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Neuroendocrine tumours (NET) are rare neoplasms, but the incidence is permanently increasing. Most of the NETs are slow proliferating and clinically silent, and for that reason, they are often diagnosed at a stage with advanced disease. The complexity and diversity of the NET-biology require the treatment of patients in specialised centres to guarantee a qualified, multidisciplinary treatment planning. At our institution, we developed an interdisciplinary model for the assessment and treatment of NET. The aim was to adapt the guidelines to the clinical practice, exchange of current knowledge, and a tailored approach to the individual patient. In our team are included medical professionals from pathology, radiology, oncology, gastroenterology, oncological surgery, and nuclear medicine. In this paper, we describe step-by-step a procedural algorithm for the management of patients with neuroendocrine tumours, focusing on midgut-NETs in terms of therapy. [ABSTRACT FROM AUTHOR]

In this study, we evaluate whether Snail is expressed in adrenocortical cancer (ACC) and if its expression is related to patient outcome. One of the best known functions of the zinc-finger transcription factor Snail is to induce epithelial-to-mesenchymal transition (EMT). Increasing evidence suggests that EMT plays a pivotal role in tumour progression and metastatic spread. Snail and E-cadherin expression were assessed by immunohistochemistry in 26 resected ACCs and real-time quantitative RT-PCR expression analysis was performed. Data were correlated with clinical outcome and in particular with overall patient survival. Seventeen of 26 (65%) ACC tumour samples expressed Snail when assessed by immunohistochemistry. Snail expression was neither detected in normal adrenocortical tissue, nor in benign adrenocortical adenomas. Expression levels were confirmed on the mRNA level by Real-Time-PCR. Survival rates were significantly decreased in Snail-positive tumours compared to Snail-negative tumours: 10 out of 16 vs one out of eight patients succumbed to disease after a median follow up of 14.5 and 28.5 months, respectively (P=0.03). Patients with Snail-expressing ACCs presented in advanced disease (11 out of 12 vs 6 out of 14, P=0.01) and tend to develop distant metastases more frequently than patients with negative staining (7 out of 11 vs two out of eight, P=0.19). In conclusion, we describe for the first time that Snail is expressed in a large subset of ACCs. Furthermore, Snail expression is associated with decreased survival, advanced disease and higher risk of developing distant metastases. [ABSTRACT FROM AUTHOR]

Background and aims: Pancreatic cancer is among the most dismal of human malignancies. Current therapeutic strategies are virtually ineffective in controlling advanced, metastatic disease. Recent evidence suggests that the Hedgehog signalling pathway is aberrantly reactivated in the majority of pancreatic cancers, and that Hedgehog blockade has the potential to prevent disease progression and metastatic spread. Methods: Here it is shown that the Hedgehog pathway is activated in the Pdx1 -Cre; LsL-KrasG12D; Ink4a/Arflox/lox transgenic mouse model of pancreatic cancer. The effect of Hedgehog pathway inhibition on survival was determined by continuous application of the small molecule cyclopamine, a smoothened antagonist. Microarray analysis was performed on non-malignant human pancreatic ductal cells overexpressing Gli1 in order to screen for downstream Hedgehog target genes likely to be involved in pancreatic cancer progression. Results: Hedgehog inhibition with cyclopamine significantly prolonged median survival in the transgenic mouse model used here (67 vs 61 days; p = 0.0261. In vitro data indicated that Hedgehog activation might at least in part be ascribed to oncogenic Kras signalling. Microarray analysis identified 26 potential Hedgehog target genes that had previously been found to be overexpressed in pancreatic cancer. Five of them, BIRC3, COL11A1, NNMT, PLAU and TGM2, had been described as upregulated in more than one global gene expression analysis before. Conclusion: This study provides another line of evidence that Hedgehog signalling is a valid target for the development of novel therapeutics for pancreatic cancer that might be worth evaluating soon in a clinical setting. [ABSTRACT FROM AUTHOR]

To date little data exist about treatment of hematologic malignancies in patients with end-stage renal disease (ESRD). While administration of immunochemotherapy comprising the CD20-antibody rituximab is a well-established treatment strategy in patients with normal renal function, little information on safety and efficacy is available in the setting of ESRD. Here we describe for the first time a hemodialysis patient suffering from diffuse large B-cell Non-Hodgkin's lymphoma (DLBCL) who was treated with polychemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone) in combination with rituximab (R-CHOP). We observed no major adverse events and treatment resulted in a partial remission of the DLBCL. Thus, administration of R-CHOP may be considered as a safe therapeutic option in this setting. Of note, this patient had a previous history of hairy cell leukemia. A review of the literature was performed and the potential etiologic link of these two B-cell malignancies is discussed in the light of available information. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C virus (HCV) infection leads to mixed cryoglobulinaemia (MC) and B-cell non-Hodgkin lymphoma (B-NHL). Aberrant somatic hypermutation and deregulation of the oncogene BCL-6 is associated with lymphomagenesis. Recently, HCV was shown to induce BCL-6 mutations in vitro. The BCL-6 gene (area B) was cloned and sequenced from peripheral blood mononuclear cells (PBMC) of 21 chronically HCV-infected patients with or without MC and B-NHL, and six healthy controls. Mutational frequencies, genetic complexity and diversity were calculated. BCL-6 mRNA from PBMC was quantified by real-time polymerase chain reaction, and additional sustained virologic responders to antiviral therapy and HBV patients served as controls. The overall/recurrent mutational frequencies tended to be lower in MC and B-NHL patients when compared with controls ( P = 0.15 and 0.06, respectively). Genetic complexity was significantly lower in MC and B-NHL patients ( P = 0.025). BCL-6 mRNA concentration was decreased in all HCV patients when compared with healthy controls, sustained virologic responder and HBV patients ( P = 0.005). Although HCV can induce BCL-6 mutations in vitro, lower mutational frequencies and decreased BCL-6 mRNA expression in vivo suggest no major role of aberrant somatic hypermutation in HCV-associated MC and B-NHL. [ABSTRACT FROM AUTHOR]

γδ T cells account for up to 10% of T lymphocytes in the peripheral blood of healthy donors. They can be activated by cytokines such as interleukin (IL)-2, IL-12 and IL-15, express natural killer (NK) cell markers such as NKG2D and show cytotoxic activity against several tumour cells, including multiple myeloma. Here, we present activated polyclonal γδ T cells from healthy donors with an NK T cell-like phenotype expressing the natural cytotoxicity receptor NKp44. Natural cytotoxicity receptors NKp30, NKp44 and NKp46 have been regarded as specific NK receptors; only two γδ T cell clones described so far expressed NKp44. Isolated polyclonal γδ T cells cultured for 7 days according to the cytokine-induced killer cell (CIK) protocol with additional IL-15 revealed a surface expression of NKp44 of 8 ± 7% ( n = 22). This could be confirmed by detection of NKp44 mRNA by reverse transcription–polymerase chain reaction (RT–PCR). γδ T cells exhibited a marked cytotoxic activity against myeloma cells, which could be reduced by inhibition of NKp44. To our knowledge, this is the first description of the expression of NKp44 on polyclonal γδ T cells. [ABSTRACT FROM AUTHOR]

Introduction: Impaired activity of natural killer (NK) cells has been proposed as a mechanism contributing to viral persistence in hepatitis C virus (HCV) infection. As the function of NK cells is primarily regulated by NK cell receptors (NKR), we analysed whether decreased NK cell function in hepatitis C may be related to dysregulated NKR expression. Patients and methods: Expression of NK cell was analysed by flow cytometry on lymphocytes from HCV(+) subjects (n=30), patients who became HCV(-) after antiviral therapy (n = 10), healthy individuals (n = 10), and hepatitis B virus (HBV) infected patients (n = 9). Cytolytic function of lymphocytes was studied in a redirected lysis assay and in a standard 51chromium release cytotoxicity assay, respectively. Results: In patients with chronic hepatitis C, we found a significantly reduced proportion of NKp46 and NKp30 expressing NK cells compared with healthy and HBV infected subjects. Low expression of natural cytotoxicity receptor (NCR) was also confirmed in in vitro activated NK cell populations derived from HCV patients compared with uninfected donors. In contrast, patients who cleared HCV under antiviral therapy showed normal expression of NKp44, NKp30, and NKp46. Reduced NCR expression in chronic hepatitis C was associated with a parallel decrease in NCR mediated target cell killing. Furthermore, we found a significantly increased proportion of NKG2A expressing NK cells and CD8+ T cells in HCV positive patients, resulting in a reduced cytolytic activity against cells incubated with the HLA-E stabilising peptide HCV core35-44. Conclusion: The present study indicates that defective expression of NKR represents a novel mechanism contributing to impaired function of NK cells and CD8+ T cells in chronic hepatitis C. [ABSTRACT FROM AUTHOR]

The C-type lectin DC-SIGNR has been shown to bind hepatitis C virus (HCV). Here, we analysed the tandem-repeat polymorphism of the DC-SIGNR gene with respect to intraindividual HCV replication. In a cross-sectional comparison HCV-infected patients ( n = 430) and healthy subjects ( n = 100) were genotyped for the DC-SIGNR polymorphism using PCR. The distribution of DC-SIGNR alleles did not differ significantly between the two groups. However, HCV-infected patients with 5-, 6-, and 7-repeat alleles had higher HCV-RNA levels when compared with carriers of 4- and 9-repeat alleles ( P < 0.05). Thus, the DC-SIGNR polymorphism might affect HCV loads supporting the concept that DC-SIGNR contributes to HCV replication efficacy. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection has been shown to be associated with reduced expression of the CC chemokine receptor (CCR) 5, and reduced responsiveness of lymphocytes to chemokines. However, the mechanism by which HCV alters CCR5 expression remains unclear. Here, we investigated whether altered CCR5 expression in hepatitis C results from interactions of CD81 with the HCV E2 protein. Peripheral blood mononuclear cells (PBMC) from HCV-negative individuals were prepared by Ficoll density gradient separation. PBMC subpopulations (CD4+, CD8+ lymphocytes, CD19+ B cells, natural killer (NK) cells and monocyte-derived dendritic cells) were isolated and stimulated with immobilized HCV E2, and changes in CCR5 expression and CC-chemokine secretion were determined. Migration assays were performed using a 5-μm nitrocellulose filter microchamber system according to the manufacturer's recommendations. Exposure of PBMC to HCV E2 induced a dose-dependent release of regulated on activation normal T-cell-expressed and secreted (RANTES), down-regulation of CCR5 expression and intracellular accumulation of CCR5. This effect was blocked by preincubation of PBMC with anti-CD81. RANTES release following exposure to HCV E2 was mainly attributable to CD8+ cells. After exposure to HCV E2 markedly fewer CD8-positive lymphocytes were attracted by RANTES when compared with CD8+ cells that were studied in the absence of HCV E2. Our results suggest that interaction of HCV E2 with CD81 leads to increased RANTES secretion by CD8+ lymphocytes which induces down-regulation of CCR5 surface via receptor internalization resulting in altered lymphocyte migration. [ABSTRACT FROM AUTHOR]

We investigated spatial pulsations in a cylindrical arc plasma column in the electric current range I = 100–200 A and gas flow rate G = 4–8 g s-1. The distribution functions of these pulsations were obtained. On the basis of experimental results we proposed a model for the description of the pulsations. In this model, the axis of the arc O' participates at the same time on two movements: random pulsation and rotation of the column axis. The lateral and radial intensities and radial temperatures were calculated for different rotation radii and standard deviations. For this study, the spectral line of Ar I 415.8 nm was chosen. Experimental and theoretical results are in good agreement. [ABSTRACT FROM AUTHOR]

Legrand A, Vadrot N, Lardeux B, Bringuier AF, Guillot R, Feldmann G. Study of the effects of interferon α on several human hepatoma cell lines: analysis of the signalling pathway of the cytokine and of its effects on apoptosis and cell proliferation. Liver International 2004: 24: 85–89. © Blackwell Munksgaard 2004 Interferon α (IFNα), currently used for the treatment of chronic viral hepatitis, is also known to prevent the development of hepatocellular carcinoma (HCC), the mechanism of this action being still debatable. To study thoroughly in human hepatoma cell lines (HHL) – Hep3B, HepG2, HuH7, SKHep1, and Chang-Liver – submitted to rhIFNα, the signalling pathway of IFNα, the binding activity of the cytokine on specific gamma-activated sequence (GAS) and interferon-stimulated regulatory element (ISRE) nuclear sequences, and its effects on apoptosis and cell proliferation. The behaviour of signal transducer and activator of transcription (STAT)1, STAT2, p48IRF9 and the binding of nuclear proteins were investigated by immunoblot and electro-mobility shift assay. Expression of some IFNα-dependent proteins – p21/WAF1, inducible nitric oxide synthase, IRF1 and 2 – were studied by immunoblot. Apoptosis and the cell cycle were studied by morphological and biochemical methods. Transduction of INFα was unaltered, although there were some variations in the different HHL. Nuclear protein binding to GAS or ISRE showed that ISRE was mainly involved. Apoptosis did not occur. The cell cycle was slightly modified in HuH7. Three GAS- and/or ISRE-dependent proteins increased, suggesting that IFNα may have some biological effects on HHL. The IFNα signalling pathway is functional in several HHL, but the cytokine has no apoptotic effect and a moderate anti-proliferative effect. This suggests that the preventive role of IFNα on HCC cannot be explained by an apoptotic and/or an anti-proliferative effect, but possibly by its action on several specific nuclear sequences that protect liver cells from transformation. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) has been detected in sperm, but no data are available on follicular fluid (FF) collected on IVF procedures. The aim of this study was to: (i) search for HCV RNA in FF and in culture media at each step of IVF undergone by HCV(+) women; (ii) investigate the impact of blood contamination of FF induced by vascular injury associated with transvaginal ovarian puncture; (iii) assess risk for the embryo and the impact on the contamination rate of the newborn; and (iv) determine the viral risk presented by these fluids in order to define guidelines for the laboratory.Methods: FF from 22 IVF procedures performed in 17 HCV(+) women were classified as either clear, lightly bloody or bloody FF. Oocytes from each FF were washed and incubated in separated fertilization media. At 20 h after puncture (day 1), the fertilized oocytes were washed and transferred to fresh media until embryo transfer. HCV RNA was detected and quantified in FF and media using Cobas Amplicor and Cobas Monitor HCV RNA kits.Results: HCV RNA was positive in 39 of 44 FF samples, and viral loads increased with blood contamination. At day 1, after rinsing of oocyte-cumulus complexes, only 8 of 44 media were still positive. Viral loads were quantified in 5 of 8 positive media, were below the test sensitivity threshold in 4 of 5 HCV RNA-positive media, and just above it in the fifth medium. The day of transfer HCV RNA was undetectable in all media.Conclusions: HCV RNA was detected in 89% of FF irrespective of the degree of blood contamination, and in 25% of the media at day 1. FF must be considered as potentially infected. Blood contamination increases HCV load in the FF. Rinsing oocytes seems significantly to discard the HCV RNA. It is too early to assess the impact of IVF on the contamination rate of HCV mothers' offspring. After counselling, attempting IVF in HCV(+) women is justified. Universal guidelines prevent nosocomial infection, and IVF does not specifically increase the professional risk. [ABSTRACT FROM AUTHOR]

Background: Our objective was to use an adapted RT-PCR technique to assess the presence of hepatitis C virus (HCV) in semen and also in different density gradient semen fractions collected from men with chronic viral hepatitis participating in an assisted reproduction programme.Methods: This study included 50 semen samples from 35 HCV(+) men, with active viral replication assessed by RT-PCR, collected the day of oocyte retrieval and used for assisted reproduction. These samples were subjected to standard assisted reproduction sperm preparation conditions, using density-gradient centrifugation with 45 and 90% layers. Aliquots of semen, 45 and 90% fractions, and embryo culture media were frozen at -80 degrees C for subsequent virological analyses. All aliquots were tested with a commercially available HCV RNA assay, adapted for use with semen after a number of technical changes. This assay yielded a sensitivity of 50-100 HCV RNA copies/ml and strongly diminished the effect of seminal amplification inhibitors.Results: HCV RNA was detected in 7/50 (14%) semen samples tested, 5/35 (14.3%) men. HCV RNA was found in only 1/50 45% fractions but never in the 90% fraction or embryo culture media. Sera from 3/5 men contained 3.19-7.40 x 10(5) IU/ml, while the two others had 4.5 and 11.7 x 10(6) IU/ml. However, HCV RNA was quantified at <600 IU/ml in the HCV(+) semen of these five patients. The ongoing pregnancy rate was of 20% (10/50) with one delivery at the time of the present report. No anti-HCV antibody was found in any of the women or the newborn.Conclusions: Although HCV is present at low concentrations in the semen of a few HCV(+) patients, no purified sperm fraction (i.e. 90% fraction) used in assisted reproduction was HCV(+) and no seroconversion was observed in the women and the newborn, thereby suggesting a very low risk of virus transmission. Nevertheless, because the presence of HCV in semen implies a possible risk of nosocomial contamination, safety regulations must be strictly applied in assisted reproduction laboratories. [ABSTRACT FROM AUTHOR]

Atractyloside (Atr) binds to the adenine nucleotide translocator (ANT) and inhibits ANT-mediated ATP/ADP exchange on the inner mitochondrial membrane. In addition, Atr can trigger opening of a non-specific ion channel, within the ANT-containing permeability transition pore complex (PTPC), which is subject to redox regulation and inhibited by cyclosporin A (CsA). Here we show that the cytotoxic effects of Atr, both in vivo and in vitro, are determined by its capacity to induce PTPC opening and consequent mitochondrial membrane permeabilization (MMP). Thus, the Atr-induced MMP and death of cultured liver cells are both inhibited by CsA as well as by glutathione (GSH) and enhanced by GSH depletion. Similarly, the hepatorenal toxicity of Atr, assessed in vivo, was reduced by treating mice with CsA or a diet rich in sulfur amino acids, a regime which enhances mitochondrial GSH levels. Atr injection induced MMP in hepatocytes and proximal renal tubular cells, and MMP was reduced by either CsA or GSH. Acetaminophen (paracetamol)-induced acute poisoning was also attenuated by CsA and GSH, both in vitro and in vivo. Altogether these data indicate that PTPC-mediated MMP may determine the hepatorenal toxicity of xenobiotics in vivo. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the relationship between the apoptosis percentage of human luteinized granulosa cells (GC) and the presence of hepatitis C virus (HCV) in follicular fluid (FF).Methods: GC were isolated from FF of 12 women undergoing 12 IVF cycles: six were HCV+ with active viral replication and six HCV- serving as controls. No male partner was HCV+. HCV detection and quantification were assessed by reverse transcriptase-polymerase chain reaction in serum, FF and embryo-incubation medium. GC were analysed by flow cytometry after propidium iodide staining to measure the percentages of apoptotic GC. Routine IVF parameters were tabulated.Results: Mean +/- standard deviation (SD) serum and FF HCV viral loads were 3.58 +/- 4.25 x 10(6) and 0.14 +/- 0.10 x 10(6) IU/ml respectively. Mean percentages of apoptotic GC from HCV+ and HCV- women were 3.08 +/- 1.14 and 3.14 +/- 1.40% respectively. No statistically significant difference was found between these two groups concerning GC apoptosis and when we compared all IVF parameters. No HCV RNA was detected in embryo incubation media after 2 days of culture.Conclusions: Comparing GC apoptosis percentages and usual IVF parameters in the HCV+ group versus the HCV- group, our preliminary study shows that active chronic HCV infection does not affect follicle development and IVF outcome in HCV+ women undergoing IVF. Furthermore, the risk of newborns becoming HCV-infected might not be increased by assisted reproductive technologies when performed in couples in which women are HCV+ and men HCV-. [ABSTRACT FROM AUTHOR]

Background: Because apoptosis may be involved in the outcome of IVF, the expression of pro- and anti-apoptosis proteins in a model of induced granulosa cell (GC) apoptosis was evaluated in 25 women with normal FSH levels undergoing IVF.Methods: After 1 day of culture, apoptosis was induced with interferon (IFN)-gamma (200 IU/ml), followed 24 h later by an agonistic anti-Fas antibody (0.5 microg/ml). On day 3, apoptotic GC, identified by chromatin condensation and/or nuclear fragmentation after DAPI staining, were counted among 1000 cells in randomly chosen fields under UV microscopy, and enabled allocation of women into two groups with either low (group 1) or high (group 2) percentages of apoptosis (11.6 +/- 4.8 and 59.5 +/- 14.8% respectively; P < 0.001). Immunoblotting was used to evaluate the following in proteins: poly (ADP-ribose) polymerase (PARP), caspases 8 and 3, Bcl-2, heat shock protein (HSP) 70, Bax, Bak and Stat-1 (a protein known to be inducible by IFN-gamma).Results: Based on densitometric analysis of immunoblots, the PARP 116 kDa bands were respectively 4.3- and 33.3-fold lower for treated groups 1 and 2. Caspase 8, caspase 3 and HSP70 were expressed slightly less in treated group 2 than treated group 1. Densitometric analysis of bands corresponding to Bcl-2 showed respectively for treated groups 1 and 2, 3.2- and 2.5-fold decreases. Bak expression was similar in both control groups, and comparably lower in the two treated groups. With regard to Stat-1, densitometry showed 3.3- and 1.3-fold increases respectively in treated groups 1 and 2.Conclusions: These results suggested that Fas-mediated apoptosis of GC is accompanied by significant changes in proteins acting in apoptosis, and that this type of programmed cell death might play a potential prognostic role for women undergoing IVF. [ABSTRACT FROM AUTHOR]

Background: The aim of our study was to measure concentrations of vascular endothelial growth factor (VEGF), platelet endothelial cell adhesion molecule-1 (PECAM-1) CD31 and vascular cell adhesion molecules (VCAM-1) in the follicular fluid of women treated with assisted reproduction technology to determine whether these proteins might be outcome markers.Methods: Follicular fluid was collected from 75 patients < or =40 years undergoing oocyte retrieval procedures at our tertiary hospital during 1997 and 1998: 50 with tubal disease, 12 with endometriosis, and 13 whose partners had been diagnosed with severe oligoasthenoteratozoospermia. This retrospective analysis considered age and information about treatment and outcome for all these women who had undergone fewer than three assisted reproduction attempts.Results: Nineteen women became pregnant (defined by human chorionic gonadotrophin concentrations and embryonic cardiac activity 1 month after follicular aspiration); 56 did not. Women did not differ significantly in their follicular fluid concentrations of VEGF, sCD31 and VCAM-1 according to cause of infertility, or assisted reproduction outcome, or age. Follicular fluid concentrations of VEGF were significantly correlated with the number of gonadotrophin ampoules administered (P < 0.012), and follicular fluid concentrations of sVCAM-1 with the fertilization rate (P < 0.01). Follicular fluid concentrations of VEGF and sVCAM-1 were also correlated (P < 0.007).Conclusions: Our results do not suggest that VEGF, CD31, or sVCAM-1 in follicular fluid predict assisted reproduction outcome, especially among patients < or =40 years old. The correlation of a high fertilization rate and sVCAM-1 in follicular fluid suggests that sVCAM-1 might be a marker of fertilization. [ABSTRACT FROM AUTHOR]

The aim of this preliminary experimental study was to test the stability of cryopreservation straws to human immunodeficiency virus-1 (HIV-1). Three kinds of straws were tested: four polyvinyl chloride (PVC), four polyethylene terephthalate glycol (PETG) and 20 high-security ionomeric resin (IR). The PVC and PETG straws were sealed ultrasonically, and the IR straw by thermosoldering. Each sealed straw was cut in half to produce two demi-straws and then filled with 100 microl of HIV-1-containing supernatant (reverse transcriptase activity: 15 000 c.p.m./50 microl). The unsealed cotton end of PVC and PETG straws and the two halves of the IR straws (cotton and plastic plug ends) were tested. Each demi-straw was two- thirds submerged in RPMI medium at 37 degrees C, and RPMI samples were withdrawn on days 3, 7 and 11. Viral RNA was extracted from the medium and then amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) followed by nested PCR using primers specific to HIV-1 protease. On day 7, no HIV-1 RNA was detected in any of the different samples of medium that had surrounded the unsealed PVC and PETG straws with cotton ends, but three IR specimens were positive. On day 11, PVC and PETG remained negative but HIV-1 RNA was detected in RPMI samples for two more IR demi-straws (n = 5). In conclusion, under these experimental conditions (at 37 degrees C), the unsealed cotton end PVC, PETG and thermosoldered cotton end IR demi-straws appeared to be safe for HIV-1, while IR straws, sealed or unsealed with a plastic plug and with unsealed cotton ends, leaked. [ABSTRACT FROM AUTHOR]

The influence of the pulsation of a plasma torch over the lateral intensity of the radiation and the radial temperature profile was studied. For the case of pulsation of the axis of a torch following a Gaussian distribution the exact integral equation was obtained relating the lateral intensity with and without pulsation. For a particular case the lateral distributions of radiation intensity were calculated for three different values of the Gaussian standard deviation. For the spectral line ArI 435.8 nm the radial temperature distributions with and without pulsations were calculated. The results show how pulsations can affect experimental results. [ABSTRACT FROM AUTHOR]

Objective and design: To determine whether the inhibition of RNA breakdown observed in ad libitum fed rats 24 h after turpentine administration [1] still occurs in inflamed rats fasted for 24 h and to examine the mechanism and factors involved.¶ Methods: RNA breakdown was measured during cyclic in situ perfusion of livers by the accumulation of [14C] cytidine after in vivo RNA labelling. Autophagic activity was determined by the morphometric analysis of lysosomal structures.¶ Results: The decrease in RNA breakdown (53%) observed in the inflamed rats was accompanied by a 38% drop in the fractional cytoplasmic volume of initial and digestive autophagic vacuoles. Among amino acids, only the portal levels of glutamate were significantly enhanced by 83%. In vivo suppression of glucocorticoid activity using RU 38486 in inflamed rats did not affect the inhibition of RNA breakdown.¶ Conclusions: The results show that turpentine-induced inflammation in fasted rats inhibits RNA degradation as well as autophagy and that glucocorticoids do not seem to be involved. [ABSTRACT FROM AUTHOR]

By using polyethylene glycol precipitation at low concentration (PEG test) and the radiolabeled C1q binding test, immune complexes were detected in sera from acute (23/28) and chronic (28/32) hepatitis patients, hemodialyzed patients with chronic hepatitis B surface (HBs) antigenemia (7/19), and asymptomatic HBs antigen carriers (2/11). After treatment of PEG precipitates with acidic pH, heating, or proteolytic enzyme (protease), electroimmunodiffusion or radioimmunoassay revealed the presence of HBs antigen or antibody in dissociated immune complexes in sera from several acute and chronic hepatitis patients. Electron microscopy showed immune complexes of HB virus in 9 of 12 PEG precipitates obtained from PEG-test-positive sera; these 9 precipitates were from patients with acute or chronic hepatitis and the other three from chronic HBs Ag carriers. Free HB virus particles were observed after protease digestion of PEG precipitates. Neither immune complexes nor virus particles were seen in precipitates from PEG-test-negative but HBs-Ag-positive sera from chronic carriers. [ABSTRACT FROM AUTHOR]

A case of apolipoprotein B-related disorder is reported in which liver fibrosis developed without long term administration of medium chain triglycerides, previously incriminated in the pathogenesis of this lesion. The patient was a young woman in whom the diagnosis of familial homozygous hypobetalipoproteinaemia was made at the age of 21. A first liver specimen taken at diagnosis revealed steatosis, hypertrophic Golgi apparatus and proliferating smooth endoplasmic reticulum. The patient was treated with vitamin A and E supplementation only. Two years later, a second liver biopsy, carried out because of increased serum alanine aminotransferase concentrations, showed fibrosis, mild cytolysis and marked mitochondrial alterations. Hepatic level of vitamin A was increased. This finding supports the hypothesis that liver disease observed in our patient might be an adverse effect of vitamin supplementation. Our observation underlines the importance of including liver function tests in the follow up of patients with apolipoprotein B-related disorders. [ABSTRACT FROM PUBLISHER]

A prospective series of 45 liver biopsies taken from 22 renal transplant patients was investigated for the presence of hepatitis B antigen core (HBc) and surface (HBs) components by electron microscopy. At the time of each biopsy serum HBs Ag was sought by radioimmunoassay. Sections were taken for the detection of HBs Ag by immunofluorescence. In seropositive patients, intravesicular tubular structures resembling HBs Ag were found in 61% of biopsies while the intranuclear core HBc was present in 69%. No correlation could be made between the ultrastructural pattern of the viral components and the intensity of the histological liver damage. During the follow up, there was an accumulation of both HBs and HBc Ag even in a period as short as 1 year. The 9 liver specimens examined after three years of transplantation showed a marked accumulation of both antigens. Thus the expression of HB Ag at the hepatocellular level seems to correlate better with the duration of antigenaemia than with the histological pattern. Lastly, on matched semithin and ultrathin sections, the ground glass appearance of cytoplasm appeared to correlate with smooth endoplasmic reticulum distorsion, irrespective of the simultaneous presence or absence of intravesicular tubular structures. The sanded nuclei expressed a rare massive accumulation of core antigen. [ABSTRACT FROM AUTHOR]

Liver electron microscopic studies were performed in 14 patients with systemic scleroderma. In 13 of these patients, giant mitochondria were demonstrated in the hepatocytes. This ultrastructal abnormality was present whatever the type and duration of the disease and was also present even when the liver was histologically normal. The mechanism of formation of giant mitochondria in systemic scleroderma is unknown. [ABSTRACT FROM AUTHOR]

ABSTRACT: Diethylmaleate is used as a model compound whose glutathione conjugates are secreted into bile, and which induce choleresis and the formation of Golgi-derived vesicles in hepatocytes. This study was performed to test the assumption that these vesicles are involved in the bile canalicular secretion of diethylmaleate. We reasoned that phalloidin and colchicine, two drugs acting on microfilaments and microtubules, respectively, can modify the movements of diethylmaleate-induced vesicles towards the bile canaliculus. Phalloidin induced the formation of a thick microfilamentous network around the bile canalicular plasma membrane domain. A significant decrease in diethylmaleate-stimulated choleresis was observed, associated with a striking accumulation of pericanalicular vesicles, which were confirmed by morphometric analysis. In contrast, in rats pretreated with colchicine, after diethylmaleate administration, only a few vesicles were observed around the bile canaliculus, while diethylmaleate-induced choleresis also decreased. These results suggest that: a) the thick microfilament network induced by phalloidin prevents diethylmaleate-associated vesicles reaching the bile canalicular plasma membrane; and b) colchicine produces a dispersion of these vesicles in the cytoplasm of hepatocytes by inhibiting the polymerization of microtubules. These observations support a role of vesicles in the transport of diethylmaleate by hepatocyte into bile, and are consistent with the existence of a vesicular pathway for the biliary secretion of diethylmaleate and possibly other organic anions. [ABSTRACT FROM AUTHOR]

ABSTRACT- 1) A NANB agent of human origin was inoculated in HBV-immunized chimpanzees. Infection was proven in two animals and serially passed to two others. The absence of anti-HBc in serum and the absence of HBsAg and HbcAg in liver are arguments against the HBV nature of the transmitted infection. Moreover, the reproducible appearance of the NANBcAg/Ab system at each passage from man to chimpanzee and from chimpanzee to chimpanzee, a response not elicited in control animals, suggests that this reaction may be a specific immunologic marker for the strain. 2) NANB infection was transmitted in all chimpanzees. 3) Distinctive hepatic morphologic features were obtained in the liver biopsies of the human donor and the inoculated chimpanzees: eosinophilic alterations of hepatocytes and numerous inflammatory cells. Inflammation was more prominent than necrosis, appearing earlier and lasting longer, but was not topographically close to the eosinophilic changes. 4) On electron microscopy, particles characteristic of NANB agent were observed in the cytoplasm of the hepatocytes. No particles were demonstrated in the nucleus of these cells. [ABSTRACT FROM AUTHOR]

Histoenzymological techniques were used to examine ATPase activity in rat heart muscle fibres after experimental infarction. 24 hours after coronary ligation, ATPase activity in all ventricular section fibres was high, homogeneous at pH 9.4 and inhibited by acid preincubation, and the same was observed for control heart sections. 48 hours after ligation, necrotic ventricular fibres appeared, leaving only a thin layer of fibres which had apparently preserved their myofibrillar ATPase. These results indicate that, unlike mitochondrial enzyme activity, myofibrillar ATPase activity is relatively resistant to ischaemia. [ABSTRACT FROM AUTHOR]

We report the cases of two renal transplant recipients suffering from idopathic portal hypertension, a condition characterised by increased portal venous pressure in the absence of both histological lesion of the liver and obstruction of the portal vein. In these two patients, perisnusoidal fibrosis, invisible by light microscopy, was demonstrated by electron microscopy; it is suggested that partial obstruction of hepatic sinusoids by perisinusoidal fibrosis could be the mechanism for increased portal venous pressure in all the patients with idiopathic portal hypertension. In these two patients, who received 6-mercaptopurine and azathioprine, perisinusoidal fibrosis might be the consequence of prolonged administration of these drugs. [ABSTRACT FROM PUBLISHER]

The ultrastructural appearance of the endoplasmic reticulum of the hepatocytes was found to be normal in a 5-year-old girl with alpha-1-antitrypsin deficiency with the genotype Pi--. The liver ultrastructure of this variant is therefore different from that of alpha-1-antitrypsin deficiency with the genotype PiZZ in which aggregates of an abnormal, unsecreted alpha-1-antitrypsin accumulate in the endoplasmic reticulum of the hepatocytes. The normal appearance of the endoplasmic reticulum in alpha-1-antitrypsin deficiency with the genotype Pi-- is compatible with the hypothesis, in this variant, synthesis of alpha-1-antitrypsin is completely, or nearly completely, absent; an alternative hypothesis would be that an abnormal alpha-1-antitrypsin is produced by the liver and secreted into the plasma, but disappears rapidly from the plasma. [ABSTRACT FROM PUBLISHER]

The possibility of detecting specific mRNA directly within tumor cells offered by the in situ hybridization (ISH) technique has provided a new dimension to the study of experimental and human hepatocarcinogenesis. The combination of ISH and immunocyto-chemical techniques on the same or adjacent tissue sections provides a more complete picture of the various changes in gene expression. ISH may also detect posttranscriptional abnormalities of gene expression at the cellular level, such as expression of mRNA with no protein translation, or translation with decreased efficiency. Undoubtedly, the development of the ISH technique will open a new area for the understanding of the complex molecular events leading to cancer. Copyright © 1990 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The potential of the soluble forms of the adhesion molecules ICAM-1 (sICAM-1), CD44std (sCD44std) and E-cadherin (sE-cadherin) was tested for the diagnosis of benign and malignant cystic epithelial tumours of the ovary. Concentrations of sICAM-1, sCD44std and sE-cadherin were measured by enzyme-linked immunosorbent assay (ELISA) in the serum and cyst fluid obtained from 23 patients with luteal cysts, 29 with cystadenomas, nine with dermoid cysts, five with borderline tumours and 11 with carcinomas. Serum concentrations of sICAM-1, but not of sCD44std and sE-cadherin, were constantly elevated compared with normal controls. Cyst fluid concentrations of sICAM-1, sCD44std and sE-cadherin were elevated in borderline and malignant tumours compared with cystadenomas (P = 0.034, 0.006 and 0.001, respectively). In conclusion, our results suggest that serum concentrations of adhesion molecules have no diagnostic value in ovarian tumours, whereas cyst fluid concentrations may facilitate distinction between benign lesions and borderline or malignant tumours. [ABSTRACT FROM PUBLISHER]

Methotrexate has been proposed as a treatment for unruptured extra-uterine pregnancy, but its effects on the tubal wall remain unknown. In order to analyse these effects, an experimental study was carried out on two groups of pregnant female rats, one receiving methotrexate (n = 8) and the other sodium chloride (n = 6). In both groups, a single intra-embryonic injection was performed in the uterine horn. The genital tract was prepared for histological examination. In all rats which received a single dose of methotrexate (5 mg per 100 g body weight) six days after mating and were killed nine days later, the labyrinthine part and the junctional zone of the placenta were necrotic at the site of the injection, with no embryonic development. The other parts of the genital tract were not visibly altered. In rats receiving sodium chloride and killed under the same conditions, necrosis of the placenta was observed at the site of injection in three animals. In the other three rats, a focal necrosis of the placenta was found, which was probably of mechanical origin. From this study, we conclude that methotrexate is efficient in killing normally implanted embryos and is, at least under light microscopy, non-toxic to the adjacent portions of the genital tract. [ABSTRACT FROM AUTHOR]