Melissa White

The present studies were undertaken to evaluate the in vitro gel stability of the hydrogels alginate and agarose. Gel strength (of alginate and agarose) and protein diffusion (of alginate only) were shown to correlate with gel stability and to be useful techniques to monitor gel stability over time. The gel strengths of alginate and agarose were followed for a 90-day period using gel strength as a measure of gel stability. The gel strength of agarose diminished in the presence of cells because the cells likely interfered with the hydrogen bond formation required for agarose gelation. In the presence of cells, the gel strength of agarose decreased by an average of 25% from time 0 to 60 days, thereafter maintaining that value to 90 days. The gel strength of calcium- or barium-crosslinked alginate decreased over 90 days, with an equilibrium gel strength being achieved after 30 days. The presence of cells did not further decrease alginate gel strength. The gel strengths of calcium- and barium-crosslinked alginates were similar at 60 days-350 +/- 20 g and 300 +/- 60 g, respectively-indicating equivalence in their stability. The stability of calcium-crosslinked sodium alginate gels over a 60-day time period was monitored by diffusion of proteins ranging in molecular weight from 14.5 to 155 kD. From these diffusion measurements, the average pore size of the calcium-crosslinked alginate gels was estimated, using a semi-empirical model, to increase from approximately 176 to 289 A over a period of 60 days. (c) 1996 John Wiley & Sons, Inc.

BACKGROUND: Most epidemiologic studies of puberty have only 1 source of pubertal development information (maternal, self or clinical). Interpretation of results across studies requires data on reliability and validity across sources. METHODS: The LEGACY Girls Study, a 5-site prospective study of girls aged 6 to 13 years (n = 1040) collected information on breast and pubic hair development from mothers (for all daughters) and daughters (if ≥10 years) according to Tanner stage (T1-5) drawings. At 2 LEGACY sites, girls (n = 282) were also examined in the clinic by trained professionals. We assessed agreement (κ) and validity (sensitivity and specificity) with the clinical assessment (gold standard) for both the mothers' and daughters' assessment in the subcohort of 282. In the entire cohort, we examined the agreement between mothers and daughters. RESULTS: Compared with clinical assessment, sensitivity of maternal assessment for breast development was 77.2 and specificity was 94.3. In girls aged ≥11 years, self-assessment had higher sensitivity and specificity than maternal report. Specificity for both mothers and self, but not sensitivity, was significantly lower for overweight girls. In the overall cohort, maternal and daughter agreement for breast development and pubic hair development (T2+ vs T1) were similar (0.66, [95% confidence interval 0.58-0.75] and 0.69 [95% confidence interval 0.61-0.77], respectively), but declined with age. Mothers were more likely to report a lower Tanner stage for both breast and pubic hair compared with self-assessments. CONCLUSIONS: These differences in validity should be considered in studies measuring pubertal changes longitudinally when they do not have access to clinical assessments.

Poly(vinyl alcohol) (PVA) foams were used as scaffolds in hollow fiber membrane-based cell encapsulation devices. The surrounding permselective membrane serves as an immunoisolation barrier while allowing metabolites and other small molecules to be freely transported. The internal matrix defines the microenvironment for the encapsulated cells. PC12 cell-containing devices represent one possible strategy for safe transplantation of dopamine-secreting cells for the treatment of dopamine-deficient diseases such as Parkinson's disease. PC12 cells--a dopamine-secreting cell line--were encapsulated with PVA foam as a matrix material in the lumen of these hollow fibers. In this work, we demonstrate the presence of the PVA matrix increased the catecholamine secretion efficiency of the cells as compared to devices containing a chitosan matrix. Devices were implanted in vivo into rodent striatum and device output of catecholamines was measured preimplant and post-explant. Evoked stores of dopamine remained constant (preimplant vs explant) for devices encapsulated with the foam matrix and increased with devices encapsulated with chitosan matrix. Cell proliferation within devices was inhibited in the presence of the foam matrix. Cell viability and distribution was significantly improved with the inclusion of the foam matrix in both in vitro and in vivo studies. In comparison to chitosan--a typical matrix material for PC12 cells--addition of a foam-type matrix altered the encapsulated cell microenvironment and resulted in more efficient secretion of catecholamines and improved distribution within the device resulting in smaller necrotic regions and a lower rate of cell proliferation.

Cell therapy-use of cells to deliver active factors-is an emerging technique in treatment of neurodegenerative disease. Successful devices maintain cell viability and functionality over extended implant periods. Use of dividing cell lines to deliver therapeutic factors has been studied extensively. One emerging issue is the tendency of cells to continue proliferation within the intracapsular environment-potentially outstripping nutrient supply. This work presents a method of controlling proliferation and delivering therapeutic molecules within a dose range. The method entails encapsulation into a hollow fiber device of discrete numbers of cell-containing microcarriers. Proliferation control is attained by embedding cell-containing microcarriers in nonmitogenic hydrogels. PC-12 cells secreting L-dopa and dopamine was the model cell line tested. Feasibility of the method in controlling growth of normally rapidly dividing cells in the intracapsular environment was demonstrated in vitro and in vivo. Control nonmicrocarrier PC-12 cell devices had approximately fourfold greater expansion in cell number compared to experimental microcarrier-containing devices over 4 weeks in vitro and in vivo after implant into rat striatum. Ability to control dose released over a several-fold range was demonstrated with encapsulated PC-12 cells delivering neurotransmitters and C2C12 mouse myoblast cells delivering neurotrophic factors (CNTF).

Abstract Background Polycyclic aromatic hydrocarbons (PAH), which are found in air pollution, have carcinogenic and endocrine disrupting properties that might increase breast cancer risk. PAH exposure might be particularly detrimental during pregnancy, as this is a time when the breast tissue of both the mother and daughter is undergoing structural and functional changes. In this study, we tested the hypothesis that ambient PAH exposure during pregnancy is associated with breast tissue composition, measured one to two decades later, in adolescent daughters and their mothers. Methods We conducted a prospective analysis using data from a New York City cohort of non-Hispanic Black and Hispanic mother–daughter dyads (recruited 1998–2006). During the third trimester of pregnancy, women wore backpacks containing a continuously operating air sampling pump for two consecutive days that measured ambient exposure to eight carcinogenic higher molecular weight nonvolatile PAH compounds (Σ8 PAH) and pyrene. When daughters ( n = 186) and mothers ( n = 175) reached ages 11–20 and 29–55 years, respectively, optical spectroscopy (OS) was used to evaluate measures of breast tissue composition (BTC) that positively (water content, collagen content, optical index) and negatively (lipid content) correlate with mammographic breast density, a recognized risk factor for breast cancer. Multivariable linear regression was used to evaluate associations between ambient PAH exposure and BTC, overall and by exposure to household tobacco smoke during pregnancy (yes/no). Models were adjusted for race/ethnicity, age, and percent body fat at OS. Results No overall associations were found between ambient PAH exposure (Σ8 PAH or pyrene) and BTC, but statistically significant additive interactions between Σ8 PAH and household tobacco smoke exposure were identified for water content and optical index in both daughters and mothers (interaction p values < 0.05). Σ8 PAH exposure was associated with higher water content ( β daughters = 0.42, 95% CI = 0.15–0.68; β mothers = 0.32, 95% CI = 0.05–0.61) and higher optical index ( β daughters = 0.38, 95% CI = 0.12–0.64; β mothers = 0.38, 95% CI = 0.12–0.65) in those exposed to household tobacco smoke during pregnancy; no associations were found in non-smoking households (interaction p values < 0.05). Conclusions Exposure to ambient Σ8 PAH and tobacco smoke during pregnancy might interact synergistically to impact BTC in mothers and daughters. If replicated in other cohorts, these findings might have important implications for breast cancer risk across generations.