17 results on '"Dasu, Mohan R. K."'
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2. Genomic analysis of insulin‐like growth factor‐I gene transfer in thermally injured rats
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Dasu, Mohan R. K., primary, Herndon, David N., additional, Spies, Marcus, additional, and Perez‐Polo, J. Regino, additional
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- 2004
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3. Alterations in Resistin Expression After Thermal Injury
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Dasu, Mohan R. K., primary, LaGrone, Lavenia, additional, and Mileski, William J., additional
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- 2004
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4. IGF-I gene transfer effects on inflammatory elements present after thermal trauma
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Dasu, Mohan R. K., primary, Herndon, David N., additional, Nesic, Olivera, additional, and Perez-Polo, J. Regino, additional
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- 2003
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5. Gene expression profiles and protein balance in skeletal muscle of burned children after β-adrenergic blockade
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Herndon, David N., primary, Dasu, Mohan R. K., additional, Wolfe, Robert R., additional, and Barrow, Robert E., additional
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- 2003
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6. Matrix metalloproteinases and their tissue inhibitors in severely burned children
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Dasu, Mohan R. K., primary, Spies, Marcus, additional, Barrow, Robert E., additional, and Herndon, David N., additional
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- 2003
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7. Gene Expression Patterns in Skeletal Muscle of Thermally Injured Children Treated With Oxandrolone
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Barrow, Robert E., primary, Dasu, Mohan R. K., additional, Ferrando, Arny A., additional, Spies, Marcus, additional, Thomas, Steven J., additional, Perez-Polo, J. Regino, additional, and Herndon, David N., additional
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- 2003
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8. Gene expression analysis in burn wounds of rats
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Spies, Marcus, primary, Dasu, Mohan R. K., additional, Svrakic, Nenad, additional, Nesic, Olivera, additional, Barrow, Robert E., additional, Perez-Polo, J. Regino, additional, and Herndon, David N., additional
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- 2002
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9. Original Research Articles – Basic Science Genomic analysis of insulin-like growth factor-I gene transfer in thermally injured rats.
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Dasu, Mohan R. K., Herndon, David N., Spies, Marcus, and Perez‐Polo, J. Regino
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BURNS & scalds , *NECROSIS , *INFLAMMATION , *CELL death , *GROWTH factors , *GENE expression , *SOMATOMEDIN , *GENETIC transformation , *POLYMERASE chain reaction - Abstract
Thermal trauma causes tissue damage by membrane destabilization and energy depletion at the cellular level, resulting in tissue necrosis and inflammation leading to delayed cell death. One therapeutic approach is to block the immediate triggering of the inflammatory cascade that results in prolonged hypermetabolic responses and immune dysfunction while promoting the expression of growth factors. In the present study, we determined hepatic gene expression responses to insulin-like growth factors-i (IGF-I) gene transfer to burned rats using high-density DNA microarray assays. The expression of 123 out of ~8,800 genes assyed (1.4% of total) were significantly altered. Of these, 42 genes were altered irrespective of treatment by burn trauma ( p < 0.05). Changes in gene expression were confirmed by measuring mRNA levels using reverse transcription-polymerase chain reaction and protein levels by Western blot assays. DNA microarray analyses showed two major mechanisms that mediated beneficial outcomes after IGF-I gene transfer in the burned rat livers. These mechanisms were the stimulation of IGF binding protein potentiation of peripheral IGF-I and the inhibition of the burn-augmented pro-apoptotic and oxidative mitochondrial metabolites stimulated by thermal trauma. [ABSTRACT FROM AUTHOR]
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- 2004
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10. Oxidative and heat stress gene changes in hypertrophic scar fibroblasts stimulated with interleukin-1beta.
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Barrow RE and Dasu MR
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- Adolescent, Cell Cycle Proteins genetics, Child, Child, Preschool, Female, Fibroblasts metabolism, HSP70 Heat-Shock Proteins genetics, Humans, Interleukin-6 genetics, Male, NF-kappa B genetics, Nuclear Proteins genetics, Cicatrix, Hypertrophic metabolism, Gene Expression Regulation drug effects, Heat-Shock Proteins genetics, Interleukin-1 pharmacology, Oxidative Stress genetics
- Abstract
Introduction: Cutaneous wounds that involve loss of tissue heal through a complex process of generating granulation tissue to initially cover the wound, followed by epithelialization, and contraction. Normal healing requires a delicate balance between cellular, matrix, and vascularity build up and breakdown. Defects in the regulation of this balance can alter normal scar formation through fibroblastic hyperproliferation, which is characteristic of hypertrophic scar formation., Methods: Primary fibroblasts cultures from hypertrophic scar or adjacent normal skin were seeded in growth medium. Half of each was stimulated with interleukin (IL)-1beta for 6 h and half served as control nonstimulated fibroblasts. Supernatants were tested for expressed proteins and the fibroblasts for changes in gene expression., Results: Comparison between normal skin and hypertrophic scar fibroblasts stimulated with IL-1beta indicate that 15 genes increased and 8 genes decreased expression. When normal skin was stimulated with IL-1beta, there were increases in the expression of heat shock transcription factor-1, hsp70, and IL-6 When hypertrophic scar was stimulated with IL-1beta, there was a decrease in nuclear factor-kappaB, GADD45-alpha, p53, p53 binding protein, and Cox-2 genes. These genes may play specific but different roles in controlling the cellular response to cell stress and apoptosis., Conclusion: Data presented suggest that oxidative and heat stress proteins, stimulated through IL-1beta, may be important mediators of abnormal scarring.
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- 2005
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11. Gene profiling in muscle of severely burned children: age- and sex-dependent changes.
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Dasu MR, Barrow RE, and Herndon DN
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- Adolescent, Age Factors, Child, Child, Preschool, Female, Humans, Male, Oligonucleotide Array Sequence Analysis, Reverse Transcriptase Polymerase Chain Reaction, Sex Factors, Burns metabolism, Gene Expression Profiling, Muscle, Skeletal metabolism
- Abstract
Background: Thermal injury is associated with a pronounced catabolic response in skeletal muscle. This study identifies gene expression changes in skeletal muscle of thermally injured girls and boys using high-density oligonucleotide arrays., Methods: Six burned children with a mean age of 8.3 +/- 1.3 years and TBSA burn size covering 51 +/- 6% admitted to our hospital with in 48 h of injury and six cleft lip and cleft palate patients were studied. Total RNA was isolated, in vitro transcribed, and hybridized to HG-U95 Av.2 Affymetrix arrays. Messenger RNA expression patterns of controls and burn patients were compared using Affymetrix GeneChip Analysis Suite 5.2 and dChip., Results: Statistical analysis of the 12,625 genes on each array showed a significant increase in the expression of 77 genes in burn children and a decrease in 21 genes when compared to controls (P < 0.05). We found three genes in burned males and two genes in burned females with decreased expression in muscle compared to controls. Chromosomes 1, 2, 7, 12, and 16 showed genes with increased expression in muscle from burned children, while chromosomes 3, 7, 8, 19, and 22 had genes with decreased expression. Categories of genes affected were related to metabolism, proliferation, transcription/translation, immune response, stress response, angiogenesis, and signal transduction., Conclusions: Genes that are differentially expressed in skeletal muscle of burned children, but whose function in muscle is unknown, include those related to various transcription factors and those known to encode proteins involved in signaling pathways. Further analysis is required to achieve the ultimate goal of making functionally relevant conclusions about the molecular pathology of burn injury.
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- 2005
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12. Gene expression profiles from hypertrophic scar fibroblasts before and after IL-6 stimulation.
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Dasu MR, Hawkins HK, Barrow RE, Xue H, and Herndon DN
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- Cells, Cultured, Child, Child, Preschool, Cicatrix, Hypertrophic pathology, Enzyme-Linked Immunosorbent Assay, Female, Fibroblasts drug effects, Gene Expression Profiling, Humans, Male, Matrix Metalloproteinase 1 biosynthesis, Matrix Metalloproteinase 1 genetics, Matrix Metalloproteinase 3 biosynthesis, Matrix Metalloproteinase 3 genetics, Reverse Transcriptase Polymerase Chain Reaction, Skin cytology, Skin metabolism, Cicatrix, Hypertrophic metabolism, Fibroblasts metabolism, Gene Expression Regulation drug effects, Interleukin-6 pharmacology
- Abstract
The structural rearrangement of collagen fibres in hypertrophic scar causes abnormal contracture, low tensile strength, and raised scars, which cause functional impairment and disfigurement. It is hypothesized that changes in the genes of cytokines, extracellular matrix proteins, and proteins regulating programmed cell death are related to hypertrophic scar formation. To test this hypothesis, fibroblasts were cultured from hypertrophic scars and their response to interleukin-6 (IL-6) stimulation was studied by defining their gene expression profiles. Affymetrix gene chip analysis was used to identify up- or down-regulation in the 12 625 genes present in the affymetrix array. RT-PCR and ELISA assays were used to validate microarray expression profiles further. Comparison of gene profiles showed an increase of 12 genes in hypertrophic scar fibroblasts compared with normal skin fibroblasts, while the expression of 14 genes decreased. Thirty-three genes were affected by IL-6 treatment in the hypertrophic scar fibroblasts, while 57 genes were affected in normal skin fibroblasts. Messenger RNA to beta-actin ratios for matrix metalloproteinase-1 (MMP-1) and MMP-3 were increased with IL-6 in normal skin fibroblasts from 2.43 +/- 0.06 to 5.50 +/- 0.45 and from 0.75 +/- 0.09 to 1.98 +/- 0.01, respectively. No change in these matrix metalloproteinases could be shown with IL-6 stimulation in hypertrophic scar fibroblasts. Secreted protein levels of pro-MMP-1 and MMP-3 were elevated in the supernatants from normal skin fibroblasts from 2.00 +/- 0.09 and 1.72 +/- 0.10 ng/ml to 4.60 +/- 0.12 and 3.41 +/- 0.20 ng/ml, respectively, after treatment with IL-6 (p < 0.05). No changes were observed in hypertrophic scar fibroblasts treated with IL-6. Values are means +/- SEM. The absence of any up-regulation of MMP-1 and MMP-3 in hypertrophic scar fibroblasts, in response to IL-6, suggests that suppression of matrix metalloproteinases may play a role in the excessive accumulation of collagen formed in hypertrophic scars. While the pathogenesis of abnormal hypertrophic scars remains poorly understood, the use of gene expression arrays may prove helpful in identifying the mechanisms responsible for this type of abnormal scar formation and in formulating an effective therapeutic protocol., (Copyright 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)
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- 2004
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13. Gene expression profiles of livers from thermally injured rats.
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Dasu MR, Cobb JP, Laramie JM, Chung TP, Spies M, and Barrow RE
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- Animals, Burns blood, Cluster Analysis, Liver pathology, Male, Oligonucleotide Array Sequence Analysis, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Rats, Sprague-Dawley, Reverse Transcriptase Polymerase Chain Reaction, alpha-Macroglobulins metabolism, Burns physiopathology, Gene Expression Profiling, Liver metabolism
- Abstract
The liver plays an important role in a severe thermal injury by modulating immune function, inflammatory processes and the acute phase response, which are an orchestrated attempt to restore homeostasis. Using high-density oligonucleotide arrays, we examined the gene expression profile in the livers of rats between 2 and 240 h after a 40% total body surface area (TBSA) burn. Alterations in gene expression unique to a thermal injury were identified. Approximately 39 genes out of 8700 genes on each array across all the time points showed a significant change in expression patterns. Real time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses verified significant changes in early growth response-1 (Egr-1) messenger RNA (mRNA) and protein levels corresponding to the array data. Significant increases in serum levels of alpha-2-macroglobulin that correspond to changes in its mRNA levels were observed at 6 and 24 h after burn, p<0.05. The genomic pattern for liver in the hypermetabolic phase after the burn injury involves transcription factors, stress and inflammatory responses, cytoskeletal and extracellular matrix modifications, and regulation of cell proliferation and differentiation. During the initial phase of thermal injury gene expression profiles in the liver may provide some insight into how cellular protection mechanisms and systemic hypermetabolism are initiated and controlled. The genome wide changes observed may provide a rational therapeutic strategy to improve burn care.
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- 2004
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14. IGF-I gene transfer effects on inflammatory elements present after thermal trauma.
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Dasu MR, Herndon DN, Nesic O, and Perez-Polo JR
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- Animals, Burns immunology, Caspase 3, Caspases metabolism, DNA-Binding Proteins metabolism, Gene Expression physiology, Immunoglobulin G metabolism, Liposomes, Male, NF-kappa B metabolism, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins c-bcl-2 genetics, Rats, Rats, Sprague-Dawley, Skin injuries, Skin metabolism, Transcription Factor AP-1 metabolism, bcl-2-Associated X Protein, bcl-X Protein, Burns metabolism, Burns therapy, Genetic Therapy, Insulin-Like Growth Factor I genetics, Wound Healing physiology
- Abstract
Major thermal injury results in severe prolonged responses with three components: a hypermetabolic response, inflammatory responses, and endogenous wound-healing processes. We showed that use of liposome-mediated gene transfer of the insulin-like growth factor I (IGF-I) reduces burn-induced inflammatory responses and enhances wound healing. In the present study, we found transient increased levels of IGF-I protein in rats exposed to thermal trauma via liposomal gene transfer in an effort to define the transcriptional events that occur after IGF-I delivery at the site of injury. The beneficial effects of IGF-I gene transfer act partly via amelioration of burn-induced inflammatory responses that mediate cell death through caspase-3 activity and Bax expression. IGF-I gene transfer induces selective stimulation of activation protein-1 DNA-binding activity and activation of antiapoptotic, but not inflammatory, NF-kappaB transcription factors. Data were consistent with our hypothesis that the beneficial effects of IGF-I gene transfer on burned rats act in part via activation protein-1 and NF-kappaB transcriptional regulation and the concordance between the results obtained with antiapoptotic, as opposed to the proapoptotic, sequences as well as the corresponding changes in measures of cell death via Bax and caspase-3 mechanisms.
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- 2003
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15. Gene expression profiles and protein balance in skeletal muscle of burned children after beta-adrenergic blockade.
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Herndon DN, Dasu MR, Wolfe RR, and Barrow RE
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- Adolescent, Burns genetics, Child, Child, Preschool, Female, Gene Expression Profiling methods, Humans, Male, Muscle Proteins genetics, Muscle, Skeletal pathology, Propranolol administration & dosage, Reference Values, Adrenergic beta-Antagonists pharmacology, Burns drug therapy, Burns metabolism, Gene Expression Regulation drug effects, Muscle Proteins metabolism, Muscle, Skeletal drug effects, Muscle, Skeletal metabolism, Propranolol pharmacology
- Abstract
Propranolol, a nonselective beta-blocker, has been shown effective in hypermetabolic burn patients by decreasing cardiac work, protein catabolism, and lipolysis. This study investigates the effect of propranolol on gene and protein expression changes in skeletal muscle of burned children by use of high-density oligonucleotide arrays to establish the genetic profiles and stable isotope technique to quantitate protein synthesis. Thirty-seven children (mean age 9.7 +/- 1.1 yr) were randomized into groups to receive placebo (n = 23) or propranolol (n = 14) titrated to reduce heart rate by 15%. Children had >40% total body surface area burns (mean 43 +/- 5.6%). Protein net balance was determined by stable-isotope infusion technique. Total RNA from muscle biopsies was isolated, labeled, and cRNA hybridized to the HG-U95Av2 Affymetrix array. Mean net balance of protein synthesis and breakdown was -14.3 +/- 12.9 nmol. min-1. 100 ml leg volume-1 for placebo and +69.3 +/- 34.9 nmol. min-1. 100 ml leg volume-1 in the propranolol-treated children (P = 0.012). Comparison of 12,000 genes in burned children receiving placebo showed increased expression of two genes with time, whereas children receiving propranolol showed increased expression of nine genes with a decrease in five genes. We conclude that burned children receiving propranolol showed a significant upregulation in genes involved in muscle metabolism and downregulation of an important enzyme involved in gluconeogenesis and insulin resistance compared with burned children receiving placebo. The upregulation of genes involved in muscle metabolism correlates well with the increase in net protein balance across the leg.
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- 2003
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16. Matrix metalloproteinase expression in cytokine stimulated human dermal fibroblasts.
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Dasu MR, Barrow RE, Spies M, and Herndon DN
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- Actins metabolism, Adult, Cells, Cultured, Fibroblasts drug effects, Fibroblasts enzymology, Humans, Interleukin-1 pharmacology, Interleukin-6 pharmacology, Skin drug effects, Tumor Necrosis Factor-alpha pharmacology, Cytokines pharmacology, Matrix Metalloproteinase 1 analysis, Skin enzymology, Tissue Inhibitor of Metalloproteinase-1 analysis
- Abstract
In this study, we investigated the effect of inflammatory cytokines on matrix metalloproteinase (MMP-1) and TIMP-1 production in human dermal fibroblasts, which play a pivotal role in wound healing, ranging from the synthesis and remodeling of extracellular matrix (ECM) to the synthesis of growth factors. The balance of MMPs and TIMPs is crucial in directing successful wound repair. Human adult dermal fibroblasts were seeded in six well plates (7.5 x 10(4) cells/ml) in complete media. Eighty to ninety percent confluent cells were treated with interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) (10 ng/ml) for 6h in serum free media with suitable controls run in triplicate. Supernatants were assayed for pro-MMP-1 & TIMP-1. Extracted total RNA was used for reverse transcription polymerase chain reaction (RT-PCR) with sequence specific primers for MMP-1, TIMP-1 and beta-actin. Signal intensity was normalized to the internal control (beta-actin). Statistical analysis used ANOVA. MMP-1 and TIMP-1 mRNA expression were markedly increased with IL-6 and TNF-alpha treatment and remains unchanged with IL-1beta. Pro-MMP-1 protein levels are unchanged with TNF-alpha and significantly increased with IL-1beta and IL-6 treatment. However, TNF-alpha significantly increases TIMP-1 protein levels. Data suggests differential regulation of MMP-1 and TIMP-1 protein levels by the cytokines found in stimulated dermal fibroblasts. Further characterization of this response will provide an understanding of the mechanisms of pathogenesis of extracellular matrix (ECM) and the potential role of metalloproteinases in tissue remodeling after injury.
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- 2003
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17. Gene expression analysis in burn wounds of rats.
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Spies M, Dasu MR, Svrakic N, Nesic O, Barrow RE, Perez-Polo JR, and Herndon DN
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- Animals, Antibody Formation, Cell Division genetics, Cell Survival genetics, Dermatitis genetics, Gene Expression, Genome, Male, Multigene Family physiology, Oligonucleotide Array Sequence Analysis, Rats, Rats, Sprague-Dawley, Skin immunology, Skin pathology, Skin physiopathology, Time Factors, Burns genetics, Gene Expression Profiling, Skin injuries
- Abstract
The events occurring early in the burn wound trigger a sequence of local and systemic responses that influence cell and tissue survival and, consequently, wound healing and recovery. Using high-density oligonucleotide arrays we identified gene expression patterns in skin samples taken from a region of injury in the burn rat model. The associated genomic events include the differential expression of genes involved in cell survival and death, cell growth regulation, cell metabolism, inflammation, and immune response. The functional gene cluster detected and their time appearance matched the time sequence known to occur in burn wound healing.
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- 2002
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