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Biomedical subjects

R W Kelly

Publications and source records attributed to R W Kelly.

At least 127 records · Page 7Linked to original sources
PubMed1986

Release of prostaglandin D2 and histamine in a case of localized heat urticaria, and effect of treatments.

A case of localized heat urticaria in a 70-year-old woman is reported. Increased plasma levels of prostaglandin D2 and blood histamine after heat challenge indicate a role for mast cell degranulation in the pathophysiology of the syndrome. Treatment with astemizole increased the temperature threshold to wealing, but not to itch or erythema. The patient was partially desensitized by repeated exposure to heat and this was further improved by indomethacin. After treatment there was no increase in plasma prostaglandin D2 on challenge. No evidence was found for the activation of the alternative complement pathway.

Aged↗
PubMed1986

Prostaglandin D2 release by endometrium and myometrium.

Prostaglandin D2 (PGD2) release was studied using a superfusion technique in endometrium and myometrium obtained at hysterectomy from 36 women with measured menstrual blood loss (range 4-840 ml). PGD2 was produced by both tissues with greater rates from endometrium. Cyclical changes in release were found only in the endometrium with increased rates during menstruation and the mid-luteal phase. In the myometrium the highest release rates were present during menstruation at the start of the superfusion. No significant correlation was found between menstrual blood loss and endometrial or myometrial PGD2 release.

Adult↗
PubMed1986

The stimulation of prostaglandin production by two antiprogesterone steroids in human endometrial cells.

Endometrial stromal cells and isolated endometrial glands obtained from women during days 6-26 of the ovarian cycle were cultured for 24 h in the presence of the progesterone antagonists 17 beta-hydroxy-11 beta-[4-dimethylaminophenyl]17 alpha-[1-propynyl] estra-4,9-dien-3-one (RU486) and 17 beta-hydroxy-11 beta-[4-dimethylaminophenyl] 17 alpha-[3-hydroxy-1-propenyl]estra-4,9-dien-3-one (ZK 98734). Both steroids stimulated prostaglandin F2 alpha (PGF2 alpha) production by stromal cells in a dose-dependent manner, in doses ranging from 10-1000 nM. Progesterone (100 nM) inhibited RU486 stimulation, except at the highest dose of antiprogestin. PGE2 was produced in smaller amounts than PGF2 alpha, but, when measurable, it also increased in the presence of RU486. In contrast, RU486 did not increase PG production by endometrial glands. In an experiment to determine the effect of pretreatment, stromal cells were incubated for 24 h with 1000 nM progesterone or RU486 (all with 100 nM 17 beta-estradiol) with either 30 or 6 microM arachidonic acid. These six batches of cells were incubated for a second 24 h with either progesterone or antiprogestin. Cells pretreated with the higher dose of arachidonic acid had a marked increase in PGF2 alpha production during the second 24 h only when also pretreated with progesterone. This finding suggests that progesterone allows an accumulation of PG precursor in a suitable accessible pool. Pretreatment with progesterone also allowed a greater conversion of PG to its 13,14-dihydro-15-keto metabolite. These results suggest that antiprogesterone steroids may act as menstrual regulators by: stimulating endogenous PG production within the endometrial stromal cells and inhibiting PG catabolism.

Dinoprost↗
PubMed1986

Changes in the concentration of prostaglandins in preovulatory human follicles after administration of hCG.

The concentrations of prostaglandins F-2 alpha, E, D-2 and 13,14-dihydro-15-keto PGE were measured in follicular fluid collected from women undergoing routine laparoscopy following induction of follicular development with clomiphene and hCG. Laparoscopy was performed before, or at 12, 24 or 36 h after administration of hCG. Prostaglandins were measured as the methyloxime derivative by radioimmunoassay. Peaks in PGE and PGF-2 alpha concentration occurred at 12 and 36 h with a significant nadir at 24 h, whereas PGD-2 production was very low at 36 h. The concentration of PGF-2 alpha rose significantly between 0 and 36 h and was greatest in follicles yielding oocytes, suggesting a possible role for this prostaglandin in the mechanism of follicle rupture.

Body Fluids↗
PubMed1986

Significance of intracellular calcium and cyclic adenosine 3',5'-monophosphate in the mechanisms by which prostaglandins influence human sperm function.

The selective ability of PGE-1 and PGE-2 to enhance the capacity of human spermatozoa for hamster oocyte penetration was dependent upon high concentrations (1.7 mM) of extracellular Ca2+ and a prolonged (4 h) duration of exposure, and insensitive to the Ca2+ channel antagonist, verapamil. Studies with the intracellular calcium indicator Quin-2 indicated that exposure to PGE-1 and PGE-2, but not PGF-2 alpha, induced a significant rise in the levels of cytoplasmic Ca2+, suggesting that an ionophore-like action might be responsible for the ability of the E-series prostaglandins to influence sperm function. Stimulation of oocyte penetration with PGE-1 and PGE-2 was significantly enhanced when these compounds were presented to the spermatozoa in medium of high osmolarity (410 mosmol). A combination of PGE-1 in hyperosmotic medium did not significantly influence sperm function in cases of oligozoospermia, although it was effective with patients exhibiting idiopathic infertility. Exposure to high doses of PGE-1 and PGE-2, but not 19-hydroxy PGE or PGF-2 alpha, also induced a significant rise in the cyclic AMP content of human spermatozoa. This effect did not appear to be involved in the enhancement of fertilization rates because it did not exhibit the same absolute dependence on high levels of extracellular Ca2+ as did the fertilization responses and the enhancement of oocyte penetration and the elevation of cAMP were independent of each other within the patient population.

Alprostadil↗
PubMed1985

Prostaglandins in the human uterus: an interaction between endometrium and myometrium.

The interaction between the prostaglandin production of the human endometrium and myometrium has been further investigated using intact pieces of endometrium in homogenates of myometrium. There was an increase in the production of 6 oxo PGF, alpha when these tissues were incubated together, whereas there was no change in the production of PGE, PGF2 alpha or 13, 14 dihydro 15 - keto PGF2 alpha. This endometrial - myometrial interaction could have important implications in the pathogenesis of menorrhagia.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Analysis of the direct effects of prostaglandins on human sperm function.

Time-exposure photomicrography and interspecies in-vitro fertilization procedures have been used to examine the influence of prostaglandins on human sperm function. An analysis of variance indicated that the presence of PGs in the incubation media was associated with a significant increase in sperm velocity and the frequency of sperm head rotation, although there were no differences between individual PGs in the degree of stimulation observed. Changes in the penetrating ability of human spermatozoa were detected after exposure to PGs, particularly PGE-1 and PGE-2. PGE-2 induced a sustained increase in penetration rates at all doses of greater than 8.4 micrograms/ml, while exposure to PGE-1 gave a bell-shaped dose-response curve which exhibited a peak between 8.4 and 33.3 micrograms/ml and progressively fell to reach control levels at the maximum concentration tested of 270 micrograms/ml. A combination of PGE-2 and PGE-1 produced a dose-response curve similar to that for PGE-1 alone, while exposure to PGF-2 alpha was without effect. Seminal extracts containing predominantly 19-hydroxy PGE-1, or equal amounts of 19-hydroxy PGE-1 + 2 induced a slight, but significant, rise in penetration rates while a combination of PGs representing the major components of human seminal plasma was without significant effect. We conclude that certain prostaglandins may have a direct action on the functional competence of human spermatozoa.

Alprostadil↗
PubMed1984

N-acetyl-5-methoxy kynurenamine, a brain metabolite of melatonin, is a potent inhibitor of prostaglandin biosynthesis.

Although the hypothesis that melatonin may act by inhibiting prostaglandin synthesis arose in part from the similar structures of melatonin and indomethacin, melatonin does not share the in vitro efficacy of indomethacin in inhibiting prostaglandin synthesis. One possibility is that a metabolite of melatonin formed within the target cell might inhibit prostaglandin synthesis and in this study we have tested this by examining the action of the two oxidised metabolites, N-formyl-N-acetyl-5-methoxy kynurenamine formed by the action of indole 2,3-dioxygenase and N-acetyl-5-methoxy kynurenamine , formed in the brain by the action of formamidase . This latter compound which has a structure resembling the fenamate inhibitors of PG biosynthesis had a marked and time dependant inhibiting effect in synthesis using bovine and ovine seminal vesicle microsome preparations and measuring the products by using (1-14C) arachidonic acid and by using a specific antiserum for PGE methyl oxime.

Animals↗
PubMed1984

The catalytic cycle of cytochrome P-450scc and intermediates in the conversion of cholesterol to pregnenolone.

Cytochrome P-450scc as isolated is a cholesterol-depleted low-spin haemoprotein; addition of cholesterol results in formation of a high-spin complex. Cytochrome P-450scc--cholesterol is a one-electron acceptor on titration with NADPH. Cytochrome P-450scc--cholesterol can be anaerobically reduced to the ferrous state which, on oxygenation, forms an oxygenated cytochrome P-450scc--cholesterol complex. This oxygenated complex in the absence of adrenodoxin autoxidises to ferric cytochrome P-450scc--cholesterol without oxidation of cholesterol. The decay of the oxygenated complex is first-order, k = 9.3 X 10(-3) S-1 at 4 degrees C. The rate of autoxidation is influenced by pH, ionic strength and the chemical nature of bound sterol. The activation energy of autoxidation is 75 kJ mol-1. Addition of equimolar amounts of adrenodoxin to cytochrome P-450scc--cholesterol followed by stoichiometric reduction under anaerobic conditions and subsequent oxygenation, allows single catalytic turnover cycles of cytochrome P-450scc to be observed. This has led to detection of intermediates in the conversion of cholesterol to pregnenolone and a precursor/product sequence of cholesterol----22-hydroxycholesterol----20,22-dihydroxy-cholesterol ----pregnenolone has been established. Addition of oxidised adrenodoxin to oxygenated cytochrome P-450scc--cholesterol results in formation of 22-hydroxycholesterol.

Adrenal Cortex↗
PubMed1984

The relationship between menstrual blood loss and prostaglandin production in the human: evidence for increased availability of arachidonic acid in women suffering from menorrhagia.

In this study we have obtained endometrium and myometrium from women whose menstrual blood loss had been measured objectively. Samples of tissue were snap frozen in liquid nitrogen for the estimation of PG content and tissue was homogenized and incubated with and without added arachidonic acid. PGE, PGF2 alpha and 6-oxo PGF1 alpha were measured by gas chromatography - mass spectometry. We confirm that the F2 alpha/E2 ratio in the snap frozen samples was significantly lower in women with a high blood loss although this was not reflected in the production by incubated homogenates. Incubation of endometrial tissue with myometrium from the same patient and with a pool of myometrium showed that the source of myometrium was not important. This suggests that previous observations of increased 6 oxo F1 alpha production in incubations of endometrium and homologous myometrium from women with high MBL, resulted from differences in endometrium. When prostaglandin E and F production by endometrium is studied there is a significant inverse correlation between the percentage difference in production with and without added arachidonic acid and menstrual blood loss which suggests that women with high MBL have relatively high levels of available arachidonic acid in their endometrium.

Arachidonic Acid↗
PubMed1984

Prostaglandins in human mammary cancer.

Prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha) were measured by Gas Liquid Chromatography-Mass Spectrometry (GLC-MS) in extracts of 100 human mammary carcinomas. All tumours contained measurable amounts of both prostaglandins but wide variations between individual tumours were observed. Values for PGE2 ranged from 7 to 762 ng g-1 tissue with a median of 100 ng g-1 tissue. Values for PGF2 alpha ranged from 3 to 475 ng g-1 tissue (median 60 ng g-1 tissue). There was a highly significant positive correlation between amounts of the 2 prostaglandins in individual tumours. Amounts of both PGE2 and PGF2 alpha were not significantly related to the menopausal status of the patients or the presence of oestrogen and progesterone receptors.

Breast Neoplasms↗
PubMed1984

Postmenopausal ovarian follicle cyst: an unusual cause of estrogen excess.

Six years after menopause, a 61-year-old woman complained of enlarging, tender breasts. The serum follicle-stimulating hormone level was 62 mIU/ml; the serum estradiol value was 91 pg/ml; and challenge with progesterone, 100 mg i.m., induced withdrawal bleeding. Histologic examination of a hysterectomy with bilateral salpingo-oophorectomy specimen showed proliferative endometrium and an involuting, luteinized follicle cyst of the left ovary. A follicle cyst causing symptomatic hyperestrogenism after a menopause documented by biochemical tests has not been previously reported.

Estrogens↗
PubMed1983

Experience with the carbon dioxide laser in gynecologic microsurgery.

The value of the carbon dioxide laser in gynecologic microsurgery remains controversial. Initial reports on the success of the laser in infertility surgery were not supported by substantial patient data. The majority of researchers involved with laser microsurgery agree that the technique has numerous advantages, including excellent hemostasis, decreased tissue destruction, exacting precision of dissection and shortened operating time. There are, however, relatively small numbers of patients treated with this modality who have been followed up for a sufficient period of time to determine the ultimate effect the laser will have on pregnancy rates. Since our first laser microsurgical procedure in November, 1980, we have performed more than 150 such procedures. The procedures have included neosalpingostomy, tubal reanastomosis, vaporization of adhesions, and removal of endometriosis. The technique is safe as shown by the absence of any laser-related complication in our cases. We now have 69 patients who have been followed up for more than 1 year since the time of the procedure. The following work is a presentation of pregnancy data and patency rates from this patient group. These results are presented in an effort to offer some objectivity to the comparison of laser microsurgery and standard microsurgery.

Adult↗
PubMed1983

The measurement of 13,14-dihydro-15-keto prostaglandin E2 by combined gas chromatography mass spectrometry.

THe main metabolite of prostaglandin E2 (PGE2) 13,14-dihydro-15-keto-PGE2 readily dehydrates and can subsequently form a cyclic derivative. This problem can be overcome by the immediate formation of oximes of the 9 and 15 ketones in aqueous solution followed by subsequent extraction, methylation and t-butyldimethyl silylation of the free hydroxyl groups at 11 and on the oximes. Deuterogenated 13,14-dihydro-15-keto-PGE2 is used as the internal standard and can be stored as the oxime and added with the oximating solution immediately the biological sample is obtained. The sensitivity of the method allows measurement of 2 ng of 13,14-dihydro-15keto-PGE2 in tissue incubates. The intra-batch precision is 11.8% and the inter-batch precision for measurement of 100 ng of metabolite is 8.1%.

Dinoprostone↗
PubMed1983

Is prostaglandin F2 alpha involved in the increased myometrial contractility of primary dysmenorrhoea?

The concentrations of prostaglandin F2 alpha (PGF2 alpha) and E2 (PGE2) in menstrual fluid collected daily from 13 women with primary dysmenorrhoea and 11 matched controls, were compared with the pattern of uterine contractility during the hour following the menstrual fluid collection. The intra-uterine pressure (IUP) was measured using a micro-transducer catheter and the tracings analysed. On Day 2 the concentration of PGF2 alpha correlated with the peak area, but not with amplitude, duration or rate of contraction. These findings add additional support to the hypothesis that increased production of PGF2 alpha could contribute to the increased uterine contractility in primary dysmenorrhoea.

Dinoprost↗
PubMed1983

Copper and zinc inhibit the metabolism of prostaglandin by the human uterus.

Prostaglandins (PGs) have often been cited as intermediates in the action of the inert and copper-bearing intrauterine contraceptive device (IUD). Although investigations have shown an effect of copper at high (approx. 1 x 10(-4) mol/l) concentrations on PG synthesis, little consideration has been given to the possible effects of copper on PG metabolism. In this study the effect of copper and zinc ions on PG metabolism by human endometrium and myometrium has been investigated using radiolabel techniques together with gas chromatography mass spectrometry (GCMS) measurements of metabolites of PGE2. These experiments showed that concentration of 1 X 10(-5) mol/l of copper and zinc were sufficient to inhibit significantly (P less than 0.01) PGE metabolism. These levels of copper are within the physiological range of levels thought to be present in the uterine tissue and fluid of wearers of the copper-containing IUD and the inhibition of PG metabolism in these women might account for the small but significant decrease in the length of the luteal phase of their menstrual cycles.

Adult↗
PubMed1983

Primary dysmenorrhoea: the importance of both prostaglandins E2 and F2 alpha.

Menstrual fluid was collected in a contraceptive diaphragm from 16 women with primary dysmenorrhoea and 12 matched control subjects without dysmenorrhoea. Prostaglandins F2 alpha (PGF2 alpha), E2 (PGE2) and 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) were extracted and measured using gas-chromatography: mass spectrometry (GC:MS). The concentrations of both PGF2 alpha and PGE2 were higher on days 1 and 2 in the dysmenorrhoea group than in the control group and the concentration of PGF2 alpha was higher on day 1 than on day 2 in the dysmenorrhoea group. The concentrations of 6-oxo-PGF1 alpha (the stable metabolite of PGI2) were low in both groups. These results confirm suggestions that PGF2 alpha is important in the aetiology of dysmenorrhoea and also indicate that PGE2 may be involved.

6-Ketoprostaglandin F1 alpha↗