Co-operative mineralization and protein self-assembly in amelogenesis: silica mineralization and assembly of recombinant amelogenins in vitro

An amorphous silica mineralization technique was used to produce inorganic/protein composites to elucidate the structure and mechanism of formation of amelogenin assemblies, which may play an important role in regulating enamel structure during the initial stages of amelogenesis. Full-length recombinant amelogenins from mouse (rM179) and pig (rP172) were investigated along with key degradation products (rM166 and native P148) lacking the hydrophilic C terminus found in parent molecules. The resulting products were examined using transmission electron microscopy and/or small-angle X-ray scattering. Using protein concentrations of 0.1–3 mg ml⁻¹, large monodisperse spheres of remarkably similar mean diameters were observed using rM179 (124 ± 4 nm) and rP172 (126 ± 7 nm). These spheres also exhibited 'internal structure', comprising nearly spherical monodisperse particles of ≈ 20 nm in diameter. In the presence of rM166, P148, and bovine serum albumin (control), large unstructured and randomly shaped particles (250–1000 nm) were observed. Without added protein, large dense spherical particles of silica (mean ≈ 500 nm) lacking internal structure were produced. These findings demonstrate that full-length amelogenins have the ability to form higher-order structures, whereas amelogenins that lack the hydrophilic C terminus do not. The results also suggest that full-length amelogenin can guide the formation of organized mineralized structures through co-operative interactions between assembling protein and forming mineral.     

Reactive arthritis and internal derangement of the temporomandibular joint.

OBJECTIVE: The objective of this study was to determine if temporomandibular joint (TMJ) samples positive for Chlamydia trachomatis have a greater presence of tumor necrosis factor-alpha (TNFalpha) or interleukin-6 (IL-6) when compared with Chlamydia-negative samples. STUDY DESIGN: Posterior bilaminar tissue samples removed during TMJ surgery from 70 patients were evaluated. Cryosections were stained using monoclonal antibody that identifies C. trachomatis. The presence of IL-6 and TNFalpha were evaluated by immunostaining in 15 samples positive and in 25 samples negative for the presence of C. trachomatis. RESULTS: Of the 70 TMJ samples, 32 (46%) were positive for C. trachomatis. In 15 samples positive for C. trachomatis, 10 (67%) were positive for TNFalpha and 7 (47%) for IL-6. In 25 samples negative for C. trachomatis, only 4 (16%) were positive for TNFalpha and only 2 (8%) for IL-6. Differences in C. trachomatis-positive samples versus negative were significant for both TNFalpha (P < .002) and IL-6 (P < .008). CONCLUSION: The presence of C. trachomatis in the TMJ is associated with a significantly increased presence of TNFalpha and IL-6.     

Adiposity and sex hormones in girls.

Greater body fatness during childhood is associated with reduced risk of premenopausal breast cancer, but few studies have addressed the relation of adiposity with sex hormones in girls. We prospectively examined associations between adiposity and circulating levels of sex hormones and sex hormone-binding globulin (SHBG) among 286 girls in the Dietary Intervention Study in Children. Participants were 8 to 10 years old at baseline and were followed for an average of 7 years. Anthropometric measurements were taken at baseline and at subsequent annual visits, and blood samples were collected every 2 years. Concentrations of dehydroepiandrosterone sulfate (DHEAS) during follow-up were higher among girls with greater body mass index (BMI) at baseline. The mean for the lowest BMI quartile was 63.0 microg/dL compared with 78.8 microg/dL for the highest quartile, and each kg/m(2) increment in baseline BMI was associated with a 4.3% increase (95% confidence interval, 1.6-7.0%) in DHEAS levels during follow-up (P(trend) = 0.002). Concentrations of SHBG during follow-up were lower among girls with greater BMI at baseline. The mean for the lowest BMI quartile was 94.8 nmol compared with 57.5 nmol for the highest quartile, and each kg/m(2) increment in baseline BMI was associated with an 8.8% decrease (95% confidence interval, 7.0-10.6%) in SHBG levels during follow-up (P(trend) < 0.0001). Estrogen and progesterone concentrations were similar across BMI quartiles. These findings suggest that adiposity may alter DHEAS and SHBG levels in girls. Whether and how these differences affect breast development and carcinogenesis requires further research.     

Developing a Peer Review Process for Web-based Curricula

The World Wide Web creates new challenges and opportunities for medical educators. Prominent among these are the lack of consistent standards by which to evaluate web-based educational tools. We present the instrument that was used to review web-based innovations in medical education submissions to the 2003 Society of General Internal Medicine (SGIM) national meeting, and discuss the process used by the SGIM web-based clinical curriculum interest group to develop the instrument. The 5 highest-ranked submissions are summarized with commentary from the reviewers.