tbuckley/cabot-search huggingface dataset:
Autoantibody Profiles and Neurological Correlations of Thymoma
Authors: Steven Vernino, Vanda A. Lennon
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Determine muscle and neuronal autoantibody frequencies in patients with thymoma, with and without paraneoplastic neurological accompaniments. Experimental Design: Analysis of IgG autoantibodies in stored serum collected between 1985 and 2003 from 201 patients with histologically diagnosed thymoma (including six with thymic carcinoma). Contemporary assays quantitated antibodies reactive with muscle and neuronal cation channels, muscle sarcomeric proteins and neuronal cytoplasmic, and nuclear proteins. Results: Neurological diagnoses included myasthenia gravis (MG), myositis, encephalitis, neuromuscular hyperexcitability, autonomic neuropathy, and subacute hearing loss, a previously unrecognized accompaniment of thymoma. Muscle acetylcholine receptor (AChR) binding antibodies were found in all patients with a diagnosis of MG. Muscle autoantibodies (AChR-binding, AChR-modulating, or striational) were also found in 59% of patients without any neurological disorder. One or more neuronal autoantibodies were found in 41% of patients without any neurological disorder, 43% of patients with MG only, and 78% of patients with other neurological disorders. Neuronal autoantibody specificities were, in descending order of frequency, as follows: glutamic acid decarboxylase, voltage-gated potassium channel, collapsin response-mediator protein-5, ganglionic AChR, and antineuronal nuclear antibody-type 1 (ANNA-1). Conclusions: Neuronal autoantibodies complement skeletal muscle autoantibodies as serological markers of thymoma in patients with and without clinical evidence of a neurological disorder. The high prevalence of glutamic acid decarboxylase autoantibody, not previously considered a paraneoplastic marker, justifies its consideration as a marker of thymoma-related neurological autoimmunity. Serological evaluation of a patient’s profile of neuronal and muscle autoantibodies may aid in preoperative identification of an indeterminate mediastinal mass.
Mapping of the Epstein-Barr virus and C3dg binding sites to a common domain on complement receptor type 2.
Authors: C A Lowell, L B Klickstein, R H Carter, J A Mitchell, D T Fearon, J M Ahearn
Journal: The Journal of Experimental Medicine (1989)

Complement receptor type 2 (CR2;CD21), a member of the superfamily of proteins containing short consensus repeats (SCRs), is the B cell receptor for both the gp350/220 envelope protein of Epstein-Barr virus (EBV), and for the C3dg protein of complement. By analysis of CR2 deletion mutants and chimeras formed with CR1 (CD35) we determined that of the 15 SCRs in CR2, the NH2-terminal two SCRs are necessary and sufficient to bind both gp350/220 and C3dg with affinities equivalent to those of the wild-type receptor. The epitope for OKB-7, a mAb that blocks binding of both EBV and C3dg and shares with these ligands B cell-activating capabilities, also requires both SCR-1 and SCR-2, whereas mAbs lacking these functions bind to other SCRs. Thus, EBV, a polyclonal activator of B cells, has selected a site that is proximate or identical to the natural ligand binding site in CR2, perhaps reflecting the relative immutability of that site as well as its signal transducing function.
Nurse practitioner-led breast cancer survivorship clinic
Authors: A. Cureton, W. Pritham, M. Royce, K. Zahn
Journal: Journal of Clinical Oncology (2009)

e20723 Background: The 2.5 million breast cancer survivors in the US demands increasing awareness of and need for healthcare organizations to address survivorship issues. Cancer survivorship care has become a specialty emphasizing health promotion, disease prevention, and patient satisfaction. It is a natural setting for advanced practice nurses to be leaders. This abstract presents a model for a nurse practitioner-led breast cancer survivorship clinic. Methods: Eligible patients are those previously diagnosed with invasive and/or in situ breast cancer and at least 5 years post-diagnosis without recurrence. Eligible survivors are identified annually through the University of New Mexico Tumor Registry. Clinic notes are reviewed to confirm the patient has not had a recurrence, new diagnosis, or death. Letters are sent to eligible survivors introducing the Breast Cancer Survivorship Clinic (Clinic) and inviting them to participate, and oncologists are encouraged to transfer eligible patients into the Clinic. Results: Eighty-six survivors are currently participating in the Clinic. Survivors are seen on an annual basis after mammogram. Each survivor receives a personalized Survivorship Care Plan at the first visit. The care plan was developed by a multi-disciplinary team of a breast oncologist, psychologist, social worker, nutritionist, and patient educator to provide input on the issues that survivors face. Components of Survivorship Care Plan: pathologic and genetic findings, summary of treatment, bloodwork, bone health, lymphedema, secondary malignancies, health maintenance recommendations, psychological assessment, nutrition/weight assessment. Conclusions: The establishment of the Clinic has several advantages: Breast cancer survivors are being followed in this specialty clinic after 5 years instead of being discharged from the Cancer Center. The Clinic has allowed oncologists more time for patients actively on therapy and more time to accommodate newly diagnosed patients. The Clinic addresses the unique issues faced by long term survivors, which could increase patient satisfaction. A multi-disciplinary team is key to developing a care plan for a survivorship clinic. However, the day-to-day operation of the clinic can be effectively led by a nurse practitioner. No significant financial relationships to disclose.
High-intensity ultraendurance promotes early release of muscle injury markers
Authors: A Bessa, M Nissenbaum, A Monteiro, P G Gandra, L S Nunes, A Bassini-Cameron, J P S Werneck-de-Castro, D Vaz de Macedo, L-C Cameron
Journal: British Journal of Sports Medicine (2008)

To evaluate the impact of high-intensity ultraendurance (HIU) cycling, using it as a possible way to understand muscle injury kinetics and blood immune cells' release during high-intensity prolonged exerciseMale amateur triathletes enrolled during a cycling race of the International Bike Championship 800 km cycling relay (approximately 23 h). Each athlete alternately cycled 20-25 minutes until exhaustion and performed a total of approximately 200 km.Creatine kinase levels in blood reached a 300% rise in a sigmoidal pattern, while lactate dehydrogenase levels increased by 30-40% following a hyperbolic pattern. Aspartate aminotransferase and alanine aminotransferase levels increased by up to 250% and 140%, respectively. Liver injury markers such as alkaline phosphatase and gamma-glutamyltransferase remained stable. Platelets increased by 20-30% from pre-exercise, and there was no change in haematocrit during the race. White blood cells rose by nearly 200%. Leucocytes rose 210% during the race, with a major component coming from neutrophils, which increased more than 300%. Triacylglycerol levels were decreased at the finish and total cholesterol levels remained unchanged. Urate increased (by up to 35%) during the first half of the race, and urea levels increased with a different pattern, increasing by 45% in the second half.This study showed the blood appearance kinetics of muscle injury markers and some metabolites. It is suggested that the increase in these enzymes came primarily from muscle damage, rather than liver damage, and that white blood cells are selectively mobilised independently of haemoconcentration. The early appearance of muscle injury markers in this kind of exercise was also shown.
Nitric Oxide Synthase Activity in Guinea Pig Ventricular Myocytes Is Not Involved in Muscarinic Inhibition of cAMP-Regulated Ion Channels
Authors: Sergey I. Zakharov, Sean Pieramici, Ganesh K. Kumar, Nanduri R. Prabhakar, Robert D. Harvey
Journal: Circulation Research (1996)

It has recently been demonstrated that NO plays an obligatory role in muscarinic inhibition of beta-adrenergically stimulated ion channels in cardiac sinoatrial node cells (J Gen Physiol. 1995;106:45-65). We looked for evidence that NO might play a similar role in ventricular cells by using histochemical staining for NO synthase (NOS) activity and whole-cell patch-clamp recording of cAMP-regulated Cl- currents. Myocytes isolated from guinea pig hearts stained positively for NADPH-diaphorase activity, suggesting that these cells do express NOS. Acetylcholine (ACh) inhibition of the R(-)-isoproterenol bitartrate (Iso)-activated Cl- current was also reversed by the cGMP-lowering agents LY-83583 and methylene blue, consistent with idea that NO activation of guanylate cyclase may contribute to muscarinic responses. However, LY-83583 and methylene blue activated the Cl- current in the presence of subthreshold concentrations of Iso alone, suggesting that their effects may not be due to antagonism of an NO/cGMP-dependent response. Furthermore, ACh inhibition of Iso-activated Cl- currents could not be mimicked by the NO donors sodium nitroprusside,3-morpholinosydnonimine, and spermine-NO. Similarly, ACh inhibition of the Iso-activated Cl- current could not be blocked by the NOS inhibitor NG-monomethyl-L-arginine. These results indicate that even though ventricular myocytes possess NOS activity, NO production does not play an important role in muscarinic inhibition of beta-adrenergically regulated Cl- channels in these cells.
Evolution of the ARF Gene Family in Land Plants: Old Domains, New Tricks
Authors: Cédric Finet, Annick Berne-Dedieu, Charles P. Scutt, Ferdinand Marlétaz
Journal: Molecular Biology and Evolution (2012)

Auxin response factors (ARF) are key players in plant development. They mediate the cellular response to the plant hormone auxin by activating or repressing the expression of downstream developmental genes. The pivotal activation function of ARF proteins is enabled by their four-domain architecture, which includes both DNA-binding and protein dimerization motifs. To determine the evolutionary origin of this characteristic architecture, we built a comprehensive data set of 224 ARF-related protein sequences that represents all major living divisions of land plants, except hornworts. We found that ARFs are split into three subfamilies that could be traced back to the origin of the land plants. We also show that repeated events of extensive gene duplication contributed to the expansion of those three original subfamilies. Further examination of our data set uncovered a broad diversity in the structure of ARF transcripts and allowed us to identify an additional conserved motif in ARF proteins. We found that additional structural diversity in ARF proteins is mainly generated by two mechanisms: genomic truncation and alternative splicing. We propose that the loss of domains from the canonical, four-domain ARF structure has promoted functional shifts within the ARF family by disrupting either dimerization or DNA-binding capabilities. For instance, the loss of dimerization domains in some ARFs from moss and spikemoss genomes leads to proteins that are reminiscent of Aux/IAA proteins, possibly providing a clue on the evolution of these modulators of ARF function. We also assessed the functional impact of alternative splicing in the case of ARF4, for which we have identified a novel isoform in Arabidopsis thaliana. Genetic analysis showed that these two transcripts exhibit markedly different developmental roles in A. thaliana. Gene duplications, domain rearrangement, and post-transcriptional regulation have thus enabled a subtle control of auxin signaling through ARF proteins that may have contributed to the critical importance of these regulators in plant development and evolution.
Hypermethylation of FHIT predicts poor prognosis in NSCLC
Authors: K Pavithran
Journal: Thorax (2004)

▴ Maruyama R, Sugio K, Yoshino I, et al . Hypermethylation of FHIT as a prognostic marker in non-small cell lung carcinoma. Cancer2004;100:1472–7. [OpenUrl][1][CrossRef][2][PubMed][3] DNA methylation of CpG sites in the promoter regions of tumour suppressor genes is a frequently acquired epigenetic event in the pathogenesis of many human cancers. The fragile histidine triad (FHIT) gene, located at chromosome 3p14.2, is a tumour suppressor gene. Methylation results in … [1]: {openurl}?query=rft.jtitle%253DCancer%26rft.stitle%253DCancer%26rft.aulast%253DMaruyama%26rft.auinit1%253DR.%26rft.volume%253D100%26rft.issue%253D7%26rft.spage%253D1472%26rft.epage%253D1477%26rft.atitle%253DHypermethylation%2Bof%2BFHIT%2Bas%2Ba%2Bprognostic%2Bmarker%2Bin%2Bnonsmall%2Bcell%2Blung%2Bcarcinoma.%26rft_id%253Dinfo%253Adoi%252F10.1002%252Fcncr.20144%26rft_id%253Dinfo%253Apmid%252F15042681%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1002/cncr.20144&link_type=DOI [3]: /lookup/external-ref?access_num=15042681&link_type=MED&atom=%2Fthoraxjnl%2F59%2F6%2F511.2.atom
Sniper: improved SNP discovery by multiply mapping deep sequenced reads
Authors: Daniel F Simola, Junhyong Kim
Journal: Genome biology (2011)

SNP (single nucleotide polymorphism) discovery using next-generation sequencing data remains difficult primarily because of redundant genomic regions, such as interspersed repetitive elements and paralogous genes, present in all eukaryotic genomes. To address this problem, we developed Sniper, a novel multi-locus Bayesian probabilistic model and a computationally efficient algorithm that explicitly incorporates sequence reads that map to multiple genomic loci. Our model fully accounts for sequencing error, template bias, and multi-locus SNP combinations, maintaining high sensitivity and specificity under a broad range of conditions. An implementation of Sniper is freely available at http://kim.bio.upenn.edu/software/sniper.shtml .
Retinoid and thiazolidinedione therapies in melanoma: an analysis of differential response based on nuclear hormone receptor expression
Authors: Joshua P Klopper, Vibha Sharma, Andrew Berenz, William R Hays, Michele Loi, Umarani Pugazhenthi, Sherif Said, Bryan R Haugen
Journal: Molecular Cancer (2009)

Metastatic melanoma has a high mortality rate and suboptimal therapeutic options. Molecular targeting may be beneficial using the rexinoid LGD1069, a retinoid × receptor selective agonist, and thiazolidinediones (TZD), PPARγ selective ligands, as novel treatments. Mouse xenograft models with human melanoma cell lines [A375(DRO) or M14(5–16)] were treated for 4 weeks with daily vehicle, RXR agonist (rexinoid, LGD1069, 30 mg/kg/d), PPARγ agonist (TZD, rosiglitazone, 10 mg/kg/d) or combination. A375(DRO) tumor growth was significantly inhibited by either ligand alone and the combination had an additive effect. M14(5–16) tumors only responded to LGD1069 100 mg/kg/day. A375(DRO) sublines resistant to rexinoid, TZD and combination were generated and all three sublines had reduced PPARγ expression but preserved RXR expression. shRNA knockdown of PPARγ or RXRγ attenuated the rexinoid, TZD and combination ligand-mediated decreased proliferation in A375(DRO) cells. Rexinoid (LGD1069) and retinoid (TTNPB) treatment of M14(5–16) cells resulted in decreased proliferation that was additive with combination of both rexinoid and retinoid. shRNA knockdown of RXRγ resulted in a decreased response to either ligand. A375 (DRO) melanoma cell growth is inhibited by rexinoid and TZD treatment, and this response is dependent on RXR and PPARγ receptor expression. M14 (5–16) melanoma cell growth is inhibited by rexinoid and retinoid treatment, and this response is dependent on RXR expression. These findings may help guide molecular-based treatment strategies in melanoma and provide insight for mechanisms of resistance to nuclear receptor targeted therapies in certain cancers.
Cardiac Resynchronization Therapy Improves Heart Rate Profile and Heart Rate Variability of Patients With Moderate to Severe Heart Failure
Authors: Cecilia Fantoni, Santi Raffa, Francois Regoli, Francesco Giraldi, Maria Teresa La Rovere, John Prentice, Francesca Pastori, Simona Fratini, Jorge A. Salerno-Uriarte, Helmut U. Klein, Angelo Auricchio
Journal: Journal of the American College of Cardiology (2005)
Risk of Cancer Among Workers Exposed to Trichloroethylene: Analysis of Three Nordic Cohort Studies
Authors: Johnni Hansen, Markku Sallmén, Anders I. Seldén, Ahti Anttila, Eero Pukkala, Kjell Andersson, Ing-Liss Bryngelsson, Ole Raaschou-Nielsen, Jørgen H. Olsen, Joseph K. McLaughlin
Journal: JNCI Journal of the National Cancer Institute (2013)

Trichloroethylene (TCE) is a widely used chlorinated solvent with demonstrated carcinogenicity in animal assays. Some epidemiologic studies have reported increased risk of cancer of the kidney, cervix, liver and biliary passages, non-Hodgkin lymphoma, and esophageal adenocarcinoma. We established a pooled cohort, including 5553 workers with individual documented exposure to TCE in Finland, Sweden, and Denmark. Study participants were monitored for the urinary TCE metabolite trichloroacetic acid from 1947 to 1989 and followed for cancer. Standardized incidence ratios (SIRs) were calculated based on cancer incidence rates in the three national populations. Cox proportionate hazard analyses were used for internal comparisons. Tests of statistical significance are two-sided. Overall, 997 cases of cancer (n = 683 in men; n = 314 in women) were identified during 154 778 person-years of follow-up. We observed statistically significant elevated standardized incidence ratios for primary liver cancer (1.93; 95% confidence interval [CI] = 1.19 to 2.95) and cervical cancer (2.31; 95% CI = 1.32 to 3.75). The standardized incidence ratio for kidney cancer was 1.01 (95% CI = 0.70 to 1.42) based on 32 cases; we did not observe a statistically significant increased risk of non-Hodgkin's lymphoma (SIR = 1.26; 95% CI = 0.89 to 1.73) or esophageal adenocarcinoma (SIR = 1.84; 95% CI = 0.65 to 4.65). Tobacco- and alcohol-associated cancers were not statistically significantly increased. Our results suggest TCE exposure is possibly associated with an increased risk for liver cancer. The relationship between TCE exposure and risks of cancers of low incidence and those with confounding by lifestyle and other factors not known in our cohort require further study.
Tumor necrosis factor plays a protective role in experimental murine cutaneous leishmaniasis.
Authors: R G Titus, B Sherry, A Cerami
Journal: The Journal of Experimental Medicine (1989)

The ability of mice to resist infection with L. major correlated directly with the capacity of their LNC to produce TNF in response to in vitro parasite challenge. Blocking TNF in vivo by passively administering anti-TNF antibodies exacerbated the course of L. major infection, resulting in substantially larger cutaneous lesions and elevated numbers of parasites within those lesions. In addition, treatment of infected mice with exogenous rHuTNF afforded host protection as evidenced by smaller lesion size and decreased parasite counts. Taken together, these results suggest a central role for TNF in resistance to L. major.
High-throughput diversity and functionality analysis of the gastrointestinal tract microbiota
Authors: E G Zoetendal, M Rajilic-Stojanovic, W M de Vos
Journal: Gut (2008)

The human gastrointestinal (GI) tract microbiota plays a pivotal role in our health. For more than a decade a major input for describing the diversity of the GI tract microbiota has been derived from the application of small subunit ribosomal RNA (SSU rRNA)-based technologies. These not only provided a phylogenetic framework of the GI tract microbiota, the majority of which has not yet been cultured, but also advanced insights into the impact of host and environmental factors on the microbiota community structure and dynamics. In addition, it emerged that GI tract microbial communities are host and GI tract location-specific. This complicates establishing relevant links between the host's health and the presence or abundance of specific microbial populations and argues for the implementation of novel high-throughput technologies in studying the diversity and functionality of the GI tract microbiota. Here, we focus on the recent developments and applications of phylogenetic microarrays based on SSU rRNA sequences and metagenomics approaches exploiting rapid sequencing technologies in unravelling the secrets of our GI tract microbiota.
Coupled Induction of iNOS and p53 Upregulation in Renal Resident Cells May Be Linked with Apoptotic Activity in the Pathogenesis of Progressive IgA Nephropathy
Authors: Lian-Qun Qiu, Raja Sinniah, Stephen I-Hong Hsu
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. In situ hybridization, immunohistochemistry, and TUNEL staining were applied to renal biopsy specimens of immunoglobulin A nephropathy (IgAN) patients to determine the expression of nitric oxide synthase (iNOS) (mRNA and protein), p53, and their potential roles in renal cell apoptosis in relation to the development of pathologic lesions. Fifty-one cases were categorized into four subgroups (A–D) according to the presence of progressive histopathological features. A cell type–specific and differential overexpression of iNOS mRNA and protein was demonstrated in glomerular cells in subgroups (A–C) and was found to correlate well with the upregulation of p53 protein by glomerular endothelium and epithelium in early- and advanced-stage disease. In the tubulointerstitium, induction of iNOS products was evident in damaged tubules in late-stage disease, in parallel with the upregulation of p53 protein levels in these tubules. Increased TUNEL staining observed in glomeruli with progressive lesions and tubules with degenerative changes positively correlated with the expression levels of iNOS and p53 in glomerular endothelium, epithelium, and their overexpression in damaged tubules. Clinicopathologic correlations demonstrated that induction of iNOS products in renal cells was associated with indices of poor renal prognosis in human IgAN. The coupled induction of iNOS and p53 upregulation in intrinsic renal cells of IgAN may be linked with both pro- and anti-apoptotic activities, thus playing an important role in mediating progressive renal injury and determining renal outcome in human IgAN.