tbuckley/cabot-search huggingface dataset:
Abstract 1888: Target sequencing of papillary renal cell carcinoma, type 2, using custom-made kidney cancer panel
Authors: Ji-Yeon Kim, Se-Hoon Lee, Jong-Il Kim, Jong-Yeon Shin, Dae seog Heo
Journal: Cancer Research (2014)

Abstract Purpose: Papillary renal cell carcinoma type2 (PRCC2) is 2nd most common kidney malignancy followed by clear cell renal cell carcinoma (CCRCC). PRCC2 has poor prognosis, treatment strategy is not established and the genetic alteration is poorly understood. We sequenced PRCC2 samples using custom-made kidney cancer panel to figure out genetic alterations of PRCC2. Methods: We have reviewed publications about the genetics of kidney cancer including all subtypes and selected 55 candidate genes. This cancer panel consisted of 1022 regions by Agilent SureSelect Target Enrichment. We sequenced 12 PRCC2 tumor samples along with 6 paired normal tissue samples. The patients' age were ranged from 26 to 82 year-old, and 3 patients were female (25%). Genomic DNA was isolated from dissected tumor tissue samples (6 fresh, frozen and 6 formalin-fixed, paraffin-embedded) and normal tissue samples. Sequencing was performed by Illumina platform and aligned to H. sapiens, hg19, GRCh37. Total probe number was 4103 and size was 283.494 kbp. Presumed germline variants, which were present in matched normal tissue, were filtered out, and manual curation was performed for each area of variants. Results: Fifty-four of 55 target genes had 100% coverage, in spite of 92.7% coverage of one target gene. We found two novel FH mutations (one single nucleotide variant and one 5bp indel) and one novel NFE2L2 mutation. Two out of 12 samples (17%) were altered in NRF2 pathway (1 NFE2L2 and 1 KEAP) which was already well-known as driver in PRCC2. Novel PBRM1 mutation in two samples and SETD2 mutation in one sample were identified. In addition, PTEN, TSC1, KDM5C and AKT1 mutation are observed in one case, respectively. No VHL mutation in PRCC2 was revealed. Conclusions: We analyzed somatic mutation of PRCC2 with custom-made kidney cancer panel. We found several candidate driver mutations of PRCC2. Our result reveals that the genetics of PRCC2 is heterogeneous, therefore, the approach using kidney cancer panel could be used to characterize individual PRCC2. The gene list of RCC panelABCB1BRAFERBB2MDM2NUDT11SDHBTP53ABL1CNTNAP4FHMDM4PBRM1SDHCTSC1AKR1B10CR1FLCNMETPCDHGA8SDHDTSC2AKT1CUL3HIF1AMTORPIK3CASTED2VEGFAALKDACH2KANK3MYCPOTECSIRT1VHLANKRD36EBPLKEAP1NBPF10PTENSPAM1WDR52ARID1AEGFRKRASNFE2L2RETSTAG3L2TSC1BAP1EPAS1KRT1NPNTROS1TERT Citation Format: Ji-Yeon Kim, Se-Hoon Lee, Jong-Il Kim, Jong-Yeon Shin, Dae seog Heo. Target sequencing of papillary renal cell carcinoma, type 2, using custom-made kidney cancer panel. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1888. doi:10.1158/1538-7445.AM2014-1888
Diastolic dysfunction in familial hypertrophic cardiomyopathy transgenic model mice
Authors: Theodore P. Abraham, Michelle Jones, Katarzyna Kazmierczak, Hsin-Yueh Liang, Aurelio C. Pinheiro, Cory S. Wagg, Gary D. Lopaschuk, Danuta Szczesna-Cordary
Journal: Cardiovascular Research (2009)

Several mutations in the ventricular myosin regulatory light chain (RLC) were identified to cause familial hypertrophic cardiomyopathy (FHC). Based on our previous cellular findings showing delayed calcium transients in electrically stimulated intact papillary muscle fibres from transgenic Tg-R58Q and Tg-N47K mice and, in addition, prolonged force transients in Tg-R58Q fibres, we hypothesized that the malignant FHC phenotype associated with the R58Q mutation is most likely related to diastolic dysfunction. Cardiac morphology and in vivo haemodynamics by echocardiography as well as cardiac function in isolated perfused working hearts were assessed in transgenic (Tg) mutant mice. The ATPase–pCa relationship was determined in myofibrils isolated from Tg mouse hearts. In addition, the effect of both mutations on RLC phosphorylation was examined in rapidly frozen ventricular samples from Tg mice. Significantly, decreased cardiac function was observed in isolated perfused working hearts from both Tg-R58Q and Tg-N47K mice. However, echocardiographic examination showed significant alterations in diastolic transmitral velocities and deceleration time only in Tg-R58Q myocardium. Likewise, changes in Ca2+ sensitivity, cooperativity, and an elevated level of ATPase activity at low [Ca2+] were only observed in myofibrils from Tg-R58Q mice. In addition, the R58Q mutation and not the N47K led to reduced RLC phosphorylation in Tg ventricles. Our results suggest that the N47K and R58Q mutations may act through similar mechanisms, leading to compensatory hypertrophy of the functionally compromised myocardium, but the malignant R58Q phenotype is most likely associated with more severe alterations in cardiac performance manifested as impaired relaxation and global diastolic dysfunction. At the molecular level, we suggest that by reducing the phosphorylation of RLC, the R58Q mutation decreases the kinetics of myosin cross-bridges, leading to an increased myofilament calcium sensitivity and to overall changes in intracellular Ca2+ homeostasis.
Identification of novel molecules and pathogenic pathways in primary biliary cirrhosis: cDNA array analysis of intrahepatic differential gene expression
Authors: N A Shackel
Journal: Gut (2001)

<h3>BACKGROUND</h3> Primary biliary cirrhosis (PBC) is an autoimmune disease in which the pathogenesis of progressive liver injury is poorly understood. <h3>AIM</h3> To provide novel insights into the pathogenesis of PBC related liver injury using cDNA array analysis, which simultaneously examines expression of many genes. <h3>METHODS</h3> Utilising cDNA arrays of 874 genes, PBC was compared with primary sclerosing cholangitis (PSC) associated cirrhosis and non-diseased liver. Differential expression of 10 genes was confirmed by real time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). <h3>RESULTS</h3> Array analysis identified many differentially expressed genes that are important in inflammation, fibrosis, proliferation, signalling, apoptosis, and oxidative stress. PBC was associated with increased expression of both Th1 and Th2 type molecules of the immune response. Fibrosis related gene expression featured upregulation of connective tissue growth factor and transforming growth factor beta3. Many more apoptosis associated molecules exhibited increased expression, consistent with apoptosis being a more active and regulated process, in PSC associated cirrhosis than in PBC. Increased expression of many genes of the Wnt and notch pathways implicated these highly conserved and linked pathways in PBC pathogenesis. The observed increases in expression of c-jun, c-myc, and c-fos related antigen 1 are consistent with increased Wnt pathway activity in PBC. Differential expression of four components of the Wnt pathway, Wnt-5a, Wnt-13, FRITZ, and beta-catenin, was confirmed by quantitative RT-PCR. <h3>CONCLUSION</h3> Many genes implicated in intrahepatic inflammation, fibrosis, and regeneration were upregulated in PBC cirrhosis. In particular, increased expression of a number of <i>Drosophila</i> homologues was seen in PBC.
Canadian Trial of Physiological Pacing
Authors: Charles R. Kerr, Stuart J. Connolly, Hoshiar Abdollah, Robin S. Roberts, Michael Gent, Salim Yusuf, Anne M. Gillis, Anthony S.L. Tang, Mario Talajic, George J. Klein, David M. Newman
Journal: Circulation (2004)

The Canadian Trial of Physiological Pacing (CTOPP) reported that the risk of stroke or cardiovascular death was similar between patients receiving ventricular versus physiological pacemakers at the end of the original follow-up period of 3 years. However, the occurrence of atrial fibrillation was significantly less frequent with physiological pacemakers. To assess a potential delayed benefit of physiological pacing, follow-up of patients in this study was extended to 6 years.A total of 1474 patients requiring a pacemaker for symptomatic bradycardia were randomized to receive ventricular and 1094 to physiological pacemakers. The primary outcome was stroke or cardiovascular death. The study was completed in July 1998, and follow-up was extended to July 2001. At a mean follow-up of 6.4 years, there was no difference between treatment groups in the primary outcome of cardiovascular death or stroke. There was no significant difference in total mortality or stroke between groups. There was a significantly lower rate of development of atrial fibrillation in the physiological group, with a relative risk reduction of 20.1% (CI, 5.4 to 32.5; P=0.009).The CTOPP extended study does not show a difference in cardiovascular death or stroke, or in total mortality, or in stroke between patients implanted with ventricular or physiological pacemakers over a mean follow-up of >6 years. However, there is a persistent significant reduction in the development of atrial fibrillation with physiological pacing.
Bilateral Risk for Subsequent Breast Cancer After Lobular Carcinoma-In-Situ: Analysis of Surveillance, Epidemiology, and End Results Data
Authors: Paul J. Chuba, Merlin R. Hamre, Johnny Yap, Richard K. Severson, David Lucas, Falah Shamsa, Amr Aref
Journal: Journal of Clinical Oncology (2005)

Noninvasive lesions involving the lobules of the breast are increasingly diagnosed as incidental microscopic findings at the time of lumpectomy or core-needle biopsy. We investigated the incidence rates of invasive breast cancer (IBC) after a diagnosis of lobular carcinoma-in-situ (LCIS) by using Surveillance, Epidemiology, and End Results (SEER) data.Patients (N = 4,853) having a diagnosis of primary LCIS in the time period of 1973 to 1998 were identified using the SEER Public Use CD-ROM data. The database was then searched for patients with subsequent primary IBC occurrences (n = 350). The clinical and pathologic characteristics of patients with subsequent primary IBCs were compared with the characteristics of patients with primary IBCs attained during the same time period (N = 255,114).The incidence of IBC increased over time from diagnosis of LCIS, with 7.1% +/- 0.5% incidence of IBC at 10 years. IBCs detected after partial mastectomy occurred in either breast (46% ipsilateral and 54% contralateral); however, after mastectomy, most IBCs were contralateral (94.7%). IBCs occurring after LCIS more often represented invasive lobular histology (23.1%) compared with primary IBCs (6.5%). The standardized incidence ratio (the ratio of observed to expected cases) for developing IBC was 2.4 (95% CI, 2.1 to 2.6) adjusted for age and year of diagnosis.LCIS is associated with increased risk of subsequent invasive disease, with equal predisposition in either breast. The minimum risk of developing IBC after LCIS is 7.1% at 10 years.
Allergic Sensitization and Determination Of Serum Eosinophil Cationic Protein and Triptase In Preschool Population In Hermosillo, Sonora, Mexico
Authors: Claudia Gallego-Corella, Guadalupe Corella, Andrea Romo, Antonio Rascón, Pablo Martínez
Journal: Journal of Allergy and Clinical Immunology (2014)
Muscarinic receptor subtype-specific effects on cigarette smoke-induced inflammation in mice
Authors: Loes E.M. Kistemaker, I.S.T. Bos, Machteld N. Hylkema, Martijn C. Nawijn, Pieter S. Hiemstra, Jürgen Wess, Herman Meurs, Huib A.M. Kerstjens, Reinoud Gosens
Journal: European Respiratory Journal (2013)

Cholinergic tone contributes to airflow obstruction in chronic obstructive pulmonary disease. Accordingly, anticholinergics are effective bronchodilators by blocking the muscarinic M3 receptor on airway smooth muscle. Recent evidence indicates that acetylcholine also contributes to airway inflammation. However, which muscarinic receptor subtype(s) regulates this process is unknown. In this study, the contribution of the M1, M2 and M3 receptor subtypes to cigarette smoke-induced airway inflammation was investigated by exposing muscarinic receptor subtype deficient mice to cigarette smoke for 4 days. In wild-type mice, cigarette smoke induced an increase in macrophages, neutrophils and lymphocytes in bronchoalveolar lavage fluid. Neutrophilic inflammation was higher in M1(-/-) and M2(-/-) mice compared to wild-type mice, but lower in M3(-/-) mice. Accordingly, the release of keratinocyte-derived chemokine (KC), monocyte chemotactic protein-1 and interleukin-6 was higher in M1(-/-) and M2(-/-) mice, and reduced in M3(-/-) mice. Markers of remodelling were not increased after cigarette smoke exposure. However, M3(-/-) mice had reduced expression of transforming growth factor-β1 and matrix proteins. Cigarette smoke-induced inflammatory cell recruitment and KC release were also prevented by the M3-receptor selective antagonist 1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP) in wild-type mice. Collectively, our data indicate a pro-inflammatory role for the M3 receptor in cigarette smoke-induced neutrophilia and cytokine release, yet an anti-inflammatory role for M1 and M2 receptors.
A sequential study of serum bacterial DNA in patients with advanced cirrhosis and ascites
Authors: Rubén Francés, Susana Benlloch, Pedro Zapater, José M. González, Beatriz Lozano, Carlos Muñoz, Sonia Pascual, Juan A. Casellas, Francisco Uceda, José M Palazón, Fernando Carnicer, Miguel Pérez-Mateo, José Such
Journal: Hepatology (2004)

Bacterial translocation is currently considered the main pathogenic mechanism leading to spontaneous bacterial peritonitis in patients with advanced cirrhosis and ascites. However, to the authors' knowledge there is no information regarding the characteristics of this process in humans. The goals of the current study were to pursue partially identified bacterial DNA in blood (what the authors consider molecular evidence of bacterial translocation) through its relative quantification in a 72-hour study period by using real-time polymerase chain reaction (PCR). A consecutive series of 17 patients with advanced cirrhosis and culture-negative, nonneutrocytic ascites were studied. Therapeutic paracentesis was performed at the time of admission, and blood samples were obtained at baseline and every 8 hours in a 3-day period. Bacterial DNA was detected by a PCR-based method, relatively quantified by real-time PCR, and identified by automated nucleotide sequencing. Seven of 17 patients demonstrated the simultaneous presence of bacterial DNA in blood and ascitic fluid at the time of admission. After therapeutic paracentesis was performed, bacterial DNA persisted in the blood for a minimum of 24 hours, and was reported to last as long as 72 hours in some patients. In addition, different patterns of bacterial DNA appearance and clearance from the blood were identified. The nucleotide sequencing process demonstrated that bacteria detected in the first sample were identical to those noted in subsequent detections over time. In conclusion, bacterial translocation is a single-species, dynamic process that appears to develop in a subgroup of patients with advanced cirrhosis.
Importance of dural ectasia in phenotypic assessment of M arfan's syndrome
Authors: Rossella Fattori, Christoph ANienaber, Benedetta Descovich, Paolo Ambrosetto, Letizia Bacchi Reggiani, Guglielmina Pepe, Ursula Kaufmann, Elena Negrini, Yskert von Kodolitsch, Gian Franco Gensini
Journal: The Lancet (1999)
Prevalence of iron deficiency across different tumors and its association with poor performance status, disease status and anemia
Authors: H. Ludwig, E. Müldür, G. Endler, W. Hübl
Journal: Annals of Oncology (2013)

BackgroundOnly limited data on the prevalence of iron deficiency (ID) and its correlation with clinical parameters are available in cancer. ID frequently contributes to the pathogenesis of anemia in patients with cancer and may lead to several symptoms such as impaired physical function, weakness and fatigue.Patients and methodsParameters of iron status and clinical parameters were evaluated in 1528 patients with cancer who presented consecutively within a four-month period at our center. One thousand fifty-three patients had solid tumors and 475 hematological malignancies.ResultsID [transferrin saturation (TSAT) < 20%] was noted in 645 (42.6%) of the 1513 patients with TSAT tests available and 500 (33.0%) were anemic. ID rates were highest in pancreatic (63.2%), colorectal (51.9%) and lung cancers (50.7%). Of the 409 iron-deficient patients in whom serum ferritin levels were available additionally to TSAT, 335 (81.9%) presented with functional ID (FID) (TSAT < 20%, serum ferritin ≥30 ng/ml) and 74 (18.1%) with absolute ID. In patients with solid tumors, prevalence of ID correlated with cancer stage at diagnosis (P = 0.001), disease status (P = 0.001) and ECOG performance status (P = 0.005).ConclusionsID was frequently noted in cancer and was associated with advanced disease, close proximity to cancer therapy, and poor performance status in patients with solid tumors.
Using acellular porcine limbal stroma for rabbit limbal stem cell microenvironment reconstruction
Authors: Minghai Huang, Naiyang Li, Zheng Wu, Pengxia Wan, Xuanwei Liang, Wei Zhang, Xiaoran Wang, Chaoyang Li, Jianhui Xiao, Qiang Zhou, Zhao Liu, Zhichong Wang
Journal: Biomaterials (2011)
Fulminant hepatic failure in acute hepatitis C: increased risk in chronic carriers of hepatitis B virus
Authors: C M Chu, C T Yeh, Y F Liaw
Journal: Gut (1999)

<h3>BACKGROUND/AIMS</h3> The role of hepatitis C virus (HCV) in fulminant hepatitis remains controversial. This study was conducted to investigate the risk of fulminant hepatitis C in relation to HCV genotypes and concurrent infection of other viruses. <h3>PATIENTS</h3> 109 HCV RNA positive patients from 334 consecutive cases hospitalised to a medical centre in northern Taiwan for overt acute viral hepatitis were prospectively evaluated. <h3>METHODS</h3> HCV RNA was detected by a combined reverse transcription-polymerase chain reaction assay. HCV genotypes were analysed using a genotype specific probe based assay in the 5' untranslated region. <h3>RESULTS</h3> 39 patients tested positive for hepatitis B surface antigen but negative for IgM antibody to hepatitis B core antigen, indicating concurrent chronic hepatitis B virus (HBV) infection. Twelve patients were hepatitis G virus (HGV) RNA positive. Genotyping of HCV disclosed 1b in 93, 1b mixed with 2a/2c or 1b mixed with 2b in 11, and not classified in five. Serum titres of HCV RNA were &lt;10<sup>5</sup> copies/ml in 77, 10<sup>5</sup>–10<sup>7</sup> copies/ml in 25, and &gt;10<sup>7</sup>copies/ml in seven. Eleven patients (10.1%) had fulminant hepatitis as a complication. Development of fulminant hepatitis did not correlate with age and gender of the patients, concurrent HGV infection, HCV genotypes, or serum titre of HCV RNA. However, the incidence (95% confidence interval) of fulminant hepatitis in patients with underlying chronic HBV infection was 23.1% (9.9 to 36.3%), which is significantly higher than in those without (2.9% (−1.0 to 6.8%)). In 39 patients with concurrent chronic HBV infection, the clinical and virological characteristics showed no significant difference between those with fulminant hepatitis and those without. <h3>CONCLUSIONS</h3> Acute hepatitis C in patients with concurrent chronic HBV infection is associated with a substantial risk of fulminant hepatitis.
Is lipoatrophia semicircularis induced by pressure?
Authors: A.C. GROOT
Journal: British Journal of Dermatology (1994)

Ten patients suffering from lipoatrophia semicircularis are reported. It is suggested that pressure from a chair on the posterior aspect of the thighs, possibly in combination with direct pressure from a desk on the anterior aspect, caused the condition in these patients. Lipoatrophia semicircularis may be quite common, but most patients do not present to a dermatologist.
Isolation and partial characterization of a human alveolar macrophage-derived neutrophil-activating factor.
Authors: J E Pennington, T H Rossing, L W Boerth, T H Lee
Journal: Journal of Clinical Investigation (1985)

Human alveolar macrophages (AM) were obtained from eight normal volunteers using fiberoptic bronchoscopic lavage to explore potential interrelationships among leukocytes in pulmonary defense against infection. AM placed in monolayer tissue cultures released material into culture supernatants with the capacity to enhance the bactericidal capacity of human neutrophils. Neutrophils preexposed to supernatants killed Pseudomonas aeruginosa from 70 to 90% more efficiently than control cells (P less than 0.02). AM culture supernatants contained this material by 4 h of incubation, and in vitro stimulation of AM cultures with heat-killed P. aeruginosa further increased its production. Gel filtration of AM culture supernatants with a G-50 Sephadex column allowed isolation of a 6,000-D neutrophil-activating factor (NAF) that was resistant to heat (56 degrees C, 30 min). The isoelectric point of NAF, as determined by chromatofocusing, was approximately 7.6. Enzyme digestion of NAF specimens, prepared sequentially by gel filtration and chromatofocusing, demonstrated 50-70% loss of activity after incubations with trypsin, chymotrypsin, and neuraminidase. NAF was only minimally chemotactic and eluted from Sephadex G-50 with particles of a different molecular size than those of AM-derived chemotactic factors (i.e., approximately 10,000 D and less than 500 D). Preincubation of neutrophils with NAF resulted in greater release of superoxide anion upon their subsequent stimulation by either bacterial phagocytosis or by phorbol myristate acetate, as compared with control neutrophils stimulated in a like manner. These studies indicate that human AM secrete a heat-stable, low molecular weight basic protein, with the capacity to enhance oxidative microbicidal activity of neutrophils.
TLR9/MyD88 signaling is required for class switching to pathogenic IgG2a and 2b autoantibodies in SLE
Authors: Marc Ehlers, Hidehiro Fukuyama, Tracy L. McGaha, Alan Aderem, Jeffrey V. Ravetch
Journal: The Journal of Experimental Medicine (2006)

Loss of tolerance in systemic lupus erythematosus (SLE) leads to the generation of autoantibodies, which accumulate in end-organs where they induce disease. Here we show that immunoglobulin (Ig)G2a and 2b autoantibodies are the pathogenic isotypes by recruiting FcγRIV expressing macrophages. Class switching, but not development, of IgM anti-self B cells to these pathogenic subclasses requires the innate immune receptor Toll-like receptor (TLR)9 and MyD88 signaling. In their absence, switching of autoreactive B cells to the IgG2a and 2b subclasses is blocked, resulting in reduced pathology and mortality. In contrast, switching of anti-self B cells to IgG1 is not perturbed and generation of nonautoreactive IgG2a and 2b antibodies is not impaired in TLR9-deficient mice. Thus, the TLR9 pathway is a potential target for therapeutic intervention in SLE.
Cooperative Groups Say NCI Trials Funding Inadequate; Some Turn to Industry
Authors: C. Schmidt
Journal: JNCI Journal of the National Cancer Institute (2007)

To calculate total funding for a given trial, investigators multiply the number of patients by the $2,000 reimbursement. The resulting value represents the bulk of what NCI will pay for a trial, including longterm follow-up. Faced with a stagnant budget, NCI hasn’t raised the reimbursement rate for 7 years, while median costs per subject have reached $6,000 and beyond, according to the Lewin Group, a health care consulting fi rm in Falls Church, Va. That means NCI funding covers at best a third of what the trial actually costs. To perform NCI trials, investigators require supplemental funds from hospitals, philanthropies, and other sources. Industry trials, meanwhile, pay at least $9,000 per patient and often more, the Lewin Group reports.
Activity-dependent silencing reveals functionally distinct itch-generating sensory neurons
Authors: David P Roberson, Sagi Gudes, Jared M Sprague, Haley A W Patoski, Victoria K Robson, Felix Blasl, Bo Duan, Seog Bae Oh, Bruce P Bean, Qiufu Ma, Alexander M Binshtok, Clifford J Woolf
Journal: Nature Neuroscience (2013)