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Biomedical subjects

W C Yu

Publications and source records attributed to W C Yu.

At least 109 records · Page 6Linked to original sources

Tamoxifen stimulates human papillomavirus type 16 gene expression and cell proliferation in a cervical cancer cell line.

The widely adopted use of tamoxifen as a chemotherapeutic agent is primarily based on its inhibition of cancer cell growth. However, we report that tamoxifen at low concentrations (10(-9) and 10(-11) M) causes stimulation of cell proliferation in a cervical cancer cell line, SFR. The facts that SFR cells do not contain estrogen receptors and are estrogen nonresponsive imply the existence of an antiestrogen-specific binding protein and suggest that the effect of tamoxifen is possibly mediated through a pathway other than estrogen receptors. Tamoxifen at low concentrations stimulated human papillomavirus type 16 (HPV-16) gene transcription and E7 protein production. Levels of HPV-16 mRNA and E7 protein reached a peak at approximately 2-4 h after tamoxifen treatment, persisted for several hours, and subsequently decreased to their prestimulation levels by about 24 h after treatment. Our results indicate for the first time that tamoxifen stimulates cell proliferation of cervical cancer cells, and we suggest that the enhanced HPV-16 mRNA and E7 protein levels are probably responsible.

Cell Division↗

Characterization of progesterone receptor subunits in breast cancer cell line, CAMA-1N.

In order to study whether cytosolic progesterone receptor (PRc) is involved in progesterone-induced proliferative arrest of breast cancer cells (CAMA-1N), subunit composition of PRc in these cells was characterized. In the TSK G3000 high-performance liquid chromatography (HPLC) column, molybdate-stabilized PRc eluted as a single sharp peak immediately following the void volume. PRc from this peak had a sedimentation coefficient of 7.6 S and was eluted at 0.22 M salt from a linear gradient (0.1 to 0.4 M NaCl) in a DEAE column. When covalently labeled with [3H]R5020, analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and visualized by fluorography, PRc from crude cytosol exhibited two major protein bands with molecular weights of 105 +/- 2.1 and 83 +/- 3.2 kD, respectively. However, HPLC-purified PRc showed only one major band of 105 kD. These results show that PRc in CAMA-1N cells has steroid-binding components similar to other target tissues and provides a basis for further quantitative and qualitative analyses of PRc during cell proliferation and progesterone-induced growth arrest of CAMA cells.

Breast Neoplasms↗

Cytosolic progesterone receptors in the oviducts of reproductively active and quiescent turkeys (Meleagris gallopavo).

Cytosolic progesterone receptors (PRcs) from the reproductive tract of the female turkey were analyzed by high-performance liquid chromatography using a diethylaminoethyl (DEAE) ion-exchange column. PRcs from oviduct tissue of laying, incubating, photorefractory and short-day turkey hens were compared. In general, three types of PRcs were identified: Receptor I, a partially displaceable species that was eluted at a 0.13 M salt concentration; and Receptors II and III, which were two specific binding species eluting at 0.23 M and 0.26 M, respectively. In the subdivided tissue from the laying hen oviduct, Receptor I was the major PRc species of the isthmus and Receptor III was the only receptor present in the uterus. The infundibulum and magnum each contained a small amount of Receptor II and a substantial amount of Receptor III. The whole oviduct of incubating hens contained a greater proportion of Receptor I than Receptor II or III, and these last two receptor types were present in equal quantity. The whole oviduct of the short-day hens had an equal distribution of the three receptor types. In the presence of sodium molybdate, an inhibitor of phosphatase and protease, only one sharp Receptor II species was seen in the magnum and uterus of the laying hen oviduct and in the whole oviducts of incubating and short-day hens. The transformation of Receptor II to Receptor III in the absence of sodium molybdate was facilitated by the aging of cytosol at 0-4 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mechanism of action of L-leucyl-glycinamide and its effect on Parkinson's disease.

PLG potentiates the action of levodopa in 6-OH-DA-treated rats. PLG plus levodopa is more effective than levodopa alone. PLG-treated rats have a decreased concentration of Leu-enkephalin in the caudate nucleus as compared with the control. Preliminary results of using PLG (400 mg/day) for 10 days for treating PD are satisfactory. The mode of action of PLG with relation to dopamine-enkephalin interaction is discussed.

Aged↗

Cytoplasmic estrogen and progesterone receptors as prognostic parameters in primary endometrial carcinoma.

Eighty-six cases of primary endometrial carcinoma were assayed for the presence or absence of cytoplasmic estrogen and progesterone receptors by the saturation point dextran-coated charcoal assay. The levels of cytoplasmic progesterone receptors and estrogen receptors were analyzed according to clinical stage, histologic type and grade of the tumor, presence or absence of lymph node metastases, myometrial invasion, and survival. The cases were divided into positive and negative receptor groups with levels chosen of greater than 10 fmol/mg of cytosol protein for progesterone receptor and 5 fmol/mg of cytosol protein for estrogen receptor as discrimination points. Statistically significant survival differences were found between estrogen receptor positive versus estrogen receptor negative patients, progesterone receptor positive versus progesterone receptor negative patients, and estrogen positive-progesterone receptor positive versus estrogen negative-progesterone receptor negative patients. Mean cytoplasmic estrogen and progesterone receptor levels were inversely proportional to grade. This report suggests that treatment protocols should be devised to reflect the prognostic significance of receptor status.

Adenocarcinoma↗

Plasma nitroglycerin concentrations and hemodynamic effects of sublingual, ointment, and controlled-release forms of nitroglycerin.

After a sublingual test dose, 12 healthy men aged 21 to 29 yr were treated with controlled-release transdermal nitroglycerin skin patches designed to deliver 10 mg/day nitroglycerin and with nitroglycerin ointment (2%) (1-in amount from the tube spread over 50 cm2) for 24 hr in a double-blind crossover study. Assessment was by measurement of nitroglycerin in plasma, blood pressure, and pulse rate. The mean plasma concentration of nitroglycerin during ointment dosing was approximately 200% to 400% that during skin patch dosing. Levels during ointment dosing were closer to those from sublingual dosing than were those during skin patch dosing. Blood pressure and pulse rate changes were much the same during both transdermal treatments. Calculations showed that delivery of nitroglycerin from the skin patches would have to be over 40 to 80 cm2 of the skin to achieve nitroglycerin exposure of the order of that induced by 1 in of ointment spread over 50 cm2 or from sublingual dosing.

Administration, Oral↗

A new Thermal Energy Analyzer for direct high-performance liquid chromatographic and gas chromatographic analysis of N-nitrosamides.

The Thermal Energy Analyzer (TEA) has been modified to make it capable of detecting compounds such as N-nitrosamides. This modified TEA(amide) can be used with both gas chromatography (GC) and high-performance liquid chromatography (HPLC). Analysis of underivatized N-nitroso amides by GC-TEA(amide) and HPLC-TEA(amide) are also described.

Chromatography, Gas↗

Two classes of estrogen receptors which differ in their activation mechanisms.

Studies on the mechanism of activation of estrogen receptor (ER) have led us to identify two classes of receptors. Effect of molybdate on the activation of ER was determined by their affinity for nuclei or DNA-cellulose. Molybdate caused inhibition of nuclear binding with rat uterine ER, but an increase in the binding was observed with rabbit uterine ER. Similar results were observed when DNA-cellulose was used instead of nuclei. To further test the diversity in ER activation, DNA-cellulose binding of ER from 10 primary breast cancer tissues was determined in the presence or absence of molybdate. ER from 8 tissues showed inhibition of binding, one showed an increase, and one was not affected by molybdate. These results indicate the presence of two classes of ER, one whose activation is inhibited by molybdate and another whose activation is either unaffected or stimulated by molybdate. Other differences between rat and rabbit uterine ER are also discussed.

Animals↗

Cytoplasmic estrogen and progesterone receptors in primary cervical carcinoma: clinical and histopathologic correlates.

From 1977 to 1981, 39 cases of primary cervical carcinoma were assayed for the presence or absence of cytoplasmic estrogen (ERc) and progesterone (PRc) receptors by a saturation point dextran-coated charcoal assay. The levels of ERc and PRc were compared with clinical stage, histologic type, histologic grade, menstrual status, age, and survival. Carcinomas were divided into positive and negative receptor groups with the use of greater than 5 fmol/mg of cytosol protein for ERc and 10 fmol/mg of cytosol protein for PRc as discrimination points. Survival of the patients studied was computed by means of the product-limit analysis according to Kaplan-Meier. A statistically significant difference in survival in the PRc + group versus the PRc - group in the total group of patients was noted with the Mantel-Cox test (P = 0.049). When patients were stratified according to menopausal status, a statistically significant difference in survival was noted between the PRc + group versus the PRc - group in the premenopausal patients only.

Adenocarcinoma↗

Examples of constant mean curvature immersions of the 3-sphere into euclidean 4-space.

Mean curvature is one of the simplest and most basic of local differential geometric invariants. Therefore, closed hypersurfaces of constant mean curvature in euclidean spaces of high dimension are basic objects of fundamental importance in global differential geometry. Before the examples of this paper, the only known example was the obvious one of the round sphere. Indeed, the theorems of H. Hopf (for immersion of S(2) into E(3)) and A. D. Alexandrov (for imbedded hypersurfaces of E(n)) have gone a long way toward characterizing the round sphere as the only example of a closed hypersurface of constant mean curvature with some added assumptions. Examples of this paper seem surprising and are constructed in the framework of equivariant differential geometry.

Journal Article↗

Variation of cytoplasmic content of estrogen and progesterone receptors in the mammary gland and uterus of rats at time of parturition.

The cytoplasmic content of estrogen and progesterone receptors (ERc and PRc) was measured in the rat uterine and mammary tissues during the period from late pregnancy through lactation. Uterine ERc and PRc, which sedimented at the 8S and 4S regions, respectively, of a 5-20% sucrose gradient, showed similar rise and decline patterns before and after parturition. Following a decline from the 15th day (114 +/- 13.7 fmol/mg protein) to the 20th day of pregnancy (57.7 +/- 10.2 fmol/mg protein), ERc levels increased almost 2.5-fold at the time of parturition. A decrease to the predelivery level by 24 h post-delivery was followed by a steady increase to 270.6 +/- 46 fmol/mg protein by 15 days of lactation. Uterine PRc levels also showed a peak similar to that of ERc at the time of parturition (24.3 +/- 1.1 fmol/mg protein). The level of ERc in mammary gland 6 h postpartum was the lowest (1.5 +/- 0.3 fmol/mg protein) and during the first 10 days of lactation ERc levels were maintained at about 10 fmol per mg of cytosol protein. Results herein suggest that levels of these steroid receptors may be hormonally regulated and that the uterus and mammary gland may have a different sensitivity to these regulatory control mechanisms. The physiological significance in the variation of these receptors in conjunction with the onset of parturition is discussed.

Animals↗

Effects of 17 beta-estradiol on progesterone receptors and the uptake of thymidine in human breast cancer cell line CAMA-1.

Two sublines, CAMA-1R and CAMA-1N, were derived from the original CAMA-1 cells after continuous passages in our laboratory. 1R cells were supplemented in culture with estradiol and retained the properties of the original cell line, whereas 1N cells, not supplemented with estradiol, had a partial loss of estrogenic responsiveness. The doubling times for 1R and 1N cells were 2 and 2.4, respectively. These two sublines showed different effects on thymidine uptake after estradiol stimulation. Cells of 1R had a 2-fold greater thymidine incorporation than did the control without estradiol. In contrast, no difference of thymidine uptake was demonstrated in cells of 1N in the presence or absence of estradiol. Both cell lines contained cytoplasmic progesterone receptors with a Kd of 0.56 nM and a sedimentation coefficient of 6 to 7S on a 5 to 20% sucrose gradient. The progesterone receptor level in 1N was about 8-fold higher than in 1R cells. Both sublines exhibited a dose-dependent increase in progesterone receptor levels in response to estradiol with the maximal stimulation (8-fold increase) reached by using 5 nmol of estradiol. The rate of increase for estradiol-induced progesterone receptor appears to be the same for both sublines; a liner increase was demonstrated between Days 3 and 7 following plating. Our results show that estrogen regulation of thymidine uptake and progesterone receptor induction may be mediated through two separate mechanisms. Thus, following a chronically deficient supply of estradiol to 1N cells, there is apparent loss of responsiveness to estradiol-induced thymidine uptake, but the ability of these cells to respond to estradiol induction of progesterone receptor was retained.

Biological Transport↗

Infertility in the turkey. I. Effects of anti-sperm immune globulins on fertilizing ability of turkey spermatozoa.

Two experiments were conducted to study the effects of globulins, isolated from sera of turkey hens immunized against semen, on the fertilizing ability of spermatozoa and the hatchability of eggs. Sperm were incubated in sera from hens immunized against semen and in sera from non-immunized hens as well as in globulin solutions isolated from these various sera. In neither experiment did sera from control hens or gamma globulins isolated from their sera affect the fertilizing ability of sperm. In contrast, all sera from immunized hens drastically reduced the fertilizing ability of sperm. In Experiment 1, .75% gamma globulin solutions from two hens did not depress fertility but a 1.5% solution from one of the immunized hens significantly (P less than .05) reduced it. In this experiment none of the treatments had a significant effect on hatchability. Antisemen globulin solutions of 2.25 and 4.50% from 12 hens significantly reduced the fertilizing ability of sperm in dose related fashion. The higher of the two levels suppressed it to the level of whole sera. Hatchability of fertile eggs was significantly reduced by the anti-semen sera and globulins isolated from it in the second experiment.

Animals↗

Infertility in the turkey. III. Effects of sera from sterile and fertile females on the fertilizing ability of spermatozoa.

In an attempt to understand the cause for spontaneous infertility in female turkeys, sera were obtained from a flock suffering this condition. These sera, from hens of known fertility, were tested for anti-fertility actions by incubating semen in them. After incubation, semen was inseminated into unrelated recipient hens. In the first of two experiments, semen incubated in sera from high fertility hens (average 89%) produced a fertility level of 72.7% over an 8 week period while semen incubated in sera from sterile hens significantly reduced fertility to 52.3%. In a second experiment sera from sterile donors again caused a significant reduction in the fertilizing ability of sperm (56.3% for sera from sterile hens vs. 73.5% for sera from high fertility hens). These results indicate the presence of a factor(s) in the sera of sterile hens which may be causally related to their infertility.

Animals↗