tbuckley/cabot-search huggingface dataset:
Neutrophil mediated damage to isolated myocytes after anoxia and reoxygenation
Authors: P. R. Hansen, G. Stawski
Journal: Cardiovascular Research (1994)

Objective: The aim was to assess the role of neutrophils in anoxia-reoxygenation induced, neutrophil mediated damage to cardiac myocytes. Methods: Neonatal rat cardiac myocytes in primary monolayer cultures were exposed to a 2 h period of anoxia, and subsequently reoxygenated for 3 h. Neutrophils were added at the time of reoxygenation, and myocyte injury was determined by release of lactate dehydrogenase (LDH). Results: Neutrophils produced a dose dependent increase in myocyte LDH release. This effect was not enhanced by coincubation with a neutrophil activator (formyl-Met-Leu-Phe), or interleukine lα (IL-lα), although IL-lα increased anoxic myocyte damage. Exposure to supematants from anoxic, or anoxic-reoxygenated, myocytes increased LDH release from normoxic myocytes, and conditioning of these supematants by neutrophils further increased their cytotoxic potential. The anoxia-reoxygenation induced, neutrophil mediated LDH release was attenuated by some oxygen radical scavengers (superoxide dismutase, histidine, and desferrioxamine), but not others (catalase). Marked decrease in LDH release was also observed after addition of L-arginine, the substrate for synthesis of nitric oxide, along with the neutrophils at the time of reoxygenation. In addition, neutrophil mediated myocyte injury was attenuated by protease inhibitors (Eglin C and α2 macroglobulin), an anti-CD 18 monoclonal antibody, and the methylxanthine derivative pentoxifylline, respectively. Conclusions: The results indicate that neutrophils increase myocyte reoxygenation damage, and that reoxygenated cardiac myocytes release potent neutrophil stimulants and cytotoxic mediators. The anoxia-reoxygenation induced, neutrophil mediated myocyte damage is dependent on oxygen free radicals, proteases, and cellular adhesion, and stimulation of endogenous NO production may be protective in this model. Cardiovascular Research 1994;28:565-569
Vanilloid receptor-1 containing primary sensory neurones mediate dextran sulphate sodium induced colitis in rats
Authors: N Kihara
Journal: Gut (2003)

<b>Background and aims:</b> The role of sensory neurones in colitis was studied by chemical denervation of primary sensory neurones as well as antagonism of the vanilloid receptor-1 (VR-1) in rats prior to administration of dextran sulphate sodium (DSS) to induce colitis. <b>Methods:</b> Neonatal rats were chemically denervated by subcutaneous administration of capsaicin; controls received capsaicin vehicle only. When animals reached maturity, colitis was induced by administration of 5% DSS in drinking water for seven days. Additionally, normal adult rats were treated with a VR-1 antagonist capsazepine (CPZ) or vehicle twice daily via an enema from day 0 to day 6 of the DSS regimen. Control rats were treated with an enema infusion of vehicle and 5% DSS, or without either an enema infusion or DSS in drinking water. For both groups of rats, severity of inflammation was quantitated by disease activity index (DAI), myeloperoxidase (MPO) activity, and histological examination. <b>Results:</b> DSS induced active colitis in all control rats with resultant epithelial ulceration, crypt shortening, and neutrophil infiltration. Both neonatal capsaicinised rats and normal adult rats treated with CPZ enemas exhibited significantly lower levels of DAI, MPO, and histological damage compared with vehicle treated rats (p&lt; 0.05). <b>Conclusions:</b> Neonatal capsaicinisation and local administration of CPZ prevents intestinal inflammation in a well established model of colitis indicating that primary sensory neurones possessing VR-1 receptors are required in the propagation of colonic inflammation.
Fluoroquinolone use delays tuberculosis treatment despite immediate mycobacteriology study
Authors: Jann-Yuan Wang, Chih-Hsin Lee, Ming-Chi Yu, Ming-Chia Lee, Li-Na Lee, Jann-Tay Wang
Journal: European Respiratory Journal (2015)

Despite its excellent activity against Mycobacterium tuberculosis [1], empirical fluoroquinolone (FQ) therapy has been associated with delayed initiation of appropriate treatment [2–4] and acquired resistance [5, 6] in tuberculosis (TB) patients presenting as community-acquired pneumonia (CAP). A previous study conducted in intensive care unit revealed immediate mycobacteriology study may possibly prevent the delay in anti-TB treatment [7]. However, this hypothesis has not been confirmed. Empirical fluoroquinolone use for ≥7 days delays antituberculosis treatment despite immediate mycobacteriology study <http://ow.ly/L8fIm> The authors thank the National Health Research Institute of Taiwan for providing the NHIRD. Details of the computer code for statistical analyses are available from the corresponding author.
Polymorphisms in the <i>CASPASE</i> Genes and Survival in Patients With Early-Stage Non–Small-Cell Lung Cancer
Authors: Seung Soo Yoo, Jin Eun Choi, Won-Kee Lee, Yi-Young Choi, Sin Kam, Min Jung Kim, Hyo-Sung Jeon, Eung-Bae Lee, Dong Sun Kim, Myung-Hoon Lee, In-San Kim, Sanghoon Jheon, Jae Yong Park
Journal: Journal of Clinical Oncology (2009)

Purpose This study was conducted to determine the impact of potentially functional polymorphisms in the CASPASE (CASP) genes on the survival of early-stage non–small-cell lung cancer (NSCLC) patients. Patients and Methods Four hundred eleven consecutive patients with surgically resected NSCLC were enrolled. Nine potentially functional polymorphisms in the CASP3, CASP7, CASP8, CASP9, and CASP10 genes were investigated. The genotype and haplotype associations with overall survival (OS) and disease-free survival (DFS) were analyzed. Results Patients with the rs2227310 GG genotype had a significantly decreased OS and DFS compared with patients with the CC + CG genotype (adjusted hazard ratio [aHR] for OS, 1.67; 95% CI, 1.19 to 2.35; P = .003; aHR for DFS, 1.62; 95% CI, 1.19 to 2.22; P = .002). The rs4645981C&gt;T genotype also had a significant effect on OS and DFS (under a recessive model; aHR for OS, 2.00; 95% CI, 1.04 to 3.85; P = .04; aHR for DFS, 2.76; 95% CI, 1.58 to 4.80; P = .0003). When the rs2227310 and rs4645981 genotypes were combined, patients with one or two bad genotypes had worse OS and DFS compared with those who had zero bad genotypes (aHR for OS, 1.75; 95% CI, 1.25 to 2.45; P = .001; aHR for DFS, 1.66; 95% CI, 1.23 to 2.26; P = .001). Conclusion The CASP7 rs2227310 and CASP9 rs4645981 polymorphisms may affect survival in early-stage NSCLC. The analysis of these polymorphisms can help identify patients at high risk for a poor disease outcome.
Comparison of Anticancer Drug Coverage Decisions in the United States and United Kingdom: Does the Evidence Support the Rhetoric?
Authors: Anne Mason, Michael Drummond, Scott Ramsey, Jonathan Campbell, Dennis Raisch
Journal: Journal of Clinical Oncology (2010)

In contrast to the United States, several European countries have health technology assessment programs for drugs, many of which assess cost effectiveness. Coverage decisions that consider cost effectiveness may lead to restrictions in access.For a purposive sample of five decision-making bodies, we analyzed US and United Kingdom coverage decisions on all anticancer drugs approved by the US Food and Drug Administration (FDA) from 2004 to 2008. Data sources for the timing and outcome of licensing and coverage decisions included published and unpublished documentation, Web sites, and personal communication.The FDA approved 59 anticancer drugs over the study period, of which 46 were also approved by the European Medicines Agency. In the United States, 100% of drugs were covered, mostly without restriction. However, the United Kingdom bodies made positive coverage decisions for less than half of licensed drugs (National Institute for Health and Clinical Excellence [NICE]: 39%; Scottish Medicines Consortium [SMC]: 43%). Whereas the Centers for Medicare and Medicaid Services (CMS) and the Department of Veterans Affairs (VA) covered all 59 drugs from the FDA license date, delays were evident for some Regence Group decisions that were informed by cost effectiveness (median, 0 days; semi-interquartile range [SIQR], 122 days; n = 22). Relative to the European Medicines Agency license date, median time to coverage was 783 days (SIQR, 170 days) for NICE and 231 days (SIQR, 129 days) for the SMC.Anticancer drug coverage decisions that consider cost effectiveness are associated with greater restrictions and slower time to coverage. However, this approach may represent an explicit alternative to rationing achieved through the use of patient copayments.
A solitary gastric metastasis from pulmonary adenocarcinoma: a case report
Authors: M. H. Lee, S. R. Kim, J. S. Soh, M. J. Chung, Y. C. Lee
Journal: Thorax (2010)

A 77-year-old male complained of persistent cough and sputum for 2 months. Chest radiography showed a solitary mass with solid opacity in the right upper lung (RUL) (figure 1A, arrow). A CT scan of the chest demonstrated an irregular mass measuring 3.8×2.8 cm in the RUL (figure 1B, arrow). Histologically, the tumour was interpreted as a poorly differentiated adenocarcinoma (figure 1C–E).



Figure 1 
(A) Chest x-ray shows a round mass in the right upper lobe measuring ∼4 cm. (B) CT scan of the chest demonstrates a solitary round mass in the right upper lobe measuring 3.8×2.8 cm with a speculated margin, pleural tagging and focal enhancement. (C) H&E staining of the lung mass tissues. This shows a papillary pattern and …
THE EFFECT OF NICOTINIC ACID IN STUPOR, LETHARGY AND VARIOUS OTHER PSYCHIATRIC DISORDERS
Authors: V. P. SYDENSTRICKER, H. M. CLECKLEY
Journal: American Journal of Psychiatry (1941)

Thirty-eight patients in stuporous states or in active psychoses without evident cause showed prompt and often very impressive improvement after treatment with nicotinic acid. The usual criteria for the clinical diagnosis of pellagra or of other deficiency syndromes were absent. This experience leads us to believe that many patients whose psychiatric status suggests the diagnosis of toxic psychosis or exhaustion delirium may be relieved of their symptoms by the administration of nicotinic acid. It is believed that in such cases and in cases who show unexplained clouding of consciousness a therapeutic trial of nicotinic acid is the only means available by which one can determine whether or not the psychosis is due to avitaminosis. In some exceptional cases, even when clinical evidence of pellagra is absent, extremely large amounts of nicotinic acid are necessary to obtain satisfactory results.
Expression of mRNA and immunoreactivity for the granulocyte/macrophage colony-stimulating factor in activated human eosinophils.
Authors: R Moqbel, Q Hamid, S Ying, J Barkans, A Hartnell, A Tsicopoulos, A J Wardlaw, A B Kay
Journal: The Journal of Experimental Medicine (1991)

Using in situ hybridization, we have shown that activated human peripheral blood eosinophils express mRNA for granulocyte/macrophage colony-stimulating factor (GM-CSF). Between 15 and 27% of eosinophils gave positive hybridization signals for GM-CSF mRNA after stimulation with the calcium ionophore A23187 or interferon gamma, and 4 and 6% after incubation with interleukin 3 (IL-3) or IL-5. Activated eosinophils also gave specific immunoreactivity with an anti-GM-CSF polyclonal antibody, suggesting translation of the mRNA. These data indicate that eosinophils may be an important source of GM-CSF at sites of allergic inflammation. Furthermore, the identification of GM-CSF production by human eosinophils suggests that the pro-inflammatory potential of this cell type may be substantially greater than hitherto recognized.
Chimeric antigen receptor (CAR)-engineered T cells redirected against hepatitis C virus (HCV) E2 glycoprotein
Authors: Giuseppe A Sautto, Karin Wisskirchen, Nicola Clementi, Matteo Castelli, Roberta A Diotti, Julia Graf, Massimo Clementi, Roberto Burioni, Ulrike Protzer, Nicasio Mancini
Journal: Gut (2015)

<h3>Objective</h3> The recent availability of novel antiviral drugs has raised new hope for a more effective treatment of hepatitis C virus (HCV) infection and its severe sequelae. However, in the case of non-responding or relapsing patients, alternative strategies are needed. To this end we have used chimeric antigen receptors (CARs), a very promising approach recently used in several clinical trials to redirect primary human T cells against different tumours. In particular, we designed the first CARs against HCV targeting the HCV/E2 glycoprotein (HCV/E2). <h3>Design</h3> Anti-HCV/E2 CARs were composed of single-chain variable fragments (scFvs) obtained from a broadly cross-reactive and cross-neutralising human monoclonal antibody (mAb), e137, fused to the intracellular signalling motif of the costimulatory CD28 molecule and the CD3ζ domain. Activity of CAR-grafted T cells was evaluated in vitro against HCV/E2-transfected cells as well as hepatocytes infected with cell culture-derived HCV (HCVcc). <h3>Results</h3> In this proof-of-concept study, retrovirus-transduced human T cells expressing anti-HCV/E2 CARs were endowed with specific antigen recognition accompanied by degranulation and secretion of proinflammatory and antiviral cytokines, such as interferon γ, interleukin 2 and tumour necrosis factor α. Moreover, CAR-grafted T cells were capable of lysing target cells of both hepatic and non-hepatic origin expressing on their surface the HCV/E2 glycoproteins of the most clinically relevant genotypes, including 1a, 1b, 2a, 3a, 4 and 5. Finally, and more importantly, they were capable of lysing HCVcc-infected hepatocytes. <h3>Conclusions</h3> Clearance of HCV-infected cells is a major therapeutic goal in chronic HCV infection, and adoptive transfer of anti-HCV/E2 CARs-grafted T cells represents a promising new therapeutic tool.
New technique improves safety of islet cell transplantation
Authors: Janice Hopkins Tanne
Journal: BMJ (2005)

Researchers at the University of Minnesota in Minneapolis have reported a new technique for closing the access site after islet cell transplantation into the portal vein of the liver. The new technique is less likely than older techniques to have complications, they told the meeting of the Radiological Society of North America in Chicago on Tuesday where they presented their results.

Dr Saravanan Krishnamoorthy, a resident in radiology at the University of Minnesota Medical Center, said that between January 2002 and March 2005 13 patients with poorly controlled type 1 diabetes received 15 islet cell transplantations through the skin into the portal vein of the liver under local anaesthesia. (Two patients …
Phase III Trial of Cisplatin Plus Gemcitabine With Either Placebo or Bevacizumab As First-Line Therapy for Nonsquamous Non–Small-Cell Lung Cancer: AVAiL
Authors: Martin Reck, Joachim von Pawel, Petr Zatloukal, Rodryg Ramlau, Vera Gorbounova, Vera Hirsh, Natasha Leighl, Jörg Mezger, Venice Archer, Nicola Moore, Christian Manegold
Journal: Journal of Clinical Oncology (2009)

Purpose Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, improves survival when combined with carboplatin/paclitaxel for advanced nonsquamous non–small-cell lung cancer (NSCLC). This randomized phase III trial investigated the efficacy and safety of cisplatin/gemcitabine (CG) plus bevacizumab in this setting. Patients and Methods Patients were randomly assigned to receive cisplatin 80 mg/m 2 and gemcitabine 1,250 mg/m 2 for up to six cycles plus low-dose bevacizumab (7.5 mg/kg), high-dose bevacizumab (15 mg/kg), or placebo every 3 weeks until disease progression. The trial was not powered to compare the two doses directly. The primary end point was amended from overall survival (OS) to progression-free survival (PFS). Between February 2005 and August 2006, 1,043 patients were randomly assigned (placebo, n = 347; low dose, n = 345; high dose, n = 351). Results PFS was significantly prolonged; the hazard ratios for PFS were 0.75 (median PFS, 6.7 v 6.1 months for placebo; P = .003) in the low-dose group and 0.82 (median PFS, 6.5 v 6.1 months for placebo; P = .03) in the high-dose group compared with placebo. Objective response rates were 20.1%, 34.1%, and 30.4% for placebo, low-dose bevacizumab, and high-dose bevacizumab plus CG, respectively. Duration of follow-up was not sufficient for OS analysis. Incidence of grade 3 or greater adverse events was similar across arms. Grade ≥ 3 pulmonary hemorrhage rates were ≤ 1.5% for all arms despite 9% of patients receiving therapeutic anticoagulation. Conclusion Combining bevacizumab (7.5 or 15 mg/kg) with CG significantly improved PFS and objective response rate. Bevacizumab plus platinum-based chemotherapy offers clinical benefit for bevacizumab-eligible patients with advanced NSCLC.
Common Variant in <i>AMPD1</i> Gene Predicts Improved Clinical Outcome in Patients With Heart Failure
Authors: Evan Loh, Timothy R. Rebbeck, Paul D. Mahoney, David DeNofrio, Judith L. Swain, Edward W. Holmes
Journal: Circulation (1999)

Background —This study was undertaken to identify gene(s) that may be associated with improved clinical outcome in patients with congestive heart failure (CHF). The adenosine monophosphate deaminase locus (AMPD1) was selected for study. We hypothesized that inheritance of the mutant AMPD1 allele is associated with increased probability of survival without cardiac transplantation in patients with CHF. Methods and Results —AMPD1 genotype was determined in 132 patients with advanced CHF and 91 control reference subjects by use of a polymerase chain reaction–based, allele-specific oligonucleotide detection assay. In patients with CHF, those heterozygous (n=20) or homozygous (n=1) for the mutant AMPD1 allele (AMPD1 +/− or −/−, respectively) experienced a significantly longer duration of heart failure symptoms before referral for transplantation evaluation than CHF patients homozygous for the wild-type allele (AMPD1 +/+; n=111; 7.6±6.5 versus 3.2±3.6 years; P &lt;0.001). The OR of surviving without cardiac transplantation ≥5 years after initial hospitalization for CHF symptoms was 8.6 times greater (95% CI: 3.05, 23.87) in those patients carrying ≥1 mutant AMPD1 allele than in those carrying 2 wild-type AMPD1 +/+ alleles. Conclusions —After the onset of CHF symptoms, the mutant AMPD1 allele is associated with prolonged probability of survival without cardiac transplantation. The mechanism by which the presence of the mutant AMPD1 allele may modify the clinical phenotype of heart failure remains to be determined.
Postinflammatory bronchiectatic cavity observed by fibreoptic bronchoscopy
Authors: S Imamura, S Negoro, M Fukuoka, M Kikui
Journal: European Respiratory Journal (1994)

A 55 year old female, complaining of bloody sputum and fever, was referred to our institution. The chest roentgenogram on admission revealed a large thin-walled cavitary shadow in the right upper lobe. We could clearly observe the inner surface of the postinflammatory bronchiectatic cavity in the right B3 bronchus by fibreoptic bronchoscopy. This is the first case in which interesting bronchoscopic findings of a bronchiectatic cavity could be directly observed.
Clarifying Conflict of Interest
Authors: Howard Brody
Journal: The American Journal of Bioethics (2011)

As the debate over how to manage or discourage physicians' financial conflicts of interest with the drug and medical device industries has become more heated, critics have questioned or dismissed the concept of "conflict of interest" itself. A satisfactory definition relates conflict of interest to concerns about maintaining social trust and distinguishes between breaches of ethical duty and temptations to breach duty. Numerous objections to such a definition have been offered, none of which prevails on further analysis. Those concerned about conflicts of interest have contributed to misunderstandings, however, by failing to demonstrate when social arrangements leading to temptations to breach duties are in themselves morally blameworthy. Clarifying "conflict of interest" is important if we are eventually going to develop productive modes of engagement between medicine and for-profit industry that avoid the serious ethical pitfalls now in evidence.
Correlation between nasal potential difference measurements, genotype and clinical condition in patients with cystic fibrosis
Authors: LP Ho, JM Samways, DJ Porteous, None Dorin, A Carothers, AP Greening, JA Innes
Journal: European Respiratory Journal (1997)

In cystic fibrosis (CF), the clinical condition of patients correlates poorly with genotype. One possible explanation is that clinical status is influenced by net preserved chloride secretion rather than the CF mutation. We tested the relationships between residual chloride secretion, as measured by nasal potential difference (PD) and the type of mutation (genotypes expressing apical cystic fibrosis transmembrane conductance regulator (CFTR) protein versus those that do not) and clinical status. Twenty two CF patients (mean age 25.7 yrs, 11 females and 11 males, mean forced expiratory volume in one second (FEV1) 53.1% of predicted) with defined genotypes were recruited. Nasal PD was measured using a standard protocol involving the perfusion of the nasal epithelium with a sodium channel blocker (amiloride), followed by a solution of low chloride and finally with isoprenaline. Patients with apical CFTR protein showed higher residual chloride secretion than those without (amiloride to isoprenaline value of 4.59 and 0.56 mV, respectively, p = 0.01). There was no correlation between mutation type and clinical condition. When these patients were recategorized as "high" (> 10 mV amiloride to isoprenaline response) or "low" (10 mV or less) chloride secretors, we found that the former group had a significantly higher FEV1 (67.7 versus 48.3% pred) and a better pulmonary radiological score (4.14 versus 7.07, by Northern scoring system). These results suggest that some cystic fibrosis patients, regardless of genotype, have an ability to secrete chloride when stimulated with chloride secretatagogues, and this is correlated with a better lung function. These results also have implications for the use of potential difference measurements in novel cystic fibrosis transmembrane conductance regulator replacement trials.
A complex of glycoproteins is associated with VpreB/lambda 5 surrogate light chain on the surface of mu heavy chain-negative early precursor B cell lines.
Authors: H Karasuyama, A Rolink, F Melchers
Journal: The Journal of Experimental Medicine (1993)

Monoclonal antibodies (mAbs) have been made specific for the pre-B cell-specific proteins VpreB and lambda 5 which together form the surrogate light (L) chain. mAbs specific for VpreB protein identified the 16-kD molecule associated on precursor B cell lines with lambda 5 protein as the product of the VpreB gene. Surrogate L chain was detectable even in the absence of mu heavy (H) chain on the surface of early precursor cell lines such as pro-B cell lines where all immunoglobulin (Ig) loci are in the germline configuration, as well as early pre-B cell lines where Ig H chain loci are DHJH rearranged in reading frame I or III, which does not allow the expression of a DHJHC mu protein. A complex of glycoproteins (200, 130, 105, and 65-35 kD) was identified as coprecipitated with the Vpreb/lamba 5 surrogate L chain in mu H chain-negative precursor B cell lines. The 130-kD protein was most strongly labeled with iodine and most consistently detected in noncovalent association with surrogate L chain. This protein turned out to be a N-linked glycoprotein with a 100-kD protein core and isoelectric point 5.8, indicating that it is distinct from CD43 and the BP-1/6C3 antigen. The surface deposition of the surrogate L chain in association with the newly identified glycoproteins suggests that the surrogate L chain may function as a receptor even before the association with mu H chain in early precursor B cells.