[GnRH agonists. New possibility for treatment of hormone-dependent gynecologic diseases].
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Biomedical subjects
Publications and source records attributed to A Bergqvist.
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The objective of the study was to compare the localization and staining intensity of oestrogen and progesterone receptors in endometrium and endometriotic tissue. Using monoclonal antibodies towards oestrogen and progesterone receptors, analysis was performed in 63 endometriotic samples from 40 women and compared to endometrium obtained simultaneously from 25 of the women. Using a staining index, 'total immuno-staining score', calculated from the staining intensity multiplied by the fraction of positive cells, the receptor content was estimated semiquantitatively. The scores for both oestrogen and progesterone receptors were lower in endometriotic epithelial cells than in endometrial epithelial cells, but the differences reached statistical significance only for the progesterone receptor. No difference was found for stromal cells. There was a significant correlation between oestrogen receptor score in endometriotic tissue and in endometrium, but not for progesterone receptor score. In endometrium and vaginal and peritoneal endometriosis, the progesterone receptor score showed similar values, higher than those in ovarian endometriosis. The data from this large immunohistochemical study support previous results of quantitative steroid receptor analyses, indicating that the regulation of steroid effects, especially those of progesterone, differs between endometriotic and endometrial tissue.
The levels of oestrogen and progesterone receptors were analysed in 62 endometriotic tissue samples obtained at laparotomy of 58 women and in samples of endometrium obtained simultaneously from 49 of the women. Both ligand techniques and enzyme immunoassays were used for the assays. The steroid receptor levels were significantly lower in endometriotic tissue than in endometrium, both in cytosol and nuclear fractions. The differences were most pronounced in follicular phase. In endometrium the oestrogen and progesterone receptor levels varied during the menstrual cycle, being highest in follicular phase. In endometriotic tissue, the oestrogen receptor level remained low throughout the cycle. The progesterone receptor level, determined by immunoassay, increased during the menstrual cycle, being higher in luteal than in follicular phase. This cycle phase pattern was found neither in the nuclear progesterone receptor level nor when the cytosol was assayed with the ligand technique. In contrast to endometrium, there were no correlations between patients' age and steroid receptor levels in endometriotic tissue. The results show that oestrogen and progesterone receptors in endometriotic tissue have a different pattern during the menstrual cycle than endometrium and that the progesterone receptors synthesized are not all biologically active. These results strengthen previous data indicating differences in the hormonal regulation of the two tissue types.
The purpose of the present investigation was to examine the estrogen and progesterone receptor status in arterial and vein walls in women and men. Biopsies from uterine arteries and veins were obtained from 14 fertile and six post menopausal women. Biopsies from saphenous veins were obtained from eight fertile women, 12 post menopausal women and 12 men. Comparative receptor assays were performed with ligand technique and monoclonal antibodies. Immunohistochemical localization of estrogen and progesterone receptors was performed using monoclonal antibodies. The ligand technique revealed estrogen and progesterone receptors in low frequency in the uterine vessels but the monoclonal antibodies showed low receptor level in all arterial and vein samples. There was no statistical difference between fertile and post menopausal women. In the few nuclear fractions examined, both estrogen and progesterone receptors were measurable. Estrogen receptors were found in all peripheral vein samples from fertile women but not in all samples from post menopausal women and men. Progesterone receptors were detected in almost all samples of peripheral veins. There were significant differences with higher levels of estrogen receptors in cytosol and nuclear fraction and of progesterone receptors in nuclear fraction, all assayed with monoclonal antibodies, in uterine veins from fertile women compared to peripheral veins from fertile women, post menopausal women and men, respectively. These data indicate that the hormonal regulation of peripheral vein walls is different than that of the uterine vessel.
Endometriotic growth may appear in any structure in the body. As well as affecting the internal genitalia, lesions are not uncommon in the bowel, urinary tract and thorax and reports of a number of cases at rarer sites have been published. This review is based on more than 1000 publications on the subject, that allows an overview of the appearance of the disease in different organs.
OBJECTIVE: To study the hormonal regulation of primary and recurrent endometriosis by comparing the levels of estrogen receptors (ER) and progesterone receptors (PR) with the levels in uterine endometrium obtained simultaneously. DESIGN: Tissue samples collected at routine operations. SETTING: One university clinic. PATIENTS: A total of 69 endometriotic samples were obtained from 61 women, and endometrium was obtained from 54 of the women. Seventeen of the patients (26%) had a recurrent disease; the others (n = 49) were operated on for the first time. MAIN OUTCOME MEASURES: Samples from recurrences constituted 18% (6/34) of the endometriomas, 37% (10/27) of the biopsies from ovarian lesions, and 4 of 5 biopsies from peritoneal endometriosis. In primary endometriotic lesions, both ER and PR were significantly lower than in endometrium. In recurrent lesions, ER levels in cytosol were significantly lower than in endometrium, but there was no difference concerning PR. In endometriotic tissue, the PR level was significantly higher in recurrent than in primary tissue, but there was no difference concerning ER. The ER level was significantly lower in ovarian but not in peritoneal endometriosis, compared with endometrium. No difference was seen concerning PR. CONCLUSION: This study shows differences in ER and PR levels in primary and recurrent endometriosis and indicates a different hormonal regulation of the two stages of the disease.
Protein phosphatase 2A is composed of three subunits: the catalytic subunit C and two regulatory subunits, A and B. The A subunit consists of 15 nonidentical repeats and has a rodlike shape. It is associated with the B and C subunits as well as with the simian virus 40 small T, polyomavirus small T, and polyomavirus medium T tumor antigens. We determined the binding sites on subunit A for subunit C and tumor antigens by site-directed mutagenesis of A. Twenty-four N- and C-terminal truncations and internal deletions of A were assayed by coimmunoprecipitation for their ability to bind C and tumor antigens. It was found that C binds to repeats 11 to 15 at the C terminus of A, whereas T antigens bind to overlapping but distinct regions of the N terminus. Simian virus 40 small T binds to repeats 3 to 6, and polyomavirus small T and medium T bind to repeats 2 to 8. The data suggest cooperativity between C and T antigens in binding to A. This is most apparent for medium T antigen, which can only bind to those A subunit molecules that provide the entire binding region for the C subunit. We infer from our results that B also binds to N-terminal repeats. A model of the small T/medium T/B-A-C complexes is presented.
Extragenital endometriosis is common and may be found in any tissue. The most pronounced symptoms are pain and local bleeding that usually (at least initially) are cyclical and more pronounced at the time of menstruation. The lesions often infiltrate neighbouring organs, and cause considerable fibrosis together with increasing symptoms. The patients have often had pain for many years, have been investigated at different clinics, and been given conflicting diagnoses, often of mental instability, before the correct diagnosis is finally made. The disease is difficult to diagnose clinically, and must be verified histologically. Often the endometriosis responds to treatment with hormones to inactivate the ovaries, but, sometimes the lesions are resistant, or respond too slowly, to drugs, and local excision is required. A gynaecologist should be called if the diagnosis is made at laparotomy or laparoscopy, to establish the extension of the endometriotic lesion and should be consulted about complementary investigations and hormonal treatment.
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To evaluate the possibility of autoimmune processes against pancreatic islets in fetal life, we tested islet cell antibody (ICA) reactivity with 14 fetal pancreata obtained after abortion at the 15th up to the 19th week of gestation. Pancreatic islets positive for a monoclonal proinsulin antibody but non-reactive with ICA negative control serum were found in 9/14 pancreata and all (9/9) of them showed a positive reaction with the ICA standard. It is concluded that ICA reactivity may be detected in fetal human pancreata. Further studies on fetal islet cell antibody reactivity in the development of insulin dependent diabetes mellitus (IDDM) are warranted.
In 21 women who had an abortion by hysterotomy between the 15th and 23rd week of pregnancy, the possibility that unfragmented heparin or low molecular weight heparin (LMWH) passed the placental barrier to the foetus was studied. Laboratory analyses included amidolytic assays of factor Xa inhibitory activity (XaI), antithrombin III (ATIII) and a direct measurement of heparin-like substances in plasma with a competitive binding assay. The ATIII concentration in foetal plasma was about 20% of that in normal human plasma and varied considerably between individuals (2-27%). The XaI activity did not differ between the two treated groups, but the mean XaI activity of the combined groups differed from zero (P less than 0.05). If the XaI activity was corrected for the ATIII concentration, the heparin activities no longer differed significantly from zero. As the concentration of heparin-like substances were above the detection limit (0.35 microgram/ml) in 6/16 analysable samples of foetal plasma, a further 15 women who had not received any heparin were included as controls. In 12/14 analysable foetal plasmas heparin-like substances in concentrations above 0.35 micrograms/ml could be detected. Determination of heparin activity in foetal plasma is thus difficult due to the influence of endogenous ATIII on heparin assays. In conclusion, this study did not demonstrate any evidence for the passage of heparin or LMWH across the placental barrier. No differences were detected whether unfragmented heparin or LMWH had been given to the mothers. Our results also indicate the presence of an endogenous glycosaminoglycan in foetal plasma.
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A putative zinc finger in polyomavirus large T-antigen was investigated. We were unable to demonstrate unequivocally a requirement for zinc in specific DNA-binding using the chelating agent 1, 10-phenanthroline. An involvement of the putative zinc finger in specific DNA-binding was nevertheless suggested by the properties of a mutant protein with a cys----ser replacement in the finger motif. Probably as a result of the defective DNA-binding, the mutant protein had lost its activity in initiation of viral DNA-replication and in negative regulation of viral early transcription. However, the trans-activation of the viral late promoter was normal. The analysis also revealed a previously unrecognized activity of large T-antigen. The mutant protein trans-activated the viral early promoter. In the wild-type protein this activity is probably concealed by the separate, negative regulatory function.
Thromboembolism during pregnancy is a rare complication with a potential fatal outcome. Very little is known about long-term effects and therefore 104 women with thrombosis during pregnancy or puerperium were identified and their subjective complaints were assessed in a questionnaire. All had their thrombosis diagnosed by objective methods and the median follow-up time was 11 years. In spite of anticoagulant treatment only 22% were without complaints; 4% had ulceration, all occurring in the group with thrombosis during pregnancy. Significantly more women who had had their thrombosis during pregnancy used compression bandages than those who had their thrombosis during puerperium. The severity of the symptoms increased with the increasing number of thromboses. Anticoagulant therapy of the acute episode does not appear to alter the degree of long-term handicap in the lower limbs.
By sending a questionnaire (response rate 93%) to 321 women with a history of venous thromboembolism and previous coagulation tests, 72 patients were identified who had a total of 87 pregnancies after the thromboembolic episode. The main aim of the study was to analyze the influence of prophylaxis during pregnancy and delivery on the development of further thromboembolic complications. During pregnancy there was no difference in frequency of thromboses between the group given prophylaxis (n = 20) and the group not receiving it (n = 67). At delivery the frequency of thrombosis was 5.3% among the 57 women given prophylaxis and 11.1% among the 30 without prophylaxis, a difference that is not significant. The implication of these findings is discussed both concerning the indications for giving prophylaxis and concerning the problem of designing relevant prophylactic trials.
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The metabolism of [3H]estrone sulfate (E1S) into [3H]estrone (E1) and [3H]estradiol-17 beta (E2) was studied in samples of endometriotic tissue and uterine endometrium obtained simultaneously from 13 patients, 7 in the proliferative and 5 in the secretory cycle phase, and 1 menstruating. E1S was efficiently converted into E1 and E2 by both types of tissue. Total hydrolysis (formation of E1 + E2), as well as the specific formation of E2, was higher in uterine endometrium than in endometriotic tissue, especially in the proliferative phase. Cycle phase associated variations in E2 formation occurred in both tissues, but were statistically significant only for uterine endometrium. E2 formation and total hydrolysis were correlated in endometriotic tissue, but not in uterine endometrium, indicating certain differences in the regulation of estrogen metabolism.
Iatrogenic vascular injuries are common in the civilian western world. The frequency seen following gynecologic surgery is not known and a questionnaire was therefore sent to all gynecologic clinics in Sweden undertaking surgery, to establish the frequency during a 5-year period and to analyse the types of injury. Case reports in the literature were also analysed. The frequencies per 10,000 operations were: after laparoscopy, 0.93, after laparotomy, 0.76 and after major vaginal surgery, 0.33. All laparoscopic injuries were localized to the iliac arteries, caused bleeding, and were treated with arterial suture without complications or late sequelae. Injuries during laparotomy were most frequently venous and all patients had hemorrhage as the main symptom. In one case the external iliac vein was ligated, with immediate postoperative swelling, and in another case the external iliac artery was ligated, after which the patient developed postoperative ischemia. The internal iliac veins were ligated, and the other vessels reconstructed. There was no mortality, but a high rate of morbidity, also with late sequelae.