Adenovirus infection in pediatric liver transplant recipients

A retrospective review of adenoviral infection in pediatric liver transplant recipients was done at Children’s Hospital of Pittsburgh to define its epidemiology and clinical importance. Medical records of patients with adenovirus were reviewed and data collected regarding clinical course, microbiologic studies, biopsy results, immunosuppression, concurrent infections, and outcome. Of 484 liver transplant recipients, 49 had 53 episodes of adenoviral infection. The most common sites of adenoviral infection were the liver, lung, and gastrointestinal tract. Serotypes 1, 2, and 5 were recovered most often; type 5 was commonly associated with hepatitis. Invasive adenoviral infection occurred in 20 children, leading to death in 9. Median time from transplantation until isolation of adenovirus was 25.5 days. This timing suggests either reactivation or donor-associated transmission. Prospective studies using molecular epidemiologic techniques will be helpful in evaluating transmission patterns of adenovirus in this population. © 1992 Oxford University Press

Screening donors for xenotransplantation: The potential for xenozoonoses

Xenotransplantation is a potential solution to the current donor shortage for solid organ transplantation. The transmission of infectious agents from donor organs or bone marrow to the recipient is a well-recognized phenomenon following allotransplantation. Thus the prospect of xenotransplantation raises the issue of xenozoonoses-i.e., the transmission of animal infections to the human host. Anticipating an increasing number of baboon to human transplants, 31 adult male baboons (Papio cynocephalus) from a single colony in the United States were screened for the presence of antibody to microbial agents (principally viral) that may pose a significant risk of infection. Antibody to simian cytomegalovirus, simian agent 8 and Epstein-Barr virus, was found in 97% of animals tested. Antibody to simian retroviruses and Toxoplasma gondii was found in 30% and 32% respectively. Discordant results were found when paired samples were examined by two primate laboratories. This was particularly noted when methodologies were based on cross-reaction with human viral antigens. These results highlight the need to develop specific antibody tests against the species used for xenotransplantation. © 1994 Williams & Wilkins

Detection of infectious baboon cytomegalovirus after baboon-to-human liver xenotransplantation

Xenotransplantation is considered to be a solution for the human donor shortage. However, there is a potential risk of transmitting animal infections from the transplanted organ. The known transmissibility and clinical significance of human cytomegalovirus (HCMV) infection after allotransplantation led us to evaluate whether baboon cytomegalovirus (BCMV) transmission could occur after a baboon-to-human liver xenotransplant. We examined serial blood samples from a baboon liver recipient and isolated replication-competent CMV-like agents on days 29, 36, and 42 after xenotransplantation. BCMV and HCMV DNAs were detected in the day 29 isolate, while only HCMV DNA was detected in the other isolates. This is the first report of detecting a replication-competent virus from a source animal after xenotransplantation and is a concern with regard to potential zoonotic transmission to others

Therapeutic effect of hyperbaric oxygen in psoriasis vulgaris: two case reports and a review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Psoriasis is an inflammatory and immunological cutaneous disease. The high morbidity in patients with psoriasis results from severe clinical manifestations and/or adverse effects of treatment. The Undersea and Hyperbaric Medical Society and Federal Medicare and Medicaid Services have approved the use of hyperbaric oxygen (HBO₂) for more than 15 indications, including wound healing, infections and late effects of radiation, which are largely unresponsive to conventional treatments. Accumulated data show that HBO₂ has anti-inflammatory effects and other positive influences on the immune system, making it a rational treatment in the management of psoriasis plaques and arthritis.</p> <p>Case presentation</p> <p>We present the cases of two patients with long histories of psoriasis vulgarus who exhibited marked improvement with use of HBO_2. The first patient was 40 years old and had pustular psoriasis and psoriatic arthritis. He was treated with six sessions of HBO₂ (at 2.8 atmospheres of pressure for 60 minutes), which successfully controlled his symptoms. At the 18-month post-treatment follow up, the patient exhibited complete remission of psoriasis and marked improvement in psoriatic arthritis without medication. The second patient was 55 years old with extensive psoriatic lesions, and exhibited marked improvement within 15 sessions of HBO₂. No adverse effects of HBO₂ were identified.</p> <p>Conclusions</p> <p>HBO₂ may possess potential therapeutic efficacy in the management of psoriasis. We outline the pathogenesis of psoriasis and the selective anti-inflammatory and immunosuppressive effects of HBO₂. We hope that this will provide a basis for elucidating the mechanisms of action and consequently pave the way for further controlled studies.</p

Lipid vesicles trigger α-synuclein aggregation by stimulating primary nucleation.

α-Synuclein (α-syn) is a 140-residue intrinsically disordered protein that is involved in neuronal and synaptic vesicle plasticity, but its aggregation to form amyloid fibrils is the hallmark of Parkinson's disease (PD). The interaction between α-syn and lipid surfaces is believed to be a key feature for mediation of its normal function, but under other circumstances it is able to modulate amyloid fibril formation. Using a combination of experimental and theoretical approaches, we identify the mechanism through which facile aggregation of α-syn is induced under conditions where it binds a lipid bilayer, and we show that the rate of primary nucleation can be enhanced by three orders of magnitude or more under such conditions. These results reveal the key role that membrane interactions can have in triggering conversion of α-syn from its soluble state to the aggregated state that is associated with neurodegeneration and to its associated disease states.This work was supported by the UK BBSRC and the Wellcome Trust (CMD, TPJK, MV), the Frances and Augustus Newman Foundation (TPJK), Magdalene College, Cambridge (AKB) , St John’s College, Cambridge (TCTM), the Cambridge Home and EU Scholarship Scheme (GM), Elan Pharmaceuticals (CMD, TPJK, MV, CG) and the Leverhulme Trust (AKB).This is the accepted manuscript. The final version is available from NPG at http://www.nature.com/nchembio/journal/v11/n3/abs/nchembio.1750.htm

Alternative splicing and differential subcellular localization of the rat FGF antisense gene product

<p>Abstract</p> <p>Background</p> <p>GFG/NUDT is a nudix hydrolase originally identified as the product of the fibroblast growth factor-2 antisense (FGF-AS) gene. While the FGF-AS RNA has been implicated as an antisense regulator of FGF-2 expression, the expression and function of the encoded GFG protein is largely unknown. Alternative splicing of the primary FGF-AS mRNA transcript predicts multiple GFG isoforms in many species including rat. In the present study we focused on elucidating the expression and subcellular distribution of alternatively spliced rat GFG isoforms.</p> <p>Results</p> <p>RT-PCR and immunohistochemistry revealed tissue-specific GFG mRNA isoform expression and subcellular distribution of GFG immunoreactivity in cytoplasm and nuclei of a wide range of normal rat tissues. FGF-2 and GFG immunoreactivity were co-localized in some, but not all, tissues examined. Computational analysis identified a mitochondrial targeting sequence (MTS) in the N-terminus of three previously described rGFG isoforms. Confocal laser scanning microscopy and subcellular fractionation analysis revealed that all rGFG isoforms bearing the MTS were specifically targeted to mitochondria whereas isoforms and deletion mutants lacking the MTS were localized in the cytoplasm and nucleus. Mutation and deletion analysis confirmed that the predicted MTS was necessary and sufficient for mitochondrial compartmentalization.</p> <p>Conclusion</p> <p>Previous findings strongly support a role for the FGF antisense RNA as a regulator of FGF2 expression. The present study demonstrates that the antisense RNA itself is translated, and that protein isoforms resulting form alternative RNA splicing are sorted to different subcellular compartments. FGF-2 and its antisense protein are co-expressed in many tissues and in some cases in the same cells. The strong conservation of sequence and genomic organization across animal species suggests important functional significance to the physical association of these transcript pairs.</p

Washing our hands of the congenital cytomegalovirus disease epidemic

BACKGROUND: Each year in the United States, an estimated 40,000 children are born with congenital cytomegalovirus (CMV) infection, causing an estimated 400 deaths and leaving approximately 8000 children with permanent disabilities such as hearing or vision loss, or mental retardation. More children are affected by serious CMV-related disabilities than by several better-known childhood maladies, including Down syndrome, fetal alcohol syndrome, and spina bifida. DISCUSSION: Congenital CMV is a prime target for prevention not only because of its substantial disease burden but also because the biology and epidemiology of CMV suggest that there are ways to reduce viral transmission. Because exposure to the saliva or urine of young children is a major cause of CMV infection among pregnant women, it is likely that good personal hygiene, especially hand-washing, can reduce the risk of CMV acquisition. Experts agree that such measures are likely to be efficacious (i.e., they will work if consistently followed) and the American College of Obstetricians and Gynecologists recommends that physicians counsel pregnant women about preventing CMV acquisition through careful attention to hygiene. However, because of concerns about effectiveness (i.e., Will women consistently follow hygienic practices as the result of interventions?), the medical and public health communities appear reluctant to embrace primary CMV prevention via improved hygienic practices, and educational interventions are rare. Current data on the effectiveness of such measures in preventing CMV infection are promising, but limited. There is strong evidence, however, that educational interventions can prevent other infectious diseases with similar transmission modes, suggesting that effective interventions can also be found for CMV. Until a CMV vaccine becomes available, effective educational interventions are needed to inform women about congenital CMV prevention. SUMMARY: Perhaps no single cause of birth defects and developmental disabilities in the United States currently provides greater opportunity for improved outcomes in more children than congenital CMV. Given the present state of knowledge, women deserve to be informed about how they can reduce their risk of CMV infection during pregnancy, and trials are needed to identify effective educational interventions

Respiratory hospitalizations and respiratory syncytial virus prophylaxis in special populations

Palivizumab utilization, compliance, and outcomes were examined in infants with preexisting medical diseases within the Canadian Registry Database (CARESS) to aid in developing guidelines for potential “at-risk” infants in the future. Infants who received ≥1 dose of palivizumab during the 2006–2010 respiratory syncytial virus (RSV) seasons at 29 sites were recruited and utilization, compliance, and outcomes related to respiratory infection/illness (RI) events were collected monthly. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for premature infants ≤35 completed weeks gestational age (GA) who met standard approval criteria (group 1) compared to those with medical disorders (group 2) using Cox proportional hazards regression models with adjustment for potential confounding factors. Of 7,339 registry infants, 4,880 were in group 1 and 952 in group 2, which included those with Down syndrome (20.3%), upper airway anomalies (18.7%), pulmonary diseases (13.3%), and cystic fibrosis (12.3%). Group 2 were older at enrolment (10.2 ± 9.2 vs. 3.5 ± 3.1 months, p < 0.0005), had higher GA (35.9 ± 6.0 vs. 31.0 ± 5.4 weeks, p < 0.0005), and were less compliant with treatment intervals (69.4% vs. 72.6%, p = 0.048). A greater proportion of group 2 infants were hospitalized for RI (9.0% vs. 4.2%, p < 0.0005) and RSV (2.4% vs. 1.3%, p = 0.003) (unadjusted). Being in group 2 was associated with an increased risk of RI (HR = 2.0, 95%CI 1.5–2.5, p < 0.0005), but not RSV hospitalization (HR = 1.6, 95%CI 0.9–2.8, p = 0.106). In infants receiving palivizumab, those with underlying medical disorders, though not currently approved for prophylaxis, are at higher risk for RI events compared with preterm infants. However, risk of RSV hospitalizations is similar

The predictive value of post-traumatic stress disorder symptoms for quality of life: a longitudinal study of physically injured victims of non-domestic violence

<p>Abstract</p> <p>Background</p> <p>Little is known about longitudinal associations between post-traumatic stress disorder (PTSD) and quality of life (QoL) after exposure to violence. The aims of the current study were to examine quality of life (QoL) and the predictive value of post-traumatic stress disorder (PTSD) for QoL in victims of non-domestic violence over a period of 12 months.</p> <p>Methods</p> <p>A single-group (n = 70) longitudinal design with three repeated measures over a period of 12 months were used. Posttraumatic psychological symptoms were assessed by using the Impact of Event Scale, a 15-item self-rating questionnaire comprising two subscales (intrusion and avoidance) as a screening instrument for PTSD. The questionnaire WHOQOL-Bref was used to assess QoL. The WHOQOL-BREF instrument comprises 26 items, which measure the following broad domains: physical health, psychological health, social relationships, and environment. Results of the analysis were summarized by fitting Structural Equation Modelling (SEM).</p> <p>Results</p> <p>For each category of PTSD (probable cases, risk level cases and no cases), the mean levels of the WHOQOL-Bref subscales (the four domains and the two single items) were stable across time of assessment. Individuals who scored as probable PTSD or as risk level cases had significantly lower scores on the QoL domains such as physical health, psychological health, social relationships and environmental than those without PTSD symptoms. In addition, the two items examining perception of overall quality of life and perception of overall health in WHOQOL showed the same results according to PTSD symptoms such as QoL domains. PTSD symptoms predicted lower QoL at all three assessments. Similarly PTSD symptoms at T1 predicted lower QoL at T2 and PTSD symptoms at T2 predicted lower QoL at T3.</p> <p>Conclusion</p> <p>The presence of PTSD symptoms predicted lower QoL, both from an acute and prolonged perspective, in victims of non-domestic violence. Focusing on the individual's perception of his/her QoL in addition to the illness may increase the treatment priorities and efforts.</p

Differential Requirement for Utrophin in the Induced Pluripotent Stem Cell Correction of Muscle versus Fat in Muscular Dystrophy Mice

Duchenne muscular dystrophy (DMD) is an incurable degenerative muscle disorder. We injected WT mouse induced pluripotent stem cells (iPSCs) into mdx and mdx∶utrophin mutant blastocysts, which are predisposed to develop DMD with an increasing degree of severity (mdx <<< mdx∶utrophin). In mdx chimeras, iPSC-dystrophin was supplied to the muscle sarcolemma to effect corrections at morphological and functional levels. Dystrobrevin was observed in dystrophin-positive and, at a lesser extent, utrophin-positive areas. In the mdx∶utrophin mutant chimeras, although iPSC-dystrophin was also supplied to the muscle sarcolemma, mice still displayed poor skeletal muscle histopathology, and negligible levels of dystrobrevin in dystrophin- and utrophin-negative areas. Not only dystrophin-expressing tissues are affected by iPSCs. Mdx and mdx∶utrophin mice have reduced fat/body weight ratio, but iPSC injection normalized this parameter in both mdx and mdx∶utrophin chimeras, despite the fact that utrophin was compromised in the mdx∶utrophin chimeric fat. The results suggest that the presence of utrophin is required for the iPSC-corrections in skeletal muscle. Furthermore, the results highlight a potential (utrophin-independent) non-cell autonomous role for iPSC-dystrophin in the corrections of non-muscle tissue like fat, which is intimately related to the muscle