tbuckley/cabot-search huggingface dataset:
LTBI: latent tuberculosis infection or lasting immune responses to M. tuberculosis? A TBNET consensus statement
Authors: U. Mack, G. B. Migliori, M. Sester, H. L. Rieder, S. Ehlers, D. Goletti, A. Bossink, K. Magdorf, C. Hölscher, B. Kampmann, S. M. Arend, A. Detjen, G. Bothamley, J. P. Zellweger, H. Milburn, R. Diel, P. Ravn, F. Cobelens, P. J. Cardona, B. Kan, I. Solovic, R. Duarte, D. M. Cirillo
Journal: European Respiratory Journal (2009)

Tuberculosis control relies on the identification and preventive treatment of individuals who are latently infected with Mycobacterium tuberculosis . However, direct identification of latent tuberculosis infection is not possible. The diagnostic tests used to identify individuals latently infected with M. tuberculosis , the in vivo tuberculin skin test and the ex vivo interferon-γ release assays (IGRAs), are designed to identify an adaptive immune response against, but not necessarily a latent infection with, M. tuberculosis . The proportion of individuals who truly remain infected with M. tuberculosis after tuberculin skin test or IGRA conversion is unknown. It is also uncertain how long adaptive immune responses towards mycobacterial antigens persist in the absence of live mycobacteria. Clinical management and public healthcare policies for preventive chemotherapy against tuberculosis could be improved, if we were to gain a better understanding on M. tuberculosis latency and reactivation. This statement by the TBNET summarises knowledge and limitations of the currently available tests used in adults and children for the diagnosis of latent tuberculosis infection. In summary, the main issue regarding testing is to restrict it to those who are known to be at higher risk of developing tuberculosis and who are willing to accept preventive chemotherapy.
THE MECHANISM OF THE INFLAMMATORY PROCESS
Authors: Harold A. Abramson
Journal: The Journal of Experimental Medicine (1927)

1. The velocity of cataphoretic migration of blood cells in plasma and serum is proportional to the potential drop applied. 2. The cataphoretic velocity of red cells, polymorphonuclear leucocytes, small lymphocytes, and large lymphocytes is described for serum and plasma. 3. The relation between the electrokinetic potential of white blood cells and the differences of potential probably existing in injured tissues are correlated quantitatively. 4. This correlation suggests that migration of leucocytes to a point of injury is, in part, dependent upon the electromotive forces at play in the tissues.
Association of Environmental Cadmium Exposure with Pediatric Dental Caries
Authors: Manish Arora, Jennifer Weuve, Joel Schwartz, Robert O. Wright
Journal: Environmental Health Perspectives (2008)

Although animal experiments have shown that cadmium exposure results in severe dental caries, limited epidemiologic data are available on this issue.We aimed to examine the relationship between environmental cadmium exposure and dental caries in children 6-12 years of age.We analyzed cross-sectional data, including urine cadmium concentrations and counts of decayed or filled tooth surfaces, from the Third National Health and Nutrition Examination Survey. We used logistic and zero-inflated negative binomial (ZINB) regression to estimate the association between urine cadmium concentrations and caries experience, adjusting these analyses for potential confounders including environmental tobacco smoke (ETS).Urine cadmium concentrations ranged from 0.01 to 3.38 ng/mL. Approximately 56% of children had experienced caries in their deciduous teeth, and almost 30% had been affected by caries in their permanent dentition. An interquartile range (IQR) increase in creatinine-corrected cadmium concentrations (0.21 microg/g creatinine) corresponded to a 16% increase in the odds of having experienced caries in deciduous teeth [prevalence odds ratio (OR)=1.16; 95% confidence interval (CI), 0.96-1.40]. This association was statistically significant in children with low ETS exposure (prevalence OR=1.30; 95% CI, 1.01-1.67). The results from the ZINB regression indicated that, among children with any caries history in their deciduous teeth, an IQR increase in cadmium was associated with 17% increase in the number of decayed or filled surfaces. We observed no association between cadmium and caries experience in permanent teeth.Environmental cadmium exposure may be associated with increased risk of dental caries in deciduous teeth of children.
Patterns of Microsatellite Variability Among X Chromosomes and Autosomes Indicate a High Frequency of Beneficial Mutations in Non-African D. simulans
Authors: Gerhard Schöfl, Christian Schlötterer
Journal: Molecular Biology and Evolution (2004)

We analyzed microsatellite variability at 42 X-linked and 39 autosomal loci from African and European populations of Drosophila simulans. The African D. simulans harbored significantly more microsatellite variability than the European flies. In the European population, X-linked polymorphism was more reduced than autosomal variation, whereas there was no significant difference between chromosomes in the African population. Previous studies also observed a similar pattern but failed to distinguish between a demographic event and a selection scenario. We performed extensive computer simulations using a wide range of demographic scenarios to distinguish between the two hypotheses. Approximate summary likelihood estimates differed dramatically among X chromosomes and autosomes. Furthermore, our experimental data showed a surplus of X-linked microsatellites with a significantly reduced variability in non-African D. simulans. We conclude that our data are not compatible with a neutral scenario. Thus, the reduced variability at X-linked loci is most likely caused by selective sweeps associated with the out-of-Africa habitat expansion of D. simulans.
Endocrinological disturbances in chronic obstructive pulmonary disease
Authors: E.C. Creutzberg, R. Casaburi
Journal: European Respiratory Journal (2003)

In this overview, the available literature on endocrinological disturbances in chronic obstructive pulmonary disease (COPD) is reviewed, with stress on growth hormone/insulin-like growth factor I (IGF-I), thyroid hormone and the anabolic steroids. In COPD, little is known about circulating growth hormone or IGF-I concentrations. Some authors find a decrease in growth hormone or IGF-I, others an increase. An increase of growth hormone might reflect a nonspecific response of the body to stress (for instance, hypoxaemia). Until now, only one controlled study on growth hormone supplementation has been published, which however did not reveal any functional benefits. Before growth hormone supplementation can be advised as part of the treatment in COPD, further controlled studies must be performed to investigate its functional efficacy. The prevalence of thyroid dysfunction in COPD and its role in pulmonary cachexia has not been extensively studied. So far, there is no evidence that thyroid function is consistently altered in COPD, except perhaps in a subgroup of patients with severe hypoxaemia. Further research is required to more extensively study the underlying mechanisms and consequences of disturbed thyroid function in this subgroup of COPD patients. A few studies have reported the results of anabolic steroid supplementation in chronic obstructive pulmonary disease. Although some studies have discerned that low circulating levels of testosterone are common in males with chronic obstructive pulmonary disease, little is known about the prevalence, the underlying causes or functional consequences of hypogonadism in these patients. The use of systemic glucocorticosteroids and an influence of the systemic inflammatory response have been suggested as contributing to low testosterone levels. It can be hypothesised that low anabolic hormones will reduce muscle mass and eventually result in a diminished muscle function. Further evidence is required before testosterone replacement can be recommended for males with chronic obstructive pulmonary disease.
Malaria: progress, perils, and prospects for eradication
Authors: Brian M. Greenwood, David A. Fidock, Dennis E. Kyle, Stefan H.I. Kappe, Pedro L. Alonso, Frank H. Collins, Patrick E. Duffy
Journal: Journal of Clinical Investigation (2008)

There are still approximately 500 million cases of malaria and 1 million deaths from malaria each year. Yet recently, malaria incidence has been dramatically reduced in some parts of Africa by increasing deployment of anti-mosquito measures and new artemisinin-containing treatments, prompting renewed calls for global eradication. However, treatment and mosquito control currently depend on too few compounds and thus are vulnerable to the emergence of compound-resistant parasites and mosquitoes. As discussed in this Review, new drugs, vaccines, and insecticides, as well as improved surveillance methods, are research priorities. Insights into parasite biology, human immunity, and vector behavior will guide efforts to translate parasite and mosquito genome sequences into novel interventions.
Complement Activated by Chimeric Anti–Folate Receptor Antibodies Is an Efficient Effector System to Control Ovarian Carcinoma
Authors: Paolo Macor, Delia Mezzanzanica, Chiara Cossetti, Paola Alberti, Mariangela Figini, Silvana Canevari, Francesco Tedesco
Journal: Cancer Research (2006)

Abstract Two chimeric monoclonal antibodies (mAb), cMOV18 and cMOV19, recognizing distinct epitopes of folate receptor highly expressed on epithelial ovarian cancer (EOC) cells were analyzed for their ability to activate complement (C) as a means to enhance their antitumor activity. The individual cMOVs failed to activate C on six EOC cell lines as documented by the marginal deposition of C components and the negligible C-dependent cytotoxicity (CDC). Conversely, the mixture of cMOVs was more effective, although the percentage of cell killing did not exceed 25%. Fluorescence-activated cell sorting analysis of EOC cells for surface expression of the membrane C regulatory proteins (mCRP) revealed high levels of CD46, variable expression of CD59, and absence of CD55. This finding was confirmed in tumor tissue specimens obtained from advanced-stage EOC patients and analyzed for the expression of mCRPs mRNA using a cDNA microarray and for the presence of proteins by immunohistochemistry. Incubation of EOC cells with neutralizing mAbs to CD46 and CD59 led to a significant increase in the CDC from 10% - 20% to 45% - 50%. The relative contribution of antibody-dependent cell cytoxicity (ADCC) and C-dependent killing of two EOC cell lines induced by the mixture of cMOV18 and cMOV19 was about 15% and 25% - 35%, respectively, bringing the total killing to about 40% - 50%. This value increased to 60% - 70% after neutralization of CD46 and CD59 without an appreciable change of ADCC. These results suggest that C is the major contributor to the killing of EOC cells induced by the mixture of cMOV18 and cMOV19. (Cancer Res 2006; 66(7): 3876-83)
Systematic Analysis of Breast Cancer Morphology Uncovers Stromal Features Associated with Survival
Authors: Andrew H. Beck, Ankur R. Sangoi, Samuel Leung, Robert J. Marinelli, Torsten O. Nielsen, Marc J. van de Vijver, Robert B. West, Matt van de Rijn, Daphne Koller
Journal: Science Translational Medicine (2011)

The morphological interpretation of histologic sections forms the basis of diagnosis and prognostication for cancer. In the diagnosis of carcinomas, pathologists perform a semiquantitative analysis of a small set of morphological features to determine the cancer's histologic grade. Physicians use histologic grade to inform their assessment of a carcinoma's aggressiveness and a patient's prognosis. Nevertheless, the determination of grade in breast cancer examines only a small set of morphological features of breast cancer epithelial cells, which has been largely unchanged since the 1920s. A comprehensive analysis of automatically quantitated morphological features could identify characteristics of prognostic relevance and provide an accurate and reproducible means for assessing prognosis from microscopic image data. We developed the C-Path (Computational Pathologist) system to measure a rich quantitative feature set from the breast cancer epithelium and stroma (6642 features), including both standard morphometric descriptors of image objects and higher-level contextual, relational, and global image features. These measurements were used to construct a prognostic model. We applied the C-Path system to microscopic images from two independent cohorts of breast cancer patients [from the Netherlands Cancer Institute (NKI) cohort, n = 248, and the Vancouver General Hospital (VGH) cohort, n = 328]. The prognostic model score generated by our system was strongly associated with overall survival in both the NKI and the VGH cohorts (both log-rank P ≤ 0.001). This association was independent of clinical, pathological, and molecular factors. Three stromal features were significantly associated with survival, and this association was stronger than the association of survival with epithelial characteristics in the model. These findings implicate stromal morphologic structure as a previously unrecognized prognostic determinant for breast cancer.
FIZZ1/RELMα, a Novel Hypoxia-Induced Mitogenic Factor in Lung With Vasoconstrictive and Angiogenic Properties
Authors: Xingwu Teng, Dechun Li, Hunter C. Champion, Roger A. Johns
Journal: Circulation Research (2003)

In a mouse chronic hypoxia model of pulmonary hypertension, we discovered a novel hypoxia-inducible gene in lung, FIZZ1/RELMalpha, first through a cDNA array analysis and then confirmed by RT-PCR. Western blot and immunohistochemistry revealed that its expression was induced by hypoxia only in lung. The hypoxia-upregulated gene expression was located in the pulmonary vasculature, bronchial epithelial cells, and type II pneumocytes. 3H-thymidine incorporation demonstrated that the recombinant protein stimulated rat pulmonary microvascular smooth muscle cell (RPSM) proliferation dose-dependently ranging from 3.3x10(-9) to 3.3x10(-8) mol/L. Therefore, we renamed this gene as hypoxia-induced mitogenic factor (HIMF). HIMF strongly activated Akt phosphorylation. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (10 micromol/L) inhibited HIMF-activated Akt phosphorylation. It also inhibited HIMF-stimulated RPSM proliferation. Thus, the PI3K/Akt pathway, at least in part, mediates the proliferative effect of HIMF. Further studies showed that HIMF had angiogenic and vasoconstrictive properties. HIMF increased pulmonary arterial pressure and vascular resistance more potently than either endothelin-1 or angiotensin II.
Corticosteroid effects on cell signalling
Authors: P. J. Barnes
Journal: European Respiratory Journal (2006)

Corticosteroids are the most effective anti-inflammatory therapy for asthma. Inflammation in asthma is characterised by the increased expression of multiple inflammatory genes regulated by pro-inflammatory transcription factors, such as nuclear factor-κB and activator protein-1, which bind to and activate coactivator molecules that acetylate core histones and switch on gene transcription. Corticosteroids suppress the multiple inflammatory genes that are activated in asthmatic airways, mainly by reversing histone acetylation of activated inflammatory genes through binding of glucocorticoid receptors to coactivators and recruitment of histone deacetylase 2 to the activated transcription complex. Activated glucocorticoid receptors also bind to recognition sites in the promoters of certain genes in order to activate their transcription, resulting in secretion of anti-inflammatory proteins, such as mitogen-activated protein kinase phosphatase-1, which inhibits mitogen-activated protein kinase signalling pathways. Glucocorticoid receptors may also interact with other recognition sites to inhibit transcription, for example of several genes linked to their side-effects. In some patients with steroid-resistant asthma, there are abnormalities in glucocorticoid receptor signalling pathways. In chronic obstructive pulmonary disease patients and asthmatic patients who smoke, histone deacetylase 2 is markedly impaired as a result of oxidative/nitrative stress, and so inflammation is resistant to the anti-inflammatory effects of corticosteroids. The therapeutic implications of these new findings are discussed.
The Transcriptional Repressor Gfi1 Affects Development of Early, Uncommitted c-Kit+ T Cell Progenitors and CD4/CD8 Lineage Decision in the Thymus
Authors: Raif Yücel, Holger Karsunky, Ludger Klein-Hitpass, Tarik Möröy
Journal: The Journal of Experimental Medicine (2003)

In the thymus, several steps of proliferative expansion and selection coordinate the maturation of precursors into antigen-specific T cells. Here we identify the transcriptional repressor Gfi1 as an important regulator of this maturation process. Mice lacking Gfi1 show reduced thymic cellularity due to an increased cell death rate, lack of proliferation, and a differentiation block in the very early uncommitted CD4−/CD8−/c-Kit+ cytokine-dependent T cell progenitors that have not yet initiated VDJ recombination. In addition, Gfi1-deficient mice show increased major histocompatibility complex class I–restricted positive selection and develop significantly more CD8+ cells suggesting a requirement of Gfi1 for a correct CD4/CD8 lineage decision. Absence of Gfi1 correlates with high level expression of the genes for lung Krüppel-like factor (LKLF), inhibitor of DNA binding (Id)1 and Id2, suggesting the existence of new regulatory pathways in pre-T cell development and thymic selection in which Gfi1 acts upstream of LKLF as well as the E-proteins, which are negatively regulated by Id1 and Id2.
Increasing Potential of HER3 Signaling in Colon Cancer Progression and Therapy
Authors: Christian Gespach
Journal: Clinical Cancer Research (2011)

HER3 protein levels at the cancer cell plasma membrane are directly correlated with reduced survival in patients with colorectal cancer. In colorectal cancer cells, HER3 blockade restricted cellular growth (G(2)-M arrest), survival, migration, and invasion, and potentiated the chemotherapeutic effect of 5-FU, supporting strategies that target HER3 in subsets of patients with colorectal cancer.
Preliminary Animal and Clinical Experiences Using an Electromechanical Endocardial Mapping Procedure to Distinguish Infarcted From Healthy Myocardium
Authors: Ran Kornowski, Mun K. Hong, Lior Gepstein, Steven Goldstein, Samer Ellahham, Shlomo A. Ben-Haim, Martin B. Leon
Journal: Circulation (1998)

A catheter-based left ventricular (LV) endocardial mapping procedure using electromagnetic field energy for positioning of the catheter tip was designed to acquire simultaneous measurements of endocardial voltage potentials and myocardial contractility. We investigated such a mapping system to distinguish between infarcted and normal myocardium in an animal infarction model and in patients with coronary artery disease.Measurements of LV endocardial unipolar (UP) and bipolar (BP) voltages and local endocardial shortening were derived from dogs at baseline (n=12), at 24 hours (n=6), and at 3 weeks (n=6) after occlusion of the left anterior descending coronary artery. Also, 12 patients with prior myocardial infarction (MI) and 12 control patients underwent the LV endocardial mapping study for assessment of electromechanical function in infarcted versus healthy myocardial regions. In the canine model, a significant decrease in voltage potentials was noted in the MI zone at 24 hours (UP, 42. 8+/-9.6 to 29.1+/-12.2 mV, P=0.007; BP, 11.6+/-2.3 to 4.9+/-1.2 mV, P<0.0001) and at 3 weeks (UP, 41.0+/-8.9 to 13.9+/-3.9 mV, P<0.0001; BP, 11.2+/-2.8 to 2.4+/-0.4 mV, P<0.0001). No change in voltage was noted in zones remote from MI. In patients with prior MI, the average voltage was 7.2+/-2.7 mV (UP)/1.4+/-0.7 mV (BP) in MI regions, 17.8+/-4.6 mV (UP)/4.5+/-1.1 mV (BP) in healthy zones remote from MI, and 19.7+/-4.4 mV (UP)/5.8+/-1.0 mV (BP) in control patients without prior MI (P<0.001 for MI values versus remote zones or control patients). In the canine model and patients, local endocardial shortening was significantly impaired in MI zones compared with controls.These preliminary data suggest that infarcted myocardium could be accurately diagnosed and distinguished from healthy myocardium by a reduction in both electrical voltage and mechanical activity. Such a diagnostic electromechanical mapping study might be clinically useful for accurate assessment of myocardial function and viability.
Outcomes of concurrent chemoradiotherapy in patients with stage III non-small-cell lung cancer and significant comorbidity
Authors: E.C.J. Phernambucq, F.O.B. Spoelstra, W.F.A.R. Verbakel, P.E. Postmus, C.F. Melissant, K.I. Maassen van den Brink, V. Frings, P.M. van de Ven, E.F. Smit, S. Senan
Journal: Annals of Oncology (2010)
Chronic Hyponatremic Encephalopathy in Postmenopausal Women
Authors: J C Ayus, A I Arieff
Journal: JAMA (1999)

Chronic hyponatremia in postmenopausal women is a common clinical problem often viewed as benign. Fluid restriction is usually the recommended therapy, largely because the extent of morbidity is unknown and because it has been postulated that intravenous (IV) sodium chloride may cause brain damage.To compare IV sodium chloride with fluid restriction in the treatment of postmenopausal women with chronic symptomatic hyponatremia.Nonrandomized prospective study.Two university medical centers and affiliated community hospitals.A total of 53 postmenopausal women with chronic symptomatic hyponatremia (chronic plasma sodium <130 mmol/L in the presence of central nervous system manifestations) treated consecutively from 1988-1997 and followed up for 1 year. The mean (SD) age of the patients was 62 (11) years.The therapeutic interventions were IV sodium chloride before respiratory insufficiency (n = 17), IV sodium chloride after respiratory insufficiency (n = 22), and fluid restriction only (n = 14).Morbidity and neurological outcome at 4 months or longer as assessed by cerebral performance category (CPC) in relation to the therapy, initial plasma sodium level, and rate of correction.Chronic symptomatic hyponatremia (mean [SD] sodium level 111 [12] mmol/L) was present for 5.2 [4.5] days. Death or major morbidity occurred in 44 (83%) of 53 patients, including 10 with orthopedic injury. Twelve patients had hypoxemia (PO2 = 63 [25] mm Hg) and cerebral edema. Among patients who received IV sodium chloride before respiratory insufficiency, plasma sodium levels were increased by 22 (10) mmol/L in 35 hours and patients had a CPC of 1.0 (normal or slight disability). Among patients who received IV sodium chloride after respiratory insufficiency, plasma sodium levels were increased by 30 (6) mmol/L in 41 hours and patients had a CPC of 3.0 (1.2) (severe disability). Among patients who had fluid restriction only, plasma sodium levels were increased by 3 (2) mmol/L in 41 hours and patients had a CPC of 4.6 (0.7) (4 = persistent vegetative state; 5 = death). The outcomes did not correlate with either the initial plasma sodium level (r=0.05, P>.12) or the rate of correction (r=0.31, P>.10).Chronic symptomatic hyponatremia in postmenopausal women can be associated with major morbidity and mortality. Therapy with IV sodium chloride was associated with significantly better outcomes than fluid restriction.