tbuckley/cabot-search huggingface dataset:
Overexpression of the Cytokine Osteopontin Identifies Aggressive Laryngeal Squamous Cell Carcinomas and Enhances Carcinoma Cell Proliferation and Invasiveness
Authors: Angela Celetti, Domenico Testa, Stefania Staibano, Francesco Merolla, Valentina Guarino, Maria Domenica Castellone, Renata Iovine, Gelsomina Mansueto, Pasquale Somma, Gaetano De Rosa, Vieri Galli, Rosa Marina Melillo, Massimo Santoro
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Osteopontin is a secreted cytokine that binds to the cell surface CD44v6 receptor. We studied osteopontin and CD44v6 expression in laryngeal squamous cell carcinomas and correlated osteopontin expression levels with clinicopathologic tumor features. Experimental Design: We used immunohistochemistry, immunoblotting, and reverse transcription-PCR to study osteopontin expression in 58 laryngeal squamous cell carcinomas. Cultured squamous carcinoma cells were treated with exogenous osteopontin or with RNA interference to knockdown osteopontin expression. Results: Osteopontin expression was higher in all the invasive carcinomas than in patient-matched normal mucosa. Its expression levels were significantly correlated with tumor stage and grade and with the presence of lymph node and distant metastases. Osteopontin positivity was negatively correlated with overall survival (P = 0.03). Osteopontin expression was paralleled by intense cell surface reactivity for CD44v6. Treatment of squamous carcinoma cells with recombinant osteopontin sharply increased proliferation and Matrigel invasion in comparison with the untreated cells parallel to activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase/mitogen-activated protein kinase signaling cascade. Osteopontin knockdown by RNA interference, anti-CD44 antibodies, and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase inhibition prevented these effects. Conclusions: These results identify osteopontin as a marker and a potential therapeutic target in cases of aggressive laryngeal squamous cell carcinomas.
AT-02 * THE HIPPO PATHWAY ACTIVITY IN AT/RT
Authors: M. Suzuki, A. Kondo, I. Ogino, H. Arai
Journal: Neuro-Oncology (2015)

BACKGROUND: Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant tumor in early childhood. Though it is widely known that over 90% of tumors show loss of INI1 nuclear staining histologically, comprehended molecular analysis of this tumor has not been done at this point. Recently Hippo pathway is discovered the pathway that plays important roles in tumorigenesis, stem cell self-renewal and differentiation, organ size control. In this study, we investigate the changes between primary, post-chemotherapy, and post-radiation therapy, focused on Hippo pathway in AT/RT. MATERIALS AND METHODS: We used the tissue diagnosed as AT/RT in our institution. Using these tumor tissues, we saw the expression of TEAD4 and YAP1, the components of Hippo pathway, and the difference between primary and recurrent tumors, using immunohistochemistry (IHC) and in situ hybridization. We also performed high throughput analysis using a commercially utilized SNP array system. RESULTS: We had 3 cases who had multiple removal after interventions because of the tumor recurrence. All tumors were diagnosed as AT/RT with the confirmation of negative staining of BAF47 and the lack of SMARCB1. IHC showed that all of the tumors were higher expression of TEAD4 and YAP1 than normal cerebrum and cerebellum through the whole clinical course. And some of samples appeared high co-expression of TEAD4 and YAP1. CONCLUSION: Our study shows high expression of TEAD4 and YAP1 in all of our samples, and that may suggest the activation of Hippo pathway in AT/RT. Further study is needed to identify the malignant characters of this tumor.
Novel Tryptophan Catabolic Enzyme IDO2 Is the Preferred Biochemical Target of the Antitumor Indoleamine 2,3-Dioxygenase Inhibitory Compound <scp>d</scp>-1-Methyl-Tryptophan
Authors: Richard Metz, James B. DuHadaway, Uma Kamasani, Lisa Laury-Kleintop, Alexander J. Muller, George C. Prendergast
Journal: Cancer Research (2007)

Abstract Small-molecule inhibitors of indoleamine 2,3-dioxygenase (IDO) are currently being translated to clinic for evaluation as cancer therapeutics. One issue related to trials of the clinical lead inhibitor, d-1-methyl-tryptophan (D-1MT), concerns the extent of its biochemical specificity for IDO. Here, we report the discovery of a novel IDO-related tryptophan catabolic enzyme termed IDO2 that is preferentially inhibited by D-1MT. IDO2 is not as widely expressed as IDO but like its relative is also expressed in antigen-presenting dendritic cells where tryptophan catabolism drives immune tolerance. We identified two common genetic polymorphisms in the human gene encoding IDO2 that ablate its enzymatic activity. Like IDO, IDO2 catabolizes tryptophan, triggers phosphorylation of the translation initiation factor eIF2α, and (reported here for the first time) mobilizes translation of LIP, an inhibitory isoform of the immune regulatory transcription factor NF-IL6. Tryptophan restoration switches off this signaling pathway when activated by IDO, but not IDO2, arguing that IDO2 has a distinct signaling role. Our findings have implications for understanding the evolution of tumoral immune tolerance and for interpreting preclinical and clinical responses to D-1MT or other IDO inhibitors being developed to treat cancer, chronic infection, and other diseases. [Cancer Res 2007;67(15):7082–7]
Imaging
Authors: Patricia K. Nguyen, Feng Lan, Yongming Wang, Joseph C. Wu
Journal: Circulation Research (2011)

Stem cells have been touted as the holy grail of medical therapy, with promises to regenerate cardiac tissue, but it appears the jury is still out on this novel therapy. Using advanced imaging technology, scientists have discovered that these cells do not survive nor engraft long-term. In addition, only marginal benefit has been observed in large-animal studies and human trials. However, all is not lost. Further application of advanced imaging technology will help scientists unravel the mysteries of stem cell therapy and address the clinical hurdles facing its routine implementation. In this review, we will discuss how advanced imaging technology will help investigators better define the optimal delivery method, improve survival and engraftment, and evaluate efficacy and safety. Insights gained from this review may direct the development of future preclinical investigations and clinical trials.
Insights from the Study of Heart Rate Variability
Authors: P.K. Stein, PhD, R.E. Kleiger, MD
Journal: Annual Review of Medicine (1999)

Indices of heart rate variability (HRV) provide a window onto autonomic modulation of the heart. HRV indices, determined in either the time or frequency domain, are closely related and reflect parasympathetic, mixed sympathetic, and parasympathetic and circadian rhythms. In population studies, decreased HRV has had predictive value for mortality among healthy adults. It is a well-established risk factor for arrhythmic events and mortality among post-myocardial-infarction patients but has only moderate sensitivity and specificity. Decreased HRV has had mixed predictive success in congestive heart failure. Reduced HRV identifies diabetic patients with autonomic neuropathy. HRV in combination with other risk stratifiers, e.g. ejection fraction, can identify cardiac patients at especially high risk of mortality. Many but not all interventions associated with increased HRV are also associated with better survival rates.
Coeliac disease in monozygotic twin girls. Synchronous presentation.
Authors: F A Khuffash, M H Barakat, H A Majeed, A G White, A J Beseda
Journal: Gut (1984)

A pair of monozygotic twin girls with coeliac disease is reported. The diagnosis was made on clinical and biochemical evidence of malabsorption, characteristic histological findings, and clinical, biochemical, and histological response to gluten elimination. Monozygosity was established on finding a single placenta at birth, exact similarity of physical appearance, similar blood group, and histocompatibility antigens, and negative reaction in mixed lymphocyte culture. This is one of six well documented cases of coeliac disease in monozygotic twins and may throw light on the importance of genetic and environmental factors in the causation and expression of the disease.
A Phase I Dose-Escalation and Pharmacokinetic Study of Brostallicin (PNU-166196A), a Novel DNA Minor Groove Binder, in Adult Patients with Advanced Solid Tumors
Authors: A. Craig Lockhart, Martin Howard, Kenneth R. Hande, Bruce J. Roth, Jordan D. Berlin, Franzanne Vreeland, Angela Campbell, Erminia Fontana, Francesca Fiorentini, Camilla Fowst, Victoria A. Paty, Odessa Lankford, Mace L. Rothenberg
Journal: Clinical Cancer Research (2004)

Abstract Purpose: This study was performed to determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetics of brostallicin, a nonalkylating DNA minor groove binder and a synthetic derivative of distamycin A, given as a weekly i.v. infusion. Experimental Design: Using an accelerated dose escalation design, patients with advanced solid tumor malignancies were treated with brostallicin administered as a 10-min i.v. infusion on days 1, 8, and 15 of a 28-day cycle. The starting dose of brostallicin was 0.3 mg/m2/week. To study the pharmacokinetic behavior of brostallicin, serial blood samples were obtained before and after the first and last infusions during cycle 1, and in cycles 2 and 4 in a limited number of patients. Results: Fourteen patients received 32 complete cycles of brostallicin. Dose-limiting toxicity was febrile neutropenia and was observed in 3 of 5 patients treated at 4.8 mg/m2/week. The maximum tolerated dose and recommended Phase II dose was 2.4 mg/m2/week. The mean ± SD terminal half-life at the maximum tolerated dose was 4.6 ± 4.1 h. There was moderate distribution of brostallicin into tissues, and the clearance was ∼20% of the hepatic blood flow. The area under the concentration time curve0-∞ of brostallicin increased in a dose-linear fashion. No significant relationship was observed between any plasma pharmacokinetic parameter and clinical toxicities. There were no objective responses during the trial, but 5 patients had stable disease after two cycles of treatment. Conclusions: The dose-limiting toxicity of weekly brostallicin was neutropenia. Systemic exposure increases linearly with dose. The recommended dose for Phase II studies is 2.4 mg/m2 on days 1, 8, and 15 of a 28-day cycle.
Lymphocyte–HEV Interactions in Lymph Nodes of a Sulfotransferase-deficient Mouse
Authors: Annemieke van Zante, Jean-Marc Gauguet, Annette Bistrup, Durwin Tsay, Ulrich H. von Andrian, Steven D. Rosen
Journal: The Journal of Experimental Medicine (2003)

The interaction of L-selectin expressed on lymphocytes with sulfated sialomucin ligands such as CD34 and GlyCAM-1 on high endothelial venules (HEV) of lymph nodes results in lymphocyte rolling and is essential for lymphocyte recruitment. HEC-GlcNAc6ST–deficient mice lack an HEV-restricted sulfotransferase with selectivity for the C-6 position of N-acetylglucosamine (GlcNAc). HEC-GlcNAc6ST−/− animals exhibit faster lymphocyte rolling and reduced lymphocyte sticking in HEV, accounting for the diminished lymphocyte homing. Isolated CD34 and GlyCAM-1 from HEC-GlcNAc6ST−/− animals incorporate ∼70% less sulfate than ligands from wild-type animals. Furthermore, these ligands exhibit a comparable reduction of the epitope recognized by MECA79, a function-blocking antibody that reacts with L-selectin ligands in a GlcNAc-6-sulfate–dependent manner. Whereas MECA79 dramatically inhibits lymphocyte rolling and homing to lymph nodes in wild-type mice, it has no effect on HEC-GlcNAc6ST−/− mice. In contrast, in vitro rolling on purified GlyCAM-1 from HEC-GlcNAc6ST−/− mice, although greatly diminished compared with that on the wild-type ligand, is inhibited by MECA79. Our results demonstrate that HEC-GlcNAc6ST contributes predominantly, but not exclusively, to the sulfation of HEV ligands for L-selectin and that alternative, non-MECA79–reactive ligands are present in the absence of HEC-GlcNAc6ST.
Influence of genetic ancestry on the risk of obstructive sleep apnoea syndrome
Authors: C. Guindalini, F.A.B. Colugnati, R. Pellegrino, R. Santos-Silva, L.R.A. Bittencourt, S. Tufik
Journal: European Respiratory Journal (2010)

The aim of the present study was to evaluate the influence of ethnicity on the risk of developing obstructive sleep apnoea syndrome (OSAS) using genomic analysis methods to estimate ancestry. DNA samples were obtained from 1,010 individuals participating in the São Paulo Epidemiologic Sleep Study, who underwent full-night polysomnography. A total of 31 genetic ancestry-informative markers were selected in order to estimate individual admixture proportions. Of patients with a diagnosis of OSAS, a higher number self-reporting Caucasian ethnicity (65.3%), as well as an increased percentage of European ancestry (78.2±16.7%) and lower percentage of West African ancestry (16.1±15.3%), than among individuals without OSAS (53.6, 73.5±18.1 and 20.1±16.8%, respectively) (p&lt;0.001) was observed. Moreover, after correcting for sex, age, body mass index and socioeconomic status, logistic regression demonstrated that European ancestry was significantly associated with an increased risk of manifesting OSAS (OR 2.80, 95% CI 1.11–7.09). Conversely, West African ancestry was associated with a reduced risk of the OSAS phenotype (OR 0.26, 95% CI 0.09–0.72). This is the first study to incorporate genomic analysis methods to measure the influence of ethnicity on the risk of OSAS. Since genetically determined ancestry may not capture unmeasured cultural and lifestyle differences, the contribution of environmental factors to the current findings should not be disregarded.
The diversity of the influenza-specific primary B-cell repertoire in BALB/c mice.
Authors: M P Cancro, W Gerhard, N R Klinman
Journal: The Journal of Experimental Medicine (1978)

The primary immune response of BALB/c mice to influenza (PR8) hemagglutinin (HA), a complex protein antigen, has been examined by the splenic focus assay, and the resulting monoclonal anti-HA antibodies have been characterized by their reactivity with heterologous viruses. The analysis of the primary B-cell response to HA revealed marked differences from responses previously defined for haptenic determinants. There were following differences: (a) the frequency of HA-specific B cells in both conventional and germ-free BALB/c mice was 1 in 1.0-1.5 X 10(5) splenic B cells, which is substantially lower than the frequency of B cells responsive to various simple haptenic determinants; (b) monoclonal anti-HA antibodies were predominantly of the IgA or IgM isotypes instead of IgG, which dominates antihapten responses; and (c) after immunization, the frequency of anti-HA-specific B cells increases by 10- to 50-fold, which is much greater increase than that observed after immunization with haptenic determinants. Fine specificity analysis of primary monoclonal HA-specific antibodies revealed extensive diversity and a considerable overlap with the specificities obtained from immune mice. Given the low overall frequency of HA-specific B cells, it could be calculated that the representation of most HA-specific clonotypes within the B-cell repertoire could not exceed 1 in 10(7) B cells. These findings indicate that the primary B-cell clonotype repertoire is extremely diverse and largely antigen independent in its generation.
The duck genome and transcriptome provide insight into an avian influenza virus reservoir species
Authors: Yinhua Huang, Yingrui Li, David W Burt, Hualan Chen, Yong Zhang, Wubin Qian, Heebal Kim, Shangquan Gan, Yiqiang Zhao, Jianwen Li, Kang Yi, Huapeng Feng, Pengyang Zhu, Bo Li, Qiuyue Liu, Suan Fairley, Katharine E Magor, Zhenlin Du, Xiaoxiang Hu, Laurie Goodman, Hakim Tafer, Alain Vignal, Taeheon Lee, Kyu-Won Kim, Zheya Sheng, Yang An, Steve Searle, Javier Herrero, Martien A M Groenen, Richard P M A Crooijmans, Thomas Faraut, Qingle Cai, Robert G Webster, Jerry R Aldridge, Wesley C Warren, Sebastian Bartschat, Stephanie Kehr, Manja Marz, Peter F Stadler, Jacqueline Smith, Robert H S Kraus, Yaofeng Zhao, Liming Ren, Jing Fei, Mireille Morisson, Pete Kaiser, Darren K Griffin, Man Rao, Frederique Pitel, Jun Wang, Ning Li
Journal: Nature Genetics (2013)

Ning Li and colleagues report the whole-genome sequence of the duck, Anas platyrhynchos, a natural host of avian influenza viruses. They examine host response to infection by comparing the lung transcriptomes of ducks that were infected with influenza A viruses. The duck (Anas platyrhynchos) is one of the principal natural hosts of influenza A viruses. We present the duck genome sequence and perform deep transcriptome analyses to investigate immune-related genes. Our data indicate that the duck possesses a contractive immune gene repertoire, as in chicken and zebra finch, and this repertoire has been shaped through lineage-specific duplications. We identify genes that are responsive to influenza A viruses using the lung transcriptomes of control ducks and ones that were infected with either a highly pathogenic (A/duck/Hubei/49/05) or a weakly pathogenic (A/goose/Hubei/65/05) H5N1 virus. Further, we show how the duck's defense mechanisms against influenza infection have been optimized through the diversification of its β-defensin and butyrophilin-like repertoires. These analyses, in combination with the genomic and transcriptomic data, provide a resource for characterizing the interaction between host and influenza viruses.
Episodic memory: It's about time (and space)
Authors: Lynn Nadel, Lee Ryan, Katrina Keil, Karen Putnam
Journal: Behavioral and Brain Sciences (1999)

Aggleton &amp; Brown rightly point out the shortcomings of the medial temporal lobe hypothesis as an approach to anterograde amnesia. Their broader perspective is a necessary corrective, and one hopes it will be taken very seriously. Although they correctly note the dangers of conflating recognition and recall, they themselves make a similar mistake in discussing familiarity; we suggest an alternative approach. We also discuss implications of their view for an analysis of retrograde amnesia. The notion that there are two routes by which the hippocampus can reactivate neuronal ensembles in the neocortex could help us understand some currently puzzling facts about the dynamics of memory consolidation.
Appointment of Certifying Surgeons under the New Factory Bill
Authors: J. I. Ikin
Journal: BMJ (1843)

71of opium, yet " he was decidedly of opinion that the child's death was caused by opium."Dr. Babington also thought the remedy, not the disease, produced death.He tells us the heart disease arose from "a difficulty of propelling blood," but does not say how he knows that the enlargement of the heart was not congenital.It should not become fashionable to punish one mani upoIi the speculative opinions and theories of other men.We suppose tliat, generally speaking, when there are doubts, the accused party will have the benefit of them; but, as far as I am able to judge from experience, this verdict was given against the party accused, under false im- pressions, not upon facts.Anid if the judgment of the medical men of England were takeni by vote, whe- ther the evidence givell at that inquest or these remnarks and opinions are thc most reasonable, I should not fear the result.Remaining, Gentlemen,
PCR on cerebrospinal fluid to show influenza-associated acute encephalopathy or encephalitis
Authors: Shinji Fujimoto, Masanori Kobayashi, Osamu Uemura, Mitsuji Iwasa, Tsunesaburo Ando, Toshiyuki Katoh, Chie Nakamura, Noriei Maki, Hajime Togari, Yoshiro Wada
Journal: The Lancet (1998)
Cytogenetic Profile Predicts Prognosis of Patients With Clear Cell Renal Cell Carcinoma
Authors: Tobias Klatte, P. Nagesh Rao, Michela de Martino, Jeffrey LaRochelle, Brian Shuch, Nazy Zomorodian, Jonathan Said, Fairooz F. Kabbinavar, Arie S. Belldegrun, Allan J. Pantuck
Journal: Journal of Clinical Oncology (2009)

The majority of cytogenetic studies in renal cell carcinoma (RCC) have been impaired by small sample size, retrospective character, and lack of a survival end point. We prospectively studied the prognostic impact of cytogenetic abnormalities on a larger cohort of patients having up to 108 months of follow-up.Tumors of 282 patients who underwent nephrectomy for clear cell RCC were cytogenetically analyzed. Results were correlated with pathological factors and disease-specific survival.The most frequently observed cytogenetic abnormalities were loss of 3p (60%), gain of 5q (33%), loss of 14q (28%), trisomy 7 (26%), loss of 8p (20%), loss of 6q (17%), loss of 9p (16%), loss of 4p (13%), and loss of chromosome Y in men (55%). Tumors with loss of 3p presented at lower TNM stages. Loss of 4p, 9p, and 14q were all associated with higher TNM stages, higher grade, and greater tumor size. A deletion of 3p was associated with better prognosis (P = .03), while loss of 4p (P < .001), loss of 9p (P < .01), and loss of 14q (P < .01) were each associated with worse prognosis. Loss of the Y chromosome led to improved progression-free survival in metastatic patients (P = .02). In multivariate analysis, loss of 9p was retained as an independent prognostic factor.This cytogenetic study serves as a proof of principal that genetic information, such as loss of chromosome 9, can be obtained from widely available technology, and can provide additional prognostic information to standard clinicopathologic variables.
Comparison of the prognostic value of genomic grade index, Ki67 expression and mitotic activity index in early node-positive breast cancer patients
Authors: F. Bertucci, P. Finetti, H. Roche, J.M. Le Doussal, L. Marisa, A.L. Martin, M. Lacroix-Triki, C. Blanc-Fournier, J. Jacquemier, H. Peyro-Saint-Paul, P. Viens, C. Sotiriou, D. Birnbaum, F. Penault-Llorca
Journal: Annals of Oncology (2012)