Examination of the Short-Term Efficacy of a Parent-Based Intervention to Prevent Skin Cancer

The research evaluated an intervention strategy designed to prevent skin cancer in young adolescents. The intervention used parents as change agents to effectively communicate the risks of skin cancer and encourage their children to avoid high-risk sun-related behaviors while increasing positive sun-safe behaviors. Three hundred and forty parents in two regions of the United States were educated about the dangers of risky sun behaviors and how to convey information about skin cancer prevention to their children. Parents were then encouraged to talk with their children about these issues over a 1-month period prior to the onset of summer. Following this time period, children whose parents received and implemented the intervention materials were compared with a control sample of 129 children. These two groups were matched on age, gender, and school on number of sunburns and sunburn severity, attitudes and beliefs, and sunbathing behavior. Children in the treatment condition differed significantly from controls in the predicted directions on all outcome variables. The findings are discussed in terms of reducing skin cancer risk behaviors of children via parent-based intervention approaches.     

Accumulation of aberrant ubiquitin induces aggregate formation and cell death in polyglutamine diseases

Polyglutamine diseases are characterized by neuronal intranuclear inclusions (NIIs) of expanded polyglutamine proteins, indicating the failure of protein degradation. UBB(+1), an aberrant form of ubiquitin, is a substrate and inhibitor of the proteasome, and was previously reported to accumulate in Alzheimer disease and other tauopathies. Here, we show accumulation of UBB(+1) in the NIIs and the cytoplasm of neurons in Huntington disease and spinocerebellar ataxia type-3, indicating inhibition of the proteasome by polyglutamine proteins in human brain. We found that UBB(+1) not only increased aggregate formation of expanded polyglutamines in neuronally differentiated cell lines, but also had a synergistic effect on apoptotic cell death due to expanded polyglutamine proteins. These findings implicate UBB(+1) as an aggravating factor in polyglutamine-induced neurodegeneration, and clearly identify an important role for the ubiquitin-proteasome system in polyglutamine diseases.     

Resistance mechanisms to plant viruses: an overview

To obtain virus-resistant host plants, a range of operational strategies can be followed nowadays. While for decades plant breeders have been able to introduce natural resistance genes in susceptible genotypes without knowing precisely what these resistance traits were, currently a growing number of (mostly) dominant resistance genes have been cloned and analyzed. This has led not only to a better understanding of the plant's natural defence systems, but also opened the way to use these genes beyond species borders. Besides using natural resistance traits, also several novel, "engineered" forms of virus resistance have been developed over the past 15 years. The first successes were obtained embarking from the principle of pathogen-derived resistance (PDR) by transforming host plants with viral genes or sequences with the purpose to block a specific step during virus multiplication in the plant. As an unforeseen spin-off of these investments, the phenomenon of post-translational gene silencing (PTGS) was discovered, which to date is by far the most successful way to engineer resistance. It is generally believed that PTGS reflects a natural defence system of the plant, and part of the hypothesized components required for PTGS have been identified. As counteracting strategy, and confirming PTGS to be a natural phenomenon, a considerable number of viruses have acquired gene functions by which they can suppress PTGS. In addition to PDR and PTGS, further strategies for engineered virus resistance have been explored, including the use of pokeweed antiviral protein (PAP), 2',5'-oligoadenylate synthetase and "plantibodies". This paper will give a brief overview of the major strategies that have become operational during the past 10 years.     

Megalencephaly in the epileptic chicken: a morphometric study of the adult brain

The epileptic chicken is a genetic model of generalized epilepsy in which epilepsy is combined with megalencephaly. We have performed a morphometric study of the brains of adult epileptic hens, using heterozygous carrier hens as controls. There is no obvious disorder of cell form or of architectural arrangement in the megalencephalic brains. We have found that the enlargement of the epileptic brain is not uniform: it is most marked in the telencephalon, and is present to a lesser degree in the cerebellum, but neither the optic tectum nor the diencephalic nucleus rotundus shows a significant increase in size. The enlarged regions are characterized by a decrease in the packing density of neurons. There is an increase in the total neuron population in some of the enlarged areas (archistriatum), despite the lower density per unit volume, but in other enlarged areas (hippocampus) there is no difference in total neuron numbers. The glial cells, by contrast, show no significant alteration in packing density. These findings suggest that the megalencephaly of the epileptic chicken is due to an increase in neuron size, with a contribution from increased numbers of neurons and glial cells. The epileptic chicken may provide a valuable model for further dynamic studies of aberrant neuronal development, and of structural-functional relationships in epilepsy.     

Familial pericentric inversion of chromosome 8

Eight children from seven presumably unrelated families were identified independently as having an unbalanced recombinant chromosome resulting in the presence of extra material on the short arm of a chromosome 8. Parental chromosomes were analyzed, and one member of each couple (four fathers and three mothers) was found to carry a pericentric inversion of a chromosome 8 [inv(8)(p23q22)]. The propositi had an unbalanced recombinant chromosome [rec(8),dup q,inv(8)(p23q22)]. The affected infants all had developmental delay, congenital heart disease, and unusual appearance. A common origin of the pericentric inversion was suggested because of geographic location and Mexican--American ancestry of the seven families.     

Human herpesvirus type 6 reactivation after haematopoietic stem cell transplantation

Human herpesvirus type 6 (HHV6) is known to reactivate after hematopoetic stem cell transplantation (HSCT) and has been suggested to be associated with increased mortality and severe clinical manifestations, including graft versus host disease (GvHD). The exact etiological role of HHV6 reactivation in increased morbidity and mortality after HSCT remains unclear. This review will focus on the current available evidence of HHV6 reactivation after HSCT and its immuno-modulatory capacities, with particular emphasis on the severe complication GvHD. At present, no effective specific antiviral treatment for HHV6 reactivation has been identified. The currently available antiviral agents are outlined, as well as possible future strategies for the treatment of HHV6 reactivation. Non-toxic, specific treatment or prevention of HHV6 reactivation might improve the safety and efficacy of the HSCT procedure.     

Subtelomeric deletions detected in patients with idiopathic mental retardation using multiplex ligation-dependent probe amplification (MLPA)

Subtelomeric rearrangements are responsible for 5% to 10% of cases of unexplained mental retardation. Despite their clinical relevance, methods to screen for these cytogenetically invisible abnormalities on a routine base are scarce. We screened patients with idiopathic mental retardation for subtelomeric aberrations using multiplex ligation-dependent probe amplification (MLPA). This recently developed technique is based on PCR amplification of ligated probes hybridized to chromosome ends. Currently, 41 telomeres can be screened in just two multiplex reactions. Four subtelomeric rearrangements (5.3%) were detected in a group of 75 patients with mild to severe mental retardation in combination with dysmorphic features and/or a familial history of mental retardation: two terminal 1p deletions, a terminal 1q deletion, and a terminal 3p deletion. Deletions could be verified by FISH and marker analysis. In one case the MLPA indicated a terminal 21q deletion due to a 3-bp deletion at the site of the probe, giving a false-positive rate of 1.3%. This study demonstrates that MLPA is a fast and reliable screening method, potentially suitable for use in routine diagnostics.     

Oligomerization and polymerization of the filovirus matrix protein VP40

The matrix protein VP40 from Ebola virus plays an important role in the assembly process of virus particles by interacting with cellular factors, cellular membranes, and the ribonuclearprotein particle complex. Here we show that the N-terminal domain of VP40 folds into a mixture of two different oligomeric states in vitro, namely hexameric and octameric ringlike structures, as detected by gel filtration chromatography, chemical cross-linking, and electron microscopy. Octamer formation depends largely on the interaction with nucleic acids, which in turn confers in vitro SDS resistance. Refolding experiments with a nucleic acid free N-terminal domain preparation reveal a mostly dimeric form of VP40, which is transformed into an SDS resistant octamer upon incubation with E. coli nucleic acids. In addition, we demonstrate that the N-terminal domain of Marburg virus VP40 also folds into ringlike structures, similar to Ebola virus VP40. Interestingly, Marburg virus VP40 rings reveal a high tendency to polymerize into rods composed of stacked rings. These results may suggest distinct roles for different oligomeric forms of VP40 in the filovirus life cycle.     

Impact of antigen expression kinetics on the effectiveness of HIV-specific cytotoxic T lymphocytes

Recent studies indicate that the time required for virus-infected cells to become vulnerable for the activity of CTL is of significance for the capacity of CTL to control ongoing viral reproduction. To investigate whether this applies to the effectiveness of HIV-1-specific CTL, we measured virus production in cultures containing CD4(+) T cells inoculated with HIV at low multiplicity of infection, and CTL directed against an early protein, Rev, or a late protein, RT. The Rev-specific CTL prevented at least 2 log(10) more HIV-1 production, in 10 days, than similar numbers of RT-specific CTL. To study how CTL effectiveness depends on variations in the potency of effector functions and kinetics of HIV protein expression, we developed a mathematical model describing CTL-target cell interactions during successive infection cycles. The results show that substantially higher CTL-mediated target cell elimination rates are required to achieve control as there is less time for CTL to act before infected cells release progeny virions. Furthermore, in vitro experiments with HIV recombinant viruses showed that the RT-specific CTL were at least as effective as the Rev-specific CTL, but only if the RT epitope was expressed as part of the early protein Nef. Together these results indicate that CTL control ongoing HIV reproduction more effectively if they are able to recognize infected cells earlier during individual viral replication cycles. This provides rationale for immunization strategies that aim at inducing, boosting or skewing CTL responses to early regulatory proteins in AIDS vaccine development.     

Urothelial cell DNA adducts in rubber workers

Workers employed in the rubber industry appear to have a significant excess cancer risk in a variety of sites, including cancer of the urinary bladder. In this cross-sectional study, we investigated the occurrence of DNA adducts in exfoliated bladder cells of currently exposed, nonsmoking rubber workers (n = 52) and their relationship with occupational exposure estimates and acetylation phenotype (NAT2). Four DNA adducts were identified, with the proportion of positive samples (e.g., DNA samples with quantifiable levels of a specific DNA adduct) ranging from 3.8 to 79%. The highest proportion of positive samples and the highest relative adduct labeling levels were in workers involved in the production functions "mixing" and "curing," areas with potential for substantial exposure to a wide range of chemical compounds used in rubber manufacturing (P < 0.05 for adducts 2 and/or 3, compared to all other departments). No statistically significant relationships were found between identified DNA adducts and urinary mutagenicity or personal inhalable and dermal exposure estimates. Interestingly, subjects with a fast NAT2 acetylation phenotype tended to have higher levels of DNA adducts. This study suggests that rubber workers engaged in mixing and curing may be exposed to compounds that can form DNA adducts in urothelial cells. Larger studies among rubber workers should be conducted to study in more detail the potential carcinogenicity of exposures encountered in these work areas.