Regulatory role of C5a in LPS-induced IL-6 production by neutrophils during sepsis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154469/1/fsb2fj030708fje-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154469/2/fsb2fj030708fje.pd

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Effect of Dibutyryl Cyclic AMP on the Kinetics of myo‐Inositol Transport in Cultured Astrocytes

: Dibutyryl cyclic AMP (dBcAMP) is known to induce maturation and differentiation in astrocytes. As myo‐inositol is an important osmoregulator in astrocytes, we examined the effects of maturation and biochemical differentiation on the kinetic properties of myo‐inositol transport. Treatment of astrocytes with dBcAMP significantly decreased the Vmax of myo‐inositol uptake, but the effect on Km was not significant. The myo‐inositol content of astrocytes was significantly decreased in cells treated for 5 days with dBcAMP as compared with untreated controls. Maximum suppression of myo‐inositol uptake occurred 7 days after exposure of astrocytes to dBcAMP; this was gradually reversible when dBcAMP was removed from the medium. After exposure to hypertonic medium for 6 h, mRNA expression of the myo‐inositol co‐transporter was diminished by ∼36% in astrocytes treated with dBcAMP as compared with untreated cells. It appears that myo‐inositol transporters in astrocytes treated with dBcAMP are either decreased in number or inactivated during maturation and differentiation, suggesting that the stage of differentiation and biochemical maturation of astrocytes is an important factor in osmoregulation

Spontaneous lymphocyte proliferation is elevated in asymptomatic HTLV-I-positive Jamaicans

Krämer A, Jacobson S, Reuben JS, et al. Spontaneous lymphocyte proliferation is elevated in asymptomatic HTLV-I-positive Jamaicans. In: Blattner WA, ed. Human retrovirology: HTLV. New York: Raven Pr.; 1990: 79-85

Ability of Antioxidant Liposomes to Prevent Acute and Progressive Pulmonary Injury

We recently showed that acute oxidant-related lung injury (ALI) in rats after application of 2-chloroethyl ethyl sulfide (CEES) is attenuated by the airway instillation of antioxidants. We investigated whether intratracheal administration of antioxidant-containing liposomes immediately after instillation of CEES would attenuate short-term as well as long-term (fibrotic) effects of CEES-induced lung injury. In the acute injury model (4 h after injury), N-acetylcysteine (NAC)-containing liposomes were protective and reduced to baseline levels both the lung permeability index and the appearance of proinflammatory mediators in bronchoalveolar lavage fluids from CEES-exposed lungs. Similar results were obtained when rat alveolar macrophages were incubated in vitro with either CEES or lipopolysaccharide in the presence of NAC-liposomes. When lung fibrosis 3 weeks after CEES was quantitated by using hydroxyproline content, liposomes containing NAC or NAC + glutathione had no effects, but liposomes containing α/γ-tocopherol alone or with NAC significantly suppressed the increase in lung hydroxyproline. The data demonstrate that delivery of antioxidants via liposomes to CEES-injured lungs is, depending on liposomal content, protective against ALI, prevents the appearance of proinflammatory mediators in bronchoalveolar fluids, and suppresses progressive fibrosis. Accordingly, the liposomal strategy may be therapeutically useful in CEES-induced lung injury in humans.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63287/1/ars.2007.1878.pd