tbuckley/cabot-search huggingface dataset:
Theranostic Potential of Oncolytic Vaccinia Virus
Authors: Juan J Rojas, Steve H Thorne
Journal: Theranostics (2012)

Biological cancer therapies, such as oncolytic, or replication-selective viruses have advantages over traditional therapeutics as they can employ multiple different mechanisms to target and destroy cancers (including direct cell lysis, immune activation and vascular collapse). This has led to their rapid recent clinical development. However this also makes their pre-clinical and clinical study complex, as many parameters may affect their therapeutic potential and so defining reason for treatment failure or approaches that might enhance their therapeutic activity can be complicated. The ability to non-invasively image viral gene expression in vivo both in pre-clinical models and during clinical testing will considerably enhance the speed of oncolytic virus development as well as increasing the level and type of useful data produced from these studies. Further, subsequent to future clinical approval, imaging of reporter gene expression might be used to evaluate the likelihood of response to oncolytic viral therapy prior to changes in tumor burden. Here different reporter genes used in conjunction with oncolytic viral therapy are described, along with the imaging modalities used to measure their expression, while their applications both in pre-clinical and clinical testing are discussed. Possible future applications for reporter gene expression from oncolytic viruses in the phenotyping of tumors and the personalizing of treatment regimens are also discussed.
Anal Dynamic Graciloplasty in the Treatment of Intractable Fecal Incontinence
Authors: Cor G.M.I. Baeten, Bastiaan P. Geerdes, Eddy M.M. Adang, Erik Heineman, Joop Konsten, Gerard L. Engel, Arnold D.M. Kester, Frank Spaans, Peter B. Soeters
Journal: New England Journal of Medicine (1995)

In patients with intractable fecal incontinence, conventional treatment is not always successful. Dynamic graciloplasty (transposition of the gracilis muscle to the anus with the implantation of stimulating electrodes) was developed to provide such patients with functional neosphincters. We evaluated the clinical results of this new surgical approach and the effects on quality of life.
Responses of the Bronchial Veins in a Heart-Lung-Bronchial Preparation
Authors: Pedro Aramendia, Juan Martinez L. de Letona, Domingo M. Aviado
Journal: Circulation Research (1962)

Blood collected from the bronchial veins of a heart-lung-bronchial preparation consists of two components: (a) fraction from the bronchial arteries, and (b) pulmonary to bronchial shunt It is estimated that the latter is more than half of total bronchial venous flow. The pulmonary to bronchial shunt is reduced by procedures which increase pulmonary arterial pressure. An intrinsic nervous reflex mechanism is suggested to explain such a response, particularly because the bronchial veins are more sensitive than the bronchial arteries to the vasoconstrictor action of epinephrine and norepinephirine, and to the vasodilator action of isoproterenol. acetylchohine, histamine, and DMPP. Alterations in bronchial venous flow induced by such chemical agents are independent of bronchoconstriction or bronchodilatation.
Maternal Heterozygous Familial Hypercholesterolemia and Its Consequences for Mother and Child
Authors: John D. Rutherford
Journal: Circulation (2011)

D uring a normal pregnancy serum lipids (total, low- density lipoprotein [LDL]-cholesterol and high-density lipoprotein cholesterol, and triglycerides) rise steadily 1 and take months to fall postpartum. 2LDL-cholesterol can increase by Ϸ66% and triglycerides can rise 3-fold, and it has been suggested that elevated cholesterol during pregnancy may be associated with spontaneous preterm delivery.
A Study of Illicit Amphetamine Drug Traffic in Oklahoma City
Authors: JOHN GRIFFITH
Journal: American Journal of Psychiatry (1966)

In this study of "at large" amphetamine drug peddlers and their clientele in Oklahoma City, the author observes, contrary to some medical opinion, that illicit traffic in these drugs is brisk, widespread in the area, and not without consequence to the indiscriminate user. An unexpected finding was that amphetamine psychosis is neither uncommon nor merely confined to borderline psychotic individuals.
EVIDENCE FOR IDENTITY OR CLOSE ASSOCIATION OF THE Fc RECEPTOR OF B LYMPHOCYTES AND ALLOANTIGENS DETERMINED BY THE <i>Ir</i> REGION OF THE <i>H-2</i> COMPLEX
Authors: Howard B. Dickler, David H. Sachs
Journal: The Journal of Experimental Medicine (1974)

Immunoglobulin complexes, composed of heat-aggregated human Ig, were shown to bind to mouse B lymphocytes of a variety of strains, but not to either thymocytes or thymus-derived (T) lymphocytes under a variety of conditions. It was shown that this binding was not due to either natural human antibodies against mouse nor to nonspecific binding of human Ig by mouse lymphocytes. Such complexes were shown to bind to the same sites which bind mouse antibody-antigen complexes. This site is known as the Fc receptor. The binding of Ig complexes to mouse B lymphocytes was markedly inhibited by pretreatment of the lymphocytes with anti-H-2 antisera. A series of experiments indicated the specificity of this result, including the fact that this inhibition was shown not to be due to the artifact of shedding of H-2 antibody-antigen complexes, nor to nonspecific steric inhibition. The antibodies within anti-H-2 antisera which were responsible for this inhibition were specific for alloantigens associated with the Ir region of the H-2 complex (Ia antigens). Antiserum specific for these Ia antigens produced inhibition, whereas antisera specific for antigens determined by the K or D regions of the H-2 complex did not. Evidence was obtained using F1 hybrid cells that at least some Ia antigens of both parental types are expressed on every B lymphocyte (i.e. codominant expression). These data indicate that the Fc receptor and a series of alloantigens controlled by the Ir region of the H-2 complex are identical or closely associated on the B-lymphocyte surface membrane. This observation may have implications for the mechanism of control of the immune response.
Best books on urology: a personal choice
Authors: P. H O' Reilly
Journal: BMJ (1995)

Urology encompasses the management of diseases of the kidney, bladder, prostate, and genitals; infections; incontinence; impotence and infertility; and oncology and reconstruction. It demands an accurate degree of preoperative diagnosis, often by complex uroradiological techniques. The books described here are just a few of the outstanding ones.

** First On Call For Urology. R K Carruthers. (pounds sterling7.99.) Macmillan, 1994. ISBN 0 333 54820 5

** Lecture Notes on Urology. 3rd edn. J P Blandy. (pounds sterling16.95.) Blackwell Scientific, 1982. ISBN 0 632 02492 5

** Essential Urology. N Bullock, G Sibley, R Whitaker. (pounds sterling15.) Churchill Livingstone, 1993. ISBN 0 443 03841 4

Robert Carruthers's First On Call For Urology is designed for those involved with the hour to hour care of urological patients. Brief but comprehensive, it deals with such mundane but essential subjects as blocked catheters, postoperative bleeding, and renal colic. It is a student's and house officers's vade mecum, to answer the questions “What is wrong? What do I do next?” It really is very good. John Blandy can write as clearly …
Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides
Authors: Spencer C. Liang, Xiang-Yang Tan, Deborah P. Luxenberg, Riyez Karim, Kyriaki Dunussi-Joannopoulos, Mary Collins, Lynette A. Fouser
Journal: The Journal of Experimental Medicine (2006)

Th17 cells are a distinct lineage of effector CD4(+) T cells characterized by their production of interleukin (IL)-17. We demonstrate that Th17 cells also expressed IL-22, an IL-10 family member, at substantially higher amounts than T helper (Th)1 or Th2 cells. Similar to IL-17A, IL-22 expression was initiated by transforming growth factor beta signaling in the context of IL-6 and other proinflammatory cytokines. The subsequent expansion of IL-22-producing cells was dependent on IL-23. We further demonstrate that IL-22 was coexpressed in vitro and in vivo with both IL-17A and IL-17F. To study a functional relationship among these cytokines, we examined the expression of antimicrobial peptides by primary keratinocytes treated with combinations of IL-22, IL-17A, and IL-17F. IL-22 in conjunction with IL-17A or IL-17F synergistically induced the expression of beta-defensin 2 and S100A9 and additively enhanced the expression of S100A7 and S100A8. Collectively, we have identified IL-22 as a new cytokine expressed by Th17 cells that synergizes with IL-17A or IL-17F to regulate genes associated with skin innate immunity.
Glioblastoma with an oligodendroglioma component: distinct clinical behavior, genetic alterations, and outcome
Authors: Y. Wang, S. Li, L. Chen, G. You, Z. Bao, W. Yan, Z. Shi, Y. Chen, K. Yao, W. Zhang, C. Kang, T. Jiang
Journal: Neuro-Oncology (2012)

Glioblastomas (GBMs) containing foci that resemble oligodendroglioma are defined as GBM with oligodendroglioma component (GBMO). However, whether GBMO is a distinct clinicopathological variant of GBM or merely represents a divergent pattern of differentiation remains controversial. We investigated 219 consecutive primary GBMs, of which 40 (18.3%) were confirmed as GBMOs. The clinical features and genetic profiles of the GBMOs were analyzed and compared with the conventional GBMs. The GBMO group showed more frequent tumor-related seizures (P= .027), higher frequency of IDH1 mutation (31% vs. <5%, P= .015), lower MGMT expression (P= .016), and longer survival (19.0 vs. 13.2 months; P= .022). In multivariate Cox regression analyses, presence of an oligodendroglioma component was predictive of longer survival (P= .001), but the extent of the oligodendroglial component appeared not to be linked to prognosis (P= .664). The codeletions of 1p/19q, somewhat surprisingly, were infrequent (<5%) in both GBMO and conventional GBM. In addition, the response to aggressive therapy differed: the GBMO group had no survival advantage associated with aggressive treatment protocols, whereas a clear treatment effect was observed in the conventional GBM group. Collectively, the clinical behavior and genetic alterations of GBMO thus differs from those of conventional GBM. Presence of an oligodendroglial component may therefore be a useful classification and stratification variable in therapeutic trials of GBMs.
Association of COPD candidate genes with computed tomography emphysema and airway phenotypes in severe COPD
Authors: W.J. Kim, E. Hoffman, J. Reilly, C. Hersh, D. DeMeo, G. Washko, E.K. Silverman
Journal: European Respiratory Journal (2010)

The principal determining factors influencing the development of the airway disease and emphysema components of chronic obstructive pulmonary disease (COPD) have not been clearly defined. Genetic variability in COPD patients might influence the varying degrees of involvement of airway disease and emphysema. Therefore, we investigated the genetic association of single nucleotide polymorphisms (SNPs) in COPD candidate genes for association with emphysema severity and airway wall thickness phenotypes. Polymorphisms in six candidate genes were analysed in 379 subjects of the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study with quantitative chest computed tomography (CT) data. Genetic association with per cent of lung area below -950 HU (LAA950), airway wall thickness, and derived square root wall area (SRWA) of 10-mm internal perimeter airways were investigated. Three SNPs in EPHX1 , five SNPs in SERPINE2 and one SNP in GSTP1 were significantly associated with LAA950. Five SNPs in TGFB1 , two SNPs in EPHX1 , one SNP in SERPINE2 and two SNPs in ADRB2 were associated with airway wall phenotypes in NETT. In conclusion, several COPD candidate genes showed evidence for association with airway wall thickness and emphysema severity using CT in a severe COPD population. Further investigation will be required to replicate these genetic associations for emphysema and airway wall phenotypes.
Stress proteins - an endogenous route to myocardial protection: fact or fiction?
Authors: D. M Yellon, D. S Latchman, M. S Marber
Journal: Cardiovascular Research (1993)

Journal Article Stress proteins – an endogenous route to myocardial protection: fact or fiction? Get access Derek M Yellon, Derek M Yellon University College and Middlesex Hospital Schools of Medicine, University College Hospital, Gower Street, London WCIE 6AU. United Kingdom – The Hatter Institute for Cardiovascular Studies, Division of Cardiology: M S Marber, D M Yellon; Division of Molecular Pathology: D S Latchman. Correspondence to Dr Yellon. Search for other works by this author on: Oxford Academic PubMed Google Scholar David S Latchman, David S Latchman University College and Middlesex Hospital Schools of Medicine, University College Hospital, Gower Street, London WCIE 6AU. United Kingdom – The Hatter Institute for Cardiovascular Studies, Division of Cardiology: M S Marber, D M Yellon; Division of Molecular Pathology: D S Latchman. Correspondence to Dr Yellon. Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael S Marber Michael S Marber University College and Middlesex Hospital Schools of Medicine, University College Hospital, Gower Street, London WCIE 6AU. United Kingdom – The Hatter Institute for Cardiovascular Studies, Division of Cardiology: M S Marber, D M Yellon; Division of Molecular Pathology: D S Latchman. Correspondence to Dr Yellon. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 2, February 1993, Pages 158–161, https://doi.org/10.1093/cvr/27.2.158 Published: 01 February 1993 Article history Received: 05 February 1992 Accepted: 11 August 1992 Published: 01 February 1993
Electrophysiological Breakthroughs From the Left Atrium to the Pulmonary Veins
Authors: Michel Haïssaguerre, Dipen C. Shah, Pierre Jaïs, Mélèze Hocini, Teiichi Yamane, Isabel Deisenhofer, Michel Chauvin, Stéphane Garrigue, Jacques Clémenty
Journal: Circulation (2000)

Background —The extent of ostial ablation necessary to electrically disconnect the pulmonary vein (PV) myocardial extensions that initiate atrial fibrillation from the left atrium has not been determined. Methods and Results —Seventy patients underwent PV mapping with a circumferential 10-electrode catheter during sinus rhythm or left atrial pacing. After assessment of perimetric distribution and activation sequence of PV potentials, ostial ablation was performed at segments showing earliest activation, with the end point of PV disconnection. A total of 162 PVs (excluding right inferior PVs) were ablated. PV potentials were present at 60% to 88% of their perimeter, but PV muscle activation was always sequential from a segment with earliest activation (breakthrough). Radiofrequency (RF) application at this breakthrough eliminated all PV potentials in 34 PVs, whereas a secondary breakthrough required RF applications at separate segments in 77; in others, &gt;2 segments were ablated. A median of 5, 6, and 4 bipoles from the circular catheter were targeted in the right superior, left superior, and inferior PVs, respectively, to achieve PV disconnection. Early recurrence of arrhythmia was observed in 31 patients as a result of new venous or atrial foci or recovery of previously targeted PVs, most related to a single recovered breakthrough that was reablated with local RF application. Conclusions —Although PV muscle covers a large extent of the PV perimeter, there are specific breakthroughs from the left atrium that allow ostial PV disconnection by use of partial perimetric ablation.
Homocysteine-Lowering Therapy and Risk for Venous Thromboembolism
Authors: Joel G. Ray, Clive Kearon, Qilong Yi, Patrick Sheridan, Eva Lonn
Journal: Annals of Internal Medicine (2007)

Background: Elevated total homocysteine levels are associated with a higher risk for venous thromboembolism. Whether decreasing homocysteine levels with vitamin therapy reduces the risk for venous thromboembolism is not known. Objective: To determine whether decreasing homocysteine levels alters the risk for symptomatic venous thromboembolism. Design: Secondary analysis of data from the randomized, placebo-controlled Heart Outcomes Prevention Evaluation 2 (HOPE-2) trial. Setting: 145 clinical centers in 13 countries. Participants: 5522 persons 55 years of age or older with known cardiovascular disease or diabetes mellitus and at least 1 other risk factor for vascular disease. Intervention: A daily supplement of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 or matching placebo for 5 years. Measurement: Prospectively diagnosed and confirmed symptomatic deep venous thrombosis or pulmonary embolism. Results: The geometric mean homocysteine level decreased by 2.2 µmol/L in the vitamin therapy group and increased by 0.80 µmol/L in the placebo group. Venous thromboembolism occurred in 88 participants during a mean follow-up of 5 years. The incidence rate of venous thromboembolism was the same in the vitamin therapy group and the placebo group (0.35 per 100 person-years; hazard ratio, 1.01 [95% CI, 0.66 to 1.53]). Vitamin therapy did not reduce the risk for deep venous thrombosis (hazard ratio, 1.04 [CI, 0.63 to 1.72]), pulmonary embolism (hazard ratio, 1.14 [CI, 0.57 to 2.28]), or unprovoked venous thromboembolism (hazard ratio, 1.21 [CI, 0.66 to 2.23]). Limitations: The proportion of patients with a previous episode of venous thromboembolism at enrollment was not known, and venous thromboembolism events were not centrally adjudicated. Conclusion: Decreasing homocysteine levels with folic acid and vitamins B6 and B12 did not reduce the risk for symptomatic venous thromboembolism. *For a list of the HOPE-2 investigators, see the Appendix. ClinicalTrials.gov registration number: NCT00106886. Current Controlled Trials registration number: ISRCTN14017017.
Comments on Concurrent and Adjuvant Chemotherapy for Nasopharyngeal Carcinoma: A Mist of Mysterious Results
Authors: Skye H. Cheng, Andrew T. Huang
Journal: Journal of Clinical Oncology (2005)

matters further, the benefit of the drug will most likely diminish with time, as the likelihood of breast cancer relapse decreases in a given patient, and yet certain drugrelated side effects such as osteoporosis may be cumulative.QOL instruments that address issues related to energy level, mood, cognitive function, activities of daily living, libido, and so on are a major step forward in our ability to address these issues, and QOL was a formal end point of the MA17 trial.However, early study closure has now compromised our ability to determine the impact of long-term letrozole therapy on QOL and to balance this against the low likelihood that the drug will prevent breast cancer recurrence in a given patient.Although the authors are certainly entitled to express their personal opinions regarding the relationship between DFS and QOL, I would have been more interested in the personal opinions of the 5,187 women enrolled on MA17, obtained after long-term follow-up.They are the ones taking the drug, they are the ones experiencing side effects, and they are the ones at risk for recurrence.I do not think that we are smart enough to predict how DFS will impact QOL in the absence of guidance from our patients, as determined objectively in the context of a well-designed clinical trial.The investigators of both MA17 and GOG178 have conducted studies that will undoubtedly serve as important milestones in the clinical investigation of breast and ovarian cancers, respectively. 2,4 The fact that early study closure has generated controversy should not diminish the importance of their findings.However, there is room for more than one point of view, and I have no doubt that continued healthy debate of this issue will lead to improvements in the design and implementation of future clinical trials.
A <i>Leishmania major</i> Response Locus Identified by Interval-specific Congenic Mapping of a T Helper Type 2 Cell Bias-controlling Quantitative Trait Locus
Authors: Aurelie Baguet, Jennifer Epler, Kwun W. Wen, Mark Bix
Journal: The Journal of Experimental Medicine (2004)

The propensity of naive CD4 T cells to become T helper (Th) type 2 cells correlates with susceptibility to infection by the protozoal parasite Leishmania major. Using genetic linkage analysis, we earlier identified Dice1 as a Th2 cell bias-controlling quantitative trait locus on chromosome 16. Using interval-specific congenic mapping, we now resolve Dice1 into two independent genetic loci, Dice1.1 and Dice1.2, which control Il4 expression from naive Th cells and thereby indirectly control Th2 cell bias. Interestingly, only one of the two congenic intervals containing Dice1.1 and Dice1.2, respectively, also contained an L. major response locus, indicating that L. major responsiveness can be insensitive to determinants that influence Th2 cell bias by controlling naive T cell Il4 expression. These results lay the groundwork for identifying the Dice1.1 and Dice1.2 genes controlling naive T cell Il4 expression and L. major responses, and for testing whether these control other Th2 cell–dependent processes such as worm expulsion, allergic asthma, and dermatitis.
Myocardial Protective Effect of Extracellular Superoxide Dismutase Gene Modified Bone Marrow Mesenchymal Stromal Cells on Infarcted Mice Hearts
Authors: Qiao Pan, Xing Qin, Sai Ma, Haichang Wang, Kang Cheng, Xinxing Song, Haokao Gao, Qiang Wang, Rannie Tao, Yabin Wang, Xiujuan Li, Lize Xiong, Feng Cao
Journal: Theranostics (2014)

Aim: Extracellular superoxide dismutase (ecSOD) is a unique scavenger of superoxide anions and a promising target of gene therapy for ischemia/reperfusion injury (I/R).However, conventional gene therapies have limitation in effectiveness and efficiency.This study aimed to investigate the protective effects of ecSOD gene modified bone marrow mesenchymal stromal cells (BMSCs) on cardiac function improvement in mice infarcted heart.METHODS & RESULTS: BMSCs were isolated from Fluc + transgenic mice (Tg FVB[Fluc + ]) and transfected by adenovirus combined with human ecSOD gene.ELISA was performed to determine ecSOD protein level.Female syngeneic FVB mice were randomized into 5 groups: (1) Sham group (sham); (2) MI group (MI); (3) MI+BMSCs group (BMSC); (4) MI+BMSCs-vector group (BMSC-vector); (5) MI+ BMSCs-ecSOD group (BMSC-ecSOD).MI was accomplished by ligation of the left anterior descending artery.BMSCs (2x10 6 ) were injected into the border zone of infarction.In vivo bioluminescence imaging (BLI) was performed to monitor transplanted BMSCs viability.Echocardiography and histological staining revealed that BMSCs-ecSOD significantly reduced myocardial infarction size and improved cardiac function.Lucigenin chemiluminescence, DHE and TUNEL staining demonstrated that BMSCs-ecSOD delivery reduced ROS level and cell apoptosis both in vivo and in vitro.Western blot assay revealed that ecSOD supplementation increased FoxO3a phosphorylation in cardiomyocytes.Moreover, quantitative real-time PCR showed that pro-apoptotic factors (bim and bax) were decreased while the anti-apoptotic factor mir-21 expression was increased after ecSOD intervention.CONCLUSION: Intra-myocardial transplantation of adenovirus-ecSOD transfected BMSCs could exert potential cardiac protection against MI, which may be partly through reduction of oxidative stress and improvement of BMSCs survival.