w. Total rFVIIa dose per procedure ranged from 16 to 37.5 mg, and the total number of doses per procedure was 16–31. None of our patients developed excessive bleeding including those in whom FVII:C trough levels returned nearly to the baseline level on the first post-op day. Preliminary results demonstrate that rFVIIa administered according to our treatment regimen is an effective and safe haemostatic agent for hypoproconvertinaemia patients

undergoing orthopaedic surgery. Inherited factor VII (FVII) deficiency has an estimated incidence of 1:300 000–1:500 000 in the general population and an autosomal recessive pattern of inheritance [1, 2]. In Poland, FVII deficiency is EGFR inhibitor the fourth most common inborn bleeding GS-1101 cell line diathesis with 195 cases registered in the nationwide database of inherited bleeding disorders [3]. Haemorrhagic manifestations in the affected individuals are variable and correlate poorly with plasma FVII activity levels (FVII:C) [4, 5]. In severely affected cases, however, significant bleeding problems have been observed including spontaneous haemarthroses

resulting in advanced arthropathy. In such cases orthopaedic surgery may be required. For bleeding prevention in FVII-deficient patients undergoing surgery therapeutic options comprise various FVII-containing preparations such as fresh frozen plasma (FFP), prothrombin complex concentrates (PCC), plasma derived FVII (pdFVII) concentrates and recombinant-activated FVII (rFVIIa) [6]. Since patients undergoing surgery may require prolonged administration of FVII-containing preparation, FFP is currently not recommended due to fluid overload. Moreover, FFP carries the risk of blood borne virus transmission. PCC concentrates contain factor II, MCE公司 factor IX, factor X and highly variable amounts of FVII and are considered to have significant thrombogenic potential; they are therefore not recommended for patients requiring frequent (e.g. daily) infusions of FVII. Plasma-derived FVII concentrates subjected to virus inactivation have been proved effective in the management of FVII

deficient patients undergoing a variety of surgical procedures [7, 8]. Theoretically, however, plasma-derived products, are still associated with some risk of transfusion-transmitted infections. The treatment of choice for FVII-deficient patients therefore seems to be rFVIIa, which provides the missing protein in a low-volume preparation, and is devoid of other human or animal proteins [9]. Despite the broad use of rFVIIa in FVII deficiency, the published data on dosage and treatment schedules in surgical setting are scarce [6, 10]. The aim of our article is to present the preliminary results of the novel treatment regimen for haemostatic management of FVII deficient patients undergoing orthopaedic surgery (Table 1). The study comprised five successive patients, four women and one man, aged 20–78 years, with inherited FVII deficiency (FVII:C below 10 IU dL−1) who required joint surgery.

, 2003;

Selleckchem Palbociclib Dixo et al., 2009). Yet, the effects of climate change and habitat fragmentation are not equal for all taxa. For example, ectothermic species unable to regulate their body temperature and species with low mobility will likely be most strongly affected by the processes of temperature change and habitat fragmentation (Deutsch et al., 2007; Huey et al., 2008; Dillon, Wang & Huey, 2010). A group of animals particularly affected by global change and habitat fragmentation are amphibians. This group is characterized by a low overall mobility and a temperature dependence of their physiology and performance, thus often resulting in a tight adaptation to their local environment (Ernst, Linsenmair & Rodel, 2006; Hillers, Veith & Rödel, 2008). How selection on mobility because of habitat fragmentation and global change may affect amphibians, and more precisely their mobility, remains largely unknown. However, studies on the invasion of Rhinella marina

in Australia have shown that strong selection for mobility at the invasion front resulted in changes in both behaviour and performance with subsequent profound impacts on morphology and life-history learn more traits (Phillips, Brown & Shine, 2010; Tracy et al., 2012). This suggests that selection on mobility may have large-scale cascading effects, and that mobility is an important trait. Here, we study the exploration behaviour in wild-caught male Xenopus (Silurana) tropicalis under laboratory conditions to test whether different behavioural strategies exist. This species is of interest not only because it

上海皓元医药股份有限公司 is a model system in biology, but more specifically because its natural habitat in the West African rain forest belt is becoming increasingly fragmented (Hillers et al., 2008). Here, we decided to study males more specifically because in many frog species, males are more mobile than females and will move during the breeding season to find sexual partners (Wells, 1977). We analyse the movements of individuals during the exploration of a novel environment and test for the presence of behavioural syndromes. Moreover, by correlating behavioural data to data on morphology and performance, we test whether these behavioural syndromes are driven by variation in underlying physiological performance (Careau & Garland, 2012). If behaviour is decoupled from performance, then this may, for example, allow animals to circumvent constraints on the evolution of locomotor capacity (i.e. because of the presence of physiological trade-offs between burst performance and endurance capacity; Wilson, James & Van Damme, 2002; Herrel & Bonneaud, 2012a). We focus on mobility in Xenopus (Silurana) tropicalis. Individuals of three sub-populations of X. tropicalis were caught in Western Cameroon in 2009. Animals were transported to France and housed at the Muséum National d’Histoire Naturelle (MNHN) in Paris.

, 2005; Christiansen & Adolfssen, 2007). Here we found that the cranial morphology

of M. dimidiata shows the same traits: adaptation for a wide gape that probably reduces bite force, and occipital morphology suggesting powerful neck muscles. Christiansen (2011) suggests that there could be several histochemical and anatomical this website adaptations to increase the force of mandibular adductor muscles to compensate for reduced lever arms. However, there are no experimental comparative studies of the bite mechanics of M. dimidiata, and the anatomy and physiology of this didelphid are poorly known. Further experimental studies of the bite force of M. dimidiata in comparison with that of other marsupials, and studies of neck and mandible adductor muscles could provide relevant information to improve our understanding of the bite mechanics of fossil sabretoothed predators. The evolutionary sequence and selective forces resulting in the extreme sabretooth condition remain unclear. The hypertrophied canines of M. dimidiata seem to be strongly selected for agonistic behaviour between males, owing to the strong selective pressure derived from the semelparous condition. The robust forearms (as the inter-epicondylar index indicates, see Table 3) may also be related to intraspecific fighting that involves energetic forearm movements (González & Claramunt,

2000). However, the canines are fully functional for killing large prey as several studies have shown VX-809 (Busch & Kravetz, 1991; González & Claramunt, 2000), and the canines are relatively the largest among living marsupial predators (see Table 4). When competing for mates and during aggressive encounters, canine display is very important in M. dimidiata and several other carnivorous marsupials (González & Claramunt,

2000; Croft, 2003). Therefore, hypertrophied canines can improve the reproductive success of M. dimidiata males, providing the selective pressures towards a primitive sabretooth 上海皓元医药股份有限公司 condition. Gittleman & Van Valkenburgh (1997) claimed that dimorphic canines are associated with sexual selection pressures. A low level of sexual dimorphism was identified in Smilodon fatalis (Van Valkenburgh & Sacco, 2002; Christiansen & Harris, 2012), but Antón et al. (2004) identified sexual dimorphism in the size of the upper canines of Machairodus aphanistus. Similar studies on more basal sabretooth groups have not been conducted, but a recent study debated the question of sexual dimorphism in sabretooth cats, and claimed that sexual dimorphism could have been important in extinct Felidae (Turner et al., 2011). Perhaps, hypertrophied canines were exaptations for functions other than those related to the ability to kill large prey (see, e.g. Turner & Antón, 1997; Turner et al., 2011 and references therein). Pine et al. (1985) consider that intersexual differences in craniodental dimensions in M.

4-fold by ethanol feeding, compared with pair-fed control mice (Fig. 6C). Note that ChIP

Rucaparib nmr assays demonstrated that the association of acetylated histone H3/Lys9 or glucocorticoid receptor (GR) with the Lpin 1-GRE site was not significantly affected by ethanol administration to mice, compared with controls (data not shown). Ethanol feeding to mice significantly reduced sumoylation levels of hepatic lipin-1, while at the same time markedly increasing its level of acetylation (Fig. 6D; Supporting Fig. 4). More important, ethanol feeding robustly increased the amount of lipin-1 in the cytoplasm and dramatically decreased it in the nucleus in the mouse livers (Fig. 7A,B). Accordingly, hepatic PAP activity was significantly increased in ethanol-fed mice, compared with the pair-fed controls (Fig. 7D). Taken together, our results clearly indicate that ethanol feeding increased hepatic lipin-1 gene expression and stimulated the cytoplasmic localization of lipin-1

in mouse livers. In the present study, we investigated the effects of ethanol on lipin-1 in cultured hepatic cells and in animal tissues and explored the underlying mechanisms. In cultured AML-12 hepatocytes, chronic ethanol exposure robustly enhanced the activity of a mouse Lpin1 promoter and buy BTK inhibitor increased cytosolic lipin-1 protein levels as well as PAP activity. The ethanol-dependent up-regulation of lipin-1 was associated with elevated cellular TG accumulation in AML-12 cells. We also showed that acetate alone, a product of ethanol metabolism, produces many of these effects

in AML-12 cells. Interestingly, ethanol-induced activation of the Lpin1 promoter and enhancement of lipin-1 mRNA levels were each inhibited by a known activator of AMPK (AICAR), as well as by overexpression of a constitutively active form of AMPK. Importantly, overexpression of nSREBP-1c largely abolished the ability of AICAR to suppress ethanol-mediated up-regulation of lipin-1, suggesting 上海皓元医药股份有限公司 that AMPK lies upstream of the SREBP-1/lipin-1 axis. Consistent with in vitro findings, feeding mice an ethanol-containing liquid diet resulted in a robust increase in lipin-1 mRNA and cytosolic protein levels. Moreover, ChIP assays revealed that ethanol exposure significantly increased the association of acetylated histone H3/Lys9 with the SRE-containing region in the promoter of the lipin-1 gene, both in vitro and in vivo. We also demonstrated, for the first time, that acetylation and sumoylation of lipin-1 displayed reciprocal patterns in livers of chronically ethanol-fed mice. Taken together, our findings suggest that chronic ethanol exposure up-regulates hepatic lipin-1 and that this effect may contribute to the development of AFLD. Importantly, we have shown that this effect is mediated, at least in part, by modulating AMPK-SREBP-1 signaling (Fig. 8). Our current data clearly suggest that ethanol metabolism through both ADH and ALDH2 are required for the effect of ethanol on lipin-1 in AML-12 cells.

4-fold by ethanol feeding, compared with pair-fed control mice (Fig. 6C). Note that ChIP

buy Cabozantinib assays demonstrated that the association of acetylated histone H3/Lys9 or glucocorticoid receptor (GR) with the Lpin 1-GRE site was not significantly affected by ethanol administration to mice, compared with controls (data not shown). Ethanol feeding to mice significantly reduced sumoylation levels of hepatic lipin-1, while at the same time markedly increasing its level of acetylation (Fig. 6D; Supporting Fig. 4). More important, ethanol feeding robustly increased the amount of lipin-1 in the cytoplasm and dramatically decreased it in the nucleus in the mouse livers (Fig. 7A,B). Accordingly, hepatic PAP activity was significantly increased in ethanol-fed mice, compared with the pair-fed controls (Fig. 7D). Taken together, our results clearly indicate that ethanol feeding increased hepatic lipin-1 gene expression and stimulated the cytoplasmic localization of lipin-1

in mouse livers. In the present study, we investigated the effects of ethanol on lipin-1 in cultured hepatic cells and in animal tissues and explored the underlying mechanisms. In cultured AML-12 hepatocytes, chronic ethanol exposure robustly enhanced the activity of a mouse Lpin1 promoter and AZD6738 cost increased cytosolic lipin-1 protein levels as well as PAP activity. The ethanol-dependent up-regulation of lipin-1 was associated with elevated cellular TG accumulation in AML-12 cells. We also showed that acetate alone, a product of ethanol metabolism, produces many of these effects

in AML-12 cells. Interestingly, ethanol-induced activation of the Lpin1 promoter and enhancement of lipin-1 mRNA levels were each inhibited by a known activator of AMPK (AICAR), as well as by overexpression of a constitutively active form of AMPK. Importantly, overexpression of nSREBP-1c largely abolished the ability of AICAR to suppress ethanol-mediated up-regulation of lipin-1, suggesting MCE公司 that AMPK lies upstream of the SREBP-1/lipin-1 axis. Consistent with in vitro findings, feeding mice an ethanol-containing liquid diet resulted in a robust increase in lipin-1 mRNA and cytosolic protein levels. Moreover, ChIP assays revealed that ethanol exposure significantly increased the association of acetylated histone H3/Lys9 with the SRE-containing region in the promoter of the lipin-1 gene, both in vitro and in vivo. We also demonstrated, for the first time, that acetylation and sumoylation of lipin-1 displayed reciprocal patterns in livers of chronically ethanol-fed mice. Taken together, our findings suggest that chronic ethanol exposure up-regulates hepatic lipin-1 and that this effect may contribute to the development of AFLD. Importantly, we have shown that this effect is mediated, at least in part, by modulating AMPK-SREBP-1 signaling (Fig. 8). Our current data clearly suggest that ethanol metabolism through both ADH and ALDH2 are required for the effect of ethanol on lipin-1 in AML-12 cells.

Results: The proliferation rate was significantly higher in the livers at one week of age compared to controls (22% vs 17%, respectively; P=0.01). Studies on these livers using Sox9 and Ki67 have excluded the Sox9 progenitor

compartment as the source of proliferation. Rather proliferation rates for both Sox9 progenitors and hepato-cytes were lower in the mutants compared to controls (10% vs 19% and 33% vs 46%, respectively). However, we identified a significant increase in single PS-341 research buy Sox9+ progenitor numbers in the one-week old Jag1+/−Rfng+/− livers when comparing them to age-matched controls (Ave =145 vs 37; P=0.0001). Co-localization studies have identified a significant increase in Hnf4α+/Sox9+ as well (Ave =65 vs 26; P=0.05), but a significant reduction in the number of CK+/Sox9+ population (Avg =178 vs 359; P=0.0004). Conclusions:

We identified a proliferation rate increase in the one-week old Jag1+/−Rfng+/−mutants and determined that neither the Sox9 progenitor compartment nor the hepatocytes were proliferating. However, due to their significant increases in overall numbers, we concluded that these compartments are aberrantly differentiating toward both cholangiocytes and hepatocytes. The reduced number of CK+/Sox9+ cells at the same time point also supports a delay in maturation of biliary cells as CK19 is a marker of the mature cholangiocyte. This work further substantiates recent findings whereby Sox9 progenitors differentiate along both AZD8055 supplier the cholangiocyte and hepatocyte lineages. Disclosures: The following people have nothing to disclose: MCE Lara A. Underkoffler, Emily K. McComb, John Dutton, Anthony Nelson, Kathleen M. Loomes, Matthew J. Ryan

Objective: Pediatric Acute Liver Failure (PALF) is a rapidly evolving clinical condition. Tools to reliably predict spontaneous survival (S) and non-survival (NS), to assess biomarkers of disease severity and trajectory, and to inform liver transplantation (LTx) decisions are not available. We hypothesized that key inflammatory interactions as well as subgroup-specific dynamic patterns using data-driven computational modeling of protein-level expression of inflammatory mediators in serum may serve as tools for predicting outcomes. Methods: During the 7 days following enrollment in the PALF study, serum samples from 140 children were collected and assayed for 27 inflammatory mediators. Outcomes (S [n=80], NS [n=18], and LTx [n=42]) were assessed within 21 days. Data were analyzed using Two-Way ANOVA, time-interval Principal Component Analysis (PCA), and Dynamic Network Analysis (DyNA). Results: Two-Way ANOVA revealed multiple inflammatory mediators that changed significantly and separated patient groups: MCP-1 and most interleukins differentiated S and LTx from NS; Eotaxin, MIG and IL-17 segregated LTx from S and NS; and sIL-2Rβ and IP-10 differentiated S from LTx.

Results: The proliferation rate was significantly higher in the livers at one week of age compared to controls (22% vs 17%, respectively; P=0.01). Studies on these livers using Sox9 and Ki67 have excluded the Sox9 progenitor

compartment as the source of proliferation. Rather proliferation rates for both Sox9 progenitors and hepato-cytes were lower in the mutants compared to controls (10% vs 19% and 33% vs 46%, respectively). However, we identified a significant increase in single Z-VAD-FMK datasheet Sox9+ progenitor numbers in the one-week old Jag1+/−Rfng+/− livers when comparing them to age-matched controls (Ave =145 vs 37; P=0.0001). Co-localization studies have identified a significant increase in Hnf4α+/Sox9+ as well (Ave =65 vs 26; P=0.05), but a significant reduction in the number of CK+/Sox9+ population (Avg =178 vs 359; P=0.0004). Conclusions:

We identified a proliferation rate increase in the one-week old Jag1+/−Rfng+/−mutants and determined that neither the Sox9 progenitor compartment nor the hepatocytes were proliferating. However, due to their significant increases in overall numbers, we concluded that these compartments are aberrantly differentiating toward both cholangiocytes and hepatocytes. The reduced number of CK+/Sox9+ cells at the same time point also supports a delay in maturation of biliary cells as CK19 is a marker of the mature cholangiocyte. This work further substantiates recent findings whereby Sox9 progenitors differentiate along both see more the cholangiocyte and hepatocyte lineages. Disclosures: The following people have nothing to disclose: 上海皓元 Lara A. Underkoffler, Emily K. McComb, John Dutton, Anthony Nelson, Kathleen M. Loomes, Matthew J. Ryan

Objective: Pediatric Acute Liver Failure (PALF) is a rapidly evolving clinical condition. Tools to reliably predict spontaneous survival (S) and non-survival (NS), to assess biomarkers of disease severity and trajectory, and to inform liver transplantation (LTx) decisions are not available. We hypothesized that key inflammatory interactions as well as subgroup-specific dynamic patterns using data-driven computational modeling of protein-level expression of inflammatory mediators in serum may serve as tools for predicting outcomes. Methods: During the 7 days following enrollment in the PALF study, serum samples from 140 children were collected and assayed for 27 inflammatory mediators. Outcomes (S [n=80], NS [n=18], and LTx [n=42]) were assessed within 21 days. Data were analyzed using Two-Way ANOVA, time-interval Principal Component Analysis (PCA), and Dynamic Network Analysis (DyNA). Results: Two-Way ANOVA revealed multiple inflammatory mediators that changed significantly and separated patient groups: MCP-1 and most interleukins differentiated S and LTx from NS; Eotaxin, MIG and IL-17 segregated LTx from S and NS; and sIL-2Rβ and IP-10 differentiated S from LTx.

14,100,101 In an extensive and influential review (see Table 2), it was suggested that neural activation releases vasoactive neurotransmitters from their afferent processes, which in turn provokes inflammatory changes in peripheral target tissues (in this instance, cerebral blood vessels).14 In addition, the data suggested that the release of substance

P (a vasodilator) from sensory fibers is important in mediating changes in vessel permeability. The finding in animals explains the unilateral distribution of migraine pain and could challenge the concept that the pain of vascular headache is due to dilating blood vessels. Finally, it Roscovitine chemical structure was suggested that there is a sterile inflammation of cranial blood vessels during migraine AUY-922 mouse attacks. Moskowitz concluded that “the relationship of trigeminovascular fibers to the pathogenesis of vascular head pain sheds light on possible mechanisms of migraine and other central nervous system conditions associated with headache and inflammation.”14 Studies along this line were carried out in the subsequent year and in 1987 a model of intracranial neurogenic inflammation was presented for use in rat.102 Electrical stimulation of the trigeminal ganglion resulted in ipsilateral

increase of tracers in the dura. In contrast, there was no extravasation in the brain.102 The neurogenic inflammation model was then used to demonstrate that ergot alkaloids, ergotamine, and dihydroergotamine, inhibited plasma extravasation and it was suggested “that the therapeutic effects of ergots in vascular headaches may result from peripheral blockade of small fiber (C or A-delta)-dependent neurogenic inflammation within the dura.103 Similar results

were obtained for indomethacin and aspirin104 and sumatriptan.105 It was suggested that the effect was mediated by 5-HT1B/1D receptors located on sensory trigeminal neurons.106,107 Up to now all effective, acute antimigraine drugs have indeed been proven to inhibit neurogenic protein extravasation (NPE).105,107,108 medchemexpress However, inhibition of NPE was not predictive for the antimigraine effect of all investigated new drug-groups. Thus, in 5 placebo-controlled clinical studies, drugs (eg, endothelin and NK-1 receptor antagonists) with potent inhibitory effect on dural NPE were not effective for acute migraine treatment.109-113 Because specific NPE inhibitors are without an effect in migraine, it has been difficult to find a pivotal role for dural neurogenic inflammation in migraine. It was shown, however, that valproate, which is effective in migraine prophylaxis, blocked plasma extravasion in the meninges.

Methods: The project was mainly based on genotype-phenotype association study in healthy controls. Its four sections were expanded step by step following its findings. Section 1 was to investigate genotype-phenotype association between genotype at rs7746082 and PRDM1 & ATG5 transcription in

terminal ileum via qPCR. Section 2 explored which cell type the identified susceptibility gene is expressed in intestinal biopsies via immunohistochemical (IHC) double staining. Section 3 investigated the found genotype-phenotype association in purified peripheral blood cells via qPCR. Section 4 explored whether genotype at rs7746082 is associated with peripheral T lymphocyte phenotype via flow cytometry (FCM). Results: Genetic variation Epigenetics Compound Library cell line at rs7746082 was related to expression of PRDM1 (p < 0.0001) Erastin manufacturer not ATG5 (p > 0.05) in terminal biopsies between CC and GG genotype. Double IHC further found that PRDM1 was expressed in neither enterocytes nor B lymphocytes, but in both T lymphocytes and plasma cells in lamina propria. Given potential confounding by the mixed cell population present in intestinal biopsies, the correlation of PRDM1 with genotype at rs7746082 was further investigated

in purified peripheral blood cells. Genetic variation at rs7746082 significantly correlated with PRDM1 expression in freshly isolated PBMCs and CD4+CD45RO+ T cells (p = 0.0012 and p = 0.0125, respectively), but not in CD4+CD45RO- T cells (p > 0.05). After 5 days of T cell stimulation, PRDM1

expression substantially increased in all cell samples, but the correlation significantly diminished. PRDM1 expression was modestly associated with this SNP in PBMCs (p = 0.048), but not in CD4+CD45RO+ and CD4+CD45RO- T cells (p > 0.005 for both). It is reported that BLIMP1 (encoded by PRDM1) regulated peripheral T cell phenotypes. Our FCM study in section 4, however, found that T cell phenotypes did not exhibit a significant difference between CC and GG groups in either CD4+ or CD8+ T cells regardless of T cell stimulation. Conclusion: This study confirmed that PRDM1 is the causal gene in a CD susceptibility locus identified via GWAS on 6q21. Peripheral T cell phenotypes did not correlate with genotype at rs7746082, although MCE BLIMP1 regulates peripheral T cell phenotypes. More studies are needed to explore how this SNP contributes to IBD susceptibility. Key Word(s): 1. PRDM1; 2. Crohn’s disease; 3. genotype; 4. phenotype; Presenting Author: XIANG GAO Additional Authors: JIAN TANG, MIN ZHI, MIN ZHANG, HUANGWEI CHEN, CHENGCHENG JI, PINJIN HU Corresponding Author: XIANG GAO Affiliations: The Sixth Affiliated Hospital of Sun Yat-sen University Objective: Platelet-index is a sub-set of parameters of standard full blood count test, measuring the variability size of thrombocytes. We investigated whether platelet-index are biomarkers of active disease in patients with Crohn’s disease (CD).

Methods: The project was mainly based on genotype-phenotype association study in healthy controls. Its four sections were expanded step by step following its findings. Section 1 was to investigate genotype-phenotype association between genotype at rs7746082 and PRDM1 & ATG5 transcription in

terminal ileum via qPCR. Section 2 explored which cell type the identified susceptibility gene is expressed in intestinal biopsies via immunohistochemical (IHC) double staining. Section 3 investigated the found genotype-phenotype association in purified peripheral blood cells via qPCR. Section 4 explored whether genotype at rs7746082 is associated with peripheral T lymphocyte phenotype via flow cytometry (FCM). Results: Genetic variation Palbociclib ic50 at rs7746082 was related to expression of PRDM1 (p < 0.0001) http://www.selleckchem.com/products/Romidepsin-FK228.html not ATG5 (p > 0.05) in terminal biopsies between CC and GG genotype. Double IHC further found that PRDM1 was expressed in neither enterocytes nor B lymphocytes, but in both T lymphocytes and plasma cells in lamina propria. Given potential confounding by the mixed cell population present in intestinal biopsies, the correlation of PRDM1 with genotype at rs7746082 was further investigated

in purified peripheral blood cells. Genetic variation at rs7746082 significantly correlated with PRDM1 expression in freshly isolated PBMCs and CD4+CD45RO+ T cells (p = 0.0012 and p = 0.0125, respectively), but not in CD4+CD45RO- T cells (p > 0.05). After 5 days of T cell stimulation, PRDM1

expression substantially increased in all cell samples, but the correlation significantly diminished. PRDM1 expression was modestly associated with this SNP in PBMCs (p = 0.048), but not in CD4+CD45RO+ and CD4+CD45RO- T cells (p > 0.005 for both). It is reported that BLIMP1 (encoded by PRDM1) regulated peripheral T cell phenotypes. Our FCM study in section 4, however, found that T cell phenotypes did not exhibit a significant difference between CC and GG groups in either CD4+ or CD8+ T cells regardless of T cell stimulation. Conclusion: This study confirmed that PRDM1 is the causal gene in a CD susceptibility locus identified via GWAS on 6q21. Peripheral T cell phenotypes did not correlate with genotype at rs7746082, although MCE BLIMP1 regulates peripheral T cell phenotypes. More studies are needed to explore how this SNP contributes to IBD susceptibility. Key Word(s): 1. PRDM1; 2. Crohn’s disease; 3. genotype; 4. phenotype; Presenting Author: XIANG GAO Additional Authors: JIAN TANG, MIN ZHI, MIN ZHANG, HUANGWEI CHEN, CHENGCHENG JI, PINJIN HU Corresponding Author: XIANG GAO Affiliations: The Sixth Affiliated Hospital of Sun Yat-sen University Objective: Platelet-index is a sub-set of parameters of standard full blood count test, measuring the variability size of thrombocytes. We investigated whether platelet-index are biomarkers of active disease in patients with Crohn’s disease (CD).