tbuckley/cabot-search huggingface dataset:
Perivascular adipose tissue-derived visfatin is a vascular smooth muscle cell growth factor: role of nicotinamide mononucleotide
Authors: Pei Wang, Tian-Ying Xu, Yun-Feng Guan, Ding-Feng Su, Guo-Rong Fan, Chao-Yu Miao
Journal: Cardiovascular Research (2008)

Perivascular adipose tissue (PVAT) inhibits vascular smooth muscle cell (VSMC) contraction and stimulates VSMC proliferation by releasing protein factors. The present study was to determine whether visfatin is involved in these paracrine actions of PVAT, and if so, to explore the underlying mechanisms. Visfatin was preferentially expressed in Sprague–Dawley rat and monkey aortic PVAT, compared with subcutaneous and visceral adipose tissues. The PVAT-derived visfatin was found to be a VSMC growth factor rather than a VSMC relaxing factor, which was proved by visfatin-specific antibody/inhibitor and direct observation of recombinant visfatin. Exogenous visfatin stimulated VSMC proliferation in a dose- and time-dependent manner via extracellular signal-regulated kinase (ERK 1/2) and p38 signalling pathways. This proliferative effect was further confirmed by enhancement of DNA synthesis and upregulation of proliferative marker Ki-67. Visfatin had no anti-apoptotic effect on normal cultured VSMCs, and it exerted an anti-apoptotic effect only during cell apoptosis induced by H2O2, excluding a role of anti-apoptosis in the visfatin-induced VSMC proliferation. Insulin receptor knockdown did not show any action on the visfatin effect. However, visfatin acted as a nicotinamide phosphoribosyltransferase to biosynthesize nicotinamide mononucleotide (NMN), which mediated proliferative signalling pathways and cell proliferation similar to the visfatin effect. Visfatin stimulates VSMC proliferation via NMN-mediated ERK1/2 and p38 signalling. The present study provides a molecular link of visfatin to the paracrine action of PVAT, demonstrates a novel function of visfatin in promoting VSMC proliferation, and reveals NMN as a novel signalling molecule that triggers the proliferative process.
Direct Proinflammatory Effect of C-Reactive Protein on Human Endothelial Cells
Authors: Vincenzo Pasceri, James T. Willerson, Edward T. H. Yeh
Journal: Circulation (2000)

The acute-phase reactant C-reactive protein (CRP) is an important risk factor for coronary heart disease. However, the possible effects of CRP on vascular cells are not known.We tested the effects of CRP on expression of adhesion molecules in both human umbilical vein and coronary artery endothelial cells. Expression of vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule (ICAM-1), and E-selectin was assessed by flow cytometry. Incubation with recombinant human CRP (10 microg/mL) for 24 hours induced an approximately 10-fold increase in expression of ICAM-1 and a significant expression of VCAM-1, whereas a 6-hour incubation induced significant E-selectin expression. Adhesion molecule induction was similar to that observed in endothelial cells activated with interleukin-1beta. In coronary artery endothelial cells, induction of ICAM-1 and VCAM-1 was already present at 5 microg/mL and reached a maximum at 50 microg/mL, at which point a substantial increase in expression of E-selectin was also evident. The CRP effect was dependent on presence of human serum in the culture medium, because no effect was seen in cells cultured with serum-free medium. In contrast, interleukin-1beta was able to induce adhesion molecule expression in the absence of human serum.CRP induces adhesion molecule expression in human endothelial cells in the presence of serum. These findings support the hypothesis that CRP may play a direct role in promoting the inflammatory component of atherosclerosis and present a potential target for the treatment of atherosclerosis.
Frequent Release of Low Amounts of Herpes Simplex Virus from Neurons: Results of a Mathematical Model
Authors: Joshua T. Schiffer, Laith Abu-Raddad, Karen E. Mark, Jia Zhu, Stacy Selke, Amalia Magaret, Anna Wald, Lawrence Corey
Journal: Science Translational Medicine (2009)

A stochastic mathematical model suggests that very low numbers of herpes simplex virus 2 particles are released frequently into the genital tract in infected individuals.
Rearrangement of the beta chain of the T cell antigen receptor and immunoglobulin genes in lymphoproliferative disorders.
Authors: H Griesser, A Feller, K Lennert, M Minden, T W Mak
Journal: Journal of Clinical Investigation (1986)

55 samples representing Hodgkin's and non-Hodgkin's lymphoma and other hyperplastic lesions of the lymph node were examined for rearrangement of the beta chain of the T cell antigen receptor (TcR) and Ig genes. In non-Hodgkin's lymphoma, rearrangement of TcR beta was found in all 14 T cell lymphomas and in two of the seven B cell lymphomas. Ig gene rearrangement was found in none of the 14 T cell lymphomas and in all seven B cell lymphomas. We also examined DNA from lymph nodes in which the lineage of the malignant cell is not clear. Rearrangement of TcR beta was found in all five lymphoepitheloid cell (Lennert's) lymphomas; four of eight Hodgkin's lymphomas; seven of ten Ki 1+ lymphomas; and all nine cases of angioimmunoblastic lymphoadenopathy (AIL). Ig gene rearrangement was found in none of five lymphoepitheloid cell lymphomas; none of eight Hodgkin's lymphomas; three of ten Ki 1+ lymphomas; and four of nine cases of AIL. These findings indicate that genetic studies of TcR and Ig genes are useful in identifying the presence of a clonal population in a lymph node, in determining the extent of the clonal population, and aid in identifying lineage. Of special interest was the finding that some cases of Hodgkin's lymphoma and AIL contain clonal rearrangement of the TcR genes, which suggests that in those cases the malignant cells may be of T cell origin.
Sexual activity as a risk factor for hepatitis C
Authors: Norah A. Terrault
Journal: Hepatology (2002)

The accumulated evidence indicates that hepatitis C virus (HCV) can be transmitted by sexual contact but much less efficiently than other sexually transmitted viruses, including hepatitis B virus and human immunodeficiency virus (HIV). However, because sex is such a common behavior and the reservoir of HCV-infected individuals is sizable, sexual transmission of HCV likely contributes to the total burden of infection in the United States. Risk of HCV transmission by sexual contact differs by the type of sexual relationship. Persons in long-term monogamous partnerships are at lower risk of HCV acquisition (0% to 0.6% per year) than persons with multiple partners or those at risk for sexually transmitted diseases (0.4% to 1.8% per year). This difference may reflect differences in sexual risk behaviors or differences in rates of exposure to nonsexual sources of HCV, such as injection drug use or shared razors and toothbrushes. In seroprevalence studies in monogamous, heterosexual partners of HCV-infected, HIV-negative persons, the frequency of antibody-positive and genotype-concordant couples is 2.8% to 11% in Southeast Asia, 0% to 6.3% in Northern Europe, and 2.7% in the United States. Among individuals at risk for sexually transmitted diseases (STDs), the median seroprevalence of antibody to HCV (anti-HCV) is 4% (range, 1.6% to 25.5%). HIV coinfection appears to increase the rate of HCV transmission by sexual contact. Current recommendations about sexual practices are different for persons with chronic HCV infection who are in steady monogamous partnerships versus those with multiple partners or who are in short-term sexual relationships.
Storage of heart valve allografts in glycerol with subsequent antibiotic sterilisation.
Authors: R Parker, R Randev, W H Wain, D N Ross
Journal: Thorax (1978)

Fresh allograft valves stored in a nutrient medium at +4 degrees C have a limited storage time of eight weeks. Dura mater has been stored in glycerol for longer periods, and this paper presents work on the glycerol storage of allograft heart valves. The elastic properties of the valve cusps showed a fall during storage in glycerol that was associated with an altered histological appearance of the cusp tissue. The loss in nuclearity in the histological sections of stored tissue was partially responsible for the observed decrease in viability during storage. All these changes during storage in glycerol, or glycerol and subsequent antibiotic treatment, were similar to the changes seen in valves stored in a nutrient medium. Glycerol therefore offers an alternative storage system to the cold nutrient medium but has no practical advantages. Glycerol alone will not sterilise the allograft tissue, and a post-storage treatment with antibiotics is essential.
Certificated sickness absence in industrial employees threatened with redundancy
Authors: N. Beale, S. Nethercott
Journal: BMJ (1988)

The proposition that workers take less sick leave when threatened by redundancy was examined in a longitudinal, controlled study using information from case records in a general practice. The hypothesis was only partly supported—certificated sickness absence dropped only in employees under the age of 40. Workers fearing job loss reported more illness, and their periods of absence were significantly longer, especially for men and for workers who had previously consulted their general practitioner infrequently. This study provides further evidence that the fear of mass redundancy is stressful to workers so threatened and costly to a society experiencing rising unemployment.
Computational Identification of Receptive Fields
Authors: Tatyana O. Sharpee
Journal: Annual Review of Neuroscience (2013)

Natural stimuli elicit robust responses of neurons throughout sensory pathways, and therefore their use provides unique opportunities for understanding sensory coding. This review describes statistical methods that can be used to characterize neural feature selectivity, focusing on the case of natural stimuli. First, we discuss how such classic methods as reverse correlation/spike-triggered average and spike-triggered covariance can be generalized for use with natural stimuli to find the multiple relevant stimulus features that affect the responses of a given neuron. Second, ways to characterize neural feature selectivity while assuming that the neural responses exhibit a certain type of invariance, such as position invariance for visual neurons, are discussed. Finally, we discuss methods that do not require one to make an assumption of invariance and instead can determine the type of invariance by analyzing relationships between the multiple stimulus features that affect the neural responses.
Do shock absorbing insoles in recruits undertaking high levels of physical activity reduce lower limb injury? A randomized controlled trial
Authors: Richard Withnall, Joanne Eastaugh, Nick Freemantle
Journal: Journal of the Royal Society of Medicine (2005)

ObjectivesTo assess the benefits, if any, of the use of shock absorbing insoles in reducing lower limb injury among Air Force recruits, and to assess the differences, if any, in the efficacy of two commonly available shock absorbing insoles. DesignRandomized controlled trial. Setting: RAF Halton, UK. Site of all basic training for RAF personnel. Participants: 1205 recruits participating in basic training between 17 September 2003 and 7 April 2004. Interventions: Participants were randomized to receive either standard issue Saran non-shock absorbing insoles, or shock absorbing Sorbothane or Poron insoles, on a 1:1:1 basis. Main Outcome MeasuresThe primary outcome measure was withdrawal from training for lower limb injury. The two primary comparisons were shock absorbing insole versus non-shock absorbing insole, and Sorbothane versus Poron (comparison of different shock absorbing insoles). Secondary outcomes were medical withdrawals for reasons other than those qualifying for the primary outcome measure. ResultsWhen comparing the non-shock absorbing insole to the shock absorbing insoles 72/401 participants (18.0%) allocated to Saran insoles were removed from training because of a qualifying lower limb injury, compared with 149/ 804 (18.5%) allocated to the shock absorbing insole (Sorbothane or Poron), odds ratio 1.04 (95% CI 0.75 to 1.44; P=0.87). When comparing the two shock absorbing insole 73/ 421 participants (17.3%) randomized to Sorbothane were removed from training because of a qualifying lower limb injury, compared with 76/383 for Poron (19.8%), odds ratio 0.85 (95% CI 0.58 to 1.23; P=0.37). ConclusionsSimilar rates of lower limb injuries were observed for all insoles (shock absorbing and non-shock absorbing) in the trial. The trial provides no support for a change in policy to the use of shock absorbing insoles for military recruits.
Innate responsiveness of CD8 memory T-cell populations nonspecifically inhibits allergic sensitization
Authors: Jamie A. Leggat, Deena L. Gibbons, Syeda F.Y. Haque, Adrian L. Smith, James W. Wells, Katherine Choy, Clare M. Lloyd, Adrian C. Hayday, Alistair Noble
Journal: Journal of Allergy and Clinical Immunology (2008)
A Prospective Study of Egg Consumption and Risk of Cardiovascular Disease in Men and Women
Authors: Frank B. Hu
Journal: JAMA (1999)

LEVATED LOW-DENSITY LIPOPROtein (LDL) cholesterol is a major risk factor for coronary heart disease (CHD). 1 Dietary cholesterol raises LDL cholesterol levels and causes atherosclerosis in numerous animal models. 2In controlled metabolic studies conducted in humans, dietary cholesterol raises levels of total and LDL cholesterol in blood, 3,4 but the effects are relatively small compared with saturated and transfatty acids. 5,6Studies have found that individuals vary widely in their responses to dietary cholesterol based on monitoring their plasma levels. 7,8][13][14][15][16][17] To avoid elevations in blood cholesterol and reduce CHD risk, the public has been advised to consume no more than 300 mg/d of cholesterol and limit consumption of eggs, which contain about 213 mg of cholesterol per egg. 1,18However, eggs contain many other nutrients
Leukotriene antagonists and Churg-Strauss syndrome: the smoking gun
Authors: R G STIRLING, K F CHUNG
Journal: Thorax (1999)

<h3>Background</h3> Chronically ill adults insured by Medicaid experience health inequities following hospitalisation. <h3>Local problem</h3> Postacute outcomes, including rates of 30-day readmissions and postacute emergency department (ED), were higher among Medicaid-insured individuals compared with commercially insured individuals and social needs were inconsistently addressed. <h3>Methods</h3> An interdisciplinary team introduced a clinical pathway called ‘THRIVE’ to provide postacute wrap-around services for individuals insured by Medicaid. <h3>Intervention</h3> Enrolment into the THRIVE clinical pathway occurred during hospitalisation and multidisciplinary services were deployed into homes within 48 hours of discharge to address clinical and social needs. <h3>Results</h3> Compared with those not enrolled in THRIVE (n=437), individuals who participated in the THRIVE clinical pathway (n=42) experienced fewer readmissions (14.3% vs 28.4%) and ED visits (14.3% vs 28.8 %). <h3>Conclusion</h3> THRIVE is a promising clinical pathway that increases access to ambulatory care after discharge and may reduce readmissions and ED visits.
Options for the management of antiviral resistance during hepatitis B therapy: reflections on battles over a decade
Authors: Hyung Joon Yim, Seong Gyu Hwang
Journal: Clinical and Molecular Hepatology (2013)

Although much advancement has been achieved in the treatment of chronic hepatitis B, antiviral resistance is still a challenging issue. Previous generation antiviral agents have already developed resistance in a number of patients, and it is still being used especially in resource limited countries. Once antiviral resistance occurs, it predisposes to subsequent resistance, resulting in multidrug resistance. Therefore, prevention of initial antiviral resistance is the most important strategy, and appropriate choice and modification of therapy would be the cornerstone in avoiding treatment failures. Until now, management of antiviral resistance has been evolving from sequential therapy to combination therapy. In the era of tenofovir, the paradigm shifts again, and we have to decide when to switch and when to combine on the basis of newly emerging clinical data. We expect future eradication of chronic hepatitis B virus infection by proper prevention and optimal management of antiviral resistance. Keywords: Antiviral resistance; Chronic hepatitis B; Hepatitis B virus; Treatment; Nucleoside analogue; Nucleotide analogue
Loss of Disialyl Lewisa, the Ligand for Lymphocyte Inhibitory Receptor Sialic Acid-Binding Immunoglobulin-Like Lectin-7 (Siglec-7) Associated with Increased Sialyl Lewisa Expression on Human Colon Cancers
Authors: Keiko Miyazaki, Katsuyuki Ohmori, Mineko Izawa, Tetsufumi Koike, Kensuke Kumamoto, Koichi Furukawa, Takayuki Ando, Makoto Kiso, Toshiyuki Yamaji, Yasuhiro Hashimoto, Akemi Suzuki, Aruto Yoshida, Makoto Takeuchi, Reiji Kannagi
Journal: Cancer Research (2004)

Abstract Expression of sialyl Lewisa is known to be increased in cancers of the digestive organs. The determinant serves as a ligand for E-selectin and mediates hematogenous metastasis of cancers. In contrast, disialyl Lewisa, which has an extra sialic acid attached at the C6-position of penultimate GlcNAc in sialyl Lewisa, is expressed preferentially on nonmalignant colonic epithelial cells, and its expression decreases significantly on malignant transformation. Introduction of the gene for an α2→6 sialyl-transferase responsible for disialyl Lewisa synthesis to colon cancer cells resulted in a marked increase in disialyl Lewisa expression and corresponding decrease in sialyl Lewisa expression. This was accompanied by the complete loss of E-selectin binding activity of the cells. In contrast, the transfected cells acquired significant binding activity to sialic acid-binding immunoglobulin-like lectin-7 (Siglec-7)/p75/adhesion inhibitory receptor molecule-1, an inhibitory receptor expressed on lymphoid cells. These results indicate that the transition of carbohydrate determinants from disialyl Lewisa-dominant status to sialyl Lewisa-dominant status on malignant transformation has a dual functional consequence: the loss of normal cell-cell recognition between mucosal epithelial cells and lymphoid cells on one hand and the gain of E-selectin binding activity on the other. The transcription of a gene encoding the α2→6 sialyltransferase was markedly down-regulated in cancer cells compared with nonmalignant epithelial cells, which is in line with the decreased expression of disialyl Lewisa and increased expression of sialyl Lewisa in cancers. Treatment of cancer cells with butyrate or 5-azacytidine induced strongly disialyl Lewisa expression, suggesting that histone deacetylation and/or DNA methylation may be involved in the silencing of the gene in cancers.
Rates of Gene Rearrangement and Nucleotide Substitution Are Correlated in the Mitochondrial Genomes of Insects
Authors: R. Shao
Journal: Molecular Biology and Evolution (2003)

A number of studies indicated that lineages of animals with high rates of mitochondrial (mt) gene rearrangement might have high rates of mt nucleotide substitution.We chose the hemipteroid assemblage and the Insecta to test the idea that rates of mt gene rearrangement and mt nucleotide substitution are correlated.For this purpose, we sequenced the mt genome of a lepidopsocid from the Psocoptera, the only order of hemipteroid insects for which an entire mtDNA sequence is not available.The mt genome of this lepidopsocid is circular, 16,924 bp long, and contains 37 genes and a putative control region; seven tRNA genes and a protein-coding gene in this genome have changed positions relative to the ancestral arrangement of mt genes of insects.We then compared the relative rates of nucleotide substitution among species from each of the four orders of hemipteroid insects and among the 20 insects whose mt genomes have been sequenced entirely.All comparisons among the hemipteroid insects showed that species with higher rates of gene rearrangement also had significantly higher rates of nucleotide substitution statistically than did species with lower rates of gene rearrangement.In comparisons among the 20 insects, where the mt genomes of the two species differed by more than five breakpoints, the more rearranged species always had a significantly higher rate of nucleotide substitution than the less rearranged species.However, in comparisons where the mt genomes of two species differed by five or less breakpoints, the more rearranged species did not always have a significantly higher rate of nucleotide substitution than the less rearranged species.We tested the statistical significance of the correlation between the rates of mt gene rearrangement and mt nucleotide substitution with nine pairs of insects that were phylogenetically independent from one another.We found that the correlation was positive and statistically significant (R 2 ¼ 0.73, P ¼ 0.01; R s ¼ 0.67, P , 0.05).We propose that increased rates of nucleotide substitution may lead to increased rates of gene rearrangement in the mt genomes of insects.
Congenital Complete Atrioventricular Block: Problems of Clinical Assessment
Authors: MILTON H. PAUL, ABRAHAM M. RUDOLPH, ALEXANDER S. NADAS
Journal: Circulation (1958)

The diagnosis of congenital complete atrioventricular block usually offers little difficulty. There remains, however, the problem of interpreting certain clinical findings, including systolic and diastolic murmurs and cardiomegaly, which are sometimes falsely suggestive of an associated congenital heart lesion. The clinical, radiologic, and electrocardiographic findings in 27 children with congenital complete heart block have been analyzed in terms of the hemodynamic abnormalities found at cardiac catheterization in 12 of these patients.
Longitudinal Investigation of Permeability and Distribution of Macromolecules in Mouse Malignant Transformation Using PET
Authors: Cecilie B. Rygh, Shengping Qin, Jai W. Seo, Lisa M. Mahakian, Hua Zhang, Roger Adamson, Jane Q. Chen, Alexander D. Borowsky, Robert D. Cardiff, Rolf K. Reed, Fitz-Roy E. Curry, Katherine W. Ferrara
Journal: Clinical Cancer Research (2010)

We apply positron emission tomography (PET) to elucidate changes in nanocarrier extravasation during the transition from premalignant to malignant cancer, providing insight into the use of imaging to characterize early cancerous lesions and the utility of nanoparticles in early disease.Albumin and liposomes were labeled with (64)Cu (half-life 12.7 hours), and longitudinal PET and CT imaging studies were conducted in a mouse model of ductal carcinoma in situ. A pharmacokinetic model was applied to estimate the tumor vascular volume and permeability.From early time points characterized by disseminated hyperproliferation, the enhanced vascular permeability facilitated lesion detection. During disease progression, the vascular volume fraction increased 1.6-fold and the apparent vascular permeability to albumin and liposomes increased ∼2.5-fold to 6.6 × 10(-8) and 1.3 × 10(-8) cm/s, respectively, with the accumulation of albumin increasing earlier in the disease process. In the malignant tumor, both tracers reached similar mean intratumoral concentrations of ∼6% ID/cc but the distribution of liposomes was more heterogeneous, ranging from 1% to 18% ID/cc compared with 1% to 9% ID/cc for albumin. The tumor-to-muscle ratio was 17.9 ± 8.1 and 7.1 ± 0.5 for liposomes and albumin, respectively, indicating a more specific delivery of liposomes than with albumin.PET imaging of radiolabeled particles, validated by confocal imaging and histology, detected the transition from premalignant to malignant lesions and effectively quantified the associated changes in vascular permeability.
Myasthenia Gravis Induced by Ipilimumab in Patients With Metastatic Melanoma
Authors: Douglas B. Johnson, Vita Saranga-Perry, Patrick J.M. Lavin, W. Bryan Burnette, Stephen W. Clark, David R. Uskavitch, Deborah E. Wallace, Mark A. Dickson, Ragini R. Kudchadkar, Jeffrey A. Sosman
Journal: Journal of Clinical Oncology (2014)