tbuckley/cabot-search huggingface dataset:
Essential Role of Bone Marrow for Microvascular Endothelial and Metabolic Functions in Mice
Authors: Sota Nakajima, Junko Ohashi, Ayuko Sawada, Kazuki Noda, Yoshihiro Fukumoto, Hiroaki Shimokawa
Journal: Circulation Research (2012)

We have previously demonstrated that the importance of endothelium-derived hyperpolarizing factor (EDHF) increases as the vessel size decreases and that endothelium-derived hydrogen peroxide (H(2)O(2)) is an EDHF in animals and humans, for which endothelial nitric oxide synthase (eNOS) is the major source. Recent studies have suggested the important role of the bone marrow (BM) in modulating cardiovascular and metabolic functions.We aimed to examine whether BM plays a role in modulating microvascular endothelial and metabolic functions in mice, and if so, to elucidate the mechanisms involved.Male eNOS(-/-) mice were transplanted with BM cells from wild-type (WT) or eNOS(-/-) mice and were maintained for 6 weeks. Endothelium-dependent relaxations and hyperpolarizations of mesenteric arteries to acetylcholine were reduced in eNOS(-/-) mice and were markedly improved when transplanted with WT-BM but not with eNOS(-/-)-BM. The enhanced component of endothelium-dependent relaxations was abolished by catalase, indicating that the improved responses were mediated by H(2)O(2). In contrast, no such beneficial effect was noted in the aorta. Reduced plasma adiponectin levels and impaired glucose tolerance in eNOS(-/-) mice were also improved by WT-BM transplantation. Neuronal nitric oxide synthase (nNOS) in mesenteric arteries of eNOS(-/-) mice was significantly upregulated only when transplanted with WT-BM. Importantly, the beneficial effects of WT-BM transplantation were absent in eNOS(-/-)/adiponectin(-/-) or eNOS(-/-)/nNOS(-/-) mice.These results provide the first evidence that BM plays an important role in modulating microvascular endothelial and metabolic functions, for which adiponectin and nNOS may be involved.
Definitions and outcome measures for bullous pemphigoid: Recommendations by an international panel of experts
Authors: Dedee F. Murrell, Benjamin S. Daniel, Pascal Joly, Luca Borradori, Masayuki Amagai, Takashi Hashimoto, Frdric Caux, Branka Marinovic, Animesh A. Sinha, Michael Hertl, Philippe Bernard, David Sirois, Giuseppe Cianchini, Janet A. Fairley, Marcel F. Jonkman, Amit G. Pandya, David Rubenstein, Detlef Zillikens, Aimee S. Payne, David Woodley, Giovanna Zambruno, Valeria Aoki, Carlo Pincelli, Luis Diaz, Russell P. Hall, Michael Meurer, Jose M. Mascaro, Enno Schmidt, Hiroshi Shimizu, John Zone, Robert Swerlick, Daniel Mimouni, Donna Culton, Jasna Lipozencic, Benjamin Bince, Sergei A. Grando, Jean-Claude Bystryn, Victoria P. Werth
Journal: Journal of the American Academy of Dermatology (2011)
Convection-Enhanced Drug Delivery: Increased Efficacy and Magnetic Resonance Image Monitoring
Authors: Yael Mardor, Ofer Rahav, Yacov Zauberman, Zvi Lidar, Aharon Ocherashvilli, Dianne Daniels, Yiftach Roth, Stephan E. Maier, Arie Orenstein, Zvi Ram
Journal: Cancer Research (2005)

Abstract Convection-enhanced drug delivery (CED) is a novel approach to directly deliver drugs into brain tissue and brain tumors. It is based on delivering a continuous infusion of drugs via intracranial catheters, enabling convective distribution of high drug concentrations over large volumes of the target tissue while avoiding systemic toxicity. Efficient formation of convection depends on various physical and physiologic variables. Previous convection-based clinical trials showed significant diversity in the extent of convection among patients and drugs. Monitoring convection has proven to be an essential, yet difficult task. The current study describes the application of magnetic resonance imaging for immediate assessment of convection efficiency and early assessment of cytotoxic tissue response in a rat brain model. Immediate assessment of infusate distribution was obtained by mixing Gd-diethylenetriaminepentaacetic acid in the infusate prior to infusion. Early assessment of cytotoxic tissue response was obtained by subsequent diffusion-weighted magnetic resonance imaging. In addition, the latter imaging methodologies were used to establish the correlation between CED extent and infusate's viscosity. It was found that low-viscosity infusates tend to backflow along the catheter track, whereas high-viscosity infusates tend to form efficient convection. These results suggest that CED formation and extent may be significantly improved by increasing the infusate's viscosities, thus increasing treatment effects.
False-Positive [<sup>18</sup>F]Fluorodeoxyglucose-Avid Lymph Nodes on Positron Emission Tomography–Computed Tomography After Allogeneic but Not Autologous Stem-Cell Transplantation in Patients With Lymphoma
Authors: Gary A. Ulaner, Joshua Lilienstein, Mithat Gönen, Jocelyn Maragulia, Craig H. Moskowitz, Andrew D. Zelenetz
Journal: Journal of Clinical Oncology (2013)

Determine the clinical significance of [(18)F]fluorodeoxyglucose (FDG)-avid lesions in patients with lymphoma treated with stem-cell transplantation.All patients who underwent stem-cell transplantation for lymphoma at Memorial Sloan-Kettering Cancer Center between January 2005 and December 2009 and had post-transplantation FDG positron emission tomography/computed tomography (PET/CT) examinations were included. PET/CT examinations were evaluated for FDG-avid lesions suggestive of disease. Clinical records, biopsy results, and subsequent imaging examinations were evaluated for malignancy.Two hundred fifty-one patients were identified, 107 with allogeneic and 144 with autologous stem-cell transplantation. Of allogeneic stem-cell transplantation recipients, 50 had FDG-avid lesions suggestive of lymphoma, defined as FDG-avidity greater than liver background. However, only 29 of these 50 demonstrated lymphoma on biopsy, whereas biopsy attempts were benign in the other 21 patients. Sensitivity analysis determined that a 1.5-cm short axis nodal measurement distinguished patients with malignant from nonmalignant biopsies. In 21 of 22 patients with FDG-avid lymph nodes ≤ 1.5 cm, biopsy attempts were benign. In the absence of treatment, these nodes either resolved or were stable on repeat imaging. Disease-free survival of patients with FDG-avid ≤ 1.5 cm lymph nodes was comparable with patients without FDG-avid lesions. In comparison, autologous stem-cell transplantation patients rarely demonstrated FDG-avid lesions suggestive of disease without malignant pathology.Twenty percent (21 of 107) of patients with an allogeneic stem-cell transplantation demonstrated FDG-avid lymph nodes up to 1.5 cm in short axis on PET/CT, which did not represent active lymphoma. After allogeneic stem-cell transplantation of patients with lymphoma, benign FDG-avid ≤ 1.5 cm lymph nodes can mimic malignancy.
Natural killer receptors: the burden of a name
Authors: Henrique Veiga-Fernandes, Dimitris Kioussis, Mark Coles
Journal: The Journal of Experimental Medicine (2010)

A population of cells that expresses the NK cell receptor NKp46 and produces interleukin (IL)-22 have recently attracted considerable attention. The identity of these cells is still the subject of speculation, being variably defined as a novel NK cell subset or as a population containing conventional NK (cNK) cell precursors. In this issue, two studies shed light on this conundrum, demonstrating that NKp46+ IL-22+ cells and cNK cells belong to distinct lineages.
Non-Sentinel Lymph Node Metastases Associated With Isolated Breast Cancer Cells in the Sentinel Node
Authors: Carolien H M van Deurzen, Maaike de Boer, Evelyn M Monninkhof, Peter Bult, Elsken van der Wall, Vivianne C G Tjan-Heijnen, Paul J van Diest
Journal: JNCI Journal of the National Cancer Institute (2008)

There are many reports on the frequency of non–sentinel lymph node involvement when isolated tumor cells are found in the sentinel node, but results and recommendations for the use of an axillary lymph node dissection differ among studies. This systematic review was conducted to give an overview of this issue and to provide recommendations for the use of an axillary lymph node dissection in these patients. We searched Medline, Embase, and Cochrane databases from January 1, 2002, through November 27, 2007, for articles on patients with invasive breast cancer who had isolated tumor cells in the sentinel lymph node (according to the sixth edition of the Cancer Staging Manual of the American Joint Committee on Cancer) and who also underwent axillary lymph node dissection. Of 411 selected articles, 29 (including 836 patients) were included in this review. These 29 studies were heterogeneous, reporting a wide range of non–sentinel lymph node involvement (defined as the presence of isolated tumor cells or micro- or macrometastases) associated with isolated tumor cells in the sentinel lymph node, with an overall pooled risk for such involvement of 12.3% (95% confidence interval = 9.5% to 15.7%). This pooled risk estimate was marginally higher than the risk of a false-negative sentinel lymph node biopsy examination (ie, 7%–8%) but marginally lower than the risk of non–sentinel lymph node metastases in patients with micrometastases (ie, approximately 20%) who are currently eligible for an axillary lymph node dissection. Because 36 (64%) of the 56 patients with isolated tumor cells in their sentinel lymph node also had non–sentinel lymph node macrometastases, those patients with isolated tumor cells in the sentinel lymph node without other indications for adjuvant systemic therapy might be candidates for axillary lymph node dissection.
Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the PLATO trial
Authors: Lars Wallentin, Stefan James, Robert F Storey, Martin Armstrong, Bryan J Barratt, Jay Horrow, Steen Husted, Hugo Katus, P Gabriel Steg, Svati H Shah, Richard C Becker
Journal: The Lancet (2010)
Efficacy of Varenicline, an α4β2 Nicotinic Acetylcholine Receptor Partial Agonist, vs Placebo or Sustained-Release Bupropion for Smoking Cessation&lt;SUBTITLE&gt;A Randomized Controlled Trial&lt;/SUBTITLE&gt;
Authors: Douglas E. Jorenby
Journal: JAMA (2006)

ContextVarenicline, a partial agonist at the α4β2 nicotinic acetylcholine receptor, has the potential to aid smoking cessation by relieving nicotine withdrawal symptoms and reducing the rewarding properties of nicotine.ObjectiveTo determine the efficacy and safety of varenicline for smoking cessation compared with placebo or sustained-release bupropion (bupropion SR).Design, Setting, and ParticipantsA randomized, double-blind, placebo-controlled trial conducted between June 2003 and March 2005 at 14 research centers with a 12-week treatment period and follow-up of smoking status to week 52. Of 1413 adult smokers who volunteered for the study, 1027 were enrolled; 65% of randomized participants completed the study.InterventionVarenicline titrated to 1 mg twice daily (n = 344) or bupropion SR titrated to 150 mg twice daily (n = 342) or placebo (n = 341) for 12 weeks, plus weekly brief smoking cessation counseling.Main Outcome MeasuresContinuous abstinence from smoking during the last 4 weeks of treatment (weeks 9-12; primary end point) and through the follow-up period (weeks 9-24 and 9-52).ResultsDuring the last 4 weeks of treatment (weeks 9-12), 43.9% of participants in the varenicline group were continuously abstinent from smoking compared with 17.6% in the placebo group (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.69-5.50; P&lt;.001) and 29.8% in the bupropion SR group (OR, 1.90; 95% CI, 1.38-2.62; P&lt;.001). For weeks 9 through 24, 29.7% of participants in the varenicline group were continuously abstinent compared with 13.2% in the placebo group (OR, 2.83; 95% CI, 1.91-4.19; P&lt;.001) and 20.2% in the bupropion group (OR, 1.69; 95% CI, 1.19-2.42; P = .003). For weeks 9 through 52, 23% of participants in the varenicline group were continuously abstinent compared with 10.3% in the placebo group (OR, 2.66; 95% CI, 1.72-4.11; P&lt;.001) and 14.6% in the bupropion SR group (OR, 1.77; 95% CI, 1.19-2.63; P = .004). Treatment was discontinued due to adverse events by 10.5% of participants in the varenicline group, 12.6% in the bupropion SR group, and 7.3% in the placebo group. The most common adverse event with varenicline was nausea, which occurred in 101 participants (29.4%).ConclusionsVarenicline is an efficacious, safe, and well-tolerated smoking cessation pharmacotherapy. Varenicline's short-term and long-term efficacy exceeded that of both placebo and bupropion SR.Trial Registrationclinicaltrials.gov Identifier: NCT00143364
Glycan-modified liposomes boost CD4+ and CD8+ T-cell responses by targeting DC-SIGN on dendritic cells
Authors: Wendy W.J. Unger, Astrid J. van Beelen, Sven C. Bruijns, Medha Joshi, Cynthia M. Fehres, Louis van Bloois, Marleen I. Verstege, Martino Ambrosini, Hakan Kalay, Kamran Nazmi, Jan G. Bolscher, Erik Hooijberg, Tanja D. de Gruijl, Gert Storm, Yvette van Kooyk
Journal: Journal of Controlled Release (2012)
Preterm Cerebellar Growth Impairment After Postnatal Exposure to Glucocorticoids
Authors: Emily W. Y. Tam, Vann Chau, Donna M. Ferriero, A. James Barkovich, Kenneth J. Poskitt, Colin Studholme, Eric D.-Y. Fok, Ruth E. Grunau, David V. Glidden, Steven P. Miller
Journal: Science Translational Medicine (2011)

Glucocorticoid exposure in preterm newborns is associated with impaired cerebellar development, pointing to a modifiable risk factor for improving motor and cognitive outcomes after premature birth.
Iron deficiency anaemia and cataracts in a patient with haemochromatosis
Authors: Kai-Henrik Peiffer, Moritz Niemeyer, Anna Buslau, Thomas Kohnen, Martina Ulrike Muckenthaler, Stefan Zeuzem, Christoph Sarrazin
Journal: Gut (2013)

A 55-year-old woman presented to our hepatology outpatient clinic with symptoms of anaemia. Her medical history included hereditary haemochromatosis type 1, psoriatic arthropathy and bilateral cataracts since early adulthood. There was a family history of early-onset cataracts. Haemochromatosis was treated by frequent phlebotomies (2–4 per month) since diagnosis 2.5 years earlier, limited by several episodes of severe symptomatic anaemia (minimal haemoglobin: 7.0 g/dL). Despite anaemia, she presented with constantly high levels of ferritin (>1000 ng/mL) throughout the period of phlebotomies so that she was referred to our clinic for further diagnostics and therapy. At presentation, physical examination showed signs of anaemia but no signs of liver cirrhosis. The levels for γ-glutamyltransferase, alanine transaminase, bilirubin, international normalised ratio (INR) and thrombocytes were within the normal …
Defective Nitric Oxide Production and Functional Renal Reserve in Patients with Type 2 Diabetes Who Have Microalbuminuria of African and Asian Compared with White Origin
Authors: KENNETH ANTHONY EARLE, SEEMA MEHROTRA, RAYMOND NEIL DALTON, ELIZABETH DENVER, RAMASAMYIYER SWAMINATHAN
Journal: Journal of the American Society of Nephrology (2001)

Diabetic nephropathy is a leading cause of end-stage renal failure. Its incidence is higher and is increasing in persons of Indo-Asian and African-Caribbean (African-Asian) compared with those of white origin. Nitric oxide deficiency is associated with progressive renal disease. It was hypothesized that differences in the capacity to increase glomerular filtration (functional renal reserve) would exist between these racial groups in relation to nitric oxide availability. Patients with type 2 diabetes of African-Asian (n = 9) and white (n = 9) origin with microalbuminuria were studied under euglycemic conditions. Glomerular filtration, renal plasma flow, and clearance of the stable metabolites of nitric oxide, nitrite, and nitrate were measured before and after a renal vasodilatory stimulus of a mixed amino acid intravenous infusion. There were no significant differences in age, duration of diabetes, and baseline glomerular filtration (57.1 [14.1] versus 55.8 [10.1] yr; P = 0.82, 14.5 [10.2] versus 9.1 [7.0] yr; P = 0.19 and 125.9 [30.9] versus 127.2 [44.6] ml/min per 1.73 m2; P = 0.94) between the African-Asian and white groups. Functional renal reserve, change in renal plasma flow, and percentage change in nitrate and nitrite clearance was significantly higher in the white compared with the African-Asian group (21.9 [45.7] versus -2.5 [28.2] ml/min per 1.73 m2; P = 0.043, 155.8 [205.9] versus -90.1 [146.0]; P = 0.03 ml/min per 1.73m2 and 26.7 [85.1] versus -44.7 [16.9] %; P = 0.013, respectively). The differences in functional reserve were not confounded after adjustment for diabetes duration (P = 0.034). The data suggest that these patients with type 2 diabetes of African and Asian origin lose functional renal reserve earlier in the evolution of nephropathy than whites. The differences appear to be due to defective nitric oxide production or bioavailability and might explain some of the propensity to develop end-stage renal disease.
P-Selectin Glycoprotein Ligand 1 (Psgl-1) Is a Physiological Ligand for E-Selectin in Mediating T Helper 1 Lymphocyte Migration
Authors: Takako Hirata, Glenn Merrill-Skoloff, Melissa Aab, Jing Yang, Barbara C. Furie, Bruce Furie
Journal: The Journal of Experimental Medicine (2000)

P-selectin glycoprotein ligand 1 (PSGL-1) is a sialomucin expressed on leukocytes that mediates neutrophil rolling on the vascular endothelium. Here, the role of PSGL-1 in mediating lymphocyte migration was studied using mice lacking PSGL-1. In a contact hypersensitivity model, the infiltration of CD4(+) T lymphocytes into the inflamed skin was reduced in PSGL-1-deficient mice. In vitro-generated T helper (Th)1 cells from PSGL-1-deficient mice did not bind to P-selectin and migrated less efficiently into the inflamed skin than wild-type Th1 cells. To assess the role of PSGL-1 in P- or E-selectin-mediated migration of Th1 cells, the cells were injected into E- or P-selectin-deficient mice. PSGL-1-deficient Th1 cells did not migrate into the inflamed skin of E-selectin-deficient mice, indicating that PSGL-1 on Th1 cells is the sole ligand for P-selectin in vivo. In contrast, PSGL-1-deficient Th1 cells migrated into the inflamed skin of P-selectin-deficient mice, although less efficiently than wild-type Th1 cells. This E-selectin-mediated migration of PSGL-1-deficient or wild-type Th1 cells was not altered by injecting a blocking antibody to L-selectin. These data provide evidence that PSGL-1 on Th1 cells functions as one of the E-selectin ligands in vivo.
Value of emergency toxicological investigations in differential diagnosis of coma.
Authors: M Helliwell, G Hampel, E Sinclair, A Huggett, R J Flanagan
Journal: BMJ (1979)

Out of 208 cases of coma of unknown aetiology referred to the poisons unit of this hospital during 1978 for emergency toxicological investigations, 108 were found to be due to self-poisoning medical conditions, mainly neurological, accounted for coma in 90 patients; the cause was not ascertained in the remaining 10 cases. More than one preparation had been ingested by 58 (54%) of the poisoned patients, although barbiturates were the drugs most commonly encountered in the severe cases. Toxicological investigations should be considered in the differential diagnosis of coma when history, physical examination, and emergency biochemical measurements yield little diagnostic information.
Idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia should stay separate
Authors: H. R. Collard, T. E. King
Journal: European Respiratory Journal (2008)

To the Editors: 

We read with interest the recent perspective by Maher et al . 1, challenging the current definition of idiopathic pulmonary fibrosis (IPF). Questioning dogma is critical to progress in science and the authors should be commended for doing so.

We agree that the relationship between disease entity ( i.e. clinical diagnosis) and histopathological pattern is …
Implementation of a Mental Health Care Package for Children in Areas of Armed Conflict: A Case Study from Burundi, Indonesia, Nepal, Sri Lanka, and Sudan
Authors: Mark J. D. Jordans, Wietse A. Tol, Dessy Susanty, Prudence Ntamatumba, Nagendra P. Luitel, Ivan H. Komproe, Joop T. V. M. de Jong
Journal: PLoS Medicine (2013)

As one article in an ongoing series on Global Mental Health Practice, Mark Jordans and colleagues describe their work developing and evaluating a community-based psychosocial and mental health care package for children in five conflict affected countries: Burundi, Indonesia, Nepal, Sri Lanka, and Sudan.
Expression of Angiogenic Factors Vascular Endothelial Growth Factor and Interleukin-8/CXCL8 Is Highly Responsive to Ambient Glutamine Availability
Authors: Ekaterina V. Bobrovnikova-Marjon, Philip L. Marjon, Olena Barbash, David L. Vander Jagt, Steve F. Abcouwer
Journal: Cancer Research (2004)

Abstract Vascular endothelial growth factor (VEGF) and interleukin-8/CXCL8 (IL-8) are prominent pro-angiogenic and pro-metastatic proteins that represent negative prognostic factors in many types of cancer. Hypoxia is thought to be the primary environmental cause of VEGF and IL-8 expression in solid tumors. We hypothesized that a lack of nutrients other than oxygen could stimulate the expression of these factors and previously demonstrated that expression of VEGF and IL-8 is responsive to amino acid deprivation. In the present study, we examined the effect of glutamine availability on the expression of these factors as well as the role of transcription factors NFκB and activating protein-1 (AP-1) in the response of TSE human breast carcinoma cells to glutamine deprivation. VEGF and IL-8 secretion and mRNA levels were dramatically induced by glutamine deprivation. mRNA stabilization contributed to this response. Glutamine deprivation increased NFκB (p65/p50) and AP-1 (Fra-1/c-Jun+JunD) DNA-binding activities. Blocking NFκB and AP-1 activation with curcumin as well as expression of dominant inhibitors, inhibitor of nuclear factor-κB (IκB) super repressor (IκBM), and a mutant form of c-Fos (A-Fos) demonstrated that the activation of NFκB and AP-1 transcription factors was necessary for the induction of IL-8 expression but dispensable for the induction of VEGF expression. A macro-array containing 111 NFκB target genes identified a total of 17 that were up-regulated 2-fold or more in response to glutamine deprivation. These included growth regulated oncogene α (GROα/GRO1/CXCL1), another neutrophil chemoattractant implicated in tumor angiogenesis and metastasis.