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Patrick Yau

Publications and source records attributed to Patrick Yau.

5 recordsLinked to original sources

Microarray-based DNA methylation profiling: technology and applications.

This work is dedicated to the development of a technology for unbiased, high-throughput DNA methylation profiling of large genomic regions. In this method, unmethylated and methylated DNA fractions are enriched using a series of treatments with methylation sensitive restriction enzymes, and interrogated on microarrays. We have investigated various aspects of the technology including its replicability, informativeness, sensitivity and optimal PCR conditions using microarrays containing oligonucleotides representing 100 kb of genomic DNA derived from the chromosome 22 COMT region in addition to 12 192 element CpG island microarrays. Several new aspects of methylation profiling are provided, including the parallel identification of confounding effects of DNA sequence variation, the description of the principles of microarray design for epigenomic studies and the optimal choice of methylation sensitive restriction enzymes. We also demonstrate the advantages of using the unmethylated DNA fraction versus the methylated one, which substantially improve the chances of detecting DNA methylation differences. We applied this methodology for fine-mapping of methylation patterns of chromosomes 21 and 22 in eight individuals using tiling microarrays consisting of over 340 000 oligonucleotide probe pairs. The principles developed in this work will help to make epigenetic profiling of the entire human genome a routine procedure.

Chromosome Mapping↗

CpG Island microarray probe sequences derived from a physical library are representative of CpG Islands annotated on the human genome.

An effective tool for the global analysis of both DNA methylation status and protein-chromatin interactions is a microarray constructed with sequences containing regulatory elements. One type of array suited for this purpose takes advantage of the strong association between CpG Islands (CGIs) and gene regulatory regions. We have obtained 20,736 clones from a CGI Library and used these to construct CGI arrays. The utility of this library requires proper annotation and assessment of the clones, including CpG content, genomic origin and proximity to neighboring genes. Alignment of clone sequences to the human genome (UCSC hg17) identified 9595 distinct genomic loci; 64% were defined by a single clone while the remaining 36% were represented by multiple, redundant clones. Approximately 68% of the loci were located near a transcription start site. The distribution of these loci covered all 23 chromosomes, with 63% overlapping a bioinformatically identified CGI. The high representation of genomic CGI in this rich collection of clones supports the utilization of microarrays produced with this library for the study of global epigenetic mechanisms and protein-chromatin interactions. A browsable database is available on-line to facilitate exploration of the CGIs in this library and their association with annotated genes or promoter elements.

Base Sequence↗

Effect of laparoscopic failure on outcome of laparoscopic nissen fundoplication: independent review.

PURPOSE: This study was undertaken to determine whether conversion or early reoperation contributed significantly to the eventual outcome of laparoscopic Nissen fundoplication. PATIENTS AND METHODS: An independent surgeon, blinded to the operative events, administered two general and one system-specific quality of life tools to the first 100 consecutive patients booked for laparoscopic fundoplication in a community hospital, where the open conversion rate was 4 patients/surgeon and the early reoperation rate 1.5 patients/surgeon for the first 20 operations. Patients were also asked about need for medication, dysphagia, satisfaction (analog scale), and whether, if given it to do over, they would opt for surgery again. RESULTS: Of the original 100 patients, 40 were studied an average of 5 years after surgery: 26 completed laparoscopically and 14 with laparoscopic failure (13 conversions and 1 early reoperation). Patient characteristics in the two groups were similar, except that there were more older patients with more fixed intrathoracic hiatus hernias in the failure group. Among the parameters examined, no statistically significant differences could be detected between laparoscopic and converted patients. CONCLUSIONS: General and system-specific quality of life, digestive symptoms, need for medication, patient satisfaction, and willingness to have surgery over again are not altered by conversion or reoperation. Thus, surgeons who have adequate laparoscopic skills, experience with open fundoplication, and training in laparoscopic Nissen fundoplication should feel free to add it to their repertoires provided the likelihood of conversion and reoperation secondary to inexperience is understood by the patient.

Female↗

Laparoscopic vertical banded gastroplasty: early results with the JOVO procedure.

BACKGROUND: Vertical banded gastroplasty (VBG) is an established treatment for morbid obesity for selected patients. This study seeks to assess the effectiveness of a laparoscopic version, the JOVO procedure, of the VBG. METHODS: An Independent surgeon interviewed all patients, who had had the JOVO procedure at one institution, evaluating weight loss, comorbid conditions, satisfaction and quality of life using the 36-item short-form health survey (SF-36). RESULTS: 14 JOVO procedures were done by two surgeons. Mean body mass index was 44 kg/m2, mean age 30 years and each patient had at least one comorbid condition. Mean operative time was 165 minutes. There was 1 complication, a suspected gastric leak requiring reoperation. Excluding this patient, mean hospital stay was less than 48 hours. Mean weight loss 4 weeks after surgery was 9 kg or 18% of excess weight. Mean excess weight loss of the 5 patients available for 1-year follow-up was 42% at 6 and 85% at 12 months; 1 did not continue to lose weight. All but 1 preoperative comorbid condition resolved or improved. 13 of the 14 patients were fully satisfied. SF-36 scores were high in the 13 that lost weight, especially in physical and social functioning areas. CONCLUSION: The JOVO procedure is safe and reproduces laparoscopically the early weight loss of open VBG with much shorter hospital stay and low complication and failure rates. Longer follow-up and larger numbers are needed.

Adult↗