tbuckley/cabot-search huggingface dataset:
Molecular Claims of Gondwanan Age for Australian Agamid Lizards are Untenable
Authors: A. F. Hugall
Journal: Molecular Biology and Evolution (2004)

A recent mtDNA study proposes a surprisingly deep (approximately 150 MYA) divergence between SE Asian and Australasian agamid lizards, consistent with ancient Gondwanan vicariance rather than dispersal across the Indonesian Archipelago. However, the analysis contains a fundamental error: use of rates of molecular evolution inferred from uncorrected sequence divergence to put a time frame on a tree with branch lengths greatly elongated by complex likelihood and rate-smoothing models. Furthermore, this date implies that basal splits within agamids occurred implausibly early, at least 300 MYA (100 Myr before the first fossil lizards and coincident with the earliest fossil reptiles). Analyses of the mtDNA data using more appropriate methods and new information from nuclear (c-mos) sequences suggest a much more recent divergence between SE Asian and Australian agamids (around 30 MYA). Using two fossil boundary dates, bootstrapping the c-mos data gives a 95% confidence interval for this divergence time that is sufficiently recent (14-41 MYA) to exclude an ancient Gondwanan vicariance and is more consistent with Miocene over-water dispersal. As with the mtDNA, the c-mos data implies implausibly old basal divergences among agamids if a Gondwanan age is assumed for the Australasian clade. The analyses also highlight how methods for creating ultrametric trees (especially nonparametric rate smoothing) can greatly modify branch lengths and, thus, always require internal calibrations. The errors associated with inferred dates in the previous study (inferred through parametric bootstrapping) were also unjustifiably low, as this method only considers stochasticity in the substitution model and ignores much larger sources of uncertainty, such as variation in character sampling, tree topology, and calibration accuracy.
Measurement of nitric oxide in human nasal airway
Authors: M Imada, J Iwamoto, S Nonaka, Y Kobayashi, T Unno
Journal: European Respiratory Journal (1996)

The nasal output of nitric oxide (NO) is known to be high, but there have been varying reports of the exact level. We attempted to establish a quantitative measurement of nasal NO, and looked for a possible relationship with nasal resistance, at rest and during exercise. Nasal airway ventilation was performed by using an air pump at a constant flow rate, whilst the soft palate was elevated voluntarily. In a preliminary study, the flow rate for sampling was changed and concentrations of NO were measured. After determination of flow rate, rhinomanometry for nasal resistance and measurement of nasal NO by chemiluminescence were carried out before and after moderate exercise. The concentration of NO ([NO]) exhibited a hyperbolic relationship with flow rate of ventilation (V'E), indicating [NO] x V'E = net nitric oxide output (V'NO) = constant. Hence, nasal NO was expressed quantitatively as V'NO (nL.min-1). For 1 L.min-1 of ventilation, [NO] varied between 2 and 500 parts per billion (ppb) (mean = 323 ppb). The average nasal V'NO in 12 healthy male subjects was 323 +/- 91 nL.min-1 (mean +/- SD). After exercise on a treadmill (10 degrees, 5 km.h-1) for 4 min, nasal V'NO decreased to 229 +/- 63 nL.min-1. At rest, expiratory and inspiratory nasal resistance was 0.27 +/- 0.04 and 0.27 +/- 0.06 Pa.s.cm-3, respectively. After exercise, expiratory and inspiratory nasal resistance decreased to 0.17 +/- 0.04 and 0.16 +/- 0.04 Pa.s.cm-3, respectively. These data indicate that nasal NO can be measured quantitatively as V'NO and might be involved in the control of nasal resistance.
Myeloma Cell-Osteoclast Interaction Enhances Angiogenesis Together with Bone Resorption: A Role for Vascular Endothelial Cell Growth Factor and Osteopontin
Authors: Yoichi Tanaka, Masahiro Abe, Masahiro Hiasa, Asuka Oda, Hiroe Amou, Ayako Nakano, Kyoko Takeuchi, Kenichi Kitazoe, Shinsuke Kido, Daisuke Inoue, Keiji Moriyama, Toshihiro Hashimoto, Shuji Ozaki, Toshio Matsumoto
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Similar to osteoclastogenesis, angiogenesis is enhanced in the bone marrow in myeloma in parallel with tumor progression. We showed previously that myeloma cells and osteoclasts are mutually stimulated to form a vicious cycle to lead to enhance both osteoclastogenesis and tumor growth. The present study was undertaken to clarify whether myeloma cell-osteoclast interaction enhances angiogenesis and whether there is any mutual stimulation between osteoclastogenesis and angiogenesis. Experimental Design: Myeloma cells and monocyte-derived osteoclasts were cocultured, and angiogenic activity produced by the cocultures was assessed with in vitro vascular tubule formation assays and human umbilical vascular endothelial cell (HUVEC) migration and survival. Osteoclastogenic activity was determined with rabbit bone cell cultures on dentine slices. Results: Myeloma cells and osteoclasts constitutively secrete proangiogenic factors, vascular endothelial growth factor (VEGF) and osteopontin, respectively. A cell-to-cell interaction between myeloma cells and osteoclasts potently enhanced vascular tubule formation. Blockade of both VEGF and osteopontin actions almost completely abrogated such vascular tubule formation as well as migration and survival of HUVECs enhanced by conditioned medium from cocultures of myeloma cells and osteoclasts. Furthermore, these factors in combination triggered the production of osteoclastogenic activity by HUVEC. Conclusions: Osteoclast-derived osteopontin and VEGF from myeloma cells cooperatively enhance angiogenesis and also induce osteoclastogenic activity by vascular endothelial cells. These observations suggest the presence of a close link between myeloma cells, osteoclasts, and vascular endothelial cells to form a vicious cycle between bone destruction, angiogenesis, and myeloma expansion.
Risk factors for death and hospitalization from pneumonia. A prospective study of a general population
Authors: P Lange, J Vestbo, J Nyboe
Journal: European Respiratory Journal (1995)

The aim of this study was to identify possible risk indicators for pneumonia leading to death and hospitalization in the general population. We followed 6,158 men and 7,265 women aged 30-70 years, who participated in the Copenhagen City Heart Study, a prospective population study, for 12 years with regard to mortality and hospital admissions for pneumonia. A total of 260 deaths with pneumonia as main or contributory death cause had occurred, and 405 subjects had been admitted to hospital at least once because of pneumonia. Mortality and hospitalization were analysed by multivariate Cox regression models. In addition to increasing age, forced expiratory volume in one second (FEV1) was strongly and consistently related to both pneumonia related mortality and hospitalization. Women with FEV1 &lt; 60% predicted had a relative risk of 5.7 (95% confidence interval: 2.9-11) and 3.6 (2.1-6.4) for death and hospitalization, respectively, when compared with women with FEV1 &gt; or = 100% predicted. Similar, although lower, relative risks were observed in men. Other significant risk indicators for hospitalization were: self-reported asthma (women), mucus hypersecretion (women and men), history of stroke (men) and smoking (women). We conclude that, in addition to age, reduced FEV1 is the most important risk indicator for severe pneumonia.
Report from the National Institute of Allergy and Infectious Diseases workshop on drug allergy
Authors: Lisa M. Wheatley, Marshall Plaut, Julie M. Schwaninger, Aleena Banerji, Mariana Castells, Fred D. Finkelman, Gerald J. Gleich, Emma Guttman-Yassky, Simon A.K. Mallal, Dean J. Naisbitt, David A. Ostrov, Elizabeth J. Phillips, Werner J. Pichler, Thomas A.E. Platts-Mills, Jean-Claude Roujeau, Lawrence B. Schwartz, Lauren A. Trepanier
Journal: Journal of Allergy and Clinical Immunology (2015)
Bronchial responsiveness in patients with mitral valve disease
Authors: G Rolla, C Bucca, E Caria, E Scappaticci, S Baldi
Journal: European Respiratory Journal (1990)

Bronchial responsiveness has been evaluated in patients with chronic lung congestion secondary to mitral valve disease. Methacholine bronchial challenge was performed by intermittent aerosol generation in 31 patients with mitral valve disease, 18 in New York Heart Association (NYHA) Class II and 13 in NYHA Class III, non-atopic and with baseline forced expiratory volume in one second/vital capacity (FEV1/VC) greater than 85% of predicted and in 30 normal controls. Haemodynamic data were available in 17 patients. The methacholine bronchial provocation dose causing a 35% fall of airway conductance (PD35sGaw) was significantly lower in patients (507 +/- C.I. 205 micrograms) than in normals (2779 +/- C.I. 358 micrograms), (p less than 0.001). In patients log PD35sGaw was significantly correlated with mean pulmonary artery pressure (r = 0.53, p less than 0.05), mean pulmonary capillary wedge pressure (r = 0.67, p less than 0.01), but not with any spirometric parameters. Bronchial hyperresponsiveness seems to be common in patients with mitral valve disease and evidence of lung congestion.
Effects of Arzoxifene on Breast Cancer Incidence in Postmenopausal Women with Osteoporosis or with Low Bone Mass.
Authors: T. Powles, S. Diem, L. Wickerham, D. Cox, M. Amewou-Atisso, D. Agnusdei, D. Muram, B. Mitlak, S. Cummings
Journal: Cancer Research (2009)

Abstract Precinical and early clinical data indicate that arzoxifene, a third generation SERM, is more potent and bioavailable than raloxifene. Here we report the results of the phase 3, multicenter, placebo-controlled, double-blind GENERATIONS trial of 9354 postmenopausal women with osteoporosis (N=5252) or low bone mineral density (BMD) (N=4102), randomly assigned to arzoxifene 20mg/d (N=4676) or placebo (N=4678). The primary endpoints were the incidences of radiographic vertebral fracture in the osteoporotic population (at 36 months) and invasive breast cancer in all study participants (after all participants had completed 48 months of treatment). Breast cancers were detected by annual mammograms and/or clinical breast examination and adjudicated centrally by an independent committee. The primary analysis compared the incidence of adjudicated invasive breast cancer between treatment groups using a log-rank test. Both treatment groups were evenly balanced for risk of breast cancer including age, previous benign breast biopsies, family history of breast cancer, estimated Gail risk and BMD. The trial met both primary endpoints with a 41% reduction in the incidence of vertebral fractures (p&amp;lt;0.001) and 56% percent reduction in incidence of invasive breast cancer (p=0.002). Table 1 summarizes the breast cancer findings after the 48 month follow-up. The incidence of invasive breast cancer in the placebo group was higher in the women who had a Gail score &amp;gt; 1.66 compared to ≤ 1.66 (1.5% vs. 0.6%) and in those with low bone mass versus osteoporosis (1.2% vs. 0.7%), but the risk reduction with arzoxifene was similar between Gail risk groups (HR 0.32 vs 0.57. p-value for interaction=0.31) and between low bone mass and osteoporosis groups (HR 0.34 vs 0.57. p-value for interaction=0.35). Other findings included no significant reduction in non-vertebral fractures or cardiovascular events. Generally, arzoxifene was well tolerated, although there was a significant increase in venous thromboembolism, gall bladder disease, pulmonary obstructive/infective disorders, hot flushes, muscle cramps and gynecological-related events in the arzoxifene group. We conclude that arzoxifene reduces the incidence of invasive breast cancer as well as vertebral fracture. The results of the GENERATIONS trial provide further support for a significant risk reduction of invasive breast cancer by SERMs in post menopausal women. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 51.
Methoxyflurance as an Obstetric Analgesic
Authors: J. S. Crawford
Journal: BMJ (1967)

MJouuMa more than 1 per 1,000 fittings.Tietze' confirms this approximate figure and shows that the original Birnberg bow is far more liable to this complication than any other type of I.U.C.D.It seems possible that some patients might feel encouraged to take legal action for damages following this contingency, but this should be rejected in 'the courts.Perforation,
YB-1 Provokes Breast Cancer through the Induction of Chromosomal Instability That Emerges from Mitotic Failure and Centrosome Amplification
Authors: Stephan Bergmann, Brigitte Royer-Pokora, Ellen Fietze, Karsten Jürchott, Barbara Hildebrandt, Detlef Trost, Frauke Leenders, Jenny-Chang Claude, Franz Theuring, Ralf Bargou, Manfred Dietel, Hans-Dieter Royer
Journal: Cancer Research (2005)

Abstract YB-1 protein levels are elevated in most human breast cancers, and high YB-1 levels have been correlated with drug resistance and poor clinical outcome. YB-1 is a stress-responsive, cell cycle–regulated transcription factor with additional functions in RNA metabolism and translation. In this study, we show in a novel transgenic mouse model that human hemagglutinin-tagged YB-1 provokes remarkably diverse breast carcinomas through the induction of genetic instability that emerges from mitotic failure and centrosome amplification. The increase of centrosome numbers proceeds during breast cancer development and explanted tumor cell cultures show the phenotype of ongoing numerical chromosomal instability. These data illustrate a mechanism that might contribute to human breast cancer development.
Sequential Flavopiridol, Cytosine Arabinoside, and Mitoxantrone: A Phase II Trial in Adults with Poor-Risk Acute Myelogenous Leukemia
Authors: Judith E. Karp, B. Douglas Smith, Mark J. Levis, Steven D. Gore, Jacqueline Greer, Catherine Hattenburg, Janet Briel, Richard J. Jones, John J. Wright, A. Dimitri Colevas
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Flavopiridol is a cyclin-dependent kinase inhibitor that is cytotoxic to leukemic blasts. In a phase I study of flavopiridol followed by 1-β-d-arabinofuranosylcytosine (ara-C) and mitoxantrone, overall response rate for adults with relapsed and refractory acute myelogenous leukemias (AML) was 31%. We have now completed a phase II study of sequential flavopiridol, ara-C, and mitoxantrone in 62 adults with poor-risk AML. Experimental Design: Flavopiridol (50 mg/m2) was given by 1-h infusion daily × 3 beginning day 1 followed by 2 gm/m2/72 h ara-C beginning day 6 and 40 mg/m2 mitoxantrone on day 9. Results: Flavopiridol caused a ≥50% decrease in peripheral blood blasts in 44% by median day 2 and ≥80% decrease in 26% by day 3. Self-limited tumor lysis occurred in 53%. Three (5%) died during therapy (2 multiorgan failure and 1 fungal pneumonia). Complete remissions (CR) were achieved in 12 of 15 (75%) newly diagnosed secondary AML, 18 of 24 (75%) first relapse after short CR (median CR, 9 months, including prior allotransplant), and 2 of 13 (15%) primary refractory but 0 of 10 multiply refractory AML. Disease-free survival for all CR patients is 40% at 2 years, with newly diagnosed patients having a 2-year disease-free survival of 50%. Conclusions: Flavopiridol has anti-AML activity directly and in combination with ara-C and mitoxantrone. This timed sequential regimen induces durable CRs in a significant proportion of adults with newly diagnosed secondary AML (including complex cytogenetics) and adults with AML in first relapse after short first CR.
Bronchus-associated Lymphoid Tissue in Pulmonary Hypertension Produces Pathologic Autoantibodies
Authors: Kelley L. Colvin, Patrick J. Cripe, D. Dunbar Ivy, Kurt R. Stenmark, Michael E. Yeager
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: Autoimmunity has long been associated with pulmonary hypertension. Bronchus-associated lymphoid tissue plays important roles in antigen sampling and self-tolerance during infection and inflammation.Objectives: We reasoned that activated bronchus-associated lymphoid tissue would be evident in rats with pulmonary hypertension, and that loss of self-tolerance would result in production of pathologic autoantibodies that drive vascular remodeling.Methods: We used animal models, histology, and gene expression assays to evaluate the role of bronchus-associated lymphoid tissue in pulmonary hypertension.Measurements and Main Results: Bronchus-associated lymphoid tissue was more numerous, larger, and more active in pulmonary hypertension compared with control animals. We found dendritic cells in and around lymphoid tissue, which were composed of CD3+ T cells over a core of CD45RA+ B cells. Antirat IgG and plasma from rats with pulmonary hypertension decorated B cells in lymphoid tissue, resistance vessels, and adventitia of large vessels. Lymphoid tissue in diseased rats was vascularized by aquaporin-1+ high endothelial venules and vascular cell adhesion molecule–positive vessels. Autoantibodies are produced in bronchus-associated lymphoid tissue and, when bound to pulmonary adventitial fibroblasts, change their phenotype to one that may promote inflammation. Passive transfer of autoantibodies into rats caused pulmonary vascular remodeling and pulmonary hypertension. Diminution of lymphoid tissue reversed pulmonary hypertension, whereas immunologic blockade of CCR7 worsened pulmonary hypertension and hastened its onset.Conclusions: Bronchus-associated lymphoid tissue expands in pulmonary hypertension and is autoimmunologically active. Loss of self-tolerance contributes to pulmonary vascular remodeling and pulmonary hypertension. Lymphoid tissue–directed therapies may be beneficial in treating pulmonary hypertension.
Poorly controlled type 2 diabetes mellitus is associated with a decreased risk of incident gout: a population-based case-control study
Authors: Saskia G Bruderer, Michael Bodmer, Susan S Jick, Christoph R Meier
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> The aim of this study was to explore the risk of incident gout in patients with type 2 diabetes mellitus (T2DM) in association with diabetes duration, diabetes severity and antidiabetic drug treatment. <h3>Methods</h3> We conducted a case-control study in patients with T2DM using the UK-based Clinical Practice Research Datalink (CPRD). We identified case patients aged ≥18 years with an incident diagnosis of gout between 1990 and 2012. We matched to each case patient one gout-free control patient. We used conditional logistic regression analysis to calculate adjusted ORs (adj. ORs) with 95% CIs and adjusted our analyses for important potential confounders. <h3>Results</h3> The study encompassed 7536 T2DM cases with a first-time diagnosis of gout. Compared to a diabetes duration &lt;1 year, prolonged diabetes duration (1–3, 3–6, 7–9 and ≥10 years) was associated with decreased adj. ORs of 0.91 (95% CI 0.79 to 1.04), 0.76 (95% CI 0.67 to 0.86), 0.70 (95% CI 0.61 to 0.86), and 0.58 (95% CI 0.51 to 0.66), respectively. Compared to a reference A1C level of &lt;7%, the risk estimates of increasing A1C levels (7.0–7.9, 8.0–8.9 and ≥9%) steadily decreased with adj. ORs of 0.79 (95% CI 0.72 to 0.86), 0.63 (95% CI 0.55 to 0.72), and 0.46 (95% CI 0.40 to 0.53), respectively. Neither use of insulin, metformin, nor sulfonylureas was associated with an altered risk of incident gout. <h3>Conclusions</h3> Increased A1C levels, but not use of antidiabetic drugs, was associated with a decreased risk of incident gout among patients with T2DM.
Central haemodynamics during oxygen breathing in angina pectoris
Authors: H. Lecerof
Journal: Thorax (1974)

<b>Lecerof, H. (1974).</b><i>Thorax</i>, <b>29</b>, 673-677. <b>Central haemodynamics during oxygen breathing in angina pectoris.</b> The haemodynamic effects of breathing 100% oxygen have been studied by right heart catheterization at rest and during bicycle exercise in nine male patients with coronary heart disease. Oxygen breathing produced no significant haemodynamic benefit during angina pectoris induced by physical exercise, although at rest a reduction in heart rate and cardiac index was evident. The favourable effects of 100% oxygen breathing described in pacing-induced angina pectoris cannot therefore be transferred to exercise-induced angina probably because the myocardial blood flow during the latter condition is hampered by an increased left ventricular end-diastolic pressure.
Perplexing plain abdominal x-ray
Authors: L. Crush, O. J. O'Connor, W. Plant, M. R. Clarkson, F. Shanahan, M. M. Maher
Journal: Gut (2010)

A 62-year-old man presented with generalised abdominal pain of 4 h duration with associated cough and pyrexia for 2 days. He had developed nephrotic syndrome 17 years previously due to focal segmental glomerulosclerosis and progressed to end-stage kidney disease for which he required haemodialysis three times a week for 6 years. The patient had undergone resection of 10 cm of his distal small bowel due to obstruction secondary to a benign stricture 5 years previously. Oesophagogastroduodenoscopy, colonoscopy, barium meal and enema studies in the previous 2 years were normal apart from the detection of a small sliding hiatus hernia. Examination revealed diffuse abdominal tenderness without …
The trans-endothelial migration of murine synovial fibroblasts of hTNF transgenic mice is controlled by JAM-C
Authors: Marianne Heitzmann, Adelheid Korb-Pap, Christina Koers-Wunrau, George Kollias, Stefan Butz, Dietmar Vestweber, Hermann Pavenstädt, Thomas Pap
Journal: Annals of the Rheumatic Diseases (2012)

Background and objectives Recent studies demonstrated the potential of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) to migrate long distances via the bloodstream and invade distant cartilage in the SCID mouse model of disease.While the mechanisms of trans-endothelial migration of RA-FLS are largely unclear the junctional adhesion molecule C (JAM-C) has become of interest due to its involvement in trans-endothelial migration of leucocytes. Here, the authors used the hTNFtg mouse as a model for human RA and studied the role of JAM-C in the transmigration of FLS derived from these mice. Materials and methods The expression of JAM-C on wild-type and hTNFtg FLS was investigated by western-blot analysis and immunocytochemistry. The transmigratory capacity of these cells was studied in a transmigration assay using murine endothelioma cells (bEnd.5) as an endothelial barrier and IL-1alpha treated murine cartilage tissue as chemoattractant stimulus. Functional analyses included the knock down of JAM-C expression by siRNA against murine JAM-C as well as its neutralisation by blocking antibodies. Results The authors found the expression of JAM-C on the surface of both wild-type and hTNFtg FLS which is prominently located on sites of cell-cell interactions. Moreover, Western blot data revealed an elevated expression of JAM-C in FLS from hTNFtg mice. Transmigration experiments demonstrated a significantly higher potential of hTNFtg FLS to migrate through the endothelial monolayer than FLS from wild-type mice (+40%, p≤0,05), and cartilage explants pretreated with IL-1α enhanced the migratory capacity of hTNFtg FLS. Interestingly, siRNA-mediated knock down of JAM-C expression on hTNFtg FLS resulted in a reduction of transmigration of about 40% compared to mock control (p≤0,01). Likewise, the neutralisation of JAM-C by blocking antibodies against murine JAM-C reduced the number of transmigrated hTNFtg FLS on a similar level. Conclusion Our data demonstrate that the inflammatory environment within the joints of hTNFtg mice induces an up-regulation of JAM-C on FLS, which is characteristic for human RA-FLS. Moreover, they indicate that this environment supports the development of a trans-migrating phenotype of FLS able to get through endothelial barriers. JAM-C seems to be involved functionally in the transmigration and, thus, in extravasation of FLS and, therefore targeting JAM-C may be a promising therapeutic strategy for RA.