tbuckley/cabot-search huggingface dataset:
A novel assay uncovers an unexpected role for SR-BI in LDL transcytosis
Authors: Susan M. Armstrong, Michael G. Sugiyama, Karen Y.Y. Fung, Yizhuo Gao, Changsen Wang, Andrew S. Levy, Paymon Azizi, Mark Roufaiel, Su-Ning Zhu, Dante Neculai, Charles Yin, Steffen-Sebastian Bolz, Nabil G. Seidah, Myron I. Cybulsky, Bryan Heit, Warren L. Lee
Journal: Cardiovascular Research (2015)

Retention of low-density lipoprotein (LDL) cholesterol beneath the arterial endothelium initiates an inflammatory response culminating in atherosclerosis. Since the overlying endothelium is healthy and intact early on, it is likely that LDL passes through endothelial cells by transcytosis. However, technical challenges have made confirming this notion and elucidating the mechanisms of transcytosis difficult. We developed a novel assay for measuring LDL transcytosis in real time across coronary endothelial cell monolayers; we used this approach to identify the receptor involved.Murine aortas were perfused ex vivo with LDL and dextran of a smaller molecular radius. LDL (but not dextran) accumulated under the endothelium, indicating that LDL transcytosis occurs in intact vessels. We then confirmed that LDL transcytosis occurs in vitro using human coronary artery endothelial cells. An assay was developed to quantify transcytosis of DiI-LDL in real time using total internal reflection fluorescence microscopy. DiI-LDL transcytosis was inhibited by excess unlabelled LDL, while degradation of the LDL receptor by PCSK9 had no effect. Instead, LDL colocalized partially with the scavenger receptor SR-BI and overexpression of SR-BI increased LDL transcytosis; knockdown by siRNA significantly reduced it. Excess HDL, the canonical SR-BI ligand, significantly decreased LDL transcytosis. Aortas from SR-BI-deficient mice were perfused ex vivo with LDL and accumulated significantly less sub-endothelial LDL compared with wild-type littermates.We developed an assay to quantify LDL transcytosis across endothelial cells and discovered an unexpected role for SR-BI. Elucidating the mechanisms of LDL transcytosis may identify novel targets for the prevention or therapy of atherosclerosis.
Correlates of Change in Functional Status of Institutionalized Geriatric Schizophrenic Patients: Focus on Medical Comorbidity
Authors: Joseph I. Friedman, Philip D. Harvey, Susan R. McGurk, Leonard White, Michael Parrella, Tenko Raykov, Thomas Coleman, David N. Adler, Kenneth L. Davis
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Impairment in basic self-care skills is common in patients with schizophrenia and is even more severe in elderly patients with a chronic course of institutional care. While cognitive impairment has proven to be a major predictor of overall functional deficit in schizophrenia, other potential factors, such as medical comorbidity, need to be considered. METHOD: Geriatric institutionalized schizophrenic patients (N=124) were assessed three times over 4 years to determine levels of positive and negative symptoms, impairment in activities of daily living, impairment in cognitive functioning, and medical problems. Path analysis was used to determine which variables best predicted changes in self-care functions. RESULTS: Functional status, negative symptoms, cognitive functions, and health status all significantly worsened during the follow-up. The path analyses showed that change in health status did not predict change in activities of daily living after the analysis accounted for negative symptoms and cognitive functions. DISCUSSION: The results highlight the relative importance of cognitive impairments in the functional impairments of older schizophrenic patients with increased medical burden.
Mite, cat, and cockroach exposure, allergen sensitisation, and asthma in children: a case-control study of three schools
Authors: R. Sporik, S. P Squillace, J. M. Ingram, G. Rakes, R. W Honsinger, T. A E Platts-Mills
Journal: Thorax (1999)

The amount of allergen necessary to sensitise genetically "at risk" children is unclear. The relation between allergen exposure and asthma is also uncertain.To ensure a wide range of allergen exposures the data from case-control studies of asthma in children aged 12-14 years attending three schools in Los Alamos, New Mexico and Central Virginia were combined. Skin prick tests to indoor and outdoor allergens and bronchial hyperreactivity to histamine were assessed in children with and without symptoms of asthma. The concentration of mite, cat, and cockroach allergens in dust from the children's homes was used as a marker of exposure.Three hundred and thirty two children (157 with asthmatic symptoms and 175 controls) were investigated. One hundred and eighty three were classified as atopic on the basis of allergen skin prick tests and 68 as asthmatic (symptoms plus bronchial responsiveness). The prevalence and degree of sensitisation to mite and cockroach, but not cat, was strongly associated in atopic children with increasing domestic concentrations of these allergens. Asthma was strongly associated with sensitisation to indoor allergens (p<10(-6)) and weakly to outdoor allergens (p = 0.026). There was an association between current asthma and the concentration of mite allergen amongst atopic children (p = 0.008) but not amongst those who were specifically mite sensitised (p = 0.16).The domestic reservoir concentration of mite and cockroach, but not cat, allergen was closely related to the prevalence of sensitisation in atopic children. However, the prevalence of current asthma had a limited relationship to these allergen measurements, suggesting that other factors play a major part in determining which allergic individuals develop asthma.
Case-Control Study of Simian Virus 40 and Non-Hodgkin Lymphoma in the United States
Authors: E. A. Engels, R. P. Viscidi, D. A. Galloway, J. J. Carter, J. R. Cerhan, S. Davis, W. Cozen, R. K. Severson, S. de Sanjose, J. S. Colt, P. Hartge
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Recent studies have reported detection of simian virus 40 (SV40) DNA in tumor tissues from 15%–43% of U.S. non-Hodgkin lymphoma (NHL) patients. SV40 accidentally contaminated U.S. poliovirus vaccines that were widely administered from 1955 through 1962. However, epidemiologic data linking SV40 with NHL are lacking. Methods: We obtained serum samples from 724 incident NHL case patients and 622 control subjects from a population-based U.S. case–control study. SV40 serostatus was analyzed by two independent laboratories (designated A and B) using similar virus-like particle (VLP) enzyme immunoassays. Associations with serostatus were assessed with logistic regression, adjusting for sex, race, birth year, and study site. VLPs for the human polyomaviruses BK and JC were used in competitive inhibition experiments to assess the specificity of SV40 reactivity. Statistical tests were two-sided. Results: SV40 antibody results from the two laboratories were correlated ( R = 0.59; P <.001). Laboratories A and B detected SV40 seropositivity in 7.2% and 9.8% of NHL case patients, respectively, and in 10.5% and 9.6% of control subjects, respectively. SV40 seropositivity was not associated with increased NHL risk (laboratory A: adjusted odds ratio [OR] = 0.68, 95% confidence interval [CI] = 0.46 to 1.00; laboratory B: adjusted OR = 1.02, 95% CI = 0.71 to 1.47). SV40 seropositivity was not associated with NHLs of any specific histology or site. Among subjects born before 1963, 1.0%–1.6% showed SV40-specific reactivity, i.e., SV40 reactivity confirmed in competitive inhibition experiments, whereas (based on limited data) none born subsequently demonstrated SV40-specific reactivity. Conclusions: In persons born before 1963, the presence of SV40-specific antibodies, although rare, could reflect exposure to SV40-contaminated vaccines. Nevertheless, NHL risk was unrelated to serologic evidence of SV40 exposure or infection.
Association of Poor Subjective Sleep Quality With Risk for Death by Suicide During a 10-Year Period
Authors: Rebecca A. Bernert, Carolyn L. Turvey, Yeates Conwell, Thomas E. Joiner
Journal: JAMA Psychiatry (2014)

Older adults have high rates of sleep disturbance, die by suicide at disproportionately higher rates compared with other age groups, and tend to visit their physician in the weeks preceding suicide death. To our knowledge, to date, no study has examined disturbed sleep as an independent risk factor for late-life suicide.
Influence of Major Postoperative Complications on Health-Related Quality of Life Among Long-Term Survivors of Esophageal Cancer Surgery
Authors: Maryam Derogar, Nicola Orsini, Omid Sadr-Azodi, Pernilla Lagergren
Journal: Journal of Clinical Oncology (2012)

Purpose To evaluate the effect of major postoperative complications on health-related quality of life (HRQL) in 5-year survivors of esophageal cancer surgery. Patients and Methods This study was based on the Swedish Esophageal and Cardia Cancer register with almost complete nationwide coverage and data on esophageal cancer surgery collected prospectively between 2001 and 2005. Patients who were alive 5 years after surgery were eligible. HRQL was assessed longitudinally until 5 years after surgery by using the validated European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and OES18. Linear mixed models were used to assess the mean score difference (MD) with 95% CIs of each aspect of HRQL in patients with or without major postoperative complications. Adjustment was made for several potential confounders. Results Of 153 patients who survived 5 years, 141 patients (92%) answered the 5-year HRQL questionnaires. Of these individuals, 46 patients (33%) sustained a major postoperative complication. Dyspnea (MD, 15; 95% CI, 6 to 23), fatigue (MD, 13; 95% CI, 5 to 20), and eating restrictions (MD, 10; 95% CI, 2 to 17) were clinically and statistically significantly deteriorated throughout the follow-up in patients with major postoperative complications compared with patients without major complications. Although problems with choking declined to levels comparable with patients without major postoperative complications, sleep difficulties and gastroesophageal reflux progressively worsened during follow-up. Conclusion The occurrence of postoperative complications exerts a long-lasting negative effect on HRQL in patients who survive 5 years after esophagectomy for cancer.
Motivation for Marihuana Use: A Correlate of Adverse Reaction
Authors: MARTIN H. KEELER
Journal: American Journal of Psychiatry (1968)

Curiosity and conformity were cited as the principal reasons for initial marihuana use by 54 users interviewed. Twenty-six of the 40 who became regular users sought an experience combining tension relief with mild stimulation of thought. Fourteen of the 40 continuing users desired some type of psychotomimetic experience. Desire for psychotomimetic experience was correlated with higher dosage and higher incidence of psychopathology.
Targeting Matrix Metalloproteinases and Endothelial Cells with a Fusion Peptide against Tumor
Authors: Yufei Zou, Yahui Chen, Yongqiang Jiang, Jin Gao, Jun Gu
Journal: Cancer Research (2007)

Abstract Development of novel therapy for patients with tumor is still a challenge at the present time. We designed a fusion peptide (RK5) with two targets as a novel agent against tumor. The fusion peptide RK5 containing the kringle 5 fragment of human plasminogen and a decapeptide (CTTHWGFTLC) was constructed and expressed in yeast. Matrix metalloproteinase (MMP) activity, proliferation, and migration of endothelial cells were examined in vitro, respectively. Angiogenesis, tumor growth, metastasis, and survival time were evaluated in in vivo models. Administration of RK5 was delivered by both protein and gene approach. The results showed that RK5 inhibited the activity of MMP-9 and exhibited more inhibitory effects on proliferation and migration of endothelial cells than that of kringle 5 fragment and decapeptide individually. RK5 also inhibited angiogenesis, tumor growth, and metastasis and increased survival time of mice bearing tumor. In addition, the effectiveness of RK5 could be achieved by both protein and gene delivery. In conclusion, RK5 has potential to inhibit tumor growth and metastasis and to prolong survival time of animals bearing tumor. Therefore, fusion peptide RK5 with two targets provides a new design for the development of antitumor drugs and has potential for clinical application. [Cancer Res 2007;67(15):7295–300]
Human macrophage activation. Modulation of mannosyl, fucosyl receptor activity in vitro by lymphokines, gamma and alpha interferons, and dexamethasone.
Authors: T Mokoena, S Gordon
Journal: Journal of Clinical Investigation (1985)

We describe a sensitive assay to measure immune activation of human macrophages in cell culture. Freshly isolated blood monocytes from normal subjects lack the ability to endocytose and degrade mannosyl-terminated glycoconjugates via specific receptors, but acquired this activity after cultivation in autologous serum for approximately 3 d. Addition of specific antigen, purified protein derivative, or T cell mitogens to mononuclear cells prevented the appearance of macrophage mannosyl receptor activity and lymphokine, gamma-, and alpha-interferons selectively down-regulated receptor activity in monocyte-macrophage targets. The effects of antigen challenge and gamma-interferon on mannosyl receptors can be prevented by 10(-8) M dexamethasone. Dexamethasone also inhibited release of another macrophage activation marker, plasminogen activator, which was increased by both gamma- and alpha-interferons. These studies show that activation of human macrophages is regulated by opposing actions of lymphokines and glucocorticoids.
Reduced soluble receptor for advanced glycation end-products in COPD
Authors: D.J. Smith, S.T. Yerkovich, M.A. Towers, M.L. Carroll, R. Thomas, J.W. Upham
Journal: European Respiratory Journal (2010)

The soluble receptor for advanced glycation end-products (sRAGE) has anti-inflammatory properties, and deficiency of circulating sRAGE is associated with various human diseases. Whether sRAGE concentrations are reduced in chronic obstructive pulmonary disease (COPD) has not been determined. The aim of this study was to determine plasma levels of sRAGE in COPD patients and establish whether sRAGE varies in relation to forced expiratory volume in 1 s (FEV(1)) and other inflammatory markers. 61 COPD patients and 42 healthy controls were recruited. Plasma sRAGE, C-reactive protein (CRP) and serum amyloid A (SAA) were measured in patients with stable COPD. A subgroup had measurements during acute exacerbations of COPD (AECOPD). sRAGE was significantly lower in stable COPD than in healthy controls (p<0.001), while CRP (p<0.001) and SAA (p = 0.015) were higher in stable COPD than in healthy controls. Multiple linear regression confirmed that COPD was negatively associated with sRAGE (p<0.001). Plasma sRAGE was positively correlated with FEV(1) (r(2) = 0.530, p<0.001), while CRP and SAA were inversely proportional to FEV(1). Multiple linear regression analysis showed that only sRAGE was a strong predictor of FEV(1). AECOPD were associated with even lower sRAGE levels that increased with convalescence. Circulating sRAGE is lower in COPD and shows a strong correlation to the degree of airflow limitation.
Plasma coagulation profiles in patients with severe primary pulmonary hypertension
Authors: MM Hoeper, M Sosada, H Fabel
Journal: European Respiratory Journal (1998)

Patients with primary pulmonary hypertension (PPH) benefit from treatment with anticoagulants, and histological findings suggest that in situ thrombosis of pulmonary vessels contributes to the pathogenesis of this disease. The mechanisms that cause a hypercoagulable state in the pulmonary vascular bed have not been fully investigated. This study compared plasminogen plasma activity, protein C and protein S plasma activities, fibrinogen and fibrin degradation products (FGDP and FBDP, respectively), von Willebrand factor antigen (vWF-Ag), prothrombin fragment F1.2, thrombin-antithrombin complexes (TAT), tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI) in 16 patients with PPH and in 16 healthy volunteers. In a subset of the PPH patients, these variables were also compared in simultaneously-obtained mixed-venous and arterial blood samples. Proteins C and S, FGDP, FBDP, and plasminogen levels as well as plasma concentrations of prothrombin fragment F1.2 and TAT were normal in the 16 patients with PPH. In contrast, the plasma activity of PAI was significantly elevated (p&lt;0.0001). Arterial PAI levels were considerably higher than mixed venous PAI levels (p=0.0018), which may reflect intrapulmonary production. Furthermore, vWF-Ag levels were significantly elevated (p&lt;0.0001), but there was no significant difference between mixed-venous and arterial blood. These data, on the whole, do not suggest increased thrombin activity in patients with primary pulmonary hypertension. However, the markedly elevated levels of plasminogen activator inhibitor as well as its transpulmonary gradient may provide a clue to locally impaired fibrinolysis in the pulmonary vascular bed.
Cavernoscopic evacuation of aspergilloma: an alternative method of palliation for haemoptysis in high risk patients.
Authors: R S Rao, P G Curzon, M F Muers, D A Watson
Journal: Thorax (1984)

Les malades ayant une spondylarthrite ankylosante ou une maladie fibrobulleuse du poumon developpent souvent des cavites chroniques ou se developpent les aspergillomes avec risques d'hemoptysie massive
E210K mutation in the gene encoding the β3 chain of laminin-5 (LAMB3) is predictive of a phenotype of generalized atrophic benign epidermolysis bullosa
Authors: None Mellerio, None Eady, None Atherton, None Lake, None Mcgrath
Journal: British Journal of Dermatology (1998)

Journal Article E210K mutation in the gene encoding the β3 chain of laminin‐5 (LAMB3) is predictive of a phenotype of generalized atrophic benign epidermolysis bullosa Get access J.E. Mellerio, J.E. Mellerio Department of Cell and Molecular Pathology, St John's Institute of Dermatology (UMDS), St Thomas' Hospital, London SE1 7EH, U.K., Search for other works by this author on: Oxford Academic Google Scholar R.A.J. Eady, R.A.J. Eady Department of Cell and Molecular Pathology, St John's Institute of Dermatology (UMDS), St Thomas' Hospital, London SE1 7EH, U.K., Search for other works by this author on: Oxford Academic Google Scholar D.J. Atherton, D.J. Atherton Department of Dermatology, Great Ormond Street Hospital for Children, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar B.D. Lake, B.D. Lake Department of Dermatology, Great Ormond Street Hospital for Children, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.A. Mcgrath J.A. Mcgrath Department of Cell and Molecular Pathology, St John's Institute of Dermatology (UMDS), St Thomas' Hospital, London SE1 7EH, U.K., Dr JohnMcGrath E‐mail: j.mcgrath@umds.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 139, Issue 2, 1 August 1998, Pages 325–331, https://doi.org/10.1046/j.1365-2133.1998.02377.x Published: 01 August 1998
Development of the Coronary Vessel System
Authors: David E. Reese, Takashi Mikawa, David M. Bader
Journal: Circulation Research (2002)

Formation of the coronary vessels is a fundamental event in heart development. Congenital abnormalities in the coronary system can have major deleterious effects on heart function. It is also possible that subtle variation in the patterning of coronary vessels has significant but uncharacterized effects on myocardial structure and function. In addition, generation of the coronary vascular system represents a complex system for analysis of regulation of cell fate determination, cell and epithelial migration, epithelial/mesenchymal transition, and patterning of a complex three-dimensional structure. In this review, we present the descriptive embryology of this process as well as the recent data that shed light on the unique developmental mechanisms underlying generation of coronary vessels. This review also attempts to identify areas where additional research is needed and highlights the questions that must be answered for a meaningful understanding of coronary vessel development.
Clinical features and contemporary management of patients with low and preserved ejection fraction heart failure: baseline characteristics of patients in the Candesartan in Heart failure—Assessment of Reduction in Mortality and morbidity (CHARM) programme
Authors: J. McMurray, J. Östergren, M. Pfeffer, K. Swedberg, C. Granger, S. Yusuf, P. Held, E. Michelson, B. Olofsson
Journal: European Journal of Heart Failure (2003)
The RAGE Axis
Authors: Shi Fang Yan, Ravichandran Ramasamy, Ann Marie Schmidt
Journal: Circulation Research (2010)

Abstract : The immunoglobulin superfamily molecule RAGE (receptor for advanced glycation end product) transduces the effects of multiple ligands, including AGEs (advanced glycation end products), advanced oxidation protein products, S100/calgranulins, high-mobility group box-1, amyloid-β peptide, and β-sheet fibrils. In diabetes, hyperglycemia likely stimulates the initial burst of production of ligands that interact with RAGE and activate signaling mechanisms. Consequently, increased generation of proinflammatory and prothrombotic molecules and reactive oxygen species trigger further cycles of oxidative stress via RAGE, thus setting the stage for augmented damage to diabetic tissues in the face of further insults. Many of the ligand families of RAGE have been identified in atherosclerotic plaques and in the infarcted heart. Together with increased expression of RAGE in diabetic settings, we propose that release and accumulation of RAGE ligands contribute to exaggerated cellular damage. Stopping the vicious cycle of AGE-RAGE and RAGE axis signaling in the vulnerable heart and great vessels may be essential in controlling and preventing the consequences of diabetes.
Return to Acute Care Following Ambulatory Surgery
Authors: Claudia A. Steiner, Melinda Maggard-Gibbons, Susan Oehme Raetzman, Marguerite L. Barrett, Greg D. Sacks, Pamela L. Owens
Journal: JAMA (2015)

This population epidemiology study used data from the Healthcare Cost and Utilization Project database to characterize rates of all-cause unplanned visits within 30 days of ambulatory surgery and the relationships between the cause for the revisit and the preceding operation.