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Biomedical subjects

S E Phillips

Publications and source records attributed to S E Phillips.

At least 91 records · Page 5Linked to original sources
PubMed1989

GnRH agonist administration in polycystic ovary syndrome.

The study was designed to examine (1) the effects of the luteinizing hormone releasing hormone (GnRH) agonist, buserelin, on pituitary and ovarian hormone secretion, and (2) the effect that pituitary-ovarian suppression with a GnRH agonist has on subsequent ovulation induction with exogenous gonadotrophins (hMG), in polycystic ovary syndrome (PCOS). Two protocols were studied where buserelin was administered intranasally to all patients in a dose of 200 micrograms, six times daily. Ten patients received buserelin until an oestrogen withdrawal bleed occurred while a further 12 patients received buserelin for 4 weeks, before hMG was co-administered. Nine of the above subjects also underwent conventional ovulation induction with hMG. Blood samples were taken daily for radioimmunoassay of LH (LH-RIA), FSH, sex steroids and inhibin and for immunoradiometric assay of LH (LH-IRMA). Following buserelin administration there was an initial rise in LH-RIA, FSH, oestradiol (E2) and inhibin (P less than 0.01). Fourteen days were needed for LH-RIA to return to the normal range, with both protocols resulting in a fall in LH-RIA and FSH (P less than 0.01) before hMG was co-administered. Twenty-eight days of buserelin administration were needed to suppress E2 into the castrate range. Inhibin and both E2 and FSH were closely correlated throughout buserelin administration (P less than 0.01). There was failure to respond to an intravenous bolus of 100 micrograms of GnRH from 7 days of buserelin administration onwards, despite the serum LH-RIA still being raised at 7 days. Serum samples assayed for LH by RIA using WHO Matched Reagents and by IRMA were closely correlated (r = 0.96, P less than 0.01). There was no difference in the proportion of ovulations (52% vs 66%) or pregnancies (1 vs 1) in the GnRH agonist or control group. Similar amounts of hMG were needed in both groups and there was multiple follicular development (greater than 3 follicles greater than 15 mm diameter; 41% vs 38%) following hMG administration. There was a close correlation between E2 and inhibin levels (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Intranasal↗
PubMed1989

Feeling OK about AIDS.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Crystallization of the met repressor from Escherichia coli.

The met repressor from Escherichia coli has been crystallized in space group P21, with unit cell dimensions a = 35.6 A, b = 62.6 A, c = 44.5 A, beta = 102.4 degrees and one aporepressor dimer per asymmetric unit. Preliminary X-ray diffraction photographs show measurable intensities to beyond 1.5 A resolution, and the crystal form is ideally suited to high-resolution crystallographic analysis (1 A = 0.1 nm).

Amino Acid Sequence↗
PubMed1988

Outpatient therapy of serious pediatric infections with ceftriaxone.

Convalescent outpatient parenteral antibiotic therapy with ceftriaxone was evaluated in an uncontrolled study of 101 children with documented serious bacterial infections, including meningitis. Criteria for outpatient therapy were established to assure that risks of complications from the illness were minimal at the time of discharge from the hospital. Daily physician visits and motivated, capable parents were considered essential in outpatient management. Ceftriaxone was given once daily to children with non-central nervous system infections and once or twice daily intravenously to children with meningitis. The mean durations of therapy for children with non-central nervous system infections and with meningitis were 2.4 and 4.6 days, respectively. No child enrolled in this study was readmitted to the hospital for medical or social reasons. Probable complications of treatment included diarrhea in 13% of children with meningitis and in 6% of children with non-central nervous system infections. One child with meningitis developed pseudomembranous colitis. For children who are infected with bacteria that are highly susceptible to ceftriaxone, single daily dose outpatient therapy is a reasonable option for management if a good clinical response to initial treatment is demonstrated and the risks of complications of the disease process are negligible.

Adolescent↗
PubMed1988

Vaginal progesterone administration before ovulation induction with exogenous gonadotropins in polycystic ovarian syndrome.

We studied the value of vaginal progesterone (P4) in suppressing serum LH concentrations and restoring normal luteal phase serum LH concentrations before administration of exogenous gonadotropins in anovulatory women with the polycystic ovarian syndrome (PCOS). P4 (50 mg every 12 h) was administered by vaginal suppository to 9 women (18 cycles) for 14 days before ovulation induction with human menopausal gonadotropin (hMG) and hCG. Serum LH, FSH, estradiol, P4, and PRL levels were measured daily. A biphasic effect on LH secretion occurred during P4 administration. Peak serum LH levels occurred on day 5 (125% of basal levels; P less than 0.05) of vaginal P4 suppository use, followed by a progressive fall (P less than 0.05) to 79% of basal levels, but serum LH levels were still higher than those in normal women despite achieving physiological luteal phase P4 concentrations. Ovulation occurred in 56% of cycles after P4 and hMG/hCG treatment and in 65% of control cycles after hMG/hCG alone. In 7 women, serum LH was measured at 10-min intervals for 6 h before and after vaginal P4 administration for 10 days. LH pulse frequency decreased from 7.4 +/- 1.1 to 4.4 +/- 1.2 pulses/6 h (P less than 0.01), and LH pulse amplitude increased from 3.8 +/- 1.8 to 6.1 +/- 2.9 IU/L (P less than 0.01) after P4 administration. We conclude that vaginal P4 (50 mg every 12 h) 1) produces serum P4 concentrations within the normal range for the luteal phase of the menstrual cycle; 2) elevates serum LH, but not FSH, within 5 days; 3) decreases LH pulse frequency and increases LH pulse amplitude after 10 days, but does not normalize serum LH values; and 5) fails to improve the results of subsequent ovulation induction with exogenous gonadotropins in patients with PCOS.

Administration, Intravaginal↗
PubMed1987

The structural basis of antigen-antibody recognition.

We have reviewed here the three-dimensional structure of an antigen-Fab complex as determined by X-ray crystallographic studies. The antigen is hen egg-white lysozyme (HEL), a protein whose three-dimensional structure and antigenic properties are well known. The Fab was prepared from a murine monoclonal anti-HEL antibody, IgGl,kappa, obtained by cell-hybridization techniques. The equilibrium association constant for the complex is 4.5 X 10(7) mol-1. The complex was crystallized and its three-dimensional structure was determined at 6-A and 2.8-A resolution. A three-dimensional model of the structure was built based on electron-density maps and the amino-acid sequence [determined from the nucleotide sequence of cDNA clones (M. Verhoeyen, C. Berek, J.M. Jarvis, G. Winter, in preparation)]. The three-dimensional structure of the complex shows that 17 antibody residues make close contacts (less than or equal to 4 A) with 16 antigen residues. Fifteen of the contacting antibody residues belong to the six complementarity-determining regions of the light chain (6 residues) and of the heavy chain (9 residues). The remaining two are located in regions of constant or nearly constant sequence ["framework" regions]. The 16 contacting lysozyme residues form a discontinuous, topographical determinant, since they are widely separated in the linear amino-acid sequence but are brought to relative spatial proximity by the three-dimensional folding of the polypeptide chain. The contacting surfaces are relatively flat, with protruding side chains of antigen and antibody penetrating each other over an area with maximum dimensions of 30 X 20 A. As in several other systems of protein-protein interactions, the contacts are chemically characterized as van der Waals interactions and hydrogen bonds. Detailed analysis of the interactions reveals that the antibody's recognition of the antigen is finely specific and is affected by antigenic variation (as observed in lysozymes from other avian species). The quaternary structure of the complexed Fab is elongated, with the axes of the variable (VH + VL) and constant (CH1 + CL) domains making an angle close to 180 degrees. Comparison of the three-dimensional structure of the complexed lysozyme with that of native lysozyme showed no significant conformational change at the current resolution (2.8 A). Comparison of the Fab moiety of the complex with other Fabs of known three-dimensional structure suggested that upon complexing no conformational change takes place in the tertiary structure of Fab either.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies↗
PubMed1986

Three-dimensional structure of an antigen-antibody complex at 2.8 A resolution.

The 2.8 A resolution three-dimensional structure of a complex between an antigen (lysozyme) and the Fab fragment from a monoclonal antibody against lysozyme has been determined and refined by x-ray crystallographic techniques. No conformational changes can be observed in the tertiary structure of lysozyme compared with that determined in native crystalline forms. The quaternary structure of Fab is that of an extended conformation. The antibody combining site is a rather flat surface with protuberances and depressions formed by its amino acid side chains. The antigen-antibody interface is tightly packed, with 16 lysozyme and 17 antibody residues making close contacts. The antigen contacting residues belong to two stretches of the lysozyme polypeptide chain: residues 18 to 27 and 116 to 129. All the complementarity-determining regions and two residues outside hypervariable positions of the antibody make contact with the antigen. Most of these contacts (10 residues out of 17) are made by the heavy chain, and in particular by its third complementarity-determining region. Antigen variability and antibody specificity and affinity are discussed on the basis of the determined structure.

Animals↗
PubMed1986

The predicted structure of immunoglobulin D1.3 and its comparison with the crystal structure.

Predictions of the structures of the antigen-binding domains of an antibody, recorded before its experimental structure determination and tested subsequently, were based on comparative analysis of known antibody structures or on conformational energy calculations. The framework, the relative positions of the hypervariable regions, and the folds of four of the hypervariable loops were predicted correctly. This portion includes all residues in contact with the antigen, in this case hen egg white lysozyme, implying that the main chain conformation of the antibody combining site does not change upon ligation. The conformations of three residues in each of the other two hypervariable loops are different in the predicted models and the experimental structure.

Amino Acid Sequence↗
PubMed1983

Physiological and x-ray studies of potential antisickling agents.

Several aromatic compounds have been found to inhibit the gelling of sickle cell hemoglobin. We have tried to correlate the antigelling activity of such compounds with the stereo-chemistry of their binding sites in the hemoglobin molecule. This approach led to the discovery that two known antilipoproteinemia drugs, clofibrate and gemfibrozil, have antigelling activity. X-ray analysis showed that three pairs of molecules of clofibric acid, the active metabolite of clofibrate, bound to the walls of the internal cavity of deoxyhemoglobin A; only one pair bound to a quite different site, between helices A, E, and H of the alpha chains of carbon monoxide hemoglobin A. Unlike other antigelling agents, clofibric acid and related compounds decrease rather than increase the oxygen affinity of hemoglobin.

Antisickling Agents↗
PubMed1978

Structure of hemoglobins Zürich [His E7(63)beta replaced by Arg] and Sydney [Val E11(67)beta replaced by Ala] and role of the distal residues in ligand binding.

In hemoglobin Zürich the side chain of the distal arginine attaches itself to the propionate of the heme, leaving the heme pocket wide open, allowing sulfanilamides easy access to the iron, and doubling the partition coefficient between CO and O2. The replacement of the distal valine by alanine in hemoglobin Sydney leaves a large gap inside the heme pocket, which is partly filled by a water molecule bonded to the distal histidine. Hemoglobin Sydney has the same partition coefficient between CO and O2 as hemoglobin A. Replacement of the distal histidine increases the stretching frequency of CO linked to the beta heme by 6 cm-1, but replacement of the distal valine increases it by only 3 cm-1, but replacement of the distal histidine leaves the O-O stretching frequency unchanged.

Alanine↗