tbuckley/cabot-search huggingface dataset:
CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells
Authors: Weihong Liu, Amy L. Putnam, Zhou Xu-yu, Gregory L. Szot, Michael R. Lee, Shirley Zhu, Peter A. Gottlieb, Philipp Kapranov, Thomas R. Gingeras, Barbara Fazekas de St. Groth, Carol Clayberger, David M. Soper, Steven F. Ziegler, Jeffrey A. Bluestone
Journal: The Journal of Experimental Medicine (2006)

Regulatory T (T reg) cells are critical regulators of immune tolerance. Most T reg cells are defined based on expression of CD4, CD25, and the transcription factor, FoxP3. However, these markers have proven problematic for uniquely defining this specialized T cell subset in humans. We found that the IL-7 receptor (CD127) is down-regulated on a subset of CD4(+) T cells in peripheral blood. We demonstrate that the majority of these cells are FoxP3(+), including those that express low levels or no CD25. A combination of CD4, CD25, and CD127 resulted in a highly purified population of T reg cells accounting for significantly more cells that previously identified based on other cell surface markers. These cells were highly suppressive in functional suppressor assays. In fact, cells separated based solely on CD4 and CD127 expression were anergic and, although representing at least three times the number of cells (including both CD25(+)CD4(+) and CD25(-)CD4(+) T cell subsets), were as suppressive as the "classic" CD4(+)CD25(hi) T reg cell subset. Finally, we show that CD127 can be used to quantitate T reg cell subsets in individuals with type 1 diabetes supporting the use of CD127 as a biomarker for human T reg cells.
IMPACT OF ENERGY LOSS INDEX USING REAL-TIME 3-DIMENSIONAL TRANSESOPHAGEAL ECHOCARDIOGRAPHY ON ASSESSMENT OF AORTIC STENOSIS
Authors: Takeji Saito, Jun Tanaka, Azusa Furugen, Kenji Harada, Swaminatha Gurudevan, Kirsten Tolstrup, Robert Siegel, Takahiro Shiota
Journal: Journal of the American College of Cardiology (2012)
The LYR Factors SDHAF1 and SDHAF3 Mediate Maturation of the Iron-Sulfur Subunit of Succinate Dehydrogenase
Authors: Un Na, Wendou Yu, James Cox, Daniel K. Bricker, Knut Brockmann, Jared Rutter, Carl S. Thummel, Dennis R. Winge
Journal: Cell Metabolism (2014)
Relevance of ineffective oesophageal motility during oesophageal acid clearance
Authors: M Simren
Journal: Gut (2003)

<b>Background:</b> Oesophageal clearance of acid reflux consists of an initial volume clearance followed by neutralisation of the acidified mucosa by swallowed saliva (chemical clearance). Ineffective oesophageal motility (IOM), a frequent finding in patients with gastro-oesophageal reflux disease (GORD), has been claimed to underlie prolonged acid clearance by affecting oesophageal emptying and saliva transport. Intraluminal impedance allows non-radiological monitoring of movement of oesophageal liquids. <b>Aims:</b> To evaluate the relevance of IOM during oesophageal volume and chemical clearance using combined pH impedance measurements. <b>Subjects:</b> Impedance was validated with fluoroscopy to study volume clearance in three healthy subjects. Acid clearance tests were performed in 10 healthy subjects in the upright and supine positions, before and after oesophageal peristaltic disruption with sildenafil 50 mg. <b>Methods:</b> After instillation of an acid bolus, simultaneous manometry, pH, and impedance were used to study oesophageal motility, chemical clearance, and volume clearance, respectively. <b>Results:</b> Impedance allowed assessment of volume clearance accurately, showing a strong correlation with fluoroscopy (<i>r</i><sup>2</sup>=0.89). Sildenafil provoked a graded impairment in oesophageal motility in healthy subjects without affecting saliva secretion. In the upright position, volume clearance was slightly prolonged only with severe IOM (&gt;80% abnormal peristaltic sequences). In the supine position, severe IOM significantly prolonged chemical and volume clearance. Moderate IOM (30–80% abnormal peristalsis) had no effect. With normal peristalsis and moderate IOM, clearance times were similar in the upright and supine positions. Severe IOM however had a greater impact on clearance in the supine than in the upright position. <b>Conclusion:</b> Ineffective oesophageal motility has little effect on oesophageal clearance during upright acid reflux. With supine reflux, only severe IOM is associated with prolonged oesophageal clearance.
Pericyte-specific expression of PDGF beta receptor in mouse models with normal and deficient PDGF beta receptor signaling
Authors: Ethan A Winkler, Robert D Bell, Berislav V Zlokovic
Journal: Molecular Neurodegeneration (2010)

Pericytes are integral members of the neurovascular unit. Using mouse models lacking endothelial-secreted platelet derived growth factor-B (PDGF-B) or platelet derived growth factor receptor beta (PDGFRβ) on pericytes, it has been demonstrated that PDGF-B/PDGFRβ interactions mediate pericyte recruitment to the vessel wall in the embryonic brain regulating the development of the cerebral microcirculation and the blood-brain barrier (BBB). Relatively little is known, however, about the roles of PDGF-B/PDGFRβ interactions and pericytes in the adult brain in part due to a lack of adequate and/or properly characterized experimental models. To address whether genetic disruption of PDGFRβ signaling would result in a pericyte-specific insult in adult mice, we studied the pattern and cellular distribution of PDGFRβ expression in the brain in adult control mice and F7 mice that express two hypomorphic Pdgfrβ alleles containing seven point mutations in the cytoplasmic domain of PDGFRβ that impair downstream PDGFRβ receptor signaling.Using dual fluorescent in situ hybridization, immunofluorescent staining for different cell types in the neurovascular unit, and a fluorescent in situ proximity ligation assay to visualize molecular PDGF-B/PDGFRβ interactions on brain tissue sections, we show for the first time that PDGFRβ is exclusively expressed in pericytes, and not in neurons, astrocytes or endothelial cells, in the adult brain of control 129S1/SvlmJ mice. PDGFRβ co-localized only with well-established pericyte markers such as Chondroitin Sulfate Proteoglycan NG2 and the xLacZ4 transgenic reporter. We next confirm pericyte-specific PDGFRβ expression in the brains of F7 mutants and show that these mice are viable in spite of substantial 40-60% reductions in regional pericyte coverage of brain capillaries.Our data show that PDGFRβ is exclusively expressed in pericytes in the adult 129S1/Sv1mJ and F7 mouse brain. Moreover, our findings suggest that genetic disruption of PDGFRβ signaling results in a pericyte-specific insult in adult F7 mutants and will not exert a primary effect on neurons because PDGFRβ is not expressed in neurons of the adult 129S1/SvlmJ and F7 mouse brain. Therefore, mouse models with normal and deficient PDGFRβ signaling on a 129S1/SvlmJ background may effectively be used to deduce the specific roles of pericytes in maintaining the cerebral microcirculation and BBB integrity in the adult and aging brain as well as during neurodegenerative and brain vascular disorders.
The cardiac adrenergic system in ischaemia: differential role of acidosis and energy depletion
Authors: Gregor Simonis, Rainer Marquetant, Jochen Röthele, Ruth H Strasser
Journal: Cardiovascular Research (1998)

Objective: Acute myocardial ischaemia has been shown to modulate the β-adrenergic system and to activate protein kinase C. The aim of this study was to investigate if two important components of ischaemia, i.e. energy depletion or acidosis, may contribute to these changes. Methods: Isolated rat hearts were perfused either with anoxia (in the absence of oxygen) or with cyanide in the absence of glucose as models of energy depletion with a loss of high energy phosphates. Alternatively, isolated hearts were perfused with acidic modified Krebs–Henseleit solution to induce acidosis. Results: Energy depletion induced by cyanide perfusion leads to an increase of β-adrenergic receptors (81±7 vs. 50±3 fmol/mg protein, p≤0.05) comparable to the changes observed in ischaemia, yet without any change of total adenylyl cyclase activity or protein kinase C activity. Similar, yet less pronounced changes were induced by anoxic perfusion. Acidic perfusion, in contrast, promotes a translocation of protein kinase C to the plasma membranes, suggesting its rapid activation. Additionally, an increased total forskolin-stimulated activity of adenylyl cyclase (515±16 vs. 428±17 pmol/min/mg, p≤0.05) was observed. Both were comparable to the sensitization observed in early ischaemia. In acidosis, the density of β-adrenergic receptors remained unaltered. Conclusions: These data suggest that the regulation of cardiac β-adrenergic receptors is susceptible to energy depletion, but not to acidosis, whereas the intracellular enzymes both adenylyl cyclase and protein kinase C may be regulated by intracellular acidosis. This is the first differentiation of distinct components of ischaemia modulating the β-adrenergic signal transduction pathway. Both components may be operative in concert in acute myocardial ischaemia and may contribute to the regulation of these components of signal transduction observed in acute ischaemia.
Predicting return to play after hamstring injuries
Authors: M H Moen, G Reurink, A Weir, J L Tol, M Maas, G J Goudswaard
Journal: British Journal of Sports Medicine (2014)

Background Previous studies on the prognostic value of clinical and MRI parameters for the time to return to play (TTRTP) in acute hamstring injuries showed only limited to moderate evidence for the various investigated parameters. Some studies had multiple methodological limitations, including retrospective designs and the use of univariate analysis only. The aim of this study was to assess the prognostic value of clinical and MRI parameters for TTRTP using multivariate analysis. Methods 28 clinical and MRI parameters were prospectively investigated for an association with TTRTP in 80 non-professional athletes with MRI positive hamstring injuries undergoing a standardised rehabilitation programme. The association between possible prognostic parameters and TTRTP was assessed with a multivariate linear regression model. Parameters that had a p value &lt;0.2 on univariate testing were included in this model. Results 74 athletes were available for analysis. A total of nine variables met the criteria for the multivariate analysis: intensity of sports, level of sports, self-predicted TTRTP by the athlete, length of discomfort on palpation, deficit in passive straight leg raise, pain score on isometric knee flexion, isometric knee flexion strength deficit and distance of the proximal pole of the MRI hyperintensity to the tuber ischiadicum. Of these, only self-predicted TTRTP by the athlete and a passive straight leg raise deficit remained significantly associated with TTRTP after stepwise logistic regression. Conclusions The clinical parameters self-predicted TTRTP and passive straight leg raise deficit are independently associated with the TTRTP. MRI parameters in grade 1 and 2 hamstring injuries, as described in the literature, are not associated with TTRTP. For clinical practice, prognosis of the TTRTP in these injuries should better be based on clinical parameters.
Nursing Home Placement, Day Care Use, and Cognitive Decline in Alzheimer’s Disease
Authors: Robert S Wilson, Judith J McCann, Yan Li, Neelum T Aggarwal, David W Gilley, Denis A Evans
Journal: American Journal of Psychiatry (2007)

Objective: People with Alzheimer's disease are often placed in a nursing home, sometimes after using adult day care services. How affected persons function during this potentially difficult transition is not well understood. The aim of this study was to examine the associations of day care use and nursing home placement with the rate of cognitive decline in Alzheimer's disease. Method: The participants were 432 older persons with Alzheimer's disease who were recruited from health care settings in the Chicago area. At baseline, they lived in the community and were using day care services a mean 1.7 days per week. At 6-month intervals for up to 4 years, they completed nine cognitive tests from which a composite measure of global cognition was derived. Results: On average, cognition declined at a gradually increasing rate during the study period. Nursing home placement was associated with a decrease in the level of cognition and an acceleration in the rate of cognitive decline. Day care use at baseline was not related to cognitive decline in initial analyses, but it interacted with nursing home placement such that higher level of day care use substantially reduced association of placement with accelerated cognitive decline. Education interacted with placement such that more schooling was associated with a greater increase in cognitive decline upon nursing home placement, but prior day care use also attenuated this association. Conclusions: Nursing home placement is associated with accelerated short-term cognitive decline in Alzheimer's disease. Prior experience in adult day care may lessen this association.
Managing gout needs more than drugs: ‘<i>Il faut le savoir-faire, l'Art et la manière</i>’
Authors: Frédéric Lioté, Hyon Choi
Journal: Annals of the Rheumatic Diseases (2013)

Introduction Many doctors believe that patients with gout are unwilling to receive urate-lowering therapy (ULT) and blame them for poor adherence to management.Objective To test the effectiveness of a complex intervention for gout that incorporates key elements of current guidelines, including full patient information, delivered in an optimal setting (specialist hospital clinic).Method Observational study of patients reporting ongoing attacks of gout recruited from primary care lists.106 participants (94 men, 12 women; mean age 61 years) were enrolled in the study.Patients received a predominantly nurse-delivered intervention that included education, individualised lifestyle advice and appropriate ULT.The predefi ned goal was to achieve serum uric acid (SUA) levels ≤360 µmol/l after 1 year in at least 70% of participants.Results Of the 106 participants at baseline, 16% had tophi; mean (SD) baseline SUA was 456 (98) µmol/l.All participants agreed to joint aspiration to confi rm gout and all wished to receive ULT.At 12 months, 92% of the 106 participants had achieved the therapeutic target (SUA≤360 µmol); 85% had SUA <300 µmol/l.Allopurinol was the most commonly used ULT, requiring a median dose of 400 mg daily to achieve the target.Improvements in Short Form-36 were observed (signifi cant for pain) after 1 year.Conclusion A predominantly nurse-led intervention including education, lifestyle advice and ULT can successfully achieve the recommended treatment target in more than 9 out of 10 patients.Full explanation and discussion about the nature of gout and its treatment options and individualisation of management probably account for this success.
Tumour necrosis factor blockers and structural remodelling in ankylosing spondylitis: what is reality and what is fiction?
Authors: G. Schett, R. Landewe, D. van der Heijde
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Background</h3> Congenital hemidysplasia with ichthyosiform erythroderma and limb defects syndrome (CHILD) syndrome is a rare X-linked dominant disorder of cholesterol metabolism that clinically expresses as an epidermical hamartoma. Using co-application of topical formulation of simvastatin and cholesterol (TFSC) on skin lesions after previous failures has recently been reported.<sup>1</sup> <h3>Purpose</h3> To describe protocol of use, efficacy and safety of TFSC. <h3>Material and methods</h3> A woman, born in 1988, presented at birth with an extensive epidermal hamartoma due to CHILD syndrome. The cutaneous presentation was ichtyosiform erythroderma with sharp midline demarcation involving the right side of the body and a homolateral lower limb. She had skeletal malformations of her upper and lower limbs. Partial lower limb amputation was necessary when she was 2 years’ old. In February 2016, since skin lesions did not improve with acitretine, topical corticoid and various types of dressings, TFSC was began after obtaining informed consent. We developed an original ethanol-free formulation with simvastatin, cholesterol in Excipial Lipocreme (Galderma). The preparation consists of incorporating simvastatin in powder and triturated ground powder of cholesterol with Excipial: physical stability was satisfactory for at least 30 days. We used the following protocol<sup>1</sup>: in the first month, 0.5% simvastatin and cholesterol in Excipial Lipocreme, twice per day on a limited area to test tolerance; then afterwards at 2%, twice per day on a wider area. Efficacy was clinically assessed (aspect and extension of the skin lesion) and tolerance was clinically and biologically assessed. <h3>Results</h3> TFSC was started in February 2016. Erythema whitened after 10 months and totally disappeared after 18 months. After 24 months, improvement began on the papillomatous aspect of the stump. After 30 months, whitening areas were stable, with persisting papillomatosis in the stump and flexion areas. A 2 month supply disruption of simvastatin powder during the first year led to the reappearance of erythema. When TFSC resumed, the lesions improved again. The main reported side effect was the skin’s dryness on application, leading to emollient use. Complete blood counts, electrolytes, urea, triglycerides, cholesterol, CPK and liver function remained normal. <h3>Conclusion</h3> This case shows the interest and safety of TFSC in hamartoma lesions, indicating a potential interest in other types of hamartoma. <h3>Reference and/or acknowledgements</h3> Alexopoulos A, Kakourou T. <i>Pediatr Dermatol</i> 2015;32:e145–7. No conflict of interest.
Intracellular Inactivation of Thyroid Hormone Is a Survival Mechanism for Muscle Stem Cell Proliferation and Lineage Progression
Authors: Monica Dentice, Raffaele Ambrosio, Valentina Damiano, Annarita Sibilio, Cristina Luongo, Ombretta Guardiola, Siham Yennek, Paola Zordan, Gabriella Minchiotti, Annamaria Colao, Alessandro Marsili, Silvia Brunelli, Luigi Del Vecchio, P. Reed Larsen, Shahragim Tajbakhsh, Domenico Salvatore
Journal: Cell Metabolism (2014)

Precise control of the thyroid hormone (T3)-dependent transcriptional program is required by multiple cell systems, including muscle stem cells. Deciphering how this is achieved and how the T3 signal is controlled in stem cell niches is essentially unknown. We report that in response to proliferative stimuli such as acute skeletal muscle injury, type 3 deiodinase (D3), the thyroid hormone-inactivating enzyme, is induced in satellite cells where it reduces intracellular thyroid signaling. Satellite cell-specific genetic ablation of dio3 severely impairs skeletal muscle regeneration. This impairment is due to massive satellite cell apoptosis caused by exposure of activated satellite cells to the circulating TH. The execution of this proapoptotic program requires an intact FoxO3/MyoD axis, both genes positively regulated by intracellular TH. Thus, D3 is dynamically exploited in vivo to chronically attenuate TH signaling under basal conditions while also being available to acutely increase gene programs required for satellite cell lineage progression.
Multiple Connexins Form Gap Junction Channels in Rat Basilar Artery Smooth Muscle Cells
Authors: Xing Li, J. Marc Simard
Journal: Circulation Research (1999)

Abstract —Three connexins, Cx43, Cx40, and Cx37, have been found by protein or mRNA analysis to be prominent in mammalian blood vessels, but electrophysiological characterization of gap junction channels in freshly isolated vascular smooth muscle cells (SMCs) has not previously been reported. We used a dual-perforated patch-clamp technique to study gap junction conductances in SMC pairs from rat basilar arteries. Macroscopic junctional conductance ( G j ) measured in 98 cell pairs with either Cs + or K + ranged between 0.68 and 24.8 nS. In weakly coupled cells ( G j &lt;5 nS), single-channel currents were readily resolved without pharmacological uncoupling agents, allowing identification of 4 major unitary conductances. Two of these conductances, 80 to 120 pS and 150 to 200 pS, corresponded to the major conductance states for homotypic channels formed from Cx43 or Cx40, which we confirmed were present in smooth muscle by immunofluorescence analysis. Two other conductances, 220 to 280 pS and &gt;300 pS, were identified that have not been previously reported in vascular SMCs. Macroscopic recordings revealed currents that deactivated incompletely over a broad range of transjunctional potentials. In about half of the pairs, we identified macroscopic as well as single-channel currents that exhibited marked voltage asymmetry, consistent with nonhomotypic, ie, either heterotypic or heteromeric channels. Our data indicate that basilar artery SMCs are coupled in vivo in a richly complex manner, involving Cx43, Cx40, and other large-conductance channels, and that a significant number of couplings involve putative nonhomotypic channels.
Relative dipolar behavior of the equivalent T wave generator: quantitative comparison with ventricular excitation in the rabbit heart.
Authors: D A Brody, D M Mirvis, R E Ideker, J W Cox, F W Keller, R A Larsen, J P Bandura
Journal: Circulation Research (1977)

We studied the relative dipolar and nondipolar content of signal energy throughout ventricular excitation and recovery in 34 isolated, perfused rabbit hearts, suspended in an electrolyte-filled spherical chamber. Computer-processed signals were derived from 20 evenly spaced tank-surface electrodes, and a single, moving, equivalent cardiac dipole generator was optimally fitted to the recorded potentials for each 1-msec sampling interval. Superimposed, time-based plots of signal energy for the 34 preparations showed ventricular excitation to be strikingly more nondipolar than was recovery. In terms of the summed square ratio of nondipolar residual energies, overall nondipolarity of QRS exceed that of ST-T by 41%. Furthermore, the maximum instantaneous ratio during QRS was considerably greater than during the ST-T. Evaluation of paired differences, comparing nondipolar behavior throughout QRS with all of ST-T, proved highly significant (P less than .005). We also found that in contrast to the considerable mobility exhibited by the equivalent QRS dipole, the ST-T dipole locus remained nearly stationary during most of ventricular recovery. Presumably because repolarization is temporally and spatially a relatively diffuse process, it may generate electrical fields which are notably more dipolar than those caused by depolarization.