tbuckley/cabot-search huggingface dataset:
Recombinant interferon gamma augments phagocyte superoxide production and X-chronic granulomatous disease gene expression in X-linked variant chronic granulomatous disease.
Authors: R A Ezekowitz, S H Orkin, P E Newburger
Journal: Journal of Clinical Investigation (1987)

We examined the potential of interferon gamma (IFN-gamma) to ameliorate the physiologic defect of chronic granulomatous disease (CGD) by studying its effects on CGD phagocyte superoxide generation, NADPH oxidase kinetics, cytochrome b559 content, and expression of X-CGD (the gene for the X-linked disease). Granulocytes and macrophages from three patients in two kindreds with "variant" X-linked CGD (i.e., with very low, but detectable, baseline superoxide-generating activity) responded to IFN-gamma with enhanced nitroblue tetrazolium reduction and two- to eightfold increases in superoxide generation. IFN-gamma did not augment the respiratory burst activity of phagocytes from patients with "classic" CGD (i.e., no detectable baseline superoxide generation) or autosomal variant CGD. Incubation of a responding patient's granulocytes with IFN-gamma nearly doubled the maximal velocity for the NADPH oxidase, but did not change its abnormal Michaelis constant. Although the interferon-treated CGD granulocytes produced superoxide at a rate 40% of normal, the cytochrome b spectrum remained undetectable. IFN-gamma treatment of cultured monocytes from an IFN-gamma-responsive CGD patient increased the steady state level of RNA transcripts from the X-CGD gene from barely detectable up to approximately 5% of normal.
One third of Chinese men will be killed by tobacco if high smoking rates persist
Authors: R. Dobson
Journal: BMJ (2009)

One hundred million people in China will be killed by tobacco in the first half of this century if current smoking trends continue, a report says ( CVD Prevention and Control 2009 Jan 20, doi:10.1016/j.cvdpc.2008.12.001).

One third of all young Chinese men will eventually die of tobacco related diseases, and the annual number of tobacco deaths will rise to three million by the middle of the century.

“The only hope of substantially limiting tobacco deaths in China in the first half of this century is …
1186 SAFETY AND ANTIVIRAL ACTIVITY OF ABT-267, A NOVEL NS5A INHIBITOR, DURING 3-DAY MONOTHERAPY: FIRST STUDY IN HCV GENOTYPE-1 (GT1)-INFECTED TREATMENT-NAIVE SUBJECTS
Authors: E. Lawitz, T. Marbury, A. Campbell, E. Dumas, M. Kapoor, T. Pilot-Matias, P. Krishnan, C. Setze, W. Xie, T. Podsadecki, B. Bernstein, L. Williams
Journal: Journal of Hepatology (2012)
Aerosolized Pentamidine and Cutaneous Eruptions
Authors: Timothy G. Berger
Journal: Annals of Internal Medicine (1989)

Letters and Corrections15 June 1989Aerosolized Pentamidine and Cutaneous EruptionsTimothy G. Berger, MD, Jordan W. Tappero, MD, Gilford S. Leoung, MD, Mark A. Jacobson, MDTimothy G. Berger, MDSearch for more papers by this author, Jordan W. Tappero, MDSearch for more papers by this author, Gilford S. Leoung, MDSearch for more papers by this author, Mark A. Jacobson, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-110-12-1035_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: Aerosolized pentamidine is being used more frequently for prophylactic therapy and treatment of Pneumocytis carinii pneumonia in persons infected with human immunodeficiency virus (1, 2). It has been reported to have fewer adverse reactions than parenteral administration (2, 3), and has even been used in patients who have had adverse reactions during parenteral pentamidine therapy (3). Nonetheless, cutaneous hypersensitivity reactions can occur.A 57-year-old homosexual white man with the acquired immunodeficiency syndrome who had cytomegalovirus retinitis and Kaposi sarcoma had been receiving bimonthly aerosolized pentamidine, 60 mg, for 1 year when he presented with a 4-day history...References1. Conte J, Hollander H, and Golden J. Inhaled or reduced-dose intravenous pentamidine for Pneumocystis carinii pneumonia. A pilot study. Ann Intern Med. 1987;107:495-8. LinkGoogle Scholar2. Montgomery A, Luce J, and Turner J. Aerosolized pentamidine as sole therapy for Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. Lancet. 1987;2:480-3. CrossrefMedlineGoogle Scholar3. Havlichek D. Aerosolized pentamidine therapy [Letter]. Ann Intern Med. 1988;109:167-8. LinkGoogle Scholar4. Leen C and Mandal B. Rash due to nebulised pentamidine. Lancet. 1988;2:1250-1. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Timothy G. Berger, MD; Jordan W. Tappero, MD; Gilford S. Leoung, MD; Mark A. Jacobson, MDAffiliations: San Francisco General Hospital San Francisco, CA 94110 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDrug ReactionsToxic Epidermal Necrolysis Caused by Aerosolized PentamidineDRUG REACTIONS AND DESENSITIZATION IN AIDSThe Mucocutaneous Problems Associated with Human Immunodeficiency Virus InfectionContact urticaria from pentamidine isethionatePentamidine: A ReviewPentamidine: A ReviewAntiprotozoal drugsLa pneumocystose au cours de l'infection a HIV : Texte du consensusLes aerosols de pentamidine (AP) en prophylaxie primaire et secondaire de la pneumopathie a Pneumocystis carinii (PPC) 15 June 1989Volume 110, Issue 12Page: 1035-1036KeywordsAdverse reactionsAIDSHIV-1HomosexualsHypersensitivityKaposi sarcomaPneumoniaRetinitis ePublished: 1 December 2008 Issue Published: 15 June 1989 PDF downloadLoading ...
Salivary Gland Branching Morphogenesis — Recent Progress and Future Opportunities
Authors: Jeff Chi‐feng Hsu, Kenneth M Yamada
Journal: International Journal of Oral Science (2010)

Salivary glands provide saliva to maintain oral health, and a loss of salivary gland function substantially decreases quality‐of‐life. Understanding the biological mechanisms that generate salivary glands during embryonic development may identify novel ways to regenerate function or design artificial salivary glands. This review article summarizes current research on the process of branching morphogenesis of salivary glands, which creates gland structure during development. We highlight exciting new advances and opportunities in studies of cell‐cell interactions, mechanical forces, growth factors, and gene expression patterns to improve our understanding of this important process.
Power spectrum analysis of heart rate variability in human cardiac transplant recipients.
Authors: K E Sands, M L Appel, L S Lilly, F J Schoen, G H Mudge, R J Cohen
Journal: Circulation (1989)

Beat-to-beat heart rate variability was studied by power spectral analysis in 17 orthotopic cardiac transplant patients. Heart rate power spectra were calculated from eighty-four 256-second recordings and compared with those taken from six normal subjects. The power spectra from the control subjects resolved into discrete peaks at 0.04-0.12 Hz and 0.2-0.3 Hz, whereas those of heart transplant recipients resembled broad-band noise without peaks. Log total power in the 0.02-1.0 Hz range was greater in the control subjects (0.982 +/- 0.084 [0.206], mean +/- SEM [SD]) than in the transplanted subjects (-0.766 +/- 0.059 [0.541]), (p less than 0.0001). Fifty-five electrocardiographic recordings from transplant patients were done within 48 hours of an endomyocardial biopsy. When the power spectra of those patients whose endomyocardial biopsies showed evidence of myocardial rejection were compared with those from patients who were found to be free of rejection, a significant difference was found in log total power (-0.602 +/- 0.090 [0.525] vs. -0.909 +/- 0.136 [0.577], p less than 0.02). We conclude that denervation of the heart significantly reduces heart rate variability and abolishes the discrete spectral peaks seen in untransplanted control subjects and that the development of allograft rejection may significantly increase heart rate variability.
Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia
Authors: K. A. Quane, J.M.S. Healy, K. E. Keating, B. M. Manning, F. J. Couch, L. M. Palmucci, C. Doriguzzi, T. H. Fagerlund, K. Berg, H. Ording, D. Bendixen, W. Mortier, U. Linz, C. R. Muller, T. V. McCarthy
Journal: Nature Genetics (1993)
Perinatal Air Pollutant Exposures and Autism Spectrum Disorder in the Children of Nurses’ Health Study II Participants
Authors: Andrea L. Roberts, Kristen Lyall, Jaime E. Hart, Francine Laden, Allan C. Just, Jennifer F. Bobb, Karestan C. Koenen, Alberto Ascherio, Marc G. Weisskopf
Journal: Environmental Health Perspectives (2013)

Air pollution contains many toxicants known to affect neurological function and to have effects on the fetus in utero. Recent studies have reported associations between perinatal exposure to air pollutants and autism spectrum disorder (ASD) in children. We tested the hypothesis that perinatal exposure to air pollutants is associated with ASD, focusing on pollutants associated with ASD in prior studies.We estimated associations between U.S. Environmental Protection Agency-modeled levels of hazardous air pollutants at the time and place of birth and ASD in the children of participants in the Nurses' Health Study II (325 cases, 22,101 controls). Our analyses focused on pollutants associated with ASD in prior research. We accounted for possible confounding and ascertainment bias by adjusting for family-level socioeconomic status (maternal grandparents' education) and census tract-level socioeconomic measures (e.g., tract median income and percent college educated), as well as maternal age at birth and year of birth. We also examined possible differences in the relationship between ASD and pollutant exposures by child's sex.Perinatal exposures to the highest versus lowest quintile of diesel, lead, manganese, mercury, methylene chloride, and an overall measure of metals were significantly associated with ASD, with odds ratios ranging from 1.5 (for overall metals measure) to 2.0 (for diesel and mercury). In addition, linear trends were positive and statistically significant for these exposures (p < .05 for each). For most pollutants, associations were stronger for boys (279 cases) than for girls (46 cases) and significantly different according to sex.Perinatal exposure to air pollutants may increase risk for ASD. Additionally, future studies should consider sex-specific biological pathways connecting perinatal exposure to pollutants with ASD.
Collective radiation biodosimetry for dose reconstruction of acute accidental exposures: a review.
Authors: B Pass
Journal: Environmental Health Perspectives (1997)

Quantification of the biologically relevant dose is required to establish cause and effect between radiation detriment or burden and important biological outcomes. Most epidemiologic studies of unanticipated radiation exposure fail to establish cause and effect because researchers have not been able to construct a valid quantification of dose for the exposed population. However, no one biodosimetric technique (biophysical or biological) meets all the requirements of an ideal dosimeter. This paper reviews how the collection of biodosimetric data for victims of radiation accidents can be used to create a dosimetric
Lower Airways Inflammation during Rhinovirus Colds in Normal and in Asthmatic Subjects
Authors: David J. Fraenkel, Philip G. Bardin, Gwendolyn Sanderson, Fiona Lampe, Sebastian L. Johnston, Stephen T. Holgate
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Human rhinoviruses (HRV) cause the majority of common colds and are etiologically linked with changes in lower airways physiology and asthma exacerbations. We hypothesized that changes in bronchial mucosal inflammatory cell populations may be responsible for HRV-induced changes in airway reactivity. We examined bronchial mucosal biopsies during experimental infections with HRV serotype 16 and measured changes in histamine reactivity. Seventeen adult volunteers (six atopic asthmatics) had baseline measurements of histamine reactivity and fiberoptic bronchoscopic biopsies, followed 2 wk later by viral inoculation. Further bronchial biopsies were taken on Day 4 of the infection and 6 to 10 wk later. Mast cells, eosinophils, lymphocytes, and neutrophils were quantified by immunohistochemical techniques. Infection was documented by viral culture, seroconversion, and symptoms. An increase in histamine responsiveness during the cold (p = 0.048) was accompanied by increases in submucosal lymphocytes (p = 0.050). There was a subsequent decrease in submucosal and epithelial lymphocytes in convalescence (p = 0.028; p = 0.030). There was an increase in epithelial eosinophils with the cold (p = 0.042), and in asthmatics this appeared to persist into convalescence. A peripheral blood lymphopenia correlated with increased responsiveness (r = 0.062, p = 0.014). Rhinoviral colds are associated with a bronchial mucosal lymphocytic and eosinophilic infiltrate that may be related to changes in airway responsiveness and asthma exacerbations.
Progressive outer retinal necrosis caused by herpes simplex virus type 1 in a patient with acquired immunodeficiency syndrome
Authors: Mitsutoshi Kashiwase, Tetsutaro Sata, Yasuyuki Yamauchi, Hiroshi Minoda, Norio Usui, Takuya Iwasaki, Takeshi Kurata, Masahiko Usui
Journal: Ophthalmology (2000)
Exosomes as drug delivery vehicles for Parkinson's disease therapy
Authors: Matthew J. Haney, Natalia L. Klyachko, Yuling Zhao, Richa Gupta, Evgeniya G. Plotnikova, Zhijian He, Tejash Patel, Aleksandr Piroyan, Marina Sokolsky, Alexander V. Kabanov, Elena V. Batrakova
Journal: Journal of Controlled Release (2015)
Bcl-2 is overexpressed and alters the threshold for apoptosis in a cholangiocarcinoma cell line
Authors: D M Harnois, F G Que, A Celli, N F LaRusso, G J Gores
Journal: Hepatology (1997)

Cholangiocarcinoma is a malignant neoplasm originating from cholangiocytes. The mechanisms responsible for oncogenesis of cholangiocytes are unknown. Resistance to apoptosis, especially by altered expression of B-cell lymphoma/leukemia 2 (Bcl-2) family members, has been implicated as a mechanism contributing to malignant transformation. Thus, our aim was to test the hypothesis that altered expression of Bcl-2 family members by cholangiocarcinoma cells renders them resistant to apoptosis. We compared the apoptotic threshold and expression of the Bcl-2 protein family members, Bcl-2, Bcl-X L , and Bax, in two human cell lines: 1) nonmalignant human cholangiocytes immortalized by transfection with the simian virus 40 (SV 40) large T antigen; and 2) a malignant human cholangiocarcinoma cell line. Apoptosis was induced pharmacologically using beauvericin. Bcl-2, Bcl-x long, and Bax protein expression were evaluated by immunoblot analysis, and Bcl-2 expression was modulated using antisense technology. The cholangiocyte and malignant/nonmaligant phenotype of both cell lines was verified using both in vitro and in vivo approaches. Beauvericin induced apoptosis of nonmalignant cholangiocytes in a concentration- (0 to 25 μmol/L) and time- (0 to 6 hours) dependent manner. In contrast, malignant cholangiocytes were resistant to apoptosis. Although expression of Bcl-x long and Bax protein were similiar in the two cell lines, Bcl-2 protein expression was 15-fold greater in malignant than in nonmalignant cholangiocytes. An 18 mer bcl-2 antisense oligonucleotide reduced expression of Bcl-2 protein by 50% and increased the rate of beauvericin-induced apoptosis more than threefold in the malignant cells. Our results support the hypothesis that resistance to apoptosis by overexpression of Bcl-2 may be a feature of cholangiocarcinoma.
Idiopathic intracranial hypertension
Authors: K. B. Digre
Journal: BMJ (2010)

Weight loss may be effective, but confirmation is needed from randomised trials

In the linked prospective cohort study (doi:10.1136/bmj.c2701), Sinclair and colleagues observed intracranial pressure in patients with idiopathic intracranial hypertension who follow a low energy diet.1 This condition is often chronic and is characterised by symptoms and signs of intracranial hypertension, with no cause found by adequate imaging studies, and normal cerebrospinal fluid.2 Visual loss from papilloedema is the most feared visual complication.2 Headaches (which are difficult to treat) and depression are common, and quality of life is often reduced.3 4

Medical treatment of idiopathic intracranial hypertension consists of acetazolamide and other diuretics, which are thought to reduce the formation of cerebrospinal fluid.5 Because most affected people are obese, weight loss has been suggested. When visual loss occurs, surgical cerebrospinal fluid drainage procedures such as lumbar or ventriculo-peritoneal shunting or optic nerve sheath fenestration are performed. A recent systematic review found no randomised or controlled trials of treatment of the condition and called for such evidence.6

The risk of this condition …
Transdiaphragmatic Pressure Control of Airway Pressure Support in Healthy Subjects
Authors: Tarek Sharshar, Gilbert Desmarais, Bruno Louis, Gilles Macadou, Raphaël Porcher, Alain Harf, Jean-Claude Raphaël, Daniel Isabey, Frédéric Lofaso
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

We designed a new servoventilator that proportionally adjusts airway pressure to transdiaphragmatic pressure (Pdi) generated by the subject during inspiration. Each cycle is triggered by either a preset Pdi increase or a preset inspiratory flow value (whichever is reached first), whereas cycling-off is flow-dependent. We evaluated the servoventilator in seven healthy subjects at normocapnia and three levels of hypercapnia (normocapnia + 3, + 6, and + 9 mm Hg) comparatively with spontaneous breathing. Triggering was by Pdi in six subjects and flow in one. At all end-tidal carbon dioxide pressure levels, time from onset of diaphragm electromyographic activity to inspiratory flow was similar with and without the servoventilator. Airway pressure increased proportionally to Pdi variation during servoventilator breathing. Flow, tidal volume, respiratory rate, intrinsic positive end-expiratory pressure, and esophageal and transdiaphragmatic pressure–time products increased significantly with hypercapnia with and without the servoventilator. Breathing pattern parameters were similar in the two breathing modes, and no differences were found for intrinsic positive end-expiratory pressure or gastric pressure variation during exhalation. Esophageal and transdiaphragmatic pressure–time products were lower with than without the servoventilator. The Pdi-driven servoventilator was well synchronized to the subjects effort, delivering a pressure proportional to Pdi and reducing respiratory effort at normocapnia and hypercapnia.
Arsenite-Induced Alterations of DNA Photodamage Repair and Apoptosis After Solar-Simulation UVR in Mouse Keratinocytes <i>in Vitro</i>
Authors: Feng Wu, Fredric J. Burns, Ronghe Zhang, Ahmed N. Uddin, Toby G. Rossman
Journal: Environmental Health Perspectives (2005)

Our laboratory has shown that arsenite markedly increased the cancer rate caused by solar-simulation ultraviolet radiation (UVR) in the hairless mouse skin model. In the present study, we investigated how arsenite affected DNA photodamage repair and apoptosis after solar-simulation UVR in the mouse keratinocyte cell line 291.03C. The keratinocytes were treated with different concentrations of sodium arsenite (0.0, 2.5, 5.0 microM) for 24 hr and then were immediately irradiated with a single dose of 0.30 kJ/m2 UVR. At 24 hr after UVR, DNA photoproducts [cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs)] and apoptosis were measured using the enzyme-linked immunosorbent assay and the two-color TUNEL (terminal deoxynucleotide transferase dUTP nick end labeling) assay, respectively. The results showed that arsenite reduced the repair rate of 6-4PPs by about a factor of 2 at 5.0 microM and had no effect at 2.5 microM. UVR-induced apoptosis at 24 hr was decreased by 22.64% at 2.5 microM arsenite and by 61.90% at 5.0 microM arsenite. Arsenite decreased the UVR-induced caspase-3/7 activity in parallel with the inhibition of apoptosis. Colony survival assays of the 291.03C cells demonstrate a median lethal concentration (LC50) of arsenite of 0.9 microM and a median lethal dose (LD50) of UVR of 0.05 kJ/m2. If the present results are applicable in vivo, inhibition of UVR-induced apoptosis may contribute to arsenite's enhancement of UVR-induced skin carcinogenesis.
A Mechanistic Understanding of the Role of Feedforward Inhibition in the Mammalian Sound Localization Circuitry
Authors: Michael T. Roberts, Stephanie C. Seeman, Nace L. Golding
Journal: Neuron (2013)

Highlights•Feedforward inhibition precedes direct excitation in MSO neurons•Bilateral EPSP summation is linear during inhibition•Decreased Kv1 activation during inhibition counters inhibitory shunting•Preceding inhibition narrows but does not shift the coincidence detection windowSummaryFeedforward inhibition sharpens the precision of neurons throughout ascending auditory pathways, including the binaural neurons of the medial superior olive (MSO). However, the biophysical influence of inhibition is poorly understood, particularly at higher frequencies at which the relative phase of inhibition and excitation becomes ambiguous. Here, we show in gerbil MSO principal cells in vitro that feedforward inhibition precedes direct excitation, providing a concurrent hyperpolarization and conductance shunt during EPSP summation. We show with dual-patch recordings and dynamic clamp that both the linearity and temporal fidelity of synaptic integration is improved by reducing Kv1 potassium channel conductance during inhibition, which counters membrane shunting even at high frequencies at which IPSPs sum. The reduction of peak excitation by preceding inhibition lowers spike probability, narrowing but not shifting the window for detecting binaural coincidence. The interplay between inhibition and potassium conductances thus improves the consistency and resolution of ITD coding across different frequencies.