Institution
University of Tennessee Health Science Center
Education•Memphis, Tennessee, United States•
About: University of Tennessee Health Science Center is a education organization based out in Memphis, Tennessee, United States. It is known for research contribution in the topics: Population & Transplantation. The organization has 15716 authors who have published 26884 publications receiving 1176697 citations.
Topics: Population, Transplantation, Kidney disease, Cancer, Receptor
Papers published on a yearly basis
Papers
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TL;DR: MTX-related clinical neurotoxicity is transient, and most patients can receive subsequent MTX without recurrence of acute or subacute symptoms, and all symptomatic patients and one in five asymptomatic patients develop leukoencephalopathy that can persist until the end of therapy.
Abstract: Purpose Methotrexate (MTX) can cause significant clinical neurotoxicity and asymptomatic leukoencephalopathy. We sought to identify clinical, pharmacokinetic, and genetic risk factors for these MTX-related toxicities during childhood acute lymphoblastic leukemia (ALL) therapy and provide data on safety of intrathecal and high-dose MTX rechallenge in patients with neurotoxicity. Patients and Methods Prospective brain magnetic resonance imaging was performed at four time points for 369 children with ALL treated in a contemporary study that included five courses of high-dose MTX and 13 to 25 doses of triple intrathecal therapy. Logistic regression modeling was used to evaluate clinical and pharmacokinetic factors, and a genome-wide association study (GWAS) was performed to identify germline polymorphisms for their association with neurotoxicities. Results Fourteen patients (3.8%) developed MTX-related clinical neurotoxicity. Of 13 patients rechallenged with intrathecal and/or high-dose MTX, 12 did not experience recurrence of neurotoxicity. Leukoencephalopathy was found in 73 (20.6%) of 355 asymptomatic patients and in all symptomatic patients and persisted in 74% of asymptomatic and 58% of symptomatic patients at the end of therapy. A high 42-hour plasma MTX to leucovorin ratio (measure of MTX exposure) was associated with increased risk of leukoencephalopathy in multivariable analysis (P .038). GWAS revealed polymorphisms in genes enriched for neurodevelopmental pathways with plausible mechanistic roles in neurotoxicity.
250 citations
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University of Miami1, University of Maryland, Baltimore2, Emory University3, New York University4, Columbia University5, University of Calgary6, University of Kansas7, Centers for Disease Control and Prevention8, New York Medical College9, Johns Hopkins University10, Harvard University11, University of Wisconsin-Madison12, University of Tennessee Health Science Center13, University of Texas at Austin14, University of Pennsylvania15
TL;DR: Women with epilepsy (WWE) should be counseled that seizure freedom for at least 9 months prior to pregnancy is probably associated with a high rate (84%–92%) of remaining seizure-free during pregnancy (Level B), however, WWE who smoke should be Counseled that they possibly have a substantially increased risk of premature contractions and premature labor and delivery during pregnancy.
Abstract: Objective: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy, including the risk of pregnancy complications or other medical problems during pregnancy in WWE compared to other women, change in seizure frequency, the risk of status epilepticus, and the rate of remaining seizure-free during pregnancy.
Methods: A 20-member committee including general neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review and classification of relevant articles published between 1985 and February 2008.
Results: For WWE taking antiepileptic drugs, there is probably no substantially increased risk (greater than two times expected) of cesarean delivery or late pregnancy bleeding, and probably no moderately increased risk (greater than 1.5 times expected) of premature contractions or premature labor and delivery. There is possibly a substantially increased risk of premature contractions and premature labor and delivery during pregnancy for WWE who smoke. Seizure freedom for at least 9 months prior to pregnancy is probably associated with a high likelihood (84%–92%) of remaining seizure-free during pregnancy.
Recommendations: Women with epilepsy (WWE) should be counseled that seizure freedom for at least 9 months prior to pregnancy is probably associated with a high rate (84%–92%) of remaining seizure-free during pregnancy (Level B). However, WWE who smoke should be counseled that they possibly have a substantially increased risk of premature contractions and premature labor and delivery during pregnancy (Level C).
250 citations
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TL;DR: Only expression of the α and long form of the human β subunits in mouse L-929 cells reconstitutes the activation of the Jak kinases and the Stat factors, as well as the antiviral response to human type I IFNs.
250 citations
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TL;DR: This is the first study to examine the expression of S. pneumoniae genes in vivo by using whole-genome microarrays available from The Institute for Genomic Research, and contributions to virulence predicted for several unknown genes with enhanced expression in vivo were confirmed.
Abstract: Streptococcus pneumoniae is a leading cause of invasive bacterial disease. This is the first study to examine the expression of S. pneumoniae genes in vivo by using whole-genome microarrays available from The Institute for Genomic Research. Total RNA was collected from pneumococci isolated from infected blood, infected cerebrospinal fluid, and bacteria attached to a pharyngeal epithelial cell line in vitro. Microarray analysis of pneumococcal genes expressed in these models identified body site-specific patterns of expression for virulence factors, transporters, transcription factors, translation-associated proteins, metabolism, and genes with unknown function. Contributions to virulence predicted for several unknown genes with enhanced expression in vivo were confirmed by insertion duplication mutagenesis and challenge of mice with the mutants. Finally, we cross-referenced our results with previous studies that used signature-tagged mutagenesis and differential fluorescence induction to identify genes that are potentially required by a broad range of pneumococcal strains for invasive disease.
250 citations
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TL;DR: The data indicate that NET formation requires functional tubulin and actin filaments and responds to engagement of Mac-1 integrins, and it is proposed that histone deimination coincides with the release of NETs, which represent overlapping mechanisms of neutrophil responses to infections.
Abstract: Neutrophils use intricate mechanisms for capturing and killing invading microorganisms. One mechanism entails the release of relaxed chromatin from the cell. Microbes are trapped by the extracellular chromatin and exposed to high local concentrations of bactericidal compounds. We examine the regulation of chromatin release by testing the contribution of microtubules and the actin cytoskeleton to the deployment of neutrophil extracellular traps (NETs). Incubation of human neutrophils with nocodazole, a tubulin polymerization inhibitor, or cytochalasin D, an inhibitor of actin filamentation, severely diminished the ability of neutrophils to respond to LPS by releasing chromatin from the cells. In addition, pretreatment of neutrophils with M1/70, a monoclonal antibody to the Mac-1 integrin adhesion receptor, drastically reduced the deployment of chromatin into NETs. Analysis of histone deimination, the conversion of arginine to citrulline in 3 of the 4 core histones by peptidylarginine deiminase 4, revealed that the treatments inhibiting NET formation also reduced histone deimination. Our data indicate that NET formation requires functional tubulin and actin filaments and responds to engagement of Mac-1 integrins. Because histone deimination coincides with the release of NETs, we propose that these events represent overlapping mechanisms of neutrophil responses to infections.
250 citations
Authors
Showing all 15827 results
Name | H-index | Papers | Citations |
---|---|---|---|
George P. Chrousos | 169 | 1612 | 120752 |
Steven N. Blair | 165 | 879 | 132929 |
Bruce L. Miller | 163 | 1153 | 115975 |
Ralph A. DeFronzo | 160 | 759 | 132993 |
Frank J. Gonzalez | 160 | 1144 | 96971 |
Robert G. Webster | 158 | 843 | 90776 |
Anne B. Newman | 150 | 902 | 99255 |
Ching-Hon Pui | 145 | 805 | 72146 |
Barton F. Haynes | 144 | 911 | 79014 |
Yoshihiro Kawaoka | 139 | 883 | 75087 |
Seth M. Steinberg | 137 | 936 | 80148 |
Richard J. Johnson | 137 | 880 | 72201 |
Kristine Yaffe | 136 | 794 | 72250 |
Leslie L. Robison | 131 | 854 | 64373 |
Gerardo Heiss | 128 | 623 | 69393 |