Immunohistochemical localization of 17 alpha-hydroxylase/C17-20 lyase (P-450(17 alpha,lyase)) and aromatase cytochrome P-450 (P-450arom) in normal human ovaries during the menstrual cycle was studied using specific polyclonal antibodies which were raised against corresponding enzymes. In the follicular phase of matured follicles, P-450(17 alpha,lyase) was localized in theca interna cells and P-450arom in granulosa cells. P-450(17 alpha,lyase) was expressed in theca interna cells before P-450arom was expressed in granulosa cells. The corpus luteum showed immunoreactivity to both enzymes and, after menstruation, immunoreactivity decreased gradually until it could not be detected in the corpus albicans. In corpus luteum graviditatis the immunoreactivity continued to be expressed strongly. In some atretic follicles, P-450(17 alpha,lyase) and/or P-450arom continued to be expressed. In the stromal layer, P-450(17 alpha,lyase was detected in secondary interstitial cells, which originated from the theca interna of atretic follicles, and P-450arom was detected in hilar cells. Immunoreactivity to both enzymes was also detected in oocytes of developing follicles. These results are consistent with the two cell theory in the human ovary. They also suggest that androgens and oestrogens are produced not only by follicles and corpora lutea but also by stroma and oocytes.

p185erbB‐2 and p180erbB‐4 are epidermal growth factor (EGF) receptor‐like tyrosine kinases, whose co‐expression is observed in many breast carcinomas. Heregulins (HRGs), which contain an immunoglobulin unit and an EGF‐like domain, bind to p180erbB‐4 and activate p180erbB‐4 and p185erbB‐2 through transphosphorylation or receptor heterodimerization. The EGF‐like domain is sufficient for the activation. Despite the sequence similarity, no cross activity is seen between the p180erbB‐4 ligands (HRGs) and the p170erbB‐1 ligands [EGF and transforming growth factor (TGF)‐alpha]. To investigate the structural basis of receptor specificity, we have determined the solution structure of the EGF‐like domain of HRG‐alpha by two‐dimensional 1H nuclear magnetic resonance spectroscopy and simulated annealing calculations. Though its main‐chain fold is similar to those of EGF and TGF‐alpha, distinctive structural features are observed on the molecular surface including an ionic cluster and hydrophobic patches, which afford HRG‐alpha the specific affinity for p180erbB‐4. The structure should provide a basis for the structure‐activity relationship of HRGs and for the design of drugs which prevent progression of breast cancer.

Aim: To evaluate the risk factors for rubeosis iridis by colour Doppler imaging (CDI) in patients with complete internal carotid artery occlusion (ICAO). Methods: 34 eyes of 32 consecutive patients with complete ICAO were enrolled. Using CDI, blood flow direction (forward, reverse, undetectable) in the ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary artery (SPCA) were determined. Arterial mean blood velocity (Vmean) and resistive index (RI) were calculated and correlations between the rubeosis iridis incidence and CDI parameters analysed. Results: The eyes were classified into four types according to blood flow direction: forward flow in OA, CRA, and SPCA (type 1; n = 11); reverse OA and forward CRA and SPCA flow (type 2a; n = 12); reverse OA and undetectable CRA and SPCA flow (type 2b; n = 8); undetectable flow in all three arteries (type 3; n = 3). Rubeosis iridis was seen only in type 2b and 3 eyes. Type 2b showed significantly (p,0.01) higher Vmean and lower RI values in the OA, indicating more rapid reverse flow than in type 2a eyes. Although in type 1 and 2a eyes OA flow was in opposite directions, they manifested no rubeosis iridis and no difference in the Vmean and RI values of the CRA and SPCA. Conclusions: The classification of eyes from patients with ICAO into four types by CDI may facilitate the identification of the eyes at high risk for rubeosis iridis. Markedly diminished flow in both the CRA and SPCA may result in rubeosis iridis, regardless of OA flow direction. I n patients with complete internal carotid artery occlusion (ICAO), chronic progressive ocular ischaemia 1-5 leads to rubeosis iridis and neovascular glaucoma. To explain the underlying mechanisms, the following hypothesis has been proposed. When ICAO occurs in patients with incomplete blood circulation in the circle of Willis, the blood flow in the ophthalmic artery (OA) reverses to supply the ipsilateral brain. This so called ''steal phenomenon'' results in ocular ischaemia, 6-8 whose prolongation leads to rubeosis iridis and neovascular glaucoma. It remains unclear, however, why some eyes deteriorate rapidly while others show no clinical symptoms of ocular ischaemia.Colour Doppler imaging (CDI) is a non-invasive, repeatable technique for measuring orbital blood flow.9 10 The haemodynamic parameters of CDI are not sex dependent and do not vary between orbits.11 Since Lieb et al 12 first reported CDI as a reliable means of evaluating ocular circulation, it has been used to measure retrobulbar blood flow in ICAO patients and to confirm the presence of the steal phenomenon.7 8 Mawn et al 13 noted that the average peak systolic velocity in the CRA and SPCA was similar, regardless of OA flow direction, and that many patients with reverse OA flow demonstrated no evidence of ocular ischaemic syndrome.To determine which eyes have a tendency to suffer from iris neovascularisation, we evaluated the ocular circulation by CDI in patients with complete ICAO with or without rubeosis iridis. PATIENTS AND METHODSBet...

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Abstract.We examined influences of estrogen and progestogen on gene expression of the growth regulatory molecules: platelet-derived growth factor (PDGF), interleukin-1 (IL-1), interleukin-6 (IL-6) and proto-oncogene cmyc in vascular smooth muscle cells (VSMC) by reverse transcription-polymerase chain reaction (RT-PCR) and Southern-blotting.VSMC were exposed to estrone-sulfate (E,-S) and medroxyprogesterone acetate (MPA) to induce differentiation.El-S inhibited the expression of PDGF-A chain, IL-1, IL-6 and c-myc mRNA, whereas MPA had no effect. Inhibition by El-S was not affected by treatment combined with MPA. These findings suggest that estrogen modulates these growth regulatory molecules and c-myc gene expression in VSMC but not progestogen.We concluded that estrogen may have a direct atheroprotective effect through inhibition of growth regulatory factors. EPIDEMIOLOGICAL studies have indicated that the risk of coronary heart disease (CHD) in women increases remarkably after menopause [1]. Before menopause, CHD is rare in women. The incidence of CHD in young and middle-aged women, compared with men of the same age, remains low until menopause [1][2][3]. After menopause, CHD mortality rate for women rapidly approaches that of men. According to 1996 statistics, cardiovascular disease accounted for 39% of all women's deaths, but only 30% of all men's deaths [4].Loss of ovarian function causes changes in plasma lipids [5][6][7][8][9][10][11], apolipoproteins [7] and blood pressure