Analysis of estrogen-responsive finger protein expression in benign and malignant human breast.

The estrogen-responsive finger protein (EFP) gene was originally identified in a screen of genomic DNA for genes containing estrogen-response elements (EREs), and its expression was subsequently shown to be estrogen-regulated and correlated with estrogen receptor (ER)alpha-positive tissues in mice. Human chromosomal mapping localized it to 17q23.1, close to BRCA1, in a region frequently lost in breast cancers. Structurally related proteins have been implicated in a variety of important cellular processes, including carcinogenisis. Given that ER is over-expressed in a large proportion of breast cancers, we reasoned that EFP may play a role in mediating the estrogen-dependent progression of breast cancer. We raised anti-sera to EFP and show that EFP is present in the cytoplasm in mammary cell lines and epithelial cells of normal breast tissue. Furthermore, EFP is present in cell culture medium, suggesting that it may be secreted. Immunohistochemistry of paraffin-embedded breast biopsy specimens showed significantly greater levels of EFP in lactating breast and fibroadenomata compared to normal breast (p<0.001 and p = 0.001, respectively), which is likely to be a result of estrogen responsiveness. Levels were reduced in breast cancer (p = 0.02), where no correlation was seen with other immunohistochemical, histopathological or clinical data. The lack of correlation between EFP and ER status of tumors could indicate escape from estrogenic control, pointing to new models of tumor pathogenesis. Increased levels of EFP in lactating breast and the reduction in malignancy suggest a role for EFP in promoting mammary gland differentiation.

Renal autotransplantation for aortic dissection in Marfan's syndrome.

Marfan's syndrome is an autosomal dominant condition with a prevalence of 4 to 6:100,000, and classically comprises skeletal changes, ectopia lentis and cystic medial necrosis of the largest arteries. The latter leads to aneurysm formation, most often commencing at the aortic root, and is responsible for an average age at death of 32 years. We describe successful preservation of threatened renal function by renal autotransplantation, without concurrent aortic replacement, following dissection of the descending aorta in a patient with Marfan's syndrome.

Testicular effects of the Leydig cell toxicant ethane dimethanesulphonate given to neonatal rats.

Neonatal rats were injected with either 50 mg/kg ethane dimethanesulphonate (EDS) or vehicle on days 1 to 5 inclusive or on day 1 alone. Studies were made on days 6, 28, and 63 of testicular structure; related endocrinologic parameters were measured in the day 1 to 5 treated animals only. Leydig cells and their activities were identified by cell counts using sections stained for 3 beta-hydroxysteroid dehydrogenase, hCG binding to LH receptors in testicular homogenates, and assays of intratesticular testosterone, plus pituitary and/or serum concentrations of testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH). Given on days 1 to 5, EDS reduced Leydig cell populations estimated by morphometry and 125I-HCG binding, and testicular and body weights between days 6 and 63, and permanently retarded the development of the seminiferous epithelium. Decreases of serum and intratesticular testosterone occurred with homeostatic rises in FSH and LH. Injection on day 1 reduced Leydig cell numbers only on day 6 although body weight remained retarded. The data illustrate the susceptibility of the developing rat testis to the cytotoxicant EDS; whether this is related to withdrawal of androgen production or nonspecific cytotoxicity remains to be evaluated.

Hereditary cerebellar degeneration with downbeat nystagmus. A case and it's treatment.

We present a female patient of 48 years with downbeat nystagmus (DBN), moderate impairment of coordination testing and a family history of cerebellar ataxia. We report that a single 2 mg dose of clonazepam (following Currie & Matsuo) resulted in a virtual disappearance of nystagmus and of the patient's symptom of oscillopsia. This result is interpreted in terms of current models of DBN.