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Biomedical subjects

D J Brown

Publications and source records attributed to D J Brown.

At least 145 records · Page 8Linked to original sources
PubMed1991

N.m.r. determination of the solution conformation and dynamics of the A.G mismatch in the d(CGCAAATTGGCG)2 dodecamer.

A.G base-paired mismatches that occur during replication are among the most difficult to detect by repair enzymes. Such purine.purine mispairs can exist in two conformations, one of which is stabilized by protons [Gao & Patel (1988) J. Am. Chem. Soc. 110, 5178-5182]. We have undertaken a 1H-n.m.r. and 31P-n.m.r. study of the mismatched dodecamer d(CGCAAATTGGCG)2 as a function of both temperature and pH to determine the conformational features of the A.G mismatch. At pH greater than 7 the mispaired bases are each in the anti conformation and are stacked in the B-like helix. As the pH is decreased, a second conformation becomes populated (apparent pKa approx. 5.9) with concomitant changes in the chemical shifts of protons of the mispaired bases and their nearest neighbours. Data from two-dimensional nuclear-Overhauser-enhancement spectroscopy show unequivocally that, at low pH, the dominant conformation is one in which the mismatched G residues are in the syn conformation and are hydrogen-bonded to the A residues that remain in the anti conformation. Residues not adjacent to the A.G sites are almost unaffected by the transition or the mispairing, suggesting considerable local flexibility of the unconstrained duplexes. Despite the bulging of the mispaired bases, the conformation of the A(anti).G(anti) duplex is very similar to the native dodecamer, whereas the AH+(anti).G(syn) duplex shows a greater variation in the backbone conformation at the mismatched site. According to the chemical shifts, the duplex retains twofold symmetry in solution. The equilibrium between the syn and anti conformations of G9/G21 is strongly dependent on pH, but only weakly dependent on temperature (delta H approx. 16 kJ.mol-1). The first-order rate constant for the transition is approx. 9 s-1 at 283 K and approx. 60 s-1 at 298 K, with an activation enthalpy of approx. 100 kJ.mol-1. The stabilization of the A(anti).G(syn) conformation by protons is consistent with models invoking N1 protonation of adenine. Using the derived glycosidic torsion angles we have used restrained molecular dynamics to build models of the neutral and protonated d(CGCAAATTGGCG)2 oligomers. The results confirm that the A(anti).G(anti) and AH+(anti).G(syn) conformations are favoured at high pH and low pH respectively, in accord with n.m.r. and single-crystal X-ray data.

Base Sequence↗
PubMed1991

Instability of multiple drug resistance plasmids in Salmonella typhimurium isolated from poultry.

Plasmids in five strains of Salmonella typhimurium resistant to ampicillin, chloramphenicol, gentamicin, neomycin/kanamycin, streptomycin, sulphonamides, tetracyclines and trimethoprim (ACGKSSuTTm), CGKSSuTTm, ACSSuT or CSSuT which had been isolated from poultry in the first 3 months of 1989 have been characterized and compared with plasmids in two strains of R-types ACGKSSuTTm and ASSuTTm isolated from two patients later in the year. With the exception of the human isolate of R-type ASSuTTm, all strains carried two non-conjugative plasmids, one coding for SSu and belonging to incompatibility group Q, and a second coding for multiple resistance and belonging to the FIme incompatibility group. The human isolate of R-type ASSuTTm did not carry the IncQ SSu plasmid but like the poultry isolates, carried a non-conjugative FIme plasmid. Restriction endonuclease digestion with the enzymes EcoR I, Pst I and Hind III demonstrated that the FIme plasmids from strains of different R-types showed a high degree of homology but exhibited numerous fragment size polymorphisms. The restriction digest fingerprint of plasmids in the human isolate of R-type ACGKSSuTTm was indistinguishable from a poultry isolate of the same R-type. Analysis of segregants of one of the poultry isolates of R-type ACGKSSuTTm demonstrated that resistance determinants could be rapidly lost from the FIme plasmid to give rise to a number of R-types and fingerprint patterns. Loss of tetracycline resistance from this plasmid appeared to be correlated with the integration of other plasmid-mediated resistances into the bacterial chromosome. Evidence is presented for the rapid loss of antimicrobial resistance determinants from a multiple resistance plasmid of the FIme incompatibility group in response to withdrawal of antibiotic selective pressure.

Animals↗
PubMed1991

Depression, disease and disability: application to patients with traumatic spinal cord injury.

Depressive symptoms are common in medically ill patients. Methodological difficulties of many of the studies demonstrating this do not allow differentiation of depressive symptoms from depressive illness. This paper examines representative samples of studies in the medically ill to highlight these problems. Data from a study of patients with traumatic spinal cord injury are used to demonstrate (1) ways of overcoming some of these difficulties and (2) the means of differentiating depressive symptoms and depressive illness. Difficulties of detection and diagnosis of depression in the medically ill are discussed.

Depression↗
PubMed1991

Diurnal blood pressure variation in quadriplegic chronic spinal cord injury patients.

1. Measurement of blood pressure and heart rate over a 24 h period was performed in 10 quadriplegic spinal cord injury patients and 10 immobilized, neurologically intact orthopaedic subjects by using the Spacelabs 90207 automated ambulatory monitoring system. 2. Systolic and diastolic blood pressure fell significantly at night in orthopaedic subjects but not in quadriplegic patients, and night-time blood pressures were similar in both groups. 3. Cumulative summation of differences from a reference value (cusum analysis) confirmed a markedly diminished diurnal blood pressure variation in the quadriplegic patients. 4. These findings could not be accounted for on the basis of blood pressure variations during chronic postural change. 5. Heart rate fell significantly at night in both groups. 6. The findings suggest that the increase in blood pressure during waking hours in neurologically intact subjects is a consequence of a diurnal variation in sympathetic activity (absent in quadriplegic patients with sympathetic decentralization) which is independent of changes in physical activity.

Adult↗
PubMed1991

Plasmid profiles of Salmonella enterica serovar berta isolated from broilers in Denmark.

Salmonella enterica serovar berta was isolated for the first time in Denmark in October 1984. This serovar has subsequently become endemic in the broiler industry. Plasmid profile analysis of 610 strains of S. berta isolated from broilers and broiler parent stock in the period October 1984 to July 1989 showed that plasmids were present in 85.7% of strains investigated, with a mean of 1.8 plasmids per strain. A significant increase in the mean number of plasmids per strain was seen during the observation period. Seventeen different plasmid sizes and 90 different plasmid profiles were identified. Plasmid profiling of S. berta appears to represent a promising tool for analysing the epidemiology of S. berta infections in broilers.

Animals↗
PubMed1991

Use of pulsed-wave Doppler echocardiography to determine aortic and pulmonary velocity and flow variables in clinically normal dogs.

Transcutaneous pulsed-wave Doppler echocardiography was used to obtain velocity signals from the aortic and pulmonary roots of clinically normal adult dogs tranquilized with acepromazine. Doppler-derived variables included peak ejection velocity, ejection time, and velocity-time integral. The cross-sectional areas of the left and right ventricular outflow tracts were estimated from diameters of the respective orifices measured from two-dimensional echocardiographic images. These data were used to calculate stroke volume and cardiac output for each ventricle. Linear, single variable regressions of ejection time, velocity-time integral, and peak velocity with body weight showed no significant correlations. Significant correlations existed between body weight and estimated left and right ventricular stroke volume and cardiac output. A close correspondence existed between pulmonary and aortic determinations of velocity-time integral, stroke volume, and cardiac output. These results provide an initial framework for interpretation of clinical data by veterinary cardiologists.

Animals↗
PubMed1990

Steady state plasma [3H]-noradrenaline kinetics in quadriplegic chronic spinal cord injury patients.

1. Steady state plasma noradrenaline kinetics were measured in eight male quadriplegic patients and in eight age and sex matched controls. 2. Plasma noradrenaline levels were significantly lower in quadriplegic patients compared to controls. Noradrenaline spillover rate was markedly reduced in quadriplegics compared to controls while noradrenaline clearance was similar in both groups. 3. Noradrenaline kinetics in quadriplegic patients differ from peripheral autonomic neuropathy patients where reductions in both the spillover and clearance of noradrenaline are present.

Adult↗
PubMed1989

Pulmonary atresia with intact ventricular septum and agenesis of the ductus arteriosus in a pup.

A 7-week-old Wire Fox Terrier was admitted with pulmonary atresia with intact ventricular septum. The right ventricle and tricuspid valve were hypoplastic, and venous return to the right atrium reached the left side through an atrial septal defect. Oxygenation was via hyperplastic bronchial arteries. There was no evidence of the ductus arteriosus. Physical examination, plain and contrast radiography, and electrocardiography were performed. Clinical findings for this combination of defects were similar to those of more common defects (tetralogy of Fallot, patent ductus arteriosus.

Angiocardiography↗
PubMed1989

Congenital cranioventral abdominal wall, caudal sternal, diaphragmatic, pericardial, and intracardiac defects in cocker spaniel littermates.

Five littermate Cocker Spaniels were born with concomitant pericardial, diaphragmatic, caudal sternal, and cranioventral abdominal wall defects. Three of the 5 pups had ventricular septal defects. A sixth pup with a cranioventral abdominal wall defect died 4 days after birth. No history of teratogen exposure was reported, and none of the pups from previous litters of the dam was affected. Each pup underwent successful surgical correction (without median sternotomy) of the diaphragmatic and cranial abdominal wall defects when they were 10 to 12 weeks old. The ventricular septal defects were not corrected. In 2 of 3 pups with ventricular septal defects, thoracic radiography 6 months after surgery revealed moderate generalized cardiomegaly. All pups were healthy one year after surgery.

Abdominal Muscles↗
PubMed1989

Blood pressure variability in tetraplegic patients with autonomic hyperreflexia.

Autonomic hyperreflexia (AH) is a syndrome characterised by profound pressor responses, sweating and headache which occurs in tetraplegic patients in response to a variety of stimuli below the level of cord injury. The pathogenesis of this syndrome is unclear but may be associated with increased blood pressure (BP) variability in these patients. To investigate this possibility, 24 hour ambulatory BP monitoring was performed utilising the Spacelabs 5300 Ambulatory BP system in 30 patients: 10 normal subjects, 10 spinal cord injury (SCI) patients who had never experienced AH and 10 SCI patients who had experienced recent episodes of AH (but with no symptoms during the study period). There were no statistically significant differences in systolic BP (SBP), diastolic BP (DBP) or heart rate (HR) between the three groups. The average of the coefficients of variation of SBP, DBP and HR within each subject over the study period were calculated. Tetraplegic patients who had recently experienced episodes of AH had greater SBP, DBP and HR variability than normal persons (p less than 0.01, p less than 0.005, p less than 0.005) and greater DBP and HR variability than SCI patients who had never experienced AH (p less than 0.01, p less than 0.05). AH may represent the symptoms associated with the upper extremes of this BP variability. The increased variability may be the result of enhanced cardiovascular responsiveness to noradrenaline and arginine vasopressin or because of the absence of descending inhibitory pathways in the decentralised cord that would normally suppress spinal sympathetic reflexes.

Adult↗
PubMed1989

Lipid Composition of Plasma Membranes and Endomembranes Prepared from Roots of Barley (Hordeum vulgare L.) : Effects of Salt.

Membrane fractions enriched in endoplasmic reticulum (ER), tonoplast and Golgi membranes (TG) and plasma membranes (PM) were prepared from barley (Hordeum vulgare L. cv CM 72) roots and the lipid compositions of the three fractions were analyzed and compared. Plants were grown in an aerated nutrient solution with or without 100 millimolar NaCl. Each membrane fraction had a characteristic lipid composition. The mole per cent of the individual phospholipids, glycolipids, and sterols in each fraction was not altered when roots were grown in 100 millimolar NaCl. The ER had the highest percentages of phosphatidylinositol and phosphatidylcholine of the three fractions (7 and 45 mole per cent, respectively, of the total lipid). The TG contained the highest percentage of glycosylceramide (13 mole per cent). The PM had the highest percentage of phosphatidylserine (3 mole per cent) and nearly equal percentages of phosphatidylethanolamine (15 mole per cent and phosphatidylcholine (18 mole per cent). The most abundant sterols in membranes prepared from barley roots were stigmasterol (10 mole per cent), sitosterol (50 mole per cent), and 24zeta-methylcholesterol (40 mole per cent of the total sterol). Salt-treated plants contained a slightly higher percentage of stigmasterol than controls. The percentage of stigmasterol increased with age and a simple cause and effect relationship between salt treatment and sterol composition was not observed.

Journal Article↗
PubMed1989

Depression following spinal cord injury. A prospective in-patient study.

In a systematic prospective study of 71 patients with acute spinal cord injury carried out in the acute and rehabilitation phases of treatment, 14 patients meeting the DSM-III criteria for major depressive disorder were identified. A further 13 patients had transient periods of depressed mood, while the majority of patients showed no clear evidence of depression. The BDI was found to be valid in this group of patients.

Adjustment Disorders↗
PubMed1988

Effect of atmospheric N deposition on surface water chemistry and the implications for fisheries.

In this paper the relative importance of NO3- and SO4(2-) as anions in oligotrophic surface waters and evidence that NO3 concentrations have been increasing in recent decades in reviewed. The relationship between NO3- and the concentrations of cations (H+ and Al3+) known to be harmful to aquatic biota is also discussed. It is generally concluded that although direct proof of an association is lacking, circumstantial evidence suggests that atmospheric input of nitrogen to soils on certain 'sensitive' geologies may be having consequences for surface waters and the biota living in them, especially at certain times of the year, e.g. snowmelt.

Journal Article↗