tbuckley/cabot-search huggingface dataset:
Human circulating AC133+ stem cells restore dystrophin expression and ameliorate function in dystrophic skeletal muscle
Authors: Yvan Torrente, Marzia Belicchi, Maurilio Sampaolesi, Federica Pisati, Mirella Meregalli, Giuseppe D’Antona, Rossana Tonlorenzi, Laura Porretti, Manuela Gavina, Kamel Mamchaoui, Maria Antonietta Pellegrino, Denis Furling, Vincent Mouly, Gillian S. Butler-Browne, Roberto Bottinelli, Giulio Cossu, Nereo Bresolin
Journal: Journal of Clinical Investigation (2004)

Duchenne muscular dystrophy (DMD) is a common X-linked disease characterized by widespread muscle damage that invariably leads to paralysis and death. There is currently no therapy for this disease. Here we report that a subpopulation of circulating cells expressing AC133, a well-characterized marker of hematopoietic stem cells, also expresses early myogenic markers. Freshly isolated, circulating AC133+ cells were induced to undergo myogenesis when cocultured with myogenic cells or exposed to Wnt-producing cells in vitro and when delivered in vivo through the arterial circulation or directly into the muscles of transgenic scid/mdx mice (which allow survival of human cells). Injected cells also localized under the basal lamina of host muscle fibers and expressed satellite cell markers such as M-cadherin and MYF5. Furthermore, functional tests of injected muscles revealed a substantial recovery of force after treatment. As these cells can be isolated from the blood, manipulated in vitro, and delivered through the circulation, they represent a possible tool for future cell therapy applications in DMD disease or other muscular dystrophies.
Vitamin A Metabolism, Action, and Role in Skeletal Homeostasis
Authors: H. Herschel Conaway, Petra Henning, Ulf H. Lerner
Journal: Endocrine Reviews (2013)

Vitamin A (retinol) is ingested as either retinyl esters or carotenoids and metabolized to active compounds such as 11-cis-retinal, which is important for vision, and all-trans-retinoic acid, which is the primary mediator of biological actions of vitamin A. All-trans-retinoic acid binds to retinoic acid receptors (RARs), which heterodimerize with retinoid X receptors. RAR-retinoid X receptor heterodimers function as transcription factors, binding RAR-responsive elements in promoters of different genes. Numerous cellular functions, including bone cell functions, are mediated by vitamin A; however, it has long been recognized that increased levels of vitamin A can have deleterious effects on bone, resulting in increased skeletal fragility. Bone mass is dependent on the balance between bone resorption and bone formation. A decrease in bone mass may be caused by either an excess of resorption or decreased bone formation. Early studies indicated that the primary skeletal effect of vitamin A was to increase bone resorption, but later studies have shown that vitamin A can not only stimulate the formation of bone-resorbing osteoclasts but also inhibit their formation. Effects of vitamin A on bone formation have not been studied in as great a detail and are not as well characterized as effects on bone resorption. Several epidemiological studies have shown an association between vitamin A, decreased bone mass, and osteoporotic fractures, but the data are not conclusive because other studies have found no associations, and some studies have suggested that vitamin A primarily promotes skeletal health. In this presentation, we have summarized how vitamin A is absorbed and metabolized and how it functions intracellularly. Vitamin A deficiency and excess are introduced, and detailed descriptions of clinical and preclinical studies of the effects of vitamin A on the skeleton are presented.
Lung cancer screening by low-dose spiral computed tomography
Authors: R.J. van Klaveren, J.D.F. Habbema, J.H. Pedersen, H.J. de Koning, M. Oudkerk, H.C. Hoogsteden
Journal: European Respiratory Journal (2001)

The poor prognosis of lung cancer has barely changed in the last decades, but the prognosis is better when the disease is detected earlier. Lung cancer screening by chest radiography did not lead to a decrease in lung cancer mortality, presumably because the chest radiograph is a poor screening tool with low sensitivity. With the advent of the low-dose spiral computed tomography (CT) scan it has become feasible to detect early invasive stage I lung cancer in 80–90% of cases. This technique could possibly decrease lung cancer mortality, but the extent of this effect is as yet unknown, and whether lung cancer screening will be cost-effective is yet to be determined. These questions can only be resolved in a randomized controlled trial with lung cancer mortality as an unbiased end-point. In this review, the initiatives to evaluate low dose spiral CT screening for lung cancer in Japan, USA and Europe are presented. In the USA and Japan, evaluation is in one-armed studies, whereas in many European countries randomized trials are now being planned and several one-armed studies have been initiated. A formal collaboration among these countries has now been set up. It is strongly recommended that lung cancer screening be evaluated in randomized trials in order to allow evidence-based health policy decisions to be made on this subject.
Pioglitazone Modulates Vascular Inflammation in Atherosclerotic Rabbits
Authors: Esad Vucic, Stephen D. Dickson, Claudia Calcagno, James H.F. Rudd, Erin Moshier, Katsumi Hayashi, Jessica S. Mounessa, Michelle Roytman, Matthew J. Moon, James Lin, Sotirios Tsimikas, Edward A. Fisher, Klaas Nicolay, Valentin Fuster, Zahi A. Fayad
Journal: JACC. Cardiovascular imaging (2011)
The pulmonary physician in critical care * 5: Acute lung injury and the acute respiratory distress syndrome: definitions and epidemiology
Authors: K Atabai
Journal: Thorax (2002)

An understanding of the epidemiology of ALI/ARDS and the effects of treatment have been hampered by the lack of a uniform definition of the syndrome. Various definitions have been proposed, and these are reviewed with particular attention to how changes in definition have affected our understanding of the natural history and treatment options for the condition.
Gray Matter Abnormalities in Childhood Maltreatment: A Voxel-Wise Meta-Analysis
Authors: Lena Lim, Joaquim Radua, Katya Rubia
Journal: American Journal of Psychiatry (2014)

Objective Childhood maltreatment acts as a severe stressor that produces a cascade of physiological and neurobiological changes that lead to enduring alterations in brain structure. However, structural neuroimaging findings have been inconsistent. The authors conducted a meta-analysis of published whole-brain voxel-based morphometry studies in childhood maltreatment to elucidate the most robust volumetric gray matter abnormalities relative to comparison subjects to date. Method Twelve data sets were included, comprising 331 individuals (56 children/adolescents and 275 adults) with a history of childhood maltreatment and 362 comparison subjects (56 children/adolescents and 306 adults). Anisotropic effect size-signed differential mapping, a voxel-based meta-analytic method, was used to examine regions of smaller and larger gray matter volumes in maltreated individuals relative to comparison subjects. Results Relative to comparison subjects, individuals exposed to childhood maltreatment exhibited significantly smaller gray matter volumes in the right orbitofrontal/superior temporal gyrus extending to the amygdala, insula, and parahippocampal and middle temporal gyri and in the left inferior frontal and postcentral gyri. They had larger gray matter volumes in the right superior frontal and left middle occipital gyri. Deficits in the right orbitofrontal-temporal-limbic and left inferior frontal regions remained in a subgroup analysis of unmedicated participants. Abnormalities in the left postcentral and middle occipital gyri were found only in older maltreated individuals relative to age-matched comparison subjects. Conclusions The findings demonstrate that the most consistent gray matter abnormalities in individuals exposed to childhood maltreatment are in relatively late-developing ventrolateral prefrontal-limbic-temporal regions that are known to mediate late-developing functions of affect and cognitive control, which are typically compromised in this population.
Cross-linking FcεRI Alters Interferon Responses to Rhinovirus Infection
Authors: S.R. Durrani, D.J. Montville, V. Rajamanickam, N.C. Levinsky, C.J. Tisler, R.E. Gangnon, M.A. Gill, D.J. Jackson
Journal: Journal of Allergy and Clinical Immunology (2011)
A Large-Scale, Consortium-Based Genomewide Association Study of Asthma
Authors: Miriam F. Moffatt, Ivo G. Gut, Florence Demenais, David P. Strachan, Emmanuelle Bouzigon, Simon Heath, Erika von Mutius, Martin Farrall, Mark Lathrop, William O.C.M. Cookson
Journal: New England Journal of Medicine (2010)

Susceptibility to asthma is influenced by genes and environment; implicated genes may indicate pathways for therapeutic intervention. Genetic risk factors may be useful in identifying subtypes of asthma and determining whether intermediate phenotypes, such as elevation of the total serum IgE level, are causally linked to disease.
Human Papillomavirus and Oral Cancer: The International Agency for Research on Cancer Multicenter Study
Authors: R. Herrero
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: Human papillomavirus (HPV), the causal agent of cervical cancer, appears to be involved in the etiology of cancer of the oral cavity and oropharynx. To investigate these associations, we conducted a multicenter case-control study of cancer of the oral cavity and oropharynx in nine countries. Methods: We recruited 1670 case patients (1415 with cancer of the oral cavity and 255 with cancer of the oropharynx) and 1732 control subjects and obtained an interview, oral exfoliated cells, and blood from all participants and fresh biopsy specimens from case patients. HPV DNA was detected by polymerase chain reaction (PCR). Antibodies against HPV16 L1, E6, and E7 proteins in plasma were detected with enzyme-linked immunosorbent assays. Multivariable models were used for case-control and case-case comparisons. Results: HPV DNA was detected in biopsy specimens of 3.9% (95% confidence interval [CI] = 2.5% to 5.3%) of 766 cancers of the oral cavity with valid PCR results and 18.3% (95% CI = 12.0% to 24.7%) of 142 cancers of the oropharynx (oropharynx and tonsil combined) with valid PCR results. HPV DNA in cancer biopsy specimens was detected less frequently among tobacco smokers and paan chewers and more frequently among subjects who reported more than one sexual partner or who practiced oral sex. HPV16 DNA was found in 94.7% of HPV DNA-positive case patients. HPV DNA in exfoliated cells was not associated with cancer risk or with HPV DNA detection in biopsy specimens. Antibodies against HPV16 L1 were associated with risk for cancers of the oral cavity (odds ratio [OR] = 1.5, 95% CI = 1.1 to 2.1) and the oropharynx (OR = 3.5, 95% CI = 2.1 to 5.9). Antibodies against HPV16 E6 or E7 were also associated with risk for cancers of the oral cavity (OR = 2.9, 95% CI = 1.7 to 4.8) and the oropharynx (OR = 9.2, 95% CI = 4.8 to 17.7). Conclusions: HPV appears to play an etiologic role in many cancers of the oropharynx and possibly a small subgroup of cancers of the oral cavity. The most common HPV type in genital cancers (HPV16) was also the most common in these tumors. The mechanism of transmission of HPV to the oral cavity warrants further investigation.
Specific lysis of allogeneic cells after activation of CD3- lymphocytes in mixed lymphocyte culture.
Authors: E Ciccone, O Viale, D Pende, M Malnati, R Biassoni, G Melioli, A Moretta, E O Long, L Moretta
Journal: The Journal of Experimental Medicine (1988)

Human CD3- lymphocyte populations were obtained by treating peripheral blood lymphocytes with mAbs directed to CD3, CD4, and CD8 surface antigens. The resulting populations were cultured with irradiated allogeneic cells; at day 4, 100 U/ml IL-2 were added and cultures continued for an additional 10 d. The resulting populations were CD3-CD2+CD7+ and displayed cytolytic activity against PHA-induced blast cells bearing the stimulating alloantigens but not against autologous or unrelated allogeneic blast cells. When CD3- populations were cultured with irradiated autologous cells, no cytolytic activity could be detected either against autologous or allogeneic blast cells. On the other hand, K562 target cells were lysed by both MLC-derived CD3- cell populations regardless of the origin (autologous or allogeneic) of the stimulating cells. CD3- clones were further derived from MLC-stimulated CD3- populations. These clones displayed a cytolytic pattern similar to the original MLC populations as only specific PHA blasts could be lysed. These clones did not express detectable surface TCR-alpha/beta or -gamma/delta molecules and lacked productive mRNA for TCR alpha and beta chains, while small amounts of TCR-gamma mRNA were detectable in one of four clones tested. Also mRNA for CD3 gamma and delta chains were undetectable in all clones, however, CD3 epsilon mRNA was consistently present.
Survival and Long-term Outcomes Following Bioprosthetic vs Mechanical Aortic Valve Replacement in Patients Aged 50 to 69 Years
Authors: Yuting P. Chiang, Joanna Chikwe, Alan J. Moskowitz, Shinobu Itagaki, David H. Adams, Natalia N. Egorova
Journal: JAMA (2014)

IMPORTANCEThe choice between bioprosthetic and mechanical aortic valve replacement in younger patients is controversial because long-term survival and major morbidity are poorly characterized.OBJECTIVE To quantify survival and major morbidity in patients aged 50 to 69 years undergoing aortic valve replacement. DESIGN, SETTING, AND PARTICIPANTSRetrospective cohort analysis of 4253 patients aged 50 to 69 years who underwent primary isolated aortic valve replacement using bioprosthetic vs mechanical valves in New York State from 1997 through 2004, identified using the Statewide Planning and Research Cooperative System.Median follow-up time was 10.8 years (range, 0 to 16.9 years); the last follow-up date for mortality was November 30, 2013.Propensity matching yielded 1001 patient pairs. MAIN OUTCOMES AND MEASURESPrimary outcome was all-cause mortality; secondary outcomes were stroke, reoperation, and major bleeding. RESULTSNo differences in survival or stroke rates were observed in patients with bioprosthetic compared with mechanical valves.Actuarial 15-year survival was 60.6% (95% CI, 56.3%-64.9%) in the bioprosthesis group compared with 62.1% (95% CI, 58.2%-66.0%) in the mechanical prosthesis group (hazard ratio, 0.97 [95% CI, 0.83-1.14]).The 15-year cumulative incidence of stroke was 7.7% (95% CI, 5.7%-9.7%) in the bioprosthesis group and 8.6% (95% CI, 6.2%-11.0%) in the mechanical prosthesis group (hazard ratio, 1.04 [95% CI, 0.75-1.43).The 15-year cumulative incidence of reoperation was higher in the bioprosthesis group (12.1% [95% CI, 8.8%-15.4%]vs 6.9% [95% CI, 4.2%-9.6%];hazard ratio, 0.52 [95% CI, 0.36-0.75]).The 15-year cumulative incidence of major bleeding was higher in the mechanical prosthesis group (13.0%[95% CI, 9.9%-16.1%]vs 6.6% [95% CI, 4.8%-8.4%];hazard ratio, 1.75 [95% CI, 1.27-2.43]).The 30-day mortality rate was 18.7% after stroke, 9.0% after reoperation, and 13.2% after major bleeding.CONCLUSIONS AND RELEVANCE Among propensity-matched patients aged 50 to 69 years who underwent aortic valve replacement with bioprosthetic compared with mechanical valves, there was no significant difference in 15-year survival or stroke.Patients in the bioprosthetic valve group had a greater likelihood of reoperation but a lower likelihood of major bleeding.These findings suggest that bioprosthetic valves may be a reasonable choice in patients aged 50 to 69 years.
Positive immunostaining with MLuC1 of bone marrow aspirate predicts poor outcome in patients with small-cell lung cancer
Authors: F Pasini, G Pelosi, G Verlato, G Guidi, F Pavanel, D Tummarello, A Masotti, G L Cetto
Journal: Annals of Oncology (1998)

Immunocytochemistry has been proven able to identify tumor cells in bone marrow aspirate (BMA) of patients with SCLC. However, few data exist about the clinical significance of the procedure.108 BMA taken from 60 patients were incubated with the MoAb MLuC1 (cluster 6) and stained by the APAAP (alkaline phosphatase-antialkaline phosphatase) method. The serum levels of LDH, TPA, NSE and CEA were also studied in relation to bone marrow involvement by means of discriminant analysis.Immunocytochemistry of the aspirate with MLuC1 detected positive cells in 23 patients (38%) (38 of 108 samples) vs. 13% of the conventional biopsies studied without MLuC1 (P < 0.001). With respect to bone marrow positivity, three groups of patients were identified: those with no positive cells in the aspirate and negative biopsy (group A); those with less than 10 positive cells in the aspirate and negative biopsy (group B); and those with more than 10 positive cells or clumps in the aspirate or positive biopsy (group C). Group C patients had poorer median survivals than those in the other two groups (5.5 vs. 11 months, respectively, P = 0.01). Discriminant analysis showed that the four serum markers were poor discriminators of the degree of bone marrow involvement, with only 55% of grouped cases being correctly classified.These results show that detection of bone marrow involvement i) can be improved by the use of MLuC1 ii) is not predictable by conventional tumor markers, and iii) is related to poor outcome.
Multicenter Phase II Trial of Immunotherapy With the Humanized Anti-CD22 Antibody, Epratuzumab, in Combination With Rituximab, in Refractory or Recurrent Non-Hodgkin's Lymphoma
Authors: Sandra J. Strauss, Frank Morschhauser, Juergen Rech, Roland Repp, Philippe Solal-Celigny, Pier L. Zinzani, Andreas Engert, Bernard Coiffier, Dieter F. Hoelzer, William A. Wegener, Nick K.W. Teoh, David M. Goldenberg, T. Andrew Lister
Journal: Journal of Clinical Oncology (2006)

A multicenter, single-arm study examining efficacy and toxicity of epratuzumab combined with rituximab was conducted in patients with recurrent or refractory non-Hodgkin's lymphoma.Sixty-five patients were enrolled; 34 patients with follicular lymphoma (FL), 15 patients with diffuse large B-cell lymphoma (DLBCL), and 16 patients with other lymphomas. The patients had received a median of two prior therapies (range, 1 to 4); 23% had received rituximab. Epratuzumab was given at 360 mg/m2 intravenously over 60 minutes followed by infusion of 375 mg/m2 rituximab, weekly for 4 consecutive weeks.Combination therapy was well tolerated without greater toxicity than rituximab alone. The objective response (OR) rate was 47% (30 of 64) in assessable patients (46%; 30 of 65 in all patients), being highest in FL (64%; 21 of 33) and DLBCL (47%; seven of 15), and with 24% (eight of 33) and 33% (five of 15) achieving complete response (CR) or complete response unconfirmed (CRu) in these two groups, respectively. Two of six patients with marginal zone lymphoma responded to treatment (one CR). There was a trend for the response rates to be higher in patients with low prognostic index scores (statistically significant with respect to the Follicular Lymphoma International Prognostic Index score in FL patients), with 12 FL patients and three DLBCL patients in groups 0 to 1 having OR (CR/CRu) rates of 83% (33%) and 100% (100%), respectively. The median duration of response was 16 months for FL, with five patients currently progression free for 18 months to 30 months, and 6 months for DLBCL, with two patients currently progression free for 12 months and 18 months.Epratuzumab combined with rituximab was well tolerated, demonstrating promising antilymphoma activity that warrants additional study.
GSK3 and p53 - is there a link in Alzheimer's disease?
Authors: Carole J Proctor, Douglas A Gray
Journal: Molecular Neurodegeneration (2010)

Recent evidence suggests that glycogen synthase kinase-3beta (GSK3beta) is implicated in both sporadic and familial forms of Alzheimer's disease. The transcription factor, p53 also plays a role and has been linked to an increase in tau hyperphosphorylation although the effect is indirect. There is also evidence that GSK3beta and p53 interact and that the activity of both proteins is increased as a result of this interaction. Under normal cellular conditions, p53 is kept at low levels by Mdm2 but when cells are stressed, p53 is stabilised and may then interact with GSK3beta. We propose that this interaction has an important contribution to cellular outcomes and to test this hypothesis we developed a stochastic simulation model.The model predicts that high levels of DNA damage leads to increased activity of p53 and GSK3beta and low levels of aggregation but if DNA damage is repaired, the aggregates are eventually cleared. The model also shows that over long periods of time, aggregates may start to form due to stochastic events leading to increased levels of ROS and damaged DNA. This is followed by increased activity of p53 and GSK3beta and a vicious cycle ensues.Since p53 and GSK3beta are both involved in the apoptotic pathway, and GSK3beta overactivity leads to increased levels of plaques and tangles, our model might explain the link between protein aggregation and neuronal loss in neurodegeneration.
Elucidation of the thromboregulatory role of CD39/ectoapyrase in the ischemic brain
Authors: David J. Pinsky, M. Johan Broekman, Jacques J. Peschon, Kim L. Stocking, Tomoyuki Fujita, Ravichandran Ramasamy, E. Sander Connolly, Judy Huang, Szilard Kiss, Yuan Zhang, Tanvir F. Choudhri, Ryan A. McTaggart, Hui Liao, Joan H.F. Drosopoulos, Virginia L. Price, Aaron J. Marcus, Charles R. Maliszewski
Journal: Journal of Clinical Investigation (2002)

Endothelial CD39 metabolizes ADP released from activated platelets. Recombinant soluble human CD39 (solCD39) potently inhibited ex vivo platelet aggregation in response to ADP and reduced cerebral infarct volumes in mice following transient middle cerebral artery occlusion, even when given 3 hours after stroke. Postischemic platelet and fibrin deposition were decreased and perfusion increased without increasing intracerebral hemorrhage. In contrast, aspirin did not increase postischemic blood flow or reduce infarction volume, but did increase intracerebral hemorrhage. Mice lacking the enzymatically active extracellular portion of the CD39 molecule were generated by replacement of exons 4-6 (apyrase-conserved regions 2-4) with a PGKneo cassette. Although CD39 mRNA 3' of the neomycin cassette insertion site was detected, brains from these mice lacked both apyrase activity and CD39 immunoreactivity. Although their baseline phenotype, hematological profiles, and bleeding times were normal, cd39(-/-) mice exhibited increased cerebral infarct volumes and reduced postischemic perfusion. solCD39 reconstituted these mice, restoring postischemic cerebral perfusion and rescuing them from cerebral injury. These data demonstrate that CD39 exerts a protective thromboregulatory function in stroke.