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Chicago Ridge, IL, United States

Hoenig H.,Duke University | Hoenig H.,Durham Medical Center | Griffiths P.,Emory University | Ganesh S.,Hines Veterans Affairs Medical Center | And 2 more authors.
American Journal of Physical Medicine and Rehabilitation | Year: 2012

OBJECTIVE: This study examined the accuracy of new wheelchair user predictions about their future wheelchair use. DESIGN: This was a prospective cohort study of 84 community-dwelling veterans provided a new manual wheelchair. RESULTS: The association between predicted and actual wheelchair use was strong at 3 mos (φ coefficient = 0.56), with 90% of those who anticipated using the wheelchair at 3 mos still using it (i.e., positive predictive value = 0.96) and 60% of those who anticipated not using it indeed no longer using the wheelchair (i.e., negative predictive value = 0.60, overall accuracy = 0.92). Predictive accuracy diminished over time, with overall accuracy declining from 0.92 at 3 mos to 0.66 at 6 mos. At all time points, and for all types of use, patients better predicted use as opposed to disuse, with correspondingly higher positive than negative predictive values. Accuracy of prediction of use in specific indoor and outdoor locations varied according to location. CONCLUSIONS: This study demonstrates the importance of better understanding the potential mismatch between the anticipated and actual patterns of wheelchair use. The findings suggest that users can be relied upon to accurately predict their basic wheelchair-related needs in the short-term. Further exploration is needed to identify characteristics that will aid users and their providers in more accurately predicting mobility needs for the long-term. Copyright © 2012 by Lippincott Williams & Wilkins. Source

Jin H.,Iowa State University | Kanthasamy A.,Iowa State University | Harischandra D.S.,Iowa State University | Kondru N.,Iowa State University | And 6 more authors.
Journal of Biological Chemistry | Year: 2014

The oxidative stress-sensitive protein kinase Cδ (PKCδ) has been implicated in dopaminergic neuronal cell death. However, little is known about the epigenetic mechanisms regulating PKCδ expression in neurons. Here, we report a novel mechanism by which the PKCδ gene can be regulated by histone acetylation. Treatment with histone deacetylase (HDAC) inhibitor sodium butyrate (NaBu) induced PKCδ expression in cultured neurons, brain slices, and animal models. Several other HDAC inhibitors also mimicked NaBu. The chromatin immunoprecipitation analysis revealed that hyperacetylation of histone H4 by NaBu is associated with the PKCδ promoter. Deletion analysis of the PKCδ promoter mapped the NaBu-responsive element to an 81-bp minimal promoter region. Detailed mutagenesis studies within this region revealed that four GC boxes conferred hyperacetylation-induced PKCδ promoter activation. Cotransfection experiments and Sp inhibitor studies demonstrated that Sp1, Sp3, and Sp4 regulated NaBu-induced PKCδ up-regulation. However, NaBu did not alter the DNA binding activities of Sp proteins or their expression. Interestingly, a one-hybrid analysis revealed that NaBu enhanced transcriptional activity of Sp1/Sp3. Overexpression of the p300/cAMP-response element-binding protein-binding protein (CBP) potentiated the NaBu-mediated transactivation potential of Sp1/Sp3, but expressing several HDACs attenuated this effect, suggesting that p300/CBP and HDACs act as coactivators or corepressors in histone acetylation-induced PKCδ up-regulation. Finally, using genetic and pharmacological approaches, we showed that NaBu up-regulation of PKCδ sensitizes neurons to cell death in a human dopaminergic cell model and brain slice cultures. Together, these results indicate that histone acetylation regulates PKCδ expression to augment nigrostriatal dopaminergic cell death, which could contribute to the progressive neuropathogenesis of Parkinson disease. © 2014, American Society for Biochemistry and Molecular Biology Inc. All rights reserved. Source

Khare S.,Hines Veterans Affairs Medical Center | Khare S.,Loyola University Chicago | Verma M.,U.S. National Institutes of Health
Methods in Molecular Biology | Year: 2012

Accumulation of genetic and epigenetic alterations transforms normal colonic epithelial cells to adenocarcinoma cells. Genetic alterations include mutations in tumor suppressor genes and oncogenes, whereas epigenetic mechanisms are defined as heritable alterations in gene expression that is independent of changes in the primary DNA sequence. Role of epigenetic mechanisms in development and maintenance of organ- and tissue-specific gene expression is now realized. Disturbances in epigenetic landscape can lead to malignant cellular makeover, and these heritable changes are maintained through various cycles of cell division that renders cells to have discrete identity with similar genetic information. Epigenetic alterations in colorectal cancer (CRC) that transform colonic epithelial cells into adenocarcinoma cells include aberrant DNA methylation, chromatin modifications, and noncoding RNAs, especially microRNA expression. CpG island DNA methylation and aberrant methylation of genes drive the initiation and progression of CRC. Histone modifications impinge on chromatin structure and gene expression and thus play an important role in gene silencing in CRC. DNA hypermethylation also leads to downregulation and inappropriate expression of certain microRNAs that act like tumor suppressor genes. Determining the causes and roles of epigenetic instability in CRC pathogenesis will lead to effective prevention and therapeutic strategies for patients with CRC. Epigenetic drugs that underscore the reversible nature of epigenetic events have led the possibility of epigenetic therapy as a treatment option in CRC. © 2012 Springer Science+Business Media, LLC. Source

Rana A.,Loyola University Chicago | Rana A.,Hines Veterans Affairs Medical Center | Rana B.,Hines Veterans Affairs Medical Center | Rana B.,Loyola University Chicago | And 8 more authors.
Genes and Cancer | Year: 2013

Mixed lineage kinases (MLKs) are members of the mitogen-activated protein kinase kinase kinase (MAP3K) family and are reported to activate MAP kinase pathways. There have been at least 9 members of the MLK family identified to date, although the physiological functions of all the family members are yet unknown. However, MLKs in general have been implicated in neurodegenerative diseases, including Parkinson and Alzheimer diseases. Recent reports suggest that some of the MLK members could play a role in cancer via modulating cell migration, invasion, cell cycle, and apoptosis. This review article will first describe the biology of MLK members and then discuss the current progress that relates to their functions in cancer. © The Author(s) 2013. Source

Ghosh A.,Iowa State University | Saminathan H.,Iowa State University | Kanthasamy A.,Iowa State University | Anantharam V.,Iowa State University | And 7 more authors.
Journal of Biological Chemistry | Year: 2013

Background: Pin1 regulates several signaling proteins by isomerizing the cis/trans conformation of the Ser(P)-Pro peptide bond. Results: Pin1 is up-regulated in dopaminergic neurons in cell culture, animal models, and human PD brains. Pin1 inhibition protects dopaminergic neurons in PD models. Conclusion: Pin1 up-regulation plays a proapoptotic function in PD. Significance: Pin1 inhibition may be a viable translational strategy in PD. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Source

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