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author:("Garg, bankit")
1.  KLHL40 deficiency destabilizes thin filament proteins and promotes nemaline myopathy 
The Journal of Clinical Investigation  2014;124(8):3529-3539.
Nemaline myopathy (NM) is a congenital myopathy that can result in lethal muscle dysfunction and is thought to be a disease of the sarcomere thin filament. Recently, several proteins of unknown function have been implicated in NM, but the mechanistic basis of their contribution to disease remains unresolved. Here, we demonstrated that loss of a muscle-specific protein, kelch-like family member 40 (KLHL40), results in a nemaline-like myopathy in mice that closely phenocopies muscle abnormalities observed in KLHL40-deficient patients. We determined that KLHL40 localizes to the sarcomere I band and A band and binds to nebulin (NEB), a protein frequently implicated in NM, as well as a putative thin filament protein, leiomodin 3 (LMOD3). KLHL40 belongs to the BTB-BACK-kelch (BBK) family of proteins, some of which have been shown to promote degradation of their substrates. In contrast, we found that KLHL40 promotes stability of NEB and LMOD3 and blocks LMOD3 ubiquitination. Accordingly, NEB and LMOD3 were reduced in skeletal muscle of both Klhl40–/– mice and KLHL40-deficient patients. Loss of sarcomere thin filament proteins is a frequent cause of NM; therefore, our data that KLHL40 stabilizes NEB and LMOD3 provide a potential basis for the development of NM in KLHL40-deficient patients.
PMCID: PMC4109545  PMID: 24960163
2.  Very Late Hazard with Stenting versus Balloon Angioplasty for ST-Elevation Myocardial Infarction: A 16-Year Single-Center Experience 
This study compares very late outcomes following primary percutaneous coronary intervention for ST-elevation myocardial infarction (STEMI) with stenting versus balloon angioplasty (BA).
Stenting compared with BA for STEMI improves outcomes at 6–12 months, but comparisons beyond 6–12 months have not been studied. Recent studies have shown that stent thrombosis (ST) continues to increase beyond 3–5 years and may be higher with drug-eluting stents (DES) than bare metal stents (BMS). We hypothesized that there may be a very late hazard with stenting versus BA due to very late ST.
From 1994 to 2010 consecutive patients with STEMI treated with BA (n = 601) or stenting (n = 1,594) were prospectively enrolled in our registry and followed for 1–16 years.
Patients treated with BA were older, were more often female, had more three-vessel disease, and had smaller vessels. Stented patients had trends for less stent/lesion thrombosis (ST/LT) and target vessel (TV) reinfarction at 1 year. In landmark analyses >1 year, stented patients had more very late ST/LT (6.1% vs. 2.9%, P = 0.002) and more TV reinfarction (7.9% vs. 3.1%, P < 0.001) which remained significant after adjusting for baseline risk. The greatest differences in very late outcomes were between DES and BA, but there were also significant differences between BMS and BA.
There appears to be a very late hazard with stenting versus BA for STEMI. These data should encourage new strategies for prevention of very late ST with both BMS and DES including the development of bioabsorbable polymers and stent platforms.
PMCID: PMC3955946  PMID: 24372979
3.  Human Cell Chips: Adapting DNA Microarray Spotting Technology to Cell-Based Imaging Assays 
PLoS ONE  2009;4(10):e7088.
Here we describe human spotted cell chips, a technology for determining cellular state across arrays of cells subjected to chemical or genetic perturbation. Cells are grown and treated under standard tissue culture conditions before being fixed and printed onto replicate glass slides, effectively decoupling the experimental conditions from the assay technique. Each slide is then probed using immunofluorescence or other optical reporter and assayed by automated microscopy. We show potential applications of the cell chip by assaying HeLa and A549 samples for changes in target protein abundance (of the dsRNA-activated protein kinase PKR), subcellular localization (nuclear translocation of NFκB) and activation state (phosphorylation of STAT1 and of the p38 and JNK stress kinases) in response to treatment by several chemical effectors (anisomycin, TNFα, and interferon), and we demonstrate scalability by printing a chip with ∼4,700 discrete samples of HeLa cells. Coupling this technology to high-throughput methods for culturing and treating cell lines could enable researchers to examine the impact of exogenous effectors on the same population of experimentally treated cells across multiple reporter targets potentially representing a variety of molecular systems, thus producing a highly multiplexed dataset with minimized experimental variance and at reduced reagent cost compared to alternative techniques. The ability to prepare and store chips also allows researchers to follow up on observations gleaned from initial screens with maximal repeatability.
PMCID: PMC2760726  PMID: 19862318
4.  LesionViewer: A Tool for Tracking Cancer Lesions Over Time 
Oncologists managing cancer patients use radiology imaging studies to evaluate changes in measurable cancer lesions. Currently, the textual radiology report summarizes the findings, but is disconnected from the primary image data. This makes it difficult for the physician to obtain a visual overview of the location and behavior of the disease. LesionViewer is a prototype software system designed to assist clinicians in comprehending and reviewing radiology imaging studies. The interface provides an Anatomical Summary View of the location of lesions identified in a series of studies, and direct navigation to the relevant primary image data. LesionViewer’s Disease Summary View provides a temporal abstraction of the disease behavior between studies utilizing methods of the RECIST guideline1. In a usability study, nine physicians used the system to accurately perform clinical tasks appropriate to the analysis of radiology reports and image data. All users reported they would use the system if available.
PMCID: PMC2655885  PMID: 18693875

Results 1-4 (4)