Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in prostatic adenocarcinoma

We studied endoglin and vascular endothelial growth factor (VEGF) expression as prognostic markers in prostatic adenocarcinoma in 50 radical prostatectomy specimens. Cases were further categorized by Gleason score as follows: 8 to 10, 9 cases; 7(4 + 3), 9 cases; 7 (3 + 4), 14 cases; 6, 13 cases; and 4 or 5, 5 cases. All cases were immunostained for endoglin, CD31, and VEGF. Positively stained microvessels were counted in densely vascular foci in a x 400 field. VEGF staining intensity was scored on a 2-tiered scale. Results were correlated with survival and other parameters. Endoglin demonstrated significantly more microvessels than did CD31 (mean +/- SD, 37 +/- 15 vs 22 +/- 17; P < .001). VEGF expression was low in 21 cases (42%) and high in 29 (58%). Endoglin correlated positively with Gleason score, lymph node metastases, tumor stage, and preoperative prostate-specific antigen level (P < .05) but not with CD31. VEGF correlated significantly with angiolymphatic invasion and Gleason score (P < .05). A high endoglin microvessel count and VEGF expression correlated with shorter survival. Endoglin is a more specific and sensitive marker for tumor angiogenesis than CD31 and may serve as a prognostic marker for prostatic adenocarcinoma.     

Multivariate Cholesky Models of Human Female Fertility Patterns in the NLSY

Substantial evidence now exists that variables measuring or correlated with human fertility outcomes have a heritable component. In this study, we define a series of age-sequenced fertility variables, and fit multivariate models to account for underlying shared genetic and environmental sources of variance. We make predictions based on a theory developed by Udry [(1996) Biosocial models of low-fertility societies. In: Casterline, JB, Lee RD, Foote KA (eds) Fertility in the United States: new patterns, new theories. The Population Council, New York] suggesting that biological/genetic motivations can be more easily realized and measured in settings in which fertility choices are available. Udry’s theory, along with principles from molecular genetics and certain tenets of life history theory, allow us to make specific predictions about biometrical patterns across age. Consistent with predictions, our results suggest that there are different sources of genetic influence on fertility variance at early compared to later ages, but that there is only one source of shared environmental influence that occurs at early ages. These patterns are suggestive of the types of gene–gene and gene–environment interactions for which we must account to better understand individual differences in fertility outcomes. Edited by John Hewitt and Wendy Slutske     

A comparison of three bioassay techniques to determine amitraz susceptibility in Boophilus microplus (Acari: Ixodidae)

The ability of the Miller, Soberanes, and White bioassay techniques to describe amitraz susceptibility in three different strains of Boophilus microplus (Canestrini) (Acari: Ixodidae) was compared. For a susceptible strain, all techniques adequately described amitraz susceptibility by producing a full range of mortality that corresponded with increasing concentration of amitraz. However, when resistant strains were evaluated, only the Miller and the Soberanes techniques adequately estimated the dose-response relationship. Lethal concentrations were not precisely estimated when all the data were included in the analyses for every strain and technique tested. Better estimates were obtained when subsets of data around the range of interest were subjected to probit analysis. For the Soberanes technique, the slope of the probit regression was steeper for the Brazilian resistant and Texan susceptible strains compared with the heterozygous Mexican strain. The pattern was different when the same strains were tested with the Miller technique. The slopes of the regressions for the Mexican and the Texan strains did not differ significantly, but the Brazilian strain had a steeper slope than the other strains. Resistance ratios were much greater when the Soberanes technique was used than when the Miller technique was used on the same strains. However, neither technique produced enough separation between susceptible and resistant strains to develop a traditional discriminating dose (DD) test that required a concentration of 2x LC99.9 estimate. A DD test at the LC99 would be possible for both techniques. We discuss the strengths and weaknesses of the three techniques, including potential improvements to the White technique. The White technique has the greatest potential to determine the mechanisms of amitraz resistance in detailed synergist studies. Currently, only the Miller method can fulfill this task. The Miller and Soberanes techniques are well suited for the study of the epidemiology of resistance worldwide, because they use commercially available, formulated amitraz that is easy and inexpensive to obtain.     

Efficacy of a single doramectin injection against adult female Boophilus microplus (Acari: Ixodidae) in the final stages of engorgement before detachment

The efficacy of injectable doramectin applied at 200 microg/kg was evaluated against adult female Boophilus microplus (Canestrini) (Acari: Ixodidae) in the later stages of engorgement before detachment. Lethal levels of doramectin in the serum of treated cattle (9.7-36.6 ppb) were reached and sustained within 24 h after treatment. However, treatment at 19 or 20 d postinfestation allowed greater tick survival and reproductive capability (IF) than at 18 d postinfestation, indicating that a significant portion of the ticks were able to engorge and detach before obtaining a lethal dose of doramectin. Thus, treatment at 18 d after infestation provided significantly higher overall control (99.5%) than treatment at 19 or 20 d postinfestation (95.8 and 89.1%, respectively). Analysis of control on a daily basis demonstrated that treatment at 18 d postinfestation provided > 99% on each day of the evaluation. Conversely, treatment at 19 or 20 d postinfestation produced levels of control ranging from 22.6 to 85.6% during the first 2 d of female detachment, and > or = 99% control was not achieved until after the fourth day of female detachment, where it remained throughout the study. Therefore, application of injectable doramectin at < or = 18 d after tick infestation was the only treatment regime considered acceptable for use in the U.S. Boophilus Eradication Program. Treatment intervals > 18 d postinfestation could pose a substantial risk of dispersing viable ticks to tick-free areas outside the permanent quarantine zone that has been established along the Texas-Mexico border.     

From nature to nurture, and back again

Gilbert Gottlieb's developmental theory views organismic development as a multilevel system involving ongoing transactions among different levels of organization. Here, I review his conception of development as it has been influenced historically and has guided several lines of empirical inquiry focusing on auditory communication in birds. Ecological factors are considered an important means of identifying possible nonlinear (i.e., subtle or nonobvious) forms of experience that play a significant role in species-typical development. Failure to consider such nonlinearities, along with obvious linear influences, undermines the developmental point of view that Gottlieb advocated as a means of teasing apart the intricate nature of organismic development.     

Immunization with heat-killed Francisella tularensis LVS elicits protective antibody-mediated immunity

Francisella tularensis (FT) has been classified by the CDC as a category A pathogen because of its high virulence and the high mortality rate associated with infection via the aerosol route. Because there is no licensed vaccine available for FT, development of prophylactic and therapeutic regimens for the prevention/treatment of infection is a high priority. In this report, heat-killed FT live vaccine strain (HKLVS) was employed as a vaccine immunogen, either alone or in combination with an adjuvant, and was found to elicit protective immunity against high-dose FT live vaccine strain (FTLVS) challenge. FT-specific antibodies produced in response to immunization with HKLVS alone were subsequently found to completely protect naive mice against high-dose FT challenge in both infection-interference and passive immunization experiments. Additional passive immunization trials employing serum collected from mice immunized with a heat-killed preparation of an O-antigen-deficient transposon mutant of FTLVS (HKLVS-OAg(neg)) yielded similar results. These findings demonstrated that FT-specific antibodies alone can confer immunity against high-dose FTLVS challenge, and they reveal that antibody-mediated protection is not dependent upon production of LPS-specific antibodies.     

Youth health outcomes from the Connect-to-Protect coalitions to prevent adolescent HIV infections

We assessed the relationships among HIV-related social and behavioral outcomes resulting from an adolescent-focused HIV structural change initiative in eight urban sites operating Connect-to-Protect coalitions. Over a 4-year period, annual cross-sectional panels of adolescents (N = 2248) completed an audio-computer-assisted interview, providing data on satisfaction with their communities as adolescent-supportive environments, internalized HIV stigma, lifetime HIV-testing, lifetime sexual risk-taking and number of sexual partners in the prior year. We used structural equation modeling to estimate hypothesized links between time since coalition mobilization to our social and behavioral outcomes. Over the 4 years, adolescents perceived their communities to become more supportive (p < .05). Positive perceptions of community support were associated with lower lifetime HIV sexual risk (p < .05). The effect of time on risk behavior was mediated by perceptions of community support. Stigma was unchanged over time. Stigma had damaging effects on risk behavior, effects which were also mediated by perceptions of community support. Special efforts are needed to address the deleterious effect of HIV stigma on high-risk urban adolescents.