Phosphorylation and lipid raft association of fibroblast growth factor receptor-2 in oligodendrocytes.

Fibroblast growth factors (FGFs) and their receptors (FGFRs) initiate diverse cellular responses that contribute to the regulation of oligodendrocyte (OL) function. To understand the mechanisms by which FGFRs elicit these cellular responses, we investigated the phosphorylation of signal transduction proteins and the role of cholesterol-glycosphingolipid-enriched "lipid raft" microdomains in differentiated OLs. Surprisingly, we found that the most abundant tyrosine-phosphorylated protein in OLs was the 120-kd isoform of FGFR2 and that it was phosphorylated even in the absence of FGF2, suggesting a potential ligand-independent function for this receptor. Furthermore, FGFR2, but not FGFR1, was associated with lipid raft microdomains in OLs and myelin (but not in astrocytes). This provides the first evidence for the association of FGFR with TX-100-insoluble lipid raft fractions. FGFR2 phosphorylated the key downstream target, FRS2 in OLs. Raft disruption resulted in loss of phosphorylated FRS2 from lipid rafts, coupled with the loss of Akt but not of Mek or Erk phosphorylation. This suggests that FGFR2-FRS2 signaling in lipid rafts operates via the PI3-Kinase/Akt pathway rather than the Ras/Mek/Erk pathway, emphasizing the importance of microenvironments within the cell membrane. Also present in lipid rafts in OLs and myelin, but not in astrocytes, was a novel 52-kd isoform of FGFR2 that lacked the extracellular ligand-binding region. These results demonstrate that FGFR2 in OLs and myelin possess unique characteristics that are specific both to receptor type and to OLs and provide a novel mechanism to elicit distinct cellular responses that mediate both FGF-dependent and -independent functions.

Corneal tensile strength in fully healed radial keratotomy wounds.

PURPOSE: To investigate the susceptibility to rupture of a human donor cornea with fully healed radial keratotomy (RK) incisions using biomechanical measurement methods and finite element analysis. METHODS: A human cornea 8 years after RK was cut into four strips and subjected to tensile testing until rupture occurred. The fellow cornea was pressurized on an artificial anterior chamber beyond the initiation of wound gape. The tensile strengths of nine strips from unincised corneas were measured as controls. To investigate the effect of epithelial plugs on the RK strip test results, a finite element model of a strip containing an epithelial plug was analyzed. RESULTS: Rupture occurred along the wound site with wide variability in the measured tensile strengths. There was no significant difference in tensile strength between the RK corneal strips (16.6 +/- 4.43 N/mm2) and the control strips (19.1 +/- 3.50 N/mm2). Four of the eight incisions of the fellow RK cornea gaped, but the cornea did not rupture up to a pressure of 2740 mm Hg. An epithelial plug of 10% of the corneal thickness was found in one of the incisions. The finite element results demonstrated higher stresses at the wound site that increased with the size of the epithelial plug. CONCLUSIONS: The presence of an epithelial plug in a fully healed radial keratotomy incision will create a stress concentration at the incision site that may predispose the cornea to rupture. The variability in the strength measurements indicates that the increase in rupture susceptibility due to RK may be hard to predict and may depend on factors such as the size of the plug and the strength of the wound collagen.

Mathematical models of picosecond laser keratomileusis for high myopia.

PURPOSE: Picosecond laser keratomileusis (PLK) is a refractive surgical procedure in which an intrastromal lenticle is created using the Nd:YLF picosecond laser and removed by lifting the anterior flap in the cornea. The purpose of this study was to assess the predictability of picosecond laser keratomileusis for high myopia. METHODS: The results from a recent clinical series of non-sighted patients who had undergone picosecond laser keratomileusis with the Nd:YLF picosecond laser were retrospectively simulated with two mathematical models. In one model, the change in corneal curvature resulting from the collapse of a lenticular intrastromal cavity was predicted from a geometric analysis. A second model was developed using the finite element method. The results of both predictive models were compared to the clinical results at 1 and 6 months following surgery. RESULTS: An average -13.30 D of flattening (range, -6.80 to -20.50 D) was measured at 6 months. The geometric model predicted an average correction of -23.10 D (range, -18.00 to -34.00 D), whereas the finite element model predicted an average curvature change of -17.40 D (range, -14.50 to -22.50 D). An average decrease in central pachymetry of 91 microm was measured at 6 months, as compared to a predicted decrease in thickness of 112 microm. CONCLUSIONS: The outcome of picosecond laser keratomileusis for high myopia predicted using a finite element based model shows greater change in the corneal curvature and corneal thickness compared to clinical results. The relatively thick lenticules that are removed for high myopia cause considerable deformational changes in the cornea, which preclude the use of a purely geometric/optical approach for predicting the resultant corneal curvature changes.

Supervisory status of charge nurses: Supreme Court ends controversy.

A recent Supreme Court decision has refuted the National Labor Relations Board's position that supervisory field RNs are not technically supervisors. This decision makes it easier for providers to supervise staff and aligns these nurses more closely with management.

On the computer-aided and optimal design of keratorefractive surgery.

BACKGROUND: Several recent papers have discussed the use of engineering-based computer methods for the analysis of keratorefractive surgical procedures. What has been lacking is a broader view of the role of engineering analysis in keratorefractive surgery. This article demonstrates how these various analysis methods can be coupled to provide a comprehensive methodology for the design of refractive surgical procedures. METHODS: A structural model of the eye, based on a linearly elastic, transversely isotropic finite element formulation is coupled to a full-eye optical model. The optical errors due to refractive keratotomy are estimated by ray tracing through the optical model and measuring the position of the resulting focal plane relative to the retina. Computer-based optimization methods are employed to determine the surgical parameters necessary to correct myopia for a given set of surgical design goals. RESULTS: Results based on a hypothetical eye demonstrate agreement with clinical trends. Radial keratotomies are designed that eliminate refractive error while minimizing invasiveness in one case and maximizing the optical zone size in another. It is also shown that there is significant potential to customize this process on a patient-by-patient basis using clinically measured data. CONCLUSIONS: We present an overview of the research necessary to bring this approach to fruition. While only a first step, the methodology presented in this article has the potential to increase the predictability of keratorefractive surgery by substantially increasing both the quality and the quantity of the information available to the refractive surgeon preoperatively.

A triphasic analysis of corneal swelling and hydration control.

Physiological studies strongly support the view that hydration control in the cornea is dependent on active ion transport at the corneal endothelium. However, the mechanism by which endothelial ion transport regulates corneal thickness has not been elaborated in detail. In this study, the corneal stroma is modeled as a triphasic material under steady-state conditions. An ion flux boundary condition is developed to represent active transport at the endothelium. The equations are solved in cylindrical coordinates for confined compression and in spherical coordinates to represent an intact cornea. The model provides a mechanism by which active ion transport at the endothelium regulates corneal hydration and provides a basis for explaining the origin of the "imbibition pressure" and stromal "swelling pressure." The model encapsulates the Donnan view of corneal swelling as well as the "pump-leak hypothesis."