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Charles Lee

Publications and source records attributed to Charles Lee.

At least 37 records · Page 2Linked to original sources
PubMed2006

EMBL Nucleotide Sequence Database: developments in 2005.

The EMBL Nucleotide Sequence Database (www.ebi.ac.uk/embl) at the EMBL European Bioinformatics Institute, UK, offers a comprehensive set of publicly available nucleotide sequence and annotation, freely accessible to all. Maintained in collaboration with partners DDBJ and GenBank, coverage includes whole genome sequencing project data, directly submitted sequence, sequence recorded in support of patent applications and much more. The database continues to offer submission tools, data retrieval facilities and user support. In 2005, the volume of data offered has continued to grow exponentially. In addition to the newly presented data, the database encompasses a range of new data types generated by novel technologies, offers enhanced presentation and searchability of the data and has greater integration with other data resources offered at the EBI and elsewhere. In stride with these developing data types, the database has continued to develop submission and retrieval tools to maximise the information content of submitted data and to offer the simplest possible submission routes for data producers. New developments, the submission process, data retrieval and access to support are presented in this paper, along with links to sources of further information.

Animals↗
PubMed2006

Effect of setting conditions on mineral trioxide aggregate flexural strength.

This study evaluated the effect of setting conditions (time and hydration) on mineral trioxide aggregate (MTA) flexural strength. MTA beam specimens were allowed to set for either 24 or 72 hours with specimens exposed to moisture on either one or two specimen surfaces. These moisture conditions were used to simulate MTA setting with only external tissue moisture (one-sided moisture) versus tissue moisture in combination with a moistened intracanal cotton pellet (two-sided moisture). Ten specimens were stored at 37 degrees C under each of the four experimental setting conditions (1) 24-hour/moist/2-sided; (2) 24-hour/moist/1-sided; (3) 72-hour/moist/2-sided; (4) 72-hour/moist/1-sided. After storage at respective setting conditions, MTA specimens were tested to failure with three-point bend test to measure flexural strength. Flexural strength of the 24h/moist/2-sided specimens, 14.27 +/- 1.96 MPa, was significantly higher (p < or = 0.05) than the flexural strength values associated with conditions two, three, and four, respectively, 10.77 +/- 1.44, 11.16 +/- 0.96, 11.18 +/- 0.99 MPa, which were not significantly different from each other (p > 0.05). Clinically, these results suggest that a moistened cotton pellet should be placed on the intracanal MTA surface under a temporary restoration; and if possible, to optimize flexural strength, the moistened pellet should only remain in place for 24 hours.

Aluminum Compounds↗
PubMed2006

Sealing ability of three materials in the orifice of root canal systems obturated with gutta-percha.

There were 130 single roots randomly assigned to one of 12 experimental or two control groups. Forty specimens each were sealed with 1, 2, 3, or 4 mm of Cavit, ProRoot MTA, or Tetric. After creation of a uniform orifice diameter, the smear layer was removed and the canal systems obturated using warm lateral compaction of gutta-percha (GP). GP was removed to the experimental depth, experimental materials placed in the orifice, and roots submerged in India ink in a vacuum flask. Specimens were demineralized and leakage measured using a 10x stereomicroscope and graded for depth of leakage by one calibrated, blinded rater. There was no significant interaction (p > 0.05) between test materials and orifice depths, nor main effect of orifice depth (p > 0.05). However, there was a statistically significant main effect of test materials with Tetric demonstrating a significantly better seal than Pro Root or Cavit (p < 0.0001) irrespective of orifice depth.

Aluminum Compounds↗
PubMed2006

Common deletion polymorphisms in the human genome.

The locations and properties of common deletion variants in the human genome are largely unknown. We describe a systematic method for using dense SNP genotype data to discover deletions and its application to data from the International HapMap Consortium to characterize and catalogue segregating deletion variants across the human genome. We identified 541 deletion variants (94% novel) ranging from 1 kb to 745 kb in size; 278 of these variants were observed in multiple, unrelated individuals, 120 in the homozygous state. The coding exons of ten expressed genes were found to be commonly deleted, including multiple genes with roles in sex steroid metabolism, olfaction and drug response. These common deletion polymorphisms typically represent ancestral mutations that are in linkage disequilibrium with nearby SNPs, meaning that their association to disease can often be evaluated in the course of SNP-based whole-genome association studies.

Databases, Genetic↗
PubMed2006

Complications in paediatric anaesthesia.

PURPOSE OF REVIEW: This review identifies the most serious complications likely to be encountered in the current practice of paediatric anaesthesia. RECENT FINDINGS: The findings of the ASA Closed Claims Project, published in 1993, showed a higher proportion of closed paediatric malpractice claims related to respiratory events than to cardiovascular events. The Pediatric Perioperative Cardiac Arrest Registry--an offshoot of the American Society of Anesthesiologists Closed Claims Project--reviewed cardiac arrest data collected between 1994 and 1997, revealing a shift in the aetiology of cardiac arrest during paediatric anaesthesia over the past 20 years. The study found that reported cardiac arrests were now more prevalent from cardiovascular causes than respiratory causes, unlike the findings in the previous Closed Claims Project. Follow-up data collected by both the Pediatric Perioperative Cardiac Arrest Registry and the American Society of Anesthesiologists Closed Claims Project confirm this trend. SUMMARY: Outcomes for paediatric patients undergoing anaesthesia have improved over the years as a result of advances in monitoring and equipment, safer and more easily titratable anaesthetic agents, and possibly the practice of subspecialization. Preventable complications still, however, occur. An awareness of frequently encountered complications during paediatric anaesthesia may lead to the earlier detection and treatment of perioperative problems, leading to better outcomes.

Anesthesia↗
PubMed2006

Detecting copy number variation in the human genome using comparative genomic hybridization.

Among human beings, it was once estimated that our genomes were 99.9% genetically identical. While this high level of genetic similarity helps to define us as a species, it is our genetic variation that contributes to our phenotypic diversity. As genomic technologies evolve to provide genome-wide analyses at higher resolution, we are beginning to appreciate that the human genome has a lot more variation than was once thought. Array-based comparative genomic hybridization (CGH) is one of these technologies that has recently revealed a newly appreciated type of genetic variation: copy number variation, in which thousands of regions of the human genome are now known to be variable in number between individuals. Some of these copy number variable regions have already been shown to predispose to certain common diseases, and others may ultimately have a significant impact on how each of us reacts to certain foods (e.g., allergic reactions), medications (e.g., pharmacogenomics), microscopic infections (i.e., immunity), and other aspects of our ever-changing environment.

Gene Dosage↗
PubMed2006

Copy number variants and pharmacogenomics.

The earliest pharmacogenomic studies focused on highly penetrant sequence polymorphisms in drug-metabolizing enzymes. The recent discovery of the widespread occurrence of copy number variants/polymorphisms in the human genome holds promise for new pharmacogenomic discoveries, aside from the commonly used single nucleotide polymorphism approach. Here we review the discovery of copy number variants and speculate on their implications for pathophysiology and pharmacogenomics.

Animals↗
PubMed2005

Spinal cord gliomas: A multi-institutional retrospective analysis.

PURPOSE: To determine the impact of postoperative radiation therapy (POXRT) on outcome in spinal cord gliomas. PATIENTS AND METHODS: Data from 242 patients were collected retrospectively from six institutions using a standardized data sheet. Pathology specimens, when available, were centrally reviewed. RESULTS: A total of 183 patients were analyzed: 82 received surgery alone as initial treatment, whereas 101 had surgery and POXRT. Demographic, diagnostic, and treatment factors were analyzed for impact on progression-free (PFS) and overall survival (OS). PFS in ependymoma patients was 74%, 60%, and 35% at 5, 10, 15 years, respectively, and was significantly influenced by treatment type, race, age, tumor grade, and type of surgery on univariate analysis, with age being the only significant factor on multivariate analysis (MVA) (p = 0.01). OS of ependymoma patients was 91%, 84%, and 75% at 5, 10, and 15 years, respectively, and was significantly influenced by both complete resection (p = 0.04) and age (p = 0.03) on MVA. In astrocytomas, PFS was 42%, 29%, and 15% at 5, 10, and 15 years, and was significantly influenced by POXRT in low- and intermediate-grade tumors on MVA (p = 0.02). OS at 5, 10, and 15 years was 59%, 53%, and 32%, respectively, and was significantly influenced by grade on MVA (p < 0.01). CONCLUSION: Postoperative radiation therapy reduced disease progression in low- and moderate-grade astrocytomas. In ependymomas, complete resection significantly influenced OS.

Adolescent↗
PubMed2005

Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer.

Recurrent chromosomal rearrangements have not been well characterized in common carcinomas. We used a bioinformatics approach to discover candidate oncogenic chromosomal aberrations on the basis of outlier gene expression. Two ETS transcription factors, ERG and ETV1, were identified as outliers in prostate cancer. We identified recurrent gene fusions of the 5' untranslated region of TMPRSS2 to ERG or ETV1 in prostate cancer tissues with outlier expression. By using fluorescence in situ hybridization, we demonstrated that 23 of 29 prostate cancer samples harbor rearrangements in ERG or ETV1. Cell line experiments suggest that the androgen-responsive promoter elements of TMPRSS2 mediate the overexpression of ETS family members in prostate cancer. These results have implications in the development of carcinomas and the molecular diagnosis and treatment of prostate cancer.

Androgens↗
PubMed2005

Long-term results of hyperfractionated radiation and high-dose intraarterial cisplatin for unresectable oropharyngeal carcinoma.

BACKGROUND: In this report, the authors present the results from a study of patients with unresectable oropharyngeal squamous cell carcinomas who were treated on a protocol of hyperfractionated radiation and high-dose intraarterial cisplatin (HYPERRADPLAT) at the University of Kentucky. METHODS: The study was designed as a prospective, single-armed case series that was conducted in the setting of a single, academic, tertiary referral center. The patient cohort consisted of 24 previously untreated patients who were diagnosed with unresectable oropharyngeal carcinoma and were treated on the HYPERRADPLAT regimen, which included hyperfractionated external beam radiotherapy (1.2 grays [Gy] twice daily) was given for 5 weeks (60 Gy) followed by high-dose intraarterial cisplatin (150 mg/m2) and sodium thiosulfate. Shrinking "large-field" portals were started on Week 6 and finished on Week 7 with a cumulative dose of 76.8-81.6 Gy. The main outcome measures of the study were the primary and neck response rates, the 2-year and 5-year overall survival and disease-specific survival rates, and acute and late treatment morbidity. RESULTS: The median follow-up was 77 months. Complete response rates at the primary and regional lymph nodes were both 88%. The 2-year overall survival and disease-specific survival rates were 57% and 68%, respectively; whereas the 5-year overall survival and disease-specific survival rates were 33% and 42%, respectively. Two patients had Grade 4 mucosal toxicity, and no patient experienced neurologic or significant hematologic toxicities. Within 1 year of treatment, 58% of patients had used a feeding tube. CONCLUSIONS: The HYPERRADPLAT regimen produced excellent response rates and overall survival rates comparable to those achieved by patients who had unresectable oropharyngeal carcinomas. Tolerance of the therapy was good, and further studies using HYPERRADPLAT with induction therapy may improve outcomes further in this subset of patients with unfavorable disease.

Adult↗
PubMed2005

A zebrafish bmyb mutation causes genome instability and increased cancer susceptibility.

A major goal of cancer research has been to identify genes that contribute to cancer formation. The similar pathology between zebrafish and human tumors, as well as the past success of large-scale genetic screens in uncovering human disease genes, makes zebrafish an ideal system in which to find such new genes. Here, we show that a zebrafish forward genetic screen uncovered multiple cell proliferation mutants including one mutant, crash&burn (crb), that represents a loss-of-function mutation in bmyb, a transcriptional regulator and member of a putative proto-oncogene family. crb mutant embryos have defects in mitotic progression and spindle formation, and exhibit genome instability. Regulation of cyclin B levels by bmyb appears to be the mechanism of mitotic accumulation in crb. Carcinogenesis studies reveal increased cancer susceptibility in adult crb heterozygotes. Gene-expression signatures associated with loss of bmyb in zebrafish are also correlated with conserved signatures in human tumor samples, and down-regulation of the B-myb signature genes is associated with retention of p53 function. Our findings show that zebrafish screens can uncover cancer pathways, and demonstrate that loss of function of bmyb is associated with cancer.

Animals↗
PubMed2005

Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma.

Systematic analyses of cancer genomes promise to unveil patterns of genetic alterations linked to the genesis and spread of human cancers. High-density single-nucleotide polymorphism (SNP) arrays enable detailed and genome-wide identification of both loss-of-heterozygosity events and copy-number alterations in cancer. Here, by integrating SNP array-based genetic maps with gene expression signatures derived from NCI60 cell lines, we identified the melanocyte master regulator MITF (microphthalmia-associated transcription factor) as the target of a novel melanoma amplification. We found that MITF amplification was more prevalent in metastatic disease and correlated with decreased overall patient survival. BRAF mutation and p16 inactivation accompanied MITF amplification in melanoma cell lines. Ectopic MITF expression in conjunction with the BRAF(V600E) mutant transformed primary human melanocytes, and thus MITF can function as a melanoma oncogene. Reduction of MITF activity sensitizes melanoma cells to chemotherapeutic agents. Targeting MITF in combination with BRAF or cyclin-dependent kinase inhibitors may offer a rational therapeutic avenue into melanoma, a highly chemotherapy-resistant neoplasm. Together, these data suggest that MITF represents a distinct class of 'lineage survival' or 'lineage addiction' oncogenes required for both tissue-specific cancer development and tumour progression.

Cell Line, Tumor↗
PubMed2005

Temporal profile of replication of human chromosomes.

Chromosomes in human cancer cells are expected to initiate replication from predictably localized origins, firing reproducibly at discrete times in S phase. Replication products obtained from HeLa cells at different stages of S phase were hybridized to cDNA and genome tiling oligonucleotide microarrays to determine the temporal profile of replication of human chromosomes on a genome-wide scale. About 1,000 genes and chromosomal segments were identified as sites containing efficient origins that fire reproducibly. Early replication was correlated with high gene density. An acute transition of gene density from early to late replicating areas suggests that discrete chromatin states dictate early versus late replication. Surprisingly, at least 60% of the interrogated chromosomal segments replicate equally in all quarters of S phase, suggesting that large stretches of chromosomes are replicated by inefficient, variably located and asynchronous origins and forks, producing a pan-S phase pattern of replication. Thus, at least for aneuploid cancer cells, a typical discrete time of replication in S phase is not seen for large segments of the chromosomes.

Chromosomes, Human↗
PubMed2005

BRAF mutations are sufficient to promote nevi formation and cooperate with p53 in the genesis of melanoma.

Melanoma is the most lethal form of skin cancer, and the incidence and mortality rates are rapidly rising. Epidemiologically, high numbers of nevi (moles) are associated with higher risk of melanoma . The majority of melanomas exhibit activating mutations in the serine/threonine kinase BRAF . BRAF mutations may be critical for the initiation of melanoma ; however, the direct role of BRAF in nevi and melanoma has not been tested in an animal model. To directly test the role of activated BRAF in nevus and melanoma development, we have generated transgenic zebrafish expressing the most common BRAF mutant form (V600E) under the control of the melanocyte mitfa promoter. Expression of mutant, but not wild-type, BRAF led to dramatic patches of ectopic melanocytes, which we have termed fish (f)-nevi. Remarkably, in p53-deficient fish, activated BRAF induced formation of melanocyte lesions that rapidly developed into invasive melanomas, which resembled human melanomas and could be serially transplanted. These data provide direct evidence that BRAF activation is sufficient for f-nevus formation, that BRAF activation is among the primary events in melanoma development, and that the p53 and BRAF pathways interact genetically to produce melanoma.

Animals↗
PubMed2005

Vive la difference!

Explore the source record for details and available documents.

Computational Biology↗
PubMed2004

Detection of large-scale variation in the human genome.

We identified 255 loci across the human genome that contain genomic imbalances among unrelated individuals. Twenty-four variants are present in > 10% of the individuals that we examined. Half of these regions overlap with genes, and many coincide with segmental duplications or gaps in the human genome assembly. This previously unappreciated heterogeneity may underlie certain human phenotypic variation and susceptibility to disease and argues for a more dynamic human genome structure.

Gene Dosage↗