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Biomedical subjects

R G Edwards

Publications and source records attributed to R G Edwards.

At least 19 recordsLinked to original sources
PubMed1978

Chemical modifications of the protein of carcinoembryonic antigen: associated changes in immunological activity and conformation.

Chemical substitution of the exposed residues of tryptophan, tyrosine, histidine and arginine in carcinoembryonic antigen (CEA), using appropriately selective reagents, caused no significant change in the capacity of the antigen to bind to anti-CEA serum. However, treatments of CEA with 2-hydroxy-5-nitrobenzyl bromide and tetranitromethane, both in the presence of guanidine HCl, caused a large reduction in binding capacity. Measurement of the circular dichroism spectra of all of the products showed that retention of conformation of the molecular correlated well with retained antigenic activity, whereas the large losses in capacity to bind to anti-CEA sera were accompanied by a probably the result of gross conformational changes. The tyrosine residues of CEA may be classified into three categories: (i) 3 freely reacting residues, (ii) 7 or 8 moderately buried residues and (iii) 15 unreactive residues.

Amino Acids↗
PubMed1978

Steroid production from 17alpha-hydroxypregnenolone and dehydroepiandrosterone by human granulosa cells in vitro.

Granulosa cells were aspirated 3--4 h before the expected time of ovulation from 10 follicles of 4 patients treated with gonadotrophins: 4 of the follicles were immediately preovulatory. The granulosa cells were cultured for 10 h with 17alpha-hydroxypregnenolone or dehydroepiandrosterone and samples of medium removed at 3 and 10 h were assayed for 6 steroids. Granulosa cells were unable to synthesize androgens from endogenous substrate or undertake conversions via the delta5 pathway, but cells from all follicles were capable of aromatizing exogenous androgens to oestrogens although this capability was reduced in cells from follicles beginning to luteinize. Granulosa cells from preovulatory follicles synthesized more progesterone from endogenous substrate than cells from follicles which had not begun to luteinize. The results provide further support for the two-cell theory of oestrogen biosynthesis whereby granulosa cells aromatize androgens which are synthesized by the thecal cells in vivo.

17-alpha-Hydroxypregnenolone↗
PubMed1978

Steroidogenesis in preovulatory follicles of patients given human menopausal and chorionic gonadotrophins as judged by the radioimmunoassay of steroids in follicular fluid.

The administration of human menopausal gonadotrophin (HMG) followed by human chorionic gonadotrophin (HCG) stimulated the development of various numbers of follicles in patients treated for infertility. Graafian follicles from these patients were aspirated 32-33 h after the injection of HCG and the levels of steroids in the follicular fluid and matching serum samples were measured by radioimmunoassay. The follicles could not be grouped into two distinct clusters as found in patients given HCG during the menstrual cycle but a broad classification of follicles into four groups was indicated from the dendrogram. Two of the groups were similar to the ovulatory and non-ovulatory groups found previously, whereas the other two groups of follicles were more intermediate in nature. The use of a discriminant analysis showed that these two groups had clearly been stimulated by the HMG and HCG, although they were not yet fully ovulatory. Our data indicate that the number of developing follicles is considerably increased by treatment with HMG and HCG but there is asynchrony in follicular development because the pattern of steroid synthesis differs in many follicles. The effects of this asynchronous development on oocyte maturation and disorders of the luteal phase are discussed.

Androgens↗
PubMed1978

Steroidogenesis by cultured granulosa cells aspirated from human follicles using pregnenolone and androgens as precursors.

Human granulosa cells from Graafian follicles aspirated 3-4 h before the expected time of ovulation were incubated with various steroid substrates, including pregnenolone, androstenedione, testosterone and dehydroepiandrosterone (DHA). Steroid production after 3 and 10 h of incubation was determined by radioimmunoassay. Progesterone and 17alpha-hydroxyprogesterone were the major products of granulosa cells in control short-term cultures with endogenous substrates. The addition of pregnenolone increased the synthesis of progesterone and 17alpha-hydroxyprogesterone compared with the controls, although the response varied considerably between paired short-term cultures. Little or no oestradiol-17beta was produced from endogenous precursors or short-term cultures to which pregnenolone had been added; one follicle, however, produced similar amounts of oestradiol-17beta in the control cultures and after incubation with pregnenolone. When granulosa cells were cultured with various amounts of androstenedione, DHA or testosterone, large amounts of oestradiol-17beta were produced, especially in short-term cultures in which larger amounts of substrate were added. Progesterone production continued and progesterone was synthesized more rapidly or in greater amounts in some short-term test cultures than in the controls. The results indicate that human granulosa cells are one source of oestradiol-17beta during the preovulatory phase. The data support the two-cell theory for oestradiol synthesis, for granulosa cells do not appear to undertake steroid conversion via the 5-unsaturated pathway, but aromatize androgens known to be produced by thecal cells. It is also suggested that either androgens or oestradiol-17beta stimulate progesterone production by granulosa cells, at least in vitro.

Androgens↗
PubMed1977

Transformations of cellobiose derivatives into analogues of lactose.

The preparation of benzyl beta-cellobioside 2,3,6,2',3'-pentabenzoate (2b) via a 4',6'-benzylidene acetal in 27% overall yield from cellobiose is described. This pentabenzoate has been utilised for conventional syntheses of the 6'-amino-, 4'-amino-, and 4',6'-diamino-analogues of lactose, via the 4',6'-dimesylate. In addition, reaction of the pentabenzoate 2b with sulphuryl chloride initially afforded the 6'-chloro derivative, which was then slowly transformed into a mixture of the 4',6'-dichloro-lactoside and an isomer in which the non-reducing ring of the disaccharide had been transformed into a 3',6'-dideoxy-3',6'-dichloro-gulopyranoside. The latter probably arose by neighbouring-group participation by the 3'-benzoloxy group prior to the introduction of the secondary 3'-chloro substituent. The former dichlorocompound was subsequently converted into 4',6'-dideoxy-4',6'-dichloro-lactose. It was found that the rate of nucleophilic displacement at C-4' of a cellobioside was much lower than that for the corresponding alpha-linked disaccharide, maltose. Furthermore, nucleophilic displacement at C-4' of a lactoside was accompanied by substantial elimination, to give the 4'-ene, together with some cleavage of the interglycosidic bond. tthe origins of these effects are discussed.

Cellulose↗
PubMed1977

Formation of oxalate in pyridoxine or thiamin deficient rats during intravenous xylitol infusions.

Glucose, fructose, sorbitol and xylitol were assessed as precursors of oxalate in normal rats and rats deficient in thiamin or vitamin B-6. Urinary excretions of oxalate, glyoxylate and glycine were increased significantly in vitamin B-6 deficient rats infused with xylitol when compared with all other groups. Using [U-14C]xylitol, oxalate was shown to be derived directly from this polyalcohol in vitamin B-6 deficient rats. These results suggest that vitamin B-6 deficiency may be a factor contributing to oxalate crystal deposition seen in some patients infused with xylitol.

Animals↗
PubMed1977

Parameters for assessing vibration-induced cardiovascular responses in awake dogs.

The vibration parameters for assessing the response of the cardiovascular system to whole-body vibration were studied. Six awake, chronically instrumented canines were restrained with their spines vertical, and exposed to GZ sinusoidal vibration of 2-12 HZ for a constant peak acceleration amplitude of +-1.0 G. Vibration exposures of 30 s with intervening recovery periods of 2 min were employed. The following variables were measured: mean heart rate (MHR), stroke volume (SV), mean aortic flow (MAF), mean aortic pressure (MAP), the peak net force transmitted to the canine/body weight (PNF/BW), and the vibration platform frequency (ft), displacement, and acceleration. The percentage change from control (no vibration) of MAF varied linearly with PNF/BW for all cases. MAF also varied linearly with the log MHR/ft for the number of dogs which primarily changed MHR during the vibration exposures. The response of MAP was minimal in all cases, indicating a decrease in total peripheral resistance with increasing PHF.

Animals↗
PubMed1977

Steroidogenesis in human follicles approaching ovulation as judged from assays of follicular fluid.

Human chorionic gonadotrophin (HCG) was given to patients at mid-cycle before the endogenous LH surge. Graafian follicles were aspirated 32-33 h later, before ovulation was expected, and the levels of several steroids in follicular fluid and in matching serum samples were measured by radioimmunoassay. Two types of Graafian follicle were identified at laparoscopy , based on the nature of the oocyte, granulosa cells and follicular fluid withdrawn from the follicles. Some were large, preovulatory and presumably becoming luteinized while others were generally smaller, non-ovulatory and still growing. The concentrations of dehydroepiandrosterone (DHEA) and 17alpha-hydroxypregnenolone (delta5 intermediates), androstenedione and testosterone were higher in non-ovulatory follicles, whereas large follicles usually contained high levels of progesterone, 17alpha-hydroxyprogesterone, pregnenolone and oestradiol-17beta. A cluster analysis of these data grouped follicles into two distinct clusters, which accorded with their identification as ovulatory or non-ovulatory at laparoscopy. Levels of progesterone, 17alpha-hydroxyprogesterone and oestradiol-17beta in follicular fluid were high in preovulatory follicles in comparison with plasma. Results in two patients indicated that plasma levels of these steroids were determined by the preovulatory follicle. Levels of plasma delta5 steroids were closer to follicular fluid concentrations, whereas DHEA was higher in plasma. The role of the theca and granulosa is discussed in relation to the synthesis of progesterone and oestradiol-17beta in follicles as ovulation approaches.

Chorionic Gonadotropin↗
PubMed1976

The metabolism of the phosphonium analogue of choline in vitro and in vivo, and its detection in phospholipids by 31P-NMR.

1. The phosphonium analogues of choline, phosphorylcholine, CDPcholine and phosphatidylcholine were synthesized chemically and characterized by 1H-NMR and 31P-NMR; in 1,2-distearoyl-DL-glycero-3-phosphorylphosphocholine, the 31P-NMR chemical shift of phosphonium relative to phosphate was--28.2 ppm. 2. A comparison was made of the rates of reaction of choline kinase, cholinephosphate cytidyltransferase, cholinephosphotransferase and phospholipase C on natural and phosphonium substrates. Enzyme reaction rates were similar for all but the cytidyltransferase, which exhibited a 3-fold preference for the normal substrate. 3. Weanling rats were maintained for 6 weeks on a diet in which choline was fully replaced by phospho[1,2-14C2]choline mixed with a trace of [Me-3H] choline. Incorporation of phosphocholine into liver lipids was detectable by 31P-NMR even in crude tissue homogenates. Choline-based phospholipids of liver, kidney, lung and brain were extracted, and phosphocholine incorporation calculated from 31P-NMR peak area ratios. The phosphatidylcholine analogues were separated by preparative thin-layer chromatography. Incorporation of phosphocholine ranged from 33% in lung phosphatidylcholine to 6% in kidney sphingomyelin. Variations in 14C/3H ratio between feed and phospholipid extracts indicated preferences for exogenous choline over phosphocholine varying from 1.3: 1 in brain to 3.2: 1 in liver. The results indicated that phosphocholine is a potentially useful 31P-NMR probe for the study of membrane lipids.

Animals↗
PubMed1976

An evaluation of multiphasic screening on admission to hospital. Precis of a report to the National Health and Medical Research Council.

A controlled study of admission multiphasic screening (AMS) at a large general hospital showed that AMS had no significant effect on a variety of indices of inpatient progress. Owing to a 64% increase in estimated cost of investigations with AMS, the total hospital admission cost was increased by approximately 5%. Under the conditions of this study, AMS added to the cost of hospitalization without associated evidence of benefit to the patient.

Australia↗