Control of cell growth. II. Requirement of thyroid hormones for the in vivo estrogen-dependent growth of rat pituitary tumor cells

A subclone of rat pituitary tumor cells, designated GH3/C14, was isolated from the parent population of GH3 pituitary cells and was estrogen-dependent for growth in vivo. GH3/C14 cells inoculated into host animals formed tumors in intact females, estrogen-treated ovariectomized females, and estrogen-treated males, but not in untreated intact or castrated males, or untreated ovariectomized females. Exogenous treatment with estrogens supported tumor formation in male animals. Radioimmunoassay of the average serum estradiol concentrations that support tumor growth in intact females, estradiol-treated intact females, and estradiol-treated intact males gave values of 41 +/- 4, 1,130 +/- 150, and 730 +/- 140 pg/ml, respectively. Tumor formation by GH3/C14 cells inoculated into male animals was not supported by either exogenous progesterone or hydrocortisone acetate. Further, these two steroid hormones had no significant effect on the estrogen-promoted growth in males or females. Exogenous testosterone treatment promoted tumor formation in males and ovariectomized females, but dihydrotestosterone was completely ineffective. Radioimmunoassay of the serum from tumor-bearing animals and the medium from the cells in culture showed that the cells produced growth hormone in vivo and in vitro but did not produce measurable amounts of luteinizing hormone or follicle-stimulating hormone. The groth of GH3/C14 cells in culture was examined in medium without added estrogen, and with estradiol added to the level of either the normal intact female rat or the estradiol-treated animals. No direct growth stimulation by estrogens could be detected in culture; the data suggested an indirect growth control mechanism.     

Apolipoprotein E polymorphism influences lipid phenotypic expression, but not the low density lipoprotein subfraction distribution in familial combined hyperlipidemia

The impact of apo E polymorphism on interindividual variation in plasma lipid, lipoprotein concentrations, and LDL subfraction profiles was studied in 201 well-defined patients (88 men and 103 women) with familial combined hyperlipidemia (FCH). When corrected for the concomitant influences of age, gender and obesity, the allelic variation in the apo E gene was shown to explain a statistically significant portion of the variability in lipid and (apo)lipoprotein concentrations. Carriers of the apo epsilon 2 allele exhibited a substantially higher plasma triglyceride concentration and a lower low density lipoprotein (LDL) cholesterol level, while subjects with the apo epsilon 4 allele had significant higher total plasma cholesterol and LDL cholesterol levels. In line with this observation, our FCH population was characterized by an over-representation of the apo E4 allele as compared with a Dutch standard population (chi 2 = 55.2, P < 0.0001). The contribution of apo E polymorphism to trait variability was different between sexes for plasma triglyceride, VLDL cholesterol, VLDL triglycerides, and high density lipoprotein (HDL) cholesterol levels. Apo E polymorphism had no impact on chemical composition of VLDL; for LDL particles the apo epsilon 2 allele was associated with a lower cholesterol to protein (C/P) ratio, whereas the opposite was true for the apo epsilon 4 allele. Despite the demonstrated impact of apo E polymorphism on plasma lipids and LDL chemical composition, in all phenotypic groups a dense LDL subfraction profile predominated. Thus, apo E polymorphism contributes to the lipid phenotypic expression in FCH, whereas further evidence was obtained that a dense LDL subfraction profile is an integral feature of FCH.     

Use of endometrial measurement as an exclusion criterion for in vitro fertilization using clomiphene citrate

OBJECTIVE: Previous reports have indicated an association between endometrial development and pregnancy outcome for patients treated with clomiphene citrate (CC) in conjunction with intrauterine insemination or intercourse. We expanded the use of CC for ovulation induction in association with in vitro fertilization (IVF). This study was designed to determine if endometrial thickness should be used as an inclusion or exclusion criterion for CC-IVF. STUDY DESIGN: One hundred twenty-eight patients were enrolled in an ovulation-induction regimen using CC for expected IVF-ET between January 1992 and December 1992. A total of 81 patients met inclusion criteria for CC-IVF and had endometrial measurement performed prior to human chorionic gonadotropin administration. Patients were categorized on the basis of endometrial measurement as follows: (A) > 4 - < 7 mm, (B) > or = 7 - < or = 10 mm, and (C) > 10 mm. Standard IVF was performed, and pregnancy rates for each category were evaluated. RESULTS: A total of 23 pregnancies (28% per retrieval) were established. Pregnancy rates were not different by category (P > .10, Fisher's Exact Test): (A) 3/15 (20%), (B) 13/41 (32%), and (C) 7/25 (28%). CONCLUSION: These data suggest that for CC-IVF. endometrial measurement should not be used as an exclusion criterion since pregnancies occurred at comparable frequencies in all the groups.     

A reappraisal of topical steroid potency

Topical corticosteroids have been one of the cornerstones of dermatologic treatment for nearly 40 years. At present the most widely used topical steroid ranking system is the vasoconstrictor assay. To determine whether this is a satisfactory measure of the agents' potency in clinical settings, we examined rankings from the published literature achieved by four different methods: vasoconstriction, clinical outcome, therapeutic index (a ratio of efficacy to systemic safety), and cost, safety, and efficacy. Overall clinical outcome (efficacy) rankings in this study corresponded in only 11 (62%) of 17 topical steroid preparations with the expected vasoconstrictor rankings. The therapeutic index rankings did not correspond with the clinical outcome (33%) or the vasoconstrictor assay (33%) rankings. It was difficult to compare studies because of lack of standardization of clinical trials. We urge that topical steroid rankings not be based solely on vasoconstrictor assays, and that a standard method be developed for clinical trials of the drugs to allow for comparison among preparations.     

Comparison of fungal viability assays using Candida albicans yeast cells undergoing prolonged incubation in the absence of nutrients

Staining methods for determining fungal viability are usually assessed by comparisons with enumeration of colony-forming units (CFU) on solid media. The purpose of the present study was to compare viability as assessed by the acridine orange (AO) and MTT methods with the numbers of CFUs obtained for Candida albicans yeast cells undergoing prolonged incubation in distilled water. In initial assessments of the assays using various proportions of control and heat-killed C. albicans, the AO and MTT methods consistently indicated significantly higher values for viability than did CFU determinations. Experiments using organisms cultured overnight revealed that approximately 95% of the cells were capable of dividing at least once in a microscopic proliferation assay, whereas only 69% were capable of forming colonies. Parallel assays comparing AO uptake and MTT reduction gave excellent agreement with the microscopic proliferation assay, but not with CFU determinations. Using organisms undergoing prolonged incubations in distilled water, much lower viabilities were obtained with the CFU method at 7 and 10 days than with the microscopic proliferation assay or the two staining methods. These results indicate that the AO and MTT assays correlate well with the ability of C. albicans to divide at least once, but may not accurately indicate the percentage of organisms actually able to form colonies.