tbuckley/cabot-search huggingface dataset:
Abstract B57: A natural plant-derived compound, Withaferin A, exploits the stress pathway to induce antitumor immunity.
Authors: Annalise R. Smith, Darlah Lopez, Samita Andreansky
Journal: Cancer Research (2013)

Abstract Recent research involving chemotherapeutic drugs such as anthracyclines have aided in redefining the definition of apoptosis from a form of cell death that is immunologically silent to the one that can activate an anti-cancer immune response. This form of apoptosis has been characterized as immunogenic cell death (ICD) and possess certain hallmarks such as the cell surface expression of heat shock proteins (HSPs) including HSP70 and HSP90 as well as ER-stress mediated pre-apoptotic expression of the ER chaperone calreticulin (CRT). One of the mechanisms by which ICD occurs is linked to the induction of an unfolded protein response (UPR) due to prolonged chemotherapeutic stress on cancer cells. Our research focuses on the development of Withaferin A (WA), a steroidal lactone derived from the Indian ayurvedic medicinal plant Withania somnifera as a chemoimmunotherapeutic agent. The benefit of using natural plant derived products is their low toxicity, multimodal action and potential ability to enhance the immune system. We initially screened the effect of Withaferin A by microarray analysis on breast cancer cells. WA induced significant alteration of 1160 genes (p-value 0.005). A pathway analysis determined that WA induces a robust heat shock response through up-regulation of several genes related to this pathway including response to unfolded proteins. The gene expression data was confirmed by the induction of intracellular HSP70, HSP40 as well as the UPR marker Bip78 by western blot. Furthermore we are able to demonstrate that WA treatment results in the translocation of known immunogenic HSPs HSP70, CRT and gp96 to the cell surface of several cancer cell lines. Additionally, WA treatment results in the induction of apoptosis and these WA mediated apoptotic cells can confer immunological protection against re-challenge with live tumor cells in vivo. Our long-term goal is to elucidate the anti-tumor immunomodulatory mechanisms of WA. Funded by: American Cancer Society (S.A.) Citation Format: Annalise R. Smith, Darlah Lopez, Samita Andreansky. A natural plant-derived compound, Withaferin A, exploits the stress pathway to induce antitumor immunity. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B57.
Accuracy of Rate Estimation Using Relaxed-Clock Models with a Critical Focus on the Early Metazoan Radiation
Authors: S. Y. W. Ho
Journal: Molecular Biology and Evolution (2005)

In recent years, a number of phylogenetic methods have been developed for estimating molecular rates and divergence dates under models that relax the molecular clock constraint by allowing rate change throughout the tree. These methods are being used with increasing frequency, but there have been few studies into their accuracy. We tested the accuracy of several relaxed-clock methods (penalized likelihood and Bayesian inference using various models of rate change) using nucleotide sequences simulated on a nine-taxon tree. When the sequences evolved with a constant rate, the methods were able to infer rates accurately, but estimates were more precise when a molecular clock was assumed. When the sequences evolved under a model of auto-correlated rate change, rates were accurately estimated using penalized likelihood and by Bayesian inference using lognormal and exponential models of rate change, while other models did not perform as well. When the sequences evolved under a model of uncorrelated rate change, only Bayesian inference using an exponential rate model performed well. Collectively, the results provide a strong recommendation for using the exponential model of rate change if a conservative approach to divergence time estimation is required. A case study is presented in which we use a simulation-based approach to examine the hypothesis of elevated rates in the Cambrian period, and it is found that these high rate estimates might be an artifact of the rate estimation method. If this bias is present, then the ages of metazoan divergences would be systematically underestimated. The results of this study have implications for studies of molecular rates and divergence dates.
American Society of Clinical Oncology Policy Statement on Medicaid Reform
Authors: Blase N. Polite, Jennifer J. Griggs, Beverly Moy, Christopher Lathan, Nefertiti C. duPont, Gina Villani, Sandra L. Wong, Michael T. Halpern
Journal: Journal of Clinical Oncology (2014)

Entitlement reform is likely to dominate the discussion of the upcoming Congress, and the Medicaid provisions of the Affordable Care Act (ACA) are being implemented this year.The American Society of Clinical Oncology (ASCO) has an opportunity to help shape the debate about how cancer care will be delivered to our most vulnerable patients.As Medicaid continues to evolve in the post-ACA era, ASCO sets forth the following guiding principles with the goal of providing access to high-quality cancer care for all low-income individuals.
GENETIC CONTROL OF BONE MARROW GRAFT REJECTION
Authors: Gustavo Cudkowicz
Journal: The Journal of Experimental Medicine (1971)

Transplantation of 5 x 10(5) DBA/2 (H-2(d)) bone marrow cells into irradiated B10 and 129-strain mice (both H-2(b)) resulted in graft failure in the first recipient strain and in graft take in the second. Transplantation of B10 (H-2(b)) cells into irradiated B10.BR and C3H mice (both H-2(k)) also resulted in failure in the congenic B10.BR recipients and take in the C3H mice. Resistance and susceptibility of B10 and 129-strain animals were specific for given H-2 alleles of donor cells. Transplantation of DBA/2 marrow into (B10 x 129)F(2) mice and of B10 marrow into (B10.BR x C3H)F(1) x C3H backcross mice revealed definite genetic control of the graft-rejection process, presumably at the level of alloantigen recognition. Resistance to allografts, or responder status, was conferred upon segregating mice by dominant alleles of two major independent autosomal loci. The effects of the loci were additive. Conversely, susceptibility to allografts, or nonresponder status, was due to the apparently recessive alleles of both loci. None of the genes was closely linked with the markers tf (tufted) and T (brachyury) of linkage group IX, A(w) (white-bellied agouti) of linkage group V, Sl (steel) of linkage group IV, and c(ch) (chinchilla) and p (pink eye, dilute) of linkage group I. There were suggestions, however, that the regulator genes of marrow graft rejection are either non-H-2 histocompatibility genes or other genetic factors closely linked with them.
Diffuse microvascular pulmonary thrombosis associated with primary antiphospholipid antibody syndrome
Authors: M Maggiorini, A Knoblauch, J Schneider, EW Russi
Journal: European Respiratory Journal (1997)

Thromboembolism is a well-known complication of the hypercoagulable state associated with antiphospholipid (aPL) antibodies. Acute respiratory failure (ARF) with diffuse pulmonary infiltrates has been reported in only a few patients with aPL antibodies. We describe a 49 year old patient with spiking fever, livedo reticularis, mild haemoptysis and ARF. Chest radiography revealed diffuse bilateral pulmonary infiltrates, and high resolution computed tomography (CT) revealed patchy distribution of areas of ground-glass attenuations. Pulmonary emboli were excluded with angiography. Lung biopsy revealed diffuse microvascular thrombosis, without capillaritis. High serum levels of anticardiolipin (aCL) antibodies were found. The patient's condition improved dramatically after intravenous infection of 1 g methylprednisolone on three consecutive days, followed by 50 mg prednisone orally. The rapid improvement following the administration of glucocorticosteroids suggests that anticardiolipin associated microvascular thrombosis, without inflammatory lesions, may depend on an interference with beta2-glycoprotein I (beta2=GPI) by anticardiolipin.
Heat Shock Protein–Peptide Complexes, Reconstituted In Vitro, Elicit Peptide-specific Cytotoxic T Lymphocyte Response and Tumor Immunity
Authors: Nathalie E. Blachere, Zihai Li, Rajiv Y. Chandawarkar, Ryuichiro Suto, Navdeep S. Jaikaria, Sreyashi Basu, Heiichiro Udono, Pramod K. Srivastava
Journal: The Journal of Experimental Medicine (1997)

Heat shock protein (HSP) preparations derived from cancer cells and virus-infected cells have been shown previously to elicit cancer-specific or virus-specific immunity. The immunogenicity of HSP preparations has been attributed to peptides associated with the HSPs. The studies reported here demonstrate that immunogenic HSP-peptide complexes can also be reconstituted in vitro. The studies show that (a) complexes of hsp70 or gp96 HSP molecules with a variety of synthetic peptides can be generated in vitro; (b) the binding of HSPs with peptides is specific in that a number of other proteins tested do not bind synthetic peptides under the conditions in which gp96 molecules do; (c) HSP-peptide complexes reconstituted in vitro are immunologically active, as tested by their ability to elicit antitumor immunity and specific CD8+ cytolytic T lymphocyte response; and (d) synthetic peptides reconstituted in vitro with gp96 are capable of being taken up and re-presented by macrophage in the same manner as gp96- peptides complexes generated in vivo. These observations demonstrate that HSPs are CD8+ T cell response-eliciting adjuvants.
In vivo expansion of CD4+CD45RO-CD25+ T cells expressing foxP3 in IL-2-treated HIV-infected patients
Authors: I. Sereti
Journal: Journal of Clinical Investigation (2005)

Administration of IL-2 to HIV-infected patients leads to expansion of a unique subset of CD4CD45ROCD25 cells. In this study, the origin, clonality, and function of these cells were investigated. Analysis of TCR excision circles revealed that the CD4CD45ROCD25 cells were the product of peripheral expansion but remained polyclonal as determined by TCR repertoire analysis. Phenotypically, these cells were distinct from naturally occurring Tregs; they exhibited intermediate features, between those of memory and naive cells, and had lower susceptibility to apoptosis than CD45ROCD25 or memory T cells. Studies of intracellular cytokine production and proliferation revealed that cytokine-expanded naive CD25 cells had low IL-2 production and required costimulation for proliferation. Despite elevated expression of forkhead transcription factor P3 (foxP3), they exerted only weak suppression compared with CD45ROCD25 cells (Tregs). In summary, in vivo IL-2 administration to HIV-infected patients leads to peripheral expansion of a population of long-lived CD4CD45ROCD25 cells that express high levels of foxP3 but exert weak suppressive function. These CD4CD25 cytokine-expanded naive cells, distinct from antigen-triggered cells and Tregs, play a role in the maintenance of a state of low turnover and sustained expansion of the CD4 T cell pool.
Hepatitis C virus infection in the general population: A community-based study in West Bengal, India
Authors: Abhijit Chowdhury, Amal Santra, Susmita Chaudhuri, Gopal Krishna Dhali, Sujit Chaudhuri, Satya Gopal Maity, Trailokya Nath Naik, Sujit Kumar Bhattacharya, Debendra Nath Guha Mazumder
Journal: Hepatology (2003)

Limited information is available about the prevalence and genotype distribution of hepatitis C virus (HCV) in the general population of India. A community-based epidemiologic study was carried out in a district in West Bengal, India. By a 1:3 sampling method, 3,579 individuals were preselected from 10,737 inhabitants of 9 villages of the district, of whom 2,973 (83.1%) agreed to participate. Twenty-six subjects (0.87%) were HCV antibody positive. The prevalence increased from 0.31% in subjects <10 years of age to 1.85% in those >or=60 years. No difference in prevalence between men and women was observed. Serum alanine aminotransferase (ALT) levels were elevated in 30.8% (8 of 26) of anti-HCV-positive subjects compared with 3.2% (94 of 2,947) anti-HCV-negative subjects (P <.001). HCV RNA was detectable in 80.8% (95% CI, 65.6%-95.91%) of the anti-HCV-positive subjects by reverse transcription-primed polymerase chain reaction (RT-PCR). The participants were HCV types 1b in 2 (9.5%), 3a in 8 (38.1%), 3b in 6 (28.6%), and unclassified in 5 (23.8%). Nucleotide sequencing and phylogenetic analysis assigned the unclassified type to genotype 3e. In conclusion, this study provides general population-based estimates of HCV prevalence, including genotypes, from a South Asian country. Although the prevalence of HCV infection in this population was lower than that reported from industrialized countries of the west, the total reservoir of infection is significant and calls for public health measures, including health education to limit the magnitude of the problem.
Fell walking injuries in Cumbria: a review.
Authors: A Goel, A K Addison
Journal: British Journal of Sports Medicine (1992)

An analysis of injuries sustained during fell walking in Cumbria and seen at the West Cumberland Hospital over a 3-year period is presented. There were 90 patients, including 19 multiple injuries and four deaths. This report focuses attention on the seriousness and magnitude of injuries associated with a pastime often thought to be harmless and risk-free.
The prevalence of chronic obstructive bronchitis in adolescents tobacco-growing region
Authors: Nematilla Aralov Ravshanovich, Muhae Holjigitova
Journal: European Respiratory Journal (2013)

The prevalence of chronic bronchitis among adolescents according to epidemiological studies in different countries varies widely, from an average of 10 to 47%. The purpose of this study was examined the incidence of chronic bronchitis among adolescent tobacco-growing district of Samarkand region.  A total of 3010 adolescents and young adults, aged 11 to 21 years are living in the tobacco-growing region of Samarkand. Conducted a study of lung ventilation function on the unit SPIROSIFT-SP-5000 with automatic processing parameters (FUKUDA DENSHI, Japan) 1750 teenager with a history of upper Confirm braeth ways. Verification of patients with chronic obstructive bronchitis conducted according to the international classification of WHO (X revision, ICD-10). The examination included assessment of general clinical research methods (survey, the study objective status, routine paraclinical tests-complete blood count, urinalysis, general analysis of sputum, ECG, X-ray examination of the chest).  Inkluding the identification of 722 patients with chronic obstructive bronchitis (23.9%). Test for salbutamol bronhodilatation with 70 patients was pozitive, while 652 patients negative. Epidemiological studies indicate that the increase in the incidence of teenage chronic obstructive bronchitis tobacco-growing district of anthropogenic impacts due to tobacco dust, breach mucociliary clearance and secondary immunodeficiency.
A Recent Adaptive Transposable Element Insertion Near Highly Conserved Developmental Loci in Drosophila melanogaster
Authors: J. Gonzalez, J. M. Macpherson, D. A. Petrov
Journal: Molecular Biology and Evolution (2009)

A recent genomewide screen identified 13 transposable elements that are likely to have been adaptive during or after the spread of Drosophila melanogaster out of Africa. One of these insertions, Bari-Juvenile hormone epoxy hydrolase (Bari-Jheh), was associated with the selective sweep of its flanking neutral variation and with reduction of expression of one of its neighboring genes: Jheh3. Here, we provide further evidence that Bari-Jheh insertion is adaptive. We delimit the extent of the selective sweep and show that Bari-Jheh is the only mutation linked to the sweep. Bari-Jheh also lowers the expression of its other flanking gene, Jheh2. Subtle consequences of Bari-Jheh insertion on life-history traits are consistent with the effects of reduced expression of the Jheh genes. Finally, we analyze molecular evolution of Jheh genes in both the long- and the short-term and conclude that Bari-Jheh appears to be a very rare adaptive event in the history of these genes. We discuss the implications of these findings for the detection and understanding of adaptation.
Effects of Fat-Modified Diets on Cholesterol and Lipoprotein Metabolism
Authors: D J McNamara
Journal: Annual Review of Nutrition (1987)

INTRODUCTION . ........ . . .. . . . . . . . . . .. . . . . . . . . . . . . . . . . . . ... . . . . . ....... . . . . ...... . . ....... . . . . ..... 273 OVERVIEW. . . . . ... .. . . . . ...... . . . . . . . . ... . . . . . . . . . . .. . . . . . . . ... . . . . . . ........ . ..   . . . . 274 OBESITY AND CALORIC INTAKE.. . .. . . . . . . . . .... . . .. . . .... . . . .. ....... . . . ....... . . . ....... . . 275 Obesity and Cholesterol Metabolism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . 275 Obesity and Lipoprotein Metabolism.... . ... . . . . . . .   . . . .........   276 DIETARY CHOLESTEROL.... . . . . . ..... . . . . . . . ... . . . . . . .. . . . . . . . .... . . . . ..... . . . . . ..... . . . . . ..... 277 Dietary Cholesterol and Cholesterol Metabolism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277 Dietary Cholesterol and Lipoprotein Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279 DIETARY FAT QUALITy.. . . . . . . . . .. . . . . . . . ... .. . . . . . . . ... . . . . . ..... . . . .... .. . . .. ...... . . . ....... 281 Dietary Fat and Cholesterol Metabolism . . . . .... . . . . .. . . . . . . . ..... .... . .   . . ....... 281 Dietary Fat and Lipoprotein Metabolism . . . ..... . . .. .... . . . .... . . . ........   . . . ..... 282 DIETARY FAT AND CARBOHYDRATE QUANTITIES ... . . . ..... . . . . .. ... . . . . .... . . . . ... 283 Dietary Fat and Carbohydrate Quantity and Cholesterol Metabolism . ..... . . . . ..... . . 283 Dietary Fat and Carbohydrate Quantity and Lipoprotein Metabolism . . ..... . . . . . ..... 284 SUMMARY AND DiSCUSSION.. ... ....... . . . ........ . ...... . . ...... . . . . . ... .. . . . .... . . . . ....... 285
Gut Virome Sequencing in Children With Early Islet Autoimmunity
Authors: Lenka Kramná, Kateřina Kolářová, Sami Oikarinen, Juha-Pekka Pursiheimo, Jorma Ilonen, Olli Simell, Mikael Knip, Riitta Veijola, Heikki Hyöty, Ondrej Cinek
Journal: Diabetes Care (2015)

OBJECTIVE This study used next-generation sequencing (NGS) technologies to characterize the gut virome at the onset of islet autoimmunity. RESEARCH DESIGN AND METHODS We conducted a case-control study nested within the Finnish Diabetes Prediction and Prevention (DIPP) cohort. The stool virome in 19 case children, who turned islet autoantibody positive before the age of 2 years and later developed clinical type 1 diabetes, and 19 tightly matched control subjects was analyzed using NGS performed from stool samples collected 3, 6, and 9 months before the onset of islet autoimmunity. Human virus findings were verified using real-time PCR. RESULTS One or more human viruses were present in 10.4% and bacteriophages were in 54% of the samples. The virome composition showed no association with islet autoimmunity. NGS was less sensitive and specific than real-time PCR. CONCLUSIONS The present data suggest no dramatic changes in the gut virome shortly before the emergence of islet autoimmunity and emphasize the need of verification of mass sequencing results when viral exposure is assessed in association studies.
Survey of Haemorrhagic Erosive Gastritis
Authors: C. E. R. Thompson, P. M. Ashurst, T. J. Butler
Journal: BMJ (1968)

Fluorescent-antibody studies in 22 patients out of a total of 40 cases of acute erosive gastritis showed no antibodies to gastric parietal cells. Hence erosive gastritis seems unlikely to be an autoimmune phenomenon.In this series 57.5% of cases belonged to blood group A. This suggests that there is a correlation between the instability of the gastric mucosa and blood group A.The operative mortality in erosive gastritis is high. Operation should be delayed as long as possible in the hope that the bleeding will stop spontaneously. Erosive gastritis may be idiopathic or precipitated by drugs, particularly aspirin. The highest risk was found to occur in those cases where bleeding was drug-induced.
Macrophage oxygen-dependent antimicrobial activity. II. The role of oxygen intermediates.
Authors: H W Murray, C W Juangbhanich, C F Nathan, Z A Cohn
Journal: The Journal of Experimental Medicine (1979)

The capacity of three populations of mouse peritoneal macrophages to generate oxidative metabolites (as judged by extracellular release of H2O2) was compared to their ability to influence the intracellular fate of virulent Toxoplasma gondii. Macrophages from normal mice released little H2O2 and allowed unrestricted multiplication of intracellular toxoplasmas. Cells from chronically infected, immune (IM) mice released 4 times more H2O2 and displayed microbistatic activity. In contrast, macrophages from immune-boosted (IB) mice released 25 times more H2O2 than normal cells and rapidly killed the bulk of ingested toxoplasmas within 1 h. When macrophage monolayers were exposed to scavengers of O2-, H2O2, OH., and 1O2, both the inhibition of intracellular toxoplasma multiplication by IM macrophages and the killing of toxoplasmas by IB macrophages were reversed. Depriving cells of glucose, which markedly reduced H2O2 release, resulted in similar reversal of IM and IB macrophage anti-toxoplasma activity. As judged by the effect of the individual oxygen intermediate scavengers, O2- and H2O2 appeared to serve as precursors for the key toxic agents which may include OH. and 1O2. Providing normal macrophages with an exogenous source of oxidative metabolites generated by xanthine and xanthine oxidase, but not glucose and glucose oxidase, resulted in inhibition of intracellular toxoplasma growth. These findings suggest the presence of an oxygen-dependent antimicrobial system in mononuclear phagocytes beyond the production of O2- and H2O2, and indicate an important role for oxygen intermediates in macrophage resistance to the intracellular pathogen T. gondii.