tbuckley/cabot-search huggingface dataset:
Persistence of airway hyperresponsiveness and viral antigen following respiratory syncytial virus bronchiolitis in young guinea-pigs
Authors: F Riedel, B Oberdieck, HJ Streckert, S Philippou, T Krusat, W Marek
Journal: European Respiratory Journal (1997)

Respiratory syncytial virus (RSV) bronchiolitis in infancy is known to be followed by chronic respiratory symptoms and airway hyperresponsiveness in a subgroup of patients. To further investigate the pathogenesis of RSV-induced chronic airway pathology, we infected young guinea-pigs at 4 weeks of age with RSV applied as an aerosol (n=30), and control guinea-pigs with virus-free culture medium (n=24). Infection was confirmed by positive antibody titre to RSV after 6 weeks, and by typical pathological changes of bronchiolitis after 1 week in six animals from each group. Airway hyperresponsiveness was measured weekly for 5 weeks by histamine challenge, using body-plethysmographic measurement of compressed air (CA). The provocative concentration of histamine producing significant airway obstruction (i.e. CA = 0.1 mL) (PC0.1 mL CA in mg x mL(-1)) was calculated from dose-response curves. Six weeks postinfection, the lungs were investigated for the presence of inflammation and of viral antigen by immunofluorescence and immunohistochemistry using a rabbit hyperimmune serum and monoclonal antibodies. Airway responsiveness was increased in the RSV group 1 week postinfection compared to the control group (PC0.1 mL CA median 2.50 vs &gt;10 mg x mL(-1); p&lt;0.001) and this persisted up to 5 weeks postinfection (PC0.1 mL CA median 1.61 vs &gt;10 mg x mL(-1); p&lt;0.001). During the same period, viral antigen persisted in the lungs of infected animals, although there was less inflammation at 6 weeks postinfection than at 1 week postinfection. In guinea-pigs, respiratory syncytial virus infection of the airways causes persistent airway hyperresponsiveness over a period of at least 5 weeks. During this time, viral antigen, but not inflammation, remains detectable in the lungs and might be responsible for ongoing airway hyperresponsiveness.
Disease assessment in psoriatic spectrum: a modular approach for use in routine clinical practice
Authors: Julekha Wajed, Philip Helliwell, Eleanor Korendowych, Kate Gadsby, Susan Oliver, Liz Parrish, Bruce Kirkham
Journal: Annals of the Rheumatic Diseases (2013)

Sir,

Psoriatic arthritis (PsA) is a complex condition involving peripheral and axial joints, enthesitis, dactylitis and psoriasis,1 which all vary significantly between individuals, and all contribute to reduced quality of life.2 For a complete understanding of disease burden necessary for optimal management, all aspects of disease need assessment.3 This can be challenging in routine practice with limited time.

The ‘Psoriatic Arthritis Assessment Academy’, a group of physicians and specialist nurses in rheumatology and dermatology, met on 7 March 2011, to discuss psoriatic disease assessment. We developed the concept of a modular approach, with skin, axial disease and peripheral joint/dactylitis/entheseal involvement considered as three separate ‘modules’ of psoriatic disease.

Rheumatology clinics routinely assess joints …
Pain Genes?: Natural Variation and Transgenic Mutants
Authors: Jeffrey S. Mogil, Lei Yu, Allan I. Basbaum
Journal: Annual Review of Neuroscience (2000)

Like many other complex biological phenomena, pain is starting to be studied at the level of the gene. Advances in molecular biological technology have allowed the cloning, mapping, and sequencing of genes, and also the ablility to disrupt their function entirely (i.e. via transgenic knoockouts). With these new tools at hand, pain researchers have begun in earnest the task of defining (a) which of the 70,000– 150,000 mammalian genes are involved in the mediation of pain, and (b) which of the pain-relevant genes are polymorphic, contributing to both natural variation in responses and pathology. Although there are only a few known examples in which single gene mutations in humans are associated with pain conditions (e.g. an inherited form of migraine and congenital insensitivity to pain), it is likely that others will be identified. Concurrently, a variety of genes have been implicated in both the transmission and control of “pain” messages in animals. The present review summarizes current progress to these ends, focusing on both transgenic (gene→behavior) and classical genetic (behavior→gene) approaches in both humans and laboratory mice.
Development of the Right Ventricular Inflow Tract and Moderator Band
Authors: M.R.M. Jongbloed, M.C.E.F. Wijffels, M.J. Schalij, N.A. Blom, R.E. Poelmann, A. van der Laarse, M.M.T. Mentink, Z. Wang, G.I. Fishman, A.C. Gittenberger-de Groot
Journal: Circulation Research (2005)

Atriofascicular accessory bundles with AV-node like conduction properties can sustain atrioventricular (AV) re-entrant tachycardia (Mahaim tachycardia). During early embryogenesis, the AV canal is situated above the primitive left ventricle (LV), and a right AV connection has not been achieved yet. We studied the formation of the right ventricular (RV) inflow tract in relation to the developing cardiac conduction system and hypothesized a morphological explanation for functional atriofascicular bypass tracts. Analysis of lacZ-expression during sequential stages of cardiogenesis was performed in CCS-lacZ transgenic mice (E9.5 to 15.5). Embryos were stained for beta-galactosidase activity and the myocardial marker HHF35. At early stages CCS-lacZ expression was observed in a ring surrounding the AV canal, which connected at the inner curvature to the primary fold. The first sign of formation of the (CCS-lacZ negative) RV inlet component was a groove in the CCS-lacZ positive tissue of the primary fold. Outgrowth of the RV inlet tract resulted in division of the primary fold in a septal part, the trabecula septomarginalis and a lateral part, the moderator band, which extended laterally up to the right AV ring. Electrophysiological measurements in embryonic hearts (E15.5) in which the right atrium (RA) and RV were isolated from the left atrium (LA) and LV supported the functionality of this AV-connection via the moderator band, by demonstrating sequential atrial and ventricular activation in both RA/RV and LA/LV preparations. In conclusion, our observations may provide a possible morphological and functional explanation for atriofascicular accessory pathways via the moderator band, underlying Mahaim tachycardia.
Current trends in contraception.
Authors: I D Nuttall, R W Burslem, M Elstein, E Fox, D Rowley, B Evans
Journal: BMJ (1979)

Membranous glomerulonephritis, dermatomyositis, and bronchial carcinomaMembranous glomerulonephritis is associated with malignant disease in about 100°, of cases.'The prevalence of neoplasia in patients with dermatomyositis is estimated at 15-20%o in those aged over 45.2The occurrence of membranous glomerulonephritis with dermato- myositis is extremely unusual and in the one documented case malig- nancy was not implicated.3 Case reportA woman aged 58 years presented with ankle swelling and proteinuria..She smoked 20-30 cigarettes a day, was taking no medication, and was normotensive.Urine microscopy showed red cells with granular and cellular casts.The proteinuria was selective and amounted to 5-2 g/24 h.Serum con- centrations were as follows: albumnin 25 g/l, urea 6-8 mmol/l (41 mg/100 ml), and creatinine 129 /umol/l (1-46 mg/100 ml), ESR 50 mm in 1 h, and C3 1-28 U (0-8-1-4).A renal biopsy specimen showed diffuse capillary loop thickening and basement membrane spikes (figure).Immunofluorescence showed granular Renal glomerulus showing basement membrane spikes.Silver stain x 350 (original magnification).IgG deposition along capillary loops.The features were typical of mem- branous glomerulonephritis.Treatment with frusemide was started.Three years later she developed dermatomyositis with periorbital oedema; dusky erythema of the face, trunk, and hands; proximal muscle weakness; and dysphagia.The serum concentration of creatinine phosphokinase was 290 U/I (10-60), aldolase 3-6 U/I (0-5-3 0), and lactate dehydrogenase 760 U/l (50-220).The proteinuria had diminished to 0 7 g/24 h, and serum concentration of albumin was 29 g/l, urea 9 mmol/l (54 mg/100 ml), creatinine 105 ,jmol/l (1.1 mg/100 ml), and ESR 60 mm in 1 h.Antinuclear anti- body was not detected.A chest radiograph was normal but lung tomography showed a 1-cm opacity in the right mid-zone.An oat cell tumour was later resected with the upper lobe.Preoperative treatment with prednisone and azathioprine dramatically improved the dermatomyositis and this improve- ment was sustained when the drugs were stopped postoperatively.
Keratinocyte growth factor protects against Clara cell injury induced by naphthalene
Authors: A. Ö. Yildirim, M. Veith, T. Rausch, B. Müller, P. Kilb, L. S. Van Winkle, H. Fehrenbach
Journal: European Respiratory Journal (2008)

Airway epithelial cells are exposed to environmental toxicants that result in airway injury. Naphthalene (NA) causes site-selective damage to Clara cells in mouse distal airways. N-terminally truncated recombinant human keratinocyte growth factor (ΔN23-KGF) protects against acute lung injury. The present study investigated whether or not ΔN23-KGF protects against NA-induced acute Clara cell damage by measuring airway responses specifically and in order to identify underlying molecular mechanisms. Mice were treated with ΔN23-KGF or PBS 33 h prior to injection of 200 mg·kg body weight −1 NA. Lung function was analysed by head-out body plethysmography. Distal airways isolated by microdissection were assessed for cell permeability using ethidium homodimer-1. Immunohistochemistry of Clara cell-specific protein in conjunction with a physical dissector was used to quantify Clara cell numbers. RNA was isolated from frozen airways in order to analyse gene expression using quantitative RT-PCR. ΔN23-KGF prevented NA-induced airflow limitation and Clara cell permeability, and resulted in twice as many Clara cells compared with PBS pre-treatment. ΔN23-KGF-pre-treated mice exhibited increased expression of proliferating cell nuclear antigen mRNA. Cytochrome P 450 isoform 2F2, which converts NA into its toxic metabolite, was reduced by ∼50%. The present results demonstrate that pre-treatment with N-terminally truncated recombinant human keratinocyte growth factor protects against naphthalene-induced injury. This suggests that N-terminally truncated recombinant human keratinocyte growth factor exerts its beneficial effect through a decrease in the expression of cytochrome P 450 isoform 2F2.
Ventricular Fibrillation and Ion Transport
Authors: A. K. ARMITAGE, J. H. BURN, A. J. GUNNING
Journal: Circulation Research (1957)

Ventricular fibrillation has been studied by driving the ventricles of the isolated rabbit heart electrically and observing whether fibrillation persisted after stimulation was stopped. The hearts were perfused by solutions of different ionic composition and the proportion of hearts in which persistent fibrillation was seen was determined for each solution. The proportion was controlled from 0 to 100 per cent according to the amount of K + , hearts fibrillating spontaneously in .25 N K + . A similar study was made by varying Ca ++ . Fibrillation was arrested by ATP and prolonged by dinitrophenol. Fibrillating hearts lost more K + than when they were not fibrillating. Fibrillation appeared to depend on disturbances of the metabolic processes concerned with ion movements.
Endotoxemia-mediated inflammation potentiates aminoglycoside-induced ototoxicity
Authors: Ja-Won Koo, Lourdes Quintanilla-Dieck, Meiyan Jiang, Jianping Liu, Zachary D. Urdang, Jordan J. Allensworth, Campbell P. Cross, Hongzhe Li, Peter S. Steyger
Journal: Science Translational Medicine (2015)

Endotoxemia-mediated inflammation potentiates cochlear uptake of aminoglycosides and subsequent cochleotoxicity.
Regulated Expression of the BTEB2 Transcription Factor in Vascular Smooth Muscle Cells
Authors: Yoichi Hoshino, Masahiko Kurabayashi, Tsugiyasu Kanda, Akira Hasegawa, Hironosuke Sakamoto, Ei-ichi Okamoto, Keiko Kowase, Noboru Watanabe, Ichiro Manabe, Toru Suzuki, Akihiko Nakano, Shin-ichi Takase, Josiah N. Wilcox, Ryozo Nagai
Journal: Circulation (2000)

We have previously shown BTEB2, a Krüppel-like zinc finger transcription factor, to regulate expression of the SMemb/NMHC-B gene, which has been implicated in phenotypic modulation of smooth muscle cells (SMCs). The present study was done to assess the developmental and pathological expression profiles of BTEB2 and to further evaluate the clinical relevance of BTEB2 expression in human coronary artery disease.Immunohistochemistry showed developmentally regulated expression of BTEB2 with abundant expression in fetal but not in adult aortic SMCs of humans and rabbits. In balloon-injured aortas, predominant expression of BTEB2 was seen in neointimal SMCs. Atherectomy specimens obtained from primary and restenotic lesions showed predominant expression of BTEB2 to stellate SMCs. The incidence of restenosis in primary lesions was significantly higher in lesions containing BTEB2-positive cells than in lesions without (55.6% versus 25.0%, P:=0.01).The present study shows that BTEB2 expression is developmentally and pathologically regulated. BTEB2 is preferentially expressed in dedifferentiated or activated SMCs. Examination of human coronary artery specimens suggests that primary lesions containing BTEB2-positive cells are associated with higher risk of restenosis than BTEB2-negative lesions. These results suggest that BTEB2 can serve as a molecular marker for phenotypic modulation of vascular SMCs.
Association of Glycation Gap With Mortality and Vascular Complications in Diabetes
Authors: Ananth U. Nayak, Alan M. Nevill, Paul Bassett, Baldev M. Singh
Journal: Diabetes Care (2013)

The "glycation gap" (G-gap), an essentially unproven concept, is an empiric measure of disagreement between HbA1c and fructosamine, the two indirect estimates of glycemic control. Its association with demographic features and key clinical outcomes in individuals with diabetes is uncertain.The G-gap was calculated as the difference between measured HbA1c and a fructosamine-derived standardized predicted HbA1c in 3,182 individuals with diabetes. The G-gap's associations with demographics and clinical outcomes (retinopathy, nephropathy, macrovascular disease, and mortality) were determined.Demographics varied significantly with G-gap for age, sex, ethnic status, smoking status, type and duration of diabetes, insulin use, and obesity. A positive G-gap was associated with retinopathy (odds ratio 1.24 [95% CI 1.01-1.52], P=0.039), nephropathy (1.55 [1.23-1.95], P<0.001), and, in a subset, macrovascular disease (1.91 [1.18-3.09], P=0.008). In Cox regression analysis, the G-gap had a "U"-shaped quadratic relationship with mortality, with both negative G-gap (1.96 [1.50-2.55], P<0.001) and positive G-gap (2.02 [1.57-2.60], P<0.001) being associated with a significantly higher mortality.We confirm published associations of G-gap with retinopathy and nephropathy. We newly demonstrate a relationship with macrovascular and mortality outcomes and potential links to distinct subpopulations of diabetes.
Cavernous sinus thrombosis presenting with diplopia in an allogeneic bone marrow transplant recipient
Authors: Vikas Gupta, Anne Keller, William Halliday, Stephen Sanche, Wanda Hassegawa, Hans Messner, Thomas Kiss, Jeffrey Lipton
Journal: American Journal of Hematology (2004)

Abstract Although neurological complications are common in patients undergoing allogeneic bone marrow transplant (alloBMT), cavernous sinus thrombosis (CST) has rarely been described. An allograft recipient is described who presented with diplopia and developed CST in the early post‐transplant period likely caused by a filamentous fungus. Clinical course and serial radiological studies of this patient are described and correlated with autopsy findings. Am. J. Hematol. 77:77–81, 2004. © 2004 Wiley‐Liss, Inc.
Molecular Pathways: Hepatitis C Virus, CXCL10, and the Inflammatory Road to Liver Cancer
Authors: Jessica Brownell, Stephen J. Polyak
Journal: Clinical Cancer Research (2013)

An estimated 170 million people worldwide are chronically infected with the hepatitis C virus (HCV), which is characterized histologically by a persistent immune and inflammatory response that fails to clear HCV from hepatocytes. This response is recruited to the liver, in part, by the chemokine CXCL10, the serum and intrahepatic levels of which have been inversely linked to the outcome of interferon-based therapies for hepatitis C. Bystander tissue damage from this ineffective response is thought to lead to increased hepatocyte turnover and the development of fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). However, CXCL10 is traditionally viewed as an orchestrator of the angiostatic and antitumor immune response. In this review, we will explore this duality and the pathways by which CXCL10 is produced by hepatocytes during HCV infection, its effects on resident and infiltrating immune cells, and how deregulation of these cell populations within the liver may lead to chronic liver inflammation. We will also discuss potential host-directed therapies to slow or reverse HCV-induced inflammation that leads to fibrosis, cirrhosis, and HCCs.
Serum Brain-Derived Neurotrophic Factor and the Risk for Dementia
Authors: Galit Weinstein, Alexa S. Beiser, Seung Hoan Choi, Sarah R. Preis, Tai C. Chen, Demetrios Vorgas, Rhoda Au, Aleksandra Pikula, Philip A. Wolf, Anita L. DeStefano, Ramachandran S. Vasan, Sudha Seshadri
Journal: JAMA Neurology (2013)

<h3>Importance</h3> In animal studies, brain-derived neurotrophic factor (BDNF) has been shown to impact neuronal survival and function and improve synaptic plasticity and long-term memory. Circulating BDNF levels increase with physical activity and caloric restriction, thus BDNF may mediate some of the observed associations between lifestyle and the risk for dementia. Some prior studies showed lower circulating BDNF in persons with Alzheimer disease (AD) compared with control participants; however, it remains uncertain whether reduced levels precede dementia onset. <h3>Objective</h3> To examine whether higher serum BDNF levels in cognitively healthy adults protect against the future risk for dementia and AD and to identify potential modifiers of this association. <h3>Design, Setting, and Participants</h3> Framingham Study original and offspring participants were followed up from 1992 and 1998, respectively, for up to 10 years. We used Cox models to relate BDNF levels to the risk for dementia and AD and adjusted for potential confounders. We also ran sensitivity analyses stratified by sex, age, and education, as well as related BDNF genetic variants to AD risk. This community-based, prospective cohort study involved 2131 dementia-free participants aged 60 years and older (mean [SD] age, 72 [7] years; 56% women). <h3>Main Outcomes and Measures</h3> Ten-year incidence of dementia and AD. <h3>Results</h3> During follow-up, 140 participants developed dementia, 117 of whom had AD. Controlling for age and sex, each standard-deviation increment in BDNF was associated with a 33% lower risk for dementia and AD (<i>P</i> = .006 and<i>P</i> = .01, respectively) and these associations persisted after additional adjustments. Compared with the bottom quintile, BDNF levels in the top quintile were associated with less than half the risk for dementia and AD (hazard ratio, 0.49; 95% CI, 0.28-0.85;<i>P</i> = .01; and hazard ratio, 0.46; 95% CI, 0.24-0.86;<i>P</i> = .02, respectively). These associations were apparent only among women, persons aged 80 years and older, and those with college degrees (hazard ratios for AD: 0.65, [95% CI, 0.50-0.85],<i>P</i> = .001; 0.63 [95% CI, 0.47-0.85],<i>P</i> = .002; and 0.27 [95% CI, 0.11-0.65],<i>P</i> = .003, respectively). Brain-derived neurotrophic factor genetic variants were not associated with AD risk. <h3>Conclusions and Relevance</h3> Higher serum BDNF levels may protect against future occurrence of dementia and AD. Our findings suggest a role for BDNF in the biology and possibly in the prevention of dementia and AD, especially in select subgroups of women and older and more highly educated persons.
Phase I, Pharmacokinetic and Pharmacodynamic Study of the Anti–Insulinlike Growth Factor Type 1 Receptor Monoclonal Antibody CP-751,871 in Patients With Multiple Myeloma
Authors: Martha Q. Lacy, Melissa Alsina, Rafael Fonseca, M. Luisa Paccagnella, Carrie L. Melvin, Donghua Yin, Amarnath Sharma, M. Enriquez Sarano, Michael Pollak, Sundar Jagannath, Paul Richardson, Antonio Gualberto
Journal: Journal of Clinical Oncology (2008)

Purpose A phase I first-in-human study was conducted to characterize the safety, tolerability, pharmacokinetic, and pharmacodynamic properties of the anti–insulinlike growth factor 1 receptor (IGF-IR) monoclonal antibody CP-751,871. Patients and Methods After informed consent and screening, 47 patients with multiple myeloma in relapse or refractory phase were enrolled into 11 dose-escalation cohorts of CP-751,871 at doses from 0.025 to 20 mg/kg for 4 weeks. Patients with less than a partial response to CP-751,871 treatment were eligible to receive CP-751,871 in combination with oral dexamethasone at the discretion of the investigator. Treatment with CP-751,871 and rapamycin with or without dexamethasone was also offered to patients enrolled in the 10 and 20 mg/kg cohorts with less than a partial response to initial therapy with single-agent CP-751,871. Results No CP-751,871-related dose-limiting toxicities were identified. Plasma CP-751,871 concentrations increased with dose and concentration-time profiles were consistent with those of antibodies with target-mediated disposition. Importantly, CP-751,871 administration led to a decrease in granulocyte IGF-IR expression and serum insulinlike growth factor 1 accumulation at high doses, suggesting systemic IGF-IR inhibition. Tumor response was assessed according to the European Group for Blood and Marrow Transplantation criteria. Nine responses were reported in 27 patients treated with CP-751,871 in combination with dexamethasone. Of interest, two of the patients with a partial response were progressing from dexamethasone treatment at study entry. Conclusion These data indicate that CP-751,871 is well tolerated and may constitute a novel agent in the treatment of multiple myeloma.
Vaccine effectiveness of the pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against clinically suspected invasive pneumococcal disease: a cluster-randomised trial
Authors: A A Palmu, J Jokinen, H Nieminen, R Syrjänen, E Ruokokoski, T Puumalainen, M Moreira, L Schuerman, D Borys, T M Kilpi
Journal: The Lancet Respiratory Medicine (2014)
Phase 3 Randomized Study (ARCHER 1050) of 1st-Line Dacomitinib vs Gefitinib for Advanced NSCLC with EGFR Mutation(S)
Authors: T.S.K. Mok, K. Nakagawa, R. Rosell, Y.-l. Wu, C. Trygstad, R. Capizzi, R. DeBenedetto, Z. Goldberg, T. Wang, V. Antic
Journal: Annals of Oncology (2013)