tbuckley/cabot-search huggingface dataset:
Smoking and pulmonary sarcoidosis: effect of cigarette smoking on prevalence, clinical manifestations, alveolitis, and evolution of the disease.
Authors: D Valeyre, P Soler, C Clerici, J Pre, J P Battesti, R Georges, A J Hance
Journal: Thorax (1988)

Patients with pulmonary sarcoidosis are less likely to smoke than persons of a similar age in the general population. This could be because smoking reduces the likelihood of developing sarcoidosis, or alternatively smoking could reduce the severity of the disease process so that smoking patients are underrepresented among patients with clinically overt disease. To evaluate these possibilities 64 patients with sarcoidosis of recent onset were studied at presentation and after a one year follow up period, clinical, functional, radiographic, and bronchoalveolar lavage fluid criteria being used to identify factors that might account for the lower incidence of sarcoidosis in smokers and to determine whether the disease is less severe in smoking patients. Smoking was less common in the patients with sarcoidosis (30%) than in the control subjects (46%). The study did not support the conclusion that sarcoidosis is less severe in smokers, as clinical, radiographic, and functional abnormalities were similar in smokers and non-smokers at initial evaluation and after a one year follow up period. Nevertheless, smoking did influence various indices used to assess disease "activity." Cigarette smoking was associated with a significant increase in the serum angiotensin converting enzyme activity (SACE), and patients with very high SACE and pulmonary gallium-67 uptake were smokers. Furthermore, more CD8+ (but not CD4+) lymphocytes were recovered by lavage from smoking than from non-smoking patients, giving a lower CD4: CD8 ratio in smokers. Fewer alveolar macrophages were recovered by lavage from smokers with sarcoidosis than from normal subjects with a similar smoking history. These finding support the possibility that smokers, particularly those with a prominent accumulation of alveolar macrophages in the lower respiratory tract, may be less likely to develop sarcoidosis.
Therapeutic Potential for HDAC Inhibitors in the Heart
Authors: Timothy A. McKinsey
Journal: The Annual Review of Pharmacology and Toxicology (2011)

Reversible protein acetylation provides a central mechanism for controlling gene expression and cellular signaling events. Two pharmacological inhibitors of protein deacetylation are currently approved for the treatment of human cancer, and numerous follow-on compounds are in clinical development for oncology and non-oncology indications. The inhibitors target members of a family of enzymes known as histone deacetylases (HDACs). Surprisingly, HDAC inhibitors have also been shown to be efficacious in preclinical models of heart failure. This review highlights roles of HDACs in the heart and the therapeutic potential of HDAC inhibitors for the treatment of heart failure.
Poverty and Response to Treatment Among Panic Disorder Patients in Primary Care
Authors: Peter Roy-Byrne, Cathy Sherbourne, Jeanne Miranda, Murray Stein, Michelle Craske, Daniela Golinelli, Greer Sullivan
Journal: American Journal of Psychiatry (2006)

Despite well-established links between poverty and poor mental illness outcome as well as recent reports exploring racial and ethnic health disparities, little is known about the outcomes of evidence-based psychiatric treatment for poor individuals.Primary care patients with panic disorder (N=232) who were participating in a randomized controlled trial comparing a cognitive behavior therapy (CBT) and pharmacotherapy intervention to usual care were divided into those patients above (N=152) and below (N=80) the poverty line. Telephone assessments at 3, 6, 9, and 12 months were used to compare the amount of evidence-based care received as well as clinical and functional outcomes.Poor subjects were more severely ill at baseline, with more medical and psychiatric comorbidity. The increases in the amount of evidence-based care and reductions in clinical symptoms and disability were comparable in the two groups such that poorer individuals, although responding equivalently, continued to be more ill and disabled at 12 months.The comparable response of poor individuals in this study suggests that standard CBT and pharmacotherapy treatments for panic disorder do not need to be "tailored" to be effective in poor populations. However, the more severe illness both at baseline and follow-up in these poor individuals suggests that treatment programs may need to be extended in order to treat residual symptoms and disability in these patients so that they might achieve comparable levels of remission.
A case of compulsory admission
Authors: M H. Symes
Journal: BMJ (1979)

results in vasodilatation and relaxation of the mammalian penis leading to erection.'-3However, there is no evidence to suggest that the transmitter responsible for this inhibitory effect is cholinergic in nature.Indeed the identity of the transmitter has so far not been established.We have previously suggested the possibility that the inhibitory transmitter leading to erection may be histamine.4The smooth muscle of the erectile corpus cavernosa of the human penis in vitro is either contracted or relaxed by histamine.The former effect is abolished by mepyramine (a histamine H,receptor antagonist), which also potentiates the relaxant effect of histamine on this tissue.The relaxant effect of histamine on the human penis is abolished by burimamide,4 which is chemically related to cimetidine and is known to antagonise actions of histamine mediated through H2 receptors.Thus cimetidine, by blocking H, receptors on the body of the penis, may prevent erection.However, definite proof that histamine is the neurotransmitter at the sacral parasympathetic nerve is lacking.
A structural basis for selection and cross-species reactivity of the semi-invariant NKT cell receptor in CD1d/glycolipid recognition
Authors: Lars Kjer-Nielsen, Natalie A. Borg, Daniel G. Pellicci, Travis Beddoe, Lyudmila Kostenko, Craig S. Clements, Nicholas A. Williamson, Mark J. Smyth, Gurdyal S. Besra, Hugh H. Reid, Mandvi Bharadwaj, Dale I. Godfrey, Jamie Rossjohn, James McCluskey
Journal: The Journal of Experimental Medicine (2006)

Little is known regarding the basis for selection of the semi-invariant αβ T cell receptor (TCR) expressed by natural killer T (NKT) cells or how this mediates recognition of CD1d–glycolipid complexes. We have determined the structures of two human NKT TCRs that differ in their CDR3β composition and length. Both TCRs contain a conserved, positively charged pocket at the ligand interface that is lined by residues from the invariant TCR α- and semi-invariant β-chains. The cavity is centrally located and ideally suited to interact with the exposed glycosyl head group of glycolipid antigens. Sequences common to mouse and human invariant NKT TCRs reveal a contiguous conserved “hot spot” that provides a basis for the reactivity of NKT cells across species. Structural and functional data suggest that the CDR3β loop provides a plasticity mechanism that accommodates recognition of a variety of glycolipid antigens presented by CD1d. We propose a model of NKT TCR–CD1d–glycolipid interaction in which the invariant CDR3α loop is predicted to play a major role in determining the inherent bias toward CD1d. The findings define a structural basis for the selection of the semi-invariant αβ TCR and the unique antigen specificity of NKT cells.
Rho (D) Immune Globulin (Human)
Authors: William Q. Ascari
Journal: JAMA (1968)

Rh<sub>O</sub>(D) immune globulin (RhoGAM) was administered to Rh negative women within 72 hours after they had given birth to Rh positive, ABO compatible infants to prevent Rh immunization. Two studies, differing only in the dose of anti-Rh immune globulin administered, have shown almost complete prevention of Rh immunization whereas in a group of Rh negative mothers who were not treated, and who were comparable by age, race, gravidity, and ABO blood group, the incidence of Rh immunization was 7%. This represents the first successful application of the concept of antibody-mediated immune suppression in humans to prevent disease.
Respiratory muscle unloading improves leg muscle oxygenation during exercise in patients with COPD
Authors: A Borghi-Silva, C C Oliveira, C Carrascosa, J Maia, D C Berton, F Queiroga, E M Ferreira, D R Almeida, L E Nery, J A Neder
Journal: Thorax (2008)

<h3>Background:</h3> Respiratory muscle unloading during exercise could improve locomotor muscle oxygenation by increasing oxygen delivery (higher cardiac output and/or arterial oxygen content) in patients with chronic obstructive pulmonary disease (COPD). <h3>Methods:</h3> Sixteen non-hypoxaemic men (forced expiratory volume in 1 s 42.2 (13.9)% predicted) undertook, on different days, two constant work rate (70–80% peak) exercise tests receiving proportional assisted ventilation (PAV) or sham ventilation. Relative changes (Δ%) in deoxyhaemoglobin (HHb), oxyhaemoglobin (O<sub>2</sub>Hb), tissue oxygenation index (TOI) and total haemoglobin (Hb<sub>tot</sub>) in the vastus lateralis muscle were measured by near-infrared spectroscopy. In order to estimate oxygen delivery (Do<sub>2</sub>est, l/min), cardiac output and oxygen saturation (Spo<sub>2</sub>) were continuously monitored by impedance cardiography and pulse oximetry, respectively. <h3>Results:</h3> Exercise tolerance (Tlim) and oxygen uptake were increased with PAV compared with sham ventilation. In contrast, end-exercise blood lactate/Tlim and leg effort/Tlim ratios were lower with PAV (p&lt;0.05). There were no between-treatment differences in cardiac output and Spo<sub>2</sub> either at submaximal exercise or at Tlim (ie, Do<sub>2</sub>est remained unchanged with PAV; p&gt;0.05). Leg muscle oxygenation, however, was significantly enhanced with PAV as the exercise-related decrease in Δ(O<sub>2</sub>Hb)% was lessened and TOI was improved; moreover, Δ(Hb<sub>tot</sub>)%, an index of local blood volume, was increased compared with sham ventilation (p&lt;0.01). <h3>Conclusions:</h3> Respiratory muscle unloading during high-intensity exercise can improve peripheral muscle oxygenation despite unaltered systemic Do<sub>2 </sub>in patients with advanced COPD. These findings might indicate that a fraction of the available cardiac output had been redirected from ventilatory to appendicular muscles as a consequence of respiratory muscle unloading.
Acute exposure to hair bleach causes airway hyperresponsiveness in a rabbit model
Authors: T Mensing, W Marek, M Raulf-Heimsoth, X Baur
Journal: European Respiratory Journal (1998)

Ammonium persulphate (APS) and hydrogen peroxide (H2O2) are used as oxidants in many industrial processes and are the main constituents of standard hair bleaching products. In a previous study, it was demonstrated that aerosols of APS induce alterations in airway responsiveness. The present study examined whether exposure for 4 h to a hair bleach composition (containing APS, potassium persulphate and H2O2) or H2O2 could induce airway hyperresponsiveness and/or an obstructive ventilation pattern in a rabbit model. Exposure to the aerosols altered neither baseline airway resistance, dynamic elastance, slope of inspiratory pressure generation nor arterial blood pressure and blood gas measurements. Similarly to APS, hair bleach aerosols containing > or =10.9 mg x m(-3) persulphate (ammonium and potassium salt) in air and > or =1.36 mg x m(-3) H2O2 in air caused airway hyperresponsiveness to acetylcholine after 4 h of exposure. Aerosolized H2O2 (> or =37 mg x m(-3) in air) did not influence airway responsiveness to acetylcholine. The results demonstrate that hair bleaching products containing persulphates dissolved in H2O2 cause airway hyperresponsiveness to acetylcholine in rabbits.
Brown's syndrome: an unusual ocular complication of rheumatoid arthritis.
Authors: C Cooper, J R Kirwan, N W McGill, P A Dieppe
Journal: Annals of the Rheumatic Diseases (1990)

A 55 year old man with rheumatoid vasculitis and an apparent left inferior oblique palsy is described. This unusual extraocular complication of rheumatoid arthritis probably resulted from a tenosynovitis of the superior oblique tendon sheath, and resolved with steroid treatment.
Monitoring toxicity in individuals receiving treatment for latent tuberculosis infection: a systematic review<i>versus</i>expert opinion
Authors: Giovanni Sotgiu, Alberto Matteelli, Haileyesus Getahun, Enrico Girardi, Monica Sañé Schepisi, Rosella Centis, Giovanni Battista Migliori
Journal: European Respiratory Journal (2015)

Latent tuberculosis infection (LTBI) is defined as a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens without evidence of clinically manifested active TB [1]. The World Health Organization (WHO) estimates that one-third of the global population is infected by Mycobacterium tuberculosis [2]. They cannot transmit tuberculosis (TB), but they can develop the disease and become infectious with a life-time risk of approximately 5–15% [3]. A significant proportion of new TB patients, especially in low burden countries, are presumed to occur from the pool of individuals with LTBI. LTBI treatment: a systematic review on the best clinical approach to monitor the adverse events of preventive therapy <http://ow.ly/HyjAH>
Intraocular Pressure-reducing Effect of PhXA41 in Patients with Increased Eye Pressure
Authors: Albert Alm, Jörgen Villumsen, Per Törnquist, Agneta Mandahl, Juhani Airaksinen, Anja Tuulonen, Anders Marsk, Bahram Resul, Johan Stjernschantz
Journal: Ophthalmology (1993)
Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells
Authors: Brad Dykstra, Sandra Olthof, Jaring Schreuder, Martha Ritsema, Gerald de Haan
Journal: The Journal of Experimental Medicine (2011)

Hematopoietic stem cell (HSC) populations change with aging, but the extent to which this is caused by qualitative versus quantitative alterations in HSC subtypes is unclear. Using clonal assays, in this study we show that the aging HSC compartment undergoes both quantitative and qualitative changes. We observed a variable increase of HSC pool size with age, accompanied by the accumulation of predominantly myeloid-biased HSCs that regenerate substantially fewer mature progeny than young myeloid-biased HSCs and exhibit reduced self-renewal activity as measured by long-term secondary transplantation. Old HSCs had a twofold reduction in marrow-homing efficiency and a similar decrease in functional frequency as measured using long-term transplantation assays. Similarly, old HSCs had a twofold reduced seeding efficiency and a significantly delayed proliferative response compared with young HSCs in long-term stromal cell co-cultures but were indistinguishable in suspension cultures. We show that these functional defects are characteristics of most or all old HSCs and are not indicative of a nonfunctional subset of cells that express HSC markers. Furthermore, we demonstrate that cells with functional properties of old HSCs can be generated directly from young HSCs by extended serial transplantation, which is consistent with the possibility that they arise through a process of cellular aging.
MITRACLIP THERAPY DEMONSTRATES CONTINUED CLINICAL BENEFIT AND FAVORABLE LEFT VENTRICULAR REMODELING AT TWO YEARS IN HIGH RISK SURGICAL PATIENTS WITH SIGNIFICANT MITRAL REGURGITATION : ANALYSIS OF THE EVEREST II HIGH RISK REGISTRY
Authors: Saibal Kar, Elyse Foster, Don Glower, Ted Feldman
Journal: Journal of the American College of Cardiology (2011)
Barriers to Blood Glucose Monitoring in a Multiethnic Community
Authors: Janice C. Zgibor, David Simmons
Journal: Diabetes Care (2002)

We studied a multiethnic community to determine factors associated with blood glucose monitoring (BGM) and to determine the independent association between barriers to diabetes care and BGM.A total of 323 participants (35.6% European, 32.2% Maori, and 32.2% Pacific Islander) from the South Auckland Diabetes Project (free of major complications by self-report) completed a qualitative survey to determine barriers to diabetes care. Five barriers to diabetes care categories were generated including internal psychological (self efficacy/health beliefs), external psychological (psychosocial environment), internal physical (comorbidities/side effects of treatment), external physical (finance/access to care), and educational (knowledge of diabetes/services) barriers.Characteristics associated with BGM greater than or equal to twice weekly were female sex, HbA(1c) >8%, higher diabetes knowledge scores, and insulin use. Multivariate analyses demonstrated that those reporting external physical barriers (OR 0.47, 95% CI 0.26-0.84), external psychological barriers (0.55, 0.30-1.0), and internal psychological barriers (0.56, 0.32-1.0) were less likely to perform BGM independent of ethnicity, insulin use, age, sex, diabetes knowledge, and glycemic control. Further multivariate analyses demonstrated that those reporting external physical barriers, particularly related to personal finance, were less likely to perform BGM.These data demonstrate that patient-reported barriers to diabetes care are associated with BGM, particularly in relation to financial, psychosocial, and self-efficacy issues. Understanding these barriers and overcoming them within the context of the patient's ethnic environment may lead to increased participation in self-care.
Second Cancers After Squamous Cell Carcinoma and Adenocarcinoma of the Cervix
Authors: Anil K. Chaturvedi, Ruth A. Kleinerman, Allan Hildesheim, Ethel S. Gilbert, Hans Storm, Charles F. Lynch, Per Hall, Froydis Langmark, Eero Pukkala, Magnus Kaijser, Michael Andersson, Sophie D. Fossa, Heikki Joensuu, Lois B. Travis, Eric A. Engels
Journal: Journal of Clinical Oncology (2008)

Although cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC) are both caused by human papillomavirus (HPV) infection, they differ in cofactors such as cigarette smoking. We assessed whether these cofactor differences translate into differences in second cancer risk.We assessed second cancer risk among 85,109 cervical SCC and 10,280 AC survivors reported to population-based cancer registries in Denmark, Finland, Norway, Sweden, and the United States. Risks compared to the general population were assessed using standardized incidence ratios (SIR).Overall cancer risk was significantly increased among both cervical SCC survivors (n = 10,559 second cancers; SIR, 1.31; 95% CI, 1.29 to 1.34) and AC survivors (n = 920 second cancers; SIR, 1.29; 95% CI, 1.22 to 1.38). Risks of HPV-related and radiation-related cancers were increased to a similar extent among cervical SCC and AC survivors. Although significantly increased in both groups when compared with the general population, risk of smoking-related cancers was significantly higher among cervical SCC than AC survivors (P = .015; SIR for cervical SCC = 2.07 v AC = 1.78). This difference was limited to lung cancer (SIR for cervical SCC = 2.69 v AC = 2.18; P = .026). The increased lung cancer risk among cervical AC survivors was observed for both lung SCC and lung AC. SIRs for second cancers of the colon, soft tissue, melanoma, and non-Hodgkin's lymphoma were significantly higher among cervical AC than SCC survivors.The second cancer profiles among cervical SCC and AC survivors mirror the similarities and differences in cofactors for these two histologies. Because smoking is not a cofactor for cervical AC, the increased lung cancer risk suggests a role for additional factors.
Postnatal thymus transplantation with immunosuppression as treatment for DiGeorge syndrome
Authors: M. Louise Markert, Marilyn J. Alexieff, Jie Li, Marcella Sarzotti, Daniel A. Ozaki, Blythe H. Devlin, Debra A. Sedlak, Gregory D. Sempowski, Laura P. Hale, Henry E. Rice, Samuel M. Mahaffey, Michael A. Skinner
Journal: Blood (2004)
Dystrophic cardiomyopathy: role of TRPV2 channels in stretch-induced cell damage
Authors: Charlotte Lorin, Isabelle Vögeli, Ernst Niggli
Journal: Cardiovascular Research (2015)

AimsDuchenne muscular dystrophy (DMD), a degenerative pathology of skeletal muscle, also induces cardiac failure and arrhythmias due to a mutation leading to the lack of the protein dystrophin. In cardiac cells, the subsarcolemmal localization of dystrophin is thought to protect the membrane from mechanical stress. The absence of dystrophin results in an elevated stress-induced Ca2+ influx due to the inadequate functioning of several proteins, such as stretch-activated channels (SACs). Our aim was to investigate whether transient receptor potential vanilloid channels type 2 (TRPV2) form subunits of the dysregulated SACs in cardiac dystrophy.
Reactive metabolites of phenacetin and acetaminophen: a review
Authors: Jack A. Hinson
Journal: Environmental Health Perspectives (1983)

Phenacetin can be metabolized to reactive metabolites by a variety of mechanisms. (1) Phenacetin can be N-hydroxylated, and the resulting N-hydroxyphenacetin can be sulfated or glucuronidated. Whereas phenacetin N-O sulfate immediately rearranges to form a reactive metabolite which may covalently bind to protein, phenacetin N-O glucuronide slowly rearranges to form reactive metabolites. Incubation of the purified phenacetin N-O glucuronide under a variety of conditions suggests that N-acetyl-p-benzoquinone imine is a reactive metabolite. This metabolite covalently binds to protein, reacts with glutathione to form an acetaminophen-glutathione conjugate, is reduced by ascorbate to acetaminophen or is partially hydrolyzed to acetamide. (2) Phenacetin can be O-deethylated to acetaminophen, and acetaminophen can be converted directly to a reactive metabolite which may be also N-acetyl-p-benzoquinone imine. (3) Phenacetin can be sequentially N-hydroxylated and O-deethylated to N-hydroxyacetaminophen which spontaneously dehydrates to N-acetyl-p-benzoquinone imine. (4) Phenacetin can be 3, 4-epoxidated to form an alkylating and an arylating metabolite. In the presence of glutathione, a S-ethylglutathione conjugate and an acetaminophen-glutathione conjugate are formed. In the absence of glutathione, the alkylating metabolite may bind to protein and the arylating metabolite is completely hydrolyzed to acetamide and another arylating metabolite which may bind to protein. The structures of the alkylating and arylating metabolites are unknown. Control experiments have shown that in pathway (1) the phenolic oxygen of the acetaminophenglutathione conjugate is derived from water, whereas in pathways (2) and (3) the phenolic oxygen of this metabolite is derived from phenacetin. In pathway (4) the phenolic oxygen was 50% derived from molecular oxygen and 50% from phenacetin. Administration of [p-180]phenacetin to hamsters revealed only a 10% loss of 180 in the acetaminophen mercapturic acid (the further metabolic product of the glutathione conjugate) which suggests that, in the hamster, pathways (2) and/or (3) are the primary mechanism of conversion of phenacetin to reactive metabolites in vivo.