tbuckley/cabot-search huggingface dataset:
Performance of the relative-rate test under nonstationary models of nucleotide substitution
Authors: N. J. Tourasse, W. H. Li
Journal: Molecular Biology and Evolution (1999)

Relative-rate tests have previously been developed to compare the substitution rates of two sequences or two groups of sequences. These tests usually assume that the process of nucleotide substitution is stationary and the same for all lineages, i.e., uniform. In this study, we conducted simulations to assess the performance of the relative-rate tests when the molecular-clock (MC) hypothesis is true (i.e., there is no rate difference between lineages), but the stationarity and uniformity assumptions are violated. Kimura's and bias-corrected LogDet distances were used. We found that the computation of the variances and covariances of LogDet distances had to be modified, because the constraint that the sum of the frequencies of the 16 nucleotide pair types is equal to 1 must be imposed. Comparison of the rates of two single sequences (Wu and Li's test) or two groups of sequences (Li and Bousquet's test) gave similar results. When the sequences are long (> or = 500 nt), the test based on LogDet distances and their appropriate variances and covariances is appropriate even when the substitution process is not stationary and/or not uniform. That is, at the 5% significance level, the test rejects the MC hypothesis in about 5% of the simulation replicates. In contrast, if the sequences are short (< or = 200 bases) and highly divergent, the LogDet test is very conservative due to overestimation of the variances of the distances. When the uniformity assumption is violated, the relative-rate test based on Kimura's distances can be severely misleading because of differences in base composition between sequences. However, if the uniformity assumption held and so the base frequencies remained similar among sequences, the rate of rejection turned out to be close to 5%, especially with short sequences. Under such conditions, the test using Kimura's distances performs better than the LogDet test. The reason seems to be that these distances are less affected by a reduction in the number of sites than the LogDet distances because they depend on only two parameters.
Adverse Events and Autopsy Findings after Intravitreous Cidofovir (HPMPC) Therapy in Patients with Acquired Immune Deficiency Syndrome (AIDS)
Authors: Ibrahim Taskintuna, Firas M. Rahhal, Narsing A. Rao, Clayton A. Wiley, Arthur J. Mueller, Alay S. Banker, Erik De Clercq, J. Fernando Arevalo, William R. Freeman
Journal: Ophthalmology (1997)
Asthma Symptom History Reported by Inner-city Parents/Guardians is More Strongly Associated with Exhaled Nitric Oxide and Lung Function than Adolescent-reported Symptoms
Authors: J.N. Saams, J. Cutrin-Brosnan, G.B. Diette, P.N. Breyesse, E.C. Matsui
Journal: Journal of Allergy and Clinical Immunology (2009)
The KCNQ1 potassium channel is down-regulated by ubiquitylating enzymes of the Nedd4/Nedd4-like family
Authors: T JESPERSEN, M MEMBREZ, C NICOLAS, B PITARD, O STAUB, S OLESEN, I BARO, H ABRIEL
Journal: Cardiovascular Research (2007)

Objective: The voltage-gated KCNQ1 potassium channel regulates key physiological functions in a number of tissues. In the heart, KCNQ1 α-subunits assemble with KCNE1 β-subunits forming a channel complex constituting the delayed rectifier current IKs. In epithelia, KCNQ1 channels participate in controlling body electrolyte homeostasis. Several regulatory mechanisms of the KCNQ1 channel complexes have been reported, including protein kinase A (PKA)-phosphorylation and β-subunit interactions. However, the mechanisms controlling the membrane density of KCNQ1 channels have attracted less attention.
Depressive Reactions in Hypertensive Patients
Authors: RICHARD M. QUETSCH, RICHARD W. P. ACHOR, EDWARD M. LITIN, ROBERT L. FAUCETT
Journal: Circulation (1959)

Because of reports that derivatives of Rauwolfia serpentina may cause severe mental depression when used in the treatment of hypertension, the depressive reactions and possible contributing factors were studied in a group of 387 hypertensive patients. Some of the patients received no specific antihypertensive medication; some were treated with Rauwolfia derivatives alone and some with Rauwolfia and other antihypertensive drugs. Of the patients receiving Rauwolfia, alone or with other drugs, 26 per cent experienced depressive reactions whereas only 5 per cent of the others had them.
Reply from Authors re: Marko Babjuk. New Insights in Intravesical Treatment for Intermediate- and High-Risk Non–Muscle-Invasive Urothelial Bladder Carcinoma. Eur Urol 2010;57:774–6
Authors: Richard J. Sylvester, Maurizio A. Brausi, Ziya Kirkali, Theo M. de Reijke
Journal: European Urology (2010)
Tumour-like ear lesion due to Mycobacterium tuberculosis diagnosed by polymerase chain reaction-reverse hybridization
Authors: A. Garcovich, L. Romano, A. Zampetti, S. Garcovich, F. Ardito, B. Posteraro, M. Sanguinetti, G. Fadda
Journal: British Journal of Dermatology (2004)

Journal Article Tumour‐like ear lesion due to Mycobacterium tuberculosis diagnosed by polymerase chain reaction–reverse hybridization Get access A. Garcovich, A. Garcovich Istituto di Clinica Dermatologica and Istituto di Microbiologia, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, I‐00168 Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar L. Romano, L. Romano Istituto di Clinica Dermatologica and Istituto di Microbiologia, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, I‐00168 Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar A. Zampetti, A. Zampetti Istituto di Clinica Dermatologica and Istituto di Microbiologia, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, I‐00168 Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar S. Garcovich, S. Garcovich Istituto di Clinica Dermatologica and Istituto di Microbiologia, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, I‐00168 Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar F. Ardito, F. Ardito Istituto di Clinica Dermatologica and Istituto di Microbiologia, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, I‐00168 Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar B. Posteraro, B. Posteraro Istituto di Clinica Dermatologica and Istituto di Microbiologia, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, I‐00168 Rome, Italy B.Posteraro, E‐mail: bposteraro@rm.unicatt.it Search for other works by this author on: Oxford Academic Google Scholar M. Sanguinetti, M. Sanguinetti Istituto di Clinica Dermatologica and Istituto di Microbiologia, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, I‐00168 Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar G. Fadda G. Fadda Istituto di Clinica Dermatologica and Istituto di Microbiologia, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, I‐00168 Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 150, Issue 2, 1 February 2004, Pages 370–371, https://doi.org/10.1111/j.1365-2133.2004.05731.x Published: 01 February 2004
Acute Respiratory Distress Syndrome
Authors: Gordon R. Bernard
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Though well described even in ancient writings, the acute respiratory distress syndrome (ARDS) gained major medical attention with the availability of mechanical ventilation and establishment of intensive care units. In the 50 years since this beginning there have been remarkable advances in the understanding of the etiology, physiology, histology, and epidemiology of this often lethal complication of common human maladies. Until recently, improvements in outcome have mainly followed improvements in intensive care unit operation and their associated life support systems, and have not come through discoveries made in the course of prospective randomized trials. In spite of the remarkable increase in research focused on ARDS, there remain a large number of unanswered clinical questions that are potentially extremely important with regard to short-term morbidity as well as long-term outcome. The ARDS Clinical Trials Network study of tidal volume has proven that randomized trials in ARDS with positive results are possible even when using difficult primary outcome measures such as mortality or ventilator-free days. Therefore, the rich combination of new trial strategies, potential treatments, experienced investigators, and increasingly standardized routine care set the stage for rapid advances to be made in the short- and long-term outcomes of this devastating syndrome.
Disclosure should strengthen governance at multiple points
Authors: R. Minhas
Journal: BMJ (2014)

When politicians are held to higher standards than doctors, tighter regulation of our conflicts of interest is surely overdue.1 Progress has been slow because it has relied on self regulation—itself a conflict of interest. Moves by the drug industry are welcome, but the General Medical Council should recognise the need to target regulation across the drug industry-doctor-publishing complex.

Information on financial ties should not only be published on a central register but be actively used to …
LKB1 Deficiency Sensitizes Mice to Carcinogen-Induced Tumorigenesis
Authors: Sushma Gurumurthy, Aram F. Hezel, Justin H. Berger, Marcus W. Bosenberg, Nabeel Bardeesy
Journal: Cancer Research (2008)

Abstract Lkb1 is a central regulator of cell polarity and energy metabolism through its capacity to activate the AMP-activated protein kinase (AMPK)–related family of protein kinases. Germ line–inactivating mutation of Lkb1 leads to Peutz-Jeghers syndrome, which is characterized by benign hamartomas and a susceptibility to malignant epithelial tumors. Mutations in Lkb1 are also found in sporadic carcinomas, most frequently in lung cancers associated with tobacco carcinogen exposure. The basis for Lkb1-dependent tumor suppression is not defined. Here, we uncover a marked sensitivity of Lkb1 mutant mice to the chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). Lkb1+/− mice are highly prone to DMBA-induced squamous cell carcinoma (SCC) of the skin and lung. Confirming a cell autonomous tumor suppressor role of Lkb1, mice with epidermal-specific Lkb1 deletion are also susceptible to DMBA-induced SCC and develop spontaneous SCC with long latency. Restoration of wild-type Lkb1 causes senescence in tumor-derived cell lines, a process that can be partially bypassed by inactivation of the Rb pathway, but not by inactivation of p53 or AMPK. Our data indicate that Lkb1 is a potent suppressor of carcinogen-induced skin and lung cancers and that downstream targets beyond the AMPK-mTOR pathway are likely mediators of Lkb1-dependent tumor suppression. [Cancer Res 2008;68(1):55–63]
Liver Damage Concurrent with Iproniazid Administration
Authors: Louis Zetzel, Herman Kaplan
Journal: New England Journal of Medicine (1958)

IPRONIAZID (1-isonicotinyl-2-isopropyl hydrazine)§ was originally introduced for the treatment of tuberculosis.1 , 2 Because of its toxicity in the dosage employed it has been replaced in the therapy of this disease by its chemical relative, isoniazid.3 4 5 However, its observed effect in these patients as a Central-nervous-system stimulant has led to renewed interest and use of this drug in an ever-increasing number of clinical situations. As a "psychic, energizer" it has been employed in the treatment of depressive and debilitating states, and more recently in the management of hypertension, ulcerative colitis, rheumatoid arthritis and angina pectoris.6 7 8 This report describes the appearance and nature . . .
Family history of severe cardiovascular disease in Marfan syndrome is associated with increased aortic diameter and decreased survival
Authors: David I. Silverman, Jonathon Gray, Mary J. Roman, Allan Bridges, Kevin Burton, Maureen Boxer, Richard B. Devereux, Petros Tsipouras
Journal: Journal of the American College of Cardiology (1995)

We attempted to determine whether a family history of severe cardiovascular disease in patients with the Marfan syndrome is associated with increased aortic dilation or decreased survival, or both. The prognostic importance of a family history of severe cardiovascular disease in patients with the Marfan syndrome has been incompletely examined. We hypothesized that such a family history would correlate with increased aortic dilation and would be associated with decreased survival. One hundred eight affected patients and 48 unaffected family members from 33 multigenerational families with the Marfan syndrome underwent echocardiographic measurement of the aortic root, arch and mid-abdominal aorta. Date of birth and age at death ascertained from family pedigrees were used to perform life table analysis and estimate survival. Aortic root and arch diameters were significantly greater in patients with a family history of severe cardiovascular disease than in patients without such a family history. Of subjects in the highest quartile for aortic size, >80% had such a family history in contrast to <10% of those in the lowest quartile (chisquare 57.37, p < 0.00001). Mean age at death and cumulative probability of survival were significantly lower in patients with such a family history. Among patients with the Marfan syndrome, aortic dilation is greater and life expectancy shorter in those with a family history of severe cardiovascular manifestations. These data suggest that such a family history is an important risk factor for cardiovascular events in patients with the Marfan syndrome.
Ultrasound tissue characterization detectspreclinical myocardial structural changes inchildren affected by Duchenne muscular dystrophy
Authors: Vincenzo Giglio, Vincenzo Pasceri, Loredana Messano, Fortunato Mangiola, Luciano Pasquini, Antonio Dello Russo, Antonello Damiani, Massimiliano Mirabella, Giuliana Galluzzi, Pietro Tonali, Enzo Ricci
Journal: Journal of the American College of Cardiology (2003)
Transforming growth factor‐beta1 in inflammatory airway disease: a key for understanding inflammation and remodeling
Authors: Y. C. Yang, N. Zhang, K. Van Crombruggen, G. H. Hu, S. L. Hong, C. Bachert
Journal: Allergy (2012)

Abstract Airway diseases such as chronic rhinosinusitis, asthma, and chronic obstructive pulmonary disorder are characterized by inflammation and remodeling. Among inflammatory and extracellular matrix regulatory cytokines, transforming growth factor‐beta ( TGF ‐β) stands central, as it possesses both important immunomodulatory and fibrogenic activities, and should be considered a key for understanding inflammation and remodeling processes. This review will briefly summarize the recent findings on the role of TGF ‐β1, from the view points of inflammation and remodeling, and discuss the role of TGF ‐β in the upper and lower airway diseases. This may reveal new perspectives in the understanding of airway inflammation and remodeling processes and may open innovative treatment strategies for the regulation of TGF ‐β1.
Viruses Associated with Acute Respiratory Infections
Authors: S. K. R. Clarke, B. D. Corner, D. M. Gambier, J. Macrae, D. B. Peacock
Journal: BMJ (1964)

Since the discovery of the rhinoviruses and respiratory syncytial virus only a few surveys have been made on the incidence of infections by the different respiratory viruses in the general population and the frequency with which they cause respiratory disease (Hilleman et al., 1962 ; Conference on Newer Respiratory Disease Viruses, 1963 ; Higgins et al., 1963). The present report describes the experience of the Public Health Laboratory, Bristol, in the isolation of viruses during a period of 17 months from (a) patients admitted to hospital with severe respiratory infections, (b) patients with respiratory infections who were seen by general practitioners, and (c) volun teers with very mild respiratory infections. The clinical features of some typical cases are described. Between 1 December 1961 and 30 April 1963 swabs were received from 521 patients with acute respiratory infections. Of these patients, 187 have been excluded from the following analysis?116 because their swabs were not inoculated on the day they were taken (see below), 42 because their swabs were tested in only one type of tissue culture, 24 because nose swabs and not throat swabs were taken, and 5 because they were swabbed more than 21 days after the onset of the illness. From the remaining 334 patients nose and throat swabs were taken from 164 and throat swabs alone from 170.
Dysplasia of the Systemic and Pulmonary Arterial System with Tortuosity and Lengthening of the Arteries
Authors: ALOIS J. BEUREN, WALDEMAR HORT, HEINRICH KALBFLEISCH, HELMUTH MÜLLER, JOACHIM STOERMER
Journal: Circulation (1969)

This article describes the case of a boy, 1 year and 5 months old, with generalized tortuosity and lengthening of all major arteries, including the coronary arteries and the pulmonary artery. The early death of the patient was attributed to coronary insufficiency and multiple severe peripheral pulmonary stenoses. The pathological changes were confined to the elastic arteries and the first part of the muscular arteries. The wall of the aorta was thickened and there was an increase of the elastic fibers. The same changes were present in the main pulmonary artery. In the large muscular arteries, the characteristic changes were thickening of the intima with hyperplasia of the elastic fibers and degenerative fragmentation of the internal elastic membrane. The walls of the coronary arteries were thickened and their lumina were narrow.
The Arkansas experience with autotransplantation (AT) for older patients (OP, age &gt; 65) with multiple myeloma (MM).
Authors: E. J. Anaissie, M. Grazziutti, J. Szymonifka, B. P. Nair, F. Van Rhee, Y. Alsayed, S. Waheed, A. Hoering, B. Barlogie
Journal: Journal of Clinical Oncology (2010)

8136 Background: According to CMM guidelines, only a single AT (AT-1) is covered for OP. Arkansas data had been the cornerstone for initial approval for AT-1 for OP. As there is no biological or clinical basis for the CMM rules, we investigated the issue of a scheduled second AT within 6mo of AT-1 (AT-2) among OP enrolled in Total Therapy (TT) protocols for newly diagnosed MM. Methods: From our MM data base, we identified 241 OP among a total of 1,202 TT patients, including 21 of 231 patients in TT1, 136 of 668 in TT2 and 84 of 303 in TT3, of whom AT-2 was applied according to patients' available resources/supplemental insurance. OS and EFS were compared among OP according to the timing of AT-2 in the context of baseline variables. Results: Among OP, CR was achieved overall in 51%, including 24% with TT1, 43% with the control arm of TT2 (TT2−), 60% with TT2 plus thalidomide (TT2+) and 60% with TT3, resulting in 5-yr CRD estimates of 57% overall (20% TT1, 50% TT2−, 50% TT2+, 76% TT3). 5-yr estimates of OS and EFS were 61%/47% (TT1 43%/29%, TT2- 58%/35%, TT2+ 59%/47%, TT3 68%/65%). Among OP, MV analysis revealed inferior OS and EFS when age was ≥68yr (OS: HR = 1.89, p<0.001; EFS: HR = 2.01, p<0.001), in the presence of metaphase cytogenetic abnormaliites (CA) (OS: HR = 1.71, p = 0.004; EFS: HR1.54, p = 0.015) and in case TT1 rather than TT2 and TT3 was applied (OS: HR = 1.72, p = 0.045; EFS: HR = 2.16, p = 0.003); however, AT-2 within 6mo was a highly significant favorable intervention (OS: HR = 0.47, p<0.001; EFS: HR = 0.52, p<0.001). CRD was also shorter with older age (HR = 2.50, p = 0.003) and CA (HR = 2.68, p = 0.001). Conclusions: As with patients less than 65yr,timelyAT-2 benefited OP and hence should be made available through CCM. No significant financial relationships to disclose.
Prognostic value of angiogenesis in solitary bone plasmacytoma
Authors: Shaji Kumar, Rafael Fonseca, Angela Dispenzieri, Martha Q. Lacy, John A. Lust, Linda Wellik, Thomas E. Witzig, Morie A. Gertz, Robert A. Kyle, Philip R. Greipp, S. Vincent Rajkumar
Journal: Blood (2003)
Beryllium-stimulated Release of Tumor Necrosis Factor- α , Interleukin-6, and Their Soluble Receptors in Chronic Beryllium Disease
Authors: SALLY S. TINKLE, LEE S. NEWMAN
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Chronic beryllium disease (CBD) provides a model system in which to evaluate the antigen-stimulated, cell-mediated, immune response that leads to granulomatous lung disease. We hypothesized that beryllium salts would stimulate bronchoalveolar lavage (BAL) cell release of tumor necrosis factor- α (TNF- α ) and interleukin-6 (IL-6), and their soluble receptors, soluble TNF receptor I (sTNF RI), sTNF RII, and sIL-6R and that chronic exposure to antigen would increase production of soluble receptors in the serum and BAL fluid (BALF) of beryllium-sensitized and CBD patients. We have demonstrated (1) similar constitutive TNF- α , IL-6, and soluble receptor production by control subjects and CBD patients, (2) a BeSO4-stimulated increase in TNF- α and IL-6 production by CBD-derived BAL cells, and (3) a BeSO4-induced decrease in sTNF RII production by BAL cells from control subjects. We measured increased serum sTNF RI and serum and BALF sIL-6R in beryllium-sensitized subjects and increased sTNF RI and RII in serum and sIL-6R and sTNF RII and BALF in CBD patients. These changes correlated with pulmonary lymphocytosis and clinical measures of disease severity, indicating that soluble receptors may reflect disease status.
P193 A role for active Vitamin D in steroid resistant asthma patients who have enhanced production of IL-17A and reduced IL-10
Authors: AM Nanzer, ES Chambers, DF Richards, AR Martineau, CJ Griffiths, C Corrigan, CM Hawrylowicz
Journal: Thorax (2013)

<h3>Background</h3> Steroid refractory (SR) asthma, a distinct disease phenotype, has a high morbidity and mortality and takes up a disproportional burden of healthcare cost. IL-17A is a pro-inflammatory cytokine that is essential for host defence against pathogens but can also lead to damage of the surrounding tissues associated with immune diseases and is linked with severe asthma. IL-10 has crucial immunregulatory properties, and we have previously shown <i>in vitro</i>, that T cells from steroid refractory asthma patients fail to respond to glucocorticosteroids for the induction of IL-10 synthesis. <h3>Methods</h3> We assessed IL-17A and IL-10 synthesis in steroid sensitive, SS, (mean% change in FEV<sub>1</sub> following 2 weeks of oral prednisolone 16%) versus SR (mean% change FEV<sub>1</sub> 0%) asthma patients and investigated their response to dexamethasone. <h3>Results</h3> PBMC from SR individuals synthesised 7-fold higher levels of IL-17A than disease-severity matched SS patients (by flow cytometry and CBA). Interestingly IL-17A levels inversely correlated with changes in lung function following oral steroids whereas higher IL-10 levels were associated with an increase in lung function. Dexamethasone failed to inhibit IL-17A, but, surprisingly, increased protein synthesis, an effect that was also seen <i>in vivo</i>: inhaled glucocorticosteroid dosages correlated with IL-17A protein levels. This suggests the potentially detrimental effects corticosteroids might have in certain asthma phenotypes. The production of IL-10 by T cells was impaired in cultures from SR asthmatics, but not in healthy controls or SS asthma patients implying an associated impaired IL-10 response with poor asthma control. 1alpha,25-dihydroxyvitamin D3 (1,25(OH)D) not only restored the capacity of T cells to produce IL-10 upon stimulation with dexamethasone in SR asthma patients, but also inhibited IL-17A synthesis in culture independently of steroid. <h3>Conclusion</h3> High IL-17A levels are associated with poor response to steroids and more severe asthma. Our data supports a steroid-enhancing property of 1,25(OH)D in severe asthma through inhibition of IL-17A and via enhancement of IL-10 synthesis.