tbuckley/cabot-search huggingface dataset:
A distinct wave of human T cell receptor gamma/delta lymphocytes in the early fetal thymus: evidence for controlled gene rearrangement and cytokine production.
Authors: M S Krangel, H Yssel, C Brocklehurst, H Spits
Journal: The Journal of Experimental Medicine (1990)

The rearrangement and expression of human T cell receptor (TCR)-gamma and -delta gene segments in clonal and polyclonal populations of early fetal and postnatal human TCR-gamma/delta thymocytes were examined. The data suggest that the TCR-gamma and -delta loci rearrange in an ordered and coordinated fashion. Initial rearrangements at the TCR-delta locus join V delta 2 to D delta 3, and initial rearrangements at the TCR-gamma locus join downstream V gamma gene segments (V gamma 1.8 and V gamma 2) to upstream J gamma gene segments associated with C gamma 1. These rearrangements are characterized by minimal junctional diversity. At later times there is a switch at the TCR-delta locus such that V delta 1 is joined to upstream D delta gene segments, and a switch at the TCR-gamma locus such that upstream V gamma gene segments are joined to downstream J gamma gene segments associated with C gamma 2. These rearrangements are characterized by extensive junctional diversity. Programmed rearrangement explains in part the origin of discrete subpopulations of peripheral blood TCR-gamma/delta lymphocytes that have been defined in previous studies. In addition, cytokine production by early fetal and postnatal TCR-gamma/delta thymocyte clones was examined. Fetal thymocyte clones produced significant levels of IL-4 and IL-5 following stimulation, whereas postnatal thymocyte clones did not produce these cytokines. Thus, these cell populations may represent functionally distinct subsets as well.
Lineage Structure of the Human Antibody Repertoire in Response to Influenza Vaccination
Authors: Ning Jiang, Jiankui He, Joshua A. Weinstein, Lolita Penland, Sanae Sasaki, Xiao-Song He, Cornelia L. Dekker, Nai-Ying Zheng, Min Huang, Meghan Sullivan, Patrick C. Wilson, Harry B. Greenberg, Mark M. Davis, Daniel S. Fisher, Stephen R. Quake
Journal: Science Translational Medicine (2013)

High-throughput sequencing suggests age-related differences in the changes in the human antibody repertoire after influenza vaccination.
Unfavorable prognosis of elderly patients with early-stage extranodal nasal-type NK/T-cell lymphoma
Authors: Z.Y. Wang, Y.X. Li, H. Wang, W.H. Wang, J. Jin, Y.P. Liu, Y.W. Song, S.L. Wang, X.F. Liu, Z.H. Yu
Journal: Annals of Oncology (2010)
Altered Expression of Cell Cycle Proteins and Prolonged Duration of Cardiac Myocyte Hyperplasia in p27 <sup>KIP1</sup> Knockout Mice
Authors: Robert A. Poolman, Jian-Mei Li, Beatrice Durand, Gavin Brooks
Journal: Circulation Research (1999)

Abstract —The precise role of cell cycle–dependent molecules in controlling the switch from cardiac myocyte hyperplasia to hypertrophy remains to be determined. We report that loss of p27 KIP1 in the mouse results in a significant increase in heart size and in the total number of cardiac myocytes. In comparison to p27 KIP1 +/+ myocytes, the percentage of neonatal p27 KIP1 −/− myocytes in S phase was increased significantly, concomitant with a significant decrease in the percentage of G 0 /G 1 cells. The expressions of proliferating cell nuclear antigen, G 1 /S and G 2 /M phase–acting cyclins, and cyclin-dependent kinases (CDKs) were upregulated significantly in ventricular tissue obtained from early neonatal p27 KIP1 −/− mice, concomitant with a substantial decrease in the expressions of G 1 phase–acting cyclins and CDKs. Furthermore, mRNA expressions of the embryonic genes atrial natriuretic factor and α-skeletal actin were detectable at significant levels in neonatal and adult p27 KIP1 −/− mouse hearts but were undetectable in p27 KIP1 +/+ hearts. In addition, loss of p27 KIP1 was not compensated for by the upregulation of other CDK inhibitors. Thus, the loss of p27 KIP1 results in prolonged proliferation of the mouse cardiac myocyte and perturbation of myocyte hypertrophy.
Temporal Gradients in Shear, but Not Spatial Gradients, Stimulate Endothelial Cell Proliferation
Authors: Charles R. White, Mark Haidekker, Xuping Bao, John A. Frangos
Journal: Circulation (2001)

Background —The effect of temporal and spatial gradients in shear on primary human endothelial cell (HUVEC) proliferation was investigated. The sudden-expansion flow chamber (SEFC) model was used to differentiate the effect of temporal gradients in shear from that of spatial gradients. With a sudden onset of flow, cells are exposed to both temporal and spatial gradients of shear. The temporal gradients can be eliminated by slowly ramping up the flow. Methods and Results —HUVEC proliferation in the SEFC remained unstimulated when the onset of flow was slowly ramped. Sudden onset of flow stimulated a 105% increase of HUVEC proliferation (relative to ramped onset) within the region of flow reattachment. To further separate temporal and spatial gradients, a conventional parallel-plate flow chamber was used. A single 0.5-second impulse of 10 dyne/cm 2 increased HUVEC proliferation 54±3% relative to control. When flow was slowly ramped over 30 seconds, HUVEC proliferation was not significantly different from controls. Steady laminar shear over 20 minutes inhibited HUVEC proliferation relative to controls regardless of step (36±8%) or ramp (21±5%) onsets of flow. Conclusions —The results indicate that temporal gradients in shear stress stimulate endothelial cell proliferation, whereas spatial gradients affect endothelial proliferation no differently than steady uniform shear stress.
Detection of <i>Chlamydia pneumoniae</i> DNA in CD3+ Lymphocytes From Healthy Blood Donors and Patients With Coronary Artery Disease
Authors: Ravi Kaul, Janet Uphoff, Jean Wiedeman, Sanjay Yadlapalli, Wanda M. Wenman
Journal: Circulation (2000)

Background — Chlamydia pneumoniae is an intracellular bacterium responsible for respiratory tract infections. Recent studies have implicated this organism in the pathogenesis of atherosclerosis. Methods and Results —To address how the organism is transported from lungs to cardiac vessels, we characterized the cell population within peripheral blood mononuclear cells (PBMCs) that harbor C pneumoniae DNA. Adherent and nonadherent PBMCs from 28 patients with coronary artery disease (CAD) and 19 healthy blood donors were evaluated for the presence of C pneumoniae DNA by touchdown nested polymerase chain reaction (nPCR). Of the 28 patients, 10 (36%) had detectable PCR product in their nonadherent and 3 (10%) in their adherent PBMC population. C pneumoniae –specific PCR results were positive for 5 of 19 (26%) healthy blood donors. PCR positivity was detected only in the nonadherent cell population among this group of individuals. Fractionation of nonadherent PBMCs identified C pneumoniae –specific PCR signal among the CD3+ T-cell population exclusively. Of the 18 PCR-positive subjects (13 patients and 5 healthy control subjects), 67% (8 patients and 4 healthy blood donors) tested positive for C pneumoniae –specific IgG serology. Interestingly, 2 patients became PCR negative on a repeated blood draw 5 months after initial detection of C pneumoniae DNA despite retaining C pneumoniae –specific antibodies. Conclusions —Our results demonstrate marginally significant prevalence of C pneumoniae DNA in patients with CAD compared with healthy subjects ( P =0.082). In contrast, the prevalence of IgG seropositivity among the 2 groups did not reach statistical significance ( P =0.306). We also provide unequivocal evidence for the presence of C pneumoniae DNA predominantly among the circulating CD3+ T-cell population.
Estimating Amino Acid Substitution Models: A Comparison of Dayhoff's Estimator, the Resolvent Approach and a Maximum Likelihood Method
Authors: Tobias Müller, Rainer Spang, Martin Vingron
Journal: Molecular Biology and Evolution (2002)

Evolution of proteins is generally modeled as a Markov process acting on each site of the sequence. Replacement frequencies need to be estimated based on sequence alignments. Here we compare three approaches: First, the original method by Dayhoff, Schwartz, and Orcutt (1978) Atlas Protein Seq. Struc. 5:345–352, secondly, the resolvent method (RV) by Müller and Vingron (2000) J. Comput. Biol. 7(6):761–776, and finally a maximum likelihood approach (ML) developed in this paper. We evaluate the methods using a highly divergent and inhomogeneous set of sequence alignments as an input to the estimation procedure. ML is the method of choice for small sets of input data. Although the RV method is computationally much less demanding it performs only slightly worse than ML. Therefore, it is perfectly appropriate for large-scale applications.
Clostridium difficile in Dutch animals: their presence, characteristics and similarities with human isolates
Authors: M.G.J. Koene, D. Mevius, J.A. Wagenaar, C. Harmanus, M.P.M. Hensgens, A.M. Meetsma, F.F. Putirulan, M.A.P. van Bergen, E.J. Kuijper
Journal: Clinical Microbiology and Infection (2011)
Can Clinical Interventions Change Care at the End of Life?
Authors: Laura C. Hanson, James A. Tulsky, Marion Danis
Journal: Annals of Internal Medicine (1997)

To review clinical interventions designed to change care at the end of life.Published results of clinical trials identified by MEDLINE searches, review of abstracts from meetings, and selected bibliographies.Studies were included if data were presented on a clinical intervention designed to change medical care at the end of life. Studies done in nonclinical settings or outside the United States were excluded.Interventions were classified as targeting patients, physicians, or both and were analyzed by their effect on four common clinical goals: increasing use of patient preferences, decreasing pain and suffering, reducing use of life-sustaining treatments, and reducing costs. Positive and negative trial results were compared for differences in intervention, target group, and strength of study methods.Educational interventions usually increased expression of patient treatment preferences. Success rates were higher when more severely ill patients were targeted and when written materials were combined with repeated discussions in clinical encounters. Educational interventions with physicians led to increased use of patient preferences, but sophisticated educational techniques were needed to motivate physicians to change their behavior. Three studies provided limited evidence that physician education reduced the use of life-sustaining treatments. No clinical intervention had an effect on pain, suffering, or cost of medical care.To change care at the end of life, intensive educational interventions for physicians and broad institutional programs seem more promising than advance directives. Future innovations should seek to change physician practices, reduce costs, and improve patient-centered outcomes, such as pain control and satisfaction.
Adiponectin: Are Measurements Clinically Useful in Pregnancy?
Authors: Sylvie Hauguel-de Mouzon, Patrick Catalano
Journal: Diabetes Care (2013)

Adiponectin (AdpN) is an abundant protein that circulates in blood in microgram quantities. Although AdpN is primarily produced by adipose tissue, the paradox of AdpN is that plasma concentrations decrease with increasing adiposity (1,2). AdpN concentrations are decreased in obesity (3) and obesity-related complications—for example, diabetes, cardiovascular diseases, nonalcoholic fatty liver disease, and in pregnancy (4,5). AdpN exerts pleiotropic actions including potent insulin sensitizing properties. Studies in obesity, type 2 diabetes, and gestational diabetes mellitus (GDM) suggest that the deficiency of AdpN triggers the progression to insulin resistance and the development of metabolic inflammation (recently reviewed in ref. 6). This has encouraged numerous groups to investigate whether AdpN could serve as a systemic biomarker that would predict the risk of diabetes.

A link between hypoadiponectinemia and reduced insulin action also exists in pregnancy. In healthy women, AdpN levels reach their lowest concentrations in the third trimester when maternal insulin resistance is greatest (5,7). The low AdpN concentrations in the third trimester are further accentuated in GDM (8). Total AdpN and high molecular weight AdpN and the high molecular weight-to-AdpN ratio are inversely related to insulin resistance as estimated by clamp studies in early and late pregnancy (5). Maternal AdpN does not cross the placenta and consequently does not contribute to fetal adiponectinemia (9). Contrary to other cytokines, AdpN is not expressed nor produced by the placenta (10–12). Similar to the nonpregnant state, these characteristics underscore that maternal adipose tissue is the major source of maternal plasma AdpN, which thus can be assessed as an independent maternal biomarker (Fig. 1). …
Histone Deacetylase 2 Modulates p53 Transcriptional Activities through Regulation of p53-DNA Binding Activity
Authors: Kelly Lynn Harms, Xinbin Chen
Journal: Cancer Research (2007)

Abstract Histone deacetylase (HDAC) inhibitors are emerging as promising cancer therapeutics. HDAC inhibitors have been found to induce cellular activities that are strikingly similar to p53-mediated responses to genotoxic stress. For example, HDAC inhibitors induce cell cycle arrest, apoptosis, and cellular senescence. Because at least 11 HDACs are affected by the current HDAC inhibitors, the HDAC critical for tumor cell survival and proliferation remains unknown. Thus, we sought to characterize the distinct roles of HDACs in the p53 pathway. Through the use of stable MCF7 cell lines which inducibly express short hairpin RNA targeting HDAC2, we found that HDAC2 plays important roles in the p53 pathway. Specifically, we found that knockdown of HDAC2 inhibited cellular proliferation in a dose-dependent manner which was also partly p53-dependent. Furthermore, knockdown of HDAC2 induced cellular senescence. Importantly, we found that knockdown of HDAC2 enhanced p53-dependent trans-repression and trans-activation of a subset of target genes. We found that the enhancement was due to increased p53-DNA binding activity but not alterations in p53 stability or posttranslational modification(s). Thus, for the first time, our data suggest that HDAC inhibitors function through the p53 pathway, at least in part, by activating p53-DNA binding activity. [Cancer Res 2007;67(7):3145–52]
Hyperactivation of NF-κB via the MEK signaling is indispensable for the inhibitory effect of cAMP on DNA damage-induced cell death
Authors: Martine M Kloster, Elin H Naderi, Harald Carlsen, Heidi K Blomhoff, Soheil Naderi
Journal: Molecular Cancer (2011)

Abstract With cAMP signaling having a profound inhibitory effect on DNA damage-induced apoptosis in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells, understanding how this signaling pathway affects the survival capacity of the cell has important implications for cancer therapy. We have recently shown that p53 is critical for the inhibitory effect of cAMP on genotoxic agents-mediated apoptosis in BCP-ALLs. Here, we show that elevation of cAMP levels in cells exposed to DNA damage enhances the nuclear translocation and DNA binding of NF-κB by accelerating the phosphorylation of IKKβ and thereby phosphorylation and degradation of IκBα. Furthermore, we show that the ability of cAMP to potentiate the ionizing radiation-induced activation of NF-κB requires the activity of MEK. Importantly, pharmacological or genetic ablation of NF-κB reversed the inhibitory effect of cAMP on DNA damage-induced apoptosis, demonstrating that, in addition to p53, cAMP relies on the activity of NF-κB to provide cells with a survival advantage in the face of DNA damage. Collectively, our results uncover a novel and important interaction between the cAMP and NF-κB pathways that may have implications for the targeted treatment of lymphoid malignancies, such as BCP-ALL, in which aberrant NF-κB activity functions as a driving force for treatment resistance.
The neurological effects of air pollution in children
Authors: J. Sunyer
Journal: European Respiratory Journal (2008)

Environmental exposures in utero and during early life may permanently change the body’s structure, physiology and metabolism, and lead to diseases in adult life [1]. Infants are particularly vulnerable because of their rapid growth and cell differentiation, immaturity of metabolic pathways and development of vital organ systems. The central nervous system has unprotected barriers and a broad time window of conformation, leading to a long period of vulnerability in the developmental process and to susceptibility to any environmental insult [2]. Research conducted among a limited series of pollutants (including lead, mercury and polycyclic aromatic hydrocarbons (PAH)) shows that early-life exposure to chemicals at current environmental levels can be neurotoxic years or even decades after exposure [3]. Traffic-related air pollution, basically urban outdoor pollution, is a global public health problem [4]. Cardiorespiratory effects and mechanisms have been fully investigated [5]. In contrast, little is known regarding neurological effects, with only some preliminary evidence. In rats, ultrafine carbon particles have been found in the olfactory bulb and the cerebrum and cerebellum after inhalation exposure [6]; this finding has been reproduced more recently with manganese particles directly translocated to the olfactory nerve from the nose to the brain [7]. In one study, dogs living in a highly polluted region in Mexico City (Mexico) had an increase in brain inflammation compared with animals living in a less polluted area [8]. The brain tissue of animals from Mexico City had higher levels of nuclear factor-kB activation and nitric oxide production, as well as the principal pro-inflammatory cytokines interleukin (IL)-1 and tumour necrosis factor (TNF)-a, compared with the animals from the nonpolluted area [9]. In a study on human autopsies in Mexico City, exposure to severe air pollution has been associated with increased levels of cyclooxygenase (COX)-2 and accumulation of the 42-amino-acid form of b-amyloid, a cause of neuronal dysfunction [10].
Melanoma and skin cancer: evaluation of a health education programme for secondary schools
Authors: B.R. HUGHES, D.G. ALTMAN, J.A. NEWTON
Journal: British Journal of Dermatology (1993)

The effectiveness of an education package for secondary schools about the sun and skin cancer was assessed using questionnaires. A variety of teaching methods was used, including pamphlets, workbooks, and a video. The effect of this material was assessed by asking pupils to complete questionnaires immediately after receiving the package (July), and after the summer holiday (September). Five-hundred and forty-three children from seven schools were recruited into the study. Results of the questionnaire demonstrated a significant difference in knowledge (P<0.001) and reported attitude (P<0.001) compared with a control group. There was no significant difference in behaviour of the taught groups compared with the control group. The only significant activity associated with increased knowledge was wearing a sunscreen (P<0.005). In contrast, In terms of attitude, those who covered up in the sun (P<0.0001), wore a sunscreen (P<0.004), and sat in the shade (P<0.02). had significantly hetter attitudes than those who did not behave in this way. This project is a first attempt to assess health education in schools, and reports changes in knowledge, attitudes, and some aspects of behaviour. Adolescents are a group who are difficult to influence, but our study has produced some useful information about how these children respond to such teaching measures.
Cellular and molecular events leading to mitochondrial toxicity of 1-(2-deoxy-2-fluoro-1-beta-D-arabinofuranosyl)-5-iodouracil in human liver cells.
Authors: L Cui, S Yoon, R F Schinazi, J P Sommadossi
Journal: Journal of Clinical Investigation (1995)

We have explored the mechanism(s) related to FIAU-induced liver toxicity, particularly focusing on its effect on mitochondrial function in a human hepatoma cell line-HepG2. The potential role of FMAU and FAU, metabolites detected in FIAU-treated patients were also ascertained. FIAU and FMAU inhibited cell growth and were effectively phosphorylated. A substantial increase in lactic acid production in medium of cells incubated with 1-10 microM FIAU or FMAU was consistent with mitochondrial dysfunction. Slot blot analysis demonstrated that a two week exposure to 10 microM FIAU or FMAU was not associated with a decrease in total mitochondrial (mt) DNA content. However, FIAU and FMAU were incorporated into nuclear and mtDNA and relative values suggest that both compounds incorporate at a much higher rate into mtDNA. Electron micrographs of cells incubated with 10 microM FIAU or FMAU revealed the presence of enlarged mitochondria with higher cristae density and lipid vesicles. In conclusion, these data suggest that despite the lack of inhibition of mtDNA content, incorporation of FIAU and FMAU into mtDNA of HepG2 cells leads to marked mitochondrial dysfunction as evidenced by disturbance in cellular energy metabolism and detection of micro- and macrovesicular steatosis.
Morbidity Risk for Obsessive-Compulsive Spectrum Disorders in First-Degree Relatives of Patients With Eating Disorders
Authors: Laura Bellodi, Maria Cristina Cavallini, Sara Bertelli, Danilo Chiapparino, Chiara Riboldi, Enrico Smeraldi
Journal: American Journal of Psychiatry (2001)

A hypothesis that eating disorders are a phenomenological variant of obsessive-compulsive disorder (OCD) has been proposed. This study was conducted to determine whether anorexia nervosa and bulimia, the two main eating disorders, are familial and whether the risk for obsessive-compulsive spectrum disorders (OCD and tic disorders) is higher in families of patients with eating disorders.The morbidity risk for obsessive-compulsive spectrum disorders in first-degree relatives of 136 female probands with eating disorders (84 with anorexia nervosa, 52 with bulimia) was compared to that for first-degree relatives of 72 female comparison subjects.The morbidity risk for obsessive-compulsive spectrum disorders was significantly higher among the 436 relatives of the eating disorder probands than among the 358 relatives of the comparison subjects (9.69% versus 0%). This finding was independent of any comorbid diagnosis of an obsessive-compulsive spectrum disorder in the eating disorder probands. The eating disorder group and the comparison group did not differ in familial risk for eating disorders and tic disorders.To better understand the genetic components of eating disorders, these disorders should be considered as part of the obsessive-compulsive spectrum of disorders.