Heart-reactive antibodies in rabbit anti-Streptococcus mutans sera fail to cross-react with Streptococcus mutans

Immunization of rabbits with Streptococcus mutans antigens results in the production of serum antibodies that bind in vitro to human, rabbit, and monkey cardiac muscle. Antibodies to heart, however, have also been reported to occur at lower titers in the sera of unimmunized rabbits. In this study, the specificities of heart-reactive antibodies (HRA) in sera of unimmunized and S. mutans-immunized rabbits were compared using indirect immunofluorescence, Western blot, and Bio-Dot immunoassays. Both groups of sera gave striational indirect immunofluorescence-staining patterns on thin sections of native human and monkey cardiac muscle. Western blot analyses revealed that antibodies in normal sera bound 9 to 20 components of human, rabbit, and monkey heart. The major bands had Mr of 205,000, 160,000, 135,000, and 70,000. Several of the normal sera did not have antibody activity to S. mutans antigens, indicating that these HRA do not cross-react with these bacteria. Although immunization of rabbits with S. mutans caused increased titers of HRA (two to three doubling dilutions), Western blot assays using anti-S. mutans sera showed banding patterns qualitatively similar to those of normal sera on heart extracts. Antibodies to skeletal muscle myosin were detected in both serum groups. Of eighteen normal rabbit sera sixteen had antimyosin titers of 10 to 40, whereas all eighteen anti-S. mutans sera had titers of 10 to 160. Affinity-purified antimyosin antibodies isolated from anti-S. mutans serum did not bind to S. mutans components. Conversely, affinity-purified antibodies to S. mutans antigens did not bind to myosin or to other cardiac muscle components. Among these were antibodies to the 185-kDa cell wall protein (also known as B, I/II, IF, Spa A, and P1) previously believed to possess antigenic mimicry. HRA were removed from anti-S. mutans sera by absorption with S. mutans but this effect was not specific, because a non-cross-reactive internal standard antibody was also absorbed to the same extent. Because previous evidence for antigenic mimicry between S. mutans and cardiac muscle was based on serum cross-absorption experiments, this immunologic relationship is not substantiated. These results indicated that naturally occurring antibodies to cardiac muscle components are present in the sera of unimmunized rabbits and that immunization with S. mutans does not stimulate production of new heart-reactive antibody, but rather serves to boost antibody production by preexisting clones of self-reactive B-lymphocytes.     

Photochemical carbon-sulfur bond cleavage in some alkyl and benzyl sulfides

Irradiation (254 nm) of five alkyl and benzyl ethyl sulfides causes efficient (Φ_r 0.27-0.90) homolytic cleavage of the C-S bond. Of the resulting fragments, thiyl radicals mainly couple, while alkyl radicals abstract hydrogen, disproportionate or couple when stabilized (benzyl). Selective trapping of either of the two types of radicals occurs in the presence of nucleophilic (methyl vinyl ether and 1-hexene) and, respectively, electrophilic (acrylonitrile) alkenes. When an easily oxidized radical is formed, e.g. cumyl, secondary electron transfer leads to the corresponding cation.     

Homozygous Mutations in ADAMTS10 and ADAMTS17 Cause Lenticular Myopia, Ectopia Lentis, Glaucoma, Spherophakia, and Short Stature

Weill-Marchesani syndrome (WMS) is a well-characterized disorder in which patients develop eye and skeletal abnormalities. Autosomal-recessive and autosomal-dominant forms of WMS are caused by mutations in ADAMTS10 and FBN1 genes, respectively. Here we report on 13 patients from seven unrelated families from the Arabian Peninsula. These patients have a constellation of features that fall within the WMS spectrum and follow an autosomal-recessive mode of inheritance. Individuals who came from two families and met the diagnostic criteria for WMS were each found to have a different homozygous missense mutation in ADAMTS10. Linkage analysis and direct sequencing of candidate genes in another two families and a sporadic case with phenotypes best described as WMS-like led to the identification of three homozygous mutations in the closely related ADAMTS17 gene. Our clinical and genetic findings suggest that ADAMTS17 plays a role in crystalline lens zonules and connective tissue formation and that mutations in ADAMTS17 are sufficient to produce some of the main features typically described in WMS.     

Prevalence of Bartonella henselae and Borrelia burgdorferi Sensu Lato DNA in Ixodes ricinus Ticks in Europe

Bartonella spp. can cause persistent bloodstream infections in humans and animals. To determine whether Bartonella henselae is present in questing Ixodes ricinus ticks, we analyzed the prevalence of B. henselae DNA among tick stages compared to the prevalence of DNA from Borrelia burgdorferi sensu lato, the pathogen most frequently transmitted by ticks. B. henselae DNA was present with a prevalence of up to ∼40% in tick populations sampled in four European sites (Eberdingen, Germany; Klasdorf, Germany; Lembach, France; and Madeira, Portugal). The odds of detecting B. henselae DNA in nymphal ticks was ∼14-fold higher than in adult ticks. No tick was found to be coinfected with B. henselae and B. burgdorferi sensu lato. Taken together, our data indicate that ticks might serve as a vector for the transmission of B. henselae to humans.In immunocompetent patients, Bartonella henselae infections often result in cat scratch disease (CSD), a self-limiting but often prolonged lymphadenitis; immunocompromised patients (e.g., AIDS patients) can suffer from vasculoproliferative disorders (bacillary angiomatosis, peliosis hepatis [1]). Cats are a confirmed reservoir host of B. henselae transmitting the pathogen by cat scratches or bites.Several Bartonella species (e.g., B. henselae, B. quintana, and B. vinsonii) cause a persistent intraerythrocytic bacteremia in their respective mammalian reservoir hosts (7). B. henselae was detected in the peripheral blood of a wide range of mammals including domestic (e.g., cats, dogs, and horses) and wild animals (e.g., porpoise, lions, cheetahs, and wild felids). Obviously, such an asymptomatic, persistent bacteremia with B. henselae represents an important factor for the spread of the pathogens via blood-sucking arthropods. Mechanistic details determining the intraerythrocytic presence of Bartonella spp. have been investigated in detail in a B. tribocorum rat infection model mimicking Trench fever (a human disease caused by B. quintana); here, the pathogen persists several weeks in the circulating blood in an immunoprivileged intraerythrocytic niche (28).Cat fleas are well established vectors for B. henselae (1). However, transmission by other arthropods, in particular ticks, has been suggested: B. henselae DNA was detected in questing Ixodes pacificus and I. persulcatus ticks in North America, Eastern Europe, and Russia, respectively (4, 13, 14, 22, 25) and in I. ricinus ticks feeding on people or domestic animals in Central Europe (24, 26). DNA of various Bartonella spp. has also been detected in keds, biting flies, and mites (reviewed in reference 2). Recently, ticks (I. ricinus) were experimentally infected with B. henselae. Inoculation of cats with salivary glands of infected ticks resulted in a B. henselae bacteremia (5). Nevertheless, controversial data about the prevalence of Bartonella spp. in ticks and their role as vectors for B. henselae exist (29).Here, we present data on the prevalence of B. henselae and Lyme disease spirochetes in 654 questing ticks (I. ricinus) collected at four locations in Europe, suggesting that ticks might serve as potential vectors for the transmission of B. henselae to humans.     

Perpetuation of the Lyme disease spirochete Borrelia lusitaniae by lizards

To determine whether the Lyme disease spirochete Borrelia lusitaniae is associated with lizards, we compared the prevalence and genospecies of spirochetes present in rodent- and lizard-associated ticks at a site where this spirochete frequently infects questing ticks. Whereas questing nymphal Ixodes ricinus ticks were infected mainly by Borrelia afzelii, one-half of the infected adult ticks harbored B. lusitaniae at our study site. Lyme disease spirochetes were more prevalent in sand lizards (Lacerta agilis) and common wall lizards (Podarcis muralis) than in small rodents. Although subadult ticks feeding on rodents acquired mainly B. afzelii, subadult ticks feeding on lizards became infected by B. lusitaniae. Genetic analysis confirmed that the spirochetes isolated from ticks feeding on lizards are members of the B. lusitaniae genospecies and resemble type strain PotiB2. At our central European study site, lizards, which were previously considered zooprophylactic for the agent of Lyme disease, appear to perpetuate B. lusitaniae.     

Production of an antigenic C4(V3)6 multiepitopic HIV protein in bacterial and plant systems

A C4(V3)6 multiepitopic protein was designed in an effort to pursue broad immunization against the human immunodeficiency virus (HIV). This C4(V3)6 chimeric protein is based on sequences of gp120, including epitopes from the fourth conserved domain (C4) and six tandem repeats of the third variable domain (V3), which represent different HIV isolates. The histidine-tagged C4(V3)6 was subsequently over-expressed in a recombinant Escherichia coli strain, and purified by immobilized metal ion affinity chromatography. Expression of the C4(V3)6 in both tobacco and lettuce plants was also achieved with no toxic effects on plant growth as transgenic plants were phenotypically normal. Moreover, the functional C4(V3)6 protein showed HIV antigenic determinants. The implications of these findings on the development of a new low-cost HIV vaccine are discussed.     

Epizootiologic investigations of selected abortive agents in free-ranging Alpine ibex (Capra ibex ibex) in Switzerland

In the early 2000s, several colonies of Alpine ibex (Capra ibex ibex) in Switzerland ceased growing or began to decrease. Reproductive problems due to infections with abortive agents might have negatively affected recruitment. We assessed the presence of selected agents of abortion in Alpine ibex by serologic, molecular, and culture techniques and evaluated whether infection with these agents might have affected population densities. Blood and fecal samples were collected from 651 ibex in 14 colonies throughout the Swiss Alps between 2006 and 2008. All samples were negative for Salmonella spp., Neospora caninum, and Bovine Herpesvirus-1. Antibodies to Coxiella burnetii, Leptospira spp., Chlamydophila abortus, Toxoplasma gondii, and Bovine Viral Diarrhea virus were detected in at least one ibex. Positive serologic results for Brucella spp. likely were false. Overall, 73 samples (11.2%) were antibody-positive for at least one abortive agent. Prevalence was highest for Leptospira spp. (7.9%, 95% CI=5.0-11.7). The low prevalences and the absence of significant differences between colonies with opposite population trends suggest these pathogens do not play a significant role in the population dynamics of Swiss ibex. Alpine ibex do not seem to be a reservoir for these abortive agents or an important source of infection for domestic livestock in Switzerland. Finally, although interactions on summer pastures occur frequently, spillover from infected livestock to free-ranging ibex apparently is uncommon.