“
“Cholangiopathies share common features

including bile duct proliferation, periportal Syk inhibitor fibrosis, and intrahepatic cholestasis. Damages of biliary epithelium by autoimunne disorder, virus infection, toxic compounds, and developmental abnormalities cause severe progressive hepatic disorders responsible for high mortality. However, the etiologies of these cholestatic diseases still remain unclear since useful models to study the pathogenic mechanisms are not available. In the present study, we have found that ezrin knockdown (Vil2kd/kd) mice develop severe intrahepatic cholestasis characterized by extensive bile duct proliferation, periductular fibrosis, and intrahepatic bile acid accumulation without developmental defects of bile duct morphology and infiltration of inflammatory cells. Ezrin is a membrane

cytoskeletal crosslinker protein, which is known to interact with transporters, scaffold proteins, and actin cytoskeleton at the plasma membrane. We found that the normal apical membrane localizations of several transport proteins including CFTR, AE-2, AQP1, and NHERF1 were disturbed in the bile ducts of Vil2kd/kd mice. Stable expression of a dominant negative form of ezrin in immortalized mouse cholangiocytes also led to the reduction of the surface expression this website of CFTR, AE-2, and AQP1. Reduced surface expression of these transport proteins was accompanied by reduced functional expression, as evidenced 上海皓元医药股份有限公司 by the fact these cells exhibited decreased CFTR-mediated Cl- efflux activity. Furthermore, bile flow and biliary HCO3- concentration were also significantly reduced in Vil2kd/kd mice. Conclusion: These data suggest that dysfunction of ezrin mimics important aspects of the pathological mechanisms responsible for cholangiopathies, and further that the Vil2kd/kd mouse may be a useful model to exploit in the development and testing of potential therapies for cholangiopathies. (Hepatology 2014;) “
“Within the last 20

years, the transjugular intrahepatic portal stent (TIPS) has gained its place in the therapeutic armamentarium for the complications of portal hypertension. Randomized controlled trials have shown that TIPS is more effective than other available treatments to reduce recurrence of refractory ascites, to control acute variceal hemorrhage, and to prevent variceal rebleeding. However, in all these clinical settings, TIPS increases the risk of hepatic encephalopathy and does not improve survival. Initially, the main drawback of the technique was shunt dysfunction, which was observed in up to 80% of patients within 2 years. This rate was tremendously reduced when PTFE-covered stents were used instead of bare ones.

Disease outbreaks may be important factors affecting populations of other carnivore species; however, we note that not all authors indicate a breakdown for

disease that would allow comparison – for example, disease and starvation/emaciation are often not distinguished. As a consequence of increased food and water availability in urban habitats, coupled with protection from predators, growth rate, body condition, survival and population densities of carnivores are predicted to be favoured. The presence of abundant, high-energy, non-seasonal food sources in urban areas may have a significant effect on the growth of carnivore species. Yom-Tov (2003) examined JQ1 mw museum specimens collected from Israel over 60 years (from 1945 to 2005), a

time span when human population in the country increased approximately eightfold, resulting in a significant increase in anthropogenic food sources (Yom-Tov, 2003). He recorded that, over this time, species that do not use anthropogenic food (the caracal Caracal caracal and jungle cat Felis chaus) did not significantly change in mass or size; however, wolves, golden jackals Canis aureus and striped hyaenas, which all feed from garbage dumps and make use of livestock carcasses, increased in body mass. The larger species appeared to be more capable Maraviroc concentration of exploiting the extra food provided by humans (Yom-Tov, 2003). A similar pattern of size increase in skull measurements was also recorded for badger and red fox populations in Denmark from 1862 to 2000, which again could be related to altered human agriculture and therefore food sources (Yom-Tov, Yom-Tov & Baagøe, 2003). Starvation due to substantial weight loss over winter is a significant cause MCE of death in skunks,

but urban skunks fare better over winter than their rural counterparts (Rosatte et al., 2010). Similarly, urban raccoons exhibit better physical condition than rural ones, possibly due to anthropogenic food (Rosatte, Power & Macinnes, 1991). Black bears in urbanized Nevada average 30% heavier than bears in rural areas due to a diet heavily supplemented by garbage (Beckmann & Lackey, 2008). Urban kit foxes demonstrate greater body mass compared with non-urban individuals (especially for juveniles) and also demonstrate different haematological characteristics (Cypher, 2010). Urban Eurasian badgers can be heavier than nearby rural badgers, presumably due to the availability of anthropogenic food (Roper 2010 and references therein). More research in this area is needed. Increased survivorship has been recorded for a number of urban carnivore species ( Table 1). Opossums are recognized as bin-raiders par excellence (Clark, 1994), and their reliance on anthropogenic sources of food is such that, in areas where one would expect their range to have been limited by the winter cold and lack of natural food, they are, in fact, well-established (Kanda, 2005).

TE Pruritus was recorded using AE data and a visual analogue scale (VAS). Protocol-allowed pruritus interventions included drug interruption, dose interval signaling pathway change and medications. Pruritus, mostly mild to moderate, was the most common dose-related AE (PBO, 38%, TITR, 56%, 10mg, 68%). Only 1 (1%) of patients in the TITR group discontinued due to pruritus (after starting 10mg), vs 10% in

the 10 mg group. Incidence and severity of TE pruritus improved during 2nd half of the trial (Table). Overall, <6% withdrew due to pruritus. Although on-Study VAS scores initially were higher in OCA patients vs PBO (p= 0.0005 at w2 and 0.0314 at 6 mo in 10 mg OCA), the difference was not statistically significant in the TITR arm and negligible for both arms at 12 mo vs PBO. Starting treatment at 5mg and increasing to 10mg, if appropriate, ameliorates OCA related pruritus while maintaining efficacy. >6-12 mo: PBO N=70, TITR N=69, 10 mg N= 64 Disclosures:

Ulrich Beuers – Consulting: Intercept, Novartis; Grant/Research Support: Zambon; Speaking and Teaching: Falk Foundation, www.selleckchem.com/products/ulixertinib-bvd-523-vrt752271.html Gilead, Roche, Scheringh, Zambon David E. Jones – Consulting: Intercept Marlyn J. Mayo – Grant/Research Support: Intercept, Salix, NGM, Lumena, Gilead Pietro Andreone – Advisory Committees or Review Panels: Roche, Janssen-Cilag, Gilead, MSD/Schering-Plough, Abbvie, Boehringer Ingelheim; Grant/Research Support: Roche, Gilead; Speaking and Teaching: Roche, MSD/Schering-Plough, Gilead Simon Hohenester – Speaking and Teaching: Dr. Falk Pharma Simone I. Strasser – Advisory Committees or Review Panels: Janssen, AbbVie, Roche Products Australia, MSD, Bristol-Myers Squibb, Gilead, Norgine, Bayer Healthcare; Speaking and Teaching: Bayer Healthcare, Bristol-Myers Squibb, MSD, Roche Products Australia, Gilead, Janssen Christopher L. Bowlus – Advisory Committees or Review Panels: Gilead Sciences, Inc; Consulting: Takeda; Grant/Research Support: Gilead Sciences, Inc, Intercept Pharmaceuticals,

Bristol Meyers Squibb, Lumena; Speaking and Teaching: Gilead Sciences, Inc Paul J. medchemexpress Pockros – Advisory Committees or Review Panels: Janssen, Merck, Genentech, BMS, Gilead, Boehinger Ingelheim, AbbVioe; Consulting: Genentech, Lumena, Regulus, Beckman Coulter, RMS; Grant/Research Support: Novartis, Intercept, Janssen, Genentech, BMS, Gilead, Vertex, Boehinger Ingelheim, Lumena, Beckman Coulter, AbbVie, RMS, Novartis, Merck; Speaking and Teaching: Genentech, BMS, Gilead Karel J. van Erpecum – Advisory Committees or Review Panels: Bristol Meyers Squibb, Abbvie Roya Hooshmand-Rad – Employment: Intercept pharmaceuticals Inc. Shawn Sheeron – Employment: Intercept Pharmaceuticals David Shapiro – Employment: Inttercept Pharmaceuticals The following people have nothing to disclose: Giuseppe Mazzella, Annarosa Floreani, Pietro Invernizzi, Joost Drenth, Jaroslaw Regula, Velimir A.

The pharmacokinetics of sumatriptan and naproxen did not differ according to whether sumatriptan/naproxen sodium was administered during a migraine attack or a migraine-free period. The pharmacokinetics of 2 sumatriptan/naproxen sodium tablets administered 2 hours apart were consistent with the pharmacokinetic predictions from a single dose of the combination tablet.

The adverse-event profile of the sumatriptan/naproxen sodium combination tablet did not appear to differ from that of the individual components of the same or similar SB203580 concentration dosage strengths administered alone or in combination. In addition, the incidence of adverse events with 2 sumatriptan/naproxen sodium tablets administered 2 hours apart was lower than that with the single dose. Conclusion.— The combination tablet of sumatriptan/naproxen sodium has unique pharmacokinetic properties. The rapid absorption of sumatriptan with the delayed-release properties of naproxen sodium from sumatriptan/naproxen sodium might contribute to its therapeutic advantage over monotherapy with either component. No clinically meaningful effects of food, administration during a migraine attack, or administration of a second tablet (2 hours after initial dose) on the pharmacokinetics or safety

of sumatriptan/naproxen sodium were observed. “
“The trigeminal autonomic cephalalgias (TACs) are a group of primary headache disorders that feature short duration, repetitive attacks of severe unilateral head pain accompanied by prominent ipsilateral cranial autoniomic features. The TACs likely have a strong genetic determination, most evidently demonstrated by selleck kinase inhibitor several cluster headache studies. Key insights into their pathophysiology are derived from the cranial distribution of the pain, prominence of cranial autonomic features, attack patterns,

and distinctive therapeutic responses. These aspects are explored with regard to studies of the trigeminovascular system, 上海皓元 the trigeminal-autonomic reflex, the neuroendocrine system, functional neuroimaging, and various treatments used in clinical practice. “
“A small case series is presented of preadolescent patients with indomethacin-responsive headache. Preadolescent indomethacin-responsive headache is a rare and poorly understood entity, with few published cases in the literature. Two young children had similar presentations of indomethacin-responsive headaches. Both patients experienced frequent paroxysmal episodes of sudden-onset severe frontal or temporal head pain. The events lasted seconds to minutes in duration, and varied in frequency ranging from multiple episodes per week to multiple events per day. There were no associated autonomic or migrainous symptoms, and a comprehensive work-up revealed no secondary causes for the debilitating headaches. Both patients had dramatic clinical improvement with indomethacin.

Multiple logistic regression models were used to assess the relationship of both fibrosis and SVR to the demographic, metabolic, and histological characteristics of patients. In the first model, the dependent variable was severe fibrosis coded as 1 = F3 to F4 in the fibrosis score versus 0 = F1 to F2. Because fibrosis grade is nonlinear, we also performed ordinal logistic regression with fibrosis F0 to F4

as the dependent variable. In the second model, the dependent variable was SVR coded 1 = present versus 0 = absent. As candidate risk factors we selected the same independent variables included in the 25(OH)D model and added 25(OH)D serum levels as an additional independent variable. In this model, we included all patients PF-02341066 cost who received at least one dose of pegylated interferon (intention-to-treat analysis). Variables associated with the dependent variable at univariate EPZ015666 clinical trial analyses (probability threshold, P ≤ 0.10) were included in the multivariate regression models.25 Regression analyses were performed by SAS. The baseline features of the 197 patients are shown in Table 1. Most of our patients were in the overweight to obesity range. One patient in four had fibrosis of at least 3 by Scheuer

score, with a high prevalence of moderate/severe necroinflammation (grading 2-3). Half of the cases had histological evidence of steatosis, though of moderate/severe grade in only 23 cases (11.7%). The control subjects (25 women and 24 men, mean age of 53.7 ± 12.8 years) were comparable for body mass index with the HCV population (26.1 ± 3.5 kg/m2). Six had arterial hypertension. Mean serum values of 25(OH)D in G1 CHC patients were significantly lower than 上海皓元 in controls (25.1 ± 9.9 μg/L versus 43.1 ± 10.2 μg/L; P < 0.0001; Fig. 1). Accordingly, 25(OH)D serum levels of less than 30 μg/L were found in 144 (73%) G1 CHC patients and in only three control subjects (6%, P < 0.001). Advanced age (P =

0.004), female sex (P < 0.001), high waist circumference (P < 0.06), high ALT (P = 0.09), and low high-density lipoprotein levels (P = 0.01), the severity of necroinflammatory activity (P = 0.01), and the severity of fibrosis (P < 0.001) were associated with lower 25(OH)D levels in G1 CHC, though only female sex (P = 0.007), the severity of necroinflammatory activity (P = 0.04), and the severity of fibrosis (P = 0.009) were independent factors in multiple linear regression analysis (Table 2). Figure 1 also shows the distribution of serum 25(OH)D levels in relation to sex. A significant difference was observed in CHC patients (27.60 ± 9.39 μg/L in men versus 22.23 ± 9.77 μg/L in women; P = 0.0001) (Fig. 1). Figure 2 shows the distribution of 25(OH)D according to necroinflammatory activity.

1002/hep.25617. “
“Liver fibrosis resulting from chronic liver injury is the Ruxolitinib harbinger of cirrhosis, with its inherent potential complications and associated morbidity and increased mortality. Hepatic fibrogenesis is a dynamic process incorporating hepatocellular injury associated with chronic inflammation and continuous extracellular matrix (ECM) protein remodeling choreographed by hepatic stellate cells.1 Knowledge of the stage of fibrosis in chronic liver disease guides clinical decisions about the timing and approach

to interventions. Although this has traditionally relied on liver biopsy, a suite of non-invasive models for liver fibrosis relying on individual or various combinations of putative biomarkers has been developed. These have been principally assessed in chronic hepatitis C virus infection

(CHC), which is a dominant cause of cirrhosis and hepatocellular carcinoma (HCC) in the ‘developed world’. CHC and chronic hepatitis B virus (HBV) infection (CHB) have different natural histories and often affect different populations, so data from CHC cannot be directly extrapolated to represent CHB. Unfortunately, most blood-based models for liver fibrosis exhibit a significant level of incompetence at lower stages of liver fibrosis.2 Further, few have been validated for use in CHB, which remains a global public health problem with over 350 million people chronically infected worldwide.3 The burden of CHB is Selumetinib research buy most significant in the Asia-Pacific region and Sub-Saharan Africa and in migrants from these regions. Historically, liver biopsy has been considered the gold standard reference diagnostic and prognostic test for assessing liver disease. Following

initial reports of liver 上海皓元 biopsy dating as far back as 1883,4 liver biopsy techniques and indications have been further refined; however, the risk of significant bleeding or death related to liver biopsy5 remains relatively unchanged over more than 50 years. As increasing pharmaco-therapeutic options for chronic liver disorders, particularly CHB and CHC, have become available, the role of liver biopsy in guiding treatment decisions has been highlighted. However, liver biopsy for histology is an imperfect gold standard for assessing liver fibrosis alone, as demonstrated by an increasing body of evidence.6–8 It has been plagued with concerns about the invasive nature of the procedure, hence complication risk and limited patient acceptance, sampling error, inter- and intra-observer variability and cost. Complications of liver biopsy include pain (up to 84%), bleeding (in up to 0.04%) and death (up to 0.01%).5 Also, histologic staging of liver fibrosis presents thedynamic process of extracellular matrix deposition and remodeling as a categorical, non-linear result. Together with the invasive nature of liver biopsy, it is clear that serial assessment of liver histology is not practical at a population level.

The following review focuses on the current view of risk factors for the development of inhibitory antibodies and whether this risk can be modulated and minimized. Treatment of haemophilia using replacement of the deficient factor has substantially improved over recent decades and life expectancy for a young boy suffering from severe haemophilia A is today, in most developed countries, similar to that of his healthy peers [1, 2]. However, severe adverse effects of replacement therapy, such as the development of neutralizing inhibitory antibodies, remain

a threat and should be considered in the management of patients. Most inhibitory antibodies will be eliminated by the use of immune tolerance Ponatinib cost induction (ITI) with or without immunosuppression, but ITI is costly and the outcome this website unpredictable [3]. Therefore, it is important to fully elucidate the factors that influence inhibitor development in one-third of patients with severe haemophilia A. This overview will summarize the current view of these risk factors in light of the immune response taking place, and will address the issue of whether it will be possible to minimize risk in the future. The mechanisms by

which inhibitory antibodies develop have been carefully studied for several years and major advances in our understanding have been made [4, 5]. However, much still remains to be resolved, and it is clear that there are several

processes that potentially influence the outcome. These include the methods by which antigen-presenting cells (APC) process and present the endocytosed factor VIII molecule to the T-helper cells, the nature of the T and B cells and the profile of the immune-regulatory molecules, including both cell-bound molecules and those secreted into the circulation (Fig. 1). In addition, regulatory T cells with suppressor activities are of major importance MCE公司 and a number of initiatives are now underway to fully appreciate the impact of these cells and to define how this knowledge may be used to modify the immune response [6]. Different subsets of these T cells have been described, such as CD4+ CD25+ FoxP3+ Treg cells, IL-10-producing Tr1 cells, transforming growth factor-β-producing Th3 cells and CD8+ Treg cells. Interestingly, an immune response not dependent on T-helper cells has recently been suggested, but so far the clinical significance of this type of immune response is not completely clear [7]. It appears that predominantly low-affinity antibodies are produced by this route and may therefore be of relevance for non-inhibitory or non-neutralizing antibodies. The reason why these antibodies can be identified in some patients but not others, and are also found in patients without haemophilia, is not known.

The following review focuses on the current view of risk factors for the development of inhibitory antibodies and whether this risk can be modulated and minimized. Treatment of haemophilia using replacement of the deficient factor has substantially improved over recent decades and life expectancy for a young boy suffering from severe haemophilia A is today, in most developed countries, similar to that of his healthy peers [1, 2]. However, severe adverse effects of replacement therapy, such as the development of neutralizing inhibitory antibodies, remain

a threat and should be considered in the management of patients. Most inhibitory antibodies will be eliminated by the use of immune tolerance selleck chemicals llc induction (ITI) with or without immunosuppression, but ITI is costly and the outcome Alectinib unpredictable [3]. Therefore, it is important to fully elucidate the factors that influence inhibitor development in one-third of patients with severe haemophilia A. This overview will summarize the current view of these risk factors in light of the immune response taking place, and will address the issue of whether it will be possible to minimize risk in the future. The mechanisms by

which inhibitory antibodies develop have been carefully studied for several years and major advances in our understanding have been made [4, 5]. However, much still remains to be resolved, and it is clear that there are several

processes that potentially influence the outcome. These include the methods by which antigen-presenting cells (APC) process and present the endocytosed factor VIII molecule to the T-helper cells, the nature of the T and B cells and the profile of the immune-regulatory molecules, including both cell-bound molecules and those secreted into the circulation (Fig. 1). In addition, regulatory T cells with suppressor activities are of major importance medchemexpress and a number of initiatives are now underway to fully appreciate the impact of these cells and to define how this knowledge may be used to modify the immune response [6]. Different subsets of these T cells have been described, such as CD4+ CD25+ FoxP3+ Treg cells, IL-10-producing Tr1 cells, transforming growth factor-β-producing Th3 cells and CD8+ Treg cells. Interestingly, an immune response not dependent on T-helper cells has recently been suggested, but so far the clinical significance of this type of immune response is not completely clear [7]. It appears that predominantly low-affinity antibodies are produced by this route and may therefore be of relevance for non-inhibitory or non-neutralizing antibodies. The reason why these antibodies can be identified in some patients but not others, and are also found in patients without haemophilia, is not known.

Hal, as he was called by friends and colleagues, attracted trainees from other countries, among them Guadalupe Garcia-Tsao from Mexico, Gregory Taggard from Australia, Simon Bar-Meir from Israel, and Jean-Pierre Vinel and Thierry Poynard from France. One of his proudest professional accomplishments was “The Histopathology of the Liver” by Klatskin and Conn, published in 1995, 9

years after Gerald Klatksin died and click here 3 years after Conn had retired. The book was a benchmark reference for the histopathological diagnosis of chronic liver diseases. It was his last big project, as he had contracted a disease unknown to him (normal pressure hydrocephalus; NPH). His NPH was erroneously diagnosed for 10 years as Parkinson’s disease and greatly affected his ability to walk or think clearly until the correct diagnosis was made. A miraculous remission followed brain surgery, and at age 78, he became an expert about, and a spokesperson for, NPH awareness. In the decade that followed, he wrote a dozen meaningful articles about NPH,

its prevalence, and heredity and appeared on national radio and TV programs. In addition, he made himself available to advise patients and the families of friends as a good Samaritan about the PI3K inhibitor diagnosis and treatment of NPH. He became a member of American Airlines’ 2 million mile club in 1990, which were primarily accumulated from giving lectures. He was an excellent lecturer, the skills for which he credits his brother, Jerome, who spoke at many of his classes and later discovered Conn’s Syndrome I (primary aldosteronism). Conn, a workaholic who spent countless hours researching articles, is the namesake for the Conn Center, a classroom at Yale’s Cushing/Whitney Medical Library. He was also an avid squash player who contributed the “Conn Family Court” to Yale’s Brady Squash 上海皓元 Center. Conn was also well known for his innovative holiday cards incorporating the family name. He is survived by his wife of 60 years, Marilyn Barr Conn, of Pompano

Beach, Florida, three children, Chrysanne (Richard) Vogt of Northford, Connecticut, Steven (Emily Resnik Conn) of Woodbridge, and Dorianne Conn (Jeff Balch) of Evanston, Illinois, and six grandchildren. The authors gratefully acknowledge Steven Conn for his many personal insights. “
“Primary intestinal lymphangiectasia (PIL) is a protein-losing enteropathy characterized by tortuous and dilated lymph channels of the small bowel. The main symptoms are bilateral lower limb edema, serosal effusions, and vitamin D malabsorption resulting in osteoporosis. We report here a case of long-lasting misdiagnosed PIL with a peculiar liver picture, characterized by a very high stiffness value at transient elastography, which decreased with clinical improvement. The complex interplay between lymphatic and hepatic circulatory system is discussed.

TRAIL−/− mice were significantly protected against ConA-hepatitis compared to WT mice as depicted by serum transaminases levels (Fig. 4A; Fig. S4A). A significant difference in liver IL-33 mRNA expression was observed between WT and TRAIL−/− mice. The up-regulation IL-33 expression was significantly reduced in TRAIL−/− livers LY294002 (Fig. 4B). Histopathology of liver tissues revealed perivascular and parenchymal zones of liver injury in TRAIL−/− and WT mice (Fig. 4C). Interestingly, only few hepatocytes were positive for IL-33 in TRAIL−/− livers compared with WT mice (Fig. 4D). Following ConA-hepatitis, we observed increased liver mRNA expression for TRAIL, DR5, FasL, and Fas but not for TNFR1 or TNFR2 in

WT mice at different time intervals (Fig. S4B). Localization of the DR5 receptor was further addressed in WT mice by immunohistochemistry showing DR5 receptor expression dominantly in noninjured liver areas, whereas low DR5 expression was evident in necrotic areas (Fig. S4C). Moreover, the expression of hepatocyte-specific nuclear IL-33 and membrane DR5 expression was selectively colocalized in the noninjured area of liver (Fig. S4C). WT and TRAIL−/− mice showed no significant difference in the regulation of liver DR5, TNFR1, and TNFR2 mRNA expression before and 10 hours after ConA

injection (Fig. S4D). However, a significant increase in liver FasL mRNA expression was observed in TRAIL−/− mice compared to WT mice 10 hours after ConA injection, whereas liver Fas and TNFα mRNA levels were significantly down-regulated in TRAIL−/− Buparlisib clinical trial compared to WT mice at this timepoint (Fig. S4D). To address the functional MCE公司 role of IL-33 in ConA liver injury, we compared hepatic injury in WT and IL-33-deficient

mice. We demonstrated significantly increased levels of serum ALT in IL-33−/− mice than WT controls at 24 hours of ConA liver injury, suggesting a protective effect of IL-33 during ConA-hepatitis (Fig. 4E). To test an essential role of TRAIL for inducing IL-33 expression in hepatocytes, we reconstituted CD1d−/− mice (NKT cells deficient) with rm-TRAIL following ConA-priming. There was no significant difference in basal TRAIL mRNA expression between WT and CD1d−/− livers (Fig. 5A). However, after ConA injection liver mRNA TRAIL expression was significantly lowered in CD1d−/− compared to WT mice (Fig. 5A). Additionally, the kinetic of higher liver DR5 mRNA expression after ConA administration was also significantly less evident in CD1d−/− compared to WT livers (Fig. 5B). We next tested the possibility of whether TRAIL administration after ConA injection was able to induce liver injury in CD1d−/− mice. The simultaneous injection of TRAIL and ConA in CD1d−/− mice significantly induced stronger liver injury as evidenced by increased serum ALT and AST levels in the ConA/TRAIL- compared to the ConA/PBS-treated group (Fig. 5C; Fig. S5).