Two cases of acute respiratory distress syndrome with high values of Chlamydophila pneumoniae-specific antibodies.

We herein report two cases of acute respiratory distress syndrome (ARDS) with high values of Chlamydophila pneumoniae-specific antibodies. In the first case (a 65-year-old man), high levels of anti-C. pneumoniae antibodies (IgG and IgA) were detected on admission, and the anti-C. pneumoniae IgA level rose by Day 30. The patient was successfully treated with quinolone and steroids. In the second case (an 85-year-old man), abnormally high levels of anti-C. pneumoniae IgM were detected on admission. The patient did not recover, despite receiving treatment with several antibiotics and anti-inflammatory agents. Neither of the patients displayed other pathogen-specific antigens or antibodies. Chlamydophila pneumonia is usually mild, although it can cause severe interstitial pneumonia and ARDS in reinfected patients and the elderly.

Targeting lysophosphatidic acid signaling retards culture-associated senescence of human marrow stromal cells.

Marrow stromal cells (MSCs) isolated from mesenchymal tissues can propagate in vitro to some extent and differentiate into various tissue lineages to be used for cell-based therapies. Cellular senescence, which occurs readily in continual MSC culture, leads to loss of these characteristic properties, representing one of the major limitations to achieving the potential of MSCs. In this study, we investigated the effect of lysophosphatidic acid (LPA), a ubiquitous metabolite in membrane phospholipid synthesis, on the senescence program of human MSCs. We show that MSCs preferentially express the LPA receptor subtype 1, and an abrogation of the receptor engagement with the antagonistic compound Ki16425 attenuates senescence induction in continually propagated human MSCs. This anti-aging effect of Ki16425 results in extended rounds of cellular proliferation, increased clonogenic potential, and retained plasticity for osteogenic and adipogenic differentiation. Expressions of p16(Ink4a), Rb, p53, and p21(Cip1), which have been associated with cellular senescence, were all reduced in human MSCs by the pharmacological inhibition of LPA signaling. Disruption of this signaling pathway was accompanied by morphological changes such as cell thinning and elongation as well as actin filament deformation through decreased phosphorylation of focal adhesion kinase. Prevention of LPA receptor engagement also promoted ubiquitination-mediated c-Myc elimination in MSCs, and consequently the entry into a quiescent state, G(0) phase, of the cell cycle. Collectively, these results highlight the potential of pharmacological intervention against LPA signaling for blunting senescence-associated loss of function characteristic of human MSCs.