Intravenous cidofovir treatment for recalcitrant warts in the setting of a patient with myelodysplastic syndrome

Cidofovir is an acyclic nucleoside phosphonate with broad-spectrum activity against DNA viruses, including human papilloma virus (HPV). However, data on the efficacy of cidofovir in an immunosuppressive setting remain contradictory. We report for the first time on the promotion of the healing of recalcitrant warts in a patient with myelodysplastic syndrome with intravenous cidofovir treatment.     

Ectopic prolactin secretion from a gonadoblastoma

A 6.5-year-old girl developed isosexual, pseudoprecocious puberty secondary to a gonadoblastoma. The tumor was found to produce and secrete both immunoassayable and bioassayable prolactin based on immunohistochemical techniques and the presence of a prolactin gradient between the tumor vein and peripheral vein. The source of the prolactin was a Sertoli-like cell. Neither growth hormone nor growth hormone-releasing hormone was detected within the tumor. This case confirms the ectopic production of prolactin by neoplastic tissue.     

Analysis of epidermal growth factor receptor and activated epidermal growth factor receptor expression in pituitary adenomas and carcinomas.

Epidermal growth factor receptor plays an important role in the pathogenesis of many malignancies. Various growth factors, including epidermal growth factor receptor, have been shown to influence pituitary tumor growth and differentiation. To analyze the role of epidermal growth factor receptor in pituitary tumor development, we examined normal pituitaries (n=8), pituitary adenomas (n=158), and pituitary carcinomas (n=7) for expression of epidermal growth factor receptor protein and messenger RNA using tissue microarrays and RT-PCR. We also examined (a) the expression of phospho-epidermal growth factor receptor, the activated form of epidermal growth factor receptor, in pituitary tumors and normal pituitaries by immunohistochemistry and (b) the effects on epidermal growth factor receptor expression of treating pituitary cells (HP75 cell line) with epidermal growth factor. Epidermal growth factor receptor and the phosphorylated variant expression were present in normal pituitary cells. Epidermal growth factor receptor messenger RNA was also detected in normal pituitaries, pituitary adenomas, and carcinomas by in situ hybridization and RT-PCR. Most pituitary adenomas showed expression of epidermal growth factor receptor and the phosphorylated variant. Nonfunctional adenomas showed higher levels of expression of epidermal growth factor receptor (76 vs 34%) and of phospho-epidermal growth factor receptor (26 vs 8%) as compared to functional adenomas. Five of seven pituitary carcinomas showed strong expression of both epidermal growth factor receptor and phospho-epidermal growth factor receptor. When a human pituitary cell line (HP75) was cultured in the presence of epidermal growth factor receptor, there was an increase in the levels of both epidermal growth factor receptor and phospho-epidermal growth factor receptor after 5 h of treatment, thus confirming that epidermal growth factor receptor signaling was active in pituitary tumors. These results indicate that activated epidermal growth factor receptor is expressed in pituitary adenomas and carcinomas. Higher levels in pituitary carcinomas suggest a role in pituitary tumor progression.     

The functional pathology of hypophyseal adenomas

This review summarizes some aspects of pituitary adenoma pathology. A new embracing pituitary adenoma classification has been developed which correlates morphologic findings with endocrine activity. It is based on hormone content, histologic, immunohistochemical and ultrastructural features, cellular composition and cytogenesis, and separates pituitary adenomas into 7 distinct entities.     

Glial cell line-derived neurotrophic factor-dependent recruitment of Ret into lipid rafts enhances signaling by partitioning Ret from proteasome-dependent degradation

The receptor tyrosine kinase (RTK) Ret is activated by the formation of a complex consisting of ligands such as glial cell line-derived neurotrophic factor (GDNF) and glycerophosphatidylinositol-anchored coreceptors termed GFRalphas. During activation, Ret translocates into lipid rafts, which is critical for functional responses to GDNF. We found that Ret was rapidly ubiquitinated and degraded in sympathetic neurons when activated with GDNF, but, unlike other RTKs that are trafficked to lysosomes for degradation, Ret was degraded predominantly by the proteasome. After GDNF stimulation, the majority of ubiquitinated Ret was located outside of lipid rafts and Ret was lost predominantly from nonraft membrane domains. Consistent with the predominance of Ret degradation outside of rafts, disruption of lipid rafts in neurons did not alter either the GDNF-dependent ubiquitination or degradation of Ret. GDNF-mediated survival of sympathetic neurons was inhibited by lipid raft depletion, and this inhibitory effect of raft disruption on GDNF-mediated survival was reversed if Ret degradation was blocked via proteasome inhibition. Therefore, lipid rafts sequester Ret away from the degradation machinery located in nonraft membrane domains, such as Cbl family E3 ligases, thereby sustaining Ret signaling.     

Nonstress test assessment of twins.

Twin pregnancies have higher perinatal morbidity and mortality rates than singleton pregnancies. Researchers have demonstrated that one major benefit of prenatal care in the twin gestation is reduced fetal death rate. This study to determine the relationship of nonstress tests (NSTs) to pregnancy outcome in twin gestations comprised 665 women who delivered at Los Angeles County-University of Southern California Women's Hospital from January 1985 to January 1989. These patients, all of whom had prenatal care (PNC), were subdivided into two groups: (1) PNC and NSTs and (2) PNC and no NSTs. The groups did not differ statistically with regard to gravidity, parity and abortions. NSTs were selectively done on twin gestations complicated by discordancy or other fetal/maternal complications. Ten pregnancies were complicated by fetal demise of one or both twins in patients who received prenatal care without NSTs. Among the NST group there was one fetal demise. Although the NST group had fewer fetal deaths, the reduction was not statistically significant (P = .062). Infant birth weight was identified as a confounder because the NST group had a statistically higher mean birth weight. Definitive proof of the ability of NSTs to reduce the fetal death rate in twin gestations complicated by discordancy or other pregnancy complications awaits a large, prospective, randomized trial.