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Biomedical subjects

R A Pattillo

Publications and source records attributed to R A Pattillo.

At least 37 records · Page 2Linked to original sources

Alpha subunit and human chorionic gonadotropin in normal pregnancy and gestational trophoblastic disease.

The reported incidence of gestational trophoblastic disease is an order of magnitude higher in Nigeria than in the United States. Sera from a total of 283 pregnant black patients, 138 United States and 148 Nigerian pregnant patients, were analyzed for their serum levels of alpha subunit and human chorionic gonadotropin (hCG). The patterns of hCG secretion were similar in the two populations during normal pregnancy. However, the level of alpha subunit was persistently higher in Nigerian women than in comparable pregnant United States patients. A statistically significantly higher alpha subunit level in the Nigerian patients was found only in the ten- to 13-week gestational period (P less than .005). The higher level of alpha subunit in pregnancy in Nigerian women may signal a population of trophoblastic cells which may be at higher risk for malignancy development in the Nigerian woman.

Black People↗

Absence of the COOH-terminal peptide on ectopic human chorionic gonadotropin beta-subunit (hCG beta).

A comparison of the physical properties and immunoreactivity of ectopic hCG beta from cultured cervical cancer cells and standard hCG beta was performed. The heterogeneity of the preparations was examined by ion-exchange chromatography, and the molecular size by analytical gel filtration. Two distinct forms of ectopic hCG beta were identified. One form was indistinguishable from standard hCG beta, while the other, although larger, lacked the characteristic COOH-terminal peptide (CTP). This was shown by the failure of antisera specific for determinants on the cTP to recognize this molecule, and by the apparent absence of the 0-linked oligosaccharides and thermolysin cleavage site normally found in this region.

Agglutinins↗

Cytogenetic analysis of choriocarcinoma cell lines.

Five permanent cell lines were established in vitro from patients with gestational choriocarcinoma. Chromosome study with Q-band technique showed a modal chromosome number per cell in the hypotetraploid range in all cell lines. There were unidentifiable, structurally altered chromosomes in each cell line. BeWo cell line from choriocarcinoma following delivery of a normal male baby lost identifiable Y chromosome, whereas Jar cell line following delivery of a normal male did have a Y chromosome. One of the two cell lines following complete hydatidiform mole had a Y chromosome. The significance of this finding is discussed.

Cell Line↗

A human parathyroid carcinoma that produces parathyroid hormone: long term maintenance in tissue culture.

Parathyroid carcinoma cells from a pulmonary metastasis of a patient with a serum Ca of 17 mg/dl and an immunoreactive parathyroid hormone (PTH) of 6.4 ng eq bovine (b) PTH/ml (normal 40--400 pg/ml) have been maintained in tissue culture for more than 2 1/2 years. The cells secrete PTH into the culture media that 1) during immunoassay dilutes in parallel to human hyperparathyroid serum, 2) has a molecular weight similar to intact highly purified bPTH, and 3) stimulates bone resorption in a manner that is equivalent and additive to synthetic bPTH-(1--34).

Adult↗

Predominance of gonadotropin alpha-subunit resulting from preferential loss of hCG beta production in an established cell line.

The BeWo line of trophoblastic cells, maintained in continuous culture since 1966, was employed to investigate the phenomenon of gonadotropin alpha-subunit predominance that exists in several cell lines. The secretion of complete human chorionic gonadotropin (hCG) relative to alpha-subunit was compared in several different BeWo sublines, all of where were derived from BeWo stock roller tube colonies. In all of the BeWo sublines, secretion of hCG originally exceeded secretion of alpha-subunit. With time in culture, however, there was a marked decline in production of hCG/hCG beta, but not in alpha-subunit. Thus it appears that the production of hCG beta by BeWo choriocarcinoma cells is more labile than the production of the alpha-subunit.

Cell Line↗

Carcinoembryonic antigen and L-fucose in malignant and benign mammary disease.

A prospective study of 123 patients was undertaken to determine whether carcinoembryonic antigen (CEA) or L-fucose could be used as "tumor markers" to distinguish patients who had mammary cancer (41) from patients who had benign mammary disease (41) and patients who did not have mammary cancer (41). The predictive value of positive test results for both L-fucose and CEA was lower for patients who smoked than for those who did not. The sensitivities of CEA and L-fucose indicators are both below 55%. There were frequent false-positive and false-negative results. A substantial overlap in the levels of CEA and L-fucose was found for the patients who had mammary cancer and those who had benign mammary disease. CEA and L-fucose performed similarly in distinguishing cancer from benign disease. For patients who smoked, however, the predictive value of L-fucose was only 44%. The effect of smoking on L-fucose levels may account for discrepancies in L-fucose data reported in previous studies of mammary cancer. Neither CEA nor L-fucose were found to be of value in screening for mammary cancer.

Breast Diseases↗

Histocompatibility antigens in pregnancy, abortions, infertility, preeclampsia, and trophoblast neoplasms.

The genetic makeup of an individual may determine the capacity of the individual to combat successfully cancer and other disease states, eg abnormal pregnancies, abortions, infertility, and preeclampsia. These factors appear to be based upon the individual's immunogenetics, as histocompatibility-restricted T-cell cytotoxicity may be deficient in the observed instances of increased histocompatibility between husband and wife found in trophoblast tumor patients and in other instances of abnormal pregnancies.

Abortion, Habitual↗

Immunodiagnosis in ovarian cancer: blocking factor activity.

Tumor immunology studies have been utilized for development of a blocking factor assay for therapy monitoring in ovarian cancer. The blocking factor index was defined as the arithmetic difference between assays conducted in the presence and absence of the patient's serum compared to incubations with normal control lymphocytes. Eighteen advanced ovarian epithelial malignancies have shown blocking factor activity during treatment. Blocking factor has abated in eight patients whose clinical disease completely regressed. Chemotherapy was discontinued after 18 to 24 months. In 10 patients, blocking factor persisted and chemotherapy has been continued. Some of these patients showed decreasing blocking factor; others have shown increases, which led to death due to disseminated disease in four cases. Blocking factor activity was found to correlate with tumor growth.

Antigen-Antibody Complex↗

Human chorionic gonadotropin in BeWo trophoblastic cells after 12 years in continuous culture: retention of intact human chorionic gonadotropin secretion in mechanically versus enzyme-dispersed cells.

Gel filtration and radioimmunological studies were used to demonstrate that BeWo malignant trophoblastic cells, subcultured for more than 12 yr as roller tube colonies using dissection by scalpel, retained the ability to secrete large quantities of intact hCG. By contrast, BeWo cells that had been subcultured weekly for 12 hr using proteolytic enzyme dispersion lost their ability to secrete intact hCG. Rather, a large form of hCG-alpha was the major secretory product, along with lesser amounts of heterogeneous low molecular weight forms of hCG-beta. The gradual loss of hormone secretory ability and fidelity of hormone product by cells in continuous culture is a well known phenomenon. Our results suggest that the habitual use of trypsin-EDTA to subculture cells may accelerate this process.

Cell Line↗

Expression of cell-mediated immunity and blocking factor using a new line of ovarian cancer cells in vitro.

A cell-mediated cytotoxicity test, quantitated by postlabeling with tritiated thymidine, was used to asses immune reactivity of cancer patients to the HeW cell line derived from serous cystadenocarcinoma of the ovary. Lymphocytes from 71.4% of serous and mucinous cystadenocarcinoma patients demonstrated a cytotoxic response towards the HeW cells, whereas no reactivity was observed towards target cells derived from nonovarian cancer. These observations indicated that the HeW cells express tumor-associated antigen. In some patients bearing similar tumors, cytotoxicity was blocked by ascitic fluid from other patients with cystadenocarcinoma. In addition, antigen obtained from the spent culture fluid of HeW cells exhibited blocking activity in a typical dose-response fashion, suggesting that blocking factor may be free tumor-associated antigen or an antigen-specific suppressor molecule. Thus, blocking of the lymphocytotoxic response of cystadenocarcinoma patients towards HeW cells may be utilized to monitor the isolation of ovarian carcinoma-associated antigen.

Antigens, Neoplasm↗

Immunocytochemical localization of human choriogonadotropin in human malignant trophoblast. Model for human choriogonadotropin secretion.

Human choriogonadotropin (HCG) and its subunits have been studied immunocytochemically using a recently developed unlabeled antibody method. Factors influencing the antigenicity of HCG and its subunits were explored, and optimum conditions were determined. HCG has been successfully localized at the cellular level using paraffin-embedded tissues. Several antibodies to HCG or its subunits were evaluated for specificity using rigorous immunologic controls. This methodology was applied to placental tissue, in vitro choriocarcinoma, and in vitro breast carcinoma. HCGbeta and HCGalpha were localized in the syncytial trophoblast of first trimester placenta with cytotrophoblast cell islands and Langhans' cells being negative. Conditions of stimulated and unstimulated HCG production have been explored in the BeWo line of malignant trophoblast. Stimulation was accomplished by treatment with dibutyryl cyclic AMP and theophylline for varying periods of time. Only 6 per cent of the cells could be shown to be producing HCGbeta and HCGalpha in the unstimulated condition. Stimulation increased this percentage to 70 and 18 per cent, respectively, after 24 hours of treatment. Ultrastructural localization has shown that the mechanism of synthesis and secretion of HCG follows a pathway that is not as extensively developed as that of the pituitary hormones.

Cells, Cultured↗

Tumor antigen and human chorionic gonadotropin in CaSki cells: a new epidermoid cervical cancer cell line.

Epidermoid cervical carcinoma cells (CaSki line) have been established in continuous culture. When leukocytes from cervical cancer patients were incubated with CaSki culture fluid concentrates, inhibition of leukocyte migration was observed in more than 70 percent of the patients tested. By contrast, significantly less inhibition was observed with normal donor leukocytes or leukocytes from patients with other types of cancer. These results were consistent with the expression of tumor-associated antigen by CaSki cells. Analysis of the serum from the donor of the cell line at the time of tumor biopsy, and of CaSki culture fluids, demonstrated the presence of the beta subunit of human chorionic gonadotropin.

Adult↗

Effect of cyclic 3':5'-AMP derivatives prostaglandins and related agents on human chorionic gonadotropin secretion in human malignant trophoblast in culture.

The secretion of human chorionic gonadotropin (hCG) is stimulated by addition of N6, O2'-dibutyryl cyclic 3':5'-AMP (dbcAMP) or theophylline to normal term placenta and human malignant trophoblast cells in vitro. To understand better the specificity of this process, malignant trophoblast cultures were incubated with 3':5'-cyclic AMP (cAMP) derivatives, prostaglandins and other agents for 1 to 3 days, and the secretion of radioimmunoassayable hCG was measured. Whereas dbcAMP was the most potent agent in stimulating secretion of hCG, the N6--and O2'-monobutyryl derivatives of cAMP and phosphodiesterase inhibitors (theophylline, papaverine, 3-isobutyl-1-methylxanthine) also increased the secretion of the hormone. A slight increase in hCG secretion was observed following addition of adenine. By contrast, butyrate, cAMP, cyclic 3':5'-GMP (cGMP), dbcGMP, 5'-AMP, adenosine, L-epinephrine and prostaglandins E1, E2, F1a and F2a were ineffective. Particulate fractions from sonicates of malignant trophoblast cultures contained adenylate cyclase activity which was stimulated more than 10-fold by NaF, but not by either catecholamines or prostaglandins. The relatively specific stimulation of hCG secretion suggested that a regulatory process involving cAMP may have physiological significance in the trophoblast.

Adenine↗