tbuckley/cabot-search huggingface dataset:
Overexpression of Interleukin (IL)-7 Leads to IL-15–independent Generation of Memory Phenotype CD8+ T Cells
Authors: William C. Kieper, Joyce T. Tan, Brea Bondi-Boyd, Laurent Gapin, Jonathan Sprent, Rhodri Ceredig, Charles D. Surh
Journal: The Journal of Experimental Medicine (2002)

Transgenic (TG) mice expressing a high copy number of interleukin (IL)-7 cDNA under the control of the major histocomaptability complex (MHC) class II promoter display a 10–20-fold increase in total T cell numbers. Here, we show that the increase in T cell numbers in IL-7 TG mice is most apparent at the level of memory phenotype CD44hi CD122hi CD8+ cells. Based on studies with T cell receptor (TCR) TG mice crossed to IL-7 TG mice, increased levels of IL-7 may provide costimulation for TCR recognition of self-MHC ligands and thus cause naive CD8+ cells to proliferate and differentiate into memory phenotype cells. In addition, a marked increase in CD44hi CD122hi CD8+ cells was found in IL-7 TG IL-15− mice. Since these cell are rare in normal IL-15− mice, the dependency of memory phenotype CD8+ cells on IL-15 can be overcome by overexpression of IL-7.
MicroRNA-566 activates EGFR signaling and its inhibition sensitizes glioblastoma cells to nimotuzumab
Authors: Kai-Liang Zhang, Xuan Zhou, Lei Han, Lu-Yue Chen, Ling-Chao Chen, Zhen-Dong Shi, Ming Yang, Yu Ren, Jing-Xuan Yang, Thomas S Frank, Chuan-Bao Zhang, Jun-Xia Zhang, Pei-Yu Pu, Jian-Ning Zhang, Tao Jiang, Eric J Wagner, Min Li, Chun-Sheng Kang
Journal: Molecular Cancer (2014)

Epidermal growth factor receptor (EGFR) is amplified in 40% of human glioblastomas. However, most glioblastoma patients respond poorly to anti-EGFR therapy. MicroRNAs can function as either oncogenes or tumor suppressor genes, and have been shown to play an important role in cancer cell proliferation, invasion and apoptosis. Whether microRNAs can impact the therapeutic effects of EGFR inhibitors in glioblastoma is unknown.miR-566 expression levels were detected in glioma cell lines, using real-time quantitative RT-PCR (qRT-PCR). Luciferase reporter assays and Western blots were used to validate VHL as a direct target gene of miR-566. Cell proliferation, invasion, cell cycle distribution and apoptosis were also examined to confirm whether miR-566 inhibition could sensitize anti-EGFR therapy.In this study, we demonstrated that miR-566 is up-regulated in human glioma cell lines and inhibition of miR-566 decreased the activity of the EGFR pathway. Lentiviral mediated inhibition of miR-566 in glioblastoma cell lines significantly inhibited cell proliferation and invasion and led to cell cycle arrest in the G0/G1 phase. In addition, we identified von Hippel-Lindau (VHL) as a novel functional target of miR-566. VHL regulates the formation of the β-catenin/hypoxia-inducible factors-1α complex under miR-566 regulation.miR-566 activated EGFR signaling and its inhibition sensitized glioblastoma cells to anti-EGFR therapy.
Cyclooxygenase-2 Expression
Authors: Labile Togba Soumaoro, Hiroyuki Uetake, Tetsuro Higuchi, Yoko Takagi, Masayuki Enomoto, Kenichi Sugihara
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Recent studies have shown that cyclooxygenase (Cox)-2 may be involved in colorectal carcinogenesis. We aimed to determine whether Cox-2 expression in itself can predict outcome of colorectal cancer patient after surgery. In addition, the expression of Cox-1 was also evaluated. Experimental Design: Tissue samples of primary and secondary tumors from 288 patients undergoing surgical resections for colorectal adenocarcinoma were immunohistochemically examined for Cox-2 and Cox-1 expressions. The specimens were graded based on the intensity and extent of staining; then, the correlations between Cox-2 and Cox-1 expressions with clinicopathologic parameters and survival time were analyzed. Results: Expression of Cox-2 was positive in 70.8% of primary tumor, 92.0% of lymph node metastases, 100.0% of hepatic metastases, and was significantly associated with tumor size, depth of invasion, lymph node metastasis, vessels invasion, stage and recurrence. In contrast, Cox-1 was positive in 42.7% of primary tumor, 84.0% of lymph node metastases, 37.5% hepatic metastases, and was associated with only tumor size. Patients with Cox-2–positive tumors had a significant shorter survival time than those with negative tumors did (P = 0.0006 by log-rank test); and, in a multivariate analysis, Cox-2 was an independent prognostic factor (P = 0.0103; relative risk 4.114; 95% confidence interval, 1.397–12.120). Cox-1 status had no statistically effect on patient survival time. Conclusions: Elevated Cox-2 expression, but not that of Cox-1, was significantly associated with reduced survival and recognized as an independent prognostic factor in our cohort of colorectal cancer patients.
Activation of hypothalamic S6 kinase mediates diet-induced hepatic insulin resistance in rats
Authors: Hiraku Ono, Alessandro Pocai, Yuhua Wang, Hideyuki Sakoda, Tomoichiro Asano, Jonathan M. Backer, Gary J. Schwartz, Luciano Rossetti
Journal: Journal of Clinical Investigation (2008)

Prolonged activation of p70 S6 kinase (S6K) by insulin and nutrients leads to inhibition of insulin signaling via negative feedback input to the signaling factor IRS-1. Systemic deletion of S6K protects against diet-induced obesity and enhances insulin sensitivity in mice. Herein, we present evidence suggesting that hypothalamic S6K activation is involved in the pathogenesis of diet-induced hepatic insulin resistance. Extending previous findings that insulin suppresses hepatic glucose production (HGP) partly via its effect in the hypothalamus, we report that this effect was blunted by short-term high-fat diet (HFD) feeding, with concomitant suppression of insulin signaling and activation of S6K in the mediobasal hypothalamus (MBH). Constitutive activation of S6K in the MBH mimicked the effect of the HFD in normal chow-fed animals, while suppression of S6K by overexpression of dominant-negative S6K or dominant-negative raptor in the MBH restored the ability of MBH insulin to suppress HGP after HFD feeding. These results suggest that activation of hypothalamic S6K contributes to hepatic insulin resistance in response to short-term nutrient excess.
Sticks, Stones, and Hurtful Words: Relative Effects of Various Forms of Childhood Maltreatment
Authors: Martin H. Teicher, Jacqueline A. Samson, Ann Polcari, Cynthia E. McGreenery
Journal: American Journal of Psychiatry (2006)

Childhood maltreatment is an important psychiatric risk factor. Research has focused primarily on the effects of physical abuse, sexual abuse, or witnessing domestic violence. Parental verbal aggression has received little attention as a specific form of abuse. This study was designed to delineate the impact of parental verbal aggression, witnessing domestic violence, physical abuse, and sexual abuse, by themselves and in combination, on psychiatric symptoms.Symptoms and exposure ratings were collected from 554 subjects 18-22 years of age (68% female) who responded to advertisements. The Verbal Abuse Questionnaire was used to assess exposure to parental verbal aggression. Outcome measures included dissociation and symptoms of "limbic irritability," depression, anxiety, and anger-hostility. Comparisons were made by using effect sizes.Verbal aggression was associated with moderate to large effects, comparable to those associated with witnessing domestic violence or nonfamilial sexual abuse and larger than those associated with familial physical abuse. Exposure to multiple forms of maltreatment had an effect size that was often greater than the component sum. Combined exposure to verbal abuse and witnessing domestic violence had a greater negative effect on some measures than exposure to familial sexual abuse.Parental verbal aggression was a potent form of maltreatment. Exposure to multiple forms of abuse was associated with very large effect sizes. Most maltreated children had been exposed to multiple types of abuse, and the number of different types is a critically important factor.
Modulation of Arachidonic Acid Release and Membrane Fluidity by Albumin in Vascular Smooth Muscle and Endothelial Cells
Authors: Richard Beck, Sophie Bertolino, Stewart E. Abbot, Philip I. Aaronson, Sergey V. Smirnov
Journal: Circulation Research (1998)

Abstract —Albumin is the major plasma protein circulating in blood. Albumin potently decreases capillary permeability, although the mechanisms are not understood completely. Albumin also effectively binds arachidonic acid (AA), which increases capillary permeability. To investigate the interactions of BSA and AA with the cell membrane, the effect of these substances on [ 3 H]AA release and membrane fluidity was studied in vascular myocytes and endothelial cells. BSA (0.2 and 1 mg · mL −1 ) stimulated a significant release of [ 3 H]AA from both intact rat aorta and cultured smooth muscle cells. This effect was not mimicked by γ-globulin or myoglobin (both 1 mg · mL −1 ) in intact tissue. BSA, but not γ-globulin and myoglobin, decreased the membrane fluidity (assessed as changes in the steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene) in a concentration-dependent manner with a half-maximum concentration between 0.007 and 0.4 mg · mL −1 in both freshly isolated and cultured rat aortic myocytes and human umbilical vein endothelial cells. AA (1 to 200 μmol/L) caused the opposite effect, increasing membrane fluidity and antagonizing the effect of BSA. BSA modified at its arginine residues, which are thought to be important in AA binding, did not stimulate [ 3 H]AA release and was significantly less potent than native BSA in altering the membrane fluidity. The effect of BSA can be explained by a high-affinity binding of AA to the protein and extraction of AA from the cell membrane. The interaction between BSA and AA could play a role in the regulation of vascular permeability.
Assessment Of Food Insecurity and Health Literacy In a Tertiary Care Pediatric Allergy Population
Authors: Meredith A. Dilley, G. Lynn Christie, Mary Price, Connelly Weeks, Mallikarjuna Rettiganti, Maria Melguizo Castro, Amy M. Scurlock, Tamara T. Perry, Robbie D. Pesek, Matthew C. Bell, Joshua L. Kennedy, Erin O'Brien, Sklar McGrath, Jared Hogan, Megan Patterson, Julia Aronson, Patrick Casey, Stacie M. Jones
Journal: Journal of Allergy and Clinical Immunology (2014)
Src-Family Kinase Fyn Phosphorylates the Cytoplasmic Domain of Nephrin and Modulates Its Interaction with Podocin
Authors: Hongping Li, Serge Lemay, Lamine Aoudjit, Hiroshi Kawachi, Tomoko Takano
Journal: Journal of the American Society of Nephrology (2004)

Visceral glomerular epithelial cells (GEC) are critical for normal permselectivity of the kidney. Nephrin is a molecule that is expressed specifically in GEC in a structure called the slit diaphragm and is required for normal morphology and permselectivity of GEC. However, the mechanisms of action of nephrin are not understood precisely. The intracellular domain of nephrin has six conserved tyrosine residues. It was hypothesized that these tyrosine residues are phosphorylated by Src-family kinases and that this phosphorylation modulates the function of nephrin. A transient transfection system was used to study the role of tyrosine phosphorylation of the cytoplasmic domain of nephrin in its function. When nephrin was co-transfected with Src-family kinases Fyn or Src in Cos-1 cells, nephrin was strongly tyrosine phosphorylated by Fyn and less so by Src. The results with tyrosine-to-phenylalanine mutations suggested that multiple tyrosine residues contribute to phosphorylation mediated by Src-family kinases. The intracellular domain of nephrin is known to interact with another slit diaphragm protein, podocin. When nephrin and podocin were transfected with Fyn, the interaction between nephrin and podocin was augmented significantly. Podocin was not tyrosine phosphorylated by Fyn; thus, the increased interaction is likely to be secondary to tyrosine phosphorylation of nephrin. Fyn also significantly augmented the activation of the AP-1 promoter induced by nephrin and podocin. In summary, Fyn phosphorylates the cytoplasmic domain of nephrin on tyrosine, leading to enhanced association with podocin and downstream signaling of nephrin.
E1A Can Provoke G1 Exit That Is Refractory to p21 and Independent of Activating Cdk2
Authors: Saïd Akli, Song Zhan, Maha Abdellatif, Michael D. Schneider
Journal: Circulation Research (1999)

Abstract —E1A can evoke G1 exit in cardiac myocytes and other cell types by displacing E2F transcription factors from tumor suppressor “pocket” proteins and by a less well-characterized p300-dependent pathway. Bypassing pocket proteins (through overexpression of E2F-1) reproduces the effect of inactivating pocket proteins (through E1A binding); however, pocket proteins associate with a number of molecular targets apart from E2F. Hence, pocket protein binding by E1A might engage mechanisms for cell cycle reentry beyond those induced by E2F-1. To test this hypothesis, we used adenoviral gene transfer to express various E2F-1 and E1A proteins in neonatal rat cardiac myocytes that are already refractory to mitogenic serum, in the absence or presence of several complementary cell cycle inhibitors—p16, p21, or dominant-negative cyclin-dependent kinase-2 (Cdk2). Rb binding by E2F-1 was neither necessary nor sufficient for G1 exit, whereas DNA binding was required; thus, exogenous E2F-1 did not merely function by competing for the Rb “pocket.” E2F-1–induced G1 exit was blocked by the “universal” Cdk inhibitor p21 but not by p16, a specific inhibitor of Cdk4/6; p21 was permissive for E2F-1 induction of cyclins E and A, but prevented their stimulation of Cdk2 kinase activity. In addition, E2F-1–induced G1 exit was blocked by dominant-negative Cdk2. Forced expression of cyclin E induced endogenous Cdk2 activity but not G1 exit. Thus, E2F-1–induced Cdk2 function was necessary, although not sufficient, to trigger DNA synthesis in cardiac muscle cells. In contrast, pocket protein–binding forms of E1A induced G1 exit that was resistant to inhibition by p21, whereas G1 exit via the E1A p300 pathway was sensitive to inhibition by p21. Both E1A pathways—via pocket proteins and via p300—upregulated cyclins E and A and Cdk2 activity, consistent with a role for Cdk2 in G1 exit induced by E1A. However, p21 blocked Cdk2 kinase activity induced by both E1A pathways equally. Thus, E1A can cause G1 exit without an increase in Cdk2 activity, if the pocket protein–binding domain is intact. E1A also overrides p21 in U2OS cells, provided the pocket protein–binding domain is intact; thus, this novel function of E1A is not exclusive to cardiac muscle cells. In summary, E1A binding to pocket proteins has effects beyond those produced by E2F-1 alone and can drive S-phase entry that is resistant to p21 and independent of an increase in Cdk2 function. This suggests the potential involvement of other endogenous Rb-binding proteins or of alternative E1A targets.
Strength training for wheelchair users.
Authors: G M Davis, R J Shephard
Journal: British Journal of Sports Medicine (1990)

Sedentary adult males with spinal lesions, all habitual wheelchair users, were allocated to exercise (n = 11) and control (n = 4) groups. A Cybex II dynamometer was used to assess peak power, average power, total work and muscular endurance for elbow flexion/extension, shoulder flexion/extension and shoulder abduction/adduction at five angular velocities, on recruitment and after eight and 16 weeks of forearm ergometer training (three days/week). Small sub-groups of the exercised subjects were assigned to high or low intensity endurance effort (70 or 40 per cent of maximal oxygen intake) and long or short training sessions (40 or 20 minutes per session). Despite the aerobic nature of the activity, gains of average power were registered by the two muscle groups most involved in the ergometer task (shoulder extension and elbow flexion). In keeping with current theories of training, gains were largest with prolonged, high intensity activity at angular velocities approximating those adopted during training.
The role of neuropeptides in psoriasis
Authors: R. Saraceno, C.E. Kleyn, G. Terenghi, C.E.M. Griffiths
Journal: British Journal of Dermatology (2006)

Journal Article The role of neuropeptides in psoriasis Get access R. Saraceno, R. Saraceno Dermatology Centre, Hope Hospital, The University of Manchester, Salford, Manchester M6 8HD, U.KDermatology Department, The University of Rome 'Tor Vergata', Rome, ItalyPlastic and Reconstructive Surgery Research, The University of Manchester, Stopford Building, Manchester M13 9PT, U.K Search for other works by this author on: Oxford Academic Google Scholar C.E. Kleyn, C.E. Kleyn Dermatology Centre, Hope Hospital, The University of Manchester, Salford, Manchester M6 8HD, U.K Search for other works by this author on: Oxford Academic Google Scholar G. Terenghi, G. Terenghi Plastic and Reconstructive Surgery Research, The University of Manchester, Stopford Building, Manchester M13 9PT, U.K Search for other works by this author on: Oxford Academic Google Scholar C.E.M. Griffiths C.E.M. Griffiths Dermatology Centre, Hope Hospital, The University of Manchester, Salford, Manchester M6 8HD, U.K C.E.M. Griffiths. E‐mail: christopher.griffiths@manchester.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 155, Issue 5, 1 November 2006, Pages 876–882, https://doi.org/10.1111/j.1365-2133.2006.07518.x Published: 01 November 2006 Article history Accepted: 19 May 2006 Published: 01 November 2006
Clinical utility of chest auscultation in common pulmonary diseases.
Authors: P E Bettencourt, E A Del Bono, D Spiegelman, E Hertzmark, R L Murphy
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

In this investigation we applied the techniques of lung sound mapping and time-expanded wave-form analysis to four common diseases that involve the lung: interstitial pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), and pneumonia (Pn). Twenty subjects were studied in each group. We also studied 15 subjects without evidence of lung disease. Differences in timing, character, and location were observed, which allowed separation among these groups. Multiple logistic regression models were created and tested by the bootstrap method. Regression models correctly classified 68 and 79% of subjects. Area under the receiver operating curve ranged from 0.96 for IPF and CHF to 0.80 for COPD. We conclude that auscultatory differences exist among common pulmonary conditions and that statistical models based on auscultatory data perform well in predicting diagnostic categories.
Analysis of Cell Cycle Regulator Proteins in Encapsulated Thymomas
Authors: Alfonso Baldi, Vincenzo Ambrogi, Davide Mineo, Pasquale Mellone, Mara Campioni, Gennaro Citro, Tommaso Claudio Mineo
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Although survival of encapsulated thymomas is usually good, some patients present a higher incidence rate of recurrence and a shorter long-term survival. Abnormalities in the components of cell cycle checkpoints are extremely common among virtually all neoplasms. In this study, three components of the cell cycle machinery (i.e., p21, p27 and p53) were examined in a series of well-characterized encapsulated thymoma specimens to analyze coregulation and influence on recurrence and survival. Experimental Design: Sixty-eight consecutive patients with thymoma were operated in our center from 1987 to 2000. Expression of p53, p21, and p27 was studied in specimens from 25 encapsulated thymomas using immunohistochemistry. Generic factors and gene expression influencing the probability of recurrence were studied. Positive expression was dichotomized defining positive when present in more than 5% of tumor cells. Mean follow up was 85.9 months; clinical data about recurrence were recorded. Results: Univariate analysis suggests that positive p53 (P &amp;lt; 0.05), negative p21 (P = 0.01), and especially negative p27 expressions (P = 0.001) significantly correlate with poor prognosis for disease-free survival. Multivariate Cox regression analysis suggests that negative p27 immunohistology is the only significant variable for poor prognosis (P = 0.03; odds ratio, 0.08; 95% confidence interval, 0.01-0.88). Conclusions: These results show that loss of control of cell cycle checkpoints is a common occurrence in thymomas and support the idea that functional cooperation between different cell cycle inhibitor proteins constitutes another level of regulation in cell growth control and tumor suppression.
P46 The Influence Of Age And Gender On Allergy Test Results: Implications For The Use As Biomarkers In Childhood Asthma
Authors: H. Mohammad, D. Belgrave, K. Harding, A. Simpson, A. Custovic
Journal: Thorax (2014)

<h3>Introduction</h3> Skin prick tests (SPTs) and measurement of allergen-specific serum (s)IgE are the main diagnostic tools for confirming atopy. Results of both tests are usually reported as dichotomous (sensitised/not sensitised), using arbitrary cut-offs which are the same across different ages and genders (SPT &gt;3 mm, sIgE &gt;0.35 kU/L). We investigated the influence of age and gender on allergy test results as biomarkers of asthma during childhood. <h3>Methods</h3> Children in a population-based birth cohort (n = 1051) were followed from birth to age 11 years. Information on asthma/wheeze (questionnaires), SPTs and sIgE to inhalant allergens (mite, cat, dog) were collected at ages 3, 5, 8 and 11 years. We investigated the association between quantitative atopy (sum of SPT mean wheal diameters [MWD]/titres of sIgE) and wheeze/asthma across ages and genders. <h3>Results</h3> There was a significant association between the SPT MWD/sIgE titre and wheeze/asthma at all ages and for both genders. However, the strength of this association was age and gender-dependent. For SPTs, the strength of the association between MWD and asthma increased with increasing age (OR 1.14–1.20, p = 0.002); we observed the opposite pattern for sIgE titre (OR 0.97–0.99, p = 0.04). For any given SPT/sIgE level, boys were significantly more likely to express clinical symptoms, particularly in early life; this difference between males and females appeared to diminish with age, and was no longer significant by age 11 years. <h3>Conclusions</h3> Age and gender have to be taken into account when interpreting the results of allergy tests (skin tests and IgE measurement) in the context of asthma during childhood.
A Later Stage of Anomalous Coronary Circulation with Origin of the Left Coronary Artery from the Pulmonary Artery
Authors: ARTHUR E. BAUE, STANLEY BAUM, WILLIAM S. BLAKEMORE, HARRY F. ZINSSER
Journal: Circulation (1967)

A 45-year-old woman with angina pectoris, beginning at the age of 16 and progressing to produce incapacitation, was found to have an anomalous left coronary artery arising from the pulmonary artery. Because of the severity of symptoms and progression of disability, the anomalous artery was ligated at its origin from the pulmonary artery. Pressure in the left coronary system increased from 35/10 to 105/30 mm Hg. Since operation the patient has been relieved of her symptoms. There was no evidence of increased myocardial ischemia after ligation. This indicates that operative treatment of this anomaly can be carried out successfully in the older age group. It is also suggested that a fourth stage of progression of this anomaly occurs in which there is an exaggeration of the intercoronary communications between the right and left coronary systems. This produces such a large arteriovenous shunt that blood flow to the myocardium is again reduced, resulting in a "coronary steal syndrome."