tbuckley/cabot-search huggingface dataset:
Gene Expression Profiling of Acute Myeloid Leukemia with Translocation t(8;16)(p11;p13) and <i>MYST3-CREBBP</i> Rearrangement Reveals a Distinctive Signature with a Specific Pattern of <i>HOX</i> Gene Expression
Authors: Mireia Camós, Jordi Esteve, Pedro Jares, Dolors Colomer, María Rozman, Neus Villamor, Dolors Costa, Ana Carrió, Josep Nomdedéu, Emili Montserrat, Elías Campo
Journal: Cancer Research (2006)

Abstract Acute myeloid leukemia (AML) with translocation t(8;16)(p11;p13) is an infrequent leukemia subtype with characteristic clinicobiological features. This translocation leads to fusion of MYST3 (MOZ) and CREBBP (CBP) genes, probably resulting in a disturbed transcriptional program of a myelomonocytic precursor. Nonetheless, its gene expression profile is unknown. We have analyzed the gene expression profile of 23 AML patients, including three with molecularly confirmed MYST3-CREBBP fusion gene, using oligonucleotide U133A arrays (Affymetrix). MYST3-CREBBP cases clustered together and clearly differentiated from samples with PML-RARα, RUNX1-RUNX1T1, and CBFβ-MYH11 rearrangements. The relative expression of 46 genes, selected according to their differential expression in the high-density array study, was analyzed by low-density arrays in an additional series of 40 patients, which included 7 MYST3-CREBBP AML cases. Thus, genes such as prolactin (PRL) and proto-oncogene RET were confirmed to be specifically overexpressed in MYST3-CREBBP samples whereas genes such as CCND2, STAT5A, and STAT5B were differentially underexpressed in this AML category. Interestingly, MYST3-CREBBP AML exhibited a characteristic pattern of HOX expression, with up-regulation of HOXA9, HOXA10, and cofactor MEIS1 and marked down-regulation of other homeobox genes. This profile, with overexpression of FLT3, HOXA9, MEIS1, AKR7A2, CHD3, and APBA2, partially resembles that of AML with MLL rearrangement. In summary, this study shows the distinctive gene expression profile of MYST3-CREBBP AML, with overexpression of RET and PRL and a specific pattern of HOX gene expression. (Cancer Res 2006; 66(14): 6947-54)
Do GOLD stages of COPD severity really correspond to differences in health status?
Authors: R. Antonelli-Incalzi, C. Imperiale, V. Bellia, F. Catalano, N. Scichilone, R. Pistelli, F. Rengo
Journal: European Respiratory Journal (2003)

The purpose of this study was to assess whether different stages of chronic obstructive pulmonary disease (COPD) severity defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria correlate with meaningful differences in health status. A total of 381 COPD patients, aged 73+/-6 yrs, were classified in the five GOLD stages. Disease-specific (St George Respiratory Questionnaire (SGRQ)) and generic indexes of health status were measured in all patients. Multivariate analysis of covariance or Kruskal Wallis tests were used to compare health status indexes across the spectrum of GOLD stages of COPD severity. GOLD stages of COPD severity significantly differed in SGRQ components and Barthel's index, but not in the indexes assessing cognitive and affective status and quality of sleep. The largest variation in health status was observed at the transition from stage IIa to stage IIb, while there were no other significant differences between consecutive stages. Both female sex and comorbidity were associated with a greater impact of COPD on the health status. In conclusion, the upper limit of stage IIb (forced expiratory volume in one second of 49%) marks a threshold for dramatic worsening of health status. Progression of chronic obstructive pulmonary disease severity from stage 0 to stage IIa does not correspond to any meaningful difference in health status.
Impact of Exacerbations on Emphysema Progression in Chronic Obstructive Pulmonary Disease
Authors: Naoya Tanabe, Shigeo Muro, Toyohiro Hirai, Tsuyoshi Oguma, Kunihiko Terada, Satoshi Marumo, Daisuke Kinose, Emiko Ogawa, Yuma Hoshino, Michiaki Mishima
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Low-attenuation areas assessed by computed tomography reflect the extent of pathological emphysema and correlate with airflow limitation and mortality in patients with chronic obstructive pulmonary disease. The cumulative size distribution of low-attenuation area clusters follows a power law characterized by an exponent, D. The values of D reflect the complexity of the terminal airspace geometry and sensitively detect alveolar structural changes. Exacerbations of chronic obstructive pulmonary disease have a negative impact on lung function and prognosis. However, the impact on emphysema progression remains unclear.We investigated the relationship between exacerbation and emphysema progression assessed by computed tomography in patients with chronic obstructive pulmonary disease.Exacerbations were prospectively recorded for 2 years. Annual changes in computed tomography parameters of emphysema were compared between patients with and without a history of exacerbations.In patients with exacerbations, increases in the percentage of low-attenuation areas and decreases in D were greater than in patients without exacerbations. To interpret these results, we established a novel simulation model and found that not only enlargement of preexisting low-attenuation areas but also coalescence of adjoining low-attenuation areas due to alveolar wall destruction caused emphysema progression in patients with exacerbations.This is the first longitudinal study to demonstrate that exacerbations are involved in emphysema progression in patients with chronic obstructive pulmonary disease. Emphysema progression should be evaluated as part of the outcomes of exacerbations in the management of chronic obstructive pulmonary disease.
Use of a catheter tip electromagnetic velocity meter to determine the cardiovascular effects of glucagon
Authors: R. L. Katz, C. J. Mills
Journal: Cardiovascular Research (1971)

The cardiovascular effects of glucagon were determined in anaesthetized dogs. Glucagon increased heart rate and myocardial contractility. Aortic, renal, and mesenteric flow increased. Neither the cardiac nor vascular dilating actions of glucagon were prevented by β-adrenergic blockade. Glucagon had a biphasic effect on carotid artery flow; an initial increase followed by a decrease. With femoral flow the initial response was variable, but the late response was usually a decrease in flow. These results were seen with intravenous injection. Intra-arterial injection of glucagon produced an increase in mesenteric, renal, carotid, and femoral flow. Results obtained with the intravascular catheter tip electromagnetic velocity probe were similar to those obtained with the external electromagnetic cuff flowmeter. An important advantage of the catheter tip probe over the cuff probe was that the former could be manipulated into various arteries via a small incision in a peripheral artery, thus avoiding extensive surgical dissection.
Population-based genetic alterations in Ewing’s tumors from Japanese and European Caucasian patients
Authors: T. Ozaki, K.-L. Schaefer, D. Wai, R. Yokoyama, S. Ahrens, R. Diallo, T. Hasegawa, T. Shimoda, S. Hirohashi, A. Kawai, N. Naito, Y. Morimoto, H. Inoue, W. Boecker, H. Juergens, W. Winkelmann, B. Dockhorn-Dworniczak, C. Poremba
Journal: Annals of Oncology (2002)
Clinical Outcome of Children With Newly Diagnosed Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia Treated Between 1995 and 2005
Authors: Maurizio Aricò, Martin Schrappe, Stephen P. Hunger, William L. Carroll, Valentino Conter, Stefania Galimberti, Atsushi Manabe, Vaskar Saha, André Baruchel, Kim Vettenranta, Keizo Horibe, Yves Benoit, Rob Pieters, Gabriele Escherich, Lewis B. Silverman, Ching-Hon Pui, Maria Grazia Valsecchi
Journal: Journal of Clinical Oncology (2010)

In a previous analysis of 326 children with Philadelphia chromosome (Ph) -positive acute lymphoblastic leukemia (ALL) treated between 1986 and 1996, hematopoietic stem-cell transplantation from HLA-matched related donors, but not from unrelated donors, offered a superior outcome than chemotherapy alone. To evaluate the impact of recent improvements in chemotherapy and transplantation, we performed a similar analysis on patients treated in the following decade.We analyzed 610 patients with Ph-positive ALL treated between 1995 and 2005 without tyrosine kinase inhibitor therapy. The median follow-up duration was 6.3 years.Complete remission was achieved in 89% of patients. The 7-year event-free survival and overall survival rates were superior in the present cohort compared with the previous cohort (32.0% ± 2.0% v 25.0% ± 3.0, respectively, P = .007; and 44.9% ± 2.2% v 36.0% ± 3.0%, respectively, P = .017). Compared with chemotherapy alone, transplantation with matched related donors or unrelated donors in first remission (325 patients) showed an advantage with increasing follow-up, suggesting greater protection against late relapses (hazard ratio at 5 years, 0.37; P < .001). In the multivariate Cox regression analysis accounting for treatment (transplantation v no transplantation), age, leukocyte count, and early response had independent impact on treatment outcome.Clinical outcome of children and adolescents with Ph-positive ALL has improved with advances in transplantation and chemotherapy. Transplantations with matched related donors and unrelated donors were equivalent and offered better disease control compared with chemotherapy alone. Age, leukocyte count, and early treatment response were independent prognostic indicators. The results of this study will serve as a historical reference to evaluate the therapeutic impact of tyrosine kinase inhibitors on the outcome of Ph-positive ALL.
Diabetes Management in the Age of National Health Reform
Authors: Robert E. Ratner
Journal: Diabetes Care (2011)

National health care policy is a relatively new concept in the U.S. with a rather tortured and painful past (1). President Theodore Roosevelt's initial efforts to establish national health insurance in 1912 failed. Twenty-three years later, his cousin Franklin Roosevelt incorporated Maternal and Child Health Grants into the original Social Security Act passed in 1935 in the midst of the New Deal. His successor, Harry Truman, attempted to extend medical care to the poor through grant authorization to the states, but met opposition from the American Medical Association, and both Senate and House versions of the bill foundered.

Until recently, the Medicare and Medicaid programs signed into law by Lyndon Johnson in 1965 were the most significant legislation addressing health care delivery and financing in the U.S.—extending care to the elderly, the disabled, and the poor. Since then, many have tried to establish national coverage, but neither the Republicans nor the Democrats have had success. Richard Nixon's Comprehensive Health Insurance Plan in 1972 was very much like the Obama Plan presented in 2009, but was considered inadequate to meet the national needs by the Democratic opposition. The Clinton administration's attempt to introduce the Health Security Act was met with bipartisan opposition so fierce that the bill was never brought to the floor of either chamber for a vote. The Patient Protection and Affordable Care Act (PPACA) of 2010 is clearly the most sweeping revision of health care delivery and finance since the introduction of Medicare and Medicaid. The questions surrounding it are numerous, and its impact remains to be seen; however, it is worthwhile to examine why health reform is necessary.

Independent of the source of payment, per capita health care expenditures in the U.S. rose over the last 30 years from approximately $1,000 to $7,000 (adjusted for inflation) (Fig. …
Constraining color categories: The problem of the baby and the bath water
Authors: I. Abramov, J. Gordon
Journal: Behavioral and Brain Sciences (1997)

No crucial experiment demonstrates that four hue categories are needed to describe color appearance. Instead, converging lines of evidence suggest that the terms red, yellow, green, and blue are sufficient and precise enough for deriving color discrimination functions and for a useful model constraining relations between color appearance and neuronal responses. Such a model need not be based on linguistic universals. Until something better is available, this “standard model” holds.
Plasmacytoid predendritic cells initiate psoriasis through interferon-α production
Authors: Frank O. Nestle, Curdin Conrad, Adrian Tun-Kyi, Bernhard Homey, Michael Gombert, Onur Boyman, Günter Burg, Yong-Jun Liu, Michel Gilliet
Journal: The Journal of Experimental Medicine (2005)

Psoriasis is one of the most common T cell–mediated autoimmune diseases in humans. Although a role for the innate immune system in driving the autoimmune T cell cascade has been proposed, its nature remains elusive. We show that plasmacytoid predendritic cells (PDCs), the natural interferon (IFN)-α–producing cells, infiltrate the skin of psoriatic patients and become activated to produce IFN-α early during disease formation. In a xenograft model of human psoriasis, we demonstrate that blocking IFN-α signaling or inhibiting the ability of PDCs to produce IFN-α prevented the T cell–dependent development of psoriasis. Furthermore, IFN-α reconstitution experiments demonstrated that PDC-derived IFN-α is essential to drive the development of psoriasis in vivo. These findings uncover a novel innate immune pathway for triggering a common human autoimmune disease and suggest that PDCs and PDC-derived IFN-α represent potential early targets for the treatment of psoriasis.
Interstitial lung diseases associated with amyopathic dermatomyositis
Authors: T. Suda, T. Fujisawa, N. Enomoto, Y. Nakamura, N. Inui, T. Naito, D. Hashimoto, J. Sato, M. Toyoshima, H. Hashizume, K. Chida
Journal: European Respiratory Journal (2006)

The aim of the present study was to clarify the clinical characteristics and prognosis of patients with interstitial lung disease (ILD) associated with amyopathic dermatomyositis (ILD-ADM). The study consisted of 14 consecutive patients with ILD-ADM. Patients were classified into two categories, acute/subacute and chronic forms, according to the clinical presentation of ILD. The clinical features, responsiveness to therapy, and prognosis between the two forms were compared. Nine ILD-ADM patients were categorised as the acute/subacute form, and five as the chronic form. Arterial oxygen tension was significantly lower in the acute/subacute ILD than chronic ILD patients. On high-resolution computed tomography, ground-glass opacities were frequently found in the two forms, but consolidation was more common in acute/subacute ILD than chronic ILD. Bronchoalveolar lavage analysis showed higher numbers of total cells and lymphocytes in acute/subacute ILD than chronic ILD. Histologically, the most common finding was nonspecific interstitial pneumonia in the two forms, while diffuse alveolar damage was only found in acute/subacute ILD. Acute/subacute ILD was generally resistant to therapy, while chronic ILD responded well. Notably, the mortality of acute/subacute ILD was much higher than that of chronic ILD (67 versus 0%, respectively). In conclusion, interstitial lung disease associated with amyopathic dermatomyositis includes two different forms, the acute/subacute and chronic forms, with distinct prognoses.
Influence of Diphosphopyridine Nucleotide (DPN) on Photodynamic Effects of Low Concentrations of Methylene Blue in Ascites Tumor Cells
Authors: J C Hunter, D Burk, M W Woods
Journal: JNCI Journal of the National Cancer Institute (1967)

When four thiazine dyes were added to ascites cell suspensions to yield 10(-4) M final concentration, the order of increasing effectiveness, for both stimulation of aerobic glycolysis in the dark and inhibition of aerobic glycolysis in the presence of added light, was thionine, methylene blue, thionine blue, and new methylene blue. After illumination, inhibition of anaerobic glycolysis occurred in the same respective dye order. Studies in depth of photodynamic effects of methylene blue on Ehrlich ascites cells revealed marked metabolic effects of light and 10(-4) M dye or lower. Diphosphopyridine nucleotide (DPN) with 5 X 10(-6) M methylene blue and light almost completely abolished the Pasteur effect after only 10 minutes' illumination of the dye-cell-coenzyme system. The ability of light, methylene blue, and exogenous DPN to specifically inhibit the Pasteur effect is consistent with the view that DPN can be important to proper functioning of the Pasteur effect mechanism. It is suggested that perfusion with some of the less toxic photosensitive dyes in combination with conventional or lasered light may result in significant selective destruction of tumor cells in vivo.
Ll-37, the Neutrophil Granule–And Epithelial Cell–Derived Cathelicidin, Utilizes Formyl Peptide Receptor–Like 1 (Fprl1) as a Receptor to Chemoattract Human Peripheral Blood Neutrophils, Monocytes, and T Cells
Authors: De Yang, Qian Chen, Albert P. Schmidt, G. Mark Anderson, Ji Ming Wang, Joseph Wooters, Joost J. Oppenheim, Oleg Chertov
Journal: The Journal of Experimental Medicine (2000)

We have previously shown that antimicrobial peptides like defensins have the capacity to mobilize leukocytes in host defense. LL-37 is the cleaved antimicrobial 37-residue, COOH-terminal peptide of hCAP18 (human cationic antimicrobial protein with a molecular size of 18 kD), the only identified member in humans of a family of proteins called cathelicidins. LL-37/hCAP18 is produced by neutrophils and various epithelial cells. Here we report that LL-37 is chemotactic for, and can induce Ca(2+) mobilization in, human monocytes and formyl peptide receptor-like 1 (FPRL1)-transfected human embryonic kidney 293 cells. LL-37-induced Ca(2+) mobilization in monocytes can also be cross-desensitized by an FPRL1-specific agonist. Furthermore, LL-37 is also chemotactic for human neutrophils and T lymphocytes that are known to express FPRL1. Our results suggest that, in addition to its microbicidal activity, LL-37 may contribute to innate and adaptive immunity by recruiting neutrophils, monocytes, and T cells to sites of microbial invasion by interacting with FPRL1.
Superinduction of interleukin 8 mRNA in activated monocyte derived macrophages from rheumatoid arthritis patients
Authors: R. J T Rodenburg, F. H J van den Hoogen, P. Barrera, W. J van Venrooij, L. B A van de Putte
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVE</h3> Synovial inflammation in patients with rheumatoid arthritis (RA) is characterised by the presence of large numbers of highly activated monocytes and macrophages. The importance of these cells in the aethiopathogenesis and prognosis of RA is increasingly recognised. The object of this report is to determine whether monocytes and monocyte derived macrophages of RA patients produce increased cytokine mRNA levels. <h3>METHODS</h3> Monocyte derived macrophages from RA patients and healthy controls were cultured either in the absence or presence of lipopolysaccharide. The expression levels of the mRNAs encoding GAPDH, interleukin 1β (IL1β), IL8, and α<sub>2</sub>macroglobulin in these cells were analysed by reverse transcriptase-polymerase chain reaction (RT-PCR). <h3>RESULTS</h3> Activated monocyte derived macrophages from RA patients produce significantly higher IL8 mRNA levels than activated macrophages from healthy controls. By contrast, resting RA and control macrophages produce similar levels of IL8 mRNA. Culturing of activated macrophages in the presence of RA or control sera has no effect on the expression levels of IL8 mRNA. No significant differences between RA and control macrophages were observed in the expression levels of IL1β and α<sub>2</sub> macroglobulin mRNAs. <h3>CONCLUSION</h3> These data indicate that the increased IL8 mRNA production capacity of RA macrophages upon activation is an intrinsic property of these cells, and is not attributable to factors present in the circulation. Based on these observations, it is postulated that this innate hyper-responsiveness of RA macrophages contributes to the high IL8 levels present in the synovial fluid of rheumatoid joints, and is implicated in the chemotactic gradient leading to the homing of leucocytes to the joints.
ADULT T-CELL LYMPHOMA-LEUKAEMIA IN BLACKS FROM THE WEST INDIES
Authors: D Catovsky, M Rose, A.W.G Goolden, J.M White, G Bourikas, A.I Brownell, W.A Blattner, M.F Greaves, D.A.G Galton, D.R Mccluskey, I Lampert, R Ireland, J.M Bridges, R.C Gallo
Journal: The Lancet (1982)
Changes in presentation, treatment, and outcomes of adult low-grade gliomas over the past fifty years
Authors: R. S. Youland, D. A. Schomas, P. D. Brown, C. Nwachukwu, J. C. Buckner, C. Giannini, I. F. Parney, N. N. Laack
Journal: Neuro-Oncology (2013)

To identify changes in patient presentation, treatment, and outcomes of low-grade gliomas (LGGs) over the past 50 years. Records of 852 adults who received a diagnosis at Mayo Clinic from 1960 through 2011 with World Health Organization grade II LGGs were reviewed and grouped by those who received a diagnosis before (group I: 1960–1989) and after (group II: 1990–2011) the routine use of postoperative MRI. Median follow-up was 23.3 and 8.7 years for groups I and II, respectively. Patients in group I more often presented with seizures, headaches, sensory/motor impairment, and astrocytoma histology. Over time, more gross total resections (GTRs) were achieved, fewer patients received postoperative radiotherapy (PORT), and more received chemotherapy. Median progression-free survival (PFS) and overall survival (OS) were 4.4 and 8.0 years, respectively. Although PFS was similar, 10-year OS was better in group II (47%) than in group I (33%; P < .0001). Improved PFS in multivariate analysis was associated with group I patients, nonastrocytoma histology, small tumor size, successful GTR, or radical subtotal resection (rSTR), PORT, and postoperative chemotherapy. Factors associated with improved OS in multivariate analysis were younger age, nonastrocytoma histology, small tumor size, and GTR/rSTR. OS for LGG has improved over the past 50 years, despite similar rates of progression. In the modern cohort, more patients are receiving a diagnosis of oligodendroglioma and are undergoing extensive resections, both of which are associated with improvements in OS. Because of risk factor stratification by clinicians, the use of PORT has decreased and is primarily being used to treat high-risk tumors in modern patients.
Methyl donor deficiency impairs fatty acid oxidation through PGC-1α hypomethylation and decreased ER-α, ERR-α, and HNF-4α in the rat liver
Authors: Shabnam Pooya, Sébastien Blaise, Maira Moreno Garcia, Jean Giudicelli, Jean-Marc Alberto, Rosa-Maria Guéant-Rodriguez, Elise Jeannesson, Naig Gueguen, Aude Bressenot, Bénédicte Nicolas, Yves Malthiery, Jean-Luc Daval, Laurent Peyrin-Biroulet, Jean-Pierre Bronowicki, Jean-Louis Guéant
Journal: Journal of Hepatology (2012)