tbuckley/cabot-search huggingface dataset:
A case for auditory temporal processing as an evolutionary precursor to speech processing and language function
Authors: Roslyn Holly Fitch, Paula Tallal
Journal: Behavioral and Brain Sciences (1995)

Abstract Wilkins &amp; Wakefield suggest that changes in the hominid brain made it uniquely “preadaptive” for language, yet no precursor functions served as adaptive substrates to the emergence of language. We present contrary evidence that the ability to discriminate and process rapid and complex auditory information is a cross-species function subserving communication processes including, but not limited to, human speech perception. We suggest that auditory temporal processing served as an evolutionary precursor to speech processing and consequent language development in humans.
Antisense Therapy against CCR3 and the Common Beta Chain Attenuates Allergen-induced Eosinophilic Responses
Authors: Gail M. Gauvreau, Louis Philippe Boulet, Donald W. Cockcroft, Adrian Baatjes, Johanne Cote, Francine Deschesnes, Beth Davis, Tara Strinich, Karen Howie, MyLinh Duong, Richard M. Watson, Paolo M. Renzi, Paul M. O'Byrne
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

The drug product TPI ASM8 contains two modified phosphorothioate antisense oligonucleotides designed to inhibit allergic inflammation by down-regulating human CCR3 and the common beta chain (beta(c)) of IL-3, IL-5, and granulocyte-macrophage colony-stimulating factor receptors.This study examined the effects of inhaled TPI ASM8 on sputum cellular influx, CCR3 and beta(c) mRNA and protein levels, and the airway physiologic response after inhaled allergen.Seventeen subjects with mild atopic asthma were randomized in a crossover study to inhale 1,500 microg TPI ASM8 or placebo by nebulizer, once daily for 4 days. On Day 3, subjects underwent allergen inhalation challenge. Sputum samples were collected before and after allergen. CCR3 and beta(c) protein levels were measured by flow cytometry, mRNA was measured using real-time quantitative polymerase chain reaction, and the FEV1 was measured over 7 hours after challenge.Compared with placebo, TPI ASM8 inhibited sputum eosinophil influx by 46% (P = 0.02) and blunted the increase in total cells (63%) after allergen challenge. TPI ASM8 significantly reduced the early asthmatic response (P = 0.04) with a trend for the late asthmatic response (P = 0.08). The allergen-induced (Day 2 to Day 3) levels of beta(c) mRNA and CCR3 mRNA in sputum-derived cells were inhibited by TPI ASM8 (P = 0.039 and P = 0.054, respectively), with no significant effects on the cell surface protein expression of CCR3 and beta(c) (P > 0.05). No serious adverse events were reported.TPI ASM8 attenuates the allergen-induced increase in target gene mRNA and airway responses in subjects with mild asthma. Clinical trial registered with www.clinicaltrials.gov (NCT 00264966).
Comparative Genomics Reveals the Origins and Diversity of Arthropod Immune Systems
Authors: William J. Palmer, Francis M. Jiggins
Journal: Molecular Biology and Evolution (2015)

Insects are an important model for the study of innate immune systems, but remarkably little is known about the immune system of other arthropod groups despite their importance as disease vectors, pests, and components of biological diversity. Using comparative genomics, we have characterized the immune system of all the major groups of arthropods beyond insects for the first time—studying five chelicerates, a myriapod, and a crustacean. We found clear traces of an ancient origin of innate immunity, with some arthropods having Toll-like receptors and C3-complement factors that are more closely related in sequence or structure to vertebrates than other arthropods. Across the arthropods some components of the immune system, such as the Toll signaling pathway, are highly conserved. However, there is also remarkable diversity. The chelicerates apparently lack the Imd signaling pathway and beta-1,3 glucan binding proteins—a key class of pathogen recognition receptors. Many genes have large copy number variation across species, and this may sometimes be accompanied by changes in function. For example, we find that peptidoglycan recognition proteins have frequently lost their catalytic activity and switch between secreted and intracellular forms. We also find that there has been widespread and extensive duplication of the cellular immune receptor Dscam (Down syndrome cell adhesion molecule), which may be an alternative way to generate the high diversity produced by alternative splicing in insects. In the antiviral short interfering RNAi pathway Argonaute 2 evolves rapidly and is frequently duplicated, with a highly variable copy number. Our results provide a detailed analysis of the immune systems of several important groups of animals for the first time and lay the foundations for functional work on these groups.
Prevention of Breast Cancer in Postmenopausal Women: Approaches to Estimating and Reducing Risk
Authors: S. R. Cummings, J. A. Tice, S. Bauer, W. S. Browner, J. Cuzick, E. Ziv, V. Vogel, J. Shepherd, C. Vachon, R. Smith-Bindman, K. Kerlikowske
Journal: JNCI Journal of the National Cancer Institute (2009)

BackgroundIt is uncertain whether evidence supports routinely estimating a postmenopausal woman's risk of breast cancer and intervening to reduce risk.
Breast feeding, nutritional state, and child survival in rural Bangladesh
Authors: A. Briend, B. Wojtyniak, M. G M Rowland
Journal: BMJ (1988)

The effect of breast feeding on nutritional state, morbidity, and child survival was examined prospectively in a community in rural Bangladesh. Every month for six months health workers inquired about breast feeding and illness and measured arm circumference in an average of 4612 children aged 12-36 months. Data from children who died within one month of a visit were compared with those from children who survived. Roughly one third of the deaths in the age range 18-36 months were attributable to absence of breast feeding. Within this age range protection conferred by breast feeding was independent of age but was evident only in severely malnourished children. In communities with a high prevalence of malnutrition breast feeding may substantially enhance child survival up to 3 years of age.
Concurrent Trastuzumab and HER2/<i>neu</i>-Specific Vaccination in Patients With Metastatic Breast Cancer
Authors: Mary L. Disis, Danelle R. Wallace, Theodore A. Gooley, Yushe Dang, Meredith Slota, Hailing Lu, Andrew L. Coveler, Jennifer S. Childs, Doreen M. Higgins, Patricia A. Fintak, Corazon dela Rosa, Kathleen Tietje, John Link, James Waisman, Lupe G. Salazar
Journal: Journal of Clinical Oncology (2009)

The primary objectives of this phase I/II study were to evaluate the safety and immunogenicity of combination therapy consisting of concurrent trastuzumab and human epidermal growth factor receptor 2 (HER2)/neu-specific vaccination in patients with HER2/neu-overexpressing metastatic breast cancer.Twenty-two patients with stage IV HER2/neu-positive breast cancer receiving trastuzumab therapy were vaccinated with an HER2/neu T-helper peptide-based vaccine. Toxicity was graded according to National Cancer Institute criteria, and antigen specific T-cell immunity was assessed by interferon gamma enzyme-linked immunosorbent spot assay. Data on progression-free and overall survival were collected.Concurrent trastuzumab and HER2/neu vaccinations were well tolerated, with 15% of patients experiencing an asymptomatic decline in left ventricular ejection fraction below the normal range during combination therapy. Although many patients had pre-existing immunity specific for HER2/neu and other breast cancer antigens while treated with trastuzumab alone, that immunity could be significantly boosted and maintained with vaccination. Epitope spreading within HER2/neu and to additional tumor-related proteins was stimulated by immunization, and the magnitude of the T-cell response generated was significantly inversely correlated with serum transforming growth factor beta levels. At a median follow-up of 36 months from the first vaccine, the median overall survival in the study population has not been reached.Combination therapy with trastuzumab and a HER2/neu vaccine is associated with minimal toxicity and results in prolonged, robust, antigen-specific immune responses in treated patients.
Sputum induction leads to a decrease of exhaled nitric oxide unrelated to airflow
Authors: J. Beier, K.M. Beeh, O. Kornmann, R. Buhl
Journal: European Respiratory Journal (2003)

Measurement of exhaled nitric oxide (eNO) and analysis of induced sputum are both established noninvasive methods for studying airway inflammation in asthma. Both methods are often used sequentially within short time frames. The aim of the present study was to evaluate the influence of sputum induction on eNO in adults and to follow the kinetics of airway eNO production after induction in relation to forced expiratory volume in one second (FEV 1 ). eNO and FEV 1 were measured in 41 adult patients (aged 29 (range 23–50) yrs, 56% male) with asymptomatic atopy or mild asthma (mean FEV 1 97.2±3% predicted) prior to and immediately after sputum induction with hypertonic saline (4%). Sputum induction with isotonic saline was also performed in 13 subjects (control group). Repeatability of eNO decrease after sputum induction was also studied in 27 patients on separate occasions and kinetics of eNO production after sputum induction were followed over 24 h in another 10 patients. Sputum induction with hypertonic, but not isotonic, saline led to a marked decrease in eNO (log) immediately after the procedure (pre: 3.85±0.13 parts per billion (ppb); post: 3.24±0.14 ppb). This decrease was shown to be highly reproducible and not related to a fall in FEV 1 following sputum induction. While FEV 1 returned to baseline within 1 h, decreased eNO levels were observed over 4 h and returned to baseline after 24 h. Hypertonic saline sputum induction leads to a prolonged reduction in exhaled nitric oxide in adult atopics that is reproducible within subjects and not related to a reduction in airflow following sputum induction. This methodological interference should be taken into account when sputum induction and exhaled nitric oxide measurements are performed in the same subject.
Capillary recruitment is impaired in essential hypertension and relates to insulin's metabolic and vascular actions
Authors: E Serné
Journal: Cardiovascular Research (2001)

Objective: In patients with essential hypertension, defects in both the metabolic and vascular actions of insulin have been described. Impaired microvascular function, a well-established abnormality in essential hypertension, may explain part of these defects. In the present study we investigated whether microvascular function is impaired in essential hypertension and relates to insulin's metabolic and vasodilatatory actions. Methods: We measured 24-h ambulatory blood pressure, capillary recruitment after arterial occlusion, and skin blood flow responses to iontophoresis of acetylcholine and sodium nitroprusside in 18 subjects with untreated essential hypertension and in 18 control subjects. Whole body insulin sensitivity and leg insulin-mediated vasodilatation were assessed with the hyperinsulinaemic clamp technique and plethysmography. Results: Hypertensive, as compared to normotensive, subjects had a decreased insulin sensitivity (0.8±0.3 vs. 1.7±0.6 mgkg−1min−1 per pmoll−1; P<0.001), capillary recruitment after arterial occlusion (21.5±5.8 vs. 45.9±10.4%; P<0.001), acetylcholine-mediated vasodilatation (331±84 vs. 688±192%; P<0.001), and insulin-mediated vasodilatation (median 29.3 vs. 47.2%; P<0.05). Correlation analyses with adjustment for sex, age, body mass index and waist-to-hip ratio showed significant relationships of capillary recruitment after arterial occlusion with blood pressure (r = −0.68; P<0.01), insulin sensitivity (r = +0.55; P<0.01) and insulin-mediated vasodilatation (r = +0.51; P<0.05), which extended from the normotensive to the hypertensive range. Conclusion: Skin microvascular function is associated with blood pressure and insulin's metabolic and vasodilatatory actions, both in normotensive and hypertensive subjects. These findings offer a potential mechanistic explanation of the links among insulin resistance, impaired insulin-mediated vasodilatation and hypertension.
Multiple gastric red spots, capillary ectasia, hypergastrinemia and hypopepsinogenemia i in cirrhosis: A new syndrome?
Authors: Michael I. Samloff
Journal: Hepatology (1988)

To characterize bleeding from gastric red spots in patients with cirrhosis, three groups of patients were studied: (a) 11 cirrhotic patients bleeding from gastric red spots, (b) 18 nonbleeding cirrhotic patients without gastric red spots, and (c) 13 non-cirrhotic patients with endoscopic normal mucosa (controls). Histologic examination of antral biopsy specimens revealed a diffuse capillary ectasia without inflammation in 8 of the 11 cirrhotic patients with gastric lesions. Morphometric analysis disclosed a significantly greater mean mucosal capillary cross-sectional area in cirrhotic patients with gastric lesions (mean ± SE, 1371 ± 320 μm 2 ) than in those without gastric lesions (541 ± 61 μm 2 ) (p &lt; 0.005) or controls (353 ± 20 μm 2 ) (p &lt; 0.001). Hypergastrinemia was detected in 8 of the 11 cirrhotic patients with lesions, in 2 of the 18 cirrhotic patients without gastric lesions, and in none of the controls (p &lt; 0.001). Gastrin serum levels correlated significantly (r = 0.80) with mean mucosal capillary cross-sectional area in patients with cirrhosis. Pepsinogen I serum levels below 20 ng/ml were observed in 7 of the 11 cirrhotic patients with lesions, in 1 of the 18 cirrhotic patients without lesions, and in none of the controls. These data indicate that bleeding from gastric red spots in patients with cirrhosis is a distinct entity characterized by vascular ectasia of the gastric mucosa. This condition seems to be associated with hypergastrinemia and low serum levels of pepsinogen I.
Hepatic bile versus gallbladder bile: A comparison of protein and lipid concentration and composition in cholesterol gallstone patients
Authors: Yolande C. Keulemans, Kam S. Mok, Laurens Th de Wit, Dirk J. Gouma, Albert K. Groen
Journal: Hepatology (1998)

Many studies have demonstrated that gallbladder bile (but not hepatic bile) of animals or patients with cholesterol gallstones contains higher protein concentrations than does gallbladder bile of control patients without stones or with pigment stones. The underlying defect has not been elucidated. To establish whether there is net production or net absorption/degradation of protein by gallbladder epithelium for different classes of protein, paired samples of hepatic and gallbladder bile were obtained from fourteen patients with cholesterol gallstones during elective cholecystectomy. In these paired samples, lipid and protein composition were determined. To obtain the concentration ratio (CR) of protein and lipid, its concentration in the gallbladder was divided by the concentration determined in the paired hepatic bile sample. The CR of bile salts was used as a parameter for water absorption in the gallbladder. Of the biliary proteins that were determined only mucin, albumin, immunoglobulin (Ig) G, and aminopeptidase N appeared to increase in the gallbladder from another cause than water absorption. A strong correlation was found between mucin, albumin, and IgG. Haptoglobin, α 1 -acid glycoprotein, IgM, and IgA appeared to be absorbed by gallbladder epithelium in the majority of patients. In cholesterol gallstone patients, total protein concentration in gallbladder bile of cholesterol gallstone patients is increased when compared with hepatic bile. The increase in protein concentration cannot be explained for all bile samples solely by water absorption. In this study we show that the defect is largely caused by a selective increase in albumin, mucin, and IgG. All other proteins which were investigated are taken up by the gallbladder.
Cardiotoxicity Induced by Chemotherapy and Antibody Therapy
Authors: Edward T.H. Yeh
Journal: Annual Review of Medicine (2006)

Modern cancer therapy employs a combination of chemotherapy, antibody-based therapy, radiotherapy, and surgery to prolong life and provide cure. However, many of the chemotherapy agents and antibodies, either singly or in combination, can affect the cardiovascular system. Common cardiovascular manifestations of these therapies include heart failure, ischemia, hypotension, hypertension, edema, QT prolongation, bradyarrhythmia, and thromboembolism. The patient's age, underlying cardiovascular status, and genetic background, as well as the route of drug administration and dosage, can all contribute to the development of cardiotoxicity. Strategies to monitor for and to manage these effects are discussed in this review.
Comparative genomic analysis of the odorant-binding protein family in 12 Drosophila genomes: purifying selection and birth-and-death evolution
Authors: Filipe G Vieira, Alejandro Sánchez-Gracia, Julio Rozas
Journal: Genome biology (2007)

Abstract Background Chemoreception is a widespread mechanism that is involved in critical biologic processes, including individual and social behavior. The insect peripheral olfactory system comprises three major multigene families: the olfactory receptor (Or), the gustatory receptor (Gr), and the odorant-binding protein (OBP) families. Members of the latter family establish the first contact with the odorants, and thus constitute the first step in the chemosensory transduction pathway. Results Comparative analysis of the OBP family in 12 Drosophila genomes allowed the identification of 595 genes that encode putative functional and nonfunctional members in extant species, with 43 gene gains and 28 gene losses (15 deletions and 13 pseudogenization events). The evolution of this family shows tandem gene duplication events, progressive divergence in DNA and amino acid sequence, and prevalence of pseudogenization events in external branches of the phylogenetic tree. We observed that the OBP arrangement in clusters is maintained across the Drosophila species and that purifying selection governs the evolution of the family; nevertheless, OBP genes differ in their functional constraints levels. Finally, we detect that the OBP repertoire evolves more rapidly in the specialist lineages of the Drosophila melanogaster group ( D. sechellia and D. erecta ) than in their closest generalists. Conclusion Overall, the evolution of the OBP multigene family is consistent with the birth-and-death model. We also found that members of this family exhibit different functional constraints, which is indicative of some functional divergence, and that they might be involved in some of the specialization processes that occurred through the diversification of the Drosophila genus.
Follistatin-Like 1 Is an Akt-Regulated Cardioprotective Factor That Is Secreted by the Heart
Authors: Yuichi Oshima, Noriyuki Ouchi, Kaori Sato, Yasuhiro Izumiya, David R. Pimentel, Kenneth Walsh
Journal: Circulation (2008)

The Akt protein kinase is an important mediator of cardiac myocyte growth and survival. To identify factors with novel therapeutic applications in cardiac diseases, we focused on the identification of factors secreted from Akt1-activated cells that have cardioprotective effects through autocrine/paracrine mechanisms.Using an inducible Akt1 transgenic mouse model, we have found that follistatin-like 1 (Fstl1) protein and transcript expression are increased 4.0- and 2.0-fold, respectively, by Akt activation in the heart (P<0.05). Fstl1 transcript was also upregulated in response to myocardial stresses including transverse aortic constriction, ischemia/reperfusion injury, and myocardial infarction. Adenovirus-mediated overexpression of Fstl1 protected cultured neonatal rat ventricular myocytes from hypoxia/reoxygenation-induced apoptosis (P<0.01), and this protective effect was dependent on the upregulation of both Akt and ERK activities. Conversely, knockdown of Fstl1 in cardiac myocytes decreased basal Akt signaling and increased the frequency of apoptotic death in vitro (P<0.01). The intravenous administration of an adenoviral encoding Fstl1 to mice resulted in a 66.0% reduction in myocardial infarct size after ischemia/reperfusion injury that was accompanied by a 70.9% reduction in apoptosis in the heart (P<0.01).These results indicate that Fstl1 is a cardiac-secreted factor that functions as an antiapoptotic protein. Fstl1 could play a role in myocardial maintenance and repair in response to harmful stimuli.
Effect of serial-day exposure to nitrogen dioxide on airway and blood leukocytes and lymphocyte subsets
Authors: C. Solomon, D.L. Christian, L.L. Chen, B.S. Welch, M.T. Kleinman, E. Dunham, D.J Erle, J.R Balmes
Journal: European Respiratory Journal (2000)

Nitrogen dioxide (NO2) is a free radical-producing oxidant gas. Inhalation of NO2 could cause airway inflammation, and decrease immune function. This experiment tested the hypothesis that exposure to NO2 would: 1) increase leukocytes in bronchoalveolar lavage (BAL); and 2) change the distribution of lymphocyte subsets and activation in BAL and peripheral blood (PB). Using a counter-balanced, repeated-measures design, 15 healthy volunteers were exposed to filtered air (FA) or 2.0 parts per million NO2 for 4 h x day(-1) (4 x 30 min of exercise), for three consecutive days. Bronchoscopy was performed 18 h following each exposure set, and PB was drawn pre-exposure and pre-bronchoscopy. Flow cytometry was used to enumerate lymphocyte subsets and activation makers in BAL and PB. In the bronchial fraction, there was an increase in the percentage of neutrophils following NO2 exposure compared to FA (median (interquartile range): 10.6 (4.8-17.2)% versus 5.3 (2.5-8.3)%; p=0.005). In the BAL, there was a decrease in the percentage of T-helper cells following NO2 exposure compared to FA (55.9 (40.8-62.7)% versus 61.6 (52.6-65.2)%; p=0.022). For PB, there were no between-condition differences in any leukocyte or lymphocyte subsets, or activation. In conclusion exposure to nitrogen dioxide results in bronchial inflammation and a minimal change in bronchoalveolar lavage T-helper cells, and no changes in peripheral blood cells.
Alterations in prescribing by general practitioner fundholders: an observational study
Authors: R. P H Wilson, I. Buchan, T Walley
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objectives</b>: To compare prescribing in general practices before and after they become fundholders to assess whether this affected prescribing patterns. <b>Design</b>: Analysis of prescribing data (PACT) for one year before and one year after practices become first, second, or third wave fundholders and comparison with practices that were not fundholders during any part of the study. <b>Main outcome measures</b>: Prescribing costs (net ingredient cost per prescribing unit), prescribing volume (items per 1000 prescribing units), net ingredient cost per item, and percentage of generic prescribing. <b>Setting</b>: Former Mersey Regional Health Authority. <b>Subjects</b>: 100 fundholders (20 first wave, 31 second wave, 49 third wave) and 312 non-fundholders. <b>Results</b>: Prescribing costs and volume rose throughout the study in all groups. In all three fundholding waves the rate of increase of prescribing costs was significantly lower than for non-fundholders. Both cost per item and prescribing volume tended to decrease, the former probably because of a significant increase in generic prescribing. Fundholding and non-fundholding practices differed in several respects. <b>Conclusion</b>: Fundholding has altered practice prescribing patterns compared with those of non-fundholders, increasing generic prescribing and reducing the rate of increase of prescribing costs.