tbuckley/cabot-search huggingface dataset:
Altered NMDA Glutamate Receptor Antagonist Response in Individuals With a Family Vulnerability to Alcoholism
Authors: Ismene L. Petrakis, Diana Limoncelli, Ralitza Gueorguieva, Peter Jatlow, Nashaat N. Boutros, Louis Trevisan, Joel Gelernter, John H. Krystal
Journal: American Journal of Psychiatry (2004)

A family history of alcoholism is a risk factor for the development of ethanol dependence. Ethanol is an antagonist of the N-methyl-d-aspartate (NMDA) glutamate receptor, and alterations in NMDA receptor function are thought to be involved in ethanol abuse and dependence. The purpose of this study was to determine in healthy individuals with no ethanol dependence whether response to the NMDA receptor antagonist ketamine would differentiate those with a family history of ethanol dependence from those without such a family history.Healthy subjects between the ages of 21 and 30 received 40-minute intravenous infusions of saline, low-dose ketamine (0.1 mg/kg), and high-dose ketamine (0.5 mg/kg) on three separate test days in a randomized order under double-blind conditions. The healthy individuals with at least one first-degree relative and another first- or second-degree relative with ethanol dependence (N=16) were compared with those who had no family history of ethanol dependence in any first- or second-degree relative (N=29). Outcome measures included the Brief Psychiatric Rating Scale, Clinician-Administered Dissociative States Scale, verbal fluency, Hopkins Verbal Learning Test, a biphasic alcohol effects scale, visual analog scales of mood states, and ketamine levels.During ketamine infusion, individuals with a family history of ethanol dependence showed an attenuated response in terms of perceptual alterations and dysphoric mood relative to those without such a family history.These data suggest that alterations in NMDA receptor function may contribute to subjective response to ethanol and therefore also to the risk of developing alcoholism.
The PAAD/PYRIN-Family Protein ASC Is a Dual Regulator of a Conserved Step in Nuclear Factor κB Activation Pathways
Authors: Christian Stehlik, Loredana Fiorentino, Andrea Dorfleutner, Jean-Marie Bruey, Eugenia M. Ariza, Junji Sagara, John C. Reed
Journal: The Journal of Experimental Medicine (2002)

Apoptosis-associated speck-like protein containing a Caspase recruitment domain (ASC) belongs to a large family of proteins that contain a Pyrin, AIM, ASC, and death domain-like (PAAD) domain (also known as PYRIN, DAPIN, Pyk). Recent data have suggested that ASC functions as an adaptor protein linking various PAAD-family proteins to pathways involved in nuclear factor (NF)-κB and pro-Caspase-1 activation. We present evidence here that the role of ASC in modulating NF-κB activation pathways is much broader than previously suspected, as it can either inhibit or activate NF-κB, depending on cellular context. While coexpression of ASC with certain PAAD-family proteins such as Pyrin and Cryopyrin increases NF-κB activity, ASC has an inhibitory influence on NF-κB activation by various proinflammatory stimuli, including tumor necrosis factor (TNF)α, interleukin 1β, and lipopolysaccharide (LPS). Elevations in ASC protein levels or of the PAAD domain of ASC suppressed activation of IκB kinases in cells exposed to pro-inflammatory stimuli. Conversely, reducing endogenous levels of ASC using siRNA enhanced TNF- and LPS-induced degradation of the IKK substrate, IκBα. Our findings suggest that ASC modulates diverse NF-κB induction pathways by acting upon the IKK complex, implying a broad role for this and similar proteins containing PAAD domains in regulation of inflammatory responses.
Insulin Resistance Modulates Iron-Related Proteins in Adipose Tissue
Authors: José María Moreno-Navarrete, Marta G. Novelle, Victoria Catalán, Francisco Ortega, Maria Moreno, Javier Gomez-Ambrosi, Gemma Xifra, Marta Serrano, Ester Guerra, Wifredo Ricart, Gema Frühbeck, Carlos Diéguez, José Manuel Fernández-Real
Journal: Diabetes Care (2014)

OBJECTIVE Circulating markers of iron overload are associated with insulin resistance. Less is known about the impact of iron overload on adipose tissue (AT). We hypothesized that gene expression markers of iron metabolism in AT could be associated with insulin action. RESEARCH DESIGN AND METHODS The AT expression of ferroportin (SLC40A1), transferrin (TF), TF receptor (TFRC), ferritin (FT) heavy polypeptide 1 (FTH1), and FT light polypeptide (FTL) was analyzed cross-sectionally in three independent cohorts and also after weight loss–induced changes in insulin sensitivity (clamp M value) in an independent fourth cohort. RESULTS In human AT, TF mRNA and protein levels were decreased with obesity and insulin resistance in the three cohorts and were positively associated with adipogenic mRNAs and insulin action. Otherwise, FTL mRNA and protein and SLC40A1 transcripts were positively associated with BMI and negatively linked to adipogenic genes and insulin action. Bariatric surgery–induced weight loss led to increased TF and decreased TFRC, FTH1, FTL, and SLC40A1 in subcutaneous AT in parallel to improved insulin action. CONCLUSIONS These results suggest that iron overload impacts on AT in association with insulin resistance.
DISTRIBUTION OF LABELED LYMPH NODE CELLS IN MICE DURING THE LYMPHOCYTOSIS INDUCED BY <i>BORDETELLA PERTUSSIS </i>
Authors: Robert N. Taub, Walter Rosett, Andy Adler, Stephen I. Morse
Journal: The Journal of Experimental Medicine (1972)

The mechanism by which Bordetella pertussis organisms and their products induce lymphocytosis in mice was analyzed in terms of the localization of syngeneic Cr-51-labeled lymph node cells. Labeled lymphoid cells incubated in vitro with the supernatant of B. pertussis cultures and then injected intravenously into normal recipients, or labeled cells injected into pertussis-treated recipients were unable to "home" to lymphoid organs but persisted for long periods in the blood. In animals "equipped" with a population of Cr-51-labeled lymphoid cells, administration of B. pertussis organisms or culture supernatant effected a shift of radioactivity from lymph nodes and spleen into the peripheral blood, coincident with the lymphocytosis. In in vitro experiments it was found that the active principle could bind to both erythrocytes and lymphocytes and could spontaneously elute from these cells onto labeled lymphocytes which were then unable to home efficiently. The data suggest that Bordetella pertussis-induced lymphocytosis involves a reversible attachment of the pertussis factor onto the surfaces of lymphocytes which prevents their recirculation to lymphoid organs. Recirculating lymphocytes are presumably affected as they emerge from lymphoid organs to enter the blood.
Safety of Outpatient Closed-Loop Control: First Randomized Crossover Trials of a Wearable Artificial Pancreas
Authors: Boris P. Kovatchev, Eric Renard, Claudio Cobelli, Howard C. Zisser, Patrick Keith-Hynes, Stacey M. Anderson, Sue A. Brown, Daniel R. Chernavvsky, Marc D. Breton, Lloyd B. Mize, Anne Farret, Jérôme Place, Daniela Bruttomesso, Simone Del Favero, Federico Boscari, Silvia Galasso, Angelo Avogaro, Lalo Magni, Federico Di Palma, Chiara Toffanin, Mirko Messori, Eyal Dassau, Francis J. Doyle
Journal: Diabetes Care (2014)

OBJECTIVE We estimate the effect size of hypoglycemia risk reduction on closed-loop control (CLC) versus open-loop (OL) sensor-augmented insulin pump therapy in supervised outpatient setting. RESEARCH DESIGN AND METHODS Twenty patients with type 1 diabetes initiated the study at the Universities of Virginia, Padova, and Montpellier and Sansum Diabetes Research Institute; 18 completed the entire protocol. Each patient participated in two 40-h outpatient sessions, CLC versus OL, in randomized order. Sensor (Dexcom G4) and insulin pump (Tandem t:slim) were connected to Diabetes Assistant (DiAs)—a smartphone artificial pancreas platform. The patient operated the system through the DiAs user interface during both CLC and OL; study personnel supervised on site and monitored DiAs remotely. There were no dietary restrictions; 45-min walks in town and restaurant dinners were included in both CLC and OL; alcohol was permitted. RESULTS The primary outcome—reduction in risk for hypoglycemia as measured by the low blood glucose (BG) index (LGBI)—resulted in an effect size of 0.64, P = 0.003, with a twofold reduction of hypoglycemia requiring carbohydrate treatment: 1.2 vs. 2.4 episodes/session on CLC versus OL (P = 0.02). This was accompanied by a slight decrease in percentage of time in the target range of 3.9–10 mmol/L (66.1 vs. 70.7%) and increase in mean BG (8.9 vs. 8.4 mmol/L; P = 0.04) on CLC versus OL. CONCLUSIONS CLC running on a smartphone (DiAs) in outpatient conditions reduced hypoglycemia and hypoglycemia treatments when compared with sensor-augmented pump therapy. This was accompanied by marginal increase in average glycemia resulting from a possible overemphasis on hypoglycemia safety.
Allelic Loss of a Common Microsatellite Marker<b><i>MYCL1</i></b>
Authors: Takeshi Kambara, Gerald B. Sharp, Takeshi Nagasaka, Masanori Takeda, Hiromi Sasamoto, Hitoshi Nakagawa, Hiroshi Isozaki, Donald G. MacPhee, Jeremy R. Jass, Noriaki Tanaka, Nagahide Matsubara
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Allelic loss involving chromosome arms 5q, 8p, 17p, and 18q is commonly detected in colorectal cancer (CRC). The short arm of chromosome 1 is also frequently affected in a whole range of cancer types, including CRC. Our aim in the present study was to determine whether allelic losses on 1p were likely to be of much value in predicting the prognosis of CRC cases. Experimental Design: Genomic DNA was prepared from tumor and corresponding normal tissue specimens from 90 patients who had undergone curative resection for CRC. Loss of heterozygosity (LOH) on chromosome arms 1p, 2p, 5q, 7q, 8p, 17p, 17q, and 18q was examined using 14 microsatellite markers, and possible correlations between LOH and clinicopathological factors (including tumor recurrence and patient survival) were investigated. LOH at the MYCL1 microsatellite marker at 1p34 was detected in 12 of 74 (16.2%) patients who were informative for this marker. Results: After controlling for tumor stage and gender and excluding findings for patients with remote metastasis, we found that patients who were positive for LOH at MYCL1 were 31 times more likely to experience recurrence than those who were negative for LOH at this locus (95% confidence intervals, 2.27-∞; P = 0.04). There were indications of a similar tendency for LOH at the 14-3-3-σ-TG microsatellite marker at 1p35, but we could find no evidence of a significant association between LOH at this site and tumor recurrence or patient survival. We were also unable to detect significant association between LOH at the various sites on 2p, 5q, 7q, 8p, 17p, 17q, and 18q and either tumor recurrence or patient survival. Conclusions: CRC patients whose tumors exhibited LOH at MYCL1 at chromosome 1p34 were likely to have a poor prognosis, suggesting that this marker may have clinical relevance.
Race Suicide (Criminal Abortion).
Authors: E. Stuver
Journal: JAMA (1906)

Fort Collins, Colo., Feb. 24, 1906. <h3>To the Editor:</h3> —For some time there have been many criminal abortions performed in our city, and the thought occurred to me that by getting the physicians and ministers together and formulating a statement as to the gravity of this crime we might do something to check it. A meeting was called and the statement I send you was formulated and signed by the persons whose names are appended. The intention was to have a lot of these printed so that each physician could have a supply and distribute them where he thought they would do the most good. While we have not yet carried out this last part of our plan, I believe our action has had an excellent effect on physicians who had been doing or might be induced to do that kind of work. E.Stuver. <h3>STATEMENT.</h3> Human life is the
Mapping and characterization of the amplicon near APOA2 in 1q23 in human sarcomas by FISH and array CGH
Authors: Stine H Kresse, Jeanne-Marie Berner, Leonardo A Meza-Zepeda, Simon G Gregory, Wen-Lin Kuo, Joe W Gray, Anne Forus, Ola Myklebost
Journal: Molecular Cancer (2005)

Abstract Background Amplification of the q21-q23 region on chromosome 1 is frequently found in sarcomas and a variety of other solid tumours. Previous analyses of sarcomas have indicated the presence of at least two separate amplicons within this region, one located in 1q21 and one located near the apolipoprotein A-II ( APOA2 ) gene in 1q23. In this study we have mapped and characterized the amplicon in 1q23 in more detail. Results We have used fluorescence in situ hybridisation (FISH) and microarray-based comparative genomic hybridisation (array CGH) to map and define the borders of the amplicon in 10 sarcomas. A subregion of approximately 800 kb was identified as the core of the amplicon. The amplification patterns of nine possible candidate target genes located to this subregion were determined by Southern blot analysis. The genes activating transcription factor 6 ( ATF6 ) and dual specificity phosphatase 12 ( DUSP12 ) showed the highest level of amplification, and they were also shown to be over-expressed by quantitative real-time reverse transcription PCR (RT-PCR). In general, the level of expression reflected the level of amplification in the different tumours. DUSP12 was expressed significantly higher than ATF6 in a subset of the tumours. In addition, two genes known to be transcriptionally activated by ATF6 , glucose-regulated protein 78 kDa and -94 kDa ( GRP78 and GRP94 ), were shown to be over-expressed in the tumours that showed over-expression of ATF6 . Conclusion ATF6 and DUSP12 seem to be the most likely candidate target genes for the 1q23 amplification in sarcomas. Both genes have possible roles in promoting cell growth, which makes them interesting candidate targets.
The role of the endocannabinoid system in gametogenesis, implantation and early pregnancy
Authors: A.H. Taylor, C. Ang, S.C. Bell, J.C. Konje
Journal: Human Reproduction Update (2007)

Maternal use of marijuana, in which the exocannabinoid Delta(9)-tetrahydrocannabinol is the most active psychoactive ingredient, is known to have adverse effects on various aspects of reproduction including ovulation, spermatogenesis, implantation and pregnancy duration. Endogenous cannabinoids of which Anandamide is the prototype are widely distributed in the body especially in the reproductive tract and pregnancy tissues and act through the same receptors as the receptor as Delta(9)-tetrahydrocannabinol. Anandamide, has been reported to have pleiotropic effects on human reproduction and in experimental animal models. It appears to be the important neuro-cytokine mediator synchronizing the embryo-endometrial development for timed implantation, the development of the embryo into the blastocyst and transport of the embryo across the fallopian tubes. The mechanisms by which it exerts these effects are unclear but could be via direct actions on the various sites within the reproductive system or its differential actions on vascular tone dependent. In this review article we bring together the current knowledge on the role of endoccanabinoids in reproduction and postulate on the potential mechanisms on how these affect reproduction. In addition, we examine its role on the endothelium and vascular smooth muscle as a potential mechanism for adverse pregnancy outcome.
Increased PiZ gene frequency for alpha 1 antitrypsin in patients with genetic haemochromatosis.
Authors: A N Elzouki, R Hultcrantz, P Stal, R Befrits, S Eriksson
Journal: Gut (1995)

The putative relationship between genetic haemochromatosis and PiZ alpha 1 antitrypsin deficiency was studied using a monoclonal antibody against the PiZ variant in 67 consecutive patients with genetic haemochromatosis seen at Karolinska Hospital and Huddinge University Hospital, Stockholm over a 10 year period. Three (4.5%) of the patients with haemochromatosis were found to be PiZ homozygotes (odds ratio = 82, confidence interval = 26, 256; p &lt; 0.0001). The prevalence of the heterozygous (PiZ) phenotype was similar to that in the general population (p = 0.937). During the ascertainment period, liver biopsy was performed in 65 (97%) of the patients; 66% (2 of 3) of the PiZ homozygotes were found to have cirrhosis compared with 10% (6/59) of the non-carriers of the PiZ variant (p = 0.039). None of the homozygous or heterozygous alpha 1 antitrypsin deficient patients had developed hepatocellular carcinoma compared with 3.4% (2 of 59) of the non-PiZ gene carriers (p = 1.0). Two of those with the homozygous phenotype had developed severe emphysema. HLA typing was performed in 18 patients, 16 (89%) of whom manifested antigens known to be linked to haemochromatosis. There were no significant differences between the PiZ gene carriers and non-carriers in mean age at onset of disease, sex distribution, or HLA type. Two of the PiZ heterozygotes had plasma alpha 1 antitrypsin concentrations below the normal range, though the group mean was lower than that of the non-PiZ carriers (p = 0.0003). The data suggest that the presence of the PiZ allele for alpha1 antitrypsin deficiency, in a double dose, is associated with genetic haemochromatosis and may contribute to the earlier onset of cirrhosis in these patients, though it does not increase the risk of hepatocellular carcinoma.
Cytomegalovirus and Child Day Care
Authors: Stuart P. Adler
Journal: New England Journal of Medicine (1989)

To determine whether day-care workers acquire cytomegalovirus infection from the children they care for, we studied 610 women employed at 34 day-care centers over two years. Forty-one percent of the caretakers were seropositive for cytomegalovirus. After adjustment for the effects of race, marital status, and age on seropositivity, the women who cared for children younger than two years of age had a significantly higher seropositivity rate (46 percent) than the women who cared for children older than two years of age (35 percent) (relative risk, 1.29; 95 percent confidence interval, 1.05 to 1.57; P<0.02). Of 202 initially seronegative caretakers (observed for an average of 305 days per woman), 19 seroconverted, for an annual seroconversion rate of 11 percent. This rate was significantly higher than the 2 percent annual rate of seroconversion among 229 seronegative women (11 of whom seroconverted) in a comparison group of female hospital employees observed for an average of 781 days per woman (relative risk, 5.0; 95 percent confidence interval, 2.4 to 10.5; P<0.001). At three day-care centers in which the children were also studied, seven of the nine women shed isolates of cytomegalovirus in their saliva or urine that had EcoRI and BamHI DNA-digestion patterns identical to the DNA patterns of isolates shed by one or more children in their care. We conclude that workers in day-care centers may acquire cytomegalovirus infection from the children in their care and that this risk is significantly greater among those who care for children less than two years of age. (N Engl J Med 1989;321:1290–6.)
Optogenetic and Potassium Channel Gene Therapy in a Rodent Model of Focal Neocortical Epilepsy
Authors: Robert C. Wykes, Joost H. Heeroma, Laura Mantoan, Kaiyu Zheng, Douglas C. MacDonald, Karl Deisseroth, Kevan S. Hashemi, Matthew C. Walker, Stephanie Schorge, Dimitri M. Kullmann
Journal: Science Translational Medicine (2012)

Light-activated gene therapy acutely suppresses seizures, and gene therapy with a potassium channel prevents epileptogenesis and treats established epilepsy in a rodent model.
The p53-targeting human phosphatase hCdc14A interacts with the Cdk1/cyclin B complex and is differentially expressed in human cancers
Authors: Michelle T Paulsen, Adrienne M Starks, Frederick A Derheimer, Sheela Hanasoge, Liwu Li, Jack E Dixon, Mats Ljungman
Journal: Molecular Cancer (2006)

Abstract Background The evolutionary conserved cyclin-dependent kinase phosphatase hCdc14A has been shown to play potential roles in the regulation of mitotic exit and in the centrosome duplication cycle. We have recently shown that hCdc14A also can interact with the tumor suppressor p53 both in vitro and in vivo and specifically dephosphorylates the ser315 site of p53 in vitro . In this study we developed antibodies against hCdc14A to investigate the expression and regulation of hCdc14A in human tissues and cancer cells. Results We show that hCdc14A is differentially expressed in human tissues and in 75 cancer cell lines examined. Treatments with the histone deacetylase inhibitor TSA, the demethylating agent 5-aza-2'-deoxycytodine or the proteasome inhibitor MG132 significantly induced expression of hCdc14A in cell lines expressing low or undetectable levels of hCdc14A. There was a strong bias for low expression of hCdc14A in cancer cell lines harboring wild-type p53, suggesting that high Cdc14A expression is not compatible with wild-type p53 expression. We present evidence for a role for hCdc14A in the dephosphorylation of the ser315 site of p53 in vivo and that hCdc14A forms a complex with Cdk1/cyclin B during interphase but not during mitosis. Conclusion Our results that hCdc14A is differentially expressed in human cancer cells and that hCdc14A can interact with both p53 and the Cdk1/cyclin B complex may implicate that dysregulation of hCdc14A expression may play a role in carcinogenesis.
A multi-gene signature predicts outcome in patients with pancreatic ductal adenocarcinoma
Authors: Syed Haider, Jun Wang, Ai Nagano, Ami Desai, Prabhu Arumugam, Laurent Dumartin, Jude Fitzgibbon, Thorsten Hagemann, John F Marshall, Hemant M Kocher, Tatjana Crnogorac-Jurcevic, Aldo Scarpa, Nicholas R Lemoine, Claude Chelala
Journal: Genome Medicine (2014)

Abstract Background Improved usage of the repertoires of pancreatic ductal adenocarcinoma (PDAC) profiles is crucially needed to guide the development of predictive and prognostic tools that could inform the selection of treatment options. Methods Using publicly available mRNA abundance datasets, we performed a large retrospective meta-analysis on 466 PDAC patients to discover prognostic gene signatures. These signatures were trained on two clinical cohorts ( n = 70), and validated on four independent clinical cohorts ( n = 246). Further validation of the identified gene signature was performed using quantitative real-time RT-PCR. Results We identified 225 candidate prognostic genes. Using these, a 36-gene signature was discovered and validated on fully independent clinical cohorts (hazard ratio (HR) = 2.06, 95% confidence interval (CI) = 1.51 to 2.81, P = 3.62 × 10 −6 , n = 246). This signature serves as a good alternative prognostic stratification marker compared to tumour grade (HR = 2.05, 95% CI = 1.45 to 2.88, P = 3.18 × 10 −5 ) and tumour node metastasis (TNM) stage (HR = 1.13, 95% CI = 0.66 to 1.94, P = 0.67). Upon multivariate analysis with adjustment for TNM stage and tumour grade, the 36-gene signature remained an independent prognostic predictor of clinical outcome (HR = 2.21, 95% CI = 1.17 to 4.16, P = 0.01). Univariate assessment revealed higher expression of ITGA5 , SEMA3A , KIF4A , IL20RB , SLC20A1 , CDC45 , PXN , SSX3 and TMEM26 was correlated with shorter survival while B3GNT1 , NOSTRIN and CADPS down-regulation was associated with poor outcome. Conclusions Our 36-gene classifier is able to prognosticate PDAC independent of patient cohort and microarray platforms. Further work on the functional roles, downstream events and interactions of the signature genes is likely to reveal true molecular candidates for PDAC therapeutics.