Reduced TH-1 cytokine release in an adult patient with chronic relapsing Mycobacterium malmoense infection.

An unusual course of infection with Mycobacterium malmoense is described in a patient receiving chronic but mild immunosuppressive therapy for rheumatoid arthritis. Symptoms mimicking Crohn's disease deteriorated under intensified immunosuppression and surgery. Judging from the patient's course under treatment specific for M. malmoense, the gastrointestinal symptoms were rather manifestations of a chronic relapsing mycobacterial infection. Detailed immunological investigation of the patient revealed a severely impaired TH-1 cytokine response as the immunological background for this uncommon course.

Antibodies to the junctional adhesion molecule cause disruption of endothelial cells and do not prevent leukocyte influx into the meninges after viral or bacterial infection.

A hallmark of infectious meningitis is the invasion of leukocytes into the subarachnoid space. In experimental meningitis triggered by tumor necrosis factor-alpha and interleukin-1beta, the interaction of leukocytes with endothelial cells and the subsequent migration of the cells through the vessel wall can be inhibited by an antibody to the junctional adhesion molecule (JAM). In contrast to the cytokine-induced meningitis model, anti-JAM antibodies failed to prevent leukocyte influx into the central nervous system after infection of mice with Listeria monocytogenes or lymphocytic choriomeningitis virus. Furthermore, in bacterial meningitis, anti-JAM IgG antibodies, but not Fab fragments, caused disruption of the endothelium. Likewise complement-dependent antibody-mediated cytotoxicity was observed in cultured brain endothelial cells treated with anti-JAM IgG but not with its Fab fragment.

Mice with an inactivation of the inducible nitric oxide synthase gene are susceptible to experimental autoimmune encephalomyelitis.

Nitric oxide (NO) generated by the inducible nitric oxide synthase (iNOS) has been implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). In this study mice genetically deficient for iNOS are shown to be susceptible to EAE induced by immunization with myelin oligodendrocyte glycoprotein (MOG). In iNOS (-/-) mice the course of disease was earlier in onset and more aggressive compared to control animals. A disease-relevant compensatory up-regulation of neuronal (n)NOS and endothelial (e)NOS with increased production of NO in iNOS (-/-) mice is excluded by 1) the failure to detect increased nNOS and eNOS mRNA, 2) the absence of detection of nitrosylated tyrosine residues in EAE tissue indicating absence of NO-derived peroxynitrite, and 3) the lack of disease-preventing effects of NG-nitro-L-arginine methyl ester. In conclusion, these results do not support the hypothesis that NO is crucial for the development of EAE.

Biochemical analysis of cervical mucus by nuclear magnetic resonance spectroscopy.

Biochemical evaluation of cervical mucus is difficult due to the characteristic rheological properties of this hydrogel. The application of high resolution nuclear magnetic resonance spectroscopy proved to be a valuable new method for differentiated biochemical analyses of human cervical mucus. A particular advantage is that it is non-destructive, that it can be applied to specimens of small volume and that no sample preparation, such as solubilization, is necessary.