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Biomedical subjects

R W Kelly

Publications and source records attributed to R W Kelly.

At least 109 records · Page 6Linked to original sources
PubMed1988

Dietary linoleic acid, gastric acid, and prostaglandin secretion.

Basal and pentagastrin-stimulated gastric acid secretion, fasting serum gastrin concentrations, and the gastric output of prostaglandin E and its major metabolite 13,14-dihydro 15-keto prostaglandin E2 were measured in 9 normal subjects before and after 14-20 days of dietary supplementation with linoleic acid. Mean maximal gastric acid output fell from 36.0 +/- 3.3 (SEM) to 30.1 +/- 2.9 mmol/h (p less than 0.05), although mean basal acid output was not significantly affected (8.3 +/- 2.1 and 7.2 +/- 1.7 mmol/h, respectively). Mean fasting serum gastrin concentrations increased from 19.2 +/- 3.1 to 30.9 +/- 3.8 ng/L (p less than 0.01) after linoleic acid, probably because of acid suppression. The mean output of prostaglandin E increased from 498 +/- 110 to 1254 +/- 465 ng/h (p less than 0.05); that of its metabolite increased from 165 +/- 18 to 1168 +/- 645 ng/h (p less than 0.01). These findings show that in normal subjects essential fatty acid weakly inhibits gastric acid secretion, but considerably increases gastric prostaglandin output.

Adult↗
PubMed1988

The release of PGF2 alpha and PGE2 from separated cells of human endometrium and decidua.

The capacity of separated glandular and stromal cells from endometrium and first trimester decidua to release prostaglandins (PGs) was studied over 48 hours in culture. Glandular preparations released more PGs than stromal preparations in all tissues. Stromal release of PGs did not alter throughout the cycle or in early pregnancy but the capacity of glandular preparations to release PGs varied considerably. Proliferative glands released most PGF2 alpha and PGE2 followed by secretory glands and decidua. Histamine (10(-5)) stimulated PG release from endometrial and decidual glands but the response of proliferative glands was greatest. Actinomycin D stimulated release of PGF2 alpha and PGE2 from glandular cells of secretory endometrium and decidua. These results suggest that in vitro release of PGs is suppressed after ovulation and is in part due to inhibition of PG release by a protein or proteins synthesized in the glandular fraction of secretory endometrium or decidua.

Dactinomycin↗
PubMed1988

Effects of preovulatory tamoxifen in regularly cycling women on folliculogenesis, oocyte recovery and luteal function.

Forty women undergoing elective sterilization and oocyte donation were randomized in a trial to study the effects of administration of 30 mg of tamoxifen 12 h before injection of human chorionic gonadotrophin and 48 h before oocyte capture. Cycles were regulated for advanced operative scheduling with norethisterone given in the luteal phase of the previous cycle and 150 mg of clomiphene given in the early follicular phase of the recovery cycle. Tamoxifen cycles showed a delay of peak urinary oestrone excretion by 2 days, associated with a slight decrease in total excretion. Tamoxifen administration lengthened treatment cycles by 0.5 days and the luteal phase by 0.4 days. The urinary excretion peak of pregnanediol was 3 days later than in controls. Total pregnanediol excretion was slightly elevated. There were no differences in oocyte recovery rate although cleavage rate was decreased (0.84 versus 0.65, not significant at P greater than or equal to 0.05). Intrafollicular oestradiol levels were similar (794 +/- 97 versus 735 +/- 102 ng/ml). Intrafollicular progesterone levels were marginally lower in tamoxifen cycles (3.5 +/- 0.5 versus 2.3 +/- 0.8 micrograms/ml).

Adult↗
PubMed1988

Effect of platelet-activating factor on the release of PGF-2 alpha and PGE-2 by separated cells of human endometrium.

Synthetic platelet-activating factor (PAF-acether, 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine) caused a dose-dependent increase in the synthesis of prostaglandin (PG) E-2 by an enriched glandular, but not stromal, fraction of human endometrium removed in the secretory phase of the menstrual cycle. PAF-acether did not alter the synthesis of PGF-2 alpha by this fraction and consequently there was a significant reduction in the ratio of the amounts of PGF-2 alpha/PGE-2 released by the cells into the culture medium. The preimplantation human embryo secretes PAF, and these findings may have relevance to the local maternal recognition of pregnancy.

Cells, Cultured↗
PubMed1987

The effect of estradiol-17 beta and actinomycin D on the release of PGF and PGE from separated cells of human endometrium.

Estradiol-17 beta selectively stimulated the release of PGF from separated glandular but not stromal cells of human secretory endometrium (p less than 0.025) but had no effect on PGF release from either type of cells obtained from proliferative endometrium. PGE release was not affected by estradiol-17 beta. Actinomycin D did not antagonise the effect of estradiol-17 beta on PGF release from secretory, glandular cells. Basal release of PGF from these cells was stimulated by actinomycin D alone (100 ng/ml) (p less than 0.025) and PGE release stimulated in the presence of estradiol-17 beta. Actinomycin D had no effect on PGF or PGE release from proliferative endometrium. These findings suggest that estradiol-17 beta stimulates PGF release by a mechanism that does not affect PGE release and which is not dependent on the synthesis of new protein. The basal release of PGF and PGE by glandular cells of secretory endometrium in vitro is regulated by protein/proteins which reduce PG release.

Cell Separation↗
PubMed1987

Glucocorticoids do not share with progesterone the potent inhibitory action on prostaglandin synthesis in human proliferative phase endometrium.

The action of progesterone and glucocorticoids on human proliferative phase endometrium has been investigated using isolated fragments of endometrium cultured for 2 to 3 days. The action of progesterone (200-500 nM) in this system is to reduce prostaglandin F (PGF) production by 93 to 96%. This inhibition is considerably greater than the inhibitions observed using collagenase dispersed stromal or glandular cells. The addition of arachidonic acid (5 micrograms/ml) increased the production of the control wells but did not overcome the inhibitory effect of progesterone. When endometrial fragments were cultured for 48 hr in the presence of progesterone and subsequently homogenized and incubated, there was no difference in PG production between the progesterone treated tissue and the controls. In a separate series of experiments the effect of progesterone (500nM) was compared with cortisol (500nM) and the synthetic glucocorticoid dexamethasone (100nM) this dose of progesterone gave a 96% reduction in PGF synthesis but neither cortisol nor dexamethasone inhibited PGF production.

Arachidonic Acid↗
PubMed1987

The effects of danazol, mefenamic acid, norethisterone and a progesterone-impregnated coil on endometrial prostaglandin concentrations in women with menorrhagia.

The effects of four medical treatments have been assessed on menstrual blood loss (MBL) and endometrial prostaglandin (PG) concentrations in 30 women with objectively confirmed menorrhagia. Patients were randomly treated with danazol, 200 mg daily (n = 6), mefenamic acid, 500 mg three times daily during menses (n = 8), norethisterone, 5 mg twice daily from day 15-25 of the cycle (n = 8) or a progesterone-impregnated coil releasing 65 micrograms progesterone daily (n = 8). Endometrial biopsies were obtained in the mid-luteal phase before and after treatment in 23 cases, and assayed for PG content using radioimmunoassay. Treatment with norethisterone had no effect on either MBL or the concentration of PGs in the endometrium. MBL was significantly reduced after treatment with mefenamic acid (P = 0.05, n = 6) and the progesterone coil (P less than 0.05, n = 6), and was reduced in each of 4 cases treated with danazol in whom endometrial biopsies were available. Although there was no consistent change in endometrial PG concentrations in either the mefenamic acid or danazol groups, the lower MBL after insertion of the progesterone coil was associated with a reduced endometrial content of PGE, PGF2 alpha and "total" PG (6oxo PGF1 alpha + PGE + PGF2 alpha)-P = 0.05. Whereas the cyclooxygenase inhibitor mefenamic acid is likely to exert its effect on endometrial PGs at the time of menstruation itself, the continuous administration of progesterone throughout the menstrual cycle could result in both an impairment in estrogen receptor generation leading to reduced estrogen-mediated cyclooxygenase activity, and an increase in endometrial PG metabolism.

Biopsy↗
PubMed1987

Progesterone and antiprogestins, a comparison of their effect on prostaglandin production by human secretory phase endometrium and decidua.

The mechanism by which progesterone inhibits PG production is not clear. In systems using isolated human endometrial fragments, progesterone has been shown to inhibit PG production markedly. We have used such a system to test the action of two antiprogesterone steroids RU486 (Roussell-Uclaf) and ZK98734 (Schering) on isolated human endometrial and decidual tissue, with and without added progesterone. Progesterone (200 nM) reduced PGF2 alpha production by the secretory phase endometrium from 10.9 ng/mg tissue/24 hr to 1.9 ng/mg/24hr on the third day of culture (p less than .01) and this effect was antagonised by the addition of either 200 nM RU486 or 200 nM ZK98734 (6.3 and 7.2 ng/mg/24 hr respectively). The antiprogestins on their own showed a slight inhibitory effect on day 3 and RU486 treatment resulted in a significant (p less than .05) decrease in PG production from control. PGE and the main 13,14-dihydro-15-keto metabolites of E and F were also significantly decreased by progesterone and restored by the antiprogestins. The PG production by decidua increased on days 2 and 3 in response to progesterone + antiprogestins but this was not significant. This data shows that the inhibition of PG production shown by progesterone, acting on secretory phase endometrium cultured as tissue fragments, is reversible by the receptor blocking antiprogestins.

Adult↗
PubMed1987

Endometrial prostaglandins in women with abnormal menstrual bleeding.

Endogenous prostaglandin (PG) concentrations (6oxo PGF1 alpha, PGE, PGF2 alpha) have been measured by radioimmunoassay in the endometrium of women with objectively assessed menstrual blood loss (MBL). The concentration of PGE and "total" PG (6oxo PGF1 alpha + PGE + PGF2 alpha) was greater in the endometrium of those women with heavy menses (median MBL 152 ml (range 86,432) n = 16) than in those individuals with a normal menstrual loss (MBL 59 ml (18,78) n = 18). The concentrations of PGE and PGF2 alpha were similar in each group, but the concentration of 6oxo PGF1 alpha was significantly less than that of both PGE and PGF2 alpha. In 19 individuals, specimens of endometrium were incubated for 1 and 2 hours in modified 199 medium to assess PG release. There was a direct correlation between endogenous PG content and the production of 6oxo PGF1 alpha, PGE, PGF2 alpha and "total" PG in the first hour, which persisted for the second hour with PGF2 alpha and "total" PG. Endometrial PGs may play a role in the mechanism underlying menstruation; however the observed relationship between the prostanoids and MBL will vary with different experimental methods.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Evaluation of the 190H analogues of prostaglandins E1, E2, F1 alpha and F2 alpha as specific markers for the identification of human semen in body fluid mixtures.

The specificity of antisera raised against each of the prostaglandin series 190H E1/E2 and 190H F1 alpha/F2 alpha, produced in males, was evaluated by radioimmunoassay. Further, the ability of these antisera to detect semen specific prostaglandins in mixtures of body fluids was examined. Antisera directed against the 190H E1/E2 series cross-reacted with prostaglandin E1 and marginally with E2. Antisera raised to the 190H F1 alpha/F2 alpha series were, however, highly specific to the semen specific prostaglandins 190H F1 alpha/F2 alpha and 190H E1/E2. It was possible to detect picogramme quantities of contaminating 190H F1 alpha/F2 alpha on vaginal swabs taken up to 72 h after intercourse and on vaginal swabs stored at room temperature for up to 2 years. These prostaglandins were not detected on semen free vaginal swabs, in faecal material, saliva, urine or in a sample of human milk (stain). A limited study of casework material is also described. Detection of the 190H F series, as a group, has considerable potential in the identification of human semen at picogramme levels, eliminating the need for alternative chemical tests and extensive microscopic examination.

Body Fluids↗
PubMed1987

Prostaglandins and prognosis in human breast cancer.

Prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha) were measured by gas liquid chromatography--mass spectrometry (glc-ms) in extracts of primary tumours from 78 patients with early breast cancer. These levels have been related to factors of established prognostic value and the patients disease-free interval. Although there was a wide variation in amounts of both prostaglandins extracted from different tumours, no significant relationship was observed between levels of prostaglandins and oestrogen receptors (ER), tumour size, presence of lymph node involvement and disease-free interval following primary treatment. It therefore seems unlikely that the level of these particular prostaglandins within breast carcinomas plays a fundamental role in the prognosis of the disease.

Breast Neoplasms↗
PubMed1987

The effect of the antiprogestins RU 486 and ZK 98734 on the synthesis and metabolism of prostaglandins F2 alpha and E2 in separated cells from early human decidua.

Enriched preparations of glandular and stromal cells were obtained from early human decidua and incubated for 24 h in the presence of two progesterone antagonists, RU 486 (17 beta-hydroxy-11 beta-[4-dimethylaminophenyl]17 alpha-[1-propynyl]-estra-4,9-dien-3-one) and ZK 98734 (17 beta-hydroxy-11 beta-4[4-dimethylaminophenyl]17 alpha-[3-hydroxy-1-propynyl]estra-4,9-dien-3-one) to determine the effect of the antiprogestins on the release of prostaglandin F2 alpha (PGF2 alpha) and PGE2 and their subsequent conversion to 15-keto-13,14-dihydro-PGF2 alpha and 15-keto-13,14-dihydro-PGE2. In the presence of exogenous arachidonic acid (AA, 30 microM), both steroids stimulated PGF2 alpha release by glandular, but not stromal, cells (P less than 0.001) and inhibited the metabolism of PGF2 alpha by the glandular fraction (P less than 0.005 and P less than 0.001 respectively). In the absence of exogenous AA, RU 486 and ZK 98734 stimulated the release of PGF2 alpha from glandular, but not stromal, cells (P less than 0.001 and P less than 0.005, respectively). Neither steroid altered the release or metabolism of PGE2 when the cells were incubated with AA, but both RU 486 and ZK 98734 increased the release of PGE2 by glandular, but not stromal, cells when incubated without AA (P less than 0.005 and P less than 0.001, respectively). Both steroids inhibited the metabolism of PGE2 under these conditions (P less than 0.05). These results suggest that 1) antiprogestins stimulate the synthesis of PGs by glandular cells in early human decidua, but do not alter the synthesis of PGs by stromal cells; 2) this stimulation of PG synthesis involves an effect on cyclooxygenase activity and is not a consequence of increased availability of endogenous AA; 3) the metabolism of PGs by glandular cells is altered by RU 486 and ZK 98734; 4) as RU 486 has greater antiglucocorticoid activity than ZK 98734, these results suggest that both steroids act on decidua by antagonizing endogenous progesterone rather than glucocorticoid activity.

Cells, Cultured↗
PubMed1986

The concentrations of prostaglandins in endometrium during the menstrual cycle in women with measured menstrual blood loss.

The concentrations of PGF2 alpha, PGE2 and 6-oxo-PGF1 alpha were measured in human uterine tissues during the menstrual cycle. The concentrations of all PGs in endometrium were greater than in myometrium. PGF2 alpha, which was found in the greatest concentrations, was high in the mid-secretory phase in both endometrium and myometrium. The concentration of PGE2 did not vary during the menstrual cycle in either tissue. The biosynthetic capacity of endometrium to produce both PGF2 alpha and PGE2 was significantly greater in the mid than the late secretory phase in the presence of exogenous arachidonic acid. Also, in spite of low endogenous concentrations, both endometrium and myometrium were able to produce significant amounts of 6-oxo-PGF1 alpha during a 30 minute incubation. The possible significance of this late secretory decline in the capacity of the endometrium to produce PGF2 alpha and PGE2 is discussed.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Measurement by radioimmunoassay of prostaglandins as their methyl oximes.

Antisera have been raised to the following prostaglandins as their methyl oximes; PGE2, PGD2, 13-14-dihydro-15-oxo PGE2, 13,14-dihydro-15-oxo PGF2 alpha, 6-oxo PGF1 alpha, 6-oxo PGE1 and thromboxane B2. These antisera have good specificity and sensitivity and their use allows the immediate treatment of biological fluids with oximating solution which prevents sample decomposition during storage. A methyl oximating reagent is described which gives greater than 95% conversion of PGs to their methyl oximes by treating samples at 20 degrees C overnight. The use of this reagent allows easy and reliable sample derivatisation prior to assay with the above antisera. Since the antisera (with the exception of that for thromboxane B2) do not recognise the underivatised PG or the oxime (=NOH) form, oxime formation can be carried out in parallel with methyl oxime formation and the oximated portion of the sample can act as a "reference" for the methyl oximated portion, which will allow non specific interference to be recognised.

Antibody Specificity↗
PubMed1986

Production of steroids and release of prostaglandins by spherical pig blastocysts in vitro.

Levels of pregnenolone and progesterone in spherical pig blastocysts (near 4 and 15 microM respectively) exceeded respective levels in histotroph by about 400-fold. When blastocysts were cultured for 5 days in a synthetic medium containing pregnenolone sulfate (1 microM), daily rates of release of pregnenolone, progesterone, androstenedione, testosterone, oestrone and oestradiol were determined to be near 320, 45, 26, 27, 0.8 and 9.2 fmol per blastocyst respectively. Daily outputs of progesterone and testosterone (fmol per blastocyst) diminished (P less than 0.05) to 1.3 and undetectable levels (less than 2) respectively in the presence of Trilostane (94 microM). Increasing the content of pregnenolone sulfate in the culture medium (to 4.5 microM) resulted in higher daily rates of release of pregnenolone and progesterone (to near 1740 and 380 fmol per blastocyst respectively), verifying activity of 3 beta-hydroxy-delta 5-steroid dehydrogenase, and of arylsulfatase, in tissues of intact spherical pig blastocysts. Prostaglandin E2 was the predominant prostaglandin (PG) released by cultured blastocysts (about 1 fmol per blastocyst per hour), hourly rates of release of PGH2 (derived) and PGF2 alpha being near 0.1 and less than 0.06 fmol per blastocyst respectively. The data establish a capacity for spherical pig blastocysts to release a range of steroids and PGs of possible significance to embryonic growth and development in vivo.

Androstenedione↗