4%) Among them, 3 case were diagnosed with gastrinoma (1 3%) Pa

4%). Among them, 3 case were diagnosed with gastrinoma (1.3%). Pancreas was the second most often seen located organ (51/233, 22.9%). Insulinoma accounted for 70.6% (36/51) of pancreatic NETs. According to the 2010 WHO classification criteria: NET G1, 84 cases (37.3%); NET G2, 63 (28.3%); NEC, RG-7388 purchase 71 (31.9%). Pathological characteristics: Expression of CgA were examined in 143 patients using immunohistochemistry staining and the positive rate was 67.1% (96/143). CgA expression

positive rate in pancreatic NETs was the highest (24/26, 92.3%), and that in rectal NETs was 41.9%(13/31). Syn expression were detected in 174 cases (78%), and the Syn positive rate was 96.6% (168/174). CgA, Syn, and NSE were combining detected in 45 cases, positive at least one marker. Endoscopy, ultrasound and CT examination were the most often used tools for diagnosis. Surgical resection as the main ways for the treatment. Conclusion: GEP – NETs usually occur in middle-aged male. The most common involved organ

is stomach, followed by pancreas. NET G1 is the most common pathological type. CgA positive rate in pNET is the highest. CgA, Syn and NSE combining test can improve diagnostic sensitivity. Key Word(s): 1. gastrointestinal ; 2. GEP – NETs; Presenting Author: TOMOTAKA SAITO Additional Authors: KNEJI HIRANO, GYOUTANE UMEFUNE, KEI SAITO, DAI AKIYAMA, SHUHEI KAWAHATA, KAORU TAKAGI, TAKEO WATANABE, RIE UCHINO, NAMINATSU TAKAHARA, TSUYOSHI HAMADA, SUGURU MIZUNO, KOUJI MIYABAYASHI, selleck chemical TAKASHI SASAKI, HIROFUMI KOGURE, NATSUYO YAMAMOTO, YOUSUKE NAKAI, HIROYUKI ISAYAMA, MINORU TADA, KAZUHIKO KOIKE Corresponding Author: TOMOTAKA SAITO Affiliations: Tokyo University Objective: Many patients of unresctable pancreas cancer become pancreatic exocrine dysfunction and secondarily digestion malabsorption. There is few report that reviews whether Pancrelipase improves nutritional condition of patients of unresectable pancreas cancer. We try to reveal short term effects of taking orally of Pncrelipase on patients of unresectable pancreas

cancer. Methods: (1)When start chemotherapy to patients of unresectable pancreas cancer,start taking orally of Pancrelipase at the same time. Measure RVX-208 BMI,serum Albumin (Alb), serum Prealbumin (Prealb), serum Total cholesterol (T. chol) when start taking orally of Pancrelipase and 8weeks after start.23 patients (male-to-female ratio 12:11, mean age 66.8). (2) Administer Pancrelipase to patients of unresectable pancreas cancer who already started chemotherapy. Measure BMI,Alb,Prealb,T. chol. when start taking orally of Pancrelipase and 8weeks after start.18 patinets(male-to-female ratio 6:11,mean age 69.4). (3) Assemble data of Patients of unresectable pancreas cancer who alredy started chemotherapy but not administered Pancrelipase. Measure BMI,Alb,Prealb,T. chol. when start chemotherapy and 8weeks after start.82 patients (male-to-female ratio 49:33,mean age 67.6). Results: In case (1).

(2011a) observed that amphipod densities on D  menziesii signific

(2011a) observed that amphipod densities on D. menziesii significantly decreased, while densities on I. cordata significantly increased at night compared to day such that the densities (per unit wet weight) on the two species were not significantly different in the dark. Overall amphipod density on P. decipiens also increased at night, but the trend was not statistically significant. However, densities of the amphipod G. antarctica, selleck inhibitor which, as noted previously, consumes P. decipiens as fresh thallus, did significantly increase on it during the night. Aumack et al. (2011a) suggested that the amphipods were leaving their chemically defended

macroalgal refuges during the night so as to forage on diatoms, other palatable microalgae and macroalgae, and other potential food sources, while their predators were less LY294002 ic50 successful at foraging on them because of the darkness. We have come to describe this association between macroalgae and amphipods as a community-wide mutualism because, as detailed previously in this mini-review, chemically defended macroalgae are the dominant structural components of the community, amphipods, and to

a lesser extent also gastropods, appear to be the major second trophic level consumers in the community, and organisms at both trophic levels appear to gain substantial benefits from their association. These interactions are summarized graphically in Figure 1. Most macroalgae in the community are chemically defended from consumption, but benefit the dense assemblage of macroalgal-associated amphipods by providing an associational refuge from fish predation. The amphipods benefit the macroalgae by keeping them relatively clean of diatoms and other epiphytes. However, the dense amphipod assemblage appears to have selected for filamentous algae with an ability to grow as endophytes within Exoribonuclease the chemically defended macroalgae, which then provide them with a refuge from amphipod grazing. The endophytes can be pathogenic to their hosts, but evidence to date suggests that this is not always true and even when it is, the effects can be relatively mild.

This community-wide mutualism can be considered at least somewhat analogous to the relationships on tropical reefs between herbivorous fish and corals where the fish reduce macroalgal cover, benefiting the corals, and the fish benefit in turn because the increased structural complexity provided by corals increases fish recruitment (Mumby and Steneck 2008, Hughes et al. 2010). Our description of this interaction as a mutualism assumes that the macroalgae in nature are indeed benefiting from the presence of the dense associated amphipods and somewhat less abundant gastropods. Since light is considered to be the main growth-limiting environmental variable for Antarctic macroalgae (Wiencke et al. 2007, Zacher et al. 2009, Wiencke and Amsler 2012), it is reasonable to expect that the removal of light-blocking epiphytes would indeed be beneficial.

2A) Micro- and

2A). Micro- and AZD9291 cost macrovesicular steatosis occurred after 1 week following alcohol administration compared with wild-type mice receiving an isocaloric diet. Hepatic fat accumulation was markedly

lower in Muc2−/− mice compared with wild-type mice following 1 week of continuous intragastric ethanol feeding (Fig. 2B). This was confirmed by lower hepatic triglycerides in Muc2−/− mice after alcohol administration (Fig. 2C). Plasma triglyceride levels were similar between wild-type and Muc2−/− mice fed an isocaloric and alcohol diet intragastrically for 1 week (Supporting Fig. 2B) suggesting no difference in intestinal lipid absorption. Hepatic oxidative stress was also significantly lower in Muc2−/− mice compared with wild-type mice following 1 week of intragastric alcohol feeding, as supported by thiobarbituric acid reactive substances (TBARS) assay (Fig. 2D) and by staining for 4-hydroxynonenal (Fig. 2E). Thus, Muc2 deficiency, and hence a thinner intestinal mucus layer, ameliorates experimental alcohol-induced steatohepatitis. To explain the different hepatic phenotype, we investigated whether Muc2 deficiency affects the intestinal absorption or hepatic metabolism of alcohol. Plasma alcohol levels were found to be comparable in wild-type and Muc2−/− mice

following 1 week of intragastric alcohol feeding (Fig. 3A). Alcohol Y-27632 ic50 dehydrogenase (Adh) and cytochrome p450 enzyme 2E1 (Cyp2E1) are the two main hepatic enzymes to metabolize alcohol and to convert alcohol to acetaldehyde.29 Microsomal Cyp2E1 protein was similarly up-regulated in the ethanol-treated groups (Fig. 3B). Despite higher hepatic Adh activity in Muc2−/− mice compared with wild-type mice after intragastric administration of an isocaloric diet that was not observed after ethanol administration (Fig. 3C), plasma acetaldehyde levels were not different following 1 week of intragastric alcohol feeding (Fig. 3D). To investigate whether the absence of Muc2 results in a compensatory up-regulation of other intestinal mucins after ethanol administration, intestinal gene and protein expression of several mucins was assessed. Deficiency in Muc2 did not result in a compensatory increase in the thickness of the intestinal Bortezomib mouse mucus layer

following intragastric alcohol feeding (Fig. 4A). There was no significant difference in the gene expression of secreted mucin Muc6 or of membrane-bound mucins (such as Muc1 and Muc4) in Muc2−/− mice relative to wild-type mice after 1 week of intragastric feeding of ethanol (Fig. 4B). These findings were confirmed using immunohistochemistry for Muc1 and Muc4 in small intestinal sections of wild-type and Muc2−/− mice fed an intragastric isocaloric or alcohol diet (Fig. 4C,D). Alcoholic steatohepatitis is dependent on endotoxin derived from intestinal bacteria.2, 30 Since Muc2 is expressed in the intestine but not the liver, we next investigated whether translocation of bacterial products from the intestine to the systemic circulation is affected by the absence of Muc2.

2) Liver damage during conA-induced hepatitis (CIH) depends main

2). Liver damage during conA-induced hepatitis (CIH) depends mainly AZD2014 manufacturer on the activities of liver T- and NKT-cells and their production of a variety of cytokines, including TNF-α and IFN-γ.14, 15 To examine the effect of VSIG4 on cytokine production by liver T- and NKT-cells, we performed intracellular cytokine staining after ConA challenge. The frequency of NKT-cells producing intracellular proinflammatory cytokines such as IFN-γ, TNF-α, and IL-17A

was significantly higher in VSIG4 KO mice than in WT mice (Fig. 2A; Supporting Table 1). A similar pattern of intracellular cytokine production was observed in liver T-cells from VSIG4 WT and KO mice. Furthermore, in vivo administration of soluble VSIG4.Ig to B6 WT mice 2 hours before ConA challenge greatly decreased the frequency of proinflammatory cytokine-producing NKT-cells compared to those given control Ig (Fig. 2B; Supporting Table 1). A similar pattern of cytokine production was observed in liver T-cells from mice given control Ig and VSIG4.Ig. We found that VSIG4.Ig bound naïve liver T- and NKT-cells in a binding assay, which was not blocked by 14G8 mAb,

an antibody that blocks C3b PF-01367338 chemical structure binding to VSIG4 (Supporting Fig. 3),16 suggesting that VSIG4 may directly suppress liver T- and NKT-cells by way of unidentified receptor(s). To demonstrate the role of VSIG4+ KCs in the regulation of liver inflammation in vivo, we adoptively transferred VSIG4 WT or Diflunisal KO KCs into mice lacking VSIG4 7 days before ConA injection. Our preliminary study using CFSE-labeled KCs showed that ∼45% of adoptively transferred KCs were localized in liver until 1 week after adoptive transfer (Supporting Fig. 4). The purified KCs expressed comparable levels of CD80, CD86, MHC class II, and B7-H1, and produced similar levels of IL-10 and TGF-β between KCs from VSIG4 WT and KO mice (Supporting Fig. 5A,B). Serum ALT levels were significantly reduced in VSIG4 KO mice that received VSIG4+

WT KCs compared to those that received VSIG4 KO KCs (P < 0.001; Fig. 3A). Similar results were obtained for serum IFN-γ. Consistently, VSIG4 KO mice were largely free of hepatic parenchymal necrosis after receiving VSIG4+ WT KCs compared to those given VSIG4 KO KCs (Fig. 3B). To examine whether VSIG4+ KCs directly regulate liver T- and NKT-cell cytokine production in vitro, we cocultured WT liver NKT-cells with KCs isolated from VSIG4 WT or KO mice in the presence of α-GalCer (KRN 7000) for 2 days. Liver NKT-cells produced more IFN-γ and IL-4 when cocultured with VSIG4 KO KCs than with WT KCs (at KC:NKT ratio of 1:1; IFN-γ, P < 0.01; IL-4, P < 0.001; Fig. 4A). NKT-cells did not produce detectable levels of IFN-γ or IL-4 in a coculture without α-GalCer stimulation (data not shown). Intracellular TNF-α was increased more in liver NKT-cells cocultured with VSIG4 KO KCs than in counterpart NKT-cells (Fig. 4B).

4 M) Taken together, our data suggest that AH-RPS


4 M). Taken together, our data suggest that AH-RPS

might maintain its clay-dispersing activity and inhibit mutual flocculation of microalgae and suspended clay in saltern brine. “
“The dinophysoid dinoflagellates are currently divided into three families: Amphisoleniaceae, Dinophysaceae (mainly Dinophysis Ehrenb. and Phalacroma F. Stein), and Oxyphysaceae, the latter including only one member, Oxyphysis oxytoxoides Kof. Phalacroma has been recently reinstated separately from Dinophysis, and its amended description is currently restricted to cells whose epithecae buy NVP-AUY922 were large but <1/4 of the cell length. With the aim of improving the phylogeny of Dinophysales, we obtained 54 new SSU rRNA gene sequences of 28 species. Taxon-rich SSU rDNA phylogenetic analysis showed that Dinophysales split into two major clades, one containing the Amphisoleniaceae (Amphisolenia F. Stein–Triposolenia Kof.) and the other containing the Dinophysaceae. The latter are divided into two well-supported sister groups, the Dinophysaceae sensu stricto (s.s.) (Dinophysis, Ornithocercus F. Stein, Histioneis F. Stein) and, tentatively, a separate family for the clade of the type and most of the Phalacroma species. Based on combined mTOR inhibitor phylogenies of new SSU rDNA and available LSU rDNA

data, O. oxytoxoides (elongated epitheca, >1/4 of the cell length) branched with a strong support with the type of Phalacroma. We therefore propose Phalacroma oxytoxoides comb. nov. for O. oxytoxoides. Our SSU rDNA phylogeny also suggests that the assumed high intraspecific variability of Dinophysis hastata F. Stein hides a number of cryptic species. According to their distinct phylogenetic placement, the forms D. hastata f. phalacromides Jørg. and D. hastata f. uracanthides Jørg. should be erected at the species level. We propose for them the names Dinophysis phalacromoides comb. nov. and Dinophysis uracanthoides comb. nov. “
“At present, there is strong commercial demand for recombinant proteins, such as antigens, antibodies, biopharmaceuticals, and industrial enzymes, which cannot be fulfilled by existing Amylase procedures. Thus, an intensive search for alternative models

that may provide efficiency, safety, and quality control is being undertaken by a number of laboratories around the world. The chloroplast of the eukaryotic microalgae Haematococcus pluvialis Flotow has arisen as a candidate for a novel expression platform for recombinant protein production. However, there are important drawbacks that need to be resolved before it can become such a system. The most significant of these are chloroplast genome characterizations, and the development of chloroplast transformation vectors based upon specific endogenous promoters and on homologous targeting regions. In this study, we report the identification and characterization of endogenous chloroplast sequences for use as genetic tools for the construction of H.

The OR were adjusted for various confounding factors, such as age

The OR were adjusted for various confounding factors, such as age and gender. All statistical analyses were carried out using spss software version 11.5 (SPSS, Chicago, IL, USA) and tests of statistical significance were two-sided and differences were taken Navitoclax nmr as significant when P-value was < 0.05. The false-positive report probability (FPRP) for statistically significant observations was estimated using the methods described by Wacholder et al.23 Polymorphism phenotyping algorithm (PolyPhen) (http://www.bork.embl-eidelberg.de/PolyPhen/)24,25 was chosen for functional impact prediction of ABCG8 D19H. PolyPhen is a computational

tool for the identification of potentially functional nsSNP. Predictions are based on a combination of phylogenetic, structural and sequence annotation information characterizing a substitution and its position in the protein.26 Molecular modeling studies were carried out to understand the effect of aspartate to histidine www.selleckchem.com/products/R788(Fostamatinib-disodium).html change (rs11887534) on the geometry of

ABCG8 protein. Modeling was carried out using the Modeller and 3D-PSSM program27,28 and superimposition studies were carried out using Discovery Studio version 2.1 (Accelrys, San Diego, CA, USA). Table 1 shows the characteristic profile of gallstone patients and healthy controls. The mean age of gallstone patients and healthy controls was 48.6 ± 11.9 and 49.0 ± 9.8, respectively. Of all the gallstone patients, 63.9% patients were females (Table 1). All the samples analyzed were of the cholesterol type (98.51%), except one that was of the pigment type (1.49%). The individual with the pigment type gallstone was excluded from the study. In our population, the observed genotype Orotidine 5′-phosphate decarboxylase distribution of the ABCG8 D19H polymorphism in healthy controls was consistent with the Hardy–Weinberg equilibrium. Among healthy controls, the frequencies of wild-type (D) and variant (H) alleles were 0.975 and 0.025, respectively

(Table 2). On comparing the genotype frequency distribution in gallstone patients with that of controls, the frequency of heterozygous DH genotype was considerably higher (10.4%) in gallstone patients than that of controls (5.0%). The difference between the frequencies of both these groups was statistically significant (P = 0.038) and was a conferring risk for the disease (OR = 2.20; 95% CI = 1.1–4.6). Also, at the allele level, there was a significant difference between the frequency distribution of the variant allele (ABCG8 H) in patients and the control group (5.2% and 2.5%, respectively). This frequency difference of the ABCG8‘H’ allele was statistically significant and was a conferring risk (P = 0.043) for cancer (OR = 2.12, 95% CI = 1.2–4.3) (Table 2). To further explore the effect of this polymorphism with respect to the gender of the patients, frequency distribution was analyzed separately in male and female patients.

6% [47/63]

6% [47/63] PS-341 datasheet vs 75.0% [24/32]). Of the 65 patients who initially received 2250 mg/day TVR, 41 were IL28B TT, 21 were IL28B non-TT and three were

undetermined. RVR (83.3% [20/24] vs 80.0% [12/15], P > 0.999) and SVR12 (81.8% [18/22] vs 94.1% [16/16], P = 0.363) rates were similar in IL28B TT patients with low and high IP-10. In contrast, the RVR rate was significantly higher in IL28B non-TT patients with low than high IP-10 (88.9% [8/9] vs 33.3% [4/12], P = 0.024), whereas SVR12 rate in patients with IL28B non-TT and low IP-10 was not significantly higher than that in patients with IL28B non-TT and high IP-10 (66.7% [6/9] vs 33.3% [4/12], P = 0.198). Of the 32 patients who initially received 1500 mg/day TVR, 26 were IL28B TT and six were IL28B non-TT. In terms of RVR and SVR12 rates, the difference between patients with IL28B

TT and low IP-10 and those with IL28B TT and high IP-10 was not significant (RVR, 100% [11/11] vs 71.4% [10/14], P = 0.105; SVR12, 91.7% [11/12] vs 71.4% [10/14], P = 0.330). Because of the small sample size (n = 6), we did not perform subgroup analyses of patients with IL28B non-TT. To our knowledge, few studies have examined the effects of pretreatment serum IP-10 concentration on virological responses in genotype 1 CHC patients treated with TVR-based triple therapy.[27] Baseline IP-10 has been found predictive of treatment outcomes in HCV genotype 1-infected patients treated with PEG IFN and RBV.[17, 18, 25] IL28B SNP has also been associated with virological responses to antiviral treatment in HCV-infected patients.[12, 13] However, MK-1775 supplier currently, data on combining these predictors in patients

with genotype 1 HCV infection treated with TVR-based triple therapy are limited; hence, the reason for the current study. Our multivariate analyses showed that pretreatment serum IP-10 concentration was a significant predictor of O-methylated flavonoid RVR, but not of SVR12. In patients with the IL28B risk allele, the RVR rate was significantly higher in those with low than high IP-10 concentrations. The SVR12 rate also tended to be higher in the former subgroup, although the difference did not reach statistical significance, probably due to the small sample size. Similar results were observed in patients receiving initial TVR doses of 1500 and 2250 mg/day per protocol. These results suggest that, in patients with HCV genotype 1 treated with TVR-based triple therapy, baseline IP-10 level is useful for predicting virological response, especially in those with the IL28B risk allele who are considered difficult to treat. We found that pretreatment serum IP-10 differed significantly (P = 0.001) in patients who did and did not achieve RVR. Low systemic IP-10 was found to predict a favorable first-phase decline in HCV RNA and RVR during treatment with PEG IFN and RBV.

It has been shown that seaweeds, like higher plants, respond to a

It has been shown that seaweeds, like higher plants, respond to an increased activity of antioxidative enzymes when exposed to stress. However, earlier investigations have shown that P. cinnamomea also compensates for stress due to UV radiation by increasing polyamine (PA) levels, especially bound-soluble and bound-insoluble PAs. The

PA precursor putrescine (PUT) can be synthesized via two enzymatic pathways: arginine decarboxylase (ADC) and ornithine decarboxylase (ODC). Both of these enzymes showed increased activity in P. cinnamomea under UV stress. In higher plants, ADC is the enzyme responsible for increased PA levels during stress exposure, while ODC is correlated with cell division and reproduction. However, there are contrary findings in the literature. Using two irreversible inhibitors, we identified the enzyme most likely responsible RO4929097 for increased PUT synthesis and therefore increased stress tolerance in P. cinnamomea. Our results show that changes in the PA synthesis pathway in P. cinnamomea under UV stress are based on an increased activity of ADC. When either inhibitor was added, lipid hydroperoxide levels increased even under photosynthetically active selleck chemicals llc radiation, suggesting that PAs are involved in protection mechanisms under normal light conditions as well. We also show that under optimum or low-stress conditions, ODC activity is correlated

with PUT synthesis. “
“W.K. Kellogg Biological Station, Michigan State

University, Hickory Corners, Michigan, USA Currently, very few studies address the relationship between diversity and biomass/lipid production in primary producer communities for biofuel production. Basic studies on the growth of microalgal communities, however, provide evidence of a positive relationship between diversity and biomass production. Recent studies have also shown BCKDHA that positive diversity–productivity relationships are related to an increase in the efficiency of light use by diverse microalgal communities. Here, we hypothesize that there is a relationship between diversity, light use, and microalgal lipid production in phytoplankton communities. Microalgae from all major freshwater algal groups were cultivated in treatments that differed in species richness and functional group richness. Polycultures with high functional group richness showed more efficient light use and higher algal lipid content with increasing species richness. There was a clear correlation between light use and lipid production in functionally diverse communities. Hence, a powerful and cost-effective way to improve biofuel production might be accomplished by incorporating diversity related, resource-use-dynamics into algal biomass production. “
“Macroalgae are important primary producers in many subtidal habitats, yet little information exists on the temporal and spatial dynamics of net primary production (NPP) by entire subtidal assemblages.

pylori infection Concomitant therapy may be more suitable for pa

pylori infection. Concomitant therapy may be more suitable for patients with dual resistance to antibiotics [59]. Probiotics may be also a useful HM781-36B chemical structure adjunct with increased rates of eradication reported in some studies [60]. Lactobacilli would appear to be the most suitable agent. In one review,

an increased pooled eradication rate from 77% to 82% was noted [61]. Culture and susceptibility testing for H. pylori is usually reserved for treatment failures, in which instance it is suggested by the Maastricht consensus [5]. Susceptibility testing is very commonly employed in other latent conditions such as tuberculosis and may well represent a useful strategy in H. pylori treatment. It is limited by the fact that in vivo resistance may not accurately reflect in vitro resistance, notably with respect to metronidazole [62]. Currently, such an approach is only carried out in specialist centers with research interest Ensartinib and expertise in the treatment of H. pylori [63]. However, should this practice become more widespread, it would lead to undoubted benefits such as more accurate prescribing

and consequently lower rates of resistance. It is probably the case that the majority of clinicians viewed H. pylori eradication treatment with a certain degree of complacency over most of the last decade. The recent decline in eradication rates has inspired a revival of interest in the topic, and there are many exciting new options and combinations which have the potential to raise eradication rates to more acceptable levels. In spite of these new developments, the two most critical concepts are those of compliance and antibiotic resistance. Compliance involves effort on behalf of both

doctor and patient and mandates a strict protocol for repeat testing to ensure the eradication of the pathogen and the prescription of defined second Florfenicol and third-line therapies if necessary. Should this be assured, it has been repeatedly illustrated that full or near full eradication of this pathogen in affected patients is eminently achievable [64–66]. If compliance is neglected, by using of unpalatable or overly prolonged or complex regimens, it is to be expected that antibiotic resistance will continue to be a problem that besets eradication therapies. Centers with a research or academic interest have a role to play in compiling data on a frequent and comprehensive basis about the levels of resistance to the most commonly anti-H. pylori antibiotics in their communities. As resistance rates are variable worldwide, this needs to be carried out in all regions. The upcoming fourth Maastricht consensus meeting will be focussing its attention further on H. pylori eradication in respect of the prevention of gastric cancers.

1) However, for everyone else, the words “ductular reaction” rem

1). However, for everyone else, the words “ductular reaction” remain an abstraction.

Although evocative in a general way, “ductular reaction” fails to convey the heterogeneity underlying the development, nature, and outcome that is necessary to give clinical or scientific relevance. That such nuances are important is clear from reviewing selleck inhibitor any contemporary literature regarding some of the key questions about hepatic physiology. DRs are now recognized to occur ubiquitously in many acute and chronic liver diseases, not just in biliary disorders, and are increasingly central to our understanding of hepatic stem and progenitor cells in liver regeneration, mechanisms underlying hepatic fibrosis, and hepatobiliary Akt inhibitor carcinogenesis. This review will focus specifically on changes and concepts derived from studies of humans,

not animal models, for concision and because much about human DRs is quite unlike their animal correlates. Although such models remain exceptionally useful, particularly for studies of hepatic regeneration, as far as fibrosis and neoplasia are concerned, the rodent models display very different processes from those seen in human livers. Where we include data from animal models, it is because they are clearly relevant to humans or they provide insights for which no human data are available. Our key emphasis will be on the diversity of DRs, the word “diverse” applying in several ways. DRs show strikingly diverse patterns that are Arachidonate 15-lipoxygenase often diagnostically specific, varying markedly, for example, between predominantly biliary and hepatocellular injuries and acute or chronic processes (Fig. 1). DRs also contain a profound diversity of cellular and tissue elements, not just the hepatobiliary epithelial cells that are most prominent on quick glance (the “ductular” component of the name), but all the other elements of the tissue “reaction” (Fig. 2). The

epithelial cells themselves show a range of differentiation states, particularly when studied by immunohistochemical expression (Fig. 3). There is also diversity of cell origin, with, in the most studied example, “intermediate hepatobiliary cells” of DRs shown to derive, variously, from activation of canals of Hering (CoH) and ductules (Fig. 4), circulating, marrow-derived precursors, biliary metaplasia of hepatocytes, and perhaps from mesenchymal-to-epithelial transition. Diverse molecular signaling pathways are also known to mediate human DRs and are the aspects of DRs perhaps best revealed by animal model analysis.5 We thus present a view of DRs from our own dual perspectives as research scientists and as diagnosticians who analyze DRs in daily clinical practice. We hope these combined perspectives will be of value for those investigators and clinicians who do not have the privilege of such intimate, daily contact with this increasingly fascinating realm, this “diversity at the interface.