tbuckley/cabot-search huggingface dataset:
Advances in understanding the cell types and approaches used for generating induced pluripotent stem cells
Authors: Jun Li, Wei Song, Guangjin Pan, Jun Zhou
Journal: Journal of Hematology & Oncology (2014)

Successfully reprogramming somatic cells to a pluripotent state generates induced pluripotent stem (iPS) cells (or iPSCs), which have extensive self-renewal capacity like embryonic stem cells (ESCs). iPSCs can also generate daughter cells that can further undergo differentiation into various lineages or terminally differentiate to reach their final functional state. The discovery of how to produce iPSCs opened a new field of stem cell research with both intellectual and therapeutic benefits. The huge potential implications of disease-specific or patient-specific iPSCs have impelled scientists to solve problems hindering their applications in clinical medicine, especially the issues of convenience and safety. To determine the range of tissue types amenable to reprogramming as well as their particular characteristics, cells from three embryonic germ layers have been assessed, and the advantages that some tissue origins have over fibroblast origins concerning efficiency and accessibility have been elucidated. To provide safe iPSCs in an efficient and convenient way, the delivery systems and combinations of inducing factors as well as the chemicals used to generate iPSCs have also been significantly improved in addition to the efforts on finding better donor cells. Currently, iPSCs can be generated without c-Myc and Klf4 oncogenes, and non-viral delivery integration-free chemically mediated reprogramming methods have been successfully employed with relatively satisfactory efficiency. This paper will review recent advances in iPS technology by highlighting tissue origin and generation of iPSCs. The obstacles that need to be overcome for clinical applications of iPSCs are also discussed.
Joint Distribution of Non-HDL and LDL Cholesterol and Coronary Heart Disease Risk Prediction Among Individuals With and Without Diabetes
Authors: Jian Liu, Christopher Sempos, Richard P. Donahue, Joan Dorn, Maurizio Trevisan, Scott M. Grundy
Journal: Diabetes Care (2005)

OBJECTIVE—To assess coronary heart disease (CHD) risk within levels of the joint distribution of non-HDL and LDL cholesterol among individuals with and without diabetes. RESEARCH DESIGN AND METHODS—We used four publicly available data sets for this pooled post hoc analysis and confined the eligible subjects to white individuals aged ≥30 years and free of CHD at baseline (12,660 men and 6,721 women). Diabetes status was defined as either “reported by physician-diagnosed and on medication” or having a fasting glucose level ≥126 mg/dl at the baseline examination. The primary end point was CHD death. Within diabetes categories, risk was assessed based on lipid levels (in mg/dl): non-HDL &amp;lt;130 and LDL &amp;lt;100 (group 1); non-HDL &amp;lt;130 and LDL ≥100 (group 2); non-HDL ≥130 and LDL &amp;lt;100 (group 3); and non-HDL ≥130 and LDL ≥100 (group 4). Group 1 within those without diabetes was the overall reference group. RESULTS—Of the subjects studied, ∼6% of men and 4% of women were defined as having diabetes. A total of 773 CHD deaths occurred during the average 13 years of follow-up time. A Cox proportional hazard model was used to estimate the relative risk (RR) of CHD death. Those with diabetes had a 200% higher RR than those without diabetes. In a multivariate model, CHD risk in those with diabetes did not increase with increasing LDL, whereas it did increase with increasing non-HDL: RR (95% confidence interval) for group 1: 5.7 (2.0–16.8); group 2: 5.7 (1.6–20.7); group 3: 7.2 (2.6–19.8); and group 4: 7.1 (3.7–13.6). CONCLUSIONS—Non-HDL is a stronger predictor of CHD death among those with diabetes than LDL and should be given more consideration in the clinical approach to risk reduction among diabetic patients.
Oncogenes and Angiogenesis: Down-regulation of Thrombospondin-1 in Normal Fibroblasts Exposed to Factors from Cancer Cells Harboring Mutant Ras
Authors: Wojciech Kalas, Joanne L. Yu, Chloe Milsom, Jack Rosenfeld, Robert Benezra, Paul Bornstein, Janusz Rak
Journal: Cancer Research (2005)

Abstract The onset of angiogenesis in cancer often involves down-regulation of endogenous angiogenesis inhibitors, of which thrombospondin-1 (TSP-1) is a paradigm. As this effect is thought to occur under the influence of transforming genetic lesions (e.g., expression of the mutant ras oncogene), its nature is regarded as intrinsic to cancer cells themselves. Here, we show that ras-transformed cancer cells can also induce TSP-1 down-regulation in their adjacent nontransformed stromal fibroblasts, but not in endothelial cells, in a paracrine and distance-dependent manner. Indeed, several H-ras-expressing fibrosarcoma (528ras1, B6ras, and NIH3T3Ras) and carcinoma (DLD-1 and IEC18Ras3) cells were found to release soluble factors capable of suppressing TSP-1 protein, mRNA, and promoter activity in nontumorigenic, immortalized dermal fibroblastic cell lines in culture (e.g., in fibroblasts expressing enhanced green fluorescent protein/TSP-1 reporter). This effect was abrogated in Id1−/− fibroblasts. At least two low molecular weight (&amp;lt;3 kDa), heat-labile, and trypsin-resistant mediators of TSP-1 suppression were found to be released from 528ras1 cells. Their effects on normal fibroblasts were inhibited (albeit to different extents) by pertussis toxin and, in one case, by dimethylsphingosine, none of which affected TSP-1 expression by 528ras1 cells. Collectively, our study suggests that the effect of mutant ras on tumor neovascularization is not limited to changes in angiogenic properties of cancer cells themselves. Rather, mutant ras, through a different signaling mechanism, may modulate the properties of the adjacent normal stroma, thus eliciting a proangiogenic field effect.
Air conditioning and source-specific particles as modifiers of the effect of PM(10) on hospital admissions for heart and lung disease.
Authors: Nicole A H Janssen, Joel Schwartz, Antonella Zanobetti, Helen H Suh
Journal: Environmental Health Perspectives (2002)

Studies on acute effects of particulate matter (PM) air pollution show significant variability in exposure-effect relations among cities. Recent studies have shown an influence of ventilation on personal/indoor-outdoor relations and stronger associations of adverse effects with combustion-related particles. We evaluated whether differences in prevalence of air conditioning (AC) and/or the contribution of different sources to total PM(10) emissions could partly explain the observed variability in exposure-effect relations. We used regression coefficients of the relation between PM(10) and hospital admissions for chronic obstructive pulmonary disease (COPD), cardiovascular disease (CVD), and pneumonia from a recent study in 14 U.S. cities. We obtained data on the prevalence of AC from the 1993 American Housing Survey and data on PM(10) emissions by source category, vehicle miles traveled (VMT), and population density from the U.S. EPA. We analyzed data using meta-regression techniques. PM(10) regression coefficients for CVD and COPD decreased significantly with increasing percentage of homes with central AC when cities were stratified by whether their PM(10) concentrations peaked in winter or non-winter months. PM(10) coefficients for CVD increased significantly with increasing percentage of PM(10) emission from highway vehicles, highway diesels, oil combustion, metal processing, decreasing percentage of PM(10) emission from fugitive dust, and increasing population density and VMT/mile(2). In multivariate analysis, only percentage of PM(subscript)10(/subscript) from highway vehicles/diesels and oil combustion remained significant. For COPD and pneumonia, associations were less significant but the patterns of the associations were similar to that for CVD. The results suggest that air conditioning and proportion of especially traffic-related particles significantly modify the effect of PM(10) on hospital admissions, especially for CVD.
Structure of a Complex of the Human α/β T Cell Receptor (TCR) HA1.7, Influenza Hemagglutinin Peptide, and Major Histocompatibility Complex Class II Molecule, HLA-DR4 (DRA0101 and DRB10401)
Authors: Jens Hennecke, Don C. Wiley
Journal: The Journal of Experimental Medicine (2002)

The α/β T cell receptor (TCR) HA1.7 specific for the hemagglutinin (HA) antigen peptide from influenza A virus is HLA-DR1 restricted but cross-reactive for the HA peptide presented by the allo-major histocompatibility complex (MHC) class II molecule HLA-DR4. We report here the structure of the HA1.7/DR4/HA complex, determined by X-ray crystallography at a resolution of 2.4 Å. The overall structure of this complex is very similar to the previously reported structure of the HA1.7/DR1/HA complex. Amino acid sequence differences between DR1 and DR4, which are located deep in the peptide binding groove and out of reach for direct contact by the TCR, are able to indirectly influence the antigenicity of the pMHC surface by changing the conformation of HA peptide residues at position P5 and P6. Although TCR HA1.7 is cross-reactive for HA presented by DR1 and DR4 and tolerates these conformational differences, other HA-specific TCRs are sensitive to these changes. We also find a dependence of the width of the MHC class II peptide-binding groove on the sequence of the bound peptide by comparing the HA1.7/DR4/HA complex with the structure of DR4 presenting a collagen peptide. This structural study of TCR cross-reactivity emphasizes how MHC sequence differences can affect TCR binding indirectly by moving peptide atoms.
Recognition of Breast Cancer Cells by CD8+ Cytotoxic T-Cell Clones Specific for NY-BR-1
Authors: Wei Wang, Jennifer Epler, Lupe G. Salazar, Stanley R. Riddell
Journal: Cancer Research (2006)

Abstract Immunotherapy for breast cancer using cytotoxic T cells (CTL) is hindered by the lack of well-characterized breast cancer antigens that are expressed in most breast tumor cells and recognized by CD8+ CTL. A recently described breast tissue differentiation antigen, NY-BR-1, is expressed in &amp;gt;80% breast tumors and elicits a humoral response in a subset of breast cancer patients. To identify potential NY-BR-1 epitopes that are recognized by CTL, CD8+ T cells were stimulated in vitro with autologous dendritic cells pulsed with NY-BR-1 peptides that were predicted to bind to HLA-A2. In multiple normal female donors and breast cancer patients, specific CD8+ CTL responses were detected by enzyme-linked immunospot assay against several NY-BR-1 peptides after two cycles of stimulation. CD8+ CTL clones against three NY-BR-1 epitopes were isolated and recognized peptide-pulsed target cells with high avidity. T-cell clones specific for one of the NY-BR-1 epitopes (p904) also recognized breast tumor cells expressing NY-BR-1, NY-BR-1− cells transfected with a cDNA encoding the NY-BR-1 protein, and autologous dendritic cells pulsed with opsonized NY-BR-1+ breast tumor cells. Taken together, these results show that the p904 epitope derived from NY-BR-1 is efficiently processed and presented endogenously and identify NY-BR-1 as a promising target for T-cell–based immunotherapy for breast cancer. (Cancer Res 2006; 66(13): 6826-33)
390 DIAGNOSTIC PERFORMANCE OF TRANSIENT ELASTOGRAPHY IS SIMILAR IN HEPATITIS B AND HEPATITIS C PATIENTS
Authors: A.C. Cardoso, R.J. Carvalho-Filho, C. Stern, A. Dipumpo, N. Giuily, M.-P. Ripault, T. Asselah, C. Castelnau, N. Boyer, T. Le Picart, M. Martinot-Peignoux, P. Bedossa, P. Marcellin
Journal: Journal of Hepatology (2010)
Guide to the Assessment of Physical Activity: Clinical and Research Applications
Authors: Scott J. Strath, Leonard A. Kaminsky, Barbara E. Ainsworth, Ulf Ekelund, Patty S. Freedson, Rebecca A. Gary, Caroline R. Richardson, Derek T. Smith, Ann M. Swartz
Journal: Circulation (2013)

The deleterious health consequences of physical inactivity are vast, and they are of paramount clinical and research importance. Risk identification, benchmarks, efficacy, and evaluation of physical activity behavior change initiatives for clinicians and researchers all require a clear understanding of how to assess physical activity. In the present report, we have provided a clear rationale for the importance of assessing physical activity levels, and we have documented key concepts in understanding the different dimensions, domains, and terminology associated with physical activity measurement. The assessment methods presented allow for a greater understanding of the vast number of options available to clinicians and researchers when trying to assess physical activity levels in their patients or participants. The primary outcome desired is the main determining factor in the choice of physical activity assessment method. In combination with issues of feasibility/practicality, the availability of resources, and administration considerations, the desired outcome guides the choice of an appropriate assessment tool. The decision matrix, along with the accompanying tables, provides a mechanism for this selection that takes all of these factors into account. Clearly, the assessment method adopted and implemented will vary depending on circumstances, because there is no single best instrument appropriate for every situation. In summary, physical activity assessment should be considered a vital health measure that is tracked regularly over time. All other major modifiable cardiovascular risk factors (diabetes mellitus, hypertension, hypercholesterolemia, obesity, and smoking) are assessed routinely. Physical activity status should also be assessed regularly. Multiple physical activity assessment methods provide reasonably accurate outcome measures, with choices dependent on setting-specific resources and constraints. The present scientific statement provides a guide to allow professionals to make a goal-specific selection of a meaningful physical activity assessment method.
Ugandan authorities deal with a mysterious ailment that leaves people nodding continuously
Authors: H. Wasswa
Journal: BMJ (2012)

Ugandan health authorities have launched strategies to deal with a strange disease that has left dozens of people dead in the north of the country and 3000 others, mostly children, nodding continuously.

The ailment, which was first detected in 2009, has mostly affected people in the three districts of Kitgum, Lamwo, and Pader but has also spread in recent weeks to two other districts of Agago and Amuru. Those affected become severely weak, have trembling …
Does cytomegalovirus cause glomerular injury in renal allograft recipients?
Authors: P E Birk, B M Chavers
Journal: Journal of the American Society of Nephrology (1997)

The case of a 16-yr-old woman who received an ABO-incompatible renal allograft for end-stage renal disease due to membranoproliferative glomerulonephritis type I is presented. The patient's posttransplant course was complicated by cytomegalovirus (CMV) infection and the rare finding of glomerular CMV inclusions on renal biopsy. This article focuses on the pathology and pathogenesis of glomerular injury associated with CMV infection in renal allograft recipients and also reviews the epidemiology, clinical implications, diagnosis and management of CMV infection in these patients.
Developmental affective neuroscience describes mechanisms at the core of dynamic systems theory
Authors: Allan N. Schore
Journal: Behavioral and Brain Sciences (2005)

Lewis describes the developmental core of dynamic systems theory. I offer recent data from developmental neuroscience on the sequential experience-dependent maturation of components of the limbic system over the stages of infancy. Increasing interconnectivity within the vertically integrated limbic system allows for more complex appraisals of emotional value. The earliest organization of limbic structures has an enduring impact on all later emotional processing.
Depressive Symptoms and 3-Year Mortality in Older Hospitalized Medical Patients
Authors: Kenneth E. Covinsky
Journal: Annals of Internal Medicine (1999)

Background: Depressive symptoms are common in hospitalized older persons. However, their relation to long-term mortality is unclear because few studies have rigorously considered potential confounders of the relation between depression and mortality, such as comorbid illness, functional impairment, and cognitive impairment. Objective: To measure the association between depressive symptoms and long-term mortality in hospitalized older persons. Design: Prospective cohort study. Setting: General medical service of a teaching hospital. Patients: 573 patients 70 years of age or older. Measurements: Depressive symptoms (Geriatric Depression Scale score), severity of acute illness (Acute Physiology and Chronic Health Evaluation II score), burden of comorbid illness (Charlson comorbidity index score), physical function (a nurse assessed dependence in six activities of daily living), and cognitive function (modified Mini-Mental State Examination) were measured at hospital admission. Mortality over the 3 years after admission was determined from the National Death Index. Mortality rates among patients with six or more depressive symptoms were compared with those among patients with five or fewer symptoms. Results: The mean age of the patients was 80 years; 68% of patients were women. Patients with six or more depressive symptoms had greater comorbid illness, functional impairment, and cognitive impairment at admission than patients with fewer depressive symptoms. Three-year mortality was higher in patients with six or more depressive symptoms (56% compared with 40%; hazard ratio, 1.56 [95% CI, 1.22 to 2.00]; P < 0.001). After adjustment for age, acute illness severity, comorbid illness, functional impairment, and cognitive impairment at the time of admission, patients with six or more depressive symptoms continued to have a higher mortality rate during the 3 years after admission (hazard ratio, 1.34 [CI, 1.03 to 1.73]). Although depressive symptoms contributed less to the mortality rate than did the total burden of comorbid medical illnesses, the excess mortality rate associated with depressive symptoms was greater than that conferred by one additional comorbid medical condition. Conclusions: Depressive symptoms are associated with long-term mortality in older patients hospitalized with medical illnesses. This association is not fully explained by greater levels of comorbid illness, functional impairment, and cognitive impairment in patients with more depressive symptoms.
The role of sports physiotherapy at the London 2012 Olympic Games
Authors: Marie-Elaine Grant, Kathrin Steffen, Philip Glasgow, Nicola Phillips, Lynn Booth, Marie Galligan
Journal: British Journal of Sports Medicine (2013)

There is a lack of information on the utilisation of physiotherapy services at the Olympic Games.To better understand the athlete and non-athlete requirements of the physiotherapy services at the Olympic Village Polyclinic during the London 2012 Olympic Games.From 16 July to 14 August 2012, physiotherapy encounters for athletes and non-athletes (National Olympic Committee (NOC) team officials, coaches, team managers, workforce, Olympic family, technical officials and press) were recorded on the ATOS electronic medical records system at the polyclinic in the main Athletes' Village in Stratford.Of the 1778 encounters, 1219 (69%) were administered to athletes and 559 (31%) to non-athletes. The anatomical areas most frequently recorded at the first visits for athletes were knee (15.4%), lumbar spine/lower back (15.2%) and upper leg (12.6%) and that for non-athletes were lumbar spine/lower back (19.8%), knee (15.8%) and neck/cervical spine. Muscle (33.3%) and joint injuries (24.8%) were the most common diagnoses in athletes and non-athletes (24.4% and 30.1%). The five most frequently used treatment modalities were therapeutic soft tissue techniques (23.3%), mobilisation techniques (21.8%), taping (8.9%), cryotherapy (6.9%) and exercise prescription (6.4%). The most common cause of athletes' injuries was overuse (43.6%).This study of the London 2012 Olympic Games workload highlights the physiotherapy needs of athletes as well as non-athletes and identifies the high numbers of pre-existing and overuse injuries in this setting, providing an insight into the reasons why the athletes seek physiotherapy support during the Olympic Games.
Hormone receptors do not predict the HER2/neu status in all age groups of women with an operable breast cancer
Authors: H.J. Huang, P. Neven, M. Drijkoningen, R. Paridaens, H. Wildiers, E. Van Limbergen, P. Berteloot, F. Amant, I. Vergote, M.R. Christiaens
Journal: Annals of Oncology (2005)
Granulocyte-colony stimulating factor for hematopoietic stem cell donation from healthy female donors during pregnancy and lactation: what do we know?
Authors: Ilias Pessach, Avichai Shimoni, Arnon Nagler
Journal: Human Reproduction Update (2013)

Hematopoietic growth factors (HGFs) are mostly used as supportive measures to reduce infectious complications associated with neutropenia. Over the past decade, the use of HGFs became a common method for mobilizing human CD34+ stem cells, either for autologous or allogeneic transplantation. However, since their introduction the long-term safety of the procedure has become a major focus of discussion and research. Most information refers to healthy normal donors and data concerning pregnant and lactating women are scarce. The clinical question, which is the core of this review, is whether stem cell donation, preceded by administration of granulocyte-colony stimulating factor (G-CSF) for mobilization, is a safe procedure for pregnant donors. Literature searches were performed in Pubmed for English language articles published before the end of May 2012, focusing on G-CSF administration during pregnancy, lactation and hematopoietic stem cell donation. Searches included animal and human studies. Data from animals (n = 15 studies) and women (n = 46 studies) indicate that G-CSF crosses the placenta, stimulates fetal granulopoiesis, improves neonatal survival mostly for very immature infants, promotes trophoblast growth and placental metabolism and has an anti-abortive role. Granulocyte macrophage-CSF is a key cytokine in the maternal immune tolerance towards the implanted embryo and exerts protective long-term programming effects to preimplantation embryos. The available data suggest that probably CSFs should not be administered during the time of most active organogenesis (first trimester), except perhaps for the first week during which implantation takes place. Provided CSF is administered during the second and third trimesters, it appears to be safe, and pregnant women receiving the CSF treatment can become hematopoietic stem cell donors. There are also risks related to the anesthesia, which is required for the bone marrow aspiration. During lactation, there should be a period of at least 3 days to allow for clearance of CSF from milk before resuming breast feeding. With regard to teratogenicity or leukaemogenity, in non-pregnant or non-lactating women reports show that CSF administration is associated with a risk for leukemia; however, this risk is not higher compared with the control population. The information available to date indicates that administration of CSF in general, and G-CSF in particular, is safe and healthy pregnant women can serve as donors of either bone marrow or peripheral blood stem cells. However, the clinical experience is rather limited and therefore until more data become available, G-CSF should not be used during pregnancy and lactation when other therapeutic options, instead of stem cell transplantation, are available.