Biomedical subjects
Publications and source records attributed to D J Williams.
This case report describes death in a young male, six months after an assault. The death was caused by a colloid cyst, a rare but important malformation in the brain. The possible relationship between the assault and the cyst is discussed.
We reviewed 31 patients at a mean of five years after mallet deformity of the finger had been treated with a thermoplastic splint. Intra-articular fractures were present in 35% of patients. Osteoarthritic changes had developed in 48%, most in association with fracture, and 29% had a swan-neck deformity. There was a loss of extension greater than 10 degrees in 35%; the average deficit at the interphalangeal joint was 8.3 degrees and the average flexion arc was 48.5 degrees. Despite these findings, patient satisfaction was generally high, with little evidence of functional impairment.
It is often accepted by hospital staff that patients would prefer to be at home for the Christmas and Easter holiday periods. This is one of the reasons that elective surgery is reduced at these times. However there is very little evidence to prove whether this is true. To investigate this question 310 patients attending surgical or urological outpatients were given a self completion questionnaire asking them whether they would accept admission over these holidays if offered it. Overall 77 per cent of males and 76 per cent of females would accept admission over the Christmas period for elective surgery. This rises to 87 per cent and 88 per cent over the Easter period. Older patients, widows or widowers, retired patients and patients with subjectively severe symptoms and conditions were groups that independently accepted such admissions more readily than others. Contrary to the perceived opinion in hospital staff, in this sample of surgical and urological patients most patients appear willing to accept admission for elective surgery over the Christmas or Easter holiday periods.
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RNA hairpins with loops of either ten or eight nucleotides, or seven nucleotides with (ethylene glycol)n spacers, have been compared in experiments that measure the NaCl dependence of their thermodynamic properties. In 1 M NaCl, the eight-nucleotide RNA hairpin/loop has the most favorable folding free energy (delta G degree = -8.6 kcal/mol), while the RNAs containing the spacers are considerably more unstable (delta G degree = -5.2 to -5.7 kcal/mol); for these RNA/linker species, there are compensating reductions in favorable entropy and unfavorable enthalpy of the helix-coil transition. Preferential interaction coefficients (delta IN) determined from analyses of melting transitions as a function of NaCl concentration are compared to determine the effect of the ethylene glycol on differential ion association. While the difference in ion association to the helix and coil states of the fully RNA molecules follows prediction, the RNAs with linkers do not, indicating that the description of their native and/or denatured state has changed.
Intense, magnetic field-aligned, bidirectional, energetic (>15 kiloelectron volts) electron beams were discovered by the Galileo energetic particles detector during the flyby of Io. These beams can carry sufficient energy flux into Jupiter's atmosphere to produce a visible aurora at the footprint of the magnetic flux tube connecting Io to Jupiter. Composition measurements through the torus showed that the spatial distributions of protons, oxygen, and sulfur are different, with sulfur being the dominant energetic (> approximately 10 kiloelectron volts per nucleon) ion at closest approach.
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The N-terminal RNA binding domain (RBD1) of the human U1A protein binds to the ten nucleotide loop in stemloop II of of U1 snRNA, and to its own 3' UTR structure. The nucleotides critical for recognition by the U1A RBD are displayed in very different geometric contexts in these two targets, leading to the question of what common features of RNA structure allow the RBD to efficiently recognize these two RNAs. The experiments described here used RNA hairpins, in which the loop size was altered by deletion, insertion or substitution with non-nucleotide (ethylene glycol)n spacers, to determine what features of this RNA structure were critical for interaction with the RBD1. Substitution of the three nucleotides on the 3' side of the RNA hairpin loop by (ethylene glycol)6-18 spacers does not significantly perturb the affinity, energetics or electrostatics of this RNA: protein association. These results confirm the suggestion that these loop nucleotides provide a flexible tether to allow the other seven nucleotides to fit onto the binding surface of the RBD, and lead to the hypothesis that conformational flexibility and the possible end-to-end distance of seven loop nucleotides are critical features of this complex formation.
It has been reported that some breeds of cattle such as the N'Dama mount a more effective antibody response to the variable surface glycoprotein coat of trypanosomes and that this may contribute to their ability to control the infection. Thus we have investigated antibody responses to surface exposed epitopes of the variable surface glycoprotein in Trypanosoma congolense-infected N'Dama (trypanotolerant) and Boran (susceptible) cattle. Similar titres and isotypes were found in both N'Damas and Borans indicating that trypanotolerance is not associated with superior antibody-mediated destruction of trypanosomes. However, significant differences in antibody responses to cryptic VSG epitopes and non-trypanosome antigens were identified. Trypanosusceptible Boran cattle had low IgG1 responses to cryptic epitopes but high IgM responses to non-trypanosome antigens such as beta-galactosidase. In contrast the N'Dama cattle had significantly higher IgG1 responses to cryptic VSG epitopes and negligible responses to beta-galactosidase. These results indicate differences in the induction of anti-trypanosome immune responses between trypanotolerant and susceptible cattle infected with T. congolense.
Dementia pugilistica is classically seen in boxers. We describe the case of a 33-yr-old achondroplastic dwarf who developed the pathological hallmarks of the condition, probably as a result of chronic occupational trauma. Dementia pugilistica has not been previously described in achondroplasia.
T-cell-mediated immune responses to defined antigens of Trypanosoma congolense were measured in cattle undergoing primary infection. The antigens used were the variable surface glycoprotein and two invariant antigens, a 33-kDa cysteine protease (congopain) and a recombinant form of a 69-kDa heat-shock protein. Proliferative responses were highest during the second week postinfection and were detected in cells obtained from the lymph node draining the site of infection but not in peripheral blood mononuclear cells. Production of IL-2 and IFN-gamma was measured in supernatants from antigen-stimulated lymph node cell cultures. Expression of IL-2, IL-4, and IFN-gamma mRNA was detected in antigen-stimulated lymph node cells by reverse transcription-polymerase chain amplification.
The novel assignment of 13C and 1H NMR data for cadina-4,10(15)-dien-3-one obtained from Hyptis verticillata is presented. The study revealed that cadina-4,10(15)-dien-3-one possesses chemosterilant activities against the economically important cattle tick, Boophilus microplus, and toxic action against adult Cylas formicarius the most destructive pest of sweet potato (I pomoea sp.).
Experiments were carried out in goats to determine the frequency with which diminazene-resistant trypanosomes occur in parasite populations before and after the intramuscular treatment of the goats with diminazene aceturate. Trypanosoma congolense IL 3274, a diminazene-resistant clone, was used to initiate infections in three groups of five goats. The goats in the first group were treated with diminazene aceturate at a dose of 7.0 mg kg-1 bodyweight within 10 seconds of infection; one of the goats was cured. All of the second group, which received no treatment, became parasitaemic. The third group of goats received the same dose of drug as the first group but three days after all of them were first detected parasitaemic; trypanosomes reappeared in all the five goats. When this third group was treated, the frequency of trypanosomes resistant to the drug dosage was estimated to be less than 1 in 10(3). The parasites which reappeared after the treatment of these animals were used to infect two additional groups of five goats intravenously. The goats in one group were treated with the same dose of drug as before, within 10 seconds of infection and were all cured. In contrast, the five goats in the second, untreated, group became parasitaemic. Finally, when the goats in which the infections had relapsed were retreated with diminazene aceturate at the same dose rate, the level of parasitaemia temporarily decreased by at least 10(3) trypanosomes ml-1. These findings suggest that diminazene-resistant T congolense occur at low levels in trypanosome populations despite attempts to select for a population resistant to the dose of drug used.
A bioassay was used to measure erythropoietin (EPO) concentrations in calves with haemorrhagic anaemia due to blood loss and in calves with anaemia due to Trypanosoma congolense infection. The bioactivity of EPO was measured in the assay by its stimulatory effect on 125I-deoxyuridine incorporation in spleen cells from phenylhydrazine-treated mice. Erythropoietin concentrations in blood-volume-depleted calves were elevated 6 h after blood loss, maximal (1225 mU/ml) at 33 h and below detection limits at 72 h. Reticulocytes (0.05 +/- 0.1%) appeared in blood by 72 h, peaked at 120 h and disappeared from the circulation by 7 days after bleeding. The packed cell volume (PCV) started increasing at 120 h and reached near pre-bleeding values by 14 days. In T. congolense-infected calves, parasites were first detected in the peripheral blood 12 days post-infection (dpi). Parasitaemia peaked (5 x 10(5) trypanosomes/ml of blood) at 15-18 dpi and, thereafter, several waves of parasitaemia were observed, but the peaks gradually diminished. Undiluted plasma from T. congolense-infected calves suppressed 125I-deoxyuridine incorporation into spleen cells from 13 dpi onwards. The suppressive effect of plasma was partly negated by five-fold dilution, which made possible the detection of increased EPO concentrations during the acute and chronic stages of the anaemia. The highest EPO peaks, reaching 2300 mU/ml in one calf, were detected during the chronic stage of the infection. At 15-39 dpi, there was a transient bone-marrow erythropoietic response characterized by an increase in mean corpuscular volume and a decrease in mean corpuscular haemoglobin concentration but with few reticulocytes (0.4%). However, from 76 dpi onwards, this response waned despite low PCV and elevated EPO concentrations. These results suggest that there is an ineffective erythroid response in the face of elevated EPO concentrations during bovine trypanosomiasis. The negative effect of plasma and serum from trypanosome-infected calves on the in-vitro bioactivity of EPO suggests the presence of inhibitory factors.
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BACKGROUND AND OBJECTIVE: Degradation of AVP by placental vasopressinase may precipitate gestational diabetes insipidus, which in some cases is accompanied by pre-eclampsia. Abnormally elevated vasopressinase has also been reported in pre-eclampsia without diabetes insipidus. This association between excessive vasopressinase production and pre-eclampsia might be explained if the products of AVP degradation by vasopressinase retained pressor activity even after anti-diuretic activity had been destroyed. Recent evidence indicates that such products may raise blood pressure in rats. The objective of this study was, therefore, to purify vasopressinase and investigate its action on both the V1 and V2 receptor-stimulating activity of AVP. DESIGN: Vasopressinase was purified from pooled pregnancy serum by ammonium sulphate precipitation, followed by sequential ion exchange, lentil lectin affinity and gel filtration chromatography. Purified enzyme was then used to degrade AVP and the loss of both immunoreactivity and biological activity monitored. Loss of V1 receptor-stimulating activity and V2 receptor-stimulating activity was compared by two-way ANOVA. PATIENTS: Blood was obtained from healthy women between week 34 and the end of pregnancy. Pooled serum from 20-30 patients was used as starting material for the purification of vasopressinase. MEASUREMENTS: AVP immunoreactivity was measured by radioimmunoassay, V1 receptor-stimulating activity by a platelet aggregation bioassay, and V2 receptor-stimulating activity by adenylate cyclase stimulation in LLC-PK1 target cells. RESULTS: Purified vasopressinase was a dimeric protein of molecular weight 330 kDa, which cleaved the synthetic substrate S-benzyl-L-cysteine-4-nitroanilide with a Km of 0.33 mM. Incubation of AVP (0.1 mM) with vasopressinase (0.66 milligrams) at 37 degrees C led to a parallel loss of both AVP immunoreactivity and biological activity. The rates of loss of V1 and V2 receptor mediated activities were not significantly different. CONCLUSIONS: We report the first direct comparison between the loss of V1 and V2 receptor mediated activities of vasopressinase degraded AVP. There was no significant retention of V1, relative to V2, receptor mediated activity. AVP degradation products are unlikely to be pathogenic in hypertensive pregnancy.