Suppression of src-induced transformed phenotype by expression of tropomyosin-1.

Suppression of high M(r) tropomyosins (TMs) is a common feature of transformed cells. Previous work from this laboratory has demonstrated that the isoform 1 of TM, TM1, acts as an anti-oncogene in ras-transformed murine fibroblasts. In this study, we have investigated whether TM1 is a ras-specific suppressor, or a general suppressor protein of the cellular transformation. V-src transformed fibroblasts, which express decreased TM1, were transduced with a full-length cDNA to overexpress TM1. Both the control and the transduced cells expressed v-src kinase at comparable levels. TM1 expressing (src-T1) cells grew at a lower rate in monolayer, exhibited well spread, flat morphology than the control cells. Enhanced expression of TM1 resulted in improved microfilamental architecture. More significantly, src-T1 cells completely failed to grow under anchorage independent conditions. These data demonstrate that TM1 is as an anti-oncogene of functionally diverse oncogenes, and it is a class II tumor suppressor protein.

Elevation of serum riboflavin carrier protein in breast cancer.

Presently available tumor markers have had a limited clinical impact. Riboflavin carrier protein (RCP) is an estrogen inducible protein that occupies a key position in riboflavin metabolism. Because other vitamin carrier proteins (VCP) have been shown to be overexpressed in patients with malignant disease, we evaluated serum RCP levels in patients with adenocarcinoma of the breast. In this prospective blinded study, patients with breast cancer, benign breast disease, and healthy controls were analyzed for RCP levels. Using a highly sensitive RIA, we observed that serum RCP levels were significantly elevated in women with breast cancer (n = 52) as compared with control subjects [n = 50; 6.06 +/- 7.27 ng/ml versus 0.70 +/- 0.19 ng/ml (mean +/- SD), respectively; P < 0.0001]. A serum RCP level of > or = 1.0 ng/ml was highly predictive of the presence of breast cancer, detecting 88% of tumors in stages I-II and 100% of tumors in stages III-IV. Overall, this RCP assay has a sensitivity of 92.3%, a specificity of 88%, a positive predictive value of 88.9%, and a negative predictive value of 91.7%. These results show increased serum levels of RCP in breast adenocarcinoma patients and suggest that RCP levels may be useful as a new marker for breast cancer. The positive predictive value in early-stage breast cancer suggests that the RCP assay may be a useful adjunct to present screening technology.

Normalization of testosterone levels using a low estrogen-containing oral contraceptive in women with polycystic ovary syndrome.

Oral contraceptives reduce the elevated androgen levels in polycystic ovary disease. However, treatment with oral contraceptives is associated with undesirable side effects because of their high estrogen content. This study was undertaken to examine the effects of low estrogen-containing oral contraceptive (Loestrin:norethindrone acetate 1.5 mg and ethinyl estradiol 30 micrograms) on 25 women with polycystic ovary disease of ovarian origin. Loestrin treatment normalized the elevated luteinizing hormone and total and unbound testosterone levels and increased testosterone binding globulin levels. In a time-course study, unbound testosterone declined within a week of initiating treatment and by 12 to 16 weeks was completely normal. Reduction in hair growth and improvement in complexion were noted by about 12 to 16 weeks. Side effects of treatment were minimal.

Endocrine and immunologic studies in a patient with resistant ovary syndrome.

A patient with the resistant ovary syndrome is reported. To evaluate the hypothesis that the hypogonadism might be the result of circulating antibodies to gonadotropin receptors or to an abnormal gonadotropin molecule, a series of clinical and laboratory studies was carried out. Administration of human menopausal gonadotropin had no effect on the serum estradiol level. The patient's serum did not affect follicle-stimulating hormone binding to a membrane preparation of monkey testes, suggesting the absence of antibodies to follicle-stimulating hormone receptors, nor did the patient's serum affect in vitro responsiveness of human granulosa cells to human menopausal gonadotropin. Unresponsiveness to exogenous gonadotropins, combined with anatomically normal follicular apparatus and the absence of serum antibodies to gonadotropin receptors, supports the concept of a gonadotropin receptor or a postreceptor defect.

Serum androgenic hormones motivate sexual behavior in adolescent boys.

In order to separate hormonal from social effects on adolescent male sexual behavior, serum hormone assays were performed and questionnaire data on sexual motivation and behavior were collected on a representative sample of 102 boys in grades 8, 9, and 10 of a public school system. Free testosterone was a strong predictor of sexual motivation and behavior, with no additional contribution of other hormones. Including measures of pubertal development and age (indexing the effects of social processes) indicated no additional effects. Free testosterone, therefore, appears to affect sexual motivation directly and does not work through the social interpretation of the accompanying pubertal development.

Structural and functional regression of polycystic ovaries by danazol.

The effects of danazol on ovarian steroidogenesis and follicular size was studied in androgen-sterilized rats bearing polycystic ovaries. Daily treatment with 4 or 20 mg of the drug caused a reduction in ovarian weight and regression of cystic follicles. Serum levels of luteinizing hormone (LH), testosterone, and estrogen were significantly decreased. The persistent estrus smears were changed to diestrus, indicating inhibition of estrogenic activity.

The removal of fallopian tubes has no adverse effect on subsequent ovarian function in rabbits.

The effect of bilateral salpingectomy on ovarian function was studied in the rabbit. Nine rabbits underwent a microsurgical removal of both fallopian tubes, and nine other rabbits underwent sham operations. Four weeks after surgery the rabbits were mated, and the number of ovulation sites were recorded 18 hours after mating. Serum progesterone (P) levels were also determined prior to the operation and at 6 days and 8 days after mating. Eight days after mating the ovaries were recovered, and the corpora lutea were removed and weighted. The mean number and weights of corpora lutea as well as serum P levels did not differ significantly between the groups. These findings suggest that the absence of fallopian tubes has no effect on subsequent ovulatory function in this animal model.

Case report: systemic hypersensitivity reaction to goserelin acetate.

Women suffering from endometriosis are treated with long-acting analogues of gonadotropin-releasing hormone (GnRH). This is a case of hypersensitivity reaction to a goserelin acetate implant that manifested as an anaphylactic reaction. This is the first report of a hypersensitivity reaction to the GnRH analogue, goserelin acetate (Zoladex, Zeneca Pharmaceuticals, Wilmington, DE).

Increased activation of pelvic macrophages in infertile women with mild endometriosis.

Pelvic fluid was collected from 66 women undergoing laparoscopic sterilization or diagnostic laparoscopy for evaluation of infertility. Cells consisting mainly of macrophages were separated, counted, and subjected to histochemical staining for acid phosphatase and myeloperoxidase as markers of cell irritation. Pelvic fluid was analyzed for acid phosphatase, neutral protease, and extractable prostaglandin E2 and F2 alpha. A higher proportion (46% versus 15%) of the macrophages in the group with mild endometriosis exhibited positive staining for acid phosphatase as compared with the fertile group. Pelvic fluid from patients with mild endometriosis had higher acid phosphatase and neutral protease activity than that from fertile patients (p less than 0.05, p less than 0.01). The content of either prostaglandin was not significantly higher in the endometriosis group as compared with the fertile group. The results suggest that mild endometriosis is associated with activation of macrophages and release of active substances into peritoneal fluid that may be responsible for the associated infertility.

Inhibition of male fertility by STS 557.

To ascertain the effects of STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one) on the reproductive and endocrine functions, male rabbits were given the substance orally daily over 8 weeks. In doses of 10 and 20 mg STS 557 per animal per day fertility inhibition was accompanied by a decrease of spermatogenesis and sexual activity. At the chosen dose of 5 mg per day, STS 557 caused a decrease of sperm motility, semen fructose content and sterility of the bucks. On the other hand, libido, semen volume, sperm number, sialic acid content in semen, serum LH and testosterone remained unaffected. Concomitant injection of testosterone did not reverse the suppressive effect of STS 557 on fertility. Motility of human sperm was lowered markedly by STS 557 in vitro. The human sperm penetration and pronuclear formation were significantly reduced in the vitro fertilization assay with zona-free hamster eggs. Findings are discussed in view of the development of male contraceptives.