tbuckley/cabot-search huggingface dataset:
Mutations in the <i>SLC34A2</i> Gene Are Associated with Pulmonary Alveolar Microlithiasis
Authors: None Huqun, Shinyu Izumi, Hitoshi Miyazawa, Kuniaki Ishii, Bine Uchiyama, Tadashi Ishida, Sawako Tanaka, Ryushi Tazawa, Shunichiro Fukuyama, Tomoaki Tanaka, Yoshiaki Nagai, Akemi Yokote, Hiroki Takahashi, Toshihiko Fukushima, Kunihiko Kobayashi, Hirofumi Chiba, Makoto Nagata, Susumu Sakamoto, Koichiro Nakata, Yuji Takebayashi, Yoshihiko Shimizu, Koichi Kaneko, Michio Shimizu, Minoru Kanazawa, Shosaku Abe, Yoshikazu Inoue, Seiichi Takenoshita, Kunihiko Yoshimura, Koichiro Kudo, Teruo Tachibana, Toshihiro Nukiwa, Koichi Hagiwara
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Pulmonary alveolar microlithiasis is an autosomal recessive disorder in which microliths are formed in the alveolar space.To identify the responsible gene that causes pulmonary alveolar microlithiasis.By means of a genomewide single-nucleotide polymorphism analysis using DNA from three patients, we have narrowed the region in which the candidate gene is located. From this region, we have identified a gene that has mutations in all patients with pulmonary alveolar microlithiasis.We identified a candidate gene, SLC34A2, that encodes a type IIb sodium phosphate cotransporter and that is mutated in six of six patients investigated. SLC34A2 is specifically expressed in type II alveolar cells, and the mutations abolished the normal gene function.Mutations in the SLC34A2 gene that abolish normal gene function cause pulmonary alveolar microlithiasis.
International Union of Pharmacology. LXIII. Retinoid X Receptors
Authors: Pierre Germain, Pierre Chambon, Gregor Eichele, Ronald M. Evans, Mitchell A. Lazar, Mark Leid, Angel R. De Lera, Reuben Lotan, David J. Mangelsdorf, Hinrich Gronemeyer
Journal: Pharmacological Reviews (2006)

The physiological effects of retinoic acids (RAs) are mediated by members of two families of nuclear receptors, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs), which are encoded by three distinct human genes, <i>RXR</i>α<i>, RXR</i>β<i>,</i> and <i>RXR</i>γ. RARs bind both all-<i>trans</i>- and 9-<i>cis</i>-RA, whereas only the 9-<i>cis</i>-RA stereoisomer binds to RXRs. As RXR/RAR heterodimers, these receptors control the transcription of RA target genes through binding to RA-response elements. This review is focused on the structure, mode of action, ligands, expression, and pharmacology of RXRs. Given their role as common partners to many other members of the nuclear receptor superfamily, these receptors have been the subject of intense scrutiny. Moreover, and despite numerous studies since their initial discovery, RXRs remain enigmatic nuclear receptors, and there is still no consensus regarding their role. Indeed, multiple questions about the actual biological role of RXRs and the existence of an endogenous ligand have still to be answered.
TCT-733 Coronary Flow Reserve Pre and Post Transcatheter Aortic Valve Implantation in Severe Aortic Stenosis: An Invasive Evaluation Study of Coronary Flow Dynamics.
Authors: Anthony C. Camuglia, Jaffer Syed, Pallav Garg, Bob Kiaii, Michael Chu, Philip M. Jones, Daniel Bainbridge, Patrick Teefy
Journal: Journal of the American College of Cardiology (2013)
Comparison of inspiratory and expiratory resistance and reactance in patients with asthma and chronic obstructive pulmonary disease
Authors: P. Paredi, M. Goldman, A. Alamen, P. Ausin, O. S Usmani, N. B Pride, P. J Barnes
Journal: Thorax (2010)

<h3>Background</h3> The usual analysis of forced oscillometry measures respiratory resistance (Rrs) and reactance (Xrs) averaged over several tidal breaths (whole-breath analysis). Recent within-breath analyses have separated Rrs and Xrs into their mean inspiratory and mean expiratory components (inspiratory–expiratory breath analysis) but these have not been used to compare patients with asthma and those with chronic obstructive pulmonary disease (COPD). Large inspiratory–expiratory variations in Xrs at 5 Hz (ΔX5) in an individual have been used as a surrogate marker of expiratory flow limitation. <h3>Methods</h3> Whole-breath and inspiratory–expiratory impulse oscillometry was assessed in 34 patients with asthma (49±3 years; 15 male, forced expiratory volume in 1 s (FEV<sub>1</sub>) 69±4% predicted), 48 patients with COPD (64±2 years; 32 male, FEV<sub>1</sub> 59±3% predicted) and 18 normal subjects (37±2 years; 8 male). <h3>Results</h3> Whole-breath analysis failed to discriminate between patients with asthma and patients with COPD either for all patients or for patients with FEV<sub>1</sub> &lt;60% predicted. Inspiratory–expiratory analysis in patients with FEV<sub>1</sub> &lt;60% predicted showed that in the COPD group mean expiratory X5 (−0.44±0.04 kPa/l/s) was greater than inspiratory X5 (−0.23±0.02 kPa/l/s, p&lt;0.001) whereas patients with asthma did not show such changes (−0.36±0.07 kPa/l/s vs −0.26±0.03 kPa/l/s, p=0.23). Even though ΔX5 was larger in patients with COPD (0.21±0.03 kPa/l/s) than in patients with asthma (0.10±0.07 kPa/l/s), this was not significant (p=0.15). <h3>Conclusions</h3> Whole-breath impulse oscillation system analysis failed to discriminate between patients with asthma and those with COPD. Inspiratory–expiratory X5 analysis differentiated patients with asthma from those with COPD presumably reflecting enhanced dynamic airway narrowing on expiration in COPD. Further studies are needed to confirm these differences and investigate their cause.
Paroxetine Treatment of Generalized Anxiety Disorder: A Double-Blind, Placebo-Controlled Study
Authors: Karl Rickels, Rocco Zaninelli, James McCafferty, Kevin Bellew, Malini Iyengar, David Sheehan
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: This study assessed the efficacy of two fixed doses of paroxetine in the treatment of generalized anxiety disorder. METHOD: Outpatients (N=566) with generalized anxiety disorder and no other axis I disorder were eligible if they scored ≥20 on the Hamilton Rating Scale for Anxiety (with a score of 2 or higher on the anxious mood and tension items). Following a 1-week placebo run-in phase, patients were randomly assigned to 8 weeks of treatment with paroxetine, 20 or 40 mg/day, or placebo. The primary outcome measure was the change from baseline in total score on the Hamilton anxiety scale. Response was defined as a rating of "very much improved" or "much improved" on the Clinical Global Impression global improvement measure; remission was defined as a Hamilton anxiety scale score ≤7. Change in functional impairment was measured with the Sheehan Disability Scale. RESULTS: At 8 weeks, reductions in total score on the Hamilton anxiety scale were significantly greater for both paroxetine groups. Response was achieved by 62% and 68% of the patients receiving 20 and 40 mg of paroxetine, respectively, compared with a 46% response rate in the placebo group. Remission was achieved by 30% and 36% of patients in the 20- and 40-mg paroxetine groups, respectively, compared with 20% given placebo. For all three domains of the Sheehan Disability Scale, significantly greater improvement was seen with paroxetine than placebo. Both doses of paroxetine were well tolerated. CONCLUSIONS: This study demonstrates that paroxetine is an efficacious and well-tolerated treatment for generalized anxiety disorder.
Mannan-MUC1–Pulsed Dendritic Cell Immunotherapy: A Phase I Trial in Patients with Adenocarcinoma
Authors: Bruce E. Loveland, Anne Zhao, Shane White, Hui Gan, Kate Hamilton, Pei-Xiang Xing, Geoffrey A. Pietersz, Vasso Apostolopoulos, Hilary Vaughan, Vaios Karanikas, Peter Kyriakou, Ian F.C. McKenzie, Paul L.R. Mitchell
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Tumor antigen-loaded dendritic cells show promise for cancer immunotherapy. This phase I study evaluated immunization with autologous dendritic cells pulsed with mannan-MUC1 fusion protein (MFP) to treat patients with advanced malignancy. Experimental Design: Eligible patients had adenocarcinoma expressing MUC1, were of performance status 0 to 1, with no autoimmune disease. Patients underwent leukapheresis to generate dendritic cells by culture ex vivo with granulocyte macrophage colony-stimulating factor and interleukin 4 for 5 days. Dendritic cells were then pulsed overnight with MFP and harvested for reinjection. Patients underwent three cycles of leukapheresis and reinjection at monthly intervals. Patients with clinical benefit were able to continue with dendritic cell-MFP immunotherapy. Results: Ten patients with a range of tumor types were enrolled, with median age of 60 years (range, 33-70 years); eight patients were of performance status 0 and two of performance status 1. Dendritic cell-MFP therapy led to strong T-cell IFNγ Elispot responses to the vaccine and delayed-type hypersensitivity responses at injection sites in nine patients who completed treatments. Immune responses were sustained at 1 year in monitored patients. Antibody responses were seen in three patients only and were of low titer. Side effects were grade 1 only. Two patients with clearly progressive disease (ovarian and renal carcinoma) at entry were stable after initial therapy and went on to further leukapheresis and dendritic cell-MFP immunotherapy. These two patients have now each completed over 3 years of treatment. Conclusions: Immunization produced T-cell responses in all patients with evidence of tumor stabilization in 2 of the 10 advanced cancer patients treated. These data support further clinical evaluation of this dendritic cell-MFP immunotherapy.
The Effect of Raloxifene on Risk of Breast Cancer in Postmenopausal Women
Authors: S R Cummings, S Eckert, K A Krueger, D Grady, T J Powles, J A Cauley, L Norton, T Nickelsen, N H Bjarnason, M Morrow, M E Lippman, D Black, J E Glusman, A Costa, V C Jordan
Journal: JAMA (1999)

ContextRaloxifene hydrochloride is a selective estrogen receptor modulator that has antiestrogenic effects on breast and endometrial tissue and estrogenic effects on bone, lipid metabolism, and blood clotting.ObjectiveTo determine whether women taking raloxifene have a lower risk of invasive breast cancer.Design and SettingThe Multiple Outcomes of Raloxifene Evaluation (MORE), a multicenter, randomized, double-blind trial, in which women taking raloxifene or placebo were followed up for a median of 40 months (SD, 3 years), from 1994 through 1998, at 180 clinical centers composed of community settings and medical practices in 25 countries, mainly in the United States and Europe.ParticipantsA total of 7705 postmenopausal women, younger than 81 (mean age, 66.5) years, with osteoporosis, defined by the presence of vertebral fractures or a femoral neck or spine T-score of at least 2.5 SDs below the mean for young healthy women. Almost all participants (96%) were white. Women who had a history of breast cancer or who were taking estrogen were excluded.InterventionRaloxifene, 60 mg, 2 tablets daily; or raloxifene, 60 mg, 1 tablet daily and 1 placebo tablet; or 2 placebo tablets.Main Outcome MeasuresNew cases of breast cancer, confirmed by histopathology. Transvaginal ultrasonography was used to assess the endometrial effects of raloxifene in 1781 women. Deep vein thrombosis or pulmonary embolism were determined by chart review.ResultsThirteen cases of breast cancer were confirmed among the 5129 women assigned to raloxifene vs 27 among the 2576 women assigned to placebo (relative risk [RR], 0.24; 95% confidence interval [CI], 0.13-0.44; P&lt;.001). To prevent 1 case of breast cancer, 126 women would need to be treated. Raloxifene decreased the risk of estrogen receptor–positive breast cancer by 90% (RR, 0.10; 95% CI, 0.04-0.24), but not estrogen receptor–negative invasive breast cancer (RR, 0.88; 95% CI, 0.26-3.0). Raloxifene increased the risk of venous thromboembolic disease (RR, 3.1; 95% CI, 1.5-6.2), but did not increase the risk of endometrial cancer (RR, 0.8; 95% CI, 0.2-2.7).ConclusionAmong postmenopausal women with osteoporosis, the risk of invasive breast cancer was decreased by 76% during 3 years of treatment with raloxifene.
The significance of antinuclear and DNA antibodies in cryptogenic fibrosing alveolitis.
Authors: S T Holgate, P Haslam, M Turner-Warwick
Journal: Thorax (1983)

The roles of antinuclear and DNA antibodies in the pathogenesis of cryptogenic fibrosing alveolitis were investigated in 53 patients. Twenty-two patients who had antinuclear antibodies detected in their serum had a significantly higher proportion of women, a higher prevalence of Raynaud phenomenon and digital vasculitis, and higher erythrocyte sedimentation rates, paralleled by raised serum globulin and IgG levels, than patients with no antinuclear antibodies detected. Serum antibodies to double-strand DNA (DS-DNA), assayed by a Farr binding technique, were significantly raised in 25% of patients with cryptogenic fibrosing alveolitis. Serum binding of single-strand DNA (SS-DNA) was greatly increased in all the patients with cryptogenic fibrosing alveolitis, achieving levels similar to those found in systemic lupus erythematosus. Serum DS-DNA binding correlated with IgA levels but not with disease activity. Thus, unlike in systemic lupus erythematosus, antibodies to DS-DNA and SS-DNA with their capacity to form immune complexes are unlikely to be of major importance in the pathogenesis of cryptogenic fibrosing alveolitis.
Cross‐reactivity between IgE‐binding proteins from <i>Anisakis</i> German cockroach, and chironomids
Authors: C. Y. Pascual, J. F. Crespo, S. San Martin, N. Ornia, N. Ortega, T. Caballero, M. Muñoz‐Pereira, M. Martin‐Esteban
Journal: Allergy (1997)

Pascual CY, Crespo JF, San Martin S, Ornia N, Ortega N, Caballero T, Munoz‐Pereira M, Martin‐Estaban M. Cross‐reactivity between IgE‐binding proteins from Anisakis German cockroach, and chironomids. Anisakis simplex larvae parasitize animals used as seafood and can produce a specific immune response in man. The ingestion of seafood contaminated with stage three of A. simplex larvae can induce a specific IgE response with clinical symptoms, usually urticaria, even if the fish is cooked before ingestion and the invasive infestation power destroyed by heating. Our preliminary studies showed a strong association of A. simplex sensitization with Ascaris lumbricoides, Daphnia chironomid spp., Atlantic shrimp ‘ Pandalus borealis ’ and German cockroach ‘ Blattella germanica’. We conducted the cross‐reactivity study with cockroach, a ubiquitous insect, and Chironomidae ‘red mosquito larvae’, a work‐related allergen, without any possibility of Anisakis contamination. Serum samples were collected from 60 pediatric patients, with serum specific IgE to A. simplex. Both specific‐IgE and immunoblot‐inhibition studies, with a serum pool from 18 patients, were performed to determine whether the association of sensitizations to nematodes and arthropods was due to immunologic cross‐reactivity. In addition, serum samples from 21 of 60 patients who showed also sensitization to German cockroach were used for individual immunoblot studies. In the serum pool, dose‐dependent inhibition of B. germanica and Chironomus spp. was observed after preincubation with the A. simplex extract. Immunoblot of Anisakis inhibited with Chironomus and German cockroach, yielded a partial blot inhibition but mainly on bands below 41 kDa. Blot inhibition of German cockroach and Chironomus with Anisakis was dose related. The band patterns in individual blots were heterogeneous, but most of them had bands of 30–43 kDa. None of these sera recognized allergens in the 14–kDa area. In our study, CAP‐inhibition and immunoblot‐inhibition analysis of Anisakis showed that several IgE‐binding components could be shared by the three allergens.
Angiotensin-Converting Enzyme Inhibitor Preserves p21 and Endothelial Nitric Oxide Synthase Expression in Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats
Authors: Shinichi Kanno, Yi-Jen L. Wu, Paul C. Lee, Timothy R. Billiar, Chien Ho
Journal: Circulation (2001)

Background — Pulmonary arterial hypertension (PAH) is associated with structural changes in the pulmonary vasculature characterized by the proliferation of cellular components of the vessels. ACE inhibitor (ACEI) may have beneficial effects in treating PAH, but its precise mechanism of action in the remodeling process is unclear. p21 is a cyclin-dependent kinase inhibitor that may have a protective role in this process by inhibiting cellular proliferation. Endothelial nitric oxide synthase (eNOS) has also been shown to be protective by its vasodilatory effect. Therefore, we investigated whether expression of p21 and eNOS was modulated by ACEI treatment in a rat model. Methods and Results — Monocrotaline (MCT) was administered to 2 groups of Sprague-Dawley rats fed a high-cholesterol diet, ie, one group received MCT concomitantly with enalapril treatment (MCT + /ACEI + rats), and the other group did not receive enalapril (MCT + /ACEI − rats). After 5 weeks, MRI showed right ventricular hypertrophy in MCT + /ACEI − rats. MCT + /ACEI + rats showed a preserved right ventricular morphology. Isolated pulmonary perfusion studies showed that ACEI significantly upregulated NO production, as measured by nitrite levels. Addition of N -methyl– d -glucamine dithiocarbamate–Fe solution, an NO-trapping agent, reversed the basal vasodilatory effect of ACEI in the pulmonary vasculature. Immunoblot analysis showed decreased p21 and eNOS expression in the lung in MCT + /ACEI − rats, whereas their expression was preserved with enalapril treatment. Conclusions — ACEI suppresses the development of MCT-induced PAH in rats. The mechanism of action might involve the preservation of p21 and eNOS expression. Both p21 and endothelium-derived NO appear to have protective roles in the development of PAH.
Population Genomic Analysis Reveals No Evidence for GC-Biased Gene Conversion in Drosophila melanogaster
Authors: Matthew C. Robinson, Eric A. Stone, Nadia D. Singh
Journal: Molecular Biology and Evolution (2013)

Gene conversion is the nonreciprocal exchange of genetic material between homologous chromosomes. Multiple lines of evidence from a variety of taxa strongly suggest that gene conversion events are biased toward GC-bearing alleles. However, in Drosophila, the data have largely been indirect and unclear, with some studies supporting the predictions of a GC-biased gene conversion model and other data showing contradictory findings. Here, we test whether gene conversion events are GC-biased in Drosophila melanogaster using whole-genome polymorphism and divergence data. Our results provide no support for GC-biased gene conversion and thus suggest that this process is unlikely to significantly contribute to patterns of polymorphism and divergence in this system.
The γ-Aminobutyric Acid (GABA) System and Hepatic Encephalopathy
Authors: Eugene Roberts
Journal: Hepatology (1984)

HepatologyVolume 4, Issue 2 p. 342-345 EditorialsFree Access The γ-Aminobutyric Acid (GABA) System and Hepatic Encephalopathy Eugene Roberts, Corresponding Author Eugene Roberts Beckman Research Institute of the City of Hope Duarte, California 91010Eugene Roberts, Ph.D., Director, Department of Neurobiochemistry, Beckman Research Institute of the City of Hope, Duarte, California 91010===Search for more papers by this author Eugene Roberts, Corresponding Author Eugene Roberts Beckman Research Institute of the City of Hope Duarte, California 91010Eugene Roberts, Ph.D., Director, Department of Neurobiochemistry, Beckman Research Institute of the City of Hope, Duarte, California 91010===Search for more papers by this author First published: March‐April 1984 https://doi.org/10.1002/hep.1840040228Citations: 23AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume4, Issue2March‐April 1984Pages 342-345 ReferencesRelatedInformation
Adrenal function in asthmatic children
Authors: S. CROWLEY;, D. FITZGERALD, P. VAN ASPEREN, C. MELLIS, M. HONNER, L. SMITH, G. AMBLER
Journal: Thorax (1999)

In a recent paper published in Thorax Fitzgerald and co-authors purport to have examined the effects of fluticasone propionate and beclomethasone dipropionate on adrenal function in children with asthma.1They state that they have used Dickstein’s low dose ACTH test 2 to do this. However, the dose of ACTH (500 ng/1.73 m2) used in Fitzgerald’s paper is a dose taken from a different paper describing a dose-response relationship between ACTH and serum cortisol concentration published by Crowley et al 3 and a later paper by the same author comparing low dose with high dose ACTH cortisol secretory dynamics.4 Dickstein’s paper described a low dose ACTH test in adults using a test dose of 1 μg. This dose was not standardised for body surface area and is approximately twice the size of the dose used by Crowley et al . The cortisol …
Evidence for Sensory Prediction Deficits in Schizophrenia
Authors: Sukhwinder S Shergill, Gabrielle Samson, Paul M Bays, Chris D Frith, Daniel M Wolpert
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Patients with schizophrenia experiencing delusions and hallucinations can misattribute their own actions to an external source. The authors test the hypothesis that patients with schizophrenia have defects in their ability to predict the sensory consequences of their actions. METHOD: The authors measured sensory attenuation of self-produced stimuli by patients with schizophrenia and by healthy subjects. RESULTS: Patients with schizophrenia demonstrated significantly less sensory attenuation than healthy subjects. CONCLUSIONS: Patients with a diagnosis of schizophrenia have a dysfunction in their predictive mechanisms.
Phase I Dose Escalation and Pharmacokinetic Study of Enzastaurin, an Oral Protein Kinase C Beta Inhibitor, in Patients With Advanced Cancer
Authors: Michael A. Carducci, Luna Musib, Merrill S. Kies, Roberto Pili, Mylene Truong, Julie R. Brahmer, Patricia Cole, Rana Sullivan, Jeanne Riddle, Jill Schmidt, Nathan Enas, Vikram Sinha, Donald E. Thornton, Roy S. Herbst
Journal: Journal of Clinical Oncology (2006)

Purpose This phase I study was conducted to determine the recommended dose of enzastaurin, an oral protein kinase C beta (PKCβ) inhibitor, for phase II trials. Secondary objectives were maximum-tolerated dose (MTD), pharmacokinetics (PK), toxicity, and response. Patients and Methods Patients at least 18 years of age with advanced cancer and an Eastern Cooperative Oncology Group performance status of 0 or 1 lower received enzastaurin orally once daily at a starting dose of 20 mg. Dose escalation proceeded using a modified Simon design. Results All 47 patients enrolled (mean age, 58 years) received at least one dose of enzastaurin, with a median of two cycles (range, one to 17 cycles). Prevalent malignancies were lung (n = 10) and head and neck cancers (n = 9). Although no MTD was identified up to 700 mg/d, 525 mg was chosen as the recommended dose, and 12 additional patients were accrued at that level. Three dose-limiting toxicities (QTc changes) occurred: one at the 700-mg dose (patient discontinued), and two in the expansion cohort at the 525-mg dose. Total analytes (enzastaurin and its metabolites) exposure increased with increasing doses up to 240 mg, and appeared to plateau at 525 and 700 mg. Grade 1 chromaturia, fatigue, and other GI toxicities were the most common, while no clinically significant grade 3/4 toxicities occurred. Two deaths, unrelated to enzastaurin, occurred. Twenty-one patients (45%) achieved stable disease (SD) for two to 16 cycles. Conclusion On the basis of plasma exposures and safety data, enzastaurin 525 mg once daily is the recommended phase II dose. Enzastaurin is well tolerated up to 700 mg/d. Evidence of early activity was seen with significant stable disease.