tbuckley/cabot-search huggingface dataset:
Prospective Analysis of Mannose-Binding Lectin Genotypes and Coronary Artery Disease in American Indians
Authors: Lyle G. Best, Michael Davidson, Kari E. North, Jean W. MacCluer, Ying Zhang, Elisa T. Lee, Barbara V. Howard, Susan DeCroo, Robert E. Ferrell
Journal: Circulation (2004)

Mannose-binding lectin (MBL) is a circulating immune factor responsible for opsonization of pathogens and directly activating complement. Common variations in the MBL gene are responsible for an opsonic deficiency that affects 5% to 7% of whites and are associated with increased susceptibility to infections. After a preliminary report associating these variations with coronary artery disease (CAD), we determined MBL genotypes in 3 American Indian communities experiencing an increased mortality and morbidity from CAD.We examined DNA from 434 participants in a population-based cohort, the Strong Heart Study. Genotypes for 3 common MBL coding variations and 1 promoter polymorphism were determined. The frequency of a composite genotype that conferred low MBL levels was 20.7% in 217 cases and 11.1% in matched controls without CAD. A conditional logistic regression model indicated a univariate OR for CAD of 2.3 (95% CI 1.3 to 4.2, P=0.005) for the variant genotypes. After adjustment for demographic and CAD risk factors, including type 2 diabetes mellitus, fibrinogen, triglycerides, and hypertension, the OR was 3.2 (95% CI 1.5 to 7.0, P=0.004).Variant MBL genotypes coding for markedly diminished levels of MBL are predictive of CAD. After adjustment for multiple traditional risk factors for ischemic heart disease, this association remains significant. A high prevalence of variant MBL alleles and CAD in this population suggests that potentially important public health benefits may accrue from future interventions based on these genotypes.
Membrane Physiology — Bridging the Gap between Medical Disciplines
Authors: Markus Bleich
Journal: New England Journal of Medicine (2009)

The general separation between medical disciplines has, for decades, been a strange tradition. For example, neurologists and nephrologists have each had their defined patient groups, and many are barely interested, if at all, in the other discipline's research. Even within a specific field of basic science, such as physiology, neurophysiologists do not necessarily talk with other physiologists. Thus, the blood–brain barrier has been dividing more than two extracellular spaces. A credible exception may be found among clinical disciplines that focus on the patient as a whole, such as pediatrics. Children often present with complex syndromes that may be considered sporadic . . .
Energy Metabolism After Ischemic Preconditioning in Streptozotocin-Induced Diabetic Rat Hearts
Authors: Tetsuya Tatsumi, Satoaki Matoba, Miyuki Kobara, Natsuya Keira, Akira Kawahara, Kouki Tsuruyama, Tetsuya Tanaka, Maki Katamura, Chiaki Nakagawa, Bon Ohta, Yasuhiro Yamahara, Jun Asayama, Masao Nakagawa
Journal: Journal of the American College of Cardiology (1998)
Genome-Wide Linkage Scan for Loci Predisposing to Social Phobia: Evidence for a Chromosome 16 Risk Locus
Authors: Joel Gelernter, Grier P. Page, Murray B. Stein, Scott W. Woods
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Social phobia is a common, sometimes disabling, fear of situations that might entail scrutiny by others. Several anxiety disorders, including social phobia, are genetically influenced. Genetic linkage analysis can provide the means to identify genomic locations harboring susceptibility loci for genetically influenced disorders. Identifying loci for social phobia was the goal of this study. METHOD: The authors conducted a genome-wide linkage scan, i.e., tested enough genetic markers to query the entire genome, in 17 American pedigrees (163 subjects) ascertained through probands with panic disorder. Several anxiety disorders segregate in these families; diagnoses were based on structured interviews. A total of 422 markers (404 autosomal, 18 on the X chromosome) with an average spacing of less than 10 centimorgans were genotyped. Multipoint lod score and nonparametric (Zlr score) linkage analyses for social phobia were completed with Allegro and Genehunter X software. RESULTS: Evidence for linkage to social phobia for chromosome 16 markers was identified. A Zlr score of 3.41 was observed for chromosome 16 near marker D16S415. The maximum observed lod score was 2.22, also for chromosome 16, between D16S415 and D16S503 (under a model of recessive inheritance). Additional areas of interest were identified on chromosomes 9, 14, and 18. CONCLUSIONS: These findings meet conservative criteria for “suggestive” linkage. The gene encoding the norepinephrine transporter protein (SLC6A2) maps to this broad region, making SLC6A2 both a positional and physiological candidate for influencing social phobia risk. To the authors’ knowledge, this is the first complete linkage genome scan for this disorder.
Quantitative analysis of minimal residual disease predicts relapse in children with B-lineage acute lymphoblastic leukemia in DFCI ALL Consortium Protocol 95-01
Authors: Jianbiao Zhou, Meredith A Goldwasser, Aihong Li, Suzanne E. Dahlberg, Donna Neuberg, Hongjun Wang, Virginia Dalton, Kathryn D McBride, Stephen E. Sallan, Lewis B Silverman, John G. Gribben
Journal: Blood (2007)
Neuroethics, National Security and Secrecy
Authors: David B. Resnik
Journal: The American Journal of Bioethics (2007)

"Neuroethics, National Security and Secrecy." The American Journal of Bioethics, 7(5), pp. 14–15 The intramural program of the National Institute of Environmental Health Sciences, National Institutes of Health, sponsored this research. It does not represent the views of the National Institute of Environmental Health Sciences or the National Institutes of Health.
Adrenergic Control of the Force-Frequency and Relaxation-Frequency Relations in Patients With Hypertrophic Cardiomyopathy
Authors: Hideo Izawa, Mitsuhiro Yokota, Yasushi Takeichi, Masafumi Inagaki, Kohzo Nagata, Mitsunori Iwase, Toshikazu Sobue
Journal: Circulation (1997)

Background Exercise-induced enhancement of the force-frequency and relaxation-frequency relations has been studied in conscious animals but not in intact diseased human hearts. Methods and Results We evaluated left ventricular (LV) isovolumic contraction (dP/dt max ) and relaxation (τ) during atrial pacing and dynamic exercise in 13 patients with nonobstructive hypertrophic cardiomyopathy (HCM) and 7 control subjects to investigate the influence of exercise on the force-frequency and relaxation-frequency relations. Group A consisted of 6 patients in whom the heart rate (HR)–dP/dt max relation was markedly enhanced during exercise (88±30%) compared with during pacing (34±15%). Group B consisted of 7 patients in whom the HR-dP/dt max relation showed similar enhancement during exercise (28±7%) and atrial pacing (28±11%). There was no difference in the HR-τ (derivative method [TD] and pressure half-time method [T 1/2 ]) relation between pacing and exercise in groups A and B. Both the mean maximal wall thickness and the hypertrophy score in group B were greater than in group A (27±5 versus 19±2 mm and 7±1 versus 5±1 points, respectively; both P &lt;.01). There was no difference in the LV peak systolic pressure, end-diastolic pressure, or the plasma level of catecholamines at baseline, at 50 W of exercise, and at peak pacing between groups A and B. The HR-dP/dt max relation in the control group was markedly enhanced during exercise (80±27%) compared with during pacing (32±14%). The HR-τ relation in the control group was enhanced during exercise (TD, 35±9%; T 1/2 , 34±8%) compared with during pacing (TD, 12±7%; T 1/2 , 14±7%). Conclusions Exercise-induced enhancement of the relaxation-frequency relation was inhibited in all HCM patients, regardless of the degree of LV hypertrophy. The patients without exercise-induced enhancement of the force-frequency relation had more severe LV hypertrophy than the patients with the enhancement, indicating that the adrenergic control of the force-frequency relation may, at least in part, depend on the severity of LV hypertrophy or the stage of HCM.
Minimal role of enhanced cell proliferation in skin tumor promotion by mirex: a nonphorbol ester-type promoter.
Authors: S A Meyer, G J Moser, N A Monteiro-Riviere, R C Smart
Journal: Environmental Health Perspectives (1993)

Mirex, a chlorinated hydrocarbon previously used as a systemic insecticide and flame retardant, is a nongenotoxic hepatocarcinogen in both rats and mice. In liver, mirex induced biochemical responses and hyperplasia characteristic of increased cell proliferation, which is consistent with its role as a liver tumor promoter. We have recently shown that mirex is a potent nonphorbol ester-type skin tumor promoter in 7, 12-dimethylbenz[a]anthracene (DMBA)-initiated mice. However, unlike its effect in liver, a single topical application of mirex to skin does not induce the acute biochemical responses, such as increased epidermal DNA synthesis and ornithine decarboxylase activity, indicative of increased cell proliferation. Multiple topical applications of mirex over a 1 month period induced only a minimal increase in the number of epidermal nucleated cell layers, which contrasts with definitive hyperplasia induced by a comparable tumor-promoting dose of 12-O-tetradecanoylphorbol-13-acetate (TPA). Collectively, these data indicated that mirex is promoting through a novel mechanism. Further evidence that mirex promotes tumors through a mechanism distinct from that of the prototypical skin tumor promoter, TPA, was obtained by examining the effect of their simultaneous co-treatment. The co-application of mirex and TPA yielded a tumor multiplicity greater than the sum of the responses of each promoter individually. In summary, our results demonstrate that mirex, a carcinogenic and hyperplastic agent in liver, is also a very effective tumor promoter in mouse skin, but suggest that mirex operates via a novel mechanism in skin that may involve only a minimal role for enhanced cell proliferation.
Protective role of endogenous carbon monoxide in hepatic microcirculatory dysfunction after hemorrhagic shock in rats.
Authors: B H Pannen, N Köhler, B Hole, M Bauer, M G Clemens, K K Geiger
Journal: Journal of Clinical Investigation (1998)

Maintenance of hepatic microcirculatory flow after ischemia of the liver is essential to prevent hepatic dysfunction. Thus, we determined the differential role of carbon monoxide (CO) and nitric oxide (NO) in the intrinsic control of sinusoidal perfusion, mitochondrial redox state, and bile production in the isolated perfused rat liver after hemorrhagic shock. Administration of tin protoporphyrin-IX (50 microM), a specific inhibitor of the CO generating enzyme heme oxygenase, caused a decrease in sinusoidal flow that was more pronounced after shock compared with sham shock, as determined by in situ epifluorescence microscopy. This was associated with a shift in hepatocellular redox potential to a more reduced state (increased fluorescence intensity of reduced pyridine nucleotides in hepatocytes, decreased acetoacetate/beta-hydroxybutyrate ratio in the perfusate) and a profound reduction in bile flow. In sharp contrast, the preferential inhibitor of the inducible isoform of NO synthase S-methylisothiourea sulfate (100 microM) did not affect sinusoidal flow, hepatic redox state, or function. This indicates that 1.) endogenously generated CO preserves sinusoidal perfusion after hemorrhagic shock, 2.) protection of the hepatic microcirculation by CO may serve to limit shock-induced liver dysfunction, and 3.) in contrast to CO, inducible NO synthase-derived NO is of only minor importance for the intrinsic control of hepatic perfusion and function under these conditions.
Functional Characteristics of Renovascular Hypertension with Emphasis on the Relationship of Renal Blood Flow to Hypertension
Authors: Thomas A. Stamey
Journal: Circulation Research (1962)

Oar studies on the functional characteristics of renovascular hypertension have been recently published 1 ' 2i 3 and will be summarized briefly in this paper with particular emphasis on the relationship between renal blood flow and renal hypertension-a relationship which, unhappily, has been depreciated in the last 20 years.The major problem four years ago was to solve the technical aspects of ureteral catheterization.The difficulties were bladder leakage, inadequate urine flow rates, ureteroreual sympathetic reflexes, postcatheterization morbidity, and a complete lack of criteria for recognizing valid reproducible data.It was clear that, unless these problems were solved first, the functional characterization of a kidney producing human arterial hypertension, as well as the conditions which affected those characteristics, would have to await a different approach.It was equally clear, however, that the normal symmetry of the kidneys in the dog and the human offered an excellent opportunity to examine the function of a kidney responsible for hypertension while the contralateral kidney served as a control. MethodsThe several problems in technique were solved us follows: (a) Bladder leakage was prevented by the use of soft polyethylene catheters.The ratio of the size of the ureteml orifice to the size of the catheter is important, (b) Urine flow rates must be at least 2 ml./min./kidney to avoid artifacts from dead space orrors and electrolyte absorption across the ureteral and bladder mucosa.(c) Ureterorenal reflexes which can produce a fall
Hepatocellular carcinoma and survival in patients with primary biliary cirrhosis
Authors: Akitaka Shibuya, Katsuaki Tanaka, Hiroshi Miyakawa, Minoru Shibata, Masao Takatori, Kazuhiko Sekiyama, Naoaki Hashimoto, Shuuichi Amaki, Tatsuji Komatsu, Toshio Morizane
Journal: Hepatology (2002)

The incidence of hepatocellular carcinoma (HCC) in patients with primary biliary cirrhosis (PBC) is not well known. The aims of this study are to determine HCC incidence and survival, and to identify risk factors associated with these outcomes in patients with PBC. We collected information on 396 patients with PBC at enrollment and followed-up from 6 to 271 months. They were all negative for hepatitis B and C virus markers. HCC was detected by scanning with ultrasonography, computed tomography, or both every 4 to 6 months. Life expectancy (LE) was approximated with the declining exponential approximation of LE. A total of 14 patients developed HCC. The cumulative appearance rate of HCC in patients with advanced-stage PBC (Scheuer's stage III or IV) was significantly higher than that for patients with early-stage (stage I or II) (12.3% and 7.7% by the tenth year, respectively. P =.021). Proportional hazards analysis showed 3 factors are independently associated with the development of HCC: age at the time of diagnosis, male gender, and history of blood transfusion. Age, male gender, and advanced-stage PBC were associated with survival, but HCC development was not. The disease-specific annual mortality rate was estimated to be 0.008 for women and 0.028 for men with advanced-stage PBC. In conclusion, HCC develops in old patients with advanced-stage PBC, but HCC does not affect the patients' survival.
Abstract 2560: The CK2 inhibitor CX-4945 enhances the antitumor activity of EGFR-targeted agents by attenuating signaling in the PI3K/AKT/mTOR pathway
Authors: Josh Bliesath, Denis Drygin, Nicole Streiner, Caroline Ho, Adam Siddiqui-Jain, Chris Proffitt, May Omori, Nanni Huser, Sean O'Brien, Kenna Anderes
Journal: Cancer Research (2011)

Abstract The epidermal growth factor receptor (EGFR) regulates several oncogenic signaling pathways including PI3K/AKT/mTOR, MEK/ERK, and STAT. A number of EGFR antagonists have been approved for treatment of late-stage tumors of epithelial origin. Despite these advances, there are several limitations to these therapies, including primary and acquired resistance, prompting the need to combine EGFR antagonists with agents that target pathways downstream of EGFR. CK2 modulates multiple pro-proliferative and pro-survival signals through many of these same signaling pathways, and co-overexpression of EGFR and CK2 has been frequently observed in solid tumors. Here we present the combination of EGFR-targeted agents with CX-4945, a first-in-class selective CK2 inhibitor currently under evaluation in a Phase I clinical trial. CK2 phosphorylates several key proteins at multiple levels within the PI3K/AKT/mTOR signaling pathway including AKT, PTEN, and p70S6K1. CK2 also regulates the Hsp90/Cdc37 machinery, whose clients include EGFR, AKT, and Src. We proposed that top-down inhibition of EGFR, combined with lateral inhibition of the PI3K/ATK/mTOR pathway by CX-4945, would result in an improved cancer therapy compared to EGFR antagonism alone. This hypothesis was tested in vitro and in vivo in A431 squamous cell carcinoma (SCC) and non-small cell lung carcinoma (NSCLC) models of various genetic backgrounds. Signaling pathways and induction of apoptosis were analyzed by western blot and cell proliferation was measured in a 96-hour cell viability assay. The combination of CX-4945 and erlotinib resulted in enhanced reduction in phosphorylation of AKT (T308), AKT (S473), PRAS40 (S246), mTOR (S2481), mTOR (S2448), p70S6K1 (T389), S6 (S235/6), S6 (240/4), and 4E-BP1 (T37/46), and decreased Mcl-1 levels. These effects were accompanied by decreased cell proliferation and synergistic induction of apoptosis. CX-4945 plus erlotinib exhibited enhanced antitumor activity in A431 SCC and NCI-H2170 NSCLC xenograft models; moreover, in the erlotinib-resistant NCI-H1975 NSCLC xenograft model, CX-4945 plus cetuximab resulted in enhanced efficacy. These data suggest that CX-4945 in combination with EGFR-targeted agents may improve clinical outcomes in patients with EGFR and CK2-driven cancers by inhibiting multiple nodes of the EGFR signaling pathway. 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 2560. doi:10.1158/1538-7445.AM2011-2560
Virtual portal pressure gradient from anatomic CT angiography
Authors: Xiaolong Qi, Zhiwei Li, Jiale Huang, Yanjie Zhu, Hao Liu, Fangyu Zhou, Changchun Liu, Chaohui Xiao, Jinghui Dong, Yongzhao Zhao, Mingxin Xu, Surong Xing, Weiguo Xu, Changqing Yang
Journal: Gut (2014)

By definition, portal hypertension means pathological elevation of the portal pressure gradient (PPG), the direct measurement of which is extremely invasive. This has prompted the use of the less invasive hepatic venous pressure gradient (HVPG), widely accepted as the PPG equivalent.1–3 In a recent article in Gut , HVPG was used as the only criterion to assess haemodynamic response (reduction in HVPG of ≥20% or to values <12 mm Hg) rates to carvedilol in propranolol non-responders.1 Although accurate, HVPG is still invasive, and thus not routinely performed in all centres.2 ,3 As HVPG becomes standard practice, repeated invasive measurement has stimulated the search for non-invasive techniques to measure PPG.3–5 Here, we present a virtual PPG (vPPG) based on CT angiography and Doppler ultrasound.

The VIRGIN Study was a multicentre, blinded, prospective, analytical trial carried out at Tongji Hospital, Shanghai and 302 Hospital, Beijing. The study was …
THE ART OF PSYCHOTHERAPY
Authors: C. A. H. Watts
Journal: BMJ (1957)

<h3>ABSTRACT</h3> The objective of this research was to identify factors that are significantly related to the degree of integration of a company9s marketing communications activities. A three-item scale was developed to measure integrated marketing communications in a cross-sectional sample of senior marketing managers in U.S. companies. Results show that firms whose marketing communications programs tend to be integrated are also likely to be small, consumer-focused, service-oriented companies. They are also more common in manufacturing, agriculture, forestry, and mining industries. Managers in firms with greater integration also tend to be more experienced, and their products or services are more likely to be experiencing market share growth. Implications of these findings for marketing communications managers and researchers are then discussed.
Research Probes Details of Poor Adherence in Antihypertensive Drug Therapy
Authors: Mike Mitka
Journal: JAMA (2007)

preventive cardiology at the University of Vermont College of Medicine, in Burlington. “You need a pretty high staff-topatient ratio if you want to do a good job,” Ades said. “Hospitals like cardiac rehabilitation because it’s a good public relations strategy . . . but they rarely break even.” Incorporating referral to cardiac rehabilitation into quality measures that affect reimbursement (pay for performance) could help boost referrals, said Ades, who helped write the 1995 guidelines and who is also one of the coauthors of the Suaya study. “I’m under pressure from the hospital leadership to prescribe aspirin and statins because they get graded on it,” he said. “So I think the single most important key is to make referral to cardiac rehabilitation a quality indicator.”