tbuckley/cabot-search huggingface dataset:
Subsecond Induction of α4 Integrin Clustering by Immobilized Chemokines Stimulates Leukocyte Tethering and Rolling on Endothelial Vascular Cell Adhesion Molecule 1 under Flow Conditions
Authors: Valentin Grabovsky, Sara Feigelson, Chun Chen, Diederik A. Bleijs, Amnon Peled, Guy Cinamon, Francoise Baleux, Frenando Arenzana-Seisdedos, Tsvee Lapidot, Yvette van Kooyk, Roy R. Lobb, Ronen Alon
Journal: The Journal of Experimental Medicine (2000)

Leukocyte recruitment to target tissue is initiated by weak rolling attachments to vessel wall ligands followed by firm integrin-dependent arrest triggered by endothelial chemokines. We show here that immobilized chemokines can augment not only arrest but also earlier integrin-mediated capture (tethering) of lymphocytes on inflamed endothelium. Furthermore, when presented in juxtaposition to vascular cell adhesion molecule 1 (VCAM-1), the endothelial ligand for the integrin very late antigen 4 (VLA-4, α4β1), chemokines rapidly augment reversible lymphocyte tethering and rolling adhesions on VCAM-1. Chemokines potentiate VLA-4 tethering within &amp;lt;0.1 s of contact through Gi protein signaling, the fastest inside-out integrin signaling events reported to date. Although VLA-4 affinity is not altered upon chemokine signaling, subsecond VLA-4 clustering at the leukocyte-substrate contact zone results in enhanced leukocyte avidity to VCAM-1. Endothelial chemokines thus regulate all steps in adhesive cascades that control leukocyte recruitment at specific vascular beds.
CDC: Hospital Antibiotic Use Promotes Resistance
Authors: Bridget M. Kuehn
Journal: JAMA (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Central Role of Calcium-Dependent Tyrosine Kinase PYK2 in Endothelial Nitric Oxide Synthase–Mediated Angiogenic Response and Vascular Function
Authors: Akihiro Matsui, Mitsuhiko Okigaki, Katsuya Amano, Yasushi Adachi, Denan Jin, Shinji Takai, Tomoya Yamashita, Seinosuke Kawashima, Tatsuya Kurihara, Mizuo Miyazaki, Kento Tateishi, Shinsaku Matsunaga, Asako Katsume, Shoken Honshou, Tomosaburo Takahashi, Satoaki Matoba, Tetsuro Kusaba, Tetsuya Tatsumi, Hiroaki Matsubara
Journal: Circulation (2007)

Background— The involvement of Ca 2+ -dependent tyrosine kinase PYK2 in the Akt/endothelial NO synthase pathway remains to be determined. Methods and Results— Blood flow recovery and neovessel formation after hind-limb ischemia were impaired in PYK2 −/− mice with reduced mobilization of endothelial progenitors. Vascular endothelial growth factor (VEGF)–mediated cytoplasmic Ca 2+ mobilization and Ca 2+ -independent Akt activation were markedly decreased in the PYK2-deficient aortic endothelial cells, whereas the Ca 2+ -independent AMP-activated protein kinase/protein kinase-A pathway that phosphorylates endothelial NO synthase was not impaired. Acetylcholine-mediated aortic vasorelaxation and cGMP production were significantly decreased. Vascular endothelial growth factor–dependent migration, tube formation, and actin cytoskeletal reorganization associated with Rac1 activation were inhibited in PYK2-deficient endothelial cells. PI3-kinase is associated with vascular endothelial growth factor–induced PYK2/Src complex, and inhibition of Src blocked Akt activation. The vascular endothelial growth factor–mediated Src association with PLCγ1 and phosphorylation of 783 Tyr-PLCγ1 also were abolished by PYK2 deficiency. Conclusion— These findings demonstrate that PYK2 is closely involved in receptor- or ischemia-activated signaling events via Src/PLCγ1 and Src/PI3-kinase/Akt pathways, leading to endothelial NO synthase phosphorylation, and thus modulates endothelial NO synthase–mediated vasoactive function and angiogenic response.
Implications of Hospital Evacuation after the Northridge, California, Earthquake
Authors: Carl H. Schultz, Kristi L. Koenig, Roger J. Lewis
Journal: New England Journal of Medicine (2003)

On January 17, 1994, an earthquake with a moment magnitude (total energy release) of 6.7 occurred in Northridge, California, leading to the evacuation of patients from several hospitals. We examined the reasons for and methods of evacuation and the emergency-management strategies used. The experience in California may have implications for hospital strategies for responding to any major disaster, including an act of terrorism.From September 1995 to September 1996, we surveyed all acute care hospitals in Los Angeles County that reported having evacuated patients after the Northridge earthquake. Physicians, nurses, hospital administrators, and staff on duty at the hospitals during the evacuation responded to a 58-item structured questionnaire.Eight of 91 acute care hospitals (9 percent) were evacuated. Six hospitals evacuated patients within 24 hours (the immediate-evacuation group), four completely and two partially. All six cited nonstructural damage such as water damage and loss of electrical power as a major reason for evacuation. Five hospitals evacuated the most seriously ill patients first, and one hospital evacuated the healthiest patients first. All hospitals used available equipment to transport patients (blankets, backboards, and gurneys) rather than specialized devices. No deaths resulted from evacuation. One hospital evacuated patients after 3 days and another after 14 days because of structural damage, even though initial inspections had shown no damage (the delayed-evacuation group). Both hospitals required demolition. Some hospitals identified destinations for their evacuated patients independently, whereas others sought the assistance of the Los Angeles County Emergency Operations Center; the two strategies were equally effective.After even a moderate earthquake, hospitals are at risk for both immediate nonstructural damage that may force them to evacuate patients and the delayed discovery of structural damage resulting in permanent closure. Evacuation of large numbers of inpatients from multiple hospitals can be accomplished quickly and safely with the use of available resources and personnel.
Obesity-associated improvements in metabolic profile through expansion of adipose tissue
Authors: Ja-Young Kim, Esther van de Wall, Mathieu Laplante, Anthony Azzara, Maria E. Trujillo, Susanna M. Hofmann, Todd Schraw, Jorge L. Durand, Hua Li, Guangyu Li, Linda A. Jelicks, Mark F. Mehler, David Y. Hui, Yves Deshaies, Gerald I. Shulman, Gary J. Schwartz, Philipp E. Scherer
Journal: Journal of Clinical Investigation (2007)

Excess caloric intake can lead to insulin resistance. The underlying reasons are complex but likely related to ectopic lipid deposition in nonadipose tissue. We hypothesized that the inability to appropriately expand subcutaneous adipose tissue may be an underlying reason for insulin resistance and β cell failure. Mice lacking leptin while overexpressing adiponectin showed normalized glucose and insulin levels and dramatically improved glucose as well as positively affected serum triglyceride levels. Therefore, modestly increasing the levels of circulating full-length adiponectin completely rescued the diabetic phenotype in ob/ob mice. They displayed increased expression of PPARγ target genes and a reduction in macrophage infiltration in adipose tissue and systemic inflammation. As a result, the transgenic mice were morbidly obese, with significantly higher levels of adipose tissue than their ob/ob littermates, leading to an interesting dichotomy of increased fat mass associated with improvement in insulin sensitivity. Based on these data, we propose that adiponectin acts as a peripheral “starvation” signal promoting the storage of triglycerides preferentially in adipose tissue. As a consequence, reduced triglyceride levels in the liver and muscle convey improved systemic insulin sensitivity. These mice therefore represent what we believe is a novel model of morbid obesity associated with an improved metabolic profile.
Future Directions in Breast Imaging
Authors: Marcia Koomen, Etta D. Pisano, Cherie Kuzmiak, Dag Pavic, Robert McLelland
Journal: Journal of Clinical Oncology (2005)

Breast cancer imaging has improved dramatically over the last decade, with higher and more uniform quality standards for mammography, the increasinguse of sonography and magnetic resonance imaging (MRI), and the widespread availability of imaging-guided percutaneous biopsy for clinically occult disease. This review paper describes the limitations that exist in the current state of the art for breast cancer imaging for detection and diagnosis. Four broad areas of future investigation are described in detail. First, we discuss the use of newer versions of mammography, such as digital mammography, with tomosynthesis and digital subtraction mammography. Secondly, new screening for occult disease might be improved through individualized strategies that stratify by patient risk, for example, through more rigorous screening with new and different tools for women at high risk. Third, the use of tools that might be useful for less invasive therapy of breast cancer with imaging to monitor the efficacy of the therapy is discussed. Finally, we describe the use of imaging tomonitor and adjust neoadjuvant chemotherapy regimens in the course of therapy for advanced breast cancers when the risk of death is high.
Hepatocyte Growth Factor Is a Downstream Effector that Mediates the Antifibrotic Action of Peroxisome Proliferator–Activated Receptor-γ Agonists
Authors: Yingjian Li, Xiaoyan Wen, Bradley C. Spataro, Kebin Hu, Chunsun Dai, Youhua Liu
Journal: Journal of the American Society of Nephrology (2005)

Peroxisome proliferator–activated receptor-γ (PPAR-γ) is a ligand-dependent transcription factor that plays an important role in the regulation of insulin sensitivity and lipid metabolism. Evidence shows that PPAR-γ agonists also ameliorate renal fibrotic lesions in both diabetic nephropathy and nondiabetic chronic kidney disease. However, little is known about the mechanism underlying their antifibrotic action. This study demonstrated that PPAR-γ agonists could exert their actions by inducing antifibrotic hepatocyte growth factor (HGF) expression. Incubation of mesangial cells with natural or synthetic PPAR-γ agonists 15-deoxy-Δ<sup>12,14</sup>-prostaglandin J2 (15d-PGJ2) or troglitazone and ciglitazone suppressed TGF-β1–mediated α-smooth muscle actin, fibronectin, and plasminogen activator inhibitor-1 expression. PPAR-γ agonists also induced HGF mRNA expression and protein secretion. Transfection studies revealed that 15d-PGJ2 stimulated HGF gene promoter activity, which was dependent on the presence of a novel peroxisome proliferator response element. Treatment of mesangial cells with 15d-PGJ2 induced the binding of PPAR-γ to the peroxisome proliferator response element in the HGF promoter region. PPAR-γ agonists also activated c-met receptor tyrosine phosphorylation, induced Smad transcriptional co-repressor TG-interacting factor expression, and blocked TGF-β/Smad-mediated gene transcription in mesangial cells. Furthermore, ablation of c-met receptor through the LoxP-Cre system in mesangial cells abolished the antifibrotic effect of 15d-PGJ2. PPAR-γ activation also induced HGF expression in renal interstitial fibroblasts and repressed TGF-β1–mediated myofibroblast activation. Both HGF and 15d-PGJ2 attenuated Smad nuclear translocation in response to TGF-β1 stimulation in renal fibroblasts. Together, these findings suggest that HGF may act as a downstream effector that mediates the antifibrotic action of PPAR-γ agonists.
Mesenchymal Stem Cells Differentiate into an Endothelial Phenotype, Enhance Vascular Density, and Improve Heart Function in a Canine Chronic Ischemia Model
Authors: Guilherme V. Silva, Silvio Litovsky, Joao A.R. Assad, Andre L.S. Sousa, Bradley J. Martin, Deborah Vela, Stephanie C. Coulter, Jing Lin, Judy Ober, William K. Vaughn, Rodrigo V.C. Branco, Edie M. Oliveira, Rumin He, Yong-Jian Geng, James T. Willerson, Emerson C. Perin
Journal: Circulation (2005)

Bone marrow-derived stem cells are under investigation as a treatment for ischemic heart disease. Mesenchymal stem cells (MSCs) have been used preferentially in the acute ischemia model; data in the chronic ischemia model are lacking.Twelve dogs underwent ameroid constrictor placement. Thirty days later, they received intramyocardial injections of either MSCs (100x10(6) MSCs/10 mL saline) (n=6) or saline only (10 mL) (controls) (n=6). All were euthanized at 60 days. Resting and stress 2D echocardiography was performed at 30 and 60 days after ameroid placement. White blood cell count (WBC), C-reactive protein (CRP), creatine kinase MB (CK-MB), and troponin I levels were measured. Histopathological and immunohistochemical analyses were performed. Mean left ventricular ejection fraction was similar in both groups at baseline but significantly higher in treated dogs at 60 days. WBC and CRP levels were similar over time in both groups. CK-MB and troponin I increased from baseline to 48 hours, eventually returning to baseline. There was a trend toward reduced fibrosis and greater vascular density in the treated group. MSCs colocalized with endothelial and smooth muscle cells but not with myocytes.In a canine chronic ischemia model, MSCs differentiated into smooth muscle cells and endothelial cells, resulting in increased vascularity and improved cardiac function.
Genetic susceptibility and resistance to tuberculosis
Authors: N. Settle
Journal: Thorax (2011)

This study investigated possible biomarkers of susceptibility and resistance to Mycobacterium tuberculosis , identifying gene expression profiles associated with active tuberculosis (TB). Among a South African cohort, genome-wide transcription profiles of whole blood were obtained from 33 TB patients, 34 healthy donors latently infected with M tuberculosis (LTBI) and 9 healthy …
Abstract 2313: Role of ferritin dysregulation in human breast cancer cells
Authors: Svitlana I. Shpyleva, Volodymyr P. Tryndyak, Olga Kovalchuk, Athena Starlard-Davenport, Vasyl’ F. Chekhun, Frederick A. Beland, Igor P. Pogribny
Journal: Cancer Research (2010)

Abstract Breast cancer is the most common malignancy in women. Successful treatment of breast cancer relies on a better understanding of the molecular mechanisms involved in breast cancer initiation and progression. Recent studies have suggested a crucial role of perturbations in ferritin levels and tightly associated with this, the deregulation of intracellular iron homeostasis; however, the underlying molecular mechanisms for the cancer-linked ferritin alterations remain largely unknown and often with conflicting conclusions. Therefore, the present study was undertaken to define the role of ferritin in breast cancer. We determined that human breast cancer cells with an epithelial phenotype, such as MCF-7, MDA-MB-361, and T-47D cells, expressed low levels of ferritin light chain (FTL), ferritin heavy chain (FTH1), transferrin (Tf), iron regulatory protein 1 (IRP1), and IRP-2. In contrast, expression of these proteins was substantially elevated in breast cancer cells with an aggressive mesenchymal phenotype, such as Hs-578T, BT-549, and especially MDA-MB-231 cells. The up-regulation of FTH1 and FTL in MDA-MB-231 cells was accompanied by alterations in the subcellular distribution of these proteins as characterized by an increased level of nuclear ferritin and a lower level of the cellular labile iron pool as compared to MCF-7 cells. We established that FTH1 is a target of miR-200b, suggesting that FTH1 up-regulation in MDA-MB-231 cells may be triggered by the low expression of miR-200b. Ectopic up-regulation of miR-200b by transfection of MDA-MB-231 cells with miR-200b substantially decreased the level of FTH1. More importantly, miR-200b-induced down-regulation of ferritin was associated with an increased sensitivity of the MDA-MB-231 cells to the chemotherapeutic agent doxorubicin. These results suggest that perturbations in ferritin levels are associated with the evolution of breast cancer toward a more advanced malignant phenotype. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2313.
Effect of Exercise on Postmenopausal Sex Hormone Levels and Role of Body Fat: A Randomized Controlled Trial
Authors: Evelyn M. Monninkhof, Miranda J. Velthuis, Petra H.M. Peeters, Jos W.R. Twisk, Albertine J. Schuit
Journal: Journal of Clinical Oncology (2009)

To examine the effects of a 1-year exercise intervention on sex hormone levels in postmenopausal women and whether any effects are mediated by changes in body fat composition.We randomly assigned 189 sedentary postmenopausal women (age 50 to 69 years, body mass index of 22 to 40 kg/m(2)) to an exercise intervention (n = 96) or a control group (n = 93). The intervention combined aerobic and strength training and comprised supervised group sessions and home-based exercises (a total of 2.5 h/wk). Between-group differences in sex hormone levels (at baseline and 4 and 12 months) were examined with generalized estimating equations.In total, 183 women (97%) completed the study. Overall, the exercise intervention did not result in favorable effects on sex hormone levels. Among women who lost more than 2% body fat, declines in all estrogens were not significantly different between exercisers and controls. Androgen levels decreased significantly in the exercise group who lost body fat compared with their peers in the control group. Furthermore, this study confirmed that fat loss was significantly associated with declines in postmenopausal estrogen levels. Although not significant, a similar trend was observed for the androgens.This study confirms that fat loss is associated with changes in postmenopausal sex hormone levels and suggests that exercise may be effective in inducing favorable changes in these hormones.
Pain and psychological health status over a 10-year period in patients with recent onset rheumatoid arthritis
Authors: S. Odegard, A. Finset, P. Mowinckel, T. K. Kvien, T. Uhlig
Journal: Annals of the Rheumatic Diseases (2007)

<b>Objective:</b> To examine rheumatoid arthritis (RA) with short disease duration over 10 years, and to identify factors that are associated with the course of pain, depression and anxiety. <b>Methods:</b> A cohort of 238 patients with RA (age 20–70 years, mean disease duration 2.3 years, 68% rheumatoid factor positive) was followed with assessments at baseline and after 1, 2, 5 and 10 years. Self-reported health status was assessed by pain on a 100 mm visual analogue scale, the Arthritis Impact Measurement Scales (AIMS), the 28-item version of General Health Questionnaires, and the Health Assessment Questionnaire. We also examined the erythrocyte sedimentation ratio, grip strength (kg) and radiographic progression of the hands (van der Heijde modified Sharp score). Repeated measures analyses of variance were used to explore the effect of time on measures of outcome among completers, whereas repeated measures analyses using a mixed model were applied to identify factors that were longitudinally associated with pain, depression and anxiety. <b>Results:</b> At the various assessment points 30% had a visual analogue scale pain score of ⩾40 mm, 5–13% had an AIMS depression score of ⩾4.0 and 20–30% had an AIMS anxiety score of ⩾4.0. The perceived level of pain was explained longitudinally by anxiety, disease activity, physical function and female gender, depression by high disease activity and anxiety, whereas anxiety was explained by low disease activity and depression. <b>Conclusion:</b> More patients had increased levels of anxiety (20–30%) than increased levels of depression (5–13%). Several factors, including anxiety, but not depression, were associated with the course of pain.
S86 Change in patient demographics and Home Mechanical Ventilation (HMV) set up for patients with chronic respiratory failure between 2006 and 2012: Abstract S86 Table 1.
Authors: S Drake, M Ramsay, J Steier, N Hart
Journal: Thorax (2013)

<h3>Introduction</h3> HMV is standard therapy for long term management of chronic respiratory failure in patients with neuromuscular disease (NMD), chest wall disease (CWD), chronic obstructive pulmonary disease (COPD) and obesity related respiratory failure (ORRF). This study investigated changing trends in patient demographics and HMV ventilator set up over a 7-year period. <h3>Methods</h3> Data from a bespoke discharge summary system (Carevue, Philips Corporation, US) of patients established on HMV from 2006 to 2012 were analysed. Patient demographic and anthropometric data, including spirometry and arterial blood gas values were analysed. Difference in length of stay (LOS) for non-invasive ventilation (NIV) set up and trends in the ventilator pressures was performed. A p-value &lt;0.05 was considered significant. <h3>Results</h3> 952 patients (518 male) were reviewed with a mean age of 57 ± 16 years. HMV set ups rose by 32.1% over the 7 years. The largest increase was observed in the ORRF group from 44% to 53% of the cohort. In comparison with 2006, NMD/CWD patients were started on HMV with lower arterial partial pressure of carbon dioxide (P<sub>a</sub>CO<sub>2</sub>) in 2012, whilst COPD patients were initiated on HMV at a higher P<sub>a</sub>CO<sub>2</sub> (Table 1). LOS for elective NIV set up fell between 2006 and 2012 (4 (2–7) vs 2 (1–3) days; &lt;0.0001). An increase in inspiratory positive airway pressure (IPAP) was demonstrated across all groups with a decrease in expiratory positive airway pressure (EPAP) demonstrated in NMD/CWD and COPD groups (Table 1). <h3>Conclusions</h3> This study demonstrated an increasing demand for HMV in the UK. This was most marked in the ORRF group in line with rising levels of obesity. In 2012, NMD/CWD patients were being initiated on HMV earlier in the course of chronic respiratory failure, whereas COPD patients were being initiated when chronic respiratory failure was well established. A significant increase was observed in the inspiratory pressures delivered across all groups with a reduction in the expiratory pressures in the NMD/CWD patients as well as the patients with COPD. Efficiency of HMV set up has improved, as reflected by the reduced LOS and this is the result of a more structured clinical pathway.