Detection of herpes simplex virus type 2-specific immunoglobulin G antibodies in African sera by using recombinant gG2, Western blotting,and gG2 inhibition

Sera (n = 781) from four African countries were used to determine the prevalence of herpes simplex virus type 2 (HSV-2) antibodies by using the HerpeSelect HSV-2 enzyme-linked immunosorbent assay (ELISA; Focus Technologies) and Western blotting (WB). Also, an HSV inhibition assay was developed to evaluate the discordant sample results between HerpesSelect and WB. The seroprevalence of HSV-2 ranged from 17% in the South African panel to nearly 70% in panels from Kenya, Uganda, and Zimbabwe. Overall, HerpeSelect was 100% sensitive and 88% specific compared to WB and 100% sensitive and 96% specific compared to the inhibition assay. There was 100% concordance among all three assays for samples from South Africa and Zimbabwe. The discordant results occurred in samples from Kenya and Uganda.     

A genome-wide association and gene-environment interaction study for serum triglycerides levels in a healthy Chinese male population

Triglyceride (TG) is a complex phenotype influenced by both genetic and environmental factors. Recent genome-wide association studies (GWAS) have identified genes or loci affecting lipid levels; however, such studies in Chinese populations are limited. A two-stage GWAS were conducted to identify genetic variants that were associated with TG in a Chinese population of 3495 men. Gene-environment interactions on serum TG levels were further investigated for the seven single nucleotide polymorphisms (SNPs) that were studied in both stages. Two previously reported SNPs (rs651821 in APOA5, rs328 in LPL) were replicated in the second stage, and the combined P-values were 9.19 × 10(-26) and 1.41 × 10(-9) for rs651821 and rs328, respectively. More importantly, a significant interaction between aldehyde dehydrogenase 2 (ALDH2) rs671 and alcohol consumption on serum TG levels were observed (P = 3.34 × 10(-5)). Rs671 was significantly associated with serum TG levels in drinkers (P = 1.90 × 10(-10)), while no association was observed in non-drinkers (P > 0.05). For drinkers, men carrying the AA/AG genotype have significantly lower serum TG levels, compared with men carrying the GG genotype. For men with the GG genotype, the serum TG levels increased with the quantity of alcohol intake (P = 1.28 × 10(-8) for trend test). We identified a novel, significant interaction effect between alcohol consumption and the ALDH2 rs671 polymorphism on TG levels, which suggests that the effect of alcohol intake on TG occurs in a two-faceted manner. Just one drink can increase TG level in susceptible individuals who carry the GG genotype, while individuals carrying AA/AG genotypes may actually benefit from moderate drinking.     

Role of hyaluronan-mediated CD44 signaling in head and neck squamous cell carcinoma progression and chemoresistance

Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy that may involve the oral cavity, pharynx, larynx, and paranasal sinuses. The mechanisms of tumor progression underlying the clinical behavior of HNSCC remain unclear. CD44 comprises a family of transmembrane receptors that can give rise to multiple CD44 variant isoforms. Hyaluronan (HA), a major extracellular matrix component is the primary ligand for CD44 receptors. HA and CD44 signaling play an important role in HNSCC progression. Several CD44 variant isoforms (including v3-, v6-, and v10-containing isoforms) are associated with advanced disease, possibly through unique growth factor interactions with binding domains in the inserted variant regions of the cytoplasmic domain of CD44. In HNSCC, HA mediates the formation of a complex including CD44 and the epidermal growth factor receptor (EGFR) which is overexpressed in a large proportion of HNSCCs. Downstream effectors under EGFR regulation are activated, promoting promote cell growth and tumor survival. The leukemia-associated Rho-guanine nucleotide exchange factor (LARG) also associates with CD44 and EGFR to promote several Ras and RhoA pathway effectors, leading to cell migration, growth, and tumor survival. The secretion of matrix metalloproteinases, necessary for tumor cell invasion, is also regulated by these HA/CD44-mediated pathways. Finally, EGFR-mediated pathways play major roles in the HA/CD44 promotion of chemoresistance in HNSCC. Understanding HA/CD44-mediated signaling pathways may lead to improved treatment of HNSCC.     

Pro‐B cells propagated in stromal cell‐free cultures reconstitute functional B‐cell compartments in immunodeficient mice

Up to now long‐term in vitro growth of pro‐B cells was thought to require stromal cells. However, here we show that fetal liver (FL) and bone marrow (BM) derived pro‐B cells can be propagated long‐term in stromal cell‐free cultures supplemented with IL‐7, stem cell factor and FLT3 ligand. Within a week, most cells expressed surface CD19, CD79A, λ5, and VpreB antigens and had rearranged immunoglobulin D‐J heavy chain genes. Both FL and BM pro‐B cells reconstituted the B‐cell compartments of immuno‐incompetent Rag2‐deficient mice, with FL pro‐B cells generating follicular, marginal zone (MZB) and B1a B cells, and BM pro‐B cells giving rise mainly to MZB cells. Reconstituted Rag2‐deficient mice generated significant levels of IgM and IgG antibodies to a type II T‐independent antigen; mice reconstituted with FL pro‐B cells generated surprisingly high IgG₁ titers. Finally, we show for the first time that mice reconstituted with mixtures of pro‐B and pro‐T cells propagated in stromal cell‐free in vitro cultures mounted a T‐cell‐dependent antibody response. This novel stromal cell‐free culture system facilitates our understanding of B‐cell development and might be applied clinically.     

Contemporary surgery of biliary atresia

The etiology of biliary atresia is not due to a congenital malformation but rather to a continuing process beginning in utero that affects not only the extrahepatic biliary ducts but also the intrahepatic parenchyma. Over the last decade, the outlook for patients who were previously felt to be uncorrectable has been significantly improved by Kasai's operation. Successful biliary reconstruction depends on early diagnosis and treatment (before three months of age). The essentials of hepatic portoenterostomy consist of excision of the entire extrahepatic duct structure with anastomosis of an intestinal conduit to the area of the transected duct at the liver hilus. After operation, many patients experience complications, including cholangitis, portal hypotension, and vitamin deficiencies. Despite these difficulties, growth and development continue on a relatively normal course, and long-term survival has been accomplished in many children. For those in whom biliary drainage is not achieved or with significant parenchymal damage, liver transplantation should be considered as part of ongoing care.