tbuckley/cabot-search huggingface dataset:
Function of the In-Situ Papillary Muscle in the Canine Left Ventricle
Authors: ROBERT CRONIN, J. A. ARMOUR, WALTER C. RANDALL
Journal: Circulation Research (1969)

From strain gauge arches applied directly to the longitudinal surface of the papillary muscle of the canine left ventricle, its force of contraction was recorded simultaneously with that on an epicardial segment of the ventricle immediately overlying it. Left ventricular and atrial pressures, as well as ECG and local electrograms were also recorded in a closed-heart, open-chest preparation. Active participation of the papillary muscle in the contractile processes of the whole heart is indicated, and under positive inotropic drive (stellate stimulation, administration of isoproterenol, norepinephrine) the force of contraction of this muscle is greatly augmented. During volume loading resulting from afterloading procedures (central vagus stimulation, methoxamine, aortic clamping) the papillary muscle participates in augmenting the contractile force, but in lesser proportion than when elicited by a direct positive inotropic procedure. The increase in contractile force during afterload was related to passive changes in length-tension relationships. Direct vagal innervation of the papillary muscle is indicated by distinct inhibition in contractile force during electrical excitation of the peripheral end of the cut vagosympathetic trunk, both in the paced and unpaced preparation.
Clobetasol propionate ointment compared with dithranol in Lassar's paste in the treatment of psoriasis
Authors: PHILIP J. MARRIOTT, D.D. MUNRO
Journal: British Journal of Dermatology (1976)

Journal Article Clobetasol propionate ointment compared with dithranol in Lassar's paste in the treatment of psoriasis Get access PHILIP J. MARRIOTT, PHILIP J. MARRIOTT Departments of Dermatology, St Bartholomew's Hospital, London, and Edgware General Hospital, Middlesex Search for other works by this author on: Oxford Academic Google Scholar D.D. MUNRO D.D. MUNRO Departments of Dermatology, St Bartholomew's Hospital, London, and Edgware General Hospital, Middlesex Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 94, Issue s12, 1 March 1976, Pages 101–106, https://doi.org/10.1111/j.1365-2133.1976.tb02277.x Published: 01 March 1976
Fibroblast Growth Factor-23 and Cardiovascular Events in CKD
Authors: Julia J. Scialla, Huiliang Xie, Mahboob Rahman, Amanda Hyre Anderson, Tamara Isakova, Akinlolu Ojo, Xiaoming Zhang, Lisa Nessel, Takayuki Hamano, Juan E. Grunwald, Dominic S. Raj, Wei Yang, Jiang He, James P. Lash, Alan S. Go, John W. Kusek, Harold Feldman, Myles Wolf
Journal: Journal of the American Society of Nephrology (2013)

An elevated level of fibroblast growth factor-23 (FGF-23) is the earliest abnormality of mineral metabolism in CKD. High FGF-23 levels promote left ventricular hypertrophy but not coronary artery calcification. We used survival analysis to determine whether elevated FGF-23 is associated with greater risk of adjudicated congestive heart failure (CHF) and atherosclerotic events (myocardial infarction, stroke, and peripheral vascular disease) in a prospective cohort of 3860 participants with CKD stages 2–4 (baseline estimated GFR [eGFR], 44±15 ml/min per 1.73 m2). During a median follow-up of 3.7 years, 360 participants were hospitalized for CHF (27 events/1000 person-years) and 287 had an atherosclerotic event (22 events/1000 person-years). After adjustment for demographic characteristics, kidney function, traditional cardiovascular risk factors, and medications, higher FGF-23 was independently associated with graded risk of CHF (hazard ratio [HR], 1.45 per doubling [95% confidence interval (CI), 1.28 to 1.65]; HR for highest versus lowest quartile, 2.98 [95% CI, 1.97 to 4.52]) and atherosclerotic events (HR per doubling, 1.24 [95% CI, 1.09 to 1.40]; HR for highest versus lowest quartile, 1.76 [95% CI, 1.20 to 2.59]). Elevated FGF-23 was associated more strongly with CHF than with atherosclerotic events (P=0.02), and uniformly was associated with greater risk of CHF events across subgroups stratified by eGFR, proteinuria, prior heart disease, diabetes, BP control, anemia, sodium intake, income, fat-free mass, left ventricular mass index, and ejection fraction. Thus, higher FGF-23 is independently associated with greater risk of cardiovascular events, particularly CHF, in patients with CKD stages 2–4.
Pathogenesis and epidemiology of precocious puberty. Effects of exogenous oestrogens
Authors: C.-J. Partsch, W.G. Sippell
Journal: Human Reproduction Update (2001)

Precocious puberty is generally defined as the appearance of secondary sex characteristics before age 8 years in girls (or menarche before age 9 years) and before 9 years in boys. The overall incidence of sexual precocity is estimated to be 1:5000 to 1:10 000 children. The female-to-male ratio is ∼10:1. In addition to the psychosocial disturbances associated with precocious puberty, the premature pubertal growth spurt (with less time for prepubertal growth) and the accelerated bone maturation result in reduced adult height. Precocious puberty may be gonadotrophin-dependent [i.e. of central origin with premature activation of the gonadotrophin-releasing hormone (GnRH) pulse generator] or gonadotrophin-independent (i.e. peripheral where the GnRH pulse generator is suppressed). This can be determined by GnRH testing. The pathophysiology is the basis for different diagnostic and therapeutic strategies, i.e. in the first case a stimulated LH/FSH ratio >1 and suppressive treatment with GnRH agonists (e.g. in hypothalamic hamartoma), and in the second decreased gonadotrophins and removal or suppression of the endogenous or exogenous sex steroid source (e.g. congenital adrenal hyperplasia). While several cases of gonadotrophin-independent precocious puberty due to oestrogen exposure via the transdermal, oral, or inhalative route have been reported, no case is known with the development of subsequent secondary central precocious puberty. Food contamination with oestrogens is theoretically possible, but would most probably be sporadic and, thus, would not lead to precocious puberty. As steroid hormones in meat production are banned in the European Union, no data on the impact of environmental oestrogenic substances on human maturation are currently available. In conclusion, the risk for children to develop precocious puberty through exposure to oestrogens (or androgens) in the environment or in food is very low. Nevertheless, studies of the effects of defined environmental oestrogenic substances on the human reproductive system and on pubertal development are warranted.
Economic evaluations of diagnostic tests, treatment and prevention for lateral ankle sprains: a systematic review
Authors: Chung-Wei Christine Lin, Kimi Uegaki, Veerle M H Coupé, Gino M Kerkhoffs, Maurits W van Tulder
Journal: British Journal of Sports Medicine (2012)

Objective To assess and summarise the economic evidence regarding diagnostic tests, treatment and prevention for lateral ankle sprains. Methods Potential studies were identified from electronic databases and trial registries and by scanning reference lists. Risk of bias and methodological quality were evaluated. Two independent reviewers screened, assessed studies and extracted data. Data were synthesised descriptively due to study heterogeneity. Results A total of 230 records were identified; 10 studies were included. Five studies conducted a full economic evaluation and five studies involved cost analyses. Lack of blinding was the main risk of bias. The methodological quality of the full economic evaluations was fairly good. Valuation of costs, measurement of outcomes and sensitivity analysis were points for improvement. Single studies showed that the Ottawa ankle rules (OAR) was cost effective for diagnosing lateral ankle sprains in the emergency setting compared with existing hospital protocols; acute treatment with anti-inflammatory medication and the plaster cast for severe sprains appeared cost effective; and neuromuscular training was cost effective in preventing ankle re-injury. Conclusions Results of this current systematic review supplements the evidence provided by reviews of effectiveness. There is evidence to support the implementation of OAR in the emergency setting, the use of anti-inflammatory medication and the plaster cast in the acute phase, and the prescription of neuromuscular exercises to prevent re-injury. Although the evidence is limited due to the low number of studies, shortcomings in methodological quality and small sample sizes, the findings may be used to inform clinical practice and practice guidelines.
Elevated Central Serotonin Transporter Binding Availability in Acutely Abstinent Cocaine-Dependent Patients
Authors: Leslie K. Jacobsen, Julie K. Staley, Robert T. Malison, Sami S. Zoghbi, John P. Seibyl, Thomas R. Kosten, Robert B. Innis
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Recent work has underscored the role of serotonergic neurotransmission in chronic neural adaptations to cocaine dependence. The authors tested for evidence of serotonergic dysfunction during acute abstinence from cocaine, a period of high risk for relapse in cocaine dependence.METHOD: Binding availability of dopamine transporters and serotonin transporters was measured in 15 cocaine-dependent subjects during acute abstinence and in 37 healthy comparison subjects by using [123I]β-CIT and single photon emission computed tomography.RESULTS: Significant increases in diencephalic and brainstem serotonin transporter binding (16.7% and 31.6%, respectively) were observed in cocaine-dependent subjects. Brainstem serotonin transporter binding was significantly inversely correlated with age across diagnostic groups.CONCLUSIONS: These findings provide further evidence of serotonergic dysfunction during acute abstinence from chronic cocaine use. Age-related decline in brainstem serotonin transporter binding may underlie the poor response to selective serotonin reuptake inhibitor antidepressants seen in some elderly depressed patients.
Adhesion receptors of vascular smooth muscle cells and their functions
Authors: E Moiseeva
Journal: Cardiovascular Research (2001)

Vascular smooth muscle cells (SMCs) are present in several phenotypic states in blood vessels. They show a high degree of plasticity, undergoing rapid and reversible phenotypic changes in response to environmental stresses and vascular injury. Thereby, SMCs play an important role in development of atherosclerosis and restenosis after angioplasty and coronary bypass grafting. Many functions of SMCs, such as adhesion, migration, proliferation, contraction, differentiation and apoptosis are determined by surface adhesion receptors involved in cell-cell binding and interactions between cells and extracellular matrix (ECM) proteins. Some cell adhesion receptors are involved in intracellular signalling and participate in cellular response to different stimuli. The adhesion receptors of vascular SMCs discussed here include the ECM adhesion receptors integrins, alpha-dystroglycan and syndecans, as well as the cell-cell adhesion receptors cadherins and cell adhesion molecules. This review is intended to provide a generalised overview of the receptors expressed in vascular SMCs in relation to their functions and implications for vascular pathology.
The genetics of asthma.
Authors: A Sandford, T Weir, P Paré
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

In this paper we have summarized the evidence for a genetic contribution to asthma as well as the recent advances in techniques for identifying the location and function of genes that cause complex diseases. We have also reviewed how these techniques have been applied to the study of asthma and allergy. It is likely that rapid additional advances will be made over the next several years. There are ongoing genome-wide searches to identify additional genes. An understanding of the genetic variation that predisposes people to asthma and the atopic diseases could open a variety of potential diagnostic and therapeutic avenues. Firstly, the identification of the specific mutations that alter the immune response could provide targets for gene therapy. However, in the short run this is unlikely because the risks and costs associated with gene therapy do not presently justify application to alleviate the relatively nonlethal manifestations of allergic diseases. The second potential avenue will be in the development of specific pharmacologic therapy. For example, if variants of the IL-4 gene with enhanced function or of the IFN-gamma gene that have deficient function are identified as causative factors, drug development could be directed toward specific modulators of their effects. However, it is possible that redundancy in the immune and inflammatory responses, coupled with the likelihood of multiple gene involvement, will make such targeting fruitless or dangerous. The third consequence of identifying genetic variants predisposing to asthma and allergy is the possibility of screening. This is perhaps the most likely beneficial outcome of the present search for atopy genes. Recent studies suggest that the clinical onset of atopic diseases can be modified by preventing exposure to cigarette smoke and highly allergenic proteins in the first few years of life (188). At present the power of such studies is limited by the inability to predict those at risk with any certainty. Genetic screening of children born to atopic parents will allow more precise identification of those carrying atopy genes, and this could allow a focused attempt at environmental modification. In the short run this will allow the design of much more powerful prospective studies of prophylaxis, and in the long run screening may prove an effective strategy for asthma prevention.
Guidance of glial cell migration and axonal growth on electrospun nanofibers of poly-ε-caprolactone and a collagen/poly-ε-caprolactone blend
Authors: Eva Schnell, Kristina Klinkhammer, Simone Balzer, Gary Brook, Doris Klee, Paul Dalton, Jörg Mey
Journal: Biomaterials (2007)
Global gene expression in neuroendocrine tumors from patients with the MEN1 syndrome.
Authors: William G Dilley, Somasundaram Kalyanaraman, Sulekha Verma, J Perren Cobb, Jason M Laramie, Terry C Lairmore
Journal: Molecular Cancer (2005)

Multiple Endocrine Neoplasia type 1 (MEN1, OMIM 131100) is an autosomal dominant disorder characterized by endocrine tumors of the parathyroids, pancreatic islets and pituitary. The disease is caused by the functional loss of the tumor suppressor protein menin, coded by the MEN1 gene. The protein sequence has no significant homology to known consensus motifs. In vitro studies have shown menin binding to JunD, Pem, Smad3, NF-kappaB, nm23H1, and RPA2 proteins. However, none of these binding studies have led to a convincing theory of how loss-of-menin leads to neoplasia. Global gene expression studies on eight neuroendocrine tumors from MEN1 patients and 4 normal islet controls was performed utilizing Affymetrix U95Av2 chips. Overall hierarchical clustering placed all tumors in one group separate from the group of normal islets. Within the group of tumors, those of the same type were mostly clustered together. The clustering analysis also revealed 19 apoptosis-related genes that were under-expressed in the group of tumors. There were 193 genes that were increased/decreased by at least 2-fold in the tumors relative to the normal islets and that had a t-test significance value of p < = 0.005. Forty-five of these genes were increased and 148 were decreased in the tumors relative to the controls. One hundred and four of the genes could be classified as being involved in cell growth, cell death, or signal transduction. The results from 11 genes were selected for validation by quantitative RT-PCR. The average correlation coefficient was 0.655 (range 0.235–0.964). This is the first analysis of global gene expression in MEN1-associated neuroendocrine tumors. Many genes were identified which were differentially expressed in neuroendocrine tumors arising in patients with the MEN1 syndrome, as compared with normal human islet cells. The expression of a group of apoptosis-related genes was significantly suppressed, suggesting that these genes may play crucial roles in tumorigenesis in this syndrome. We identified a number of genes which are attractive candidates for further investigation into the mechanisms by which menin loss causes tumors in pancreatic islets. Of particular interest are: FGF9 which may stimulate the growth of prostate cancer, brain cancer and endometrium; and IER3 (IEX-1), PHLDA2 (TSS3), IAPP (amylin), and SST, all of which may play roles in apoptosis.
Critical-Period Plasticity in the Visual Cortex
Authors: Christiaan N. Levelt, Mark Hübener
Journal: Annual Review of Neuroscience (2012)

In many regions of the developing brain, neuronal circuits undergo defined phases of enhanced plasticity, termed critical periods. Work in the rodent visual cortex has led to important insights into the cellular and molecular mechanisms regulating the timing of the critical period. Although there is little doubt that the maturation of specific inhibitory circuits plays a key role in the opening of the critical period in the visual cortex, it is less clear what puts an end to it. In this review, we describe the established mechanisms and point out where more experimental work is needed. We also show that plasticity in the visual cortex is present well before, and long after, the peak of the critical period.
Functional Variant of <i>CYP4A11</i> 20-Hydroxyeicosatetraenoic Acid Synthase Is Associated With Essential Hypertension
Authors: James V. Gainer, Aouatef Bellamine, Elliott P. Dawson, Kristie E. Womble, Sarah W. Grant, Yarong Wang, L. Adrienne Cupples, Chao-Yu Guo, Serkalem Demissie, Christopher J. O’Donnell, Nancy J. Brown, Michael R. Waterman, Jorge H. Capdevila
Journal: Circulation (2004)

The CYP4A11 arachidonic acid monooxygenase oxidizes endogenous arachidonic acid (AA) to 20-hydroxyeicosatetraenoic acid (20-HETE), a metabolite with renovascular and tubular functions. Mice with targeted disruption of Cyp4a14, a murine homologue of CYP4A11, have severe hypertension. We combined molecular and biochemical approaches to identify a functional variant of the CYP4A11 20-HETE synthase and determine its association with hypertensive status in 2 independent human populations.
The Paradox of the “Ancient” Bacterium Which Contains “Modern” Protein-Coding Genes
Authors: Heather Maughan, C. William Birky Jr., Wayne L. Nicholson, William D. Rosenzweig, Russell H. Vreeland
Journal: Molecular Biology and Evolution (2002)

The isolation of microorganisms from ancient materials and the verification that they are as old as the materials from which they were isolated continue to be areas of controversy. Almost without exception, bacteria isolated from ancient material have proven to closely resemble modern bacteria at both morphological and molecular levels. This fact has historically been used by critics to argue that these isolates are not ancient but are modern contaminants introduced either naturally after formation of the surrounding material (for further details, see Hazen and Roeder 2001 and the reply by Powers, Vreeland, and Rosenzweig 2001) or because of flaws in the methodology of sample isolation (reviewed recently in Vreeland and Rosenzweig 2002). Such criticism has been addressed experimentally by the development of highly rigorous protocols for sample selection, surface sterilization, and contamination detection and control procedures. Using the most scrupulous and well-documented sampling procedures and contamination-protection techniques reported to date, Vreeland, Rosenzweig, and Powers (2000) reported the isolation of a sporeforming bacterium, Bacillus strain 2-9-3, from a brine inclusion within a halite crystal recovered from the 250-Myr-old Permian Salado Formation in Carlsbad, NM. As had been noted in earlier studies, a striking observation by Vreeland, Rosenzweig, and Powers (2000) was that the 16S rDNA of isolate 2-9-3 is 99% identical to that of Salibacillus marismortui, a bacterium isolated from the Dead Sea in 1936 (Arahal et al. 1999). In fact, Arahal et al. (1999) identified as S. marismortui three strains with 16S rDNA sequences differing by 0.01%, suggesting that isolate 2-9-3 might also be classified as S. marismortui. Two groups have since used phylogenetic analyses of 16S rDNA sequences to argue that isolate 2-9-3 is unlikely to be 250 Myr old. Graur and Pupko (2001) used a relative rate test to compare evolutionary rates of 16S rDNA on the branches leading to isolate 2-9-3 and S. marismortui and found no differences between the evolutionary rates. Considering the possibility that S. marismortui may also be ancient (Arahal et al. 1999; Vreeland, Rosenzweig, and Powers 2000), they also
Abstract 5474: Targeting endothelial tubulogenesis for anticancer therapeutic development
Authors: Anshu Mittal Roy, Ling Zhai, Krister Wennerberg, William R. Waud, Gregory S. Gormon, Lori Coward, Rongbao Li, Subramaniam Ananthan, Zhican Qu
Journal: Cancer Research (2010)

Abstract The clinical successes of VEGF-targeted agents in recent years have demonstrated that antiangiogenic therapy can be developed as effective anti-cancer treatment. However, the field of oncology is facing a new challenge of overcoming the resistance to VEGF-targeted therapy; therefore, novel angiogenesis inhibitors are required for new therapeutic development. During the growth of new blood capillaries, following proliferation and migration, endothelial cells undergo morphological changes and adhere to each other forming tubular structures as a process of tubulogenesis, which presents a unique target for inhibitory action of antiangiogenic agents. Southern Research angiogenesis research team has identified a structurally related series of heterocyclic compounds SRI-24637 and its analogs as a new class of antiangiogenic agents. SRI-24637 demonstrated selective potent inhibition of endothelial tube-formation and significant activity in blocking tumor-induced blood vessel formation using an ex vivo human cancer xenograft-CAM assay model system. The mechanism of action of SRI-24637 is different from the clinical VEGF-targeted drugs; therefore, it may provide a complementary mechanism to overcome the resistance to VEGF-targeted therapies. Bioavailability studies showed that SRI-24637 dosed at 40 mg/kg in DMSO/PEG400 reached systemic concentration levels much higher than the IC50 concentration for in vitro endothelial tube-formation. Comparing with the clinical VEGF-targeted drug Sunitinib, the cytotoxic activities of SRI-24637 against normal human fibroblast and epithelial cells suggest that the toxic side effects of SRI-24637 may be within a tolerable range. Ongoing preclinical efficacy studies with animal tumor models will aid in the development of SRI-24637 as an anti-cancer drug. Based on the outcome of these studies, further lead optimization will be done if required, before entering it into the clinical Phase I and II trials using protocols similar to those employed for Sunitinib and Sorafenib, or other investigational small molecules targeting tumor angiogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5474.