tbuckley/cabot-search huggingface dataset:
Functional single nucleotide polymorphisms of the CCL5 gene and nonemphysematous phenotype in COPD patients
Authors: N. Hizawa, H. Makita, Y. Nasuhara, M. Hasegawa, K. Nagai, Y. Ito, T. Betsuyaku, S. Konno, M. Nishimura
Journal: European Respiratory Journal (2008)

It was previously reported that the gain-of-function -28 guanine allele of the promoter single nucleotide polymorphism (SNP; cytosine to guanine substitution of nucleotide -28 (-28C&gt;G)) in the CC chemokine ligand 5 gene ( CCL5 ) was associated with susceptibility to late-onset asthma in patients who developed asthma at age ≥40 yrs. The clinical diagnosis of chronic obstructive pulmonary disease (COPD) includes emphysema and small airway disease, and upregulation of CCL5 has been described in the airways of patients with COPD. It was hypothesised that CCL5 has a genetic impact upon the variable expression of emphysema in patients with COPD. Patients with COPD were studied (n = 267). All of the patients underwent pulmonary high-resolution computed tomography (CT), and visual scoring (CT score) was performed to determine emphysema severity. Three SNPs of CCL5 were genotyped, including -403G&gt;A, -28C&gt;G and 375T&gt;C. A significant difference was found in CT score according to CCL5 genotype; the -28G allele was inversely associated with CT score. When the analysis was confined to 180 patients with bronchial reversibility of &lt;15%, even stronger evidence for this association was noted. Functional single nucleotide polymorphisms in the CC chemokine ligand 5 gene were associated with milder emphysema. Together with previous findings, the present study may identify the CC chemokine ligand 5 gene as part of a common pathway in the pathogenesis of late-onset asthma and chronic obstructive pulmonary disease with milder emphysema.
Eye diseases in sleep related breathing disorders
Authors: Yavuz Selim Intepe, Hasan Ali Bayhan, Seray Aslan Bayhan, Canan Gurdal
Journal: European Respiratory Journal (2014)

Introduction:The aim of this study is to determine diseases of the eye found in patients with sleep related breathing disorders.  Aim:Sleep related breathing disorders are defined as disordered respiration during sleep.There is episodes of upper airway obstruction during sleep causing repetitive hypoxemia and sleep fragmentation.Studies in recent time show a relationship between sleep disorders and eye diseases.Its tought that pathophysiology due to hypoxia arising during apnea episodes can be reason to ophtalmologic disorders.  Methods:This prospective study was conducted between january and september 2013.Patients who have major symptoms of sleep related breating disordes underwent polysomnography.These patients have detailed ophthalmic examination.  Results:In this syudy 143 patients are taken,100 were with obstructive sleep apnea syndrome and 43 were normal according to apnea-hypopnea index.Mean age of patient group was 50,25±13,87 years and control group was 51,11±9,42 years. There was not difference between groups for gender.In patients group 15 have glaucoma,18 dry eye,11 floppy eye lid and 1 keratoconus,11 suspect keratoconus and 1 ischemic optic neuropathy.In control group 4 patients have glaucoma,2 dry eye,2 floppy eye lid,5 suspect keratoconus and none have keratoconus. There was statistically difference between patient and control groups for dry eye and floppy eye lid (p 0,05)  Conclusions :Patients with osas could be asked for eye diseases symptoms and sent to ophthalmologist for examination after polysomnography results. Our results show that there is increase risk for dry eye and floppy eye lid for osas patients.
Pathophysiological Role of Angiotensin II Type 2 Receptor in Cardiovascular and Renal Diseases
Authors: Hiroaki Matsubara
Journal: Circulation Research (1998)

Abstract —Since the discovery of nonpeptidic ligands, the receptors for angiotensin (Ang) II have been classified into 2 subtypes (Ang II type 1 receptor [AT 1 -R] and Ang II type 2 receptor [AT 2 -R]). AT 1 -R mediates most of the cardiovascular actions of Ang II. AT 2 -R is expressed at very high levels in the developing fetus. Its expression is very low in the cardiovascular system of the adult. The expression of AT 2 -R can be modulated by pathological states associated with tissue remodeling or inflammation. In failing hearts or neointima formation after vascular injury, AT 2 -R is reexpressed in cells proliferating in interstitial regions or neointima and exerts an inhibitory effect on Ang II-induced mitogen signals or synthesis of extracellular matrix proteins, resulting in attenuation of the tissue remodeling. An extreme form of cell growth inhibition ends in programmed cell death, and this process, which is initiated by the withdrawal of growth factors, is also enhanced by AT 2 -R. Cardiac myocyte- or vascular smooth muscle–specific mice that overexpress AT 2 -R display an inhibition of Ang II-induced chronotropic or pressor actions, suggesting the role of AT 2 -R on the activity of cardiac pacemaker cells and the maintenance of vascular resistance. AT 2 -R also activates the kinin/nitric oxide/cGMP system in the cardiovascular and renal systems, resulting in AT 2 -R–mediated cardioprotection, vasodilation, and pressure natriuresis. These effects, transmitted by AT 2 -R, are mainly exerted by stimulation of protein tyrosine or serine/threonine phosphatases in a Gi protein–dependent manner. The expression level of AT 2 -R is much higher in human hearts than in rodent hearts, and the AT 2 -R–mediated actions are likely enhanced, especially by clinical application of AT 1 -R antagonists. Thus, in this review, the regulation of AT 2 -R expression, its cellular localization, its pathological role in cardiovascular and kidney diseases, and pharmacotherapeutic effects of AT 2 -R stimulation are discussed.
Genome-Wide Promoter Analysis of the <i>SOX4</i> Transcriptional Network in Prostate Cancer Cells
Authors: Christopher D. Scharer, Colleen D. McCabe, Mohamed Ali-Seyed, Michael F. Berger, Martha L. Bulyk, Carlos S. Moreno
Journal: Cancer Research (2009)

Abstract SOX4 is a critical developmental transcription factor in vertebrates and is required for precise differentiation and proliferation in multiple tissues. In addition, SOX4 is overexpressed in many human malignancies, but the exact role of SOX4 in cancer progression is not well understood. Here, we have identified the direct transcriptional targets of SOX4 using a combination of genome-wide localization chromatin immunoprecipitation–chip analysis and transient overexpression followed by expression profiling in a prostate cancer model cell line. We have also used protein-binding microarrays to derive a novel SOX4-specific position-weight matrix and determined that SOX4 binding sites are enriched in SOX4-bound promoter regions. Direct transcriptional targets of SOX4 include several key cellular regulators, such as EGFR, HSP70, Tenascin C, Frizzled-5, Patched-1, and Delta-like 1. We also show that SOX4 targets 23 transcription factors, such as MLL, FOXA1, ZNF281, and NKX3-1. In addition, SOX4 directly regulates expression of three components of the RNA-induced silencing complex, namely Dicer, Argonaute 1, and RNA Helicase A. These data provide new insights into how SOX4 affects developmental signaling pathways and how these changes may influence cancer progression via regulation of gene networks involved in microRNA processing, transcriptional regulation, the TGFβ, Wnt, Hedgehog, and Notch pathways, growth factor signaling, and tumor metastasis. [Cancer Res 2009;69(2):709–17]
Impact of Age, Sex, and Comorbidity on Cancer Therapy and Disease Progression
Authors: Sumanta Kumar Pal, Arti Hurria
Journal: Journal of Clinical Oncology (2010)

A theme of personalized medicine was highlighted at the 2009 Annual Meeting of the American Society of Clinical Oncology. To this end, the current review focuses on the impact of host characteristics (such as age, sex, and comorbidity) as they pertain to cancer biology, treatment efficacy, and tolerance. Increasing age is associated with complex changes in physiology, including alterations in renal and hepatic function, and decreased bone marrow reserve. These may in turn result in alterations in pharmacokinetics and toxicity related to many commonly used anticancer agents. Using tools, such as the geriatric assessment, may help to elucidate the physiologic age of the patient as opposed to the chronologic age. Increasing age is paralleled by an increase in comorbidity, and comorbidity may have independent prognostic implications and substantially impact medical decision making in the patient with cancer. Numerous biologic ties between cancer and comorbidity exist, one example being an association of diabetes with an increased risk of disease recurrence and mortality in the setting of colon cancer. Biologic features can also vary by sex; several biomarkers with either prognostic or predictive value (ie, excisionrepair cross-complementation group 1 expression, epidermal growth factor receptor mutation, or dihydropyrimidine dehydrogenase polymorphism) may differentiate efficacy or toxicity in males and females. Taken together, age, sex, and comorbidity each encompass a complex array of physiologic and molecular variations that may each aid in personalizing care for the patient with cancer.
Rapid monocyte kinetics in acute myocardial infarction are sustained by extramedullary monocytopoiesis
Authors: Florian Leuschner, Philipp J. Rauch, Takuya Ueno, Rostic Gorbatov, Brett Marinelli, Won Woo Lee, Partha Dutta, Ying Wei, Clinton Robbins, Yoshiko Iwamoto, Brena Sena, Aleksey Chudnovskiy, Peter Panizzi, Edmund Keliher, John M. Higgins, Peter Libby, Michael A. Moskowitz, Mikael J. Pittet, Filip K. Swirski, Ralph Weissleder, Matthias Nahrendorf
Journal: The Journal of Experimental Medicine (2012)

Monocytes (Mo) and macrophages (MΦ) are emerging therapeutic targets in malignant, cardiovascular, and autoimmune disorders. Targeting of Mo/MΦ and their effector functions without compromising innate immunity’s critical defense mechanisms first requires addressing gaps in knowledge about the life cycle of these cells. Here we studied the source, tissue kinetics, and clearance of Mo/MΦ in murine myocardial infarction, a model of acute inflammation after ischemic injury. We found that a) Mo tissue residence time was surprisingly short (20 h); b) Mo recruitment rates were consistently high even days after initiation of inflammation; c) the sustained need of newly made Mo was fostered by extramedullary monocytopoiesis in the spleen; d) splenic monocytopoiesis was regulated by IL-1β; and e) the balance of cell recruitment and local death shifted during resolution of inflammation. Depending on the experimental approach, we measured a 24 h Mo/MΦ exit rate from infarct tissue between 5 and 13% of the tissue cell population. Exited cells were most numerous in the blood, liver, and spleen. Abrogation of extramedullary monocytopoiesis proved deleterious for infarct healing and accelerated the evolution of heart failure. We also detected rapid Mo kinetics in mice with stroke. These findings expand our knowledge of Mo/MΦ flux in acute inflammation and provide the groundwork for novel anti-inflammatory strategies for treating heart failure.
Lupus erythematosus profundus: a cutaneous marker for a distinct clinical subset?
Authors: T. WATANABE, T. TSUCHIDA
Journal: British Journal of Dermatology (1996)

Sixteen patients with histologically confirmed lupus erythematosus profundus were followed for a decade (on average). At the initial examination, two of 16 (12%) patients fulfilled the 1982 American Rheumatism Association (ARA) criteria for systemic lupus erythematosus (SLE). During the period of observation, SLE developed in another two (12%) patients, both of whom developed a malar rash. The remaining 12 (75%) patients never met the criteria for SLE. Four of the 16 (25%) had no extracutaneous manifestation. In conclusion, most patients with lupus erythematosus profundus have a relatively mild disease course, although a few develop systemic abnormalities and have abnormal laboratory findings.
Eating Disorders and Risk of Death
Authors: Scott Crow
Journal: American Journal of Psychiatry (2013)

Eating disorders are common and well known to be associated with a variety of medical complications and elevated risk of mortality.For anorexia nervosa, these associations have been known as far back as some of the earliest descriptions of the illness.For example, in 1689, Richard Morton (1) described two cases of what in retrospect appear to have been anorexia nervosa; one of the two patients died, apparently of the illness.Similarly, in describing and naming anorexia nervosa, Sir William Gull (2) (in 1874) included mortality in his description.A substantial body of more recent work has systematically documented high mortality, including suicide risk (3, 4).However, while these relationships are well known, the timing of mortality risk across the course of the illness remains unclear.One could imagine a scenario of elevated mortality early in the illness, wherein those particularly prone to medical complications from malnutrition would be at high risk for death.Conversely, risk of death might climb after prolonged illness as complications of starvation mount.Similar predictions about the timing of suicide risk might be made as well.A number of potential predictors of mortality, including certain medical complications, severity of weight loss, severity of co-occurring psychopathology, and severity of the eating disorder symptoms themselves, may be important.However, our knowledge of predictors of mortality in eating disorders is limited (5).In this issue of the Journal, Franko et al. ( 6) report on a long-term follow-up study of a cohort of individuals with eating disorders.The report examines mortality both in those with anorexia nervosa and in those with bulimia nervosa.The main findings of the study were that mortality was concentrated mostly in those with anorexia nervosa.Notably, standardized mortality ratios were high early in the study (7.7 in the first 10 years) but dropped with increasing length of follow-up.On the other hand, standardized mortality ratios increased with duration of illness (3.2 for duration under 15 years and 6.6 for duration over 15 years).The authors had previously reported very elevated standardized mortality ratios for suicide in this sample (greater than 50), but over the course of this much longer follow-up period, no further suicides occurred.Thus, the standardized mortality ratios for suicide remained high for the sample as a whole (25.2) but appeared to decrease with time.This study has many strengths.The sample was well defined, and participants underwent careful follow-up assessment.The period of observation was long (a median of 20 years).
Infection as a comorbidity of COPD
Authors: S. Sethi
Journal: European Respiratory Journal (2010)

The normal lung has several defence mechanisms to deal with microorganisms. Lower respiratory infections in the absence of lung disease are therefore relatively infrequent as compared with upper respiratory tract infections in healthy adults. In the setting of chronic obstructive pulmonary disease (COPD), lower respiratory tract infections, both acute and chronic, occur with increased frequency. As these infections contribute considerably to the clinical course of the patient with COPD, they constitute a significant comorbidity in COPD. Recurrent acute infections by bacterial and/or viral pathogens are now clearly linked with the occurrence of exacerbations of COPD. In addition, the occurrence of pneumonia in COPD has received considerable recent attention as it appears to be increased by the use of inhaled corticosteroids. The role of chronic infection in the pathogenesis of COPD is an active area of research with several different types of pathogens potentially implicated. Additionally, COPD patients with HIV infection have a more rapidly progressive decline in lung function than non-HIV-infected patients. Enhanced understanding of the host-pathogen interaction is needed to better prevent and treat respiratory tract infection in COPD.
Foreign-Body Reaction to Wound Seal
Authors: Laura J. Lester, Aaron K. Joseph
Journal: JAMA Dermatology (2013)

Wound Seal (Biolife LLC) is a product composed of a hydrophilic polymer and potassium iron oxyacid salt that aids in hemostasis in wounds that are left to heal by secondary intention. We report a foreign-body reaction that results in the dermis following its use.
Total body fat percentage and body mass index and the association with lower extremity injuries in children: a 2.5-year longitudinal study
Authors: Eva Jespersen, Evert Verhagen, René Holst, Heidi Klakk, Malene Heidemann, Christina Trifonov Rexen, Claudia Franz, Niels Wedderkopp
Journal: British Journal of Sports Medicine (2013)

Overweight youths are generally recognised as being at increased risk of sustaining lower extremity injuries in sports. However, previous studies are inconclusive and choices for measuring overweight are manifold.To examine two different measures of overweight, body mass index (BMI) and total body fat percentage (TBF%), as risk factors for lower limb injuries in a school-based cohort.A longitudinal cohort study.A total of 632 school children, baseline age 7.7-12.0 years, were investigated. Whole body dual energy x-ray absorptiometry scans provided measures of TBF%. Measures of BMI were obtained by standard anthropometric methods. Musculoskeletal complaints were reported by parents answering weekly mobile phone text messages during 2.5 years. Injuries were diagnosed by clinicians. Leisure time sports participation was reported weekly using text messaging.During 2.5 years of follow-up, 673 lower extremity injuries were diagnosed. Children being overweight by both BMI and TBF% showed the highest risk of sustaining lower extremity injuries (IRR 1.38 (95% CI 1.05 to 1.81)). Children who were overweight using BMI and TBF% showed the highest risk of sustaining lower extremity injuries (IRR 1.38 (95% CI 1.05 to 1.81)).The risk of lower extremity injuries appeared to be increased for overweight children. When comparing two different measures of overweight, overweight by TBF% is a higher risk factor than overweight by BMI. This suggests that a high proportion of adiposity is more predictive of lower extremity injuries, possibly due to a lower proportion of lean muscle mass.
THE DEPRESSION OF ESTRONE-INDUCED UTERINE GROWTH BY PHENOLIC ESTROGENS WITH OXYGENATED FUNCTIONS AT POSITIONS 6 OR 16: THE IMPEDED ESTROGENS
Authors: Charles Huggins, Elwood V. Jensen
Journal: The Journal of Experimental Medicine (1955)

Two small groups of steroids in the estrane series-here designated as impeded estrogens,-represent a class of compounds which differ from the majority of estrogenic substances in exerting certain unusual influences on growth of the uterus. The induction of these effects previously was considered to be peculiar to estriol. The unusual growth properties common to impeded estrogens are twofold: (a) after the threshold dosage required to initiate growth has been reached, the slope of the curve of increment of uterine weight in response to increased steroid dosage is very gradual rather than steep; (b) these compounds possess the ability to inhibit to a limited extent the uterine growth induced by estrone administered concurrently. The partial inhibition of estrone-induced growth of the uterus is confined to a critical dosage of the impeded estrogen and is overcome by increased dosage of the inhibitor. Estrone-induced growth of the vagina is not inhibited by impeded estrogens. Furthermore the simultaneous administration of impeded estrogens and testosterone does not lessen the amount of uterine growth evoked by the latter. The impeded estrogens so far encountered are 3-hydroxyestratriene derivatives possessing either a ketone group at position 6 or a hydroxyl group at position 16. Oxygenated functions at these positions in phenolic estrogens have special significance in the excitation and restraint of uterine growth unshared by similar groups at certain other sites of the estrane molecule.
Platelet aggregation in acute coronary syndromes: use of a new aggregometer with laser light scattering to assess platelet aggregability
Authors: Koji Eto, Satoshi Takeshita, Masahiko Ochiai, Yukio Ozaki, Tomohide Sato, Takaaki Isshiki
Journal: Cardiovascular Research (1998)

Objective: Platelet aggregation has been implicated in the pathogenesis of acute coronary syndromes. Small aggregates consisting of ≤100 platelets cannot be quantified with a conventional aggregometer employing optical density. Using a recently developed aggregometer based on laser light scattering, we studied platelet aggregability in patients with acute coronary syndromes. Methods: Peripheral blood samples were obtained from 39 patients with acute myocardial infarction or unstable angina who had received no prior antiplatelet or anticoagulant therapy, to be assayed immediately using a PA-100 platelet aggregometer. Blood samples from 14 healthy volunteers were used as controls. Results: Spontaneous formation of platelet aggregates was observed only in patients with acute coronary syndromes. The size of these aggregates was small, consisting of ≤100 platelets (primary aggregation). Agonist-induced aggregation consisted of two phases. In the first few minutes, the number of small aggregates increased markedly (primary aggregation), followed by an increase in larger aggregates (secondary aggregation). The EC50 of epinephrine for primary aggregation was nearly 50 times lower in acute coronary patients than in controls (P<0.001), while the EC50 for secondary aggregation was only 2 times lower (P<0.001). Conclusions: Aggregometry using light scattering suggests that platelet hyperaggregability and hypersensitivity in acute coronary syndromes may occur in primary but not secondary aggregation.
Sympathy for t-PA
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2006)

Signaling between a T cell and an antigen-presenting cell (APC) is orchestrated through a bull's eye-like structure known as the immunological synapse.But no one had ever spotted these structures in vivo, causing many to wonder whether they are immunology's equivalent of the Loch Ness monster.Synapse devotees can now rest easy, thanks to Barcia et al., who provide the first in vivo glimpse of these elusive cellular structures on page 2095.When first described, immunological synapses-their centers rich with T cell receptor (TCR)-MHC/peptide complexes and their outer rings with stabilizing integrins and adhesion molecules-provided a satisfying spatial model of how T cells get activated and signal to target APCs.But although these structures formed readily when T cells bumped into artificial lipid bilayers or cultured APCs, they have proven difficult to capture in real-life settings-in part due to limitations of live imaging and the touch-and-go nature of T cell-APC interactions.Barcia et al. used a well-characterized model of viral brain infection in rats to help them pinpoint when and where to look for cytotoxic T cells engaging infected brain cells.The use of a nonreplicating virus-which infected brain cells but did not destroy them-also aided the synapse hunt.Three-dimensional reconstructions of confocal images revealed both the polarization of phosphorylated signaling kinases toward the T cell-APC contact site (an early sign of T cell activation) and-voilà!-thecharacteristic bull's-eye structure of the synapse.The formation of synapses preceded viral clearance, suggesting that these ordered structures might indeed be necessary for T cell activation and subsequent elimination of infected cells.Formal proof of this, however, awaits the development of inhibitors or genetic mutations that selectively interfere with synapse formation.At least now we can rest assured that synapses really are more than just visually pleasing in vitro phenomena.