Evaluation of in vivo and in vitro responses of endometrial adenocarcinoma to progestins.
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Biomedical subjects
Publications and source records attributed to H Fleming.
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Studies of hormone-related biochemical parameters of human endometrium are facilitated by the availability of a variety of types of endometrial tissue resulting from changes in hormonal environment during the menstrual cycle or from decidual, hyperplastic, and neoplastic transformations. Estrogen and progesterone receptors levels, rates of metabolism of ovarian hormones, enzymatic activities regulated by hormones or affecting intracellular concentrations of steroids, rates of production of prolactin and prostaglandins, and endogenous levels of hormones have been measured in samples of endometrial tissue and in separated glands and stroma. These studies have also included an evaluation of effects of estrogens and progestins administered to patients or added to the medium during in vito incubations of endometrium under organ culture conditions. Epithelial cells derived from isolated glands and stromal cells have been grown in primary cultures and also subcultured. These studies have revealed two mechanisms by which progestins exert an antiestrogenic effect on the endometrial tissue: viz, they were found to provoke a decline in estrogen receptor levels and to increase the metabolism of E2 through stimulation of estradiol 17 beta-dehydrogenase activity. In addition, studies of cells in culture have led to the unexpected finding of wide and rapid fluctuations in the levels of estrogen receptors, thus providing an opportunity to investigate factors involved in the regulation of concentrations of specific E2-binding sites.
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Immunoglobulin obtained from the serum of rabbits immunized with a highly purified preparation of estradiol-receptor complex from calf uterine nuclei has been shown to contain specific antibodies to the receptor protein (estrophilin) by four criteria: (a) precipitation of the radioactive steroid upon addition of goat antibody against rabbit gamma globulin to a mixture of the tritiated estradiol-receptor complex and the immunoglobulin, (b) adsorption of the estradiol-receptor complex by the immunoglobulin linked to Sepharose, (c) adsorption of the estradiol-receptor complex in the presence of the immunoglobulin by Staphylococcus aureus protein-A linked to Sepharose, and (d) the ability of the immunoglobulin to increase the sedimentation rate of the estradiol-receptor complex. Antibodies to calf nuclear estrophilin were shown to crossreact with the nuclear receptor of rat uterus, as well as with the extranuclear receptor of calf, rat, mouse, and guinea pig uterus and of human breast cancer. The antibodies do not react with either the nuclear or extranuclear dihydrotestosterone-receptor complexes of rat prostate or with the extranuclear progesterone-receptor complex of chick oviduct. These findings indicate an immunochemical similarity among estrophilins from several mammalian species, as well as between extranuclear and nuclear forms of the receptor, but not among receptor proteins for different steroid hormones.
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Cellular differentiation can be observed in certain filamentous blue-green algae after transfer of the cells from medium containing NH(4) (+) or NO(3) (-) to nitrogen-free medium. The appearance of differentiated cells (heterocysts) is accompanied by an increase in the activity of nitrogenase, an enzyme complex that reduces N(2) to NH(3). We have separated vegetative cells from heterocysts in differentiated filaments of Nostoc muscorum, and analyzed their proteins by polyacrylamide-gel electrophoresis. The pattern of incorporation of (35)SO(4) (-) into proteins of the two cell types during differentiation indicates that the increase in nitrogenase activity is due to the de novo synthesis of nitrogenase proteins predominantly, if not exclusively, in heterocysts.
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Photochemical reaction centers prepared from Rhodopseudomonas spheroides were treated with reduced cytochrome c (cyt c), and in some cases with ubiquinone (UQ), and illuminated. The light-induced oxidation of cy and reduction of UQ were observed, and also the variations in fluorescence of P870. These observations indicated that each reaction center contains a primary photochemical electron acceptor capable of holding just one electron. Depending on the method of preparation, the reaction centers may also contain secondary electron acceptor pools consisting mainly of UQ. The role of native UQ as an electron acceptor could be duplicated by added UQ. The yield of P870 fluorescence increased by a factor of 3-4, at most, during illumination of reaction centers in the presence of an electron donor such as reduced cyt. This suggests that the quantum efficiency for the primary photoact is about 0.7, rather than 0.9-1.0 as concluded in the past from optical absorption measurements. The apparent quantum efficiency for the oxidation of cyt by illuminated reaction centers can be increased by the addition of UQ and is decreased at higher concentrations of the detergent lauryl dimethylamine oxide (LDAO). These treatments do not affect the quantum efficiency of P870 oxidation, measured in the absence of cyt.
Reaction centers from Rhodopseudomonas spheroides mediate the photochemical oxidation of cytochrome c (cyt c), and show a time-varying fluorescence of P870. Analyses of these effects indicate that the reaction centers contain a primary photochemical electron acceptor capable of holding one electron. Native or added ubiquinone (UQ) can act as a secondary electron acceptor. Orthophenanthroline (o-phen) blocks electron transfer from primary to secondary acceptors, and allows the primary acceptor to be exhibited in the foregoing experiments. Other chelators (with the possible exception of 8-hydroxyquinoline) and dichlorophenyldimethylurea (DCMU) are without apparent effect on reaction centers. o-Phen also inhibits the primary photochemical act in reaction centers; this effect is prevented by the presence of UQ. 2-n-Nonyl-4-hydroxyquinoline-N-oxide (NQNO) inhibits the primary photochemistry in reaction centers but does not affect secondary electron transfer.
A 62 year old man with severe angina pectoris underwent aoroto-coronary saphenous vein graft implantation. After a four month asymptomatic period the patient underwent aorto-coronary graft angiography. Left anterior descending graft opacification demonstrated multiple venous aneurysmal dilations. The clinical significance of this finding is currently unknown but such saphenous vein disease warrants further investigation. Saphenous vein grafts have been utilized to replace or bypass obstructed and diseased peripheral arteries such as those of the carotid and femoral-popliteal vascular systesm. In 1967 Favaloro introduced the saphenous vein as a means for bypassing local obstructions in diseased coronary arteries of human subjects. Since the advent of the aorto-coronary saphenous vein bypass graft procedure several studies have reported pathologic alterations of these grafts at post-mortem examination or at the time of re-operation. Other investigators have also noted changes in these venous grafts when they have been implanted in peripheral vessels. We report here a patient with aneruysmal dilations of an aorto-coronary artery saphenous vein bypass graft. Furthermore, possible mechanisms which might produce such venous aneurysms and the clinical significance of such an entity are discussed.
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A case of the solid variant of lobular carcinoma of the breast occurred. The cytologic findings are discussed, with particular reference to the resemblance to non-Hodgkin's lymphoma.