A new magneto-optical system has been developed to expand the range of high speed real time magneto-optical imaging. A special source for the external magnetic field has also been designed, using a pump solenoid to rapidly excite the field coil. Together with careful modifications of the cryostat, to reduce eddy currents, ramping rates reaching 3000 T/s have been achieved. Using a powerful laser as the light source, a custom designed optical assembly, and a high speed digital camera, real time imaging rates up to 30 000 frames per seconds have been demonstrated.

The saturated cores FCL exhibits several attractive technological advantages: inherent fail-safe and selectivity design, superconductivity is maintained during both nominal and fault states, the limiting process as well as the recovery after fault are passive and immediate, operation in limiting state is not time-limited, and the superconducting bias coil is made of wires available as commercial shelf-product. Despite these advantages, saturated cores FCL did not make it to commercial phase because of the large volume and heavy weight associated with its realization, a coupling problem between the AC and bias coils while in limiting state, and non-optimal limitation resulting from the presence of the bias field during fault. This work presents a novel, improved saturated cores FCL concept that overcomes the above difficulties and reopens the possibility for commercialization. Unique design topography reduces the cores volume and at the same time reduces the AC and DC magnetic coupling to about 2%. In addition, a control circuit, triggered by voltage drop across the FCL terminals, is added and disconnects the bias coil during a fault for increased limiting performances. All above-mentioned advantages of the saturated cores concept are maintained in this new design. First, a 4.2 kVA laboratory scale FCL has been designed built and studied proving the feasibility of the new design. Then, an up-scaled, 120 kVA model has been designed, built and tested at the testing laboratory of the Israel Electric Company. The prospective short current in the test bed was 5000 A, successfully limited to 2400 A. The 120 kVA model is a single phase FCL designed for 400 V, 300 A nominal conditions. Core losses and AC coils losses are 0.09% and 0.18%, respectively.

We have developed and tested a laboratory scale High-TC Superconducting Magnetic Energy Storage (HT-SMES) system with storage capacity of up to 1.2 kJ. It was designed to improve the power quality for a consumer supplied by 3-phase standard commercial electric power grid at a consumer power of up to 20 kW. This SMES is based on a high-TC superconducting coil with a ferromagnetic core, immersed in liquid nitrogen at 65 K to provide efficient thermal contact with the coolant. We also developed a cryogenic DC-DC converter based on low resistance power MOSFET transistors, providing low losses in the stored energy and high operational efficiency. The power conditioning capability of our HT-SMES was proved, and compensation of voltage drops in the electric grid was successfully demonstrated.

A laboratory-scale superconducting energy storage (SMES) device based on a high-temperature superconducting coil was developed. This SMES has three major distinctive features: (a) it operates between 64 and 77K, using liquid nitrogen (LN2) for cooling; (b) it uses a ferromagnetic core with a variable gap to increase the stored energy while retaining the critical current value; (c) it has the option for simultaneous energy charge and discharge which increases the power available at the SMES output by a factor of ≤2 when operating as a converter. The present prototype of liquid nitrogen operating SMES stores 130J at 64K and 60J at 77K.

AIMS: To evaluate whether endometrial pathology is more likely to be diagnosed in gynaecologically symptomatic rather than in gynaecologically asymptomatic postmenopausal breast cancer patients with tamoxifen treatment; and to evaluate the possible influence of various clinical factors on the incidence of endometrial pathology. METHODS: Endometrial histological findings, transvaginal ultrasonographic endometrial thickness, demographic characteristics, health habits, and risk factors for endometrial cancer were compared between 14 gynaecologically symptomatic (group I) and 224 gynaecologically asymptomatic (group II) postmenopausal breast cancer patients with tamoxifen treatment. RESULTS: Overall, 28.6% of the study population had endometrial pathology. The incidence of overall positive endometrial histological findings was significantly higher in group I than in group II (92.9% v 24.6%, p < 0.0001). Atrophic endometrium was more common in group II than in group I (75.3% v 7.1%, p < 0.0001). Most other endometrial pathology was significantly more common in group I than in group II (endometrial hyperplasia, 35.7% v 5.6%, p < 0.0001; endometrial polyps, 35.7% v 13.4%, p < 0.0111; endometrial carcinoma, 21.5% v 0.9%, p < 0.0001). Endometrial pathology appeared considerably later in the gynaecologically asymptomatic patients than in gynaecologically symptomatic patients (p = 0.0002). Vaginal bleeding or spotting occurred exclusively in group I. The incidence of endometrial pathology in the entire study population was consistent with that reported elsewhere, and higher than that reported for healthy postmenopausal women. CONCLUSIONS: Endometrial pathology is more likely to be diagnosed in gynaecologically symptomatic postmenopausal breast cancer patients with tamoxifen treatment, and after a shorter duration of time, than in gynaecologically asymptomatic patients.

To establish whether the conversion of androstenedione (A) to estrogens and 5 alpha-reduced metabolites in human adipose tissue was determined by the site of origin of the tissue, studies were carried out on adipose stromal cells from different body sites. Adipose tissue was obtained from the breast, omentum, abdomen, lower thigh, upper thigh, buttock, and flank from patients undergoing liposuction for cosmetic reasons or at surgery. Stromal cells were isolated after incubation of the adipose tissue with collagenase and were grown in culture using alpha-minimal essential medium (MEM) + 15% fetal calf serum. Studies of A metabolism were carried out when the cells were between days 4 and 12 in culture. After an 8-hour incubation with (3H)-A as substrate, estrone (E1), testosterone (T), 5 alpha-androstanedione (5 alpha-A-dione), androsterone (AND), and dihydrotestosterone (DHT) were isolated using thin layer and paper chromatography. The conversion per 1 x 10(6) cells of A of E1 was more than 10-fold greater in the upper thigh, buttock, and flank than in the breast, lower thigh, abdomen, or omentum (0.13-3.0 vs 0.01-0.09%). The formation of 5 alpha-reduced androgens varied from 0.86-10% and was similar in tissue from different body sites. Cortisol (10(-7) M) stimulated E1 formation 3- to 10-fold in cells from all sites, whereas 5 alpha-reductase activity was either unchanged or increased moderately (up to twofold). In cells from the abdomen, omentum, and lower thigh, the formation of 5 alpha-reduced androgens was more than 10-fold greater than the formation of E1. In cells from the upper thigh, buttock, and flank, E1 formation was comparable to 5 alpha-reduced androgen formation. These studies show marked differences in the relative conversion of A to estrogens and 5 alpha-reduced androgens in adipose stromal cells depending on their site of origin, and they suggest that the distribution of body fat may be a major factor in determining the biologic effects of secreted androgens.

Cortisol and steroids with progestational or androgenic activity were studied to determine the effects of these steroids on the conversion of androstenedione (A) to estrone (E1) in human cultured breast carcinoma cells. Cortisol (10−6M) stimulated aromatase activity in two estrogen unresponsive cell lines (MD, DM) and in an estrogen responsive cell line (MCF7) with the maximum stimulation occurring during confluence. Cortisol inhibited the replication of MCF7 cells but not MD and DM. Dihydrotestosterone, androsterone and 5α-androstanedione (10−6M) inhibited the conversion of A to E1 by greater than 90% under basal and cortisol stimulated conditions. Progesterone (10−6M) had no effect on aromatase activity while the progestational agent R5020 (10−6M) produced a 30% inhibition. The anabolic steroids 19-nortestosterone and 19-norandrostenedione which also have progestational activity inhibited the conversion of A to E1 in a dose dependent manner with 90% inhibition at 10−6M. Danazol (10−6M) a drug with both androgenic and progestational activity inhibited E1 formation by 30%. Under the same conditions, the known inhibitor of aromatase, 4-hydroxyandrostenedione (10−6M) decreased E1 formation by more than 90% and aminoglutethimide (10−6M) caused only 25% inhibition. These studies demonstrate that endogenous and exogenous steroids may have significant effects in modulating the local formation of estrogens from androgen precursors in cultured breast carcinoma cells. This effect on estrogen formation may be a factor in the biological response of breast tissue.

The present study was designed to determine if stromal cells derived from human breast adipose tissue contain 5 alpha-reductase activity, and to study the effect of 5 alpha-reduced androgens on aromatase activity under basal and cortisol stimulated conditions. Stromal cells were prepared from breast adipose tissue obtained at the time of surgery from four patients. The cells were isolated after collagenase digestion and were cultured in alpha-minimum essential medium with 15% fetal calf serum. Studies were carried out between days 4 and 11 of the third subculture in the presence or absence of cortisol (10(-6) M). Metabolism of androstenedione (A) was studied over a period of 8 h after addition of medium containing 20 X 10(6) dpm (100 pM) [3H]A. The cells metabolized A to estrone (E1), testosterone (T), 5 alpha-androstane 3, 17-dione (5 alpha-A-dione), androsterone (AND), and dihydrotestosterone. On day 7 of culture, product formation expressed as percent conversion of A per 1 X 10(6) cells ranged as follows: E1, 0.02-0.13; T, 0.12-0.36; 5 alpha-A-dione, 2.05-9.91; and a fraction containing AND and dihydrotestosterone, 0.38-0.59. In the presence of cortisol the rate of cell growth was decreased by 25% to 50%. The formation of E1 increased 150- to 1500-fold and AND formation increased 2- to 8-fold. There was no consistent change in the formation of 5 alpha-A-dione and T. The addition of 5 alpha-A-dione (10(-6) M) to the culture medium at the time of assay resulted in greater than 90% inhibition of E1 formation under both basal and cortisol stimulated conditions. The studies indicate that adipose tissue is an important site for the formation of 5 alpha-reduced androgens.

The conversion of androstenedione (A) to estrogens, testosterone (T) and 5 α-reduced metabolites was studied in different phases of cell growth in 4 lines of cultured human breast carcinoma cells. Aromatase activity was 10-fold greater in MD and DM than in MCF7 cells and was undetectable in ZR75 cells. Estrogen formation in MD and DM lines increased during the phase of exponential growth and decreased to 20% of maximum during confluence. 5α-Reductase activity was determined by the formation of 5α-androstane-3,17-dione (5α-A-dione) and androsterone (AND), and was 5-fold greater in ZR75 cells than MD cells and 2-fold greater than in MCF7 cells. This activity was relatively constant during exponential growth and decreased during confluence. T accumulation was inversely related to 5α-reductase activity. The MCF7 and ZR75 cells which contain estrogen receptors had the highest levels of 5α-reductase activity while the MD line which lacks estrogen receptors had the lowest 5α-reductase activity.

Four cell lines, each derived from a primary tumor from a patient with breast carcinoma, were grown to confluence in alpha-Minimum Essential Medium with 15% fetal calf serum and incubated for 24 h with [3H]androstenedione. The two lines (SA and PP) with the lowest formation of estrone and estradiol (less than 0.1% conversion) were the most active in the formation of the 5 alpha-reduced androgen metabolites androsterone (AND), 5 alpha-androstanedione (5 alpha-A-dione), and dihydrotestosterone (DHT). The two lines with the highest aromatase activity (DM and MD) had the lowest formation of 5 alpha-reduced metabolites. To determine if the 5 alpha-reduced androgen metabolites formed within the breast carcinoma cells could influence aromatase activity, the MD line was further studied. After 24-h preincubation with AND, DHT, or 5 alpha-A-dione at concentrations of 10(-6), 10(-7), and 10(-8) M, [3H]androstenedione was added to the culture medium, and aliquots were removed at 0, 4, 8, and 24 h. An 8-h incubation period was found to be optimum for inhibition studies. In comparison to control levels of estrone (2.5%) and estradiol (0.35%) formation, inhibition of aromatization was evident with all three compounds at 10(-8) M, with 5 alpha-A-dione producing the greatest inhibition (50%). At 10(-7) M, inhibition ranged from 45% (AND) to 70% (5 alpha-A-dione), and at 10(-6) M, inhibition was greater than 90% for each compound. 5 alpha-A-dione produced slightly greater inhibition than AND or DHT at each concentration tested. Since each of these compounds was capable of inhibiting aromatization, the cumulative effect of these 5 alpha-reduced metabolites could be an important factor in the intracellular regulation of aromatase activity.

In previous studies from our laboratory of the metabolism of androstenedione (A) and testosterone (T) in breast adipose and breast carcinoma tissue, the aromatization of these compounds, and their interconversion were demonstrated. The present study describes the conversion of androstenedione and testosterone to C19 metabolites in homogenates of normal breast tissue and breast carcinoma tissue and examines the C19 metabolites in homogenates of benign prostatic hypertrophy (BPH) tissue under similar conditions.

A method for analysis of metabolic profiles of free and conjugated steroids in milk has been developed. Milk is diluted with aqueous triethylamine sulphate and liquid-solid extraction is achieved on a Sep-Pak C18 cartridge at 60–64°C. Steroids are purified by chromatography on small columns of Lipidex 5000 and sulphohydroxypropyl Sephadex LH-20 [H+ prior to separation into neutral and phenolic compounds, glucuronide, mono- and disulphate conjugate groups on the lipophilic strong anion exchanger triethylaminohydroxypropyl Sephadex LH-20 (TEAP-LH-20). Conjugated steroids are released by enzymatic or solvolytic procedures and separated into a neutral and a phenolic fraction on TEAP-LH-20. The O-methyloxime and trimethylsilyl ether derivatives of the steroids are analyzed by capillary column gas chromatography-mass spectrometry. Fifty steroids were identified in milk collected from women a few days after delivery. Quantitatively about 80% were present as sulphates, 15% as glucuronides and only 5% were unconjugated steroids. The steroid pattern was similar to that in late pregnancy plasma with pregnanolone, pregnanediol and pregnanetriol isomers and dehydroepiandrosterone being predominant. About 10% of the steroid content consisted of estrogens. The total concentration of steroids 2 days after delivery was 20–116 ng/ml, i.e. about 1–5% of the concentration in plasma. The concentrations of pregnanes and estrogens rapidly decreased and the steroid concentration was about 10 ng/ml 1 month after delivery. In one milk sample, collected 2 days after delivery, the steroid concentration (3.6 μg/ml) was similar to that in plasma.

The effects of 4-hydroxy-4-androstene-3, 17-dione (4-OH-A) and 10-propargylestr-4-ene-3, 17-dione (PED) on the aromatization of androstenedione (A) and the conversion of A to testosterone (T) were studied in incubations with breast carcinoma and breast adipose tissues. Parallel studies were carried out to determine the effects of 4-OH-A and PED on A metabolism in tissue from 5 patients with breast carcinoma. At 11 micro M, both compounds fully inhibited aromatization, whereas the conversion of A to T was decreased in only 2 incubations. Studies with varying concentrations of 4-OH-A and PED demonstrated that both compounds inhibited estrone (E1) formation by 80% at a concentration of 0.085 micro M, with maximum effect at 0.34 micro M. 90% inhibition of estradiol (E2) formation was observed at inhibitor concentrations of 0.17 micro M or greater. T formation was slightly affected at 0.67 microM, but was progressively inhibited with increasing 4-OH-A or PED concentrations, reaching 70% at 11 micro M. Similar experiments with 4-OH-A in breast adipose tissue homogenates showed that a concentration of 0.1 micro M was sufficient to inhibit aromatization while T inhibition required 11 micro M. 4-OH-A and PED are selective inhibitors of aromatization in human breast tissues and may provide a mechanism for controlling estrogen responsive processes.

Incubation studies have been carried out using normal breast tissue and breast tissue from patients with gynecomastia, mammary dysplasia and breast carcinoma to determine the pattern of androstenedione metabolism. All tissues formed estrone (E1) and testosterone (T) in all incubations. Estradiol (E2) was isolated in incubations of tissue from 1 to 6 patients with mammary dysplasia, 5 of 6 patients with gynecomastia and in all incubations with normal and carcinoma tissue. Estrone formation was lowest in mammary dysplasia and gynecomastia, and higher in apparently normal breast tissue. The greatest E1 formation was found in incubations with breast carcinoma tissue, although there was considerable variation within this tissue group. Estradiol formation was low in all tissues, with the highest conversion rates in carcinoma tissue. Testosterone formation in carcinoma tissue was greater than in mammary dysplasia or gynecomastia, but similar to apparently normal tissue. These results indicate that breast tissue from different pathological states varies in its capacity to aromatize androstenedione (A) to estrogenic products and to convert it to other androgens. They have also shown that the pattern of metabolism is distinctive for the nature of the pathological abnormality.

In vitro studies have been carried out to compare the conversion of androstenedione to testosterone, estrone and 17β-estradiol in breast adipose and parenchymal tissue from patients undergoing reduction mammoplasty and in breast adipose and carcinoma tissue from patients undergoing mastectomy.

Incubations have been carried out to study the interconversion and aromatization of androstenedione and testosterone in human adipose tissue. In abdominal and omental fat using androstenedione at a variety of substrate concentrations, testosterone was isolated from all incubations, estrone from 8 out of 12 incubations and estradiol from 3 out of 12 incubations. Using breast adipose tissue from male and female subjects, testosterone, estrone and estradiol were isolated from all incubations. No consistent difference in the capacity of adipose tissue to aromatize androstenedione was noted in adipose tissue from different sources. In studies on isolated fat cells and the fibromascular stroma of adipose tissue the interconversion of testosterone and androstenedione was demonstrated in both tissues. Human adipocyte precursors isolated from the stromal-vascular fraction of human omental adipose tissue converted androstenedione to testosterone and estrone. These studies confirm the aromatization of androstenedione in adipose tissue from a variety of sources. They also demonstrate the interconversion of androgens in adipose tissue and emphasize that the net effect of a gonadal steroid acting on a peripheral tissue may depend on the nature of the metabolites formed in that tissue.