Effect of lipopolysaccharide from periodontal pathogens on the production of tissue plasminogen activator and plasminogen activator inhibitor 2 by human gingival fibroblasts

Both tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 2 (PAI-2) are important proteolysis factors present in inflamed human periodontal tissues. The aim of the present study was to investigate the effect of lipopolysaccharide (LPS) on the synthesis: of t-PA and PAI-2 by human gingival fibroblasts (HGF). LPS from different periodontal pathogens including Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum were extracted by the hot phenol water method. The levels of t-PA and PAI-2 secreted into the cell culture media were measured by enzyme-linked immunosorbent assays (ELISA). The mRNA for t-PA and PAI-2 were measured by RT-PCR. The results showed t-PA synthesis was increased in response to all types of LPS studied and PAI-2 level was increased by LPS from A. actinomycetemcomitans and F. nucleatum, but not P. gingivalis. When comparing the effects of LPS from non-periodontal bacteria (Escherichia coli and Salmonella enteritidis) with the LPS from periodontal pathogens, we found that the ratio of t-PA to PAI-2 was greater following exposure of the cells to LPS from periodontal pathogens. The highest ratio of t-PA to PAI-2 was found in those cells exposed to LPS from P. gingivalis. These results indicate that LPS derived from periodontal pathogens may cause unbalanced regulation of plasminogen activator and plasminogen activator inhibitor by HGF and such an effect may, in part, contribute to the destruction of periodontal connective tissue through dysregulated pericellular proteolysis.

Tissue-specific induction of SOCS gene expression by PRL

The mechanisms whereby tissue sensitivity to PRL is controlled are not well understood. Here we report that expression of mRNA and protein for members of the SOCS/CIS/JAB family of cytokine signaling inhibitors is increased by PRL administration in ovary and adrenal gland of the lactating rat deprived of circulating PRL and pups for 24 h but not in mammary gland. Moreover, suckling increases SOCS mRNA in the ovary but not in the mammary gland of pup-deprived rats. Deprivation of PRL and pups for 48 h allows the mammary gland to induce SOCS genes in response to PRL administration, and this is associated with a decrease in basal SOCS-3 mRNA and protein expression to the level seen in other tissues, suggesting that SOCS-3 induced refractoriness related to filling of the gland. In reporter assays, SOCS-1, SOCS-3, and CIS, but not SOCS-2, are able to inhibit transactivation of the STAT 5-responsive beta -lactoglobulin promoter in transient transfection assays. Moreover, suckling results in loss of ovarian and adrenal responsiveness to PRL administered 2 h after commencement of suckling, as determined by STAT 5 gel shift assay. Immunohistochemistry was used to localize the cellular sites of SOCS-3 and CIS protein expression in the ovary and adrenal gland. We propose that induced SOCS-1, SOCS-3, and CIS are actively involved in the cellular inhibitory feedback response to physiological PRL surges in the corpus luteum and adrenal cortex during lactation, but after pup withdrawal, the mammary gland is rendered unresponsive to PRL by increased levels of SOCS-3.

Being breastfed in infancy and breast cancer incidence in adult life: Results from the two Nurses' Health studies

Events during perinatal and early life may influence the incidence of breast cancer in adult life, and some case-control studies suggest that having been breastfed may reduce breast cancer risk. The authors studied this association among premenopausal and postmenopausal women by using data from the two Nurses' Health Studies, the Nurses' Health Study (using data from 1992 to 1996) and the Nurses' Health Study II (using data from 1991 to 1997). A history of being breastfed was self-reported by the study participants. During a total of 695,655 person-years, 1,073 cases of invasive breast cancer were diagnosed. The authors did not observe any important overall association between having been breastfed and the development of breast cancer later in life among premenopausal women (covariate-adjusted relative risk = 0.97, 95% confidence interval (CI): 0.78, 1.20) or postmenopausal women (covariate-adjusted relative risk = 1.12, 95% CI: 0.92, 1.37). No significant trend was observed with increasing duration of breastfeeding. The authors also used data on breastfeeding retrospectively collected from 2,103 mothers of participants of the two Nurses' Health Studies. With the mothers' reports, the covariate-adjusted odds ratio of breast cancer was 1.11 (95% CI: 0.88, 1.39) for women who were breastfed compared with those who were not. Data from these two large cohorts do not support the hypothesis that being breastfed confers protection against subsequent breast cancer.

A new genus of viviparous gyrodactylid (Monogenea) from the Great Barrier Reef, Australia with descriptions of seven new species

Acanthoplacatus gen. nov., a new genus of viviparous gyrodactylid, is described from the rns and skin of siganid fishes from the Great Barrier Reef, Australia. The genus is characterized by a muscular, tube-like haptor with 16 marginal hooks on the posterior margin. The ventral lobe of the haptor is located anteriorly relative to the dorsal lobe and contains a pair of hamuli and a ventral bar with posteriorly-projecting ventral bar membrane. A dorsal bar is absent. Five pairs of posterior gland cells surround the posterior terminations of the gut. The male copulatory organ is a muscular, non-eversible bulb with several spines around the distal opening. Species of Acanthoplacatus have a bilateral excretory system consisting of six pairs of flame cells and a pair of excretory bladders. Seven new species are described: Acanthoplacatus adlardi sp. nov. and A. amplihamus sp. nov. from Siganus punctatus (Forster, 1801), A. brauni sp. nov. from S. corallinus (Valenciennes, 1835), A. parvihamus sp. nov. from S. vulpinus (Schlegel and Mueller, 1845), A. puelli sp. nov. from S. puellus Schlegel, 1852, A. shieldsi sp. nov. from S. lineatus (Valenciennes, 1835) and A. sigani sp. nov. from S. fuscescens (Houttuyn, 1782). Species can be discriminated by shape and size of the hamuli, marginal hooks and ventral bar and by male copulatory organ sclerite morphology. Three species (A. brauni sp. nov., A. shieldsi sp. nov. and A. sigani sp. nov.) were assessed for seasonal variation of sclerite size. Ten of thirteen morphological characters showed seasonal variation in size for at least one of the species. The characters were longer in winter except dorsal root tissue cap width. Only one character, marginal hook length, showed significant seasonal variation for all three species. Species of Acanthoplacatus were observed to attach using only the marginal hooks and the role of hamuli in attachment is unclear. The dorsal rn of the host is the preferred site for most species but the anal fin, caudal fin and body surfaces are preferred by some species. Prevalences for species range from 57 to 100%.

Comparison of differentiated dendritic cell infiltration of autoimmune and osteoarthritis synovial tissue

Objective. Infiltration of rheumatoid arthritis (RA) synovial tissue (ST) by differentiated dendritic cells (DC) is a consistent feature in patients with active disease. However, mononuclear cells (MNC), including DC, may be nonspecifically chemoattracted to inflammatory sites regardless of etiology, Therefore, to evaluate the specificity of ST infiltration by differentiated DC, synovial biopsies from patients with RA, spondylarthropathy (SpA), osteoarthritis (OA), and gout were examined. Methods. Formalin-fixed ST sections were analyzed by double immunohistochemical staining for vascularity and infiltration by differentiated DC, lymphocytes, and macrophages. Results, DC containing nuclear RelB were found in perivascular MNC aggregates from patients with all arthritides studied. Infiltration by differentiated DC was similar in RA and SpA ST, but reduced in OA ST. Differentiated DC were always observed in close association with lymphocytes, and the correlation between these variables suggested that the infiltration of inflammatory sites by DC and lymphocytes was associated. Conclusion, Perivascular infiltration by DC, lymphocytes, and macrophages is nonspecifically related to inflammation, but signals present in RA and SpA ST lead to more intense cellular infiltration and accumulation.

Postmenopausal Hormone Use, Screening, and Breast Cancer: Characterization and Control of a Bias

Previous investigators have suggested that screening-related biases may explain associations between postmenopausal hormone use and breast cancer. To investigate these biases, we studied postmenopausal women in the Nurses' Health Study from 1988 to 1994. Hormone use is associated with increased subsequent screening. Among women not screened in the previous 2 years, the probability difference, comparing current hormone users with others, for having mammography in the following 2 years is 19.5%; among women previously screened, the difference is 4.9%. These differences persist after control for other factors. If the increase in screening is causal, screening by mammogram could be intermediate in the causal pathway to breast cancer diagnosis. To deal with this problem, we restrict attention to a subset of the cohort in which the effect of postmenopausal hormone use on screening is small (women previously screened). In this subset, the rate ratio comparing breast cancer rates among current postmenopausal hormone users with others is 1.28. In a sensitivity analysis, the bias could not by itself plausibly account for the associations in our data. Our data provide evidence of an association between postmenopausal hormone use and breast cancer that is not solely the product of a detection bias.

Effect of tissue Doppler on the accuracy of novice and expert interpreters of Dobutamine echocardiography

The subjective interpretation of dobutamine echocardiography (DBE) makes the accuracy of this technique dependent on the experience of the observer, and also poses problems of concordance between observers. Myocardial tissue Doppler velocity (MDV) may offer a quantitative technique for identification of coronary artery disease, but it is unclear whether this parameter could improve the results of less expert readers and in segments with low interobserver concordance. The aim of this study was to find whether MDV improved the accuracy of wall motion scoring in novice readers, experienced echocardiographers, and experts in stress echocardiography, and to identify the optimal means of integrating these tissue Doppler data in 77 patients who underwent DBE and angiography. New or worsening abnormalities were identified as ischemia and abnormalities seen at rest as scarring. Segmental MDV was measured independently and previously derived cutoffs were applied to categorize segments as normal or ab normal. Five strategies were used to combine MDV and wall motion score, and the results of each reader using each strategy were compared with quantitative coronary angiography. The accuracy of wall motion scoring by novice (68 +/- 3%) and experienced echocardiographers (71 +/- 3%) was less than experts in stress echocardiography (88 +/- 3%, p < 0.001). Various strategies for integration with MDV significantly improved the accuracy of wall motion scoring by novices from 75 +/- 2% to 77 +/- 5% (p < 0.01). Among the experienced group, accuracy improved from 74 +/- 2% to 77 +/- 5% (p < 0.05), but in the experts, no improvement was seen from their baseline accuracy. Integration with MDV also improved discordance related to the basal segments. Thus, use of MDV in all segments or MDV in all segments with wall motion scoring in the apex offers an improvement in sensitivity and accuracy with minimal compromise in specificity. (C) 2001 by Excerpta Medica, Inc.