PubMed Health⌕ Search

Biomedical subjects

S Stenmark

Publications and source records attributed to S Stenmark.

6 recordsLinked to original sources

Rapid local expression of interleukin-12, tumor necrosis factor alpha, and gamma interferon after cutaneous Francisella tularensis infection in tularemia-immune mice.

Francisella tularensis LVS is an effective live vaccine strain used for cutaneous vaccination against tularemia in man. In mice, injection of LVS causes invasive disease and subsequent development of immunity that is characterized by effective control of otherwise lethal doses of the organism. In the present investigation, it is shown that LVS-immune mice controlled an intradermal infection much more effectively than did naive mice; bacterial counts in skin samples were 1.5 to 2.0 log10 lower 24 h after injection and 6 log10 lower 72 h after injection in immune mice. Moreover, in contrast to naive mice, no bacteria were demonstrated in samples from livers and spleens of immune mice. By immunohistochemistry, skin samples from immune mice showed an intense staining for interleukin-12 (IL-12) and a moderate staining for tumor necrosis factor alpha (TNF-alpha) at 24 h postinoculation, after which staining for both cytokines faded. In naive mice, the staining for IL-12 was weak at all time points and no staining for TNF-alpha was observed. No staining for gamma interferon (IFN-gamma) was observed in any group before 72 h. At that time point, skin samples from immune mice showed moderate staining and skin samples from naive mice showed weak staining. Reverse transcriptase PCR showed an induction of mRNA of the three cytokines in the skin within the first day after injection. A quantitative analysis demonstrated higher IFN-gamma and TNF-alpha mRNA levels in immune mice at 24 h postinoculation. In conclusion, immunization with F. tularensis LVS conferred a capability to respond to cutaneous reinfection, with rapid local expression of IL-12, TNF-alpha, and IFN-gamma, and this expression was paralleled by containment and mitigation of the infection. The cytokine response may be part of a local barrier function of the skin, important to host protection against tularemia.

Animals↗

Expansion of Vgamma9 Vdelta2 T cells is triggered by Francisella tularensis-derived phosphoantigens in tularemia but not after tularemia vaccination.

Tularemia is a disease caused by the facultative intracellular bacterium Francisella tularensis. Here we demonstrate that during the first weeks of infection, a significant increase in levels of Vgamma9 Vdelta2 cells occurred in peripheral blood: in 13 patients analyzed 7 to 18 days after the onset of disease, these lymphocytes represented, on average, 30.5% of CD3+ cells and nearly 100% of gammadelta+ T cells. By contrast, after vaccination with the live vaccine strain (LVS) of F. tularensis, only a minor increase occurred. Eleven days after vaccination, gammadelta T cells represented an average of 6.7% and Vgamma9 Vdelta2 cells represented an average of 5.3% of T cells, as in control subjects. Since derivatives of nonpeptidic pyrophosphorylated molecules, referred to as phosphoantigens, are powerful stimuli for Vgamma9 Vdelta2 cells, this observation prompted an investigation of phosphoantigens in F. tularensis strains. The F. tularensis phosphoantigens triggered in vitro a proliferative response of human Vgamma9 Vdelta2 peripheral blood leukocytes as well as a cytotoxic response and tumor necrosis factor release from a Vgamma9 Vdelta2 T-cell clone. Quantitatively similar phosphoantigenic activity was detected in acellular extracts from two clinical isolates (FSC171 and Schu) and from LVS. Taken together, the chemical nature of the stimulus from the clinical isolates and the significant increase in levels of Vgamma9 Vdelta2 cells in peripheral blood of tularemia patients indicate that phosphoantigens produced by virulent strains of F. tularensis trigger in vivo expansion of gammadelta T cells in tularemia.

Adult↗

Reducing childhood disability in the 80s.

Childhood disability is now known to be a major public health problem throughout the world. It is estimated that in 1975 about 10 percent of the world's 1.4 billion children suffered from one or more disabilities. The authors discuss the patterns and causes of childhood disability from an international perspective and outline a number of factors that will continue to influence the incidence of disability in the 1980s. They conclude by suggesting several strategies for change, both national and international in nature, to help prevent disability and to care for disabled children.

Accidents↗

Immunoglobulin G and M antibodies to pneumococcal polysaccharides detected by enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay has been developed to detect serum immunoglobulin G and M antibodies against pneumococcal polysaccharide antigens. Parameters affecting the specificity and sensitivity of the assay are described. A vigorous antibody response involving both the immunoglobulin G and M classes was demonstrated after pneumococcal polysaccharide immunization in normal adults. Studies with this enzyme-linked immunosorbent assay technique will allow further understanding of the biology of the primary and secondary immune response to Streptococcus pneumoniae in normals as well as in those persons most susceptible to infection with that organism.

Adult↗