tbuckley/cabot-search huggingface dataset:
Predictive Value of Recent QuantiFERON Conversion for Tuberculosis Disease in Adolescents
Authors: Shingai Machingaidze, Suzanne Verver, Humphrey Mulenga, Deborah-Ann Abrahams, Mark Hatherill, Willem Hanekom, Gregory D. Hussey, Hassan Mahomed
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Conversions and reversions occur with IFN-γ release assay (IGRA) serial testing, as with the tuberculin skin test (TST). Recent TST conversion is associated with an established risk of developing tuberculosis (TB) disease, but the risk associated with recent IGRA conversions is unknown.To compare the incidence rate of TB disease after recent QuantiFERON TB Gold In-Tube (QFT) conversion compared with nonconverters.Adolescents with converted IGRA status (QFT converters [n = 534]) and randomly chosen adolescents whose IGRA status had remained negative over a period of 2 years (QFT nonconverters [n = 629]) were identified in a cohort study of TB infection and disease. Subsequent TB disease incidence was compared between the two groups.For QFT converters, the TB incidence rate (all cases) was 1.46 cases per 100 person-years (95% confidence interval [CI], 0.82-2.39), and the cumulative incidence was 2.8% (95% CI, 1.58-4.59). A significantly lower TB incidence rate (0.17 cases per 100 person-yr [95% CI, 0.02-0.62]) and cumulative incidence (0.32% [95% CI, 0.03-1.14]) was observed for QFT nonconverters. The incidence rate ratio was 8.54 (95% CI, 2.51-29.13) for all cases of TB and 9.1 (95% CI, 1.65-50.36) for protocol-defined TB.Recent QFT conversion was indicative of an approximately eight fold higher risk of progression to TB disease (compared with nonconverters) within 2 years of conversion in a cohort of adolescents in a high-TB burden population.
Allogeneic T cell responses are regulated by a specific miRNA-mRNA network
Authors: Yaping Sun, Isao Tawara, Meng Zhao, Zhaohui S. Qin, Tomomi Toubai, Nathan Mathewson, Hiroya Tamaki, Evelyn Nieves, Arul M. Chinnaiyan, Pavan Reddy
Journal: Journal of Clinical Investigation (2013)

Donor T cells that respond to host alloantigens following allogeneic bone marrow transplantation (BMT) induce graft-versus-host (GVH) responses, but their molecular landscape is not well understood. MicroRNAs (miRNAs) regulate gene (mRNA) expression and fine-tune the molecular responses of T cells. We stimulated naive T cells with either allogeneic or nonspecific stimuli and used argonaute cross-linked immunoprecipitation (CLIP) with subsequent ChIP microarray analyses to profile miR responses and their direct mRNA targets. We identified a unique expression pattern of miRs and mRNAs following the allostimulation of T cells and a high correlation between the expression of the identified miRs and a reduction of their mRNA targets. miRs and mRNAs that were predicted to be differentially regulated in allogeneic T cells compared with nonspecifically stimulated T cells were validated in vitro. These analyses identified wings apart-like homolog (Wapal) and synaptojanin 1 (Synj1) as potential regulators of allogeneic T cell responses. The expression of these molecular targets in vivo was confirmed in MHC-mismatched experimental BMT. Targeted silencing of either Wapal or Synj1 prevented the development of GVH response, confirming a role for these regulators in allogeneic T cell responses. Thus, this genome-wide analysis of miRNA-mRNA interactions identifies previously unrecognized molecular regulators of T cell responses.
Healthy Individuals Have Goodpasture Autoantigen-Reactive T Cells
Authors: Juan Zou, Sigrid Hannier, Lindsay S. Cairns, Robert N. Barker, Andrew J. Rees, A. Neil Turner, Richard G. Phelps
Journal: Journal of the American Society of Nephrology (2008)

Autoreactive T cells in patients with Goodpasture's disease are specific for epitopes in the Goodpasture antigen (the NC1 domain of the alpha3 chain of type IV collagen) that are rapidly destroyed during antigen processing to a degree that diminishes their presentation to T cells. We hypothesized that patients' autoreactive T cells exist because antigen processing prevents presentation of the self-epitopes they recognize, circumventing specific tolerance mechanisms. We predicted that autoreactive T cells specific for these peptides should also exist in healthy individuals, albeit at low frequency and in an unprimed state. We obtained blood from healthy unrelated donors and, using a panel of 45 alpha3(IV)NC1 peptides, identified alpha3(IV)NC1-specific T cells in all donors. Thirty-six of 45 peptides elicited a proliferative T cell response from at least one subject, and 6 of the peptides evoked a response in >50% of the individuals. This consistency was not caused by selectivity of HLA class II molecules because the donors expressed a diversity of HLA antigens, but was largely a result of the substrate-specificity of the endosomal proteases Cathepsin D and E. There was a significant correlation between high susceptibility to Cathepsin D digestion and the capacity to stimulate primary T cell responses (P = 0.00006). In summary, healthy individuals have low frequencies of unstimulated alpha3(IV)NC1-reactive T cells with similar specificities to the autoreactive T cells found in patients with Goodpasture disease. In both cases, existence of the alpha3(IV)NC1-reactive T cells can be accounted for by destructive processing.
<i>Chlamydophila Psittaci</i> Eradication With Doxycycline As First-Line Targeted Therapy for Ocular Adnexae Lymphoma: Final Results of an International Phase II Trial
Authors: Andrés J.M. Ferreri, Silvia Govi, Elisa Pasini, Silvia Mappa, Francesco Bertoni, Francesco Zaja, Carlos Montalbán, Caterina Stelitano, Maria Elena Cabrera, Antonio Giordano Resti, Letterio Salvatore Politi, Claudio Doglioni, Franco Cavalli, Emanuele Zucca, Maurilio Ponzoni, Riccardo Dolcetti
Journal: Journal of Clinical Oncology (2012)

Purpose The pathogenic association between Chlamydophila psittaci (Cp) and ocular adnexal marginal zone lymphoma (OAMZL) and the efficacy of doxycycline monotherapy have been investigated in retrospective series with variations in stage, management, and follow-up duration. To our knowledge, this is the first international phase II trial aimed at clarifying Cp prevalence and activity of first-line doxycycline in a homogeneous series of consecutive patients with newly diagnosed stage I OAMZL. Patients and Methods Forty-seven patients were registered. Tumor tissue, conjunctival swabs, and peripheral blood from 44 patients were assessed for seven Chlamydiaceae infections by three polymerase chain reaction protocols. Thirty-four patients with measurable or parametrable disease were treated with doxycycline and assessed for chlamydial eradication and lymphoma response (primary end point). Results Cp DNA was detected in biopsies of 39 patients (89%); no other Chlamydiaceae were detected. Twenty-nine patients had Cp DNA in baseline swabs and/or blood samples and were evaluable for chlamydial eradication, which was achieved in 14 patients (48%). Lymphoma regression was complete in six patients and partial in 16 (overall response rate, 65%; 95% CI, 49% to 81%); 11 had stable disease, and one had progressive disease. At a median follow-up of 37 months (range, 15 to 62 months), 20 patients remained relapse free (5-year progression-free survival [PFS] ± standard deviation, 55% ± 9%). Cp eradication was associated with improved response rate (86% v 47%; P = .02) and 5-year PFS (68% v 47%; P = .11). Conclusion Upfront doxycycline is a rational and active treatment for patients with stage I Cp-positive OAMZL. Lymphoma regression is consequent to Cp eradication, which can easily be monitored on conjunctival and blood samples. Prospective trials aimed at identifying more effective administration schedules for doxycycline are warranted.
Inhibition of Activator Protein-1 by Sulforaphane Involves Interaction with Cysteine in the cFos DNA-Binding Domain: Implications for Chemoprevention of UVB-Induced Skin Cancer
Authors: Sally E. Dickinson, Tania F. Melton, Erik R. Olson, Jian Zhang, Kathylynn Saboda, G. Timothy Bowden
Journal: Cancer Research (2009)

Abstract Sulforaphane is an isothiocyanate derived from cruciferous vegetables that has been linked to decreased risk of certain cancers. Although the role of sulforaphane in the induction of the transcription factor Nrf2 has been studied extensively, there is also evidence that inhibition of the transcription factor activator protein-1 (AP-1) may contribute to the chemopreventive properties of this compound. In this study, we show for the first time that sulforaphane is effective at reducing the multiplicity and tumor burden of UVB-induced squamous cell carcinoma in a mouse model using cotreatment with the compound and the carcinogen. We also show that sulforaphane pretreatment is able to reduce the activity of AP-1 luciferase in the skin of transgenic mice after UVB. Chromatin immunoprecipitation analysis verified that a main constituent of the AP-1 dimer, cFos, is inhibited from binding to the AP-1 DNA binding site by sulforaphane. Electrophoretic mobility shift assay analysis of nuclear proteins also shows that sulforaphane and diamide, both known to react with cysteine amino acids, are effective at inhibiting AP-1 from binding to its response element. Using truncated recombinant cFos and cJun, we show that mutation of critical cysteines in the DNA-binding domain of these proteins (Cys154 in cFos and Cys272 in cJun) results in loss of sensitivity to both sulforaphane and diamide in electrophoretic mobility shift assay analysis. Together, these data indicate that inhibition of AP-1 activity may be an important molecular mechanism in chemoprevention of squamous cell carcinoma by sulforaphane. [Cancer Res 2009;69(17):7103–10]
Statistical and Molecular Analyses of Evolutionary Significance of Red-Green Color Vision and Color Blindness in Vertebrates
Authors: S. Yokoyama
Journal: Molecular Biology and Evolution (2005)

Red-green color vision is strongly suspected to enhance the survival of its possessors. Despite being red-green color blind, however, many species have successfully competed in nature, which brings into question the evolutionary advantage of achieving red-green color vision. Here, we propose a new method of identifying positive selection at individual amino acid sites with the premise that if positive Darwinian selection has driven the evolution of the protein under consideration, then it should be found mostly at the branches in the phylogenetic tree where its function had changed. The statistical and molecular methods have been applied to 29 visual pigments with the wavelengths of maximal absorption at approximately 510-540 nm (green- or middle wavelength-sensitive [MWS] pigments) and at approximately 560 nm (red- or long wavelength-sensitive [LWS] pigments), which are sampled from a diverse range of vertebrate species. The results show that the MWS pigments are positively selected through amino acid replacements S180A, Y277F, and T285A and that the LWS pigments have been subjected to strong evolutionary conservation. The fact that these positively selected M/LWS pigments are found not only in animals with red-green color vision but also in those with red-green color blindness strongly suggests that both red-green color vision and color blindness have undergone adaptive evolution independently in different species.
Brown adipose tissue activity controls triglyceride clearance
Authors: Alexander Bartelt, Oliver T Bruns, Rudolph Reimer, Heinz Hohenberg, Harald Ittrich, Kersten Peldschus, Michael G Kaul, Ulrich I Tromsdorf, Horst Weller, Christian Waurisch, Alexander Eychmüller, Philip L S M Gordts, Franz Rinninger, Karoline Bruegelmann, Barbara Freund, Peter Nielsen, Martin Merkel, Joerg Heeren
Journal: Nature Medicine (2011)
Light-Activated Content Release from Liposomes
Authors: Sarah J. Leung, Marek Romanowski
Journal: Theranostics (2012)

Successful integration of diagnostic and therapeutic actions at the level of individual cells requires new materials that combine biological compatibility with functional versatility.This review focuses on the development of liposome-based functional materials, where payload release is activated by light.Methods of sensitizing liposomes to light have progressed from the use of organic molecular moieties to the use of metallic plasmon resonant structures.This development has facilitated application of near infrared light for activation, which is preferred for its deep penetration and low phototoxicity in biological tissues.Presented mechanisms of light-activated liposomal content release enable precise in vitro manipulation of minute amounts of reagents, but their use in clinical diagnostic and therapeutic applications will require demonstration of safety and efficacy.
Outcome and clinical–biological characteristics of patients with advanced breast cancer undergoing removal of ovarian/pelvic metastases
Authors: E. Munzone, E. Botteri, A. Esposito, A. Sciandivasci, D. Franchi, G. Pruneri, N. Rotmensz, G. Curigliano, L. Adamoli, L. Bocciolone, A. Goldhirsch, F. Nolé
Journal: Annals of Oncology (2012)
Dual Regulation of Cofilin Activity by LIM Kinase and Slingshot-1L Phosphatase Controls Platelet-Derived Growth Factor–Induced Migration of Human Aortic Smooth Muscle Cells
Authors: Alejandra San Martín, Moo Yeol Lee, Holly C. Williams, Kensaku Mizuno, Bernard Lassègue, Kathy K. Griendling
Journal: Circulation Research (2007)

Platelet-derived growth factor (PDGF) plays a central role in vascular healing, atherosclerosis, and restenosis, partly by stimulating vascular smooth muscle cell (VSMC) migration. Migration requires rapid turnover of actin filaments, which is partially controlled by cofilin. Although cofilin is negatively regulated by Ser3 phosphorylation, the upstream signaling pathways have not been defined, nor has its role in VSMC migration been studied. We hypothesized that PDGF-induced migration of VSMCs involves cofilin activation and that this is regulated by the serine kinase LIM kinase (LIMK) and the novel phosphatase Slingshot (SSH)1L. In human VSMCs, stimulation with PDGF increased G-actin incorporation into the actin cytoskeleton. PDGF transiently activated the cofilin kinase, LIMK, with a peak at 5 minutes. However, cofilin was dephosphorylated between 5 and 45 minutes, with a maximum of 43±5% dephosphorylation at 30 minutes, suggesting that PDGF also activates a cofilin phosphatase. We found that VSMCs express SSH1L, which is induced and activated (564±73 versus 1021±141 picomoles of PO 4 ; P =0.015) by PDGF. Of importance, small interfering RNA directed against SSH1L blocked cofilin dephosphorylation and decreased migration (528±33 versus 318±25 cells/field; P &lt;0.01). Taken together, our results suggest that PDGF participates in actin dynamics by dual regulation of cofilin activity via LIMK and SSH1L.
A registry-based study of non-Aspergillus mould infections in recipients of allogeneic haematopoietic cell transplantation
Authors: M.L. Fox, P. Barba, I. Heras, M. López-Parra, M. González-Vicent, R. de la Cámara, M. Batlle, R. Parody, C. Vallejo, I. Ruiz-Camps, L. Vázquez
Journal: Clinical Microbiology and Infection (2014)
The foot core system: a new paradigm for understanding intrinsic foot muscle function
Authors: Patrick O McKeon, Jay Hertel, Dennis Bramble, Irene Davis
Journal: British Journal of Sports Medicine (2014)

The foot is a complex structure with many articulations and multiple degrees of freedom that play an important role in static posture and dynamic activities. The evolutionary development of the arch of the foot was coincident with the greater demands placed on the foot as humans began to run. The movement and stability of the arch is controlled by intrinsic and extrinsic muscles. However, the intrinsic muscles are largely ignored by clinicians and researchers. As such, these muscles are seldom addressed in rehabilitation programmes. Interventions for foot-related problems are more often directed at externally supporting the foot rather than training these muscles to function as they are designed. In this paper, we propose a novel paradigm for understanding the function of the foot. We begin with an overview of the evolution of the human foot with a focus on the development of the arch. This is followed by a description of the foot intrinsic muscles and their relationship to the extrinsic muscles. We draw the parallels between the small muscles of the trunk region that make up the lumbopelvic core and the intrinsic foot muscles, introducing the concept of the foot core. We then integrate the concept of the foot core into the assessment and treatment of the foot. Finally, we call for an increased awareness of the importance of the foot core stability to normal foot and lower extremity function.
Fatigue in Long-Term Hodgkin's Disease Survivors: A Follow-Up Study
Authors: Marianne J. Hjermstad, Sophie D. Fosså, Line Oldervoll, Harald Holte, Anne B. Jacobsen, Jon H. Loge
Journal: Journal of Clinical Oncology (2005)

To describe total fatigue (TF) and chronic fatigue (CF) in 476 long-term Hodgkin's disease survivors (HDSs). The development in CF over time was explored in 280 of the patients who had also been assessed 8 years earlier.In 2003, the Fatigue Questionnaire was mailed to 610 successfully treated HDSs at the Norwegian Radium Hospital from 1971 to 1997. Mean TF scores and occurrence of CF were compared with general population (GP) values.Four hundred seventy-six complete forms (81%) were received (median age, 46 years; 56% males, median follow-up time, 195 months). There was a positive association between age and TF (P < .05), whereas presence of B symptoms at diagnosis and treatment before 1980 were associated with CF. Mean TF scores were elevated in HDSs compared with the GP (mean TF score, 14.6; 95% CI, 14.1 to 15.7 v 12.1; 95% CI, 11.9 to 12.3, respectively; P < .001), as was the proportion of persons with CF (30% v 11%, respectively; odds ratio = 3.6; P < .001). The 70 patients with CF 8 years earlier still reported higher TF at follow-up than the 210 patients without CF at the previous assessment (mean TF score, 17.0; 95% CI, 15.6 to 18.3 v 13.1; 95% CI, 12.9 to 14.1, respectively; P < .001). Significantly more patients with persisting CF had B symptoms at diagnosis compared with patients who had recovered (P = .05). No significant association with treatment modality and intensity was found.Fatigue remains a major complaint in HDSs several years after treatment, but the association between treatment and fatigue still remains unclear. Many HDSs may recover from CF, particularly patients without B symptoms at diagnosis.
A Protein-Bound Form of Porcine Renal Renin
Authors: GRAHAM W. BOYD
Journal: Circulation Research (1974)

Two interconvertible renins were isolated from extracts of the pig renal cortex at neutral pH and shown to be protein-bound (renin B, molecular weight 60,000) and free (renin A, molecular weight 40,000) forms of renin. The protein-bound form (renin B) gave a much more prolonged pressor response than did the free form (renin A) on direct bioassay in the rat; it could be converted to renin A by the action of various salts or by acidification below pH 3. The renin-binding protein associated with renin B was isolated by DEAE-cellulose column chromatography under special conditions of elution and appeared to be specific for renin. When pig kidneys were perfused in situ with Krebs-Ringer's solution, isoproterenol stimulation (1-8 µg/min) resulted in release of renin in the protein-bound form. It is suggested that renin-binding protein may act as a carrier for the transport of renin to local tissue sites of uptake under some circumstances and thus alter the mode of expression of the renin-angiotensin system in vivo to one of local angiotensin generation and effect.
Motif composition, conservation and condition-specificity of single and alternative transcription start sites in the Drosophila genome
Authors: Elizabeth A Rach, Hsiang-Yu Yuan, William H Majoros, Pavel Tomancak, Uwe Ohler
Journal: Genome biology (2009)

Abstract Background Transcription initiation is a key component in the regulation of gene expression. mRNA 5' full-length sequencing techniques have enhanced our understanding of mammalian transcription start sites (TSSs), revealing different initiation patterns on a genomic scale. Results To identify TSSs in Drosophila melanogaster , we applied a hierarchical clustering strategy on available 5' expressed sequence tags (ESTs) and identified a high quality set of 5,665 TSSs for approximately 4,000 genes. We distinguished two initiation patterns: 'peaked' TSSs, and 'broad' TSS cluster groups. Peaked promoters were found to contain location-specific sequence elements; conversely, broad promoters were associated with non-location-specific elements. In alignments across other Drosophila genomes, conservation levels of sequence elements exceeded 90% within the melanogaster subgroup, but dropped considerably for distal species. Elements in broad promoters had lower levels of conservation than those in peaked promoters. When characterizing the distributions of ESTs, 64% of TSSs showed distinct associations to one out of eight different spatiotemporal conditions. Available whole-genome tiling array time series data revealed different temporal patterns of embryonic activity across the majority of genes with distinct alternative promoters. Many genes with maternally inherited transcripts were found to have alternative promoters utilized later in development. Core promoters of maternally inherited transcripts showed differences in motif composition compared to zygotically active promoters. Conclusions Our study provides a comprehensive map of Drosophila TSSs and the conditions under which they are utilized. Distinct differences in motif associations with initiation pattern and spatiotemporal utilization illustrate the complex regulatory code of transcription initiation.
Randomised controlled trial of an occupational therapy intervention to increase outdoor mobility after stroke
Authors: P A Logan, J R F Gladman, A Avery, M F Walker, J Dyas, L Groom
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To evaluate an occupational therapy intervention to improve outdoor mobility after stroke. <b>Design</b> Randomised controlled trial. <b>Setting</b> General practice registers, social services departments, a primary care rehabilitation service, and a geriatric day hospital. <b>Participants</b> 168 community dwelling people with a clinical diagnosis of stroke in previous 36 months: 86 were allocated to the intervention group and 82 to the control group. <b>Interventions</b> Leaflets describing local transport services for disabled people (control group) and leaflets with assessment and up to seven intervention sessions by an occupational therapist (intervention group). <b>Main outcome measures</b> Responses to postal questionnaires at four and 10 months: primary outcome measure was response to whether participant got out of the house as much as he or she would like, and secondary outcome measures were response to how many journeys outdoors had been made in the past month and scores on the Nottingham extended activities of daily living scale, Nottingham leisure questionnaire, and general health questionnaire. <b>Results</b> Participants in the treatment group were more likely to get out of the house as often as they wanted at both four months (relative risk 1.72, 95% confidence interval 1.25 to 2.37) and 10 months (1.74, 1.24 to 2.44). The treatment group reported more journeys outdoors in the month before assessment at both four months (median 37 in intervention group, 14 in control group: P &lt; 0.01) and 10 months (median 42 in intervention group, 14 in control group: P &lt; 0.01). At four months the mobility scores on the Nottingham extended activities of daily living scale were significantly higher in the intervention group, but there were no significant differences in the other secondary outcomes. No significant differences were observed in these measures at 10 months. <b>Conclusion</b> A targeted occupational therapy intervention at home increases outdoor mobility in people after stroke.