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Michael A Lee

Publications and source records attributed to Michael A Lee.

9 recordsLinked to original sources
PubMed2006

Establishment of a pipeline to analyse non-synonymous SNPs in Bos taurus.

BACKGROUND: Single nucleotide polymorphisms (SNPs) are an abundant form of genetic variation in the genome of every species and are useful for gene mapping and association studies. Of particular interest are non-synonymous SNPs, which may alter protein function and phenotype. We therefore examined bovine expressed sequences for non-synonymous SNPs and validated and tested selected SNPs for their association with measured traits. RESULTS: Over 500,000 public bovine expressed sequence tagged (EST) sequences were used to search for coding SNPs (cSNPs). A total of 15,353 SNPs were detected in the transcribed sequences studied, of which 6,325 were predicted to be coding SNPs with the remaining 9,028 SNPs presumed to be in untranslated regions. Of the cSNPs detected, 2,868 were predicted to result in a change in the amino acid encoded. In order to determine the actual number of non-synonymous polymorphic SNPs we designed assays for 920 of the putative SNPs. These SNPs were then genotyped through a panel of cattle DNA pools using chip-based MALDI-TOF mass spectrometry. Of the SNPs tested, 29% were found to be polymorphic with a minor allele frequency >10%. A subset of the SNPs was genotyped through animal resources in order to look for association with age of puberty, facial eczema resistance or meat yield. Three SNPs were nominally associated with resistance to the disease facial eczema (P < 0.01). CONCLUSION: We have identified 15,353 putative SNPs in or close to bovine genes and 2,868 of these SNPs were predicted to be non-synonymous. Approximately 29% of the non-synonymous SNPs were polymorphic and common with a minor allele frequency >10%. Of the SNPs detected in this study, 99% have not been previously reported. These novel SNPs will be useful for association studies or gene mapping.

Amino Acid Substitution↗
PubMed2006

Performance of a new single-chamber ICD algorithm: discrimination of supraventricular and ventricular tachycardia based on vector timing and correlation.

AIMS: Interval- and morphology-based algorithms have been used in modern implantable cardioverter defibrillators (ICDs) to discriminate supraventricular tachycardia (SVT) from other rhythms. A newly developed ICD discrimination algorithm, Rhythm ID (Guidant Corporation, St Paul, MN, USA), uses both interval-based metrics and an electrogram vector timing and correlation (VTC) algorithm in a dual-chamber ICD. In a single-chamber ICD, Rhythm ID contains only the VTC component. This study conducted a retrospective analysis of the performance of Rhythm ID for the detection of induced and spontaneous rhythms in a single-chamber ICD. METHODS AND RESULTS: This study gathered the data from a prospective, multicentre clinical trial. Ninety-six patients were implanted with a dual-chamber ICD. For this study, each episode was analysed to determine the performance of the single-chamber ICD Rhythm ID algorithm. The mean age of the patients implanted with the device was 67+/-11 years. Seventy-eight patients were male. The primary cardiovascular disease was coronary artery disease and the primary tachyarrhythmia was monomorphic ventricular tachycardia (VT). The mean follow-up time was 11.4 months. A total of 369 induced and spontaneous ventricular arrhythmias was analysed. The algorithm detected 100% of ventricular arrhythmias. Four hundred and forty-two SVT episodes were analysed, including 145 induced and 297 spontaneous. The SVTs were atrial fibrillation (n=199), atrial flutter (n=135), and 1:1 SVT (n=108). The single-chamber ICD Rhythm ID algorithm successfully discriminated 403 SVT episodes and achieved a specificity of 91%. CONCLUSION: The single-chamber version of Rhythm ID demonstrated high specificity without compromising sensitivity.

Aged↗
PubMed2005

Regulation of sphingosine-1-phosphate lyase gene expression by members of the GATA family of transcription factors.

Sphingosine-1-phosphate is a bioactive sphingolipid that regulates proliferation, differentiation, migration, and apoptosis. Sphingosine-1-phosphate is irreversibly degraded by the highly conserved enzyme sphingosine-1-phosphate lyase. Recent studies have suggested that sphingosine-1-phosphate lyase expression affects animal development and cell fate decisions. Despite its crucial role, mechanisms affecting expression of sphingosine-1-phosphate lyase remain poorly understood. In this study, regulation of sphingosine-1-phosphate lyase gene expression was investigated in Caenorhabditis elegans, where lyase expression is spatially restricted to cells of the developing and adult gut and is essential for normal development. Deletion analysis and generation of transgenic worms combined with fluorescence microscopy identified a 350-nucleotide sequence upstream of the ATG start site necessary for maximal lyase expression in adult worms. Site-specific mutagenesis of a GATA transcription factor-binding motif in the promoter led to loss of reporter expression. Knockdown of the gut-specific GATA transcription factor ELT-2 by RNA interference similarly led to loss of reporter expression. ELT-2 interacted with the GATA factor-binding motif in vitro and was also capable of driving expression of a Caenorhabditis elegans lyase promoter-beta-galactosidase reporter in a heterologous yeast system. These studies demonstrate that ELT-2 regulates sphingosine-1-phosphate lyase expression in vivo. Additionally, we demonstrate that the human sphingosine-1-phosphate lyase gene is regulated by a GATA transcription factor. Overexpression of GATA-4 led to both an increase in activity of a reporter gene as well as an increase in endogenous sphingosine-1-phosphate lyase protein.

Aldehyde-Lyases↗
PubMed2005

Green's function Monte Carlo method with exact imaginary-time propagation.

We present a general formulation of the Green's function Monte Carlo method in imaginary-time quantum Monte Carlo which employs exact propagators. This algorithm has no time-step errors and is obtained by minimal modifications of the time-independent Green's function Monte Carlo method. We describe how the method can be applied to the many-body Schrödinger equation, lattice Hamiltonians, and simple field theories. Our modification of the Green's function Monte Carlo algorithm is applied to the ground state of liquid 4He. We calculate the zero-temperature imaginary-time diffusion constant and relate that to the effective mass of a mass-four "impurity" atom in liquid 4He.

Journal Article↗
PubMed2005

Clinical results of an advanced SVT detection enhancement algorithm.

INTRODUCTION: Supraventricular tachycardia (SVT) has many characteristics that are similar to ventricular tachycardia (VT). This presents a significant challenge for the SVT-detection algorithms of an implantable cardioverter defibrillator (ICD). A newly developed ICD, which utilizes a Vector Timing and Correlation algorithm as well as interval-based conventional SVT discrimination algorithms (Rhythm ID), was evaluated in this study. MATERIALS AND METHODS: This study was a prospective, multicenter trial that evaluated 96 patients implanted with an ICD at 21 U.S. centers. All patients were followed at 2 weeks, 1 month, and every 3 months post implant. A manual Rhythm ID reference vector was acquired prior to any arrhythmia induction. During testing, atrial tachyarrhythmias were induced first, followed by ventricular arrhythmia induction. Induced and spontaneous SVT and VT/ventricular fibrillation (VF) episodes recorded during the trial were annotated by physician investigators. RESULTS: The mean age of the patients implanted with an ICD was 67.3 +/- 10.8 years. Eighty-one percent of patients were male. The primary cardiovascular disease was coronary artery disease, and the primary tachyarrhythmia was monomorphic VT. Implementation of the Rhythm ID algorithm did not affect the VT/VF detection time. There were a total of 370 ventricular tachyarrhythmias (277 induced and 93 spontaneous) and 441 SVT episodes (168 induced and 273 spontaneous). Sensitivity for ventricular tachyarrhythmias was 100%, and specificity for SVT was 92% (94% and 91% for induced and spontaneous SVT, respectively). All patients had a successful manual Rhythm ID acquisition prior to atrial tachyarrhythmia induction. At the 1-month follow-up, the Rhythm ID references were updated automatically an average of 167.8 +/- 122.7 times. Stored Rhythm ID references correlated to patients' normally conducted rhythm 100% at 2 weeks, and 98% at 1 month. CONCLUSIONS: The Rhythm ID algorithm achieved 100% sensitivity for VT/VF, and 92% specificity for SVT. The manual and automatic Rhythm ID update algorithms successfully acquired references, and the updated references were highly accurate.

Aged↗
PubMed2003

The effect of atrial pacing therapies on atrial tachyarrhythmia burden and frequency: results of a randomized trial in patients with bradycardia and atrial tachyarrhythmias.

OBJECTIVES: The Atrial Therapy Efficacy and Safety Trial (ATTEST) was a prospective, randomized study to evaluate preventive pacing and antitachycardia pacing (ATP) in patients with symptomatic atrial fibrillation (AF) or atrial tachycardia (AT). BACKGROUND: The effect of the combination of atrial prevention and termination algorithms on AT/AF burden and frequency in pacemaker patients is unknown. METHODS: A DDDRP pacemaker (AT500, Medtronic Inc., Minneapolis, Minnesota) with three atrial preventive pacing algorithms and two ATP algorithms was implanted in 368 patients. Patients were randomized one-month post-implant to all prevention and ATP therapies ON or OFF and followed for three months. The OFF group had DDDR pacing at a lower programmed rate of 60 ppm. The AT/AF burden and frequency were determined from daily device counters in 324 patients treated according to protocol. RESULTS: In 17,018 episodes with stored electrograms, appropriate detection was confirmed in 17,004 (99.9%). The median percentage of atrial pacing was 98% in the ON group versus 75% in the OFF group (p < 0.001). Using device-defined criteria for successful termination, ATP terminated 8,590 (54%) of 15,789 treated episodes. The median AT/AF burden during the three-month study period was 4.2 h/month ON versus 1.1 h/month OFF (p = 0.20). The median AT/AF frequency was 1.3 episodes/month ON versus 1.2 episodes/month OFF (p = 0.65). System-related, complication-free survival at four months was 90.2% (Kaplan-Meier estimate). CONCLUSIONS: This DDDRP pacemaker is safe, has accurate AT/AF detection, and provides ATP with 54% efficacy as defined by the device. The atrial prevention and termination therapies combined did not reduce AT/AF burden or frequency in this patient population.

Aged↗
PubMedDate not supplied

Adolescent concussions--management recommendations: a practical approach.

There is an epidemic in our midst that most of us are unaware of. Untold numbers of young people are suffering concussions at an alarming rate. Many go unreported. The public as well as the medical profession have failed to appreciate the consequences of this problem and have been unaware of its significance and its long-term complications. In order to prevent both the short and potentially long-term functional brain impairment that may occur if a concussion is not treated properly, the following management recommendations are outlined.

Adolescent↗