Clinical Streptococcus pneumoniae isolates induce differing CXCL8 responses from human nasopharyngeal epithelial cells which are reduced by liposomes.

BACKGROUND: Streptococcus pneumoniae causes several human diseases, including pneumonia and meningitis, in which pathology is associated with an excessive inflammatory response. A major inducer of this response is the cholesterol dependent pneumococcal toxin, pneumolysin. Here, we measured the amount of inflammatory cytokine CXCL8 (interleukin (IL)-8) by ELISA released by human nasopharyngeal epithelial (Detroit 562) cells as inflammatory response to a 24 h exposure to different pneumococcal strains. RESULTS: We found pneumolysin to be the major factor influencing the CXCL8 response. Cholesterol and sphingomyelin-containing liposomes designed to sequester pneumolysin were highly effective at reducing CXCL8 levels from epithelial cells exposed to different clinical pneumococcal isolates. These liposomes also reduced CXCL8 response from epithelial cells exposed to pneumolysin knock-out mutants of S. pneumoniae indicating that they also reduce the CXCL8-inducing effect of an unidentified pneumococcal virulence factor, in addition to pneumolysin. CONCLUSION: The results indicate the potential of liposomes in attenuating excessive inflammation as a future adjunctive treatment of pneumococcal diseases.

Polarity chron boundaries and foraminiferal 87Sr/86Sr ratios of ODP Sites 162-986 and 162-987

Cores recovered at Sites 986 and 987 comprise glacial fan sedimentation associated with the Svalbard-Barents Sea and Greenland Ice Sheets, respectively. At Site 986, the top 150 m and the basal 250 m yielded interpretable magnetic stratigraphies. The record from the intervening 550 m is compromised by drilling-related core deformation, poor recovery, and numerous debris flows. The uppermost 150 m appears to record the Brunhes/Matuyama boundary and the Jaramillo Subchron. The base of the drilled section (at ~950 meters below seafloor [mbsf]) is interpreted to lie within the Matuyama Chron (age <2.58 Ma) with an apparent normal polarity interval in the ~730-750 mbsf interval. Dinoflagellate cyst biostratigraphy and Sr isotopic ratios are consistent with a Matuyama age for the base of the drilled section and with the normal polarity interval as the Olduvai Subchron. On the other hand, the last occurrence of Neogloboquadrina atlantica (sinistral) and the last common occurrence of the warm-dwelling Globigerina bulloides at 647-650 mbsf in Hole 986D indicate an age for this level of ~2.3 Ma, inconsistent with the designation of the Olduvai Subchron in the ~730-750 mbsf interval. If the age at 647-650 mbsf in Hole 986D is taken as 2.3 Ma and the base of the hole lies within the Matuyama Chron, then the sedimentation rate in the basal 300 m of the cored section averages 1 m/k.y. At Site 987, the magnetic stratigraphy is fairly unambiguous throughout the section and yields an age of 7.5 Ma (Chron 4n) for the base of the drilled section. The paucity of calcareous and siliceous microfossils precludes biostratigraphic corroboration of the magnetostratigraphic interpretation, although dinoflagellate cysts provide general support, particularly at the base of the section. The age model indicates relatively low sedimentation rates (~5 cm/k.y.) at the base of the section with rates at least four to five times greater during intervals of debris flows at ~5-4.6 and ~2.6 Ma.

Polarity chron boundaries and interval sedimentation rates of ODP Leg 162 sites

Magnetic polarity stratigraphies for Sites 980-984 are based on shipboard measurements from the pass-through magnetometer after alternating field (AF) demagnetization at a peak field of 25 mT and shore-based stepwise AF demagnetization of discrete samples. The characteristic magnetization component was determined after AF demagnetization removed the steep downward drill-string-related magnetic overprint. Peak AF fields in the 20-30 mT range were required to resolve the component, carried by magnetite, that was used to produce unambiguous Pliocene-Pleistocene magnetic stratigraphies at all five sites. At Sites 980 and 983, magnetic stratigraphies were resolved to the base of the recovered advanced hydraulic piston corer (APC) section, which lies in the Matuyama Chron (1r.2r) and Olduvai Subchron (2n), respectively. At Sites 981 and 982, magnetization intensities decrease sharply in the normal polarity zone corresponding to the Gauss Chron (2An), and magnetic stratigraphies below this level could not be resolved. At Site 984, the resolution of magnetic stratigraphy was curtailed at ~250 meters below seafloor (Olduvai Subchron) by core deformation at the base of the APC section and in the underlying extended core barrel section. As the magnetic stratigraphies at all four sites are unequivocal, polarity chron interpretations can be made without aid from the biostratigraphy. Mean sedimentation rates within polarity chrons have been calculated and Pliocene-Pleistocene biomagnetostratigraphic correlations tested.

Polarity,

"Edition of 600 copies of which 500 are for sale."

Operator, organizational, direct and general support, and depot maintenance manual (including repair parts) : welding machine, arc, inert shielded, transformer, 300 amp, 10 to 400 amp AC straight polarity, 10 to 00 amp DC reverse polarity (Midstates model MAG 00 AC/DC T 14) FSN 3431-862-6670.

"February 1967."

Establishment and characterization of a new epithelial cell line, KC-1, from koala (Phascolarctos cinereus) conjunctiva

A novel, untransformed koala cell line (KC-1) was established by culturing koala conjunctival tissue in growth medium, which has permitted the study of the cell biology of this unique system. After the establishment of the KC-1 cell line, the cells were characterized by light microscopy, doubling time, and Western blot analysis. Light microscopy revealed that the cells have an epithelial morphology. Doubling times were significantly different (P < 0.015) depending on fetal calf serum (FCS) concentration (16.5 h in 10% FCS and 26.5 h in 2% FCS). Cells constricted while in suspension but were shown to attach to the coverslip (or flask) and flatten rapidly, less than 1 h after seeding. To confirm the epithelial nature of the cells, protein was extracted and Western blot analysis was performed. Subsequent probing with primary and secondary antibodies (monoclonal anticytokeratin clone C-11 IgG1 and anti-mouse IgG) revealed two bands at 45 and 52 kDa (compared against a protein molecular weight marker) that correspond to primary type I keratin and major type II keratin, respectively, expressed in simple epithelial cells. The koala cell line was adapted to grow continuously in Dulbecco modified Eagle medium containing 10% FCS for at least 30 passages. This unique cell line is an ideal toot for further investigation on koala cell biology and cytogenetics and for exploration of the pathophysiological mechanism of eye infections caused by different pathogens in koalas.

Ovulation and risk of epithelial ovarian cancer

Incessant ovulation is thought to be one of the primary causes of epithelial ovarian cancer. However, the effects of ovulation at different ages and of the various exposures or events that suppress ovulation have not been established. We used data from an Australian case-control study of 791 ovarian cancer cases and 853 controls to examine the effect of ovulation on ovarian cancer risk. The total number of lifetime ovulations was calculated using information provided in a monthly contraceptive/reproductive calendar, as well as incorporating other information such as average menstrual cycle length. An increase of I year's worth of ovulation was associated with a 6% increase in risk of ovarian cancer (95% confidence interval [CI] = 4-8%). Ovulations in the 20-29-year age group were associated with the greatest risk, with a 20% increase in risk associated with each year of ovulation during this age period (95% Cl = 13-26%). When the effects of different exposures that suppress ovulation were compared, there was an indication that some factors may have a greater effect than others. These findings support the theory that incessant ovulation is a major contributor to the occurrence of ovarian cancer and suggest that ovulations during the 20s may be those most associated with disease risk. (C) 2003 Wiley-Liss, Inc.

Effector ExoU from the type III secretion system is an important modulator of gene expression in lung epithelial cells in response to Pseudomonas aeruginosa infection

Pseudomonas aeruginosa is an important pathogen in immunocompromised patients and secretes a diverse set of virulence factors that aid colonization and influence host cell defenses. An important early step in the establishment of infection is the production of type III-secreted effectors translocated into host cells by the bacteria. We used cDNA microarrays to compare the transcriptomic response of lung epithelial cells to P. aeruginosa mutants defective in type IV pili, the type III secretion apparatus, or in the production of specific type III-secreted effectors. Of the 18,000 cDNA clones analyzed, 55 were induced or repressed after 4 It of infection and could be classified into four different expression patterns. These include (i) host genes that are induced or repressed in a type III secretion-independent manner (32 clones), (ii) host genes induced specifically by ExoU (20 clones), and (iii) host genes induced in an ExoU-independent but type III secretion dependent manner (3 clones). In particular, ExoU was essential for the expression of immediate-early response genes, including the transcription factor c-Fos. ExoU-dependent gene expression was mediated in part by early and transient activation of the AN transcription factor complex. In conclusion, the present study provides a detailed insight into the response of epithelial cells to infection and indicates the significant role played by the type III virulence mechanism in the initial host response.

Alcohol, wine, and risk of epithelial ovarian cancer

Moderate alcohol intake can influence sex hormone levels and affect ovarian function as well as increasing breast cancer risk. This suggests that alcohol might also influence ovarian cancer risk. We have evaluated this among 696 Australian women with histologically confirmed epithelial ovarian cancer and 786 cancer-free control women, selected at random from the electoral roll. Sociodemographic information and a detailed reproductive history were collected in a face-to-face interview, and information about diet and alcohol consumption was obtained from a food frequency questionnaire. Logistic regression was used to calculate adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Overall, 59% of women drank