tbuckley/cabot-search huggingface dataset:
Mechanical Circulatory Support for Advanced Heart Failure
Authors: O.H. Frazier, Reynolds M. Delgado
Journal: Circulation (2003)

oday, the lifetime risk of developing heart failure is 1 in 5 for both men and women. 1 This high risk underscores the need for effective therapies to treat terminal heart failure unresponsive to conventional treatment.Cardiac transplantation, when possible, offers not only significant palliation but also a real opportunity for meaningful long-term survival.However, posttransplantation mortality and morbidity have improved little over the past decade, and because of the shortage of suitable donor organs, this therapy will never have more than a minimal epidemiological impact on heart failure.To expand the therapeutic options for treating end-stage heart failure, the National Institutes of Health initiated research in the mid-1970s designed to develop mechanical circulatory support (MCS) devices that could provide destination therapy for this condition.The devices developed from this program were first used clinically, however, as bridges to transplantation in the mid-1980s.These implantable MCS devices have now been employed as a bridge to transplantation in more than 4000 patients worldwide.In 2002, on the basis of the results of the Randomized Evaluation of Mechanical Assistance for the Treatment of Chronic Heart failure (REMATCH) trial, 2 implantable MCS systems were approved for destination therapy in patients who were not acceptable candidates for cardiac transplantation.Despite these advances, numerous questions remain about the ultimate goals of MCS and the role of this technology in treating heart failure.Who are the best candidates for these devices, and what should be the therapeutic goals in each case?What adjuncts can be expected to maximize the benefits of MCS? How can future devices best be developed and studied?To illustrate where this technology stands in 2003 and how it can be expected to develop, we will consider its present and future capabilities in light of these questions.
Expression of Matrix Metalloproteinase-9 in Head and Neck Squamous Cell Carcinoma
Authors: Henni Ruokolainen, Paavo Pääkkö, Taina Turpeenniemi-Hujanen
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Previous studies have shown that matrix metalloproteinase-9 (MMP-9) is expressed in malignant head and neck squamous cell carcinoma. The prognostic role of MMP-9 is still unclear. The aim of this study was to investigate the role of MMP-9 immunoreactive protein as a prognostic marker for survival in head and neck squamous cell carcinoma. Experimental Design: Overexpression of the immunoreactive protein for MMP-9 was evaluated in tissue sections of 74 primary head and neck carcinomas with a monoclonal antibody using a biotin-streptavidin immunohistochemical staining method. The staining results were compared with the clinical data and to the patients’ outcome. Results: Positive immunostaining for MMP-9 was observed in 82% of the head and neck carcinomas, 39% of the cases being extensively positive. MMP-9 protein expression was independent of the stage or the grade of the tumor. The expression of MMP-9 was prognostic for shortened survival, the 5-year cause-specific survival being 45% in MMP-9 positive cases, and 92% in cases negative for MMP-9 (P = 0.013). MMP-9 positivity also correlated to the relapse-free survival (P = 0.019). At the 5-year follow-up, the cumulative relapse-free survival rate was 79% for patients with MMP-9-negative tumor and 42% for the patients with positive immunostaining for MMP-9. High expression of MMP-9 seemed to be linked with more aggressive relapses, appearing in 33% of the cases in local relapses, in 52% of cases with lymph node relapses, and in 60% of the cases with hematogenic relapses. Conclusions: This is the first study with a long follow-up showing that the immunoreactive protein of MMP-9 in head and neck carcinoma is associated with shortened relapse-free and cause-specific survival, suggesting that MMP-9 has a role in tumor progression of head and neck carcinomas, as well as in estimation of the prognosis of these diseases.
Innovative new diagnostic test to detect TB and rifampin resistance
Authors: N. B. Chinnappa
Journal: Thorax (2010)

Tuberculosis remains a major public health concern. Existing diagnostic tools are slow and result in delays initiating appropriate treatment. This is particularly a problem in patients with HIV, in whom sputum–smear analysis is frequently negative and those with multi-drug resistant strains.

In this study, the performance of an automated molecular assay for …
In vivo sensitization to purified Hevea brasiliensis proteins in health care workers sensitized to natural rubber latex
Authors: David I. Bernstein, Raymond E. Biagini, Ravi Karnani, Robert Hamilton, Karen Murphy, Cheryl Bernstein, Siti Arija M. Arif, Brian Berendts, H.Y. Yeang
Journal: Journal of Allergy and Clinical Immunology (2003)
Feasibility of upfront dose‐intensive chemotherapy in children with advanced‐stage Hodgkin's lymphoma: preliminary results from the Children's Cancer Group Study CCG‐59704
Authors: K.M. Kelly, R.J. Hutchinson, R. Sposto, M.A. Weiner, M.A. Lones, S.L. Perkins, V. Massey, R. Cohen
Journal: Annals of Oncology (2002)
Rates of noninsulin-mediated glucose uptake are elevated in type II diabetic subjects.
Authors: A D Baron, O G Kolterman, J Bell, L J Mandarino, J M Olefsky
Journal: Journal of Clinical Investigation (1985)

Although insulin is extremely potent in regulating glucose transport in insulin-sensitive tissues, all tissues are capable of taking up glucose by facilitated diffusion by means of a noninsulin-mediated glucose uptake (NIMGU) system. Several reports have estimated that in the postabsorptive state the majority of glucose disposal occurs via a NIMGU mechanism. However, these estimates have been either derived or extrapolated in normal humans. In the present study we have directly measured NIMGU rates in 11 normal (C) and 7 Type II noninsulin-dependent diabetic subjects (NIDDM; mean +/- SE fasting serum glucose, 249 +/- 24 mg/dl). To accomplish this, the serum glucose was clamped at a desired level during a period of insulin deficiency induced by a somatostatin infusion (SRIF, 550 micrograms/h). With a concomitant [3-3H]glucose infusion, we could isotopically quantitate glucose disposal rates (Rd) during basal (basal insulin present) and insulin-deficient (SRIF) conditions. With this approach we found that (a) basal Rd was greater in NIDDM than in C, 274 +/- 31 vs. 150 +/- 7 mg/min, due to elevated hepatic glucose output, (b) NIMGU composes 75 +/- 5% of basal Rd in C and 71 +/- 4% in NIDDM, (c) NIDDMS have absolute basal NIMGU rates that are twice that of C (195 +/- 23 vs. 113 +/- 8 mg/min, P less than 0.05), (d) when C were studied under conditions of insulin deficiency (SRIF infusion) and at a serum glucose level comparable to that of the NIDDM group (250 mg/dl), their rates of NIMGU were the same as that of the NIDDM group (186 +/- 19 vs. 195 +/- 23 mg/min; NS). We conclude that (a) in the postabsorptive state, NIMGU is the major pathway for glucose disposal for both C and NIDDM; (b) for a given glucose level the efficiency of NIMGU (NIMGU divided by serum glucose level) is equal in C and NIDDM, but since basal Rd is elevated in NIDDMs their absolute basal rates of NIMGU are higher; and (c) elevated basal rates of NIMGU in NIDDM may play a role in the pathogenesis of the late complications of diabetes.
Lymphotoxin β receptor signaling promotes tertiary lymphoid organogenesis in the aorta adventitia of aged <i>ApoE</i>−/− mice
Authors: Rolf Gräbner, Katharina Lötzer, Sandra Döpping, Markus Hildner, Dörte Radke, Michael Beer, Rainer Spanbroek, Beatrix Lippert, Catherine A. Reardon, Godfrey S. Getz, Yang-Xin Fu, Thomas Hehlgans, Reina E. Mebius, Michael van der Wall, Dagmar Kruspe, Christoph Englert, Agnes Lovas, Desheng Hu, Gwendalyn J. Randolph, Falk Weih, Andreas J.R. Habenicht
Journal: The Journal of Experimental Medicine (2009)

Atherosclerosis involves a macrophage-rich inflammation in the aortic intima. It is increasingly recognized that this intimal inflammation is paralleled over time by a distinct inflammatory reaction in adjacent adventitia. Though cross talk between the coordinated inflammatory foci in the intima and the adventitia seems implicit, the mechanism(s) underlying their communication is unclear. Here, using detailed imaging analysis, microarray analyses, laser-capture microdissection, adoptive lymphocyte transfers, and functional blocking studies, we undertook to identify this mechanism. We show that in aged apoE−/− mice, medial smooth muscle cells (SMCs) beneath intimal plaques in abdominal aortae become activated through lymphotoxin β receptor (LTβR) to express the lymphorganogenic chemokines CXCL13 and CCL21. These signals in turn trigger the development of elaborate bona fide adventitial aortic tertiary lymphoid organs (ATLOs) containing functional conduit meshworks, germinal centers within B cell follicles, clusters of plasma cells, high endothelial venules (HEVs) in T cell areas, and a high proportion of T regulatory cells. Treatment of apoE−/− mice with LTβR-Ig to interrupt LTβR signaling in SMCs strongly reduced HEV abundance, CXCL13, and CCL21 expression, and disrupted the structure and maintenance of ATLOs. Thus, the LTβR pathway has a major role in shaping the immunological characteristics and overall integrity of the arterial wall.
Char Syndrome, an Inherited Disorder With Patent Ductus Arteriosus, Maps to Chromosome 6p12-p21
Authors: Masahiko Satoda, Mary Ella M. Pierpont, George A. Diaz, Renee A. Bornemeier, Bruce D. Gelb
Journal: Circulation (1999)

Background —Patent ductus arteriosus (PDA) is a relatively common form of congenital heart disease. Although polygenic inheritance has been implicated, no specific gene defects causing PDA have been identified to date. Thus, a positional cloning strategy was undertaken to determine the gene responsible for the Char syndrome, an autosomal dominant disorder characterized by PDA, facial dysmorphism, and hand anomalies. Methods and Results —A genome scan was performed with 46 members of 2 unrelated families in which the disease was fully penetrant but the phenotype differed. Significant linkage was achieved with several polymorphic DNA markers mapping to chromosome 6p12-p21 (maximal 2-point LOD score of 8.39 with D6S1638 at θ=0.00). Haplotype analysis identified recombinant events that defined the Char syndrome locus with high probability to a 3.1-cM region between D6S459/D6S1632/D6S1541 and D6S1024. Conclusions —A familial syndrome in which PDA is a common feature was mapped to a narrow region of chromosome 6p12-p21. Additional analysis with other families and polymorphic markers as well as evaluation of potential candidate genes should lead to the identification of the Char syndrome gene, which will provide insights into cardiogenesis as well as limb and craniofacial development.
Impact of new diagnostic criteria for diabetes on different populations.
Authors: J E Shaw, M de Courten, E J Boyko, P Z Zimmet
Journal: Diabetes Care (1999)

OBJECTIVE: For epidemiological purposes, it has now been recommended that a fasting plasma glucose value of 7.0 mmol/l can be used to diagnose diabetes, instead of a 2-h value of 11.1 mmol/l. This study assesses the impact of making this change on the prevalence of diabetes and on the phenotype of individuals identified. RESEARCH DESIGN AND METHODS: Data were collated from nine population based southern hemisphere studies in which a 75-g oral glucose tolerance test was performed. Comparisons were made between the prevalence derived from fasting values only and the prevalence derived from 2-h values only. Cardiovascular risk was assessed in all individuals. RESULTS: There were 20,624 subjects in the nine surveys of whom 1,036 had previously diagnosed diabetes and 1,714 had newly diagnosed diabetes, according to either fasting or 2-h glucose. The differences in prevalence within each population resulting from changing the diagnostic criteria ranged from +30 to -19% (relative difference) and +4.1 percentage points to -2.8 percentage points (absolute difference). BMI was the most important determinant of disagreement in classification. A total of 31% of those individuals who were diabetic on the fasting value were not diabetic on the 2-h value, and 32% of those with diabetes on the 2-h value were not diabetic on the fasting value. Apart from obesity, there were no differences in cardiovascular risk between those identified by the fasting and the 2-h values. CONCLUSIONS: Changing the diagnostic criteria is likely to have variable and sometimes quite large effects on the prevalence of diabetes in different populations. Furthermore, the fasting criterion identifies different people as being diabetic than those identified by the 2-h criterion.
Maximal T Cell–Mediated Antitumor Responses Rely upon CCR5 Expression in Both CD4+ and CD8+ T Cells
Authors: Alicia González-Martín, Lucio Gómez, Joseph Lustgarten, Emilia Mira, Santos Mañes
Journal: Cancer Research (2011)

Abstract Immune responses against cancer rely upon leukocyte trafficking patterns that are coordinated by chemokines. CCR5, the receptor for chemotactic chemokines MIP1alpha, MIP1beta, and RANTES (CCL3, CCL4, CCL5), exerts major regulatory effects on CD4+- and CD8+ T cell-mediated immunity. Although CCR5 and its ligands participate in the response to various pathogens, its relevance to tumoral immune control has been debated. Here, we report that CCR5 has a specific, ligand-dependent role in optimizing antitumor responses. In adoptive transfer studies, efficient tumor rejection required CCR5 expression by both CD4+ and CD8+ T cells. CCR5 activation in CD4+ cells resulted in CD40L upregulation, leading to full maturation of antigen-presenting cells and enhanced CD8+ T-cell crosspriming and tumor infiltration. CCR5 reduced chemical-induced fibrosarcoma incidence and growth, but did not affect the onset or progression of spontaneous breast cancers in tolerogenic Tg(MMTV-neu) mice. However, CCR5 was required for TLR9-mediated reactivation of antineu responses in these mice. Our results indicate that CCR5 boosts T-cell responses to tumors by modulating helper-dependent CD8+ T-cell activation. Cancer Res; 71(16); 5455–66. ©2011 AACR.
A comprehensive evaluation of IL4 variants in ethnically diverse populations: association of total serum IgE levels and asthma in white subjects
Authors: Monica J. Basehore, Timothy D. Howard, Leslie A. Lange, Wendy C. Moore, Gregory A. Hawkins, Patricia L. Marshik, Michelle S. Harkins, Deborah A. Meyers, Eugene R. Bleecker
Journal: Journal of Allergy and Clinical Immunology (2004)
Screening for Prostate Cancer Decreases the Risk of Developing Metastatic Disease: Findings from the European Randomized Study of Screening for Prostate Cancer (ERSPC)
Authors: Fritz H. Schröder, Jonas Hugosson, Sigrid Carlsson, Teuvo Tammela, Liisa Määttänen, Anssi Auvinen, Maciej Kwiatkowski, Franz Recker, Monique J. Roobol
Journal: European Urology (2012)
Intragastric maldistribution of a liquid meal in patients with reflux oesophagitis assessed by three dimensional ultrasonography
Authors: S Tefera
Journal: Gut (2002)

Background and aims: Our aim was to study intragastric volume and distribution of a liquid meal in patients with reflux oesophagitis using three dimensional ultrasonography. Methods: Twenty patients and 20 healthy controls underwent ultrasonographic measurements of the stomach using a position sensor based on magnetic scanhead tracking for acquisition of three dimensional images. In vivo accuracy of the method was evaluated by scanning a soup filled barostat bag positioned in the proximal stomach of six healthy subjects. Results: In the volume range 100–700 ml, our three dimensional system showed excellent correlation (<i>r</i>=0.99) between estimated and true volumes (limits of agreement −3.4 to 11.0 ml) and a low interobserver variation (limits of agreement −10.9 to 6.7 ml). After ingestion of a 500 ml meat soup meal, patients with reflux oesophagitis revealed a larger volume of the total and proximal stomach at two and 10 minutes (p=0.05; p=0.01, respectively), and an increased proximal/distal intragastric volume ratio at 10 minutes (p=0.04). Patients also experienced more epigastric fullness than controls (p=0.0006). Conclusions: The present three dimensional ultrasound system showed excellent agreement with true volumes and low interobserver variation. Soon after a liquid meal, patients with reflux oesophagitis have abnormal pooling of the ingested liquid in the proximal stomach.
Loss of LIN-35, the Caenorhabditis elegans ortholog of the tumor suppressor p105Rb, results in enhanced RNA interference.
Authors: Ben Lehner, Andrea Calixto, Catriona Crombie, Julia Tischler, Angelo Fortunato, Martin Chalfie, AndrewG Fraser
Journal: Genome biology (2006)

Genome-wide RNA interference (RNAi) screening is a very powerful tool for analyzing gene function in vivo in Caenorhabditis elegans. The effectiveness of RNAi varies from gene to gene, however, and neuronally expressed genes are largely refractive to RNAi in wild-type worms. We found that C. elegans strains carrying mutations in lin-35, the worm ortholog of the tumor suppressor gene p105Rb, or a subset of the genetically related synMuv B family of chromatin-modifying genes, show increased strength and penetrance for many germline, embryonic, and post-embryonic RNAi phenotypes, including neuronal RNAi phenotypes. Mutations in these same genes also enhance somatic transgene silencing via an RNAi-dependent mechanism. Two genes, mes-4 and zfp-1, are required both for the vulval lineage defects resulting from mutations in synMuv B genes and for RNAi, suggesting a common mechanism for the function of synMuv B genes in vulval development and in regulating RNAi. Enhanced RNAi in the germline of lin-35 worms suggests that misexpression of germline genes in somatic cells cannot alone account for the enhanced RNAi observed in this strain. A worm strain with a null mutation in lin-35 is more sensitive to RNAi than any other previously described single mutant strain, and so will prove very useful for future genome-wide RNAi screens, particularly for identifying genes with neuronal functions. As lin-35 is the worm ortholog of the mammalian tumor suppressor gene p105Rb, misregulation of RNAi may be important during human oncogenesis.
Inhaled transmembrane ion transport modulators and non-steroidal anti-inflammatory drugs in asthma
Authors: S Bianco
Journal: Thorax (2000)

Several stimuli which affect the osmolarity of airway surface liquid may induce bronchoconstriction in asthmatic subjects, indicating that in these patients the control of the bronchial calibre is affected by the physicochemical characteristics of the airways lining fluid.1 In the last few years this hypothesis has been confirmed using a number of drugs which are known to affect cellular ion transport.2 Loop diuretics inhibit the bronchial obstructive response to ultrasonically nebulised distilled water (UNW) in a dose dependent fashion.3 It is still unclear, however, whether this protective activity is attributable to the main pharmacological activity of frusemide—the inhibition of the Cl–/Na+/K+ co-transport—since loop diuretics far more potent than frusemide on this mechanism, such as piretanide, torasemide or bumetanide, are markedly less effective than frusemide in preventing UNW induced bronchoconstriction when given by inhalation in equipotent diuretic doses (fig 1).4 In addition to UNW, frusemide was also found to be effective in reducing the bronchoconstriction induced by a variety of “indirect” stimuli including exercise, allergens, hyperosmotic aerosols, metabisulphite, and aspirin.4 5



Figure 1 
Protective effect against UNW induced bronchoconstriction of increasing doses of inhaled frusemide, administered from a pressurised metered canister (5 mg/puff) and piretanide administered through a jet nebuliser. Data are expressed as the percentage protection attained in the same patient using an optimal dose of 40 mg frusemide through a jet nebuliser. Values are mean (SE) of 8–12 asthmatic patients.



The natriuretic activity of frusemide is known to be partially inhibited by cyclo-oxygenase (COX) inhibitors, and a single study found a complete abrogation of the protective effect …
Specificity of T cell clones for antigen and autologous major histocompatibility complex products determines specificity for foreign major histocompatibility complex products.
Authors: S R Abromson-Leeman, H Cantor
Journal: The Journal of Experimental Medicine (1983)

We have analyzed a panel of T cell clones that corecognize defined epitopes of the insulin molecule in association with Ia for their patterns of recognition of alloantigens. A striking correlation is observed between recognition of the I-Ab gene product and cow insulin alpha loop and recognition of I-Eu of the PL/J haplotype. These results are consistent with the notion that reactions to foreign major histocompatibility complex (MHC) products reflect molecular mimicry by foreign class II antigens of 'physiologic' complexes formed by autologous class II MHC molecules and antigen.
Large-Scale CpG Methylation Analysis Identifies Novel Candidate Genes and Reveals Methylation Hotspots in Acute Lymphoblastic Leukemia
Authors: Kristen H. Taylor, Keila E. Pena-Hernandez, J. Wade Davis, Gerald L. Arthur, Deiter J. Duff, Huidong Shi, Farah B. Rahmatpanah, Ozy Sjahputera, Charles W. Caldwell
Journal: Cancer Research (2007)

Abstract This study examined DNA methylation associated with acute lymphoblastic leukemia (ALL) and showed that selected molecular targets can be pharmacologically modulated to reverse gene silencing. A CpG island (CGI) microarray containing more than 3,400 unique clones that span all human chromosomes was used for large-scale discovery experiments and led to 262 unique CGI loci being statistically identified as methylated in ALL lymphoblasts. The methylation status of 10 clones encompassing 11 genes (DCC, DLC-1, DDX51, KCNK2, LRP1B, NKX6-1, NOPE, PCDHGA12, RPIB9, ABCB1, and SLC2A14) identified as differentially methylated between ALL patients and controls was independently verified. Consequently, the methylation status of DDX51 was found to differentiate patients with B- and T-ALL subtypes (P = 0.011, Fisher's exact test). Next, the relationship between methylation and expression of these genes was examined in ALL cell lines (NALM-6 and Jurkat) before and after treatments with 5-aza-2-deoxycytidine and trichostatin A. More than a 10-fold increase in mRNA expression was observed for two previously identified tumor suppressor genes (DLC-1 and DCC) and also for RPIB9 and PCDHGA12. Although the mechanisms that lead to the CGI methylation of these genes are unknown, bisulfite sequencing of the promoter of RPIB9 suggests that expression is inhibited by methylation within SP1 and AP2 transcription factor binding motifs. Finally, specific chromosomal methylation hotspots were found to be associated with ALL. This study sets the stage for acquiring a better biological understanding of ALL and for the identification of epigenetic biomarkers useful for differential diagnosis, therapeutic monitoring, and the detection of leukemic relapse. [Cancer Res 2007;67(6):2617–25]