Erzsébet Balázs

Hemodynamic changes after ruthenium irradiation of hippel's angiomatosis

The authors report a case of Hippels angiomatosis successfully treated with contact beta irradiation. The area of the multiplex retinal angioma and the accompanying retinal detachment was irradiated with a 106Ru/106Rh radioactive applicator. Hemodynamic changes due to irradiation were followed up in the ipsilateral ophthalmic artery with transcranial Doppler sonography. Scarring was also demonstrated by fluorescein angiography and A- and B-scan ultrasonography. Irradiation caused the narrowing and later the occlusion of the precapillaries and capillaries (i.e. the resistance vessels) and that of the shunts inside the angioma; consequently, vascular resistance increased. Transcranial Doppler sonographic recordings showed a decrease in blood flow velocity as compared to pathologically increased blood flow velocity in angiomas, and a gradual increase in vascular resistance which was lower before treatment.

Expression of betaig-h3 is lower than normal in keratoconus corneas but increases with scarring.

PURPOSE Keratoconus is a progressive ectatic disease of the cornea. Despite extensive clinical and laboratory investigations, its pathogenesis remains unclear. In this study, we examined the localization of betaig-h3, a recently described extracellular matrix protein in keratoconus corneas both in the absence and presence of subepithelial scarring. METHODS Two normal corneas and central corneal buttons of 10 patients with keratoconus were excised during perforating keratoplasty and examined, including one case with acute corneal hydrops. In one case, keratoconus was associated with Down syndrome. Immunodetection was done with an antipeptide antibody reacting with the N-terminal part of betaig-h3. RESULTS We found decreased betaig-h3 levels in the basal epithelial layer and keratocytes of keratoconus corneas. In the scarred corneas, however, betaig-h3 levels were increased in the basal epithelial layers and in activated keratocytes at the places of scarring. In the cornea of the patient with Down syndrome, we found an additional betaig-h3-positive zone in the anterior stroma. CONCLUSIONS The decreased levels of betaig-h3 corneas seem to be specific for keratoconus. Considering the putative role of betaig-h3 as a cellular-attachment protein, paucity of betaig-h3 in the corneal stroma may lead to decreased mechanical stability and contribute to the development of keratoconus.

Immunohistochemical detection of βIG-H3 in scarring human corneas

Abstract · Background: βIG-H3 is a recently described extracellular matrix protein that is present in various organs. In rabbit corneas, increased βIG (the rabbit form of βIG-H3) mRNA levels were shown during corneal development and wound healing. In this study, we investigated the localization of βIG-H3 protein in scarring human corneas. · Methods: Corneal buttons obtained during keratoplasty were examined. Immunohistological detection using a polyclonal antipeptide antibody against the βIG-H3 protein was performed on 24 pathological corneas (9 ulcerations, 8 alkali burns, 2 perforating injuries, 5 bullous keratopathy) and 2 normal corneas. · Results: In normal corneas, strong staining was present in the basal layer of the epithelium and in the endothelium; the stromal fibers showed faint, uniform immunoreactivity. In all scarring corneas, the epithelium was usually thickened and all of its layers were reactive with the βIG-H3 antibody. The cytoplasm of the stromal fibroblasts, as well as the stromal fibers around them also showed staining with the antibody. These changes were present in all scarring corneas, irrespective of the pathological process leading to scar formation. · Conclusion: These results prove, at the protein level, the presence of increased amounts of βIG-H3 at the sites of scarring in human corneas.

Three novel germ-line VHL mutations in Hungarian von Hippel-Lindau patients, including a nonsense mutation in a fifteen-year-old boy with renal cell carcinoma

BackgroundVon Hippel-Lindau disease is an autosomal dominantly inherited highly penetrant tumor syndrome predisposing to retinal and central nervous system hemangioblastomas, renal cell carcinoma and phaeochromocytoma among other less frequent complications.MethodsMolecular genetic testing of the VHL gene was performed in five unrelated families affetced with type I VHL disease, including seven patients and their available family members.ResultsMolecular genetic investigations detected three novel (c.163 G > T, c.232A > T and c.555C > A causing p.Glu55X, p.Asn78Tyr and p.Tyr185X protein changes, respectively) and two previously described (c.340 + 1 G > A and c.583C > T, resulting in p.Gly114AspfsX6 and p.195GlnX protein changes, respectively) germline point mutations in the VHL gene. Molecular modeling of the VHL-ElonginC-HIF-1alpha complex predicted that the p.Asn78Tyr amino acid exchange remarkably alters the 77-83 loop structure of VHL protein and destabilizes the VHL-HIF-1alpha complex suggesting that the mutation causes type I phenotype and has high risk to associate to renal cell carcinoma. The novel p.55X nonsense mutation associated to bilateral RCC and retinal angioma in a 15-year-old male patient.ConclusionWe describe the earliest onset renal cell carcinoma in VHL disease reported so far in a 15-year-old boy with a nonsense VHL mutation. Individual tailoring of screening schedule based on molecular genetic status should be considered in order to diagnose serious complications as early as possible. Our observations add to the understanding of genotype-phenotype correlation in VHL disease and can be useful for genetic counseling and follow-up of VHL patients.