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.     

Diabetic neuropathic foot ulcers and amputation

A neuropathic foot ulcer is a severe complication of diabetes that can result in a more severe complication, a lower extremity amputation. We conducted a cohort study of 24,616 individuals with a diabetic neuropathic foot ulcer treated within a multicenter wound care network. A total of 1653 (6.7%) individuals had an amputation and 46.3% of these amputations were of a toe or ray (minor amputation). In the more than 10-year follow-up period that we studied, the percentage of those who had an amputation varied between 5.6% and 8.4%. Of those who had an amputation, the percentage that had a minor amputation increased over time from 4.0% in the earliest years to more than 60% in the later years of observation. The single most important determinant of amputation was the observation of fascia, tendon, and bone at the initial assessment. In conclusion, about 7% of those with a diabetic neuropathic foot ulcer will have an amputation and in the past 10 years there has been a remarkable increase in the number of minor as compared to major amputations.     

Selective photothermolysis: contribution to the treatment of flat angiomas (port wine stains) by laser

Since 1962, lasers have been used in dermatology and have become the first choice in the treatment of superficial, vascular ectasia. Lasers are unique sources of light; they are coherent, monochromatic, collimated and intense. By careful selection of wavelength, pulse duration, and intensity, it is often possible to selectively confine a laser effect to a specific histologic structure in tissue, depending upon the tissue properties. The ideal treatment of Port Wine Stains (PWS) should irreversibly damage the ectatic vessels but minimize heating of the epidermis and superficial dermis. A theory, called selective photothermolysis, predicts the optimal combination of laser parameters of achieving this ideal treatment of PWS to be a wavelength of 577 nm, a pulse duration of 0.35-10 msec, and an energy per surface area of about 7-8 J/cm2. Laser wavelength: The wavelength of 577 nm is preferred because it: maximizes the selective absorption by hemoglobin, minimizes absorption by epidermal melanin, provides sufficient depth of penetration in the blood to coagulate 0.1 mm vessels allows penetration of light into dermis up to 1 mm. Laser pulse duration: A pulse-width in the range of 0.35-10 msec allows the temperature elevation to be uniform inside the vessel and to be confined to the vessel area. Shorter pulses superheat the red blood cells causing explosive boiling and hemorrhage. Longer pulses allow heat to diffuse away from vessels, requiring greater energies per pulse to achieve vessel damage. An increased energy per pulse increases the risk of excessive damage to surrounding tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Monoclonal antibody-mediated detection of lung cancer antigens in serum

We assessed the ability of three monoclonal antibodies (MAbs) (5E8, 5C7, and 1F10) to detect tumor-associated antigens (TAAs) in the sera of patients seen in consultation by the Pulmonary Disease Section at the Philadelphia Veterans Administration Medical Center from September through November 1987. Eighteen of the 61 sera were obtained from patients with histologically established lung cancer. Using a semiquantitative enzyme-linked immunoassay (ELISA), TAAs were detected by the MAb panel in the sera of 12 lung cancer patients, yielding a sensitivity of 67% with a 95% confidence interval of 44 to 84%. The frequency of TAA detection varied among cell types and stages of disease. There were eight false positives and 35 true negatives, giving a specificity of 81% with a 95% confidence interval of 67 to 90%. Two of the false positives came from patients with nonpulmonary tumors known to cross-react with the MAbs (laryngeal and gastric carcinoma). The panel was able to distinguish patients with lung cancer from those without to a highly significant degree (chi 2 = 11.2 with 1 df, p less than 0.001). This study suggests that MAb-mediated detection of serum TAAs may be useful in diagnosing and characterizing lung cancers.