tbuckley/cabot-search huggingface dataset:
Associations between the 17q21 region and allergic rhinitis in 5 birth cohorts
Authors: Elaine Fuertes, Cilla Söderhäll, Nathalie Acevedo, Allan Becker, Michael Brauer, Moira Chan-Yeung, F. Nicole Dijk, Joachim Heinrich, Johan de Jongste, Gerard H. Koppelman, Dirkje S. Postma, Juha Kere, Anita L. Kozyrskyj, Göran Pershagen, Andrew Sandford, Marie Standl, Carla M.T. Tiesler, Melanie Waldenberger, Marit Westman, Christopher Carlsten, Erik Melén
Journal: Journal of Allergy and Clinical Immunology (2014)
Surveillance for the detection of early lung cancer in patients with bronchial dysplasia
Authors: P. Jeremy George, A. K Banerjee, C. A Read, C. O'Sullivan, M. Falzon, F. Pezzella, A. G Nicholson, P. Shaw, G. Laurent, P. H Rabbitts
Journal: Thorax (2006)

<b>Background:</b> The natural history of bronchial preinvasive lesions and the risk of developing lung cancer in patients with these lesions are not clear. Previous studies have treated severe dysplasia and carcinoma in situ (CIS) on the assumption that most will progress to invasive carcinoma. <b>Aims:</b> To define the natural history of preinvasive lesions and assess lung cancer risk in patients with these lesions. <b>Hypothesis:</b> Most preinvasive lesions will not progress to invasive carcinoma but patients with these lesions will be at high risk. <b>Methods:</b> A cohort of patients with preinvasive lesions underwent fluorescence bronchoscopy every 4–12 months and computed tomography of the chest annually. The main end point was the development of invasive carcinoma. <b>Results:</b> 22 patients with 53 lesions were followed up for 12–85 months. 11 cancers were diagnosed in 9 patients. Of the 36 high-grade lesions (severe dysplasia and CIS), 6 progressed to invasive cancers. 5 separate cancers developed at remote sites in patients with high-grade lesions. All cancers were N0M0 and curative treatment was given to 8 of the 9 patients. The cumulative risk of developing lung cancer in a patient with a high-grade lesion was 33% and 54% at 1 and 2 years, respectively. Of the 17 low-grade lesions, none progressed to invasive carcinoma. <b>Conclusions:</b> Although the risk of malignant progression of individual preinvasive lesions is relatively small, patients with high-grade lesions are at high risk of lung cancer. Surveillance facilitated early detection and treatment with curative intent in most patients.
Characteristics of people with recurrent ankle sprains: a systematic review with meta-analysis
Authors: Claire E Hiller, Elizabeth J Nightingale, Chung-Wei Christine Lin, Garrett F Coughlan, Brian Caulfield, Eamonn Delahunt
Journal: British Journal of Sports Medicine (2011)

Objective To examine whether people with recurrent ankle sprain, have specific physical and sensorimotor deficits. Design A systematic review of journal articles in English using electronic databases to September 2009. Included articles compared physical or sensorimotor measures in people with recurrent (≥2) ankle sprains and uninjured controls. Main outcome groups Outcome measures were grouped into: physical characteristics, strength, postural stability, proprioception, response to perturbation, biomechanics and functional tests. A meta-analysis was undertaken where comparable results within an outcome group were inconsistent. Results Fifty-five articles met the inclusion criteria. Compared with healthy controls, people with recurrent sprains demonstrated radiographic changes in the talus, changes in foot position during gait and prolonged time to stabilisation after a jump. There were no differences in ankle range of motion or functional test performance. Pooled results showed greater postural sway when standing with eyes closed (SMD=0.9, 95% CI 0.4 to 1.4) or on unstable surfaces (0.5, 0.1 to 1.0) and decreased concentric inversion strength (1.1, 0.2 to 2.1) but no difference in evertor strength, inversion joint position sense or peroneal latency in response to a perturbation. Conclusion There are specific impairments in people with recurrent ankle sprain but not necessarily in areas commonly investigated.
The excess numbers of peritoneal macrophages in granulocyte-macrophage colony-stimulating factor transgenic mice are generated by local proliferation.
Authors: D Metcalf, M J Elliott, N A Nicola
Journal: The Journal of Experimental Medicine (1992)

Mice transgenic for the hemopoietic growth factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), exhibit a sustained elevation of GM-CSF levels and a 50-100-fold elevation of peritoneal macrophage cell numbers. The excess cell numbers were found to be generated in pre-adult life, with numbers remaining relatively constant thereafter. In the pre-adult period, no abnormalities were noted in the number or composition of blood, bone marrow, or spleen cells, the type or number of GM progenitor cells in the marrow or spleen, or the rate of appearance of newly formed monocytes in the peripheral blood. Peritoneal macrophages in pre-adult transgenic mice exhibited elevated mitotic activity and, after tritiated thymidine labeling, a more rapid accumulation of labeled progeny. The increase in peritoneal macrophage cell numbers appears, therefore, to be based on a GM-CSF-induced increase in local proliferative activity by peritoneal macrophages. This increased activity declined at the age of 8-10 wk, in parallel with a change in the morphology of the transgenic macrophages and an increase in binucleate and multinucleate macrophages arising by cell fusion. This change in macrophage phenotype was restricted to the transgenic mice and may therefore be a consequence of continued overstimulation by GM-CSF.
REPORT ON THE USE OF SUCCINYL CHOLINE DICHLORIDE (A CURARE-LIKE DRUG) IN ELECTROCONVULSIVE THERAPY
Authors: B. F. MOSS, C. H. THIGPEN, W. P. ROBISON
Journal: American Journal of Psychiatry (1953)

Succinyl choline dichloride i.v. is a useful drug to produce muscular relaxation in patients receiving ECT who would otherwise be poor risks because of susceptibility to fractures and pre-existing fractures. It has also proved of value in treating severely disabled cardiac patients for whom even slight exertion may be dangerous. This drug is potent and effective, but ultra-short-acting, seldom lasting more than 5 minutes. Artificial respiration is easily and adequately performed by standard routine methods. Oxygenation can be maintained at levels superior to that of bed rest. No untoward effects have yet been observed in over 300 electric treatments.
Serum hepatitis delta virus RNA in patients with delta hepatitis and in liver graft recipients
Authors: Anna Linda Zignego, Frederic Dubois, Didier Samuel, Urania Georgopoulou, Michel Reynes, Paolo Gentilini, Alain Bismuth, Jean-Pierre Benhamou, Stephanos J. Hadziyannis, Henry Bismuth, Christian Bréchot
Journal: Journal of Hepatology (1990)
Positional Conservation of Clusters of Overlapping Promoter-Like Sequences in Enterobacterial Genomes
Authors: Araceli M Huerta, Julio Collado-Vides, M Pilar Francino
Journal: Molecular Biology and Evolution (2006)

The selective mechanisms operating in regulatory regions of bacterial genomes are poorly understood. We have previously shown that, in most bacterial genomes, regulatory regions contain high densities of sigma70 promoter-like signals that are significantly above the densities detected in nonregulatory genomic regions. In order to investigate the molecular evolutionary forces that operate in bacterial regulatory regions and how they affect the observed redundancy of promoter-like signals, we have undertaken a comparative analysis across the completely sequenced genomes of enteric gamma-proteobacteria. This analysis detects significant positional conservation of promoter-like signal clusters across enterics, some times in spite of strong primary sequence divergence. This suggests that the conservation of the nature and exact position of specific nucleotides is not necessarily the priority of selection for maintaining the transcriptional function in these bacteria. We have further characterized the structural conservation of the regulatory regions of dnaQ and crp across all enterics. These two regions differ in essentiality and mode of regulation, the regulation of crp being more complex and involving interactions with several transcription factors. This results in substantially different modes of evolution, with the dnaQ region appearing to evolve under stronger purifying selection and the crp region showing the likely effects of stabilizing selection for a complex pattern of gene expression. The higher flexibility of the crp region is consistent with the observed less conservation of global regulators in evolution. Patterns of regulatory evolution are also found to be markedly different in endosymbiotic bacteria, in a manner consistent with regulatory regions suffering some level of degradation, as has been observed for many other characters in these genomes. Therefore, the mode of evolution of bacterial regulatory regions appears to be highly dependent on both the lifestyle of the bacterium and the specific regulatory requirements of different genes. In fact, in many bacteria, the mode of evolution of genes requiring significant physiological adaptability in expression levels may follow patterns similar to those operating in the more complex regulatory regions of eukaryotic genomes.
A Proteasome Inhibitor, Bortezomib, Inhibits Breast Cancer Growth and Reduces Osteolysis by Downregulating Metastatic Genes
Authors: Marci D. Jones, Julie C. Liu, Thomas K. Barthel, Sadiq Hussain, Erik Lovria, Dengfeng Cheng, Jesse A. Schoonmaker, Sudhanshu Mulay, David C. Ayers, Mary L. Bouxsein, Gary S. Stein, Siddhartha Mukherjee, Jane B. Lian
Journal: Clinical Cancer Research (2010)

The incidence of bone metastasis in advanced breast cancer (BrCa) exceeds 70%. Bortezomib, a proteasome inhibitor used for the treatment of multiple myeloma, also promotes bone formation. We tested the hypothesis that proteasome inhibitors can ameliorate BrCa osteolytic disease.To address the potentially beneficial effect of bortezomib in reducing tumor growth in the skeleton and counteracting bone osteolysis, human MDA-MB-231 BrCa cells were injected into the tibia of mice to model bone tumor growth for in vivo assessment of treatment regimens before and after tumor growth.Controls exhibited tumor growth, destroying trabecular and cortical bone and invading muscle. Bortezomib treatment initiated following inoculation of tumor cells strikingly reduced tumor growth, restricted tumor cells mainly to the marrow cavity, and almost completely inhibited osteolysis in the bone microenvironment over a 3- to 4-week period as shown by [(18)F]fluorodeoxyglucose positron emission tomography, micro-computed tomography scanning, radiography, and histology. Thus, proteasome inhibition is effective in killing tumor cells within the bone. Pretreatment with bortezomib for 3 weeks before inoculation of tumor cells was also effective in reducing osteolysis. Our in vitro and in vivo studies indicate that mechanisms by which bortezomib inhibits tumor growth and reduces osteolysis result from inhibited cell proliferation, necrosis, and decreased expression of factors that promote BrCa tumor progression in bone.These findings provide a basis for a novel strategy to treat patients with BrCa osteolytic lesions, and represent an approach for protecting the entire skeleton from metastatic bone disease.
Diagnosis of a posterior mediastinal goitre via endobronchial ultrasound-guided transbronchial needle aspiration
Authors: V. Jeebun, S. Natu, R. Harrison
Journal: European Respiratory Journal (2009)

To the Editors :

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a rapidly developing diagnostic tool. Its utility as a minimally invasive and safe procedure in mediastinal node staging in lung cancer is defined and gaining widespread acceptance. The role of this procedure in the diagnosis of benign diseases is less clear. We report the first case of a posterior mediastinal intrathoracic goitre diagnosed with the aid of EBUS-TBNA.

A 46-yr-old female was referred to the outpatient chest clinic for further investigation of a superior mediastinal mass. She complained of a 4-month history of progressive shortness of breath on exertion. She denied any dysphagia. Examination was unremarkable. A chest radiograph showed a right superior mediastinal mass. Her thyroid function tests were within normal limits. Contrast-enhanced thoracic computed tomography revealed a large posterior mediastinal mass, containing areas of punctate calcification (fig. 1⇓). There was no associated mediastinal adenopathy and the lung parenchyma was normal. Histological confirmation was considered necessary to the planning of surgical …
The occurrence of graft-versus-host disease is the major predictive factor for response to donor lymphocyte infusions in multiple myeloma
Authors: Henk M. Lokhorst, Kalung Wu, Leo F. Verdonck, Laurens L. Laterveer, Niels W. C. J. van de Donk, Marinus H. J. van Oers, Jan J. Cornelissen, Anton V. Schattenberg
Journal: Blood (2004)
Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8α+ conventional dendritic cells
Authors: Brian T. Edelson, Wumesh KC, Richard Juang, Masako Kohyama, Loralyn A. Benoit, Paul A. Klekotka, Clara Moon, Jörn C. Albring, Wataru Ise, Drew G. Michael, Deepta Bhattacharya, Thaddeus S. Stappenbeck, Michael J. Holtzman, Sun-Sang J. Sung, Theresa L. Murphy, Kai Hildner, Kenneth M. Murphy
Journal: The Journal of Experimental Medicine (2010)

Although CD103-expressing dendritic cells (DCs) are widely present in nonlymphoid tissues, the transcription factors controlling their development and their relationship to other DC subsets remain unclear. Mice lacking the transcription factor Batf3 have a defect in the development of CD8α+ conventional DCs (cDCs) within lymphoid tissues. We demonstrate that Batf3−/− mice also lack CD103+CD11b− DCs in the lung, intestine, mesenteric lymph nodes (MLNs), dermis, and skin-draining lymph nodes. Notably, Batf3−/− mice displayed reduced priming of CD8 T cells after pulmonary Sendai virus infection, with increased pulmonary inflammation. In the MLNs and intestine, Batf3 deficiency resulted in the specific lack of CD103+CD11b− DCs, with the population of CD103+CD11b+ DCs remaining intact. Batf3−/− mice showed no evidence of spontaneous gastrointestinal inflammation and had a normal contact hypersensitivity (CHS) response, despite previous suggestions that CD103+ DCs were required for immune homeostasis in the gut and CHS. The relationship between CD8α+ cDCs and nonlymphoid CD103+ DCs implied by their shared dependence on Batf3 was further supported by similar patterns of gene expression and their shared developmental dependence on the transcription factor Irf8. These data provide evidence for a developmental relationship between lymphoid organ–resident CD8α+ cDCs and nonlymphoid CD103+ DCs.
Muscarinic Modulation of the Sodium-Calcium Exchanger in Heart Failure
Authors: Shao-kui Wei, Abdul M. Ruknudin, Matie Shou, John M. McCurley, Stephen U. Hanlon, Eric Elgin, Dan H. Schulze, Mark C.P. Haigney
Journal: Circulation (2007)

The Na-Ca exchanger (NCX) is a critical calcium efflux pathway in excitable cells, but little is known regarding its autonomic regulation.We investigated beta-adrenergic receptor and muscarinic receptor regulation of the cardiac NCX in control and heart failure (HF) conditions in atrially paced pigs. NCX current in myocytes from control swine hearts was significantly increased by isoproterenol, and this response was reversed by concurrent muscarinic receptor stimulation with the addition of carbachol, demonstrating "accentuated antagonism." Okadaic acid eliminated the inhibitory effect of carbachol on isoproterenol-stimulated NCX current, indicating that muscarinic receptor regulation operates via protein phosphatase-induced dephosphorylation. However, in myocytes from atrially paced tachycardia-induced HF pigs, the NCX current was significantly larger at baseline but less responsive to isoproterenol compared with controls, whereas carbachol failed to inhibit isoproterenol-stimulated NCX current, and 8-Br-cGMP did not restore muscarinic responsiveness. Protein phosphatase type 1 dialysis significantly reduced NCX current in failing but not control cells, consistent with NCX hyperphosphorylation in HF. Protein phosphatase type 1 levels associated with NCX were significantly depressed in HF pigs compared with control, and total phosphatase activity associated with NCX was significantly decreased.We conclude that the NCX is autonomically modulated, but HF reduces the level and activity of associated phosphatases; defective dephosphorylation then "locks" the exchanger in a highly active state.
A Copeptin-Based Classification of the Osmoregulatory Defects in the Syndrome of Inappropriate Antidiuresis
Authors: Wiebke Kristin Fenske, Mirjam Christ-Crain, Anna Hörning, Jessica Simet, Gabor Szinnai, Martin Fassnacht, Jonas Rutishauser, Daniel G. Bichet, Stefan Störk, Bruno Allolio
Journal: Journal of the American Society of Nephrology (2014)

Hyponatremia, the most frequent electrolyte disorder, is caused predominantly by the syndrome of inappropriate antidiuresis (SIAD). A comprehensive characterization of SIAD subtypes, defined by type of osmotic dysregulation, is lacking, but may aid in predicting therapeutic success. Here, we analyzed serial measurements of serum osmolality and serum sodium, plasma arginine vasopressin (AVP), and plasma copeptin concentrations from 50 patients with hyponatremia who underwent hypertonic saline infusion. A close correlation between copeptin concentrations and serum osmolality existed in 68 healthy controls, with a mean osmotic threshold±SD of 282±4 mOsM/kg H2O. Furthermore, saline-induced changes in copeptin concentrations correlated with changes in AVP concentrations in controls and patients. With use of copeptin concentration as a surrogate measure of AVP concentration, patients with SIAD could be grouped according to osmoregulatory defect: Ten percent of patients had grossly elevated copeptin concentrations independent of serum osmolality (type A); 14% had copeptin concentrations that increased linearly with rising serum osmolality but had abnormally low osmotic thresholds (type B); 44% had normal copeptin concentrations independent of osmolality (type C), and 12% had suppressed copeptin concentrations independent of osmolality (type D). A novel SIAD subtype discovered in 20% of patients was characterized by a linear decrease in copeptin concentrations with increasing serum osmolality (type E or "barostat reset"). In conclusion, a partial or complete loss of AVP osmoregulation occurs in patients with SIAD. Although the mechanisms underlying osmoregulatory defects in individual patients are presumably diverse, we hypothesize that treatment responses and patient outcomes will vary according to SIAD subtype.
Estrogen Therapy and the Risk of Breast Cancer-Reply
Authors: Karen E. Steinberg
Journal: JAMA (1993)

<h3>In Reply.</h3> —Dr Meyer discusses the implication that increased parenchymal density of breast tissue associated with HRT will obscure occult malignant masses. This is a legitimate concern that should be taken into account by women who are at high risk for breast cancer, who are on HRT, and who have increased breast density. Meyer speculates that increased density, when focal, may presage the development of a malignant process. Since he saw that densities regressed soon after HRT was terminated, one can infer that the hormones may promote tumor growth. This inference may be supported by recent evidence from a large epidemiologic study that showed that current use of HRT was associated with a small but significant increase in risk of breast cancer.<sup>1</sup>Meyer also wonders why the increase in parenchymal density was only seen in 24% of women on HRT. That the increase occurred in a minority of the
ROLE OF THE THYMUS IN IMMUNE REACTIONS IN RATS
Authors: Byron H. Waksman, Barry G. Arnason, Branislav D. Janković
Journal: The Journal of Experimental Medicine (1962)

In rats thymectomized at birth, there was a profound depletion of small lymphocytes in various lymphatic organs. In the spleen, these cells were completely lacking from the Malpighian bodies and splenic white pulp. Empty reticular structures remained surrounding the white pulp arterioles. In the lymph nodes, large masses and nodules of small lymphocytes (primary lymphoid nodules) were either markedly depleted or absent, as were the zones of these cells normally surrounding germinal centers. In both spleen and nodes, germinal centers appeared normal in size, number, and cellular make-up; and plasma cells were found in normal or even increased number in their customary position. Rats which in spite of thymectomy developed intense Arthus or delayed reactivity showed incomplete depletion of the lymphoid tissue. It is concluded that small lymphocytes of the spleen and lymph nodes may come, in large part, directly from the thymus and are not derived from medium and large lymphocytes of the germinal centers. It is suggested that there may be a second population of small lymphocytes whose function is unrelated to the thymus lymphocytes.
Progression of Retinopathy During Pregnancy in Type 1 Diabetic Women Treated With Insulin Lispro
Authors: Sirpa Loukovaara, Ilkka Immonen, Kari Atle Teramo, Risto Kaaja
Journal: Diabetes Care (2003)

OBJECTIVE— To evaluate the progression of retinopathy during pregnancy and postpartum in (insulin-dependent) women with type 1 diabetes treated with insulin lispro or with regular human insulin. RESEARCH DESIGN AND METHODS— A prospective open study of 69 pregnant women with diabetes was performed. A total of 36 of the women were treated with insulin lispro (lispro group) and 33 were treated with conventional short-acting human insulin (regular insulin group). The retinopathy level was estimated by color fundus photography every trimester and postpartum. Glycemic control during pregnancy, hypoglycemia (blood glucose level &amp;lt;3 mmol/l) in 24-h glucose profile, blood pressure, and proteinuria were registered. RESULTS— HbA1c values were similar at baseline in the first trimester but thereafter were lower in the lispro group than in the regular insulin group throughout pregnancy (P = 0.022, repeated-measures ANOVA). The number of hypoglycemic episodes did not differ between the treatment groups. In multivariable logistic regression analysis with retinopathy severity (Diabetes Control and Complications Trial level) in the third trimester as the dependent variable, only nulliparity qualified as a predictor in the model [Exp(B) = 4.0, 95% CI 1.1–13.7, P = 0.030]. Factors such as duration of diabetes, type of insulin used, mean HbA1c level throughout pregnancy, blood pressure (systolic or diastolic), preeclampsia in the current pregnancy, smoking, or prepregnancy planning did not explain the retinopathy progression. CONCLUSIONS— Insulin lispro improves glycemic control during diabetic pregnancy compared with regular insulin with no adverse impact on progression of diabetic retinopathy.