PubMed Health⌕ Search

Biomedical subjects

J C Tsibris

Publications and source records attributed to J C Tsibris.

At least 19 recordsLinked to original sources
PubMed1995

Estrogen-induced guinea pig model for uterine leiomyomas: do the ovaries protect?

A guinea pig model was used to study the hormonal control of uterine leiomyomas. Twenty female guinea pigs were divided into four groups--young, old, ovariectomized (OVX), and non-OVX animals--and were given two estradiol-17 beta (E2) silastic implants each for 3-10 mo; another four older OVX animals served as controls and received empty implants. After 3 mo, 100% (8 of 8) of the OVX animals, but none of the OVX controls, developed tumors, mainly on the uterine serosa and the abdominal wall. Electron microscopy and desmin immunostaining demonstrated that the tumors were leiomyomas. In E2-treated animals, E2 levels in serum, leiomyomas, or leiomyoma-free uterine segments rose significantly while serum progesterone (P4) was negligible. Surprisingly, only 8% (1 of 12) of the non-OVX animals developed a tumor. This apparent "ovarian protection" was transient: after 6-9 mo, 50% of the remaining non-OVX animals developed leiomyomas, but these were smaller and fewer than in OVX animals. On the basis of this model, we propose the hypothesis that some factors from the ovaries suppress leiomyoma growth in response to estrogen but that as the ovaries age this protection is diminished, allowing the clinical development of leiomyomas.

Animals↗
PubMed1994

Carbohydrate metabolism studies after one year of using an oral contraceptive containing gestodene and ethinyl estradiol.

UNLABELLED: The objective of the study is to evaluate the effects of a gestodene-containing oral contraceptive on carbohydrate metabolism. The design of the study is prospective. The setting is at University of South Florida Outpatient Unit. The patients consisted of twenty-three normal women desiring contraception. Serum glucose and insulin levels were measured during a three-hour glucose tolerance test at control time and after one year of drug use. RESULTS: All of the one-year glucose values were significantly elevated as well as the fasting and three-hour insulin values. These changes were mostly confined to women over 26 years of age and not in the younger 18 to 23 year olds. An oral contraceptive containing 75 micrograms of gestodene and 30 micrograms of ethinylestradiol can significantly alter carbohydrate metabolism in older women.

Adolescent↗
PubMed1992

Carbohydrate metabolism after three months of using a gestodene-containing monophasic oral contraceptive.

Carbohydrate metabolism was prospectively evaluated in twenty-one normal women prior to and during their use for three months of a monophasic oral contraceptive containing the progestin gestodene plus ethinyl estradiol. The women had a three-hour oral glucose tolerance test using a 75 gram glucose load, measuring serum glucose and insulin levels. The results demonstrate no significant changes in either of the carbohydrate metabolic indices between the two tests. These data support the safety of this new progestin-containing contraceptive.

Adult↗
PubMed1992

Six-month carbohydrate metabolism studies in women using oral contraceptives containing gestodene and ethinyl estradiol.

Twenty-five women had their carbohydrate metabolism prospectively evaluated during the six months that they used a gestodene and ethinyl estradiol monophasic oral contraceptive. Serum glucose and insulin levels were measured during a 75-gram three-hour oral glucose tolerance test. At the six-month test, the three-hour glucose and the fasting and three-hour insulin values were significantly elevated. The literature on carbohydrate metabolism during gestodene oral contraceptive use is also reviewed.

Adult↗
PubMed1991

Carbohydrate metabolic studies in women using a levonorgestrel/ethinyl estradiol containing triphasic oral contraceptive for eighteen months.

Carbohydrate metabolism was evaluated in 17 women before and after 18 months of triphasic oral contraceptive use. The triphasic oral contraceptive contained levonorgestrel and ethinyl estradiol. An oral glucose tolerance test was utilized and both plasma glucose and insulin levels were measured. There were no significant changes in the glucose levels. The fasting insulin level was raised at the 18-month test, whereas the other insulin values were similar. These results demonstrate that the new triphasic oral contraceptive preparations produce minimal carbohydrate metabolic changes.

Adult↗
PubMed1990

Two-year carbohydrate metabolism studies in women using a norethindrone or levonorgestrel triphasic oral contraceptive.

Carbohydrate metabolism was prospectively studied in 28 women using triphasic oral contraceptives (TOC) for two years. They were tested using a 100-gram oral glucose tolerance test with measurements of plasma glucose and insulin levels during the three-hour test. The women were randomly assigned to either a norethindrone-containing TOC or a levonorgestrel-containing TOC. Both types of drugs contained the estrogen ethinyl estradiol. No significant changes were noted in the norethindrone TOC group. The levonorgestrel TOC two-year test had a significant elevation of the 0.5- and 2-hour plasma glucose values and the fasting insulin value. These data show that the two triphasic oral contraceptive preparations affect carbohydrate metabolism differently.

Adult↗
PubMed1990

Plasma glucose and insulin levels during the menstrual cycles of normal women and premenstrual syndrome patients.

Three-hour oral glucose tolerance tests were performed on days 5 and 25 of ovulatory menstrual cycles in 26 women. The women were divided into normal (n = 9) and premenstrual syndrome (PMS) (n = 17) categories. Ovulation was confirmed by basal body temperature records and plasma progesterone levels. There were no statistically significant changes in the plasma glucose or insulin levels between the two tests in either group. Except for a higher two-hour plasma insulin concentration on the day 5 test in normal women, no statistically significant carbohydrate differences were noted between the groups. The data suggest that alterations in carbohydrate metabolism are not important in PMS.

Blood Glucose↗
PubMed1989

Selective inhibition of protein disulfide isomerase by estrogens.

Protein disulfide isomerase (PDI) is a multifunctional microsomal enzyme that participates in the formation of protein disulfide bonds. PDI catalyzes the reduction of protein disulfide bonds in the presence of excess reduced glutathione and has been implicated in the reductive degradation of insulin; E. coli thioredoxin is homologous to two regions in PDI and can also degrade insulin. PDI activity, measured by 125I-insulin degradation or reactivation of randomly oxidized RNase in the presence of reduced glutathione, is non-competitively inhibited by estrogens; half-maximal inhibition was observed at approximately 100 nM estrogen. Other steroid hormones at 1 microM had little or no effect. PDI segment 120-163 (which corresponds to exon 3 of the PDI gene) and 182-230 have significant similarity with estrogen receptor segments 350-392 and 304-349, respectively, located in the estrogen binding domain but not with the steroid domains of the progesterone and glucocorticoid receptors or with thioredoxin, which is insensitive to estrogens. We propose the hypothesis that enzymes can acquire sensitivity to a hormone via exon shuffling to the enzyme gene from the DNA region coding for the hormone binding domain of the hormone's receptor.

Amino Acid Sequence↗
PubMed1989

Carbohydrate studies in women using a norethindrone triphasic oral contraceptive for eighteen months.

Twenty women were tested before and after eighteen months of use of triphasic oral contraceptive (TOC) containing norethindrone and ethinyl estradiol (7-7-7). The evaluation was with an oral glucose tolerance test and plasma glucose and insulin levels were measured. The results showed a lower fasting glucose and elevated one-hour insulin values after TOC use. These results suggest improved safety with these contraceptives.

Contraceptives, Oral↗
PubMed1989

The effects of two triphasic oral contraceptives on carbohydrate metabolism in women during 1 year of use.

Sixty-one women were randomly assigned to use one of two different triphasic oral contraceptives (OCs), for one year's time (Ortho Novum 777, Ortho Pharmaceutical Corp., Raritan, NJ, and Triphasil, Wyeth Laboratories, Philadelphia, PA), containing the progestins norethindrone and levonorgestrel, respectively. The carbohydrate metabolism was evaluated using the oral glucose tolerance test before OC use and at the end of the 12th month. Both plasma glucose and insulin levels were measured. The fasting glucose value in the norethindrone-containing OC group (777) was significantly lower at the 1-year testing. All other values were unchanged. These data demonstrate that the triphasic oral contraceptive preparations currently in use have minimal effects on carbohydrate metabolism.

Adult↗
PubMed1989

Insulin and insulin-like growth factor I in brain tumors: binding and in vitro effects.

We have measured insulin and insulin-like growth factor I (IGF-I) binding in human gliomas, meningiomas, and normal brain and studied the effect of insulin on the morphology, proliferation, and differentiation of central nervous system tumor and normal fetal cells in culture. Specific 125I-insulin and 125I-IGF-I binding was demonstrated by competition-inhibition binding assays. Insulin binding was measured in plasma membrane preparations from 9 freshly isolated human meningiomas, 4 glioblastomas multiforme (GBMs), a low-grade glioma, a normal adult brain, and a fetal brain. IGF-I binding was measured in similar preparations from 5 meningiomas, 4 GBMs, a low-grade glioma, and a normal adult brain. Incubations were carried out at 4 degrees C for 18 to 20 hours. Meningiomas showed higher specific insulin binding per 0.25 mg of protein than GBMs (19% versus 3%, P less than 0.005), and this difference was not related to small differences observed in insulin degradation. By contrast, IGF-I binding was significantly higher in gliomas than in meningiomas (27% versus 12%, P less than 0.05). Also, IGF-I binding was significantly higher than insulin binding in GBMs (27% versus 3%, P less than 0.03); binding of both IGF and insulin was high in meningiomas. In normal adult brain IGF-I and insulin binding was 7 to 10%. The ability of insulin to support and enhance the growth of central nervous system tumor cells in culture was investigated. Cell cultures were derived from a freshly isolated glioblastoma, a low-grade glioma, and 3 meningiomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Human uterine leiomyoma cells: binding and growth responses to epidermal growth factor, platelet-derived growth factor, and insulin.

The specific binding of epidermal growth factor (EGF), platelet-derived growth factor (PDGF) and insulin were measured in matching cultures of human leiomyoma and myometrial cells, along with the effects of these proteins on DNA and protein syntheses. Scatchard analyses of the binding data revealed that the EGF receptor sites/cell were significantly lower in leiomyoma than myometrial cultures. Two types of PDGF binding were observed when porcine PDGF was used, and one type was seen with human PDGF. By contrast to EGF, more PDGF receptor sites/cell were found in leiomyoma than myometrium but the receptor affinity was higher in the latter. Insulin binding was similar among the myometrial and leiomyoma cells. Protein synthesis was stimulated 3-fold by EGF, PDGF, or insulin in both cell types. DNA synthesis, was higher in myometrial than leiomyoma cells in the basal state and was stimulated by EGF, insulin, or PDGF. A synergistic stimulation (p less than 0.02) of DNA synthesis was observed in both myometrial and leiomyoma cells when EGF was added with insulin. The addition of PDGF with insulin caused only additive stimulation of DNA synthesis. However, the addition of EGF with PDGF caused a synergistic decrease (p less than 0.05) in DNA synthesis by myometrial but no leiomyoma cells. Cultures of human vascular smooth muscle cells obtained from umbilical veins gave results similar to those from myometrium. These findings single out the EGF receptor and EGF, or perhaps an EGF-like growth factor, and to a lesser degree PDGF, as potential regulators of uterine leiomyomata.

Adult↗
PubMed1989

Glucose and insulin levels after six months of treatment with a triphasic oral contraceptive containing ethinyl estradiol and norethindrone.

A prospective study of carbohydrate metabolism was done on 33 women who used a triphasic oral contraceptive (OC) containing ethinyl estradiol and norethindrone for six months. A three-hour oral glucose tolerance test was administered before and after the OC usage, and both the blood glucose and insulin levels were determined. A significant decrease in the fasting glucose level was found with treatment. All other glucose values and insulin levels were unchanged.

Adult↗
PubMed1988

Plasma glucose and insulin levels in women using a levonorgestrel-containing triphasic oral contraceptive for three months.

Plasma glucose and insulin levels were measured for three hours after an oral glucose challenge in twenty-nine women before and after using a triphasic oral contraceptive containing ethinyl estradiol and levonorgestrel for three months. There were significant elevations in the glucose levels during the three-month tolerance test, while the insulin levels were unchanged. These data suggest that this OC can alter carbohydrate metabolism and that long-term studies are needed to assess the extent of this metabolic change.

Adolescent↗
PubMed1988

Prospective study of carbohydrate metabolism in women using a triphasic oral contraceptive containing norethindrone and ethinyl estradiol for 3 months.

Thirty-five women with normal carbohydrate metabolism were administered a 3-hour oral glucose tolerance test before and after 3 months' use of a triphasic oral contraceptive that contained ethinyl estradiol and norethindrone. The results show no significant change in either the plasma glucose or the insulin values. This is the first published study with regard to this type of triphasic oral contraceptive, and the study supports claims of the preparation's improved safety.

Adolescent↗
PubMed1986

Cervicovaginal peroxidases: markers of the fertile period.

The specific activity of guaiacol peroxidase was measured daily in human cervical mucus, vaginal fluids, and saliva during 45 cycles in 31 women. Also determined were basal body temperatures and serum hormones (luteinizing hormone [LH], estradiol, progesterone). The guaiacol peroxidase was extracted with 0.5 M CaCl2 and thus may be a different peroxidase from that obtained by noncalcium extraction procedures. The guaiacol peroxidase specific activity did not vary in the saliva during the cycle but fell sharply in the cervical mucus and vaginal fluid four to five days before the ovulation time, estimated by the LH peak, and rose again one to two days after ovulation. Anovulatory cycles did not show the midcycle drop in guaiacol peroxidase. Growth curve analysis gave excellent fitting of the guaiacol peroxidase data to a polynominal model. These data suggest that cervicovaginal guaiacol peroxidase may be clinically useful in detecting the fertile period for population control and for infertility treatment.

Adult↗
PubMed1985

In vitro binding of insulin and epidermal growth factor to human endometrium and endocervix.

The distribution of receptors for insulin and epidermal growth factor along the longitudinal axis of the uterine cavity was studied in 28 uteri obtained from women of reproductive age undergoing hysterectomy for benign conditions. Insulin binding to crude plasma membranes was higher (p less than 0.05) in the secretory than in the proliferative phase of the menstrual cycle in all uterine segments (fundus to cervix). Epidermal growth factor binding did not change during the menstrual cycle but the number of epidermal growth factor binding sites was higher in the cervix than in the fundus (p less than 0.05). Scatchard plots of binding data, obtained with crude plasma membranes from pooled uteri, were curvilinear; the high-affinity sites had dissociation constants of 1 to 4 nmol/L and receptor concentrations of 100 to 300 fmol/mg of protein, for both iodine 125-labeled insulin and 125I-labeled epidermal growth factor. In plasma membranes, obtained from another 15 uteri, mouse nerve growth factor (3.3 micrograms/ml) decreased the binding of insulin by an average of 17% (p less than 0.005); in the decidua of a pregnant uterus at 12 weeks Scatchard analysis showed that nerve growth factor decreased the affinity but not the number of insulin-binding sites. Nerve growth factor had no effect on epidermal growth factor binding. Human prolactin (2 micrograms/ml) also decreased insulin binding by an average of 18% (n = 5, p less than 0.025) but had no effect on epidermal growth factor binding. These "baseline" data will be useful in further studies of the possible interactions between (1) receptors for various peptide growth factors and (2) sex steroid hormones, in normal and neoplastic endometrium and cervix.

Animals↗