tbuckley/cabot-search huggingface dataset:
Hypoxic Pulmonary Vasoconstriction in the Rat
Authors: STEVEN BERKOV
Journal: Circulation Research (1974)

In isolated blood-perfused rat lungs, brief periods of ventilation hypoxia (2% O 2 ) produce pulmonary vasoconstriction. In isolated lungs perfused with a salt-albumin solution, hypoxia produces no pulmonary vasoconstrictor responses in most preparations and only minimal responses in others. Vasoactive agents including angiotensin II, phenylephrine, epinephrine, norepinephrine, bradykinin, histamine, serotonin, and methoxamine were added to the salt-albumin perfusate to determine which substance, if any, was necessary for a pulmonary vasoconstrictor response during hypoxia. The addition of angiotensin II (12-120 nM) to the perfusate during hypoxia resulted in marked pulmonary vasoconstriction in proportion to the amount of angiotensin II added (a maximal response to hypoxia occurred with 120 nM angiotensin II). None of the other agents had the same effect, nor was their vasoactivity dependent on angiotensin II. Angiotensin II augmented the hypoxic response in doses that are themselves subpressor; tachyphylaxis to the direct pressor activity of angiotensin II was not associated with attenuation of the hypoxic response. These results suggest that an action of angiotensin II that is separate from its pressor activity is specifically required for a significant vasoconstrictor response to hypoxia in isolated rat lungs.
Motor activity of the distal oesophagus and gastrooesophageal reflux.
Authors: E Corazziari, I Bontempo, F Anzini, A Torsoli
Journal: Gut (1984)

The relationship between intraoesophageal pH value and motor activity of the lower oesophageal body and sphincter was investigated by simultaneous evaluation of intraluminal pressure and pH in 13 patients complaining of heartburn and regurgitation. One hundred and thirty one episodes of gastro-oesophageal reflux were recorded. One hundred and eighteen (90.1%) were preceded by a swallow (one to 12 seconds), 13 reflux episodes (9.9%) were not preceded by a swallow. Gastro-oesophageal refluxes preceded by swallow were accompanied by an equal number of normal and abnormal primary peristaltic sequences and, while recording at level of the lower oesophageal sphincter, occurred during inhibition of the sphincter. Frequency of abnormal primary peristalsis increased (p less than 0.01) during periods of low intraluminal pH (less than 5.0). An increase of at least 0.5 U in intraluminal pH occurred with 45.2% of normal primary peristalsis, 29.3% of abnormal primary peristalsis, 4.3% of secondary peristalsis, 3.5% of non-peristaltic contractions. The results of this study indicate that in patients with symptoms of reflux oesophagitis, gastro-oesophageal reflux appears to be related to swallow-induced lower oesophageal sphincter inhibition and not related to abnormal motor activity of the distal oesophageal body where an increased frequency of abnormal primary peristalsis appears to occur during low intraluminal pH and primary peristalsis appears to be the most important mechanism of oesophageal clearing.
DIFFERENTIAL DIAGNOSIS AND MANAGEMENT OF CUSHING'S SYNDROME
Authors: Constantine Tsigos, M.D., Ph.D, George P. Chrousos, M.D
Journal: Annual Review of Medicine (1996)

▪ Abstract The diagnosis of endogenous Cushing's syndrome requires demonstration of an increased cortisol secretion rate, best achieved by urinary free cortisol excretion determinations. In borderline or confusing cases, loss of diurnal cortisol rhythmicity, a combined dexamethasone/corticotropin releasing hormone (CRH) test, or close monitoring of the patient for a few months will be helpful in ruling out pseudo- Cushing's. Primary adrenal Cushing's syndrome can be ruled out on the basis of a normal or elevated basal and/or CRH-stimulated plasma adrenocorticotropin (ACTH) and a negative adrenal computed tomography. ACTH-dependent Cushing's syndrome can then be differentiated on the basis of a CRH test and imaging procedures. A discrete pituitary lesion on magnetic resonance imaging and a standard CRH test with results consistent with such a lesion are sufficient to proceed to transsphenoidal surgery. If no discrete pituitary lesion is present, or if the CRH test is equivocal, bilateral simultaneous inferior petrosal sinus sampling with CRH administration is necessary to distinguish between a pituitary and an ectopic source. Surgery is the treatment of choice for all types of Cushing's syndrome. In the few cases in which transsphenoidal surgery fails or the disease recurs, repeat transsphenoidal surgery, or radiation therapy in association with mitotane treatment, is a reasonable alternative. Bilateral adrenalectomy effectively cures hypercortisolism if resection of the ACTH-secreting tumor is unsuccessful and radiation/medical therapy fails.
Effect of diazepam and hyoscine butylbromide on response to secretin and cholecystokinin-pancreozymin in man.
Authors: J H Saunders, G Masoero, K G Wormsley
Journal: Gut (1976)

Ten subjects received secretin and cholecystokinin or, in duplicate tests, the two hormones together with either diazepam or diazepam plus hyoscine butylbromide in order to determine whether these drugs, which are often used during retrograde endoscopic cannulation of the pancreatic duct, affect pancreatic and biliary secretion in response to the hormones. Diazepam with hyoscine butylbromide reduced the secretion of trypsin into the duodenum and delayed the appearance of both trypsin and bilirubin in duodenal aspirate. These effects must be taken into account when interpreting pancreatic and biliary responses measured during direct cannulation of the pancreatic duct.
Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis
Authors: Changli Wei, Shafic El Hindi, Jing Li, Alessia Fornoni, Nelson Goes, Junichiro Sageshima, Dony Maiguel, S Ananth Karumanchi, Hui-Kim Yap, Moin Saleem, Qingyin Zhang, Boris Nikolic, Abanti Chaudhuri, Pirouz Daftarian, Eduardo Salido, Armando Torres, Moro Salifu, Minnie M Sarwal, Franz Schaefer, Christian Morath, Vedat Schwenger, Martin Zeier, Vineet Gupta, David Roth, Maria Pia Rastaldi, George Burke, Phillip Ruiz, Jochen Reiser
Journal: Nature Medicine (2011)
Self-induced correction of the genetic defect in tyrosinemia type I.
Authors: E A Kvittingen, H Rootwelt, R Berger, P Brandtzaeg
Journal: Journal of Clinical Investigation (1994)

A mosaic pattern of immunoreactive fumarylacetoacetase (FAH) protein was found in liver tissue in 15 of 18 tyrosinemia type I patients of various ethnic origins. One additional patient had variable levels of FAH enzyme activity in liver tissue. In four patients exhibiting mosaicism of FAH protein, analysis for the tyrosinemia-causing mutations was performed in immunonegative and immunopositive areas of liver tissue by restriction digestion analysis and direct DNA sequencing. In all four patients the immunonegative liver tissue contained the FAH mutations demonstrated in fibroblasts of the patients. In the immunopositive nodules of regenerating liver tissue one of the mutated alleles apparently had reverted to the normal genotype. This genetic correction was observed for three different tyrosinemia-causing mutations. In each case a mutant AT nucleotide pair was reverted to a normal GC pair.
Expression and Regulation of Estrogen Receptors in Mesangial Cells
Authors: MYLENE POTIER, SHARON J. ELLIOT, IVAN TACK, OLIVER LENZ, GARY E. STRIKER, LILIANE J. STRIKER, MICHAEL KARL
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Diabetic glomerulosclerosis is characterized by the accumulation of extracellular matrix (ECM) in the mesangium. Estrogens seem to retard whereas estrogen deficiency seems to accelerate progressive glomerulosclerosis. Thus, mesangial cells (MC) may be a target for estrogens. Estrogen action is mediated via estrogen receptor (ER) subtypes ERα and ERβ. Both ER subtypes were expressed in human and mouse MC. Using an estrogen-responsive reporter construct in transfection assays, it also was demonstrated that the nuclear ER were transcriptionally active. In the presence of 17β-estradiol (E 2 ; 10 -10 to 10 -8 M), there was a progressive increase in the mRNA levels of both ERα (approximately 1.8-fold and approximately 2.7-fold after 24 and 72 h, respectively) and ERβ (approximately 1.3-fold and approximately 2.2-fold after 24 and 72 h, respectively). ERα protein levels increased approximately 2.5-fold after 24 h (10 -10 M, E 2 ) and up to approximately 5.4-fold after 72 h (10 -9 M, E 2 ). ERβ protein levels increased approximately 2.1-fold in the presence of E 2 (10 -9 M) after 24 h. Thus, estrogens positively regulate the expression of the ER subtypes, thereby maintaining or increasing MC responsiveness to estrogens. Because diabetic glomerulosclerosis may be due partly to a decrease in ECM degradation, the effects of estrogens on matrix metalloproteinases (MMP) were studied. It was found that E 2 (10 -10 to 10 -8 M) increased both MMP-9 mRNA and MMP-9 activity in MC. This may be an important mechanism by which estrogens influence ECM turnover and protect against progression of diabetic glomerulosclerosis.
Ascomycin: an advance in the management of atopic dermatitis
Authors: C.E.M. Griffiths
Journal: British Journal of Dermatology (2001)

Professor Griffiths is an advisor to Novartis Pharmaceuticals U.K. Ltd., manufacturers of ascomycin. The demonstration that topical glucocorticosteroids are an effective treatment for atopic dermatitis1 was one of the major breakthroughs in dermatological therapy in the past 50 years. Any new therapy that has marked efficacy is subject to an initial flurry of overuse with scant regard for potential side‐effects, particularly if used in areas with a previously unmet need. As a consequence, the undoubted efficacy of topical glucocorticosteroids has been overshadowed by a litany of side‐effects ranging from suppression of the hypothalamic–pituitary axis to cutaneous atrophy and striae. Unfortunately, this had reached such a stage at the end of the 20th century that, in the UK at least, a steroid phobia2 reigned, particularly amongst patients, parents of children with atopic dermatitis and general practitioners. As a consequence many patients were opting for the seemingly safer haven of alternative or herbal remedies, not all of which are steroid‐free3 and are certainly more expensive. Thus the opportunity was ripe for the introduction of a topical immunosuppressive or immunomodulator that was not a steroid.
New direct-acting antiviral agents for the treatment of hepatitis C virus infection and perspectives
Authors: Christoph Welsch, Arun Jesudian, Stefan Zeuzem, Ira Jacobson
Journal: Gut (2012)

Until recently, the standard of care (SOC) for patients with chronic hepatitis C virus (HCV) infection has consisted of a combination of pegylated interferon-N1 plus ribavirin, administered for 24- to 48-weeks depending on the HCV genotype. The sustained virologic response rate for this SOC has been only about 50% in patients infected with genotype 1 HCV, the most prevalent genotype in Europe and North America. HCV therapy has been revolutionised recently by the approval of two direct-acting antiviral agents (DAA) against the NS3/4A serine protease for use in genotype 1 HCV, the ketoamide inhibitors boceprevir and telaprevir. The novel SOC marks the beginning of an extraordinary new era in HCV therapy. We review this new SOC with an emphasis on practical issues related to protease inhibitors, e.g. prescribing guidelines, futility rules and management of adverse events. We also give a perspective on what to expect in the coming years. Newer DAA with simplified dosing regimens and/or minimal toxicity which, when used in combination, will lead to viral eradication in most if not all CHC patients who undergo treatment. The novel agents in clinical development are paving the way for future interferon-sparing regimens.
A prospective study of 123I-labeled monoclonal antibody imaging in ovarian cancer.
Authors: M Granowska, K E Britton, J H Shepherd, C C Nimmon, S Mather, B Ward, R J Osborne, M L Slevin
Journal: Journal of Clinical Oncology (1986)

Thirty patients presenting with a pelvic mass were entered into a prospective study on the use of radioimmunoscintigraphy with the 123I-labeled monoclonal antibody HMFG2. The imaging data was obtained without knowledge of the clinical data and compared with subsequent surgical findings. A false-positive diagnosis of ovarian cancer was made in five of ten patients subsequently shown not to have ovarian cancer; thus the technique cannot be used as a screening test. A true-positive diagnosis was made in 19 out of 20 patients shown subsequently to have ovarian cancer. In 18 of these patients the distribution of uptake closely fitted the surgical findings. Methods of improving these results are described. In conclusion, radioimmunoscintigraphy is of no use in determining whether a pelvic mass is due to ovarian cancer, but has benefit in the evaluation of chemotherapy and may, in the future, prevent the need for second-look operations in some circumstances.
Assessment of bronchial inflammation using an automated cell recognition system based on colour analysis
Authors: P Berger, J Lavallee, R Rouiller, F Laurent, R Marthan, JM Tunon-de-Lara
Journal: European Respiratory Journal (1999)

The aim of this study was to develop an automated system of cell recognition based upon colour analysis suitable for microscopic examination of bronchial inflammation. Human bronchi obtained from 17 patients undergoing thoracotomy were embedded in glycolmethacrylate to perform immunohistochemistry with antibodies against: neutrophil elastase, tryptase, chymase, eosinophil cationic protein, CD68, CD3 and immunoglobulin E. The image analysis system calculates three independent criteria (optic density, hue density, hue) combined with morphological parameters to specifically recognize a positive staining. This automated analysis was applied to the study of bronchial inflammation in smokers and nonsmokers in terms of the absolute number of cells and the expression of different markers by a single cell. The use of these criteria enabled the characterization of a positive stain on single (intraclass correlation coefficient (ICC) = 0.88 or serial (ICC = 0.84) sections. Cell counts obtained by the automated system were highly reproducible. Regarding bronchial inflammation, it was found that the number of inflammatory cells was significantly higher in smokers than in nonsmokers, the majority of these cells bearing immunoglobulin E. These results demonstrate that such computerized analysis of colours is a valuable method for quantifying inflammatory cells in bronchial tissue and for analysing the expression of different markers by a single cell.
Network Analysis: An Integrative Approach to the Structure of Psychopathology
Authors: Denny Borsboom, Angélique O.J. Cramer
Journal: Annual Review of Clinical Psychology (2013)

In network approaches to psychopathology, disorders result from the causal interplay between symptoms (e.g., worry → insomnia → fatigue), possibly involving feedback loops (e.g., a person may engage in substance abuse to forget the problems that arose due to substance abuse). The present review examines methodologies suited to identify such symptom networks and discusses network analysis techniques that may be used to extract clinically and scientifically useful information from such networks (e.g., which symptom is most central in a person's network). The authors also show how network analysis techniques may be used to construct simulation models that mimic symptom dynamics. Network approaches naturally explain the limited success of traditional research strategies, which are typically based on the idea that symptoms are manifestations of some common underlying factor, while offering promising methodological alternatives. In addition, these techniques may offer possibilities to guide and evaluate therapeutic interventions.
Supporting Informed Consumer Health Care Decisions: Data Presentation Approaches that Facilitate the Use of Information in Choice
Authors: Judith H. Hibbard, Ellen Peters
Journal: Annual Review of Public Health (2003)

▪ Abstract To make informed choices and navigate within a complex health care system, consumers must have easily available, accurate, and timely information, and they must use it. Contrary to the consumer-driven approach, however, the evidence demonstrates that having an abundance of information does not always translate into its being used to inform choices. The challenge is not merely to communicate accurate information to consumers, but to understand how to present and target that information so that it is actually used in decision-making. This paper reviews what is known from studies of human judgment and decision-making and discusses their implications for supporting informed consumer choice. We delineate the types of decisions that consumers and patients are making, the barriers to using information effectively in choice, and draw upon the evidence for the efficacy of different presentation strategies to propose an initial framework for evaluating and choosing comparative information presentation approaches.
Open-Source Genomic Analysis of Shiga-Toxin–Producing<i>E. coli</i>O104:H4
Authors: Holger Rohde, Junjie Qin, Yujun Cui, Dongfang Li, Nicholas J. Loman, Moritz Hentschke, Wentong Chen, Fei Pu, Yangqing Peng, Junhua Li, Feng Xi, Shenghui Li, Yin Li, Zhaoxi Zhang, Xianwei Yang, Meiru Zhao, Peng Wang, Yuanlin Guan, Zhong Cen, Xiangna Zhao, Martin Christner, Robin Kobbe, Sebastian Loos, Jun Oh, Liang Yang, Antoine Danchin, George F. Gao, Yajun Song, Yingrui Li, Huanming Yang, Jian Wang, Jianguo Xu, Mark J. Pallen, Jun Wang, Martin Aepfelbacher, Ruifu Yang
Journal: New England Journal of Medicine (2011)

An outbreak caused by Shiga-toxin–producing Escherichia coli O104:H4 occurred in Germany in May and June of 2011, with more than 3000 persons infected. Here, we report a cluster of cases associated with a single family and describe an open-source genomic analysis of an isolate from one member of the family. This analysis involved the use of rapid, bench-top DNA sequencing technology, open-source data release, and prompt crowd-sourced analyses. In less than a week, these studies revealed that the outbreak strain belonged to an enteroaggregative E. coli lineage that had acquired genes for Shiga toxin 2 and for antibiotic resistance.
Simultaneously Targeting Epidermal Growth Factor Receptor Tyrosine Kinase and Cyclooxygenase-2, an Efficient Approach to Inhibition of Squamous Cell Carcinoma of the Head and Neck
Authors: Zhuo (Georgia) Chen, Xin Zhang, Mengfeng Li, Zhiqiang Wang, H. Samuel Wieand, Jennifer R. Grandis, Dong M. Shin
Journal: Clinical Cancer Research (2004)

Epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (Cox-2) contribute to development of squamous cell carcinoma of the head and neck (SCCHN). Simultaneously blocking both EGFR and Cox-2-mediated pathways may be an efficient means of inhibiting cancer cell growth in SCCHN.A combination of EGFR-selective tyrosine kinase inhibitors (TKIs) AG1478 or ZD1839 (Iressa or gefitinib) with a Cox-2 inhibitor (Cox-2I) celecoxib (Celebrex) was studied for its effects on cell growth, cell cycle progression, and apoptosis in SCCHN cell lines by cell growth assay, clonogenic assay, flow cytometric analysis, and terminal deoxynucleotidyl transferase-mediated nick end labeling assay. A potential effect of EGFR TKIs and Cox-2I on angiogenesis was examined by endothelial capillary tube formation assay. Primary and secondary targets of EGFR TKIs and Cox-2I were also examined using immunoblotting and immunoprecipitation after the combined treatment.The combination of AG1478 or ZD1839 with celecoxib either additively or synergistically inhibited growth of the five SCCHN cell lines examined, significantly induced G(1) arrest and apoptosis, and suppressed capillary formation of endothelium. Furthermore, the combination showed strong reductions of p-EGFR, p-extracellular signal-regulated kinase 1/2, and p-Akt in SCCHN cells as compared with the single agents. Both AG1478 and ZD1839 inhibited expression of Cox-2 protein, whereas celecoxib mainly blocked the production of prostaglandin E(2).These results suggest that cell growth inhibition induced by a combination of EGFR TKIs and Cox-2I is mediated through simultaneously blocking EGFR and Cox-2 pathways. This combination holds a great potential for the treatment and/or prevention of SCCHN.
Type 2 immunity is controlled by IL-4/IL-13 expression in hematopoietic non-eosinophil cells of the innate immune system
Authors: David Voehringer, Tiffany A. Reese, Xiaozhu Huang, Kanade Shinkai, Richard M. Locksley
Journal: The Journal of Experimental Medicine (2006)

Nippostrongylus brasiliensis infection and ovalbumin-induced allergic lung pathology are highly interleukin (IL)-4/IL-13 dependent, but the contributions of IL-4/IL-13 from adaptive (T helper [Th]2 cells) and innate (eosinophil, basophils, and mast cells) immune cells remain unknown. Although required for immunoglobulin (Ig)E induction, IL-4/IL-13 from Th2 cells was not required for worm expulsion, tissue inflammation, or airway hyperreactivity. In contrast, innate hematopoietic cell-derived IL-4/IL-13 was dispensable for Th2 cell differentiation in lymph nodes but required for effector cell recruitment and tissue responses. Eosinophils were not required for primary immune responses. Thus, components of type 2 immunity mediated by IL-4/IL-13 are partitioned between T cell-dependent IgE and an innate non-eosinophil tissue component, suggesting new strategies for interventions in allergic immunity.