Congenital malformations, mental retardation and genetic disorders together constitute a major source of morbidity and mortality in childhood and beyond. Some 25-30% of all admissions to children's hospitals in the western world are for these categories of disease. The serious personal, family and societal health burden and costs require no emphasis. The most common major congenital defects are neural tube defects (NTD's) and trisomies. For NTD's maternal serum alfa-fetoprotein (MSAFP) screening has been available for 10 years and second trimester screening by MSAFP for both NTD's (high values) and trisomies (low values) now serves as a non-specific signal of pregnancies at risk. We have developed a highly sensitive and specific monoclonal radioimmunometric assay (M-IRMA) for measurement of MSAFP that is very accurate at low serum levels (0.5-10 ng/ml). A preliminary study has been performed in women undergoing chorionic villus biopsy (CVS) to determine whether it would be possible in the first trimester to recognize a group of women who unknowing had an increased risk of carrying a fetus with a serious chromosome defect. Overall, we demonstrated that 30% of all chromosome defects were reflected by MSAFP values less than 0.6 MOM which is remarkedly similar to the observations of others in the second trimester. More importantly, during the previous grant period, we developed new monoclonal and antipeptide monoclonal IRMAs for hCG and its free subunits (beta hCG and alpha CG) to study trophoblastic differentiation since it seemed possible that the trophoblast may be abnormal under these conditions. Indeed, using our M-RMAs in combination, we found in a high risk population that 80% (14/18) of all trisomies had MSAFP and the beta HCG ratio of less than 0.6 MOM in the first trimester and thus identified such pregnancies at risk (P less than 10-8). We wish to consolidate and extend these gains and perform a large scale prospective first trimester clinical trial to screen non-selected pregnancies for fetal chromosome abnormalities. Finally, we will explore the mechanism(s) of hCG free beta HCG and alpha HCG subunit production and secretion by trophoblastic tissue and examine the value of these IRMAs in the diagnosis and follow- up of patients with trophoblastic disease. Thus, we have provided new clinical tools, the comparative value of which will be determined in an established program and are optimistic that new data of biologic and clinical significance will be forthcoming and the evolution of a better standard of patient care may be possible.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
Project #
Application #
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts General Hospital
United States
Zip Code
de la Monte, S M; Wands, J R (1994) Diagnostic utility of quantitating neurofilament-immunoreactive Alzheimer's disease lesions. J Histochem Cytochem 42:1625-34
Marcillac, I; Troalen, F; Bidart, J M et al. (1992) Free human chorionic gonadotropin beta subunit in gonadal and nongonadal neoplasms. Cancer Res 52:3901-7
Nebiolo, L; Ozturk, M; Brambati, B et al. (1990) First-trimester maternal serum alpha-fetoprotein and human chorionic gonadotropin screening for chromosome defects. Prenat Diagn 10:575-81
Ozturk, M; Milunsky, A; Brambati, B et al. (1990) Abnormal maternal serum levels of human chorionic gonadotropin free subunits in trisomy 18. Am J Med Genet 36:480-3
Ozturk, M; Motte, P; Takahashi, H et al. (1989) Identification and characterization of a Mr 50,000 adrenal protein in human hepatocellular carcinoma. Cancer Res 49:6764-73
Takahashi, H; Ozturk, M; Wilson, B et al. (1989) In vivo expression of two novel tumor-associated antigens and their use in immunolocalization of human hepatocellular carcinoma. Hepatology 9:625-34
Ozturk, M; de la Monte, S M; Gross, J et al. (1989) Elevated levels of an exocrine pancreatic secretory protein in Alzheimer disease brain. Proc Natl Acad Sci U S A 86:419-23
Takahashi, H; Carlson, R; Ozturk, M et al. (1989) Radioimmunolocation of hepatic and pulmonary metastasis of human colon adenocarcinoma. Gastroenterology 96:1317-29
Motte, P; Takahashi, H; Ozturk, M et al. (1989) Characterization of a malignant phenotype-associated cell surface glycoprotein common to various human tumor cells and preferentially expressed on adenocarcinoma of the lung. Cancer Res 49:1349-56
Berkowitz, R; Ozturk, M; Goldstein, D et al. (1989) Human chorionic gonadotropin and free subunits' serum levels in patients with partial and complete hydatidiform moles. Obstet Gynecol 74:212-6

Showing the most recent 10 out of 28 publications