tbuckley/cabot-search huggingface dataset:
Direct demonstration of antigenic substitution of Borrelia burgdorferi ex vivo: exploration of the paradox of the early immune response to outer surface proteins A and C in Lyme disease.
Authors: R R Montgomery, S E Malawista, K J Feen, L K Bockenstedt
Journal: The Journal of Experimental Medicine (1996)

The outer surface proteins (Osps) of Borrelia burgdorferi, the etiologic agent of Lyme disease, are principle targets of protective immune responses against this organism. Whereas most North American strains of B. burgdorferi in culture express an abundant amount of Osp A, antibodies to this protein are either absent or only weakly detected in the sera of naturally infected patients or experimentally infected mice. In contrast, Osp C, which has variable expression on cultured organisms; elicits an early, strong humoral response. To examine this paradox, we have studied the in vivo adaptation of a cloned population of B. burgdorferi strain N40 during the early course of experimental murine borreliosis. As in human disease, antibodies to Osp A were only weakly present in the early immune repertoire after murine inoculation with low dose (10(3)) spirochetes. In contrast, antibodies to Osp C were prominent, even though on cultured spirochetes Osp C mRNA and protein expression could not be detected by reverse transcription polymerase chain reaction (RT-PCR) or indirect immunofluorescence, respectively. These observations led us to investigate the expression of Osp A and Osp C in vivo. By direct fluorescent staining of uncultured spirochetes ex vivo and by PCR amplification of spirochetal mRNA, we show that Osp C is indeed expressed by some spirochetes after infection in the mouse. Spirochetes expressing Osp A could also be detected within the first 2 wk of infection, but not at 30 d. Osp A mRNA, although present at day 14 of infection, could not be amplified by RT-PCR at day 30, suggesting that the expression of this Osp is transient. This further implies that the late burst in Osp A antibodies in both mice and humans may be anamnestic. These results indicate that either Osp C is upregulated on spirochetes after infection, or Osp C-expressing spirochetes expand preferentially over those expressing Osp A during infection. These results have important implications for vaccine design and offer one explanation for the failure of Osp A antibodies to eradicate spirochetes from the infected host.
eNOS inhibition of proliferation: a role for p21Sdi1/Cip1/Waf1 and p27kip1
Authors: C Holt
Journal: Cardiovascular Research (2000)

See article by Sato et al. [12] (pages 697–706) in this issue. 

It is over 10 years since NO donors were shown to reduce proliferation of vascular smooth muscle cells (VSMC) [1]. More recently, increase in vessel wall thickness and hyperplasia were shown to occur following ligation of the carotid artery in NO synthase (eNOS) knockout mice suggesting NO to be a negative regulator of vascular cell proliferation [2]. Due to the short half-life and limited solubility of NO, NO synthase (NOS) is often used as a way of enhancing local NO production within the vessel wall, with potential therapeutic effects in vascular proliferative disorders. In addition to inhibiting VSMC proliferation, NOS also causes vasodilation, reduces platelet aggregation and adhesion as well as inhibiting leucocyte adhesion to the endothelium [3]. Thus it has been proposed as a useful inhibitor of neointimal hyperplasia, the hallmark of restenosis following angioplasty and stenting. Indeed, the last few years have seen a plethora of studies investigating gene transfer of NOS to various vascular systems for potential therapeutic benefit. One of the early studies showed that eNOS gene transfer using HVJ virus–liposome complexes delivered … 

* Corresponding author. Tel.: +44-114-271-4973; fax: +44-114-261-9587 c.holt{at}sheffield.ac.uk
Toll-like receptor alterations in myelodysplastic syndrome
Authors: Y Wei, S Dimicoli, C Bueso-Ramos, R Chen, H Yang, D Neuberg, S Pierce, Y Jia, H Zheng, H Wang, X Wang, M Nguyen, S A Wang, B Ebert, R Bejar, R Levine, O Abdel-Wahab, M Kleppe, I Ganan-Gomez, H Kantarjian, G Garcia-Manero
Journal: Leukemia (2013)
Do gliadin and tissue transglutaminase mediate PPAR downregulation in intestinal cells of patients with coeliac disease?: Figure 1
Authors: V De Re, M P Simula, A Notarpietro, V Canzonieri, R Cannizzaro, G Toffoli
Journal: Gut (2010)

The accumulation of toxic gliadin peptide was proposed to initiate tissue transglutaminase (tTG) upregulation in coeliac intestine.1 Upregulation of tTG drives inflammation through the ubiquitination and proteasomal degradation of the anti-inflammatory peroxisome proliferator-activated receptor (PPAR). To understand further the contribution to mucosal-associated damage in coeliac disease caused by tTG upregulation, we have quantified the expression levels of several proteins directly involved in the PPAR signalling pathway and/or related to PPAR activation. Our study population consisted of patients with coeliac disease at first diagnosis with gut inflammation (n=1 Marsh 2; n=5 Marsh 3; immunoglobulin A (IgA)-tTG ≥cut-off); IgA-tTG-negative patients with coeliac disease who had recovered from intestinal damage while on a gluten-free diet (GFD) (n=4 Marsh 0–1); and control patients with excluded …
Reflex Vasoconstrictor and Vasodilator Responses in Man
Authors: FRANCOIS M. ABBOUD, JOHN W. ECKSTEIN
Journal: Circulation Research (1966)

The application of ice to the forehead and the Valsalva maneuver are known to cause reflex vasoconstriction by stimulation of adrenergic pathways of the sympathetic nervous system. In the experiments reported here, the effects of these stimuli on blood flow to the forearm of man were studied after intra-arterial injection of adrenergic blocking drugs. Changes in flow were measured with water plethysmographs applied to both forearms. One forearm served as "control," and the other forearm, into which the drugs were injected, was the "experimental" one. The stimuli caused a consistent reduction of flow to the control forearm, but after the intra-arterial infusion of small doses of guanethidine there was increased flow to the experimental arm simultaneous with decreased flow to the control arm. The increased flow in response to the stimuli was accentuated after phentolamine and reduced after atropine. The results indicate that the application of ice to the forehead and the Valsalva maneuver stimulate adrenergic vasoconstrictor pathways and cholinergic vasodilator pathways simultaneously. The vasoconstrictor response predominates, and the vasodilator effect is unmasked only after adrenergic blockade. It appears, therefore, that mental stresses are not the only stimuli which can cause reflex cholinergic vasodilatation in the forearm of man. Work by others would suggest that leg exercise may also cause cholinergic dilatation after adrenolytic agents. It is possible that cholinergic vasodilatation may play a role in the severe orthostatic fall in blood pressure, as well as in the exercise hypotension, observed in patients treated with guanethidine.
The prevalence of asthma and asthma-like symptoms among adults in rural Beijing, China
Authors: M. Chan-Yeung, L-X. Zhang, D-H. Tu, B. Li, G-X. He, R. Kauppinen, M. Nieminen, D.A. Enarson
Journal: European Respiratory Journal (2002)

No data have been reported on the prevalence of asthma in rural areas of China. The objective of the present study was to determine the prevalence of asthma-like symptoms, reported asthma and reported asthma attacks in rural Beijing, China, and to compare the prevalence in 20–44-yr-old participants with those reported for Canada and the European Community Respiratory Health Survey (ECRHS). For a cross-sectional survey, 30 villages were randomly selected in the counties of Shunyi and Tongxian, 50 km north and east respectively of the city of Beijing and within the municipality of Beijing. The International Union Against Tuberculosis and Lung Disease questionnaire on bronchial symptoms translated into Chinese was completed by village doctors for each individual of &gt;15 yrs. The survey was completed by 22,561 individuals, representing 98% of the eligible population. The prevalence of asthma-like symptoms and reported asthma attacks was higher in females than in males and increased with age. Smoking significantly increased the prevalence of symptoms; the effect in females was greater than in males. Among the 20–44-yr-olds, the prevalence of reported asthma attacks in the previous 12 months was 0.67% in rural Beijing, very much lower than that reported in ECRHS centres (3.1%), urban Canada (6.9%) and semirural Canada (5.1%), after adjusting for age and sex. The prevalence of asthma-like symptoms was also very low in rural Beijing compared with ECRHS centres and Canada. It is concluded that the prevalence of asthma-like symptoms and reported asthma was low in rural China compared with other countries, consistent with reports of the relative scarcity of asthma in farms and the "hygiene hypothesis".
Static (Isometric) Exercise and the Heart: Physiological and Clinical Considerations
Authors: J H Mitchell, K Wildenthal
Journal: Annual Review of Medicine (1974)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Electrophysiological changes in heart failure and their relationship to arrhythmogenesis
Authors: M Janse
Journal: Cardiovascular Research (2003)

This review focuses mainly on studies in non-ischemic animal models of heart failure. These animals develop ventricular arrhythmias, mostly non-sustained ventricular tachycardia, and often die suddenly. Clinical studies suggest that sudden death is due to ventricular tachycardia or fibrillation in about 50% of cases, the other half to bradyarrhythmias or electromechanical dissociation.
The Hypercalciurias CAUSES, PARATHYROID FUNCTIONS, AND DIAGNOSTIC CRITERIA
Authors: Charles Y. C. Pak, Masahiro Ohata, E. Clint Lawrence, W. Snyder
Journal: Journal of Clinical Investigation (1974)

The causes for the hypercalciuria and diagnostic criteria for the various forms of hypercalciuria were sought in 56 patients with hypercalcemia or nephrolithiasis (Ca stones), by a careful assessment of parathyroid function and calcium metabolism. A study protocol for the evaluation of hypercalciuria, based on a constant liquid synthetic diet, was developed. In 26 cases of primary hyperparathyroidism, characteristic features were: hypercalcemia, high urinary cyclic AMP (cAMP, 8.58±3.63 SD μmol/g creatinine; normal, 4.02±0.70 μmol/g creatinine), high immunoreactive serum parathyroid hormone (PTH), hypercalciuria, the urinary Ca exceeding absorbed Ca from intestinal tract (CaA), high fasting urinary Ca (0.2 mg/mg creatinine or greater), and low bone density by 125I photon absorption. The results suggest that hypercalciuria is partly secondary to an excessive skeletal resorption (resorptive hypercalciuria). The 22 cases with renal stones had normocalcemia, hypercalciuria, intestinal hyperabsorption of calcium, normal or low serum PTH and urinary cAMP, normal fasting urinary Ca, and normal bone density. Since their CaA exceeded urinary Ca, the hypercalciuria probably resulted from an intestinal hyperabsorption of Ca (absorptive hypercalciuria). The primacy of intestinal Ca hyperabsorption was confirmed by responses to Ca load and deprivation under a metabolic dietary regimen. During a Ca load of 1,700 mg/day, there was an exaggerated increase in the renal excretion of Ca and a suppression of cAMP excretion. The urinary Ca of 453±154 SD mg/day was significantly higher than the control group's 211±42 mg/day. The urinary cAMP of 2.26±0.56 μmol/g creatinine was significantly lower than in the control group. In contrast, when the intestinal absorption of calcium was limited by cellulose phosphate, the hypercalciuria was corrected and the suppressed renal excretion of cAMP returned towards normal. Two cases with renal stones had normocalcemia, hypercalciuria, and high urinary cAMP or serum PTH. Since CaA was less than urinary Ca, the hypercalciuria may have been secondary to an impaired renal tubular reabsorption of Ca (renal hypercalciuria). Six cases with renal stones had normal values of serum Ca, urinary Ca, urinary cAMP, and serum PTH (normocalciuric nephrolithiasis). Their CaA exceeded urinary Ca, and fasting urinary Ca and bone density were normal. The results support the proposed mechanisms for the hypercalciuria and provide reliable diagnostic criteria for the various forms of hypercalciuria.
Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995–2007 (the International Cancer Benchmarking Partnership): an analysis of population-based cancer registry data
Authors: MP Coleman, D Forman, H Bryant, J Butler, B Rachet, C Maringe, U Nur, E Tracey, M Coory, J Hatcher, CE McGahan, D Turner, L Marrett, ML Gjerstorff, TB Johannesen, J Adolfsson, M Lambe, G Lawrence, D Meechan, EJ Morris, R Middleton, J Steward, MA Richards
Journal: The Lancet (2010)
Result of interim analysis of overall survival in the GCIG ICON7 phase III randomized trial of bevacizumab in women with newly diagnosed ovarian cancer.
Authors: G. Kristensen, T. Perren, W. Qian, J. Pfisterer, J. A. Ledermann, F. Joly, M. S. Carey, P. J. Beale, A. Cervantes, A. M. Oza
Journal: Journal of Clinical Oncology (2011)

LBA5006 The full, final text of this abstract will be available in Part II of the 2011 Annual Meeting Proceedings, distributed onsite at the Meeting on June 4, 2011, and as a supplement to the June 20, 2011, issue of Journal of Clinical Oncology.
Outcomes of patients with systemic sclerosis-associated polyarthritis and myopathy treated with tocilizumab or abatacept: a EUSTAR observational study
Authors: Muriel Elhai, Marine Meunier, Marco Matucci-Cerinic, Britta Maurer, Gabriela Riemekasten, Tifenn Leturcq, Raffaele Pellerito, Carlos Alberto Von Mühlen, Alessandra Vacca, Paolo Airo, Francesca Bartoli, Ginevra Fiori, Maria Bokarewa, Valeria Riccieri, Mike Becker, Jérôme Avouac, Ulf Müller-Ladner, Oliver Distler, Yannick Allanore
Journal: Annals of the Rheumatic Diseases (2012)

To evaluate the safety and effectiveness of tocilizumab and abatacept in systemic sclerosis (SSc)-polyarthritis or SSc-myopathy.20 patients with SSc with refractory polyarthritis and seven with refractory myopathy from the EUSTAR (EULAR Scleroderma Trials and Research) network were included: 15 patients received tocilizumab and 12 patients abatacept. All patients with SSc-myopathy received abatacept. Clinical and biological assessments were made at the start of treatment and at the last infusion.After 5 months, tocilizumab induced a significant improvement in the 28-joint count Disease Activity Score and its components, with 10/15 patients achieving a EULAR good response. Treatment was stopped in two patients because of inefficacy. After 11 months' treatment of patients with abatacept, joint parameters improved significantly, with 6/11 patients fulfilling EULAR good-response criteria. Abatacept did not improve muscle outcome measures in SSc-myopathy. No significant change was seen for skin or lung fibrosis in the different groups. Both treatments were well tolerated.In this observational study, tocilizumab and abatacept appeared to be safe and effective on joints, in patients with refractory SSc. No trend for any change of fibrotic lesions was seen but this may relate to the exposure time and inclusion criteria. Larger studies with longer follow-up are warranted to further determine the safety and effectiveness of these drugs in SSc.
The Use of Real-Time Reverse Transcription-PCR for Prostate-Specific Antigen mRNA to Discriminate between Blood Samples from Healthy Volunteers and from Patients with Metastatic Prostate Cancer
Authors: Kinnari Patel, Peter J. Whelan, Stephen Prescott, Samantha C. Brownhill, Colin F. Johnston, Peter J. Selby, Susan A. Burchill
Journal: Clinical Cancer Research (2004)

Abstract Purpose: A clinical role for nonquantitative reverse transcription-PCR (RT-PCR) using prostate-specific antigen in blood samples from patients with prostate cancer remains undefined. Assay variation and detection of prostate-specific antigen mRNA illegitimate transcription may explain inconsistent results between studies. Defining levels of prostate-specific antigen mRNA expression in blood samples from healthy volunteers and patients with prostate cancer would allow cutoffs to be established to distinguish the two groups. Experimental Design: Quantitative real-time RT-PCR for prostate-specific antigen mRNA was established and levels of prostate-specific antigen mRNA measured in bloods samples from healthy volunteers (n = 21) and patients with localized (n = 27) and metastatic (n = 40) prostate cancer. Results: Levels of prostate-specific antigen mRNA were significantly higher in blood samples from patients with metastatic prostate cancer than in blood samples from patients with localized prostate cancer (P &amp;lt; 0.001) or in blood samples from healthy volunteers (P &amp;lt; 0.01); levels between patients with localized prostate cancer and healthy volunteers were no different. Assay sensitivity to detect patients with metastatic prostate cancer was 68% with specificity of 95%. In patients with newly diagnosed metastatic prostate cancer, monitoring response to hormonal therapy was possible with this assay. No correlation between levels of prostate-specific antigen mRNA and serum prostate-specific antigen protein levels was found, suggesting that prostate-specific antigen mRNA and serum prostate-specific antigen protein levels reflect different features of prostate cancer, i.e., circulating tumor cells and total tumor bulk, respectively. Conclusions: Quantitative RT-PCR discriminates patients with metastatic prostate cancer from healthy volunteers and patients with localized prostate cancer but cannot discriminate patients with localized prostate cancer from healthy volunteers. A role for quantitative RT-PCR has been identified in the assessment and monitoring of patients with metastatic prostate cancer.
Dose-Ranging Study to Evaluate the Efficacy and Safety of Four Doses of Fluticasone Propionate/Salmeterol Multidose Dry Powder Inhaler (FS MDPI) Compared with Fluticasone Propionate (Fp) Mdpi and FS DPI in Subjects with Persistent Asthma
Authors: Jonathan Steinfeld, Gloria Yiu, S. David Miller
Journal: Journal of Allergy and Clinical Immunology (2015)
Negative Regulation of TSC1-TSC2 by Mammalian D-Type Cyclins
Authors: Sima J. Zacharek, Yue Xiong, Stuart D. Shumway
Journal: Cancer Research (2005)

Abstract The metazoan cell cycle is driven by the timely and composite activities of cyclin-dependent kinases (CDKs). Among these, cyclin D- and cyclin E-dependent kinases phosphorylate the pRb family proteins during G1 phase of the cell cycle and thereby advance cells beyond the restriction point. Increasing evidence suggests that cyclin D-dependent kinases might affect events other than Rb pathway-mediated entry into S phase, such as accumulation of cell mass. However, little is known about cyclin D activity toward Rb-independent pathway(s) or non-pRb substrates. In this article, we show that the tumor suppressor TSC2 is a cyclin D binding protein. Coexpression of cyclin D1-CDK4/6 in cultured cells leads to increased phosphorylation and decreased detection of both TSC2 and TSC1, and promotes the phosphorylation of the mTOR substrates, 4E-BP1 and S6K1, two key effectors of cell growth that are negatively regulated by the TSC1-TSC2 complex. At the cellular level, ectopic expression of cyclin D1 restores the cell size decrease caused by TSC1-TSC2 expression. Intriguingly, down-regulation of TSC proteins was also observed by the expression of a mutant cyclin D1 that is unable to bind to CDK4/6, or by the coexpression of cyclin D1 with either an INK4 inhibitor or with catalytically inactive CDK6, indicating that cyclin D may regulate TSC1-TSC2 independently of CDK4/6. Together, these observations suggest that mammalian D-type cyclins participate in cell growth control through negative regulation of TSC1-TSC2 function. (Cancer Res 2005; 65(24): 11354-60)
Nonpharmacological Interventions for ADHD: Systematic Review and Meta-Analyses of Randomized Controlled Trials of Dietary and Psychological Treatments
Authors: Edmund J.S. Sonuga-Barke, Daniel Brandeis, Samuele Cortese, David Daley, Maite Ferrin, Martin Holtmann, Jim Stevenson, Marina Danckaerts, Saskia van der Oord, Manfred Döpfner, Ralf W. Dittmann, Emily Simonoff, Alessandro Zuddas, Tobias Banaschewski, Jan Buitelaar, David Coghill, Chris Hollis, Eric Konofal, Michel Lecendreux, Ian C.K. Wong, Joseph Sergeant
Journal: American Journal of Psychiatry (2013)

A meta-analytic review of six types of nonpharmacological interventions, including dietary and psychological treatments, for children with ADHD found positive effects on ADHD symptoms for all types when raters were aware of treatment allocation (unblinded conditions). However, when raters were blinded, statistically significant effects on ADHD symptoms were found only for supplementation with omega-3/omega-6 free fatty acids or elimination of artificial food colorings, effects that were small or restricted to food-sensitive individuals.
Human Cd1b and Cd1c Isoforms Survey Different Intracellular Compartments for the Presentation of Microbial Lipid Antigens
Authors: Volker Briken, Robin M. Jackman, Gerald F.M. Watts, Rick A. Rogers, Steven A. Porcelli
Journal: The Journal of Experimental Medicine (2000)

CD1b and CD1c are antigen-presenting molecules that mediate recognition of bacterial lipids by T cells, but it is currently not known whether these two molecules are redundant or are specialized to perform different immunological functions. Here, we show that the distribution of CD1c in human dendritic cells was characterized by a high ratio of cell surface to intracellular molecules, whereas CD1b showed a reciprocal pattern of distribution. In contrast to the accumulation of CD1b in lysosomal major histocompatibility complex class II compartments, intracellular CD1c molecules accumulated in other endocytic compartments, most likely early and late endosomes. Deletion of the cytoplasmic tail of CD1c, containing a tyrosine-based internalization motif, abolished most of its intracellular localization. Functional studies using T cells specific for defined lipid antigens revealed that in contrast to CD1b-mediated antigen presentation, antigen presentation by CD1c was resistant to drugs inhibiting endosomal acidification and was independent of endosomal localization of CD1c. Taken together, these results support the hypothesis that CD1b and CD1c are specialized to survey the lipid content of different intracellular compartments.
Biochemical nature of an Fc mu receptor on human B-lineage cells.
Authors: T Ohno, H Kubagawa, S K Sanders, M D Cooper
Journal: The Journal of Experimental Medicine (1990)

An IgM-binding protein of approximately 60 kD has been identified on activated B cells, but not on resting and activated T cells, monocytes, or granulocytes. Here, we characterize this IgM-binding protein as a receptor for the Fc portion (CH3 and/or CH4 domains) of IgM molecules (Fc microR). The Fc microR can be expressed as a cell surface activation antigen throughout the pre-B and B cell stages in differentiation. Receptor expression is not directly linked with IgM production, as both mu- pre-B cells and isotype-switched B cells may express the Fc microR. The receptor molecules produced by both pre-B and B cells are identical in size and are characterized as an acidic sialoglycoprotein with O-linked, but no N-linked, oligosaccharide. The Fc microR is anchored to the surface of B-lineage cells via a glycosyl phosphatidylinositol linkage. The Fc microR is thus the third member of a family of Fc receptors expressed on B-lineage cells, and its preferential expression on activated B cells suggests a potential role in the response to antigens.