tbuckley/cabot-search huggingface dataset:
CONTRIBUTION OF A THYMIC HUMORAL FACTOR TO THE DEVELOPMENT OF AN IMMUNOLOGICALLY COMPETENT POPULATION FROM CELLS OF MOUSE BONE MARROW
Authors: Myra Small, Nathan Trainin
Journal: The Journal of Experimental Medicine (1971)

The hypothesis that cells located in mouse bone marrow can acquire immunological competence by a process that involves interaction with a noncellular component of the thymus was tested using an in vitro assay of graft-versus-host reactivity as a criterion of cell competence. When suspensions of C57BL bone marrow cells were incubated in thymus extract and injected into mice incapable of inducing a response in the graft-versus-host assay as a result of neonatal thymectomy, or adult thymectomy plus irradiation, or because of genetic similarity with the (C3H x C57BL)F(1) tissue used for challenge in the assay, competent cells were recovered from the spleens of the injected mice. The reactive cells were shown to be of bone marrow origin since immune reactivity was related to the genetic makeup of the bone marrow cells rather than that of the intermediate recipients. A thymic factor was involved in the process leading to immune reactivity by these cells, as bone marrow cells incubated in xenogeneic or syngeneic thymic extracts induced a graft-versus-host response after passage through nonresponsive mice, whereas incubation of bone marrow cells in xenogeneic lymph node or spleen extracts or in culture medium only did not lead to subsequent reactivity. Participation of peripheral lymphoid tissue seemed essential in this process since bone marrow cells tested directly after exposure to thymic extract failed to induce a graft-versus-host response. C57BL bone marrow cells exposed to thymus extract and cultured together with fragments of (C3H x C57BL)F(1) spleen tissue in vitro were competent to induce a graft-versus-host response; thus, these components would seem to be sufficient as well as necessary for the immunodifferentiation process leading to graft-versus-host activity. It is concluded that one step in the process by which bone marrow cells acquire competence vis-a-vis the graft-versus-host response depends upon a thymic agent that is noncellular and extractable, and that another stage in this process is under the influence of components found within the peripheral lymphoid tissue environment. It is suggested that differentiation of precursor cells to competence could occur by progressive development of the cells in separate compartments of the lymphoid system.
The etiology and incidence of anaphylaxis in Rochester, Minnesota: A report from the Rochester Epidemiology Project
Authors: Wyatt W. Decker, Ronna L. Campbell, Veena Manivannan, Anuradha Luke, Jennifer L. St. Sauver, Amy Weaver, M. Fernanda Bellolio, Eric J. Bergstralh, Latha G. Stead, James T.C. Li
Journal: Journal of Allergy and Clinical Immunology (2008)
Over 20% of patients with chronic lymphocytic leukemia carry stereotyped receptors: pathogenetic implications and clinical correlations
Authors: Kostas Stamatopoulos, Chrysoula Belessi, Carol Moreno, Myriam Boudjograh, Giuseppe Guida, Tatjana Smilevska, Lynda Belhoul, Stefania Stella, Niki Stavroyianni, Marta Crespo, Anastasia Hadzidimitriou, Laurent Sutton, Francesc Bosch, Nikolaos Laoutaris, Achilles Anagnostopoulos, Emili Montserrat, Athanasios Fassas, Guillaume Dighiero, Federico Caligaris-Cappio, Hélène Merle-Béral, Paolo Ghia, Frédéric Davi
Journal: Blood (2006)
Dual Effect of Ceramide on Human Endothelial Cells
Authors: Huige Li, Peter Junk, Andrea Huwiler, Christian Burkhardt, Thomas Wallerath, Josef Pfeilschifter, Ulrich Förstermann
Journal: Circulation (2002)

Background— Generation of the second-messenger molecule ceramide by stimulated sphingomyelinase activity has been implicated in the inflammatory processes contributing to the pathogenesis of atherosclerosis. However, reports of stimulatory effects of ceramide on endothelial NO production in animal models suggest antiatherosclerotic effects of the molecule. Therefore, we investigated long-term effects of ceramide on NO generation in human endothelial cells. Methods and Results— In human umbilical vein endothelial cells (HUVECs) and in HUVEC-derived EA.hy 926 endothelial cells, C6-ceramide ( N -hexanoyl- d -erythro-sphingosine) reduced the generation of bioactive NO (RFL-6 reporter-cell assay). At the same time, the signaling molecule increased endothelial NO synthase (eNOS) mRNA (RNase protection assay) and protein expression (Western blot). C6-ceramide stimulated eNOS transcription by a signaling mechanism involving protein phosphatase PP2A but did not modify the stability of the eNOS mRNA. Endothelial generation of reactive oxygen species (ROS) was increased by C6-ceramide [5-(and-6)-chloromethyl-2′, 7′-dichlorodihydrofluorescein diacetate (CM-H 2 DCFDA) oxidation-based fluorescence assay], and this effect was partially reversed by the NOS inhibitor N G -nitro- l -arginine methyl ester (L-NAME). On the other hand, (6 R )-5,6,7,8-tetrahydro- l -biopterin (BH 4 ) normalized in part the ceramide-induced reduction in bioactive NO. Conclusions— Ceramide produces oxidative stress in human endothelial cells, thereby reducing bioactive NO. The partial reversal of this reduction by BH 4 and the diminution of ROS generation by L-NAME suggest that ceramide promotes NADPH oxidase activity of eNOS, leading to ROS formation at the expense of NO synthesis. The ceramide-induced upregulation of eNOS gene transcription can be considered an ineffective compensatory mechanism. The decreased bioavailability of NO is likely to favor a proatherogenic role of ceramide.
A Novel Methionine Aminopeptidase-2 Inhibitor, PPI-2458, Inhibits Non–Hodgkin's Lymphoma Cell Proliferation <i>In vitro</i> and <i>In vivo</i>
Authors: Andrew C. Cooper, Russell M. Karp, Edward J. Clark, Nazbeh R. Taghizadeh, Jennifer G. Hoyt, Matthew T. Labenski, Michael J. Murray, Gerhard Hannig, William F. Westlin, Charles D. Thompson
Journal: Clinical Cancer Research (2006)

Fumagillin and related compounds have potent antiproliferative activity through inhibition of methionine aminopeptidase-2 (MetAP-2). It has recently been reported that MetAP-2 is highly expressed in germinal center B cells and germinal center-derived non-Hodgkin's lymphomas (NHL), suggesting an important role for MetAP-2 in proliferating B cells. Therefore, we determined the importance of MetAP-2 in normal and transformed germinal center B cells by evaluating the effects of MetAP-2 inhibition on the form and function of germinal centers and germinal center-derived NHL cells.To examine the activity of PPI-2458 on germinal center morphology, spleen sections from cynomolgus monkeys treated with oral PPI-2458 were analyzed. Antiproliferative activity of PPI-2458 was assessed on germinal center-derived NHL lines in culture. A MetAP-2 pharmacodynamic assay was used to determine cellular MetAP-2 inhibition following PPI-2458 treatment. Finally, inhibition of MetAP-2 and proliferation by PPI-2458 was examined in the human SR NHL line in culture and in implanted xenografts.Oral PPI-2458 caused a reduction in germinal center size and number in lymphoid tissues from treated animals. PPI-2458 potently inhibited growth (GI(50) = 0.2-1.9 nmol/L) of several NHL lines in a manner that correlated with MetAP-2 inhibition. Moreover, orally administered PPI-2458 significantly inhibited SR tumor growth, which correlated with inhibition of tumor MetAP-2 (>85% at 100 mg/kg) in mice.These results show the potent antiproliferative activity of PPI-2458 on NHL lines in vitro and oral antitumor activity in vivo and suggest the therapeutic potential of PPI-2458 as a novel agent for treatment of NHL should be evaluated in the clinical setting.
Appreciating the poverty of the stimulus in second language acquisition
Authors: Rex A. Sprouse
Journal: Behavioral and Brain Sciences (1996)

Abstract The most compelling evidence for Epstein et al.'s central thesis that adult second language acquisition is constrained by the innate cognitive structures that constrain native language acquisition would be evidence of poverty of the stimulus. Although there are studies that point to such evidence, Epstein et al.'s primary form of argumentation, targetlike performance by second-language acquiring adults, is much less convincing.
Steatocystoma multiplex with unusually prominent cysts on the face
Authors: R. HOLMES, M. M. BLACK
Journal: British Journal of Dermatology (1980)

Journal Article Steatocystoma multiplex with unusually prominent cysts on the face Get access R. HOLMES, R. HOLMES St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH Search for other works by this author on: Oxford Academic Google Scholar M. M. BLACK M. M. BLACK St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 102, Issue 6, 1 June 1980, Pages 711–713, https://doi.org/10.1111/j.1365-2133.1980.tb06573.x Published: 01 June 1980
MET Signaling Pathway: A Rational Target for Cancer Therapy
Authors: Leonard J. Appleman
Journal: Journal of Clinical Oncology (2011)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2011.37.7929 Journal of Clinical Oncology - published online before print October 31, 2011 PMID: 22042966 MET Signaling Pathway: A Rational Target for Cancer Therapy Leonard J. ApplemanxLeonard J. ApplemanSearch for articles by this author Show More University of Pittsburgh Cancer Institute, Pittsburgh, PA https://doi.org/10.1200/JCO.2011.37.7929 Full Text PDF Figures and Tables Supplements "MET Signaling Pathway: A Rational Target for Cancer Therapy." Journal of Clinical Oncology, 29(36), pp. 4837–4838© 2011 by American Society of Clinical Oncology
Occupational asthma in electronics workers caused by colophony fumes: follow-up of affected workers.
Authors: P S Burge
Journal: Thorax (1982)

Thirty-nine electronics workers were investigated by bronchial provocation testing to soldering fluxes containing colophony and were followed up one to four years later. At presentation and on follow-up each worker had nonspecific bronchial reactivity measured with inhaled histamine, and also had detailed measurements of lung function and estimation of total immunoglobulin levels. They completed a questionnaire designed to detect residual disability. The workers were divided into three groups. Twenty had left work after their initial diagnosis, eight had been moved to alternative work within their original factories, and 11 were thought to have asthma unrelated to colophony exposure as they failed to react to colophony at presentation. Histamine reactivity had returned to normal in half the workers who had left their original factories, but in only one worker who had moved within her original factory. This suggested that the nonspecific bronchial reactivity to histamine was the result rather than the cause of the occupational asthma, and that indirect exposure at work was sufficient to delay recovery of histamine reactivity. However, only two of the 20 affected workers who had left their original factories were symptom free on follow-up, and most had a considerable reduction in their quality of life by continuing asthma, which was particularly provoked by exercise, respiratory infections, and nonspecific irritants. Continuing symptoms may have been caused by domestic sources of colophony, or possibly the failure to eliminate colophony from the lungs.
Regulation of cholesterol synthesis by low density lipoprotein in isolated human lymphocytes
Authors: YK Ho, Faust JR, DW Bilheimer, MS Brown, JL Goldstein
Journal: The Journal of Experimental Medicine (1977)

The rate of cholesterol synthesis from [14C]acetate was low in circulating blood lymphocytes freshly isolated from 17 normal subjects and 4 subjects with homozygous FH. On the other hand, the rate of cholesterol synthesis was two to fourfold above normal in freshly isolated lymphocytes from two subjects with abetalipoproteinemia. When the lymphocytes from subjects with all three genotypes were incubated for 48-72 h in the absence of lipoproteins, the rate of cholesterol synthesis increased by 5-15-fold. The subsequent addition of plasma LDL, but not HDL, rapidly suppressed cholesterol synthesis in the lymphocytes from normal subjects. In contrast, lymphocytes from the FH homozygotes, which have been shown previously to be deficient in cell surface LDL receptors, were resistant to LDL-mediated suppression of cholesterol synthesis. In addition to its ability to suppress cholesterol synthesis after it had been elevated by incubation of the cells in the absence of lipoproteins, LDL was able to suppress the induction of the enhanced rate of sterol synthesis when added to normal lymphocytes immediately after their isolation from the bloodstream. In contrast to the former action of LDL, the latter action of LDL-i.e., the suppression of induction of sterol synthesis-also occurred to a limited extent in lymphocytes from FH homozygotes. However, the FH lymphocytes, but not the normal cells, could be made resistant to this action of LDL by inclusion in the incubation medium of lipoprotein-deficient serum (30 percent, vol/vol) plus HDL (1 mg protein/ml). Considered together with previous data demonstrating a deficiency of LDL receptors in freshly isolated lymphocytes from FH homozygotes, the current studies provide evidence in support of the hypothesis that the interaction of plasma LDL with its cell surface receptor serves to regulate cholesterol synthesis in human lymphocytes.
Peroxisome Proliferator–Activated Receptor Activators Inhibit Lipopolysaccharide-Induced Tumor Necrosis Factor-α Expression in Neonatal Rat Cardiac Myocytes
Authors: Hiroyuki Takano, Toshio Nagai, Masayuki Asakawa, Tetsuya Toyozaki, Toru Oka, Issei Komuro, Toshihiro Saito, Yoshiaki Masuda
Journal: Circulation Research (2000)

Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily. Recently, PPAR activators have been shown to inhibit the production of proinflammatory cytokines in macrophages or vascular smooth muscle cells. It has been reported that tumor necrosis factor-alpha (TNF-alpha) expression is elevated in the failing heart and that TNF-alpha has a negative inotropic effect on cardiac myocytes. Therefore, we examined the effects of PPARalpha and PPARgamma activators on expression of TNF-alpha in neonatal rat cardiac myocytes. Northern blot analysis revealed expression of PPARalpha and PPARgamma mRNA in cardiac myocytes. Immunofluorescent staining demonstrated that both PPARalpha and PPARgamma were expressed in the nuclei of cells. When cardiac myocytes were transfected with PPAR responsive element (PPRE)-luciferase reporter plasmid, both PPARalpha and PPARgamma activators increased the promoter activity. Cardiomyocytes were stimulated with lipopolysaccharide (LPS), and the levels of TNF-alpha in the medium were measured by ELISA. After exposure to LPS, the levels of TNF-alpha significantly increased. However, pretreatment of myocytes with PPARalpha or PPARgamma activators decreased LPS-induced expression of TNF-alpha in the medium. Both PPARalpha and PPARgamma activators also inhibited LPS-induced increase in TNF-alpha mRNA in myocytes. In addition, electrophoretic mobility shift assays demonstrated that PPAR activators reduced LPS-induced nuclear factor-kappaB activation. These results suggest that both PPARalpha and PPARgamma activators inhibit cardiac expression of TNF-alpha in part by antagonizing nuclear factor-kappaB activity and that treatment with PPAR activators may lead to improvement in congestive heart failure.
Hepatitis C virus RNA and liver histology in blood donors reactive to a single antigen by second-generation recombinant immunoblot assay
Authors: Alberto Zanella, Dario Conte, Daniele Prati, Fulvio Mozzi, Carmen Capelli, Francesco Zanuso, Mirella Fraquelli, Patrizia Bosoni, Luciana Vianello, Marco Pappalettera, Pietro Velio, Glanguido Montagnolo, Paolo A. Bianchi, Girolamo Sirchia
Journal: Hepatology (1995)

The clinical significance of single band reactivity (indeterminate pattern) at anti-hepatitis C virus (HCV) second-generation recombinant immunoblot assay (RIBA-2) was investigated in symptomless subjects with normal liver function tests to obtain data for their counseling and clinical management. Serum and hepatic HCV RNA were determined by the nested polymerase chain reaction, and liver histology was evaluated in 40 symptomless blood donors with stable indeterminate RIBA-2 pattern, including 38 reactive to c22-3. All but one had normal alanine aminotransferase (ALT) levels. Two new immunoblot tests, RIBA-3 and INNO-LIA HCV Ab III (LIA-III), which incorporate additional HCV antigens, were also done to assess whether they could identify the viremic subjects. Ten cases (25%, confidence interval 12 to 38) were HCV RNA positive. Three of the HCV RNA-positive and none of the HCV RNA-negative subjects had chronic hepatitis. RIBA-2 strong intensity of reaction (score > 2+) was observed in all the HCV RNA-positive and in 12 HCV RNA-negative subjects. RIBA-3 and LIA-III gave positive results in 9 of 10 and 10 of 10 HCV RNA-positive, but also in 8 of 30 and 24 of 30 HCV RNA-negative subjects. A c-22-3 reactivity score of 4+ by RIBA-3 and E2/NS1 reactivity by LIA-III were both strongly associated with HCV RNA (P < .001). Based on relatively high prevalence of chronic hepatitis in our series (30%), apparently healthy subjects with stable indeterminate RIBA-2 pattern and HCV RNA positivity should be considered for liver biopsy independently of ALT profile.(ABSTRACT TRUNCATED AT 250 WORDS)
Promoting urinary continence in women after delivery: randomised controlled trial
Authors: P. Chiarelli
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objectives:</b> To test the effectiveness of a physiotherapist delivered intervention designed to prevent urinary incontinence among women three months after giving birth. <b>Design:</b> Prospective randomised controlled trial with women randomised to receive the intervention (which entailed training in pelvic floor exercises and incorporated strategies to improve adherence) or usual postpartum care. <b>Setting:</b> Postpartum wards of three tertiary teaching hospitals in the Hunter region, New South Wales, Australia. <b>Participants:</b> Women who had forceps or ventouse deliveries or whose babies had a high birth weight (4000 g), or both—676 (348 in the intervention group and 328 in the usual care group) provided endpoint data at three months. <b>Main outcome measures:</b> Urinary incontinence at three months measured as a dichotomous variable. The severity of incontinence was also measured. Self report of the frequency of performance of pelvic floor exercises was recorded. <b>Results:</b> At three months after delivery, the prevalence of incontinence in the intervention group was 31.0% (108 women) and in the usual care group 38.4% (125 women); difference 7.4% (95% confidence interval 0.2% to 14.6%, P=0.044). At follow up significantly fewer women with incontinence were classified as severe in the intervention group (10.1%) <i>v</i> (17.0%), difference 7.0%, 1.6% to 11.8%). The proportions of women reporting doing pelvic floor exercises at adequate levels was 84% (80% to 88%) for the intervention group and 58% (52% to 63%) for the usual care group (P=0.001). <b>Conclusions:</b> The intervention promoting urinary continence reduced the prevalence of urinary incontinence after giving birth, particularly its severity, and promoted the performance of pelvic floor exercises at adequate levels; both continence and adherence to the programme were measured at three months after delivery in women who had forceps or ventouse deliveries or babies weighing 4000 g or more. <h3>What is already known on this topic</h3> Intensive pelvic floor exercise programmes can reduce urinary incontinence in selected groups of female patients The effectiveness of interventions promoting continence in reducing urinary incontinence in the female population overall has not been investigated Pelvic floor exercises are widely held to be an important component of continence promotion programmes <h3>What this study adds</h3> Continence promotion programmes delivered to a selected population are able to prevent urinary incontinence in that population Few studies have examined the efficacy of compliance aiding strategies in helping women adhere to prescribed pelvic floor exercise programmes
External exercise information provides no immediate additional performance benefit to untrained individuals in time trial cycling
Authors: C A Williams, S D Bailey, A R Mauger
Journal: British Journal of Sports Medicine (2011)

To determine the importance of the provision of external exercise information to the setting of the pacing strategy, in subjects unfamiliar with a cycling task.Twenty-two healthy, untrained cyclists (VO(2max), 50 ± 9 mL-(1)·kg-(1)·min-(1)) were randomly assigned to a control (CON) group or an experimental (EXP) group and two successive 4 km time trials (TT) were performed, separated by a 17 min recovery. The CON group received distance knowledge and distance feedback; the EXP group received neither, but knew that each TT was to be of the same distance.No significant difference in completion time (p>0.05) was observed between the groups for either time to complete TT one (TT1) (CON=443 ± 33 s versus EXP=471 ± 63 s) or time to complete TT two (time trial 2) (CON=461 ± 37 s versus EXP=501 ± 94 s). No significant difference in the final RPE was observed between groups. However, a significant interaction for RPE (rating of perceived exertion)×TT in the CON was observed (F7,70=5.32, p<0.05), with significantly higher RPE values in the final kilometre of TT2 (p<0.05).The lack of any performance improvement in either group, despite the differences in exercise information received, indicates both a reliance on the afferent feedback for setting a pacing strategy and slow learning effect from practice in subjects unfamiliar with the task. The modification in RPE profile observed in the CON, despite no performance improvement, suggests exercise perception based changes may pre-empt work rate based changes and thus not immediately translate to improved performance.
Construction of a binding site for human immunodeficiency virus type 1 gp120 in rat CD4.
Authors: G A Schockmel, C Somoza, S J Davis, A F Williams, D Healey
Journal: The Journal of Experimental Medicine (1992)

The human immunodeficiency virus (HIV-1) infects T lymphocytes via an interaction between the virus envelope glycoprotein gp120 and the CD4 antigen of T helper cells. Previous studies demonstrated that mutations in various regions of CD4 domain 1 lead to the loss of gp120 binding. In the present study the gp120 binding site was constructed in rat CD4 by replacing rat with human CD4 sequence. A series of mutants was constructed the best of which bound gp120 with an affinity only twofold less than that of human CD4. The data indicate that the gp120 binding site of human CD4 is constituted by residues 33-58 of domain 1.