tbuckley/cabot-search huggingface dataset:
Chemokine receptor CCR5 promotes leukocyte trafficking to the brain and survival in West Nile virus infection
Authors: William G. Glass, Jean K. Lim, Rushina Cholera, Alexander G. Pletnev, Ji-Liang Gao, Philip M. Murphy
Journal: The Journal of Experimental Medicine (2005)

The molecular immunopathogenesis of West Nile virus (WNV) infection is poorly understood. Here, we characterize a mouse model for WNV using a subcutaneous route of infection and delineate leukocyte subsets and immunoregulatory factors present in the brains of infected mice. Central nervous system (CNS) expression of the chemokine receptor CCR5 and its ligand CCL5 was prominently up-regulated by WNV, and this was associated with CNS infiltration of CD4+ and CD8+ T cells, NK1.1+ cells and macrophages expressing the receptor. The significance of CCR5 in pathogenesis was established by mortality studies in which infection of CCR5−/− mice was rapidly and uniformly fatal. In the brain, WNV-infected CCR5−/− mice had increased viral burden but markedly reduced NK1.1+ cells, macrophages, and CD4+ and CD8+ T cells compared with WNV-infected CCR5+/+ mice. Adoptive transfer of splenocytes from WNV-infected CCR5+/+ mice into infected CCR5−/− mice increased leukocyte accumulation in the CNS compared with transfer of splenocytes from infected CCR5−/− mice into infected CCR5−/− mice, and increased survival to 60%, the same as in infected CCR5+/+ control mice. We conclude that CCR5 is a critical antiviral and survival determinant in WNV infection of mice that acts by regulating trafficking of leukocytes to the infected brain.
Neurally Mediated and Direct Effects of Acetylstrophanthidin on Canine Skeletal Muscle Vascular Resistance
Authors: JAMES J. STARK, CHARLES A. SANDERS, W.M. John POWELL
Journal: Circulation Research (1972)

The effects of acetylstrophanthidin on the vascular resistance of the isolated canine gracilis muscle were examined in 38 anesthetized mongrel dogs. The neurally mediated effect of intravenous acetylstrophanthidin (0.5 mg) on the vascular resistance of the innervated, separately perfused (constant flow) right gracilis muscle was a transient mean fall of 4.0 ± 0.9 resistance units (RU) ( P &lt; 0.001) at 1 minute followed by a sustained rise to 4 RU ( P &lt; 0.05) above control from 8 to 18 minutes after injection. The sustained increase in resistance was blocked by intra-arterial phenoxybenzamine. The combined direct and neurally mediated effects of intravenous acetylstrophanthidin were directionally similar and greater in magnitude in the innervated, autoperfused (intact circulation) left gracilis. Following denervation of the muscle, however, the initial decrease in vascular resistance was abolished and the prolonged subsequent rise was greatly reduced. Hence the initial fall and most of the subsequent rise in vascular resistance are neurally mediated. There was no consistent change in aortic pressure to explain either of these changes in vascular resistance solely on a reflex basis. Thus, systemically administered acetylstrophanthidin produces skeletal muscle vasoconstriction through both a direct and a neurally mediated effect. The latter is mediated through alphareceptor stimulation and appears to be the predominant mechanism whereby this drug increases muscle vascular resistance.
Duodenal ulcer and refined carbohydrate intake: a case-control study assessing dietary fibre and refined sugar intake.
Authors: B D Katschinski, R F Logan, M Edmond, M J Langman
Journal: Gut (1990)

An association between duodenal ulceration and a low fibre intake and a high refined carbohydrate diet has been reported. We therefore compared the current diet, smoking habits, social class, and possible other risk factors of 78 patients with duodenal ulcer and a community control group matched for age and sex. Logistic regression for matched sets was used to calculate the relative risks for successive quintiles of dietary fibre and sugar intake before and after adjustment for total calorie intake and for the possible confounding effect of other known risk factors. Relative risks did not differ materially or consistently for total dietary fibre or for the cereal moiety whether adjusted or not for calorie intake. By contrast, relative risks tended to be reduced with high vegetable fibre intake and with low refined sugar intake. After controlling for smoking and social class, both of which were associated with ulcer disease, and for relative weight (Quetelet9s index), the relation between ulcer disease and low refined sugar intake persisted, while that with high vegetable fibre intake was reduced. The results of this study indicate that a lack of cereal or total fibre intake plays no part in duodenal ulcer development but that a low refined sugar intake may be a protective factor.
Monoclonal antibodies specific for interleukin 3-sensitive murine cells.
Authors: R Palacios, T Neri, M Brockhaus
Journal: The Journal of Experimental Medicine (1986)

The mAb CC11 and CB5 reacted against all 18 IL-3-dependent cell lines tested, but not against cells insensitive to IL-3. Up to 53% nucleated cells from fetal liver (14th day of gestation) and 79% bone marrow cells of young adult mice were positive for both CC11 and CB5 antigens, but cells from thymus, lymph node, heart, and kidney were negative. The molecule recognized by both antibodies has an Mr of 50,000-70,000, a pI of 5.7-6.2, and carries heterogeneous N-linked glycans of high Mr. Both CC11 and CB5 specifically inhibited the growth of clones supported by rIL-3. Neither antibody affected the action of IL-1, IL-2, or B cell maturation factor; the proliferative responses of splenocytes to Con A, PWM, and LPS; nor the maturation of spleen B cells into antibody-secreting cells stimulated by LPS. rIL-3 specifically modulated the expression of the CC11/CB5 glycoprotein on the cell membrane of IL-3-dependent clones. Finally, freshly isolated bone marrow cells that have the CC11/CB5 glycoprotein on the cell membrane proliferated in response to IL-3, whereas cells that lack this molecule did not. We suggest that CC11 and CB5 react against receptors for mouse IL-3.
SOME CONSIDERATIONS REGARDING BASIC MECHANISMS OF POSITIVE AND NEGATIVE TYPES OF MOTIVATIONS
Authors: JOHN C. LILLY
Journal: American Journal of Psychiatry (1958)

In recent years the exploration of the brain has shown some of those systems which are involved in the production and maintenance of certain motivational states. In rats, Olds and Milner demonstrated rewarding effects of stimulating certain systems; in cats, Delgado, Robert, and Miller, and Delgado, Rosvold, and Looney showed punishing effects from stimulating other zones. Brady et al. confirmed Olds and Milner in the cat and monkey. We have confirmed both effects in the monkey, and have investigated in some detail the reward and the punishment effects in various loci. We have found also the same effects from a few loci in the porpoise's (dolphin) brain; this animal's brain is as large as the human one and hence is of interest A number of workers have been doing exploratory studies on healthy intact human individuals in isolation from other persons and from their usual levels of exchange with the physical environment; by such means one may investigate positive and negative motivations in more or less pure culture in the subjective psychological sphere. Such research is full of technical problems and pitfalls; it shows that in these special conditions some minds tend to disguise the presently acting true motives and to project them in multitudinuous forms into the minimally stimulating and non-reactive reality. Some useful data are also derived from autobiographical accounts written by those who have been exposed to isolation at sea or in the polar regions; the dominance of the positive or of the negative motivations can be seen operating especially clearly in such accounts. Such exploratory studies are slowly adding to an understanding of positive and negative motivations and offer powerful tools for further studies.
Future Research Directions in Idiopathic Pulmonary Fibrosis
Authors: Ronald G. Crystal, Peter B. Bitterman, Brooke Mossman, Marvin I. Schwarz, Dean Sheppard, Laura Almasy, Harold A. Chapman, Scott L. Friedman, Talmadge E. King, Leslie A. Leinwand, Lance Liotta, George R. Martin, David A. Schwartz, Gregory S. Schultz, Carston R. Wagner, Robert A. Musson
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Idiopathic pulmonary fibrosis (IPF) is an insidious inflammatory fibroproliferative disease whose cause and course before diagnosis are unknown, and for which existing treatments are of limited benefit. The National Heart, Lung, and Blood Institute convened a working group to develop specific recommendations for future IPF research. Inflammatory and immune processes are involved in IPF pathogenesis, and current therapeutic strategies are aimed at suppressing the inflammation. Recent data suggest that the molecular processes underlying the fibrogenesis may provide new opportunities for therapeutic intervention. Specific areas of future research recommended by the working group include studies to elucidate the etiology of IPF, to develop novel diagnostic techniques and molecular diagnostics, to establish a program for identification of molecular targets for IPF treatment and identification and generation of agonists or antagonists that inhibit fibrogenesis, to foster investigations that couple the use of new technologies (e.g., laser capture microdissection, microarrays, and mass spectroscopic analysis of proteins) with data from the human genome project, to establish a national consortium of Clinical Centers of Excellence to conduct coordinated clinical and laboratory studies of well-characterized patients and patient-derived materials, and to stimulate research to develop animal models of persistent and progressive pulmonary fibrosis for evaluation of new intervention approaches.
Self-renewal as a therapeutic target in human colorectal cancer
Authors: Antonija Kreso, Peter van Galen, Nicholas M Pedley, Evelyne Lima-Fernandes, Catherine Frelin, Thomas Davis, Liangxian Cao, Ramil Baiazitov, Wu Du, Nadiya Sydorenko, Young-Choon Moon, Lianne Gibson, Yadong Wang, Cherry Leung, Norman N Iscove, Cheryl H Arrowsmith, Eva Szentgyorgyi, Steven Gallinger, John E Dick, Catherine A O'Brien
Journal: Nature Medicine (2013)
Isometric tension development and its calcium sensitivity in skinned myocyte-sized preparations from different regions of the human heart
Authors: J van der Velden
Journal: Cardiovascular Research (1999)

Objective: In this study we investigated whether differences exist or develop in patients with aortic or mitral valve disease in myofibrillar contractile function and contractile protein composition between subendo- and subepicardial human ventricular tissue. Isometric tension, its calcium sensitivity and contractile protein composition were studied in left ventricular subendo- and subepicardial and in atrial biopsies obtained during open heart surgery from 24 patients with mitral or aortic valve disease. Methods: Isometric tension was measured in mechanically isolated skinned myocyte-sized preparations at different free calcium concentrations at 15°C. Protein composition was analysed by one-dimensional gel electrophoresis. A comparison was made between the results of subendo- and subepicardial ventricular tissue within each New York Heart Association class and within the different hemodynamically overloaded groups. Results: Maximal isometric tension was significantly lower in atrial than in ventricular preparations. The concentration of calcium required for half-maximal activation was significantly higher in atrial than in ventricular preparations. Within the ventricle no differences were found in contractile protein composition, isometric tension and its calcium sensitivity between subendo- and subepicardial tissue when all patients were treated as one group or when patients were subdivided according to severity of heart disease or hemodynamic overload. Conclusions: In this group of patients with ventricular volume or pressure overload no regional differences exist or develop during cardiac disease in left ventricular myofibrillar protein composition and force production. Maximal isometric tension and its calcium sensitivity are smaller in atrial than in ventricular preparations.
Video analysis of situations with a high-risk for injury in Norwegian male professional football; a comparison between 2000 and 2010
Authors: John Bjørneboe, Roald Bahr, Thor Einar Andersen
Journal: British Journal of Sports Medicine (2013)

A recent study from Norwegian male professional football found that the risk of acute match injuries increased from 2002 to 2007.To compare the incidence of incidents with a propensity for injury, from the 2000 season to the 2010 season in Norwegian male professional football using video analysis.We conducted a video analysis of incidents in Norwegian professional football. An incident was recorded if the match was interrupted by the referee, and the player lay down for more than 15 s, and appeared to be in pain or received medical treatment. We also conducted a video analysis of all player-to-player contact situations occurring during 30 randomly selected matches.A total of 1287 incidents were identified during the two seasons. The corresponding rate of incidents was 74.4 (95% CI 67.3 to 81.5) in the 2000 season and 109.6 (95% CI 102.3 to 116.9) in the 2010 season, a significant increase from 2000 to 2010 (rate ratio 1.47, 95% CI 1.31 to 1.66). We observed a significantly higher rate of opponent-to-player contact and non-contact incidents in the 2010 season, but no change in the proportion of fouls or sanctions awarded by the referee. The rate of player-to-player contact situations in both heading and tackling duels was lower during the 2010 season.We found an increased rate of non-contact and opponent-to-player contact incidents in both heading and tackling duels in the 2010 season compared with 10 years earlier, even if there was no increase in the frequency of player-to-player contact situations.
Computed Tomography Response, But Not Positron Emission Tomography Scan Response, Predicts Survival After Neoadjuvant Chemotherapy for Resectable Non–Small-Cell Lung Cancer
Authors: Tawee Tanvetyanon, Edward A. Eikman, Eric Sommers, Lary Robinson, David Boulware, Gerold Bepler
Journal: Journal of Clinical Oncology (2008)

Tumor response is considered a surrogate marker of survival. We investigated whether tumor response based on computed tomography (CT) scan or whole-body [(18)F]fluorodeoxyglucose positron emission tomography (PET) scan after neoadjuvant chemotherapy for resectable non-small-cell lung cancer (NSCLC) is prognostic of survival.Two consecutive phase II clinical trials were jointly analyzed. Patients underwent CT and PET scans before and after completion of neoadjuvant chemotherapy, followed by surgery.Eighty-nine patients were included. Patients with a partial or complete response based on Response Evaluation Criteria in Solid Tumors categories (n = 33) had a better overall survival than those with stable or progressive disease (n = 56; median survival time, not reached v 36 months, respectively; P = .04). Of all patients, those with response in the highest quartile had 1- and 2-year survival rates of 100% and 81%, respectively, compared with 77% and 61%, respectively, among patients in the lowest quartile. However, on the basis of visual analysis of PET scan, patients with a metabolic response (n = 28) had no significant difference in survival compared with patients without response (n = 61; median survival time, 35.6 months v not reached, respectively; P = .94). In addition, on the basis of a semiquantitative analysis of PET scan, using at least 30% reduction in tumor metabolism as a response (n = 59), we also found no significant difference in survival among those with or without response.Among patients with resectable NSCLC treated with neoadjuvant chemotherapy, we found no evidence that tumor response by PET scan after chemotherapy is prognostic of survival; however, response by CT scan was associated with better survival.
Mechanisms of Ascorbate-Induced Cytotoxicity in Pancreatic Cancer
Authors: Juan Du, Sean M. Martin, Mark Levine, Brett A. Wagner, Garry R. Buettner, Sih-han Wang, Agshin F. Taghiyev, Changbin Du, Charles M. Knudson, Joseph J. Cullen
Journal: Clinical Cancer Research (2010)

Pharmacologic concentrations of ascorbate may be effective in cancer therapeutics. We hypothesized that ascorbate concentrations achievable with i.v. dosing would be cytotoxic in pancreatic cancer for which the 5-year survival is <3%.Pancreatic cancer cell lines were treated with ascorbate (0, 5, or 10 mmol/L) for 1 hour, then viability and clonogenic survival were determined. Pancreatic tumor cells were delivered s.c. into the flank region of nude mice and allowed to grow at which time they were randomized to receive either ascorbate (4 g/kg) or osmotically equivalent saline (1 mol/L) i.p. for 2 weeks.There was a time- and dose-dependent increase in measured H(2)O(2) production with increased concentrations of ascorbate. Ascorbate decreased viability in all pancreatic cancer cell lines but had no effect on an immortalized pancreatic ductal epithelial cell line. Ascorbate decreased clonogenic survival of the pancreatic cancer cell lines, which was reversed by treatment of cells with scavengers of H(2)O(2). Treatment with ascorbate induced a caspase-independent cell death that was associated with autophagy. In vivo, treatment with ascorbate inhibited tumor growth and prolonged survival.These results show that pharmacologic doses of ascorbate, easily achievable in humans, may have potential for therapy in pancreatic cancer.
IMMUNOCHEMICAL STUDIES ON THE SPECIFIC CARBOHYDRATE OF GROUP G STREPTOCOCCI
Authors: Stephen N. Curtis, Richard M. Krause
Journal: The Journal of Experimental Medicine (1964)

Group G hemolytic streptococcal cell walls which have been treated with trypsin are composed of a group-specific polysaccharide moiety and a mucopeptide matrix. The mucopeptide contains N-acetylglucosamine, N-acetylmuramic acid, alanine, glutamic acid, lysine, and glycine, a composition similar to that of other groups of streptococci. The Group G carbohydrate is composed of rhamnose, N-acetylgalactosamine, and galactose. Serological studies suggest that the monosaccharide of L-rhamnose is a major component of the determinant of antigenic specificity.
Integrative Predictive Model of Coronary Artery Calcification in Atherosclerosis
Authors: Michael McGeachie, Rachel L. Badovinac Ramoni, Josyf C. Mychaleckyj, Karen L. Furie, Jonathan M. Dreyfuss, Yongmei Liu, David Herrington, Xiuqing Guo, João A. Lima, Wendy Post, Jerome I. Rotter, Stephen Rich, Michèle Sale, Marco F. Ramoni
Journal: Circulation (2009)

Many different genetic and clinical factors have been identified as causes or contributors to atherosclerosis. We present a model of preclinical atherosclerosis based on genetic and clinical data that predicts the presence of coronary artery calcification in healthy Americans of European descent 45 to 84 years of age in the Multi-Ethnic Study of Atherosclerosis (MESA).We assessed 712 individuals for the presence or absence of coronary artery calcification and assessed their genotypes for 2882 single-nucleotide polymorphisms. With the use of these single-nucleotide polymorphisms and relevant clinical data, a Bayesian network that predicts the presence of coronary calcification was constructed. The model contained 13 single-nucleotide polymorphisms (from genes AGTR1, ALOX15, INSR, PRKAB1, IL1R2, ESR2, KCNK1, FBLN5, PPARA, VEGFA, PON1, TDRD6, PLA2G7, and 1 ancestry informative marker) and 5 clinical variables (sex, age, weight, smoking, and diabetes mellitus) and achieved 85% predictive accuracy, as measured by area under the receiver operating characteristic curve. This is a significant (P<0.001) improvement on models that use just the single-nucleotide polymorphism data or just the clinical variables.We present an investigation of joint genetic and clinical factors associated with atherosclerosis that shows predictive results for both cases, as well as enhanced performance for their combination.
Acquired Lymphedema: An Urgent Need for Adequate Animal Models
Authors: Catarina Hadamitzky, Reinhard Pabst
Journal: Cancer Research (2008)

In cancer patients, the removal of tumor-draining lymph nodes during tumor resection can lead to acquired lymphedema. This disease, which is characterized by tissue swelling and increased risk of infection due to restricted lymph flow, lacks an effective treatment. Limitations to the design and conduct of randomized trials to date have limited the evaluation of proposed surgical techniques. As a result, animal models have provided an important research base. This review summarizes work in canine, rabbit, and rodent models of acquired lymphedema, focusing on arising limitations and potential applications.
Induction of nitric oxide release by MRC OX-44 (anti-CD53) through a protein kinase C-dependent pathway in rat macrophages.
Authors: L Boscá, P A Lazo
Journal: The Journal of Experimental Medicine (1994)

Many membrane proteins are implicated in the control of cell function by triggering specific signaling pathways. There is a new family of membrane proteins, defined by its structural motifs, which includes several lymphoid antigens, but lacks a function. To study its biological role, we determined which signaling pathways are affected by the CD53 antigen, a prototypic member of this family, in rat macrophages. Activation of CD53 by cross-linking results in an increase in inositol phosphates and diacylglycerol and in Ca2+ mobilization, which are insensitive to pertussis or cholera toxins. There is a translocation of protein kinase C to the membrane accompanied by nitric oxide (NO) release in macrophages. This effect is the result of the expression of the inducible nitric oxide synthase (iNOS), which is dependent on protein kinase C and protein synthesis. These results have linked a new receptor with a specific pathway of NO induction and thus have opened up a novel aspect of NO regulation in cell biology.