Mechanisms of neisserial serum resistance

Pathogenic Neisseria use a variety of mechanisms to survive the bactericidal action of the complement system. Serum resistance is a crucial virulence factor for the development of severe meningococcal disease, meningococcal meningitis and disseminated gonococcal infection. Furthermore, local inflammation at the site of gonococcal infection exposes the bacteria to moderate concentrations of complement factors. We review current concepts of neisserial serum resistance with emphasis on porins and polysaccharides exposed on the neisserial surface and their interaction with components of normal human serum.     

Biochemical and cytogenetic studies on the Nucleolus Organizing Regions (NOR) of Man

Summary The hybridization kinetics of DNA with labeled (18s+28s)rRNA from HeLa cells was determined in patients with trisomy 21, healthy probands with normal karyotype and in carriers of a t(DqGq) centric fusion. The results are in, accordance with the saturation values obtained earlier for these probands:Three patients with trisomy 21 showed an increased saturation level. In 2 of these patients the excess of rDNA exceeded the expected value considerably.Three of the investigated translocation carriers t(14q21q) showed significantly reduced saturation values, while results of a fourth proband with a dicentric chromosome t(15q21q) were found to be within the range of normal probands.The heterogeneous results were correlated with the cytogenetic characteristics of the acrocentric chromosomes. It is expected that these differences could be explained on the basis of family analysis.

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Zusammenfassung Hybridisierungskinetiken der DNA mit markierter (18s+28s)rRNA aus HeLa-Zellen wurden ermittelt bei Patienten mit Trisomie 21, gesunden Probanden mit normalem Karyotyp und Trägern einer zentrischen Fusion t(DqGq). Die Ergebnisse bestätigen die bereits früher ermittelten Sättigungswerte von Hybridisierungen bei diesen Probanden:3 Patienten mit Trisomie 21 zeigten erhöhte Sättigungsniveaus. Bei 2 dieser Patienten übersteigt der Überschuß an rDNA den Erwartungswert erheblich.3 der untersuchten Translokationsträger t(14q21q) hatten signifikant erniedrigte Sättigungswerte, während die vierte Probandin mit dem dizentrischen Chromosom t(15q21q) im Normbereich lag.Die unterschiedlichen Befunde werden mit den cytogenetischen Eigenschaften der akrozentrischen Chromosomen in Zusammenhang gebracht. Es wird erwartet, daß diese Unterschiede sich durch Familienuntersuchungen aufklären lassen.

     

A comparative study on steroid sulfatase and arylsulfatase C in fibroblast clones from 45,X/47,XXX and 69,XXY

Summary Steroid sulfatase (STS) and arylsulfatase C (ARSC) were studied in fibroblast clones from a 45,X/47,XXX mosaic and from a 69,XXY triploidy with one or two active X chromosomes. The comparison of the 47,XXX with 45,X clones showed an incomplete gene dosage effect (1.8 for STS and 2.0 for ARSC). This was not the case for the triploid clones with different X-inactivation patterns. These results confirm previous reports on the non-inactivation of the STS gene, and establish X linkage and non-inactivation for the ARSC gene as well.     

Parasite accessory cell interactions in murine leishmaniasis. I. Evasion and stimulus-dependent suppression of the macrophage interleukin 1 response by Leishmania donovani

Interleukin 1 (IL 1) is a principal mediator of the host immune response to microbial challenge. Accessory cells of the monocyte-macrophage series are a major source of this cytokine and are also chronically parasitized by protozoa of the genus Leishmania. This suggests that characterization of the macrophage IL 1 response to Leishmania would increase our understanding of the regulation of host immunity to these organisms. In the present study, the macrophage IL 1 response to Leishmania donovani was examined because infections with this organism have findings consistent with parasite-specific T cell unresponsiveness. Cytokine activity was measured either by direct stimulation or by co-stimulation of thymocytes. Conditioned media from BALB/c resident peritoneal macrophages infected with amastigotes of L. donovani contained no more IL 1 than did supernatant fluids of control cells. In contrast, supernatants from cells stimulated with lipopolysaccharide or heat-killed Listeria monocytogenes had significantly increased cytokine content. Resident cells infected with L. donovani for 4 hr before being stimulated with Listeria demonstrated a suppressed IL 1 response (approximately 40% of Listeria alone) to this secondary particulate stimulus. In contrast, the secondary response of leishmania-preinfected cells to lipopolysaccharide was not affected. To examine whether accessory cell nonresponsiveness to L. donovani (with respect to IL 1) was related to the state of macrophage activation, elicited peritoneal macrophages obtained by injection of proteose peptone were also studied. These cells responded to stimulation with lipopolysaccharide and fixed Staphylococcus aureus with increases in intracellular, membrane, and secreted cytokine activities. In contrast, L. donovani failed to induce any of these activities. This was found to be the case irrespective of whether amastigotes were alive or killed or opsonized with specific antibodies. Elicited cells preinfected with Leishmania responded normally to secondary stimulation with lipopolysaccharide, but not S. aureus (64% of Staphylococcus alone). In addition, attachment and penetration of L. donovani promastigotes and their subsequent conversion to amastigotes within macrophages failed to induce IL 1 synthesis. The findings of this study indicate that L. donovani has the ability to both evade and suppress the macrophage IL 1 response. Because this monokine provides an obligatory signal during macrophage-dependent T cell activation, evasion of signal transduction for IL 1 synthesis may be related to defects in cell-mediated immunity which occur during infections with this organism.