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Pseudomonas sp. strain MM223, Pseudomonas sp. strain MM227, and Rheinheimera sp. strain MM224 were isolated from a muddy soil sample from the edge of a pond. Here, we present whole-genome sequences and phylogenetic classifications for all three bacterial isolates.

Long-term administration of the monoamine oxidase (MAO)-B inhibitor selegiline may reduce neuronal death based on preclinical findings and reduce progression of chronic neurodegeneration due to outcomes of long-term clinical trials in patients with Parkinson's disease. Additional modes of action of this compound are immune system modulating and neurotrophic properties. We investigated the impact of simultaneous selegiline and cisplatin administration on the degree of cisplatin-induced cell death in SH-SY 5Y human neuroblastoma cells. We found a significantly reduced cell death rate after 50 and 74 hours after 2 hours lasting cisplatin exposure of SH-SY 5Y cells with additional selegiline treatment in comparison with cultures without selegiline. No previous incubation of cell cultures with selegiline was necessary to achieve this neuroprotective effect. We suggest that the neuroprotective effect of selegiline is predominantly associated with neurotrophic actions but not MAO-B inhibition, because SH-SY 5Y human neuroblastoma cells only contain MAO-A. Clinically, our findings support an early start of long-term treatment with selegiline in view of the various neurotoxin hypotheses and mechanisms of neuronal death in chronic neurodegenerative disorders.

Objective: Human umbilical cord blood (hUCB)-derived mononuclear cells were previously shown to exert therapeutic effects in a number of animal models of nervous system impairment. However, the mechanisms underlying the structural and functional improvements are still unclear. As cell replacement seems to be a rare or absent event in vivo, we suggest secondary mechanisms, by which the therapeutic effect of transplanted mononuclear cells might be mediated. We investigated the potential of hUCB-derived mononuclear cells in vitro to proliferate, differentiate, and to secrete factors possibly beneficial for the host brain tissue in vivo., Methods: Using a succession of distinct culture media, mononuclear cells were stimulated by growth factor combinations, e.g., epidermal growth factor (EGF)/fibroblast growth factor-2 (FGF-2) or nerve growth factor (NGF)/retinoic acid (RA). Expression of hematological and neural marker proteins was investigated by immunoblotting, immunocytochemistry, and fluorescence-activated cell analysis. Secretion of proteins was assayed using a human cytokine antibody array, and quantified via enzyme-linked immunosorbent assay., Results: Mononuclear cells were shown to undergo proliferation in the presence of EGF/FGF-2. When cells were cultured in NGF/RA-containing medium, neuronal and glial marker proteins were expressed, indicating differentiation. In the presence of either growth factor combination, cells in vitro secrete interleukins, growth factors, and chemotactic proteins., Conclusion: Although capable of incipient differentiation, cytokine secretion of hUCB-derived mononuclear cells envisages the potential of an indirect effect in vivo. Most factors detected in conditioned medium are renowned for their anti-inflammatory, neuroprotective, angiogenic, or chemotactic actions, thus, providing the means for a therapeutic outcome mediated by secondary effects.

Rationale: Subjects with high levels of daily stress suffer from an increased risk of coronary heart disease. Increased concentrations of the intercellular adhesion molecule-1 (ICAM-1) contribute to atherosclerosis. Cell adhesion molecules may be activated by psychological stress exposure, depending on their interaction with the interleukin network, sex hormones and cortisol secretion., Objectives: To assess effects of acute psychological stress on the interaction between cell adhesion molecules, interleukins, sex hormones and cortisol in healthy male subjects., Methods: Cell adhesion molecules, interleukin-1 beta (IL-1beta), IL-2, IL-6, sex hormones and cortisol levels of 18 healthy male physicians were measured before and after an academic oral presentation and on a control day., Results: The oral presentation was perceived as a stressful event and was accompanied by a significant increase in cortisol secretion in all volunteers. Soluble ICAM-1 and IL-1beta also increased in all subjects after psychological stress exposure. The stress-associated increase in IL-2 concentrations approached statistical significance and correlated negatively with luteinizing hormone plasma levels. Estradiol concentrations correlated positively with IL-6 levels., Conclusions: Subjective ratings and the increase in cortisol plasma concentrations support the validity of the chosen stress model. Acute stress exposure was followed by an increase in IL-1beta, IL-2 and soluble ICAM-1 plasma concentrations, which can contribute to coronary heart disease and immunological disorders.

Glatiramer acetate (GA), a mixture of synthetic polypeptides, has beneficial effects on the clinical course and the MRI-defined disease activity of patients with multiple sclerosis (MS). In MS, evidence has been provided that the apoptosis of disease-relevant T cells is dysregulated. In this study, we investigated the effect of GA on T cell apoptosis, T cell activation, and cytokine profile of lymphocytes derived from 19 relapsing-remitting MS patients during the first year of GA therapy. Analysis of blood samples obtained every 6 weeks showed an increase in apoptotic T helper cells after 30 weeks of therapy. This effect remained until the end of the study and was accompanied by an increase in activated T cells and interleukin-4-producing lymphocytes. Thus, in addition to the established effect of GA on the cytokine network, GA-mediated immunomodulation might involve the apoptotic elimination of T helper cells., (Copyright 2003 S. Karger AG, Basel)

We have previously reported that the serine protease plasmin generated during contact activation of human plasma triggers biosynthesis of leukotrienes (LTs) in human peripheral monocytes (PMs), but not in polymorphonuclear neutrophils (PMNs). We now show that purified plasmin acts as a potent chemoattractant on human monocytes, but not on PMNs. Human plasmin or plasminogen activated with urokinase, but not active site-blocked plasmin or plasminogen, elicited monocyte migration across polycarbonate membranes. Similarly, stimulation of monocytes with plasmin, but not with active site-blocked plasmin or plasminogen, induced actin polymerization. As assessed by checkerboard analysis, the plasmin-mediated monocyte locomotion was a true chemotaxis. The plasmin-induced chemotactic response was inhibited by the lysine analog trans-4-(aminomethyl)cyclohexane-1-carboxylic acid (t-AMCA), which prevents binding of plasmin/ogen to the appropriate membrane binding sites. In addition, active site-blocked plasmin inhibited monocyte migration triggered by active plasmin. Further, plasmin-induced monocyte chemotaxis was inhibited by pertussis toxin (PTX) and 1-O-hexadecyl-2-O-methyl-rac-glycerol (HMG) and chelerythrine, two structurally unrelated inhibitors of protein kinase C (PKC). Plasmin, but not active site-blocked plasmin or plasminogen, triggered formation of cyclic guanosine monophosphate (cGMP) in monocytes. LY83583, an inhibitor of soluble guanylyl cyclase, inhibited both plasmin-induced cGMP formation and the chemotactic response. The latter effect could be antagonized by 8-bromo-cGMP. In addition, KT5823 and (Rp)-8-(p-chlorophenylthio)guanosine-3',5'-cyclic monophosphorothioate [(Rp)-8-pCPT-cGMPs], two structurally unrelated inhibitors of cGMP-dependent protein kinase, inhibited plasmin-mediated monocyte chemotaxis. Thus, beyond being a stimulus for lipid mediator release, plasmin is a potent and specific chemoattractant for human monocytes acting via a cGMP-dependent mechanism. Therefore, plasmin represents a proinflammatory activator for human monocytes.

Intravenous immunoglobulins (IVIG) are now used to treat various diseases, including autoimmune diseases, systemic inflammatory diseases, allografts and for replacement therapy in the case of IgG deficiency. Only in some of the indications has the efficacy of this treatment been confirmed in large-scale studies. Also, in many cases the modes of action remain unclear. Principally, the following therapeutic strategies can be differentiated: Replacement treatment, blocking of the effector molecules, influencing of the cellular and humoral limbs of the immune defence system and interaction with cytokines. In certain CNS diseases, displacement of pathological immunoglobulins may be involved. It would be desirable to acquire more detailed knowledge about modes of action with the aim of using IVIG with greater specificity in the future.