tbuckley/cabot-search huggingface dataset:
Growth Inhibition of Human Multiple Myeloma Cells by an Oncolytic Adenovirus Carrying the CD40 Ligand Transgene
Authors: Margret S. Fernandes, Erica M. Gomes, Lindsay D. Butcher, Reuben Hernandez-Alcoceba, Dongkun Chang, Joe Kansopon, Joseph Newman, Marvin J. Stone, Alex W. Tong
Journal: Clinical Cancer Research (2009)

The growth-inhibitory activity of recombinant CD40 ligand (CD40L) is well documented in human multiple myeloma (MM). We examined MM-targeted delivery of CD40L by a conditional replicative oncolytic adenovirus, AdEHCD40L.The growth-regulatory activity of AdEHCD40L was determined in vitro and in vivo. Differential analysis with AdEHCD40L and parental virus (AdEHNull)-infected cultures allowed the identification of cellular and molecular pathways modulated by the CD40L transgene.Conditional expression of viral E1A and CD40L transgene was shown in human MM lines RPMI 8226 [interleukin (IL)-6 independent] and Kas-6/1 (IL-6 dependent) under hypoxic conditions commonly found in MM in situ. AdEHCD40L inhibited MM cell growth more effectively than AdEHNull. This enhanced growth-inhibitory activity was abrogated by cotreatment with a CD40L antibody. Chemoresistant MM lines (MR20 and LR5) were similarly susceptible to AdEHCD40L treatment. AdEHCD40L induced apoptosis and S-phase cell cycle blockade while uniquely up-regulating the previously described proapoptotic elements tumor necrosis factor-related apoptosis-inducing ligand, Fas, and IL-8. Intratumoral injections of AdEHCD40L reduced the growth of severe combined immunodeficient/hu RPMI 8226 xenografts by >50% compared with 28% reduction by AdEHNull. Adenoviral hexon and CD40L were detected in AdEHCD40L-treated tumors at day 35 after infection primarily in necrotic areas, suggesting viral replicative activity.These findings show that CD40L acts in concert with viral oncolysis to produce MM growth inhibition through activation of cellular apoptosis. The direct growth-inhibitory activity of AdEHCD40L, together with the well-known immune-potentiating features of CD40L, may be clinically applicable for the experimental treatment of MM or plasma cell leukemia.
Treatment and Survival Differences in Older Medicare Patients With Lung Cancer as Compared With Those Who Are Dually Eligible for Medicare and Medicaid
Authors: Cathy J. Bradley, Bassam Dahman, Charles W. Given
Journal: Journal of Clinical Oncology (2008)

This study compares non-small-cell lung cancer (NSCLC) treatments provided to older patients (age > or = 66 years) who are dually eligible for Medicare and Medicaid with treatments provided to similar patients who are insured by Medicare. We extend the analysis to include a comparison of survival rates between Medicare and dually eligible patients. Dual eligibility is associated with low socioeconomic status. However, Medicaid coverage in addition to Medicare removes many financial barriers to care.The sample included 2,626 older patients with local and regional stage NSCLC diagnosed between 1997 and 2000. Four outcomes were studied: the likelihood of receiving resection, chemotherapy, radiation therapy, and survival (perioperative and longer-term). Logistic regression was used to predict the likelihood of treatment, and stratified and multivariate analyses were used to evaluate differences in survival.Dually eligible patients were half as likely to undergo resection as Medicare patients (P < .001) and were more likely to receive radiation than Medicare patients. Stratified and multivariate analyses showed that surgically treated dually eligible patients had slightly inferior survival as compared with that of Medicare patients. Survival was equivalent among patients who did not undergo resection, regardless of insurance coverage.Older dually eligible patients with NSCLC had a lower likelihood of undergoing resection despite controls for socioeconomic factors and comorbidities. However, if such patients were surgically treated, survival improved substantially, but it remained inferior to the survival of Medicare patients. Additional research is needed to understand why resection rates were substantially lower among dually eligible patients.
Association Between Sentinel Lymph Node Excision With or Without Preoperative SPECT/CT and Metastatic Node Detection and Disease-Free Survival in Melanoma
Authors: Ingo Stoffels, Christian Boy, Thorsten Pöppel, Jasna Kuhn, Kerstin Klötgen, Joachim Dissemond, Dirk Schadendorf, Joachim Klode
Journal: JAMA (2012)

Malignant melanoma has become an increasing interdisciplinary public health challenge worldwide. Sentinel lymph node excision (SLNE) is considered the most sensitive and specific staging test for the detection of micrometastatic melanoma in regional lymph nodes.To compare metastatic node detection and disease-free survival using single-photon emission computed tomography/computed tomography (SPECT/CT)-aided SLNE vs standard SLNE in patients with melanoma.A prospective, computerized melanoma patient database at the University Hospital Essen, Skin Cancer Center, Essen, Germany, was used to identify a cohort of 464 patients eligible for SLNE between March 2003 and April 2011. A total of 403 patients with clinically negative lymph nodes, who underwent SLNE with or without preoperative SPECT/CT, qualified for subsequent analysis.Metastatic node detection and disease-free survival.Between March 2003 and October 2008, 254 patients underwent the standard SLNE technique. After November 2008, 149 patients underwent the SPECT/CT technique. Patients who did not receive SNLE in both intervals (46/300 [15.34%] for standard cohort vs 15/164 [9.15%] for SPECT/CT cohort; P = .06) did not differ in either age (difference, 69.20 years; 95% CI, 62.84-72.07 years; P = .38), tumor depth (difference, 2.90 mm; 95% CI, 2.87-4.54 mm; P = .54), or ulceration of the primary tumor (difference, -8.00%; 95% CI, -35.74% to 19.81%; P = .59). However, using SPECT/CT allowed SLNE in the head and neck area more frequently (2.0% for standard vs 23.5% for SPECT/CT; difference, 21.1%; 95% CI, 14.1%-28.2%; P < .001). In the SPECT/CT cohort, more sentinel lymph nodes per patient were detected than in the standard cohort (2.40 vs 1.87; 95% CI, 1.93-2.18; P < .001). The number of positive sentinel lymph nodes per patient was significantly higher in the SPECT/CT cohort than in the standard cohort (0.34 vs 0.21; 95% CI, 0.21-0.31; P = .04). The local relapse rate in the SPECT/CT cohort was lower than in the standard cohort (6.8% vs 23.8%, P = .03), which prolonged 4-year disease-free survival (93.9% vs 79.2%; P = .02).Among patients with clinically lymph node-negative melanoma, the use of SPECT/CT-aided SLNE compared with SLNE alone was associated with a higher frequency of metastatic involvement and a higher rate of disease-free survival.
2006 Association of American Physicians Presidential Address: The US's changing competitiveness in the biomedical sciences
Authors: Jerrold M. Olefsky
Journal: Journal of Clinical Investigation (2007)

Fellow AAP members, friends, and guests, it’s been a true pleasure serving the Association for the past 11 years, first as a Council member, then as an Officer, and this year as President. The entire 11 years has been a real honor and privilege, and also a thoroughly enjoyable experience. I’m glad to report that the organization is strong, financially stable, and moving forward, and I think this year’s meeting has been an excellent one, at least to this point. And this of course, brings me to the annual ritual of the Presidential Address.
Molecular characterization of rat glomerular epithelial cell complement receptors.
Authors: R J Quigg, A E Sneed
Journal: Journal of the American Society of Nephrology (1994)

Complement receptor type 1 (CR1) has previously been isolated from cultured rat glomerular epithelial cells (GEC) by C3b affinity chromatography. In addition, the presence of Crry in GEC and in rat glomeruli has been demonstrated. Crry appears to be the rodent analogue of human decay accelerating factor, which was previously described in human GEC and in human glomeruli. In this study, the molecular biology of these rat complement receptors is examined. A specific cDNA probe for rat CR1 was generated by reverse transcription of GEC mRNA, followed by polymerase chain reaction (PCR). The oligonucleotide primers were chosen from conserved regions spanning 271 bases in human and mouse CR1. A 271-base-pair PCR product was generated from rat GEC cDNA, the nucleotide sequence of which was 70.1% and 77.2% identical to those of the respective mouse and human sequences. This PCR product, designated rCR1-p, was then used to probe for CR1 mRNA. By northern blot analysis, rCR1-p hybridized to 4.5-kilobase (kb) mRNA from both cultured GEC and rat glomeruli and also weakly hybridized to 4.5-kb CR1 mRNA from mouse spleen. In additional northern blots, a nucleotide probe for mouse Crry hybridized to mRNA of 2.1 to 2.4 kb from rat GEC, slightly larger than the 1.9- to 2.1-kb mouse Crry mRNA. Therefore, mRNA for CR1 and Crry are present in cultured rat GEC and in rat glomeruli in vivo. To further investigate the composition of rat CR1 mRNA, northern hybridizations were performed with nucleotide probes for mouse and human CR1.(ABSTRACT TRUNCATED AT 250 WORDS)
Hepatic stellate cells: role in microcirculation and pathophysiology of portal hypertension
Authors: H Reynaert
Journal: Gut (2002)

Accumulating evidence suggests that stellate cells are involved in the regulation of the liver microcirculation and portal hypertension. Activated hepatic stellate cells have the necessary machinery to contract or relax in response to a number of vasoactive substances. Because stellate cells play a role in both fibrosis and portal hypertension, they are currently regarded as therapeutic targets to prevent and treat the complications of chronic liver disease.
COL4A5 deletions in three patients with Alport syndrome and posttransplant antiglomerular basement membrane nephritis.
Authors: J Ding, J Zhou, K Tryggvason, C E Kashtan
Journal: Journal of the American Society of Nephrology (1994)

Mutations in the COL4A5 gene encoding the alpha 5 chain of Type IV collagen were identified in three men with Alport syndrome and posttransplant antiglomerular basement membrane (GBM) nephritis by the use of Southern analysis, polymerase chain reaction amplification of genomic DNA, and reverse transcription and amplification of lymphocyte RNA. Two related patients (M.C. and J.M.) exhibited deletion of COL4A5 beginning in the 5'-most portion of the gene and extending through the 3' untranslated region, whereas the third patient (J.E.) had an intragenic deletion encompassing Exons 4 through 47. Combined with previously reported data, these findings suggest that the incidence of deletions of COL4A5, as opposed to other COL4A5 mutations, is much higher in Alport patients who develop posttransplant anti-GBM nephritis than in the general Alport population. Immunofluorescence studies of kidney from Patient J.E. showed no reactivity of GBM with monoclonal antibodies directed against the alpha 3, alpha 4, and alpha 5 chains of Type IV collagen. This finding confirms that the mutation affecting the alpha 5(IV) chain can interfere with the incorporation of alpha 3(IV) and alpha 4(IV) into the GBM.
Depression of peripheral chemosensitivity by a dopaminergic mechanism in patients with obstructive sleep apnoea syndrome
Authors: S Osanai, Y Akiba, S Fujiuchi, H Nakano, H Matsumoto, Y Ohsaki, K Kikuchi
Journal: European Respiratory Journal (1999)

In the present study, respiratory drives to chemical stimuli and peripheral chemosensitivity were evaluated in patients with obstructive sleep apnoea (OSAS). The effects of oral administration of domperidone, a selective dopamine D2-receptor antagonist, were also examined, to study the respiratory effects of endogenous dopamine on peripheral chemoreceptors. Sixteen patients with OSAS and nine normal control subjects were studied. Respiratory responses to hypercapnia and hypoxia were measured using the rebreathing method and isocapnic progressive hypoxia method, respectively. The hypoxic withdrawal test, which measures the decrease in ventilation caused by two breaths of 100% O2 under mild hypercapnic hypoxic conditions (end-tidal oxygen and carbon dioxide tensions approximately 8.0 kPa and 5.3-6.7 kPa, respectively), was used to evaluate peripheral chemosensitivity. In the patients with OSAS, ventilatory responses to hypercapnia and hypoxia were significantly decreased compared with those of control subjects. Hypoxic withdrawal tests showed that peripheral chemosensitivity was significantly lower in patients with OSAS than in normal subjects. Hypercapnic ventilatory response and peripheral chemosensitivity were enhanced by administration of domperidone in the patients with OSAS, although no changes in either of these were observed in the control subjects. The hypoxic ventilatory response and peripheral chemosensitivity in the patients with OSAS were each significantly correlated with severity of hypoxia during sleep. These findings suggest that peripheral chemosensitivity in patients with obstructive sleep apnoea syndrome may be decreased as a result of abnormality in dopaminergic mechanisms and that the reduced chemosensitivity observed in patients with obstructive sleep apnoea syndrome may affect the severity of hypoxia during sleep.
Guidelines in general practice
Authors: R. Hanka, I. Hill-Smith, M. G McCullagh, D. S Meldrum
Journal: BMJ (1999)

Editor—Hibble et al have quantified the extent to which general practitioners are being buried under an avalanche of paper on their desks.1 This problem does not occur only in general practice; neither is it specific to the NHS. As Muir Gray points out, the present position is intolerable and counterproductive and is getting worse, affecting not only professionals but also patients and carers.2

With the prevailing enthusiasm to convert all paper based information into electronic form and make it accessible over the internet, we are creating a situation in which we are gradually being overwhelmed by electronic communications. Three quarters of all business communications in Britain are now estimated to use electronic media3; even though this has not yet happened in the NHS, the long awaited expansion of NHSNet could bring about this degree of penetration in the not too distant future. Given the widely different designs and organisations of electronic documents placed on the multitude of websites, the internet contains mostly unorganised data, frequently of doubtful origin, instead of information. This effectively exacerbates the information overload rather than alleviates it.

Searching the world wide web to see whether certain information exists (and potentially being faced with thousands of hits) and accessing information that one knows is there require very different strategies. Accessing information that one knows is there requires clearly defined organisation of knowledge sources and different search strategies to be used by the computer system than are used by current web browsers. Over 50 general practices are now taking part in a pilot study evaluating WAX ActiveLibrary (a software system developed by the University of Cambridge; www.medinfo.cvam.ac.uk/WAX). WAX has been designed to eliminate overload on a general practitioner’s desk and to ensure that relevant information can be accessed at the right time (usually within 15 seconds) and in the right form, without creating another, this time virtual, mountain.

The National Electronic Library for Health, proposed in the new information strategy for the NHS, will have an important role in providing access to national reference material. It will also ensure that this material represents more than just a collection of paper material converted into electronic form.
Immunologically Active Autoantigens: The Role of Toll-Like Receptors in the Development of Chronic Inflammatory Disease
Authors: Ann Marshak-Rothstein, Ian R. Rifkin
Journal: Annual Review of Immunology (2007)

Pattern recognition receptors (PRRs), expressed on cells of both the innate and adaptive immune systems, serve as sentinels, waiting to alert the host to the first signs of microbial infection and to activate the initial line of immune defense. Research has increasingly demonstrated that many of the same PRRs also recognize self-epitopes that either are released from dying or damaged cells or are present at the surface of apoptotic cells or apoptotic bodies. In this context, PRRs play a critical role in tissue repair and the clearance of cellular debris. However, failure to appropriately regulate self-responses triggered by certain PRRs can have serious pathological consequences. The Toll-like receptor (TLR) gene family represents a case in point. TLR7, 8, and 9 were originally identified as receptors specific for bacterial and viral RNA and DNA, but more recent in vitro and in vivo studies have now linked these receptors to the detection of host RNA, DNA, and RNA- or DNA-associated proteins. In this context, they likely play a key role in the development of systemic autoimmune diseases.
PROFESSOR CHARLES MACFIE CAMPBELL
Authors: D. K. HENDERSON
Journal: American Journal of Psychiatry (1943)

and intimate friends he was all this and more-strong in love, patient in understanding, staunch in loyalty. His ability to help others, so essential to his professional and to his personal relations, was due to his moral quality as well as to his learning and skill. The Golden Rule was instinctive with him. He could always place himself at the center of another’s life and make allowances even for what he condemned. He had both integrity and humanity. In his own conduct he was exceedingly scrupulous, in his judgment of men and events he adhered firmly to principle, but at the same time he gave his fellows the benefit of the doubt and ascribed their conduct, sometimes humorously but always sincerely, to some motive with which it was possible to sympathize. HARRY C. SOLOMON.
Premenstrual Dysphoric Disorder: Evidence for a New Category for DSM-5
Authors: C. Neill Epperson, Meir Steiner, S. Ann Hartlage, Elias Eriksson, Peter J. Schmidt, Ian Jones, Kimberly A. Yonkers
Journal: American Journal of Psychiatry (2012)

Premenstrual dysphoric disorder, which affects 2%–5% of premenopausal women, was included in Appendix B of DSMIV, "Criterion Sets and Axes Provided for Further Study." Since then, aided by the inclusion of specific and rigorous criteria in DSM-IV, there has been an explosion of research on the epidemiology, phenomenology, pathogenesis, and treatment of the disorder. In 2009, the Mood Disorders Work Group for DSM-5 convened a group of experts to examine the literature on premenstrual dysphoric disorder and provide recommendations regarding the appropriate criteria and placement for the disorder in DSM-5. Based on thorough review and lengthy discussion, the work group proposed that the information on the diagnosis, treatment, and validation of the disorder has matured sufficiently for it to qualify as a full category in DSM-5. A move to the position of category, rather than a criterion set in need of further study, will provide greater legitimacy for the disorder and encourage the growth of evidence-based research, ultimately leading to new treatments.
Left ventricular assist device support reverses altered cardiac expression and function of natriuretic peptides and receptors in end-stage heart failure
Authors: M KUHN, M VOS, D MITKO, J STYPMANN, C SCHMID, N KAWAGUCHI, F GRABELLUS, H BABA
Journal: Cardiovascular Research (2004)

Objective: Atrial (ANP) and B-type natriuretics peptides (BNP) via their guanylyl cyclase-A (GC-A) receptor not only regulate arterial blood pressure and volume but also exert local antihypertrophic, antifibrotic and lusitropic effects in the heart. To elucidate whether cardiac hypertrophy/insufficiency and reversal is associated with changes in the local responsiveness to NPs, we compared the mRNA expression of ANP, BNP and receptors and the responsiveness of GC-A to ANP in left ventricular tissue obtained from 10 patients with congestive heart failure (CHF) before and after hemodynamic unloading by left ventricular assist device (LVAD) support.
Role of substance P in cough during bronchoconstriction in awake guinea pigs.
Authors: K Sekizawa, T Ebihara, H Sasaki
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

To examine the role of substance P (SP) in cough during bronchoconstriction, we studied the effects of an aerosolized beta-adrenoceptor agonist, procaterol, and a specific inhibitor of SP (NK1) receptor, FK 888, on bronchoconstriction and cough induced by aerosols of histamine and acetylcholine (ACh) in unsensitized guinea pigs and by those of ovalbumin (OA) antigen in guinea pigs sensitized to OA. Intensity of bronchoconstriction was evaluated by the time to onset of bronchoconstriction after the inhalation of bronchoconstrictors. Both procaterol (10(-6) to 10(-4) M, 2 min) and FK 888 (10(-7) to 10(-5) M, 2 min) dose dependently decreased the number of coughs and increased the time to onset of bronchoconstriction induced by histamine (10(-2) M, 15 s). Procaterol attenuated histamine-induced cough only at the concentrations effective to inhibit bronchoconstriction. However, FK 888 at concentrations of 10(-7) and 10(-6) M decreased the number of coughs without effect on bronchoconstriction. Likewise, the inhibitory effects of procaterol (10(-5) M, 2 min) on the number of coughs were parallel to those on bronchoconstriction induced by ACh (10(-1) M, 15 s) and OA antigen (0.1% concentration, 30 s), but FK 888 (10(-6) M, 2 min) decreased the number of coughs without effect on bronchoconstriction induced by them. The number of coughs induced by histamine (10(-2) M, 15 s) was inhibited by systemic capsaicin treatment and enhanced by phosphoramidon (10(-5) M, 5 min) without effect on bronchoconstriction. (ABSTRACT TRUNCATED AT 250 WORDS)
Effect of prostaglandin-E2 on phagocytosis of carbon black and particulate matter by rat alveolar macrophages
Authors: Andrew Balme, Rossa Brugha, Naseem Mushtaq, Jonathan Grigg
Journal: European Respiratory Journal (2013)

Background: Alveolar Macrophages (AMs) are responsible for clearing inhaled particles. Since prostaglandin E2 (PGE2) suppresses AMs phagocytosis of opsonised bacteria (Aronoff et al. 2004), we sought to test the hypothesis that that PGE2 suppresses phagocytosis of inhaled particulate matter air pollution in vitro.

Methods: Rat AM were pre-incubated in PGE2 (10-6M) then incubated with 10 μg of either ultrafine carbon black (ufCB) or urban Particulate Matter less than 10 μm in aerodynamic diameter (PM10) for 1 h. Phagocytosis of PM was assessed using image analysis of 50 AM per experiment. Results were compared using the Wilcoxon signed rank test.

Results: PGE2 attenuated AM phagocytosis of both ufCB to 75% of medium control (p <0.05, Figure 1A), and urban PM10 to 76.9% of medium control (p <0.05, figure 1B).

![Figure][1] 



Conclusion: PGE2 inhibits AM phagocytosis of ufCB and PM10. This mechanism may contribute to the adverse health effects of poor air quality in conditions associated with increased airway PGE2, such as asthma and COPD.

 [1]: pending:yes
Chronologic distribution of stroke after minimally invasive versus conventional coronary artery bypass
Authors: Garrett K. Peel, Sotiris C. Stamou, Mercedes K.C. Dullum, Peter C. Hill, Kathleen A. Jablonski, Ammar S. Bafi, Steven W. Boyce, Kathleen R. Petro, Paul J. Corso
Journal: Journal of the American College of Cardiology (2004)