Bipolaris spicifera causes fungus balls of the sinuses and triggers polypoid chronic rhinosinusitis in an immunocompetent patient

We report the rare case of a 19-year-old immunocompetent male suffering both from fungus balls of the sinuses and from chronic rhinosinusitis with massive polyposis. Endoscopic sinus surgery revealed grayish brown necrotic masses embedded in viscous eosinophilic mucus. Inoculated onto petri dishes, these masses as well as the mucus grew a dark pigmented fungus, which was identified as Bipolaris spicifera.     

Analysis of cytokine profiles in synovial T cell clones from chlamydial reactive arthritis patients: predominance of the Th1 subset.

Subpopulations of human T cells (Th0, Th1 and Th2) can be distinguished by their cytokine-secretion pattern. Evidence is increasing from other studies that the outcome of a human disease may depend on the subpopulation of T cells that predominates at the site of inflammation. Reactive arthritis serves as a useful model of chronic inflammatory diseases, because the triggering antigen can be identified. Using this triggering antigen we raised 33 T cell clones reactive with Chlamydia trachomatis and 25 T cell clones that were not reactive, all from the synovial fluid of two patients suffering from Chlamydia-induced arthritis. Their cytokine secretion patterns for interferon-gamma (IFN-gamma), IL-2 and IL-4 were analysed, as also were mRNAs for IFN-gamma and IL-10 by in situ hybridization. Out of the 33 antigen-reactive clones 23 showed a Th1 pattern with IFN-gamma but not IL-4 secretion, while the remaining 10 exhibited a Th0 pattern. The clones that did not react with Chlamydia expressed all patterns of cytokine secretion, including a Th2 pattern, thus providing a control population that excludes bias in the sampling procedure. CD4 and CD8 clones displayed a similar cytokine-secretion pattern. In addition this study demonstrates for the first time the expression of IL-10 mRNA in T cell clones derived from synovial fluid, and this was not confined to the Th2 subset. The Th1 response that Chlamydia provoke can be regarded as appropriate for such an obligate intracellular pathogen.     

Neurotrophins: a link between airway inflammation and airway smooth muscle contractility in asthma?

BACKGROUND: Bronchial asthma (BA) is characterized by a unique type of airway inflammation, epithelial cell damage and increased airway smooth muscle (ASM) contractility. The regulatory network between the immunological events and the neuronal control of ASM contractility remains to be defined. METHODS: Utilizing a well-characterized mouse model of airway inflammation and BA, we analyzed the production and function of neurotrophins in allergic asthma. To confirm these data in humans, segmental allergen provocation was performed in mild asthmatics. RESULTS: Allergen-induced airway inflammation was associated with increased local production of the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in mice as well as in humans. In bronchoalveolar lavage fluid (BALF), NGF levels were increased 4- to 5-fold in men and mice 1 day after allergen provocation. The increase in BDNF was about 2-fold in both models. Treatment of mice with anti-NGF prevented development of airway hyperresponsiveness (AHR). In the human study group, NGF levels in BALF after allergen provocation were correlated significantly with baseline FEV1 levels. CONCLUSION: These data strongly suggest that neurotrophins serve as a link between airway inflammation and neuronal control of ASM constriction in BA.     

Iron regulation of Serratia marcescens hemolysin gene expression.

The hemolytic activity of Serratia marcescens was examined as a function of iron availability. Restriction of iron by the nonmetabolizable chelator 2,2'-dipyridyl or the iron-binding protein transferrin produced a marked increase in hemolytic activity. The hemolytic activity of S. marcescens is determined by two adjacent genes, 5'-shlB-shlA-3', where shlA encodes the hemolysin which requires the ShlB protein for activity. A gene fusion between the promoter-proximal portion of shlA and phoA, the Escherichia coli alkaline phosphatase gene, was subcloned into a medium-copy-number vector, and the recombinant plasmid was introduced into S. marcescens. The expression of shlA was measured as a function of alkaline phosphatase activity, which increased threefold under iron-restricted conditions. Removal of the 5' noncoding region upstream of shlB in the fusion vector resulted in a 10-fold decrease in alkaline phosphatase activity under iron-sufficient conditions, with no effect of iron limitation on this residual activity. This suggested that the site mediating iron regulation of shlA expression occurs upstream of shlB. Consistent with this, we observed iron-regulated synthesis of the ShlB protein in Western immunoblots of isolated outer membranes. The hemolysin determinant was subsequently expressed on a medium-copy-number vector in fur+/fur isogenic strains of E. coli K-12, where a 10-fold-higher activity was observed in the mutant strain compared with the wild type. A sequence exhibiting some homology to the Fur-binding consensus sequence was identified upstream of the shlB coding region, overlapping the -35 region of a putative promoter.     

Protection against murine listeriosis by an attenuated recombinant Salmonella typhimurium vaccine strain that secretes the naturally somatic antigen superoxide dismutase.

A recombinant (r)-Salmonella typhimurium aroA vaccine strain was constructed which secretes the naturally somatic protein of Listeria monocytogenes, superoxide dismutase (SOD), by the HlyB/HlyD/TolC export machinery. Vaccine efficacy of the SOD-bearing carrier strain was compared with that of the p60-secreting construct, S. typhimurium p60s (J. Hess, I. Gentschev, D. Miko, M. Welzel, C. Ladel, W. Goebel, and S. H. E. Kaufmann, Proc. Natl. Acad. Sci. USA 93:1458-1463, 1996). Vaccination of mice with both constructs induced protection against a lethal challenge with the intracellular pathogen, L. monocytogenes. While the somatic listerial antigen, SOD, is immunologically uncharacterized, the naturally secreted protein of L. monocytogenes, p60, is known to be highly immunogenic. Our data emphasize the high vaccine potential of r-Salmonella constructs secreting antigens of somatic or secreted origin. Moreover, they suggest that the HlyB/HlyD/TolC-based antigen delivery system with attenuated Salmonella spp. as the carrier is capable of potentiating the immune response against foreign proteins independent from their immunogenicity in and display by the natural host.     

Helicobacter pylori-Specific Immune Responses of Children: Implications for Future Vaccination Strategy

We analyzed the specific anti-Helicobacter pylori immunoglobulin G (IgG) antibody profile for a sample of 824 asymptomatic schoolchildren in southern Germany (mean age, 10.7 ± 0.65 years) with an H. pylori-specific IgG enzyme-linked immunosorbent assay and Western blot analysis. The prevalence of infection was 19.8% (95% confidence interval, 17.1 to 22.7%). The immunoresponses were characterized predominantly by antibodies against low-molecular-mass antigens of 14 and 29 kDa, with a significant difference between children of German and Turkish nationalities (P = 0.0012 and P < 0.0001, respectively).     

Identification of two different mutations in the PDS gene in an inbred family with Pendred syndrome

Recently the gene responsible for Pendred syndrome (PDS) was isolated and several mutations in the PDS gene have been identified in Pendred patients. Here we report the occurrence of two different PDS mutations in an extended inbred Turkish family. The majority of patients in this family are homozygous for a splice site mutation (1143-2A-->G) affecting the 3' splice site consensus sequence of intron 7. However, two affected sibs with non-consanguineous parents are compound heterozygotes for the splice site mutation and a missense mutation (1558T-->G), substituting an evolutionarily conserved amino acid. The latter mutation has been found previously in two Pendred families originating from The Netherlands, indicating that the 1558T-->G mutation may be a common mutation.     

Recombinant dissection of myosin heavy chain of Toxocara canis shows strong clustering of antigenic regions

Myosins from nematode parasites elicit strong humoral and cellular immune responses and have been investigated as vaccine candidates. In this study we cloned and sequenced a cDNA coding for myosin heavy chain from Toxocara canis, a nematode parasite of canids which may also infect humans and cause various unspecific symptoms. To determine the major antigenic regions the myosin heavy chain was systematically dissected into ten overlapping recombinant fusion polypeptides which were purified by metal chelate chromatography. Single fragments were then tested for their IgG reactivity in sera from toxocarosis patients and healthy probands. Two regions, one region at the mid to carboxy-terminal end of the head domain and one region in the rod domain, were identified as major antigens, which in combination were positive with 86% of the sera. The other domains were less reactive. This shows that the patients' IgG reactivity was not directed evenly against all parts of the molecule, but was rather clustered in few regions.     

Oligonucleotide typing is a perfect tool to identify antigens stimulatory in the mixed lymphocyte culture

An important criterion for the selection of donors for bone marrow transplantation is the grade of matching for HLA between donor and recipient. For patients that lack an HLA-identical sibling, an extending pool of unrelated volunteers for bone marrow donation is available. From these donors the best matched candidate can be selected by serological typing, followed by a mixed lymphocyte culture (MLC).Oligonucleotide genotyping for HLA class II antigens is considered to be valuable for the prediction of MLC reactivity. We investigated whether this typing method, in combination with serological typing, would cover the recognition of all MLC stimulatory determinants. One hundred thirty-six combinations of HLA-A, -B, and -DR serologically identical individuals were tested in the MLC. Additional typing for HLA-DRB and HLA-DPB by oligonucleotide genotyping made it possible to evaluate the influence of these genes on MLC reactivity. Combinations that were matched for HLA-DRB gave significantly lower responses than those that were mismatched. Nevertheless, in the matched combinations responses were observed to 94% relative response index. These responses could all be attributed to HLA-DP, since all combinations that were identical by HLA-DPB genotyping were negative in the MLC. In conclusion, with the combined use of serology and oligonucleotide genotyping, responder-stimulator combinations can be selected that are identical for all MLC stimulatory determinats. 245 (1991)     

Precipitable immune complexes in healthy homosexual men, acquired immune deficiency syndrome and the related lymphadenopathy syndrome.

Increased levels of 3% PEG precipitable circulating immune complexes (CIC) were found in healthy homosexual men, in homosexual patients with the acquired immune deficiency syndrome (AIDS), and in the AIDS related lymphadenopathy syndrome (LAS). The degree of CIC elevation increases from healthy homosexual men to LAS and AIDS. Patients suffering from AIDS associated with opportunistic infections had a more pronounced increase in CIC than patients with AIDS associated Kaposi's sarcoma. In LAS and AIDS the amount of CIC correlated with the degree of inversion of the T4/T8 lymphocyte ratio, whereas in healthy homosexual men with increased levels of CIC the T4/T8 ratio was not significantly altered. Laser nephelometric partial components analysis revealed that these complexes were of a complement poor subtype with low component levels of C4, C1q and C3c. IgM and IgG were found to be the major components. It is suggested that these CIC might represent a marker of the total antigenic burden of the immune system. Possibly, they are of prognostic and monitoring value for clinical handling of patients at risk for AIDS.