tbuckley/cabot-search huggingface dataset:
Validation and Extension of the Memorial Sloan-Kettering Prognostic Factors Model for Survival in Patients With Previously Untreated Metastatic Renal Cell Carcinoma
Authors: Tarek M. Mekhail, Rony M. Abou-Jawde, Gabriel BouMerhi, Sareena Malhi, Laura Wood, Paul Elson, Ronald Bukowski
Journal: Journal of Clinical Oncology (2005)

To validate the Motzer et al prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma (RCC) and to identify additional independent prognostic factors.Data were collected on 353 previously untreated metastatic RCC patients enrolled onto clinical trials between 1987 and 2002.Four of the five prognostic factors identified by Motzer were independent predictors of survival. In addition, prior radiotherapy and presence of hepatic, lung, and retroperitoneal nodal metastases were found to be independent prognostic factors. Using the number of metastatic sites as surrogate for individual sites (none or one v two or three sites), Motzer's definitions of risk groups were expanded to accommodate these two additional prognostic factors. Using this expanded criteria, favorable risk is defined as zero or one poor prognostic factor, intermediate risk is two poor prognostic factors, and poor risk is more than two poor prognostic factors. According to Motzer's definitions, 19% of patients were favorable risk, 70% were intermediate risk, and 11% were poor risk; median overall survival times for these groups were 28.6, 14.6, and 4.5 months, respectively (P < .0001). Using the expanded criteria, 37% of patients were favorable risk, 35% were intermediate risk, and 28% were poor risk; median overall survival times of these groups were 26.0, 14.4, and 7.3 months, respectively (P < .0001).These data validate the model described by Motzer et al. Additional independent prognostic factors identified were prior radiotherapy and sites of metastasis. Incorporation of these additional prognostic factors into the Motzer et al model can help better define favorable risk, intermediate risk, and poor risk patients.
974 DIAGNOSTIC ALGORITHM FOR HEPATOCELLULAR CARCINOMA (HCC) IN HYPOVASCULAR NODULE OF THE LIVER; A MULTICENTER NATIONWIDE STUDY
Authors: N. Izumi, K. Tsuchiya, O. Matsui, M. Sata, R. Kuromatsu, F. Moriyasu, Y. Imai, Y. Aoyagi, H. Iijima, S. Arii
Journal: Journal of Hepatology (2011)
The emulation theory of representation: Motor control, imagery, and perception
Authors: Rick Grush
Journal: Behavioral and Brain Sciences (2004)

The emulation theory of representation is developed and explored as a framework that can revealingly synthesize a wide variety of representational functions of the brain. The framework is based on constructs from control theory (forward models) and signal processing (Kalman filters). The idea is that in addition to simply engaging with the body and environment, the brain constructs neural circuits that act as models of the body and environment. During overt sensorimotor engagement, these models are driven by efference copies in parallel with the body and environment, in order to provide expectations of the sensory feedback, and to enhance and process sensory information. These models can also be run off-line in order to produce imagery, estimate outcomes of different actions, and evaluate and develop motor plans. The framework is initially developed within the context of motor control, where it has been shown that inner models running in parallel with the body can reduce the effects of feedback delay problems. The same mechanisms can account for motor imagery as the off-line driving of the emulator via efference copies. The framework is extended to account for visual imagery as the off-line driving of an emulator of the motor-visual loop. I also show how such systems can provide for amodal spatial imagery. Perception, including visual perception, results from such models being used to form expectations of, and to interpret, sensory input. I close by briefly outlining other cognitive functions that might also be synthesized within this framework, including reasoning, theory of mind phenomena, and language.
Circulating tumor cells (CTCs) monitoring in HER2-negative early breast cancer: Implications for secondary anti-HER2 adjuvant treatment strategies
Authors: M. Ignatiadis, M. Perraki, S. Apostolaki, N. Xenidis, E. Stathopoulos, E. Lianidou, M. E. Buyse, C. Sotiriou, V. Georgoulias, D. Mavroudis
Journal: Journal of Clinical Oncology (2008)

11502 Background: We have shown that the detection of peripheral blood CK19mRNA+ and HER2mRNA+ cells predicts poor outcome in early breast cancer and that trastuzumab can effectively eliminate these cells. Methods: We used real-time and nested RT-PCR for the detection of peripheral blood CK19mRNA+ and HER2mRNA+ cells, respectively, before and after adjuvant chemotherapy in 260 HER2-negative (HER2 0,1+ by immunohistochemistry) early breast cancer patients. Furthermore, we compared 3 prognosticators that classify a patient into poor vs good prognosis group: (A:CK19mRNA pre-chemotherapy alone; positive vs negative, B:CK19mRNA pre- and post-chemotherapy; at least once positive vs all negative, C:CK19mRNA and HER2mRNA pre- and post-chemotherapy; see Table) Results: Patient groups and their clinical outcome based on CTCs’ monitoring with CK19mRNA and HER2mRNA pre- and post- chemotherapy are depicted in Table. The median follow-up for patients that did not relapse was 52 months (range 10–106 months). The prognosticators A, B and C classified 114, 140 and 76 of the 260 patients, respectively, to the poor prognosis group. Relapse rates of poor vs good prognosis patients were 26.3% vs 10.9% (p=.001), 24.3% vs 11.1% (p=.003) and 32.9% vs 11.4% (p<.001) for prognosticators A,B and C, respectively. The area under the curve (AUC) values of the receiver operating characteristics (ROC) curve for prognosticators A, B and C were 0.630 (p=.006), 0.622 (p=.010) and 0.653 (p=.001), respectively. Prognosticator C identified patients at high risk of relapse better than the others, subject to further validation. Conclusion: CTCs’ monitoring (two molecular markers, pre- and post-chemotherapy) identifies poor prognosis patients with HER2-negative tumors who are suitable candidates for secondary, anti-HER2, adjuvant treatment strategies. Patients Groups CK19 Pre HER2 Pre CK19 Post HER2 Post Patients Relapses Deaths Good Prognosis 0 Neg Neg Neg Neg 120 184 12 21 3 7 1 Pos Neg Neg Neg 44 7 3 2 Neg Neg Pos Neg 20 2 1 Poor Prognosis 3 Pos Neg Pos Neg 23 76 6 25 4 12 4 Pos Pos Neg Neg 17 4 1 5 Neg Neg Pos Pos 6 2 1 6 Pos Neg Pos Pos 1 0 0 7 Pos Pos Pos Neg 2 1 0 8 Pos Pos Pos Pos 27 12 6 Total 260 260 46 46 19 19 No significant financial relationships to disclose.
Air-pollutant chemicals and oxidized lipids exhibit genome-wide synergistic effects on endothelial cells
Authors: Ke Wei Gong, Wei Zhao, Ning Li, Berenice Barajas, Michael Kleinman, Constantinos Sioutas, Steve Horvath, Aldons J Lusis, Andre Nel, Jesus A Araujo
Journal: Genome biology (2007)

Ambient air pollution is associated with increased cardiovascular morbidity and mortality. We have found that exposure to ambient ultrafine particulate matter, highly enriched in redox cycling organic chemicals, promotes atherosclerosis in mice. We hypothesize that these pro-oxidative chemicals could synergize with oxidized lipid components generated in low-density lipoprotein particles to enhance vascular inflammation and atherosclerosis.
Increase in autism due to change in definition, not MMR vaccine
Authors: Janice Hopkins Tanne
Journal: BMJ (2005)

Changes in the definition of autism, rather than use of the measles, mumps, and rubella vaccine (MMR vaccine), led to increased diagnosis of autism in the United States and probably in Europe, says a study from the Mayo Clinic in Rochester, Minnesota ( Archives of Pediatrics and Adolescent Medicine 2005;159:37-44).

Before the late 1980s and early 1990s, these children were diagnosed as retarded or having developmental delay, lead author William Barbaresi, a developmental paediatrician, told the BMJ .

The prevalence of autism increased more than eightfold in the United States, from 5.5 (95% confidence interval 1.4 to 9.5) per 100 000 children in 1980-3 to 44.9 (32.9 to 56.9) per 100 000 in …
Medically unexplained symptoms: (Letter 3 of 5)
Authors: R. E Yodaiken
Journal: Journal of the Royal Society of Medicine (2003)

The admirers of Thomas Willis are indebted to Dr O'Connor (March 2003 JRSM 1 ) for adding further evidence that Cerebri Anatome (1664) reflects the religious and political practices of mid-17th-century England.Keele previously noted that the dedication of this famous book can leave no reasonable doubt that Willis
Familial cases of Behcet's disease
Authors: S.V. DUNDAR, U. GENCALP, H. ŞIMŞEK
Journal: British Journal of Dermatology (1985)

Seven families with Behcet's disease are presented. HLA-B5 tissue type was shown in the three families in whom lymphocyte microcytotoxicity tests were carried out. Genetic factors appear to be important in the pathogenesis of Behcet's disease.
Basic Fibroblast Growth Factor Selectively Enhances TNF-α—Induced Apoptotic Cell Death in Glomerular Endothelial Cells
Authors: UDO K. MESSMER, VERENA A. BRINER, JOSEF PFEILSCHIFTER
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Endothelial cell damage of glomeruli and kidney arterioles seems to play a pivotal role in several pathologic situations, such as Gram-negative sepsis, glomerulonephritis, and acute renal failure. Bacterial lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α) have been identified as potent inducers of apoptotic cell death in bovine glomerular endothelial cells. Both agents elicited apoptotic DNA laddering within 12 to 24 h. Basic fibroblast growth factor (bFGF) was generally described as a protective factor for endothelial cells against radiation-, TNF-α—, and UV-light—induced programmed cell death. Therefore, whether bFGF also affects apoptosis of microvascular endothelial cells was questioned. Surprising was that simultaneous treatment of glomerular endothelial cells with bFGF and either LPS or TNF-α left LPS-induced death unaffected, whereas TNF-α—induced death induction was potentiated, amounting to 48.9 ± 6.3% versus 22.4 ± 4.3% DNA degradation with TNF-α alone. Comparably, acidic FGF also selectively potentiated TNF-α—induced apoptosis. In mechanistic terms, bFGF synergistically increased TNF-α—induced mitochondrial permeability transition, the release of cytochrome c from mitochondria to the cytosol, and upregulation of the proapoptotic protein Bak and significantly enhanced activation of caspase-8 protease activity. In contrast, stress-activated protein kinase and nuclear factor κB activation, which represent primary signals of TNF/TNF receptor interaction, downregulation of the antiapoptotic protein Bcl-xL, and caspase-3—like protease activation, were unaffected. As bFGF did not affect LPS-induced apoptotic cell death, bFGF also left LPS-induced Bak upregulation and Bcl-xL downregulation unaffected. The results point to a selective bFGF-mediated enhancement of distinct proapoptotic pathways induced by TNF-α in glomerular endothelial cells.
Estimation of the additional costs of chemotherapy for patients with advanced non-small cell lung cancer
Authors: L Maslove, N Gower, S Spiro, R Rudd, R Stephens, P West
Journal: Thorax (2005)

<b>Background:</b> A large multicentre randomised trial, the Big Lung Trial, which in part compared supportive care with or without cisplatin-based chemotherapy in patients with advanced non-small cell lung cancer, provided an opportunity to evaluate the impact on the UK National Health Service of the costs incurred with the use of chemotherapy. <b>Methods:</b> This costing study was based on the retrospective collection of resource use data from hospital records. Case notes from 194 patients (98 chemotherapy + supportive care (C), 96 supportive care alone (NoC)) were inspected in eight centres recruiting the largest numbers of patients into the Big Lung Trial. Quantities were multiplied by fixed unit costs to calculate a total cost for each patient. The main outcome measure was the total cost incurred by the use of secondary care resources (including investigations, chemotherapy, radiotherapy, surgical procedures, inpatient days, outpatient attendances, and hospice inpatient care) in the two groups. <b>Results:</b> Patients randomised to receive cisplatin-based chemotherapy had an average of 3.4 more inpatient bed days than the mean of 11.9 days for patients randomised to supportive care alone, and more outpatient attendances. NoC patients were more likely to have received palliative radiotherapy. The mean total cost for C patients was £5355 compared with £3595 for the NoC group, difference £1760 (95% CI £781 to £2742). When split, the cost in the C group associated with the administration of chemotherapy was £1233 and non-chemotherapy costs were £4122. <b>Conclusion:</b> The additional cost of chemotherapy was not offset by a reduction in subsequent costs (as the non-chemotherapy costs were similar), so the survival benefit of about 10 weeks observed in the C group was achieved with the cost of chemotherapy administration.
A gain of function polymorphism in the interleukin 6 receptor influences RA susceptibility
Authors: I Marinou, K Walters, J Winfield, D E Bax, A G Wilson
Journal: Annals of the Rheumatic Diseases (2009)

To investigate the possible role of a functional polymorphism in the soluble interleukin 6 receptor (sIL-6R) gene in the genetic background of rheumatoid arthritis (RA).An association between disease status and the sIL-6R rs8192284 (A358D) variant was tested in 965 patients with RA and 988 unrelated healthy controls. Odds ratios (ORs) for disease were calculated with asymptotic 95% CI; p values <0.05 were considered statistically significant after adjustment for multiple testing. To determine the relationship between protein levels and IL-6R A358D genotype, the protein levels of sIL-6R in 100 plasma samples from healthy controls were measured using an ELISA and compared across the genotype groups.The allele frequency of the C allele (alanine) was lower in cases than in controls (38.4% vs 41.7%, p=0.04, OR 0.9, 95% CI 0.8 to 1.0), as were the CC/AC genotypes compared with AA genotype frequencies (61.0% in RA cases vs 67.5% in controls, p=0.004, OR 0.8, 95% CI 0.6 to 0.9). Plasma levels of sIL-6R differed significantly according to genotype in the controls: 17.00 + or - 2.03 ng/ml for A/A, 20.08 + or - 1.83 ng/ml for A/C and 21.57 + or - 2.10 ng/ml for C/C (p=0.0001).These data suggest a role for genetically determined lower sIL-6R levels as a risk factor for RA. The proinflammatory role of the IL6 system in established RA has been highlighted by the use of anti-sIL-6R antibodies. However, the findings of this study suggest a protective effect of IL6 on the risk of developing RA.
Brain atrophy by computerized tomography: Does brain matter matter?
Authors: Lewis L. Levy
Journal: Hepatology (1988)

Brain computerized axial tomography scans were performed in 18 consecutive liver cirrhosis patients with chronic persistent encephalopathy (8 alcoholic and 10 nonalcoholic) in order to evaluate the incidence of brain atrophy in this pathological condition. Fifteen patients of similar age with liver cirrhosis of Child’s class B but with acute episodic hepatic encephalopathy were studied in parallel. Brain atrophy was detected in 87.5% of alcoholic and in 50% of nonalcoholic liver cirrhosis patients with chronic persistent encephalopathy, whereas the patients with acute episodic encephalopathy were normal. The high frequency of brain atrophy in alcoholic patients with chronic encephalopathy can be attributed at least in part to the toxic effect of alcohol. The presence of brain atrophy in nonalcoholic liver cirrhosis patients with chronic persistent encephalopathy seems to indicate that the chronic exposure to toxins which are involved in the pathogenesis of hepatic encephalopathy leads to neuronal alterations which develop mainly in the cortex and which can be demonstrated by in vivo imaging only in a long-lasting state of coma. Moreover, alcohol and toxins causing hepatic encephalopathy seem to potentiate each other in inducing brain atrophy.
Induction of Retrovirus Particles in Human Testicular Tumor (Tera-1) Cell Cultures: An Electron Microscopic Study&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: D L Bronson, E E Fraley, J Fogh, S S Kalter
Journal: JNCI Journal of the National Cancer Institute (1979)

The Tera-1 and Tera-2 cell lines, established from germ-cell tumors of the human testis, were examined by electron microscopy for particles with the morphology of retroviruses. Extracellular and budding particles were observed at low frequencies only in cultures of Tera-1 cells that had been treated with 5-iodo-2'-deoxyuridine and dexamethasone. No particles were detected in untreated cultures of Tera-1 cells or in any preparations of Tera-2 cells.
Mice from a genetically resistant background lacking the interferon γ receptor are susceptible to infection with <i>Leishmania major</i> but mount a polarized T helper cell 1-type CD4+ T cell response.
Authors: K Swihart, U Fruth, N Messmer, K Hug, R Behin, S Huang, G Del Giudice, M Aguet, J A Louis
Journal: The Journal of Experimental Medicine (1995)

Mice with homologous disruption of the gene coding for the ligand-binding chain of the interferon (IFN) gamma receptor and derived from a strain genetically resistant to infection with Leishmania major have been used to study further the role of this cytokine in the differentiation of functional CD4+ T cell subsets in vivo and resistance to infection. Wild-type 129/Sv/Ev mice are resistant to infection with this parasite, developing only small lesions, which resolve spontaneously within 6 wk. In contrast, mice lacking the IFN-gamma receptor develop large, progressing lesions. After infection, lymph nodes (LN) and spleens from both wild-type and knockout mice showed an expansion of CD4+ cells producing IFN-gamma as revealed by measuring IFN-gamma in supernatants of specifically stimulated CD4+ T cells, by enumerating IFN-gamma-producing T cells, and by Northern blot analysis of IFN-gamma transcripts. No biologically active interleukin (IL) 4 was detected in supernatants of in vitro-stimulated LN or spleen cells from infected wild-type or deficient mice. Reverse transcription polymerase chain reaction analysis with primers specific for IL-4 showed similar IL-4 message levels in LN from both types of mice. The IL-4 message levels observed were comparable to those found in similarly infected C57BL/6 mice and significantly lower than the levels found in BALB/c mice. Anti-IFN-gamma treatment of both types of mice failed to alter the pattern of cytokines produced after infection. These data show that even in the absence of IFN-gamma receptors, T helper cell (Th) 1-type responses still develop in genetically resistant mice with no evidence for the expansion of Th2 cells.
Type 2 iodothyronine deiodinase in rat pituitary tumor cells is inactivated in proteasomes.
Authors: J Steinsapir, J Harney, P R Larsen
Journal: Journal of Clinical Investigation (1998)

The goal of these studies was to define the rate-limiting steps in the inactivation of type 2 iodothyronine deiodinase (D2). We examined the effects of ATP depletion, a lysosomal protease inhibitor, and an inhibitor of actin polymerization on D2 activity in the presence or absence of cycloheximide or 3,3', 5'-triiodothyronine (reverse T3, rT3) in rat pituitary tumor cells (GH4C1). We also analyzed the effects of the proteasomal proteolysis inhibitor carbobenzoxy- L-leucyl-L-leucyl-L-leucinal (MG132). The half-life of D2 activity in hypothyroid cells was 47 min after cycloheximide and 60 min with rT3 (3 nM). rT3 and cycloheximide were additive, reducing D2 half-life to 20 min. D2 degradation was partially inhibited by ATP depletion, but not by cytochalasin B or chloroquine. Incubation with MG132 alone increased D2 activity by 30-40% for several hours, and completely blocked the cycloheximide- or rT3-induced decrease in D2 activity. These results suggest that D2 is inactivated by proteasomal uptake and that substrate reduces D2 activity by accelerating degradation through this pathway. This is the first demonstration of a critical role for proteasomes in the post-translational regulation of D2 activity.
LongSAGE analysis of skeletal muscle at three prenatal stages in Tongcheng and Landrace pigs
Authors: Zhonglin Tang, Yong Li, Ping Wan, Xiaoping Li, Shuhong Zhao, Bang Liu, Bin Fan, Mengjin Zhu, Mei Yu, Kui Li
Journal: Genome biology (2007)

Abstract Background Obese and lean pig breeds show obvious differences in muscle growth; however, the molecular mechanism underlying phenotype variation remains unknown. Prenatal muscle development programs postnatal performance. Here, we describe a genome-wide analysis of differences in prenatal skeletal muscle between Tongcheng (a typical indigenous Chinese breed) and Landrace (a leaner Western breed) pigs. Results We generated transcriptome profiles of skeletal muscle from Tongcheng and Landrace pigs at 33, 65 and 90 days post coitus (dpc), using long serial analysis of gene expression (LongSAGE). We sequenced 317,115 LongSAGE tags and identified 1,400 and 1,201 differentially expressed transcripts during myogenesis in Tongcheng and Landrace pigs, respectively. From these, the Gene Ontology processes and expression patterns of these differentially expressed genes were constructed. Most of the genes showed different expression patterns in the two breeds. We also identified 532, 653 and 459 transcripts at 33, 65 and 90 dpc, respectively, that were differentially expressed between the two breeds. Growth factors, anti-apoptotic factors and genes involved in the regulation of protein synthesis were up-regulated in Landrace pigs. Finally, 12 differentially expressed genes were validated by quantitative PCR. Conclusion Our data show that gene expression phenotypes differ significantly between the two breeds. In particular, a slower muscle growth rate and more complicated molecular changes were found in Tongcheng pigs, while genes responsible for increased cellular growth and myoblast survival were up-regulated in Landrace pigs. Our analyses will assist in the identification of candidate genes for meat production traits and elucidation of the development of prenatal skeletal muscle in mammals.