Receptive music therapy and salivary histamine secretion.

INTRODUCTION: Receptive music therapy (rMT) not only provides a good feeling but also a more effective healing process and mastery of stress. METHODS AND RESULTS: In a preliminary study it could be shown that American Doudouk-music (feel-good music) suppressed salivary histamine secretion in two groups (n = 4) of allergic and non-allergic young volunteers. Stress was induced by eating adverse food/allergenic food during music exposure. There was no response in the vein blood samples and no significant difference between the allergic and non-allergic groups. CONCLUSION: It can be concluded that saliva is an appropriate medium for histamine measurements during music exposure.

Proteins of the secretory pathway govern virus productivity during lytic gammaherpesvirus infection.

BACKGROUND: Diseases caused by gammaherpesviruses continue to be a challenge for human health and antiviral treatment. Most of the commonly used antiviral drugs are directed against viral gene products. However, the emergence of drug-resistant mutations ma limit the effectiveness of these drugs. Since viruses require a host cell to propagate, the search for host cell targets is an interesting alternative. METHODS: In this study, we infected three different cell types (fibroblasts, endothelial precursor cells and macrophages with a murine gammaherpesvirus and analysed the host cell response for changes either common to all or unique to a particular cell type using oligonucleotide microarrays. RESULTS: The analysis revealed a number of genes whose transcription was significantly up- or down-regulated in either one or two of the cell types tested. After infection, only two genes, Lman1 (also known as ERGIC53) an synaptobrevin-like 1 (sybl1) were significantly up-regulated in all three cell types, suggestive for a general role for the virus life cycl independent of the cell type. Both proteins have been implicated in cellular exocytosis and transport of glycoproteins through the secretory pathway. To test the significance of the observed up-regulation, the functionality of these proteins was modulated, and the effect on virus replication was monitored. Inhibition of either Lman1 or sybl1 resulted in a significant reduction in virus production. CONCLUSIONS: This suggests that proteins of the secretory pathway which appear to be rate limiting for virus production may represent new targets for intervention.

Interferon-gamma-dependent mechanisms of mycobacteria-induced pulmonary immunopathology: the role of angiostasis and CXCR3-targeted chemokines for granuloma necrosis.

The mechanisms leading to granuloma caseation, a hallmark of tuberculosis (TB) in humans, are poorly understood. Lung histopathology of C57BL/6 (WT) mice 16 weeks after aerosol infection with Mycobacterium avium strain TMC724 is uniquely characterized by centrally necrotizing granulomas, strongly resembling human TB lesions. However, IFN-gamma-deficient (GKO) and IFN-gamma-receptor-deficient (GRKO) mice did not develop granuloma necrosis following M. avium infection. Comparison of differentially expressed genes in infected WT and GKO lungs by DNA microarray and RNase protection assays revealed that the angiostatic chemokines CXCL9-11 were significantly reduced in GKO mice. In contrast, angiogenic mediators such as angiopoietin and vascular endothelial growth factor, and angiogenic chemokines such as CXCL2, CCL3, and CCL4, remained unchanged or were expressed at higher levels than in infected WT mice, suggesting impaired neovascularization of the granuloma as a possible mechanism for caseation in WT mice. Granuloma vascularization was significantly decreased in central, but not peripheral, areas of granulomas of infected WT compared to GKO mice. In contrast to GRKO mice, WT mice showed signs of severe hypoxia in cells immediately surrounding the necrotic core of granulomas as measured immunohistochemically with a reagent detecting pimonidazole adducts. To test the hypothesis that CXCR3, the common receptor for the angiostatic chemokines CXCL9-11, is involved in granuloma caseation, histomorphology was assessed in M. avium-infected mice deficient for CXCR3 (CXCR3-KO). 16 weeks after infection, these mice developed caseating granulomas similar to WT mice. We conclude that IFN-gamma causes a dysbalance between angiostatic and angiogenic mediators and a concomitant reduction in granuloma vascularization, but that CXCR3-targeted chemokines are not sufficient to induce granuloma necrosis in a mouse model of mycobacteria-induced immunopathology.

Hepatitis A virus-specific immunoglobulin A mediates infection of hepatocytes with hepatitis A virus via the asialoglycoprotein receptor.

The mechanisms underlying the hepatotropism of hepatitis A virus (HAV) and the relapsing courses of HAV infections are unknown. In this report, we show for a mouse hepatocyte model that HAV-specific immunoglobulin A (IgA) mediates infection of hepatocytes with HAV via the asialoglycoprotein receptor, which binds and internalizes IgA molecules. Proof of HAV infection was obtained by detection of HAV minus-strand RNA, which is indicative for virus replication, and quantification of infectious virions. We demonstrate that human hepatocytes also ingest HAV-anti-HAV IgA complexes by the same mechanism, resulting in infection of the cells, by using the HepG2 cell line and primary hepatocytes. The relevance of this surrogate receptor mechanism in HAV pathogenesis lies in the fact that HAV, IgA, and antigen-IgA complexes use the same pathway within the organism, leading from the gastrointestinal tract to the liver via blood and back to the gastrointestinal tract via bile fluid. Therefore, HAV-specific IgA antibodies produced by gastrointestinal mucosa-associated lymphoid tissue may serve as carrier and targeting molecules, enabling and supporting HAV infection of IgA receptor-positive hepatocytes and, in the case of relapsing courses, allowing reinfection of the liver in the presence of otherwise neutralizing antibodies, resulting in exacerbation of liver disease.