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Biomedical subjects

M T Story

Publications and source records attributed to M T Story.

35 records · Page 2Linked to original sources

The prostate of the gorilla.

The prostate gland from a 32-year-old gorilla was examined. The prostate weighed 15 g and was composed primarily of dilated cystic acinar areas with only modest stromal thickening. The acini were lined by a low cuboidal epithelium. A second minor population of smaller glands with extensive papillary projections was also present. The epithelial cells stained densely for acid phosphatase and prostatic-specific antigen. Human prostatic acid phosphatase content of the gland as determined by radioimmunoassay was 2.3 mg/g protein. This is the first published histologic description of a gorilla prostate. The animal was in late middle age but did not display predominant prostatic stromal hyperplasia. Prostatic acid phosphatase from the gorilla cross-reacts immunologically, or is identical to human prostatic acid phosphatase.

Acid Phosphatase↗

Partial purification of a prostatic growth factor.

A 5-step fractionation procedure was used to isolate a prostatic growth factor from a tissue homogenate of human benign prostatic hyperplasia. The procedure made use of the property of prostatic growth factor to occur predominately as a large molecule (greater than 67,000) in low ionic strength solution (Tris with 0.05 M NaCl) but as a smaller molecule (less than 33,000) in high salt buffer (Tris with 1.55 M NaCl). The fractionation scheme consisted of ammonium sulfate precipitation, gel filtration (low ionic strength) and DEAE chromatography. The growth factor activity was eluted from DEAE with high ionic strength buffer followed by 2 gel filtration steps in high ionic strength buffer. The fractionation scheme produced greater than a 200-fold increase in prostatic growth factor activity and 10 per cent recovery. Additional separation steps will be required to purify prostatic growth factor to homogeneity.

Chemical Fractionation↗

Epidermal growth factor is not the major growth-promoting agent in extracts of prostatic tissue.

Extracts of benign prostatic hyperplasia (BPH) contain a factor which is mitogenic for human foreskin fibroblasts in culture. Because of the similarity of BPH extract and epidermal growth factor (EGF) in stimulating quiescent fibroblasts to divide, it was of interest to determine if the prostate-associated growth factor competes for EGF receptor binding. BPH extract was found to compete poorly for 125I-EGF-receptor binding, did not influence the dissociation of cell-bound 125I-EGF and caused only a slight down-regulation of the EGF receptor. These findings indicate that EGF and BPH extract do not recognize the same receptor and that the major growth stimulating activity of BPH extract is not due to EGF.

Binding, Competitive↗

A procedure using immobilized antibody for the isolation of the beta-subunit of human chorionic gonadotropin from the culture fluid of a beta-subunit-secreting nontrophoblastic cell line.

Antibody produced against the beta-subunit of hCG was linked to Sepharose 4B and used to isolate ectopic hCG beta secreted by DoT cervical cancer cells in culture. beta-Subunit was eluted with 3 M guanidine-hydrochloride, pH 3.0 (three treatments, 15 min each, at 20 C). The eluted hCG beta was desalted with Sephadex G-25 and concentrated by lyophilization. A single batch of antibody-bound Sepharose was used repeatedly to adsorb hCG beta from liter quantities of spent culture fluid containing 10% fetal bovine serum. The material recovered from 15.75 liters of fluid was pooled and treated a second time with immobilized antibody. Using only immobilized antibody, purification of more than 200,000-fold was achieved, with an overall recovery of about 28%.

Antigen-Antibody Reactions↗

Ectopic secretion of complete human chorionic gonadotropin and beta-subunit by human cervical carcinoma cells lines.

The CaSki and DoT cervical cancer cell lines were reported to secrete the beta-subunit of hCG in the absence of complete hCG or alpha-subunit (Science 196: 1456, 1977; J Clin Endocrinol Metab 46: 69, 1978). In the present study, concentrates of fluids from large numbers of CaSki or DoT cultures were analyzed for the presence of hCG beta and complete hCG. Although some CaSki and DoT preparations contained no detectable complete hCG, others were found to contain as much as 18% hCG. The reason for the variation in the amount of hCG relative to hCG beta in CaSki and DoT cultures is unknown.

Cell Line↗

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↗

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↗

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↗

Regulation of human chorionic gonadotropin (hCG) secretion by serum and dibutyryl cyclic AMP in malignant trophoblast cells in vitro.

Human chorionic gonadotropin (hCG) secretion was studied in human malignant trophoblast cells (Jar line) in continuous culture. Radioimmunoassayable hCG in the cells and in the daily culture fluid was increased for at least 3 days by 10% newborn calf serum and by 1 mN N-6, 0-2'-dibutyryl cyclic adenosine 3', 5'-monophosphoric acid (dbcAMP) plus 1 mM theorphylline. Incubation of the cells in the presence of serum, dbcAMP and theorphylline resulted in additive stimulation of hCG secretion after 1 day. After 2 or 3 days, a supra-additive stimulation was observed, which was prevented by Actinomycin D. When cells were preincubated for 2 days in the absence of serum but with dbcAMP plus theorphylline, subsequent addition of serum resulted in supra-additive stimulation of hCG secretion within a single day; the continued presence of dbcAMP plus theophylline was not necessary for this stimulation by serum. These findings suggested that dbcAMP activates a slow process requiring RNA synthesis, resulting in increased hCG secretion. Serum appears to protect the hCG synthesizing system from degradation.

Animals↗