Human cytomegalovirus DNA detection in a recurrent glioblastoma multiforme tumour,but not in whole blood: a case report and discussion about the HCMV latency and therapy perspectives

Journal of NeuroVirology - In the current study, a 58-year-old male patient presented with recurrent glioblastoma multiforme (GBM). The patient underwent surgical resection, 4 months...     

Sexual dimorphism in shape and size of the neurocranium

International Journal of Legal Medicine - Sex identification is a primary step in forensic analysis of skeletal remains. The accuracy of sex estimation methods greatly depends on the sexual...     

Thermodynamic stability of wild-type and mutant p53 core domain

Some 50% of human cancers are associated with mutations in the core domain of the tumor suppressor p53. Many mutations are thought just to destabilize the protein. To assess this and the possibility of rescue, we have set up a system to analyze the stability of the core domain and its mutants. The use of differential scanning calorimetry or spectroscopy to measure its melting temperature leads to irreversible denaturation and aggregation and so is useful as only a qualitative guide to stability. There are excellent two-state denaturation curves on the addition of urea that may be analyzed quantitatively. One Zn²⁺ ion remains tightly bound in the holo-form of p53 throughout the denaturation curve. The stability of wild type is 6.0 kcal (1 kcal = 4.18 kJ)/mol at 25°C and 9.8 kcal/mol at 10°C. The oncogenic mutants R175H, C242S, R248Q, R249S, and R273H are destabilized by 3.0, 2.9, 1.9, 1.9, and 0.4 kcal/mol, respectively. Under certain denaturing conditions, the wild-type domain forms an aggregate that is relatively highly fluorescent at 340 nm on excitation at 280 nm. The destabilized mutants give this fluorescence under milder denaturation conditions.     

Endocrinology: Comparative pharmacokinetics of two urinary human follicle stimulating hormone preparations in healthy female and male volunteers

These studies were designed to compare the pharmacokinetic characteristicsof a very highly purified urinary human follicle stimulatinghormone (FSH-HP) preparation (sp. act. 9000 IU FSH/mg of protein),Metrodin HP^®, with a standard urinary FSH preparation Metrodin^®(FSH). The two preparations were administered in a balanced,random-order, cross-over sequence as single doses of 150IU,separated by 1 week of washout to 12 female volunteers by i.v.injection and to 12 male volunteers by i.m. and s.c. routes.FSH concentrations were measured by immunoradiometric assayand by an in-vitro rat granulosa cell aromatase bioassay. Afteran i.v. bolus, the pharmacokinetics of the two FSH preparationswere identical. Total clearance was 0.5 and 0.15 1/h respectivelyfor immunoassay and bioassay data. Immunoassay showed that thetwo preparations were similar for renal clearance (0.1 1/h),volumes of distribution at steady state (9 1), distributionand terminal half-lives (2 and 17 h, respectively). After parenteraladministrations, the absorption half-life of FSH was 3 h andthe apparent terminal half-life was 1.5 days. Both preparationshad relative bio-availabilities close to 100% for i.m. and s.c.administrations. Immunopurification, which results in a veryhighly purified FSH-HP, does not modify the pharmacokineticproperties of FSH. This study also confirmed that s.c. and i.m.doses of FSH-HP are equivalent from the pharmacokinetic andpharmacodynamic points of view.     

The role of the carbohydrate chains in complement (C3) fixation by solid-phase-bound human IgA.

In contrast to antigen-antibody complexes containing native human IgA, solid-phase-deposited IgA activates the alternative complement pathway and binds C3b. To investigate the role of carbohydrate chains in this, various human IgA preparations were treated with neuraminidase alone or together with N-glycanase or O-glycanase, or with mixed glycosidases from the oral bacterium, Streptococcus mitis. Depletion of oligosaccharides was determined by carbohydrate analysis. Removal of sialic acid and N-linked glycan chains greatly increased the C3b-fixing properties of normal serum IgA1 and IgA2. Myeloma IgA1 and IgA2 proteins and secretory IgA had higher C3b-binding activity than normal serum IgA, and this was further increased by removal of sialic acid and N-linked glycans. Fc alpha and Fc alpha-SC fragments of myeloma and secretory IgA1, respectively, but not Fab alpha fragments, obtained by cleavage with bacterial IgA1 proteases and also free secretory component, fixed C3b by the alternative pathway.     

BY55/CD160 acts as a co-receptor in TCR signal transduction of a human circulating cytotoxic effector T lymphocyte subset lacking CD28 expression

In the present study, we examined the role of the recently identified glycosylphosphatidylinositol (GPI)-anchored cell surface molecule BY55, assigned as CD160, in TCR signaling. CD160 is expressed by most intestinal intraepithelial lymphocytes and by a minor subset of circulating lymphocytes including NK, TCRgammadelta and cytotoxic effector CD8bright+CD28- T lymphocytes. We report that CD160, which has a broad specificity for MHC class Ia and Ib molecules, behaves as a co-receptor upon T cell activation. Anti-CD160 mAb enhance the CD3-induced proliferation of freshly isolated CD160-enriched peripheral blood lymphocytes and CD160+ T cell clones. Further, the engagement of CD160 receptors on normal clonal T lymphocyte populations lacking CD4, CD8 and CD28 molecules by MHC class I molecules results in an increased CD3-induced cell proliferation. Further, we found that CD160 co-precipitates with the protein tyrosine kinase p56lck and tyrosine phosphorylated zeta chains upon TCR-CD3 cell activation. Thus, we demonstrate that CD160 provides co-stimulatory signals leading to the expansion of a minor subset of circulating lymphocytes including double-negative CD4/CD8 T lymphocytes and CD8bright+ cytotoxic effector T lymphocytes lacking CD28 expression.     

Administering the U.S. Family Violence Option: The role of stigma in waiver recommendations

The Family Violence Option (FVO) was designed to help survivors of domestic violence (DV) more easily secure income support in the United States (U.S.), without placing them at risk of further abuse. The objective of this study is to determine whether the decision-making of advocates responsible for determining waiver recommendations under the FVO is influenced by the relationship status of DV survivors. Recursive partitioning was used to analyse data from a sample of 237 survivor risk assessments from four New Jersey counties to determine which women receive waiver recommendations and which do not. Advocates completed risk assessments for the women and were instructed to make recommendations on waivers based on their assessment. Workers’ decision-making was examined using classification and regression trees (CART) to determine what case factors made it more or less likely for survivors to be recommended waivers. The CART results were supplemented with logistic regression analyses to ensure validity. For two of three waivers, survivors who reported currently residing with their abuser or who had ended the relationship recently were less likely to receive waiver recommendations than those who had been out of the relationship for a longer period of time (OR = 0.09–0.21), even when accounting for the type and severity of DV and the impacts of the violence on survivors’ mental health. The results indicate that DV advocates’ decision-making is complicated by factors independent of survivors’ case characteristics. This can affect the safety and well-being of women attempting to leave violent relationships by affecting their access to resources.     

Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: Imatinib Target Exploration Consortium Study B2225.

PURPOSE: The cutaneous malignant tumor dermatofibrosarcoma protuberans (DFSP) is typically associated with a translocation between chromosomes 17 and 22 that places the platelet-derived growth factor-B (PDGFB) under the control of the collagen 1A1 promoter. The purpose of this study was to evaluate molecular, cytogenetic, and kinase activation profiles in a series of DFSPs and to determine whether these biologic parameters are correlated with the clinical responses of DFSP to imatinib. PATIENTS AND METHODS: We analyzed the objective radiologic and clinical response to imatinib at 400 mg twice daily in eight patients with locally advanced DFSP and two patients with metastatic disease. RESULTS: Each of eight patients with locally advanced DFSP had evidence of t(17;22) and showed a clinical response to imatinib. Four of these patients had complete clinical responses. The two patients with metastatic disease had fibrosarcomatous histology and karyotypes that were substantially more complex than those typically associated with localized DFSP. One patient with metastatic DFSP and an associated t(17;22) had a partial response to imatinib but experienced disease progression after 7 months of therapy. In contrast, the other patient with metastatic disease had a tumor lacking t(17;22), and there was no clinical response to imatinib. Unexpectedly, there was minimal platelet-derived growth factor receptor-beta phosphorylation in the untreated DFSP, despite the documented presence of a PDGFB autocrine mechanism. CONCLUSION: Imatinib has clinical activity against both localized and metastatic DFSP with t(17;22). However, fibrosarcomatous variants of DFSP lacking t(17;22) may not respond to imatinib.     

Orange Juice and Cancer Chemoprevention

Orange juice (OJ) is among the most consumed fruit juices worldwide, and its chemopreventive action is fairly addressed in the literature. This review critically presents the available evidence linking OJ with cancer chemoprevention and on discussing the putative mechanisms and negative health effects. The chemopreventive action of OJ is related to its effect on metabolic enzymes and its antiinflammatory, cytoprotective/apoptotic, hormonal, cell signaling-modulating, antioxidant, and antigenotoxic effects. Most studies on OJ are in vitro, and few are conducted in vivo. Results from in vitro studies must be interpreted carefully because these findings do not consider in vivo bioavailability. However, such results are useful for studying the impact of different processing and storage methods on OJ's chemopreventive effect. Evidence of OJ's chemoprevention in humans is limited. OJ is antimutagenic in bacteria and antigenotoxic in humans and rodents. Studies using rodent cancer models showed that OJ is cancer chemopreventive, influencing either the induction stage or the promotion stage. The composition and, therefore, the chemopreventive action of OJ might be influenced by different cultivars, climates, extraction methods, packaging, storage temperatures, and shelf lives, among other factors. Epidemiological studies and randomized controlled intervention studies in humans evaluating the chemopreventive effect of OJ, taking into consideration variability in OJ composition, are needed.