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S Greenhouse

Publications and source records attributed to S Greenhouse.

6 recordsLinked to original sources
PubMed1999

Antibodies to human ZP3 induce reversible contraception in transgenic mice with 'humanized' zonae pellucidae.

The initial spermatozoon-egg interaction of mammalian fertilization is mediated by the zona pellucida, an extracellular matrix composed of three glycoproteins (ZP1, ZP2, ZP3). These proteins are sufficiently conserved between human and mouse to form chimeric zonae pellucidae, and genetically engineered mice in which the endogenous mouse ZP3 has been replaced by human ZP3 have 'humanized' zonae, but normal fertility. Administration of monoclonal antibodies to mouse ZP3 does not affect fertility in these animals, but administration of antibodies to human ZP3 results in long-term, reversible contraception. The antibodies coat the zonae pellucidae surrounding growing oocytes within the ovary and their presence in the zona matrix inhibits, but does not eliminate, sperm binding. The contraceptive effect is attributed to steric hindrance that decreases sperm binding and prevents penetration through the zona pellucida. The resumption of fertility is associated with the disappearance of antibodies from the zona matrix. No adverse effect on mating behaviour, ovarian histology or fetal development (if administered after fertilization) is detected in treated females. These results suggest that transgenic mice expressing human proteins will prove useful in assessing contraceptive efficacy of zona epitopes in the rational design of immunocontraception directed at the human zona pellucida.

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PubMed1992

Clinical implications of K-ras mutations in malignant epithelial tumors of the endometrium.

Tumorigenesis in humans and experimental animals appears to involve the activation of ras protooncogenes for a number of organ systems and seems to be important to the development of the metastatic phenotype in several model systems. Clinically, the presence of activated ras protooncogenes has been reported to be a negative prognostic factor in the myelodysplastic syndrome and in adenocarcinoma of the lung. In the present study we examined 49 cases of endometrial carcinoma for mutations in the first exon of K-ras using the polymerase chain reaction and direct sequencing. Mutations in codon 12 or 13 of K-ras were detected in 6 of 49 cases (12.2%). These six cases consisted of five endometrioid endometrial carcinomas, each of which had a mutation in codon 12, and one case of clear cell carcinoma, which had a mutation in codon 13. In our study the presence of mutations in K-ras appeared to be an unfavorable prognostic factor. Three of six patients with the mutation died during follow-up, while only 7% of the 43 patients without K-ras mutations expired during this same period. In multivariate analysis using the Cox proportional hazard model, K-ras activation appeared to be an independent risk factor when compared with clinical stage, depth of myometrial invasion, and patient age. Thus, our findings support the hypothesis that K-ras protooncogene activation plays an important role in determining the aggressiveness of endometrial carcinoma.

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