Bryan Lee Hui Young - Academia.edu (original) (raw)

Papers by Bryan Lee Hui Young

Journal of Oral Pathology & Medicine, 2008

BACKGROUND: Oral submucous fibrosis (OSF) is a high-risk pre-cancerous condition where 7-13% of t... more BACKGROUND: Oral submucous fibrosis (OSF) is a high-risk pre-cancerous condition where 7-13% of these patients develop head and neck squamous cell carcinoma (HNSCC). To date there is no cancer predictive markers for OSF patients. Genomic instability hallmarks early genetic events during malignant transformation causing loss of heterozygosity (LOH) and chromosomal copy number abnormality. However, to date there is no study on genomic instability in OSF. Although this condition is known as a high-risk pre-cancerous condition, there is no data regarding the genomic status of this disease in terms of genetic susceptibility to malignant transformation. METHODS: In this study, we investigated the existence of genetic signatures for carcinogenesis in OSF. We employed the high-resolution genome-wide Affymetrix Mapping single nucleotide polymorphism microarray technique to Ôfingerprint' global genomic instability in the form of LOH in 15 patient-matched OSF-blood genomic DNA samples. RESULTS: This rapid high-resolution mapping technique has revealed for the first time that a small number of discrete hot-spot LOH loci appeared in 47-53% of the OSF tissues studied. Many of these LOH loci were previously identified regions of genomic instability associated with carcinogenesis of the HNSCC. CONCLUSION: To our knowledge, this is the first evidence that genomic instability in the form of LOH is present in OSF. We hypothesize that the genomic instability detected in OSF may play an important role in malignant transformation. Further functional association studies on these putative genes may reveal potential predictive oral cancer markers for OSF patients.

PLoS ONE, 2012

Methylated DNA immunoprecipitation followed by high-throughput sequencing (MeDIP-seq) has the pot... more Methylated DNA immunoprecipitation followed by high-throughput sequencing (MeDIP-seq) has the potential to identify changes in DNA methylation important in cancer development. In order to understand the role of epigenetic modulation in the development of acute myeloid leukemia (AML) we have applied MeDIP-seq to the DNA of 12 AML patients and 4 normal bone marrows. This analysis revealed leukemia-associated differentially methylated regions that included gene promoters, gene bodies, CpG islands and CpG island shores. Two genes (SPHKAP and DPP6) with significantly methylated promoters were of interest and further analysis of their expression showed them to be repressed in AML. We also demonstrated considerable cytogenetic subtype specificity in the methylomes affecting different genomic features. Significantly distinct patterns of hypomethylation of certain interspersed repeat elements were associated with cytogenetic subtypes. The methylation patterns of members of the SINE family tightly clustered all leukemic patients with an enrichment of Alu repeats with a high CpG density (P,0.0001). We were able to demonstrate significant inverse correlation between intragenic interspersed repeat sequence methylation and gene expression with SINEs showing the strongest inverse correlation (R 2 = 0.7). We conclude that the alterations in DNA methylation that accompany the development of AML affect not only the promoters, but also the non-promoter genomic features, with significant demethylation of certain interspersed repeat DNA elements being associated with AML cytogenetic subtypes. MeDIP-seq data were validated using bisulfite pyrosequencing and the Infinium array.

Genes, Chromosomes and Cancer, 2008

In a small fraction (2%) of cases of childhood acute lymphoblastic leukemia (ALL) clinical presen... more In a small fraction (2%) of cases of childhood acute lymphoblastic leukemia (ALL) clinical presentation of leukemia is preceded, some 2-9 months earlier, by a transient, remitting phase of nonclassical aplastic anemia, usually in connection with infection. The potential ''preleukemic'' nature of this prodromal phase has not been fully explored. We have retrospectively analyzed the blood and bone marrow of a child who presented with aplastic anemia 9 months before the development of ETV6-RUNX1 fusion gene positive ALL. High resolution SNP genotyping arrays identified 11 regions of loss of heterozygosity, with and without concurrent copy number changes, at the presentation of ALL. In all cases of copy number change, the deletion or gain identified by single nucleotide polymorphism (SNP) analysis was confirmed in the ALL blasts by FISH. Retrospective analysis of aplastic phase bone marrow showed that the ETV6-RUNX1 fusion was present along with all of the additional genetic changes assessed, albeit subclonal to ETV6-RUNX1. These data identify for the first time the leukemic genotype of an aplasia preceding clinical ALL and indicate that multiple secondary genetic abnormalities can contribute to a dominant subclone several months before a diagnosis of ALL. These data have implications for the biology of ALL and for management of similar patients. V V C

AJOB Neuroscience, 2015

ABSTRACT Recent research suggests that a minority of patients diagnosed as vegetative using tradi... more ABSTRACT Recent research suggests that a minority of patients diagnosed as vegetative using traditional behavioral assessments may be covertly aware. One of the most pressing concerns with respect to these patients is their welfare. This article examines foundational issues concerning the application of a theory of welfare to these patients, and develops a research agenda with patient welfare as a central focus. We argue that patients diagnosed as vegetative with covert awareness likely have sentient interests, and because sentient interests are sufficient for moral status, others have an obligation to take the welfare interests of these patients seriously. However, we do not view sentient interests as necessary for moral status, and thus it is possible that vegetative patients who lack such interests have moral status for other reasons. We propose four areas in which future research is needed to guide the ethical treatment of these patients: the assessment and management of pain; the development of quality of life assessments; end-of-life decision making; and enriching the day-to-day lives of these patients.

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ABSTRACT Greenhouse studies were conducted to determine the influence of spray-solution pH, adjuv... more ABSTRACT Greenhouse studies were conducted to determine the influence of spray-solution pH, adjuvant, light intensity, temperature, and glyphosate on the efficacy of saflufenacil on horseweed. Control of glyphosate-resistant horseweed from saflufenacil alone was greatest with a spray-solution pH of 5, compared with pH 7 or 9. However, when glyphosate was added to saflufenacil, similar GR50 values were measured with spray solutions adjusted to pH 5 and 9, and horseweed control at pH 9 was 38% greater than at pH 7. The efficacy of saflufenacil on horseweed was 36% greater when crop oil concentrate was used as an adjuvant compared with nonionic surfactant, regardless of the addition of glyphosate or the sensitivity of the horseweed population to glyphosate (resistant vs. susceptible). The addition of glyphosate to low rates of saflufenacil increased control over saflufenacil applied alone on glyphosate-susceptible and -resistant horseweed. Saflufenacil activity was greater under low light intensity (300 μmol m−2 s−1) than high light intensity (1,000 μmol m−2 s−1). Although initial horseweed control was greater under high temperature (27 C) compared with low temperature (10 C), by 21 d after treatment horseweed dry weight was similar from saflufenacil applied under high and low temperatures. Nomenclature: Glyphosate, saflufenacil, horseweed, Conyza canadensis (L.) Cronq.

J Urol, 2006

Testicular germ-cell tumors (TGCTs) show exquisite sensitivity to cisplatin-based chemotherapy, a... more Testicular germ-cell tumors (TGCTs) show exquisite sensitivity to cisplatin-based chemotherapy, and therefore this is considered a good model system for studying the mechanism of chemotherapy resistance. Although the genetic alterations related to TGCT have been well studied, little is known about the genetic basis of chemotherapy resistance, which occurs in a small proportion of TGCTs. In this study, we investigated genomic and expression differences between three cisplatin-sensitive and their paired cisplatin-resistant lines using combined whole-genome screen approaches. Comparative genomic hybridization (CGH) analysis on chromosomes revealed genetic differences between the resistant and parent cell lines in each pair, but did not show any consistent chromosome changes in all three lines. Microarray CGH analysis generated some additional information of DNA copy number gains and losses including some important oncogenes, tumor-suppressor genes, and drug-resistance-related genes. However, no consistent genomic region changes were found in the three cell lines. Interestingly, when comparative expressed sequence hybridization, a technique for gene expression profiling along chromosomes, was applied, we discovered a consistently overexpressed chromosomal region in all three resistant lines compared with their parent lines. The minimum overlapping chromosomal region is at 16q22-23. Further definition of genes in this chromosomal region will aid our understanding of the mechanism of cisplatin resistance and may offer novel therapeutic targets. '

Leukemia, May 1, 1994

Cytogenetic analysis of a bone marrow aspirate from a patient with acute lymphoblastic leukemia (... more Cytogenetic analysis of a bone marrow aspirate from a patient with acute lymphoblastic leukemia (ALL) revealed the presence of a complex karyotype containing the translocation, t(14;18)(q32;q21). Further investigations using fluorescence in situ hybridization (FISH) allowed the characterization of an additional translocation, t(8;9)(q24;p1?). The association of t(14;18)(q32;q21) and t(8;9)(q24;p13) has recently been described in two patients with de novo ALL (Nacheva et al. Blood 1993;82:231-240) and this report supports these findings.

International Journal of Oncology, Sep 1, 1997

The incidence of mutations within the first 582 bp of the open reading frame of the bcl-2 gene, h... more The incidence of mutations within the first 582 bp of the open reading frame of the bcl-2 gene, has been investigated in presentation lymph node samples, from 7 cases with follicular non-Hodgkin's lymphoma (NHL), 1 case with centroblactic NHL, the DOHH, cell line derived from the immunoblastic transformation of a follicular NHL and one case with benign follicular hyperplasia. A total number of 43 point mutations within the examined portion of the bcl-2 gene were detected in the cases analysed including the DOHH, cell line. Similar analysis of peripheral blood lymphocytes from 2 normal individuals that lacked the t(14;18), revealed no mutations in one case and a single 101 bp A-->G transition in clone, in the other. Missense mutations were detected in 7/8 NHLs, the DOHH2 cell line and the case of benign follicular hyperplasia. There was a significantly higher frequency of mutations within the region corresponding to the BH1, one of the two known functional domains, of the bcl-2 protein. The same position, 445 bp of the bcl-2 gene, was found to be involved in missense mutations affecting the DOHH2 cell line and 3 cases with follicular NHL.

ABSTRACT The resource-ratio hypothesis of succession proposes that plant species are specialized ... more ABSTRACT The resource-ratio hypothesis of succession proposes that plant species are specialized on different proportions of limiting resources. If resource levels are sufficient, species will have positive growth, drawing down resource levels leading to a reduction in population growth rate. Four herbaceous species in the Amaranthaceae family were studied in southern Illinois to test the applicability of the resource-ratio hypothesis. Achyranthes japonica is a non-native, invasive species that is becoming a threat to natural forested areas. Iresine rhizomatosa also occurs in forest habitats but is an endangered species in Illinois. These forest herbs were compared with two summer annual agricultural weeds, Amaranthus palmeri and A. rudis. The objective of this study was to determine the relative competitiveness of the closely related species in comparison to Glycine max. A greenhouse study was conducted in which each species was grown in a closed system to assess resource drawdown of an aboveground (light) and belowground (nitrogen) resource. Resource manipulation treatments were implemented by adding nitrogen as ammonium nitrate and by shading using a 60% shade cloth. In comparison to the controls, the species each drew down light, but not nitrogen. A competitive R* ranking was determined: A. palmeri > A. rudis  A. japonica > I. rhizomatosa. Biomass was reduced in the presence of the shading treatment (P=0.006), but increased in the presence of nitrogen (P=0.08). Applicability of the resource ratio theory could lead to more effective management tactics by allowing prediction of susceptible areas of infestation or competitive outcomes based on resource levels.

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... David R. Shaw, Wade A. Givens, Luke A. Farno, Patrick D. Gerard, David Jordan, William G. Joh... more ... David R. Shaw, Wade A. Givens, Luke A. Farno, Patrick D. Gerard, David Jordan, William G. Johnson, Stephen C. Weller, Bryan G. Young, Robert G. Wilson, and Michael DK Owen*. Abstract. ... Weed Technol 18:940946. [Abstract]. Tuesca, D. , E. Puricelli , and JC Papa . 2001. ...

A general framework is proposed for using precipitation estimates from NEXRAD weather radars in r... more A general framework is proposed for using precipitation estimates from NEXRAD weather radars in raingage network design. NEXRAD precipitation products are used to simulate space-time rainfall elds, which can be sampled by hypothetical raingage networks. A stochastic model is used to simulate gage observations from areal-average precipitation for radar grid cells. The stochastic model accounts for spatial variability within the cell and gage measurement errors. The approach is ideally suited to raingage network design in regions with strong climatic variations in rainfall patterns, where conventional methods are sometimes lacking. A case study example, involving the estimation of areal-average precipitation for catchments in the Catskill Mountains, illustrates the approach. Although limitations are imposed by the quality of NEXRAD precipitation estimates, weather radars can provide valuable information for empirical simulations of rainfall elds. Results from the case study show that small-scale spatial variability of rainfall is very important for quantifying errors in precipitation estimates for short sampling durations (e.g., hours).

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A phone survey was administered to 1,195 growers in six states (Illinois, Indiana, Iowa, Mississi... more A phone survey was administered to 1,195 growers in six states (Illinois, Indiana, Iowa, Mississippi, Nebraska, and North Carolina). The survey measured producers' crop history, perception of glyphosate-resistant (GR) weeds, past and present weed pressure, tillage practices, and herbicide use as affected by the adoption of GR crops. This article describes the changes in tillage practice reported in the survey. The adoption of a GR cropping system resulted in a large increase in the percentage of growers using no-till and reduced-till systems. Tillage intensity declined more in continuous GR cotton and GR soybean (45 and 23%, respectively) than in rotations that included GR corn or non-GR crops. Tillage intensity declined more in the states of Mississippi and North Carolina than in the other states, with 33% of the growers in these states shifting to more conservative tillage practices after the adoption of a GR crop. This was primarily due to the lower amount of conservation tillage adoption in these states before GR crop availability. Adoption rates of no-till and reduced-till systems increased as farm size decreased. Overall, producers in a crop rotation that included a GR crop shifted from a relatively more tillage-intense system to reduced-till or no-till systems after implementing a GR crop into their production system. Nomenclature: 2,4-D, glyphosate; corn, Zea mays L.; cotton, Gossypium hirsutum L; soybean, Glycine max (L.) Merr.

Cell, Jul 28, 2006

Development and homeostasis of the cardiovascular system require intimate interactions between en... more Development and homeostasis of the cardiovascular system require intimate interactions between endothelial and smooth muscle cells, which form a seamless circulatory network. We show that histone deacetylase 7 (HDAC7) is specifically expressed in the vascular endothelium during early embryogenesis, where it maintains vascular integrity by repressing the expression of matrix metalloproteinase (MMP) 10, a secreted endoproteinase that degrades the extracellular matrix. Disruption of the HDAC7 gene in mice results in embryonic lethality due to a failure in endothelial cell-cell adhesion and consequent dilatation and rupture of blood vessels. HDAC7 represses MMP10 gene transcription by associating with myocyte enhancer factor-2 (MEF2), a direct activator of MMP10 transcription and essential regulator of blood vessel development. These findings reveal an unexpected and specific role for HDAC7 in the maintenance of vascular integrity and have important implications for understanding the processes of angiogenesis and vascular remodeling during cardiovascular development and disease.

ABSTRACT Background/Question/Methods Studying species within the same family allows determination... more ABSTRACT Background/Question/Methods Studying species within the same family allows determination of life history traits that are most likely to be the result of adaptation of each species to its environment rather than the result of a common shared ancestor. Four species within the Amaranthaceae family were studied in southern Illinois. Amaranthus palmeri and A. rudis are summer annuals typically found as problematic agricultural weeds, Achyranthes japonica and Iresine rhizomatosa are two perennial species that occur in similar habitats but differ in invasiveness. Achryanthes japonica is a non-native, invasive species that is becoming a threat to natural forested areas and is also observed in agricultural field margins. Iresine rhizomatosaalso occurs in forest habitats but is an endangered species in Illinois. The objective of this study was to undertake a comparative life history analysis of these closely related species in habitats where they occur. Fifty seedlings of each species were observed at each of two sites through the 2012 growing season. Seedlings were assigned to life stages (seedling, juvenile, non-flowering adults and flowering adults) based upon node counts and performance recorded. Fecundity was determined by seed counts for the perennial species and from seed weight estimates for the annual species. Results/Conclusions Seedlings of the two perennial species exhibited a type II survivorship curve. Both annual species exhibited a type I survivorship curve at one of the two sites, and a type III survivorship curve at the other site, with site differences in survivorship likely reflecting precipitation regime. Sixty percent of seedlings of both Amaranthus species survived through the season with all survivors flowering, a 1:1 sex ratio, and a mean fecundity of 21,274 ± 4,121 seeds per plant for A. palmeri, and 93,725 ± 22,653 seeds per plant for A. rudis. Fifty-seven percent of A. japonica seedlings survived their first season to flower, with adult plant fecundity of 132 ± 20 seeds per plant, whereas for I. rhizomatosa only 38% of seedlings survived and flowered, with adult fecundity of 702 ± 139 seeds per plant. Seed germination rates were low for the annuals (A. rudis seed = 12%, A. palmeri = 29%, under ideal conditions), whereas the perennials had widely divergent germination rates (A. japonica = 98% and I. rhizomatosa < 1%), reflecting their invasive and endangered status, respectively. Thus, seedling survivorship, fecundity, and germination rates of these four Amaranthaceae species help us understand their life history status.

Asian Journal of Andrology, May 1, 2008

To investigate the existence of TMPRSS2:ERG fusion gene in circulating tumor cells (CTC) from pro... more To investigate the existence of TMPRSS2:ERG fusion gene in circulating tumor cells (CTC) from prostate cancer patients and its potential in monitoring tumor metastasis. Methods: We analyzed the frequency of TMPRSS2: ERG and TMPRSS2:ETV1 transcripts in 27 prostate cancer biopsies from prostatectomies, and TMPRSS2:ERG transcripts in CTC isolated from 15 patients with advanced androgen independent disease using reverse transcription polymerase chain reaction (RT-PCR). Fluorescence in situ hybridization (FISH) was applied to analyze the genomic truncation of ERG, which is the result of TMPRSS2:ERG fusion in 10 of the 15 CTC samples. Results: TMPRSS2: ERG transcripts were found in 44% of our samples, but we did not detect expression of TMPRSS2:ETV1. Using FISH analysis we detected chromosomal rearrangements affecting the ERG gene in 6 of 10 CTC samples, including 1 case with associated TMPRSS2:ERG fusion at the primary site. However, TMPRSS2:ERG transcripts were not detected in any of the 15 CTC samples, including the 10 cases analyzed by FISH. Conclusion: Although further study is required to address the association between TMPRSS2:ERG fusion and prostate cancer metastasis, detection of genomic truncation of the ERG gene by FISH analysis could be useful for monitoring the appearance of CTC and the potential for prostate cancer metastasis. (Asian J Androl 2008 May; 10: 467-473)