Epstein-Barr virus infection and risk of lymphoma: immunoblot analysis of antibody responses against EBV-related proteins in a large series of lymphoma subjects and matched controls

Epstein-Barr Virus (EBV) is consistently associated with distinct lymphoproliferative malignancies and aberrant EBV antibody patterns are found in most EBV cancer patients. We evaluate the detection of an abnormal reactive serological pattern to EBV (ab_EBV) infection and the risk of lymphoma in a multicentric case-control study. Serum samples were collected at study entry from 1,085 incident lymphoma cases from Spain, France, Germany, Czech Republic, Italy and 1,153 age, sex and country matched controls. EBV immunoglobulin G (IgG) serostatus was evaluated through a peptide-based ELISA combining immunodominant epitopes of EBNA1 (BKRF1) and VCA-p18 (BFRF3). Further, immunoblot analysis was performed to evaluate distinct antibody diversity patterns to EBV early antigens (EA), besides EBNA1, VCA-p18, VCA-p40 (BdRF1) and Zebra (BZLF1). Patients with chronic active EBV infection and aberrant EBV activity were characterized as having an abnormal reactive pattern (ab_EBV). Ab_EBV was observed in 20.9% of 2,238 included subjects with an increased proportion of cases presenting ab_EBV as compared to the control population (23.9% vs. 18.0% p = 0.001). Ab_EBV positivity was a risk factor for all lymphomas combined (odds ratio [OR] = 1.42, 95% confidence interval [CI]=1.15-1.74), and specifically for chronic lymphocytic leukaemia (OR = 2.96, 95%CI = 2.22-3.95). Lower levels of ab_EBV were observed for follicular lymphoma (OR = 0.38, 95%CI = 0.15-0.98). EBV may be involved in a larger subset of lymphomas among clinically immunocompetent subjects than previously thought, probably explained by an underlying loss of immune control of EBV latent infection. Ab_EBV is a useful tool to explore EBV imbalances preceding or paralleling possible EBV associated oncogenic events.     

Candidate markers for the detection of hepatocellular carcinoma in low-molecular weight fraction of serum

Hepatocellular carcinoma (HCC) represents an important public health problem in Egypt where up to 90% of HCC cases are attributable to hepatitis C viral (HCV) infection. Serum alpha-fetoprotein is elevated in only approximately 60% of HCC patients. The development of effective markers for the detection of HCC could have an impact on cancer mortality and significant public health implications worldwide. The objective of our study was to assess six candidate markers for detection of HCC identified by mass spectrometric analysis of enriched serum. The study examined 78 HCC cases and 72 age- and gender-matched cancer-free controls recruited from the Egyptian population. Matrix-assisted laser desorption-ionization time-of-flight mass spectrometric analysis of enriched low-molecular weight fraction of serum was used for identification of the candidate markers. Our analyses show that all six candidate markers are associated with HCC after adjustment for important covariates including HCV and hepatitis B viral infections. The marker candidates are independently predictive of HCC with areas under the receiver operating characteristic (AuROC) curve ranging from 63-93%. A combination of the six markers improves prediction accuracy to 100% sensitivity, 91% specificity and 98% AuROC curve in an independent test set of 50 patients. Two of the candidate markers were identified by sequencing as fragments of complement C3 and C4. In conclusion, a set of six peptides distinguished with high prediction accuracy HCC from controls in an Egyptian population with a high rate of chronic HCV infection. Further evaluation of these marker candidates for the diagnosis of HCC is needed.     

Myrica rubra leaves as a potential source of a dual 5-LOX/COX inhibitor

Myrica rubra Sieb. et Zucc. is a valuable fruit tree that is used in Chinese, Japanese and Taiwanese traditional medicine. We investigated the anti-inflammatory activity of M. rubra leaves extracted with four different solvents. Total phenolics were determined using the Folin–Ciocalteu method. Extracts were investigated for their inhibitory activity toward the pro-inflammatory enzymes cyclooxygenase-1 and -2 (COX-1, COX-2) and 5-lipoxygenase (5-LOX). The ethanol extract of M. rubra leaves demonstrated a strong inhibition of prostaglandin E₂ (PGE₂) biosynthesis catalyzed by both COX-1 (93.42%) and COX-2 (75.71%) and leukotriene B₄ (LTB₄) formation catalyzed by 5-LOX (82.72%). Further we identified selective COX-1 inhibition by the n-butanol and aqueous fractions of the ethanol extract (with an IC₅₀ for COX-1 inhibition of 1.07 and 0.71?µg?mL^?1 _, respectively) and dual 5-LOX/COX inhibition by the ethyl acetate fraction (with an IC₅₀ of 3.29 for COX-1, 2.54 for COX-2 and 8.30?µg?mL^?1 for 5-LOX).     

TGF-beta -- an excellent servant but a bad master

ABSTRACT: The transforming growth factor (TGF-beta) family of growth factors controls an immense number of cellular responses and figures prominently in development and homeostasis of most human tissues. Work over the past decades has revealed significant insight into the TGF-beta signal transduction network, such as activation of serine/threonine receptors through ligand binding, activation of SMAD proteins through phosphorylation, regulation of target genes expression in association with DNA-binding partners and regulation of SMAD activity and degradation. Disruption of the TGF-beta pathway has been implicated in many human diseases, including solid and hematopoietic tumors. As a potent inhibitor of cell proliferation, TGF-beta acts as a tumor suppressor; however in tumor cells, TGF-beta looses anti-proliferative response and become an oncogenic factor. This article reviews current understanding of TGF-beta signaling and different mechanisms that lead to its impairment in various solid tumors and hematological malignancies.     

Clone-based haplotyping of Giardia intestinalis assemblage B human isolates

Parasitology Research - The level of genetic variability of Giardia intestinalis clinical isolates is an intensively studied and discussed issue within the scientific community. Our collection of...     

Nephrocalcinosis in rabbits – correlation of ultrasound, computed tomography, pathology and renal function

Objective. The purpose of this study was to induce nephrocalcinosis (NC) in rabbits with phosphate, vitamin D, oxalate and furosemide, to determine the effect on renal function and to correlate detection on ultrasound (US) and computed tomography (CT) with pathology. Materials and methods. Seventy-five immature New Zealand white rabbits were divided into five groups of 15. In each group, 5 animals were controls and 10 were given oral phosphate, furosemide, vitamin D or oxalate. Unilateral nephrectomy was performed at 3–6 weeks, and 5 rabbits of each test group were withdrawn from the substance. Weekly US was performed as well as US, CT and measurement of serum creatinine at the time of nephrectomy and prior to planned demise. Results. A total of 140 kidneys in 75 rabbits had both pathological and US correlation, with CT correlation in 126. Forty rabbits developed nephrocalcinosis with early (post nephrectomy at 3–6 weeks) or late (post demise at 12–20 weeks) pathological correlation obtained in 53 kidneys. Forty-one of these kidneys were from test animals: 23 developed NC early, 18 late. Twelve controls developed NC: 4 early, 8 late. Comparing US and CT to pathology, the sensitivity was 96 % for US, 64 % for CT. Specificity was 85 % for US and 96 % for CT. In 109 kidneys, information on serum creatinine level was available to correlate with pathology. The mean creatinine level was 138 mmol/l for those with NC and 118 mmol/l for those without NC (P < 0.001). Conclusion. In this study, the presence of NC was significantly associated with increasing serum creatinine. Overall, US was more sensitive and CT was more specific in the detection of NC. Received: 20 August 1996 Accepted: 12 August 1997     

Salvage treatment with upfront melphalan 100 mg/m2 and consolidation with novel drugs for fulminant progression of multiple myeloma

Patients (pts) with fulminant progression (FPG) of multiple myeloma (MM) after autologous stem cell transplantation (ASCT) have poor prognosis. Pancytopenia, extramedullary disease, and/or renal impairment are often present, and treatment options are limited. We have retrospectively evaluated 31 pts with FPG of MM after ASCT who were treated upfront salvage therapy with melphalan 100 mg/m² (MEL 100) followed by PBSC support and consolidation therapy using regimens containing thalidomide (n?=?16) or bortezomib (n?=?15). The overall response rate (ORR) was 58% (18/31). After MEL 100, one patient achieved complete remission (3%), 26% of pts very good partial remission, 29% of pts partial remission, and 42% of pts stable disease. Progression within 3 months after MEL 100 occurred in 35% of pts. The median follow-up from MEL 100 was 8 months. The median TTP was 5 months (range, 2–15 months), and the median OS was 8 months (range, 3–23 months). There were no treatment-related deaths. In fulminant progression of MM, upfront MEL 100 is a safe salvage regimen with good response rate (ORR, 58%). Treatment with upfront MEL 100 followed by a thalidomide- or bortezomib-based regimen can prolong overall survival to more than 12 months in 33% of pts with fulminant progression of MM.     

Prognosis of patients with chronic coronary artery disease and severe left ventricular dysfunction. The importance of myocardial viability

BACKGROUND AND AIM: The choice of optimal treatment strategy in patients with coronary artery disease (CAD) and severe left ventricular (LV) dysfunction is often difficult. The aim of this study was to compare long-term results of patients with chronic CAD, severe heart failure and a defined scope of myocardial viability treated with coronary revascularization, heart transplantation, or kept on medical therapy. METHODS: From 1993 to 2000, viability evaluation using low-dose dobutamine echocardiography was performed in 124 patients with CAD and LV ejection fraction 相似文献   

Prognostic importance of the quantification of myocardial viability in revascularized patients with coronary artery disease and moderate-to-severe left ventricular dysfunction

The aim of this study was to assess the prognostic value of the amount of dysfunctional but viable myocardium in revascularized patients with coronary artery disease and left ventricular dysfunction. To quantify the amount of dysfunctional but viable myocardium, low-dose dobutamine echocardiography was performed. The wall motion was scored using a 16-segment model. The dysfunctional segments were defined as viable if they exhibited functional improvement of at least 1 grade with any dose of dobutamine, or only worsening with dobutamine infusion. Two hundred and twenty patients were revascularized and followed-up for a mean period of 33+/-23 months (range, 0-86) for cardiac-related death and hospitalization for heart failure. Standard follow-up echocardiography was performed 3-6 months after revascularization. Receiver operating characteristic curve analysis identified six dysfunctional but viable segments as the optimal cutoff value for discriminating patients with and without risk of cardiac events. Thirty-eight patients exhibited a large amount of dysfunctional but viable myocardium (>or=6 segments, group A), 103 patients had a small amount of dysfunctional but viable myocardium (2-5 segments, group B), and 79 patients were found to have dysfunctional myocardium irreversibly damaged (group C). Similar baseline left ventricular ejection fractions of 36+/-4, 34+/-5, 35+/-5% in groups A, B, and C increased to 46+/-6% (P<0.01 versus baseline and versus groups B and C), to 39+/-5% (P<0.01 versus baseline and group C), and to 36+/-7% (P<0.01 versus baseline), respectively, after revascularization. The greatest functional improvement after revascularization in group A patients was accompanied by a lower frequency of cardiac events during follow-up (1 vs. 27 in group B, P<0.01, and versus 18 in group C, P<0.01) and by a better cardiac event-free survival according to Kaplan-Meier survival analysis (P<0.01 versus groups B and C, respectively). In conclusion, in revascularized patients with coronary artery disease and moderate-to-severe left ventricular dysfunction, the presence of >or=6 dysfunctional but viable segments identifies patients with the best prognosis.