tbuckley/cabot-search huggingface dataset:
VEGFR-1–Selective VEGF Homologue PlGF Is Arteriogenic
Authors: Frederic Pipp, Matthias Heil, Katja Issbrücker, Tibor Ziegelhoeffer, Sandra Martin, Joop van den Heuvel, Herbert Weich, Borja Fernandez, Gershon Golomb, Peter Carmeliet, Wolfgang Schaper, Matthias Clauss
Journal: Circulation Research (2003)

Two signaling receptors for vascular endothelial growth factor (VEGF) in the vasculature are known with not yet well-understood roles in collateral vessel growth (arteriogenesis). In this study, we examined the involvement of the two VEGF receptors in arteriogenesis. Therefore, we used the VEGF homologue placenta growth factor (PlGF), which only binds to VEGFR-1 and VEGF-E, which only recognizes VEGFR-2. These peptides were locally infused over 7 days after ligation of the femoral artery in the rabbit. Evaluation of collateral growth by determining collateral conductance and angiographic scores demonstrated that the VEGFR-1–specific PlGF contributed significantly more to arteriogenesis than the VEGFR-2 specific VEGF-E. The combination of VEGF-E and PlGF did not exceed the effect of PlGF alone, indicating that cooperation of the two VEGF receptors in endothelial cell signaling is not required for arteriogenesis. In an in vitro model of angiogenesis, VEGF and VEGF-E were comparably active, whereas PlGF displayed no activity when given alone and did not further increase the effects of VEGF or VEGF-E. However, PlGF was as potent as VEGF when monocyte activation was assessed by monitoring integrin surface expression. In addition, accumulation of activated monocytes/macrophages in the periphery of collateral vessels in PlGF-treated animals was observed. Furthermore, in monocyte-depleted animals, the ability of PlGF to enhance collateral growth in the rabbit model and to rescue impaired arteriogenesis in PlGF gene–deficient mice was abrogated. Together, these data indicate that the arteriogenic activity observed with the VEGFR-1–specific PlGF is caused by its monocyte-activating properties.
Mortality Associated With Influenza and Respiratory Syncytial Virus in the United States
Authors: William W. Thompson, David K. Shay, Eric Weintraub, Lynnette Brammer, Nancy Cox, Larry J. Anderson, Keiji Fukuda
Journal: JAMA (2003)

<h3>Context</h3> Influenza and respiratory syncytial virus (RSV) cause substantial morbidity and mortality. Statistical methods used to estimate deaths in the United States attributable to influenza have not accounted for RSV circulation. <h3>Objective</h3> To develop a statistical model using national mortality and viral surveillance data to estimate annual influenza- and RSV-associated deaths in the United States, by age group, virus, and influenza type and subtype. <h3>Design, Setting, and Population</h3> Age-specific Poisson regression models using national viral surveillance data for the 1976-1977 through 1998-1999 seasons were used to estimate influenza-associated deaths. Influenza- and RSV-associated deaths were simultaneously estimated for the 1990-1991 through 1998-1999 seasons. <h3>Main Outcome Measures</h3> Attributable deaths for 3 categories: underlying pneumonia and influenza, underlying respiratory and circulatory, and all causes. <h3>Results</h3> Annual estimates of influenza-associated deaths increased significantly between the 1976-1977 and 1998-1999 seasons for all 3 death categories (<i>P</i>&lt;.001 for each category). For the 1990-1991 through 1998-1999 seasons, the greatest mean numbers of deaths were associated with influenza A(H3N2) viruses, followed by RSV, influenza B, and influenza A(H1N1). Influenza viruses and RSV, respectively, were associated with annual means (SD) of 8097 (3084) and 2707 (196) underlying pneumonia and influenza deaths, 36 155 (11 055) and 11 321 (668) underlying respiratory and circulatory deaths, and 51 203 (15 081) and 17 358 (1086) all-cause deaths. For underlying respiratory and circulatory deaths, 90% of influenza- and 78% of RSV-associated deaths occurred among persons aged 65 years or older. Influenza was associated with more deaths than RSV in all age groups except for children younger than 1 year. On average, influenza was associated with 3 times as many deaths as RSV. <h3>Conclusions</h3> Mortality associated with both influenza and RSV circulation disproportionately affects elderly persons. Influenza deaths have increased substantially in the last 2 decades, in part because of aging of the population, underscoring the need for better prevention measures, including more effective vaccines and vaccination programs for elderly persons.
Outcomes of adults hospitalised with severe influenza
Authors: N. Lee, K. W. Choi, P. K. S. Chan, D. S. C. Hui, G. C. Y. Lui, B. C. K. Wong, R. Y. K. Wong, W. Y. Sin, W. M. Hui, K. L. K. Ngai, C. S. Cockram, R. W. M. Lai, J. J. Y. Sung
Journal: Thorax (2010)

The aim of this study was to investigate factors affecting clinical outcomes of adults hospitalised with severe seasonal influenza.A prospective, observational cohort study was conducted over 24 months (2007-2008) in two acute, general hospitals. Consecutive, hospitalised adult patients were recruited and followed once their laboratory diagnosis of influenza A/B was established (based on viral antigen detection and virus isolation from nasopharyngeal aspirates collected per protocol). Outcomes studied included in-hospital death, length of stay and duration of oxygen therapy. Factors affecting outcomes were analysed using multivariate Cox proportional hazards models. Sequencing analysis on the neuraminidase gene was performed for available H1N1 isolates.754 patients were studied (influenza A, n=539; >75% H3N2). Their mean age was 70+/-18 years; co-morbidities and serious complications were common (61-77%). Supplemental oxygen and ventilatory support was required in 401 (53.2%) and 41 (5.4%) patients, respectively. 39 (5.2%) patients died; pneumonia, respiratory failure and sepsis were the causes. 395 (52%) patients received antiviral (oseltamivir) treatment. Omission of antiviral treatment was associated with delayed presentation or negative antigen detection results. The mortality rate was 4.56 and 7.42 per 1000 patient-days in the treated and untreated patients, respectively; among those with co-morbidities, it was 5.62 and 11.64 per 1000 patient-days, respectively. In multivariate analysis, antiviral use was associated with reduced risk of death (adjusted HR (aHR) 0.27 (95% CI 0.13 to 0.55); p<0.001). Improved survival was observed with treatment started within 4 days from onset. Earlier hospital discharge (aHR 1.28 (95% CI 1.04 to 1.57); p=0.019) and faster discontinuation of oxygen therapy (aHR 1.30 (95% CI 1.01 to 1.69); p=0.043) was associated with early treatment within 2 days. Few (n=15) H1N1 isolates in this cohort had the H275Y mutation.Antiviral treatment for severe influenza is associated with reduced mortality and improved clinical outcomes.
Editorial: Autoimmunity to Vimentin and Lupus Nephritis
Authors: Anne Davidson
Journal: Arthritis & Rheumatology (2014)

Lupus nephritis affects up to 60% of adults and 80% of children with lupus. Despite vast improvements in the survival and well being of patients with this disease our current understanding of its pathogenesis is incomplete and the risk of end stage renal disease is still unacceptably high.
Effect of potassium intake on blood pressure.
Authors: G G Krishna
Journal: Journal of the American Society of Nephrology (1990)

Epidemiologic, experimental, and clinical studies suggest that potassium is an important regulator of blood pressure. Surveys conducted in widely divergent geographic locations indicate higher prevalence of hypertension in populations ingesting diets low in potassium. Amelioration of hypokalemia lowers blood pressure in mineralocorticoid-induced hypertension in rats and in essential hypertensive patients receiving thiazide diuretics. We observed that in normotensive subjects ingesting normal amounts of sodium, short-term potassium depletion increases the mean arterial pressure from 90.9 +/- 2.2 mm Hg to 95.0 +/- 2.2 mm Hg (P less than 0.01). Furthermore, acute sodium loading increases blood pressure in potassium-depleted subjects but it had no effect in subjects ingesting normal amounts of potassium. Preliminary studies indicate that short-term potassium depletion also elevates blood pressure in hypertensive patients. Potassium supplementation lowers blood pressure in hypertensive patients ingesting normal amounts of sodium. Blacks appear to be more sensitive to the hypotensive effects of potassium. The mechanism of potassium-induced changes in blood pressure is not well understood. Potassium depletion consistently induces sodium retention. The hypertensive effects of potassium depletion and hypotensive effects of potassium supplementation are not observed when sodium intake is kept low. Direct vasoconstrictive effects of hypokalemia may contribute to the pressor effect of potassium depletion. The role of altered vascular sensitivity to vasoactive hormones and alterations in divalent cation metabolism in mediating the potassium-induced changes in blood pressure require further study.
A human postnatal lymphoid progenitor capable of circulating and seeding the thymus
Authors: Emmanuelle M. Six, Delphine Bonhomme, Marta Monteiro, Kheira Beldjord, Monika Jurkowska, Corinne Cordier-Garcia, Alexandrine Garrigue, Liliane Dal Cortivo, Benedita Rocha, Alain Fischer, Marina Cavazzana-Calvo, Isabelle André-Schmutz
Journal: The Journal of Experimental Medicine (2007)

Identification of a thymus-seeding progenitor originating from human bone marrow (BM) constitutes a key milestone in understanding the mechanisms of T cell development and provides new potential for correcting T cell deficiencies. We report the characterization of a novel lymphoid-restricted subset, which is part of the lineage-negative CD34+CD10+ progenitor population and which is distinct from B cell–committed precursors (in view of the absence of CD24 expression). We demonstrate that these Lin−CD34+CD10+CD24− progenitors have a very low myeloid potential but can generate B, T, and natural killer lymphocytes and coexpress recombination activating gene 1, terminal deoxynucleotide transferase, PAX5, interleukin 7 receptor α, and CD3ε. These progenitors are present in the cord blood and in the BM but can also be found in the blood throughout life. Moreover, they belong to the most immature thymocyte population. Collectively, these findings unravel the existence of a postnatal lymphoid-polarized population that is capable of migrating from the BM to the thymus.
Proliferating cell nuclear antigen (PCNA): a new marker to study human colonic cell proliferation.
Authors: F J Kubben, A Peeters-Haesevoets, L G Engels, C G Baeten, B Schutte, J W Arends, R W Stockbrugger, G H Blijham
Journal: Gut (1994)

Immunohistochemistry of the S phase related proliferating cell nuclear antigen (PCNA) was studied as an alternative to ex-vivo bromodeoxyuridine (BrdU) immunohistochemistry for assessment of human colonic cell proliferation. From 16 subjects without colonic disease biopsy specimens were collected from five different sites along the colorectum and processed for BrdU and PCNA immunohistochemistry. The mean proliferation index of PCNA was significantly higher at 133% of the value obtained with BrdU. There was, however, a good correlation between the results from both techniques (r = 0.6275; p < 0.05). Decrease in proliferation index along the colorectum was seen with both staining methods but was clearer with PCNA immunohistochemistry (caecum/ascending colon v rectum: 12.0 v 7.2; p < 0.004). The total number of crypt cells also decreased from proximal to distal (134 to 128; p < 0.06) but at no site correlated significantly with the proliferation index. It is concluded that in clinical cell kinetic studies staining for PCNA may serve as an attractive alternative to the BrdU incorporation assay.
Modulation of cardiac autonomic neurotransmission by epicardial superfusion. Effects of hexamethonium and tetrodotoxin.
Authors: T Miyazaki, H P Pride, D P Zipes
Journal: Circulation Research (1989)

The heart contains superficial cardiac nerves whose effects may be modulated by pericardial fluid bathing the epicardium. We tested this hypothesis in open-chest dogs anesthetized with secobarbital. Oxygenated normal Tyrode's solution (NT) or NT containing hexamethonium, a ganglionic blocker (500 microM), or tetrodotoxin, a blocker of axonal neurotransmission (5 microM, TTX), was instilled into the pericardial cavity to superfuse the epicardium of the whole heart. During each superfusion, effective refractory period (ERP) was determined in deep intramyocardium (greater than or equal to 4 mm in depth from the epicardium) of anterior and posterior left ventricle and in the subendocardium of the right ventricle in the baseline state and during bilateral cervical vagal stimulation (VS) or ansae subclaviae stimulation (SS). Lengthening of ERP induced by VS during superfusion with NT (6.9 +/- 0.3 msec, mean +/- SEM, n = 36) was eliminated during subsequent superfusion with hexamethonium (0.9 +/- 0.5 msec, p less than 0.001). Hexamethonium also prevented sinus arrest induced by VS but did not affect shortening of ERP induced by SS (17.3 +/- 1.3 to 16.6 +/- 1.0 msec, n = 26). TTX suppressed VS-induced changes in ERP (6.3 +/- 0.3 to 1.5 +/- 0.5 msec, n = 32, p less than 0.001) and SS-induced changes in ERP (18.8 +/- 1.6 to 6.0 +/- 0.9 msec, n = 23, p less than 0.001) but did not affect changes in ERP induced by intravenous administration of norepinephrine or methacholine.(ABSTRACT TRUNCATED AT 250 WORDS)
Dyslipidaemia in Behcet's disease as a thrombotic risk factor
Authors: J M Ricart, A Vaya, M Santaolaria, F Espana, J Aznar
Journal: Annals of the Rheumatic Diseases (2006)

Leiba et al 1 recently suggested that hyperlipidaemia, particularly hypertriglyceridaemia, may be a risk factor for thrombosis in Behcet’s disease. Published studies suggest an association between increased levels of plasma lipids and deep-vein thrombosis,2–4 although the pathogenic mechanism is controversial. In an ongoing study on the association between thrombophilic defects and thrombotic events in patients with Behcet’s disease, we have also evaluated the possible contribution of plasma lipids to the genesis of thrombotic events in these patients. We conducted a case–control study in patients with Behcet’s disease recruited from the records of the La Fe, General and Peset University Hospitals …
Genetic and Epigenetic Analysis of the Putative Tumor Suppressor <i>km23</i> in Primary Ovarian, Breast, and Colorectal Cancers
Authors: Ian G. Campbell, Wayne A. Phillips, David Y.H. Choong
Journal: Clinical Cancer Research (2006)

A very high frequency of somatic mutations in the transforming growth factor-beta signaling component km23 has been reported in a small series of ovarian cancers (8 of 19, 42%). Functional studies showed that some mutations disrupt km23 function, resulting in aberrant transforming growth factor-beta signaling and presumably enhanced tumorigenicity. If verified, this would elevate mutation of km23 as the single most frequent somatic event in ovarian cancer.We sought to verify the frequency of silencing of km23 among 104 primary ovarian cancers (49 serous, 18 mucinous, 29 endometrioid/clear cell, and 8 undifferentiated) as well as 72 breast and 61 colorectal cancers by undertaking both somatic mutation and promoter methylation analyses. All four exons of km23 were individually amplified from genomic DNA with primers complementary to surrounding intronic sequences and analyzed by single-stranded conformational polymorphism analysis.Two germ line polymorphisms were identified, but none of the 237 tumors analyzed harbored somatic km23 mutations. In addition, promoter methylation analysis showed that in all cases, the 5' CpG island was unmethylated.Our data suggest that silencing of km23, either through somatic genetic mutation or promoter hypermethylation, is rare in ovarian, breast, and colorectal cancers.
Unique neoantigens expressed by melanomas and common epithelial cancers presented by multiple HLA alleles can be efficiently identified utilizing peptide prediction algorithms
Authors: Kasia Trebska-Mcgowan, Mini Bharathan, Jared J Gartner, Todd D Prickett, Steven A Rosenberg, Paul F Robbins
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Previous observations indicate that complete regression of metastatic melanoma can be mediated by CD8 lymphocytes that predominantly recognize unique tumor specific mutations predicted in-silico to bind in context of HLA-A*02:01 [[1][1]]. The goal of this project was to expand
Rapid and sensitive analysis of cyclobenzaprine by LC–MS/MS: Application to a pharmacokinetic study of cyclobenzaprine in dog
Authors: Wenhong Yu, Xiaojing Yang, Wenwen Sui, Haiyan Xu, Xinyi Luan, Xiangjun Wang, Yi Jin, Bo Yuan
Journal: Asian Journal of Pharmaceutical Sciences (2014)

A rapid and sensitive liquid chromatography–tandem mass spectrometry method was developed and validated for the quantification of cyclobenzaprine in dog plasma. After extracted with organic solvent, post-treatment samples were separated on an Agela C18 column interfaced with a triple quadrupole tandem mass spectrometer in positive electrospray ionization mode. Multiple reaction monitoring was performed using the transitions of m/z 276.2 → 216.1 and m/z 325.1 → 109.0 to quantify cyclobenzaprine and escitalopram (internal standard), respectively. The mobile phase consisted of acetonitrile: 5 mM ammonium acetate: formic acid (90:10:0.01, v/v/v) at a flow rate of 0.3 ml/min. The total analysis time was 2.4 min. The method was linear over the concentration range of 0.0200–10.0 ng/ml. The intra- and inter-day precision was within 12.8% in terms of relative standard deviation (RSD%) and the accuracy within 5.6% in terms of relative error. This method was successfully applied in a pharmacokinetic study of extended-release cyclobenzaprine in dogs.
Comparison of Leukolysin/MT6-MMP in Bronchoalveolar Lavage Fluid from Lung Transplant Patients and Asthmatics
Authors: J.P. Raasch, C.L. Liebeler, C.H. Wendt, J.B. Sweet, N.N. Jarjour, R.S. DeGrauw, D. Pei, M.N. Blumenthal
Journal: Journal of Allergy and Clinical Immunology (2006)
Platelet Gene Therapy by Lentiviral Gene Delivery to Hematopoietic Stem Cells Restores Hemostasis and Induces Humoral Immune Tolerance in FIXnull Mice
Authors: Yingyu Chen, Jocelyn A Schroeder, Erin L Kuether, Guowei Zhang, Qizhen Shi
Journal: Molecular Therapy (2013)

Here, we developed a clinically translatable platelet gene therapy approach for hemophilia B. Platelet-targeted FIX (2bF9) expression was introduced by transplantation of hematopoietic stem cells (HSCs) transduced with 2bF9 lentivirus (LV). Sustained therapeutic levels of platelet-FIX expression were obtained in FIXnull mice that received 2bF9 LV-transduced HSCs. Approximately 6–39% of the platelets expressed FIX in the transduced recipients, which was sufficient to rescue the bleeding diathesis in FIXnull mice in tail clipping models. Sequential bone marrow transplantation demonstrated that platelet-FIX expression in the secondary recipients was sustained, leading to phenotypic correction. Notably, none of the transduced recipients developed anti-FIX antibodies after platelet gene therapy. Only one of the nine recipients developed a low titer of inhibitory antibodies (1.6 BU/ml) after challenge with rhFIX. These data suggest that platelet gene therapy can not only restore hemostasis but also induce immune tolerance in hemophilia B mice, indicating that this approach may be a promising strategy for gene therapy of hemophilia B in humans. Here, we developed a clinically translatable platelet gene therapy approach for hemophilia B. Platelet-targeted FIX (2bF9) expression was introduced by transplantation of hematopoietic stem cells (HSCs) transduced with 2bF9 lentivirus (LV). Sustained therapeutic levels of platelet-FIX expression were obtained in FIXnull mice that received 2bF9 LV-transduced HSCs. Approximately 6–39% of the platelets expressed FIX in the transduced recipients, which was sufficient to rescue the bleeding diathesis in FIXnull mice in tail clipping models. Sequential bone marrow transplantation demonstrated that platelet-FIX expression in the secondary recipients was sustained, leading to phenotypic correction. Notably, none of the transduced recipients developed anti-FIX antibodies after platelet gene therapy. Only one of the nine recipients developed a low titer of inhibitory antibodies (1.6 BU/ml) after challenge with rhFIX. These data suggest that platelet gene therapy can not only restore hemostasis but also induce immune tolerance in hemophilia B mice, indicating that this approach may be a promising strategy for gene therapy of hemophilia B in humans.
High-Dose Parenteral Ascorbate Enhanced Chemosensitivity of Ovarian Cancer and Reduced Toxicity of Chemotherapy
Authors: Yan Ma, Julia Chapman, Mark Levine, Kishore Polireddy, Jeanne Drisko, Qi Chen
Journal: Science Translational Medicine (2014)

Pharmacological use of ascorbate (vitamin C) enhanced chemosensitivity of ovarian cancer in preclinical models and reduced chemotherapy-associated toxicity in patients.
White Matter Abnormalities in Veterans With Mild Traumatic Brain Injury
Authors: Ricardo E. Jorge, Laura Acion, Tonya White, Diana Tordesillas-Gutierrez, Ronald Pierson, Benedicto Crespo-Facorro, Vincent A. Magnotta
Journal: American Journal of Psychiatry (2012)

Objective It has been estimated that 10%–20% of U.S. veterans of the wars in Iraq and Afghanistan experienced mild traumatic brain injury (TBI), mostly secondary to blast exposure. Diffusion tensor imaging (DTI) may detect subtle white matter changes in both the acute and chronic stages of mild TBI and thus has the potential to detect white matter damage in patients with TBI. The authors used DTI to examine white matter integrity in a relatively large group of veterans with a history of mild TBI. Method DTI images from 72 veterans of the wars in Iraq and Afghanistan who had mild TBI were compared with DTI images from 21 veterans with no exposure to TBI during deployment. Conventional voxel-based analysis as well as a method of identifying spatially heterogeneous areas of decreased fractional anisotropy ("potholes") were used. Veterans also underwent psychiatric and neuropsychological assessments. Results Voxel-based analysis did not reveal differences in DTI parameters between the veterans with mild TBI and those with no TBI. However, the veterans with mild TBI had a significantly higher number of potholes than those without TBI. The difference in the number of potholes was not influenced by age, time since trauma, a history of mild TBI unrelated to deployment, or coexisting psychopathology. The number of potholes was correlated with the severity of TBI and with performance in executive functioning tasks. Conclusions Veterans who had blast-related mild TBI showed evidence of multifocal white matter abnormalities that were associated with severity of the injury and with relevant functional measures. Overall, white matter potholes may constitute a sensitive biomarker of axonal injury that can be identified in mild TBI at acute and chronic stages of its clinical course.