Psoriasis confined strictly to vitiligo areas – a Koebner‐like phenomenon?

Vitiligo and psoriasis are both common skin disorders. However, psoriasis strictly confined to pre-existing vitiligo areas is rare and suggests a causal relationship. We report here on two patients with a strict anatomical colocalization of vitiligo and psoriasis. The histopathological examinations showed typical changes for both diseases together with a dense infiltrate of CD4+ and CD8+ T cells. By immunohistochemistry, intracytoplasmatic granzyme B and tumour necrosis factor alpha (TNF-alpha) were detected within the T-cell population, suggesting the functional activity of these cells and the creation of a local T helper 1 (Th1)-cytokine milieu. Additionally, in one patient we could identify anti-melanocytic T cells by tetramer staining and enzyme-linked immunospot (ELISPOT) analysis. These skin-infiltrating lymphocytes might trigger, by the local production of Th-1 cytokines such as TNF-alpha and interferon-gamma (IFN-gamma), the eruption of psoriatic plaques in patients with a genetic predisposition for psoriasis.     

Circannual variation in lymphocyte subsets, revisited

BACKGROUND: Circadian and circannual variations in lymphocyte subsets, especially CD8+ T-lymphocytes, have been reported. This study focuses on CD4+ T-lymphocyte seasonal variation over a 6-year 8-month period. STUDY DESIGN AND METHODS: Lymphocyte subsets were quantitated monthly for four healthy individuals from 1986 through 1992 as part of a flow cytometry quality-control program. RESULTS: In general, there were no significant seasonal changes in the total number of white cells or in total lymphocyte counts. The absolute numbers of CD4+ T-lymphocytes were lowest in summer when the CD8+ T-lymphocytes were highest. Mean CD4+ T-lymphocyte counts were 846, 967, 618, and 695 per microL for Subjects 1 through 4, respectively, in winter and 432, 670, 355, and 766 per microL, respectively, in summer. Two healthy subjects had CD4+ T-lymphocyte counts lower than 300 per microL on one or more occasions during the study period. In three of the four subjects, the percentage of B-lymphocytes in winter was almost double that in summer. In one of the four subjects, no circannual rhythm was observed in these lymphocyte subpopulations. CONCLUSION: The seasonal variation in CD4+ T- lymphocyte counts demonstrated in three healthy individuals over almost 7 years is again of interest in light of renewed consideration of using surrogate tests, such as CD4+ T-lymphocyte counts, to screen for AIDS- like diseases that may be in the blood supply.     

A rapid microagglutination test for the diagnosis of Legionella pneumophila (serogroup 1) infection

A rapid microagglutination test has been developed which can be performed in 30 minutes. Ninety-seven percent of 96 patients diagnosed as having Legionella pneumophila (serogroup 1) infection by indirect immunofluorescence were also detected by the rapid microagglutination test.     

At Least Four Percent of the Salmonella typhimurium Genome Is Required for Fatal Infection of Mice

Salmonella typhimurium infection of mice is an established model system for studying typhoid fever in humans. Using this model, we identified S. typhimurium genes which are absolutely required to cause fatal murine infection by testing independently derived transposon insertion mutants for loss of virulence in vivo. Of the 330 mutants tested intraperitoneally and the 197 mutants tested intragastrically, 12 mutants with 50% lethal doses greater than 1,000 times that of the parental strain were identified. These attenuated mutants were characterized by in vitro assays which correlate with known virulence functions. In addition, the corresponding transposon insertions were mapped within the S. typhimurium genome and the nucleotide sequence of the transposon-flanking DNA was obtained. Salmonella spp. and related bacteria were probed with flanking DNA for the presence of these genes. All 12 attenuated mutants had insertions in known genes, although the attenuating effects of only two of these were previously described. Furthermore, the proportion of attenuated mutants obtained in this study suggests that mutations in about 4% of the Salmonella genome lead to 1,000-fold or greater attenuation in the mouse typhoid model of infection. Most of these genes appear to be required during the early stages of a natural infection.     

Contribution of fimbrial operons to attachment to and invasion of epithelial cell lines by Salmonella typhimurium.

The role of the Salmonella typhimurium fimbrial operons, lpf, fim, and pef, in adhesion to and invasion of epithelial cell lines was investigated. An S. typhimurium lpfC mutant was unable to adhere to or to invade HEp-2 cells, while an S. typhimurium fim deletion mutant did not attach to or enter HeLa cells. These results suggest that adhesion is a prerequisite for invasion and that distinct fimbrial adhesins select different target cells for invasion by S. typhimurium.     

Studies on the origin of redox enzymes in seminal plasma and their relationship with results of in-vitro fertilization

Glutathione (GSH), GSH peroxidase (GPX), GSH reductase (GRD), superoxide dismutase (SOD) and catalase-like enzyme activity were quantified in seminal plasma from normozoospermic patients, men with known distal ductal occlusion, proven fathers and male partners of couples receiving in-vitro fertilization (IVF) treatment for both male and female causes. Glutathione was non-detectable (< 2.5 microM) in seminal plasma. None of the enzyme activities per unit volume were lower in semen from vasectomized men, suggesting that they did not originate substantially from the testis or epididymis. The strongest relationships between enzyme activities and accessory gland markers were between zinc and GRD (r = 0.678), SOD (r = 0.602) and GPX (r = 0.548), suggesting a largely prostatic origin of these enzymes. Only weak relationships between accessory gland markers and catalase-like activity suggested a multi-glandular source of this enzyme. There was no relationship between the activity of any of the enzymes in the IVF patients with their fertilization rates in vitro or the establishment of pregnancy after IVF. Nor was there any correlation of enzyme activity with the morphology and percentage of motile spermatozoa in semen or with the percentage motility of spermatozoa immediately after swim-up or after overnight incubation. These findings suggest that the protective enzymes in the seminal plasma are contributed largely by the prostate and little by the epididymis, and that in most cases of IVF, they have no major influence on the outcome.      

Synergistic effect of mutations in invA and lpfC on the ability of Salmonella typhimurium to cause murine typhoid.

Penetration of the intestinal mucosa at areas of Peyer's patches is an important first step for Salmonella typhimurium to produce lethal systemic disease in mice. However, mutations in genes that are important for intestinal invasion result in only moderately decreased virulence of S. typhimurium for mice. Here we report that combining mutations in invA and lpfC, two genes necessary for entry into Peyer's patches, results in a much stronger attenuation of S. typhimurium than inactivation of either of these genes alone. An S. typhimurium invA lpfC mutant was 150-fold attenuated by the oral route of infection but was fully virulent when the intestine was bypassed by intraperitoneal challenge of mice. During mixed-infection experiments, the S. typhimurium invA lpfC mutant showed a strong defect in colonizing Peyer's patches and mesenteric lymph nodes. These data suggest that mutations in invA and lpfC deactivate distinct pathways for intestinal penetration and colonization of Peyer's patches. While the inv-mediated pathway is widely distributed, the lpf operon is absent from many phylogenetic groups within the genus Salmonella. To investigate how acquisition of the lpf-mediated pathway for mucosal penetration contributed to evolution of virulence, we studied the relationship between the presence of the lpf operon and the pathogenicity for mice of 18 isolates representing 14 Salmonella serotypes. Only strains possessing the lpf operon were able to cause lethal infection in mice. These data show that both the invA- and lpfC-mediated pathways of intestinal perforation are conserved in mouse virulent Salmonella serotypes.     

Salmonella pathogenicity island 1-independent induction of apoptosis in infected macrophages by Salmonella enterica serotype typhimurium

The enteric pathogen Salmonella enterica serotype Typhimurium induces apoptosis in infected macrophages. This process is rapid, specific, and depends on the type III protein secretion system encoded within Salmonella pathogenicity island 1 (SPI1). Here, we demonstrate that serotype Typhimurium can activate programmed macrophage cell death independently of SPI1. SPI1 independent induction of apoptosis in infected macrophages is observed as early as 12 to 13 h postinfection, even in the absence of intracellular bacterial replication. Delayed activation of programmed macrophage cell death is not observed with serotype Typhimurium strains mutated in ompR or SPI2. Even though SPI2 mutants have a defect in intracellular proliferation, our results indicate that long-term intracellular survival and growth are not required for delayed macrophage killing per se, since Salmonella mutants that are severely defective in intracellular growth still induce delayed apoptosis. Inactivation of genes required for either rapid or delayed induction of apoptosis results in a conditional noncytotoxic phenotype, whereas simultaneous inactivation of genes required for both rapid and delayed induction of apoptosis renders serotype Typhimurium noncytotoxic under all conditions tested. Our hypothesis is that differential activation of programmed macrophage cell death by serotype Typhimurium occurs under discrete physiological conditions at distinct locations within an infected host.