Structure and biological activities of acapsular Cryptococcus neoformans 602 complemented with the CAP64 gene.

The extracellular polysaccharide capsule of Cryptococcus neoformans is a well-recognized virulence factor. Strain 602 is an acapsular clinical isolate of unknown serotype which has been widely used in studies of virulence and host-parasite interactions. In previous studies, strain 602 was compared with genetically unrelated strains of various serotypes because the wild-type equivalent of strain 602 was not available. We created an encapsulated strain, TYCC38-602, by transforming strain 602 with the CAP64 gene which was isolated from a serotype D strain. Serological tests and chemical analysis of the major polysaccharide capsule of TYCC38-602 indicated that strain 602 was originally derived from a serotype A strain. Restoration of the ability to produce a capsule enabled strain 602 to cause fatal infection in mice, whereas the acapsular strain 602 remained avirulent. Capsule-restored yeast cells of strain 602 activated the human complement system and bound C3 fragments in a manner that is characteristic of encapsulated cryptococci. In addition, the capsule in TYCC38-602 masked the ability of the organism to induce tumor necrosis factor alpha and subsequent nitric oxide synthase production in primed macrophage-like cells. These results indicate that the lack of capsule in strain 602 is the reason for its inability to cause fatal infection. Moreover, the acapsular phenotype accounts for differences in various biological activities of strain 602 compared to encapsulated strains. The results also indicate that the gene product of CAP64 does not contribute to serotype specificity of capsules in C. neoformans.     

CD8 CTL responses in vaccines: emerging patterns of HLA restriction and epitope recognition

We evaluated MHC-class I-restricted CTL responses induced by HIV-1 clade B-based vaccines in nine HIV-1 seronegative vaccine recipients with regard to their patterns of HLA restriction and epitope recognition. We found that seven of nine volunteers developed detectable CTL reactivities against novel epitopes within the HIV-1 Env and Gag proteins. Although four of nine subjects were HLA-A*0201, none of the cellular responses was restricted in the context of this allele. The type of responses observed in this sampling of vaccines appeared similar to those reported during primary infection and among long term non-progressors, with three out of nine subjects recognizing HLA-B27 or HLA-B17(57)-restricted epitopes. Although the majority of CTL responses were directed against novel epitopes, these effectors were still able to mediate cross-clade reactivities.     

Murine in vitro antigenic modification of tumor cells: effect on susceptibility to natural cell-mediated cytotoxicity

A 3-methylcholanthrene [(MCA) CAS: 56-49-5]-induced fibrosarcoma cell line and its Friend murine leukemia virus-infected counterpart were assessed for their susceptibility to lysis by so-called "natural" effector cells in a series of 51Cr release assays. Detailed functional and phenotypic analysis of lytic effector cell populations from normal C57BL/6 mouse spleens revealed an identity most closely associated with natural cytotoxic cells. Neither tumor cell line was found to be sensitive to natural killer-mediated lysis. Additionally, virus infection of the MCA-induced fibrosarcoma cell line did not affect susceptibility to natural cell-mediated cytotoxicity.     

Quantitative examination of isometric tongue protrusion forces in children with oro‐facial dysfunctions or myofunctional disorders

Oro‐facial dysfunctions (OFD) or oro‐facial myofunctional disorders in children lead to severe problems in teeth and jaw position, articulation, chewing and swallowing. The forces of the tongue, the central muscle for articulation, chewing and swallowing are focused on in several studies. In this examination, isometric tongue protrusion forces (TPF) of children with OFD and controls were compared. Thirty participants with OFD and 30 controls were presented a target force level as a straight line on a monitor that they were supposed to match by generating an isometric tongue force for different target levels (0.25 N and 0.5 N). Correlations of the severity of OFD (symptom score) with the capacities of the TPF 0.25 N and 0.5 N were calculated. Statistical differences were obvious in TPF variability and the accuracy, depending on the weight. Tongue contact time, expressed as per cent (TCT, total contact: 100%), was significantly lower in children with OFD (P = .005). Mean and median TPF was not different between groups. The predictive value of TPF for OFD revealed a level of 58.6% for TPF 0.25 N and 74.5% for TPF 0.5 N. Correlations of the severity of OFD were seen for some parameters. Subjects with OFD show significantly lower competencies in accuracy and endurance of tongue protrusion forces. This may have a high impact on phenotyping children with OFD and influence therapeutical approaches.