tbuckley/cabot-search huggingface dataset:
Use of DNA-mediated gene transfer to analyze the role of H-2Ld in controlling the specificity of anti-vesicular stomatitis virus cytotoxic T cells.
Authors: J Forman, R S Goodenow, L Hood, R Ciavarra
Journal: The Journal of Experimental Medicine (1983)

Mouse thymidine kinase (tk-) C3H L (H-2k) cells transformed by the technique of DNA-mediated gene transfer with the herpes simplex virus tk gene together with the BALB/c H-2Ld gene express H-2Ld molecules indistinguishable from their counterparts on spleen cells. An established cloned cell line (8-5) was used to assess the function of the H-2Ld antigen in determining the specificity of alloreactive as well as anti-vesicular stomatitis virus (VSV) cytotoxic T cells (CTL). Both anti-H-2d and anti-H-2Ld CTL displayed a cytotoxic effect against 8-5 cells but not a control cell line transformed with the tk gene only (tk+ cells). Further evidence that 8-5 cells express H-2Ld was provided by the finding that monoclonal anti-H-2Ld but not H-2Dd antibodies blocked target cell lysis by the effector cells. Both BALB/c (H-2d) and DBA/2 (H-2d) animals generated anti-VSV CTL that lysed infected 8-5 but not tk+ cells. To further establish that H-2Ld controlled the specificity of the effector cells, a monoclonal antibody directed against H-2Ld was shown to inhibit lysis of infected 8-5 target cells. To determine whether other H-2d-encoded gene products could serve as restricting antigens for anti-VSV CTL in BALB/c animals, unlabeled VSV infected 8-5 cells were tested for their ability to block lysis of 51chromium-labeled P815 (H-2d)-infected target cells. The 8-5-VSV inhibitor cells inhibited lysis to a slightly lesser extent than unlabeled P815-VSV cells, indicating that H-2Ld plays a major if not exclusive role in restricting anti-VSV CTL in H-2d animals.
Cyclooxygenase-2 Genetic Variants Are Associated with Survival in Unresectable Locally Advanced Non–Small Cell Lung Cancer
Authors: Nan Bi, Ming Yang, Li Zhang, Xiabin Chen, Wei Ji, Guangfei Ou, Dongxin Lin, Luhua Wang
Journal: Clinical Cancer Research (2010)

Cyclooxygenase-2 (COX-2) plays important roles in the modulation of apoptosis, angiogenesis, immune response, and tumor invasion. Elevated COX-2 expression has been reported to be correlated with reduced survival after radiotherapy. This study examined whether genetic variations in the COX-2 gene are associated with different survival in inoperable locally advanced non-small cell lung cancer (NSCLC) treated with chemoradiotherapy or radiotherapy alone.One hundred and thirty-six patients with inoperable stage IIIA-B NSCLC receiving thoracic irradiation between 2004 and 2007 were recruited in this study. Five functional COX-2 polymorphisms were genotyped using DNA from blood lymphocytes. Kaplan-Meier methods were used to compare survival by different genotypes. Cox proportional hazards models were used to identify independently significant variables.During the median 22.4 months of follow-up, the favorable COX-2 -1195GA and GG genotypes were significantly correlated with better overall survival (20.2 months versus 15.7 months; P = 0.006; hazard ratio (HR), 0.58; 95% confidence interval (CI), 0.39-0.86) and with longer progress-free survival (11.9 months versus 9.5 months; P = 0.034) compared with the -1195AA genotype. No significant associations were found among other COX-2 polymorphisms and clinical outcomes. In the multivariate Cox proportional hazards model, COX-2 -1195G/A polymorphism was independently associated with overall survival after adjusting the clinicopathologic factors (P = 0.008; HR, 0.58; 95% CI, 0.39-0.87).COX-2 -1195G/A polymorphism is a potential predictive marker of survival in locally advanced NSCLC patients treated with chemoradiotherapy or radiotherapy alone.
Density of phenotypic markers on BAL T-lymphocytes in hypersensitivity pneumonitis, pulmonary sarcoidosis and bronchiolitis obliterans with organizing pneumonia
Authors: N Satake, S Nagai, A Kawatani, H Kaneshima, S Tanaka, M Takeuchi, T Izumi
Journal: European Respiratory Journal (1993)

In vitro studies have shown that the density of surface antigens reflects the degree of activation of T-cells. We therefore studied the density of surface antigens on T-cells from bronchoalveolar lavage fluid (BALF) and blood in patients with sarcoidosis, hypersensitivity pneumonitis (HP) and bronchiolitis obliterans with organizing pneumonia (BOOP). BALF cells were stained with anti-CD3, anti-CD4, anti-CD8 and anti-human leucocyte antigen-DR(HLA-DR) monoclonal antibodies, and were analysed by cytoflowmetry. The density was evaluated by measuring the Mean Channel fluorescence intensity of the stained cells. The results demonstrated a significant increase in the CD3 density in patients with hypersensitivity pneumonitis (108.2 +/- 20.2 MC), compared with those with pulmonary sarcoidosis (51.2 +/- 12.6), BOOP (74.5 +/- 29.3), and healthy controls (57.1 +/- 11.5). Similar results were obtained for the CD4 and CD8 density in patients with HP. Although the number of HLA-DR positive cells was increased, the density was lower in patients with sarcoidosis (57.4 +/- 11.6) and hypersensitivity pneumonitis (57.4 +/- 14.8), than in healthy controls (72.2 +/- 15.1). Comparable changes were not observed in the peripheral blood. These results suggest that T-cell activation in hypersensitivity pneumonitis may be associated with an increase in the CD3, CD4, and CD8 density on BALF T-cells.
Functional Decline in Peripheral Arterial Disease
Authors: Mary McGrae McDermott, Kiang Liu, Philip Greenland, Jack M. Guralnik, Michael H. Criqui, Cheeling Chan, William H. Pearce, Joseph R. Schneider, Luigi Ferrucci, Lillian Celic, Lloyd M. Taylor, Ed Vonesh, Gary J. Martin, Elizabeth Clark
Journal: JAMA (2004)

Among individuals with lower-extremity peripheral arterial disease (PAD), specific leg symptoms and the ankle brachial index (ABI) are cross-sectionally related to the degree of functional impairment. However, relations between these clinical characteristics and objectively measured functional decline are unknown.To define whether PAD, ABI, and specific leg symptoms predict functional decline at 2-year follow-up.Prospective cohort study among 676 consecutively identified individuals (aged > or =55 years) with and without PAD (n = 417 and n = 259, respectively), with baseline functional assessments occurring between October 1, 1998, and January 31, 2000, and follow-up assessments scheduled 1 and 2 years thereafter. PAD was defined as ABI less than 0.90, and participants with PAD were categorized at baseline into 1 of 5 mutually exclusive symptom groups.Mean annual changes in 6-minute walk performance and in usual-paced and fast-paced 4-m walking velocity, adjusted for age, sex, race, prior-year functioning, comorbid diseases, body mass index, pack-years of cigarette smoking, and patterns of missing data.Lower baseline ABI values were associated with greater mean (95% confidence interval) annual decline in 6-minute walk performance (-73.0 [-142 to -4.2] ft for ABI <0.50 vs -58.8 [-83.5 to -34.0] ft for ABI 0.50 to <0.90 vs -12.6 [-40.3 to 15.1] ft for ABI 0.90-1.50, P =.02). Compared with participants without PAD, PAD participants with leg pain on exertion and rest at baseline had greater mean annual decline in 6-minute walk performance (-111 [-173 to -50.0] ft vs -8.67 [-36.9 to 19.5] ft, P =.004), usual-pace 4-meter walking velocity (-0.06 [-0.09 to -0.02] m/sec vs -0.01 (-0.03 to 0.003] m/sec, P =.02), and fastest-pace 4-meter walking velocity (-0.07 [-0.11 to -0.03] m/sec vs -0.02 [-0.04 to -0.006] m/sec, P =.046). Compared with participants without PAD, asymptomatic PAD was associated with greater mean annual decline in 6-minute walk performance (-76.8 (-135 to -18.6] ft vs -8.67 (-36.9 to 19.5] ft, P =.04) and an increased odds ratio for becoming unable to walk for 6 minutes continuously (3.63; 95% confidence interval, 1.58-8.36; P =.002).Baseline ABI and the nature of leg symptoms predict the degree of functional decline at 2-year follow-up. Previously reported lack of worsening in claudication symptoms over time in patients with PAD may be more related to declining functional performance to than lack of disease progression.
THE LYMPHATICS AND LYMPH FLOW IN THE EDEMATOUS SKIN OF HUMAN BEINGS WITH CARDIAC AND RENAL DISEASE
Authors: Philip D. McMaster
Journal: The Journal of Experimental Medicine (1937)

Local intradermal injections of dye have disclosed the fact that the skin lymphatics in regions of cardiac edema are patent, full of fluid and much widened. Intercommunication between them is ready and dye escapes from them more rapidly than from the vessels of normal skin. A retrograde distribution of dye by way of the lymphatics often occurs and it may pass unseen along the deeper channels to emerge in the skin at unexpected, distant situations. A valvular incompetence of the lymphatics consequent on dilatation would appear to be the cause of these phenomena. In regions of cardiac edema lymph stagnates, despite the fact that the channels are open. In nephritic edema the lymphatic capillaries are wider than normal but not as wide as in cardiac edema. No sign of incompetency of the valves is to be observed. Instead lymph flow is considerably greater than normal, even when edema fluid is accumulating. It was noted to be greater in the periods of fluid equilibrium also and extraordinarily rapid in periods of diuresis.
Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study
Authors: Gillian I Rice, Gabriella M A Forte, Marcin Szynkiewicz, Diana S Chase, Alec Aeby, Mohamed S Abdel-Hamid, Sam Ackroyd, Rebecca Allcock, Kathryn M Bailey, Umberto Balottin, Christine Barnerias, Genevieve Bernard, Christine Bodemer, Maria P Botella, Cristina Cereda, Kate E Chandler, Lyvia Dabydeen, Russell C Dale, Corinne De Laet, Christian G E L De Goede, Mireia del Toro, Laila Effat, Noemi Nunez Enamorado, Elisa Fazzi, Blanca Gener, Madli Haldre, Jean-Pierre S-M Lin, John H Livingston, Charles Marques Lourenco, Wilson Marques, Patrick Oades, Pärt Peterson, Magnhild Rasmussen, Agathe Roubertie, Johanna Loewenstein Schmidt, Stavit A Shalev, Rogelio Simon, Ronen Spiegel, Kathryn J Swoboda, Samia A Temtamy, Grace Vassallo, Catheline N Vilain, Julie Vogt, Vanessa Wermenbol, William P Whitehouse, Doriette Soler, Ivana Olivieri, Simona Orcesi, Mona S Aglan, Maha S Zaki, Ghada M H Abdel-Salam, Adeline Vanderver, Kai Kisand, Flore Rozenberg, Pierre Lebon, Yanick J Crow
Journal: The Lancet Neurology (2013)
Recent cardiovascular drugs from Chinese medicinal plants
Authors: M. C Sutter, Y.-X. Wang
Journal: Cardiovascular Research (1993)

This paper describes the pharmacology of some recent cardiovascular drugs derived from plants used in Chinese traditional medicine. The groups of compounds discussed are benzylisoquinolines (several), tetrahydropyrazine (also called ligustrazine), rhynchophylline and hirsutine, ginkgolides and other PAF inhibitors, coumarins, and ginsenosides, plus a miscellaneous group; approximately 30 substances in all. The plant sources and the pharmacology are indicated for the drugs in each group. By far the most studied compounds are the benzylisoquinolines, especially tetrandrine. The types of pharmacological activity recently described for cardiovascular drugs from plants include calcium antagonism, adrenoceptor antagonism, antagonism of platelet activating factor (PAF), and the ability to act as antioxidants. Hundreds of chemicals have been isolated and identified as constituents of thousands of plants but the basic and clinical pharmacology is known for only a handful of these drugs. Much more research is needed, especially with regard to the pharmacology, both basic and clinical, of the pure chemicals derived from plants.
Loss of Nuclear p53 Protein in Preneoplastic Rat Hepatocytes Is Accompanied by Mdm2 and Bcl-2 Overexpression and by Defective Response to DNA Damage In Vivo
Authors: H Van Gijssel
Journal: Hepatology (2000)

Previous studies have indicated that isolated preneoplastic rat hepatocytes in vitro fail to induce nuclear p53 protein and fail to block replication in response to genotoxic compounds. This suggests that defects in the protection of genomic integrity are part of their premalignant character. In the present study, we have investigated if similar defects occur in vivo. Preneoplastic glutathione-S-transferase (GST) 7-7-positive foci were induced in male Wistar rats by diethylnitrosamine (DEN) initiation and promotion with 2-acetylaminofluorene (2-AAF)/partial hepatectomy (PH). The response to genotoxic damage was studied by X-irradiation. p53 protein was moderately expressed in nuclei in surrounding hepatocytes. This nuclear p53 staining had decreased 2 weeks after 2-AAF treatment. In foci, the protein was detected in the cytoplasm whereas the nuclei were negative. Levels of p21waf1/cip1 protein were high in nuclei and cytoplasm of surrounding hepatocytes, whereas the expression in foci was low. A low level of Mdm2 in nuclei was observed in surrounding liver, while both Mdm2 and Bcl-2 protein were strongly expressed in the cytoplasm in foci. X-ray exposure further induced nuclear expression of p53, p21waf1/cip1, and Mdm2 in surrounding hepatocytes, but focal nuclei were still negative. DNA replication was strongly reduced by X-irradiation in surrounding hepatocytes, but only partially reduced in the foci. These results indicate that the p53 pathway of response to genomic stress is impaired in preneoplastic cells in vivo. This may support their clonal expansion and their further malignant transformation because protection against genetic damage is diminished.
A novel self-lipid antigen targets human T cells against CD1c+ leukemias
Authors: Marco Lepore, Claudia de Lalla, S. Ramanjaneyulu Gundimeda, Heiko Gsellinger, Michela Consonni, Claudio Garavaglia, Sebastiano Sansano, Francesco Piccolo, Andrea Scelfo, Daniel Häussinger, Daniela Montagna, Franco Locatelli, Chiara Bonini, Attilio Bondanza, Alessandra Forcina, Zhiyuan Li, Guanghui Ni, Fabio Ciceri, Paul Jenö, Chengfeng Xia, Lucia Mori, Paolo Dellabona, Giulia Casorati, Gennaro De Libero
Journal: The Journal of Experimental Medicine (2014)

T cells that recognize self-lipids presented by CD1c are frequent in the peripheral blood of healthy individuals and kill transformed hematopoietic cells, but little is known about their antigen specificity and potential antileukemia effects. We report that CD1c self-reactive T cells recognize a novel class of self-lipids, identified as methyl-lysophosphatidic acids (mLPAs), which are accumulated in leukemia cells. Primary acute myeloid and B cell acute leukemia blasts express CD1 molecules. mLPA-specific T cells efficiently kill CD1c+ acute leukemia cells, poorly recognize nontransformed CD1c-expressing cells, and protect immunodeficient mice against CD1c+ human leukemia cells. The identification of immunogenic self-lipid antigens accumulated in leukemia cells and the observed leukemia control by lipid-specific T cells in vivo provide a new conceptual framework for leukemia immune surveillance and possible immunotherapy.
614 PLATELET COUNT IN CIRRHOSIS DEPENDS ON SPLEEN SIZE AND PERIPHERAL THROMBOPOIETIN, BUT NOT ON HEPATIC VENOUS PRESSURE GRADIENT
Authors: R. Latorre, C. Ripoll, M. Puerto, M.D. Ponce, D. Rincón, J.A. Matamoros, E. Ramón, R. Bañares
Journal: Journal of Hepatology (2011)
14-day triple, 5-day concomitant, and 10-day sequential therapies for Helicobacter pylori infection in seven Latin American sites: a randomised trial
Authors: E Robert Greenberg, Garnet L Anderson, Douglas R Morgan, Javier Torres, William D Chey, Luis Eduardo Bravo, Ricardo L Dominguez, Catterina Ferreccio, Rolando Herrero, Eduardo C Lazcano-Ponce, María Mercedes Meza-Montenegro, Rodolfo Peña, Edgar M Peña, Eduardo Salazar-Martínez, Pelayo Correa, María Elena Martínez, Manuel Valdivieso, Gary E Goodman, John J Crowley, Laurence H Baker
Journal: The Lancet (2011)
The promise of stem cells in Parkinson disease
Authors: J. William Langston
Journal: Journal of Clinical Investigation (2005)

Neurotransplantation as a treatment for Parkinson disease reached the stage of human trials over 15 years ago, but the field, which is still in its infancy, has encountered a number of roadblocks since then, both political and scientific. With hope that stem cells may be used as a new source of dopaminergic neurons to replace the degenerating nerve cells in Parkinson disease looming, it is critical that we learn from the past as we work toward achieving new milestones aimed at making this new therapeutic strategy a reality. One of those milestones, which is an important translational step in the development of stem cell technology and the subject of a report in this issue of the JCI, involves transplanting new dopaminergic cell lines to a primate model of Parkinson disease.
Reduced Cortical Thickness of Brain Areas Involved in Pain Processing in Patients With Chronic Pancreatitis
Authors: Jens Brøndum Frøkjær, Stefan A.W. Bouwense, Søren Schou Olesen, Flemming H. Lundager, Simon F. Eskildsen, Harry van Goor, Oliver H.G. Wilder–Smith, Asbjørn Mohr Drewes
Journal: Clinical Gastroenterology and Hepatology (2011)
The Role of CD133 in Normal Human Prostate Stem Cells and Malignant Cancer-Initiating Cells
Authors: Donald J. Vander Griend, Wouter L. Karthaus, Susan Dalrymple, Alan Meeker, Angelo M. DeMarzo, John T. Isaacs
Journal: Cancer Research (2008)

Resolving the specific cell of origin for prostate cancer is critical to define rational targets for therapeutic intervention and requires the isolation and characterization of both normal human prostate stem cells and prostate cancer-initiating cells (CIC). Single epithelial cells from fresh normal human prostate tissue and prostate epithelial cell (PrEC) cultures derived from them were evaluated for the presence of subpopulations expressing stem cell markers and exhibiting stem-like growth characteristics. When epithelial cell suspensions containing cells expressing the stem cell marker CD133+ are inoculated in vivo, regeneration of stratified human prostate glands requires inductive prostate stromal cells. PrEC cultures contain a small subpopulation of CD133+ cells, and fluorescence-activated cell sorting-purified CD133+ PrECs self-renew and regenerate cell populations expressing markers of transit-amplifying cells (DeltaNp63), intermediate cells (prostate stem cell antigen), and neuroendocrine cells (CD56). Using a series of CD133 monoclonal antibodies, attachment and growth of CD133+ PrECs requires surface expression of full-length glycosylated CD133 protein. Within a series of androgen receptor-positive (AR+) human prostate cancer cell lines, CD133+ cells are present at a low frequency, self-renew, express AR, generate phenotypically heterogeneous progeny negative for CD133, and possess an unlimited proliferative capacity, consistent with CD133+ cells being CICs. Unlike normal adult prostate stem cells, prostate CICs are AR+ and do not require functional CD133. This suggests that (a) AR-expressing prostate CICs are derived from a malignantly transformed intermediate cell that acquires "stem-like activity" and not from a malignantly transformed normal stem cell and (b) AR signaling pathways are a therapeutic target for prostate CICs.
Repaglinide acutely amplifies pulsatile insulin secretion by augmentation of burst mass with no effect on burst frequency.
Authors: C B Juhl, N Pørksen, M Hollingdal, J Sturis, S Pincus, J D Veldhuis, A Dejgaard, O Schmitz
Journal: Diabetes Care (2000)

Repaglinide is a new oral hypoglycemic agent that acts as a prandial glucose regulator proposed for the treatment of type 2 diabetes by stimulating insulin secretion. The aim of this study was to explore actions of repaglinide on the rapid pulsatile insulin release by high-frequency insulin sampling and analysis of insulin-concentration time series.We examined 8 healthy lean male subjects in a single-dose double-blind placebo-controlled crossover design. After the subjects underwent an overnight fast, blood sampling was initiated and continued every minute for 120 min. After 40 min, a single dose (0.5 mg) of repaglinide or placebo was given. Serum insulin-concentration time series were assessed by deconvolution analyses and the regularity statistic by approximate entropy (ApEn).Average insulin concentration was increased after repaglinide administration (basal vs. stimulated period, P values are placebo vs. repaglinide) (25.1 +/- 3.6 vs. 33.5 +/- 4.1 pmol/l, P < 0.001). Insulin secretory burst mass (15.8 +/- 2.2 vs. 19.6 +/- 2.8 pmol x l(-1) x pulse(-1), P = 0.02) and amplitude (6.1 +/- 0.9 vs. 7.7 +/- 1.2 pmol x l(-1) x min(-1), P = 0.008) were augmented after repaglinide administration. A concomitant trend toward an increase in basal insulin secretion was observed (2.5 +/- 0.3 vs. 3.2 +/- 0.4 pmol x l(-1) x min(-1), p = 0.06), while the interpulse interval was unaltered (6.8 +/- 1.0 vs. 5.4 +/- 0.4 min/pulse, P = 0.38). ApEn increased significantly after repaglinide administration (0.623 +/- 0.045 vs. 0.670 +/- 0.034, P = 0.04), suggesting less orderly oscillatory patterns of insulin release.In conclusion, a single dose of repaglinide amplifies insulin secretory burst mass (and basal secretion) with no change in burst frequency. The possible importance of these mechanisms in the treatment of type 2 diabetes characterized by disrupted pulsatile insulin secretion remains to be clarified.
Transluminal endoscopic necrosectomy after acute pancreatitis: a multicentre study with long-term follow-up (the GEPARD Study)
Authors: H Seifert, M Biermer, W Schmitt, C Jurgensen, U Will, R Gerlach, C Kreitmair, A Meining, T Wehrmann, T Rosch
Journal: Gut (2009)

<h3>Background</h3> Patients may accrue wait time for kidney transplantation when their eGFR is ≤20 ml/min. However, Black patients have faster progression of their kidney disease compared with White patients, which may lead to disparities in accruable time on the kidney transplant waitlist before dialysis initiation. <h3>Methods</h3> We compared differences in accruable wait time and transplant preparation by CKD-EPI estimating equations in Chronic Renal Insufficiency Cohort participants, on the basis of estimates of kidney function by creatinine (eGFR<sub>cr</sub>), cystatin C (eGFR<sub>cys</sub>), or both (eGFR<sub>cr-cys</sub>). We used Weibull accelerated failure time models to determine the association between race (non-Hispanic Black or non-Hispanic White) and time to ESKD from an eGFR of ≤20 ml/min per 1.73 m<sup>2</sup>. We then estimated how much higher the eGFR threshold for waitlisting would be required to achieve equity in accruable preemptive wait time for the two groups. <h3>Results</h3> By eGFR<sub>cr</sub>, 444 CRIC participants were eligible for waitlist registration, but the potential time between eGFR ≤20 ml/min per 1.73 m<sup>2</sup> and ESKD was 32% shorter for Blacks versus Whites. By eGFR<sub>cys</sub>, 435 participants were eligible, and Blacks had 35% shorter potential wait time compared with Whites. By the eGFR<sub>cr-cys</sub> equation, 461 participants were eligible, and Blacks had a 31% shorter potential wait time than Whites. We estimated that registering Blacks on the waitlist as early as an eGFR of 24–25 ml/min per 1.73 m<sup>2</sup> might improve racial equity in accruable wait time before ESKD onset. <h3>Conclusions</h3> Policies allowing for waitlist registration at higher GFR levels for Black patients compared with White patients could theoretically attenuate disparities in accruable wait time and improve racial equity in transplant access.