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Biomedical subjects

K Hillier

Publications and source records attributed to K Hillier.

At least 37 records · Page 2Linked to original sources
PubMed1988

The secretory characteristics of mast cells isolated from the human large intestinal mucosa and muscle.

The use of a collagenase dispersion technique has allowed us to compare size, histamine content and the secretory characteristics of mast cells from the mucosal and muscle layers of the human large intestine. Mast cells from the mucosa, which constituted 1.8% of the total nucleated cells, contained approximately equal numbers of formalin-sensitive and -insensitive mast cells. Those dispersed from the muscle layer constituted 3.2% of the total nucleated cells and were almost all formalin insensitive. The cells from both layers were similar with respect to size and mean cell histamine content. Anti-IgE released up to 15.1% and 16.5% of total cell histamine in the mucosa and muscle, respectively, with similar concentration-response characteristics. The kinetics of anti-IgE-induced release, however, were different, mucosal mast cells releasing histamine 55 seconds (P less than 0.05) faster than cells dispersed from intestinal muscle. Cells from both layers also released histamine in response to A23187 in a similar concentration-related fashion. Neither mucosal or muscle mast cells released significant amounts of histamine in response to compound 48/80, substance P, morphine, poly-L-lysine or f-met-leu-phe. Our results show intestinal mast cells possess secretory characteristics similar to those of human lung, adenoids and tonsils, but are different from human skin mast cells. The absence of significant histamine release in response to basic secretagogues from either layer of the human intestine contrasts with studies in the rodent intestine. Furthermore it suggests that in human mast cells, histochemical properties, protease content and secretory characteristics may not be closely associated.

Cell Count↗
PubMed1987

Increased arachidonic acid levels in phospholipids of human colonic mucosa in inflammatory bowel disease.

1. Colonic mucosa from 19 patients with ulcerative colitis, eight with Crohn's disease and 14 controls were analysed for arachidonic acid (C20:4), linoleic acid (C18:2), oleic acid (C18:1), stearic acid (C18:0) and palmitic acid (C16:0). 2. Gas-liquid chromatography of lipid extracts showed that arachidonic acid was significantly higher in ulcerative colitis (19 +/- 4) and Crohn's disease (20 +/- 3) than in controls (13 +/- 5 micrograms/mg of protein) (means +/- SD). Neither the degree of inflammation nor treatment with sulphasalazine or prednisolone appeared to influence the fatty acid concentrations. 3. Seventy-five to ninety-five per cent of the arachidonic acid was found in the phospholipid fraction after separation by thin-layer chromatography. There were no significant changes in the concentrations of the other fatty acids measured, although oleic acid was lower in inflammatory bowel disease. The ratios of oleic acid to stearic acid and to palmitic acid were lower in inflammatory bowel disease. 4. The alteration in the fatty acid profile may partly explain the increased synthesis of eicosanoids in colonic mucosa in inflammatory bowel disease.

Adolescent↗
PubMed1987

Effect of human chorionic gonadotrophin and indomethacin on ovulation, steroidogenesis and prostaglandin synthesis in preovulatory follicles of PMSG-primed immature rats.

Immature rats were treated with PMSG followed 56 h later by 10 i.u. hCG. Follicles were removed at intervals after hCG injection. Transient increases in progesterone, testosterone and oestradiol synthesis were first evident 1 h after hCG, but values peaked at 3-5 h and returned to control levels by 10 h. Increased synthesis of PGE-2 and PGF-2 alpha was not evident until 3 h and peaked at more than 10 h after hCG. Ovulation began between 8 and 10 h after hCG and 83% of animals had ovulated within 12 h. Doses of 90 or 1800 micrograms indomethacin given together with hCG substantially inhibited ovulation and PG synthesis, but only the higher dose inhibited the hCG-induced elevation of progesterone and testosterone synthesis; hCG-induced oestradiol synthesis was not affected by either dose of indomethacin. We conclude that the peak of PG synthesis after hCG treatment related closely to the timing of ovulation; the steroidogenic response to hCG was not blocked by doses of indomethacin sufficient to inhibit synthesis of PGE-2 and PGF-2 alpha by more than 80%.

Animals↗
PubMed1987

Inflammatory bowel disease: the in vitro effect of sulphasalazine and other agents on prostaglandin synthesis by human rectal mucosa.

1. Prostaglandin (PG) E2 and F2 alpha synthesis in vitro by human rectal mucosa was significantly greater in patients with Inflammatory Bowel Disease (IBD) than in controls. 2. The addition of 250 microM sulphasalazine (SASP) significantly increased synthesis by rectal mucosa from patients with IBD, (ulcerative colitis and Crohn's disease) and controls after 1 h of incubation in Krebs' solution at 37 degrees C. 3. Flurbiprofen, indomethacin, sodium salicylate and 5-aminosalicylic acid decreased PGE2 and F2 alpha synthesis. 4. Sodium carbenoxolone decreased PGF2 alpha synthesis but had no effect on PGE2. Disodium cromoglycate, sulphapyridine, salicylazosulphadimidine and methylsulphasalazine had no effect on PG synthesis. 5. The data show marked variations in effect on PG synthesis in vitro of substances that have been investigated clinically for their actions on IBD.

Aged↗
PubMed1986

Kinetics of prostaglandin E2 and thromboxane A2 synthesis and suppression of PHA-stimulated peripheral blood mononuclear leucocytes.

The immunomodulatory effects of thromboxane A2 and prostaglandin E2 on peripheral blood mononuclear leucocytes stimulated with PHA in vitro, and the relationship of this to the time-course of their synthesis in culture, were investigated using prostaglandin E2, a thromboxane A2 synthesis inhibitor (UK37248), a thromboxane A2 mimic (U46619) and a thromboxane A2 receptor blocker (EP045). The inhibitory effect of prostaglandin E2 on PHA-induced human peripheral blood mononuclear leucocyte proliferation diminishes if the addition of PGE2 is delayed. If added 4 hr after a maximum concentration of PHA (5 micrograms/ml), the effect of PGE2 was reduced by 60%. If a submaximal concentration of PHA (1 microgram/ml) was used, the effect of PGE2 was not reduced if added 4 hr later but fell by about 60% after 16 hr. UK37248 moderately inhibited PHA-induced activation while substantially inhibiting thromboxane A2 synthesis and simultaneously enhancing PGE2 synthesis. The enhanced accumulation of PGE2 occurs while sensitivity to PGE2 is dropping. U46619, exogenously applied as a thromboxane A2 mimic, inhibited PHA-induced activation at concentrations that did not significantly alter PGE2 synthesis. EP045, which may modulate the effects of endogenous thromboxane A2 by blocking receptors, did not alter PHA-induced activation. We conclude that thromboxane A2 may have a role in inhibiting PHA-induced activation on the basis of the effect of U46619. However, this study highlights difficulties in utilizing prostaglandin and thromboxane receptor and synthesis inhibitors to examine their endogenous role in the modulation of mitogen-induced activation in vitro. If sensitivity to the purported endogenous substance is limited to the early stages of culture and if only low levels are synthesized at this early stage, then blocking drugs would have little effect.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1985

Stability of ascorbic acid and uptake of the vitamin by embryonic chick femurs during long-term culture.

Ascorbic acid was added to organ cultures of 15-day-old embryonic chick femurs. The ascorbate that was taken up into the cultured tissue reached maximal concentrations after 1.5 h. The half-life of tissue ascorbate was 12-24 h, whereas the half-life of medium ascorbate was 1-2 h. 24 h after supplementing with ascorbate, the tissue concentrations were still 30-60-fold higher than the medium concentrations at that time. If no ascorbate was added to the culture medium, the tissue concentration declined over a period of days: after 6 days 2-7% of the pre-culture tissue concentrations were still present. Embryonic chick femurs in vitro are therefore shielded from massive fluctuations in the concentration of ascorbic acid in the medium, resulting from intermittent supplementation. Hence, feeding a culture with the vitamin once every 24 h is sufficient to ensure adequate levels in the tissue.

Animals↗
PubMed1985

Ascorbic acid requirements for collagen synthesis (proline hydroxylation) during long-term culture of embryonic chick femurs.

Although ascorbate is essential for collagen synthesis, especially the hydroxylation of prolyl residues, femurs from 15-day-old chick embryos could be cultured for at least 5 days without ascorbate additions to the medium before the hydroxylation of proline was significantly impaired. Only when the ascorbate concentration in the tissue was less than 6 micrograms/g wet weight (compared with 50-70 micrograms/g wet weight in fresh tissue), was hydroxyproline formation reduced by 75-85%. When sufficient ascorbate was present in the culture medium, the femurs accumulated and stored the vitamin at concentrations which were 5-10-fold above the threshold required for collagen synthesis. This may represent an adaptive mechanism to the instability of the vitamin. Above the minimum required level, synthesis of collagen was not quantitatively related to ascorbate concentration. To obtain comprehensive data on changes in collagen content and collagen synthesis during culture, total hydroxyproline was measured as well as [3H]proline uptake and the formation of [3H]hydroxyproline. These three parameters were assessed with a new combined assay, which was modified from existing methods, yet was more sensitive and less tedious.

Animals↗
PubMed1985

Duodenal mucosa synthesis of prostaglandins in duodenal ulcer disease.

Synthesis of prostaglandins (PGE2, PGI2 and PGF2 alpha) and thromboxane A2 was investigated in short term incubates of duodenal mucosa biopsies. Mucosa close to the ulcer site synthesised significantly less PGF2 alpha (p less than 0.001) and PGI2 (p less than 0.002) measured as its stable metabolite 6-oxo-PGF1 alpha than healthy mucosa from non-ulcer patients. In paired biopsies taken from the ulcer site and opposite the ulcer in the same patient PGF2 alpha and PGI2 syntheses were both significantly and similarly depressed when compared with normal mucosa. Synthesis of PGE2 and TxA2 (as its stable metabolite TxB2) was not different in any tissue. There is a defect in the ability of the human duodenal mucosa in duodenal ulcer disease to synthesise PGF2 alpha and PGI2; the defect is not limited to the ulcer site.

Dinoprost↗
PubMed1982

The effect of arachidonic acid and prostanoids on collagen dissolution in human uterine cervix in vitro.

Explants of human non-pregnant cervix produce collagenolytic enzymes which degrade collagen over a 10 day period in culture. This is significantly enhanced by the presence of very low concentrations of arachidonic acid (10(-16) - 10(-11)M). Prostaglandin E2, F2 alpha and 6-keto-F1 alpha were synthesised in declining amounts over the 10 day period and synthesis was not increased by adding arachidonic acid (10(-11)M). Meclofenamic acid (10(-6)M) and indomethacin (10(-5)M), but not tranylcypromine (10(-5)M) suppressed prostaglandin synthesis yet all reduced collagen dissolution. Mepacrine (phospholipase A2 inhibitor) also suppressed collagen dissolution. Remodelling of the structure of the cervix matrix may, in part, depend upon arachidonic acid or one of its cyclo-oxygenase or lipoxygenase derived products.

Adult↗
PubMed1982

Stimulation of prostaglandin synthesis in rat cerebral cortex via a beta-adrenoceptor.

1. Synthesis of prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) in rat cerebral cortex slices is increased by beta-adrenoceptor agonists. 2. Phenylephrine, an alpha-adrenoceptor agonist, has no effect while oxymetazoline increased PGF2 alpha only. 3. PG synthesis stimulation by noradrenaline (NA) was prevented by beta- but not by alpha-adrenoceptor antagonists. 4. Dibutyryl cyclic AMP and inhibitors of cyclic nucleotide phosphodiesterase augment PG synthesis. 5. Stimulation of PG synthesis in rat cerebral cortex by NA is mediated by a beta-adrenoceptor.

Animals↗
PubMed1982

Ulcerative colitis: effect of sulphasalazine, its metabolites and indomethacin on the ability of human colonic mucosa to metabolize prostaglandins in vitro.

1 Homogenates of mucosa from human colon metabolize [3H]-prostaglandin E1 in the presence of nicotinamide adenine dinucleotide to 15-oxo prostaglandin E1 or 15-oxo, 13,14 dihydro prostaglandin E1. 2 Metabolic capacity of tissue from patients with active ulcerative colitis under treatment with sulphasalazine (0.021 +/- 0.004 nmol/Mg protein +/- s.e. mean) did not differ from mucosa of normal patients (0.02 +/- 0.004 nmol/mg protein) during 1 h incubation. 3 Sulphasalazine inhibits prostaglandin E1 metabolism by mucosal homogenates in a dose-dependent manner with an ID50 of 125 microM. Its therapeutically active metabolite, 5-aminosalicylic acid (2.6 mM) was without significant inhibitory activity. 4 Indomethacin inhibits prostaglandin E1 metabolism by colonic mucosa with an ID50 of 388 microM. 5 At present we cannot clearly relate the therapeutic benefit of sulphasalazine and its therapeutically active metabolite, 5-aminosalicylic acid, in ulcerative colitis to their effects on prostaglandin E synthesis or metabolism in vitro.

Alprostadil↗
PubMed1982

Collagen solubility and tensile properties of the rat uterine cervix in late pregnancy: effects of arachidonic acid and prostaglandin F 2 alpha.

The collagen concentration in rat uterine cervix was less on day 18 of pregnancy than in the non-pregnant animal but did not diminish further as pregnancy proceeded. The solubility of cervical collagen in warm acetic acid (0.5 mol/l) was increased on day 22 compared with days 19, 20 and 21 of pregnancy, and there was a positive correlation of increasing solubility with the tissue rate of creep (a measure of reducing stiffness of the cervix). Treatment of rats subcutaneously with arachidonic acid or prostaglandin F 2 alpha (PGF 2 alpha) on day 18 of pregnancy decreased the stiffness of the tissue when assessed on day 19 and this was accompanied by increased solubility in cold saline (0.45 mol/1), cold acetic acid and warm acetic acid and a reduction in collagen concentration. These results suggest that collagen properties rather than concentration are important in determining the stiffness of the rat uterine cervix at term and that exogenous PGF 2 alpha and arachidonic acid cause biochemical changes in collagen structure unlike those seen at term in untreated animals.

Animals↗
PubMed1981

Prostaglandin E and F concentrations in placentae of normal, hypertensive and pre-eclamptic patients.

The prostaglandins E and F were measured by radioimmunoassay in placentae from 23 normotensive, 25 hypertensive and 13 pre-eclamptic patients. The prostaglandin E levels were respectively (pg/mg +/- SEM) 16.34 +/- 2.06, 16.75 +/- 2.52 and 12.10 +/- 3.63. The prostaglandin F levels were 2.43 +/- 0.41, 2.70 +/- 0.42 and 2.06 +/- 0.31. These prostaglandin concentrations did not differ significantly. Local ischaemia may, therefore, be explained by altered responsiveness to these prostaglandins or to changes in other prostaglandins (such as the vasodilator PGI2) or other vasoactive agents.

Adolescent↗
PubMed1981

Regulation of collagen dissolution in the human cervix by oestradiol-17 beta and progesterone.

Explants of non-pregnant human cervix in culture for 10 days spontaneously synthesized collagenolytic enzymes with dissolved the collagen in the tissue, resulting in the release of hydroxyproline-containing peptides. Progesterone at 8 X 10(-7) M and oestradiol-17 beta at 4 X 10(-6) M reduced this breakdown by 50%, but oestradiol-17 beta was only inhibitory if the tissue was maintained in an oestrogen-containing environment throughout the preparation of the tissue explants. We conclude that the connective tissue matrix of the human cervix is partly under hormonal control.

Cervix Uteri↗
PubMed1980

Regulation of noradrenaline overflow in rat cerebral cortex by prostaglandin E2.

1 The effects of prostaglandin E2 (PGE2), PGF2 alpha and PGI2 and of inhibitors of prostaglandin synthesis and action, on the K+-evoked [3H]-noradrenaline ([3H]-NA) overflow from rat cerebral cortex slices have been investigated. 2 PGE2 reduced, while indomethacin (a prostaglandin synthesis inhibitor) or SC 19220 (a prostaglandin receptor antagonist) increased, the evoked overflow compared with controls. 3 The inhibition of [3H]-NA overflow by PGE2 was dose-dependently antagonized by SC 19220. 4 The results indicate that PGE2 modulates NA release in rat cerebral cortex in vitro.

Adrenergic alpha-Agonists↗