Publications by authors named "Justin Price"

20 Publications

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Transaxillary TAVR Leads to Shorter Ventilator Duration and Hospital Length of Stay Compared to Transapical TAVR.

Curr Probl Cardiol 2021 Mar 22;46(3):100624. Epub 2020 May 22.

John Ochsner Heart and Vascular Center, New Orleans, LA.

There is an increasing need for alternative access in patients with prohibitive surgical risk who have unsuitable anatomy for transfemoral transcatheter aortic valve replacement (TAVR). Data on differences in periprocedural outcomes via alternative access sites are scarce. We performed a retrospective analysis of patients who underwent Transaxillary (TAX) or Transapical (TAP) TAVR at our center from 2012 to 2019. All data was summarized and displayed as mean ± SD for continuous variables and number of patients in each group. A propensity score was created for each patient in the dataset to determine the probability of axillary vs apical access. We adjusted for propensity score using multivariate logistic regression. A total of 102 patients underwent TAVR via alternative access: 28 patients (27%) via TAX and 74 patients (73%) via transapical (TAP) access. The average time to extubation in the TAX group was 5.3 ± 3.5 hours vs 9.1 ± 8.8 hours in the TAP patients (P = 0.03). None of the TAX patients required reintubation compared to 23% of TAP TAVR (P = 0.003). The average hospital length of stay for TAX was 2.4 ± 2.0 days compared to 6.9 ± 3.3 days (P < 0.0001) for TAP. TAX TAVR patients had significantly lower re-intubation rates, shorter time to extubation and in-hospital length of stay, but higher pacemaker implantation rates. TAX TAVR had improved periprocedural outcomes compared to TAP TAVR and remains the preferred TAVR alternative access.
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http://dx.doi.org/10.1016/j.cpcardiol.2020.100624DOI Listing
March 2021

Low risk TAVR: Long- term considerations and appropriate patient selection.

Prog Cardiovasc Dis 2020 May - Jun;63(3):377-382. Epub 2020 Apr 8.

John Ochsner Heart and Vascular Center, New Orleans, LA, USA.

Recent trials have shown impressive results in low-risk patients undergoing Transcatheter Aortic Valve Replacement (TAVR) with low procedural complication rates, short hospital length of stay, zero mortality, and zero disabling stroke at 30 days and have led to a Food and Drug Administration indication for TAVR in these patients. The long-term data on subclinical leaflet thrombosis, valve durability, effects of pacemaker implantation, right ventricular pacing, and progressive paravalvular leak is unclear. We describe clinical and procedural considerations for patient selection and introduce future potential procedural challenges. Finally, we discuss the importance of considering life expectancy and durability prior to TAVR in this low risk relatively young cohort and emphasize the importance of a heart team approach.
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http://dx.doi.org/10.1016/j.pcad.2020.04.002DOI Listing
August 2020

The landing zone - Ground for model transfer in chemistry.

Authors:
Justin Price

Stud Hist Philos Sci 2019 10 29;77:21-28. Epub 2018 Jun 29.

University of South Carolina, Philosophy Department, James F. Byrnes Building, Columbia, SC, 29201, USA. Electronic address:

This essay proposes a new notion - the landing zone - in order to identify conceptual features that allow modelers to transfer mathematical tools across disciplinary borders. This discussion refers to the transferable models as 'templates'. Templates are functions, equations, or computational methods that are capable of being generalized from a particular subject matter. There are formal and conceptual prerequisites for the transfer of a template to a new domain. A landing zone is an ontology that contributes to the satisfaction of these conditions for successful transfer. This paper presents a case study on a model in chemistry - the Quantum Theory of Atoms in Molecules (QTAIM) - that makes use of transferred templates from physics - the virial theorem and the wave function. The landing zone in this case is a new ontological notion, that of the topological atom, which prepares ground for the use of the virial theorem and the wave function in chemistry. The virial theorem requires that there exists in-principle stability to the system that it represents, and the wave function requires transformation in its representation that is justified. The ontology of QTAIM - the landing zone for these templates - grounds the scientific use of these templates in the context of chemistry.
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http://dx.doi.org/10.1016/j.shpsa.2018.06.010DOI Listing
October 2019

The landing zone - Ground for model transfer in chemistry.

Authors:
Justin Price

Stud Hist Philos Sci 2019 10 29;77:21-28. Epub 2018 Jun 29.

University of South Carolina, Philosophy Department, James F. Byrnes Building, Columbia, SC, 29201, USA. Electronic address:

This essay proposes a new notion - the landing zone - in order to identify conceptual features that allow modelers to transfer mathematical tools across disciplinary borders. This discussion refers to the transferable models as 'templates'. Templates are functions, equations, or computational methods that are capable of being generalized from a particular subject matter. There are formal and conceptual prerequisites for the transfer of a template to a new domain. A landing zone is an ontology that contributes to the satisfaction of these conditions for successful transfer. This paper presents a case study on a model in chemistry - the Quantum Theory of Atoms in Molecules (QTAIM) - that makes use of transferred templates from physics - the virial theorem and the wave function. The landing zone in this case is a new ontological notion, that of the topological atom, which prepares ground for the use of the virial theorem and the wave function in chemistry. The virial theorem requires that there exists in-principle stability to the system that it represents, and the wave function requires transformation in its representation that is justified. The ontology of QTAIM - the landing zone for these templates - grounds the scientific use of these templates in the context of chemistry.
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http://dx.doi.org/10.1016/j.shpsa.2018.06.010DOI Listing
October 2019

Use of ViperSlide Lubricant to Extract Entrapped Sheath after Severe Radial Artery Spasm during Coronary Angiography.

Tex Heart Inst J 2018 06 1;45(3):186-187. Epub 2018 Jun 1.

Radial artery spasm is a known complication of transradial cardiac catheterization. However, severe spasm with sheath entrapment is rare. We describe such a case, and the condition's response to an alternative removal method after conventional efforts failed. A 68-year-old man presented for coronary angiography. We introduced a 5F sheath into the right radial artery, but, because of severe arterial spasm, we could not aspirate blood from the sheath or retract it. We sedated the patient and waited for the spasm to subside; however, the radial sheath remained entrapped. Nitroglycerin injection enabled blood aspiration and vasodilator injection, but not sheath removal. Finally, we injected ViperSlide lubricant into the sheath for its rapid, easy extraction. When sedation and vasodilator therapy fail, we recommend using ViperSlide for radial sheath removal before applying nerve block or general anesthesia.
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http://dx.doi.org/10.14503/THIJ-17-6394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059514PMC
June 2018

Hybrid Procedure (Endo/Epicardial) versus Standard Manual Ablation in Patients Undergoing Ablation of Longstanding Persistent Atrial Fibrillation: Results from a Single Center.

J Cardiovasc Electrophysiol 2016 05 25;27(5):524-30. Epub 2016 Feb 25.

Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA.

Introduction: Ablation of longstanding persistent atrial fibrillation (LSPAF) is the most challenging procedure in the treatment of AF, either by surgical or by percutaneous approach.

Objective: We investigated the difference in success and complication rates between combined surgical epicardial and endocardial catheter ablation procedure and our standard endocardial ablation procedure.

Methods And Results: Twenty-four consecutive patients (group 1) with LSPAF and enlarged left atrium (>4.5 cm) underwent a combined procedure, consisting of surgical, closed-chest, epicardial, radiofrequency ablation (nContact, NC, USA) via pericardial access, and concomitant endocardial ablation (hybrid procedure). Procedural complications and long-term outcomes were compared to those of 35 consecutive patients who refused the hybrid procedure and underwent standard endocardial only ablation (group 2). Baseline characteristics were comparable. In group 1, 1 patient (4.2%) developed post-procedural cardio-embolic stroke and 3 (12.5%) died (1 atrio-esophageal fistula, 1 fatal stroke, 1 of unknown cause in early follow-up), while no strokes or deaths occurred in group 2. Overall complication rates were higher for group 1 (P = 0.036). At 24-month follow-up, 4 (19%) patients in group 1 and 19 (54.3%) in group 2 were arrhythmia-free after a single procedure, on or off antiarrhythmic drugs (P<0.001). Total procedural time (276.9 ± 63.5 vs. 203.15 ± 67.3 minutes) and length of hospital stay (5 [IQR 3-8] vs. 1 [IQR 1-3] days were significantly shorter for group 2 (P <0.001).

Conclusions: In patients with LSPAF and enlarged left atrium, a concomitant combined surgical/endocardial ablation approach increases complication rate and does not improve outcomes when compared to extensive endocardial ablation only.
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http://dx.doi.org/10.1111/jce.12926DOI Listing
May 2016

White Fluorescent Light.

Authors:
Justin H Price

J Med Humanit 2016 Sep;37(3):351

Montana Family Medicine Residency, Billings, MT, USA.

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http://dx.doi.org/10.1007/s10912-015-9345-5DOI Listing
September 2016

Characterization of the mitofusin 2 R94W mutation in a knock-in mouse model.

J Peripher Nerv Syst 2014 Jun;19(2):152-64

Department of Human Genetics, Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.

Charcot-Marie-Tooth disease (CMT) comprises a group of heterogeneous peripheral axonopathies affecting 1 in 2,500 individuals. As mutations in several genes cause axonal degeneration in CMT type 2, mutations in mitofusin 2 (MFN2) account for approximately 90% of the most severe cases, making it the most common cause of inherited peripheral axonal degeneration. MFN2 is an integral mitochondrial outer membrane protein that plays a major role in mitochondrial fusion and motility; yet the mechanism by which dominant mutations in this protein lead to neurodegeneration is still not fully understood. Furthermore, future pre-clinical drug trials will be in need of validated rodent models. We have generated a Mfn2 knock-in mouse model expressing Mfn2(R94W), which was originally identified in CMT patients. We have performed behavioral, morphological, and biochemical studies to investigate the consequences of this mutation. Homozygous inheritance leads to premature death at P1, as well as mitochondrial dysfunction, including increased mitochondrial fragmentation in mouse embryonic fibroblasts and decreased ATP levels in newborn brains. Mfn2(R94W) heterozygous mice show histopathology and age-dependent open-field test abnormalities, which support a mild peripheral neuropathy. Although behavior does not mimic the severity of the human disease phenotype, this mouse can provide useful tissues for studying molecular pathways associated with MFN2 point mutations.
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http://dx.doi.org/10.1111/jns5.12066DOI Listing
June 2014

Does periprocedural anticoagulation management of atrial fibrillation affect the prevalence of silent thromboembolic lesion detected by diffusion cerebral magnetic resonance imaging in patients undergoing radiofrequency atrial fibrillation ablation with open irrigated catheters? Results from a prospective multicenter study.

Heart Rhythm 2014 May 4;11(5):791-8. Epub 2014 Mar 4.

Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin, Texas; Department of Biomedical Engineering, University of Texas, Austin, Texas; California Pacific Medical Center, San Francisco, California; Division of Cardiology, Stanford University, Palo Alto, California; Heart and Vascular Center, Case Western Reserve University, Cleveland, Ohio. Electronic address:

Background: Silent cerebral ischemia (SCI) has been reported in 14% of cases after catheter ablation of atrial fibrillation (AF) with radiofrequency (RF) energy and discontinuation of warfarin before AF ablation procedures.

Objective: The purpose of this study was to determine whether periprocedural anticoagulation management affects the incidence of SCI after RF ablation using an open irrigated catheter.

Methods: Consecutive patients undergoing RF ablation for AF without warfarin discontinuation and receiving heparin bolus before transseptal catheterization (group I, n = 146) were compared with a group of patients who had protocol deviation in terms of maintaining the therapeutic preprocedural international normalized ratio (patients with subtherapeutic INR) and/or failure to receive pretransseptal heparin bolus infusion and/or ≥2 consecutive ACT measurements <300 seconds (noncompliant population, group II, n = 134) and with a group of patients undergoing RF ablation with warfarin discontinuation bridged with low molecular weight heparin (group III, n = 148). All patients underwent preablation and postablation (within 48 hours) diffusion magnetic resonance imaging.

Results: SCI was detected in 2% of patients (3/146) in group I, 7% (10/134) in group II, and 14% (21/148) in group III (P <.001). "Therapeutic INR" was strongly associated with a lower prevalence of postprocedural silent cerebral ischemia (SCI). Multivariable analysis demonstrated nonparoxysmal AF (odds ratio 3.8, 95% confidence interval 1.5-9.7, P = .005) and noncompliance to protocol (odds ratio 2.8, 95% confidence interval 1.5-5.1, P <.001] to be significant predictors of ischemic events.

Conclusion: Strict adherence to an anticoagulation protocol significantly reduces the prevalence of SCI after catheter ablation of AF with RF energy.
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http://dx.doi.org/10.1016/j.hrthm.2014.03.003DOI Listing
May 2014

WITHDRAWN: Hybrid Procedure (Endo/Epicardial) Versus Standard Manual Ablation in Patients Undergoing Ablation of Longstanding Persistent Atrial Fibrillation: Results from a Single Center.

Heart Rhythm 2013 Nov 16. Epub 2013 Nov 16.

Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA; Department of Biomedical Engineering, University of Texas at Austin, Texas, USA; University of Foggia, Foggia, Italy; Albert Einstein College of Medicine at Montefiore Hospital, New York, USA.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
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http://dx.doi.org/10.1016/j.hrthm.2013.11.013DOI Listing
November 2013

Efficacy of catheter ablation in nonparoxysmal atrial fibrillation patients with severe enlarged left atrium and its impact on left atrial structural remodeling.

J Cardiovasc Electrophysiol 2013 Nov 10;24(11):1224-31. Epub 2013 Sep 10.

Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin, Texas, USA; Heart Institute, Faculty of Medicine, University of Pecs, Pecs, Hungary.

Introduction: The effect of catheter ablation on severe left atrial enlargement especially in nonparoxysmal atrial fibrillation (NPAF) patients is not well understood. Whether reverse remodelling may occur after ablation has not been evaluated in this setting.

Methods And Results: Fifty consecutive patients with left atrial diameter (LAD) ≥50 mm, and LA volume >200 cc undergoing catheter ablation for drug-refractory NPAF were included in this study. Transthoracic echocardiographic measurements were performed at baseline and at 12-months postprocedure. Left ventricular end-diastolic and end-systolic dimensions were indexed by body surface area (LVEDDI, LVESDI). Electroanatomic mapping system (Carto or NavX system) and computed tomography (CT) were used for 3-dimensional reconstruction of the LA. All patients underwent posterior wall isolation and pulmonary vein (PV) antrum and extra PV trigger ablations. Long-term follow-up was monitored by event recordings, 7-day Holter monitors and office visits. The mean age was 65 ± 10 years, 78% male, persistent AF 22 (44%), longstanding AF 28 (56%), LAD diameter 56.9 ± 7.8 mm, left ventricular ejection fraction (LVEF) 53 ± 14 and median AF duration 72 (49-96) months. At 12-month follow-up, 27 patients (54%) remained arrhythmia-free off antiarrhythmic drugs. Significant reduction in LAD at follow-up (≥10% reduction) was observed in 52% (26/50) of the total population and among the 63% (17/27) of recurrence-free patients. Magnitude of LA reduction was identically distributed among the persistent and longstanding persistent AF cohorts (16 ± 12% vs 14 ± 16%, respectively, P = 0.15). A significant 20% improvement in LVEF (from 53 ± 14 to 58 ± 9, P = 0.03) was found in the overall population. Improvement was noted in recurrence-free patients. No significant change in LVEDDI and LVESDI was noted. After adjusting for baseline risk factors in a multivariable model, a reduction in LAD was identified as a strong predictor of long-term success (beta = -11.1, P = 0.013). Preexisting LA scarring was associated with increased LAD (beta = 2.7, P = 0.023). No periprocedural or long-term complications were reported.

Conclusion: Our results show that atrial fibrillation ablation is effective in NPAF patients with severe LA enlargement and is associated with LA reverse remodeling and improvement in LVEF.
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http://dx.doi.org/10.1111/jce.12253DOI Listing
November 2013

Advances in catheter ablation: atrial fibrillation ablation in patients with mitral mechanical prosthetic valve.

Curr Cardiol Rev 2012 Nov;8(4):362-7

Texas Cardiac Arrhythmia Institute - St. David's Medical Center, Austin, TX 78705, USA.

Atrial fibrillation (AF) is common in patients with mitral valve replacement (MVR). Treatment of AF in these subjects is challenging, as the arrhythmia is often refractory to antiarrhythmic drug therapy. Radiofrequency catheter ablation (RFCA) is usually avoided or delayed in patients with MVR due to the higher perceived risks and difficulty of left atrial catheter manipulation in the presence of a mechanical valve. Over the last few years, several investigators have reported the feasibility and safety of RFCA of AF in patients with MVR. Five case-control studies have evaluated the feasibility and safety of RFCA of AF or perimitral flutter (PMFL) in patients with MVR. Overall, a total of 178 patients with MVR have been included (21 undergoing ablation of only PMFL), and have been compared with a matched control group of 285 patients. Total procedural duration (weighted mean difference [WMD] = +24.5 min, 95% confidence interval [CI] +10.2 min to +38.8 min, P = 0.001), and fluoroscopy time (WMD = +13.5 min, 95% CI +3.7 min to +23.4 min, P = 0.007) were longer in the MVR group. After a mean follow-up of 11.5 ± 8.6 months, 64 (36%) patients in the MVR group experienced recurrence of AF/PMFL, as compared to 73 (26%) patients in the control group, accounting for a trend toward an increased rate of recurrences in patients with MVR (odds ratio [OR] = 1.66, 95% CI 0.99 to 2.78, P = 0.053). Periprocedural complications occurred in 10 (5.6%) patients in the MVR group, and in 8 (2.8%) patients in the control group (OR = 2.01, 95% CI 0.56 to 7.15, P = 0.28). In conclusion, a quantitative analysis of the available evidence supports a trend toward a worse arrhythmia-free survival and a higher absolute rate of periprocedural complications in patients with MVR undergoing RFCA of AF or PMFL, as compared to a matched control group without mitral valve disease. These data would encourage the adoption of RFCA of AF in MVR patients mostly by more experienced Institutions.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3492819PMC
http://dx.doi.org/10.2174/157340312803760767DOI Listing
November 2012

Vitamin D receptor and Alzheimer's disease: a genetic and functional study.

Neurobiol Aging 2012 Aug 4;33(8):1844.e1-9. Epub 2012 Feb 4.

Hussman Institute for Human Genomics, University of Miami Miller School of Medicine 1501 NW 10 Ave, Miami, Florida, USA.

Genetic studies on late-onset Alzheimer's disease (AD) have repeatedly mapped susceptibility loci onto chromosome 12q13, encompassing the vitamin D receptor (VDR) gene. Epidemiology studies have indicated vitamin D insufficiency as a risk factor for AD. Given that VDR is the major mediator for vitamin D's actions, we sought to clarify the role of VDR in late-onset AD. We conducted an association study in 492 late-onset AD cases and 496 controls with 80 tagging single nucleotide polymorphisms (SNPs). The strongest association was found at a promoter SNP rs11568820 (P = 9.1 × 10(-6), odds ratio (OR) = 1.69), which resides within the transcription factor Cdx-2 binding site and the SNP has been also known as CDX2. The risk-allele at rs11568820 is associated with lower VDR promoter activity (p < 10(-11)). The overexpression of VDR or vitamin D treatment suppressed amyloid precursor protein (APP) transcription in neuroblastoma cells (p < 0.001). We provide both statistical evidence and functional data suggesting VDR confers genetic risk for AD. Our findings are consistent with epidemiology studies suggesting that vitamin D insufficiency increases the risk of developing AD.
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http://dx.doi.org/10.1016/j.neurobiolaging.2011.12.038DOI Listing
August 2012

Mutations in the ER-shaping protein reticulon 2 cause the axon-degenerative disorder hereditary spastic paraplegia type 12.

J Clin Invest 2012 Feb 9;122(2):538-44. Epub 2012 Jan 9.

Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA.

Hereditary spastic paraplegias (HSPs) are a group of genetically heterogeneous neurodegenerative conditions. They are characterized by progressive spastic paralysis of the legs as a result of selective, length-dependent degeneration of the axons of the corticospinal tract. Mutations in 3 genes encoding proteins that work together to shape the ER into sheets and tubules - receptor accessory protein 1 (REEP1), atlastin-1 (ATL1), and spastin (SPAST) - have been found to underlie many cases of HSP in Northern Europe and North America. Applying Sanger and exome sequencing, we have now identified 3 mutations in reticulon 2 (RTN2), which encodes a member of the reticulon family of prototypic ER-shaping proteins, in families with spastic paraplegia 12 (SPG12). These autosomal dominant mutations included a complete deletion of RTN2 and a frameshift mutation predicted to produce a highly truncated protein. Wild-type reticulon 2, but not the truncated protein potentially encoded by the frameshift allele, localized to the ER. RTN2 interacted with spastin, and this interaction required a hydrophobic region in spastin that is involved in ER localization and that is predicted to form a curvature-inducing/sensing hairpin loop domain. Our results directly implicate a reticulon protein in axonopathy, show that this protein participates in a network of interactions among HSP proteins involved in ER shaping, and further support the hypothesis that abnormal ER morphogenesis is a pathogenic mechanism in HSP.
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http://dx.doi.org/10.1172/JCI60560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266795PMC
February 2012

In vivo electroporation and non-protein based screening assays to identify antibodies against native protein conformations.

Hybridoma (Larchmt) 2011 Oct;30(5):409-18

Department of Microbiology and Immunology, University of Miami, Miami, Florida, USA.

In vivo electroporation has become a gold standard method for DNA immunization. The method assists the DNA entry into cells, results in expression and the display of the native form of antigens to professional cells of the immune system, uses both arms of immune system, has a built-in adjuvant system, is relatively safe, and is cost-effective. However, there are challenges for achieving an optimized reproducible process for eliciting strong humoral responses and for the screening of specific immune responses, in particular, when the aim is to mount humoral responses or to generate monoclonal antibodies via hybridoma technology. Production of monoclonal antibodies demands generation of high numbers of primed B and CD4 T helper cells in lymphoid organs needed for the fusion that traditionally is achieved by a final intravenous antigen injection. The purified antigen is also needed for screening of hundreds of clones obtained upon fusion of splenocytes. Such challenges make DNA vaccination dependent on purified proteins. Here, we have optimized methods for in vivo electroporation, production, and use of cells expressing the antigen and an in-cell Western screening method. These methods resulted in (1) reproducibly mounting robust humoral responses against antigens with different cell localizations, and (2) the ability to screen for antigen eliminating a need for protein/antigen purification. This process includes optimized parameters for in vivo electroporation, the use of transfected cells for final boost, and mild fixation/permeabilization of cells for screening. Using this process, upon two vaccinations via in vivo electroporation (and final boost), monoclonal antibodies against nucleus and cytoplasmic and transmembrane proteins were achieved.
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http://dx.doi.org/10.1089/hyb.2010.0120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241927PMC
October 2011

Mutation screening of mitofusin 2 in Charcot-Marie-Tooth disease type 2.

J Neurol 2011 Jul 22;258(7):1234-9. Epub 2011 Jan 22.

Department of Human Genetics, John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Biomedical Research Building, Room 523, LC: M-860, 1501 NW 10th Avenue, Miami, FL 33136, USA.

Charcot-Marie-Tooth (CMT) disease is among the most common inherited neurological disorders. Mutations in the gene mitofusin 2 (MFN2) cause the axonal subtype CMT2A, which has also been shown to be associated with optic atrophy, clinical signs of first motor neuron involvement, and early onset stroke. Mutations in MFN2 account for up to 20-30% of all axonal CMT type 2 cases. To further investigate the prevalence of MFN2 mutations and to add to the genotypic spectrum, we sequenced all exons of MFN2 in a cohort of 39 CMT2 patients. We identified seven variants, four of which are novel. One previously described change was co-inherited with a PMP22 duplication, which itself causes the demyelinating form CMT1A. Another mutation was a novel in frame deletion, which is a rare occurrence in the genotypic spectrum of MFN2 characterized mainly by missense mutations. Our results confirm a MFN2 mutation rate of ~15-20% in CMT2.
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http://dx.doi.org/10.1007/s00415-011-5910-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3125445PMC
July 2011

Intoxication with a ramp (Allium tricocca) mimicker. False hellebore (Veratrum viride) ingestion.

Wilderness Environ Med 2010 Mar 22;21(1):61-3. Epub 2009 Dec 22.

Division of Medical Toxicology, Department of Emergency Medicine, University of Virginia, Charlottesville, VA.

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http://dx.doi.org/10.1016/j.wem.2009.12.004DOI Listing
March 2010

A truncating mutation in SERPINB6 is associated with autosomal-recessive nonsyndromic sensorineural hearing loss.

Am J Hum Genet 2010 May 6;86(5):797-804. Epub 2010 May 6.

Dr. John T. Macdonald Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.

More than 270 million people worldwide have hearing loss that affects normal communication. Although astonishing progress has been made in the identification of more than 50 genes for deafness during the past decade, the majority of deafness genes are yet to be identified. In this study, we mapped a previously unknown autosomal-recessive nonsyndromic sensorineural hearing loss locus (DFNB91) to chromosome 6p25 in a consanguineous Turkish family. The degree of hearing loss was moderate to severe in affected individuals. We subsequently identified a nonsense mutation (p.E245X) in SERPINB6, which is located within the linkage interval for DFNB91 and encodes for an intracellular protease inhibitor. The p.E245X mutation cosegregated in the family as a completely penetrant autosomal-recessive trait and was absent in 300 Turkish controls. The mRNA expression of SERPINB6 was reduced and production of protein was absent in the peripheral leukocytes of homozygotes, suggesting that the hearing loss is due to loss of function of SERPINB6. We also demonstrated that SERPINB6 was expressed primarily in the inner ear hair cells. We propose that SERPINB6 plays an important role in the inner ear in the protection against leakage of lysosomal content during stress and that loss of this protection results in cell death and sensorineural hearing loss.
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http://dx.doi.org/10.1016/j.ajhg.2010.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2869020PMC
May 2010

Copy number variations are a rare cause of non-CMT1A Charcot-Marie-Tooth disease.

J Neurol 2010 May 1;257(5):735-41. Epub 2009 Dec 1.

Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL 33136,, USA.

Hereditary peripheral neuropathies present a group of clinically and genetically heterogeneous entities. All known forms, including the various forms of Charcot-Marie-Tooth disease (CMT) are characterized as Mendelian traits and over 35 genes have been identified thus far. The mutational mechanism of the most common CMT type, CMT1A, is a 1.5 Mb chromosomal duplication at 17p12 that contains the gene PMP22. Only recently it has been realized that such copy number variants (CNV) are a widespread phenomenon and important for disease. However, it is not known whether CNVs play a wider role in hereditary peripheral neuropathies outside of CMT1A. In a phenotypically heterogeneous sample of 97 patients, we performed the first high-density CNV study of 34 genomic regions harboring known genes for hereditary peripheral neuropathies including the 17p12 duplication region, with comparative genomic hybridization (CGH) microarrays. We identified three CNVs that affected coding exons. A novel shorter form of a PMP22 duplication was detected in a CMT1A family previously tested negative in a commercial test. Two other CNVs in MTMR2 and ARHGEF10 are likely not disease associated. Our results indicate that CNVs are a rare cause for non-CMT1A CMT. Their potential relevance as disease modifiers remains to be evaluated. The present study design cannot rule out that specific CMT forms exist where CNVs play a larger role.
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http://dx.doi.org/10.1007/s00415-009-5401-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2865568PMC
May 2010