tbuckley/cabot-search huggingface dataset:
The vascular endothelial growth factor family in adverse pregnancy outcomes
Authors: P. H. Andraweera, G. A. Dekker, C. T. Roberts
Journal: Human Reproduction Update (2012)

Pre-eclampsia, small-for-gestational-age infants, preterm birth and recurrent miscarriage complicate a significant number of pregnancies. The vascular endothelial growth factor (VEGF) family of angiogenic growth factors is implicated in the pathophysiology of these complications. We aimed to elucidate the role of these angiogenic factors in placentation and to evaluate the predictive value of their protein concentrations and genetic variations in pregnancy complications. We performed a systematic search of PubMed, and retrieved original articles. The search included a combination of terms such as VEGF-A, placental growth factor (PlGF), kinase insert domain receptor, fms-like-tyrosine-kinase receptor 1, soluble fms-like-tyrosine-kinase receptor 1, pre-eclampsia, small-for-gestational-age infants, preterm birth, recurrent miscarriage, placenta, prediction and polymorphisms. This review summarizes the current knowledge of the roles of the VEGF family in early placentation and of the abnormalities in maternal plasma and placental expression of angiogenic proteins in adverse pregnancy outcomes compared with normal pregnancy. PlGF and sFLT-1 in combination with other clinical and biochemical markers in late first or second trimester appear to predict early-onset pre-eclampsia with a high sensitivity and specificity. However, VEGF family proteins do not have sufficient power to accurately predict late-onset pre-eclampsia, small-for-gestational age pregnancies or preterm birth. Functional polymorphisms in these angiogenic genes are implicated in pregnancy complications, but their contribution appears to be minor. Although the VEGF family has important roles in normal and complicated pregnancy, the current predictive value of the VEGF family as biomarkers appears to be limited to early-onset pre-eclampsia.
Anatomy of Venous Return from the Foot
Authors: J. M. Pegum, W. G. Fegan
Journal: Cardiovascular Research (1967)

Studies of amputated feet by dissection and phlebography have demonstrated the anatomical position of the perforating veins between the deep veins of the foot and the dorsal venous arch, and the position of the valves in these vessels. Valves allow flow towards the dorsal venous arch. A condensed layer of superficial fascia overlies, and may help to support, the dorsal venous arch.
Valve replacement in patients with active infective endocarditis.
Authors: W R Wilson, G K Danielson, E R Giuliani, J A Washington, P M Jaumin, J E Geraci
Journal: Circulation (1978)

Eleven of 138 patients with infective endocarditis (IE) who underwent cardiac valve replacement for IE during a 12 1/2-year period had active IE. Eight of the 11 (all with aortic IE) had positive blood cultures within 48 hours preoperatively; six of the eight had positive Gram stains and cultures of the excised cardiac tissue. All 11 patients had Class IV cardiac functional disability (New York Heart Association classification) at the time of surgery. Staphylococci (three patients with Staphylococcus aureus and one with S. epidermidis) were the most frequent isolates. Three patients died; two of these three deaths occurred in patients who had a sudden onset preoperatively of severe aortic regurgitation and heart failure. In one patient (S. epidermidis infection) prosthetic valve endocarditis developed. Cardiac valve replacement may be performed successfully in patients with active IE even when blood cultures are positive in the immediate perioperative period. The hemodynamic status of patients with IE should be the determining factor in the timing of cardiac valve replacement, rather than the activity of the infection or the length of preoperative antimicrobial therapy. A radical surgical procedure may be necessary in patients with myocardial or aortic abscesses in whom conventional aortic valve replacement is not possible.
Cryptogenic Organizing Pneumonia
Authors: ROMAIN LAZOR, ANDRÉ VANDEVENNE, ANTOINE PELLETIER, PASCAL LECLERC, ISABELLE COURT-FORTUNE, JEAN-FRANÇOIS CORDIER
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Cryptogenic organizing pneumonia (COP) is a clinicopathologic syndrome characterized by rapid resolution with corticosteroids, but frequent relapses when treatment is tapered or stopped. We retrospectively studied relapses in 48 cases of biopsy-proven COP. One or more relapses (mean 2.4 ± 2.2) occurred in 58%. At first relapse, 68% of patients were still under treatment for the initial episode. Compared with the no-relapse group, nine patients with multiple ( ⩾ 3) relapses had longer delays between first symptoms and treatment onset (22 ± 17 versus 11 ± 8 wk, p = 0.02), and elevated γ -glutamyltransferase (124 ± 98 versus 29 ± 13 IU/L, p = 0.001) and alkaline phosphatase (190 ± 124 versus 110 ± 68 IU/L, p = 0.04) levels. Relapses did not adversely affect outcome. Corticosteroid treatment side effects occurred in 25% of patients. Standardized treatment in 14 patients allowed a reduction of prednisone cumulated doses (p < 0.05) without affecting outcome or relapse rate. We conclude that: (1) delayed treatment increases the risk of relapses; (2) mild cholestasis identifies a subgroup of patients with multiple relapses; (3) relapses do not affect outcome, and prolonged therapy to suppress relapses appears unnecessary; (4) a standardized treatment allows a reduction in steroid doses.
An "Experimental" Epidemic of Reiter's Syndrome
Authors: H. Rolf Noer
Journal: JAMA (1966)

Nine cases of Reiter's syndrome followed 602 cases of proven bacillary dysentery, while none of an equally large group escaping dysentery developed Reiter's disease. All patients were observed from the ingestion of Shigella until their initial return to duty. Venereal disease was excluded as a causative factor. Antibiotics, antihistaminics, and steroids proved ineffective. We have concluded that Reiter's disease may occur as a sequella of bacillary dysentery, with a definite time relationship between the two disorders, that severe conjunctivitis appears to herald severe or recurrent arthritis, and that arthritis seems worst in joints previously weakened by other disease. If initial disability lasts over three months, permanent or recurrent disability is likely, and recurrence is presaged by a rise in the erythrocyte sedimentation rate.
161 EVEROLIMUS IN LIVER TRANSPLANTATION TO PREVENT HEPATOCELLULAR CARCINOMA RECURRENCE IN THE PRESENCE OF EXTENDED MILAN CRITERIA
Authors: P. Houssel, M. Latournerie, C. Jezequel, E. Bardou-Jacquet, A. Patrizi, M. Rayar, M. Lakehal, K. Boudjema
Journal: Journal of Hepatology (2013)
Functional Reconstitution of the Angiotensin II Type 2 Receptor and G <sub>i</sub> Activation
Authors: Jakob Lerche Hansen, Guy Servant, Thomas J. Baranski, Toshiro Fujita, Taroh Iiri, Søren P. Sheikh
Journal: Circulation Research (2000)

Abstract —On the basis of the patterns of conserved amino acid sequence, the angiotensin II type 2 (AT 2 ) receptor belongs to the family of serpentine receptors, which relay signals from extracellular stimuli to heterotrimeric G proteins. However, the AT 2 receptor signal transduction mechanisms are poorly understood. We have measured AT 2 -triggered activation of purified heterotrimeric proteins in urea-extracted membranes from cultured COS-7 cells expressing the recombinant receptor. This procedure removes contaminating GTP-binding proteins without inactivating the serpentine receptor. Binding studies using [ 125 I] angiotensin (Ang) II revealed a single binding site with a K d =0.45 and a capacity of 627 fmol/mg protein in the extracted membranes. The AT 2 receptor caused a rapid activation of α i and α o but not of α q and α s , as measured by radioactive guanosine 5′-3- O -(thio)triphosphate (GTPγS) binding. Activation required the presence of activated receptors, βγ, and α subunits. As a first step aimed at developing an in vitro assay to examine AT 2 receptor pharmacology, we tested a battery of Ang II–related ligands for their ability to promote AT 1 or AT 2 receptor–catalyzed G i activation. Two proteolytic fragments of Ang II, Ang III and Ang1–7, also promoted activation of α i through the AT 2 receptor. Furthermore, we found that [Sar 1 ,Ala 8 ]Ang II is an antagonist for both AT 1 and AT 2 receptors and that CPG42112 behaves as a partial agonist for the AT 2 receptor. In combination with previous observations, these results show that the AT 2 receptor is fully capable of activating G i and provides a new tool for exploring AT 2 receptor pharmacology and interactions with G-protein trimers.
Membrane traffic and turnover in TRP-ML1–deficient cells: a revised model for mucolipidosis type IV pathogenesis
Authors: Mark T. Miedel, Youssef Rbaibi, Christopher J. Guerriero, Grace Colletti, Kelly M. Weixel, Ora A. Weisz, Kirill Kiselyov
Journal: The Journal of Experimental Medicine (2008)

The lysosomal storage disorder mucolipidosis type IV (MLIV) is caused by mutations in the transient receptor potential–mucolipin-1 (TRP-ML1) ion channel. The “biogenesis” model for MLIV pathogenesis suggests that TRP-ML1 modulates postendocytic delivery to lysosomes by regulating interactions between late endosomes and lysosomes. This model is based on observed lipid trafficking delays in MLIV patient fibroblasts. Because membrane traffic aberrations may be secondary to lipid buildup in chronically TRP-ML1–deficient cells, we depleted TRP-ML1 in HeLa cells using small interfering RNA and examined the effects on cell morphology and postendocytic traffic. TRP-ML1 knockdown induced gradual accumulation of membranous inclusions and, thus, represents a good model in which to examine the direct effects of acute TRP-ML1 deficiency on membrane traffic. Ratiometric imaging revealed decreased lysosomal pH in TRP-ML1–deficient cells, suggesting a disruption in lysosomal function. Nevertheless, we found no effect of TRP-ML1 knockdown on the kinetics of protein or lipid delivery to lysosomes. In contrast, by comparing degradation kinetics of low density lipoprotein constituents, we confirmed a selective defect in cholesterol but not apolipoprotein B hydrolysis in MLIV fibroblasts. We hypothesize that the effects of TRP-ML1 loss on hydrolytic activity have a cumulative effect on lysosome function, resulting in a lag between TRP-ML1 loss and full manifestation of MLIV.
γ-Secretase Inhibitors Enhance Temozolomide Treatment of Human Gliomas by Inhibiting Neurosphere Repopulation and Xenograft Recurrence
Authors: Candace A. Gilbert, Marie-Claire Daou, Richard P. Moser, Alonzo H. Ross
Journal: Cancer Research (2010)

Malignant gliomas are treated with a combination of surgery, radiation, and temozolomide (TMZ), but these therapies ultimately fail due to tumor recurrence. In glioma cultures, TMZ treatment significantly decreases neurosphere formation; however, a small percentage of cells survive and repopulate the culture. A promising target for glioma therapy is the Notch signaling pathway. Notch activity is upregulated in many gliomas and can be suppressed using gamma-secretase inhibitors (GSI). Using a neurosphere recovery assay and xenograft experiments, we analyzed if the addition of GSIs with TMZ treatment could inhibit repopulation and tumor recurrence. We show that TMZ + GSI treatment decreased neurosphere formation and inhibited neurosphere recovery. This enhancement of TMZ treatment occurred through inhibition of the Notch pathway and depended on the sequence of drug administration. In addition, ex vivo TMZ + GSI treatment of glioma xenografts in immunocompromised mice extended tumor latency and survival, and in vivo TMZ + GSI treatment blocked tumor progression in 50% of mice with preexisting tumors. These data show the importance of the Notch pathway in chemoprotection and repopulation of TMZ-treated gliomas. The addition of GSIs to current treatments is a promising approach to decrease brain tumor recurrence.
Once-daily Fluticasone Furoate∗ Nasal Spray (FF) Effectively Treats Ocular Symptoms Of Seasonal Allergic Rhinitis (SAR) Caused By Mountain Cedar Pollen ∗USAN Approved Name
Authors: P. Ratner, C. Andrews, J. van Bavel, T. Toler, A. Ellsworth, E. Philpot
Journal: Journal of Allergy and Clinical Immunology (2007)
K-ras Mutation Targeted to Gastric Tissue Progenitor Cells Results in Chronic Inflammation, an Altered Microenvironment, and Progression to Intraepithelial Neoplasia
Authors: Tomoyuki Okumura, Russell E. Ericksen, Shigeo Takaishi, Sophie S.W. Wang, Zinaida Dubeykovskiy, Wataru Shibata, Kelly S. Betz, Sureshkuma Muthupalani, Arlin B. Rogers, James G. Fox, Anil K. Rustgi, Timothy C. Wang
Journal: Cancer Research (2010)

Chronic infectious diseases, such as Helicobacter pylori infection, can promote cancer in a large part through induction of chronic inflammation. Oncogenic K-ras mutation in epithelial cells activates inflammatory pathways, which could compensate for a lack of infectious stimulus. Gastric histopathology and putative progenitor markers [doublecortin and calcium/calmodulin-dependent protein kinase-like 1 (Dcamkl1) and keratin 19 (K19)] in K19-K-ras-V12 (K19-kras) transgenic mice were assessed at 3, 6, 12, and 18 months of age, in comparison with Helicobacter felis-infected wild-type littermates. Inflammation was evaluated by reverse transcription-PCR of proinflammatory cytokines, and K19-kras mice were transplanted with green fluorescent protein (GFP)-labeled bone marrow. Both H. felis infection and K-ras mutation induced upregulation of proinflammatory cytokines, expansion of Dcamkl1(+) cells, and progression to oxyntic atrophy, metaplasia, hyperplasia, and high-grade dysplasia. K19-kras transgenic mice uniquely displayed mucous metaplasia as early as 3 months and progressed to high-grade dysplasia and invasive intramucosal carcinoma by 20 months. In bone marrow-transplanted K19-kras mice that progressed to dysplasia, a large proportion of stromal cells were GFP(+) and bone marrow-derived, but only rare GFP(+) epithelial cells were observed. GFP(+) bone marrow-derived cells included leukocytes and CD45(-) stromal cells that expressed vimentin or α smooth muscle actin and were often found surrounding clusters of Dcamkl1(+) cells at the base of gastric glands. In conclusion, the expression of mutant K-ras in K19(+) gastric epithelial cells can induce chronic inflammation and promote the development of dysplasia.
Inhaled Iloprost Reverses Vascular Remodeling in Chronic Experimental Pulmonary Hypertension
Authors: Ralph Theo Schermuly, Hüseyin Yilmaz, Hossein Ardeschir Ghofrani, Kathrin Woyda, Soni Pullamsetti, Andreas Schulz, Tobias Gessler, Rio Dumitrascu, Norbert Weissmann, Friedrich Grimminger, Werner Seeger
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: Inhaled iloprost is an effective therapy for pulmonary arterial hypertension (PAH). However, no study to date has addressed the effects of inhaled iloprost on changes to pulmonary vascular structure that occur in PAH. Objectives: The present study was designed to investigate chronic antiremodeling effects of inhaled iloprost in monocrotaline (MCT)-induced PAH in rats. Methods: Four weeks after a single injection of MCT, after full establishment of PAH, rats were nebulized with iloprost at a dose of 6 μg · kg–1 · day–1, or underwent sham nebulization with saline. Results: After 2 weeks of inhalation therapy, right ventricular pressure and pulmonary vascular resistance were reversed in rats treated with iloprost, but not in sham-treated control animals. Systemic arterial pressure was unaffected. In addition, right heart hypertrophy, the degree of pulmonary artery muscularization, and the medial wall thickness of intraacinar pulmonary arteries regressed in response to iloprost. Furthermore, the MCT-induced increase in matrix metalloproteinase-2 and -9 activities and tenascin-C expression was suppressed. Conclusions: We conclude that the inhalation of iloprost reverses PAH and vascular structural remodeling in MCT-treated rats. This regimen suggests the possibility of an antiremodeling therapy in PAH.
No effects of high-dose omeprazole in patients with severe airway hyperresponsiveness and (a)symptomatic gastro-oesophageal reflux
Authors: MJ Boeree, FT Peters, DS Postma, JH Kleibeuker
Journal: European Respiratory Journal (1998)

Acid gastro-oesophageal reflux may aggravate respiratory symptoms in patients with asthma and chronic obstructive pulmonary disease (COPD) by increasing airway hyperresponsiveness through vagally-mediated pathways. We wanted to determine whether elimination of acid reflux could improve symptoms in such patients. In a randomized, double-blind, placebo-controlled study, 36 allergic and nonallergic subjects (17 males and 19 females, mean age 52 yrs), with airway obstruction and severe airway hyperresponsiveness despite maintenance treatment with an inhaled corticosteroid and with increased acid gastro-oesophageal reflux, were treated either with omeprazole, 40 mg b.i.d., or placebo for 3 months. Primary endpoints were: airway hyperresponsiveness, as determined by the provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20); and airway obstruction. Secondary endpoints were: peak expiratory flow variability; reversibility to inhaled ipratropium bromide as a parameter of vagal activity; asthma symptoms scores; and medication used. Reflux was measured by 24 h ambulatory intraoesophageal pH measurement. Omeprazole, 40 mg b.i.d., for 3 months had no beneficial effect on any of the pulmonary parameters, despite its profound effect on acid reflux and improvement of reflux symptoms scores, compared to placebo. The results of this study do not support a role for intensive antireflux therapy to improve pulmonary symptoms and function in patients with asthma and chronic obstructive pulmonary disease, who have severe airway hyperresponsiveness despite maintenance treatment with inhaled corticosteroids.
Effect of freezing of sputum samples on flow cytometric analysis of lymphocyte subsets
Authors: E. Jaksztat, O. Holz, K. Paasch, M.M. Kelly, F.E. Hargreave, G. Cox, H. Magnussen, R.A. Jörres
Journal: European Respiratory Journal (2004)

Sputum samples should be processed shortly after induction to prevent cell degradation. For intermediate storage, freezing of homogenised samples or immediate fixation have been shown to be suitable for cytospins. The aim of this study was to investigate whether freezing or immediate fixation of sputum affect the analysis of lymphocyte subsets by flow cytometry. Selected plugs from 24 sputum samples were homogenised. One aliquot was processed immediately and analysed by flow cytometry. A second aliquot was homogenised, frozen at −20°C after addition of dimethylsulfoxide and stored for a median time of 6 days. In six samples a third aliquot was fixed in formalin after induction and stored for up to 72 h before further processing. Compared to immediate processing, percentages of total lymphocytes and T‐suppressor cells were elevated after being frozen, with a minor decrease in the T4/T8 ratio. Proportions of total lymphocytes, T‐helper and T‐suppressor cells correlated between native and frozen samples, intra-class correlation coefficients being 0.74, 0.85 and 0.70, respectively. The formalin-fixed aliquots could not be analysed with the antibodies used. In conclusion, freezing seems to be a suitable technique to store sputum samples for flow cytometry of CD3, CD4 and CD8 lymphocyte subsets. Its effects were minor compared to the variation between subjects.
The Challenge of Treating Heart Failure
Authors: Rhondalyn C. McLean, Mariell Jessup
Journal: JAMA (2013)

Heart failure affects nearly 6 million people in the United States alone, 1 and the prevalence has reached alarming proportions. It is estimated that approximately 2% of Americans have heart failure, and 35% of cardiovascular deaths are directly related to heart failure. 1 The costs for treating patients with heart failure now approach $32 billion annually. 2 Successful and significant advances have been made in the treatment strategies for heart failure. Pharmacologic therapy includes agents such as β-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers and aldosterone antagonists. Further advances in cardiac resynchronization therapy (CRT), cardiac transplantation, and mechanical circulatory support have provided additional options for patients with this debilitating and frequently fatal chronic illness. However, an important question is whether all patients are being afforded the same advantages of current treatment approaches. Are there groups of patients, as defined by sex, race, and ethnicity, being left behind?
MPs raise fears over unfair funding of public health services
Authors: A. O'Dowd
Journal: BMJ (2015)

Around a third of local authorities are not receiving their fair share of money to spend on public health, and money for these services is not guaranteed to remain ringfenced in the future, MPs have claimed.

MPs on the House of Commons Public Accounts Committee published a report on 6 March in which they praised Public Health England for its performance since it came into being in 2013 but raised some concerns over funding, the body’s influence, and staff shortages in director of public health positions.1

The committee said it was concerned that the Department of Health was not moving local authorities to their target funding allocations for public health quickly enough.

A third (51) …
Assessing agreement between measurements recorded on a ratio scale in sports medicine and sports science.
Authors: A M Nevill, G Atkinson
Journal: British Journal of Sports Medicine (1997)

The consensus of opinion suggests that when assessing measurement agreement, the most appropriate statistic to report is the "95% limits of agreement". The precise form that this interval takes depends on whether a positive relation exists between the differences in measurement methods (errors) and the size of the measurements--that is, heteroscedastic errors. If a positive and significant relation exists, the recommended procedure is to report "the ratio limits of agreement" using log transformed measurements. This study assessed the prevalence of heteroscedastic errors when investigating measurement agreement of variables recorded on a ratio scale in sports medicine and sports science.Measurement agreement (or repeatability) was assessed in 13 studies (providing 23 examples) conducted in the Centre for Sport and Exercise Sciences at Liverpool John Moores University over the past five years.The correlation between the absolute differences and the mean was positive in all 23 examples (median r = 0.37), eight being significant (P < 0.05). In 21 of 23 examples analysed, the correlation was greater than the equivalent correlation using log transformed measurements (median r = 0.01). Based on a simple meta-analysis, the assumption that no relation exists between the measurement differences and the size of measurement must be rejected (P < 0.001).When assessing measurement agreement of variables recorded on a ratio scale in sports medicine and sports science, this study (23 examples) provides strong evidence that heteroscedastic errors are the norm. If the correlation between the absolute measurement differences and the means is positive (but not necessarily significant) and greater than the equivalent correlation using log transformed measurements, the authors recommend reporting the "ratio limits of agreement".
An acute fall in estimated glomerular filtration rate during treatment with losartan predicts a slower decrease in long-term renal function
Authors: Frank A. Holtkamp, Dick de Zeeuw, Merlin C. Thomas, Mark E. Cooper, Pieter A. de Graeff, Hans J.L. Hillege, Hans-Henrik Parving, Barry M. Brenner, Shahnaz Shahinfar, Hiddo J. Lambers Heerspink
Journal: Kidney International (2011)