tbuckley/cabot-search huggingface dataset:
Clinical patterns and injury exposure rates in elite road cycling are changing over the last decade
Authors: C Barrios, N de Bernardo, P Vera, C Laíz, M Hadala
Journal: British Journal of Sports Medicine (2011)

Background The latest bicycle technical advances and the new training protocols might have an incidence of injury occurrence in professional cycling. Objective To analyze changes in injury incidence of a group of elite cyclist in active and compare the injury rates with those reported for an historical group (HG). Design Epidemiologic retrospective study based on clinical oriented interviews. Setting Clinical survey of all traumatic and overuse injuries occurred in male elite cyclists engaged in three professional teams. Participants The HG consisted in 65 professional road cyclists surveyed from 1983 to 1995. Mean age, 25 years (range 21 32). The current series (CS) included 51 elite cyclists with a mean age of 27 (19–36). The CS was studied from 2003 to 2009. Main outcome measures Abbreviated Injury Scale (AIS) and the Ekstrand 3 point scale for absence from sports activity. Injury exposure rates: injuries per racer, per year and per 1000 km of both competing and training. Results Traumatic injuries increased from 38.4% to 48.6%. However, AIS severe lesions decrease from 51.2% to 8%. Tendinopaties were the most common overuse injuries in the HG (41.5%). Contrary, 56.6% of overuse injuries were due to muscular lesions in the CS group. In HG cyclists, the injury rates for traumatic injuries were 0.54 per racer, 0.11 per year, and 0.003 per 1000 km of training and competition. The rates for overuse injury were 0.86 per racer, 0.17 per year, and 0.005 per 1000 km. In CS cyclists, injury rates for traumatic injuries were found to be higher: 0.98 per racer, 0.24 per year, 0.007 per 1.000 km. Overuse injury rates were 1.04 per racer, 0.26 per year, and 0.009 per 1.000 km. Conclusion Professional cyclists still in active are exposed to a double risk of traumatic injuries than those competing in the 80's and 90's. Exposure to overuse remains almost equal, but with a complete different clinical pattern imposed by the high incidence of muscular injuries.
Medical Director Responsibilities for Outpatient Cardiac Rehabilitation/Secondary Prevention Programs: 2012 Update
Authors: Marjorie King, Vera Bittner, Richard Josephson, Karen Lui, Randal J. Thomas, Mark A. Williams
Journal: Circulation (2012)

Medical directors of cardiac rehabilitation/secondary prevention (CR/SP) programs are responsible for the safe and effective delivery of high-quality CR/SP services to eligible patients. Yet, the training and resources for CR/SP medical directors are limited. As a result, there appears to be considerable variability throughout CR/SP programs in the United States in the roles, responsibilities, and engagement of CR/SP medical directors. Since the publication of the 2005 scientific statement from the American Heart Association and American Association of Cardiovascular and Pulmonary Rehabilitation regarding medical director responsibilities for outpatient CR/SP programs, significant changes have occurred. This statement updates the responsibilities of CR/SP medical directors, in view of changes in federal legislation and regulations and changes in health care delivery and clinical practice that impact the roles and responsibilities of CR/SP medical directors.
Expression of Human Scavenger Receptor Class B Type I in Cultured Human Monocyte-Derived Macrophages and Atherosclerotic Lesions
Authors: Ken-ichi Hirano, Shizuya Yamashita, Yumiko Nakagawa, Takeshi Ohya, Fumihiko Matsuura, Kosuke Tsukamoto, Yoshihisa Okamoto, Akifumi Matsuyama, Kengo Matsumoto, Jun-ichiro Miyagawa, Yuji Matsuzawa
Journal: Circulation Research (1999)

Abstract —The scavenger receptor class B type I (SR-BI) and its human homologue CLA-1 ( C D36 and L IMPII A nalogous- 1 ) have recently been identified to bind HDL and mediate the selective uptake of HDL lipids. Tissue distribution of both murine and human receptors is quite similar, in that they are expressed abundantly in liver and steroidogenic tissues. However, expression and function of the human SR-BI (hSR-BI), in the periphery of reverse cholesterol transport such as macrophages, are still unclear. In the present study, we have raised two different kinds of anti–hSR-BI polypeptide antibodies (Abs): one against the extracellular domain and the other against the intracellular domain. We have investigated the expression of hSR-BI mRNA and immunoreactive mass in freshly isolated cultured human monocyte-derived macrophages (hMφ) and in atherosclerotic lesions. Contrary to the earlier report, hSR-BI mRNA was expressed in cultured hMφ and markedly upregulated with differentiation, determined by Northern blot and reverse transcriptase–based polymerase chain reaction analyses. The mRNA expression pattern during differentiation of hMφ was very similar to those of SR class A and another member of SR class B, CD36. Protein expression was confirmed by Western blot analyses with the above Abs to show a major 83-kDa band. Modified lipoproteins such as oxidized LDL and acetylated LDL induced a 5-fold increase in mRNA and protein expression of hSR-BI. Confocal immunofluorescence microscopy demonstrated that hSR-BI immunoreactive mass was detectable as a heterogeneous, punctate staining pattern. Furthermore, immunohistochemical analysis showed that immunoreactive mass of hSR-BI was detected in foam cells in human aortic atherosclerotic lesions and that there was no significant difference of staining patterns between the two Abs. This study clearly demonstrates that hSR-BI is expressed in the lipid-laden macrophages in human atherosclerotic lesions, suggesting that it is very important to know its function and regulation in hMφ to understand the biological utility of this molecule.
A novel interaction between FlnA and Syk regulates platelet ITAM-mediated receptor signaling and function
Authors: Hervé Falet, Alice Y. Pollitt, Antonija Jurak Begonja, Sarah E. Weber, Daniel Duerschmied, Denisa D. Wagner, Steve P. Watson, John H. Hartwig
Journal: The Journal of Experimental Medicine (2010)

Filamin A (FlnA) cross-links actin filaments and connects the Von Willebrand factor receptor GPIb-IX-V to the underlying cytoskeleton in platelets. Because FlnA deficiency is embryonic lethal, mice lacking FlnA in platelets were generated by breeding FlnAloxP/loxP females with GATA1-Cre males. FlnAloxP/y GATA1-Cre males have a macrothrombocytopenia and increased tail bleeding times. FlnA-null platelets have decreased expression and altered surface distribution of GPIbα because they lack the normal cytoskeletal linkage of GPIbα to underlying actin filaments. This results in ∼70% less platelet coverage on collagen-coated surfaces at shear rates of 1,500/s, compared with wild-type platelets. Unexpectedly, however, immunoreceptor tyrosine-based activation motif (ITAM)- and ITAM-like–mediated signals are severely compromised in FlnA-null platelets. FlnA-null platelets fail to spread and have decreased α-granule secretion, integrin αIIbβ3 activation, and protein tyrosine phosphorylation, particularly that of the protein tyrosine kinase Syk and phospholipase C–γ2, in response to stimulation through the collagen receptor GPVI and the C-type lectin-like receptor 2. This signaling defect was traced to the loss of a novel FlnA–Syk interaction, as Syk binds to FlnA at immunoglobulin-like repeat 5. Our findings reveal that the interaction between FlnA and Syk regulates ITAM- and ITAM-like–containing receptor signaling and platelet function.
Predictors of Clinical Improvement in Rituximab‐Treated Refractory Adult and Juvenile Dermatomyositis and Adult Polymyositis
Authors: Rohit Aggarwal, Andriy Bandos, Ann M. Reed, Dana P. Ascherman, Richard J. Barohn, Brian M. Feldman, Frederick W. Miller, Lisa G. Rider, Michael O. Harris‐Love, Marc C. Levesque, Chester V. Oddis
Journal: Arthritis & Rheumatology (2013)

Objective To identify the clinical and laboratory predictors of clinical improvement in a cohort of myositis patients treated with rituximab. Methods We analyzed data for 195 patients with myositis (75 with adult polymyositis [PM], 72 with adult dermatomyositis [DM], and 48 with juvenile DM) in the Rituximab in Myositis trial. Clinical improvement was defined as 20% improvement in at least 3 of the following 6 core set measures of disease activity: physician's and patient's/parent's global assessment of disease activity, manual muscle testing, physical function, muscle enzymes, and extramuscular disease activity. We analyzed the association of the following baseline variables with improvement: myositis clinical subgroup, demographics, myositis damage, clinical and laboratory parameters, core set measures, rituximab treatment, and myositis autoantibodies (antisynthetase, anti–Mi‐2, anti–signal recognition particle, anti–transcription intermediary factor 1γ [TIF‐1γ], anti‐MJ, other autoantibodies, and no autoantibodies). All measures were univariately assessed for association with improvement using time‐to‐event analyses. A multivariable time‐dependent proportional hazards model was used to evaluate the association of individual predictive factors with improvement. Results In the final multivariable model, the presence of an antisynthetase, primarily anti–Jo‐1 (hazard ratio [HR] 3.08, P &lt; 0.01), anti–Mi‐2 (HR 2.5, P &lt; 0.01), or other autoantibody (HR 1.4, P = 0.14) predicted a shorter time to improvement compared to the absence of autoantibodies. A lower physician's global assessment of damage (HR 2.32, P = 0.02) and juvenile DM (versus adult myositis) (HR 2.45, P = 0.01) also predicted improvement. Unlike autoantibody status, the predictive effect of physician's global assessment of damage and juvenile DM diminished by week 20. Rituximab treatment did not affect these associations. Conclusion Our findings indicate that the presence of antisynthetase and anti–Mi‐2 autoantibodies, juvenile DM subset, and lower disease damage strongly predict clinical improvement in patients with refractory myositis.
RAFTK, a Novel Member of the Focal Adhesion Kinase Family, Is Phosphorylated and Associates with Signaling Molecules upon Activation of Mature T Lymphocytes
Authors: Ramesh K. Ganju, William C. Hatch, Hava Avraham, Mel A. Ona, Brian Druker, Shalom Avraham, Jerome E. Groopman
Journal: The Journal of Experimental Medicine (1997)

The related adhesion focal tyrosine kinase (RAFTK), a recently discovered member of the focal adhesion kinase family, has previously been reported to participate in signal transduction in neuronal cells, megakaryocytes, and B lymphocytes. We have found that RAFTK is constitutively expressed in human T cells and is rapidly phosphorylated upon the activation of the T cell receptor (TCR). This activation also results in an increase in the autophosphorylation and kinase activity of RAFTK. After its stimulation, there was an increase in the association of the src cytoplasmic tyrosine kinase Fyn and the adapter protein Grb2. This association was mediated through the SH2 domains of Fyn and Grb2. RAFTK also co-immunoprecipitates with the SH2 domain of Lck and with the cytoskeletal protein paxillin through its COOH-terminal proline-rich domain. The tyrosine phosphorylation of RAFTK after T cell receptor-mediated stimulation was reduced by the pretreatment of cells with cytochalasin D, suggesting the role of the cytoskeleton in this process. These observations indicate that RAFTK participates in T cell receptor signaling and may act to link signals from the cell surface to the cytoskeleton and thereby affect the host immune response.
Impairment in the Specificity of Emotion Processing in Schizophrenia
Authors: Frank Schneider, Ruben C. Gur, Kathrin Koch, Volker Backes, Katrin Amunts, N. Jon Shah, Warren Bilker, Raquel E. Gur, Ute Habel
Journal: American Journal of Psychiatry (2006)

OBJECTIVE: Deficits in emotion processing are a hallmark of schizophrenia, with consequences for social functioning and subjective well-being. However, their specificity and characteristics have not been ascertained psychometrically. The authors' purpose was to examine a differential deficit for processing emotional facets of the face compared to judgment of nonemotional features (age) and facial memory. The authors also sought to establish whether the deficit affects sensitivity or specificity of performance. METHOD: Participants were 20 patients with schizophrenia and 20 healthy subjects matched for age, gender, and parental education. The authors examined emotional discrimination abilities compared to age discrimination and recognition memory for faces with standardized faces displaying the universal emotions of happiness, sadness, anger, and fear. Percent correct in each condition and for each emotion were assessed as well as sensitivity (correct identification of a target emotion) and specificity (correct rejection of a nontarget emotion) for emotion recognition. RESULTS: Patients with schizophrenia were differentially impaired in the discrimination of emotional aspects of facial expressions compared to nonemotional aspects and memory. Within the emotional task, patients showed differential impairment in specificity and insensitivity to the emotion displayed. CONCLUSIONS: When identical stimuli were used across tasks, differential impairment was seen in patients with schizophrenia for processing emotional faces, although the nonemotional task proved harder for both groups. Impairment in the specificity of emotion identification may lead to misunderstanding of social communication and may underlie difficulties in social adjustment experienced by people with schizophrenia. Emotion discrimination tests could augment the neurobehavioral evaluation of patients.
Core body temperature during competition in the heat: national boys' 14s junior tennis championships
Authors: Michael F Bergeron, Kathryn S McLeod, John F Coyle
Journal: British Journal of Sports Medicine (2007)

To examine on-court core body temperature (T(C)) and sweat loss, as well as pre- and post-play hydration status, in elite adolescent tennis players during a national championships event in a hot climate.Eight healthy, fit, young male tennis players (mean (SD) age 13.9 (0.9) years; mass 56.0 (10.7) kg; height 169.2 (14.7) cm) were evaluated during first-round singles competition at the National Boys' 14s Junior Championships in the heat (wet-bulb globe temperature (WBGT) 29.6 (0.4) degrees C). Five of those same players were also evaluated during a same-day doubles match (WBGT 31.3 (0.5) degrees C).During doubles (4.37 (0.35) h after singles), pre-play urine specific gravity (USG) (1.025 (0.002); p = 0.06) and total sweat loss (1.9 (0.2) litres; p = 0.10) tended to be higher before and during doubles, respectively, compared to singles. However, percentage change in body mass (-0.5 (0.3) %) tended to be comparatively less (p = 0.08), even though the doubles matches were generally longer (106.6 (11.2) vs 78.8 (10.9) min; p = 0.09) and the degree minutes total was greater (p = 0.04). T(C) increased (p<0.001) during singles and remained elevated, even after 10 min following the end of play. Notably, pre-play (singles) USG was strongly associated (p = 0.005) with the players' final T(C) (38.7 (0.3) degrees C) recorded at the end of singles play.Junior tennis players who begin a match not well hydrated could have progressively increasing thermal strain and a greater risk for exertional heat illness as the match advances.
High Pressure Induces Superoxide Production in Isolated Arteries Via Protein Kinase C–Dependent Activation of NAD(P)H Oxidase
Authors: Zoltan Ungvari, Anna Csiszar, An Huang, Pawel M. Kaminski, Michael S. Wolin, Akos Koller
Journal: Circulation (2003)

Oxidative stress seems to be present in all forms of hypertension. Thus, we tested the hypothesis that high intraluminal pressure (Pi) itself, by activating vascular oxidases, elicits increased superoxide (O2*-) production interfering with flow-induced dilation.Isolated, cannulated rat femoral arterial branches were exposed in vitro (for 30 minutes) to normal Pi (80 mm Hg) or high Pi (160 mm Hg). High Pi significantly increased vascular O2*- production (as measured by lucigenin chemiluminescence and ethidium bromide fluorescence) and impaired endothelium-dependent dilations to flow; these effects could be reversed by superoxide dismutase. Administration of the NAD(P)H oxidase inhibitor diphenyleneiodonium, apocynin, the protein kinase C (PKC) inhibitor chelerythrine or staurosporin or the removal of extracellular Ca2+ during high Pi treatment prevented the increases in O2*- production, whereas administration of losartan or captopril had no effect. High Pi resulted in significant increases in intracellular Ca2+ ([Ca2+]i) in the vascular wall (fura 2 fluorescence) and phosphorylation of PKCalpha (Western blotting). The PKC activator phorbol myristate acetate significantly increased vascular O2*- production, which was inhibited by superoxide dismutase, diphenyleneiodonium, chelerythrine, or removal of extracellular Ca2+. Both high Pi and phorbol myristate acetate increased the phosphorylation of the NAD(P)H oxidase subunit p47phox.High Pi itself elicits arterial O2.- production, most likely by PKC-dependent activation of NAD(P)H oxidase, thus providing a potential explanation for the presence of oxidative stress and endothelial dysfunction in various forms of hypertension and the vasculoprotective effect of antihypertensive agents of different mechanisms of action.
Isthmin is a novel vascular permeability inducer that functions through cell-surface GRP78-mediated Src activation
Authors: Shruthi Venugopal, Mo Chen, Wupeng Liao, Shi Yin Er, Wai-Shiu Fred Wong, Ruowen Ge
Journal: Cardiovascular Research (2015)

Isthmin (ISM) is a recently identified 60 kDa secreted angiogenesis inhibitor. Two cell-surface receptors for ISM have been defined, the high-affinity glucose-regulated protein 78 kDa (GRP78) and the low-affinity αvβ5 integrin. As αvβ5 integrin plays an important role in pulmonary vascular permeability (VP) and ISM is highly expressed in mouse lung, we sought to clarify the role of ISM in VP. Recombinant ISM (rISM) dose-dependently enhances endothelial monolayer permeability in vitro and local dermal VP when administered intradermally in mice. Systemic rISM administration through intravenous injection leads to profound lung vascular hyperpermeability but not in other organs. Mechanistic investigations using molecular, biochemical approaches and specific chemical inhibitors revealed that ISM-GRP78 interaction triggers a direct interaction between GRP78 and Src, leading to Src activation and subsequent phosphorylation of adherens junction proteins and loss of junctional proteins from inter-endothelial junctions, resulting in enhanced VP. Dynamic studies of Src activation, VP and apoptosis revealed that ISM induces VP directly via Src activation while apoptosis contributes indirectly only after prolonged treatment. Furthermore, ISM is significantly up-regulated in lipopolysaccharide (LPS)-treated mouse lung. Blocking cell-surface GRP78 by systemic infusion of anti-GRP78 antibody significantly attenuates pulmonary vascular hyperpermeability in LPS-induced acute lung injury (ALI) in mice. ISM is a novel VP inducer that functions through cell-surface GRP78-mediated Src activation as well as induction of apoptosis. It induces a direct GRP78-Src interaction, leading to cytoplasmic Src activation. ISM contributes to pulmonary vascular hyperpermeability of LPS-induced ALI in mice.
Acute myocardial infarction: a comparison of short-term survival in national outcome registries in Sweden and the UK
Authors: Sheng-Chia Chung, Rolf Gedeborg, Owen Nicholas, Stefan James, Anders Jeppsson, Charles Wolfe, Peter Heuschmann, Lars Wallentin, John Deanfield, Adam Timmis, Tomas Jernberg, Harry Hemingway
Journal: The Lancet (2014)
Never-Smoking Senile-Onset Asthmatics Show Atypical and Mild Asthma Symptoms
Authors: C. Oshikata, M. Taniguchi, Y. Takeuchi, E. Ono, T. Tsuburai, N. Tsurikisawa, M. Ohtomo, Y. Maeda, A. Mori, M. Hasegawa, H. Mita, K. Akiyama
Journal: Journal of Allergy and Clinical Immunology (2006)
Renalase Protects against Ischemic AKI
Authors: H. Thomas Lee, Joo Yun Kim, Mihwa Kim, Peili Wang, Lieqi Tang, Sara Baroni, Vivette D. D’Agati, Gary V. Desir
Journal: Journal of the American Society of Nephrology (2013)

Elevated levels of plasma catecholamines accompany ischemic AKI, possibly contributing the inflammatory response. Renalase, an amine oxidase secreted by the proximal tubule, degrades circulating catecholamines and reduces myocardial necrosis, suggesting that it may protect against renal ischemia reperfusion injury. Here, mice subjected to renal ischemia reperfusion injury had significantly lower levels of renalase in the plasma and kidney compared with sham-operated mice. Consistent with this, plasma NE levels increased significantly after renal ischemia reperfusion injury. Furthermore, renal tubular inflammation, necrosis, and apoptosis were more severe and plasma catecholamine levels were higher in renalase-deficient mice subjected to renal ischemia reperfusion compared with wild-type mice. Administration of recombinant human renalase reduced plasma catecholamine levels and ameliorated ischemic AKI in wild-type mice. Taken together, these data suggest that renalase protects against ischemic AKI by reducing renal tubular necrosis, apoptosis, and inflammation, and that plasma renalase might be a biomarker for AKI. Recombinant renalase therapy may have potential for the prevention and treatment of AKI.
Checkpoint Kinase 2–Mediated Phosphorylation of BRCA1 Regulates the Fidelity of Nonhomologous End-Joining
Authors: Jing Zhuang, Junran Zhang, Henning Willers, Hong Wang, Jay H. Chung, Dik C. van Gent, Dennis E. Hallahan, Simon N. Powell, Fen Xia
Journal: Cancer Research (2006)

Abstract The tumor suppressor gene BRCA1 maintains genomic integrity by protecting cells from the deleterious effects of DNA double-strand breaks (DSBs). Through its interactions with the checkpoint kinase 2 (Chk2) kinase and Rad51, BRCA1 promotes homologous recombination, which is typically an error-free repair process. In addition, accumulating evidence implicates BRCA1 in the regulation of nonhomologous end-joining (NHEJ), which may involve precise religation of the DSB ends if they are compatible (i.e., error-free repair) or sequence alteration upon rejoining (i.e., error-prone or mutagenic repair). However, the precise role of BRCA1 in regulating these different subtypes of NHEJ is not clear. We provide here the genetic and biochemical evidence to show that BRCA1 promotes error-free rejoining of DSBs in human breast carcinoma cells while suppressing microhomology-mediated error-prone end-joining and restricting sequence deletion at the break junction during repair. The repair spectrum in BRCA1-deficient cells was characterized by an increase in the formation of &amp;gt;2 kb deletions and in the usage of long microhomologies distal to the break site, compared with wild-type (WT) cells. This error-prone repair phenotype could also be revealed by disruption of the Chk2 phosphorylation site of BRCA1, or by expression of a dominant-negative kinase-dead Chk2 mutant in cells with WT BRCA1. We suggest that the differential control of NHEJ subprocesses by BRCA1, in concert with Chk2, reduces the mutagenic potential of NHEJ, thereby contributing to the prevention of familial breast cancers. (Cancer Res 2006; 66(3): 1401-8)