Interaction of herpes simplex virus glycoprotein gC with mammalian cell surface molecules

The entry of herpes simplex virus (HSV) into mammalian cells is a multistep process beginning with an attachment step involving glycoproteins gC and gB. A second step requires the interaction of glycoprotein gD with a cell surface molecule. We explored the interaction between gC and the cell surface by using purified proteins in the absence of detergent. Truncated forms of gC and gD, gC1(457t), gC2(426t), and gD1(306t), lacking the transmembrane and carboxyl regions were expressed in the baculovirus system. We studied the ability of these proteins to bind to mammalian cells, to bind to immobilized heparin, to block HSV type 1 (HSV-1) attachment to cells, and to inhibit plaque formation by HSV-1. Each of these gC proteins bound to conformation-dependent monoclonal antibodies and to human complement component C3b, indicating that they maintained the same conformation of gC proteins expressed in mammalian cells. Biotinylated gC1(457t) and gC2(426t) each bind to several cell lines. Binding was inhibited by an excess of unlabeled gC but not by gD, indicating specificity. The attachment of gC to cells involves primarily heparan sulfate proteoglycans, since heparitinase treatment of cells reduced gC binding by 50% but had no effect on gD binding. Moreover, binding of gC to two heparan sulfate-deficient L-cell lines, gro2C and sog9, both of which are mostly resistant to HSV infection, was markedly reduced. Purified gD1 (306t), however, bound equally well to the two mutant cell lines. In contrast, saturating amounts of gC1(457t) interfered with HSV-1 attachment to cells but failed to block plaque formation, suggesting a role for gC in attachment but not penetration. A mutant form of gC lacking residues 33 to 123, gC1(delta 33-123t), expressed in the baculovirus system, bound significantly less well to cells than did gC1(457t) and competed poorly with biotinylated gC1(457t) for binding. These results suggest that residues 33 to 123 are important for gC attachment to cells. In contrast, both the mutant and wild-type forms of gC bound to immobilized heparin, indicating that binding of these proteins to the cell surface involves more than a simple interaction with heparin. To determine that the contribution of the N-terminal region of gC is important for HSV attachment, we compared several properties of a mutant HSV-1 which contains gC lacking amino acids 33 to 123 to those of its parental virus, which contains full-length gC. The mutant bound less well to cells than the parental virus but exhibited normal growth properties.(ABSTRACT TRUNCATED AT 400 WORDS)     

Brief coping skills treatment for cocaine abuse: substance use outcomes at three months

AIMS: Coping skills training, a promising treatment approach for alcoholics, was adapted for use with cocaine abusers and effects on outcome were investigated. DESIGN: A cocaine-specific coping skills training (CST) package was compared to an attention placebo control when both were added to a comprehensive treatment program. SETTING: The sites were two private substance abuse treatment facilities, one residential and rural, and one an urban partial hospital. PARTICIPANTS: Substance abusers in treatment with cocaine abuse or dependence were selected. INTERVENTION: The CST intervention was conducted in individual sessions. It involved functional analysis of high risk situations and coping skills training based on the functional analysis. FINDINGS: Clients who received CST had significantly fewer cocaine use days and the length of their longest binge was significantly shorter during the 3-month follow-up period compared to clients in the control condition. CST did not affect relapse rates or use of other substances. CONCLUSIONS: Results support the notion that cocaine-specific CST is a promising adjunct to treatment for cocaine abusers.     

Perceptions of stranger and acquaintance rape: The role of benevolent and hostile sexism in victim blame and rape proclivity.

In Studies 1 and 2, after reading an acquaintance-rape but not a stranger-rape scenario, higher benevolent sexist but not hostile sexist participants blamed the victim significantly more. In Study 2, higher hostile sexist but not benevolent sexist male participants showed significantly greater proclivity to commit acquaintance (but not stranger) rape. Studies 3 and 4 supported the hypothesis that the effects of benevolent sexism and hostile sexism are mediated by different perceptions of the victim, as behaving inappropriately and as really wanting sex with the rapist. These findings show that benevolent sexism and hostile sexism underpin different assumptions about women that generate sexist reactions toward rape victims. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Human placental cytotrophoblasts produce the immunosuppressive cytokine interleukin 10

The mechanism by which the mammalian mother accepts the implanting fetus as an allograft remains unexplained, but is likely to be the result of a combination of factors. Mononuclear cytotrophoblasts, the specialized fetal cells of the placenta that invade the uterus, play an important role. These cells express HLA-G, an unusual major histocompatibility complex class I-B molecule, and secrete cytokines and pregnancy-specific proteins that can regulate immune function. We investigated whether cytotrophoblasts secrete interleukin 10 (IL-10), a cytokine that potently inhibits alloresponses in mixed lymphocyte reactions. Cytotrophoblasts from all stages of pregnancy produced IL-10 in vitro, but neither placental fibroblasts nor choriocarcinoma (malignant trophoblast) cell lines did so. Spontaneous IL-10 production averaged 650, 853, and 992 pg/10(6) cells in the first, second, and third trimesters of pregnancy, respectively. IL-10 secretion dropped approximately 10-fold after the first 24 h of culture, and was paralleled by a decrease in messenger RNA. IL-10 messenger RNA was detected in biopsies of the placenta and the portion of the uterus that contains invasive cytotrophoblasts, suggesting that this cytokine is also produced in vivo. IL-10 secreted by cytotrophoblasts in vitro is bioactive, as determined by its ability to suppress interferon gamma production in an allogeneic mixed lymphocyte reaction. We conclude that human cytotrophoblast IL-10 may be an important factor that contributes to maternal tolerance of the allogeneic fetus.     

Expression of microfibrillar proteins by bovine bladder urothelium

OBJECTIVE: To compare hydrodynamic characteristics of a new bileaflet heart valve, the CarboMedics kinetic cardiac valve prosthesis, with those of a St. Jude Medical (SJM) heart valve. METHODS: Hydrodynamic characteristics were determined in the mitral and aortic positions of a Vivitro Systems pulse duplicator for size 23 Kinetic aortic values, size 23 SJM aortic valves, size 29 Kinetic mitral valves and size 29 SJM mitral valves. Test conditions were 72 beats per min with cardiac outputs of 2, 5 and 7 l/min. Values of forward flow pressure drop (delta P), regurgitant and energy loss were determined for each valve. The test results for the two valve designs were compared by valve size. RESULTS: The test results show that both the size 23 and size 29 Kinetic valves have 8-14% lower delta P values and 5-10% greater effective orifice area (EOA) values. The size 29 Kinetic mitral valve has a 1-2 ml lower regurgitant volume, while the size 23 Kinetic aortic valve has a 0.5 ml greater regurgitant volume than the corresponding SJM values. These factors combine to provide a 5-10% lower energy loss for size 23 Kinetic aortic valves and a 15-25% lower energy loss for size 29 Kinetic mitral valves over the cardiac cycle than for corresponding sizes of SJM valves. CONCLUSIONS: The Kinetic valve's fluid dynamics are superior to equivalent sizes of SJM valves. This is especially impressive considering that the tissue annulus diameters for Kinetic valves are approximately 0.5 mm less than equivalent size SJM valves. The primary reasons for the superior hydrodynamic performance of Kinetic valves are (1) the larger orifices which result in lower forward flow delta P values and (2) the opening angles, which have been customized for each valve size to minimize energy loss.     

Testicular epidermoid cysts in prepubertal children: case report and review of the world literature

Epidermoid cysts of the testes are rare, benign lesions that account for approximately 1% of all testicular tumors. They present most often between the second and fourth decade of life, and have been reported in prepubertal children rarely. The authors report the clinical and sonographic findings in a 4 1/2-year-old child with a testicular epidermoid cyst, and they analyze the 22 prepubertal cases found in the world literature. As described below, the clinical and sonographic features of this tumor are not specific for an epidermoid cyst and do not preclude a teratomatous or malignant neoplasm. This case adds to the varied sonographic appearance of prepubertal testicular epidermoid cysts. The lack of either unique clinical or sonographic features would suggest that extreme caution be used if local excision is considered for a patient with presumed epidermoid cyst of the testicle.