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Background:Variations in systemic inflammatory response biomarker levels have been associated with adverse clinical outcome in various malignancies. This study determined the prognostic significance of preoperative neutrophil:lymphocyte (NLR), platelet:lymphocyte (PLR) and monocyte:lymphocyte (MLR) ratios in endometrial cancer.Methods:Clinicopathological and 5-year follow-up data were obtained for a retrospective series of surgically treated endometrial cancer patients (n=605). Prognostic significance was determined for overall (OS) and cancer-specific survival (CSS) using Cox proportional hazards models and Kaplan-Meier analysis. Receiver-operator characteristic and log-rank functions were used to optimise cut-offs. NLR, PLR and MLR associations with clinicopathological variables were determined using non-parametric tests.Results:Applying cut-offs of ⩾2.4 (NLR), ⩾240 (PLR) and ⩾0.19 (MLR), NLR and PLR (but not MLR) had independent prognostic significance. Combining NLR and PLR scores stratified patients into low (NLR-low and PLR-low), intermediate (NLR-high or PLR-high) and high risk (NLR-high and PLR-high) groups: multivariable hazard ratio (HR) 2.51; P<0.001 (OS); HR 2.26; P<0.01 (CSS) for high vs low risk patients. Increased NLR and PLR were most strongly associated with advanced stage (P<0.001), whereas increased MLR was strongly associated with older age (P<0.001).Conclusion:Both NLR and PLR are independent prognostic indicators for endometrial cancer, which can be combined to provide additional patient stratification. [ABSTRACT FROM AUTHOR]

Background: Premenstrual syndrome (PMS) is a common condition. Some of the most widely prescribed medications are selective serotonin reuptake inhibitors (SSRIs), based on the hypothesized role of serotonin in the production of PMS symptoms. PMS sufferers, especially those experiencing mild to moderate symptoms, are often reluctant to take this form of medication and instead buy over-the-counter preparations to treat their symptoms, for which the evidence base with regard to efficacy is limited. Hypericum perforatum (St John's wort) influences the serotonergic system. As such, this widely available herbal remedy deserves attention as a PMS treatment.Objective: To investigate the effectiveness of Hypericum perforatum on symptoms of PMS.Study Design: This randomized, double-blind, placebo-controlled, crossover study was conducted between November 2005 and June 2007.Setting: Institute of Psychological Sciences, University of Leeds, Leeds, UK.Participation: 36 women aged 18-45 years with regular menstrual cycles (25-35 days), who were prospectively diagnosed with mild PMS.Intervention: Women who remained eligible after three screening cycles (n = 36) underwent a two-cycle placebo run-in phase. They were then randomly assigned to receive Hypericum perforatum tablets 900 mg/day (standardized to 0.18% hypericin; 3.38% hyperforin) or identical placebo tablets for two menstrual cycles. After a placebo-treated washout cycle, the women crossed over to receive placebo or Hypericum perforatum for two additional cycles.Main Outcome Measures: Symptoms were rated daily throughout the trial using the Daily Symptom Report. Secondary outcome measures were the State Anxiety Inventory, Beck Depression Inventory, Aggression Questionnaire and Barratt Impulsiveness Scale. Plasma hormone (follicle-stimulating hormone [FSH], luteinizing hormone [LH], estradiol, progesterone, prolactin and testosterone) and cytokine (interleukin [IL]-1beta, IL-6, IL-8, interferon [IFN]-gamma and tumour necrosis factor [TNF]-alpha) levels were measured in the follicular and luteal phases during Hypericum perforatum and placebo treatment.Results: Hypericum perforatum was statistically superior to placebo in improving physical and behavioural symptoms of PMS (p < 0.05). There were no significant effects of Hypericum perforatum compared with placebo treatment for mood- and pain-related PMS symptoms (p > 0.05). Plasma hormone (FSH, LH, estradiol, progesterone, prolactin and testosterone) and cytokine (IL-1beta, IL-6, IL-8, IFNgamma and TNFalpha) levels, and weekly reports of anxiety, depression, aggression and impulsivity, also did not differ significantly during the Hypericum perforatum and placebo cycles (p > 0.05).Conclusion: Daily treatment with Hypericum perforatum was more effective than placebo treatment for the most common physical and behavioural symptoms associated with PMS. As proinflammatory cytokine levels did not differ significantly between Hypericum perforatum and placebo treatment, these beneficial effects are unlikely to be produced through this mechanism of action alone. Further work is needed to determine whether pain- and mood-related PMS symptoms benefit from longer treatment duration. Trial registration number (International Standard Randomised Controlled Trial Number Register) ISRCTN31487459. [ABSTRACT FROM AUTHOR]

The JC virus (JCV) is generally considered the etiological agent of progressive multifocal leukoencephalopathy (PML), a demyelinating brain illness, often associated with immunosuppression and significantly frequent in acquired immunodeficiency syndrome (AIDS) patients. The primary infection by JCV is usually asymptomatic and the virus can remain in a latent status in the kidney. As a consequence of immunological alterations of the host, the virus can show a genetic variability in the noncoding control region (NCCR) due to deletions, duplications, and insertions as compared with the archetype. The NCCR of the archetype strain can be divided into six regions, named boxes A to F. In this study, the authors evaluated the presence of the JCV genome in different biological samples, such as urine, peripheral blood mononuclear cells (PBMCs) and cerebral spinal fluid (CSF) by means of polymerase chain reaction (PCR). After sequencing of the PCR fragments, the NCCR structure of isolated JCV strains was analyzed in order to verify the presence of different viral variants. An analysis of the homology and of the multiple alignment of the obtained sequences in comparison with the archetype strain has been carried out. The results indicated the presence of different rearrangements among the analyzed samples. Whereas in the urine, the NCCR structure always appeared very similar to that of the archetype, in the PBMCs and CSF, the NCCR sequences showed specific and characteristic rearrangements as compared to the archetype. These different rearrangements could be correlated with the emerging of an NCCR organization more suitable for the development of PML. [ABSTRACT FROM AUTHOR]

The effect of some cellular function inhibitors on hepatitis A virus (HAV) adsorption and on the successive events of infection in a monkey cell line (Frp/3 cells) was investigated. Treatments of Frp/3 cells with colcemide, vinblastine and cytochalasin D, which affect cytoskeleton organization, indicated that neither microtubules nor microfilaments play an important role in the early events of HAV infection. Monensin, which acts as an ionophore on intracellular vesicle compartments inhibited HAV infection probably at the uncoating step. Inhibition of viral replication to a different degree was observed with both inhibitors of oxidative phosphorylation, such as dinitrophenol and sodium azide, and with an inhibitor of glycolysis, 2-deoxy-D-glucose. However, none of these compounds significantly affected the early steps of infection, thus demonstrating that HAV replication is largely dependent upon cell energy. [ABSTRACT FROM AUTHOR]

Membrane receptors for rubella virus (RV) in Vero cells were studied by means of two different approaches: (i) by enzyme treatment of the whole cell membrane and (ii) by testing the ability of isolated plasma membrane molecules to compete with cells for virus binding. The replication of RV was studied with both indirect immunofluorescence assay and molecular hybridization techniques. Phospholipases A2 and C digestion of cells greatly reduced the infectivity by the virus, pointing towards the involvement of lipid structures as receptor sites for RV. Furthermore, susceptibility of Vero cells to virus infection was also reduced after β- N-acetyl- d-glucosaminidase, α-glucosidase and β-galactosidase treatment, suggesting that carbohydrate residues may participate in a complex cellular receptor structure for RV. When the major membrane lipids were examined separately for their ability to inhibit viral infectivity, several phospholipids (phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, phosphatidylcholine, sphingomyelin) and glycolipids (gangliosides, lactosylceramide, cerebroside sulphate) showed a strong neutralizing activity, confirming the role of membrane lipid moiety in the cell surface receptor for RV. [ABSTRACT FROM AUTHOR]

The antibacterial activity of metal complexes of ovotransferrin was tested 'in vitro' against different bacterial species and the Zn saturated ovotransferrin appeared to be the most active by comparison with the apo-protein and other metal complexes. Appropriate controls showed that such an effect was neither due to Zn ions, nor to iron deprivation, but to a specific activity of the Zn-ovotransferrin complex. This antibacterial activity required a direct contact of Zn-ovotransferrin with the bacterial surface. In vivo experiments confirmed the higher antibacterial activity of Zn-ovotransferrin as compared with the apo-form. [ABSTRACT FROM AUTHOR]

Research has been carried out in order to clarify the chemical nature of cell receptors interacting with a fast growing strain of hepatitis A virus (HAV) producing a cytopathic effect on Frp/3 cells. Cell surface susceptibility to HAV attachment has been studied after treatment with enzymes acting on different chemical groupings. Results obtained showed a lowering of cell susceptibility to HAV infection following the action of phospholipase A, phospholipase C, trypsin and β-galactosidase. These data suggested that phospholipids, proteins and galactose participate to the cellular receptorial area for HAV. [ABSTRACT FROM AUTHOR]

To clarify the role of electrostatic interactions in the binding of Sindbis virus (SNV) to cell membrane receptors, we investigated the effect of different polyions on the initial steps of infection of Vero cells by the virus. Several polyanions (mucin, heparin, polygalacturonic acid) and polycations (polylysine, protamine, polybrene) were able to reduce the replication of SNV when present in the viral adsorption period, whereas others (chondroitin sulfate, polymyxin B sulfate, histone) were devoid of any activity. Therefore the electric charge alone is not sufficient to explain the action of compounds. The effects of polyions on receptor binding, on bound virus, and on internalized virus have been examined. All the drugs inhibited SNV infection by affecting its binding to the cellular receptor. The results indicated that heparin and mucin act directly on the virus particle while polycations bind to the cell membrane receptor for the virus, protamine being effective on both targets. Since among polyanions glycosaminoglycans showed a strong inhibiting activity, the involvement of these molecules in the virus surface receptor was assessed by enzyme digestion of cell membrane with heparinase and chondroitin ABC lyase. [ABSTRACT FROM AUTHOR]

BK virus infectivity was inhibited by gangliosides extracted from Vero cells and by standard preparations of different gangliosides. Gangliosides were also able to restore the susceptibility of glycosidase-treated Vero cells to BK virus infection. [ABSTRACT FROM AUTHOR]

To identify molecule(s) with the properties of rubella virus (RV) receptor, goose erythrocyte membranes were isolated and tested for their ability to compete with whole cells for viral binding and fusion. Solubilized membranes showed a dose-dependent inhibiting activity on either rubella virus attachment or its fusion with erythrocytes at acidic pH. The inhibitory activity was enhanced by trypsin and neuraminidase, and inactivated by phospholipase A2 digestion, pointing towards the involvement of lipid structures as receptor sites for RV. After isolation of the different membrane components, only the lipid moiety, specifically phospholipids and glycolipids, was found to inhibit viral biological activities. When the major membrane lipids were examined separately, phosphatidylserine and cerebroside sulfate showed a strong inhibiting activity on viral hemagglutination and subsequent hemolysis. The capacity of several pure phospholipids (phosphatidylinositol, phosphatidylcholine and sphingomyelin) to inhibit the hemolysis but not the binding of the virus to the erythrocytes indicated that different membrane lipid components are involved in the attachment and the fusion step. Enzymatic and chemical modifications of whole erythrocytes confirmed the role of membrane lipid molecules in the cell surface receptor for RV. [ABSTRACT FROM AUTHOR]

Human serum high density lipoproteins (HDL), low density lipoproteins (LDL) and very low density lipoproteins (VLDL) were isolated and tested for their ability to inhibit Sindbis virus infectivity, hemagglutination and hemolysis. VLDL and LDL produced a strong reduction on both viral infectivity on Vero cell monolayers and attachment and fusion with erythrocytes, whereas HDL appeared to be only a weak inhibitor. Lipid and protein components were extracted from each class of lipoproteins to identify the molecules responsible for the inhibiting activity. Only the lipid moiety was found to inhibit Sindbis virus biological activities. Among the individual lipid components of lipoproteins, neutral lipids (cholesterol, oleic acid and palmitic acid) and negatively charged phospholipids (phosphatidylserine and phosphatidylinositol) and glycolipids (GM 3 ganglioside and cerebroside sulphate) were able to neutralize the virus suggesting that either hydrophobic or electrostatic interactions are involved in the inhibition. [ABSTRACT FROM AUTHOR]

The chemical nature of the binding sites for vesicular stomatitis virus (VSV) was studied by measuring the ability of solubilized rat brain cell membranes (SRBM) to compete with cultured cells for viral binding. SRBM significantly reduced both binding and infectivity of VSV. After separation of protein and lipid components from membranes, VSV infection was unaffected by the protein fraction, whereas the lipid moiety, specifically phospholipids and glycolipids, showed a dose-dependent inhibitory effect. The essential role of phospholipid and sialic acid-containing glycolipid molecules as receptors for VSV was also suggested by the sensitivity of the inhibitory activity of SRBM and lipid components to phospholipase C and neuraminidase digestion. [ABSTRACT FROM AUTHOR]

This paper describes the inhibitory effect of a normal rat brain solubilized membrane preparation (RBSM-liposomes) on rabies virus infection. Rabies virus was incubated with RBSM-liposomes or their separated components (proteins, phospholipids, gangliosides) before infection of CER or neuroblastoma cells. In addition, both RBSM-liposomes and target cells were treated with enzymes prior to the infection step. All these experimental procedures showed that the active components were mainly lipids. [ABSTRACT FROM AUTHOR]

The effect of lipophilic amines on hepatitis A virus infection in a monkey cell line (Frp/3 cells) was studied. Ammonium chloride, amantadine, methylamine and dansylcadaverine inhibited viral antigen synthesis when added to the cells at least one hour after the attachment step. Results obtained suggest that the HAV entry pathway in Frp/3 cells follows an endocytic route and that viral uncoating takes probably place in endosomes and/or lysosomes. [ABSTRACT FROM AUTHOR]

Gangliosides from different cells were tested for their inhibiting activity on VSV attachment to CER cells and goose erythrocytes. This inhibiting activity was enhanced when gangliosides were inserted into liposomes, in particular if containing phosphatidylserine. [ABSTRACT FROM AUTHOR]

The effect of phospholipases on rhabdovirus attachment to CER cells and the competitive binding of phospholipids and viruses to cells were studied. Results obtained indicate that, although to a different extent, some phospholipids represent a binding site for both Vesicular Stomatitis Virus (VSV) and rabies virus. [ABSTRACT FROM AUTHOR]

Focuses on the prevalence of infection with polyomaviruses JC and BK. Indication of respiratory symptoms during primary childhood infections by BK virus; Association of reactivated infections to cases of haemorrhagic cystitis and ureteric stenosis; Potential of BK virus for transformation of cell cultures from various species.

Focuses on the human polyomavirus JC virus considered as the etiological agent of progressive multifocial leukoencephalopathy associated with immunodepression and frequent in AIDS patients. Evidence of genetic variability in the non-coding control region in virus; Characterization of viral variants; Assessment on the presence of JC virus genome in different biological samples.