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Biomedical subjects

A Cooper

Publications and source records attributed to A Cooper.

At least 217 records · Page 12Linked to original sources
PubMed1994

Small arteries and hypertension.

AIM: To review current knowledge on the behaviour of small arteries in hypertension and when the blood pressure is lowered. METHOD: Literature review. CONCLUSIONS: The evidence available at present suggests that despite normalization of blood pressure, the flow reserve in small coronary arteries is not necessarily restored to normal. Therefore the risk of cardiac ischaemia may remain and this may explain the current failure to reduce all cardiac risk associated with hypertension despite effective antihypertensive treatment.

Animals↗
PubMed1993

Characterization of the type I dehydroquinase from Salmonella typhi.

The type I dehydroquinase from the human pathogen Salmonella typhi was overexpressed in an Escherichia coli host and purified to homogeneity. The S. typhi enzyme was characterized in terms of its kinetic parameters, important active-site residues, thermal stability and c.d. and fluorescence properties. In all important respects, the enzyme from S. typhi behaves in a very similar fashion to the well-characterized enzyme from E. coli, including the remarkable conformational stabilization observed on reduction of the substrate/product mixture by NaBH4. This gives confidence that the information from X-ray studies on the S. typhi enzyme [Boys, Fawcett, Sawyer, Moore, Charles, Hawkins, Deka, Kleanthous and Coggins (1992) J. Mol. Biol. 227, 352-355] can be applied to other type I dehydroquinases. Studies of the quenching of fluorescence of the S. typhi enzyme by succinimide show that NaBH4 reduction of the substrate/product imine complex involves a dramatic decrease in the flexibility of the enzyme, with only very minor changes in the overall secondary and tertiary structure.

Circular Dichroism↗
PubMed1993

Binding of a substrate analogue can induce co-operative structure in the plasmin serine-proteinase domain.

Human miniplasminogen and miniplasmin were studied by n.m.r. spectroscopy and differential scanning calorimetry (d.s.c.) in order to investigate the structural properties of the serine-proteinase domain. The d.s.c. thermograms of both miniplasminogen and non-inactivated miniplasmin at pH 4.0 can be closely fitted to two transitions, at 62 +/- 2 and 72 +/- 2 degrees C, corresponding to unfolding of the kringle 5 and proteinase domains respectively. No evidence was found, under these conditions, for non-co-operative unfolding of the proteinase domain. On inactivation of miniplasmin with an affinity label, a number of additional resonances arising from residues of the proteinase domain are observed in resolved regions of the n.m.r. spectrum. A combination of variable-temperature n.m.r. and d.s.c. has shown that part of the proteinase domain undergoes a major conformational transition on heating which is distinct from the unfolding of the remainder of the proteinase domain or the kringle 5 domain. This additional transition occurs at a temperature that depends on the nature of the affinity label present and is not observed in the absence of an inactivating agent. These results provide direct evidence for the existence of a region of the proteinase domain which, under these conditions, becomes structured only in the presence of a bound substrate.

Affinity Labels↗
PubMed1993

Protein folding in the absence of the solvent ordering contribution to the hydrophobic interaction.

Despite considerable effort there is no consensus as to what interaction, or set of interactions, provides the dominant force that drives protein folding and specifies folded protein structures. A key thermodynamic observation is that a large drop in heat capacity (delta Cp) usually accompanies folding in water. Various factors may contribute to this effect, especially changes in the structure of the solvent upon exposure of both non-polar and polar groups in the unfolded state. The unfavourable Gibbs free energy of solvating non-polar groups, in particular, is thought to provide a central driving force for folding (the hydrophobic effect) but the role of solvent ordering in this remains a matter of controversy. We report here a series of experiments that show that a protein can fold into its native conformation under conditions where solvent ordering effects are demonstrably negligible. In methanol/water mixtures ubiquitin unfolds reversibly with a delta Cp value that falls close to zero above about 30% (v/v) methanol. We are able to reason, on the basis of these data, that the net contribution to the heat capacity change arising primarily from the protein structure itself is not significant and that contributions from changes in solvent ordering are rendered negligible by the change in composition. Nuclear magnetic resonance measurements, however, indicate that non-polar side-chains do still become exposed to solvent in the denatured state under these conditions. The combination of these results and model compound studies suggests that the elimination of ordering effects is an intrinsic property of the mixed solvent. We can, therefore, conclude that the solvent ordering component of the hydrophobic effect is not an obligatory factor in determining the three-dimensional structure into which the protein will fold.

Animals↗
PubMed1993

Long-term clinical progress in bone marrow transplanted mucopolysaccharidosis type I patients with a defined genotype.

Two mucopolysaccharidosis type I (MPS-I) patients, subjected to bone marrow transplantation (BMT) more than 10 years ago, have recently had their alpha-L-iduronidase genotypes defined. Both patients, homozygous for the relatively common W402X mutation, received BMT when they were 14 and 11 months of age, and are now 12 and 14 years old, respectively. Untreated MPS-I patients, homozygous for W402X, have an extremely severe clinical phenotype with rapid clinical deterioration and death before 6 years of age. The 12-year-old patient, with limited mobility, is coping well at school, while the other patient is wheelchair-bound with severe disability in his lower limbs, and attends a school for the physically handicapped. Both patients have less than normal intelligence with slowly continuing losses. A third MPS-I patients, diagnosed at the age of 6 months, was felt, prior to BMT at 14 months, to have a severe phenotype. Twelve years post-BMT, he is ambulatory, albeit with restricted movement, and has normal intelligence. This patient did not have a defined MPS-I genotype and had alpha-L-iduronidase protein and activity consistent with a less severe outcome than the first two patients. We conclude that BMT has significantly slowed down the clinical regression of the W402X phenotype. We propose that if further gains are to be made, BMT should be performed within the first few months of life. Early diagnosis is therefore essential.

Adolescent↗
PubMed1993

Efficacy of pediatric trauma care: results of a population-based study.

To determine concordance between regional outcome and national norms with respect to pediatric injury diagnosis, severity, and mortality in a state lacking a well-organized trauma system, we compared summary data from all pediatric trauma-related hospital discharge abstracts compiled by the [New York State Department of Health] Statewide Planning and Research Cooperative [Mandatory Hospital Reporting] System (SPARCS), with comparable data from pediatric trauma centers participating in the National Pediatric Trauma Registry (NPTR), for similar epochs in the late 1980s. Analysis was based on 14,234 cases from SPARCS and 17,098 cases from NPTR. Data were grouped by principal anatomic diagnosis (ICD-9-CM N-code) and injury severity score (ISS), for each of which incidence and mortality were calculated, both individually and collectively, then compared item by item for sources of variance. Overall, the two data sets showed the expected discordance, with NPTR being skewed toward more complex and severe injury. However, when analyzed cell by cell, a striking degree of concordance emerged in both incidence and mortality for injuries of comparable severity in all but a few selected subsets. Isolated skeletal injuries were treated less frequently in pediatric trauma centers, and combined system injuries to the skeleton, brain, and internal organs were treated more frequently in pediatric trauma centers. However, while the fatality rates were similar between SPARCS and NPTR for most diagnoses, given comparable ISS, survival was some ten times greater in pediatric trauma centers for patients with either brain or internal injuries--the leading causes of pediatric injury mortality--and for skeletal injuries, when the injuries sustained were of moderately great severity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

A long-term follow-up of surgically treated vesicoureteric reflux in girls.

Ninety-six girls with surgically treated vesicoureteric reflux (VUR) operated on between 1970 and 1975 were studied to determine their post mature growth (height and weight); the incidence of hypertension; the incidence, progression, and development of new renal scars; the incidence of urinary infection; and the outcome of any pregnancies. The average age at follow-up was 20 years 2 months (range, 16 years to 25 years). The final "post mature" height was significantly greater than that of a group of controls from all regions of Great Britain; the incidence of hypertension was 4.5% and the incidence of urinary infections was 37.6%. The majority of subsequent pregnancies were uneventful but urinary infections occurred in 36.4% and 3 of the 20 infants born had VUR.

Adolescent↗
PubMed1993

A comparison of epidural diamorphine with intravenous patient-controlled analgesia using the Baxter infusor following caesarean section.

In a randomised study of analgesia following Caesarean section, we compared the efficacy and side effects of on-demand epidural diamorphine 2.5 mg with intravenous patient-controlled analgesia using diamorphine from the Baxter infusor system. Pain scores fell more rapidly in the epidural group, but by the fourth hour, and thereafter, both techniques had a similar analgesic effect. The patient-controlled analgesia group used significantly more diamorphine (p < 0.001), median 62 mg (range 18-120 mg) compared to the epidural group, median 10 mg (range 2.5-20 mg), over a significantly longer time period (p < 0.001), median 54.25 h (range 38-68 h) compared to the epidural group, median 40.75 h (range 6-70 h). The frequency and severity of nausea, vomiting and pruritus were similar in the two groups, however, the patient-controlled analgesia group were more sedated during the first postoperative day. This reached statistical significance (p < 0.05) between 9-24 h. Overall satisfaction scores (0-100) were high, but the patient-controlled analgesia group scored significantly higher: mean 85.5 (SD 12.2) compared to mean 77.0 (SD 11.7) in the epidural group.

Adult↗
PubMed1993

Augmented lymphocyte binding to cultured endothelium in psoriasis.

Lymphocyte binding to cultured human umbilical vein endothelial cells was evaluated using a modified centrifugation binding assay in 15 patients with psoriasis and compared with three patients with atopic dermatitis, 11 patients with rheumatoid arthritis and 28 normal controls. Patients with psoriasis demonstrated 61% augmented lymphocyte binding compared with normal controls (P < 0.0001), which was not explained by differences in age and sex or an effect of psoriatic sera. In serial studies of six patients, this difference was found to be reversible with treatment and clinical improvement. Lymphocytes from patients with atopic dermatitis demonstrated decreased binding to endothelium (P < 0.005), while those from patients with rheumatoid arthritis were not different from normal controls. This is the first skin disease described in which augmented lymphocyte binding to endothelium occurs, and may represent a mechanism by which lymphocytes are targeted to psoriatic skin.

Adolescent↗
PubMed1993

Histological evaluation of the effect of 0.05% tretinoin in the treatment of photo damaged skin. Geographic differences in elastosis in baseline biopsies.

In a randomised double-blind vehicle controlled trial of 0.05% tretinoin cream in the treatment of photodamaged skin, the histological results of paired biopsies from 28 individuals who applied tretinoin for 26 weeks are compared with 28 paired biopsies from a control group applying vehicle alone. There was a significant increase in epidermal thickness in the tretinoin-treated group (P < .001). Epidermal atrophy was reversed in ten patients applying tretinoin cream. Baseline biopsies obtained from participants in Melbourne, Victoria (38 degrees latitude) showed significantly less elastosis than those in Sydney (34 degrees latitude) and Newcastle in N.S.W., although the two groups did not show significant differences in age or sex, and the differences could not be correlated with skin type. Tretinoin cream had no effect on the degree of solar elastosis after 26 weeks application. Tretinoin cream appears effective in reversing epidermal atrophy and clinically diminishes fine wrinkling, mottled hyperpigmentation and skin roughness. Tretinoin cream may not offer a solution to the gross solar damage seen in the Australian population who have marked solar elastosis as a principal, clinical and histologic finding. However it is possible that dermal repair and reversal of solar elastosis may require topical application of tretinoin cream for a longer period than the six months used in this trial.

Administration, Topical↗
PubMed1993

In vitro interaction of heavy metals with ouabain receptors in rat brain microsomes.

This study investigates the influence of heavy metals on ouabain-binding in presence of thiol (sulfhydryl) compounds. The data on in vitro effects of mercury (Hg), lead (Pb) and cadmium (Cd) showed significant inhibition of 3H-ouabain binding to microsomal membrane in a concentration-dependent manner. Maximum inhibition of 3H-ouabain binding was observed at 1 microM for Hg and 100 microM each for Pb and Cd. Preincubation with monothiol (L-cysteine or glutathione) or dithiol (dithiothreitol) protected inhibition of 3H-ouabain binding to the membranes by Hg or Pb. Dithiol but not monothiols partially protected Cd-inhibition. The present data confirm that the heavy metals interact with ouabain receptors in a manner similar to SH-blocking agents and protection of metal-inhibited 3H-ouabain binding by thiol compounds is metal specific.

Animals↗
PubMed1993

Indirect latex contact causes urticaria/anaphylaxis.

Recurrent urticaria/anaphylaxis is a most perplexing and critical problem, often of unknown cause. Though difficult and time consuming, identification of causes(s) can be life saving and cost saving for the patient(s). We report a complex case of urticaria/anaphylaxis induced by latex allergen in a former intensive care unit nurse, in which the allergen contact occurred remotely and indirectly by intimate contact with the spouse. Diagnosis of the latex allergy was confirmed by epicutaneous skin test in vivo as well as RAST.

Adult↗
PubMed1992

Differential scanning calorimetry of thermal unfolding of the methionine repressor protein (MetJ) from Escherichia coli.

The thermal stability of the methionine repressor protein from Escherichia coli (MetJ) has been examined over a wide range of pH (pH 3.5-10) and ionic strength conditions using differential scanning calorimetry. Under reducing conditions, the transitions are fully reversible, and thermograms are characteristic of the cooperative unfolding of a globular protein with a molecular weight corresponding to the MetJ dimer, indicating that no dissociation of this dimeric protein occurs before unfolding of the polypeptide chains under most conditions. In the absence of reducing agent, repeated scans in the calorimeter show only partial reversibility, though the thermodynamic parameters derived from the first scans are comparable to those obtained under fully reversible conditions. The protein is maximally stable (Tm 58.5 degrees C) at about pH 6, close to the estimated isoelectric point, and stability is enhanced by increasing ionic strength in the range I = 0.01-0.4 M. The average calorimetric transition enthalpy (delta Hm) for the dimer is 505 +/- 28 kJ mol-1 under physiological conditions (pH 7, I = 0.125, Tm = 53.2 degrees C) and shows a small temperature dependence which is consistent with an apparent denaturational heat capacity change (delta Cp) of about +8.9 kJ K-1 mol-1. The effects of both pH and ionic strength on the transition temperature and free energy of MetJ unfolding are inconsistent with any single amino acid contribution and are more likely the result of more general electrostatic interactions, possibly including significant contributions from electrostatic repulsion between the like-charged monomers which can be modeled by a Debye-Hückel screened potential.

Bacterial Proteins↗
PubMed1992

Independent origins of New Zealand moas and kiwis.

Two groups of flightless ratite birds existed in New Zealand during the Pleistocene: the kiwis and the moas. The latter are now extinct but formerly included 11 species. We have enzymatically amplified and sequenced approximately 400 base pairs of the mitochondrial 12S rRNA gene from bones and soft tissue remains of four species of moas as well as eight other species of ratite birds and a tinamou. Contrary to expectation, the phylogenetic analysis shows that the kiwis are more closely related to Australian and African ratities than to the moas. Thus, New Zealand probably was colonized twice by ancestors of ratite birds.

Animals↗
PubMed1992

Thermodynamic consequences of the removal of a disulphide bridge from hen lysozyme.

Differential scanning calorimetry experiments as a function of pH have been carried out for native hen egg white lysozyme and a three-disulphide derivative (CM6,127-lysozyme). The results indicate that the enthalpy (delta H298) and heat capacity changes (delta Cp) for unfolding are closely similar for the two proteins. This shows that the substantial reduction (25 degrees C at pH 3.8) in Tm resulting from removal of the 6-127 disulphide bond can, to a good approximation, be attributed totally to an increase in the entropy difference between the native and denatured states. The significance of this result for understanding the factors influencing the stability of folded proteins is discussed.

Animals↗