Eisen
Journal: Journal of the American Academy of Dermatology (2014)
The socio-relational framework of expressive behaviors as an integrative psychological paradigm
Authors: Jacob Miguel Vigil
Journal: Behavioral and Brain Sciences (2009)

Abstract This response shows how the socio-relational framework of expressive behaviors may be used to understand and predict social psychological processes, beyond sex differences in the expression of emotion. I use this opportunity to elaborate on several key concepts on the epigenesis of evolved social behaviors that were not fully addressed in the target article. These are: evidence of a natural history of masculine and feminine specialization (sect. R1); phenotypic plasticity and range of reactivity of social behaviors (sect. R2); exploitive and protective functions of social behaviors (sect. R3); and the role of cognition in some affective responses (sect. R4). I conclude by highlighting (in sect. R5) future directions for psychological research from a socio-relational basis.
Serial measurements of exhaled nitric oxide during exacerbations of chronic obstructive pulmonary disease
Authors: A.G.n. Agustí, J.m. Villaverde, B. Togores, None with the technical collaboration of M. Bosch
Journal: European Respiratory Journal (1999)

Excessive inflammation seems important in chronic obstructive pulmonary disease (COPD), particularly during exacerbations of the disease. Exhaled nitric oxide concentration ([NOexh]) is a sensitive marker of bronchial inflammation in asthma; it is unclear if this is also the case in COPD. This study: 1) quantifies [NOexh] in patients with COPD (during an exacerbation and while clinically stable); 2) investigates the response of [NOexh] to i.v. steroid therapy, and its potential relationship with other relevant physiological variables; and 3) assesses the relative contributions of the central and peripheral airways to [NOexh] by collecting exhaled air in two different bags connected in series. Seventeen COPD patients (forced expiratory volume in one second (FEV1) 37.6+/-3.4% of the predicted value (+/-SEM)) hospitalized because of an exacerbation of the disease (arterial oxygen tension (Pa,O2) (7.46+/-0.72 kPa 56.1+/-5.4 mmHg), arterial carbon dioxide tension (Pa,CO2) 5.63+/-0.37 kPa 42.3+/-2.8 mmHg), pH 7.41+/-0.02) and 10 healthy subjects that served as controls were studied. On admission, [NOexh] in COPD was higher than normal (41.0+/-5.1 versus 13.3+/-0.8 parts per billion (ppb), respectively, p&lt;0.001). Despite i.v. steroid therapy, [NOexh] remained elevated throughout recovery (37.9+/-4.8 ppb, p&lt;0.001) until discharge (40.9+/-4.3 ppb, p&lt;0.001). In contrast, when the patients were clinically stable (several months later), [NOexh] was significantly reduced (15.8+/-3.8 ppb, p&lt;0.001), and no longer different from control values. [NOexh] was not related to any of the physiological variables measured during recovery (pulmonary gas exchange) or at discharge (forced spirometry, lung volumes, diffusing capacity). Finally, the contribution of the central and peripheral airways to [NOexh] was not different at any point in time. These results indicate that during exacerbations of chronic obstructive pulmonary disease, the exhaled nitric oxide concentration: 1) is higher than normal; 2) is not reduced acutely by i.v. steroids but is normalized several months after discharge; 3) is unrelated to several physiological indices of disease severity; and 4) appears to be produced homogeneously in central and peripheral airways. Overall, these results are different from those reported in asthma, suggesting that different inflammatory mechanisms are operating in both diseases.
Systematic Review: Comparative Effectiveness of Radiofrequency Catheter Ablation for Atrial Fibrillation
Authors: Teruhiko Terasawa, Ethan M. Balk, Mei Chung, Ann C. Garlitski, Alawi A. Alsheikh-Ali, Joseph Lau, Stanley Ip
Journal: Annals of Internal Medicine (2009)

Background: Atrial fibrillation is the most common sustained arrhythmia. Medical treatment often fails to control symptoms. Purpose: To compare the benefits and harms of radiofrequency catheter ablation and medical therapy in adults with atrial fibrillation. Data Sources: MEDLINE and the Cochrane Central Register of Controlled Trials (2000 to December 2008) were searched for English-language reports of studies in adults. Study Selection: 6 independent reviewers screened abstracts to identify longitudinal studies of adults with atrial fibrillation who underwent radiofrequency catheter ablation. Studies reported arrhythmia or other cardiovascular outcomes at least 6 months after ablation or any adverse events. Data Extraction: Data were extracted by 1 of 4 reviewers and were verified by a cardiac electrophysiologist. Study quality and overall strength of evidence for each question were rated by 2 independent reviewers; disagreements were resolved by consensus. Data Synthesis: 108 studies met eligibility criteria. Moderate strength of evidence (3 trials; n = 30 to 198) showed that radiofrequency ablation after a failed drug course was more likely than continuation of drug therapy alone to lead to maintained sinus rhythm. Low strength of evidence (4 trials [n = 30 to 137] and 1 retrospective study [n = 1171]) suggested that radiofrequency ablation improved quality of life, promoted avoidance of anticoagulation, and decreased readmission rates compared with medical treatment. Major adverse events occurred in fewer than 5% of patients in most of 84 studies. Limitations: Study follow-up was generally 12 months or less. Large heterogeneity of applied techniques and reporting of outcomes precluded many definitive conclusions. Reporting of adverse events was poor. Publication and selective reporting biases could not be ruled out. Studies with small samples and studies reported in a language other than English were excluded. Conclusion: Radiofrequency catheter ablation is effective for up to 12 months of rhythm control when used as a second-line therapy for atrial fibrillation in relatively young patients with near-intact cardiac function. Longer studies that use primary end points of stroke and mortality are needed.
Safety of research bronchoscopy, biopsy and bronchoalveolar lavage in asthma
Authors: W.J. Elston, A.J. Whittaker, L.N. Khan, P. Flood-Page, C. Ramsay, P.K. Jeffery, N.C. Barnes
Journal: European Respiratory Journal (2004)

Bronchoscopy with endobronchial biopsy (EBB) and/or bronchoalveolar lavage (BAL) has become an important research tool in asthma. A recent report has suggested audit and reporting of the safety of these procedures. A total of 159 asthmatic patients (84 males, 75 females), aged 18–52 (median 27) yrs, forced expiratory volume in one second 53–120 (median 88) % predicted, underwent 273bronchoscopies in six clinical research studies. On 228 occasions, EBB and BAL were performed and, on 45 occasions, EBB was performed alone. On 48 occasions, bronchoscopy was performed 24 h post-allergen challenge. Adverse events occurred on 34 out of 273 occasions, none of which were following allergen challenge. Post-EBB and BAL, four patients developed pleuritic chest pain, shortness of breath and fever. A further two patients experienced pleuritic chest pain alone post-EBB/BAL. Bronchospasm or worsening of asthma symptoms occurred on 14 occasions, 13 post-EBB/BAL and on one occasion post-EBB alone. Fever/flu-like symptoms were reported on nine occasions following EBB and BAL. One subject had haemoptysis post-EBB/BAL, but required no intervention. In conclusion, bronchoscopy, endobronchial biopsy and bronchoalveolar lavage can be performed safely in asthmatic patients. Most of the complications were seen where bronchoalveolar lavage and endobronchial biopsy were both performed, suggesting that bronchoalveolar lavage accounts for most of the adverse events.
GPs will lead UK's swine flu vaccination campaign
Authors: A. O'Dowd
Journal: BMJ (2009)

The government is planning a large scale but non-compulsory campaign of vaccination against the A/H1N1 virus.

The news comes as the virus continues to spread around the country and as confirmation came that the first health professional, a Bedfordshire GP, had died from the infection.

Michael Day died on Saturday 11 July at the Luton and Dunstable Hospital. A swab test confirmed that Dr Day had the virus, but the cause of his death is still unknown. An apparently healthy 6 year old girl also died last week.

The World Health Organization’s latest update on Monday 6 July gave worldwide figures of 94 512 confirmed cases and 429 deaths.⇓



As the BMJ went to press on Tuesday 14 July the United Kingdom had 9718 confirmed cases and 17 deaths, the Department of Health said. However, the actual total, including unconfirmed cases, is thought to be considerably higher.

The department has confirmed that it is considering a large scale vaccination programme against the virus later in the year, which would be the biggest such …
Subsets of RP105-negative plasmablasts in IgG4-related disease: Table 1
Authors: Syuichi Koarada, Satoko Tashiro, Yukiko Tokuda, Yukihide Ono, Yuri Sadanaga, Rie Suematsu, Nobuyuki Ono, Akihide Ohta, Yoshifumi Tada
Journal: Annals of the Rheumatic Diseases (2014)

We read with interest the paper by Wallace ZS, plasmablasts as a biomarker for IgG4-related disease (IgG4-RD), independent of serum IgG4 concentrations.1 Evidently, the study showed that patients with active, untreated IgG4-RD have elevations in their circulating plasmablast counts. We strongly approve their results and propose new insights into plasmablast subsets in …
Validation of two activity monitors in patients with COPD
Authors: D Langer, R Gosselink, R Sena, C Burtin, M Decramer, T Troosters
Journal: Thorax (2009)

obesity in COPD.Unfortunately van den Bemt et al were not able to distinguish in their study between the prevalence of fat abundance in absolute or relative terms (ie, obesity vs sarcopenic obesity).In our review, we specifically focused on the impact of excessive fat mass (in both absolute and relative terms) on the pathogenesis of systemic features of COPD such as systemic inflammation and cardiovascular disease rather than that of a high BMI per se, since pulmonary disease severity appears to be associated not only with a decline in BMI but also with a shift in body composition.Insight into the pathogenesis of a disturbed energy balance in COPD patients with fat abundance is needed to determine if a generic-or a disease-(and maybe even disease state-) specific intervention approach is needed.Fat mass is merely determined by an imbalance between dietary intake and energy expenditure.No data are yet available regarding dietary intake in obese and non-obese patients with COPD adjusting for GOLD stage.Several studies, however, have consistently demonstrated a very low physical activity level (the most variable component of energy expenditure) in patients with COPD. 3 The studies so far therefore clearly point towards promoting exercise in early-stage COPD patients with obesity in order to improve energy balance, decrease dyspnoea and possibly also prevent adverse effects of fat abundance on cardiometabolic risk as outlined in our review.
Chemical modulation of in situ intrinsic cardiac neurones influences myocardial blood flow in the anaesthetised dog
Authors: J. G Kingma, J A. Armour, J. R Rouleau
Journal: Cardiovascular Research (1994)

Objective: The aim was to determine whether modulation of intrinsic cardiac neurones influences the distribution of myocardial blood flow in canine anaesthetised open chest experimental preparations. Methods: Intrinsic cardiac neurones were modified by locally applied nicotine (100 μg) or bradykinin (50 μg) while changes were recorded in cardiac haemodynamics and myocardial blood flow (radiolabeled microspheres). Right and left ventricular intramyocardial tissue pressures were measured with high fidelity microtip transducers. Results: Control injections of saline (vehicle; 0.1 ml) into active loci did not produce cardiovascular responses. Nicotine modulation of intrinsic cardiac neurones did not change coronary artery conductance, but total myocardial blood flow [116(SEM 17) v 532(97) ml·mirr−1·100 g−1; p = 0.001 v baseline] and oxygen consumption [7.92(1.10) v 20.14(1.86) ml·min−1·100 g−1; p = 0.001] increased in direct relation to heart rate-blood pressure product changes. Locally administered bradykinin increased coronary artery conductance [2.62(0.39) v 4.71(1.07) ml·min−1·100 g·mm Hg−1], total myocardial blood flow, to 263(72) ml·min−1·100 g−1, and oxygen consumption, to 14.9(4.4) ml·min−1100 g−1; however, heart rate-blood pressure product did not change. Conclusions: These results support earlier findings that intrinsic neurones are involved in cardiac regulation. Furthermore, modification of intrinsic cardiac neurones by nicotine or bradykinin significantly alters the distribution of myocardial blood flow, possibly because of increased myocardial metabolism. Cardiovascular Research 1994;28:1403-1406
Abstract P6-07-25: Annexin expression and survival outcomes in women with breast cancer
Authors: S Dawood, AM Gonzalez-Angulo, S Liu, H Chen, Y Li, CT Albarracin
Journal: Cancer Research (2012)

Abstract Background: The annexin superfamily of proteins has been implicated in several cellular processes. In particular, annexin A1 is known to have anti-inflammatory, anti-proliferative and pro-apoptotic functions. The expression and precise role of annexin A1 in breast cancer have been conflicting. The goal of this retrospective study was to explore the association of annexin A1 expression and survival outcome among women with breast cancer. Methods: 426 women with breast cancer whose tumor samples and associated data was available were identified. Annexin A1 expression was measured using RPPA and was considered as a categorical and continuous variable. Range of annexin A1 levels for the cohort was −1.90 to 2.36. Patients were divided into four groups according to the annexin A1 level: a) negative (annexin A1 &amp;lt;-0.84), b) low (annexin A1 &amp;gt; = −0.84 and &amp;lt;0.23), c) medium (annexin A1 &amp;gt;=0.23 and &amp;lt; 1.29) and d) high (annexin A1 &amp;gt;=1.29). Recurrence free survival (RFS) was estimated using the Kaplan-Meier product limit methods and compared across groups using log rank statistic. Cox proportional hazards models were used to determine the association of survival outcomes and annexin expression (continuous variable) adjusted by patient and tumor characteristics. Results: Median age at diagnosis was 62 years. 41 (9.6%), 245 (57.5%), 25 (5.9) and 115 (27.0%) patients had Her2 positive, hormone receptor (HR) positive, metaplastic and triple negative (TNBC) disease respectively. For the whole cohort 44 (10%), 235 (55.2%), 119 (27.9%), 28 (6.6%) breast tumors were classified as having negative, low, medium and high annexin expression respectively. High annexin A1 levels were associated with hormone receptor positive disease, increased age, post-menopausal status, low grade and lower disease stage. Median annexin A1 level was −0.19, 0.0, −0.34, −0.2 among tumors that were HER2 positive, HR positive, metaplastic and TNBC disease respectively. 5-yearRFS was 65.8% and 84.9% respectively among women with negative/low and medium/high annexin A1 levels respectively (p &amp;lt; 0.0001). Among women with Her2 positive, HR positive, metaplastic or TNBC disease 5-year RFS was significantly higher among tumors with medium/high annexin A1 levels. In the multivariable model an increase in annexin was associated with a 13% reduction in the risk of recurrence (HR = 0.87, 95% CI 0.60–1.26, p = 0.46). Conclusion: In this large dataset with long follow up our results indicate that high annexin A1 expression among women with breast cancer was associated with favorable patient and tumor characteristics and an improved RFS. Annexin A1 should be explored further as a potential prognostic biomarker. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-07-25.
KITENIN recruits Dishevelled/PKC to form a functional complex and controls the migration and invasiveness of colorectal cancer cells
Authors: D H Kho, J A Bae, J H Lee, H J Cho, S H Cho, J H Lee, Y-W Seo, K Y Ahn, I J Chung, K K Kim
Journal: Gut (2008)

KITENIN was previously reported to promote metastasis in mouse colon tumour models; however, the signalling mechanism of KITENIN at the cellular level was unknown. Here the functional role of KITENIN with respect to colorectal cancer (CRC) cell invasion and its expression in CRC tissues were investigated.The effect of KITENIN on cell motility was analysed in a migration and invasion assay upon its overexpression and knockdown. Immunoprecipitation was used to elucidate binding partners, and immunohistochemistry was used to study expression levels.KITENIN overexpression enhanced the migration of rat intestinal epithelial cells, whereas a loss of invasiveness was observed in CRC cells after KITENIN knockdown. Mechanically, KITENIN served as a scaffolding molecule that simultaneously recruited both Dishevelled (Dvl) and protein kinase C delta (PKC delta) through the membrane-spanning C-terminal region to form a complex that stimulated extracellular signal-regulated kinase (ERK)/activating protein-1 (AP-1) via a PKC delta component but also organised the actin filament via a Dvl component. The KITENIN complex controlled the invasiveness of CRC cells aetiologically harbouring various mutations in APC, beta-catenin or K-ras, in which AP-1 activation is redundant but the organisation of the actin filament is indispensable for cell motility. Clinically, KITENIN expression was significantly higher in colon cancer tissues from advanced stage (III, IV) than that of stage I CRC and also in corresponding metastatic tissues.The functional KITENIN complex acts as an executor with regard to cell motility and thereby controls CRC cell invasion, which may contribute to promoting metastasis.
Efficacy of Radiofrequency Ablation Combined With Endoscopic Resection for Barrett's Esophagus With Early Neoplasia
Authors: Roos E. Pouw, Katja Wirths, Pierre Eisendrath, Carine M. Sondermeijer, Fiebo J. Ten Kate, Paul Fockens, Jacques Devière, Horst Neuhaus, Jacques J. Bergman
Journal: Clinical Gastroenterology and Hepatology (2009)