tbuckley/cabot-search huggingface dataset:
Prevalence and risk factors of airflow obstruction in an elderly Chinese population
Authors: F. W. S. Ko, J. Woo, W. Tam, C. K. W. Lai, J. Ngai, T. Kwok, D. S. C. Hui
Journal: European Respiratory Journal (2008)

It is common practice to use a forced expiratory volume in one second (FEV 1 )/ forced vital capacity (FVC) ratio of &lt;70% as evidence of airflow obstruction. As the FEV 1 /FVC ratio falls with age, the lower limit of normal range (LLN), defined as the bottom 5% in a health reference population, of FEV 1 /FVC ratio has been suggested as a better index to reduce over-diagnosis of chronic obstructive pulmonary disease (COPD), particularly in the elderly. However, there are no large scale studies that focus on the diagnosis of COPD in the elderly based on these definitions. The present prospective epidemiological study involved 1,149 elderly subjects aged ≥60 yrs in the community. Detailed questionnaires, pre- and post-bronchodilator spirometry were performed. In total, 1,008 subjects (mean age 74.2±6.4 yrs; 271 males) completed satisfactory spirometry testing. Airflow obstruction was present in 25.9% as defined by the post-bronchodilator FEV 1 /FVC ratio of &lt;70% and in 12.4% defined by the LLN of FEV 1 /FVC ratio. Moderate COPD, at least, was found in 14.0% of patients according to the post-bronchodilator FEV 1 /FVC ratio of &lt;70% and in 8.5% of patients according to LLN of FEV 1 /FVC ratio. In the present elderly Chinese population (mostly females, with low education level and previous exposure to biomass during formative years), the prevalence of chronic obstructive pulmonary disease varied markedly depending on definitions adopted. Further longitudinal studies are needed to determine the precise definition of chronic obstructive pulmonary disease.
Multisystemic production of interleukin 10 limits the severity of acute pancreatitis in mice
Authors: J-L Van Laethem, R Eskinazi, H Louis, F Rickaert, P Robberecht, J Devière
Journal: Gut (1998)

Background —Interleukin 10 (IL-10) decreases the severity of experimental acute pancreatitis. The role of endogenous IL-10 in modulating the course of pancreatitis is currently unknown. Aims —To examine the systemic release of IL-10 and its messenger RNA production in the pancreas, liver, and lungs and analyse the effects of IL-10 neutralisation in caerulein induced acute pancreatitis in mice. Methods —Acute necrotising pancreatitis was induced by intraperitoneal caerulein. Serum levels of IL-10 and tumour necrosis factor (TNF), and tissue IL-10 and TNF-α gene expression were assessed. After injecting control antibody or after blocking the activity of endogenous IL-10 by a specific monoclonal antibody, the severity of acute pancreatitis was assessed in terms of serum enzyme release, histological changes, and systemic and tissue TNF production. Results —In control conditions, serum IL-10 levels increased and correlated with the course of pancreatitis, with a maximal value eight hours after induction. Both IL-10 and TNF-α messengers showed a similar course, and were identified in the pancreas, liver, and lungs. Neutralisation of endogenous IL-10 significantly increased the severity of pancreatitis and associated lung injury as well as serum TNF protein levels (+75%) and pancreatic, pulmonary, and hepatic TNF messenger expression (+33%, +29%, +43%, respectively). Conclusions —In this non-lethal model, systemic release of IL-10 correlates with the course of acute pancreatitis. This anti-inflammatory response parallels the release of TNF and both cytokines are produced multisystemically. Endogenous IL-10 controls TNF-α production and plays a protective role in the local and systemic consequences of the disease.
Deletion of von Hippel–Lindau Protein Converts Renin-Producing Cells into Erythropoietin-Producing Cells
Authors: Birguel Kurt, Alexander Paliege, Carsten Willam, Ilona Schwarzensteiner, Kathrin Schucht, Hanna Neymeyer, Maria Luisa S. Sequeira-Lopez, Sebastian Bachmann, R. Ariel Gomez, Kai-Uwe Eckardt, Armin Kurtz
Journal: Journal of the American Society of Nephrology (2013)

States of low perfusion pressure of the kidney associate with hyperplasia or expansion of renin-producing cells, but it is unknown whether hypoxia-triggered genes contribute to these changes. Here, we stabilized hypoxia-inducible transcription factors (HIFs) in mice by conditionally deleting their negative regulator, Vhl, using the Cre/loxP system with renin-1d promoter-driven Cre expression. Vhl (−/−(REN)) mice were viable and had normal BP. Deletion of Vhl resulted in constitutive accumulation of HIF-2α in afferent arterioles and glomerular cells and HIF-1α in collecting duct cells of the adult kidney. The preglomerular vascular tree developed normally, but far fewer renin-expressing cells were present, with more than 70% of glomeruli not containing renin cells at the typical juxtaglomerular position. Moreover, these mice had an attenuated expansion of renin-producing cells in response to a low-salt diet combined with an ACE inhibitor. However, renin-producing cells of Vhl (−/−(REN)) mice expressed the erythropoietin gene, and they were markedly polycythemic. Taken together, these results suggest that hypoxia-inducible genes, regulated by VHL, are essential for normal development and physiologic adaptation of renin-producing cells. In addition, deletion of Vhl shifts the phenotype of juxtaglomerular cells from a renin- to erythropoietin-secreting cell type, presumably in response to HIF-2 accumulation.
Differential muscarinic receptor mRNA expression by freshly isolated and cultured bovine aortic endothelial cells.
Authors: W R Tracey, M J Peach
Journal: Circulation Research (1992)

Endothelial cells, either in vivo or freshly isolated, respond when exposed to muscarinic agonists with an increase in cytosolic free calcium concentration ([Ca2+]i) and release of endothelium-derived relaxing factor (EDRF). When placed in culture, however, endothelial cells rapidly lose these responses, which may be related to changes in muscarinic receptor expression. Northern blot analysis of poly(A) + RNA from freshly isolated or cultured bovine aortic endothelial cells was used to address this problem. Through the use of specific cDNA probes complementary to the nonconserved regions of the m1, m2, m3, m4, and m5 muscarinic receptors, mRNA transcripts for the m1 (3.9 kb), m2 (3.8 kb), and m3 (3.1 kb) receptor subtypes were identified in freshly isolated endothelial cells, whereas m1 and m3 transcripts were identified in aortic smooth muscle. In contrast, cultured endothelial cells contained mRNA for only the m2 receptor subtype. Transcripts for the m4 or m5 receptors were not detected in either freshly isolated or cultured endothelial cells. Since m1 and m3 receptor subtypes are coupled to phospholipase C, activation of which is required for EDRF release, these observations may explain the failure of muscarinic agonists to elicit a rise in [Ca2+]i and EDRF release from cultured endothelial cells.
Effects of Acute Angiotensin II Type 1 Receptor Antagonism and Angiotensin Converting Enzyme Inhibition on Plasma Fibrinolytic Parameters in Patients With Heart Failure
Authors: Nicholas E. R. Goodfield, David E. Newby, Christopher A. Ludlam, Andrew D. Flapan
Journal: Circulation (2000)

Angiotensin converting enzyme (ACE) inhibition after myocardial infarction is associated with an improvement in plasma fibrinolytic parameters. The aim of the present study was to determine whether acute ACE inhibition and angiotensin II type 1 (AT1) receptor antagonism have similar effects in patients with heart failure.Twenty patients with moderately severe chronic heart failure received enalapril 10 mg and losartan 50 mg on 2 separate occasions in a single-blind, randomized, crossover design. Plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) antigen and activity were measured at baseline and 6 hours after the dose. Acute administration of losartan but not of enalapril reduced plasma t-PA (11%; P=0.003) and PAI-1 (38%; P<0.001) antigen concentrations, which was associated with increases in t-PA (29%; P=0.03) and decreases in PAI-1 (48%; P=0.01) activity. Changes in plasma fibrinolytic parameters were more marked during losartan treatment (P<0.02), with a 3-fold greater reduction in plasma PAI-1 antigen concentrations (P<0.05).Acute AT1 antagonism in patients with heart failure is associated with a significant improvement in plasma fibrinolytic parameters that is greater than during ACE inhibition. These beneficial effects of AT1 antagonism and ACE inhibition would therefore appear to be mediated principally through suppression of angiotensin II.
Improvement in Sexual Functioning in Patients With Type 2 Diabetes and Depression Treated With Bupropion
Authors: G. S. Sayuk, B. M. Gott, B. D. Nix, P. J. Lustman
Journal: Diabetes Care (2011)

OBJECTIVE-Major depressive disorder (MDD) and type 2 diabetes have independent adverse effects on sexual functioning (SF).Bupropion (BU) reportedly has few sexual side effects, but its use in diabetes has not been studied.RESEARCH DESIGN AND METHODS-This article reports a planned secondary analysis of SF in 90 patients with type 2 diabetes treated with BU for MDD.RESULTS-At baseline, 71.1% of patients had insufficient SF.Mean Sexual Energy Scale (SES) scores improved during treatment (P , 0.0001), as did the percentage with sufficient SF (30.6 vs. 68.1%,P = 0.001).Patients with persistent hyperglycemia had higher rates of sexual dysfunction; however, SES improvement was evident in some with persistent depression or hyperglycemia (18.2% and 25.9%, respectively).CONCLUSIONS-Insufficient SF is prevalent and may be suspected in patients with MDD and type 2 diabetes.BU treatment of MDD had few sexual side effects and was associated with significant improvements in SF.
Aggressive juvenile fibromatosis of the paranasal sinuses: case report and brief review
Authors: Shaheen E Lakhan, Robert M Eager, Lindsey Harle
Journal: Journal of Hematology & Oncology (2008)

Desmoid fibromatoses are benign, slow growing fibroblastic neoplasms, arising from musculoaponeurotic stromal elements. Desmoids are characterized by local invasion, with a high rate of local recurrence and a tendency to destroy adjacent structures and organs. Desmoid fibromatoses are rare in children, and though they may occur in the head and neck region, are extremely rare in the paranasal sinuses. Here we report a case of extraabdominal desmoid fibromatosis in a seven-year-old boy involving the sphenoid sinus, one of only six published reports of desmoid fibromatosis of the paranasal sinuses. The expansile soft tissue mass eroded the walls of the sphenoid sinus as well as the posterior ethmoid air cells extending cephalad through the base of the skull. We discuss the clinicopathologic features of this lesion, including structural and ultrastructural characteristics, and we review the literature regarding treatment and outcome.
Mutant <i>KRAS</i> Codon 12 and 13 Alleles in Patients With Metastatic Colorectal Cancer: Assessment As Prognostic and Predictive Biomarkers of Response to Panitumumab
Authors: Marc Peeters, Jean-Yves Douillard, Eric Van Cutsem, Salvatore Siena, Kathy Zhang, Richard Williams, Jeffrey Wiezorek
Journal: Journal of Clinical Oncology (2012)

Panitumumab, a fully human monoclonal antibody targeting the epidermal growth factor receptor (EGFR), has demonstrated significant improvements in progression-free survival (PFS) in patients with wild-type KRAS metastatic colorectal cancer (mCRC) in studies 20050203 (first line), 20050181 (second line), and 20020408 (monotherapy). Mutations in KRAS codons 12 and 13 are recognized biomarkers that predict lack of response to anti-EGFR antibody therapies. This retrospective analysis of three randomized phase III studies assessed the prognostic and predictive impact of individual mutant KRAS codon 12 and 13 alleles.Patients were randomly assigned 1:1 to FOLFOX4 (infusional fluorouracil, leucovorin, and oxaliplatin) in study 20050203, FOLFIRI (fluorouracil, leucovorin, and irinotecan) in study 20050181, or best supportive care in study 20020408 with or without panitumumab 6.0 mg/kg once every 2 weeks. In all, 441 (20050203), 486 (20050181), and 126 (20020408) patients with mutant KRAS codon 12 or 13 alleles were included in the analysis.No mutant KRAS allele in patients treated on the control arm emerged as a consistent prognostic factor for PFS or overall survival (OS). In addition, no mutant KRAS allele was consistently identified as a predictive factor for PFS or OS in patients receiving panitumumab treatment. Significant interactions for individual mutant KRAS alleles were observed only in study 20050203 with G13D negatively and G12V positively associated with OS in the panitumumab-containing arm. Pooled analysis indicated that only G12A was associated with a negative predictive effect on OS.In this retrospective analysis, results across three treatment regimens suggest that patients with mutant KRAS codon 12 or 13 mCRC tumors are unlikely to benefit from panitumumab therapy. Currently, panitumumab therapy should be limited to patients with wild-type KRAS mCRC.
Fluorine Magnetic Resonance Spectroscopy Measurement of Brain Fluvoxamine and Fluoxetine in Pediatric Patients Treated for Pervasive Developmental Disorders
Authors: Wayne L. Strauss, Alan S. Unis, Charles Cowan, Geraldine Dawson, Stephen R. Dager
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Pediatric populations, including those with autistic disorder or other pervasive developmental disorders, increasingly are being prescribed selective serotonin reuptake inhibitors (SSRIs). Little is known about the age-related brain pharmacokinetics of SSRIs; there is a lack of data regarding optimal dosing of medications for children. The authors used fluorine magnetic resonance spectroscopy (19F MRS) to evaluate age effects on whole-brain concentrations of fluvoxamine and fluoxetine in children taking SSRIs. METHOD: Twenty-one pediatric subjects with diagnoses of autistic disorder or other pervasive developmental disorders, 6–15 years old and stabilized with a consistent dose of fluvoxamine or fluoxetine, were recruited for the study; 16 successfully completed the imaging protocol. Whole-brain drug levels in this group were compared to similarly acquired data from 28 adults. RESULTS: A significant relationship between dose and brain drug concentration was observed for both drugs across the age range studied. Brain fluvoxamine concentration in the children was lower, consistent with a lower dose/body mass drug prescription; when brain concentration was adjusted for dose/mass, age effects were no longer significant. Brain fluoxetine concentration was similar between age groups; no significant age effects on brain fluoxetine drug levels remained after adjustment for dose/mass. Observations of brain fluoxetine bioavailability and elimination half-life also were similar between age groups. CONCLUSIONS: These findings suggest that fluvoxamine or fluoxetine prescriptions adjusted for dose/mass are an acceptable treatment approach for medicating children with autistic disorder or other pervasive developmental disorders. It must be determined whether these findings can be generalized to other pediatric populations.
Routine double treatments of superficial basal cell carcinomas using aminolaevulinic acid‐based photodynamic therapy
Authors: J.C. Haller, F. Cairnduff, G. Slack, J. Schofield, C. Whitehurst, R. Tunstall, S.B. Brown, D.J.H. Roberts
Journal: British Journal of Dermatology (2000)

Journal Article Routine double treatments of superficial basal cell carcinomas using aminolaevulinic acid‐based photodynamic therapy Get access J.C. Haller, J.C. Haller School of Medicine, Search for other works by this author on: Oxford Academic Google Scholar F. Cairnduff, F. Cairnduff Cookridge Hospital, Leeds LS16 6QB, U.K. Search for other works by this author on: Oxford Academic Google Scholar G. Slack, G. Slack Cookridge Hospital, Leeds LS16 6QB, U.K. Search for other works by this author on: Oxford Academic Google Scholar J. Schofield, J. Schofield Department of Colour Chemistry, Schools of Search for other works by this author on: Oxford Academic Google Scholar C. Whitehurst, C. Whitehurst Paterson Institute for Cancer Research, Manchester M20 9BX, U.K. Search for other works by this author on: Oxford Academic Google Scholar R. Tunstall, R. Tunstall Biomedical Sciences, and Search for other works by this author on: Oxford Academic Google Scholar S.B. Brown, S.B. Brown Biochemistry and Molecular Biology, University of Leeds, LS2 9JT, U.K. Search for other works by this author on: Oxford Academic Google Scholar D.J.H. Roberts D.J.H. Roberts Biomedical Sciences, and Dr David Roberts. E‐mail: d.j.h.roberts@leeds.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 143, Issue 6, 1 December 2000, Pages 1270–1275, https://doi.org/10.1046/j.1365-2133.2000.04000.x Published: 01 December 2000 Article history Accepted: 01 June 2000 Published: 01 December 2000
Differential Distribution of Electrophysiologically Distinct Myocytes in Conduit and Resistance Arteries Determines Their Response to Nitric Oxide and Hypoxia
Authors: Stephen L. Archer, James M.C. Huang, Helen L. Reeve, Václav Hampl, Simona Tolarová, Evangelos Michelakis, E. Kenneth Weir
Journal: Circulation Research (1996)

Abstract The cellular mechanisms that determine differences in reactivity of arteries of varying size and origin are unknown. We evaluated the hypothesis that there is diversity in the distribution of K + channels between vascular smooth muscle (VSM) cells within a single segment of the pulmonary arteries (PAs) and that there are differences in the prevalence of these cell types between conduit and resistance arteries, which contribute to segmental differences in the vascular response to NO and hypoxia. Three types of VSM cells can be identified in rat PAs on the basis of their whole-cell electrophysiological properties—current density and the pharmacological dissection of whole-cell K + current (I K )—and morphology. Cells are referred to as “K Ca , K DR , or mixed,” acknowledging the type of K + channel that dominates the I K : the Ca 2+ -sensitive (K Ca ) channel, delayed rectifier (K DR ) channel, or a mixture of both. The three cell types were identified by light and electron microscopy. K Ca cells are large and elongated, and they have low current density and currents that are inhibited by tetraethylammonium (5 mmol/L) or charybdotoxin (100 nmol/L). K DR cells are smaller, with a perinuclear bulge, but have high current density and currents that are inhibited by 4-aminopyridine (5 mmol/L). Conduit arteries contain significant numbers of K Ca cells, whereas resistance arteries have a majority of K DR cells and few K Ca cells. NO rapidly and reversibly increases I K and hyperpolarizes K Ca cells because of an increase in open probability of a 170-pS K Ca channel. Hypoxia depolarizes K DR cells by rapidly and reversibly inhibiting one or more of the tonically active K DR channels (including a 37-pS channel) that control resting membrane potential. The effects of both hypoxia and NO on K + channels are evident at negative membrane potentials, supporting their physiological relevance. The functional correlate of this electrophysiological diversity is that K DR -enriched resistance vessels constrict to hypoxia, whereas conduit arteries have a biphasic response predominated by relaxation. Although effective in both segments, NO relaxes conduit more than resistance rings, in both cases by a cGMP-dependent mechanism. We conclude that regional electrophysiological diversity among smooth muscle cells is a major determinant of segmental differences in vascular reactivity.
Evidence for an Essential Role of Megalin in Transepithelial Transport of Retinol
Authors: ERIK ILSØ CHRISTENSEN, JAN ØIVIND MOSKAUG, HENRIK VORUM, CHRISTIAN JACOBSEN, THOMAS E. GUNDERSEN, ANDERS NYKJÆR, RUNE BLOMHOFF, THOMAS E. WILLNOW, SØREN K. MOESTRUP
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Transepithelial transport of retinol is linked to retinol-binding protein (RBP), which is taken up and also synthesized in a number of epithelia. By immunocytochemistry of human, rat, and mouse renal proximal tubules, a strong staining in apical endocytic vacuoles, lysosomes, endoplasmic reticulum, Golgi, and basal vesicles was observed, in accordance with luminal endocytic uptake as well as a constitutive synthesis and basal secretion of RBP. Analysis of mice with target disruption of the gene for the major endocytic receptor of proximal tubules, megalin, revealed no RBP in proximal tubules of these mice. Western blotting and HPLC of the urine of the megalin-deficient mice instead revealed a highly increased urinary excretion of RBP and retinol, demonstrating that glomerular filtered RBP-retinol of megalin-deficient mice escapes uptake by proximal tubules. A direct megalin-mediated uptake of purified RBP-retinol was indicated by surface plasmon resonance analysis and uptake in immortalized rat yolk sac cells. Uptake was partially inhibited by a polyclonal megalin antibody and the receptor-associated protein. The present data show that the absence of RBP-binding megalin causes a significantly increased loss of RBP and retinol in the urine, demonstrating a crucial role of megalin in vitamin A homeostasis.
Relationships Among the Metabolic Patterns That Correlate With Mnemonic, Visuospatial, and Mood Symptoms in Parkinson’s Disease
Authors: Marc J. Mentis, Anthony R. McIntosh, Kenneth Perrine, Vijay Dhawan, Brian Berlin, Andy Feigin, Christine Edwards, Paul Mattis, David Eidelberg
Journal: American Journal of Psychiatry (2002)

A multivariate analysis of baseline brain metabolism was used to investigate the relationships among pathophysiological mechanisms responsible for cognitive dysfunction and dysphoria in nondemented patients with Parkinson's disease.Using [(18)F]fluorodeoxyglucose positron emission tomography and neuropsychological tests, the authors studied 15 nondemented patients who had Parkinson's disease without major depression (DSM-III-R). Their mean age was 59.2 years (SD=9.2), the mean rating of Parkinson's disease stage (Hoehn and Yahr scale) was 3.3 (SD=0.9), and all had Mini-Mental State Examination scores of 24 or higher. To identify specific regional patterns of brain metabolism associated with abnormal cognitive and mood functioning, the data were analyzed by using brain-behavior partial least squares. This multivariate voxel-based analysis allowed detection of significant topographic patterns of metabolic activity and quantification of the extent to which each topographic pattern correlated with scores on mnemonic, visuospatial, and dysphoric tests.Two significant, independent topographic patterns were identified. Pattern 1 included parieto-occipito-temporal and medial temporal brain regions, and pattern 2 included the lateral frontal and anterior limbic cortex. Patterns 1 and 2 exhibited a double dissociation in their behavioral correlates: pattern 1 correlated with both visuospatial and mnemonic functioning but not with dysphoria; pattern 2 correlated with dysphoria but not with the cognitive measures.The authors used the independence of topographic patterns and the size of correlations between topographic patterns and behavior to infer relationships among the pathophysiological processes responsible for the correlations. The finding that mildly abnormal mnemonic and visuospatial functioning correlated with the same topographic pattern suggests that a common pathophysiology underlies this marker of cognition in Parkinson's disease. By contrast, the independence of the two topographic patterns supports the notion that different mechanisms underlie cognitive and dysphoric symptoms in nondemented patients with Parkinson's disease.