tbuckley/cabot-search huggingface dataset:
Substitute Adrenergic Transmitters
Authors: J. RICHARD CROUT
Journal: Circulation Research (1966)

Substitute, or false, transmitters are compounds which replace norepinephrine (the normal transmitter) in adrenergic nerve endings end which are released by nerve stimulation. Adrenergic function may be depressed by a substitute transmitter if the substitute is less potent than norepinephrine on adrenergic receptors. It is currently believed that methyldopa exerts its antihypertensive effect by this mechanism. Metaraminol may also serve as a substitute transmitter, and the drug can be shown to have antihypertensive properties in man under certain conditions. The antihypertensive effect of monoamine oxidase inhibition may also be mediated by a substitute-transmitter mechanism.
The MYO9B Gene Is a Strong Risk Factor for Developing Refractory Celiac Disease
Authors: Victorien M. Wolters, Wieke H.M. Verbeek, Alexandra Zhernakova, Charlotte Onland–Moret, Marco W.J. Schreurs, Alienke J. Monsuur, Willem Verduijn, Cisca Wijmenga, Chris J.J. Mulder
Journal: Clinical Gastroenterology and Hepatology (2007)
Rescue of Defective Branching Nephrogenesis in Renal-Coloboma Syndrome by the Caspase Inhibitor, Z-VAD-fmk
Authors: Patsy Clark, Alison Dziarmaga, Michael Eccles, Paul Goodyer
Journal: Journal of the American Society of Nephrology (2004)

In renal-coloboma syndrome (RCS), null mutations of the PAX2 gene cause renal hypoplasia due to a congenital deficit of nephrons; affected individuals may develop renal insufficiency in childhood. During normal kidney development, PAX2, is expressed at high levels throughout the arborizing ureteric bud (UB); recent observations suggest that one of its key roles is to suppress apoptosis in this collecting duct lineage. The authors hypothesized that increased UB cell apoptosis due to PAX2 haploinsufficiency must directly influence the rate of branching morphogenesis in developing kidney and the number of nephrons that can be formed before birth, when nephrogenesis in humans comes to an end. If so, the authors reasoned that caspase inhibitors might be used to suppress unwanted UB cell apoptosis during kidney development in Pax2(1Neu) mutant mice and rescue the genetic UB branching defect. E17.5 kidneys from Pax2(1Neu) mutant mice had smaller (-25%) longitudinal cross-sectional area and 3.5-fold increase in collecting duct cell apoptosis versus wild-type littermates; mutant E13.5 kidney explants allowed to arborize for 50 h in vitro had 18% fewer terminal branches than wild-types. However, exposure to the caspase inhibitor, Z-VAD-fmk (25 micro M), significantly increased terminal branch number in mutant explants (23%). It also increased branching in wild-type explants, apparently reflecting an effect of Z-VAD-fmk on basal apoptosis induced by ex vivo culture conditions. Similarly, when pregnant mice were injected daily with Z-VAD-fmk (10 micro g/g weight from E10.5 to E17.5), apoptosis of Pax2(1Neu) fetal collecting duct cells was suppressed to 40% of untreated mutants; by E14, terminal branch number was increased to 152% that of untreated litters. These studies support the hypothesis that PAX2 normally optimizes the rate of branching morphogenesis in fetal kidney by suppressing UB apoptosis. Furthermore, it suggests that caspase inhibitors can rescue the branching defect caused by PAX2 mutations.
Reactivation of Developmentally Expressed p63 Isoforms Predisposes to Tumor Development and Progression
Authors: Maranke I. Koster, Shi-Long Lu, Lisa D. White, Xiao-Jing Wang, Dennis R. Roop
Journal: Cancer Research (2006)

Abstract Genes that are active during normal development are frequently reactivated during neoplastic transformation. We now report that developmentally expressed TAp63 isoforms are frequently reactivated in human squamous cell carcinomas. To determine the consequences of TAp63 reactivation, we induced TAp63α expression during chemically-induced skin carcinogenesis. Deregulated TAp63α expression dramatically accelerated tumor development and progression, frequently resulting in epithelial-mesenchymal transitions to spindle cell carcinomas and lung metastases. Consistent with this observation, we detected high levels of Twist and N-cadherin in tumors overexpressing TAp63α. Thus, as observed for other developmental pathways, aberrant reactivation of TAp63 predisposes to tumor development and progression. (Cancer Res 2006; 66(8): 3981-6)
Genomic analysis of metabolic pathway gene expression in mice.
Authors: Anatole Ghazalpour, Sudheer Doss, Sonal S Sheth, Leslie A Ingram-Drake, Eric E Schadt, Aldons J Lusis, Thomas A Drake
Journal: Genome biology (2005)

Abstract Background A segregating population of (C57BL/6J × DBA/2J)F2 intercross mice was studied for obesity-related traits and for global gene expression in liver. Quantitative trait locus analyses were applied to the subcutaneous fat-mass trait and all gene-expression data. These data were then used to identify gene sets that are differentially perturbed in lean and obese mice. Results We integrated global gene-expression data with phenotypic and genetic segregation analyses to evaluate metabolic pathways associated with obesity. Using two approaches we identified 13 metabolic pathways whose genes are coordinately regulated in association with obesity. Four genomic regions on chromosomes 3, 6, 16, and 19 were found to control the coordinated expression of these pathways. Using criteria that included trait correlation, differential gene expression, and linkage to genomic regions, we identified novel genes potentially associated with the identified pathways. Conclusion This study demonstrates that genetic and gene-expression data can be integrated to identify pathways associated with clinical traits and their underlying genetic determinants.
TB and MDR/XDR-TB in European Union and European Economic Area countries: managed or mismanaged?
Authors: G.B. Migliori, G. Sotgiu, L. D’Ambrosio, R. Centis, C. Lange, G. Bothamley, D.M. Cirillo, S. De Lorenzo, G. Guenther, K. Kliiman, R. Muetterlein, V. Spinu, M. Villar, J.P. Zellweger, A. Sandgren, E. Huitric, D. Manissero
Journal: European Respiratory Journal (2012)

In spite of the growing awareness of emerging drug-resistant Mycobacterium tuberculosis , the extent of inappropriate tuberculosis (TB) case management may be underestimated, even in Europe. We evaluated TB case management in the European Union/European Economic Area countries, with special focus on multidrug-resistant (MDR) and extensively drug-resistant (XDR)-TB, using a purposely developed, standardised survey tool. National reference centres in five countries representing different geographical, socioeconomic and epidemiological patterns of TB in Europe were surveyed. 40 consecutive, original clinical TB case records (30 MDR/XDR-TB cases) were reviewed in each of the five countries. The findings were recorded and, through the survey tool, compared with previously agreed and identified international standards. Deviations from international standards of TB care were observed in the following areas: surveillance (no information available on patient outcomes); infection control (lack of respiratory isolation rooms/procedures and negative-pressure ventilation rooms); clinical management of TB, MDR-TB and HIV co-infection (inadequate bacteriological diagnosis, regimen selection and treatment duration); laboratory support; and diagnostic/treatment algorithms. Gaps between present international standards of care and the management of MDR/XDR-TB patients were identified. Training, increased awareness, promotion of standards and allocation of appropriate resources are necessary to ensure appropriate care and management as well as to prevent further emergence of drug resistance.
Daytime sleepiness, cognitive performance and mood after continuous positive airway pressure for the sleep apnoea/hypopnoea syndrome.
Authors: H M Engleman, K E Cheshire, I J Deary, N J Douglas
Journal: Thorax (1993)

Patients with the sleep apnoea/hypopnoea syndrome often receive continuous positive airway pressure to improve their symptoms and daytime performance, yet objective evidence of the effect of this treatment on cognitive performance is lacking.A prospective parallel group study was performed comparing the change in objective daytime sleepiness as assessed by multiple sleep latency, cognitive function, and mood in 21 patients (mean (SE) number of apnoeas and hypopnoeas/hour 57 (6)) who received continuous positive airway pressure for three months and 16 patients (49(6) apnoeas and hypopnoeas/hour) who received conservative treatment for a similar period.Both groups showed significant within group changes in cognitive function between baseline and three months, but when comparisons were made between groups the only significant difference was a greater improvement in multiple sleep latency with continuous positive airway pressure. However, the improvement in sleep latency with continuous positive airway pressure was relatively small (3.5 (0.5) to 5.6 (0.7) min). The group treated with continuous positive airway pressure was divided into those who complied well with treatment (> 4.5 hours/night) and those who did not. Those who complied well (n = 14) showed significant improvement in mean sleep latency and also in depression score compared with the controls but no greater improvement in cognitive function.This study confirms significant improvements in objective sleepiness and mood with continuous positive airway pressure, but shows no evidence of major improvements in cognitive function.
Understanding and Addressing Unique Needs of Diabetes in Asian Americans, Native Hawaiians, and Pacific Islanders
Authors: George L. King, Marguerite J. McNeely, Lorna E. Thorpe, Marjorie L.M. Mau, Jocelyn Ko, Lenna L. Liu, Angela Sun, William C. Hsu, Edward A. Chow
Journal: Diabetes Care (2012)

The Asian American (AA) population is currently the fastest growing population in the U.S., having expanded six times faster than the general population in the 1990s (1). In addition, diabetes prevalence continues to rise in this population, as observed for other populations around the world. However, given the diverse natures, cultures, and physiologies among the AA, Native Hawaiian (NH), and Pacific Islander (PI) (AANHPI) populations, and in particular the distinct diabetes profiles, an understanding of these factors can provide important clues to understand the genesis, pathophysiology, and treatment response of diabetes, as well as characterize community outreach programs needed for the wider net of diverse communities throughout the U.S. In this regard, a meeting, whose theme was “Diabetes in Asian Americans, Native Hawaiians, and Pacific Islanders: A Call to Action,” was held in Honolulu, Hawaii, in September 2011 by a coalition of health care organizations and scientists with strong interests in the topic and in the health of AANHPI populations. There was consensus that there is a great need to understand the prevalence and pathophysiology and discuss potential intervention strategies regarding diabetes in AANHPI populations given the unique characteristics of this population. This information may help health care providers understand and improve diabetes prevention, treatment outcomes, and complications in AANHPI populations. In this review, we examine diabetes prevalence in different AANHPI populations to highlight the similarities and differences.

The various groups that comprise AANHPI populations are hugely diverse geographically, culturally, and genetically. The U.S. census defines AAs as persons who have origins in the East, Southeast, or South Asia. NHs and PIs are people who have origins in Hawaii, Samoa, or any other Pacific island (2,3). Diversity within each of these groups is also large. For example, although grouped as AAs, the language, culture, and genetics of someone …
Reproducibility of an asthma symptoms and rescue medication diary: Paper and AM3™ modes
Authors: Andrea Ireland, Ingela Wiklund, Peter Dale, Ray Hsieh, Erin O'Rourke
Journal: European Respiratory Journal (2011)

Objective: This study investigated the test-retest reliability of a twice-daily (morning and evening) asthma symptoms and rescue medication diary within two modes of administration: 1) paper-and-pencil; and 2) AM3™ electronic device in patients with persistent asthma.

Methods: Prospective cross-over study where key inclusion criteria were Asthma Control Test (ACT) scores ≥16, ICS with or without LABA use, <2 nocturnal awakenings due to asthma (past week), and activity limitations ≤1 per week. Participants were randomly allocated to complete the diary in each mode for 15 days. Spirometry was performed at randomisation, cross over, and end of study and changes in asthma resource use were captured. Weekly percentage of symptom-free days (SFD) and rescue-free days (RFD) were calculated using diary data. Intraclass correlation coefficients (ICC) of mean Week 1 SFD and RFD (test) and Week 2 mean SFD and RFD (retest) were estimated for three groups of stable participants: 1) patient who reported little or no change in asthma symptoms and rescue use at Day 15; 2) <±15% change in FEV1 (L); and 3) ACT change scores <|3| (final visit versus baseline).

Results: The mean age of the participants (n=50) was 36.5±17.5 years. Independent of mode of administration, SFD demonstrated acceptable test-retest reliability (ICC≥0.70) based upon all three definitions of asthma stability. By comparison, acceptable reproducibility of the percentage of RFD (ICC 0.78) was only observed for the electronic diary using the FEV1 stability criterion.

Conclusion: This study provides evidence of the test-retest reliability of SFD and RFD diary as well as concordance between the two modes of administration.

Funded by GSK
Thromboxane A2 and peptidoleukotrienes contribute to the myocardial ischemia and contractile dysfunction in response to intracoronary infusion of complement C5a in pigs.
Authors: B R Ito, D M Roth, R L Engler
Journal: Circulation Research (1990)

Intracoronary infusions of activated complement C5a result in myocardial ischemia, contractile dysfunction, and leukocyte accumulation. The hypothesis was tested that the generation of the coronary vasoconstrictors, thromboxane A2 and the 5-lipoxygenase leukotrienes (LTC4 and LTD4), contributes to the C5a-induced decrease in coronary blood flow and contractile function. The left anterior descending coronary artery in anesthetized swine was cannulated and servo pump-perfused with arterial blood at constant pressure and measured flow. Regional subendocardial contractile function was assessed with sonomicrometry. The interventricular vein was cannulated for sampling of coronary venous blood for leukocyte count. The responses in left anterior descending coronary artery blood flow and percent segment shortening to intracoronary infusions of LTC4 (1 microgram), LTD4 (1 microgram), thromboxane agonist U46619 (7.5 micrograms), and C5a (500 ng) were assessed before and after 1) LTD4/LTE4 receptor blockade with leukotriene receptor blocker LY171883 (10 mg/kg i.v.) (n = 5), 2) thromboxane A2/prostaglandin H2 receptor blockade with thromboxane receptor blocker BM13505 (2 mg/kg i.v.) (n = 5), and 3) combined thromboxane and leukotriene receptor blockade (n = 5). In the absence of receptor blockade, intracoronary C5a decreased coronary flow (50-60%) and regional segment function (60-70%) compared with the preinfusion levels. This was accompanied by a fall in coronary venous blood leukocyte levels by 5-6 x 10(6) cells/ml in the absence of alterations in arterial blood leukocyte count. Intracoronary injections of LTD4, LTC4, or U46619 also resulted in prompt decreases in coronary blood flow (50-60%) and segment function (70-80%) from preinfusion levels. Leukotriene receptor blockade with LY171883 abolished these responses to LTD4 and LTC4. Administration of LY171883 also attenuated (p less than 0.05) the myocardial response to C5a; coronary flow and segment function decreased by approximately 28% from preinfusion levels. Thromboxane receptor blockade with BM13505 eliminated the response in coronary flow and segment function to intracoronary U46619. Similar to LY171883, administration of BM13505 blunted (p less than 0.05) the C5a-induced decreases in coronary flow and contractile function, which fell by approximately 20-25% from the preinfusion level. After the combined LTD4/LTE4 receptor and thromboxane A2/prostaglandin H2 receptor blockade, intracoronary C5a resulted in little change in both coronary blood flow and segment shortening. In contrast to the flow and function effects, the C5a-induced myocardial leukocyte extraction was not decreased by leukotriene and/or thromboxane receptor blockade.(ABSTRACT TRUNCATED AT 400 WORDS)
EULAR recommendations for the management of early arthritis: report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT)
Authors: B Combe, R Landewe, C Lukas, H D Bolosiu, F Breedveld, M Dougados, P Emery, G Ferraccioli, J M W Hazes, L Klareskog, K Machold, E Martin-Mola, H Nielsen, A Silman, J Smolen, H Yazici
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objective:</b> To formulate EULAR recommendations for the management of early arthritis. <b>Methods:</b> In accordance with EULAR's "standardised operating procedures", the task force pursued an evidence based approach and an approach based on expert opinion. A steering group comprised of 14 rheumatologists representing 10 European countries. The group defined the focus of the process, the target population, and formulated an operational definition of "management". Each participant was invited to propose issues of interest regarding the management of early arthritis or early rheumatoid arthritis. Fifteen issues for further research were selected by use of a modified Delphi technique. A systematic literature search was carried out. Evidence was categorised according to usual guidelines. A set of draft recommendations was proposed on the basis of the research questions and the results of the literature search.. The strength of the recommendations was based on the category of evidence and expert opinion. <b>Results:</b> 15 research questions, covering the entire spectrum of "management of early arthritis", were formulated for further research; and 284 studies were identified and evaluated. Twelve recommendations for the management of early arthritis were selected and presented with short sentences. The selected statements included recognition of arthritis, referral, diagnosis, prognosis, classification, and treatment of early arthritis (information, education, non-pharmacological interventions, pharmacological treatments, and monitoring of the disease process). On the basis of expert opinion, 11 items were identified as being important for future research. <b>Conclusions:</b> 12 key recommendations for the management of early arthritis or early rheumatoid arthritis were developed, based on evidence in the literature and expert consensus.
Aplastic anemia occurring as amegakaryocytic thrombocytopenia with and without an inhibitor of granulopoiesis
Authors: Lewis M. Slater, Jacob Katz, Barbara Walter, Steven A. Armentrout
Journal: American Journal of Hematology (1985)

Abstract Two patients with aplastic anemia evolving from cellular bone marrows with severely diminished megakaryocytes are reported. During this evolution a plasma inhibitor of in vitro granulocyte‐macrophage colony formation was demonstrated associated with non‐A, non‐B hepatitis in one patient. The second patient had abnormal liver function that corrected after the delivery of a normal newborn but there was persistence of pancytopenia without evidence of a plasma inhibitor.
Pronatriodilatin Gene Polymorphisms, Microvascular Permeability, and Diabetic Nephropathy in Type 1 Diabetes Mellitus
Authors: MONICA NANNIPIERI, GIUSEPPE PENNO, LAURA PUCCI, HELEN COLHOUN, CORRADINO MOTTI, ANNA BERTACCA, LOREDANA RIZZO, LAMBERTO DE GIORGIO, GIAMPAOLO ZERBINI, RUGGERO MANGILI, RENZO NAVALESI
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Approximately 30% of diabetic patients develop nephropathy, the appearance of which is partially under genetic control. Atrial natriuretic peptide (ANP) has associated physiologic effects on the kidney. This study was conducted to examine the relationship between a newly identified and known polymorphism at the pronatriodilatin (PND) gene locus and renal involvement in type 1 diabetic subjects. Of 454 type 1 diabetic patients (219 men, 235 women), 323 showed no sign of nephropathy, 79 had incipient renal involvement, and 52 established nephropathy; 58 healthy control subjects were examined for comparison. Allele frequencies (C 708 versus T 708 ) were: 0.95 and 0.05 in normoalbuminuric patients, respectively; 0.88 and 0.12 in microalbuminuric patients; 0.96 and 0.04 both in those with overt nephropathy and in healthy control subjects ( P = 0.011). Patients with incipient nephropathy were in disequilibrium compared with the total diabetic cohort ( P = 0.02). In the same populations, an additional genotype for Sca I polymorphism of the PND gene was tested. The A 1 and A 2 allele frequencies were: 0.21 and 0.79 in normoalbuminuric patients; 0.13 and 0.87 in microalbuminuric patients; 0.06 and 0.94 in type 1 diabetic subjects with overt nephropathy; and 0.20 and 0.80 in healthy control subjects, respectively ( P &lt; 0.0001). A subset of 55 normotensive patients with type 1 diabetes, well matched for clinical features, plasma ANP levels, and microvascular permeability to macromolecules, was investigated on the basis of the C 708 /T and A 2 /A 1 polymorphisms. Both transcapillary escape rate of albumin (TER alb ) and plasma ANP levels were significantly lower in patients with the T 708 than with C 708 allele, as well as in the A 1 than in A 2 allele (TER alb : T 708 versus C 708 : 5.5 ± 1.7 versus 7.8 ± 2.0%/h, P = 0.0001; plasma ANP levels: 8.3 ± 3.9 versus 15.3 ± 7.7 pg/ml, P = 0.0003; A 1 versus A 2 : 6.05 ± 2.2 versus 7.3 ± 2.1%/h, P = 0.044; 8.53 ± 4.6 versus 14.5 ± 7.4 pg/ml, P = 0.0024, respectively). Thus, in a large ethnically homogeneous cohort of diabetic subjects, our data show: ( 1 ) a significant association of C 708 /T polymorphism with microalbuminuria in long-term diabetes and with both lower plasma ANP levels and widespread albumin leakage; and ( 2 ) a strong association between Sca I polymorphism and both diabetic nephropathy and plasma ANP concentrations. These results suggest a possible role of PND gene in conferring protection from nephropathy and microvascular damage in type 1 diabetes.