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Biomedical subjects

C S Wright

Publications and source records attributed to C S Wright.

14 recordsLinked to original sources
PubMed1992

Crystal structure of a wheat germ agglutinin/glycophorin-sialoglycopeptide receptor complex. Structural basis for cooperative lectin-cell binding.

The crystal structure of wheat germ agglutinin isolectin 1 (WGA1) complexed with a tryptic sialoglycopeptide fragment (T-5) from its erythrocyte receptor glycophorin A, which contains the O-linked tetrasaccharide NeuNAc-alpha 2,3-Gal-beta 1,3-(alpha 2,6-NeuNAc) Gal-NAc-alpha 1-O-Thr, has been determined by molecular replacement techniques and refined at 2.0-A resolution (R = 18.1%). The structure reveals that association between WGA1 dimers, composed of two identical four-domain (A-D) monomers, and T-5 is asymmetric and involves sialic acid binding at three nonequivalent aromatic residue-rich sites. Two independent binding modes are observed. In the dominant ("major") binding mode, the two highest affinity sites are utilized to cross-link neighboring crystallographically related WGA1 dimers. The branched tetrasaccharide has an extended rigid conformation, and its terminal alpha 2,6-NeuNAc and alpha 2,3-NeuNAc residues occupy specificity sites in domains B1 (monomer 1) and C2 (monomer 2) on opposing dimers, respectively. This asymmetric selection of binding sites leads to infinite open-ended arrays of interlinked lectin molecules. In the subsidiary "minor" binding mode, only the terminal alpha 2,6-NeuNAc, anchored to the aromatic residue-rich binding site in domain A2, is clearly visible. The remaining portion of T-5 is disordered. This structure presents the first evidence for NeuNAc binding in the aromatic residue-rich sites of domains A and C and suggests a preference of WGA for alpha 2,6-linked NeuNAc. Moreover, the unusual asymmetric WGA1-tetrasaccharide association, involving domain binding sites that differ in their binding affinities for NeuNAc, offers explanations for the widely observed cooperative cell binding behavior of WGA.

Amino Acid Sequence↗
PubMed1991

Evolution of a family of N-acetylglucosamine binding proteins containing the disulfide-rich domain of wheat germ agglutinin.

A disulfide-rich domain, first identified in wheat germ agglutinin, has now been identified in the amino acid and DNA sequences of a large number of other chitin-binding proteins. This 43-residue domain includes eight disulfide-linked cysteines and has been implicated in the binding of N-acetylglucosamine and its polymers. This study used 12 complementary DNA sequences and 1 amino acid sequence of proteins with one, two, and four copies of this domain to infer a 44-amino acid residue ancestor sequence for this domain, and to derive an evolutionary tree relating these domains in the different proteins. The tree relating these single-domain sequences is divided into two major branches, one consisting of the multidomain dimeric lectins, which we have earlier suggested arose by duplication of a single copy of the disulfide-rich domain, and the other branch consisting of the monomeric chitinases and wound-inducible proteins, which have a single copy of the domain fused to a larger polypeptide. Reference to the three-dimensional structure of WGA and its saccharide complexes shows that the saccharide-binding residues as well as cysteine and glycine residues are conserved among all available sequences. In contrast, many residues at the dimer interface of the domains of WGA are not conserved in those proteins with a single domain, implying that the aggregation state of the domains in these proteins differs from that of the gras lectins. Also, the base compositions of the four-domain and one-domain branches of the tree differ, indicating distinct selective pressures at the level of both protein structure and the gene or its transcript.

Acetylglucosamine↗
PubMed1991

Evaluating the quality of the maternity services--a discussion paper.

OBJECTIVE: A review of the use of computer collected audit data in assessing the quality of maternity services. SETTING: All maternity units managed by the North West Thames Regional Health Authority. RECOMMENDATIONS: A system of audit must supply information that is both credible and of interest to clinicians managers and consumers. The information should be adjusted for differences in populations to allow valid comparisons between units. It needs to be presented in an easily digested form. One way of implementing audit would be to establish a regional group representative of clinicians, patients and managers who would initially interpret the data and make recommendations. A local group of similar composition would be asked to comment on and respond to these with a plan for the following year. Changes would be monitored by analysis of the routinely collected data. CONCLUSIONS: Medical audit in the maternity services requires new concepts if it is to influence the quality of clinical care and the use of resources available to provide that care. The appropriate balance needs to be found between the perspectives of clinicians, patients and managers. A major challenge is the collection of valid data. This has largely been overcome by the St Mary's maternity information system. The next stage is to devise a system of audit that is epidemiologically sound and is acceptable to those who will be asked to implement the lessons that emerge. Only then will it be possible to determine whether clinical practice and the use of resources can be altered to the benefit of patients.

Data Collection↗
PubMed1979

Value of bromocriptine in unexplained primary infertility: a double-blind controlled trial.

In a double-blind controlled study, 47 women with unexplained primary infertility were allocated at random to treatment with either bromocriptine 2.5 mg twice daily (24 patients) or placebo (23). Both groups showed a fall in serum prolactin concentrations but the reduction was much greater in the bromocriptine-treated group. Neither group showed a change in serum oestrogen or progesterone concentrations. Bromocriptine significantly reduced the duration of the follicular phase of the menstrual cycle but had no effect on the luteal phase. Five women conceived during treatment with placebo and seven during treatment with bromocriptine, but analysis of the cumulative conception rates showed no significant difference between the groups. The women who conceived were significantly younger and had a significantly shorter history of infertility than the women who did not conceive, but subtracting the number of years of infertility from age eliminated this difference. The results show that bromocriptine in the dose and duration of administration used in the trial is of no value in unexplained primary infertility.

Adult↗
PubMed1979

Spontaneous pregnancy in a patient with hypergonadotrophic ovarian failure.

A 27-year-old woman was referred to the gynaecological endocrine clinic because of infertility and secondary amenorrhoea. Serum luteinizing hormone and follicle stimulating hormone levels were raised and oestradiol concentrations were subnormal. In spite of these findings, spontaneous resumption of menstrual cycles associated with a fall of gonadotrophin concentrations was followed by a normal pregnancy.

Adult↗
PubMed1979

The hemolytic anemias.

Hemolytic anemias usually present with persistent reticulocytosis, a characteristic that differentiates them from other types of anemia. Once the presence of a hemolytic process has been documented, simple observation of red blood cell morphology will yield important etiologic information. Hemolysis may result from inherent defects in the red cell or from excessive environmental stress on normal cells. Immune mechanisms of hemolysis should be investigated early because of the frequency of their occurrence.

Anemia, Hemolytic↗
PubMed1979

Inhibition of erythropoiesis by plasma component(s) from sheep, goats, and rabbits.

Plasma from hypertransfused and normal sheep and experimentally induced anemic and normal goats was fractionated by ultrafiltration. Fractions obtained were assayed for erythropoiesis stimulatory factor (ESF) or erythropoiesis inhibitory factor (EIF) activity (or both) in the posthypoxic polycythemic mouse assay. The most potent sheep plasma-inhibitor fraction was found in the retentate on a membrane with a cutoff at mol wt 50,000. The most potent EIF fraction from anemic goats passed into the ultrafiltrate, but the comparable EIF from normal goats remained in the retentate on a membrane with a cutoff at mol wt 500. The yield of the most potent EIF fraction was higher from anemic goats than was the yield from normal goats. During thin-layer chromatography, EIF extracted from goat plasma fractions had the same mobility as did prostaglandin F2 alpha. Cohn rabbit plasma fraction IV-4 had an inhibitory factor, and a benzene extract of the fraction contained a component that had the same mobility as did prostaglandin F2 alpha. Cohn rabbit plasma fraction V contained a component that potentiated an erythropoietin-generating factor.

Animals↗
PubMed1978

Menstrual patterns after laparoscopic sterilization using a spring-loaded clip.

Details of the menstrual cycles in 504 women were recorded before laparoscopic sterilization with a spring-loaded clip and at six months and one year after the procedure. The operation did not affect the length of the menstrual cycle or duration of menstrual flow, nor the patient's assessment of the amount of blood losss or the incidence of dysmenorrhoea. The previous method of contraception was significantly related to subsequent menstrual patterns.

Adult↗
PubMed1977

Laparoscopic sterilization with spring-loaded clips: double-puncture technique.

The application of a spring-loaded clip to each fallopian tube using a second-incision clip applicator is a safe and effective method of laparoscopic sterilization. The operation is quick and easy to perform and is suitable for use with local anesthesia. The method avoids the dangers of hemorrhage, for the clip only alters 3 mm of the fallopian tube and does not transect the tube or mesosalpinx. No pregnancies have followed the sterilization procedure. An intrauterine pregnancy has occurred after a reversal procedure in one patient.

Abdomen↗
PubMed1975

Response in mice to an erythropoietin-generating factor.

The bioassay for erythropoietin-stimulating factor (ESF) was compared in 3 strains of mice. One strain was made polycythemic by hypertransfusion and the other 2 by hypoxia. An erythropoiesis-generating factor (EGF) measured in the 3 strains generated approximately the same amounts of ESF, determined with log dose-log response curves for the respective techniques, after incubation with normal rabbit serum (NRS). The amount of ESF generated by EGF without prior incubation with NRS was also approximately the same in the 3 strains of mice.

Altitude↗