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Velpula K.K.,Illinois College | Dasari V.R.,Illinois College | Asuthkar S.,Illinois College | Gorantla B.,Illinois College | Tsung A.J.,Illinois Neurological Institute
Translational Oncology | Year: 2012

Receptor tyrosine kinases (RTK) and their ligands control critical biologic processes, such as cell proliferation, migration, and differentiation. Aberrant expression of these receptor kinases in tumor cells alters multiple downstream signaling cascades that ultimately drive the malignant phenotype by enhancing tumor cell proliferation, invasion, metastasis, and angiogenesis. As observed in human glioblastoma (hGBM) and other cancers, this dysregulation of RTK networks correlates with poor patient survival. Epidermal growth factor receptor (EGFR) and c-Met, two well-known receptor kinases, are coexpressed in multiple cancers including hGBM, corroborating that their downstreamsignaling pathways enhance a malignant phenotype. The integration of c-Met and EGFR signaling in cancer cells indicates that treatment regimens designed to target both receptor pathways simultaneously could prove effective, though resistance to tyrosine kinase inhibitors continues to be a substantial obstacle. In the present study, we analyzed the antitumor efficacy of EGFR inhibitors erlotinib and gefitinib and c-Met inhibitor PHA-665752, along with their respective small hairpin RNAs (shRNAs) alone or in combination with human umbilical cord blood stem cells (hUCBSCs), in glioma cell lines and in animal xenograft models.We also measured the effect of dual inhibition of EGFR/c-Met pathways on invasion and wound healing. Combination treatments of hUCBSC with tyrosine kinase inhibitors significantly inhibited invasion and wound healing in U251 and 5310 cell lines, thereby indicating the role of hUCBSC in inhibition of RTK-driven cell behavior. Further, the EGFR and c-Met localization in glioma cells and hGBM clinical specimens indicated that a possible cross talk exists between EGFR and c-Met signaling pathway. © 2012 Neoplasia Press, Inc.

Ji R.,Tiantan Comprehensive Stroke Center | Wang D.,Illinois Neurological Institute | Shen H.,University of North Carolina at Chapel Hill | Pan Y.,Tiantan Comprehensive Stroke Center | And 4 more authors.
Stroke | Year: 2013

BACKGROUND AND PURPOSE - Medical complications are common among patients with stroke. However, little is known about the potential interrelationship among them. In the present study, we aimed to investigate the association between common in-hospital medical complications after acute ischemic stroke (AIS) and spontaneous intracerebral hemorrhage (ICH). METHODS - We analyzed patients enrolled in the China National Stroke Registry from 2007 to 2008. The occurrence of 11 common stroke-associated medical complications during acute hospitalization was prospectively registered. Multivariable analysis using generalized estimation equation was performed to assess association between medical complications in AIS and ICH cohort, respectively. RESULTS - A total of 14 702 patients with AIS and 5221 patients with ICH were enrolled. The median age was 65 years (interquartile range, 55-74 years), and 38.1% were female. The median length of hospital stay was 14 days (interquartile range, 10-20 days) for AIS and 18 days (interquartile range, 11-26 days) for ICH. Pneumonia was the most common medical complication after AIS (11.4%) and ICH (16.8%). In the AIS cohort, after adjusting for potential confounders, pneumonia was significantly associated with development of gastrointestinal bleeding (adjusted odds ratio [OR], 8.35; 95% confidence interval [CI], 6.27-11.1; P<0.001), decubitus ulcer (adjusted OR, 5.31; 95% CI, 3.39-8.31; P<0.001), deep vein thrombosis (adjusted OR, 4.27; 95% CI, 2.41-7.59; P<0.001), epileptic seizure (adjusted OR, 3.96; 95% CI, 2.67-5.88; P<0.001), urinary tract infection (adjusted OR, 3.34; 95% CI, 2.73-4.10; P<0.001), atrial fibrillation/flutter (adjusted OR, 3.17; 95% CI, 2.58-3.90; P<0.001), and recurrent stroke (adjusted OR, 2.65; 95% CI, 2.07-3.40; P<0.001). Similar significant association between pneumonia and development of several nonpneumonia medical complications was verified in ICH cohort as well. CONCLUSIONS - Pneumonia is closely associated with the development of several nonpneumonia medical complications after AIS and ICH. © 2013 American Heart Association, Inc.

Learmonth Y.C.,University of Illinois at Urbana - Champaign | Motl R.W.,University of Illinois at Urbana - Champaign | Sandroff B.M.,University of Illinois at Urbana - Champaign | Pula J.H.,Illinois College | And 2 more authors.
BMC Neurology | Year: 2013

Background: The Patient Determined Disease Steps (PDDS) is a promising patient-reported outcome (PRO) of disability in multiple sclerosis (MS). To date, there is limited evidence regarding the validity of PDDS scores, despite its sound conceptual development and broad inclusion in MS research. This study examined the validity of the PDDS based on (1) the association with Expanded Disability Status Scale (EDSS) scores and (2) the pattern of associations between PDDS and EDSS scores with Functional System (FS) scores as well as ambulatory and other outcomes.Methods: 96 persons with MS provided demographic/clinical information, completed the PDDS and other PROs including the Multiple Sclerosis Walking Scale-12 (MSWS-12), and underwent a neurological examination for generating FS and EDSS scores. Participants completed assessments of cognition, ambulation including the 6-minute walk (6 MW), and wore an accelerometer during waking hours over seven days.Results: There was a strong correlation between EDSS and PDDS scores (ρ = .783). PDDS and EDSS scores were strongly correlated with Pyramidal (ρ = .578 & ρ = .647, respectively) and Cerebellar (ρ = .501 & ρ = .528, respectively) FS scores as well as 6 MW distance (ρ = .704 & ρ = .805, respectively), MSWS-12 scores (ρ = .801 & ρ = .729, respectively), and accelerometer steps/day (ρ = -.740 & ρ = -.717, respectively).Conclusion: This study provides novel evidence supporting the PDDS as valid PRO of disability in MS. © 2013 Learmonth et al.; licensee BioMed Central Ltd.

Crockett C.D.,University of Iowa | Ruggieri A.,Hospital for Sick Children | Gujrati M.,Illinois College | Zallek C.M.,Illinois Neurological Institute | And 3 more authors.
Muscle and Nerve | Year: 2014

Introduction: X-linked myopathy with excessive autophagy (XMEA) is characterized by autophagic vacuoles with sarcolemmal features. Mutations in VMA21 result in insufficient lysosome acidification, causing progressive proximal weakness with onset before age 20 years and loss of ambulation by middle age. Methods: We describe a patient with onset of slowly progressive proximal weakness of the lower limbs after age 50, who maintains ambulation with the assistance of a cane at age 71. Results: Muscle biopsy at age 66 showed complex muscle fiber splitting, internalized capillaries, and vacuolar changes characteristic of autophagic vacuolar myopathy. Vacuoles stained positive for sarcolemmal proteins, LAMP2, and complement C5b-9. Ultrastructural evaluation further revealed basal lamina reduplication and extensive autophagosome extrusion. Sanger sequencing identified a known pathologic splice site mutation in VMA21 (c.164-7T>G). Conclusions: This case expands the clinical phenotype of XMEA and suggests VMA21 sequencing be considered in evaluating men with LAMP2-positive autophagic vacuolar myopathy. © 2014 Wiley Periodicals, Inc.

Beck A.R.,Illinois State University | Thompson J.R.,Illinois State University | Kosuwan K.,Srinakharinwirot University | Prochnow J.M.,Illinois Neurological Institute
Journal of Speech, Language, and Hearing Research | Year: 2010

Purpose: Study 1 developed the Assessment of Attitudes Toward Augmentative and Alternative Communication-2 (AATAAC-2) to assess adolescents' attitudes toward peers who use AAC. Study 2 used the AATAAC-2 to examine influences of familiarity with people with disabilities; type of AAC device; and various combinations of gender of rater, AAC user, and communication partner on adolescents' attitudes. Method: In Study 1, 194 adolescents viewed videotapes depicting adolescents using AAC, then completed AATAAC-2. Study 2 utilized 8 videotapes depicting 4 different gender combinations of AAC user and communication partner as experimental stimuli. Each gender combination was filmed twice: once with a static touch screen device, and once with a dynamic touch screen device. One-hundred thirty-six adolescents were randomly assigned to view 1 of the 8 videos. Participants then completed AATAAC-2. Results: Study 1 demonstrated that AATAAC-2 has adequate psychometric properties. Raters' responses in Study 2 indicated no main effect of device type; girls were more positive than boys; and familiarity with peers with disabilities was associated with more positive attitudes. No 2-way interactions were significant; 3-way interaction of level of familiarity, gender, and type of device used was significant. Conclusions: Familiarity and gender contribute to adolescents' attitudes; type of AAC device combined with these factors to influence attitudes © American Speech-Language-Hearing Association.

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