tbuckley/cabot-search huggingface dataset:
Microarray Analysis of Epigenetic Silencing of Gene Expression in the KAS-6/1 Multiple Myeloma Cell Line
Authors: Celine Pompeia, David R. Hodge, Christoph Plass, Yue-Zhong Wu, Victor E. Marquez, James A. Kelley, William L. Farrar
Journal: Cancer Research (2004)

The epigenetic control of gene transcription in cancer has been the theme of many recent studies and therapeutic approaches. Carcinogenesis is frequently associated with hypermethylation and consequent down-regulation of genes that prevent cancer, e.g., those that control cell proliferation and apoptosis. We used the demethylating drug zebularine to induce changes in DNA methylation, then examined patterns of gene expression using cDNA array analysis and Restriction Landmark Genomic Scanning followed by RNase protection assay and reverse transcription-PCR to confirm the results. Microarray studies revealed that many genes were epigenetically regulated by methylation. We concluded that methylation decreased the expression of, or silenced, several genes, contributing to the growth and survival of multiple myeloma cells. For example, a number of genes (BAD, BAK, BIK, and BAX) involved in apoptosis were found to be suppressed by methylation. Sequenced methylation-regulated DNA fragments identified by Restriction Landmark Genomic Scanning were found to contain CpG islands, and some corresponded to promoters of genes that were regulated by methylation. We also observed that after the removal of the demethylating drug, the addition of interleukin 6 restored CpG methylation and re-established previously silenced gene patterns, thus implicating a novel role of interleukin 6 in processes regulating epigenetic gene repression and carcinogenesis.
language impairment and colour categories
Authors: jules davidoff, claudio luzzatti
Journal: Behavioral and Brain Sciences (2005)

goldstein (1948) reported multiple cases of failure to categorise colours in patients that he termed amnesic or anomic aphasics. these patients have a particular difficulty in producing perceptual categories in the absence of other aphasic impairments. we hold that neuropsychological evidence supports the view that the task of colour categorisation is logically impossible without labels.
Eliciting the Low-Activity Aldehyde Dehydrogenase Asian Phenotype by an Antisense Mechanism Results in an Aversion to Ethanol
Authors: Eric Garver, Guang-chou Tu, Qing-Na Cao, Maria Aini, Feng Zhou, Yedy Israel
Journal: The Journal of Experimental Medicine (2001)

A mutation in the gene encoding for the liver mitochondrial aldehyde dehydrogenase (ALDH2-2), present in some Asian populations, lowers or abolishes the activity of this enzyme and results in elevations in blood acetaldehyde upon ethanol consumption, a phenotype that greatly protects against alcohol abuse and alcoholism. We have determined whether the administration of antisense phosphorothioate oligonucleotides (ASOs) can mimic the low-activity ALDH2-2 Asian phenotype. Rat hepatoma cells incubated for 24 h with an antisense oligonucleotide (ASO-9) showed reductions in ALDH2 mRNA levels of 85% and ALDH2 (half-life of 22 h) activity of 55% equivalent to a >90% inhibition in ALDH2 synthesis. Glutamate dehydrogenase mRNA and activity remained unchanged. Base mismatches in the oligonucleotide rendered ASO-9 virtually inactive, confirming an antisense effect. Administration of ASO-9 (20 mg/kg/day for 4 d) to rats resulted in a 50% reduction in liver ALDH2 mRNA, a 40% inhibition in ALDH2 activity, and a fourfold (P < 0.001) increase in circulating plasma acetaldehyde levels after ethanol (1 g/kg) administration. Administration of ASO-9 to rats by osmotic pumps led to an aversion (-61%, P < 0.02) to ethanol. These studies provide a proof of principle that specific inhibition of gene expression can be used to mimic the protective effects afforded by the ALDH2-2 phenotype.
Pleural infection on the increase but with a better evidence base to inform clinical care
Authors: N. M. Rahman, N. A. Maskell
Journal: Thorax (2011)

Infection of the pleural space is an ancient disease, with the earliest recorded description more than 5000 years ago,1 and the first consistent description of its manifestations and treatment credited to the father of modern medicine, Hippocrates.2 Open thoracic drainage, with its associated high mortality, remained the standard treatment for pleural infection until the influenza pandemic of 1919, when closed tube drainage techniques described in the 19th century3 4 were used, and significantly reduced the associated mortality.5 The treatment principles described almost 100 years ago remain to this day in the treatment of pleural infection.6

For many years, pleural infection was considered to be a result of ‘pneumonia gone bad’ with fluid leaking out of the infected lung parenchyma resulting in an infected fluid collection which was poorly accessible to the immune system. The term ‘parapneumonic effusion’ exemplifies this possible aetiology. However, recent studies7 describing the microbiology associated with pleural infection suggest that this may be a too simplistic understanding of the pathological processes occurring. There are markedly different bacteriological patterns in pleural infection7 compared with pneumonia, suggesting microbiologically distinct diseases. Nonetheless, the more widespread use of early antibiotic therapy for pneumonia may be expected to result in decreasing rates of pleural infection, if all pleural infection is simply a complication of pneumonia not treated early enough.

Recent evidence suggests that this may …
Exploring the Benefits of Early Access to Palliative Care in Advanced Lung Cancer: Living Better, Living Longer, or Both?
Authors: Iain B. Tan, Grace S. Pang, Alethea Yee, Sze-Huey Tan, Eng Huat Tan, Min-Han Tan
Journal: Journal of Clinical Oncology (2012)

TO THEEDITOR: The article by Greer et al 1 explores the effects of earlyaccesstopalliativecareonpatternsofchemotherapyadministration and hospice use. This is a secondary analysis of a randomized trial. 2 From available information (clinicaltrials.gov [NCT01038271] andtheirprotocol 2 [onlinesupplement]),theprimaryobjectiveofthis trial was to “access the impact of early integration with palliative care on QOL in patients with advanced NSCLC.” 2 It was statistically poweredtoaccrue120patientstoevaluatechangeinTrialsOutcomeIndex
Octreotide (somatostatin analog) treatment reduces endothelial cell dysfunction in patients with diabetes mellitus
Authors: Andreas Clemens, Martina S. Klevesath, Marion Hofmann, Friedrich Raulf, Mechthild Henkels, Jean Amiral, Markus J. Seibel, Jürgen Zimmermann, Reinhard Ziegler, Peter Wahl, Peter P. Nawroth
Journal: Metabolism (1999)
Perioperative docetaxel, cisplatin, and 5-fluorouracil (DCF) for locally advanced esophageal and gastric adenocarcinoma: a multicenter phase II trial
Authors: L.E. Ferri, S. Ades, T. Alcindor, M. Chasen, V. Marcus, M. Hickeson, G. Artho, M.P. Thirlwell
Journal: Annals of Oncology (2011)
Ventromedial hypothalamus–specific Ptpn1 deletion exacerbates diet-induced obesity in female mice
Authors: Franck Chiappini, Karyn J. Catalano, Jennifer Lee, Odile D. Peroni, Jacqueline Lynch, Abha S. Dhaneshwar, Kerry Wellenstein, Alexandra Sontheimer, Benjamin G. Neel, Barbara B. Kahn
Journal: Journal of Clinical Investigation (2014)

Protein-tyrosine phosphatase 1B (PTP1B) regulates food intake (FI) and energy expenditure (EE) by inhibiting leptin signaling in the hypothalamus. In peripheral tissues, PTP1B regulates insulin signaling, but its effects on CNS insulin action are largely unknown. Mice harboring a whole-brain deletion of the gene encoding PTP1B (Ptpn1) are lean, leptin-hypersensitive, and resistant to high fat diet–induced (HFD-induced) obesity. Arcuate proopiomelanocortin (POMC) neuron–specific deletion of Ptpn1 causes a similar, but much milder, phenotype, suggesting that PTP1B also acts in other neurons to regulate metabolism. Steroidogenic factor-1–expressing (SF-1–expressing) neurons in the ventromedial hypothalamus (VMH) play an important role in regulating body weight, FI, and EE. Surprisingly, Ptpn1 deletion in SF-1 neurons caused an age-dependent increase in adiposity in HFD-fed female mice. Although leptin sensitivity was increased and FI was reduced in these mice, they had impaired sympathetic output and decreased EE. Immunohistochemical analysis showed enhanced leptin and insulin signaling in VMH neurons from mice lacking PTP1B in SF-1 neurons. Thus, in the VMH, leptin negatively regulates FI, promoting weight loss, whereas insulin suppresses EE, leading to weight gain. Our results establish a novel role for PTP1B in regulating insulin action in the VMH and suggest that increased insulin responsiveness in SF-1 neurons can overcome leptin hypersensitivity and enhance adiposity.
Pre-TCRα and TCRα Are Not Interchangeable Partners of TCRβ during T Lymphocyte Development
Authors: Christine Borowski, Xiaoyan Li, Iannis Aifantis, Fotini Gounari, Harald von Boehmer
Journal: The Journal of Experimental Medicine (2004)

In contrast with the αβ T cell receptor (TCR), the pre-TCR spontaneously segregates to membrane rafts from where it signals in a cell-autonomous fashion. The disparate behaviors of these two receptors may stem either from differences inherent to the distinct developmental stages during which they are expressed, or from features intrinsic and unique to the receptor components themselves. Here, we express TCRα precisely at the pre-TCR checkpoint, at levels resembling those of endogenous pre-TCRα (pTα), and in the absence of endogenous pTα. Both in isolation and more dramatically when in competition with pTα, TCRα induced defective proliferation, survival, and differentiation of αβ T lymphocyte precursors, as well as impaired commitment to the αβ T lymphocyte lineage. Substitution of TCRα transmembrane and cytoplasmic domains with those of pTα generated a hybrid molecule possessing enhanced competitive abilities. We conclude that features intrinsic to the pre-TCR, which are absent in TCRα, are essential for its unique function.
Molecular Pathways: Context-Dependent Approaches to Notch Targeting as Cancer Therapy
Authors: Ann Marie Egloff, Jennifer R. Grandis
Journal: Clinical Cancer Research (2012)

Recent high-throughput genomic sequencing studies of solid tumors, including head and neck squamous cell carcinoma (SCC), ovarian cancer, lung adenocarcinoma, glioblastoma, breast cancer, and lung SCC, have highlighted DNA mutation as a mechanism for aberrant Notch signaling. A primary challenge of targeting Notch for treatment of solid malignancies is determining whether Notch signaling is cancer promoting or tumor suppressing for a specific cancer. We compiled reported Notch receptor and ligand missense and nonsense mutations to glean insights into aberrant Notch signaling. Frequencies of coding mutations differed for the 4 NOTCH genes. A total of 4.7% of tumors harbored NOTCH1 missense or nonsense mutations. NOTCH2, and NOTCH3 had similar overall mutation rates of 1.5% and 1.3%, respectively, whereas NOTCH4 mutations were rarer. Notch ligand genes were rarely mutated. The combined mutation frequency and position spectra of the 4 Notch paralogs across the different cancers provide an opportunity to begin to illuminate the different contributions of each Notch paralog to each tumor type and to identify opportunities for therapeutic targeting. Notch signaling pathway activators and inhibitors are currently in early clinical development for treatment of solid malignancies. Defining the status and consequences of altered Notch signaling will be important for selection of appropriate treatment.
Case of Malignant OEdema: Amputation at the Thigh: Recovery
Authors: J. M. Mason
Journal: BMJ (1899)

Ye';;; 'I273 there was some nausea and migraine it was found that the motility of the stomach was very markedly delayed.In this case (Table VI) we see that although the stomach contents, as far as hydrochloric acid was concerned, were practically normal, the volatile acidity on the contrary was very markedly increased; in fact, the average was not less
HLA antigen familial study in complete Behcet's syndrome affecting three sisters.
Authors: J L Villanueva, J Gonzalez-Dominguez, R Gonzalez-Fernandez, J L Prada, J Pena, R Solana
Journal: Annals of the Rheumatic Diseases (1993)

Behçet9s disease is a multisystemic disease affecting most organs. Although a tendency towards an association with a certain genetic type and with HLA-B51 is suspected, the incidence of several siblings with Behçet9s disease in a single family is rare. A family, in which three sisters were affected with Behçet9s disease, uveitis being the most severe manifestation, was studied. In this family all siblings were B51 positive. Only the female siblings, however, with a positive identical HLA phenotype: A2, A11, B51, B44, Cw6, Cw5, DR4, DRw13, DRw53, DRw52, DQw7, DQw6, developed the disease symptoms, whereas none of the male siblings was affected.
Hepatic biochemical changes as a result of acute cocaine administration in the mouse
Authors: Scott C. Boyer, Dennis R. Petersen
Journal: Hepatology (1991)

The biochemical mechanism of cocaine hepatotoxicity is thought to involve enzymatic formation of reactive metabolites. The exact hepatocellular effects of these metabolites have yet to be established. This study was designed to monitor, in a time course after an acute cocaine dose, biochemical parameters that are important in cellular defense and homeostasis in vivo. The hepatic parameters measured were ATP as an indicator of cellular energetic status, reduced and oxidized glutathione, NADH and NADPH as measures of redox changes, and thiobarbituric acid-reactive products and microsomal conjugated dienes to determine the extent of lipid peroxidation. In addition, serum ALT levels were determined at each time point to assess the extent of toxicity. Inbred mouse strains selected for their relative sensitivity (male DBA/2Ibg) and resistance (male C57BL/6Ibg) to cocaine-mediated hepatotoxicity were used in this study. Animals were given an acute 50 mg/kg intraperitoneal dose of cocaine, and at various times after administration the hepatic and serum determinations were made. The results of this study confirm the strain difference in cocaine-induced hepatotoxicity and also indicate that there are changes in the biochemistry of the liver that are brought about by acute cocaine administration. In particular, depletions of hepatic GSH, NADH, NADPH and ATP coupled with significant increases in oxidized glutathione were observed in the DBA mouse. C57BL mice showed similar decreases in reduced glutathione, NADH and NADPH but exhibited no significant depletion of hepatic ATP. A similar extent of lipid peroxidation was seen in both mouse strains after cocaine administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Safety and tolerability of eltrombopag versus placebo for treatment of thrombocytopenia in patients with advanced myelodysplastic syndromes or acute myeloid leukaemia: a multicentre, randomised, placebo-controlled, double-blind, phase 1/2 trial
Authors: Uwe Platzbecker, Raymond S M Wong, Amit Verma, Camille Abboud, Sergio Araujo, Tzeon-Jye Chiou, John Feigert, Su-Peng Yeh, Katharina Götze, Norbert-Claude Gorin, Peter Greenberg, Suman Kambhampati, Yoo-Jin Kim, Je-Hwan Lee, Roger Lyons, Marco Ruggeri, Valeria Santini, Gregory Cheng, Jun Ho Jang, Chien-Yuan Chen, Brendan Johnson, John Bennett, Frank Mannino, Yasser Mostafa Kamel, Nicole Stone, Souria Dougherty, Geoffrey Chan, Aristoteles Giagounidis
Journal: The Lancet Haematology (2015)
Phase I and Correlative Biology Study of Cilengitide in Patients With Recurrent Malignant Glioma
Authors: L. Burt Nabors, Tom Mikkelsen, Steven S. Rosenfeld, Fred Hochberg, Narasimha S. Akella, Joy D. Fisher, Gretchen A. Cloud, Yu Zhang, Kathryn Carson, Sabine M. Wittemer, A. Dimitrios Colevas, Stuart A. Grossman
Journal: Journal of Clinical Oncology (2007)

Purpose This multi-institutional phase I trial was designed to determine the maximum-tolerated dose (MTD) of cilengitide (EMD 121974) and to evaluate the use of perfusion magnetic resonance imaging (MRI) in patients with recurrent malignant glioma. Patients and Methods Patients received cilengitide twice weekly on a continuous basis. A treatment cycle was defined as 4 weeks. Treatment-related dose-limiting toxicity (DLT) was defined as any grade 3 or 4 nonhematologic toxicity or grade 4 hematologic toxicity of any duration. Results A total of 51 patients were enrolled in cohorts of six patients to doses of 120, 240, 360, 480, 600, 1,200, 1,800, and 2,400 mg/m 2 administered as a twice weekly intravenous infusion. Three patients progressed early and were inevaluable for toxicity assessment. The DLTs observed were one thrombosis (120 mg/m 2 ), one grade 4 joint and bone pain (480 mg/m 2 ), one thrombocytopenia (600 mg/m 2 ) and one anorexia, hypoglycemia, and hyponatremia (800 mg/m 2 ). The MTD was not reached. Two patients demonstrated complete response, three patients had partial response, and four patients had stable disease. Perfusion MRI revealed a significant relationship between the change in tumor relative cerebral blood flow (rCBF) from baseline and area under the plasma concentration versus time curve after 16 weeks of therapy. Conclusion Cilengitide is well tolerated to doses of 2,400 mg/m 2 , durable complete and partial responses were seen in this phase I study, and clinical response appears related to rCBF changes.
A prospective evaluation of bacteremic patients with chronic liver disease
Authors: Peter F. Barnes, Cecilia Arevalo, Linda S. Chan, Sandra F. Wong, Telfer B. Reynolds
Journal: Hepatology (1988)

We prospectively studied 51 consecutive bacteremic patients with chronic liver disease in order to evaluate their clinical presentation and to assess the relationship of various clinical parameters to mortality. Forty-two patients had alcoholic liver disease and 40 were in Class C, by the Pugh modification of Child’s criteria. Soft tissue infections were the most common source of bacteremia, followed by pneumonia, spontaneous bacterial peritonitis and urinary tract infection. Gram positive organisms were isolated in 69% of cases, and Gram negative ones in 31%. In nine patients, no source of bacteremia was detected. Leukocytosis occurred in 59% of patients and bandemia in only 41%. Although appropriate antibiotic therapy was begun in all cases on admission, 17 patients (33%) died in the hospital. Of 38 clinical parameters evaluated, multivariate analysis revealed that the three variables contributing the most independent information toward predicting in-hospital mortality were the absence of a history of fever, an elevated serum creatinine and marked leukocytosis. Improved understanding of the pathophysiologic relationship between these parameters and patient outcome may enable us to improve the therapy of bacteremic patients with chronic liver disease.
Smoking related COPD and facial wrinkling: is there a common susceptibility?
Authors: B D Patel
Journal: Thorax (2006)

<b>Background:</b> Cigarette smoking causes accelerated facial wrinkling and predisposes to chronic obstructive pulmonary disease (COPD). However, it has long been recognised that there is a subgroup of susceptible smokers who are at increased risk of developing airflow obstruction. We have tested the hypothesis that there is a common susceptibility for the development of COPD and facial wrinkling in cigarette smokers. <b>Methods:</b> One hundred and forty nine current and ex-smokers were recruited from a family based study of COPD genetics, 68 (45.6%) of whom fulfilled the definition of COPD. 124 (83.2%) had no or minor facial wrinkling (Daniell &lt;IV) and 25 (16.8%) were wrinkled (Daniell score ⩾IV). Generalised estimating equations were used to adjust for familial correlations between related individuals and the potential confounding effects of age and pack years smoked. <b>Results:</b> Forced expiratory volume in 1 second (FEV<sub>1</sub>) was significantly lower in those with wrinkles than in those without (mean difference in FEV<sub>1</sub> % predicted −13.7%, 95% CI −27.5 to 0.0, p = 0.05) and facial wrinkling was associated with a substantially increased risk of COPD (adjusted OR 5.0, 95% CI 1.3 to 18.5, p&lt;0.02). The Daniell score correlated with the extent of emphysema on the CT scan (p&lt;0.05) and facial wrinkling was also associated with a greater risk of more extensive emphysema (adjusted OR 3.0, 95% CI 1.0 to 9.3, p = 0.05). <b>Conclusion:</b> Facial wrinkling is associated with COPD in smokers, and both disease processes may share a common susceptibility. Facial wrinkling in smokers may therefore be a biomarker of susceptibility to COPD.
"Toot-Toot" and Health to Boot
Authors: Zenonas Danilevicius
Journal: JAMA (1976)

"Kill the umpire! Get that SOB out of there! Why can't that guy learn to make an easy lay up?" Do these statements sound familiar? Isn't this the voice of a 250-pound fat man with a "beer gut" that gets no exercise himself and is the first to criticize an official, umpire, or player from the stands? Is this decadence, laziness, or, at best, purely a boredom-fighting activity? So state Proctor and Eckerd<sup>1</sup>in their article on therapeutic implications of spectator sports. They end their well-done article by extrapolating as follows: People's emotions are similar to steam locomotives. If you build a fire in the boiler of a locomotive, keep raising the steam pressure, and let it sit on the tracks, sooner or later something will blow. However, if you take it and spin the wheels and toot the whistle, the steam pressure can be kept at a safe
Dual-Affinity Re-Targeting proteins direct T cell–mediated cytolysis of latently HIV-infected cells
Authors: Julia A.M. Sung, Joy Pickeral, Liqin Liu, Sherry A. Stanfield-Oakley, Chia-Ying Kao Lam, Carolina Garrido, Justin Pollara, Celia LaBranche, Mattia Bonsignori, M. Anthony Moody, Yinhua Yang, Robert Parks, Nancie Archin, Brigitte Allard, Jennifer Kirchherr, JoAnn D. Kuruc, Cynthia L. Gay, Myron S. Cohen, Christina Ochsenbauer, Kelly Soderberg, Hua-Xin Liao, David Montefiori, Paul Moore, Syd Johnson, Scott Koenig, Barton F. Haynes, Jeffrey L. Nordstrom, David M. Margolis, Guido Ferrari
Journal: Journal of Clinical Investigation (2015)

Enhancement of HIV-specific immunity is likely required to eliminate latent HIV infection. Here, we have developed an immunotherapeutic modality aimed to improve T cell-mediated clearance of HIV-1-infected cells. Specifically, we employed Dual-Affinity Re-Targeting (DART) proteins, which are bispecific, antibody-based molecules that can bind 2 distinct cell-surface molecules simultaneously. We designed DARTs with a monovalent HIV-1 envelope-binding (Env-binding) arm that was derived from broadly binding, antibody-dependent cellular cytotoxicity-mediating antibodies known to bind to HIV-infected target cells coupled to a monovalent CD3 binding arm designed to engage cytolytic effector T cells (referred to as HIVxCD3 DARTs). Thus, these DARTs redirected polyclonal T cells to specifically engage with and kill Env-expressing cells, including CD4+ T cells infected with different HIV-1 subtypes, thereby obviating the requirement for HIV-specific immunity. Using lymphocytes from patients on suppressive antiretroviral therapy (ART), we demonstrated that DARTs mediate CD8+ T cell clearance of CD4+ T cells that are superinfected with the HIV-1 strain JR-CSF or infected with autologous reservoir viruses isolated from HIV-infected-patient resting CD4+ T cells. Moreover, DARTs mediated CD8+ T cell clearance of HIV from resting CD4+ T cell cultures following induction of latent virus expression. Combined with HIV latency reversing agents, HIVxCD3 DARTs have the potential to be effective immunotherapeutic agents to clear latent HIV-1 reservoirs in HIV-infected individuals.