Citations

Purpose: To describe an exceedingly rare presentation of vitreoretinal involvement of metastatic tonsillar squamous cell carcinoma and illustrate the utility of therapeutic and diagnostic epiretinal membrane biopsy. Methods: Case report. Results: A 57-year-old man presented with new vitreous opacities in the left eye. He had a history of tonsillar squamous cell carcinoma status postsurgical excision and was undergoing chemotherapy and radiation therapy. The patient underwent vitreous biopsy that revealed scant cellularity with concern for squamous neoplasia. Soon after, the patient developed a rapidly progressive epiretinal membrane. Membrane peel surgery with en-bloc removal of the epiretinal membrane was performed. Hematoxylin and eosin stain of the sample revealed multiple squamous eddies and mitotic figures, and cytokeratin AE1/AE3 marker was strongly positive, confirming the diagnosis of metastatic squamous cell carcinoma. Intravitreal melphalan injections were started in the left eye. The patient achieved anatomic and visual improvement. Conclusion: Intraocular squamous cell metastasis is rare, and diagnosis can be challenging. Despite initial inconclusive vitreous biopsy cytology in this case, an epiretinal membrane en-bloc sample was obtained, which confirmed involvement by the squamous cell carcinoma and prompted appropriate treatment.

This cross-sectional study examines the frequency of increased intracranial pressure and its association with myelin oligodendrocyte glycoprotein antibody-associated disease in patients of various ages.

Several studies have demonstrated that the amino acid residues flanking the Arg-Gly-Asp (RGD) sequence of high-affinity ligands modulate their specificity of interaction with integrin complexes. Because of the absence of structural data for integrin complexes with bound ligand, the molecular basis for this specificity modulation remains obscure. In a previous paper [Rahman, Lu, Kakkar and Authi (1995) Biochem. J. 312, 223-232] we demonstrated that two genetically distinct venom-derived RGD proteins, kistrin and dendroaspin (both containing the sequence PRGDMP), were simple competitors, indicating the recognition of an identical binding site on the αIIbβ3 complex. Furthermore, both kistrin and dendroaspin inhibited the binding of the disintegrin elegantin (containing the sequence ARGDNP) via a non-competitive mechanism, suggesting that the binding of elegantin to the αIIbβ3 complex was at a remote site and down-regulated via an allosteric mechanism. Here we present further evidence for distinct RGD ligand recognition sites on the αIIbβ3 complex that exhibit a negative allosteric relationship. A panel of well-characterized recombinant dendroaspin and elegantin derivatives were employed for this study. These recombinant molecules were constructed as glutathione S-transferase fusion proteins with either an Ala or Pro residue N-terminal to the RGD sequence in combination with either a Met or an Asn residue immediately C-terminal. Equilibrium competition experiments showed that elegantin binding to ADP-treated platelets was inhibited by derivatives Eleg. AM (ARGDMP) and Eleg. PM (PRGDMP) via an allosteric competitive mechanism, providing direct evidence that modulation of the RGD motif can alter competitive behaviour. In addition, recombinant kistrin and dendroaspin both inhibited elegantin binding via a non-competitive mechanism, confirming our previous observations. Further evidence for distinct binding sites employing an independent approach was obtained by analysing the binding of the panel of venom proteins to the functionally defective heterodimer αIIbβ3 Ser123 → Ala expressed on Chinese hamster ovary cells. These studies demonstrated that simple competitors kistrin and dendroaspin bound with high affinity to the variant integrin complex. In contrast, the binding of elegantin and most significantly, recombinant Dendro. PN (PRGDNP) and Dendro. AN (ARGDNP) were abolished. These observations, taken together, are consistent with a model depicting the presence of distinct sites of RGD ligand recognition on the αIIbβ3 complex that show the preferential recognition of specific RGD motifs. Competition experiments demonstrate a negative allosteric relationship between these RGD recognition sites.