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Objective: To investigate the utility of 13N-ammonia PET/CT imaging in the differential diagnosis of gliomas and brain inflammations.Methods: 13N-ammonia PET/CT imaging data of 77 patients with gliomas and 34 patients with brain inflammations were retrospectively analyzed. No patients received any treatment before 13N-ammonia imaging. All the patients were diagnosed by stereotactic biopsy or clinical follow-up. Visual and semi-quantitative analysis was performed to analyze the results of 13N-ammonia imaging. Finally, the uptake ratios of each lesion were calculated and its differences among different groups were tested with one-way ANOVA.Results: 29.4% inflammations, 51.6% low-grade gliomas and 91.3% high-grade gliomas were positive by visual analysis in 13N-ammonia imaging. The sensitivity, specificity and accuracy for the diagnosis of gliomas were 75.3%, 55.8% and 67.8%, respectively. As for semi-quantitative analysis, the T/G ratios of inflammatory lesions, low-grade gliomas and high-grade gliomas were 0.88 ± 0.24, 1.04 ± 0.43 and 1.43 ± 0.49, respectively. One-way ANOVA revealed that the T/G ratios of high-grade gliomas were significantly higher than those of low-grade gliomas and inflammations (P < 0.05), but there was no statistical difference between low-grade gliomas and inflammations (P = 0.118). Among the inflammatory lesions, T/G ratios were not statistically different between infectious and demyelinating lesions (P > 0.05). ROC curve analysis showed that the optimal cut-off value of T/G ratio in distinguishing gliomas from inflammations was 1.21 with the AUC 0.78. The sensitivity, specificity, accuracy, PPV and NPV were 52.9%, 94.4%, 65.3%, 95.7% and 45.9%, respectively. ROC curve analysis showed that the optimal cut-off value of T/G ratio in distinguishing high-grade gliomas from low-grade gliomas was 1.06 with the AUC 0.78. The sensitivity, specificity, accuracy, PPV and NPV were 81.5%, 67.7%, 76.5%, 81.5% and 67.7%, respectively. ROC curve analysis showed that the optimal cut-off value of T/G ratio in distinguishing high-grade gliomas from low-grade gliomas and inflammations was 1.19 with the AUC 0.84. The sensitivity, specificity, accuracy, PPV and NPV were 70.4%, 85.1%, 78.5%, 79.2% and 78.1%, respectively.Conclusions: 13N-ammonia imaging is effective in distinguishing high-grade gliomas from low-grade gliomas and inflammations, but its role in the differential diagnosis of low-grade gliomas and brain inflammatory lesions is limited, and the accuracy needs to be improved. [ABSTRACT FROM AUTHOR]

Ammonia is diffused and transported across all plasma membranes. This entails that hyperammonemia leads to an increase in ammonia in all organs and tissues. It is known that the toxic ramifications of ammonia primarily touch the brain and cause neurological impairment. However, the deleterious effects of ammonia are not specific to the brain, as the direct effect of increased ammonia (change in pH, membrane potential, metabolism) can occur in any type of cell. Therefore, in the setting of chronic liver disease where multi-organ dysfunction is common, the role of ammonia, only as neurotoxin, is challenged. This review provides insights and evidence that increased ammonia can disturb many organ and cell types and hence lead to dysfunction. [ABSTRACT FROM AUTHOR]

Purpose: Betaine deficiency is a probable cardiovascular risk factor and a cause of elevated homocysteine. Urinary betaine excretion is increased by fibrate treatment, and is also often elevated in diabetes. Does fibrate further increase betaine excretion in diabetes, and does it affect the plasma concentrations and excretions of related metabolites and of other osmolytes? Methods: Samples from a previous study of type 2 diabetes were selected if participants were taking bezafibrate ( n = 32). These samples were compared with participants matched for age and gender and not on a fibrate (comparator group, n = 64). Betaine, related metabolites, and osmolytes were measured in plasma and urine samples from these 96 participants. Results: Median urinary betaine excretion in those on bezafibrate was 5-fold higher than in the comparator group ( p < 0.001), itself 3.5-fold higher than the median reported for healthy populations. In the bezafibrate group, median dimethylglycine excretion was higher (9-fold, p < 0.001). Excretions of choline, and of the osmolytes myo-inositol, taurine and glycerophosphorylcholine, were not significantly different between groups. Some participants excreted more betaine than usual dietary intakes. Several betaine fractional clearances were >100 %. Betaine excretion correlated with excretions of the osmolytes myo-inositol and glycerophosphorylcholine, and also with the excretion of choline and N,N-dimethylglycine, but it was inconclusive whether these relationships were affected by bezafibrate therapy. Conclusions: Increased urinary betaine excretions in type 2 diabetes are further increased by fibrate treatment, sometimes to more than their dietary intake. Concurrent betaine supplementation may be beneficial. [ABSTRACT FROM AUTHOR]

Summary.  Using microdialysis, we have monitored extracellular levels of amino acids and related amines in the human liver at three stages of the transplantation procedure: donor retrieval, back table preparation and during 48 h post-implantation. By comparing the ratio of mean levels at the donor and back table stages, with the ratio between early (2–6 h) and late (43–48 h) post-reperfusion, these amines were classified into one of three groups. In one group, back table levels were markedly higher than during the donor stage, with levels declining over time post-reperfusion. A second group had much lower levels in the back table than during the donor phase, and post-reperfusion levels were either stable or increased over time. Concentrations of amino acids in the final group remained relatively constant at all stages. This study illustrates the value of microdialysis in providing organ-specific metabolic data that may indicate specific mechanisms of poor graft function. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The mechanisms of Fas–Fas ligand (Fas–FasL)-mediated apoptosis in the pathogenesis of fulminant hepatic failure (FHF) have not been well defined. This clinical study was carried out to assess which cells expressed Fas–FasL and to determine their involvement. METHODS: The subjects were 24 patients with FHF who underwent liver transplantation at our institution. For comparison, nine chronic hepatitis (CH) patients and six living liver donors (LD) were also enrolled. Liver tissues were obtained for histological (hematoxylin–eosin, terminal deoxynucleotidyl transferase [TdT]-mediated dUTP-biotin nick-end labeling [TUNEL], immunohistochemistry, and double immunofluorescence staining) and reverse transcription PCR (RT-PCR; cytokines and chemokines) analysis. RESULTS: The numbers of TUNEL-, FasL-, and CD68-positive cells in the livers of patients with FHF were significantly larger than in those with CH or with normal livers. Double immunofluorescence staining showed that FasL was expressed predominantly on liver macrophages and rarely on CD8-positive lymphocytes. RT-PCR study showed increased expression of FasL; interferon-γ; interleukin-18; macrophage inhibitory protein-1β; and regulated upon activation, normal T cell expressed and secreted in the livers of patients with FHF compared with those of LD. CONCLUSIONS: Macrophages and their expression of FasL may play roles in the pathogenesis of FHF. [ABSTRACT FROM AUTHOR]

Subepithelial fibroblasts form a cellular network with gap junctions under the epithelium of the gastrointestinal tract. Previously, we have reported their unique characteristics, such as reversible rapid cell-shape changes from a flat to a stellate configuration induced by dBcAMP and endothelins (ETs), and Ca2+ responses to, for example, ETs, ATP, and substance-P. We have now investigated the subtypes of ET receptors both in the rat small intestine and in primary cultured subepithelial fibroblasts isolated from rat duodenal villi. Their properties were compared between wild-type and endothelin-B-receptor-mutant sl/sl rats. Light- and electron-microscopic immunohistochemistry showed intense ETA immunoreactivity in the subepithelial fibroblasts from the small intestine and colon of both wild-type and sl/sl rats. In culture, immunocytochemistry, reverse transcription/polymerase chain reaction analysis, Ca2+ response measurements, and cell-shape change analysis indicated functional ETA and ETB receptors in the wild-type cells, but only ETA in the sl/sl cells. However, wild-type cells were more sensitive to ET-1 than to ET-3 by about one order of magnitude. ETA seemed to be dominant both in vivo and in vitro. The relationship between cell-shape change and gap junction permeability was examined by fluorescence recovery after photobleaching; the gap junctions were usually open but were blocked by carbenoxolone. Permeability did not change significantly with cell-shape change. This network of differentiated subepithelial fibroblasts may maintain intercellular communication via gap junctions to transduce signals evoked in the local network to the whole network. The cell-shape change of the cells through ETA activation may play an important role as a barrier and for intercellular signaling in the intestinal villi. [ABSTRACT FROM AUTHOR]

Many biological effects of taurine rely upon its cellular concentration, which is primarily controlled by taurine biosynthetic enzymes cysteine dioxygenase (CDO) and cysteine sulfinate decarboxylase (CSD) and taurine transporter (TauT). The cloning of CDO, CSD and Taut in various species provided first-hand information on these proteins, as well as molecular tools to investigate their regulations. CDO upregulation in hepatocytes in response to high sulfur amino acids appears clearly as the most spectacular among the regulations of the biosynthetic enzymes. Downregulation of Taut activity by activation of PKC appears particularly well documented. A unique serine residue could be identified as a phosphorylation site that leads to an inactive form of TauT. The previously revealed downregulation of Taut expression by taurine and hypertonicity-induced upregulation of Taut expression were shown to result from a modified transcription rate of Taut gene, but the precise molecular mechanisms are not yet formally established. Other regulations of taurine transporter expression were more recently reported, which involve glucose, tumor suppressor protein p53, tumor necrosis factor-α, and nitric oxid. This review reports the experimental models and data that support these various regulations but also points out the aspects that remain poorly understood or unknown concerning their molecular basis and physiological significance. [ABSTRACT FROM AUTHOR]

Planktonic organisms exhibit diverse morphological, behavioural and life-history responses to the chemical presence of potential predators. Prey organisms have been found to sense such predators via predator-derived kairomones. The induced reactions are assumed to reduce predation risk and thus to be adaptive. Numerous studies have investigated various aspects of inducible defences in different crustaceans, in rotifers, planktonic ciliates and algae. As a first step, we summarise recent work on chemically induced anti-predator defences in morphology, life history and behaviour. Morphological defences have been found in a wide range of different plankton organisms and recent studies on predator-induced morphologies mainly addressed the question of costs for these changes. Life-history responses were mainly studied in cladocerans and several studies have recently addressed some novel topics, such as diapause induction and the influence of predator kairomones on hatching of resting stages. Behavioural anti-predator defences also have been found for several plankton species and are characterised by relatively fast induction times. We further identified four research directions in which substantial progress has been made recently: (I) The effects of simultaneous exposure to infochemicals from different predators and the consequences of a complex chemical environment. Some environmental contaminants, such as synthetic chemicals or heavy metals, have been found to potentially disturb natural chemical communication in aquatic predator-prey systems. (II) The influence of genetic variation on the reaction to infochemicals and its implications. Clonal differences have not only been found for the presence or absence of a certain trait but also with respect to the type of response. (III) The degree to which different types of responses to a specific kairomone are coupled. Recent studies underline the uncoupling of different anti-predator responses of which some have been considered to be coupled. (IV) Studies on the chemical properties and on the metabolic origin of predator kairomones. Substantial progress has been made recently, especially with respect to the identification of predator kairomones that are important for planktonic ciliates. The identification and isolation of kairomones are an important step towards studies addressing the consequences of predator-induced defences on the level of populations, communities and ecosystems. So far most studies have considered effects and consequences on the level of individual prey organisms and studies taking the consequences at higher ecological levels into account are rare. [ABSTRACT FROM AUTHOR]

Semiochemicals play an important role in interactions between living organisms in aquatic environments. Although the presence of chemical cues is confirmed in more and more systems, the chemical structures remain predominantly elusive. To create more accurate prey–predator interaction models and to advance the research on chemical communication, it is essential to identify these compounds. A literature overview of cues involving Daphnia (either as producer or receiver) is given and the progress towards their isolation and structure elucidation is described. Most of the research so far has concentrated on the elucidation of kairomones produced by predators of Daphnia (especially Chaoborus and several species of fish). Although some progress has been made, these cues have not been isolated and identified yet. Additionally new results on the isolation and identification of the kairomone responsible for the colony formation in Scenedesmus using differential diagnosis and bioassay-directed fractionation of Daphnia exudates are presented. The importance of suitable and well performing bioassays herein cannot be underestimated. Some preliminary results with solid-phase extraction with C18 proved to be reproducible for extracting the active compound from Daphnia water, although it was not possible to get the biological activity into a single fraction. The cue was not extractable with an anion exchanger (SAX). Subjecting the extract to HPLC led to one active fraction. [ABSTRACT FROM AUTHOR]

Describes the genetically controlled expression of surface variant antigens in free-living protozoa. Ability of some free-living ciliates to exhibit alternative types of proteins on their cell surface; Utilization of immunochemical techniques; Expression of one type of surface antigen at constant environmental conditions.

The Fas/Fas ligand (FasL) system is suggested to be correlated to the onset of inflammation and apoptosis in various diseases. However, whether Fas and FasL are expressed in chronic pancreatitis is unknown. The aim of this study was to examine the expression of the Fas/FasL system and to analyze its correlation with apoptosis in a spontaneous chronic pancreatitis model (the WBN/Kob rat). Four-week-old male WBN/Kob rats were fed a special pellet diet (MB-3). Different groups of rats were killed every four weeks, and pancreata were histopathologically examined. Fas and FasL mRNAs in the pancreas were detected with a reverse transcription-polymerase chain reaction method. The cellular localization of Fas and FasL mRNA and protein was determined with in situ hybridization (ISH) and immunohistochemistry (IHC). Apoptosis was detected with a terminal deoxynucleotidyltransferase-mediated method. Fas and FasL mRNA were expressed when the pancreas was still pathologically normal, and showed a biphasic peak at 12 and 20 weeks. ISH and IHC confirmed that Fas and FasL are expressed in the cytoplasm of acinar cells, ductal cells, and lymphocytes. An apoptotic index in acinar cells correlated to the expression of Fas and FasL mRNAs. These results suggest that the expression of the Fas/FasL system is involved in acinar cell apoptosis and the onset and progression of chronic pancreatitis in the WBN/Kob rat. [ABSTRACT FROM AUTHOR]

Background: Evidence tends to support a relative preservation of the systemic immune response with laparoscopy as compared with laparotomy. However, the role of hepatic macrophages, or Kupffer cells, in modulating this immune advantage is unknown. This study investigated the functions of Kupffer cells after either laparoscopy or laparotomy in a rat model.Methods: Rats underwent laparoscopy, laparotomy, or control operations. Kupffer cells were harvested, cultured, and stimulated with lipopolysaccharide. Culture supernatants were analyzed for tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6). Cytoplasmic lysates were analyzed for activation of two mitogen-activated protein kinases (MAPKs).Results: Production of TNF-alpha and IL-6 was similar in laparoscopy, laparotomy, and control groups. Both laparotomy and laparoscopy showed increased activation of p38 MAPK as compared with controls. Activation of ERK1/2 was decreased during laparotomy as compared with laparoscopy.Conclusions: Although cytokine production was similar in the laparoscopy and laparotomy groups, changes in MAPK activation suggest that intracellular pathways are more affected during laparotomy than during laparoscopy. [ABSTRACT FROM AUTHOR]

The CD95 (Apo-1/Fas) receptor-ligand system is one of the key regulators of apoptosis and is particularly important for the maintenance of lymphocyte homeostasis. There is now broad evidence that susceptibility of tumor cells towards CD95-mediated apoptosis is largely reduced. In the human, germline and somatic mutations of the CD95 gene are associated with a high risk of both lymphoid and solid tumors. Based on these observations a new concept defining CD95 as a tumor suppressor gene is discussed. In addition to CD95, its natural ligand (CD95L) is also implicated in malignant progression. Compared to their nonmalignant counterparts, malignant cells frequently exhibit aberrant de novo expression of CD95L and are able to induce CD95L-mediated apoptosis in bystander cells. The role for neoplastic CD95L expression in local tissue destruction, invasion, and metastatic spread has been established for many tumor types. CD95L expression by malignant cells may counteract the host's antitumor immunity and favors immune escape of the tumor. On this basis, the significance of loss of CD95 and gain of CD95L expression for tumor progression is discussed. [ABSTRACT FROM AUTHOR]

ciliate cells communicate with each other, for example, in sexual propagation. A variety of sexual signals have been found to function in preconjugant interaction. Many phenomena of cellular communication in ciliates appear to be similar to those found in multicellular organisms. [ABSTRACT FROM AUTHOR]

Infection with hepatitis C virus (HCV) is characterized by inflammatory liver damage and a long viral persistence associated with an increased risk of developing hepatocellular carcinoma. Both in liver damage and in oncogenesis a disturbance of apoptosis has been implicated, although the underlying mechanisms in these apparently opposite processes are incompletely understood. HCV-triggered liver injury is mediated mainly by host immune mechanisms and eventually by direct cytopathic effects of HCV. Recent data shows that caspase activation, either triggered by death ligands, other cytokines, granzyme B or HCV proteins, is considerably upregulated in HCV-infected liver. Interestingly, caspase activation appears to correlate closely with the inflammatory response. Data about the role of single HCV proteins, either in cultured cells or transgenic animals models, however, are contradictory, as both pro- and anti-apoptotic effects have been observed. Nevertheless, apoptosis induction upon HCV infection may critically contribute to liver damage, while inhibition of apoptosis may result in HCV persistence and development of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]