tbuckley/cabot-search huggingface dataset:
Role of N-linked glycans in the interaction between the envelope glycoprotein of human immunodeficiency virus and its CD4 cellular receptor. Structural enzymatic analysis.
Authors: E Fenouillet, B Clerget-Raslain, J C Gluckman, D Guétard, L Montagnier, E Bahraoui
Journal: The Journal of Experimental Medicine (1989)

gp120 and CD4 are two glycoproteins that are considered to interact together to allow the binding of HIV to CD4+ cells. We have utilized enzymatic digestion by endoglycosidases in order to analyze N-linked carbohydrate chains of these proteins and their possible role in the interaction of gp120 or gp160 with CD4. SDS denaturation was not necessary to obtain optimal deglycosylation of either molecule, but deglycosylation of CD4, nonetheless, depended on the presence of 1% Triton X-100. Endo H and Endo F that cleave high mannose type and biantennary glycans diminish the molecular mass of the glycoproteins from 120 or 160 Kd to 90 or 130 Kd, respectively; but these enzymes had no action on CD4 glycans. Endo F N-glycanase mixture, which acts on all glycan species, including triantennary chains, led to complete deglycosylation of gp120/160 and of CD4. Therefore, probably half of the glycan moieties of gp120/160 are composed of high mannose and biantennary chains, the other half being triantennary species. The carbohydrate structures of CD4 seems to be triantennary chains. To analyze the binding of gp120/160 to CD4, we used a molecular assay in which an mAb (110-4) coupled to Sepharose CL4B allowed the attachment of soluble gp120/160 to the beads; 125I-sCD4 was then added to measure the binding of CD4 to different amounts of gp120/160. Binding to gp160 was not modified when using completely deglycosylated 125I-sCD4, while deglycosylation of gp120 or of gp160 resulted in the decrease of the binding to native CD4 by two- and fivefold, respectively. Native and deglycosylated gp120/160 bound to CD4+ cells with comparable affinities. In addition, deglycosylated gp120 displaced 125I-gp160 binding to CD4+ cells and inhibited fusion of fresh Molt-T4 cells with CEM HIV1- or HIV2-infected cells to the same extent. Taken together, these results indicate that carbohydrates of CD4 and of gp120/160 do not play a significant role in the in vitro interaction between these two molecules.
Pharmacokinetic Model-Predicted Anticancer Drug Concentrations in Human Tumors
Authors: James M. Gallo, Paolo Vicini, Amy Orlansky, Shaolan Li, Feng Zhou, Jianguo Ma, Sharon Pulfer, Michel A. Bookman, Ping Guo
Journal: Clinical Cancer Research (2004)

Abstract In an era when molecular and targeted anticancer therapeutics is a major focus and when understanding drug dynamics in tumor is critical, it seems advantageous to be able to relate drug concentrations in tumors to corresponding biological end points. To that end, a novel method, based on physiologically based hybrid pharmacokinetic models, is presented to predict human tumor drug concentrations. Such models consist of a forcing function, describing the plasma drug concentration-time profile, which is linked to a model describing drug disposition in tumors. The hybrid models are originally derived from preclinical data and then scaled to humans. Integral to the scale-up procedure is the ability to derive human forcing functions directly from clinical pharmacokinetic data. Three examples of this approach are presented based on preclinical investigations with carboplatin, topotecan, and temozolomide. Translation of these preclinical hybrid models to humans used a Monte Carlo simulation technique that accounted for intrasubject and intersubject variability. Different pharmacokinetic end points, such as the AUC tumor, were extracted from the simulated human tumor drug concentrations to show how the predicted drug concentrations might be used to select drug-dosing regimens. It is believed that this modeling strategy can be used as an aid in the drug development process by providing key insights into drug disposition in tumors and by offering a foundation to optimize drug regimen design.
Docetaxel and atrasentan versus docetaxel and placebo for men with advanced castration-resistant prostate cancer (SWOG S0421): a randomised phase 3 trial
Authors: David I Quinn, Catherine M Tangen, Maha Hussain, Primo N Lara, Amir Goldkorn, Carol M Moinpour, Mark G Garzotto, Philip C Mack, Michael A Carducci, J Paul Monk, Przemyslaw W Twardowski, Peter J Van Veldhuizen, Neeraj Agarwal, Celestia S Higano, Nicholas J Vogelzang, Ian M Thompson
Journal: The Lancet Oncology (2013)
THE EEG. IN LATE POST-TRAUMATIC CASES
Authors: MILTON GREENBLATT
Journal: American Journal of Psychiatry (1943)

About one-half (48%) of late post-traumatic cases have abnormal EEGs. The presence of fracture or unconsciousness does not appreciably alter this percentage. Post-traumatic cases with epilepsy have a higher percentage of abnormal EEGs. and post-traumatic cases with headache have a lower percentage of abnormal EEGs. than the average. Post-traumatic cases with psychosis have a slightly greater percentage of abnormal EEGs. than do those without psychosis. Late post-traumatic cases suffering primarily from headaches have essentially the same percentage abnormality of EEGs. as non-traumatic cases suffering primarily from headaches. Late post-traumatic cases suffering from psychosis (organic reaction type) have essentially the same percentage abnormality as non-traumatic cases suffering from organic psychosis. Late post-traumatic cases suffering primarily from epilepsy have essentially the same percentage abnormality as non-traumatic cases suffering from epilepsy. In almost all post-traumatic cases having evide...
The Glasgow alcoholic hepatitis score identifies patients who may benefit from corticosteroids
Authors: E H Forrest, A J Morris, S Stewart, M Phillips, Y H Oo, N C Fisher, G Haydon, J O'Grady, C P Day
Journal: Gut (2007)

<h3>Introduction:</h3> There is no consensus on the pharmacological treatment of alcoholic hepatitis. The Glasgow alcoholic hepatitis score (GAHS) has been shown to be more accurate than the modified Maddrey's discriminant function (mDF) in the prediction of outcome from alcoholic hepatitis. This study aimed to determine whether the GAHS was able to identify those patients who would benefit from corticosteroids. <h3>Methods:</h3> 225 patients with an mDF greater than or equal to 32 from five hospital centres in the United Kingdom were reviewed. Patient survival relative to the GAHS and the use of corticosteroids was recorded. <h3>Results:</h3> 144 patients with an mDF greater than or equal to 32 (64%) also had a GAHS greater than or equal to 9. There was no difference in survival between untreated or corticosteroid-treated patients for those with a GAHS less than 9. For patients with a GAHS greater than or equal to 9 the 28-day survival for untreated and corticosteroid-treated patients was 52% and 78% (p = 0.002), and 84-day survival was 38% and 59% (p = 0.02), respectively. <h3>Conclusions:</h3> Among patients with an mDF greater than or equal to 32, there was no appreciable benefit from treatment with corticosteroids in patients with a GAHS less than 9. Patients with a GAHS greater than or equal to 9 have an extremely poor prognosis if they are not treated with corticosteroids, or if such treatment is contraindicated.
Isolated Left Anterior Descending Coronary Artery Disease : Percutaneous Transluminal Coronary Angioplasty Versus Stenting Versus Left Internal Mammary Artery Bypass Grafting
Authors: J. H. O Keefe, T. R. Kreamer, P. G. Jones, J. L. Vacek, M. E. Gorton, G. F. Muehlebach, B. D. Rutherford, B. D. McCallister
Journal: Circulation (1999)

Single-vessel coronary artery disease is usually treated with PTCA; however, this approach when applied to the left anterior descending coronary artery (LAD) is hampered by high restenosis rates, often approaching 50%. Coronary stenting (STENT) and left internal mammary artery bypass grafting of the LAD (LIMA-LAD) are other options that have been successfully used for single-vessel LAD disease. The optimal mode of revascularization for patients with isolated single-vessel LAD disease is unclear. The purpose of the present study was to examine PTCA versus STENT versus LIMA-LAD with respect to short- and intermediate-term outcomes.This was an observational retrospective cohort study comparing in-hospital and intermediate-term outcomes and functional class among patients with isolated single-vessel LAD disease revascularization. Consecutive eligible patients were grouped according to their initial revascularization procedure and systematically followed up. A total of 704 patients qualified for the study: 469 in the PTCA group, 137 in the STENT group, and 98 in the LIMA-LAD group. Follow-up data were complete for 97% of patients and averaged 27+/-13 months. In-hospital mortality for the PTCA, STENT, and LIMA-LAD groups was 1.1%, 0%, and 0% (P=0.51), respectively. Median hospital stays after the procedure for the respective treatment groups were 1, 1, and 5 days (P<0.001), and occurrences of in-hospital myocardial infarction were 0.9%, 1.5%, and 1.0% (P=NS). Repeat revascularization procedures were performed in 30%, 24%, and 5% of the PTCA, STENT, and LIMA-LAD groups (P=<0. 001 for LIMA-LAD versus other groups, P=0.11 for PTCA versus STENT). Actuarial 2-year mortality was 3.9%, 2.6%, and 1% in the PTCA, STENT, and LIMA-LAD groups (P=0.33).Revascularization for isolated LAD disease using PTCA, STENT, or LIMA-LAD results in low in-hospital adverse event rates and good long-term results. Repeat procedures are required less often after LIMA-LAD than after either PTCA or STENT. Long-term mortality was not statistically different, but the trend was for the lowest mortality with LIMA-LAD, a somewhat higher mortality with STENT, and the highest mortality with PTCA.
Leukocyte Recruitment in the Cerebrospinal Fluid of Mice with Experimental Meningitis Is Inhibited by an Antibody to Junctional Adhesion Molecule (Jam)
Authors: Aldo Del Maschio, Ada De Luigi, Ines Martin-Padura, Manfred Brockhaus, Tamas Bartfai, Paolo Fruscella, Luciano Adorini, GianVito Martino, Roberto Furlan, Maria Grazia De Simoni, Elisabetta Dejana
Journal: The Journal of Experimental Medicine (1999)

The mechanisms that govern leukocyte transmigration through the endothelium are not yet fully defined. Junctional adhesion molecule (JAM) is a newly cloned member of the immunoglobulin superfamily which is selectively concentrated at tight junctions of endothelial and epithelial cells. A blocking monoclonal antibody (BV11 mAb) directed to JAM was able to inhibit monocyte transmigration through endothelial cells in in vitro and in vivo chemotaxis assays. In this study, we report that BV11 administration was able to attenuate cytokine-induced meningitis in mice. The intravenous injection of BV11 mAb significantly inhibited leukocyte accumulation in the cerebrospinal fluid and infiltration in the brain parenchyma. Blood–brain barrier permeability was also reduced by the mAb. We conclude that JAM may be a new target in limiting the inflammatory response that accompanies meningitis.
Mature miR-184 as Potential Oncogenic microRNA of Squamous Cell Carcinoma of Tongue
Authors: Thian-Sze Wong, Xiao-Bing Liu, Birgitta Yee-Hang Wong, Raymond Wai-Man Ng, Anthony Po-Wing Yuen, William Ignace Wei
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The aim of this study was to evaluate the microRNA expression patterns in squamous cell carcinoma (SCC) of the tongue. Experimental Design: Expression levels of 156 human mature microRNAs were examined using real-time quantitative PCR (Taq Man MicroRNA Assays; Human Panel) on laser microdissected cells of 4 tongue carcinomas and paired normal tissues. Expression of mature miR-184 was further validated in 20 paired tongue SCC and the normal tissues. Potential oncogenic functions of miR-184 were evaluated in tongue SCC cell lines (Cal27, HN21B, and HN96) with miR-184 inhibitor. Plasma miR-184 levels were evaluated using real-time quantitative PCR. Results: Using 3-fold expression difference as a cutoff level, we identified 24 up-regulated mature miRNAs including miR-184, miR-34c, miR-137, miR-372, miR-124a, miR-21, miR-124b, miR-31, miR-128a, miR-34b, miR-154, miR-197, miR-132, miR-147, miR-325, miR-181c, miR-198, miR-155, miR-30a-3p, miR-338, miR-17-5p, miR-104, miR-134, and miR-213; and 13 down-regulated mature miRNAs including miR-133a, miR-99a, miR-194, miR-133b, miR-219, miR-100, miR-125b, miR-26b, miR-138, miR-149, miR-195, miR-107, and miR-139. Overexpression of miR-184 was further validated in 20 paired tongue SCC and normal tissues (P = 0.002). Inhibition of miR-184 in tongue SCC cell lines could reduce cell proliferation rate. Down-regulation of c-Myc was observed in two cell lines in response to miR-184 inhibitor. Suppressing miR-184 could induce apoptosis in all three cell lines. Plasma miR-184 levels were significantly higher in tongue SCC patients in comparison with normal individuals, and the levels were significantly reduced after surgical removal of the primary tumors. Conclusions: Overexpression of miR-184 might play an oncogenic role in the antiapoptotic and proliferative processes of tongue SCC. In addition, plasma miR-184 levels were associated with the presence of primary tumor. Further studies on the aberrantly expressed miRNAs in tongue SCC as well as using plasma miRNAs as novel tumor markers are warranted.
Hypomethylating Therapy in an Aggressive Stroma-Rich Model of Pancreatic Carcinoma
Authors: Reena Shakya, Tamas Gonda, Michael Quante, Martha Salas, Samuel Kim, Jenna Brooks, Steffen Hirsch, Justine Davies, Angelica Cullo, Kenneth Olive, Timothy C. Wang, Matthias Szabolcs, Benjamin Tycko, Thomas Ludwig
Journal: Cancer Research (2012)

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that resists current treatments. To test epigenetic therapy against this cancer, we used the DNA demethylating drug 5-aza-2'-deoxycytidine (DAC) in an aggressive mouse model of stromal rich PDAC (KPC-Brca1 mice). In untreated tumors, we found globally decreased 5-methyl-cytosine (5-mC) in malignant epithelial cells and in cancer-associated myofibroblasts (CAF), along with increased amounts of 5-hydroxymethyl-cytosine (5-HmC) in CAFs, in progression from pancreatic intraepithelial neoplasia to PDAC. DAC further reduced DNA methylation and slowed PDAC progression, markedly extending survival in an early-treatment protocol and significantly though transiently inhibiting tumor growth when initiated later, without adverse side effects. Escaping tumors contained areas of sarcomatoid transformation with disappearance of CAFs. Mixing-allografting experiments and proliferation indices showed that DAC efficacy was due to inhibition of both the malignant epithelial cells and the CAFs. Expression profiling and immunohistochemistry highlighted DAC induction of STAT1 in the tumors, and DAC plus IFN-γ produced an additive antiproliferative effect on PDAC cells. DAC induced strong expression of the testis antigen deleted in azoospermia-like (DAZL) in CAFs. These data show that DAC is effective against PDAC in vivo and provide a rationale for future studies combining hypomethylating agents with cytokines and immunotherapy.
Abdominal Pain and a Biliary Abnormality
Authors: James L. Crawford, Michael J. Pucci, Charles J. Yeo, Harish Lavu
Journal: JAMA Surgery (2013)

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Effects of cigarette smoking and its cessation on lipid metabolism and energy expenditure in heavy smokers.
Authors: M K Hellerstein, N L Benowitz, R A Neese, J M Schwartz, R Hoh, P Jacob, J Hsieh, D Faix
Journal: Journal of Clinical Investigation (1994)

The relationship between thermogenic and potentially atherogenic effects of cigarette smoking (CS) and its cessation was investigated. Heavy smokers (n = 7, serum cotinine > 200 ng/ml, > 20 cigarettes/d) were maintained on isoenergetic, constant diets for 2 wk, 1 wk with and 1 wk without CS. Stable isotope infusions with indirect calorimetry were performed on day 7 of each phase, after an overnight fast. CS after overnight abstention increased resting energy expenditure by 5% (not significant vs. non-CS phase; P = 0.18). CS increased the flux of FFA by 77%, flux of glycerol by 82%, and serum FFA concentrations by 73% (P < 0.02 for each), but did not significantly affect fat oxidation. Hepatic reesterification of FFA increased more than threefold (P < 0.03) and adipocyte recycling increased nonsignificantly (P = 0.10). CS-induced lipid substrate cycles represented only 15% (estimated 11 kcal/d) of observed changes in energy expenditure. De novo hepatic lipogenesis was low (< 1-2 g/d) and unaffected by either acute CS or its chronic cessation. Hepatic glucose production was not affected by CS, despite increased serum glycerol and FFA fluxes. Cessation of CS caused no rebound effects on basal metabolic fluxes. In conclusion, a metabolic mechanism for the atherogenic effects of CS on serum lipids (increased hepatic reesterification of FFA) has been documented. Increased entry of FFA accounts for CS-induced increases in serum FFA concentrations. The thermogenic effect of CS is small or absent in heavy smokers while the potentially atherogenic effect is maintained, and cessation of CS does not induce a rebound lipogenic milieu that specifically favors accrual of body fat in the absence of increased food intake.
Is bowling workload a risk factor for injury to Australian junior cricket fast bowlers?
Authors: R J Dennis, C F Finch, P J Farhart
Journal: British Journal of Sports Medicine (2005)

To examine whether bowling workload is a risk factor for overuse injury to Australian junior cricket fast bowlers and to evaluate the appropriateness of current bowling workload guidelines.Forty four male fast bowlers (mean (standard deviation) age 14.7 (1.4) years) were monitored prospectively over the 2002-2003 season. Bowlers completed a daily diary to record bowling workloads and self reported injuries, which were validated by a physiotherapist. Bowling workload prior to the first injury (for those bowlers who were injured) was compared to workload across the whole season for uninjured bowlers.Eleven (25%) bowlers reported an overuse-type injury, with seven of these sustaining a back injury. Injured bowlers had been bowling significantly more frequently than uninjured bowlers (median number of days since the previous bowling day: 3.2 v 3.9 days, Mann-Whitney U = 105.0, p = 0.038). Compared with bowlers with an average of > or =3.5 rest days between bowling, bowlers with an average of <3.5 rest days were at a significantly increased risk of injury (risk ratio (RR) = 3.1, 95% confidence interval (CI) 1.1 to 8.9). There were also trends towards an increased risk of injury for those who bowled an average of > or =2.5 days per week (RR = 2.5, 95% CI 0.9 to 7.4) or > or =50 deliveries per day (RR = 2.0, 95% CI 0.7 to 5.4).This study has identified high bowling workload as a risk factor for overuse injury to junior fast bowlers. Continued research is required to provide scientific evidence for bowling workload guidelines that are age-specific for junior fast bowlers.
Symptoms and stool patterns in patients with ulcerative colitis.
Authors: S S Rao, C D Holdsworth, N W Read
Journal: Gut (1988)

The prevalence of symptoms and stool patterns was assessed prospectively in 96 patients with ulcerative colitis subdivided according to the extent and activity of the disease. Increased frequency of defecation (83%), urgency (85%), a feeling of incomplete evacuation (78%) and tenesmus (63%) were the most frequent symptoms experienced by patients with active colitis. All were significantly more common (p less than 0.001) in patients with active than quiescent colitis and their prevalence was similar in those with total and distal colitis, indicating that these symptoms are related to an inflamed and irritable distal colon. Twenty seven per cent of patients with active colitis voided hard stools indicative of constipation, however, and this was more common in active, than quiescent colitis (p less than 0.05). This feature is probably secondary to faecal stasis in the proximal colon, and an apt description of the bowel disturbance in ulcerative colitis, irrespective of the extent of disease is that the colon suffers from proximal constipation and distal irritability.
Early Atherosclerosis Relates to Urinary Albumin Excretion and Cardiovascular Risk Factors in Adolescents With Type 1 Diabetes: Adolescent Type 1 Diabetes cardio-renal Intervention Trial (AdDIT)
Authors: Oana Maftei, Alexia S. Pena, Thomas Sullivan, Timothy W. Jones, Kim C. Donaghue, Fergus J. Cameron, Elizabeth Davis, Andrew Cotterill, Maria E. Craig, Roger Gent, Neil Dalton, Denis Daneman, David Dunger, John Deanfield, Jenny J. Couper
Journal: Diabetes Care (2014)

The origins of cardiovascular and renal disease in type 1 diabetes begin during childhood. We aimed to evaluate carotid (cIMT) and aortic intima-media thickness (aIMT) and their relationship with cardiovascular risk factors and urinary albumin excretion in adolescents with type 1 diabetes in the Adolescent Type 1 Diabetes cardio-renal Intervention Trial (AdDIT).
A lady with unresolved loin pain
Authors: Kai Ming Chow, Kirsty Wai Chung Lee, Tiffany Cho Lam Wong, Cheuk Chun Szeto
Journal: Journal of the Royal Society of Medicine (2008)

A history of cardiac disease, especially atrial fibrillation, together with symptoms such as loin or abdominal pain, and accompanied by an elevated lactate dehydrogenase should prompt a computed tomography scan to exclude the diagnosis of acute renal infarction.