tbuckley/cabot-search huggingface dataset:
Synaptosomal glutamate transport in thioacetamide-induced hepatic encephalopathy in the rat
Authors: Kofi N. W. Oppong, Kim Bartlett, Christopher O. Record, Hanan Al Mardini
Journal: Hepatology (1995)

Dysfunction of excitatory glutamatergic neurotransmission has been implicated in the cause of hepatic encephalopathy. Brain microdialysis studies in various animal models of portal systemic encephalopathy (PSE) and encephalopathy associated with acute liver failure, have established that an increase in extracellular glutamate occurs but the mechanisms of this are unclear. We have measured oxygen consumption, citrate synthase activity (as indices of energy state and mitochondrial content, respectively), calcium-dependent glutamate release, and high-affinity, sodium-dependent glutamate uptake by synaptosomes prepared from rats with thioacetamide-induced encephalopathy. (2 doses of thioacetamide 200 mg/kg with a 24-hour interval). Synaptosomes were prepared either by a modified P2 method (glutamate release study) or by discontinuous sucrose density gradient centrifugation (all other studies). There was no significant difference in synaptosomal oxygen consumption, citrate synthase activity, glutamate release, total synaptosomal glutamate content, or the Kd for glutamate uptake between the encephalopathy group and the controls. However, there was a marked decrease in the maximal velocity of transport (Vmax) for glutamate uptake in synaptosomes from encephalopathic rats, 2.64 versus 4.40 nmol/min/mg (P < .05). The results of this study provide evidence of impaired glutamate uptake in the rat thioacetamide model of hepatic encephalopathy, which could account for the elevated extracellular glutamate seen in the condition.
Prostate-specific antigen as a measure of disease outcome in metastatic hormone-refractory prostate cancer.
Authors: W K Kelly, H I Scher, M Mazumdar, V Vlamis, M Schwartz, S D Fossa
Journal: Journal of Clinical Oncology (1993)

To evaluate the prognostic significance of pretreatment parameters and posttherapy declines in prostate-specific antigen (PSA) in relation to the survival of patients with hormone-refractory prostate cancer.One hundred ten assessable patients treated on seven sequential protocols at Memorial Sloan-Kettering Cancer Center (MSKCC) for hormone-refractory prostate cancer were evaluated for 29 different pretherapy and posttherapy parameters, including a posttherapy decline in PSA of 50% and 80% from baseline.In the univariate analysis, initial Karnofsky performance status (KPS) > or = 80% was associated with a favorable outcome (P = .005), while age, extent of disease on bone scan, and individual sites of metastatic disease were not significant. No difference in survival was observed between patients with measurable or assessable (bone only) disease. Initial hemoglobin (HGB; P = .0012), alkaline phosphatase (ALK; P = .0015), and lactate dehydrogenase (LDH; P = .0002) levels were significant discriminators, while the initial PSA was not. Using a landmark analysis, a significantly longer median survival rate was observed for patients with a > or = 50% decline in PSA (median not reached) versus patients with a less than 50% decline in PSA (median, 8.6 months; P = .0001). Multivariate analysis using the Cox proportional hazards model showed that a > or = 50% decline in PSA (P = .0004) and the natural log of LDH (P = .0001) were the two most significant variables predicting survival. The model was confirmed on an independent data set from the Norwegian Radium Hospital (NRH) in Oslo, Norway.The results suggest that posttherapy PSA declines can be used as a surrogate end point to evaluate new agents in hormone-refractory prostate cancer. The criteria for response need prospective validation in phase III trials.
Tumor cycling hypoxia induces chemoresistance in glioblastoma multiforme by upregulating the expression and function of ABCB1
Authors: Chii-Wen Chou, Chi-Chung Wang, Chung-Pu Wu, Yu-Jung Lin, Yu-Chun Lee, Ya-Wen Cheng, Chia-Hung Hsieh
Journal: Neuro-Oncology (2012)

Tumor cycling hypoxia is now a well-recognized phenomenon in animal and human solid tumors. However, how tumor cycling hypoxia impacts chemotherapy is unclear. In the present study, we explored the impact and the mechanism of cycling hypoxia on tumor microenvironment-mediated chemoresistance. Hoechst 33342 staining and hypoxia-inducible factor-1 (HIF-1) activation labeling together with immunofluorescence imaging and fluorescence-activated cell sorting were used to isolate hypoxic tumor subpopulations from human glioblastoma xenografts. ABCB1 expression, P-glycoprotein function, and chemosensitivity in tumor cells derived from human glioblastoma xenografts or in vitro cycling hypoxic stress-treated glioblastoma cells were determined using Western blot analysis, drug accumulation and efflux assays, and MTT assay, respectively. ABCB1 expression and P-glycoprotein function were upregulated under cycling hypoxia in glioblastoma cells concomitant with decreased responses to doxorubicin and BCNU. However, ABCB1 knockdown inhibited these effects. Moreover, immunofluorescence imaging and flow cytometric analysis for ABCB1, HIF-1 activation, and Hoechst 3342 in glioblastoma revealed highly localized ABCB1 expression predominantly in potentially cycling hypoxic areas with HIF-1 activation and blood perfusion in the solid tumor microenvironment. The cycling hypoxic tumor cells derived from glioblastoma xenografts exhibited higher ABCB1 expression, P-glycoprotein function, and chemoresistance, compared with chronic hypoxic and normoxic cells. Tumor-bearing mice that received YC-1, an HIF-1α inhibitor, exhibited suppressed tumor microenvironment-induced ABCB1 induction and enhanced survival rate in BCNU chemotherapy. Cycling hypoxia plays a vital role in tumor microenvironment-mediated chemoresistance through the HIF-1-dependent induction of ABCB1. HIF-1 blockade before and concurrent with chemotherapy could suppress cycling hypoxia-induced chemoresistance.
Compensation for Energy Intake From Fast Food Among Overweight and Lean Adolescents
Authors: Cara B. Ebbeling, Kelly B. Sinclair, Mark A. Pereira, Erica Garcia-Lago, Henry A. Feldman, David S. Ludwig
Journal: JAMA (2004)

ContextFast food consumption has increased greatly among children in recent years, in tandem with the obesity epidemic. Fast food tends to promote a positive energy balance and, for this reason, may result in weight gain. However, if fast food and obesity are causally related, the question arises of why some children who frequently eat fast food do not become overweight.ObjectiveTo test the hypothesis that overweight adolescents are more susceptible to the adverse effects of fast food than lean adolescents.Design and SettingIn study 1, we fed participants an "extra large" fast food meal in a naturalistic setting (a food court). The participants were instructed to eat as much or little as desired during this 1-hour meal. In study 2, we assessed energy intake under free-living conditions for 2 days when fast food was consumed and 2 days when it was not consumed. Data were collected in Boston, Mass, between July 2002 and March 2003.ParticipantsOverweight (n = 26) and lean (n = 28) adolescents aged 13 to 17 years. Overweight was defined as a body mass index exceeding sex- and age-specific 85th percentiles based on the 2000 Centers for Disease Control and Prevention growth charts.Main Outcome MeasuresEnergy intake determined by direct observation in study 1 and by unannounced 24-hour dietary recalls, administered by telephone, in study 2.ResultsIn study 1, mean (SEM) energy intake from the fast food meal among all participants was extremely large (1652 [87] kcal), accounting for 61.6% (2.2%) of estimated daily energy requirements. Overweight participants ate more than lean participants whether energy was expressed in absolute terms (1860 [129] vs 1458 [107] kcal, P = .02) or relative to estimated daily energy requirements (66.5% [3.1%] vs 57.0% [2.9%], P = .03). In study 2, overweight participants consumed significantly more total energy on fast food days than non–fast food days (2703 [226] vs 2295 [162] kcal/d; +409 [142] kcal/d; P = .02), an effect that was not observed among lean participants (2575 [157] vs 2622 [191] kcal/d; –47 [173] kcal/d; P = .76).ConclusionsIn this study, adolescents overconsumed fast food regardless of body weight, although this phenomenon was especially pronounced in overweight participants. Moreover, overweight adolescents were less likely to compensate for the energy in fast food, by adjusting energy intake throughout the day, than their lean counterparts.
SOME CONSTITUENTS OF ELEMENTARY BODIES OF VACCINIA
Authors: Joseph E. Smadel, George I. Lavin, René J. Dubos
Journal: The Journal of Experimental Medicine (1940)

Treatment of elementary bodies of vaccinia with dilute solutions of sodium hydroxide resulted in the extraction of certain soluble materials accounting for half of the dry weight of the virus. Elementary bodies contained about 0.4 per cent inorganic phosphorus, practically all of which occurred in the form of a nucleoprotein containing thymus nucleic acid. In addition, a substance was recovered that reacted with S antibodies. From past experience one is led to believe that S antigen, as ordinarily encountered, is a protein which is not in combination with nucleic acid.
Absolute Risk Reductions for Local Recurrence After Postoperative Radiotherapy After Sector Resection for Ductal Carcinoma In Situ of the Breast
Authors: Lars Holmberg, Hans Garmo, Bengt Granstrand, Anita Ringberg, Lars-Gunnar Arnesson, Kerstin Sandelin, Per Karlsson, Harald Anderson, Stefan Emdin
Journal: Journal of Clinical Oncology (2008)

Evaluate the effects of radiotherapy after sector resection for ductal carcinoma in situ of the breast (DCIS) in patient groups as defined by age, size of the lesion, focality, completeness of excision and mode of detection.A total of 1,067 women in Sweden were randomly assigned to either postoperative radiotherapy (RT) or control from 1987 to 1999, and 1,046 were followed for a mean of 8 years. The main outcome was new ipsilateral breast cancer events and distant metastasis-free survival analyzed according to intention to treat.There were 64 ipsilateral events in the RT arm and 141 in the control group corresponding to a risk reduction of 16.0 percentage points at 10 years (95% CI, 10.3% to 21.6%) and a relative risk of 0.40 (95% CI, 0.30 to 0.54). There was no statistically significant difference in distant metastasis-free survival. There was an effect modification by age, yielding a low effect of RT in women younger than 50, but substantial protection in women older than 60 years. The age effect was not confounded by focality, lesion size, completeness of excision, or detection mode. There was no group as defined by our stratification variables that had a low risk without radiotherapy.Our results indicate that younger women have a low protective effect of conventional RT after sector resection. Older women benefit substantially. We caution that the age effect was seen in a subgroup analysis. Further search with conventional clinical variables for a low risk group that does not need RT does not seem fruitful.
Childhood Trajectories of Inattention and Hyperactivity and Prediction of Educational Attainment in Early Adulthood: A 16-Year Longitudinal Population-Based Study
Authors: Jean-Baptiste Pingault, Richard E. Tremblay, Frank Vitaro, René Carbonneau, Christophe Genolini, Bruno Falissard, Sylvana M. Côté
Journal: American Journal of Psychiatry (2011)

Literature clearly documents the association between mental health problems, particularly attention deficit hyperactivity disorder (ADHD), and educational attainment. However, inattention and hyperactivity are generally not considered independently from each other in prospective studies. The aim of the present study was to differentiate the unique, additive, or interactive contributions of inattention and hyperactivity symptoms to educational attainment.The authors randomly selected 2,000 participants from a representative sample of Canadian children and estimated developmental trajectories of inattention and hyperactivity between the ages of 6 and 12 years using yearly assessments. High school graduation status, at age 22-23 years, was obtained from official records.Four trajectories of inattention and four trajectories of hyperactivity were observed between the ages of 6 and 12 years. After controlling for hyperactivity and other confounding variables, a high inattention trajectory (compared with low inattention) strongly predicted not having a high school diploma at 22-23 years of age (odds ratio=7.66, 95% confidence interval [CI]=5.06-11.58). To a lesser extent, a declining or rising trajectory of inattention also made a significant contribution (odds ratios of 2.67 [95% CI=1.90-3.75] and 3.87 [95% CI=2.75-5.45], respectively). Hyperactivity was not a significant predictor once inattention was taken into account.Inattention rather than hyperactivity during elementary school significantly predicts long-term educational attainment. Children with attention problems, regardless of hyperactivity, need preventive intervention early in their development.
Arthritogenic Monoclonal Antibodies from K/BxN Mice
Authors: Mariana Maccioni, Gabrielle Zeder-Lutz, Haochu Huang, Claudine Ebel, Philippe Gerber, Josiane Hergueux, Patricia Marchal, Veronique Duchatelle, Claude Degott, Marc van Regenmortel, Christophe Benoist, Diane Mathis
Journal: The Journal of Experimental Medicine (2002)

Arthritis in the K/BxN mouse model is provoked by pathogenic antibodies (Abs) directed against a ubiquitously expressed protein, glucose-6-phosphate isomerase (GPI). To begin dissecting the repertoire of arthritogenic immunoglobulins (Igs) in the K/BxN model, and to provide a basis for comparison with RA patientswe have generated anti-GPI monoclonal Abs (mAbs) from spontaneously activated B cells in the lymphoid organs of arthritic mice. B cell clones with anti-GPI specificities were present at extraordinarily high frequencies in the spleen, and less frequently in other lymphoid organs and in the synovial fluid. None of the anti-GPI mAbs induced arthritis when injected individually into healthy recipients, but most were effective when combined in pairs or larger pools. Arthritogenic combinations depended on mAbs of the IgG1 isotype, which bound to GPI with Kd in the 10−9 M range, with no indication of cooperative binding between complementing pairs. Pathogenicity was not associated with recognition of a particular epitope, but the ability to form mAb/GPI multimers by simultaneous recognition of different epitopes was clearly required, consistent with the known role of complement and FcRs in this model. Sequence analysis revealed structural similarities amongst the mAbs, indicating that a particular subset of B cells may evade tolerance in K/BxN mice, and that affinity maturation by somatic mutation likely takes place. These results confirm that GPI itself, rather than a cross-reactive molecule, is the target of pathogenic Igs.
Does a Statistical Method Suggest a New Pathobiology for Hemodialysis Patients?
Authors: Edmund G. Lowrie
Journal: Journal of the American Society of Nephrology (2009)

You will find elsewhere in these pages of JASN 1 a paper by Argyropoulos et al. entitled “Considerations in the Statistical Analysis of Hemodialysis Patient Survival.” The claim of this work—a comparative statistical analysis—is that the authors have proven their a priori hypothesis that the natural history ofdialysis patients proceeds in an accelerating fashion. As such, they say their chosen statistical method, the accelerated failure time model (AFTM), should be used when evaluating survival on dialysis. The evidence and its interpretation, however, are weak, and both should be considered critically and viewed skeptically. I have several reasons for this view.

Contrary to the authors' assertions, there is widespread agreement that dialysis dose is important to the survival of dialysis patients. The National Cooperative Dialysis Study2 proved many years ago that small molecule–directed dialysis is important. Later analyses using those data, but ignoring length of dialysis ( t ),3 suggested that a Kt/V of 0.9 was a suitable initial threshold. The Hemodialysis Study4 used higher Kt/V values, but even so, there remains the implication that women had worse survival in the low than the high Kt/V arm.4,5 More to the point, there is widespread transnational agreement that dose is important.5–9 Although some might argue about the best formula for describing dose, opinion converges on a Kt/V ratio of 1.2 to 1.4 per session.6–9

Furthermore, the authors' database is quite small1—only …
Tissue Culture Studies on Human Leukemia and Malignant Lymphoma
Authors: J. A. Sykes, L. Dmochowski, C. C. Shullenberger, C. D. Howe
Journal: Cancer Research (1962)

A study was made of long-term cultures of cells from lymph nodes of 72 patients with leukemia and lymphoma. This study comprised eleven cases of lymphatic, two cases of monocytic, and three cases of granulocytic leukemia, 30 cases of malignant lymphoma, and 26 cases of Hodgkin's disease. Cells from lymph nodes of seventeen patients apparently free from leukemia were also studied. Cells of the cultures derived from approximately 50 per cent of the cases of leukemia, lymphoma, and Hodgkin's disease showed a similar sequence of changes leading eventually to the death of the cultures. These changes consisted of alterations in the perinuclear zone and the occurrence of cytoplasmic inclusions suggestive of the presence of a virus. These changes were not seen in the cells of cultures derived from nonleukemic lymph nodes. The relationship of these changes to the origin of the different types of leukemia and lymphoma is discussed.
Chemogenetic Tools to Interrogate Brain Functions
Authors: Scott M. Sternson, Bryan L. Roth
Journal: Annual Review of Neuroscience (2014)

Elucidating the roles of neuronal cell types for physiology and behavior is essential for understanding brain functions. Perturbation of neuron electrical activity can be used to probe the causal relationship between neuronal cell types and behavior. New genetically encoded neuron perturbation tools have been developed for remotely controlling neuron function using small molecules that activate engineered receptors that can be targeted to cell types using genetic methods. Here we describe recent progress for approaches using genetically engineered receptors that selectively interact with small molecules. Called "chemogenetics," receptors with diverse cellular functions have been developed that facilitate the selective pharmacological control over a diverse range of cell-signaling processes, including electrical activity, for molecularly defined cell types. These tools have revealed remarkably specific behavioral physiological influences for molecularly defined cell types that are often intermingled with populations having different or even opposite functions.
Dual Effect of Nitric Oxide Donors on Cyclooxygenase-2 Expression in Human Mesangial Cells
Authors: MANUELA DÍAZ-CAZORLA, DOLORES PÉREZ-SALA, SANTIAGO LAMAS
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Nitric oxide (NO) is emerging as a key regulator of gene expression, capable of playing either positive or negative roles. The results of this study indicate that NO exerts a dual effect on cyclooxygenase-2 (COX-2) expression in human mesangial cells (HMC). Treatment of HMC with NO synthase inhibitors attenuated interleukin-1β (IL-1β)/tumor necrosis factor-α (TNF-α)-elicited COX-2 protein and mRNA expression, suggesting a positive role of endogenous NO on COX-2 induction. However, NO donors (sodium nitroprusside [SNP] and S-nitroso- N -acetylpenicillamine [SNAP]) amplified cytokine-elicited COX-2 expression at early time points of treatment (up to 8 h for mRNA and up to 24 h for protein expression), but were inhibitory at later times. Oligonucleotide decoy experiments confirmed the importance of nuclear factor κB (NF-κB) activation for COX-2 induction by IL-1β/TNF-α. Treatment with N G -nitro-L-arginine methyl ester (L-NAME) did not affect initial activation of NF-κB by IL-1β/TNF-α, but unveiled an inhibitory effect of NO generation on NF-κB activity after 4 h. In HMC supplemented with SNP, cytokine-induced NF-κB activation was potentiated at early times of induction (5 to 15 min), but inhibited at later times (1 to 4 h), suggesting a dual effect of NO donors on NF-κB activation. Interestingly, IκBα protein levels followed a reciprocal pattern of expression: IκBα levels were lower at early times of induction in NO donor-supplemented cells; however, after 1 h of treatment, IκBα levels became higher than in cells treated only with cytokines. In the presence of SNP, cytokine-elicited IκBα mRNA induction was initially delayed, but was amplified at later times. These changes in IκBα expression could contribute to the dual effects of NO donors on NF-κB activation and COX-2 expression in HMC.
Structure and Characterization of the 5′-Flanking Region of the Mouse Smooth Muscle Myosin Heavy Chain (SM1/2) Gene
Authors: Masafumi Watanabe, Yasunari Sakomura, Masahiko Kurabayashi, Ichiro Manabe, Masanori Aikawa, Makoto Kuro-o, Toru Suzuki, Yoshio Yazaki, Ryozo Nagai
Journal: Circulation Research (1996)

We have previously shown that smooth muscle myosin heavy chain isoforms (SMs), including SM1, SM2, and SMemb, are differentially expressed during vascular development, and in vascular lesions, such as atherosclerosis. The SM1/2 gene is expressed exclusively in smooth muscle cells and generates SM1 and SM2 mRNAs by alternative splicing. Whereas SM1 is constitutively expressed from early development, SM2 appears only after birth. In this study, we have isolated and characterized the 5'-flanking region of the mouse SM1/2 gene. Transient transfection assays using a series of promoter-luciferase chimeric constructs demonstrated that tandem elements of the CCTCCC sequence, located at -89 and -61 bp relative to the transcription start site, were essential for transcriptional activity of the SM1/2 gene in primary cultured rabbit aortic smooth muscle cells and smooth muscle cell lines derived from the rabbit aorta but not in non-smooth muscle cells. Gel mobility shift assays indicated that CCTCCC was a binding site for nuclear proteins prepared from smooth muscle cells. Double-stranded oligonucleotides containing either the CACC box or the Sp1 consensus sequence efficiently competed with the CCTCCC elements for binding the nuclear extracts. Site-specific mutations of CCTCCC elements resulted in a significant reduction of the promoter activity. Moreover, CCTCCC elements are evolutionary conserved between mouse and rabbit. In conclusion, the results of this study indicate an important role for the interaction of the CCTCCC sequence with Sp1 or related factors in activating transcription from the SM1/2 gene promoter.