La Crosse virus infectivity, pathogenesis, and immunogenicity in mice and monkeys

<p>Abstract</p> <p>Background</p> <p>La Crosse virus (LACV), family Bunyaviridae, was first identified as a human pathogen in 1960 after its isolation from a 4 year-old girl with fatal encephalitis in La Crosse, Wisconsin. LACV is a major cause of pediatric encephalitis in North America and infects up to 300,000 persons each year of which 70–130 result in severe disease of the central nervous system (CNS). As an initial step in the establishment of useful animal models to support vaccine development, we examined LACV infectivity, pathogenesis, and immunogenicity in both weanling mice and rhesus monkeys.</p> <p>Results</p> <p>Following intraperitoneal inoculation of mice, LACV replicated in various organs before reaching the CNS where it replicates to high titer causing death from neurological disease. The peripheral site where LACV replicates to highest titer is the nasal turbinates, and, presumably, LACV can enter the CNS via the olfactory neurons from nasal olfactory epithelium. The mouse infectious dose₅₀and lethal dose₅₀was similar for LACV administered either intranasally or intraperitoneally. LACV was highly infectious for rhesus monkeys and infected 100% of the animals at 10 PFU. However, the infection was asymptomatic, and the monkeys developed a strong neutralizing antibody response.</p> <p>Conclusion</p> <p>In mice, LACV likely gains access to the CNS via the blood stream or via olfactory neurons. The ability to efficiently infect mice intranasally raises the possibility that LACV might use this route to infect its natural hosts. Rhesus monkeys are susceptible to LACV infection and develop strong neutralizing antibody responses after inoculation with as little as 10 PFU. Mice and rhesus monkeys are useful animal models for LACV vaccine immunologic testing although the rhesus monkey model is not optimal.</p

A Case Study of Pseudo-Neuropathic Pseudogout

Background This interesting case highlights the clinical progression of a rare disease process and the important role of a multi-disciplinary team in achieving a diagnosis and successful management plan. Case Presentation A 76-year-old male with a history of coronary artery disease, hypertension and hyperlipidemia presented as an outpatient with left foot pain and swelling. He had spent a week bicycling in Colorado one month prior to presentation. The pain was initially localized to the plantar surface of his foot and progressed to involve the lateral and dorsal aspects of the foot, as well as his great toe. The pain was accompanied by swelling of the midfoot without erythema and he was unable to bear weight. His podiatrist prescribed Ibuprofen and a foot brace for empiric treatment of tendonitis. An outpatient MRI demonstrated extensive bony edema and synovial enhancement within the midfoot, as well as severe superficial edema and peroneal tendonitis with mild subluxation. The patient was sent to the emergency department to be evaluated for osteomyelitis

Longitudinal assessment of cognitive and psychosocial functioning after Hurricanes Katrina and Rita: Exploring disaster impact on middle-aged, older, and oldest-old adults

The authors examined the effects of Hurricanes Katrina and Rita on cognitive and psychosocial functioning in a lifespan sample of adults 6-14 months after the storms. Participants were recruited from the Louisiana Healthy Aging Study. Most were assessed during the immediate impact period and retested for this study. Analyses of pre- and post-disaster cognitive data confirmed that storm-related decrements in working memory for middle-aged and older adults observed in the immediate impact period had returned to pre-hurricane levels in the post-disaster recovery period. Middle-aged adults reported more storm-related stressors and greater levels of stress than the two older groups at both waves of testing. These results are consistent with a burden perspective on post-disaster psychological reactions. © 2012 Wiley Periodicals, Inc

Epigenetic silencing of DSC3 is a common event in human breast cancer

INTRODUCTION: Desmocollin 3 (DSC3) is a member of the cadherin superfamily of calcium-dependent cell adhesion molecules and a principle component of desmosomes. Desmosomal proteins such as DSC3 are integral to the maintenance of tissue architecture and the loss of these components leads to a lack of adhesion and a gain of cellular mobility. DSC3 expression is down-regulated in breast cancer cell lines and primary breast tumors; however, the loss of DSC3 is not due to gene deletion or gross rearrangement of the gene. In this study, we examined the prevalence of epigenetic silencing of DSC3 gene expression in primary breast tumor specimens. METHODS: We used bisulfite genomic sequencing to analyze the methylation state of the DSC3 promoter region from 32 primary breast tumor specimens. We also used a quantitative real-time RT-PCR approach, and analyzed all breast tumor specimens for DSC3 expression. Finally, in addition to bisulfite sequencing and RT-PCR, we used an in vivo nuclease accessibility assay to determine the chromatin architecture of the CpG island region from DSC3-negative breast cancer cells lines. RESULTS: DSC3 expression was downregulated in 23 of 32 (72%) breast cancer specimens comprising: 22 invasive ductal carcinomas, 7 invasive lobular breast carcinomas, 2 invasive ductal carcinomas that metastasized to the lymph node, and a mucoid ductal carcinoma. Of the 23 specimens showing a loss of DSC3 expression, 13 (56%) were associated with cytosine hypermethylation of the promoter region. Furthermore, DSC3 expression is limited to cells of epithelial origin and its expression of mRNA and protein is lost in a high proportion of breast tumor cell lines (79%). Lastly, DNA hypermethylation of the DSC3 promoter is highly correlated with a closed chromatin structure. CONCLUSION: These results indicate that the loss of DSC3 expression is a common event in primary breast tumor specimens, and that DSC3 gene silencing in breast tumors is frequently linked to aberrant cytosine methylation and concomitant changes in chromatin structure

Efficacy and Safety of Infliximab in Older Inflammatory Bowel Disease Patients

Background: The limited data regarding treatment of inflammatory bowel disease (IBD) with anti-tumor necrosis factor antibodies in older patients suggest equal efficacy but higher morbidity and mortality compared to younger patients. This retrospective case control study aims to clarify the efficacy and safety of infliximab (IFX) in older IBD patients

La Crosse virus infectivity, pathogenesis, and immunogenicity in mice and monkeys-5

Ark gray, 33% light gray, 0% no data entry. Mean virus titer calculated only for virus positive tissues. Areas left blank indicate virus titer below detection limit of 0.7 log10 PFU/tissue.<p><b>Copyright information:</b></p><p>Taken from "La Crosse virus infectivity, pathogenesis, and immunogenicity in mice and monkeys"</p><p>http://www.virologyj.com/content/5/1/25</p><p>Virology Journal 2008;5():25-25.</p><p>Published online 11 Feb 2008</p><p>PMCID:PMC2276200.</p><p></p