Skin rash for 15 years.
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Amphotericin B↗
Biomedical subjects
L Gregory
Publications and source records attributed to L Gregory.
Characterization of cembranoid interaction with the nicotinic acetylcholine receptor.
The class of diterpenoids with a 14-carbon cembrane ring, the cembranoids, includes both competitive and noncompetitive inhibitors of the nicotinic acetylcholine receptor (AChR). All 20 coelenterate-derived cembranoids studied in this report inhibited [piperidyl-3,4-3H]-phencyclidine ([3H]-PCP) binding to its high-affinity site on the electric organ AChR, with IC50s ranging from 0.9 microM for methylpseudoplexaurate to 372 microM for lophotoxin. Inhibition was complete with all cembranoids but lophotoxin and most Hill coefficients were close to 1. Methylpseudoplexaurate and [3H]-PCP binding was competitive. Methylpseudoplexaurate and the fourth most potent cembranoid, eunicin, competed with each other for [3H]-PCP displacement, indicating that there exist one or more cembranoid sites on the AChR. Cembranoid affinity for the AChR correlated with hydrophobicity, but was also dependent on other features. Methylpseudoplexaurate and n-octanol also competed with each other for [3H]-PCP displacement, indicating that the cembranoid site is linked to the n-octanol site on the AChR. Unlike lophotoxin, the five cembranoids tested did not inhibit [125I]Tyr54-alpha-bungarotoxin binding to the AChR agonist sites. All seven cembranoids tested on oocyte-expressed electric organ AChR reversibly blocked acetylcholine-induced currents, although the inhibitor concentration curves were shallow and the inhibition was incomplete.
Acetylcholine↗
Dynamic multi-planar EPI of the urinary bladder during voiding with simultaneous detrusor pressure measurement.
Magnetic resonance imaging gives high quality images of the urinary bladder with excellent contrast. We report here the first application of dynamic, multi-slice, echo planar imaging to a study of urinary bladder emptying. Changes in urinary bladder volumes and rates of urine expulsion from the bladder have been measured simultaneously with bladder pressure. The method shows promise for clinical applications involving compromised bladder function, for reappraising bladder contraction strength-volume relationships, and for investigating the rate of change of length, three-dimensional shape, and wall tension in different parts of the bladder during micturition.
Echo-Planar Imaging↗
Follicular vascularity--the predictive value of transvaginal power Doppler ultrasonography in an in-vitro fertilization programme: a preliminary study.
The aim of this prospective study was to investigate the ability of transvaginal power Doppler ultrasonography to assess the relationship between follicular vascularity and outcome in women undergoing in-vitro fertilization. Each of 38 subjects underwent a single transvaginal power Doppler ultrasound scan on the day of oocyte collection, where the vascularity of individual ovarian follicles was assessed, using a subjective system, and graded 1 to 4. In addition, conventional pulsatility indices (PI) of the uterine and intra-ovarian (stromal) arteries were calculated, which showed no significant differences between the pregnant and non-pregnant groups. Using power Doppler ultrasonography, a total of 188 follicles was studied. The follicular vascularity grade was found to be independent of follicular size and there was no significant difference in fertilization rates with different degrees of vascularity, although there was a trend towards higher fertilization rates with higher grade vascularity. There were 10 pregnancies, giving a pregnancy rate of 26.3% per embryo transfer. Pregnancies were confined to those women whose embryos were derived from follicles with grade 3 and 4 vascularity (pregnancy rates per embryo transfer of 12.5 and 61.5% respectively), with only those from grade 4 follicles resulting in livebirths. This preliminary study suggested that high grade follicular vascularity is associated with increased pregnancy rate and that there is a possible link between follicular vascularity and implantation potential.
Adult↗
Functional magnetic resonance image analysis of a large-scale neurocognitive network.
Many "higher-order" mental functions are subserved by large-scale neurocognitive networks comprising several spatially distributed and functionally specialized brain regions. We here report statistical and graphical methods of functional magnetic resonance imaging data analysis which can be used to elucidate the functional relationships (i.e., connectivity and distance) between elements of a neurocognitive network in a single subject. Data were acquired from a normal right-handed volunteer during periodic performance of a task which demanded visual and semantic processing of words and subvocalization of a decision about the meaning of each word. Major regional foci of activation were identified (by sinusoidal regression modeling and spatiotemporal randomization tests) in left extrastriate cortex, angular gyrus, supramarginal gyrus, superior and middle temporal gyri, lateral premotor cortex, and Broca's area. Principal component (PC) analysis was initially undertaken by singular value decomposition (SVD) of the "raw" time series observed at 170 activated voxels. This revealed a large functional distance (negative connectivity) between visual processing systems and all other brain regions in the space of the first PC. SVD of a matrix of fitted time series, and a matrix of six sinusoidal regression parameters estimated at each activated voxel, were developed as less noisy (more informative) alternatives to SVD of the "raw" data. Canonical variate analysis of denoised data was then used to clarify functional relationships between the major regional foci. Visual input analysis systems (extrastriate cortex and angular gyrus) were colocalized in the space of the first canonical variate (CV) and significantly separated from all other brain regions. Semantic analysis systems (supramarginal and temporal gyri) were colocalized and significantly separated in the space of the second CV from the subvocal output system (Broca's area). These results are provisionally interpreted in terms of underlying hemodynamic events and cognitive psychological theory.
Adult↗
Follicular variation in ovarian 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) activities: evidence for the paracrine inhibition of 11 beta HSD in human granulosa-lutein cells.
We have previously shown that detectable metabolism of cortisol to cortisone by 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) in human granulosa-lutein cells, pooled for each patient from all aspirated ovarian follicles, is associated with failure to conceive by in vitro fertilization and embryo transfer. The aims of the present study were to assess: (1) the variation in the 11 beta HSD activities of granulosa-lutein cells obtained from individual follicles in relation to oocyte maturity and (2) whether the 11 beta HSD activity of pooled granulosa-lutein cells reflects the 11 beta HSD activities of the individual follicles for a given patient. 11 beta HSD activities were measured in intact cells in serum-free medium by a radiometric conversion assay (100 nmol/l [3H]cortisol to [3H]cortisone). Follicular 11 beta HSD activities ranged from < 10 (undetectable) to 514 pmol/mg protein per 4 h (n = 105 follicles from 12 patients) and did not correlate with oocyte maturity. In three separate patients, the follicular 11 beta HSD activities ranged from < 10 to 117 pmol/mg protein per 4 h (n = 8 follicles), 19 to 514 pmol/mg per 4 h (n = 9) and 60 to 390 pmol/mg per 4 h (n = 8). The 11 beta HSD activities of the corresponding multi-follicular pools of cells were < 10, < 10 and 44 pmol/mg per 4 h respectively, all of which were significantly lower (P < 0.05) than the arithmetic means for the activities in the individual follicles (52, 132 and 215 pmol/mg per 4 h respectively). Likewise, the 11 beta HSD activities of two independent multi-patient pools of cells were significantly lower than the mean values of the 11 beta HSD activities of the appropriate individual patients. We conclude that ovarian 11 beta HSD activity varies between follicles and that co-culture of granulosa-lutein cells with low enzyme activity can suppress the ovarian 11 beta HSD activity in cells from different follicles (or patients) with high rates of cortisol metabolism. Hence, these data indicate the potential for paracrine inhibition of ovarian 11 beta HSD activity in human granulosa-lutein cells.
11-beta-Hydroxysteroid Dehydrogenases↗
In vitro oxyhaemoglobin saturation measurements in haemoglobin solutions using fibreoptic pulmonary artery catheters.
We compared in vitro oxyhaemoglobin saturations using two pulmonary artery catheters (catheter SO2), with oxyhaemoglobin saturations (SO2) measured by the IL282 co-oximeter and derived partial oxyhaemoglobin saturations (partial SO2) at different oxygen tensions (PO2) in six solutions: whole blood, 50:50 mixture of whole blood and Plasmalyte A (haemodiluted blood), 50:50 mixture of whole blood and 8% pyridoxylated haemoglobin-polyoxyethylene (PHP) conjugate (WB-PHP), 75:25 mixture of 8% PHP and Plasmalyte A solution (PHP66), 50:50 mixture of 8% PHP and Plasmalyte A solution (PHP44) and stroma-free haemoglobin solution (SFH). Calculated P50 values (PO2 vs SO2) were 3.79, 3.58, 3.49, 3.15, 3.04 and 2.07 kPa, respectively. However, if partial SO2 was used the curves were shifted to the left, reducing P50. Catheter SO2 correlated well with SO2 in whole blood (r2 > 0.99 for both catheters), haemodiluted blood (r2 > 0.98 for both catheters) and WB-PHP solution (r2 = 0.94 for both catheters). In PHP44 (r2 = 0.64 and r2 = 0.57), PHP66 (r2 = 0.40 for the Oximetrix and r2 = 0.25 for the Edwards catheter) and SFH solutions (r2 = 0.33 for the Oximetrix and r2 = 0.22 for the Edwards catheter) both catheters performed poorly. We conclude that mixed venous oxyhaemoglobin saturations measured by oximetric pulmonary artery catheters are inaccurate in the presence of haemoglobin solutions. For accuracy a multi-wavelength co-oximeter should be used if blood containing PHP or SFH is to be analysed.
Catheterization, Peripheral↗
Ovarian 11 beta-hydroxysteroid dehydrogenase activity is inversely related to the outcome of in vitro fertilization-embryo transfer treatment cycles.
OBJECTIVES: To determine the relationship of ovarian 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) activity to the outcome of IVF-ET and to establish whether 11 beta-HSD activities vary for a given patient between consecutive treatment cycles. DESIGN: Retrospective correlation analysis. SETTING: Patients were treated and ovarian 11 beta-HSD activities were measured at independent fertility and biochemistry departments, respectively. PATIENTS: Random series of 137 women undergoing a total of 172 treatment cycles for IVF-ET. INTERVENTIONS: Subcutaneous buserelin acetate plus IM hMG and hCG for controlled ovarian hyperstimulation; blood samples were collected for plasma LH and steroid determinations. MAIN OUTCOME MEASURES: Presence or absence of detectable ovarian 11 beta-HSD activity, oocyte fertilization rates, and the identification of clinical pregnancies. RESULTS: None of the 101 cycles associated with 11 beta-HSD positive granulosa-lutein cells resulted in clinical pregnancies, whereas the pregnancy rate for the 71 patients with undetectable ovarian 11 beta-HSD activity was 63.4% per cycle. The incidence of total fertilization failure was lower and the median oocyte fertilization rate was higher in cycles characterized by 11 beta-HSD-negative cells. Plasma concentrations of LH and E2 were higher in cycles yielding 11 beta-HSD-negative cells, whereas plasma P, patient age, and the number of oocytes retrieved did not relate to ovarian 11 beta-HSD activity. For the 35 patients studied in repeat cycles, ovarian 11 beta-HSD activities did not relate to those in the initial cycles. CONCLUSIONS: Ovarian 11 beta-HSD activity is associated with failure to conceive by IVF-ET. For a given patient, ovarian 11 beta-HSD activity varies between consecutive treatment cycles. Hence, ovarian 11 beta-HSD activities may predict the outcome of this assisted reproduction protocol independently in each treatment cycle.
11-beta-Hydroxysteroid Dehydrogenases↗
Human gonadotrophin preparations. Use luteinising hormone also.
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Female↗
Biochemical characterization of the interaction of lipid phosphoric acids with human platelets: comparison with platelet activating factor.
A series of lipid phosphoric acids, including 1-O-alkyl-2-lyso-glycerophosphoric acid, 1-O-acyl-2-lyso-glycerophosphoric acid, hexadecylpropanediolphosphoric acid, N-acyl-2-aminoethanolphosphoric acid, sphingosine phosphoric acid, and certain homologues and analogues, were synthesized and characterized by thin-layer chromatography, fast-atom bombardment mass spectrometry, and their ability to aggregate human platelets. The presence of a receptor for these lipid phosphoric acids that is distinct from the PAF receptor is strongly suggested from experiments involving a desensitization procedure, platelet-activating factor (PAF) receptor antagonists, and inhibitors of the lipid phosphoric acids. The unique features of the interaction of these lipid phosphoric acids with platelets include: (a) evidence for a separate receptor(s) for this diverse group of synthetic compounds, (b) no requirement for stereospecificity (i.e., no glycerol backbone), and (c) a structural requirement for a long-chain hydrocarbon residue covalently bound to a phosphoric acid residue. In the interaction of these compounds with the platelet, it is mandatory that extracellular Ca2+ and ADP be present for maximum biological activity. The potential involvement of a lipid phosphoric acid receptor, which could form a component of the activation pathway associated with various lysophospholipids and analogues, such as PAF, via a phospholipase D activation, is discussed.
Blood Platelets↗
A pilot study of gonadotrophin releasing hormone agonist (GnRHa)/superovulation/donor intrauterine insemination (IUI) after unsuccessful artificial insemination with donor sperm (DI).
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Adult↗
A study of the cumulus-corona cell complex in in-vitro fertilization and embryo transfer; a prognostic indicator of the failure of implantation.
In-vitro morphological changes and proliferation of cells of the cumulus oophorus, in particular cells of the corona radiata, were seen to differ between individuals and between oocytes of the same cohort in an unselected series of 159 IVF cycles. Cell proliferation did not relate to indications for treatment, type and length of ovarian stimulation, age of patient, ovarian response and quality of oocyte, fertilization rate or embryo morphology. A direct relationship, however, was demonstrated between the proliferative capacity of these cells and the incidence of clinical pregnancy. No pregnancies resulted when there was an absence of morphological change or proliferation of these cells. In cycles where the proliferative capacity of these cells varied between oocytes of a single cohort the pregnancy rate was 40% per cycle, and in cycles where cells associated with all oocytes underwent extensive proliferation the pregnancy rate was 49% (P < 0.001). Thus, regardless of the apparent quality of gametes or embryo, no pregnancies arose if the cumulus-corona complex was incapable of replication. We have, therefore, identified two populations of oocytes based on the proliferative capacity of cumulus-corona cells in vitro, one being associated with a failure of implantation.
Adult↗
Ovarian 11 beta-hydroxysteroid dehydrogenase: potential predictor of conception by in-vitro fertilisation and embryo transfer.
Cortisol is converted to the inactive glucocorticoid, cortisone, in several tissues by 11 beta-hydroxysteroid dehydrogenase (11 beta HSD). We have recently measured 11 beta HSD activity in cultured human granulosa-lutein cells recovered from patients undergoing in-vitro fertilisation and embryo transfer (IVF-ET). We now report an association between the outcome of IVF-ET and 11 beta HSD activity in these cells. Of the 64 patients studied, 32 had detectable 11 beta HSD activity and none became pregnant; whereas 76% of the remaining "11 beta HSD-negative" patients achieved pregnancies. Hence 11 beta HSD activity may predict the outcome of IVF-ET.
11-beta-Hydroxysteroid Dehydrogenases↗
A comparison of intrauterine insemination, intraperitoneal insemination, and natural intercourse in superovulated women.
In a prospective comparison of IP, IUI, and natural intercourse following superovulation in couples diagnosed as having unexplained infertility, semen factors, or sperm antibodies, pregnancy rates were found to be significantly higher after IP. Pregnancy rates were also higher in the unexplained infertility group when compared with those with semen factors. It was concluded that IP in combination with superovulation offered a simple, inexpensive, safe alternative to GIFT.
Administration, Intravaginal↗
Unacceptable potassium measurements.
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Blood Chemical Analysis↗
Peripheral blood platelet counts in the management of very early pregnancy failure following gamete intrafallopian transfer.
Early pregnancy-associated thrombocytopenia has been described previously in the peripheral blood of in vitro fertilization (IVF) patients and is evaluated here in 26 women undergoing gamete intrafallopian transfer (GIFT). No consistent fall in platelets was seen in ongoing pregnancies. It is suggested that a fall in peripheral blood platelets in the early luteal phase may be observed only in pregnancies where more than one embryo is present.
Chorionic Gonadotropin↗
[Differences in the dietary intake of diabetics with and without early nephropathy].
The dietary regimen of 70 patients with insulin dependent diabetes mellitus is discussed. 24 of these patients are with microalbuminuria (initial nephropathy). The age of manifestation of diabetes and the mean age of these patients are lower and the retinopathy is more frequent than in the patients without microalbuminuria. Only 18% of the diabetic patients studied keep a diet according to contemporary conceptions. In the group with initial nephropathy a higher consumption of fat (130.9 +/- 42.5 g) and proteins (109.6 +/- 28.8 g) is registered than in the other patients. There are no significant differences in the consumption of carbohydrates and fiber products. The possible role of longterm high consumption of fats and proteins by patients with diabetes mellitus in the pathogenesis of diabetic nephropathy is discussed.
Adult↗
Independent control of respiration in cytochrome c oxidase vesicles by pH and electrical gradients.
The effects of altering the pH and electrical components of the membrane potential on the visible spectra and oxygen consumption rates of cytochrome oxidase vesicles were examined during steady-state respiration using cytochrome c as the substrate. Heme a was found to be 30-55% reduced in the presence of a membrane potential, becoming more reduced when the electrical gradient (delta psi) was abolished by valinomycin and more oxidized when the pH gradient (delta pH) was abolished by nigericin, with little increase (1.2-1.8-fold) in the rates of oxygen consumption in either case. When both gradients were eliminated, heme a reduction was close to initial levels, and activity was stimulated up to 8-fold. The magnitude of the changes in heme a reduction levels upon elimination of a gradient component was shown to be positively correlated with the magnitude of the respiratory control ratio of the vesicle preparation. Kinetic analysis of the dependence of oxidase activity on cytochrome c concentration indicated that changes in the Michaelis constant of the enzyme for its substrate are not a major factor in regulation by either delta pH or delta psi. These results suggest a dual mechanism for respiratory control in cytochrome oxidase vesicles under steady-state conditions, in which the electrical gradient predominantly affects electron transfer from cytochrome c to heme a, possibly by altering the reduction potential of heme a, while the pH gradient affects electron transfer from heme a (CuA) to heme a3 (CuB), possibly by a conformationally mediated change in the reduction potential of heme a3 or in the kinetics of the electron-transfer process.
Animals↗