tbuckley/cabot-search huggingface dataset:
Dynamics of mitochondrial heteroplasmy in three families investigated via a repeatable re-sequencing study
Authors: Hiroki Goto, Benjamin Dickins, Enis Afgan, Ian M Paul, James Taylor, Kateryna D Makova, Anton Nekrutenko
Journal: Genome biology (2011)

Originally believed to be a rare phenomenon, heteroplasmy - the presence of more than one mitochondrial DNA (mtDNA) variant within a cell, tissue, or individual - is emerging as an important component of eukaryotic genetic diversity. Heteroplasmies can be used as genetic markers in applications ranging from forensics to cancer diagnostics. Yet the frequency of heteroplasmic alleles may vary from generation to generation due to the bottleneck occurring during oogenesis. Therefore, to understand the alterations in allele frequencies at heteroplasmic sites, it is of critical importance to investigate the dynamics of maternal mtDNA transmission. Here we sequenced, at high coverage, mtDNA from blood and buccal tissues of nine individuals from three families with a total of six maternal transmission events. Using simulations and re-sequencing of clonal DNA, we devised a set of criteria for detecting polymorphic sites in heterogeneous genetic samples that is resistant to the noise originating from massively parallel sequencing technologies. Application of these criteria to nine human mtDNA samples revealed four heteroplasmic sites. Our results suggest that the incidence of heteroplasmy may be lower than estimated in some other recent re-sequencing studies, and that mtDNA allelic frequencies differ significantly both between tissues of the same individual and between a mother and her offspring. We designed our study in such a way that the complete analysis described here can be repeated by anyone either at our site or directly on the Amazon Cloud. Our computational pipeline can be easily modified to accommodate other applications, such as viral re-sequencing.
Dual pathways of p53 mediated glucolipotoxicity-induced apoptosis of rat cardiomyoblast cell: activation of p53 proapoptosis and inhibition of Nrf2-NQO1 antiapoptosis
Authors: Hye Jin Wang, Eun Young Lee, Seung Jin Han, Soo Hyun Kim, Byung-Wan Lee, Chul Woo Ahn, Bong Soo Cha, Hyun Chul Lee
Journal: Metabolism (2011)
Genetic deficiency of α<sub>1</sub>‐PI in mice influences lung responses to bleomycin
Authors: E. Cavarra, P.A. Martorana, B. Bartalesi, S. Fineschi, F. Gambelli, M. Lucattelli, L. Ortiz, G. Lungarella
Journal: European Respiratory Journal (2001)

It has recently been suggested that proteinase inhibitors modulate the fibrotic response in the lung. This study investigated the development of bleomycin-induced pulmonary changes in pallid mice, deficient in serum α 1 ‐proteinase inhibitor, and with a lower elastase inhibitory capacity, and in congenic C57Bl/6J mice. Male pallid and C57Bl/6J mice received a single intratracheal instillation of either saline or bleomycin. The investigation was carried out by means of biochemical, morphological and morphometrical methods. In both strains, 21 and 72 h after bleomycin, the lungs showed foci of inflammatory cell infiltration associated with emphysema. Fibrosis developed with time after bleomycin. At 14 days fibrosis affected 23.46±9.48% (mean± sd) and 40.62±13.34% (p&lt;0.01) of the lungs of C57Bl/6J and pallid mice, respectively. Emphysema affected 3.68±3.11% and 12.57±4.13% (p&lt;0.01) of lung in C57Bl/6J and pallid mice, respectively. In C57Bl/6J mice bleomycin increased lung hydroxyproline content by 34% and desmosine content by 44% (p&lt;0.01 for both). In pallid mice these increases were only 21% (p&lt;0.01) and 6%, which may reflect parenchymal loss. Thus, the lung destructive response (emphysema) and the subsequent proliferative reaction (fibrosis) to bleomycin are potentiated in α 1 ‐proteinase inhibitor deficiency.
INFECTION OF RABBITS WITH THE VIRUS OF POLIOMYELITIS
Authors: Henry K. Marks
Journal: The Journal of Experimental Medicine (1911)

The question whether rabbits succumb to the inoculation of the virus of epidemic poliomyelitis has been disputed.Krause and Meinicke I and, later, Lentz and Huntemfiller" have claimed that rabbits may be infected with the virus, to the effects of which many succumb.On the other hand, Flexner and Lewis, ~ Landsteiner and Levaditi, 4 R6mer and Joseph, 5 and Leiner and yon Wiesner e all failed to produce effects in rabbits by inoculation of tissues of the spinal cord and brain from cases of human and of experimental (monkey) poliomyelitis.It has now been established beyond peradventure that the monkey is regularly to be infected with the virus of poliomyelitis by means of intracerebral inoculation, with the result that an experimental disease is set up agreeing in all essential clinical and pathological effects with epidemic poliomyelitis in man.Conversely, the inoculation of the virus into the peritoneal cavity, subcutaneous tissue, blood, or other part distant from the central nervous system, is followed much less constantly by infection.The majority of the negative inoculations of the rabbit were made intracerebrally, and the remainder, with rare exception, intraperitoneally.Grown rabbits were usually employed.The inoculated rabbits remained well or succumbed to intercurrent diseases.However, Flexner and
Effects of Inverse Ratio Ventilation and Positive End-Expiratory Pressure in Oleic Acid–Induced Lung Injury
Authors: PETER NEUMANN, JAN E. BERGLUND, LARS G. ANDERSSON, ENN MARIPU, ANDERS MAGNUSSON, GÖRAN HEDENSTIERNA
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Continuous as well as cyclic (with each expiration) lung collapse in acute respiratory failure can be reduced by positive end-expiratory pressure (PEEP) or short expiration times, as in inverse ratio ventilation (IRV). In 20 pigs with oleic acid-induced lung edema, we compared the effects of a PEEP of 20 cm H2O with IRV, using an inspiratory-to-expiratory ratio of 3:1 without external PEEP. During IRV, expiration times of 0.5 or 1.0 s were obtained with respiratory rates of 30 breaths/min or 15 breaths/min, respectively. In 15 animals, ventilation–perfusion relationships were studied through the multiple inert gas elimination technique, and lung morphology was studied with computed tomography. In another five pigs, blood flow distribution was studied with perfusion scintigraphy. All three ventilatory modes had similar effects on mean arterial blood pressure, cardiac output, oxygen delivery, and mean airway pressure. PEEP reduced shunt and improved oxygenation to a greater extent than the two modes of IRV, although there was a large variation within each group. The improvement, irrespective of which ventilatory mode was superior in a particular pig, was caused by greater and more even aeration of the lung, whereas the perfusion distribution with PEEP was the same as with IRV. Thus, the strategy of stabilizing the lungs through short expiration times, as in IRV, did not offer any advantages in our lung injury model.
Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, Associated With Coinfection of Human Herpesvirus 6 and 8
Authors: Shoko Nakayama-Ichiyama, Taiji Yokote, Satoko Oka, Kazuki Iwaki, Kichinosuke Kobayashi, Yuji Hirata, Nobuya Hiraoka, Ayami Takayama, Toshikazu Akioka, Takuji Miyoshi, Takayuki Takubo, Motomu Tsuji, Toshiaki Hanafusa
Journal: Journal of Clinical Oncology (2011)
Science and Set in Treatment Decisions
Authors: MYRON G. SANDIFER
Journal: American Journal of Psychiatry (1972)

This pilot study attempted to explain why psychiatrists differ in their decisions regarding treatment. Differences over the usage of phenothiazines were best explained by differences in diagnosis; differences in psychotherapy were best explained by the psychiatrists' "set" regarding psychotherapy. However, differences regarding the decision to hospitalize a patient could not be accounted for.
Coagulase-negative Staphylococcus aureus
Authors: F. Vandenesch, M. Bes, C. Lebeau, T. Greenland, Y. Brun, J. Etienne, K. Alshafi, S. Lacey, A.D. Mackay, R.R. Marples, A. Quick, S.H. Gillespie, C.C. Kibbler
Journal: The Lancet (1993)
Hepatitis C virus: From epidemiology and molecular virology to immunobiology
Authors: Johnson Y.N. Lau
Journal: Hepatology (1994)

Hepatitis C virus (HCV) is a major cause of posttransfusion and community–acquired hepatitis, and a majority of individuals infected with this virus will subsequently develop chronic hepatitis. Characterization of the host immune response to this infection is an important first step that should facilitate the development of immunomodulatory agents and vaccines. Cellular immune responses, especially those mediated by cytotoxic T lymphocytes (CTL), are important in the control of many viral diseases. In this study, liver–infiltrating lymphocytes from persons with chronic HCV hepatitis were examined for evidence of HCV–specific CTL by using target cells infected with recombinant vaccinia viruses expressing the HCV core, E1, E2, and part of the NS2 proteins. Bulk expansion of liver–derived CD8+ lymphocytes resulted in the detection of HCV–specific CTL activity, whereas activity could not be found in CD8+ lymphocytes expanded from peripheral blood. Epitopes recognized by these CTL were defined by using CTL clones obtained by limiting dilution and target cells sensitized with synthetic HCV peptides. Four distinct HLA class I–restricted epitopes were identified, including two epitopes in the amino–terminal portion of the core protein. These studies provide evidence that the highly conserved core protein is a target for HCV–specific CTL and identify CTL epitopes within the more highly variable E2 envelope protein. Our studies also suggest that HCV–specific CTL are localized at the site of tissue injury in infected persons with chronic hepatitis. Identification of the epitopes recognized by HCV–specific CTL will facilitate exploration of their role in disease pathogenesis and may provide information useful in development of therapeutic interventions or vaccines.
A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium
Authors: William Checkley, A Clinton White, Devan Jaganath, Michael J Arrowood, Rachel M Chalmers, Xian-Ming Chen, Ronald Fayer, Jeffrey K Griffiths, Richard L Guerrant, Lizbeth Hedstrom, Christopher D Huston, Karen L Kotloff, Gagandeep Kang, Jan R Mead, Mark Miller, William A Petri, Jeffrey W Priest, David S Roos, Boris Striepen, R C Andrew Thompson, Honorine D Ward, Wesley A Van Voorhis, Lihua Xiao, Guan Zhu, Eric R Houpt
Journal: The Lancet Infectious Diseases (2014)
Development and characterization of sorafenib-loaded PLGA nanoparticles for the systemic treatment of liver fibrosis
Authors: Ts-Ting Lin, Dong-Yu Gao, Ya-Chi Liu, Yun-Chieh Sung, Dehui Wan, Jia-Yu Liu, Tsaiyu Chiang, Liying Wang, Yunching Chen
Journal: Journal of Controlled Release (2015)
Kinetics of 64copper in primary biliary cirrhosis
Authors: Roelof A. Janssens, Cornelis J.A. Van Den Hamer
Journal: Hepatology (1982)

To assess the pathogenetic mechanisms involved in the accumulation of copper in primary biliary cirrhosis (PBC), the kinetics of 64 Copper ( 64 Cu) were studied in 6 healthy volunteers, 3 patients with PBC (Stages I to III) and a normal liver copper, and 7 patients with PBC (Stages II to IV) and a high liver copper. The kinetics of oral and i.v. administered 64 Cu in patients with a normal liver copper were similar to those in controls. In patients with a high liver copper, the initial disappearance rate from the plasma of i.v. administered 64 Cu was more rapid, the disappearance rate from the liver of 64 Cu taken up by this organ was slower, and the fecal excretion of 64 Cu less as compared with the two other groups of subjects. In addition, the fecal excretion of orally administered 64 Cu was less in these patients. Computation of the rate of absorption of orally administered 64 Cu revealed no differences between the three groups. Two of the patients with a high liver copper were decopperized by treatment with D–penicillamine. In these patients, the disappearance rate of i.v. administered 64 Cu from the liver and the secondary reappearance rate of 64 Cu into plasma became normal; however, the fecal excretion of 64 Cu remained low. It is concluded that there is no pathognomonic alteration of copper metabolism in PBC, but that in some patients, copper accumulates in the liver due to decreased biliary excretion and increased clearance from the plasma, and that dilution of the tracer dose a large amount of stable copper is responsible for all abnormalities of 64 Cu kinetics encountered in PBC, except low fecal excretion, which is caused by impairment of biliary excretion.
Prediction of Survival following First-Line Chemotherapy in Men with Castration-Resistant Metastatic Prostate Cancer
Authors: Andrew J. Armstrong, Elizabeth Garrett-Mayer, Ronald de Wit, Ian Tannock, Mario Eisenberger
Journal: Clinical Cancer Research (2009)

We sought to evaluate predictors of overall survival following progression after systemic chemotherapy in men with metastatic castration-resistant prostate cancer.For our study population, we used the TAX327 multicenter randomized phase III trial comparing administration of docetaxel and prednisone every 3 weeks, weekly administration of docetaxel and prednisone, and administration of mitoxantrone and prednisone every 3 weeks. Progression was defined as the earliest of prostate-specific antigen (PSA), tumor, or pain progression. We analyzed predictors of postprogression survival according to both prechemotherapy and postchemotherapy variables with adjustment for potential confounders.Among 1,006 men, 640 had evaluable information on protocol-defined progression leading to further therapy. Median postprogression survival was 14.5 months. In the multivariable analysis, several pretreatment factors were associated with postprogression survival: pain, performance status, alkaline phosphatase, number of sites of metastatic disease, liver metastases, hemoglobin, PSA, and time since diagnosis. In addition, we found that the number of progression factors (PSA, pain, and tumor size), the duration of first-line chemotherapy, and whether progression occurred during chemotherapy independently predicted postprogression survival. We found evidence for the benefit of continuation of chemotherapy beyond progression only for men who had isolated worsening of pain. A nomogram was constructed and internally validated with a concordance index of 0.70.An internally validated model to predict postchemotherapy survival was developed. Evaluation of men in the postdocetaxel setting should consider the type of progression, duration of therapy, and known pretreatment prognostic factors. Definitions of progression in castration-resistant prostate cancer that include pain should also consider composite measures of tumor or PSA progression. External validation is planned.
Abdominal pain following cardiac transplantation
Authors: C. Hanck, B. Werth, F. Fleisch, W. Reinhart
Journal: Gut (2007)

<h3>Aims</h3> Both the Clauss and prothrombin time-derived fibrinogen (PT-Fib) methods have widely been used in fibrinogen (Fib) evaluation. We aimed to improve the interchangeability between these two methods. <h3>Methods</h3> Thirty fresh plasmas of low, normal and high Fib concentration were mixed to prepare the pooled human plasma. The Fib concentration was assessed by the Clauss method. The PT-Fib values were further recalibrated by the assigned plasma pools and the precision, linearity and reference intervals were verified according to the guidelines of American Society for Clinical and Laboratory Standards (CLSI) EP15-A and EP6-A documents. Finally, the recalibrated PT-Fib method was compared with Clauss method by the simultaneous Fib test of total 5259 coagulation samples. <h3>Results</h3> The results indicated that the recalibrated PT-Fib method can detect the Fib concentration with clinically acceptable third-order linearity in the range of 1.27–8.00 g/L. Only one result out of 39 healthy people tested using the recalibrated PT-Fib method did not fall within the reference range defined by the manufacturer. We also found more than 99% of results between these two methods were interchangeable in the range of 1.51–8.00 g/L. The disagreement between these two methods was found only in patients with certain underlying conditions. <h3>Conclusions</h3> After recalibration, the consistency between the PT-Fib and Clauss methods was enhanced and the interchangeability was improved. The application of the recalibrated PT-Fib method provided accurate and reliable results with the manufacturer-provided reagents and improved detection speed and cost-effectiveness.
Topography, Cell Response, and Nerve Regeneration
Authors: Diane Hoffman-Kim, Jennifer A. Mitchel, Ravi V. Bellamkonda
Journal: Annual Review of Biomedical Engineering (2010)

In the body, cells encounter a complex milieu of signals, including topographical cues, in the form of the physical features of their surrounding environment. Imposed topography can affect cells on surfaces by promoting adhesion, spreading, alignment, morphological changes, and changes in gene expression. Neural response to topography is complex, and it depends on the dimensions and shapes of physical features. Looking toward repair of nerve injuries, strategies are being explored to engineer guidance conduits with precise surface topographies. How neurons and other cell types sense and interpret topography remains to be fully elucidated. Studies reviewed here include those of topography on cellular organization and function as well as potential cellular mechanisms of response.
Runx proteins regulate Foxp3 expression
Authors: Ludovica Bruno, Luca Mazzarella, Maarten Hoogenkamp, Arnulf Hertweck, Bradley S. Cobb, Stephan Sauer, Suzana Hadjur, Marion Leleu, Yoshinori Naoe, Janice C. Telfer, Constanze Bonifer, Ichiro Taniuchi, Amanda G. Fisher, Matthias Merkenschlager
Journal: The Journal of Experimental Medicine (2009)

Runx proteins are essential for hematopoiesis and play an important role in T cell development by regulating key target genes, such as CD4 and CD8 as well as lymphokine genes, during the specialization of naive CD4 T cells into distinct T helper subsets. In regulatory T (T reg) cells, the signature transcription factor Foxp3 interacts with and modulates the function of several other DNA binding proteins, including Runx family members, at the protein level. We show that Runx proteins also regulate the initiation and the maintenance of Foxp3 gene expression in CD4 T cells. Full-length Runx promoted the de novo expression of Foxp3 during inducible T reg cell differentiation, whereas the isolated dominant-negative Runt DNA binding domain antagonized de novo Foxp3 expression. Foxp3 expression in natural T reg cells remained dependent on Runx proteins and correlated with the binding of Runx/core-binding factor beta to regulatory elements within the Foxp3 locus. Our data show that Runx and Foxp3 are components of a feed-forward loop in which Runx proteins contribute to the expression of Foxp3 and cooperate with Foxp3 proteins to regulate the expression of downstream target genes.
Sirolimus-Eluting vs Uncoated Stents for Prevention of Restenosis in Small Coronary Arteries
Authors: Diego Ardissino, Claudio Cavallini, Ezio Bramucci, Ciro Indolfi, Antonio Marzocchi, Antonio Manari, Giulia Angeloni, Giuseppe Carosio, Erminio Bonizzoni, Stefania Colusso, Monica Repetto, Piera Angelica Merlini, for the SES-SMART Investigators
Journal: JAMA (2004)

Percutaneous coronary revascularization of small vessels is associated with a high restenosis rate. Sirolimus-eluting stents reduce restenosis in simple and previously untreated lesions of large coronary arteries, but their outcomes in small vessels have not been adequately investigated.To determine whether sirolimus-eluting stents are associated with a reduced 8-month rate of angiographic restenosis in comparison with an uncoated stent.This was a randomized, multicenter, single-blind, prospective trial performed with 257 patients undergoing percutaneous coronary revascularization for ischemic heart disease, and who had a previously untreated atherosclerotic lesion located in a small segment with a diameter of 2.75 mm or less, in 20 Italian centers between August 2002 and December 2003.Patients were randomly assigned to receive a sirolimus-eluting stent (129 patients) or an uncoated stent having an identical architecture and radiographic appearance (128 patients).The primary end point was the 8-month binary in-segment restenosis rate; secondary end points included procedural success and the 8-month rate of major adverse cardiac and cerebrovascular events.The mean (SD) reference diameter of the treated segment was 2.2 (0.28) mm; the lesion length, 11.84 (6.15) mm. After 8 months, the binary in-segment restenosis rate was 53.1% (60/113) in the patients receiving an uncoated stent and 9.8% (12/123) in those receiving a sirolimus-eluting stent (relative risk [RR], 0.18; 95% confidence interval [CI], 0.10-0.32; P<.001). Fewer patients randomized to sirolimus-eluting stents experienced major adverse cardiac events (12/129 [9.3%] vs 40/128 [31.3%]; RR, 0.30; 95% CI, 0.15-0.55; P<.001) mainly because of a reduction in target lesion revascularization (9/129 [7%] vs 27/128 [21.1%]; RR, 0.33; 95% CI, 0.14-0.70; P = .002) and myocardial infarction (2/129 [1.6%] vs 10/129 [7.8%]; RR, 0.20; 95% CI, 0.01-0.93; P = .04).The use of sirolimus-eluting stents to treat atherosclerotic lesions in small coronary arteries reduces restenosis and may also reduce major adverse cardiac events.
Familial Multiple Endocrine Neoplasia Type I: A New Look at Pathophysiology
Authors: M. L. BRANDI, S. J. MARX, G. D. AURBACH, L. A. FITZPATRICK
Journal: Endocrine Reviews (1987)

FAMILIAL multiple endocrine endocrine neoplasia type I (FMENI) is a complex hereditary disorder encompassing pancreatic and pituitary tumors and hyperplasia of the parathyroid glands. Hyperparathyroidism is the most frequently expressed endocrinopathy in the syndrome which may also include one or more of the following: hyperinsulinism, Zollinger-Ellison syndrome, pancreatic cholera, acromegaly, Cushing's syndrome, and hyperprolactinemia. The earliest suggestion of such a complex syndrome generally is thought to be Erdheim's description (1) of parathyroid enlargement and pituitary adenoma discovered coexisting at autopsy. Rossier and Dressler (2) reported on two siblings with Cushing's syndrome, hypoglycemia, and kidney stones. In 1945 Shelbourne and McLaughlin (3) observed another subject displaying hypoglycemia, kidney stones, and a pituitary adenoma. Wermer (4) described several cases of multiple glandular hyperfunction in a family and called attention to the likely genetic nature of the disorder. In 1968 Steiner and his colleagues (5) reported that the syndrome could be divided into two classes, MENI (pituitary, pancreatic, and parathyroid involvement) and MENII (thyroid medullary cancer plus adrenal medullary and parathyroid disease).