Positivity for anti-HSV IgM, a sign of reactivated infection, was found to almost double the risk for AD, whereas the presence of anti-HSV IgG antibodies did not affect the risk.

The genus Hantavirus of the family Bunyaviridae comprises to the retroperitoneal space, and the kidneys are usually not affected [7]. at least 15 viruses, including those that cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary Slovenia is situated in the northern part of the Balkan Peninsula. Evidence of the circulation of PUU and DOB viruses syndrome. Each hantavirus is carried primarily by a specific throughout the Balkans has been collected recently [5, 8]. The rodent or insectivore host and is transmitted by inhalation of presence of HFRS in Slovenia was first reported in 1954 [9]. virus-contaminated aerosols of rodent excreta [1, 2]. Because Since then, 110 cases occurring sporadically or in small epiof the virus-rodent association, each hantavirus has a characterdemics have been documented [authors' unpublished data]. istic geographic distribution. HFRS, which is caused by HanBoth severe and mild clinical courses of the disease are seen, taan (HTN), Seoul (SEO), Dobrava (DOB), and Puumala with an overall mortality rate of 4.5% [10]. The presence of (PUU) viruses, occurs endemically on the Eurasian continent, two different hantaviruses responsible for human infections in whereas hantavirus pulmonary syndrome caused by Sin NomSlovenia has already been reported [11]. Broad epidemiological bre and related viruses occurs in the Americas [3 -5]. Both studies have shown that 10% to 35% of the rodents captured syndromes involve a sudden onset of high fever, headache, and in areas in Slovenia where HFRS is endemic have antibodies myalgia. HFRS may appear as a mild, moderate, or severe to hantavirus [12]. disease with renal impairment as the predominant organ maniIn 1988, DOB virus was isolated from the lungs of a yellowfestation. The mortality rate varies from õ0.5% for HFRS necked field mouse (Apodemus flavicollis) captured in the vilcaused by PUU virus to Ç5% to 10% for HFRS caused by HTN lage of Dobrava (Dolenjska region, Slovenia) where a number virus [6]. Hantavirus pulmonary syndrome is characterized by of cases of severe HFRS had occurred. Complete genetic and acute noncardiac pulmonary edema and is associated with a antigenic characterization identified DOB virus as a unique mortality rate of Ç50%; capillary leakage in hantavirus pulmohantavirus [13]. Recent reports have shown that DOB virus is nary syndrome is localized exclusively to the lungs, rather than the etiologic agent of the severe form of HFRS that occurs in the Balkans [5, 8,14]. In this report, we describe the clinical presentation of patients with HFRS who were hospitalized from 1985 to 1995 at the

Seoul virus (SEOV) is one of four known hantaviruses causing hemorrhagic fever with renal syndrome (HFRS). Candidate naked DNA vaccines for HFRS were constructed by subcloning cDNA representing the medium (M; encoding the G1 and G2 glycoproteins) or small (S; encoding the nucleocapsid protein) genome segment of SEOV into the DNA expression vector pWRG7077. We vaccinated BALB/c mice with three doses of the M or S DNA vaccine at 4-week intervals by either gene gun inoculation of the epidermis or needle inoculation into the gastrocnemius muscle. Both routes of vaccination resulted in antibody responses as measured by ELISA; however, gene gun inoculation elicited a higher frequency of seroconversion and higher levels of antibodies in individual mice. We vaccinated Syrian hamsters with the M or S construct using the gene gun and found hantavirus-specific antibodies in five of five and four of five hamsters, respectively. Animals vaccinated with the M construct developed a neutralizing antibody response that was greatly enhanced in the presence of guinea pig complement. Immunized hamsters were challenged with SEOV and, after 28 days, were monitored for evidence of infection. Hamsters vaccinated with M were protected from infection, but hamsters vaccinated with S were not protected.

BackgroundThe conversion of soluble peptides and proteins into polymeric amyloid structures is a hallmark of many age-related degenerative disorders, including Alzheimer's disease, type II diabetes and a variety of systemic amyloidoses. We report here that amyloid formation is linked to another major age-related phenomenon − prostate tissue remodelling in middle-aged and elderly men.Methodology/Principal FindingsBy using multidisciplinary analysis of corpora amylacea inclusions in prostate glands of patients diagnosed with prostate cancer we have revealed that their major components are the amyloid forms of S100A8 and S100A9 proteins associated with numerous inflammatory conditions and types of cancer. In prostate protease rich environment the amyloids are stabilized by dystrophic calcification and lateral thickening. We have demonstrated that material closely resembling CA can be produced from S100A8/A9 in vitro under native and acidic conditions and shows the characters of amyloids. This process is facilitated by calcium or zinc, both of which are abundant in ex vivo inclusions. These observations were supported by computational analysis of the S100A8/A9 calcium-dependent aggregation propensity profiles. We found DNA and proteins from Escherichia coli in CA bodies, suggesting that their formation is likely to be associated with bacterial infection. CA inclusions were also accompanied by the activation of macrophages and by an increase in the concentration of S100A8/A9 in the surrounding tissues, indicating inflammatory reactions.Conclusions/SignificanceThese findings, taken together, suggest a link between bacterial infection, inflammation and amyloid deposition of pro-inflammatory proteins S100A8/A9 in the prostate gland, such that a self-perpetuating cycle can be triggered and may increase the risk of malignancy in the ageing prostate. The results provide strong support for the prediction that the generic ability of polypeptide chains to convert into amyloids could lead to their involvement in an increasing number of otherwise apparently unrelated diseases, particularly those associated with ageing.