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Biomedical subjects

D R Hall

Publications and source records attributed to D R Hall.

At least 37 records · Page 2Linked to original sources

Identification of methyl salicylate as the principal volatile component in the methanol extract of root bark of Securidaca longepedunculata Fers.

Securidaca longepedunculata Fers (Polygalaceae) is commonly used as a medicine in many parts of Africa and shows promise for protecting stored grain against insect pests. Analysis of a methanol extract of the root bark by gas chromatography linked to mass spectrometry (GC/MS) showed a major component accounting for over 90% of the volatile material. This was identified as methyl 2-hydroxybenzoate (methyl salicylate) by comparison of the GC retention times and mass spectrum with those of synthetic standards. This conflicts with an earlier report that the major component is methyl 4-hydroxybenzoate. Two minor components had mass spectra characteristic of 2-hydroxybenzoate esters and were identified as methyl 2-hydroxy-6-methoxybenzoate and its benzyl analogue, again conflicting with an earlier report.

Benzoates↗

Urinary protein excretion and expectant management of early onset, severe pre-eclampsia.

OBJECTIVE: To evaluate the importance of proteinuria in the expectant management of early onset, severe pre-eclampsia. METHODS: In this prospective series of 340 women, 24-h urine collections were performed and monitored twice weekly in a high-care ward. RESULTS: Seventy-four women with at least two 24-h urine collections were grouped into women with a proteinuria increase of > or =2 g (n=29) and with women whose proteinuria decreased, or increased by <2 g (n=45). Major maternal complications, prolongation of gestation, and perinatal outcomes were comparable. Fifty-six (75%) women experienced an increase in proteinuria. When patients with heavy proteinuria (n=83) were compared to those with moderate proteinuria (n=257), maternal and perinatal outcomes were comparable. More days were gained before delivery in the heavy proteinuria group than in the moderate (12 vs. 9; P<0.001). CONCLUSION: Most patients experienced increased proteinuria. Neither the rate of increase nor the amount of proteinuria affected maternal and perinatal outcomes.

Abruptio Placentae↗

Primipaternity and duration of exposure to sperm antigens as risk factors for pre-eclampsia.

OBJECTIVE: To establish whether primipaternity and duration of unprotected sexual cohabitation is associated with an increased risk of pre-eclampsia. METHOD: At a tertiary referral center, the study had a case and control group of 60 multigravid women each, as well as a case and control group of 50 primigravid women each. Information was compiled by means of a confidential questionnaire. RESULT: After multiple logistic regression analysis using age, smoking, hypertension in previous pregnancies, change of paternity and duration of unprotected sexual cohabitation as predictors, the regression coefficients for change of paternity and sexual cohabitation of longer than 6 months in multigravid women were -0.4 (P = 0.15) and -1.4 (P = 0.03), respectively. CONCLUSION: Multigravid women with a period of unprotected sexual cohabitation of longer than 6 months had a decreased risk of pre-eclampsia. Primipaternity was not a significant risk factor for pre-eclampsia.

Adult↗

Intermale variation in aggregation pheromone release in Prostephanus truncatus.

Intermale variation in pheromone signaling has been confirmed and quantified by measurements of pheromone produced by single adult male Prostephanus truncatus (Horn) (Coleoptera: Bostrichidae). Males varied in both the amounts of the two components of their aggregation pheromone and the ratio of one component to the other. The mean rates of production of the pheromone components T1 and T2 were 1.9 and 0.5 microg/day, respectively. There were repeatable differences among males in the amounts of T2 produced and the proportion of T1 in the pheromone blend over two weeks. Of the 15 males studied, one released a large burst of pheromone in a short period, while the remainder, if they did release, did so over an extended period. This suggested that there may be two alternative release strategies and the significance of this is discussed.

Animals↗

The crystal and molecular structures of diferric porcine and rabbit serum transferrins at resolutions of 2.15 and 2.60 A, respectively.

The serum transferrins are monomeric proteins with a molecular mass of around 80 kDa and are responsible for the transport of iron in vertebrates. The three-dimensional structures of diferric porcine and rabbit serum transferrin have been refined against X-ray diffraction data extending to 2.15 and 2.60 A, respectively. Data for both proteins were collected using synchrotron radiation at temperatures of 277 K. The porcine protein crystallizes in the space group C2, with unit-cell parameters a = 223.8, b = 44.9, c = 78.9 A, beta = 105.4 degrees with one molecule in the asymmetric unit. The structure was solved by molecular-replacement methods using rabbit serum transferrin as the search model. The structure was refined using REFMAC, with a final residual of 13.8% (R(free) = 18.2% for a 5% data sample) for all data to 2.15 A. The final model comprises 5254 protein atoms, two Fe(3+) cations and two CO(3)(2-) anions, one N-acetyl glucosamine moiety and 494 water molecules. The rabbit protein crystallizes in space group P4(3)2(1)2, with unit-cell parameters a = 127.2, c = 144.9 A and one molecule per asymmetric unit. The structure was solved using the method of multiple isomorphous replacement and refined using REFMAC to give a final residual of 18.6% (R(free) = 22.2% for a 5% data sample) for all data to 2.60 A. The final model comprises 5216 protein atoms, two Fe(3+) cations and two CO(3)(2-) anions, a Cl(-) anion and 206 solvent molecules; there is no clear indication of the carbohydrate moiety attached to Asn490 (rabbit serum numbering). Both molecules adopt a bilobal structure typical for members of the transferrin family. Each of the structurally homologous lobes contains two dissimilar domains with a single iron-binding site buried within the interdomain cleft. The porcine serum protein lacks an interdomain disulfide bridge close to the connecting peptide between the lobes, but this seems to have little effect on the overall orientation of the lobes. The N-lobes of both proteins possess lysine residues, one from each of the two domains, that lie in close proximity to one another to form the so-called dilysine trigger. The more acid-labile release of iron from serum transferrins than from lactoferrins is discussed.

Animals↗

RadA protein from Archaeoglobus fulgidus forms rings, nucleoprotein filaments and catalyses homologous recombination.

Proteins that catalyse homologous recombination have been identified in all living organisms and are essential for the repair of damaged DNA as well as for the generation of genetic diversity. In bacteria homologous recombination is performed by the RecA protein, whereas in the eukarya a related protein called Rad51 is required to catalyse recombination and repair. More recently, archaeal homologues of RecA/Rad51 (RadA) have been identified and isolated. In this work we have cloned and purified the RadA protein from the hyperthermophilic, sulphate-reducing archaeon Archaeoglobus fulgidus and characterised its in vitro activities. We show that (i) RadA protein forms ring structures in solution and binds single- but not double-stranded DNA to form nucleoprotein filaments, (ii) RadA is a single-stranded DNA-dependent ATPase at elevated temperatures, and (iii) RadA catalyses efficient D-loop formation and strand exchange at temperatures of 60-70 degrees C. Finally, we have used electron microscopy to visualise RadA-mediated joint molecules, the intermediates of homologous recombination. Intriguingly, RadA shares properties of both the bacterial RecA and eukaryotic Rad51 recombinases.

Adenosine Diphosphate↗

Delivery of patients with early onset, severe pre-eclampsia.

OBJECTIVES: To compare the effects of induction/labor to delivery before labor in early onset, severe pre-eclampsia. METHODS: Five-year prospective case series. Delivery course and neonatal outcome were examined for 335 women with viable singletons. RESULTS: Induction was successful in 45% of attempts. Women exposed to labor had longer (5.5 days, P<0.0001) admissions to delivery periods and were more often delivered for maternal indications (RR=2.87, 95% CI=1.98-4.16). Their babies were born 1.6 weeks older (P<0.0001) and 352 g heavier (P<0.0001) than those delivered before labor. Babies exposed to labor needed intensive care less often (RR=0.4, 95% CI=0.27-0.58), had lower rates of severe hyaline membrane disease (RR=0.26, 95% CI=0.11-0.59) and sepsis (RR=0.56, 95% CI=0.33-0.93), and were discharged earlier (P<0.0001). CONCLUSIONS: Exposure to induction/labor in selected patients is not detrimental to neonatal outcome in early, severe pre-eclampsia.

Adult↗

Expectant management of severe pre-eclampsia in the mid-trimester.

OBJECTIVE: To determine maternal and perinatal outcomes with expectant management of severe pre-eclampsia in the mid-trimester, using a defined entry point. DESIGN: Prospective case series. Thirty-nine women admitted from 24 to 27 week's gestation with severe pre-eclampsia, whose pregnancies were otherwise stable, were managed expectantly with careful clinical and biochemical monitoring of maternal and foetal status, together with careful blood pressure control, in a high-care obstetric ward. The aim was to safely prolong the pregnancies and thereby improve perinatal outcome. RESULTS: Gestation was prolonged by a median of 12 (range 3--47) days, with greater periods gained at earlier gestations. The overall perinatal loss was 26% and the neonatal loss 17%. The rates of significant maternal complications were low. CONCLUSION: Expectant management of selected women with severe pre-eclampsia from 24 to 27 weeks' gestation in a tertiary care unit is acceptably safe and improves perinatal outcome.

Adolescent↗

Components of male aggregation pheromone of strawberry blossom weevil, Anthonomus rubi herbst. (Coleoptera:Curculionidae).

The strawberry blossom weevil, Anthonomus rubi, is a major pest of strawberries in the United Kingdom and continental Europe. As part of a project to develop noninsecticidal control methods, the pheromone system of this species was investigated. Comparison of volatiles produced by field-collected, overwintering individuals of each sex led to identification of three male-specific compounds--(Z)-2-(3,3-dimethylcyclohexylidene)ethanol, (cis)-1-methyl-2-(1-methylethenyl)cyclobutaneethanol, and 2-(1-methylethenyl)-5-methyl-4-hexen-1-ol (lavandulol)--in amounts of 6.1, 1.2, and 0.82 microg/day/ male. The first two compounds are components of the aggregation pheromone of the boll weevil, Anthonomus grandis, grandlure II and grandlure I, respectively. Grandlure I was the (1R,2S)-(+) enantiomer and lavandulol was a single enantiomer, although the absolute configuration was not determined. Trace amounts of the other two grandlure components (Z)-(3,3-dimethylcyclohexylidene)acetaldehyde (grandlure III) and (E)-(3,3-dimethylcyclohexylidene)acetaldehyde (grandlure IV) were also detected. (E,E)-1-(1-Methylethyl)-4-methylene-8-methyl-2,7-cyclo-decadiene (germacrene-D), a known volatile from strawberry plants, Fragaria ananassa, was collected in increased amounts in the presence of pheromone-producing weevils. Male weevils only produced pheromone on F. ananassa and not on scented mayweed, Matracaria recutita, or cow parsley, Anthriscus sylvestris, although these are known food sources. In field trials using various combinations of synthetic grandlures I, II, III, and IV and lavandulol, significantly more weevils were caught in traps baited with blends containing grandlure I and II and lavandulol than in those baited with blends without lavandulol or unbaited controls. Addition of grandlure III and IV had no significant effect on attractiveness. Horizontal sticky traps were found to be more effective than vertical sticky traps or standard boll weevil traps. In mid-season females predominated in the catches, but later more males than females were trapped.

Animals↗

Female sex pheromone of brinjal fruit and shoot borer, Leucinodes orbonalis blend optimization.

The brinjal fruit and shoot borer, Leucinodes orbonalis is the major pest of eggplant in South Asia. Analysis of female pheromone gland extracts prepared from insects of Indian and Taiwanese origin confirmed (E)-11-hexadecenyl acetate (E11-16:Ac) as the major pheromone component with 0.8 to 2.8% of the related (E)-11-hexadecen-1-ol (E11-16:OH), as previously reported from Sri Lanka. The average quantity of E11-16:Ac extracted per female was estimated to be 33 ng, with a range of 18.9 to 46.4 ng when collected 2 to 3 hr into the scotophase. In field trials conducted in India, blends containing between 1 and 10% E11-16:OH caught more male L. orbonalis than E11-16:Ac alone. At the 1,000 microg dose, on white rubber septa, addition of 1% E11-16:OH to E11-16:Ac was found to be more attractive to male L. orbonalis than either 0.1 or 10% E11-16:OH. Trap catch was found to be positively correlated with pheromone release rate, with the highest dose tested, 3,000 microg, on white rubber septa catching more male moths than lower doses. Field and wind tunnel release rate studies confirmed that E11-16:OH released from white rubber septa and polyethylene vials at approximately twice the rate of E11-16:Ac and that the release rate of both compounds was doubled in polyethylene vials compared to white rubber septa. This difference in release rate was reflected in field trials conducted in Bangladesh where polyethylene vial dispensers caught more male moths than either black or white rubber septa, each loaded with the same 100:1 blend of E11-16:Ac and E11-16:OH in a 3,000 microg loading.

Animals↗

The effects of inadvertent intramuscular injection of BCG vaccine.

We report on a case of inadvertent intramuscular injection of BCG vaccine into an already tuberculin-sensitive individual which resulted in a severe and prolonged local reaction. There is no consensus on the best management of this complication, although in this case healing appeared to be hastened by anti-tuberculous chemotherapy.

Abscess↗

Pregnancy outcome in women with prosthetic heart valves.

The pregnancy outcome of 59 pregnancies in 38 women with prosthetic heart valves, managed at a tertiary referral centre from 1989-98 were reviewed. Ten women underwent valve replacement during pregnancy. The main outcome measures were major maternal complications and perinatal outcome. The maternal mortality rate for pregnancies following valve replacement surgery was 6.1%, with a 21% pregnancy loss before viability and a perinatal loss of 8%. Major morbidity in this group was as follows: haemorrhage 29.8%, cardiac failure 12.8%, thromboembolism 8.5%, infective endocarditis 6.4% and valve thrombosis 4.3%. No maternal mortality occurred among those who underwent valve replacement during pregnancy but their perinatal loss was 25%. We conclude that although maternal mortality and morbidity rates in women with prosthetic heart valves who became pregnant were high, the perinatal outcome was good except for women who underwent valve replacement during pregnancy who experienced a high perinatal loss rate.

Journal Article↗

The influence of maternal age on pregnancy outcome in patients with early onset, severe pre-eclampsia.

Pregnancy outcomes of women in three age categories, < or = 19, 20-34 and > or = 35 years, who underwent expectant management of early onset, severe pre-eclampsia were evaluated. This formed part of a prospective study involving 340 selected women from April 1992 to March 1997. Frequent monitoring of maternal and fetal status in a high-care obstetric ward was performed. Main outcome measures were major maternal complications, prolongation of gestation and perinatal outcome. Pregnancy was prolonged by a comparable number (10, 9 and 12) of days in the groups. Placental abruption was the most frequent major maternal complication, occurring more often in the youngest group (P=0.04). Women in this group also had the highest perinatal mortality and more often required anti-hypertensive medication at discharge (P<0.001). Younger women (< or = 19 years) appear to be at higher risk for maternal and perinatal complications.

Journal Article↗

Interpretation of thermodynamic non-ideality in sedimentation equilibrium experiments on proteins.

This investigation re-examines theoretical aspects of the allowance for effects of thermodynamic non-ideality on the sedimentation equilibrium distribution for a single macromolecular solute, and thereby resolves the question of the constraints that pertain to the definition of the activity coefficient term in the basic sedimentation equilibrium expression. Sedimentation equilibrium results for ovalbumin are then presented to illustrate a simple procedure for evaluating the net charge (valence) of a protein from the magnitude of the second virial coefficient in situations where the effective radius of the protein can be assigned. Finally, published sedimentation equilibrium results on lysozyme are reanalysed to demonstrate the feasibility of employing the dependence of the second virial coefficient upon ionic strength to evaluate both the valence and the effective radius of the non-interacting solute.

Animals↗

The three-dimensional structure of a Plasmodium falciparum cyclophilin in complex with the potent anti-malarial cyclosporin A.

Cyclosporin A (CsA) is a potent anti-malarial compound in vitro and in vivo in mice though better known for its immunosuppressive properties in humans. Crystal structures of wild-type and a double mutant Plasmodium falciparum cyclophilin (PfCyP19 and mPfCyP19) complexed with CsA have been determined using diffraction terms to a resolution of 2.1 A (1 A=0.1 nm). The wild-type has a single PfCyP19/CsA complex per asymmetric unit in space group P1 and refined to an R-work of 0.15 and R-free of 0.19. An altered cyclophilin, with two accidental mutations, Phe120 to Leu in the CsA binding pocket and Leu171 to Trp at the C terminus, presents two complexes per asymmetric unit in the orthorhombic space group P2(1)2(1)2. This refined to an R-work of 0.18 and R-free 0.21. The mutations were identified from the crystallographic analysis and the C-terminal alteration helps to explain the different crystal forms obtained. PfCyP19 shares approximately 61 % sequence identity with human cyclophilin A (hCyPA) and the structures are similar, consisting of an eight-stranded antiparallel beta-barrel core capped by two alpha-helices. The fold creates a hydrophobic active-site, the floor of which is formed by side-chains of residues from four antiparallel beta-strands and the walls from loops and turns. We identified C-H.O hydrogen bonds between the drug and protein that may be an important feature of cyclophilins and suggest a general mode of interaction between hydrophobic molecules. Comparisons with cyclophilin-dipeptide complexes suggests that a specific C-H.O hydrogen bonding interaction may contribute to ligand binding. Residues Ser106, His99 and Asp130, located close to the active site and conserved in most cyclophilins, are arranged in a manner reminiscent of a serine protease catalytic triad. A Ser106Ala mutant was engineered to test the hypothesis that this triad contributes to CyP function. Mutant and wild-type enzymes were found to have similar catalytic properties.

Amino Acid Sequence↗

Risk factors for and perinatal mortality of abruptio placentae in patients hospitalised for early onset severe pre-eclampsia - a case controlled study.

We set out to determine which patients admitted for expectant management of early onset severe pre-eclampsia develop abruptio placentae and to compare the perinatal mortality rate of patients who developed abruptio placentae with those who did not have this complication. This was a case controlled study, using gestational age at delivery to select a control group for 69 patients who developed abruptio placentae. The only significant difference on admission was the higher uric acid levels in patients who developed abruptio placentae. Mean admission to delivery intervals were 11.9 and 8.8 days for the control and abruption groups respectively (P = 0.0083). Fifty-eight per cent of the babies in the abruptio placentae group developed late decelerations, as determined by fetal heart rate monitoring compared with 32% in the control group. Lactate dehydrogenase levels before delivery were significantly higher in the abruption group, but it only became elevated shortly before delivery and in the minority of cases. There were two intrauterine and four neonatal deaths in the abruption group and two neonatal deaths in the control group. Late decelerations detected by frequent fetal heart rate monitoring in patients with early onset severe pre-eclampsia is the only early warning of abruptio placentae.

Journal Article↗