Both groups had similar rates of histologic regression between baseline and Week 240. Patients with HVL generally took high throughput screening compounds longer to achieve HBV DNA <400 copies/mL but had caught up with the non-HVL patients by Week 96. The authors stated that no patient with baseline HVL had persistent viremia at Week 240 or amino acid substitutions associated with TDF resistance. These results are remarkable and suggest that monotherapy with a potent NUC that has a high barrier to resistance such as TDF

is sufficient in maintaining viral suppression during long-term treatment even in patients with HVL. However, the results should be interpreted with caution. Persistent viremia in this study was defined as never having HBV DNA <400 copies/mL and this endpoint was only reported on patients who remained on treatment at Week 240. Thus, patients with HBV DNA <400 copies/mL at a single timepoint and higher levels of HBV DNA subsequently would not be considered to have persistent viremia and those who were no longer on treatment at Week 240 were not counted. Of the 129 patients with baseline HVL, 46 discontinued the

study before Week 240 of whom 28 had HBV DNA <400 copies/mL at the last visit. In the remaining 83 patients, 73 had HBV DNA <400 copies/mL, three had HBV DNA ≥400 copies/mL, and HBV DNA of the other seven were unknown at Week 240. Thus, based on intention to treat analysis, only 56.6% (73/129) patients Selleck SB431542 had HBV DNA <400 copies/mL at Week 240. If the last result was carried forward, 78.3% (101/129) patients had HBV DNA <400 copies/mL. By contrast, HBV DNA <400 copies/mL at Week 240 was achieved in 76.0% (389/512) non-HVL patients by intention to treat analysis and in 91.0% (466/512) if the last result was carried forward. Furthermore, 35 HVL patients were eligible to add FTC between Week 72 Casein kinase 1 and 240 and 28 eligible plus one noneligible patient had FTC added. Adding FTC did not appear to affect HBV DNA outcomes, with 66% (19/29) on FTC/TDF and 86% (6/7) on TDF having HBV DNA <400 copies/mL at Week 240 or last visit. The difference was not statistically significant

but this may be related to the small number of patients. HBV DNA levels of the 11 patients with HBV DNA ≥400 copies/mL were not provided. That patients with HVL take longer to achieve virologic response had also been observed by other investigators. Yuen et al.[6] studied 222 NUC-naïve patients and found that 100% and 76.5% of patients with baseline HBV DNA < and ≥8 log10 copies/mL, respectively, had undetectable HBV DNA at Year 3 of ETV therapy. The only patient in whom ETV resistance was detected had baseline HBV DNA 8.1 log10 copies/mL. In a randomized trial comparing ETV monotherapy versus combination of ETV plus TDF in NUC naïve patients, Lok et al.[14] showed that 76.4% and 83.2% patients, respectively, achieved the primary endpoint of HBV DNA <50 IU/mL (∼300 copies/mL) at Week 96 (P = 0.088).

The separation Akt inhibitor of hepatic parenchymal and nonparenchymal cells was performed essentially as previously described.24 The procedure is described in detail in the supporting information. A rat hepatic SEC line (NP31)25 was cultured on type I collagen–coated dishes (Iwaki, Chiba, Japan) in Dulbecco’s modified Eagle’s medium with 10% fetal bovine serum, penicillin (100 U/mL), and streptomycin (100 μg/mL) at 37°C with 5% CO2. A retrovirus vector (pMxIG)26 and a retrovirus packaging cell line (Plat-E)27 were used to

generate recombinant retroviruses. Hemagglutinin (HA)-tagged complementary DNAs (cDNAs) of full-length Cas (Cas FL) and a Cas mutant lacking the SH3 domain (Cas ΔSH3)28 were subcloned into pMxIG, and ecotropic retroviruses were produced by the transient transfection of Plat-E cells with viral vectors using FuGENE (Roche, Basel, Switzerland). Infection was performed in the presence of 8 μg/mL Polybrene (Sigma, St Louis, MO). After fixation Selleckchem RO4929097 in 4% paraformaldehyde in phosphate-buffered saline for 10 minutes, cells were permeabilized with 0.5% Triton X-100 in phosphate-buffered saline for 5 minutes at room temperature and incubated with Alexa 594–conjugated phalloidin (1:40; Invitrogen, Carlsbad, CA) in 1% bovine serum albumin in phosphate-buffered saline for 30 minutes at 37°C. Cells were mounted

with Vectashield 4-Aminobutyrate aminotransferase and observed on an Axioplan2 microscope with AxioCam MRm controlled by Axiovision software (Carl Zeiss, Germany). NP31 cells, cultured on glass cover

slips, were fixed in 2% glutaraldehyde buffered with a 1 M cacodylate buffer (pH 7.4) for 12 hours at 4°C and then with 1% osmium tetroxide in a cacodylate buffer (pH 7.4) for 1 hour at 4°C. After dehydration in a graded series of ethanol solutions, cells were dried to a critical point and sputter-coated with osmium. Cell surfaces were examined with an S-4300 scanning microscope (Hitachi, Tokyo, Japan) at a 30-kV accelerating voltage. To create a reduction-of-function Cas allele by gene targeting, we deleted exon 2 of the Cas gene, which encodes the entire SH3 and the N-terminal part of the SD domain containing one YLVP motif and four YQxP motifs. To this end, we constructed a targeting vector containing Cas exon 2 flanked by two locus of X-over P1 (loxP) sequences and followed by the Frt-flanked neomycin resistance (Neo) gene (Fig. 1A). When the floxed Cas exon 2 was correctly excised, exon 1 joined in frame to exon 3, and this resulted in a Cas transcript devoid of the exon 2–derived segment. Correctly targeted embryonic stem cells, identified by Southern blotting and genomic polymerase chain reaction (PCR; Fig. 1B, left and middle panels), were selected and used for the generation of heterozygous mice (Cas+/floxNeo).

The 43 patients who underwent transplant accounted for $17,025,037 of the overall costs at $395,000 per transplanted patient compared to $5,817,300 for the non transplant

patients for a mean cost of $100,299 per patient. CONCLUSIONS: Pharmaco-economic studies of HCV treatment need to model real life estimations of true direct cost of HCC care. Disclosures: Daniel Mansuri – Stock Shareholder: Gilead Sciences Nezam H. Afdhal – Consulting: Merck, Vertex, Idenix, GlaxoSmithKline, Spring-bank, Gilead, Pharmasett, Abbott; Grant/Research Support: Merck, Vertex, Ide-nix, GlaxoSmithKline, Springbank, Gilead, Pharmasett, Abbott The following people have nothing to disclose: Andreea M. Catana, Nidhi Sethi, Annie Vong, Saurabh Sethi “
“MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by interacting with the 3′ untranslated region (3′-UTR) of multiple mRNAs. Recent studies have linked miRNAs to the development of cancer metastasis. In this study, we show find more that miR-194 is specifically expressed in the human gastrointestinal tract and kidney. Moreover, miR-194 is highly expressed in hepatic epithelial cells, but not in Kupffer cells or hepatic stellate cells, two

types of mesenchymal cells in the liver. miR-194 expression was decreased in hepatocytes cultured in vitro, which had undergone a dedifferentiation process. Furthermore, selleck chemicals expression of miR-194 was low in liver mesenchymal-like cancer cell lines. The overexpression of miR-194 in liver mesenchymal-like cancer cells reduced the expression of the mesenchymal cell marker N-cadherin

and suppressed invasion and migration of the mesenchymal-like cancer cells both in vitro and in vivo. We further demonstrated that miR-194 targeted the 3′-UTRs of several genes that were involved in epithelial-mesenchymal transition and cancer metastasis. Conclusion: These results support a role of miR-194, mafosfamide which is specifically expressed in liver parenchymal cells, in preventing liver cancer cell metastasis. (HEPATOLOGY 2010;.) The liver is the central organ of metabolism in mammals, controlling energy equilibrium, synthesizing plasma proteins and bile acids, and detoxifying metabolic wastes and xenobiotics. Hepatocytes, the parenchymal cells of the liver, make up more than 80% of liver mass and form its epithelial layer.1 The transformation of hepatocytes following chronic injury, induced by viral infection or alcohol abuse, leads to hepatocellular carcinoma (HCC). The long-term survival of HCC patients is unsatisfactory due to a high incidence of recurrence and metastasis after tumor resection, with a 5-year actuarial recurrence rate of 75%-100%.2 Emerging evidence indicates that aberrant activation of epithelial-mesenchymal transition (EMT) is an early step in cancer metastasis.3 EMT is characterized by loss of cell adhesion, down-regulation of the epithelial gatekeeper protein E-cadherin, and up-regulation of N-cadherin and vimentin, two mesenchymal cell markers.

To study the biological effect of miR-216a elevation further in early hepatocarcinogenesis, we tried to identify its target

gene(s) in hepatocytes. By comparing the gene expression profile between HepG2 cells infected with lenti-miR-216a and with lenti-si-GFP control viruses, the results from our microarray analysis indicated the increase in proliferation and migration activities as putative biological functions affected by the elevation of miR-216a (Supporting Table 2S). As predicted by the miRanda algorithm (MicroRNA.org, http://www.microrna.org, September 2008 release), the tumor suppressor gene TSLC1/IGSF4/CADM1 (Tumor suppressor in lung cancer 1/Immunoglobulin superfamily 4/Cell adhesion molecule 1) was pointed out as one putative Venetoclax target for miR-216a (ranked

second on the list), with major functions to control the cell proliferation and migration activities. Three putative miR-216a target sites were predicted in the 3′ untranslated region (UTR) of the TSLC1 gene, targeting to nucleotide 400–421 (target site 1), 736–759 (target site 2), and 1155–1177 (target site U0126 in vitro 3), respectively (Fig. 5A). Two reporter constructs were established to evaluate the regulation of TSLC1 by miR-216a through these putative target sites. One is pGL3-TSLC1-3′ UTR(WT), which contains the wildtype target sites; the other is pGL3-TSLC1-3′ UTR(Mut), which contains the mutated target sites (Fig. 5A). HepG2 cells expressing either reporter constructs Buspirone HCl or the pGL3-vector (as a control) were infected with lenti-si-GFP or lenti-miR-216a, with the aim of evaluating the effect of miR-216a on the reporter activity. As a control, the cells transfected with pGL3-vector were not affected by either lenti-si-GFP or lenti-miR-216a (Fig. 5B, lanes 1-3). In contrast, infection with lenti-miR-216a (≈5-fold increase of miR-216a expression, revealed by RT-qPCR) led to a decrease of luciferase activity in cells transfected with TSLC1-3′ UTR(WT) compared with that caused by lenti-si-GFP (Fig. 5B, lane 6 versus lane 5). This effect was diminished when the three putative

target sites were mutated in cells transfected with the TSLC1-3′ UTR-mut reporter construct (Fig. 5B, lane 9 versus lane 6). The results suggested that through these three putative target sites within 3′ UTR, miR-216a can regulate the expression of TSLC1. Moreover, we evaluated the effect of elevated miR-216a on the endogenous TSLC1 protein. Relative to the cells infected with lenti-si-Luc or lenti-si-GFP control viruses, TSLC1 protein was decreased ≈50% in cells infected with lenti-miR-216a (Fig. 5C), suggesting the targeting of TSLC1 by miR-216a. To examine any biological functions for the elevation of miR-216a in hepatocytes, we focused on the proliferation and migration activities due to the well-characterized function of its target gene, TSLC1.

001; and r = 0.8099, one-tailed P < 0.0001 respectively).

A comparison of corpora counts in three age groups of false killer whales from Japan (8–20, 20–32, and 32–44 yr) failed to demonstrate a significant difference in the mean numbers of corpora in pregnant and nonpregnant animals (3.8 vs. 3.9, t = 0.162, P = 0.437; 7 vs. 8.2, t = 0.569, P = 0.294; and 12.5 vs. 13.9, t = 0.771, P = 0.261 respectively), even though in all three age groups the means were lower in pregnant animals, albeit weakly so in the younger animals. These results do not support the resorption of CLs in false killer whales. The relationship between age and corpora count for both the South African and Japanese females is clearly non-linear and declines with find protocol age (Fig. 6), with South www.selleckchem.com/products/Vorinostat-saha.html African females apparently ovulating less frequently than the Japanese false killer whales and ceasing to ovulate at an earlier age. Such a phenomenon would be consistent with the comparatively lower reproductive output of South African females suggested by the lower incidence of pregnant females and nursing age calves indicated earlier. An alternative explanation could be that the lower counts in South African females were a consequence of the poorer state of fixation of their ovaries, leading to some of the smaller corpora being overlooked. To test this hypothesis, the size distribution

of old CAs was compared between South African and Japanese females. The data were stratified into three age groups (6–20 yr, 20–45 yr, 45 +  yr), to control for the naturally Montelukast Sodium occurring decrease in corpus size with age. Overall the old CAs of the South African females ranged in diameter from 2.3 to 13.4 mm with

a mean of 5.8 mm (n = 177), while those of the Japanese females were significantly larger, ranging from 1.2 to 13.3 mm with a mean of 6.3 mm (n = 599, t = 2.85, two-tailed P = 0.0045). The mean corpus size was smaller in the South African sample for all three age groups (5.9 ± 1.2 vs. 7.5 ± 1.9 cm, 6.2 ± 1.7 vs. 6.4 ± 1.7 cm, and 5.3 ± 1.7 vs. 5.8 ± 1.9 cm, respectively), and significantly so in the 6–20 and 45 +  age groups (t-test, P = 0.0326 and 0.0155, respectively). Contrary to the prediction that a postmortem effect would result in smaller corpora not being as detectable, old CAs in the South African whales were consistently smaller than those from Japan across all age groupings. Accordingly, the hypothesis that the lower ovulation rate in the South African false killer whales is an artifact arising from poorer fixation was not supported by the results of this analysis. The generally larger size of the old corpora in the Japanese females could reflect their larger body size. Quantitative expression of the overall ovulation rate in both populations is complicated by the high individual variation, trend with age and (especially in South African whales) the relatively low sample size (Fig. 6).

In households with check details an annual income ≥$90,000, 13.6% of females and 4.2% of males met criteria for migraine. A similar pattern was observed in the prevalence of PM for both sexes. Compared with persons aged 12-17 (the reference group), PRs for migraine were highest for both males and females in the 30 to 39-year-old age group. Females in this age group were 3.8 times more likely (PR = 3.80, 95% CI = 3.47-4.15), and males were 1.7 times more likely (PR = 1.72, 95% CI = 1.53-1.94) to have migraine compared with

teenage respondents (Table 3). Individuals aged ≥60 were significantly less likely to have migraine than those in adolescence (females: PR = 0.77, 95% CI = 0.70-0.85; males: PR = 0.36, 95% CI = 0.31-0.42). A similar pattern was observed for PRs of PM by age for both sexes. Individuals in their 30s and 40s had the highest rates of PM. Other severe headache was more likely at all ages compared with the 12-17 year age group for both sexes and generally increased over the lifespan. However, Fulvestrant absolute differences with age were

small. Within sex by race, adjusted PRs for African Americans (compared with Caucasians as the reference group) were well below 1.0 for migraine for both sexes (female: PR = 0.69, 95% CI = 0.65-0.73; male: PR = 0.65, 95% CI = 0.56-0.74), but significantly greater than 1.0 for PM for both sexes (female: PR = 1.38, 95% CI = 1.26-1.51; male: PR = 1.20, 95% CI = 1.05-1.37) (Table 3). Thus,

African Americans of both sexes are less likely to have migraine but more likely to have PM than Caucasians. African Americans had higher risk for Digestive enzyme other severe headache compared with Caucasians, although this difference was only significant for females (PR = 1.39, 95% CI = 1.12-1.72). Adjusted PRs for average annual household income were similar between sexes. Using the lowest annual household income group as the reference, both females and males in the highest income group were significantly less likely to have migraine (female: PR = 0.54, 95% CI = 0.51-0.57; male: PR = 0.45, 95% CI = 0.41-0.50) and PM (female: PR = 0.64, 95% CI = 0.58-0.70; male: PR = 0.48, 95% CI = 0.43-0.54) (Table 3). When compared with the lowest income level, the PRs for migraine and PM decreased as household income increased for both sexes. Household size revealed a similar pattern for both sexes as those in households with more members had lower risk of migraine or PM (data not shown). Females had higher prevalence of migraine than males at all ages, although the differences varied across the lifespan. Female to male adjusted PRs for migraine peaked at 3.25 (95% CI = 3.00-3.52) among those aged 18-29. Prevalence of migraine was still higher among females at both ends of the age spectrum although the difference was not as pronounced, with a female to male PR during ages 12-17 of 1.48 (95% CI = 1.30-1.69) to 2.91 (95% CI = 2.62-3.

After optimization of the membrane-engineering process, the virus detection limit for TMV

and CLRV with the bacteria-based biosensor system was 1 pg/ml, representing a 1000-fold improvement over currently available methods. Although the novel biosensor is still in its proof-of-concept stage of development, its sensitivity and speed (assay time: 60–100 s) could make it a very promising tool for high throughput, field-based virus screening. “
“To clarify the phytoplasma associated with Huanglongbing (HLB), a detection survey of phytoplasma in field citrus trees was performed using the standardized nested PCR assay with primer set P1/16S-Sr and R16F2n/R16R2. The HLB-diseased see more citrus trees with typical RGFP966 clinical trial HLB symptoms showed a high detection of 89.7% (322/359) of HLB-Las, while a low detection of phytoplasma at 1.1% (4/359) was examined in an HLB-affected Wentan pummelo (Citrus grandis) tree (1/63) and Tahiti lime (C. latifolia) trees (3/53) that were co-infected with HLB-Las. The phytoplasma alone was also detected

in a healthy Wentan pummelo tree (1/60) at a low incidence total of 0.3% (1/347). Healthy citrus plants were inoculated with the citrus phytoplasma (WP-DL) by graft inoculation with phytoplasma-infected pummelo scions. Positive detections of phytoplasma were monitored only in the Wentan pummelo plant 4 months and 3.5 years after inoculation, and no symptoms developed. The citrus phytoplasma infected and persistently

survived in a low titre and at a very uneven distribution in citrus plants. Peanut witches’ broom (PnWB) phytoplasma (16SrII-A) and periwinkle leaf yellowing (PLY) phytoplasma belonging to the aster yellows group (16SrI-B) maintained in periwinkle plants were inoculated into healthy citrus plants by dodder transmission. The PnWB phytoplasma showed infection through positive detection of the nested PCR assay in citrus 17-DMAG (Alvespimycin) HCl plants and persistently survived without symptom expression up to 4 years after inoculation. Positive detections of the phytoplasma were found in a low titre and several incidences in the other inoculated citrus plants including Ponkan mandarin, Liucheng sweet orange, Eureka lemon and Hirami lemon. None of the phytoplasma-infected citrus plants developed symptoms. Furthermore, artificial inoculation of PLY phytoplasma (16SrI-B) into the healthy citrus plants demonstrated no infection. The citrus symptomless phytoplasma was identified to belong to the PnWB phytoplasma group (16SrII-A). “
“This study investigated whether foliar sprays of potassium silicate (KSi), sodium molybdate (NaMo) or a combination of both (KSi + NaMo), with or without the fungicide azoxystrobin (Azox), could reduce anthracnose symptoms, improve photosynthesis and increase yield.

It was demonstrated that a substantial portion of the response was non-virus-specific in the study of the plasmablasts and the secreted IgM. We detected HAV-specific plasmablasts by staining with fluorochrome-tagged VP1 protein and compared them with non-HAV-specific plasmablasts. Non-HAV-specific plasmablasts have the phenotype

of Ki-67low/CD138high/CD31high/CD38high as compared with HAV-specific plasmablasts, demonstrating that non-HAV-specific plasmablasts have a bone marrow (BM) plasma cell-like phenotype while HAV-specific plasmablasts have a typical phenotype of circulating plasmablasts. Conclusions : These data suggest that non-HAV-specific plasmablasts are mobilized ASCs from the BM niches of plasma cells, whereas HAV-specific plasmablasts are newly generated ASCs. In this study, we demonstrated that pre-existing BM plasma cells are released DAPT to circulation during AHA and contribute to the

non-virus-specific ASC response and IgM secretion. Phenotypes of HAV-specific and non-HAV-specific ASCs in the peripheral blood Disclosures: Selleck JNK inhibitor The following people have nothing to disclose: Hyun Woong Lee, Seokchan Hong, Dong-Yeop Chang, Hyung J. Kim, Eui-Cheol Shin Background/Aim: Human homologue of Prp24p is an RNA-binding nuclear protein and also known as squamous cell carcinoma antigen recognized by T cells (SART3). It is expressed in many malignant tumor cell lines and function as tumor rejection antigens (TRA). In addition, peptides containing SART3 epi-topes are capable of generating cytotoxic T cells (CTLs), and therefore, have been used for immunotherapy to treat several kinds of cancers.

In this study, we examined human homologue Roflumilast of Prp24p expression in various hepatoma cell lines and HCC tissues of patients, and analyzed immune responses to this molecule using peripheral blood mononuclear cells (PBMCs) and tumor-infiltrating lymphocytes (TILs) to investigate the usefulness of this molecule as an immunotherapeutic target in hepatocellular carcinoma (HCC). Methods: The expression of human homologue of Prp24p in hepatoma cell lines and HCC tissues was confirmed by immunofluorescence and immunohistochem-ical analysis. Two peptides derived from human homologue of Prp24p were synthesized (SART3–109 and SART3–315). CTL responses were investigated by interferon gamma enzyme-linked immunospot (ELISPOT) and CTL assays using PBMCs and TILs in 9 healthy donors and 49 patients with HCC. The safety of immunotherapy using human homologue of Prp24p-derived peptide was investigated by s.c. vaccinations of the peptide (SART3–109) to 12 patients with HCC (trial registration: UMIN000005677). Results: Immunofluorescence and immuno-histochemical analysis showed human homologue of Prp24p to be expressed in 7 HCC cell lines and in HCC tissue including alpha-fetoprotein (AFP)-negative individuals.

1 The account of pruritus among patients with cholestasis is common but essentially subjective and doesn’t provide a reliable base for diagnosis. However, its presence as a symptom should prompt the consideration

of cholestatic disease in the differential diagnosis. Moreover, pruritus in cholestatic liver disease has specific clinical aspects lacking in other causes of pruritus; it is often generalized and described with terms such as “lying on learn more a bed of cactus,”“irritation,”“hard to get to,”“pins and needles” and “crawling” by patients and unlike other causes of pruritus scratching does not appear to relieve cholestatic pruritus.3 Pruritus is also an important aspect in defining intrahepatic cholestasis of pregnancy (ICP) which carries a high risk for adverse perinatal outcome. Pruritus in ICP is usually localized to the palms and soles of patients with ICP.4 Pruritus is a common symptom in patients with cholestatic disease. In recent years, several mechanisms have been recognized in mediating cholestatic pruritus. It is proposed that cholestasis leads to release of pruritogens from the liver; this stimulates neural Sotrastaurin itch fibers in the skin, which transmit the stimulus to the spinal cord and

subsequently the brain. Pruritogens accumulating in the plasma of patients with cholestasis may also enter the brain and alter neurotransmission.5 It remains unclear how peripheral and central encoding of itch takes place, with several theories proposed to explain this process, and the neural circuits involved in the transmission of itch yet to be clarified. We list below a few of the hypothesized neural circuits and receptors involved in the itch response, in an attempt to clarify the pathogenesis of pruritus. Figure 1 aims to list the main hypothesized pathways involved

in this pathogenesis. Neural circuits.  Several theories that Phosphoglycerate kinase aim at explaining how itch is encoded peripherally have been investigated. The intensity theory states that itch is carried by the same neuronal group carrying pain stimuli, where itch stimuli produce a weaker neuronal response than pain stimuli.6 This difference in intensity aims to explain the difference in the perception of itch and pain. This theory was challenged in human studies when increasing the intensity of the itch stimulus did not transition the itch sensation to a perception of pain.7 Similarly, decreasing the frequency of pain stimuli did not transition the perception from pain to itch.8 On the other hand, the specificity theory proposes that a distinct set of afferent fibers carries sensations of itch or pain. This theory was supported by the discovery of high threshold, low intensity fibers activated by histamine that are distinct from the nociceptive neurons.9 This theory was, however, weakened when these fibers were found to detect nociceptive stimuli induced by administration of capsaicin, and therefore were denoted selective but not specific.

Because these results identify novel immune-mediated mechanisms that contribute to fibrosis progression in NAFLD, the findings have potential clinical implications for one of the

most common types of chronic liver injury. The authors thank Dr. Alisan Kahraman (Essen, Germany) for technical advice; Patrice McDermott (Human Vaccine Institute Flow Cytometry Core Facility, Duke University, NC) for help with primary mononuclear cell sort; selleck screening library Dr. R.J. Wechsler-Reya (Duke University Medical Center, NC) for providing the Patched-deficient (Ptc+/−) mice; Dr. G.J. Gores (Mayo Clinic, Rochester, MN) and Yoshiyuki Ueno (Tohoku University, Sendai, Japan) for providing the murine immature ductular cell line (603B); Dr. M Rojkind (George Washington University, Washington, DC) for providing the rat hepatic stellate cell (HSC) line 8B; and Dr. A. learn more Bendelac (University of Chicago, Chicago, IL) for providing the mouse invariant hybridoma cell line (DN32). CD1d-tetramers were obtained through the NIH Tetramer Facility (NIAID, MHC Tetramer Core Facility, Atlanta, GA). The authors also thank Dr. Jiawen Huang for assistance with animal care and Mr. Carl Stone for administrative support. Additional

Supporting Information may be found in the online version of this article. “
“Aim:  To evaluate the usefulness of a platelet-derived growth factor (PDGF)-B specific monoclonal antibody (mAb) as

a therapeutic agent to treat chronic liver fibrosis. Methods:  Liver fibrosis was induced in Chloroambucil ICR mice by bile duct ligation (BDL) or BALB/c mice by weekly injection of concanavalin A (ConA) for 4 or 8 weeks. A mAb specific for mouse and human PDGF-B chain, AbyD3263, was generated, tested in vitro and administered twice a week throughout the experimental period. Results:  AbyD3263 showed neutralizing activity against mouse and human PDGF-B chain in cell-based assays, as measured in vitro by inhibition of phosphorylation of PDGF receptor β and proliferation of hepatic stellate cells induced by PDGF-BB. The half life of AbyD3263 in mice exceeded 7 days and dosing of animals twice a week resulted in constant plasma levels of the mAb. Induction of liver fibrosis by BDL and ConA resulted in elevated levels of alanine aminotransferase (ALT) in plasma and hydroxyproline in the liver. Treatment with AbyD3263 did not modify ALT levels, but significantly reduced hydroxyproline content in the liver with a maximum reduction of 39% and 54% in the BDL and ConA models, respectively, compared to controls.