Spiral computed tomography in the diagnosis of limb osteomyelitis

The results of radiation studies in 121 patients of different age (4 to 75 years) examined for limb osteomyelitis are analyzed. All the patients underwent routine X-ray study and computed tomography (CT), 26 patients had X-ray fistulography; 8, linear tomography; 10, CT fistulography; 6, scintigraphy, and 15, ultrasound study. Acute hematogenous osteomyelitis (AHO), chronic hematogenous osteomyelitis (CHO), and atypical (here Garre's sclerosing osteomyelitis and Brodie's abscess) osteomyelitis were ascertained in 10.6, 26.4, and 10.1% of cases, respectively. Posttraumatic osteomyelitis was diagnosed in almost 50% of the patients. CT defined the phase of chronic limb osteomyelitis. Spiral CT has proven to be the most effective technique for diagnosing limb osteomyelitis as compared with routine X-ray study: the accuracy of X-ray study was 81.8%, its sensitivity, 84.9%, and specificity, 60.0% and those of computed tomography were 96.7, 99.1, and 80.0%, respectively.     

Mutants highlight the modular control of butterfly eyespot patterns

SUMMARY The eyespots on butterfly wings are thought to be serially homologous pattern elements. Yet eyespots differ greatly in number, shape, color, and size, within and among species. To what extent do these serially homologues have separate developmental identities, upon which selection acts to create diversity? We examined x‐ray–induced mutations for the eyespots of the nymphalid butterfly Bicyclus anynana that highlight the modular control of these serially homologous wing pattern elements. These mutations reduce or eliminate individual eyespots, or groups of eyespots, with no further effect on the wing color pattern. The collection of mutants highlights a greater potential developmental repertoire than that observed across the genus Bicyclus. We studied in detail one such mutation, of codominant effect, that causes the elimination of two adjacent eyespots on the ventral hindwing. By analyzing the expression of genes known to be involved in eyespot formation, we found an alteration in the differentiation of the “organizing” cells at the eyespot's center. No such cells differentiate in the wing subdivisions lacking the two eyespots in the mutants. We propose several developmental models, based on wing compartmentalization in Drosophila, that provide the first framework for thinking about the molecular evolution of butterfly wing pattern modularity.     

Lipopolysaccharide-free heat shock protein 60 activates T cells

A possible function of eukaryotic heat shock protein 60 (Hsp60) as endogenous danger signal has been controversially discussed in the past. Hsp60 was shown to induce the secretion of proinflammatory cytokines in professional antigen-presenting cells and to enhance the activation of T cells in primary stimulation. However, in vitro activation of macrophages by Hsp60 was attributed to contaminating endotoxin in the recombinant Hsp60 protein preparations. Here, we employ low endotoxin recombinant human Hsp60 and murine Hsp60 expressed by eukaryotic cell lines to dissect the Hsp60 protein-mediated effects from biologic effects that are mediated by prokaryotic contaminants in the Hsp60 protein preparation. The induction of tumor necrosis factor-alpha secretion in mouse macrophages is lost after endotoxin removal and is not mediated by Hsp60 expressed in eukaryotic systems. In contrast, the Hsp60-mediated enhancement of antigen-specific T cell activation does not correlate with endotoxin contamination. Moreover, Hsp60 that is expressed on the surface of different eukaryotic cell lines increases the activation of T cells in primary stimulation. Taken together, we provide evidence that endogenous Hsp60, which is thought to be released from dying infected cells in vivo, has a biological function that is not due to contaminating pathogen-associated molecules.     

Systemic approach to radiobiological studies

The principles of information theory were applied for analysis of radiobiological effects. The perception of ionizing radiations as a signal enables living organism to discern their benefits or harm, to react to absolute and relatively small deviations, to keep the logic and chronicle of events, to use the former experience for reacting in presence, to forecast consequences. The systemic analysis of organism's response to ionizing radiations allows explaining the peculiarities of effects of different absorbed doses, hormesis, apoptosis, remote consequences and other post-radiation effects.     

Foxp3+ Regulatory T Cells Delay Expulsion of Intestinal Nematodes by Suppression of IL-9-Driven Mast Cell Activation in BALB/c but Not in C57BL/6 Mice

Accumulating evidence suggests that IL-9-mediated immunity plays a fundamental role in control of intestinal nematode infection. Here we report a different impact of Foxp3⁺ regulatory T cells (Treg) in nematode-induced evasion of IL-9-mediated immunity in BALB/c and C57BL/6 mice. Infection with Strongyloides ratti induced Treg expansion with similar kinetics and phenotype in both strains. Strikingly, Treg depletion reduced parasite burden selectively in BALB/c but not in C57BL/6 mice. Treg function was apparent in both strains as Treg depletion increased nematode-specific humoral and cellular Th2 response in BALB/c and C57BL/6 mice to the same extent. Improved resistance in Treg-depleted BALB/c mice was accompanied by increased production of IL-9 and accelerated degranulation of mast cells. In contrast, IL-9 production was not significantly elevated and kinetics of mast cell degranulation were unaffected by Treg depletion in C57BL/6 mice. By in vivo neutralization, we demonstrate that increased IL-9 production during the first days of infection caused accelerated mast cell degranulation and rapid expulsion of S. ratti adults from the small intestine of Treg-depleted BALB/c mice. In genetically mast cell-deficient (Cpa3-Cre) BALB/c mice, Treg depletion still resulted in increased IL-9 production but resistance to S. ratti infection was lost, suggesting that IL-9-driven mast cell activation mediated accelerated expulsion of S. ratti in Treg-depleted BALB/c mice. This IL-9-driven mast cell degranulation is a central mechanism of S. ratti expulsion in both, BALB/c and C57BL/6 mice, because IL-9 injection reduced and IL-9 neutralization increased parasite burden in the presence of Treg in both strains. Therefore our results suggest that Foxp3⁺ Treg suppress sufficient IL-9 production for subsequent mast cell degranulation during S. ratti infection in a non-redundant manner in BALB/c mice, whereas additional regulatory pathways are functional in Treg-depleted C57BL/6 mice.     

Nematode-Induced Interference with Vaccination Efficacy Targets Follicular T Helper Cell Induction and Is Preserved after Termination of Infection

One-third of the human population is infected with parasitic worms. To avoid being eliminated, these parasites actively dampen the immune response of their hosts. This immune modulation also suppresses immune responses to third-party antigens such as vaccines. Here, we used Litomosoides sigmodontis-infected BALB/c mice to analyse nematode-induced interference with vaccination. Chronic nematode infection led to complete suppression of the humoral response to thymus-dependent vaccination. Thereby the numbers of antigen-specific B cells as well as the serum immunoglobulin (Ig) G titres were reduced. T_H2-associated IgG1 and T_H1-associated IgG2 responses were both suppressed. Thus, nematode infection did not bias responses towards a T_H2 response, but interfered with Ig responses in general. We provide evidence that this suppression indirectly targeted B cells via accessory T cells as number and frequency of vaccine-induced follicular B helper T cells were reduced. Moreover, vaccination using model antigens that stimulate Ig response independently of T helper cells was functional in nematode-infected mice. Using depletion experiments, we show that CD4⁺Foxp3⁺ regulatory T cells did not mediate the suppression of Ig response during chronic nematode infection. Suppression was induced by fourth stage larvae, immature adults and mature adults, and increased with the duration of the infection. By contrast, isolated microfilariae increased IgG2a responses to vaccination. This pro-inflammatory effect of microfilariae was overruled by the simultaneous presence of adults. Strikingly, a reduced humoral response was still observed if vaccination was performed more than 16 weeks after termination of L. sigmodontis infection. In summary, our results suggest that vaccination may not only fail in helminth-infected individuals, but also in individuals with a history of previous helminth infections.     

IL-15/IL-15 receptor biology: a guided tour through an expanding universe

The cytokine interleukin-15 (IL-15) has a key role in promoting survival, proliferation and activation of natural killer (NK) and CD8+ T cells. Despite its functional similarities to IL-2, IL-15 affects a wider range of target cell populations and utilizes different mechanisms of signaling. Here, we review recent advances in the IL-15-mediated signaling, and in the functional properties on cells besides T lymphocytes and NK cells. These are discussed in the context of their potential clinical and therapeutic relevance.     

Ellipsoids of the spleen (ellipsoid macrophagal-lymphoid sheaths

The ellipsoids of the spleen are considered as one of the links of the immune (lymphoid) apparatus of the lymphoreticular organ. Anatomical peculiarities of interrelations between the wall of the terminal part of the arterial bed, capillary, ellipsoid macrophagal-lymphoid microenvironment and reticular stroma of the ellipsoids of the spleen are discussed. Certain ultrastructural and immune-histological differences in the structure of the endothelial lining and cells, forming the ellipsoid sheaths, demonstrate functional interconnection of these formations not only with regulation of blood stream in the spleen vascular bed, but with transport of the antigenic material and lymphocytes into the white pulp. However, the functional appointment, as well as using of terminology of these formations still remain to be cleared out. An analogy is made, concerning the function of the splenic ellipsoid sheaths and postcapillary venules of the lymph node. The formation of the structural mechanism of immune response to the antigen-antibody complexes are analyzed, using some examples of evolutionary development of the ellipsoid macrophagal-lymphoid sheaths in various animal species.     

Cytogenetic effect of thaliblastine in a culture of human peripheral blood lymphocytes

The mutagenicity of thaliblastine (Bulgarian potential antitumor drug) was investigated in vitro in lymphocytes from healthy donors, and in vivo in lymphocytes of oncological patients after thaliblastine administration. No increase in the rate of chromosome aberrations was noted with increasing thaliblastine concentrations in vitro and in the course of therapy in vivo. Some polyploid metaphases were found in the lymphocytes of the patients treated with thaliblastine, as a result of the statmokinetic effect of the drug. Thaliblastine exerts extraordinarily slight mutagenic effect, as compared with other cytostatics.