tbuckley/cabot-search huggingface dataset:
Magnetic Resonance Versus Radionuclide Pharmacological Stress Perfusion Imaging for Flow-Limiting Stenoses of Varying Severity
Authors: Daniel C. Lee, Orlando P. Simonetti, Kathleen R. Harris, Thomas A. Holly, Robert M. Judd, Edwin Wu, Francis J. Klocke
Journal: Circulation (2004)

Although magnetic resonance first-pass imaging (MRFP) has potential advantages in pharmacological stress perfusion imaging, direct comparisons of current MRFP and established radionuclide techniques are not available.Graded regional differences in coronary flow were produced during global coronary vasodilation in chronically instrumented dogs by partially occluding the left circumflex artery. Regional differences in full-thickness flow quantified using microspheres were compared with regional differences obtained with MRFP and radionuclide SPECT imaging (99mTc-sestamibi and 201Tl). Relative regional flows (RRFs) derived from the initial areas under MRFP signal intensity-time curves were linearly related to reference microsphere RRFs over the full range of vasodilation (y=0.93x+4.3; r2=0.77). Relationships between 99mTc-sestamibi and 201Tl RRFs and microsphere RRFs were curvilinear, plateauing as flows increased. The high spatial resolution of the MRI enabled transmural flow to be evaluated in 3 to 5 layers across the myocardial wall. Reductions in subendocardial flow were visually apparent in MRFP images for > or =50% reductions in full-thickness flow. Endocardial-to-epicardial gradients in MRFP flow increased progressively with stenosis severity, whereas transmural flow patterns in remote normally perfused myocardium remained normal. Flow reductions of > or =50% not identified by radionuclide imaging were apparent in MRFP full-thickness and transmural analyses.High-resolution MRFP can identify regional reductions in full-thickness myocardial blood flow during global coronary vasodilation over a wider range than current SPECT imaging. Transmural flow gradients can also be identified; their magnitude increases progressively as flow limitations become more severe and endocardial flow is compromised increasingly.
Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a tissue biomarker for detection of early Hepatocellular carcinoma in patients with cirrhosis
Authors: Yantong Guo, Jingming Zhao, Jingtao Bi, Quan Wu, Xin Wang, Quanyou Lai
Journal: Journal of Hematology & Oncology (2012)

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors occurring mainly in patients with chronic liver disease. Detection of early HCC is critically important for treatment of these patients. We employed a proteomic profiling approach to identify potential biomarker for early HCC detection. Based on Barcelona Clinic Liver Cancer (BCLC) staging classification, 15 early HCC and 25 late HCC tissue samples from post-operative HCC patients and their clinicopathological data were used for the discovery of biomarkers specific for the detection of early HCC. Differential proteins among cirrhotic, early, and late tissue samples were separated by two-dimensional gel electrophoresis (2-DE) and subsequently identified by mass spectrometry (MS). Receiver operating characteristic (ROC) curves analysis were performed to find potential biomarkers associated with early HCC. Diagnosis performance of the biomarker was obtained from diagnosis test. Protein spot SSP2215 was found to be significantly overexpressed in HCC, particularly in early HCC, and identified as heterogeneous nuclear ribonucleoprotein K (hnRNP K) by tandem mass spectrometry (MALDI TOF/TOF). The overexpression in HCC was subsequently validated by western blot and immunohistochemistry. ROC curve analysis showed that hnRNP K intensity could detect early HCC at 66.67 % sensitivity and 84 % specificity, which was superior to serum α-fetoprotein (AFP) in detection of early HCC. Furthermore, the diagnosis test demonstrated, when combined with hnRNP K and serum AFP as biomarker panel to detect early HCC at different cut-off value, the sensitivity and specificity could be enhanced to 93.33 % and 96 %, respectively. hnRNP K is a potential tissue biomarker, either alone or in combination with serum AFP, for detection of early HCC. High expression of hnRNP K could be helpful to discriminate early HCC from a nonmalignant nodule, especially for patients with liver cirrhosis.
Infection, Inflammation, and Lung Function Decline in Infants with Cystic Fibrosis
Authors: Naveen Pillarisetti, Elizabeth Williamson, Barry Linnane, Billy Skoric, Colin F. Robertson, Phil Robinson, John Massie, Graham L. Hall, Peter Sly, Stephen Stick, Sarath Ranganathan
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Better understanding of evolution of lung function in infants with cystic fibrosis (CF) and its association with pulmonary inflammation and infection is crucial in informing both early intervention studies aimed at limiting lung damage and the role of lung function as outcomes in such studies.To describe longitudinal change in lung function in infants with CF and its association with pulmonary infection and inflammation.Infants diagnosed after newborn screening or clinical presentation were recruited prospectively. FVC, forced expiratory volume in 0.5 seconds (FEV(0.5)), and forced expiratory flows at 75% of exhaled vital capacity (FEF(75)) were measured using the raised-volume technique, and z-scores were calculated from published reference equations. Pulmonary infection and inflammation were measured in bronchoalveolar lavage within 48 hours of lung function testing.Thirty-seven infants had at least two successful repeat lung function measurements. Mean (SD) z-scores for FVC were -0.8 (1.0), -0.9 (1.1), and -1.7 (1.2) when measured at the first visit, 1-year visit, or 2-year visit, respectively. Mean (SD) z-scores for FEV(0.5) were -1.4 (1.2), -2.4 (1.1), and -4.3 (1.6), respectively. In those infants in whom free neutrophil elastase was detected, FVC z-scores were 0.81 lower (P=0.003), and FEV(0.5) z-scores 0.96 lower (P=0.001), respectively. Significantly greater decline in FEV(0.5) z-scores occurred in those infected with Staphylococcus aureus (P=0.018) or Pseudomonas aeruginosa (P=0.021).In infants with CF, pulmonary inflammation is associated with lower lung function, whereas pulmonary infection is associated with a greater rate of decline in lung function. Strategies targeting pulmonary inflammation and infection are required to prevent early decline in lung function in infants with CF.
Clodronate induced uveitis
Authors: P Fietta
Journal: Annals of the Rheumatic Diseases (2003)

We are reporting on a 68 year old woman, treated for postmenopausal osteoporosis with clodronate, a non-nitrogen, halogen containing bisphosphonate (BP), who developed a bilateral, drug related, anterior acute uveitis. BPs are generally well tolerated. Uveitis is an ocular adverse effect hitherto described only for nitrogen containing bisphosphonates (N-BPs).1,2 To our knowledge, this is the first report of uveitis induced by a non-N-BP.

In April 2001 the patient presented with a three month history of spinal pain, following an accidental fall. Spine and pelvis x ray examination showed osteoporotic fractures in T12, L1, and L2 vertebral bodies. Bone densitometry dual energy x ray absorptiometry evaluation showed remarkably reduced mineral density in both vertebral and femoral neck sites (T score −4.3 …
Clinical course, late results, and pathological nature of inflammatory disease of the colon initially sparing the rectum.
Authors: B I Korelitz
Journal: Gut (1967)

The Bethune Round Table is an annual conference on international surgery that is unique in North America. Hosted by the Office of International Surgery at the University of Toronto, the conference provides a forum for profiling the global realities of surgical need, particularly as they relate to vulnerable and disadvantaged people of low-income countries. The 2004 Bethune Round Table, drawing on input from 4 continents, highlighted “emerging directions.” Presentations and discussions focused on the themes of current surgical realities, the implications for surgical education, the role of specialized surgical services and the function of surgical partnerships.
Practice in remote areas could disintegrate, report says
Authors: B. Christie
Journal: BMJ (2002)

Action is needed now in Scotland to prevent the disintegration of health services in remote areas, according to a report which that calls for new ways of working to help isolated health professionals.

The report from the Remote and Rural Areas Resource Initiative (RARARI) proposes a number of possible solutions and also recommends that examples of good practice should be sought from in countries such as Norway, Canada, and Australia, which also have to deliver health services to populations thinly scattered over large geographical areas.

Scotland is already experiencing difficulties in recruiting family doctors to work in remote areas. A recent survey revealed showed that 10% of posts in Argyll …
Health Disparities among Travelers Visiting Friends and Relatives Abroad
Authors: Sonia Y. Angell, Martin S. Cetron
Journal: Annals of Internal Medicine (2005)

For an estimated 10 million trips abroad by U.S. residents in 2002, "visiting friends and relatives" (VFR) was a purpose for travel. Made up largely of foreign-born U.S. residents and their children, this population shows disparities in the number of reported cases of many preventable travel-related illnesses compared with people who travel for other purposes, such as tourism. High-risk illnesses in VFR travelers include childhood vaccine-preventable illnesses, hepatitis A and B, tuberculosis, malaria, and typhoid fever. Gaps in the prevalence of disease and access to care both between countries and within the United States uniquely influence disease risk in this population of travelers. We describe this population, a framework for understanding travel-related health disparities, and recommendations for improving the effective delivery of preventive travel-related care to VFR travelers. In addition to transnational efforts to control and eradicate disease, preventing illness in U.S. resident VFR travelers requires focused efforts to remove barriers to their care. In the United States, barriers exist at the systems level (for example, low insurance coverage), patient level (for example, misperception of disease risk), and provider level (for example, inadequate knowledge of travel medicine).
Oligometastatic cancer: an entity, a useful concept, or a therapeutic opportunity?
Authors: Tom Treasure
Journal: Journal of the Royal Society of Medicine (2012)

Theword ‘oligometastases’ was coined in 1995 by Hellman and Weichselbaum who proposed ‘the existence of a clinical significant state of oligometastases’. It seemed to them to be a useable term by which to identify a subset of patients who have disseminated cancer, but in whom metastases were few in number. The diagnostic term oligometastatic disease is now being used with increasing frequency in the argot of multidisciplinary team meetings. It provided the title of a session at the 14th World Conference on Lung Cancer (IASLC July 2011). How has this come about? In this analysis I consider the usage of the term from four view points.
MTP regulated by an alternate promoter is essential for NKT cell development
Authors: Stephanie K. Dougan, Paul Rava, M. Mahmood Hussain, Richard S. Blumberg
Journal: The Journal of Experimental Medicine (2007)

Microsomal triglyceride transfer protein (MTP), an endoplasmic reticulum lipid transfer protein critical for apolipoprotein B (apoB) secretion, regulates CD1d antigen presentation. We identified MTP variant 1 (MTPv1), a novel splice variant of mouse MTP, by polymerase chain reaction and Northern analysis in non–apoB-secreting tissues, including thymocytes and antigen-presenting cells (APCs). Edman degradation of MTPv1 isolated from transfected cells revealed three unique residues; however, recombinant MTP and MTPv1 had an equivalent protein disulfide isomerase association, subcellular localization, triglyceride transfer, phospholipid transfer, response to inhibitors, and ability to support apoB secretion. MTP and MTPv1 efficiently transferred phosphatidylethanolamine to CD1d in vitro. NKT cells fail to develop in fetal thymic organ culture (FTOC) treated with MTP antagonists. MTP-inhibited FTOCs produced negligible numbers of CD1d tetramer–positive cells and exhibited marked defects in IL-4 production upon stimulation with anti-CD3 or α-galactosylceramide–pulsed APCs. CD1d expression on CD4+CD8+ FTOC cells was unaffected by MTP inhibition. Thus, our results demonstrate that MTPv1 in thymocytes is critical to NKT cell development. We hypothesize that, when MTP is inactive, CD1d traffics to the cell surface and presents no lipid or a lipid that is incapable of mediating NKT cell selection and/or is refractory to lysosomal editing.
Comparative Efficiency and Safety of Pharmacological Approaches to the Management of Obesity
Authors: Vojtech Hainer
Journal: Diabetes Care (2011)

Obesity and overweight are reaching global epidemic proportions affecting more than 1.1 billion individuals worldwide. Excess weight is associated with an increased mortality, chronic morbidity (including type 2 diabetes, arterial hypertension, cardiovascular diseases, and certain cancers), decreased quality of life, and considerable health care costs (1).

Antiobesity drugs work through different mechanisms either in the central nervous system (CNS) or in the peripheral tissues. These mechanisms include: 1 ) suppression of food intake in the CNS, 2 ) decreased gut absorption of nutrients, and 3 ) increased energy expenditure or oxidation of nutrients. The efficacy of antiobesity drugs should be evaluated by their ability to reduce fat stores (preferentially visceral adipose tissue), maintain weight loss, diminish obesity-related health risks, and thus decrease morbidity and mortality, and improve quality of life. An ideal antiobesity drug should be administered orally, devoid of major side effects, and distributed at affordable price. Treatment with antiobesity drugs can be considered in obese patients who failed to achieve a sufficient weight loss to a program of lifestyle change, diet, and physical activity. However, the drug treatment of obesity should be an integral part of the comprehensive obesity treatment program that includes diet, exercise, and cognitive behavioral intervention (2,3). Treatment of obesity should be individually tailored taking into account the degree and character of obesity, age, sex, and the presence of comorbidities (4). Drugs used for the treatment of obesity in the past were associated with serious side effects (psycho-stimulatory, depression, addiction, cardio-excitatory effects, pulmonary hypertension, and valve disease). Antiobesity agents that possess cardio-excitatory and psycho-stimulatory effects (e.g., phentermine, ephedrine, and caffeine mixture) have still been available for the short-term use in some countries (<3 months).

Currently, only two drugs, sibutramine and orlistat, are prescribed for long-term administration. The most important trial evaluating the long-term efficacy of …
Asthma, chlamydia trachomathis infection and women reproductive health
Authors: Vladimir Tsarev, N. Rudenya, Svetlana Tsareva, Zhanna Antanovich
Journal: European Respiratory Journal (2011)

Background:  As a result of decrease in functional activity of T helper type 1 lymphocytes patients with asthma are predisposed to Chlamydia trachomathis (ChT) infection.   Objective:  The aim of this study was to reveal the prevalence of ChT infection among asthma sick women and its influence on women reproductive health.   Methods:  44 asthmatic women aged from 17 to 45 years and 20 matched healthy women participated in the study. All were submitted to detailed clinical history, gynecologic examination and ultrasound of reproductive organs. Specific IgG, IgA and IgM antibodies were defined in serum by enzyme-linked immunosorbent assay. Research of antigenes to ChT in cervical smears was spent by polymerase chain reaction.   Results:  A diagnostic titer of IgG antibodies to ChT was defined in 29,5% (13) asthmatic women and in 10,0% (2) healthy women. 53,8% (7) from 13 positive to ChT infection patients had the raised titers of IgG and IgA antibodies simultaneously. Antigenes to ChT have been revealed in cervical smears in 18,2% (8) asthmatic women and in 5,0% (1) healthy women. In ChT infected asthmatic women, in comparison with the patients without ChT infection and with the control, the increase in prevalence of chronic inflammatory diseases of uterus and ovaries (46,2±13,8% vs 12,9±6,0% and 20,0±8,9%), colpitis (53,8±13,2% vs 22,6±7,5% and 20,0±8,9%) and dysfunctional uterine bleedings (53,8±13,2% vs 6,45±4,4% and 10,0±6,7%) was marked.   Conclusion:  Reproductive aged asthma sick women should be examined for an exception of ChT infection.
Defucosylated Anti–CC Chemokine Receptor 4 Monoclonal Antibody Combined with Immunomodulatory Cytokines: A Novel Immunotherapy for Aggressive/Refractory Mycosis Fungoides and Sézary Syndrome
Authors: Hiroki Yano, Takashi Ishida, Atsushi Inagaki, Toshihiko Ishii, Jianmin Ding, Shigeru Kusumoto, Hirokazu Komatsu, Shinsuke Iida, Hiroshi Inagaki, Ryuzo Ueda
Journal: Clinical Cancer Research (2007)

Sézary syndrome (SS) and Mycosis fungoides (MF) in the advanced stage have dismal prognoses. Because CC chemokine receptor 4 (CCR4) has an important role in the skin-homing capacity of MF/SS cells, we postulated that anti-CCR4 monoclonal antibody (mAb) could represent a novel therapeutic agent against aggressive/refractory MF/SS.The defucosylated next-generation therapeutic mAb KM2760 induces enhanced antibody-dependent cellular cytotoxicity (ADCC). Here, we assessed the therapeutic potential of this antibody against aggressive MF/SS tumor cells in vitro and in animal models in vivo.KM2760 induced robust ADCC by peripheral blood mononuclear cell (PBMC) from healthy controls against a MF/SS cell line as well as against primary tumor cells from patients with aggressive MF/SS. KM2760 also showed significant antitumor activity in disseminated and nondisseminated MF/SS mouse models. In addition, approximately 30% of autologous MF/SS tumor cells were killed in in vitro assays of KM2760-induced ADCC mediated by patients' PBMC after only 4 h, despite the low numbers of natural killer cells present in these PBMCs. It is also shown that ADCC induced by defucosylated therapeutic mAb can be greatly augmented by the immunomodulatory cytokines interleukin-12, IFN-alpha-2b, and IFN-gamma.The present study has encouraged us in the conducting of a phase I clinical trial of a completely defucosylated anti-CCR4 mAb in patients with CCR4-positive T-cell lymphomas, including aggressive MF/SS (ClinicalTrials.gov identifier: NCT00355472). In the near future, the efficacy not only of defucosylated anti-CCR4 mAb single-agent treatment but also of combination therapy with immunomodulatory cytokines will be clinically established to target aggressive/refractory MF/SS.
The infrapatellar fat pad of patients with osteoarthritis has an inflammatory phenotype
Authors: I. R. Klein-Wieringa, M. Kloppenburg, Y. M. Bastiaansen-Jenniskens, E. Yusuf, J. C. Kwekkeboom, H. El-Bannoudi, R. G. H. H. Nelissen, A. Zuurmond, V. Stojanovic-Susulic, G. J. V. M. Van Osch, R. E. M. Toes, A. Ioan-Facsinay
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> Obesity is a risk factor for the development of osteoarthritis (OA) in hands and knees. Adipose tissue can secrete different adipokines with powerful immunomodulatory effects. The infrapatellar fat pad (IFP) is an intra-articular organ in the vicinity of the synovium and cartilage. It is hypothesised that IFP-derived soluble factors could contribute to pathological processes in the knee joint. A study was therefore undertaken to compare the release of inflammatory mediators in the IFP and subcutaneous adipose tissue (ScAT) and to characterise the adipocytes and immune cell infiltrate in these tissues. <h3>Methods</h3> Paired IFP and ScAT samples were obtained from 27 patients with primary OA. The stromal vascular cell fraction (SVF) was isolated and characterised by fluorescence activated cell sorting. Cytokine and adipokine release in fat- and adipocyte-conditioned media was measured by luminex. <h3>Results</h3> IFP secreted higher levels of inflammatory mediators such as interleukin 6 (IL-6), adipsin, adiponectin and visfatin than ScAT. This could be due to differences in the phenotype of adipocytes and/or in the composition and phenotype of the SVF cells. IFP adipocyte-conditioned media showed a trend towards more IL-6 and adipsin than ScAT. Moreover, the SVF fraction of IFP contained more cells/g tissue, a lower percentage of T cells and a higher percentage of mast cells than ScAT. In addition, T cells had a predominantly pro-inflammatory phenotype while macrophages had a mixed pro- and anti-inflammatory phenotype in the IFP. <h3>Conclusion</h3> There are profound differences in secreted inflammatory factors and immune cell composition between the IFP and ScAT. These data indicate that IFP-derived soluble mediators could contribute to pathophysiological processes in the OA knee joint.
Phenotypic Reversion or Death of Cancer Cells by Altering Signaling Pathways in Three-Dimensional Contexts
Authors: F. Wang, R. K. Hansen, D. Radisky, T. Yoneda, M. H. Barcellos-Hoff, O. W. Petersen, E. A. Turley, M. J. Bissell
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: We previously used a three-dimensional (3D) reconstituted basement membrane (rBM) assay to demonstrate that tumorigenic HMT-3522 T4–2 human breast cells can be induced to form morphologically normal structures (“reversion”) by treatment with inhibitors of β1 integrin, the epidermal growth factor receptor (EGFR), or mitogen-activated protein kinase (MAPK). We have now used this assay to identify reversion and/or death requirements of several more aggressive human breast cancer cell lines. Methods: Breast tumor cell lines MCF7, Hs578T, and MDA-MB-231 were cultured in 3D rBM and treated with inhibitors of β1 integrin, MAPK, or phosphatidylinositol 3-kinase (PI3K). MDA-MB-231 cells, which lack E-cadherin, were transfected with an E-cadherin cDNA. The extent of reversion was assessed by changes in morphology and polarity, growth in 3D rBM or soft agar, level of invasiveness, and tumor formation in nude mice. Results: All three cell lines showed partial reversion (MCF7 the greatest and Hs578T the least) of tumorigenic properties treated with a single β1 integrin, MAPK, or PI3K inhibitor. Combined inhibition of β1 integrin and either PI3K or MAPK resulted in nearly complete phenotypic reversion (MDA-MB-231, MCF7) or in cell death (Hs578T). E-cadherin-transfected MDA-MB-231 cells showed partial reversion, but exposure of the transfectants to an inhibitor of β1 integrin, PI3K, or MAPK led to nearly complete reversion. Conclusion: The 3D rBM assay can be used to identify signaling pathways that, when manipulated in concert, can lead to the restoration of morphologically normal breast structures or to death of the tumor cells, even highly metastatic cells. This approach may be useful to design therapeutic intervention strategies for aggressive breast cancers.