PubMed Health⌕ Search

Biomedical subjects

R W Shaw

Publications and source records attributed to R W Shaw.

At least 199 records · Page 11Linked to original sources
PubMed1982

Determination of pathophysiological mechanisms in subjects with amenorrhoea and their value in predicting ovulation induction therapy.

A scheme of investigation to determine the pathophysiological mechanisms in 142 women with amenorrhoea is described together with the results of a selective ovulation induction programme. Initial screening tests were performed to identify patients with conditions which were unlikely to respond to any form of treatment (e.g. primary ovarian failure) or in whom other well defined absolute causes of infertility were present. The site of defect within the hypothalamic-pituitary-ovarian axis was then determined by a series of dynamic test procedures. On the basis of these results ovulation induction treatment was selected and given for six treatment cycles. Ovulation was induced in 89.2% of 556 treatment cycles and 60.2% of 125 patients treated for up to six cycles conceived. The rationale and benefits of such an investigative protocol are discussed.

Amenorrhea↗
PubMed1981

Oxidation of reduced cytochrome c oxidase with 18O2. A search for mu-oxo-bridged metal species in the oxidized enzyme.

We have measured the increase in 18O content of water produced from single turnover oxidations of anerobically reduced cytochrome c oxidase with 18O2 in order to test the hypothesis that a reduced atom of oxygen, originating from dioxygen, remains bound to oxidized cytochrome c oxidase in the form of a mu-oxo-bridge between two metal components when a single turnover occurs. When water samples produced by oxidizing the reduced enzyme with 18O2 were compared to natural abundance control samples obtained by oxidizing with 16O2, all of the 18O2 reduced in a single turnover could be accounted for in the form of additional H218O produced. We conclude that neither atom of the dioxygen reduced is incorporated into the enzyme as a bridge which is stable in the absence of oxidoreductive reactions on the time scale of several minutes.

Anaerobiosis↗
PubMed1981

Extended x-ray absorption fine structure of copper in cytochrome c oxidase: Direct evidence for copper-sulfur ligation.

The copper x-ray fluorescence excitation spectrum of cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) has been recorded in the 245-270 K range. The beat pattern observed in the extended x-ray absorption fine structure can be accounted for only by postulating a combination of sulfur and nitrogen (or oxygen) ligands to the copper. The average Cu-S distance is 2.27 +/- 0.02 A and the average Cu-N (or Cu-O) distance is 1.97 +/- 0.02 A. The amplitudes require ca, 1-1.5 sulfurs and 2 nitrogens (or oxygens) per copper. The distribution of sulfur ligands between Cu(A) and Cu(B) sites is not known, although there is some evidence that two sulfur atoms are bound to Cu(A).

Journal Article↗
PubMed1980

Electron spin echo studies of cytochrome c oxidase.

We have studied the linear electric field effect in pulsed EPR of the "EPR-detectable copper" signal of beef heart cytochrome c oxidase and have compared our results with those for a variety of square planar and tetrahedral Cu(II) model compounds and with Cu(II) proteins containing either type 1 or type 2 copper. The electric field induced g shifts (linear electric field effect) for cytochrome oxidase are comparable in magnitude to those for simple Cu(II) complexes and for some copper proteins containing type 2 sites. The shifts are smaller than those for tetrahedral copper complexes and for type 1 copper sites. However, the magnetic field dependence of the linear electric field effect does not resemble that observed for any Cu(II) complex studied nor for type 1 copper. These findings cannot be reconciled with the tetrahedral Cu(II) model proposed by Greenaway, Chan, and Vincow ((1977) Biochim. Biophys. Acta 490, 62-78, 1977) to explain the unusual EPR spectrum of cytochrome oxidase.

Animals↗
PubMed1980

Studies on the origin of the near-infrared (800-900 nm) absorption of cytochrome c oxidase.

Data are presented which were collected in the course of the past ten years and bear on the correlation of absorbance at 800 nm and the EPR signal at g = 2 ('copper signal') of cytochrome c oxidase in various states of oxidation and ligation. Both EPR and optical reflectance spectra were obtained at low temperature (-170 to -190 degrees C). For some sets of samples spectra were recorded in the range 500-1100 nm. A particular efFort was made to study this correlation with what are called 'mixed valence' states (Greenwood, C., Wilson, M.T. and Brunori, M. (1974) Biochem. J. 137, 205-215), when cytochrome a and the EPR-detectable copper are thought to be oxidized and the other components reduced and vice versa. These data show no evidence that the copper component of cytochrome oxidase which has so far not been detected by EPR makes a contribution to the absorption between 800 and 900 nm exceeding 10-15% of the total, which is close to or within the error of the respective measurements. For the various states of the oxidase examined in this work the 700-800 nm region did not appear to be more useful than the 800-900 nm region for determining the state of the EPR-undetectable copper in a reliable way. These conclusions are in agreement with results presented previously from other laboratories concerning the relationship of optical (approx. 800 nm) and EPR spectroscopic (g = 2) data obtained with the enzyme.

Animals↗
PubMed1979

The oxygen reactions of reduced cytochrome c oxidase. Position of a form with an unusual EPR signal in the sequence of early intermediates.

The order of appearance of intermediates in the reoxidation of reduced cytochrome c oxidase by oxygen has been examined. Particular emphasis was placed on determining where the intermediate with the EPR signal at g = 5, 1.78, 1.69 (Shaw, R.W., Hansen, R.E. and Beinert, H. (1978) J. Biol. Chem. 253, 6637--6640) appears in the sequence of events during reoxidation. Flash photolysis of reduced, CO-complexed samples of cytochrome c oxidase in the presence of oxygen in a buffer containing 30% (v/v) ethylene glycol at 77 K and 195 K has been used to generate states of partial reoxidation. The intermediate with the EPR signal at g = 5, 1.78, and 1.69 can be detected as a product of the photolysis and subsequent oxidation but does not appear until the photolyzed sample is incubated at temperatures well above 196 K. In the course of the reoxidation, the intermediate characterized by the g = 5, 1.78, 1.69 signal occurs in the reaction sequence after the states referred to as 'Compound A' and 'Compound B' (Chance, B., Saronio, C., and Leigh, J.S. (1975) J. Biol. Chem. 250, 9226--9237). Its appearance is within the time range reported for the formation of 'oxygenated' cytochrome c oxidase (Orii, Y. (1979) in Cytochrome Oxidase (King, T.E., Orii, Y., Chance, B. and Okunuki, K., eds.), pp. 331--340, Elsevier/North-Holland Biomedical Press, Amsterdam).

Animals↗
PubMed1979

Hyperfine structure resolved by 2 to 4 GHz EPR of cytochrome c oxidase.

Using low frequency 2 to 4 GHz EPR at 10 K, we have resolved previously unseen hyperfine structure associated with the EPR-detectable copper signal of cytochrome c oxidase. The observed hyperfine structure appears consistent with hyperfine coupling to copper; although to account for all of the observed structure, an additional magnetic interaction is required as well. This work points out the utility of the 2 to 4 GHz EPR technique for resolving electronic hyperfine structural information from copper and possibly other paramagnetic sites in biomolecules when random variation in electronic g values is a cause of EPR line-broadening.

Copper↗
PubMed1979

Ovary.

Explore the source record for details and available documents.

Adrenal Gland Diseases↗
PubMed1979

Oestrogen-gonadotrophin feedback abnormalities in hyperprolactinaemic amenorrhoea demonstrated by the response to clomiphene administration.

Clomiphene was administered to 16 patients with elevated serum prolactin levels in doses of 100, 200 and 300 mg/day for five days in succeeding months and total urinary oestrogens estimated on days 0, 5, 8, 12 and 15 following commencement of treatment. The responses were compared with six patients who were amenorrhoeic but had normal serum prolactin levels and absent positive feedback to oestrogen. The increased outputs of oestrogens were similar in the two groups. In the hyperprolactinaemic group 5 out of 16 subjects showed evidence of ovulation whilst the remainder showed a secondary failure of response. Six subjects who failed to ovulate were treated with clomiphene and human chorionic gonadotrophin (HCG) and ovulations were induced in 31 out of 34 treatment cycles but no pregnancies were achieved. The responses to clomiphene therapy in the hyperprolactinaemic subjects were compared to the assessment of positive feedback mechanisms by means of oestrogen provocation and oestrogen amplification tests and good correlation was obtained. Only those with evidence of positive feedback to these tests were likely to ovulate on clomiphene.

Amenorrhea↗
PubMed1978

Responses of the a3 component of cytochrome c oxidase to substrate and ligand addition.

We have previously described a transient high spin ferric heme species in cytochrome c oxidase (EC 1.9.3.1) which represent a3+(3) (Beinert, H. and Shaw, R.W.(1977) Biochim. Biophys. Acta 462, 12u--130), and can be detected and quantitatively determined by EPR. We have now used out ability to generate this species to study reactions of a3+(3) with substrates and ligands and also responses to pH changes. This was accomplished by multiple rapid mixing and freezing techniques in conjunction with low temperature EPR and optical reflectance spectroscopies. The substrates used were O2 and ferrocytochrome c and the ligands cyanide, sulfide, azide and carbon monoxide. Contrary to the oxidized, resting form of the enzyme, the transient high spin species of a3+(3) reacts within less than 10 ms stoichiometrically with cyanide and sulfide and at a slower rate with azide. The transient a3+(3) species responds to O2 and CO by changes in signal size or shape, although no oxidoreduction is involved, indicating that a3+(3) registers the presence of these gases. The high spin signal of the transient species is readily abolished by ferrocytochrome c or on raising the pH. Decreasing the pH induces a shift from the rhombic towards the axial component of the signal. Since the responses to CO and pH are analogous for the rhombic transient species to those observed with the rhombic high spin ferric heme species produced on partial reduction, it is suggested that the rhombic signals represent a3+(3) in either case. In all these experiments, in which EPR detectable a3+(3) was observed in large yield, no extra signals for copper or correspondingly increased intensity in the copper signal at g = 2 were seen. The relationship is discussed of the obviously reactive transient species of a3+(3) to other 'activated' species that have been reported and to the oxidized resting form of the enzyme, which is known to react only slowly with ligands and to respond sluggishly to substrate.

Azides↗
PubMed1978

A novel electron paramagnetic resonance signal of "oxygenated" cytochrome c oxidase.

It had been observed previously that a pair of transient EPR resonances (g = 1.78 and 1.69) appears within less than 5 ms on reoxidation of reduced cytochrome c oxidase by O2. Since the location of other lines that are part of the same signal was not known, the quantity of the paramagnetic species involved, and thus the significance of the observed resonances, remained questionable. We have now found a broad resonance at g = 5 which is obviously associated with those at g = 1.78 and 1.69. The width of the signal (approximately 250 mT) at the observed intensity suggests that it represents a significant fraction of one of the components of the enzyme. The signal disappears within less than 5 ms on addition of cyanide or sulfide but only within several hundred milliseconds after addition of ferrocytochrome c. This behavior suggests that it originates from the a3 component of the enzyme. It is suggested that the species represented in the signal is either identical with or part of what has been named collectively the "oxygenated" form and recently described "activated" forms of the enzyme. On reoxidation of reduced oxidase with oxygen enriched 90% in 17O, no change of signal shape was seen.

Cyanides↗
PubMed1978

Sex hormone levels and gonadotrophin release in premature ovarian failure.

Premature ovarian failure was studied in ten women under the age of 30; eight had an ovarian biopsy and five of these showed primordial follicles. Plasma levels of oestradiol and progesterone were similar to the follicular phase of a normal menstrual cycle, but in eight patients cervical smears showed a cornification index of less than one per cent. Levels of both androgens and of sex hormone binding globulin capacity were generally normal. Administration of LH-RH caused a release of FSH which was similar to post menopausal women and higher than both. Two patients were treated with exogenous gonadotrophins without effect.

Adolescent↗
PubMed1978

Randomized controlled trial of Syn-Ergel and an active placebo in the treatment of heartburn of pregnancy.

A randomized controlled trial was performed to study the efficacy of Syn-Ergel with an active placebo in the treatment of heartburn of pregnancy in ninety-two patients completing 7 days of therapy. Syn-Ergel was significantly better (p less than 0.001) in all groups of pre-treatment pain severity in relieving the symptoms, and had a longer duration of action, than the active placebo. Complete relief of pain was achieved in 79.5% of Syn-Ergel treatments with a further 10% of treatments resulting in marked easing of discomfort at 1 hour following administration. The corresponding figures for the 'active placebo' were 56% and 20%. The combination of an antacid and a protective mucosal coating agent would appear to be a useful approach in the treatment of heartburn of pregnacy.

Agar↗