Publications by authors named "Joshua Brady"

4 Publications

  • Page 1 of 1

Racial Disparities in Patients with Melanoma: A Multivariate Survival Analysis.

Clin Cosmet Investig Dermatol 2021 24;14:547-550. Epub 2021 May 24.

Department of Dermatology, Wayne State University, Detroit, MI, USA.

Purpose: As the most common cause of skin cancer death, incidence and mortality of melanoma vary widely between ethnic and racial groups.

Methods: Surveillance, Epidemiology, and End Results (SEER) data were used to examine the incidence and survival in patients with melanoma concerning race and ethnicity in Wayne County, Michigan between 2000 and 2016.

Results: Analysis of data revealed significantly higher melanoma-specific death in non-Hispanic black patients compared to their non-Hispanic white counterparts (p <0.001). However, no increased risk of death due to melanoma was observed following adjustment of data for the stage, age, and sex (H.R. = 1.00, 95% CI 0.64-1.56).

Conclusion: Non-Hispanic black patients have the highest percentage of late-stage melanoma. Increased incidence of melanoma mortality in non-Hispanic black patients is likely a consequence of late-stage diagnosis.
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http://dx.doi.org/10.2147/CCID.S311694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163579PMC
May 2021

The Accessory Helix of Complexin Stabilizes a Partially Unzippered State of the SNARE Complex and Mediates the Complexin Clamping Function .

eNeuro 2021 Mar-Apr;8(2). Epub 2021 Apr 7.

Ophthalmology, Visual and Anatomical Sciences Department, Wayne State University School of Medicine, Detroit, MI 48202

Spontaneous synaptic transmission is regulated by the protein complexin (Cpx). Cpx binds the SNARE complex, a coil-coiled four-helical bundle that mediates the attachment of a synaptic vesicle (SV) to the presynaptic membrane (PM). Cpx is thought to clamp spontaneous fusion events by stabilizing a partially unraveled state of the SNARE bundle; however, the molecular detail of this mechanism is still debated. We combined electrophysiology, molecular modeling, and site-directed mutagenesis in to develop and validate the atomic model of the Cpx-mediated clamped state of the SNARE complex. We took advantage of botulinum neurotoxins (BoNTs) B and G, which cleave the SNARE protein synaptobrevin (Syb) at different sites. Monitoring synaptic depression on BoNT loading revealed that the clamped state of the SNARE complex has two or three unraveled helical turns of Syb. Site-directed mutagenesis showed that the Cpx clamping function is predominantly maintained by its accessory helix (AH), while molecular modeling suggested that the Cpx AH interacts with the unraveled C terminus of Syb and the SV lipid bilayer. The developed molecular model was employed to design new Cpx poor-clamp and super-clamp mutations and to tested the predictions employing molecular dynamics simulations. Subsequently, we generated lines harboring these mutations and confirmed the poor-clamp and super-clamp phenotypes Altogether, these results validate the atomic model of the Cpx-mediated fusion clamp, wherein the Cpx AH inserts between the SNARE bundle and the SV lipid bilayer, simultaneously binding the unraveled C terminus of Syb and preventing full SNARE assembly.
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http://dx.doi.org/10.1523/ENEURO.0526-20.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026252PMC
June 2021

Vasoprotective endothelial effects of a standardized grape product in humans.

Vascul Pharmacol 2009 Jan-Feb;50(1-2):20-6. Epub 2008 Sep 7.

Heart Center Research Program and Center for Cardiovascular and Pulmonary Research, Nationwide Children's Hospital & Research Institute, United States.

The pathogenesis of coronary lesion development is a multi-factorial process involving a number of different cell types and covariates, and injury and dysfunction of the vascular endothelium is an important marker and likely participant in the initiation and/or progression of most forms of heart disease. In addition to chronic dysfunction of endothelial responses in patients with established heart disease, there is evidence that 'acute insults' can cause measurable dysfunction in vascular response in humans (drug toxicities, hypoxia, high fat meal). Such repeated acute insults may contribute to disease risk in otherwise healthy individuals or promote disease progression in established patients. Consumption of grape products, especially wine, has been linked to lower cardiovascular risk but the vascular endothelial effects of grape products in healthy normal subjects, in the absence of ethanol, have not been evaluated. We therefore tested the hypotheses that 1) a standardized product derived from fresh grapes (GP, acute and chronic consumption) improves endothelial performance in healthy normal young subjects, and 2) that concomitant grape consumption affects the 'acute endothelial insult' caused by a single standardized high fat meal (HF). Acute consumption of GP equivalent to 1.25 cups of fresh grapes caused significant improvement in brachial artery flow mediated dilation (FMD) within 3 h of consumption, when compared to control consumption of sugar solution (p<0.05). No acute changes in heart rate, hemodynamics, or lipid profiles were observed. When this 'dose' was then consumed twice daily for 3 weeks FMD was further improved and total antioxidant capacity in plasma was slightly increased (p<0.05), with no change in heart rate, hemodynamics, or lipid profiles. A single HF meal (900 cal, 49 g total fat) caused a 50% reduction in FMD response when consumed alone, and this effect coincided with increased blood triglyceride levels within 3 h post-consumption. In contrast the concomitant consumption of GP with the HF meal completely prevented this HF-induced vascular endothelial dysfunction (p<0.05), but had no effect on rising triglycerides. These data demonstrate that a modest intake of fresh grapes can have acute favorable effects on vascular endothelial function in normal healthy subjects, that chronic intake can further improve performance and concomitant intake can blunt the 'acute insult' to endothelium caused by a typical western HF meal. This effect is likely to be related to antioxidant effects at the endothelium, rather than changes in blood lipids. These data support epidemiological data of the health benefits of grapes, and demonstrate that 'favorable' food consumption can apparently reduce some toxicities induced by 'unfavorable' food consumption.
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http://dx.doi.org/10.1016/j.vph.2008.08.004DOI Listing
April 2009

Modulation of protein adsorption and cell adhesion by poly(allylamine hydrochloride) heparin films.

Biomaterials 2005 Jun;26(16):2975-81

Department of Chemical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0211, USA.

Electrostatic layer-by-layer film assembly is an attractive way to non-covalently incorporate proteins and bioactive moieties into the surface of conventional biomaterials. Selection of polycationic and polyanionic components and deposition conditions can be used to control the interfacial properties, and through them protein adsorption, cell adhesion, and tissue development. In this study the polycation was poly(allylamine hydrochloride) (PAH), which is a weak base and consequently adsorbs at interfaces in a pH-dependent manner, and the polyanion was heparin, which is capable of interacting with many adhesion ligands and growth factors. PAH/heparin multilayer films were formed using PAH solutions of pH 6.4, 7.4, 8.4, and 9.4. Film thickness increased both with the number of PAH/heparin bilayers and the pH of the PAH solution. Films consisting of 10 bilayers with heparin topmost exhibited similar bulk atomic compositions and penetration of PAH into the heparin top layer. Finally, fibronectin adsorption and cell adhesion were maximal at an intermediate pH (pH 8.4>pH 9.4>pH 7.4). These results demonstrate that heparin-containing electrostatic films support cell adhesion and protein adsorption in a manner sensitive to film deposition conditions.
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http://dx.doi.org/10.1016/j.biomaterials.2004.08.013DOI Listing
June 2005