Role of Merlin/NF2 inactivation in tumor biology.

Merlin (Moesin-ezrin-radixin-like protein, also known as schwannomin) is a tumor suppressor protein encoded by the neurofibromatosis type 2 gene NF2. Loss of function mutations or deletions in NF2 cause neurofibromatosis type 2 (NF2), a multiple tumor forming disease of the nervous system. NF2 is characterized by the development of bilateral vestibular schwannomas. Patients with NF2 can also develop schwannomas on other cranial and peripheral nerves, as well as meningiomas and ependymomas. The only potential treatment is surgery/radiosurgery, which often results in loss of function of the involved nerve. There is an urgent need for chemotherapies that slow or eliminate tumors and prevent their formation in NF2 patients. Interestingly NF2 mutations and merlin inactivation also occur in spontaneous schwannomas and meningiomas, as well as other types of cancer including mesothelioma, glioma multiforme, breast, colorectal, skin, clear cell renal cell carcinoma, hepatic and prostate cancer. Except for malignant mesotheliomas, the role of NF2 mutation or inactivation has not received much attention in cancer, and NF2 might be relevant for prognosis and future chemotherapeutic approaches. This review discusses the influence of merlin loss of function in NF2-related tumors and common human cancers. We also discuss the NF2 gene status and merlin signaling pathways affected in the different tumor types and the molecular mechanisms that lead to tumorigenesis, progression and pharmacological resistance.

Behçet's disease in Brazil--a review of 49 cases with emphasis on ophthalmic manifestations.

At the Uveitis Clinic of the Department of Ophthalmology of the Escola Paulista de Medicina, São Paulo, Brazil, Behçet's disease was diagnosed in 49 patients, representing 2.0% of the total uveitis cases attended during the 16-year period from February 1974 to June 1990. Of these, 71% were men. The age of onset of the disease was between 9 and 61 years, with a mean of 29.6 years. The ethnic distribution was the following: 76% Caucasian, 14% darkly pigmented, 8% Mongoloid and 2% Negroid. HLA-B5 was found in 45.5% of the 11 Caucasian patients typed. In 34.5% of the cases, the ocular attack was the initial manifestation, alone or associated with other symptoms. Oral aphthae were recorded in 98% of the patients, genital ulcers in 55.1%, and skin lesions in 51%. Joint involvement was present in 44.9%, neurologic symptoms were evidenced in 3 patients, and 2 patients had major vascular involvement. The mean interval between the first manifestation of the disease and the onset of ocular involvement was 3.1 years, with a range of 4 months to 14 years. The interval between affections of both eyes ranged from 0 to 2 years; in 38.4% of the cases it occurred within one month. Anterior and posterior segment involvement was seen in 85.7% of the patients. Hypopyon was observed in 34.7% of the cases. Seven patients did not present iridocyclitis at any time in the course of their disease. We did not see any cases with only anterior segment involvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Vogt-Koyanagi-Harada's disease in Brazil.

A retrospective analysis of 33 patients with Vogt-Koyanagi-Harada disease (VKH disease) seen in São Paulo, Brazil, from 1976 to 1985 at a uveitis referral clinic revealed that VKH disease represents 2.5% of the total uveitis cases seen. All cases were bilateral, 30% being men and 70% women. The ethnic distribution was the following: 60% white (with variable Indian or black extraction), 24% darkly pigmented, 9% Orientals (Sansei, third-generation Japanese) and 6% black. The frequency among Orientals was 7 times higher than what would be expected according to the relative frequency of Japanese in the Brazilian population. The age distribution at the onset of the disease was as follows: 12% less than 20 years of age, 60% between 20 and 40 years of age and 27% over 40 years of age. The disease was classified into 3 types with variable extraocular signs. Type I disease was present in 24% of the patients, type II in 51% and type III disease in 24% of the patients. Cataract was present in 40% of the cases and glaucoma was present in 9%. No correlation was found between sex, age at onset, race, type of extraocular involvement and number of extraocular manifestations in considering either visual status or visual prognosis. All patients were treated with systemic steroids. Most of them also received cytotoxic immunosuppressive agents. In this uncontrolled clinical study cytotoxic drug-treated patients seemed to have a better clinical course.

Ultrasonic fragmentation of cataract in uveitis.

Thirty-nine eyes with uveitis from various causes, and complicated by cataract and vitreous opacification, underwent pars plana lensectomy and vitrectomy by ultrasonic fragmentation. Anatomical results were excellent, with clearing of all lens and vitreous opacities in all eyes. Visual results showed that there was no exacerbation and no recurrence of uveitis. Visual results depended mainly on the presence of previous damage of the uveitis to the retina and optic nerve. Visual results did not depend on the presence of uveitis activity at the time of the surgery. Complications that occurred were cystoid macular edema, which was present in 17.94% of the eyes and diagnosed in some eyes at the surgery, retinal detachment in one eye (2.56%), sterile hypopyon in one eye (2.56%), and ultrasonic lesion of the retina in one eye (2.56%). Visions of 20/20 to 20/40 were obtained in 23% of the eyes, 20.5% had vision between 20/50 and 20/80, and 56.4% had vision of 20/100 or less. The good results justify the surgical intervention in cases of cataracts associated with uveitis. Pars plana lensectomy and vitrectomy appears to be the procedure of choice in removal of cataracts secondary to uveitis.

Facofragmentacao ultra-sonica via "pars plana" associada a vitrectomia em pacientes com catarata e uveite. / Ultrasonic phacofragmentation via pars plana associated with vitrectomy in patients with cataract and uveitis

Os autores apresentam os resultados obtidos em 39 olhos com catarata secundaria a uveite, que foram operados via pars plana, usando a tecnica de Girard de facofragmentacao. Foram observados os seguintes resultados. l. Resultados anatomicos: bons, sem casos de persistencia de opacidade cristalinianas ou vitreas. 2. Resultados visuais: dependeram da presenca de alteracoes previas tais como lesoes de retina e nervo optico. Nao foram observados, em nenhu,m caso, inflamacao grave, recurrencia de toxoplasmose ocular, nem exarcebacao da uveite. Foram observadas as seguintes complicacoes: - edema cistico de macula: frequente. - hipopio esteril: um caso que melhorou com o uso de esteroides. - descolamento de retina: um caso operado com sucesso. - lesao de retina causada pelo ultrasom: um caso