Soluble and membranous endothelial protein C receptor in systemic lupus erythematosus patients: Relation to nephritis

Aim of the work

To investigate the role of endothelial protein C receptor (EPCR) (membrane and soluble forms) as a biomarker of lupus nephritis (LN) in systemic lupus erythematosus (SLE) patients and to study its relation to the prognosis and response to treatment.

Neuropathy caused by cisplatin. 7 cases including one with an autopsy study

The clinical, electrophysiological and histopathological features in seven cases of cisplatinum peripheral neuropathy are reported and compared with the literature data. The neuropathy appears for an average intake of 500 mg/m2 of DDP. The symptoms are those of a symmetric, distal, predominantly sensitive neuropathy of an axonal type with major involvement of proprioception. Neurological improvement is poor after withdrawal of the drug. A post mortem study performed in one case showed a degeneration of the posterior column in the cord and residual nodules of Nageotte in a lumbar spinal ganglion. The systematic study of the tendon reflexes and distal pallesthesia in subjects treated with the drug, may reveal the neuropathy before the onset of the most disabling symptoms (paresthesia, ataxia, pain, Lhermitte's sign).     

Impact of IL12B Gene rs 3212227 Polymorphism on Fibrosis,Liver Inflammation,and Response to Treatment in Genotype 4 Egyptian Hepatitis C Patients

Introduction. Hepatitis C virus (HCV) infection affects almost 3% of the world''s population with the highest prevalence in Egypt (15%). The standard therapy; pegylated interferon (PEG-IFN) and ribavirin, is effective in only 60% of Egyptian patients; moreover it is costly, prolonged, and has severe side effects, so prediction of response is essential to reduce burden of unfavorable treatment. Several viral and host factors have been proved to affect response to the treatment PEG-IFN and ribavirin; the strongest of them is polymorphisms near IL28B; nonetheless, nonresponse in patients with favorable IL28B is still unexplained, which implies the importance of studying other immunological factors that may correlate with response. Interleukin 12 (IL-12) is one of the most important proinflammatory cytokine presented with the initiation of immune response, determining Th1 and Th2 differentiation. A functional single nucleotide polymorphism (A/C) at the 3′ untranslated region (3′UTR) at position 1188 (NCBI SNP database no 3212227) was reported to be associated with responding more efficiently to antiviral combination therapy in HCV genotype 1 infected patients. The present study aims to evaluate association between this polymorphism with fibrosis stages, necroinflammation activity, response to the combined therapy, and gender in Egyptian HCV genotype 4. Material and Methods. A total of 133 Egyptian chronic HCV (CHCV) patients were treated with IFN/RBV and were followed up. IL12B 1188 A/C genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PRC-RFLP) analysis. Results. A nonsignificant trend for higher sustained virological response (SVR) was observed in patients homozygote for IL12B 1188 A/C SNP CC genotype (69% SVR versus 30.8% NR) only but not in AC and AA genotypes. No association was detected between IL12B 1188 A/C polymorphism and less severe fibrosis or less liver activity. By stratification of response according to gender genotype, a significant difference in response between males and females was seen among AA genotype carriers only due to high number of non responder females. Conclusion. IL12B CC genotype appears to have some influence on SVR achievement but not on severe fibrosis and severe necroinflamation activity. Females carrying A/A genotype of IL12B 1188 A/C SNP achieve less SVR than those carrying AC and CC genotypes.     

Redistribution of the Lamin B1 genomic binding profile affects rearrangement of heterochromatic domains and SAHF formation during senescence

Senescence is a stress-responsive form of stable cell cycle exit. Senescent cells have a distinct gene expression profile, which is often accompanied by the spatial redistribution of heterochromatin into senescence-associated heterochromatic foci (SAHFs). Studying a key component of the nuclear lamina lamin B1 (LMNB1), we report dynamic alterations in its genomic profile and their implications for SAHF formation and gene regulation during senescence. Genome-wide mapping reveals that LMNB1 is depleted during senescence, preferentially from the central regions of lamina-associated domains (LADs), which are enriched for Lys9 trimethylation on histone H3 (H3K9me3). LMNB1 knockdown facilitates the spatial relocalization of perinuclear H3K9me3-positive heterochromatin, thus promoting SAHF formation, which could be inhibited by ectopic LMNB1 expression. Furthermore, despite the global reduction in LMNB1 protein levels, LMNB1 binding increases during senescence in a small subset of gene-rich regions where H3K27me3 also increases and gene expression becomes repressed. These results suggest that LMNB1 may contribute to senescence in at least two ways due to its uneven genome-wide redistribution: first, through the spatial reorganization of chromatin and, second, through gene repression.     

A Hybrid Algorithm to Enhance Colour Retinal Fundus Images Using a Wiener Filter and CLAHE

Journal of Digital Imaging - Digital images used in the field of ophthalmology are among the most important methods for automatic detection of certain eye diseases. These processes include image...     

Potential deleterious role of anti‐Neu5Gc antibodies in xenotransplantation

Human beings do not synthesize the glycolyl form of the sialic acid (Neu5Gc) and only express the acetylated form of the sugar, whereas a diet‐based intake of Neu5Gc provokes a natural immunization and production of anti‐Neu5Gc antibodies in human serum. However, Neu5Gc is expressed on mammal glycoproteins and glycolipids in most organs and cells. We review here the relevance of Neu5Gc and anti‐Neu5Gc antibodies in the context of xenotransplantation and the use of animal‐derived molecules and products, as well as the possible consequences of a long‐term exposure to anti‐Neu5Gc antibodies in recipients of xenografts. In addition, the importance of an accurate estimation of the anti‐Neu5Gc response following xenotransplantation and the future contribution of knockout animals mimicking the human situation are also assessed.     

Prognostic Impact of Circulating CD28 Negative Suppressor T Cells and Memory B Cells on Treatment Outcomes of Patients with Breast Cancer

Background: It has been suggested that routine assessment and quantification of different lymphocyte subsets can provide clinically meaningful prognostic information in breast cancer (BC). Objective: To determine the relationship between peripheral blood lymphocyte subsets and pathological parameters and response to therapy in patients with BC. Methods: Thirty patients with operable breast cancer treated surgically with either modified radical mastectomy or breast conservative surgery, and 20 healthy controls were included. For detection of lymphocyte subsets in peripheral blood; Fluorochrome-labeled monoclonal antibodies were used and cells were analyzed by flow cytometry. Patients were treated with chemotherapy, radiotherapy and hormonal treatment, and followed up to determine relapse and recurrence-free survival (RFS). Results: Significant differences were found in the frequencies of B, T, NK, NKT, and CD28‒T cells between patients with BC and controls. Moreover, a significant difference was found in the percentage of CD8+CD28‒ T cells between patients with different pathologic subtypes of BC and negative correlations were observed between the frequency of CD8+CD28‒T cells and memory B cells, and RFS. Also, a significant difference in the frequency of naïve B cells was found in patients with different tumor grades and a negative correlation was found between the frequencies of B cells and NKT cells. Conclusion: NK, NKT, lymphocytes, and CD28‒ T cells significantly differed between healthy controls and BC patients. Also, memory B cells were associated with good response to treatment while CD28‒ T cells were associated with shorter RFS.     

Platelet-albumin-bilirubin score-a predictor of outcome of acute variceal bleeding in patients with cirrhosis

BACKGROUND The albumin-bilirubin(ALBI) score was validated as a prognostic indicator in patients with liver disease and hepatocellular carcinoma. Incorporating platelet count in the platelet-albumin-bilirubin(PALBI) score improved validity in predicting outcome of patients undergoing resection and ablation.AIM To evaluate the PALBI score in predicting outcome of acute variceal bleeding in patients with cirrhosis.METHODS The data of 1517 patients with cirrhosis presenting with variceal bleeding were analyzed. Child Turcotte Pugh(CTP) class, Model of End-stage Liver Disease(MELD), ALBI and PALBI scores were calculated on admission, and were correlated to the outcome of variceal bleeding. Areas under the receivingoperator characteristic curve(AUROC) were calculated for survival and rebleeding.RESULTS Mean age was 52.6 years; 1176 were male(77.5%), 69 CTP-A(4.5%), 434 CTP-B(29.2%), 1014 CTP-C(66.8%); 306 PALBI-1(20.2%), 285 PALBI-2(18.8%), and 926 PALBI-3(61.1%). Three hundred and thirty-two patients died during hospitalization(21.9%). Bleeding-related mortality occurred in 11% of CTP-B,28% of CTP-C, in 21.8% of PALBI-2 and 34.4% of PALBI-3 patients. The AUROC for predicting survival of acute variceal bleeding was 0.668, 0.689, 0.803 and 0.871 for CTP, MELD, ALBI and PALBI scores, respectively. For predicting rebleeding the AUROC was 0.681, 0.74, 0.766 and 0.794 for CTP, MELD, ALBI and PALBI scores, respectively.CONCLUSION PALBI score on admission is a good prognostic indicator for patients with acute variceal bleeding and predicts early mortality and rebleeding.