tbuckley/cabot-search huggingface dataset:
Mechanism of Glomerular Hyperfiltration After a Protein Meal in Humans: Role of hormones and amino acids
Authors: K Sreekumaran Nair, Rufino C Pabico, Joseph A Truglia, Barbara A McKenna, Marcia Statt, Dean H Lockwood
Journal: Diabetes Care (1994)

OBJECTIVES Previous studies demonstrated that protein meals and amino acid (AA) infusions increase glomerular nitration rate (GFR) and renal plasma flow (RPF) and that somatostatin (SRIH) infusion inhibits these increments. We tested whether a single AA such as alanine could increase GFR and RPF and whether the changes in GFR and RPF could be explained on the basis of changes in glucagon, growth hormone (GH), and insulin. RESEARCH DESIGN AND METHODS In the first experiment, alanine was infused with or without SRIH in five normal subjects. In the second experiment, five other subjects were infused with SRIH on three separate occasions. In a control study, insulin, glucagon, and GH were given at replacement doses; in a hyperglucagonemia study, glucagon was given at a rate of 0.2 μ · kg−1 · h−1 (hypoglucagonemia); and in a high GH study, GH was given at a rate of 2 /μg · kg−1· h−1. GFR and RPF were measured using inulin and para-aminohippurate, respectively. RESULTS Alanine increased GFR and RPF, whereas SRIH inhibited these changes (P &amp;lt; 0.05). Hyperglucagonemia or high GH with or without insulin failed to increase RPF or GFR. CONCLUSIONS A single AA such as alanine increases GFR and RPF, and this increase is dependent on a factor inhibited by SRIH. Although GH, glucagon, and insulin are factors inhibited by SRIH, none of these factors explains the changes in RPF and GFR in our acute studies.
Improved cardiac risk stratification in major vascular surgery with dobutamine-atropine stress echocardiography
Authors: Don Poldermans, Mariarosaria Arnese, Paolo M. Fioretti, Alessandro Salustri, Eric Boersma, Ian R. Thomson, Jos R.T.C. Roelandt, Hero Van Urk
Journal: Journal of the American College of Cardiology (1995)
Impact of Sleep Deprivation and Subsequent Recovery Sleep on Cortisol in Unmedicated Depressed Patients
Authors: Ulrich Voderholzer, Fritz Hohagen, Torsten Klein, Julia Jungnickel, Clemens Kirschbaum, Mathias Berger, Dieter Riemann
Journal: American Journal of Psychiatry (2004)

One night of sleep deprivation induces a transient improvement in about 60% of depressed patients. Since depression is associated with abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis, the authors measured cortisol secretion before, during, and after therapeutic sleep deprivation for 1 night.Fifteen unmedicated depressed inpatients participated in a combined polysomnographic and endocrine study. Blood was sampled at 30-minute intervals during 3 consecutive nights before, during, and after sleep deprivation. Saliva samples were collected at 30-minute intervals during the daytime before and after the sleep deprivation night.During the night of sleep deprivation, cortisol levels were significantly higher than at baseline. During the daytime, cortisol levels during the first half of the day were higher than at baseline in the patients who responded to sleep deprivation but not in the nonresponders. During recovery sleep, cortisol secretion returned to baseline values.This study demonstrated a significant stimulatory effect of 1 night of sleep deprivation on the HPA axis in unmedicated depressed patients. The results suggest that the short-term effects of antidepressant treatments on the HPA axis may differ from their long-term effects. A higher cortisol level after sleep deprivation might transiently improve negative feedback to the hypothalamus or interact with other neurotransmitter systems, thus mediating or contributing to the clinical response. The fast return to baseline values coincides with the short clinical effect.
Forkhead Box F1 Regulates Tumor-Promoting Properties of Cancer-Associated Fibroblasts in Lung Cancer
Authors: Roy-Akira Saito, Patrick Micke, Janna Paulsson, Martin Augsten, Cristina Peña, Per Jönsson, Johan Botling, Karolina Edlund, Leif Johansson, Peter Carlsson, Karin Jirström, Kohei Miyazono, Arne Östman
Journal: Cancer Research (2010)

Cancer-associated fibroblasts (CAF) attract increasing attention as potential cancer drug targets due to their ability to stimulate, for example, tumor growth, invasion, angiogenesis, and metastasis. However, the molecular mechanisms causing the tumor-promoting properties of CAFs remain poorly understood. Forkhead box F1 (FoxF1) is a mesenchymal target of hedgehog signaling, known to regulate mesenchymal-epithelial interactions during lung development. Studies with FoxF1 gain- and loss-of-function fibroblasts revealed that FoxF1 regulates the contractility of fibroblasts, their production of hepatocyte growth factor and fibroblast growth factor-2, and their stimulation of lung cancer cell migration. FoxF1 status of fibroblasts was also shown to control the ability of fibroblasts to stimulate xenografted tumor growth. FoxF1 was expressed in CAFs of human lung cancer and associated with activation of hedgehog signaling. These observations suggest that hedgehog-dependent FoxF1 is a clinically relevant lung CAF-inducing factor, and support experimentally the general concept that CAF properties can be induced by activation of developmentally important transcription factors.
Prior Endocrine Therapy Impact on Abiraterone Acetate Clinical Efficacy in Metastatic Castration-resistant Prostate Cancer: Post-hoc Analysis of Randomised Phase 3 Studies
Authors: Joaquim Bellmunt, Thian Kheoh, Margaret K. Yu, Matthew R. Smith, Eric J. Small, Peter F.A. Mulders, Karim Fizazi, Dana E. Rathkopf, Fred Saad, Howard I. Scher, Mary-Ellen Taplin, Ian D. Davis, Dirk Schrijvers, Andrew Protheroe, Arturo Molina, Peter De Porre, Thomas W. Griffin, Johann S. de Bono, Charles J. Ryan, Stéphane Oudard
Journal: European Urology (2015)
Prevalence of untreated asthma in a population sample of 6000 older adults in Bristol, UK
Authors: L Dow, L Fowler, L Phelps, K Waters, D Coggon, A L Kinmonth, S T Holgate
Journal: Thorax (2001)

A study was undertaken to estimate the prevalence of untreated asthma in older adults.A cross sectional population based survey of 6000 men and women aged 65 years and over was performed in 21 general practices in north Bristol, south west England. The main outcome measure was untreated asthma as defined by a two stage process comprising a respiratory questionnaire (symptoms suggestive of asthma or doctor diagnosed asthma not receiving respiratory treatment) followed by lung function tests (significant reversibility following bronchodilators or corticosteroids and/or significant within day variability in peak expiratory flow).4792 of the 6000 participants (80%) completed the respiratory questionnaire and, of those not receiving respiratory treatment, 55 reported a previous doctor diagnosis of asthma and a further 696 had symptoms suggestive of asthma. Lung function testing in 280 of 501 randomly selected individuals from these groups resulted in 38 being defined as having asthma and an estimated population prevalence for untreated asthma of 2.4% (95% CI 1.6% to 3.6%) in men and 1.2% (95% CI 0.7% to 2.1%) in women. Most subjects (84%) with untreated asthma had moderate or severe disease. Untreated asthma was most common in individuals with doctor diagnosed asthma (21%) and those with breathlessness or wheeze (13-20%).Untreated asthma in the elderly is a common and important problem. Opportunistic use of appropriate lung function tests in older people with a history of doctor diagnosed asthma or wheeze or breathlessness at rest could identify untreated asthmatics who might benefit from treatment.
Associations of Uric Acid with Polymorphisms in the δ-Aminolevulinic Acid Dehydratase, Vitamin D Receptor, and Nitric Oxide Synthase Genes in Korean Lead Workers
Authors: Virginia M. Weaver, Brian S. Schwartz, Bernard G. Jaar, Kyu-Dong Ahn, Andrew C. Todd, Sung-Soo Lee, Karl T. Kelsey, Ellen K. Silbergeld, Mark E. Lustberg, Patrick J. Parsons, Jiayu Wen, Byung-Kook Lee
Journal: Environmental Health Perspectives (2005)

Recent research suggests that uric acid may be nephrotoxic at lower levels than previously recognized and that it may be one mechanism for lead-related nephrotoxicity. Therefore, in understanding mechanisms for lead-related nephrotoxicity, it would be of value to determine whether genetic polymorphisms that are associated with renal outcomes in lead workers and/or modify associations between lead dose and renal function are also associated with uric acid and/or modify associations between lead dose and uric acid. We analyzed data on three such genetic polymorphisms: delta-aminolevulinic acid dehydratase (ALAD), endothelial nitric oxide synthase (eNOS), and the vitamin D receptor (VDR). Mean (+/- SD) tibia, blood, and dimercaptosuccinic acid-chelatable lead levels were 37.2 +/- 40.4 microg/g bone mineral, 32.0+/- 15.0 g/dL, and 0.77+/- 0.86 microg/mg creatinine, respectively, in 798 current and former lead workers. Participants with the eNOSAsp allele had lower mean serum uric acid compared with those with the Glu/Glu genotype. Among older workers (age > or = median of 40.6 years), ALAD genotype modified associations between lead dose and uric acid levels. Higher lead dose was significantly associated with higher uric acid in workers with the ALAD1-1 genotype; associations were in the opposite direction in participants with the variant ALAD1-2 genotype. In contrast, higher tibia lead was associated with higher uric acid in those with the variant VDRB allele; however, modification was dependent on participants with the bb genotype and high tibia lead levels. We conclude that genetic polymorphisms may modify uric acid mediation of lead-related adverse renal effects.
INDUCTION OF TOLERANCE TO SHEEP RED BLOOD CELLS
Authors: Traute-Heidi Anderson, Joan Roethle, Robert Auerbach
Journal: The Journal of Experimental Medicine (1972)

Adult mice injected with a sheep red blood cell hemolysate supernatant fraction were found to have a severely reduced responsiveness to subsequent immunization with sheep red blood cells. The induced unresponsiveness was found to be specific, as tested by reciprocal experiments involving horse and sheep erythrocyte preparations. The tolerogenic material did not appear to be immunogenic.
Inverted Formin 2 Regulates Actin Dynamics by Antagonizing Rho/Diaphanous-related Formin Signaling
Authors: Hua Sun, Johannes Schlondorff, Henry N. Higgs, Martin R. Pollak
Journal: Journal of the American Society of Nephrology (2013)

Mutations in inverted formin 2 INF2 are a common cause of familial FSGS. INF2 interacts with diaphanous-related formins (mDia) and antagonizes mDia-mediated actin polymerization in response to active Rho signaling, suggesting that dysregulation of these pathways may mediate the development of INF2-related FSGS. However, the precise mechanisms by which INF2 regulates actin-dependent podocyte behavior remain largely unknown. Here, we investigated the possible role of INF2 in both lamellipodia-associated actin dynamics and actin-dependent slit diaphragm (SD) protein trafficking by manipulating the expression of INF2 and the activity of Rho/mDia signaling in cultured podocytes. Activation of mDia in the absence of INF2 led to defective formation of lamellipodia and abnormal SD trafficking. Effects of mutations disrupting the INF2-mDia interaction suggested the specificity of the mDia-antagonizing effect of INF2 in maintaining the lamellipodium. Furthermore, we found that SD trafficking requires INF2 interaction with lipid raft components. In summary, INF2 regulates lamellipodial actin dynamics and the trafficking of slit diaphragm proteins by opposing Rho/mDia-mediated actin polymerization. Thus, in podocytes, INF2 appears to be an important modulator of actin-dependent behaviors that are under the control of Rho/mDia signaling.
Developing the role of patients as teachers: literature review
Authors: G. Wykurz
Journal: BMJ (2002)

To identify the roles and settings in which patients participate as teachers in medical education and the benefits to learners, their educational institutions, and participating patients.Review of publications from 1970 to October 2001 providing descriptions, evaluations, or research of programmes involving patients as teachers in medical education.1848 references were identified from various electronic databases. Applying inclusion criteria to abstracts generated 100 articles, from which 23 were selected after independent scrutiny.13 articles discussed the role of patients in teaching physical examination skills, mostly musculoskeletal examination. Patients also taught pelvic and male genitorectal examination skills. Teaching roles varied, and 19 articles referred to patients' involvement as assessors. 18 articles described patients' training, with some patients being assessed. Reports of learners' experiences were all positive, many valuing the insights and confidence gained from practising skills on patients in a teaching role. Some learners preferred being taught by trained patients rather than doctors. Patients who were consulted enjoyed their teaching role. Several articles commented on the high quality of patients' teaching. Remuneration varied from payment of expenses to an hourly rate. Motivation for recruiting patients included the desire to reduce costs and the value attributed to the consumers' perspective.Involving patients as teachers has important educational benefits for learners. Patients offer unique qualities that can enhance the acquisition of skills and change attitudes towards patients.
Allelotypes and Fluorescence <i>In situ</i> Hybridization Profiles of Poorly Differentiated Endocrine Carcinomas of Different Sites
Authors: Daniela Furlan, Barbara Bernasconi, Silvia Uccella, Roberta Cerutti, Ileana Carnevali, Carlo Capella
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The aim of this work was to investigate the genotypic profiles of 36 poorly differentiated endocrine carcinoma (PDEC) of different sites to verify if their very similar phenotype may reflect similar pattern of genetic anomalies and if useful diagnostic or prognostic markers may be pointed out. Experimental Design: All tumors were microallelotyped at 57 microsatellite on 11 autosomes and the allelotypes of a selected panel of tumors were validated by interphasic fluorescence in situ hybridization with centromeric probes for chromosomes 1, 3, 6, 11, 17, and 18 and a probe specific for p53. Results: Regardless of the primary sites, PDECs exhibit very complex allelotypes (86%) and TP53 allelic imbalance (89%). Among these cases, fluorescence in situ hybridization analysis confirmed the presence of multiple aneusomies and a chromosome instability phenotype. Very low percentage of allelic imbalance (AI) and few aneuploidies were detected in only five PDECs for which an overall longer survival was observed. We found recurrent AI on 3p, 5, and 11q13 in lung PDECs, on 5q21, 8p, and 18q21 in colorectal PDECs and on 7 and 11q22 in gastric PDECs. Significantly better outcome was observed in patients with PDEC exhibiting 8q AIs and absence of AI at chromosome regions 6q25 and 6p. Conclusions: The concurrence of p53 inactivation and aneuploidies or chromosome instability are the main features of PDECs. However, the specific allelotypes observed in relation to primary site support the hypothesis that PDECs and exocrine carcinomas of all sites may share early pathogenetic mechanisms. Molecular markers of potential diagnostic and prognostic values for PDECs of different sites have been identified.
Differential activity of nitric oxide synthase in human nasal mucosa and polyps
Authors: I Ramis, J Lorente, J Rosello-Catafau, P Quesada, E Gelpi, O Bulbena
Journal: European Respiratory Journal (1996)

Nitric oxide (NO) plays an important regulatory role in airway function and seems to be implicated in the pathophysiology of several airway diseases. To better understand the involvement of NO in the upper airways, we examined the presence of nitric oxide synthase (NOS) activity in human nasal mucosa and nasal polyp tissues. Nasal mucosa was obtained from seven patients undergoing septoplasty, and nasal polyps came from nine patients following polypectomy. NOS activity was quantified in tissue homogenates using the citrulline release assay and localized in tissue sections using reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry. The results showed that nasal polyps (n = 9) contained higher levels of total NOS activity (mean +/- SD 5.94 +/- 5.71, range 1.29-18.0 pmol.min-1.mg protein) than nasal mucosa tissues (n = 7) (0.28 +/- 0.22, range 0.01-0.57 pmol.min-1.mg protein). In addition, nasal polyps mainly contained inducible NOS activity (4.67 +/- 4.57, range 1.23-15.5 pmol.min-1.mg protein) whereas in nasal mucosa all NOS activity detected was in constitutive form. In both cases, NOS activity was localized in the epithelial cells. Since NO synthase is induced in inflamed upper airways, we conclude that NO may be an important inflammatory mediator in the respiratory system and that the epithelium may be a source of NO production in the human upper airways.
Shared<i>Pseudomonas aeruginosa</i>genotypes are common in Australian cystic fibrosis centres
Authors: Timothy J. Kidd, Kay A. Ramsay, Honghua Hu, Guy B. Marks, Claire E. Wainwright, Peter T. Bye, Mark R. Elkins, Philip J. Robinson, Barbara R. Rose, John W. Wilson, Keith Grimwood, Scott C. Bell
Journal: European Respiratory Journal (2012)

Recent molecular-typing studies suggest cross-infection as one of the potential acquisition pathways for <i>Pseudomonas aeruginosa</i> in patients with cystic fibrosis (CF). In Australia, there is only limited evidence of unrelated patients sharing indistinguishable <i>P. aeruginosa</i> strains. We therefore examined the point-prevalence, distribution, diversity and clinical impact of <i>P. aeruginosa</i> strains in Australian CF patients nationally. 983 patients attending 18 Australian CF centres provided 2887 sputum <i>P. aeruginosa</i> isolates for genotyping by enterobacterial repetitive intergenic consensus-PCR assays with confirmation by multilocus sequence typing. Demographic and clinical details were recorded for each participant. Overall, 610 (62%) patients harboured at least one of 38 shared genotypes. Most shared strains were in small patient clusters from a limited number of centres. However, the two predominant genotypes, AUST-01 and AUST-02, were widely dispersed, being detected in 220 (22%) and 173 (18%) patients attending 17 and 16 centres, respectively. AUST-01 was associated with significantly greater treatment requirements than unique <i>P. aeruginosa</i> strains. Multiple clusters of shared <i>P. aeruginosa</i> strains are common in Australian CF centres. At least one of the predominant and widespread genotypes is associated with increased healthcare utilisation. Longitudinal studies are now needed to determine the infection control implications of these findings.
Lineage-Specific Differences in Evolutionary Mode in a Salamander Courtship Pheromone
Authors: Catherine A. Palmer, Richard A. Watts, Ron G. Gregg, Maureen A. McCall, Lynne D. Houck, Richard Highton, Stevan J. Arnold
Journal: Molecular Biology and Evolution (2005)

Functionally equivalent genes may evolve heterogeneously across closely related taxa as a consequence of lineage-specific selective pressures. Such disparate evolutionary modes are especially prevalent in genes that encode postcopulatory reproductive proteins, presumably as a result of sexual selection. We might therefore expect genes that mediate reproduction prior to insemination to evolve in a similar manner. Plethodontid receptivity factor (PRF), a proteinaceous salamander pheromone produced by the male, increases female receptivity during courtship interactions. To test for lineage-specific differences in PRF's evolution, we intensively sampled PRF genes across the eastern Plethodon phylogeny (27 spp.; 34 populations) to compare gene diversification, rates of evolution, modes of selection, and types of amino acid substitution. Our analyses indicate that PRF evolutionary dynamics vary considerably from lineage to lineage. Underlying this heterogeneity, however, are two well-defined transitions in evolutionary mode. The first mode is representative of a typical protein profile, wherein neutral divergence and purifying selection are the dominant features. The second mode is characterized by incessant, cyclical evolution driven by positive selection. In this mode, the positively selected sites are bound by a limited assortment of acceptable amino acids that appear to evolve independently of other sites, resulting in a tremendous number of unique PRF alleles. Several of these selected sites are implicated in receptor binding. These sites are apparently involved in a molecular tango in which the male signal and female receptors coevolve within a confined molecular space. PRF's lineage-specific evolutionary dynamics, in combination with evidence of a molecular tango, highlight the molecular action of sexual selection on a chemical signal that is used during courtship.