tbuckley/cabot-search huggingface dataset:
Safety of Inducing Sputum in Patients with Asthma of Varying Severity
Authors: PHILIPPE TARODO de la FUENTE, MICAELA ROMAGNOLI, PHILIPPE GODARD, JEAN BOUSQUET, PASCAL CHANEZ
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Inducing sputum using hypertonic saline is a noninvasive method to investigate airway inflammation in people with asthma. However, hypertonic saline may also induce bronchoconstriction in some patients. The aim of the study was to examine whether the overall safety of using hypertonic saline to induce sputum in patients with mild to moderate asthma could be extended to patients with severe and/or uncontrolled asthma. Nine control subjects and 64 asthmatic patients with varying severity of the disease (FEV1 40-126% predicted values) were studied. Twenty-one of those patients had uncontrolled asthma. Sputum was induced in a standardized manner using hypertonic saline. The safety of the procedure was evaluated by assessing the clinical response and measuring FEV1 just before and during sputum induction. The procedure was well tolerated in most patients, but it had to be stopped due to side effects in 11.6% of patients with severe asthma. None of the side reactions were severe. Few patients with uncontrolled (17.3%) or severe asthma (18.6%) had a drop in FEV1 of 10-20%. The fall in FEV1 was significantly greater in patients with severe asthma than those with mild disease (p < 0.02 Mann-Whitney U test). We conclude that hypertonic saline-induced sputum is a safe technique even in patients with severe asthma.
The capacity of mitogen-responsive T cells to home to their tissue of origin, analyzed by means of chromosome markers
Authors: MJ Doenhoff, AJS Davies
Journal: The Journal of Experimental Medicine (1976)

Lance and Taub (1) showed that when radioactively labeled lymphocytes were injected into a syngeneic mouse and the lymph node cells of this animal transferred to a second syngeneic recipient, the proportion of radioactivity found in the lymph node relative to the amount present in the spleen of the secondary recipient had increased markedly. The interpretation of this result was that some lymphocytes have the capacity to "home" to their organ of origin. The purpose of the experiments described here was to test the "homing" copacity of T cells by a method that did not involve radioactive labeling. It has been shown elsewhere that some or all mouse T cells are stimulated to divide in culture by the mitogens phytohemagglutinin (PHA) and concanavalin A (Con A) (2). We therefore elected to inject karyotypically distinct lymphocytes into syngeneic recipients and to follow their subsequent distribution by culture of lymph node and spleen cells of the recipient with PHA or Con A. In this manner the homing capacities of spleen and lymph node T cells could be determined, and furthermore, the effects of labeling with chromium-51 ((51)Cr) could be assayed with respect to the persistence of mitogen responsiveness in the injected cells.
Long Noncoding <scp>RNAs</scp>: Insights from Biological Features and Functions to Diseases
Authors: Xiaolei Li, Zhiqiang Wu, Xiaobing Fu, Weidong Han
Journal: Medicinal Research Reviews (2012)

Abstract Over the past decade, genome‐wide transcriptomic studies have shown that the mammalian genome is pervasively transcribed and produces many thousands of transcriptomes without bias from previous genome annotations. This finding, together with the discovery of a plethora of unexpected RNAs that have no obvious coding capacities, have challenged the traditional views that proteins are the main protagonists of cellular functions and that RNA is merely an intermediary between DNA sequence and its encoded protein. There are many different kinds of products that are generated by this pervasive transcription; this review focuses on long noncoding RNAs (lnc RNAs ) that have shown spatial and temporal specific patterns of expression and regulation in a wide variety of cells and tissues, adding significant complexity to the understanding of their biological roles. Recent research has shed new light onto the biological function significance of lnc RNAs . Here, we review the rapidly advancing field of lnc RNAs , describing their biological features and their roles in regulation of gene expression. Moreover, we highlight some recent advances in our understanding of nc RNA ‐mediated regulation of stem cell pluripotency, morphogenesis, and development, focusing mainly on the regulatory roles of lnc RNAs . Finally, we consider the potential medical implications, and the potential use of lnc RNAs in drug development and discovery and in the identification of molecular markers of diseases, including cancer.
Treatment of Nail Psoriasis
Authors: Jeffrey J. Crowley, Jeffrey M. Weinberg, Jashin J. Wu, Andrew D. Robertson, Abby S. Van Voorhees
Journal: JAMA Dermatology (2014)

Nail psoriasis can be difficult to treat and has a significant effect on quality of life. Relatively few controlled trials evaluating treatments for nail psoriasis have been published. There is an unmet need for treatment recommendations to guide therapeutic decisions.To develop treatment recommendations for nail psoriasis from the Medical Board of the National Psoriasis Foundation.A PubMed search for publications on nail psoriasis treatments was performed from January 1, 1947, through May 11, 2014, without language restrictions.Treatment recommendations for 4 clinical nail psoriasis scenarios were developed based on the evidence reviewed in this study and expert opinion of the Medical Board of the National Psoriasis Foundation. Treatment of nail psoriasis should balance consideration of the extent of skin disease, psoriatic arthritis, and severity of nail disease with concomitant impairment of quality of life. All patients should be evaluated for onychomycosis because this may complicate psoriatic nail disease. For disease limited to the nails, high-potency topical corticosteroids with or without calcipotriol are initial options. For patients with significant nail disease for whom topical therapy has failed, treatment with adalimumab, etanercept, intralesional corticosteroids, ustekinumab, methotrexate sodium, and acitretin are recommended. For patients with significant skin and nail disease, adalimumab, etanercept, and ustekinumab are strongly recommended, and methotrexate, acitretin, infliximab, and apremilast are recommended. Finally, for a patient with significant nail, skin, and joint disease, adalimumab, etanercept, ustekinumab, infliximab, methotrexate, apremilast, and golimumab are recommended.Treatment of nail psoriasis poses a clinical challenge. Clinical trial data are limited, and results are reported inconsistently, making comparisons among treatment options difficult. The treatment recommendations from the Medical Board of the National Psoriasis Foundation will help guide treatment decisions for clinicians who are treating patients with nail psoriasis.
Different features of ca2+ oscillations in differentiated and undifferentiated hepatocyte doublets
Authors: Tsuneo Kitamura, Sumio Watanabe, Ken-Ichi Ikejima, Miyoko Hirose, Akihisa Miyazaki, Atsuko Yumoto, Satoko Suzuki, Toshio Yamada, Noriyuki Kitami, Nobuhiro Sato
Journal: Hepatology (1995)

Cytosolic free Ca2+ ([Ca2+]i) oscillations are postulated to play a critical role in cellular proliferation. By using doublets of normal rats (NR) and those 18 hours after two-thirds hepatectomy (PHR), we investigated cytosolic free Ca2+ ([Ca2+]i) responses in liver regeneration. Normal rat hepatocyte doublets that retain their bile canaliculi are polarized and well differentiated. PHR doublets, which also retain their bile canaliculi, were characterized as undifferentiated by (1) decreased canalicular secretion of fluorescein-isothiocyanate-labeled glycocholate; (2) increased labeling index of hepatocytes in BrdU staining (approximately 30%); and (3) impaired transfer of fluorescent dye injected into one cell of the pair to the other. Addition of phenylephrine to NR and PHR doublets in the presence of extracellular Ca2+ resulted in [Ca2+]i oscillations or a nonoscillatory-sustained increase in [Ca2+]i followed by a gradual return to the baseline. Extracellular Ca2+ was not required for [Ca2+]i oscillations but was necessary for a sustained increase in [Ca2+]i. Simultaneous addition of prazosin, alpha 1-receptor blocker, to doublets immediately abolished these [Ca2+]i responses. The [Ca2+]i level in each of the adjacent cells was synchronous in sustained increase in [Ca2+]i but asynchronous in [Ca2+]i oscillations. As the phenylephrine concentration was increased (1 to 100 mumol/L), oscillations were replaced by a sustained increase in [Ca2+]i in NR doublets. In contrast, in PHR doublets, oscillations remained, whereas the frequency of oscillations increased in a dose-dependent manner. These results indicate that the mechanisms of phenylephrine-evoked [Ca2+]i responses are different in differentiated and undifferentiated doublets and that the frequency modulation of [Ca2+]i oscillations may be involved in the intracellular signal transduction in the cellular proliferation process during liver regeneration.
Risk factors for hamstring muscle strain injury in sport: a systematic review and meta-analysis
Authors: Grant Freckleton, Tania Pizzari
Journal: British Journal of Sports Medicine (2012)

Hamstring muscle strain-type injuries are common in sports that involve sprinting,1 acceleration, deceleration, rapid change in direction and jumping.2 ,3 Occurring in both recreational and professional sports, these injuries can result in substantial time lost from sport and commonly recur.4 ,5

In the Australian Football League (AFL), hamstring muscle strain-type injuries have displayed a high incidence rate, with a 10 year mean of 6.1 new injuries per club each year and a 23% average recurrence rate.6 A recurrence rate of 17% has been reported in elite soccer players7 with hamstring injuries also recorded as the most common injury accounting for 12% of all injuries and resulting in an average of four missed games per injury.8

The high incidence of hamstring muscle strain-type injuries and potential associated costs has resulted in a substantial amount of research into the factors related to such injuries. Two recent systematic reviews have been completed in an attempt to collate the evidence around risk factors for hamstring injuries.9 ,10 Both reviews identified hamstring muscle weakness and thigh muscle imbalance, muscle flexibility, previous hamstring injury, other previous injury and age as potential risk factors; however, these reviews concluded that single variables were inconsistently identified as associated factors. Both reviews provided a qualitative synthesis of the literature and included risk factor studies as well as intervention studies, where a potential risk factor was modified with a training programme. The inclusion of intervention studies may potentially complicate risk factor analyses, as such studies assume that the factor being modified is associated with the injury and that the factor can be modified by the treatment programme.

The aim of the current review was to assemble all available knowledge and data to identify the intrinsic and extrinsic risk factors associated with …
HKI-272 in Non–Small Cell Lung Cancer
Authors: Kwok-Kin Wong
Journal: Clinical Cancer Research (2007)

Somatic mutations in the kinase domain of the epidermal growth factor receptor (EGFR) gene are found in approximately 10% of lung adenocarcinomas sequenced in the United States and in approximately 30% sequenced in Asia. These mutations are associated with sensitivity to the EGFR inhibitors gefitinib and erlotinib. Many patients who initially respond to erlotinib or gefitinib subsequently relapse. Studies have identified EGFR T790M mutations in tumors from patients who initially responded and then relapsed. The T790M mutation, when combined in vitro with treatment-sensitizing EGFR mutations, permits the continued growth of tumor cells in the presence of erlotinib and gefitinib. HKI-272 is an irreversible EGFR/HER/ErbB inhibitor that has been shown to inhibit the growth of T790M mutant cells in vitro in human lung cancer cell lines and in murine cells transfected with sensitizing EGFR mutations. A phase I HKI-272 monotherapy trial in patients with solid tumors is close to completion. Preliminary analyses of the trial, presented at the 2006 annual meeting of American Society of Clinical Oncology, showed that HKI-272 can achieve stable disease control for over 6 months in some patients with non-small cell lung cancer that has progressed after treatment with gefitinib or erlotinib. A phase II trial of HKI-272 in non-small cell lung cancer patients has been initiated. HKI-272 might offer benefits to non-small cell lung cancer patients who have relapsed after an initial response to erlotinib.
Surgeon Training, Protocol Compliance, and Technical Outcomes From Breast Cancer Sentinel Lymph Node Randomized Trial
Authors: D. N. Krag, T. Ashikaga, S. P. Harlow, J. M. Skelly, T. B. Julian, A. M. Brown, D. L. Weaver, N. Wolmark
Journal: JNCI Journal of the National Cancer Institute (2009)

BackgroundThe National Surgical Adjuvant Breast and Bowel Project B-32 trial was designed to determine whether sentinel lymph node resection can achieve the same therapeutic outcomes as axillary lymph node resection but with fewer side effects and is one of the most carefully controlled and monitored randomized trials in the field of surgical oncology. We evaluated the relationship of surgeon trial preparation, protocol compliance audit, and technical outcomes.
Aetiology and prognostic factors of patients with AIDS presenting life-threatening acute respiratory failure
Authors: A Torres, M El-Ebiary, R Marrades, JM Miro, JM Gatell, JM Sanchez-Nieto, A Xaubet, C Agusti, R Rodriguez-Roisin
Journal: European Respiratory Journal (1995)

Respiratory failure is a significant contributor to morbidity and mortality in patients with the acquired immune deficiency syndrome (AIDS). We performed a study to investigate the aetiology, prognostic factors, and short- and long-term outcome of AIDS patients with life-threatening respiratory failure and pulmonary infiltrates. Forty-two AIDS patients (29 of whom required mechanical ventilation), admitted to a Respiratory Intensive Care Unit (ICU) from 1985 to 1992 because of severe respiratory failure (arterial oxygen tension/fractional inspiratory oxygen (Pa,O2/FI,O2) ratio at hospital admission 19 +/- 14 kPa (mean +/- SD)) and diffuse pulmonary infiltrates, were studied for evaluation of the aetiology and outcome. Necropsy studies were performed in 14 out of 23 (61%) patients who died. Pneumocystis carinii was the most common aetiology of pulmonary infiltrates (28 patients (67%)). Overall, 19 patients survived (45%) and 23 (55%) died. A multivariate analysis of prognostic factors influencing the outcome of the whole population showed that the presence of P. carinii pneumonia and the requirement for mechanical ventilation (MV) were the major determinants of outcome for this type of patient. The median survival time after ICU discharge for P. carinii pneumonia patients was lower (49 days) when compared to that of the remaining patients (154 days). Median survival time after ICU discharge for patients needing MV (112 days) did not differ from that observed in patients not requiring artificial ventilatory support (154 days). Although the ICU survival rate in this study was reasonable, 55% for the whole population, and 36% for P. carinii pneumonia patients, the poor outcome after ICU discharge, in particular for P. carinii pneumonia patients, deserves the reassessment of ICU admission criteria for this type of AIDS population.
Effect of renal insufficiency on the active transport of calcium by the small intestine
Authors: Richard D. Baerg, Daniel V. Kimberg, Elaine Gershon
Journal: Journal of Clinical Investigation (1970)

The intestinal absorption of calcium is often depressed in patients with chronic renal insufficiency. Furthermore, the malabsorption of calcium and the osteodystrophy which occur in association with chronic renal disease are often "resistant" to vitamin D; the basis for this resistance remains uncertain however. Recent studies by others have emphasized the role of an abnormality in the metabolism of vitamin D in accounting for the alterations in the calcium absorption and the apparent vitamin D-resistance which accompany the uremic syndrome. The present studies with an experimentally uremic animal model demonstrate a defect in the active transport of calcium by duodenal gut sacs in vitro. This abnormality is not due to the semistarvation associated with renal insufficiency and cannot be corrected by the administration of physiologic amounts of vitamin D(3): it is reversed by massive doses of the vitamin. Neither the metabolism of vitamin D(3) nor the levels of calcium binding protein activity in the duodenal mucosa are affected by renal insufficiency under the conditions employed in the present studies. The results of the present studies strongly suggest that in addition to the recently proposed mechanism involving an interference with the metabolism of vitamin D renal insufficiency also affects the cellular mechanisms for calcium transport in a manner which, while opposite in direction to that of vitamin D, is independent of a direct interaction with the vitamin or its metabolites.
Prediction of Survival in Diffuse Large-B-Cell Lymphoma Based on the Expression of Six Genes
Authors: Izidore S. Lossos, Debra K. Czerwinski, Ash A. Alizadeh, Mark A. Wechser, Rob Tibshirani, David Botstein, Ronald Levy
Journal: New England Journal of Medicine (2004)

Several gene-expression signatures can be used to predict the prognosis in diffuse large-B-cell lymphoma, but the lack of practical tests for a genome-scale analysis has restricted the use of this method.We studied 36 genes whose expression had been reported to predict survival in diffuse large-B-cell lymphoma. We measured the expression of each of these genes in independent samples of lymphoma from 66 patients by quantitative real-time polymerase-chain-reaction analyses and related the results to overall survival.In a univariate analysis, genes were ranked on the basis of their ability to predict survival. The genes that were the strongest predictors were LMO2, BCL6, FN1, CCND2, SCYA3, and BCL2. We developed a multivariate model that was based on the expression of these six genes, and we validated the model in two independent microarray data sets. The model was independent of the International Prognostic Index and added to its predictive power.Measurement of the expression of six genes is sufficient to predict overall survival in diffuse large-B-cell lymphoma.
Studies of Contractile Force in Man
Authors: W. GERALD AUSTEN
Journal: Circulation (1965)

Forty-five patients undergoing open-heart surgery for acquired aortic valve disease were studied with measurements of left ventricular contractile force. The data presented clearly indicate that coronary perfusion afforded, on the average, better protection to left ventricular contractility as recorded by a strain-gage arch than did hypothermia. This was particularly true in the usual case, which required an hour or longer of aortic occlusion. Patients who required 40 minutes or less of aortic occlusion demonstrated approximately identical decreases in contractile force with hypothermia or coronary perfusion. Bilateral coronary perfusion did not usually afford much additional left ventricular protection as compared to unilateral left coronary perfusion. In a small number of patients with significant coronary arterial occlusion, bilateral coronary perfusion appeared to give better left ventricular protection.
OSTα‐OSTβ
Authors: Nazzareno Ballatori, Whitney V. Christian, Jin Young Lee, Paul A. Dawson, Carol J. Soroka, James L. Boyer, Michael S. Madejczyk, Na Li
Journal: Hepatology (2005)

The cellular and subcellular localization and mechanism of transport of the heteromeric organic solute transporter (OST) OSTalpha-OSTbeta was examined in human and rodent epithelia. The two subunits of the transporter were expressed together in human small intestine, kidney, and liver, tissues that also express the apical sodium-dependent bile acid uptake transporter ASBT (SLC10A2). Indirect immunofluorescence microscopy localized OSTalpha and OSTbeta to the basolateral membrane of mouse, rat, and human ileal enterocytes, renal proximal tubular cells, and cholangiocytes. Transport in OSTalpha-OSTbeta-expressing Xenopus laevis oocytes was unaffected by depletion of intracellular adenosine triphosphate, or by changes in transmembrane Na(+), K(+), H(+), or Cl(-) concentration gradients. However, the oocytes demonstrated robust substrate efflux and trans-stimulation, indicating that transport occurs by facilitated diffusion. Madin Darby canine kidney cells coexpressing mouse Ostalpha and Ostbeta exhibited enhanced apical to basolateral transport of the major glycine and taurine conjugated bile acid species. In conclusion, the selective localization of OSTalpha and OSTbeta to the basolateral plasma membrane of epithelial cells responsible for bile acid and sterol reabsorption, the substrate selectivity of the transporter, and the facilitated diffusion transport mode collectively indicate that OSTalpha-OSTbeta is a key basolateral transporter for the reabsorption of these important steroid-derived molecules.
Dual Role of IL-22 in Allergic Airway Inflammation and its Cross-talk with IL-17A
Authors: Anne-Gaelle Besnard, Robert Sabat, Laure Dumoutier, Jean-Christophe Renauld, Monique Willart, Bart Lambrecht, Mauro M. Teixeira, Sabine Charron, Lizette Fick, François Erard, Katarzyna Warszawska, Kerstin Wolk, Valerie Quesniaux, Bernhard Ryffel, Dieudonnée Togbe
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

IL-22 has both proinflammatory and antiinflammatory properties. Its role in allergic lung inflammation has not been explored.To investigate the expression and roles of IL-22 in the onset and resolution of experimental allergic asthma and its cross-talk with IL-17A.IL-22 expression was assessed in patient samples and in the lung of mice immunized and challenged with ovalbumin. IL-22 functions in allergic airway inflammation were evaluated using mice deficient in IL-22 or anti-IL-22 neutralizing antibodies. Moreover, the effects of recombinant IL-22 and IL-17A neutralizing antibodies were investigated.Increased pulmonary IL-22 expression is found in the serum of patients with asthma and mice immunized and challenged with ovalbumin. Allergic lung inflammation is IL-22 dependent because eosinophil recruitment, Th2 cytokine including IL-13 and IL-33, chemokine production, airway hyperreactivity, and mucus production are drastically reduced in mice deficient in IL-22 or by IL-22 antibody neutralization during immunization of wild-type mice. By contrast, IL-22 neutralization during antigen challenge enhanced allergic lung inflammation with increased Th2 cytokines. Consistent with this, recombinant IL-22 given with allergen challenge protects mice from lung inflammation. Finally, IL-22 may regulate the expression and proinflammatory properties of IL-17A in allergic lung inflammation.IL-22 is required for the onset of allergic asthma, but functions as a negative regulator of established allergic inflammation. Our study reveals that IL-22 contributes to the proinflammatory properties of IL-17A in experimental allergic asthma.