- Email: [email protected]
205. Osteopontin Mediates Stat1 Degradation to Inhibit iNOS Transcription in a Cecal Ligation and Puncture Model of Sepsis
268 ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS ptosis (annexin V staining) in cells with altered expression of ATDC were assessed. Participation of ATDC in the phosphorylation of the ATR substrates p53 and Chk1, key regulators of the replication checkpoint, was determined following exposure to gemcitabine. The effect of ATDC on “stalled replication forks” was measured indirectly by examining phosphorylation of the histone variant ␥H2AX following gemcitabine treatment. Co-localization of ATDC and ␥H2AX in response to gemcitabine was determined by immunohistochemistry. Results: Overexpression of ATDC protected cells from gemcitabineinduced apoptosis while silencing of ATDC augmented apoptosis induced by gemcitabine (18.5 ⫾ 7.2% vs 60.1 ⫾ 15.8%, p ⬍ 0.05, n⫽3). ATDC overexpression increased phosphorylation of the ATR substrates p53 and Chk1, while ATDC silencing decreased phosphorylation of these molecules after gemcitabine treatment. ATDC silencing resulted in increased ␥H2AX phosphorylation following gemcitabine. Gemcitabine treatment of Panc-1 cells resulted in trafficking of ATDC to the nucleus and co-localizing with ␥H2AX at DNA damage repair foci. Conclusions: ATDC is a novel DNA damage response protein highly expressed in the majority of pancreatic cancers. ATDC appears to function in the ATR-mediated DNA damage signaling cascade, as evidenced by trafficking to the nucleus, colocalizing with ␥H2AX and modulating phosphorylation of the replication checkpoint regulators p53 and Chk1. This work has important implications for better understanding the role of ATDC in pancreatic tumorigenesis and the DNA damage response in both neoplastic and normal cells, a topic not explored previously. Furthermore, targeting ATDC for inactivation should have therapeutic value by increasing the susceptibility of pancreatic cancer cells to chemotherapeutic agents that utilize the ATR-mediated DNA damage signaling cascade. 204. THE TLR9 AGONIST CPG-DNA PROTECTS AGAINST LPS-INDUCED ENTEROCYTE APOPTOSIS THROUGH THE UP-REGULATION OF HEAT SHOCK PROTEIN 70 AND REDUCES THE SEVERITY OF NECROTIZING ENTEROCOLITIS IN MICE. Steven C. Gribar, Anna C. Evans, Ward M. Richardson, Rahul J. Anand, Jeffrey W. Kohler, Maria F. Branca, Theresa D. Dubowski, Jun Li, Chhinder P. Sodhi, David J. Hackam; Children’s Hospital of Pittsburgh, Pittsburgh, PA Introduction: Necrotizing enterocolitis (NEC) is a severe intestinal inflammatory disorder characterized by increased circulating endotoxin (LPS) and apoptosis of ileal enterocytes. Heat shock protein 70 (Hsp70) is a molecular chaperone that prolongs cellular survival, although a role in enterocyte apoptosis remains ill defined. We have recently shown that the TLR9 agonist CpG-DNA is protective against LPS-induced apoptosis, although the mechanisms involved remain unclear. We now seek to determine whether CpG-DNA acts via the up-regulation of Hsp70, and whether CpG-DNA may have a protective role in the treatment of NEC. Methods: Primary enterocytes that were harvested from embryonic intestine or IEC-6 enterocytes were exposed to heat shock (43 oC, 60m), the Hsp70 inhibitor quercetin (200M, 1h), LPS (50g/ml, 18h) or CpG-DNA (1M, 24h) and the expression and distribution of Hsp70 were assessed by RT-PCR, SDS-PAGE and immunoconfocal microscopy while apoptosis was quantified by caspase-3 activation and TUNEL staining. CpG-DNA was synthesized from demethylated monomers under strict endotoxin-free conditions. NEC was induced in newborn mice by hypoxia/gavage for four days, and CpG-DNA was administered i.p. daily and NEC severity was graded by blinded pathologist. The expression of Hsp70 in ileal mucosal scrapings from mice with and without NEC or from human infants undergoing either intestinal resection for NEC or at stoma closure was assessed by RT-PCR and SDS-PAGE. Results: Primary murine and IEC-6 enterocytes expressed Hsp70, which was detected in a cytoplasmic distribution, and was increased after heat exposure or treatment with CpG-DNA. LPS treatment led to increased apoptosis of IEC-6 enterocytes and a
loss of enterocyte expression of Hsp70, while the induction of Hsp70 with heat shock protected against LPS-induced apoptosis (ctrl: 11⫾2%, LPS: 27⫾5%, LPS⫹heat: 18⫾2%, p⬍0.05). This protective effect was reversed by pre-treatment with the Hsp70 inhibitor quercetin (LPS⫹heat⫹quercetin: 30⫾5%). Treatment of IEC-6 cells with the TLR9 ligand CpG-DNA similarly protected against LPS-induced enterocyte apoptosis (LPS⫹CpG-DNA: 9⫾1%), suggesting a potential protective role for CpG-DNA-induced Hsp70 expression in the treatment of NEC, a disease characterized by enterocyte apoptosis. In support of this possibility, newborn mice with NEC and human newborns with NEC demonstrated reduced intestinal Hsp70 expression compared to controls. Strikingly, treatment of experimental NEC in mice with CpG-DNA restored intestinal Hsp70 expression and markedly reduced the severity of NEC compared with NECanimals given vehicle alone (see Figure). Conclusions: The TLR9 ligand CpG-DNA enhances intestinal expression of Hsp70 leading to protection against enterocyte apoptosis and a reduction in the severity of NEC in mice. These findings provide a rationale for the therapeutic potential of TLR9 ligands in the treatment of intestinal inflammation.
205. OSTEOPONTIN MEDIATES STAT1 DEGRADATION TO INHIBIT INOS TRANSCRIPTION IN A CECAL LIGATION AND PUNCTURE MODEL OF SEPSIS. Hongtao Guo, Philip Y. Wai, Zhiyong Mi, Chengjiang Gao, Jinping Zhang, Paul C. Kuo; Duke University, Durham, NC Inducible nitric oxide synthase (iNOS) expression is central to many systemic effects associated with sepsis. iNOS expression regulates cardiac contractility, vasomotor tone, intestinal epithelial permeability, and leukocyte recruitment. Little is known of the counterregulatory pathways which inhibit iNOS expression. In cell culture systems, we have previously demonstrated that osteopontin (OPN) is a potent trans-repressor of iNOS expression by increasing ubiquitin (Ub)-proteasome mediated degradation of Stat1, a critical transcription factor for iNOS expression. In these studies, we investigate the in vivo relevance of our findings in a cecal ligation and puncture (CLP) model of sepsis. Wild type (WT; n⫽24) and OPN null (n⫽24) 129 male mice (12-16 weeks old) were utilized. Via a midline laparotomy incision, the cecum was ligated by 4.0 silk distal to the ileocecal junction; a 18-gauge needle was passed through both walls of the cecum. After a small amount of fecal matter was expressed, the cecum was returned to the peritoneal cavity, and the abdomen was closed. Sham operated animals served as Controls. A saline bolus (20 mL/kg) was administered subcutaneously, to provide resuscitation. At 0, 12, and 24 hrs, bone marrow macrophages (BMM) and whole liver tissue were isolated. Western blot analysis was performed for iNOS, OPN, NF-B p65 and activated phosphorylated Stat1 (P-Stat1) proteins. In OPN null, expression of iNOS and P-Stat1 is significantly greater in BMM and Liver at 12h and 24h when compared to that found in WT. (p⬍0.01; at 24h and 12h for both iNOS and P-Stat1 in BMM and Liver) Nuclear NF-B p65 did not differ between WT and OPN null animals. P-Stat1 was then immunoprecipitated, and immunoblots performed to determine Ub-P-Stat1 expression in BMM and liver tissue at 24h. In BMM and liver tissue, CLP was associated with ubiquitination of P-Stat1; in OPN null animals, Ub-P-Stat1 is sig-
ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS 269 nificantly less that that noted in WT. (p⬍0.01; WT vs OPN null) Recruitment of RNA polymerase II to the iNOS promoter was determined by real time PCR-ChIP assays to determine iNOS transcription. Sequences were identified for the mouse iNOS promoter (Genbank no. L09126). Transcription of iNOS was significantly increased in both WT and OPN null BMM and liver at 24h. However, when compared to WT, OPN null BMM and Liver transcription of iNOS was significantly increased by over 2-3 fold. (p⬍0.05 vs WT for BMM and Liver) ChIP assays for P-Stat1 found significantly increased P-Stat1 binding to the iNOS promoter in OPN null. (p⬍0.01 vs WT) Ex vivo gain-of-function studies using BMM from WT and OPN null were performed. MG132 (10 M), an inhibitor of 26S proteasome function, and/or exogenous OPN (50 M) were used; Ub-P-Stat1 and iNOS expression were determined. Cells were treated with LPS (50 ng/ml) for 12 hours; IP was performed for Ub-P-Stat1 and IB was performed for iNOS. Ub- P-Stat1 was decreased in OPN null BMM treated with LPS; conversely, iNOS was increased. Exogenous repletion of OPN (or proteasome inhibition) restored Ub-P-Stat1 and iNOS to levels equivalent to that seen in WT animals. In BMM and Liver from a CLP model, our results indicate that absence of OPN is associated with: 1) increased iNOS and P-Stat1 protein, 2) decreased ubiquitination and degradation of P-Stat1, and 3) increased iNOS transcription. We conclude that OPN downregulates iNOS expression by accelerating ubiquitination and ultimately, degradation of Stat1. This unique observation has not been previously demonstrated in vivo. 206. DEFINING THE TRANSCRIPTIONAL REGULATION OF INTESTINAL SGLT1 USING RNA-INTERFERENCE MEDIATED GENE SILENCING. Anita Balakrishnan1, Adam T. Stearns1, David B. Rhoads2, Stanley W. Ashley1, Ali Tavakkolizadeh1; 1Brigham and Women’s Hospital and Harvard Medical School, Boston, MA; 2Massachusetts General Hospital and Harvard Medical School, Boston, MA Introduction: The sodium glucose co-transporter (SGLT1) is responsible for over 90% of intestinal apical glucose uptake. Dysregulation of SGLT1 is associated with diabetes and obesity, and understanding SGLT1 regulation may yield novel therapeutic options for these conditions. Hepatocyte nuclear factors HNF1␣ and  are known transcription factors of SGLT1. GATA-5 and CDX2 are transcription factors for other intestinal genes, however their role in the regulation of SGLT1 remains unknown. We aimed to further define the transcriptional regulation of SGLT1 expression and hypothesized that intestinal SGLT1 transcription is regulated via interactions between HNF1␣, HNF1, GATA-5 and CDX2. To investigate this, we used a combination of promoter studies and RNAinterference mediated gene silencing. Methods: Chinese Hamster Ovary (CHO) cells, a cell line with no endogenous SGLT1 expression, were transiently co-transfected with an SGLT1-luciferase promoter construct and combinations of expression vectors for HNF1␣, HNF1, CDX2 and GATA-5. Lentiviral plasmid vectors bearing short-hairpin RNA sequences unique to either HNF1␣ or HNF1 were transfected into Caco2 cells, which differentiate into small bowel epithelium upon confluence. Stable cell lines of HNF1␣ knockdowns (shHNF1␣), HNF1 knockdowns (shHNF1) and scrambled RNA negative controls (shcontrol) were created via puromycin selection. mRNA levels of HNF1␣, HNF1 and SGLT1 were determined using quantitative real-time PCR. Statistical significance was determined with ANOVA and post-hoc TUKEY analysis. Results: 1) Cooperative stimulation of SGLT1 promoter activity by HNF1␣ and GATA-5. Luciferase activity in CHO cells was significantly increased by HNF1␣, GATA-5, and to a lesser extent by HNF1 (p⬍0.05 vs. promoter alone). Co-transfection of GATA-5 with HNF1␣ had an additive effect on SGLT1 promoter activity compared to HNF1␣ alone. Co-transfection of HNF1 or CDX2 with HNF1␣ or GATA-5 antagonized the increase in luciferase activity produced by HNF1␣ or GATA-5 alone. 2) Transcriptional interdependence of
HNF1␣ and HNF1 in vitro. Knockdown of HNF1␣ in Caco2 cells reduced the expression of both HNF1␣ and HNF1 by over 50% and vice versa (p⬍0.0005 vs. controls, Fig. 1). 3) HNF1 is an essential transcription factor for enterocyte SGLT1 expression in vitro. SGLT1 expression was more than 2-fold higher in negative controls than in HNF1␣ or HNF1 knockdowns (p⬍0.001,Fig. 1). Conclusions: Using RNA interference technology we show for the first time that HNF1␣ and HNF1 are essential transcription factors for SGLT1 expression in vitro and identify interdependence in HNF1␣ and HNF1 expression. In addition we report GATA-5 and CDX2 activity on the SGLT1 promoter, suggesting novel roles for these transcription factors in the regulation of SGLT1. We therefore propose a multifactorial model for the regulation of SGLT1 expression, involving interactions between HNF1␣, HNF1, GATA-5 and CDX2 in maintaining homeostasis of intestinal glucose absorption. Greater insight into these relationships will improve our understanding of intestinal SGLT1 expression, facilitating novel therapies to modulate glucose absorption in diabetes and obesity.
207. SUS/AAS ABSTRACTS: WHAT IS THE SCIENTIFIC IMPACT? Nadine Housri, Michael Cheung, Juan C. Gutierrez, Teresa A. Zimmers, Leonidas G. Koniaris; University of Miami, Miami, FL Aim: To evaluate the scientific impact of abstracts presented at two widely recognized, national surgical conferences: the annual meetings of the Society of University Surgeons (SUS) and the Association for Academic Surgery (AAS). Methods: Publications resulting from abstracts presented at the 2002, 2003, and 2004 annual conferences of the AAS and the SUS were identified by PubMed query. The number of times each publication was cited through August 1, 2007 and the impact factor for the journal and year of publication were determined using ISI Web of Science. One way ANOVA with Bonferonni Multiple Comparison test were used for statistical analysis. Results: All 1200 abstracts from the 2002, 2003 and 2004 SUS (n ⫽ 543, 45%) and AAS (n ⫽ 657, 55%) annual meetings were reviewed. Abstracts were classified according to presentation sessions (Plenary, Parallel, and Poster) at each conference, as well as Basic Science Forum and Resident Conferences at SUS. Statistical analysis of SUS results across session types demonstrated significant differences in publication rates (p ⬍ 0.0001), but no difference in impact factors (p ⫽ 0.2556) or number of citations (p ⫽ 0.3947). AAS results demonstrated significant differences for publication rate (p ⬍ 0.0001), impact factor (p ⫽ 0.0351), and number of citations (p ⫽ 0.0383) across sessions. Comparison of abstracts between meetings demonstrated a higher overall publication rate, impact factor and citation rate for SUS publications versus AAS. Although plenary sessions in both meetings were statistically equivalent, there was a trend toward a higher publication rate, impact factor and citation rate for SUS publications. Conclusion: Overall and individually, the average impact factors of publications resulting from SUS and AAS abstracts are considerably higher than the aggregate impact factor (1.913) of the 138 surgical journals in the Journal Citation Index and are near the aggregate impact factor for all journals in research and experimental medicine (3.552).This result suggests that SUS and AAS presentations constitute high-quality, cutting
loss of enterocyte expression of Hsp70, while the induction of Hsp70 with heat shock protected against LPS-induced apoptosis (ctrl: 11⫾2%, LPS: 27⫾5%, LPS⫹heat: 18⫾2%, p⬍0.05). This protective effect was reversed by pre-treatment with the Hsp70 inhibitor quercetin (LPS⫹heat⫹quercetin: 30⫾5%). Treatment of IEC-6 cells with the TLR9 ligand CpG-DNA similarly protected against LPS-induced enterocyte apoptosis (LPS⫹CpG-DNA: 9⫾1%), suggesting a potential protective role for CpG-DNA-induced Hsp70 expression in the treatment of NEC, a disease characterized by enterocyte apoptosis. In support of this possibility, newborn mice with NEC and human newborns with NEC demonstrated reduced intestinal Hsp70 expression compared to controls. Strikingly, treatment of experimental NEC in mice with CpG-DNA restored intestinal Hsp70 expression and markedly reduced the severity of NEC compared with NECanimals given vehicle alone (see Figure). Conclusions: The TLR9 ligand CpG-DNA enhances intestinal expression of Hsp70 leading to protection against enterocyte apoptosis and a reduction in the severity of NEC in mice. These findings provide a rationale for the therapeutic potential of TLR9 ligands in the treatment of intestinal inflammation.
205. OSTEOPONTIN MEDIATES STAT1 DEGRADATION TO INHIBIT INOS TRANSCRIPTION IN A CECAL LIGATION AND PUNCTURE MODEL OF SEPSIS. Hongtao Guo, Philip Y. Wai, Zhiyong Mi, Chengjiang Gao, Jinping Zhang, Paul C. Kuo; Duke University, Durham, NC Inducible nitric oxide synthase (iNOS) expression is central to many systemic effects associated with sepsis. iNOS expression regulates cardiac contractility, vasomotor tone, intestinal epithelial permeability, and leukocyte recruitment. Little is known of the counterregulatory pathways which inhibit iNOS expression. In cell culture systems, we have previously demonstrated that osteopontin (OPN) is a potent trans-repressor of iNOS expression by increasing ubiquitin (Ub)-proteasome mediated degradation of Stat1, a critical transcription factor for iNOS expression. In these studies, we investigate the in vivo relevance of our findings in a cecal ligation and puncture (CLP) model of sepsis. Wild type (WT; n⫽24) and OPN null (n⫽24) 129 male mice (12-16 weeks old) were utilized. Via a midline laparotomy incision, the cecum was ligated by 4.0 silk distal to the ileocecal junction; a 18-gauge needle was passed through both walls of the cecum. After a small amount of fecal matter was expressed, the cecum was returned to the peritoneal cavity, and the abdomen was closed. Sham operated animals served as Controls. A saline bolus (20 mL/kg) was administered subcutaneously, to provide resuscitation. At 0, 12, and 24 hrs, bone marrow macrophages (BMM) and whole liver tissue were isolated. Western blot analysis was performed for iNOS, OPN, NF-B p65 and activated phosphorylated Stat1 (P-Stat1) proteins. In OPN null, expression of iNOS and P-Stat1 is significantly greater in BMM and Liver at 12h and 24h when compared to that found in WT. (p⬍0.01; at 24h and 12h for both iNOS and P-Stat1 in BMM and Liver) Nuclear NF-B p65 did not differ between WT and OPN null animals. P-Stat1 was then immunoprecipitated, and immunoblots performed to determine Ub-P-Stat1 expression in BMM and liver tissue at 24h. In BMM and liver tissue, CLP was associated with ubiquitination of P-Stat1; in OPN null animals, Ub-P-Stat1 is sig-
ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS 269 nificantly less that that noted in WT. (p⬍0.01; WT vs OPN null) Recruitment of RNA polymerase II to the iNOS promoter was determined by real time PCR-ChIP assays to determine iNOS transcription. Sequences were identified for the mouse iNOS promoter (Genbank no. L09126). Transcription of iNOS was significantly increased in both WT and OPN null BMM and liver at 24h. However, when compared to WT, OPN null BMM and Liver transcription of iNOS was significantly increased by over 2-3 fold. (p⬍0.05 vs WT for BMM and Liver) ChIP assays for P-Stat1 found significantly increased P-Stat1 binding to the iNOS promoter in OPN null. (p⬍0.01 vs WT) Ex vivo gain-of-function studies using BMM from WT and OPN null were performed. MG132 (10 M), an inhibitor of 26S proteasome function, and/or exogenous OPN (50 M) were used; Ub-P-Stat1 and iNOS expression were determined. Cells were treated with LPS (50 ng/ml) for 12 hours; IP was performed for Ub-P-Stat1 and IB was performed for iNOS. Ub- P-Stat1 was decreased in OPN null BMM treated with LPS; conversely, iNOS was increased. Exogenous repletion of OPN (or proteasome inhibition) restored Ub-P-Stat1 and iNOS to levels equivalent to that seen in WT animals. In BMM and Liver from a CLP model, our results indicate that absence of OPN is associated with: 1) increased iNOS and P-Stat1 protein, 2) decreased ubiquitination and degradation of P-Stat1, and 3) increased iNOS transcription. We conclude that OPN downregulates iNOS expression by accelerating ubiquitination and ultimately, degradation of Stat1. This unique observation has not been previously demonstrated in vivo. 206. DEFINING THE TRANSCRIPTIONAL REGULATION OF INTESTINAL SGLT1 USING RNA-INTERFERENCE MEDIATED GENE SILENCING. Anita Balakrishnan1, Adam T. Stearns1, David B. Rhoads2, Stanley W. Ashley1, Ali Tavakkolizadeh1; 1Brigham and Women’s Hospital and Harvard Medical School, Boston, MA; 2Massachusetts General Hospital and Harvard Medical School, Boston, MA Introduction: The sodium glucose co-transporter (SGLT1) is responsible for over 90% of intestinal apical glucose uptake. Dysregulation of SGLT1 is associated with diabetes and obesity, and understanding SGLT1 regulation may yield novel therapeutic options for these conditions. Hepatocyte nuclear factors HNF1␣ and  are known transcription factors of SGLT1. GATA-5 and CDX2 are transcription factors for other intestinal genes, however their role in the regulation of SGLT1 remains unknown. We aimed to further define the transcriptional regulation of SGLT1 expression and hypothesized that intestinal SGLT1 transcription is regulated via interactions between HNF1␣, HNF1, GATA-5 and CDX2. To investigate this, we used a combination of promoter studies and RNAinterference mediated gene silencing. Methods: Chinese Hamster Ovary (CHO) cells, a cell line with no endogenous SGLT1 expression, were transiently co-transfected with an SGLT1-luciferase promoter construct and combinations of expression vectors for HNF1␣, HNF1, CDX2 and GATA-5. Lentiviral plasmid vectors bearing short-hairpin RNA sequences unique to either HNF1␣ or HNF1 were transfected into Caco2 cells, which differentiate into small bowel epithelium upon confluence. Stable cell lines of HNF1␣ knockdowns (shHNF1␣), HNF1 knockdowns (shHNF1) and scrambled RNA negative controls (shcontrol) were created via puromycin selection. mRNA levels of HNF1␣, HNF1 and SGLT1 were determined using quantitative real-time PCR. Statistical significance was determined with ANOVA and post-hoc TUKEY analysis. Results: 1) Cooperative stimulation of SGLT1 promoter activity by HNF1␣ and GATA-5. Luciferase activity in CHO cells was significantly increased by HNF1␣, GATA-5, and to a lesser extent by HNF1 (p⬍0.05 vs. promoter alone). Co-transfection of GATA-5 with HNF1␣ had an additive effect on SGLT1 promoter activity compared to HNF1␣ alone. Co-transfection of HNF1 or CDX2 with HNF1␣ or GATA-5 antagonized the increase in luciferase activity produced by HNF1␣ or GATA-5 alone. 2) Transcriptional interdependence of
HNF1␣ and HNF1 in vitro. Knockdown of HNF1␣ in Caco2 cells reduced the expression of both HNF1␣ and HNF1 by over 50% and vice versa (p⬍0.0005 vs. controls, Fig. 1). 3) HNF1 is an essential transcription factor for enterocyte SGLT1 expression in vitro. SGLT1 expression was more than 2-fold higher in negative controls than in HNF1␣ or HNF1 knockdowns (p⬍0.001,Fig. 1). Conclusions: Using RNA interference technology we show for the first time that HNF1␣ and HNF1 are essential transcription factors for SGLT1 expression in vitro and identify interdependence in HNF1␣ and HNF1 expression. In addition we report GATA-5 and CDX2 activity on the SGLT1 promoter, suggesting novel roles for these transcription factors in the regulation of SGLT1. We therefore propose a multifactorial model for the regulation of SGLT1 expression, involving interactions between HNF1␣, HNF1, GATA-5 and CDX2 in maintaining homeostasis of intestinal glucose absorption. Greater insight into these relationships will improve our understanding of intestinal SGLT1 expression, facilitating novel therapies to modulate glucose absorption in diabetes and obesity.
207. SUS/AAS ABSTRACTS: WHAT IS THE SCIENTIFIC IMPACT? Nadine Housri, Michael Cheung, Juan C. Gutierrez, Teresa A. Zimmers, Leonidas G. Koniaris; University of Miami, Miami, FL Aim: To evaluate the scientific impact of abstracts presented at two widely recognized, national surgical conferences: the annual meetings of the Society of University Surgeons (SUS) and the Association for Academic Surgery (AAS). Methods: Publications resulting from abstracts presented at the 2002, 2003, and 2004 annual conferences of the AAS and the SUS were identified by PubMed query. The number of times each publication was cited through August 1, 2007 and the impact factor for the journal and year of publication were determined using ISI Web of Science. One way ANOVA with Bonferonni Multiple Comparison test were used for statistical analysis. Results: All 1200 abstracts from the 2002, 2003 and 2004 SUS (n ⫽ 543, 45%) and AAS (n ⫽ 657, 55%) annual meetings were reviewed. Abstracts were classified according to presentation sessions (Plenary, Parallel, and Poster) at each conference, as well as Basic Science Forum and Resident Conferences at SUS. Statistical analysis of SUS results across session types demonstrated significant differences in publication rates (p ⬍ 0.0001), but no difference in impact factors (p ⫽ 0.2556) or number of citations (p ⫽ 0.3947). AAS results demonstrated significant differences for publication rate (p ⬍ 0.0001), impact factor (p ⫽ 0.0351), and number of citations (p ⫽ 0.0383) across sessions. Comparison of abstracts between meetings demonstrated a higher overall publication rate, impact factor and citation rate for SUS publications versus AAS. Although plenary sessions in both meetings were statistically equivalent, there was a trend toward a higher publication rate, impact factor and citation rate for SUS publications. Conclusion: Overall and individually, the average impact factors of publications resulting from SUS and AAS abstracts are considerably higher than the aggregate impact factor (1.913) of the 138 surgical journals in the Journal Citation Index and are near the aggregate impact factor for all journals in research and experimental medicine (3.552).This result suggests that SUS and AAS presentations constitute high-quality, cutting