tbuckley/cabot-search huggingface dataset:
Cancer Clinical Trials — A Chronic but Curable Crisis
Authors: Robert C. Young
Journal: New England Journal of Medicine (2010)

In April, the Institute of Medicine (IOM) released a comprehensive review of the clinical trials program of the National Cancer Institute (NCI), in which it concluded that "the system for conducting clinical trials in the United States is approaching a state of crisis."1 The report, which was commissioned by the National Cancer Institute, drew the attention of the New York Times, which published an editorial on April 25 highlighting cumbersome procedures, excessive bureaucracy, poor coordination, and failure to complete 40% of the trials.2 On May 5, during hearings of the Senate Appropriations Committee, which holds jurisdiction over funding for the . . .
Increased Expression in Dorsolateral Prefrontal Cortex of CAPON in Schizophrenia and Bipolar Disorder
Authors: Bin Xu, Naomi Wratten, Erik I Charych, Steven Buyske, Bonnie L Firestein, Linda M Brzustowicz
Journal: PLoS Medicine (2005)

We have previously reported linkage of markers on chromosome 1q22 to schizophrenia, a finding supported by several independent studies. Within this linkage region, we have identified significant linkage disequilibrium between schizophrenia and markers within the gene for carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (CAPON). Prior sequencing of the ten exons of CAPON failed to reveal a coding mutation associated with illness.We screened a human fetal brain cDNA library and identified a new isoform of CAPON that consists of the terminal two exons of the gene, and verified the expression of the predicted corresponding protein in human dorsolateral prefrontal cortex (DLPFC). We examined the expression levels of both the ten-exon CAPON transcript and this new isoform in postmortem brain samples from the Stanley Array Collection. Quantitative real-time PCR analysis of RNA from the DLPFC in 105 individuals (35 with schizophrenia, 35 with bipolar disorder, and 35 psychiatrically normal controls) revealed significantly (p < 0.005) increased expression of the new isoform in both schizophrenia and bipolar disorder. Furthermore, this increased expression was significantly associated (p < 0.05) with genotype at three single-nucleotide polymorphisms previously identified as being in linkage disequilibrium with schizophrenia.Based on the known interactions between CAPON, neuronal nitric oxide synthase (nNOS), and proteins associated with the N-methyl-D-aspartate receptor (NMDAR) complex, overexpression of either CAPON isoform would be expected to disrupt the association between nNOS and the NMDAR, leading to changes consistent with the NMDAR hypofunctioning hypothesis of schizophrenia. This study adds support to a role of CAPON in schizophrenia, produces new evidence implicating this gene in the etiology of bipolar disorder, and suggests a possible mechanism of action of CAPON in psychiatric illness.
Abstract 3245: Novel anticancer agents – lead discovery and optimization
Authors: Liping Meng, Don-Hong Wang, Chun-Yi Wu, Kit S. Lam
Journal: Cancer Research (2011)

Abstract Though cancer chemotherapy helps in successful treating some types of solid tumors, lymphomas, and leukemias, cancer is still responsible for about one in every four deaths in the United States nowadays. Thus, it is urgent to develop novel anticancer agents to overcome the problems of toxicity and resistance of existing cancer chemotherapeutic agents, and eventually to cure cancer. Recently we have found some lead compounds possessing anticancer effects through a novel ultra-high-throughput multiplex screening of OBOC (one-bead-one-compound) small molecule combinatorial library against a M13 phage display cDNA expression proteome library derived from T-lymphoma Jurkat cell. These compounds were able to kill both Jurkat cells and HepG2 hepatocarcinoma cells with IC50s ranging from 15 µM to 80 µM. Further biopanning and pull down results showed that some compounds bounded to EIF5B – a eukaryotic translation imitation factor, which might inhibit the cellular translation initiation and result in apoptosis and eventually cause cell death. The lead optimization was carried out by using the method of “methyl walking” and “deletion studies”. A series of novel derivatives have been synthesized and structure-activity relationship will be investigated. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3245. doi:10.1158/1538-7445.AM2011-3245
HIV-Specific Cytolytic CD4 T Cell Responses During Acute HIV Infection Predict Disease Outcome
Authors: Damien Z. Soghoian, Heiko Jessen, Michael Flanders, Kailan Sierra-Davidson, Sam Cutler, Thomas Pertel, Srinika Ranasinghe, Madelene Lindqvist, Isaiah Davis, Kimberly Lane, Jenna Rychert, Eric S. Rosenberg, Alicja Piechocka-Trocha, Abraham L. Brass, Jason M. Brenchley, Bruce D. Walker, Hendrik Streeck
Journal: Science Translational Medicine (2012)

HIV-specific CD4 T cell responses during acute infection show robust cytolytic activity and correlate with a lower viral set point and better clinical outcome.
Dual Inhibition of Cathepsin G and Chymase Is Effective in Animal Models of Pulmonary Inflammation
Authors: Bruce E. Maryanoff, Lawrence de Garavilla, Michael N. Greco, Barbara J. Haertlein, Grace I. Wells, Patricia Andrade-Gordon, William M. Abraham
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: Mast cells and neutrophils are key contributors to the pathophysiological inflammatory processes that underpin asthma and chronic obstructive pulmonary disease, partly through the release of noxious serine proteases, including cathepsin G (Cat G) and chymase. From this standpoint, a dual inhibitor of neutrophil Cat G and mast cell chymase could protect against these disease-related inflammatory responses.Objectives: We examined the antiinflammatory pharmacology of RWJ-355871, a dual inhibitor of Cat G and chymase, in animal models of inflammation that evince pathophysiological pathways relevant to asthma and chronic obstructive pulmonary disease to determine the therapeutic potential of this compound.Methods: In an ovalbumin (OVA)-sensitized rat model, RWJ-355871 was administered to block the mast-cell–mediated increase in paw volume caused by OVA injection. In a sheep asthma model, antigen-induced airway responses were assessed with and without aerosol treatment with RWJ-355871. In a murine tobacco-smoke model of airway inflammation, the effect of RWJ-355871 on smoke-induced neutrophilia was determined.Measurements and Main Results: Intravenous treatment of OVA-sensitized rats with RWJ-355871 provided dose-dependent reduction in the increase in rat paw volume. In allergic sheep, aerosol pretreatment with RWJ-355871 showed dose-dependent inhibition of the antigen-induced early response, late response, and post–antigen-induced airway hyperreponsiveness. In tobacco-smoke–exposed mice, nebulized RWJ-355871 significantly reduced the smoke-induced neutrophilia from the levels observed in untreated mice.Conclusions: The preclinical antiinflammatory effects of RWJ-355871 in these animal models of inflammation indicate that this dual inhibitor may have therapeutic utility for treating airway inflammatory diseases involving mechanisms that depend on Cat G and/or chymase.
Effect of school based physical activity programme (KISS) on fitness and adiposity in primary schoolchildren: cluster randomised controlled trial
Authors: S. Kriemler, L. Zahner, C. Schindler, U. Meyer, T. Hartmann, H. Hebestreit, H. P. Brunner-La Rocca, W. van Mechelen, J. J Puder
Journal: BMJ (2010)

To assess the effectiveness of a school based physical activity programme during one school year on physical and psychological health in young schoolchildren.Cluster randomised controlled trial.28 classes from 15 elementary schools in Switzerland randomly selected and assigned in a 4:3 ratio to an intervention (n=16) or control arm (n=12) after stratification for grade (first and fifth grade), from August 2005 to June 2006.540 children, of whom 502 consented and presented at baseline.Children in the intervention arm (n=297) received a multi-component physical activity programme that included structuring the three existing physical education lessons each week and adding two additional lessons a week, daily short activity breaks, and physical activity homework. Children (n=205) and parents in the control group were not informed of an intervention group. For most outcome measures, the assessors were blinded.Primary outcome measures included body fat (sum of four skinfolds), aerobic fitness (shuttle run test), physical activity (accelerometry), and quality of life (questionnaires). Secondary outcome measures included body mass index and cardiovascular risk score (average z score of waist circumference, mean blood pressure, blood glucose, inverted high density lipoprotein cholesterol, and triglycerides).498 children completed the baseline and follow-up assessments (mean age 6.9 (SD 0.3) years for first grade, 11.1 (0.5) years for fifth grade). After adjustment for grade, sex, baseline values, and clustering within classes, children in the intervention arm compared with controls showed more negative changes in the z score of the sum of four skinfolds (-0.12, 95 % confidence interval -0.21 to -0.03; P=0.009). Likewise, their z scores for aerobic fitness increased more favourably (0.17, 0.01 to 0.32; P=0.04), as did those for moderate-vigorous physical activity in school (1.19, 0.78 to 1.60; P<0.001), all day moderate-vigorous physical activity (0.44, 0.05 to 0.82; P=0.03), and total physical activity in school (0.92, 0.35 to 1.50; P=0.003). Z scores for overall daily physical activity (0.21, -0.21 to 0.63) and physical quality of life (0.42, -1.23 to 2.06) as well as psychological quality of life (0.59, -0.85 to 2.03) did not change significantly.A school based multi-component physical activity intervention including compulsory elements improved physical activity and fitness and reduced adiposity in children. Trial registration Current Controlled Trials ISRCTN15360785.
Effects of a chronic treatment by nisoldipine, a calcium antagonistic dihydropyridine, on arteries of spontaneously hypertensive rats.
Authors: T Godfraind, S Kazda, M Wibo
Journal: Circulation Research (1991)

Earlier studies have shown that relaxation in response to several agents is impaired in arteries from spontaneously hypertensive rats (SHR). We had previously reported that SHR aortas present a delayed relaxation when first exposed for 35 minutes to a 100 mM KCl solution and then transferred into physiological solution. The first phase of relaxation appeared similar in SHR and Wistar-Kyoto rat arteries, but the second phase was markedly slowed down in SHR arteries, giving rise to a postcontraction tone. In this study, we found that this postcontraction tone could be demonstrated not only in the aorta but also in the mesenteric artery, was independent of the presence of endothelium, increased with the age of SHR, and disappeared progressively when arterial segments were submitted to successive cycles of KCl depolarization followed by reimmersion in physiological solution. Chronic treatment of SHR with nisoldipine at doses that blocked the development of hypertension and attenuated the concomitant hypertrophy of heart and aorta, or in vitro pretreatment of SHR arteries with nisoldipine, decreased the contractile force developed by arteries in response to KCl depolarization and normalized the subsequent relaxation. [3H] (+)-PN200-110 binding studies on heart and brain homogenates indicated an increase in apparent Kd in nisoldipine-fed rats without significant change in Bmax. Binding data were compatible with the view that occupation of dihydropyridine receptors by nisoldipine after chronic oral administration was responsible for the modifications observed ex vivo in the mechanical activity of arteries. We conclude that the postcontraction tone of SHR arteries was mainly due to an abnormally prolonged activation of calcium channels after transfer of depolarized arteries into the physiological solution and that a labile or slowly releasable factor was probably involved in this phenomenon. We suggest that the antihypertensive action of nisoldipine might be related to the mechanisms involved in the suppression of the postcontraction tone as observed in vitro and that this mode of action could be more important than the vasodilating effect of this drug.
Hyperaldosteronism Associated With Liver Metastases
Authors: Kishan J. Pandya
Journal: JAMA (1980)

Plasma aldosterone levels were measured in 50 patients with confirmed liver metastases from various histologically proved primary tumors. None of these patients had electrolyte abnormalities or history of benign liver disease, congestive heart failure, hypertension, or renal disease. Patients with edema, ascites, or both had significantly greater elevation of plasma aldosterone levels compared to nonedematous patients; these patients also demonstrated a substantial degree of hepatic dysfunction as evidenced by lower serum albumin levels and higher bilirubin and alkaline phosphatase levels. This study provides a rational basis for the use of the specific aldosterone inhibitor spironolactone in the treatment of patients with advanced metastatic liver disease and edematous states. (<i>JAMA</i>244:171-172, 1980)
Accuracy in Estimating Fasting Blood Glucose Levels by Patients with Diabetes
Authors: Rena R Wing, Leonard H Epstein, Danuta Lamparski, Sigrid A Hagg, Mary Patricia Nowalk, Nancy Scott
Journal: Diabetes Care (1984)

This study was designed to assess the accuracy with which diabetic patients can estimate their fasting blood sugars (FBS) and to determine whether experience with self-monitoring of blood glucose improves this ability. Twenty patients with type II diabetes who had no experience with self-monitoring of blood glucose were compared with 17 patients who had been monitoring blood sugar regularly for the previous 8 mo. All patients were asked to estimate FBS immediately before it was measured in the laboratory. Patients were very accurate in estimating their FBS; the average error in estimation was 2 mg/dl, and 65% of patients estimated FBS within 20% of actual FBS. However, there was no evidence that experience in self-monitoring of blood glucose improved the accuracy of estimation. Additional studies are needed to determine the types of cues that patients use in estimating blood sugar.
Effect of a critical coronary stenosis on myocardial neutrophil accumulation during ischemia and early reperfusion in dogs.
Authors: V J Richard, S E Brooks, R B Jennings, K A Reimer
Journal: Circulation (1989)

In many experimental models of ischemia and reperfusion, reperfusion is performed abruptly, allowing full reactive hyperemia to occur. In the clinical setting, however, reperfusion after thrombolysis is often limited by residual stenosis. Some experimental models attempt to mimic this situation with a "critical stenosis" (defined as a coronary constriction sufficient to abolish reactive hyperemia without altering baseline flow). The purpose of this study was to determine whether preventing reactive hyperemia during the initial phase of reperfusion would modify the transmural distribution of myocardial blood flow or the myocardial accumulation of polymorphonuclear leukocytes (PMNs). The left circumflex artery was occluded for 90 minutes and then reperfused for 60 minutes in anesthetized, open-chest dogs. Autologous PMNs were isolated, labeled with 111In, and reinjected 1 hour before coronary occlusion. 125I-labeled albumin was injected simultaneously to correct for 111In associated with plasma proteins and to permit calculation of the number of PMNs in the inner, middle, and outer thirds of nonischemic and ischemic-reperfused tissue. The presence of a critical stenosis abolished reactive hyperemia during the first 5 minutes of reperfusion, but did not substantially affect blood flow measured after 55 minutes of reperfusion. In both groups, there was a significant accumulation of PMNs in all layers of the ischemic-reperfused bed compared with the nonischemic bed, and the magnitude of this PMN accumulation was not altered by the presence of a critical stenosis. Moreover, infarct size, estimated by triphenyl tetrazolium chloride (TTC) loss after 60 minutes of reperfusion, was not affected by the presence of a critical stenosis. Thus, the presence of a critical stenosis abolished the hyperemic blood flow after reperfusion but did not influence the early PMN response to ischemia and reperfusion or the early loss of TTC staining.
Use of microsatellite marker loss of heterozygosity in accurate diagnosis of pancreaticobiliary malignancy from brush cytology samples
Authors: A Khalid
Journal: Gut (2004)

Brush cytology of biliary strictures to diagnose pancreaticobiliary malignancy suffers from poor sensitivity.To improve the diagnostic yield of pancreaticobiliary brush cytology through analysis of tumour suppressor gene linked microsatellite marker loss of heterozygosity (LOH) and k-ras codon 12 mutation detection.Twenty six patients with biliary strictures underwent endoscopic retrograde cholangiography with brush cytology. A panel of 12 polymorphic microsatellite markers linked to six tumour suppressor genes was developed. Genomic DNA from cell clusters acquired from brush cytology specimens and microdissected surgical malignant and normal tissue underwent polymerase chain amplification reaction (PCR). PCR products were compared for LOH and k-ras codon 12 mutations.Seventeen patients were confirmed to have pancreaticobiliary adenocarcinoma. Nine patients had benign strictures (eight proven surgically, one by follow up). Cytomorphological interpretation was positive for malignancy (n = 8), indeterminate (n = 10), and negative for malignancy (n = 8). Selected malignant appearing cytological cell clusters and microdissected histological samples from cancer showed abundant LOH characteristic of malignancy while brushings from nine cases without cancer carried no LOH (p<0.001). LOH and k-ras mutations profile of the cytological specimens was almost always concordant with the tissue samples. Presence of k-ras mutation predicted malignancy of pancreatic origin (p<0.001).LOH and k-ras codon 12 mutation analysis of PCR amplified DNA from biliary brush cytology discriminates reactive from malignant cells, with 100% sensitivity, specificity, and accuracy. Minor variations in LOH in brushings and in different sites within the same tumour likely reflect intratumoral mutational heterogeneity during clonal expansion of pre- and neoplastic lineages.
Intrathoracic Abnormalities Demonstrated by Technetium-99m Sulfur Colloid Imaging
Authors: WEI-JEN SHIH, PEGGY A. DOMSTAD, BRUCE FRIEDMAN, FRANK H. DeLAND
Journal: Clinical Nuclear Medicine (1986)

Since the scintillation camera enables us to include lower thorax in the views obtained during Tc-99m colloid imaging of the liver and spleen, intrathoracic pathology may be identified as relatively cold or hot areas in the thoracic cavity. Eighteen patients who underwent Tc-99m sulfur colloid imaging during a one-year period were found to have intrathoracic pathology demonstrated either as photopenic areas or as areas of increased radioactivity. These patients' clinical data and the results of other diagnostic modalities, including autopsy, were correlated with the Tc-99m images. The intrathoracic disease processes recognized were bacteremia, two cases; pleural effusion, two cases; lung pathology, one case; and cardiomegaly, 13 cases. With the Exception of two patients with bacteremia who had substantial radiocolloid sequestration by the lung, all the other patients had hepatic dysfunction. The presence of compromised hepatic function allows the visualization of intrathoracic abnormalities: photopenia suggesting pleural fluid collection or an enlarged cardiac silhouette (either photopenia or increased radioactivity occupying a large space in the anterior view to yield cardiothoracic ratio of greater than 50%). Therefore, Tc-99m sulfur during colloid liver–spleen imaging, patients with hepatic dysfunction may incidentally demonstrate intrathoracic pathology, especially cardiomegaly.
The Role of Hematological Parameters on Prognosis of Metastatic Gastric Carcinoma
Authors: Dilek Erdem, Bahiddin Yilmaz, Emre Erdem, Fatih Mehmet Cilingir, Engin Kut, Selim Kocasarac, Guzin Demirag, Idris Yucel
Journal: Annals of Oncology (2013)
RECENT INVESTIGATIONS BEARING ON INFECTIOUS DISEASES OF UNKNOWN ETIOLOGY.
Authors: LUDVIG HEKTOEN
Journal: JAMA (1903)

Bacteriologic and microscopic examination of the blood has given no constant results. Nevertheless the injection of a few drops of blood invariably causes death in two or three days. Indeed, the mere insertion of a needle into the blood suffices to carry over sufficient virus to cause death. Fatal infection by way of the stomach follows the mixing of a few drops of blood with the food, and the clearest serum is as infectious as the whole blood. By inoculating a series of animals, one from another, Centanni shows that it does not concern a toxin or enzyme, but a viable virus capable of endless reproduction. He further found that the infectious agent passes through Berkefeld and Chamberland (F) filters in virulent form. Maggiora and Valenti find that the Chamberland filter K under a pressure of 11/2 atmospheres holds back the infectious agent. Lode and Gruber made the
What is in the differential diagnosis of a B-type natriuretic peptide level of 1,000 pg/ml?
Authors: Peter A. McCullough, Richard M. Nowak, James McCord, Torbjorn Omland, Catherine W. Knudsen, Phillippe Duc, Judd E. Hollander, Phillippe Gabriel Steg, Marie-Claude Aumont, Arne Westheim, Alan B. Storrow, William T. Abraham, Sumant Lamba, Alan H. Wu, Alan S. Maisel
Journal: Journal of the American College of Cardiology (2003)
The Threat of Artemisinin-Resistant Malaria
Authors: Arjen M. Dondorp, Rick M. Fairhurst, Laurence Slutsker, John R. MacArthur, Joel G. Breman M.D., Philippe J. Guerin, Thomas E. Wellems, Pascal Ringwald, Robert D. Newman, Christopher V. Plowe
Journal: New England Journal of Medicine (2011)

Since the 1970s, when Chinese researchers demonstrated the artemisinins' antimalarial potency, artemisinin-based combination therapy has become key to malaria control. But reduced susceptibility of Plasmodium falciparum to artemisinin is now being seen in some places.
Eye surgeon claims that new treatment centre is a threat to NHS
Authors: O. Dyer
Journal: BMJ (2003)

Doctors at the Oxford Eye Hospital say their service is threatened by government plans to farm out cataract operations to a diagnostic and treatment centre run by a private foreign company.

John Elston, a consultant surgeon at the hospital, told BBC Radio 4's Today programme that the private scheme was a “serious threat.”

“The cataract work subsidises the work in chronic eye disease so it could well mean that we would lose numbers of our trainees, and if we lose staff, then we lose the ability to offer the full range of services,” he said. “You need a critical mass to attract the referrals and to provide …