St. Jude Children's Research Hospital

About: St. Jude Children's Research Hospital is a healthcare organization based out in Memphis, Tennessee, United States. It is known for research contribution in the topics: Population & Virus. The organization has 9344 authors who have published 19233 publications receiving 1233399 citations. The organization is also known as: St. Jude Children's Hospital & St. Jude Hospital.

Developmental model relating white matter volume to neurocognitive deficits in pediatric brain tumor survivors.

Abstract: BACKGROUND The primary objective of this study was to test the hypothesis that, among survivors of pediatric brain tumors, the association between reduced volumes of normal-appearing white matter (NAWM) and intellectual/academic achievement deficits can be explained by patient problems with memory and attention. METHODS Quantitative tissue volumes from magnetic resonance imaging scans and neurocognitive assessments were obtained for 40 long-term survivors of pediatric brain tumors. They were treated with radiotherapy (RT) with or without chemotherapy 2.6–15.3 years earlier (median, 5.7 years) at an age of 1.7–14.8 years (median, 6.5 years). Neurocognitive assessments included standardized tests of intellect (intelligence quotient [IQ]), attention, memory, and academic achievement. RESULTS Analyses revealed significant impairments in patients' neurocognitive test performance on all measures. After statistically controlling for age at RT and time from RT, significant associations were found between NAWM volumes and both attentional abilities and IQ, and between attentional abilities and IQ. Subsequent analyses supported the hypothesis that attentional abilities, but not memory, could explain a significant amount of the relationship between NAWM and IQ. The final developmental model predicting academic achievement based on NAWM, attentional abilities, and IQ explained approximately 60% of the variance in reading and spelling and almost 80% of the variance in math. CONCLUSIONS The authors demonstrated that the primary consequence of reduced NAWM among pediatric patients treated for brain tumors was decreased attentional abilities, leading to declining IQ and academic achievement. Cancer 2003;10:2512–9. © 2003 American Cancer Society. DOI 10.1002/cncr.11355

Characterization of RIPK3-mediated phosphorylation of the activation loop of MLKL during necroptosis

Abstract: Mixed lineage kinase domain-like pseudokinase (MLKL) mediates necroptosis by translocating to the plasma membrane and inducing its rupture. The activation of MLKL occurs in a multimolecular complex (the 'necrosome'), which is comprised of MLKL, receptor-interacting serine/threonine kinase (RIPK)-3 (RIPK3) and, in some cases, RIPK1. Within this complex, RIPK3 phosphorylates the activation loop of MLKL, promoting conformational changes and allowing the formation of MLKL oligomers, which migrate to the plasma membrane. Previous studies suggested that RIPK3 could phosphorylate the murine MLKL activation loop at Ser345, Ser347 and Thr349. Moreover, substitution of the Ser345 for an aspartic acid creates a constitutively active MLKL, independent of RIPK3 function. Here we examine the role of each of these residues and found that the phosphorylation of Ser345 is critical for RIPK3-mediated necroptosis, Ser347 has a minor accessory role and Thr349 seems to be irrelevant. We generated a specific monoclonal antibody to detect phospho-Ser345 in murine cells. Using this antibody, a series of MLKL mutants and a novel RIPK3 inhibitor, we demonstrate that the phosphorylation of Ser345 is not required for the interaction between RIPK3 and MLKL in the necrosome, but is essential for MLKL translocation, accumulation in the plasma membrane, and consequent necroptosis.

Inflammasomes and Cancer

Abstract: Inflammation affects all stages of tumorigenesis. A key signaling pathway leading to acute and chronic inflammation is through activation of the caspase-1 inflammasome. Inflammasome complexes are assembled on activation of certain nucleotide-binding domain, leucine-rich repeat-containing proteins (NLR), AIM2-like receptors, or pyrin. Of these, NLRP1, NLRP3, NLRC4, NLRP6, and AIM2 influence the pathogenesis of cancer by modulating innate and adaptive immune responses, cell death, proliferation, and/or the gut microbiota. Activation of the inflammasome and IL18 signaling pathways is largely protective in colitis-associated colorectal cancer, whereas excessive inflammation driven by the inflammasome or the IL1 signaling pathways promotes breast cancer, fibrosarcoma, gastric carcinoma, and lung metastasis in a context-dependent manner. The clinical relevance of inflammasomes in multiple forms of cancer highlights their therapeutic promise as molecular targets. In this review, we explore the crossroads between inflammasomes and the development of various tumors and discuss possible therapeutic values in targeting the inflammasome for the prevention and treatment of cancer. Cancer Immunol Res; 5(2); 94-99. ©2017 AACR.

The X chromosome and sex-specific effects in infectious disease susceptibility

Abstract: The X chromosome and X-linked variants have largely been ignored in genome-wide and candidate association studies of infectious diseases due to the complexity of statistical analysis of the X chromosome. This exclusion is significant, since the X chromosome contains a high density of immune-related genes and regulatory elements that are extensively involved in both the innate and adaptive immune responses. Many diseases present with a clear sex bias, and apart from the influence of sex hormones and socioeconomic and behavioural factors, the X chromosome, X-linked genes and X chromosome inactivation mechanisms contribute to this difference. Females are functional mosaics for X-linked genes due to X chromosome inactivation and this, combined with other X chromosome inactivation mechanisms such as genes that escape silencing and skewed inactivation, could contribute to an immunological advantage for females in many infections. In this review, we discuss the involvement of the X chromosome and X inactivation in immunity and address its role in sexual dimorphism of infectious diseases using tuberculosis susceptibility as an example, in which male sex bias is clear, yet not fully explored.

The central nervous system in childhood leukemia: I. The arachnoid

Abstract: A histopathologic study was performed to evaluate the distribution and extension of intracranial leukemic infiltrates and their relationship to other morphological disturbances of the central nervous system (CNS) in childhood acute lymphocytic leukemia Of 126 brains examined, 70 had arachnoid leukemia at the time of autopsy The earliest evidence of leukemia was seen in the walls of superficial arachnoid veins With more advanced arachnoid leukemia, the disease was seen to extend into the deep arachnoid surrounding blood vessels as they course through the brain The arachnoid leukemia followed a predictable expanding pattern to eventual invasion of brain parenchyma with destruction of the pia-glial membrane Leukemic infiltrate at the capillary-neural tissue interface was present only following destruction of pia-glial membrane secondary to deep arachnoid leukemia Arachnoid fibrosis and certain brain parenchymatous lesions were found in association with arachnoid leukemia The brain lesions included gliosis, necrosis, cerebral hemorrhage, and nonhemorrhagic degenerative encephalopathy This study demonstrates that CNS leukemia is primarily an arachnoid disease Disturbances of brain parenchyma apparently result from leukemic extension through pia-glial membrane or interference with local perfusion due to constriction of blood vessels by perivascular arachnoid leukemia