31 results on '"Holley T"'
Search Results
2. An innovative approach to downgrade mronj- an answer for long term management of mronj morbidity
- Author
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Holley, T., primary, Desa, V., additional, and Chandra, S., additional
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- 2019
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3. Hypothermia deaths in Jefferson County, Alabama
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Taylor, A J., McGwin Jr, G, Davis, G G., Brissie, R M., Holley, T D., and Rue III, L W.
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Jefferson County, Alabama -- Health aspects ,Mortality -- Alabama ,Hypothermia -- Patient outcomes -- Health aspects ,Health ,Patient outcomes ,Health aspects - Abstract
Abstract Introduction--Some reported characteristics associated with hypothermia mortality include older age, alcohol consumption, male sex, and black race. The purpose of this paper is to present the epidemiology of hypothermia [...]
- Published
- 2001
4. Abstract PD4-7: Deep clonal profiling of primary breast cancer and distant lymph node metastases
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Francis, P, primary, Lenkiewicz, E, additional, Holley, T, additional, Evers, L, additional, Thompson, A, additional, McCullough, AE, additional, Barrett, MT, additional, and Pockaj, BA, additional
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- 2013
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5. Genome sequence and identification of candidate vaccine antigens from the animal pathogen Dichelobacter nodosus
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Myers, GSA, Parker, D, Al-Hasani, K, Kennan, RM, Seemann, T, Ren, Q, Badger, JH, Selengut, JD, DeBoy, RT, Tettelin, H, Boyce, JD, McCarl, VP, Han, X, Nelson, WC, Madupu, R, Mohamoud, Y, Holley, T, Fedorova, N, Khouri, H, Bottomley, SP, Whittington, RJ, Adler, B, Songer, JG, Rood, JI, Paulsen, IT, Myers, GSA, Parker, D, Al-Hasani, K, Kennan, RM, Seemann, T, Ren, Q, Badger, JH, Selengut, JD, DeBoy, RT, Tettelin, H, Boyce, JD, McCarl, VP, Han, X, Nelson, WC, Madupu, R, Mohamoud, Y, Holley, T, Fedorova, N, Khouri, H, Bottomley, SP, Whittington, RJ, Adler, B, Songer, JG, Rood, JI, and Paulsen, IT
- Abstract
Dichelobacter nodosus causes ovine footrot, a disease that leads to severe economic losses in the wool and meat industries. We sequenced its 1.4-Mb genome, the smallest known genome of an anaerobe. It differs markedly from small genomes of intracellular bacteria, retaining greater biosynthetic capabilities and lacking any evidence of extensive ongoing genome reduction. Comparative genomic microarray studies and bioinformatic analysis suggested that, despite its small size, almost 20% of the genome is derived from lateral gene transfer. Most of these regions seem to be associated with virulence. Metabolic reconstruction indicated unsuspected capabilities, including carbohydrate utilization, electron transfer and several aerobic pathways. Global transcriptional profiling and bioinformatic analysis enabled the prediction of virulence factors and cell surface proteins. Screening of these proteins against ovine antisera identified eight immunogenic proteins that are candidate antigens for a cross-protective vaccine. © 2007 Nature Publishing Group.
- Published
- 2007
6. Abstract 969: Amplifications, gene fusions, and therapeutic targets in triple negative and refractory ER+ and HER2+ breast cancers
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Lai, Zhongwu, primary, Wu, Haiguo, additional, Morosini, Deborah, additional, Webster, Kevin, additional, Yu, Lihua, additional, Lenkiewicz, Elizabeth, additional, Evers, L, additional, Holley, T, additional, Tembe, Wibhav, additional, and Barrett, Mike, additional
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- 2012
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7. Wide azimuths ‐ why not?
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Padhi, T., primary and Holley, T. K., additional
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- 1997
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8. 431. Steroids and walden inversion. Part LIV. The Grignard oxygenation of epicholesteryl bromide and partial synthesis of 3α-hydroxycholest-6-ene.
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Shoppee, C. W., Holley, T. F., and Newsoroff, G. P.
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- 1965
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9. 519. The constitution of Marrubiin. Part I.
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Cocker, Wesley, Cross, B. E., Duff, S. R., Edward, J. T., and Holley, T. F.
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- 1953
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10. La femme du marin : Aunis / harmonisation et arrangement d'Arthur Honegger ; M. T. Holley, S ; J. Peyron, T ; solistes ; la Chorale Yvonne Gouverné ; choeurs et orchestre ; Roger Désormière, dir.. Le condamné à mort : Angoumois / harmonisation et arrangement de Marcel Delannoy ; J. Peyron ; la Chorale Yvonne Gouverné ; choeurs et orchestre ; Roger Désormière, dir.
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Honegger, Arthur (1892-1955). Harmonisateur, Holley, T.. Interprète, Peyron, Joseph (1912-1976). Ténor, Désormière, Roger (1898-1963). Direction d'orchestre, Honegger, Arthur (1892-1955). Harmonisateur, Holley, T.. Interprète, Peyron, Joseph (1912-1976). Ténor, and Désormière, Roger (1898-1963). Direction d'orchestre
- Abstract
Appartient à l’ensemble documentaire : BmLHav000, Contient une table des matières
- Published
- 1940
11. Radiative-decay-induced four-level crossover signals in saturation spectroscopy
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Anderson, C. J., primary, Lawler, J. E., additional, Anderson, L. W., additional, Holley, T. K., additional, and Filippelli, A. R., additional
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- 1978
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12. To what extent do oral and maxillofacial surgery residents suffer from imposter syndrome?
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Deek AJ, Deek RA, Clegg DJ, Blackburn C, Holley T, and Gotcher JE
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- Humans, Male, Female, Cross-Sectional Studies, Surveys and Questionnaires, Adult, United States, Sexism, Education, Dental, Graduate, Self Concept, Anxiety Disorders, Internship and Residency, Surgery, Oral education
- Abstract
Objective: This study aims to evaluate the frequency and severity of imposter syndrome (IS) in oral and maxillofacial surgery (OMS) residents and identify factors associated with higher Clance Imposter Phenomenon Survey (CIPS) scores., Study Design: A cross-sectional study was performed with a survey including CIPS, demographic, and training program structure questions distributed to all OMS training programs and residents in the United States. The primary predictor variable was gender, and the main outcome variable was the CIPS score. Statistical analyses were performed using linear regression in R v4.3.1; statistical significance was set to P value < .05., Results: A total of 175 OMS residents responded. The average CIPS score was 59.8 (IQR 52, 70). Statistically significant differences were found between average male and female resident scores (56.5 vs 66.9; P < .001) and male and female single-degree residents (54.3 vs 73.1; P < .001), but not for dual-degree residents (58.8 vs 63.9; P = .35)., Conclusions: The average male resident experiences moderate IS, whereas the average female resident experiences frequent IS. Loss of significance between male and female dual-degree resident scores may be due to the completion of a doctoral degree, an internship, and/or dental board exams upon entering medical school, leading to more favorable accomplishment comparisons among medical school peers., Competing Interests: Declarations of interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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13. A retrospective study of orthognathic surgery reimbursement and volume changes at an American academic medical center over a 13-year period.
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Deek AJ, Clegg DJ, Blackburn C, Roberson PN, Holley T, and Gotcher JE
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- Humans, Retrospective Studies, Male, Female, United States, Adult, Insurance, Health, Reimbursement economics, Academic Medical Centers economics, Orthognathic Surgical Procedures economics, Orthognathic Surgical Procedures statistics & numerical data
- Abstract
Objective: This study aimed to measure the association between orthognathic surgeon reimbursement and surgical volume over time., Study Design: A retrospective cohort study of patients who underwent orthognathic surgery from January 1, 2010, to December 23, 2022, at an academic medical center was performed. Five patients per year were randomly selected and evaluated for insurance type and associated costs to create representative averages. Pearson correlation analysis was performed to test associations over 13 years with 2-tailed significance reported and statistical significance set at P < .05., Results: A total of 618 patients who underwent 942 procedures were included. The average procedure charge was $6,153.76, and the average total surgeon collection was $1,535.75 per procedure. When monetary values were adjusted to reflect 2010 purchasing power, there was a negative correlation between the average charge per procedure and the year (r[11] = -0.59, P = .04). The year was not significantly correlated with the average amount collected (r[11] = -0.09, P = .78) or average insurance reimbursement (r[11] = -0.52, P = .07)., Conclusions: Collections by surgeons did not change significantly over 13 years and were not correlated with the volume of procedures performed. Increased collections were correlated with increased patient costs. The stagnation of surgeon collection is concerning in the face of increased monetary inflation during this period. Increased volume of surgeries per year was correlated with decreases in patient cost and total collections., Competing Interests: Declaration of interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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14. Risk Factors for Pediatric Facial Trauma in an Appalachian Region: An Epidemiological Review at a Single Institution.
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Deek AJ, Clegg DJ, Deek RA, Blackburn C, Scott CA, Holley T, and Gotcher JE
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- Adolescent, Child, Child, Preschool, Humans, Appalachian Region epidemiology, Retrospective Studies, Risk Factors, Socioeconomic Factors, Infant, Male, Female, Rural Population
- Abstract
Background: Rural and low-income pediatric populations are at higher risk for trauma. Craniomaxillofacial (CMF) trauma in this population has not been studied., Purpose: This study's purpose was to determine if rural populations or low-income populations are at higher risk for pediatric CMF trauma than urban or high-income populations, respectively, and to determine differences in mechanism of injury (MOI)., Study Design, Setting, Sample: A retrospective cohort study of CMF trauma patients younger than 17 years-old, living in the region served by one institution in Tennessee, and requiring oral and maxillofacial surgery consultation between January 2011 and December 2022 was performed. Exclusion criteria were incomplete medical records., Predictor Variable: The primary predictor variable was geographic residence of the patient grouped into two categories: rural or urban defined by the state of Tennessee. Secondary variables were postal code (PC) average median household income (MHI) and PC population density., Main Outcome Variable(s): The main outcome variable was pediatric CMF injury rate per 100,000 people. MOI is a secondary outcome variable., Covariate(s): Covariates included sex, age, and race., Analyses: Frequencies and percentages, Fisher's exact test, and Poisson regression models were utilized. Statistical significance was assumed at P-value <.05., Results: Rural or urban county designation was not associated with differing trauma rates (incident risk ratio (IRR) = 0.91; 95% confidence interval (CI) 0.78 to 1.05; P = .18) by itself. One standard deviation increase in MHI decreased CMF trauma rates in rural designation counties by 24% (IRR: 0.76, 95% CI: 0.66, 0.88) and 6% in urban designation counties (IRR: 0.94, 95% CI: 0.87, 1.02). Lower rates of CMF trauma were associated with residence in higher income PCs (IRR = 0.91; 95% (CI) 0.86 to 0.97; P = .004), and higher population density (IRR = 0.87; 95% CI 0.79 to 0.94; P < .001). Dog bites and falls were more common in infancy and early childhood. Interpersonal violence was more common in older patients., Conclusions and Relevance: Patients in PCs with lower population density or incomes were at highest risk for CMF injuries. MOI differences by age were similar to findings in other studies. Tennessee's urban/rural county designation has complex interactions with MHI and pediatric CMF trauma rates., (Copyright © 2023 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)
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- 2024
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15. Gastrocardiac Fistula as a Complication of Prior Bariatric Surgery.
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Hlavaty J, Holley T, Tymitz K, Kerlakian G, and Meister K
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- Female, Humans, Gastrointestinal Hemorrhage surgery, Obesity, Morbid surgery, Gastric Bypass adverse effects, Bariatric Surgery adverse effects, Fistula surgery, Laparoscopy
- Abstract
Gastrocardiac fistula is a rare, typically fatal, diagnosis which has been reported infrequently in post-esophagectomy patients and, to a much lesser extent, patients with history of Roux-en-Y gastric bypass. This case describes a patient with a history of an eroded adjustable gastric band and subsequent removal with conversion to Roux-en-Y gastric bypass that initially presented with an upper gastrointestinal bleed. She was found to have a transdiaphragmatic fistula between the gastric lumen and left ventricle.
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- 2023
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16. Gastrocardiac Fistula as a Complication of Prior Bariatric Surgery.
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Hlavaty J, Holley T, Tymitz K, Kerlakian G, and Meister K
- Abstract
Gastrocardiac fistula is a rare, typically fatal, diagnosis which has been reported infrequently in post-esophagectomy patients and, to a much lesser extent, patients with history of Roux-en-Y gastric bypass. This case describes a patient with a history of an eroded adjustable gastric band and subsequent removal with conversion to Roux-en-Y gastric bypass that initially presented with an upper gastrointestinal bleed. She was found to have a transdiaphragmatic fistula between the gastric lumen and left ventricle.
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- 2021
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17. Transscleral Diode Laser Cyclophotocoagulation: A Comparison of Slow Coagulation and Standard Coagulation Techniques.
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Duerr ER, Sayed MS, Moster S, Holley T, Peiyao J, Vanner EA, and Lee RK
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- Aged, Female, Glaucoma physiopathology, Humans, Male, Middle Aged, Retrospective Studies, Ciliary Body surgery, Glaucoma surgery, Intraocular Pressure physiology, Laser Coagulation methods, Lasers, Semiconductor therapeutic use, Sclera surgery, Visual Acuity
- Abstract
Purpose: To compare the outcomes of standard pop-titrated transscleral cyclophotocoagulation (TSCPC) and slow-coagulation TSCPC in the treatment of glaucoma., Design: Retrospective case series., Subjects: This study included 78 eyes with glaucoma of any type or stage that underwent TSCPC as part of their treatment course., Methods: This study compared 52 eyes treated with slow coagulation TSCPC to 26 eyes treated with standard pop-titrated TSCPC. Patient demographics, treatment course, surgical techniques, settings and outcomes were assessed., Main Outcome Measures: The main outcome measures were visual acuity (VA), intraocular pressure (IOP) and post-surgical complications., Results: The initial LogMAR VA was 1.94 (0.73) [mean (SD)] in the slow coagulation TSCPC group and 1.71 (0.90) in the standard TSCPC group (p=0.507). Initial IOP was 37 (13) mm Hg in the slow coagulation group and 39 (13) mm Hg in the standard group (p=0.297). The follow-up periods were 16.36 months and 24.68 months for the slow coagulation and standard groups (p=0.124). VA remained better than light-perception in 71.1% of slow coagulation treated patients and 65.0% of standard TSCPC treated patients (p=0.599). IOP remained below 20 mm Hg in 46% of slow coagulation treated patients and 44% of standard TSCPC treated patients (p=0.870). The mean number of complications was higher in the standard group [1.46 (1.24)] versus the slow coagulation group [0.62 (0.75)] (p=0.002). The incidence of the need for a second procedure (slow coagulation- 28.8%, standard- 23.1%, p=0.588) and maximum number of medications needed to control IOP postoperatively (p=0.771) were similar between the two groups., Conclusions: In this case series, slow coagulation TSCPC and standard pop-titrated TSCPC resulted in similar VA and IOP outcomes in the treatment of glaucomatous eyes. The complication profiles of the techniques were also comparable, although standard TSCPC had a higher incidence of prolonged inflammation postoperatively. This study suggests that slow coagulation TSCPC may achieve equivalent control of IOP while reducing the incidence of prolonged post-operative inflammation-a feared complication of TSCPC-when compared to standard "pop-titrated" TSCPC., Competing Interests: b- Financial Disclosures: All authors have no conflicts of interest regarding any of the products or material discussed in this article.
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- 2018
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18. Clinical study of genomic drivers in pancreatic ductal adenocarcinoma.
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Barrett MT, Deiotte R, Lenkiewicz E, Malasi S, Holley T, Evers L, Posner RG, Jones T, Han H, Sausen M, Velculescu VE, Drebin J, O'Dwyer P, Jameson G, Ramanathan RK, and Von Hoff DD
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- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biopsy, Carcinoma, Pancreatic Ductal drug therapy, Carcinoma, Pancreatic Ductal secondary, Cyclin-Dependent Kinase Inhibitor p16, Cyclin-Dependent Kinase Inhibitor p18 genetics, DNA Copy Number Variations, DNA Mutational Analysis, DNA Repair genetics, Disease-Free Survival, Enhancer Elements, Genetic, Exome, Female, Genes, myc, Homozygote, Humans, Malate Dehydrogenase genetics, Male, Microtubule-Associated Proteins genetics, Middle Aged, Pancreas pathology, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms pathology, Proto-Oncogene Proteins p21(ras) genetics, Purine-Nucleoside Phosphorylase genetics, Smad4 Protein genetics, Survival Rate, Tumor Suppressor Protein p53 genetics, Base Sequence, Carcinoma, Pancreatic Ductal genetics, Pancreatic Neoplasms genetics, Sequence Deletion
- Abstract
Background: Pancreatic ductal adenocarcinoma (PDA) is a lethal cancer with complex genomes and dense fibrotic stroma. This study was designed to identify clinically relevant somatic aberrations in pancreatic cancer genomes of patients with primary and metastatic disease enrolled and treated in two clinical trials., Methods: Tumour nuclei were flow sorted prior to whole genome copy number variant (CNV) analysis. Targeted or whole exome sequencing was performed on most samples. We profiled biopsies from 68 patients enrolled in two Stand Up to Cancer (SU2C)-sponsored clinical trials. These included 38 resected chemoradiation naïve tumours (SU2C 20206-003) and metastases from 30 patients who progressed on prior therapies (SU2C 20206-001). Patient outcomes including progression-free survival (PFS) and overall survival (OS) were observed., Results: We defined: (a) CDKN2A homozygous deletions that included the adjacent MTAP gene, only its' 3' region, or excluded MTAP; (b) SMAD4 homozygous deletions that included ME2; (c) a pancreas-specific MYC super-enhancer region; (d) DNA repair-deficient genomes; and (e) copy number aberrations present in PDA patients with long-term (⩾ 40 months) and short-term (⩽ 12 months) survival after surgical resection., Conclusions: We provide a clinically relevant framework for genomic drivers of PDA and for advancing novel treatments.
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- 2017
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19. STAG2 is a clinically relevant tumor suppressor in pancreatic ductal adenocarcinoma.
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Evers L, Perez-Mancera PA, Lenkiewicz E, Tang N, Aust D, Knösel T, Rümmele P, Holley T, Kassner M, Aziz M, Ramanathan RK, Von Hoff DD, Yin H, Pilarsky C, and Barrett MT
- Abstract
Background: Pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer characterized by complex aberrant genomes. A fundamental goal of current studies is to identify those somatic events arising in the variable landscape of PDA genomes that can be exploited for improved clinical outcomes., Methods: We used DNA content flow sorting to identify and purify tumor nuclei of PDA samples from 50 patients. The genome of each sorted sample was profiled by oligonucleotide comparative genomic hybridization and targeted resequencing of STAG2. Transposon insertions within STAG2 in a KRAS (G12D)-driven genetically engineered mouse model of PDA were screened by RT-PCR. We then used a tissue microarray to survey STAG2 protein expression levels in 344 human PDA tumor samples and adjacent tissues. Univariate Kaplan Meier analysis and multivariate Cox Regression analysis were used to assess the association of STAG2 expression relative to overall survival and response to adjuvant therapy. Finally, RNAi-based assays with PDA cell lines were used to assess the potential therapeutic consequence of STAG2 expression in response to 18 therapeutic agents., Results: STAG2 is targeted by somatic aberrations in a subset (4%) of human PDAs. Transposon-mediated disruption of STAG2 in a KRAS (G12D) genetically engineered mouse model promotes the development of PDA and its progression to metastatic disease. There was a statistically significant loss of STAG2 protein expression in human tumor tissue (Wilcoxon-Rank test) with complete absence of STAG2 staining observed in 15 (4.3%) patients. In univariate Kaplan Meier analysis nearly complete STAG2 positive staining (>95% of nuclei positive) was associated with a median survival benefit of 6.41 months (P = 0.031). The survival benefit of adjuvant chemotherapy was only seen in patients with a STAG2 staining of less than 95% (median survival benefit 7.65 months; P = 0.028). Multivariate Cox Regression analysis showed that STAG2 is an independent prognostic factor for survival in pancreatic cancer patients. Finally, we show that RNAi-mediated knockdown of STAG2 selectively sensitizes human PDA cell lines to platinum-based therapy., Conclusions: Based on these iterative findings we propose that STAG2 is a clinically significant tumor suppressor in PDA.
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- 2014
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20. Elucidating potentially significant genomic regions involved in the initiation and progression of undifferentiated pleomorphic sarcoma.
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Kurywchak P, Kiefer J, Lenkiewicz E, Evers L, Holley T, Barrett M, and Weiss GJ
- Abstract
Sarcomas are cancers that arise in soft tissues or bone and make up a small percentage of malignancies. In an effort to identify potential genetic targets for therapy, this study explores the genomic landscape of a metastatic undifferentiated pleomorphic sarcoma (UPS) with spindle cell morphology. Thick sections (50 µm) of formalin-fixed, paraffin-embedded tissue from a primary, recurrent, and metastatic tumor were collected and processed from a single patient for DNA content-based flow-sorting and analyses. Nuclei of diploid and aneuploid populations were sorted from the malignant tissues and their genomes interrogated with array comparative genomic hybridization. The third sample was highly degraded and did not contain any intact ploidy peaks in our flow assays. A 2.5N aneuploid population was identified in the primary and recurrent sample. We detected a series of shared and unique genomic aberrations in the sorted aneuploid populations. The patterns of aberrations suggest that two similar but independent clonal populations arose during the clinical history of this rare tumor. None of these aberrations were detected in the matching sorted diploid samples. The targeted regions of interest might play a role in UPS and may lead to clinical significance with further investigation.
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- 2013
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21. Clonal evolution and therapeutic resistance in solid tumors.
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Barrett MT, Lenkiewicz E, Evers L, Holley T, Ruiz C, Bubendorf L, Sekulic A, Ramanathan RK, and Von Hoff DD
- Abstract
Tumors frequently arise as a result of an acquired genomic instability and the subsequent evolution of neoplastic populations with variable genomes. A barrier to the study of the somatic genetics of human solid tumors in vivo is the presence of admixtures of non-neoplastic cells with normal genomes in patient samples. These can obscure the presence of somatic aberrations including mutations, homozygous deletions, and breakpoints in biopsies of interest. Furthermore, clinical samples frequently contain multiple neoplastic populations that cannot be distinguished by morphology. Consequently, it is difficult to determine whether mutations detected in a sample of interest are concurrent in a single clonal population or if they occur in distinct cell populations in the same sample. The advent of targeted therapies increases the selection for preexisting populations. However the asymmetric distribution of therapeutic targets in clonal populations provides a mechanism for the rapid evolution of resistant disease. Thus, there is a need to not only isolate tumor from normal cells, but to also enrich distinct populations of clonal neoplastic cells in order to apply genome technologies to identify clinically relevant genomic aberrations that drive disease in patients in vivo. To address this we have applied single and multiparameter DNA content based flow assays to the study of solid tumors. Our work has identified examples of clonal resistance to effective therapies. This includes androgen withdrawal in advanced prostate cancer. In addition we demonstrate examples of co-existing clonal populations with highly aberrant genomes and ploidies in a wide variety of solid tumors. We propose that clonal analysis of tumors, based on flow cytometry and high resolution genome analyses of purified neoplastic populations, provides a unique approach to the study of therapeutic responses and the evolution of resistance.
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- 2013
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22. Genomic analysis and selected molecular pathways in rare cancers.
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Liu SV, Lenkiewicz E, Evers L, Holley T, Kiefer J, Ruiz C, Glatz K, Bubendorf L, Demeure MJ, Eng C, Ramanathan RK, Von Hoff DD, and Barrett MT
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- Adrenal Gland Neoplasms genetics, Adrenal Glands metabolism, Aged, Anal Canal metabolism, Aneuploidy, Anus Neoplasms genetics, Bile Duct Neoplasms genetics, Bile Ducts, Intrahepatic metabolism, Cholangiocarcinoma genetics, Diploidy, Female, Humans, Leiomyosarcoma genetics, Male, Middle Aged, Neuroendocrine Tumors genetics, Pancreas metabolism, Pancreatic Neoplasms genetics, DNA genetics, Genomics methods, Neoplasms genetics
- Abstract
It is widely accepted that many cancers arise as a result of an acquired genomic instability and the subsequent evolution of tumor cells with variable patterns of selected and background aberrations. The presence and behaviors of distinct neoplastic cell populations within a patient's tumor may underlie multiple clinical phenotypes in cancers. A goal of many current cancer genome studies is the identification of recurring selected driver events that can be advanced for the development of personalized therapies. Unfortunately, in the majority of rare tumors, this type of analysis can be particularly challenging. Large series of specimens for analysis are simply not available, allowing recurring patterns to remain hidden. In this paper, we highlight the use of DNA content-based flow sorting to identify and isolate DNA-diploid and DNA-aneuploid populations from tumor biopsies as a strategy to comprehensively study the genomic composition and behaviors of individual cancers in a series of rare solid tumors: intrahepatic cholangiocarcinoma, anal carcinoma, adrenal leiomyosarcoma, and pancreatic neuroendocrine tumors. We propose that the identification of highly selected genomic events in distinct tumor populations within each tumor can identify candidate driver events that can facilitate the development of novel, personalized treatment strategies for patients with cancer.
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- 2012
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23. Deep clonal profiling of formalin fixed paraffin embedded clinical samples.
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Holley T, Lenkiewicz E, Evers L, Tembe W, Ruiz C, Gsponer JR, Rentsch CA, Bubendorf L, Stapleton M, Amorese D, Legendre C, Cunliffe HE, McCullough AE, Pockaj B, Craig D, Carpten J, Von Hoff D, Iacobuzio-Donahue C, and Barrett MT
- Subjects
- Adenocarcinoma genetics, Adenocarcinoma pathology, Cloning, Molecular, Comparative Genomic Hybridization, Humans, Pancreatic Neoplasms genetics, Pancreatic Neoplasms pathology, Formaldehyde metabolism, High-Throughput Nucleotide Sequencing methods, Paraffin Embedding, Sequence Analysis, DNA methods, Tissue Fixation
- Abstract
Formalin fixed paraffin embedded (FFPE) tissues are a vast resource of annotated clinical samples. As such, they represent highly desirable and informative materials for the application of high definition genomics for improved patient management and to advance the development of personalized therapeutics. However, a limitation of FFPE tissues is the variable quality of DNA extracted for analyses. Furthermore, admixtures of non-tumor and polyclonal neoplastic cell populations limit the number of biopsies that can be studied and make it difficult to define cancer genomes in patient samples. To exploit these valuable tissues we applied flow cytometry-based methods to isolate pure populations of tumor cell nuclei from FFPE tissues and developed a methodology compatible with oligonucleotide array CGH and whole exome sequencing analyses. These were used to profile a variety of tumors (breast, brain, bladder, ovarian and pancreas) including the genomes and exomes of matching fresh frozen and FFPE pancreatic adenocarcinoma samples.
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- 2012
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24. Advancing a clinically relevant perspective of the clonal nature of cancer.
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Ruiz C, Lenkiewicz E, Evers L, Holley T, Robeson A, Kiefer J, Demeure MJ, Hollingsworth MA, Shen M, Prunkard D, Rabinovitch PS, Zellweger T, Mousses S, Trent JM, Carpten JD, Bubendorf L, Von Hoff D, and Barrett MT
- Subjects
- Biopsy, Clone Cells, Comparative Genomic Hybridization, DNA Primers genetics, Flow Cytometry, Genomics methods, Humans, In Situ Hybridization, Fluorescence, Male, Microarray Analysis, Polymerase Chain Reaction, Precision Medicine methods, Sequence Analysis, DNA, Adenocarcinoma genetics, Evolution, Molecular, Genetic Variation, Neoplasm Metastasis genetics, Pancreatic Neoplasms genetics, Prostatic Neoplasms genetics
- Abstract
Cancers frequently arise as a result of an acquired genomic instability and the subsequent clonal evolution of neoplastic cells with variable patterns of genetic aberrations. Thus, the presence and behaviors of distinct clonal populations in each patient's tumor may underlie multiple clinical phenotypes in cancers. We applied DNA content-based flow sorting to identify and isolate the nuclei of clonal populations from tumor biopsies, which was coupled with array CGH and targeted resequencing. The results produced high-definition genomic profiles of clonal populations from 40 pancreatic adenocarcinomas and a set of prostate adenocarcinomas, including serial biopsies from a patient who progressed to androgen-independent metastatic disease. The genomes of clonal populations were found to have patient-specific aberrations of clinical relevance. Furthermore, we identified genomic aberrations specific to therapeutically responsive and resistant clones arising during the evolution of androgen-independent metastatic prostate adenocarcinoma. We also distinguished divergent clonal populations within single biopsies and mapped aberrations in multiple aneuploid populations arising in primary and metastatic pancreatic adenocarcinoma. We propose that our high-definition analyses of the genomes of distinct clonal populations of cancer cells in patients in vivo can help guide diagnoses and tailor approaches to personalized treatment.
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- 2011
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25. The role of multihaem cytochromes in the respiration of nitrite in Escherichia coli and Fe(III) in Shewanella oneidensis.
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Clarke TA, Holley T, Hartshorne RS, Fredrickson JK, Zachara JM, Shi L, and Richardson DJ
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- ATP-Binding Cassette Transporters chemistry, ATP-Binding Cassette Transporters genetics, ATP-Binding Cassette Transporters metabolism, Amino Acid Sequence, Bacterial Proteins chemistry, Bacterial Proteins genetics, Bacterial Proteins metabolism, Cytochrome c Group chemistry, Cytochrome c Group genetics, Cytochrome c Group metabolism, Cytochromes genetics, Electron Transport physiology, Heme genetics, Heme metabolism, Models, Molecular, Molecular Sequence Data, Oxidoreductases chemistry, Oxidoreductases genetics, Oxidoreductases metabolism, Protein Structure, Tertiary, Sequence Alignment, Cell Respiration physiology, Cytochromes chemistry, Cytochromes metabolism, Escherichia coli physiology, Heme chemistry, Nitrites metabolism, Shewanella physiology
- Abstract
The periplasmic nitrite reductase system from Escherichia coli and the extracellular Fe(III) reductase system from Shewanella oneidensis contain multihaem c-type cytochromes as electron carriers and terminal reductases. The position and orientation of the haem cofactors in multihaem cytochromes from different bacteria often show significant conservation despite different arrangements of the polypeptide chain. We propose that the decahaem cytochromes of the iron reductase system MtrA, MtrC and OmcA comprise pentahaem 'modules' similar to the electron donor protein, NrfB, from E. coli. To demonstrate this, we have isolated and characterized the N-terminal pentahaem module of MtrA by preparing a truncated form containing five covalently attached haems. UV-visible spectroscopy indicated that all five haems were low-spin, consistent with the presence of bis-His ligand co-ordination as found in full-length MtrA.
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- 2008
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26. Genome sequence and identification of candidate vaccine antigens from the animal pathogen Dichelobacter nodosus.
- Author
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Myers GS, Parker D, Al-Hasani K, Kennan RM, Seemann T, Ren Q, Badger JH, Selengut JD, Deboy RT, Tettelin H, Boyce JD, McCarl VP, Han X, Nelson WC, Madupu R, Mohamoud Y, Holley T, Fedorova N, Khouri H, Bottomley SP, Whittington RJ, Adler B, Songer JG, Rood JI, and Paulsen IT
- Subjects
- Animals, Antigens genetics, Chromosome Mapping methods, Dichelobacter nodosus immunology, Dichelobacter nodosus metabolism, Foot Rot prevention & control, Genome, Bacterial genetics, Antigens immunology, Antigens therapeutic use, Dichelobacter nodosus genetics, Dichelobacter nodosus pathogenicity, Foot Rot immunology, Foot Rot microbiology, Sequence Analysis, DNA methods
- Abstract
Dichelobacter nodosus causes ovine footrot, a disease that leads to severe economic losses in the wool and meat industries. We sequenced its 1.4-Mb genome, the smallest known genome of an anaerobe. It differs markedly from small genomes of intracellular bacteria, retaining greater biosynthetic capabilities and lacking any evidence of extensive ongoing genome reduction. Comparative genomic microarray studies and bioinformatic analysis suggested that, despite its small size, almost 20% of the genome is derived from lateral gene transfer. Most of these regions seem to be associated with virulence. Metabolic reconstruction indicated unsuspected capabilities, including carbohydrate utilization, electron transfer and several aerobic pathways. Global transcriptional profiling and bioinformatic analysis enabled the prediction of virulence factors and cell surface proteins. Screening of these proteins against ovine antisera identified eight immunogenic proteins that are candidate antigens for a cross-protective vaccine.
- Published
- 2007
- Full Text
- View/download PDF
27. Whole-genome sequence analysis of Pseudomonas syringae pv. phaseolicola 1448A reveals divergence among pathovars in genes involved in virulence and transposition.
- Author
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Joardar V, Lindeberg M, Jackson RW, Selengut J, Dodson R, Brinkac LM, Daugherty SC, Deboy R, Durkin AS, Giglio MG, Madupu R, Nelson WC, Rosovitz MJ, Sullivan S, Crabtree J, Creasy T, Davidsen T, Haft DH, Zafar N, Zhou L, Halpin R, Holley T, Khouri H, Feldblyum T, White O, Fraser CM, Chatterjee AK, Cartinhour S, Schneider DJ, Mansfield J, Collmer A, and Buell CR
- Subjects
- Bacterial Proteins genetics, Bacterial Proteins physiology, DNA, Bacterial chemistry, DNA, Bacterial genetics, Molecular Sequence Data, Pseudomonas syringae classification, Pseudomonas syringae pathogenicity, Pseudomonas syringae physiology, Species Specificity, Virulence, Genes, Bacterial, Genome, Bacterial, Pseudomonas syringae genetics
- Abstract
Pseudomonas syringae pv. phaseolicola, a gram-negative bacterial plant pathogen, is the causal agent of halo blight of bean. In this study, we report on the genome sequence of P. syringae pv. phaseolicola isolate 1448A, which encodes 5,353 open reading frames (ORFs) on one circular chromosome (5,928,787 bp) and two plasmids (131,950 bp and 51,711 bp). Comparative analyses with a phylogenetically divergent pathovar, P. syringae pv. tomato DC3000, revealed a strong degree of conservation at the gene and genome levels. In total, 4,133 ORFs were identified as putative orthologs in these two pathovars using a reciprocal best-hit method, with 3,941 ORFs present in conserved, syntenic blocks. Although these two pathovars are highly similar at the physiological level, they have distinct host ranges; 1448A causes disease in beans, and DC3000 is pathogenic on tomato and Arabidopsis. Examination of the complement of ORFs encoding virulence, fitness, and survival factors revealed a substantial, but not complete, overlap between these two pathovars. Another distinguishing feature between the two pathovars is their distinctive sets of transposable elements. With access to a fifth complete pseudomonad genome sequence, we were able to identify 3,567 ORFs that likely comprise the core Pseudomonas genome and 365 ORFs that are P. syringae specific.
- Published
- 2005
- Full Text
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28. Preliminary analysis of polyhydroxyalkanoate inclusions using atomic force microscopy.
- Author
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Dennis D, Liebig C, Holley T, Thomas KS, Khosla A, Wilson D, and Augustine B
- Subjects
- Polyesters metabolism, Sodium Dodecyl Sulfate, Sonication, Cupriavidus necator metabolism, Cupriavidus necator ultrastructure, Inclusion Bodies ultrastructure, Microscopy, Atomic Force methods
- Abstract
Atomic force microscopy analysis of polyhydroxyalkanoate (PHA) inclusions isolated from sonicated Ralstonia eutropha cells revealed that they exhibit two types of surface structure and shape; rough and ovoid, or smooth and spherical. Smooth inclusions possessed linear surface structures that were in parallel arrays with 7-nm spacing. Occasionally, cracks or fissures could be seen on the surface of the rough inclusions, which allowed a measurement of approximately 4 nm for the thickness of the boundary layer. When the rough inclusions were imaged at higher resolution, globular structures, 35 nm in diameter, having a central pore could be seen. These globular structures were connected by a network of 4-nm-wide linear structures. When the inclusions were treated with sodium lauryl sulfate, the boundary layer of the inclusion deteriorated in a manner that would be consistent with a lipid envelope. When the boundary layer was largely gone, 35-nm globular disks could be imaged laying on the surface of the filter beside the inclusions. These data have facilitated the development of a preliminary model for PHA inclusion structure that is more advanced than previous models.
- Published
- 2003
- Full Text
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29. Effect of high doses of radiation on human neutrophil chemotaxis, phagocytosis and morphology.
- Author
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Holley TR, Van Epps DE, Harvey RL, Anderson RE, and Williams RC Jr
- Subjects
- Cell Nucleus radiation effects, Cell Survival, Cytological Techniques, Cytoplasm radiation effects, Dose-Response Relationship, Radiation, Humans, Microscopy, Electron, Neutrophils cytology, Staphylococcus, Trypan Blue, Chemotaxis radiation effects, Neutrophils radiation effects, Phagocytosis radiation effects, Radiation Effects
- Abstract
Human neutrophils were exposed to varying amounts of ionizing radiation up to 1,000,000 rad and evaluated as to their ability to respond to chemotactic stimuli and phagocytize and kill bacteria. Striking morphologic and functional resistance to radiation was apparent. At doses up to 5,000 rad there was little or no impairment of chemotaxis. As the dosage increased to 50,000 rad, chemotaxis decreased to approximately 50% of nonirradiated control values. At very high doses of radiation (250,000 to 1,000,000 rad) neutrophils failed to respond significantly to chemotactic stimuli. Effects of radiation as measured by phagocytosis and the degree of ultrastructural change paralleled the chemotaxis results.
- Published
- 1974
30. Opiate antagonism fails to reverse hypnotic-induced analgesia.
- Author
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Nasrallah HA, Holley T, and Janowsky DS
- Subjects
- Adult, Clinical Trials as Topic, Humans, Male, Pain prevention & control, Endorphins antagonists & inhibitors, Hypnosis, Anesthetic, Naloxone pharmacology
- Published
- 1979
- Full Text
- View/download PDF
31. Hypothalamic stimulation facilitates contralateral visual control of a learned response.
- Author
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Beagley WK and Holley TL
- Subjects
- Animals, Discrimination Learning physiology, Functional Laterality, Male, Rats, Hypothalamus physiology, Visual Perception physiology
- Abstract
Rats that ate during hypothalamic stimulation were trained to press a lever for food only while receiving light signals from head-mounted lights. During stimulation, they pressed if the signal was visible to the eye contralateral to the electrode, but ignored the signal if it was visible only to the ipsilateral eye.
- Published
- 1977
- Full Text
- View/download PDF
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