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Biomedical subjects

M J Allen

Publications and source records attributed to M J Allen.

At least 19 recordsLinked to original sources
PubMed1992

Diffusion-limited rates for monoclonal antibody binding to cytochrome c.

The kinetic and spectroscopic changes accompanying the binding of two monoclonal antibodies to the oxidized form of horse heart cytochrome c have been investigated. The two epitopes recognized by the antibodies are distinct and noninteracting: antibody 2B5 binds to native cytochrome c near a type II turn (residue 44) while antibody 5F8 binds on the opposite face of the protein near the amino terminus of an alpha-helical segment (residue 60). Antibody-cytochrome c binding obeys a simple bimolecular reaction mechanism with second-order rate constants approaching those expected for diffusion-limited protein-protein interactions. The association rate constants have small activation enthalpies and are inversely dependent on solvent viscosity, as expected for diffusion-controlled reactions. There is a moderate ionic strength dependence of the rate of association between the 2B5 antibody and cytochrome c, with the rate constant increasing about 4-fold as the ionic strength is varied between 0.14 and 0 M. Comparison of the rates for antibody-cytochrome c complex formation for binding to the reduced-native, oxidized-native, and alkaline conformations shows that for MAb 2B5 the forward rate constant depends slightly on cytochrome c conformation. Investigation of the pH-induced transition between the native and alkaline conformational states for free cytochrome c and for antibody-cytochrome c complexes shows that antibody binding stabilizes the native form of the protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Tip-radius-induced artifacts in AFM images of protamine-complexed DNA fibers.

Isolated DNA fibers complexed with protamine (the chromosomal protein that packages DNA in mammalian sperm) have been produced by partially decondensing the highly compacted mouse sperm chromatin particle on a glass coverslip. These DNA fibers were then scanned with the atomic force microscope (AFM). While the smallest of the fibers appear in AFM images as ribbon-like structures 250-350 A wide and 10-25 A high, experiments indicate that these images are the result of a convolution of the imaging-tip's shape with the object's actual shape. In such convolutions the height of the object is affected only by the compressibility of the object, while the width is affected in addition by the sharpness of the tip. Images of polyamidoamine particles also appear to show this artifact. We have also deduced the tip's radius of curvature from images of sharp steps and attempt to demonstrate the artifacts associated with a relatively large imaging tip.

Animals↗
PubMed1992

Identification of the skeletal remains of Josef Mengele by DNA analysis.

There has been considerable controversy over the identity of the skeletal remains exhumed in Brazil in 1985 and believed to be those of Dr Josef Mengele, the Auschwitz 'Angel of Death'. Bone DNA analysis was therefore conducted in an attempt to provide independent evidence of identity. Trace amounts of highly degraded human DNA were successfully extracted from the shaft of the femur. Despite the presence of a potent inhibitor of DNA amplification, microsatellite alleles could be reproducibly amplified from the femur DNA. Comparison of the femur DNA with DNA from Josef Mengele's son and wife revealed a bone genotype across 10 different loci fully compatible with paternity of Mengele's son. Less than 1 in 1800 Caucasian individuals unrelated to Mengele's son would by chance show full paternal inclusion. DNA analysis therefore provides very strong independent evidence that the remains exhumed from Brazil are indeed those of Josef Mengele.

Concentration Camps↗
PubMed1992

Color defective drivers and safety.

At least seven million drivers in North American cannot reliably identify red and green lights. The common assumption by traffic authorities that no serious problems exist is contradicted by the data on color vision, the testimonies of color defective drivers, studies under controlled conditions, and by reliable accident statistics. Color defective drivers can be provided with the same measure of traffic light safety as for normals. Brake lights on vehicles can be made equally effective for color defectives. Suggestions are provided to help those with color defective vision to compensate for their problems.

Accidents, Traffic↗
PubMed1992

Compartment pressures after closed tibial shaft fracture. Their relation to functional outcome.

We measured pressures in the anterior and deep posterior compartments continuously for up to 72 hours in 20 patients with closed fractures of the tibial shaft treated primarily in plaster casts. All were examined independently after periods of three to 14 months. Pressures above 40 mmHg occurred in seven (35%) and above 30 mmHg in 14 (70%). No patient had the symptoms of compartment syndrome during monitoring. Abnormalities at review did not correlate with the maximum consecutive time periods during which the compartment pressures were raised. Thus, in the absence of symptoms the monitored pressures did not relate to outcome. Routine monitoring in this type of patient is therefore of doubtful benefit.

Adolescent↗
PubMed1992

Dofetilide, a novel class III antiarrhythmic agent.

Dofetilide is a potent and selective class III antiarrhythmic agent that is under development for the treatment of re-entrant tachyarrhythmias (ventricular tachycardia/ventricular fibrillation, atrial fibrillation/atrial flutter, and paraoxysmal supraventricular tachycardia). In animal studies, dofetilide selectively inhibits the rapid component of the time-dependent outward potassium current (IKr) and therefore increases the effective refractory period and action potential duration without affecting the fast inward sodium current. Studies in dogs have shown that dofetilide (a) prolongs the effective refractory period in a dose-dependent manner, (b) elevates ventricular fibrillation threshold, (c) facilitates conversion of electrically induced ventricular fibrillation or fibrilloflutter to sinus rhythm, (d) does not influence conduction within the His-Purkinje system or within the myocardium, (e) does not impair cardiac contractility, and (f) reduces dispersion of ventricular repolarization. Dofetilide has been administered to healthy volunteers as well as to patients with ischemic heart disease or with supraventricular arrhythmias; the compound has generally been well tolerated. Side effects have occasionally been reported, but have generally been transient and mild and occur in placebo-treated subjects as well. No clinically significant changes in laboratory safety tests have been detected. The pharmacokinetic profile of dofetilide both in healthy volunteers and patients includes a linear dose-plasma concentration relationship and also a linear plasma concentration-QTc relationship. The terminal plasma elimination half-life is approximately 9-10 h and systemic bioavailability in the region of 100%. The elimination pattern is balanced, with 50% being excreted unchanged via the kidney, the remaining 50% being metabolized in the liver to inactive metabolites, with greater than 90% of circulating drug-related material being unchanged dofetilide. After intravenous administration of the compound, a slight hysteresis in the plasma drug level-QTc relationship has been detected. Pharmacodynamic data demonstrate dose- and concentration-dependent effects on myocardial repolarization as evidenced by prolongations of the QTc interval. This is reflected in significant prolongations in the effective and functional refractory periods and monophasic action potential duration throughout the myocardium. No effects on sinus node function, conduction parameters, or cardiac contractility have been detected in any of the clinical studies, supporting the contention that dofetilide is a highly selective class III antiarrhythmic agent.

Action Potentials↗
PubMed1991

Preventable deaths after head injury: a clinical audit of performance.

A retrospective trauma audit of 267 consecutive patients presenting to the resuscitation room of an accident and emergency department identified 107 (M = 0.73) patients with CNS predominant injuries in a period of 1 year. The mortality rate was 33 per cent. Application of the TRISS method indicated that 18 (51 per cent) of the 35 deaths (Z = 5.74, P less than 0.001) were mathematically unexpected; no unexpected survivors were identified. Subsequent peer review agreed that death was preventable in 11 cases. The peer panel suggested that the lack of an on-site neurosurgical service may have affected the outcome of this group of patients adversely.

Adolescent↗
PubMed1991

Effects of alterations in left ventricular filling, contractility, and systemic vascular resistance on the ascending aortic blood velocity waveform of normal subjects.

OBJECTIVES: To confirm the consistent effects on Doppler-measured aortic blood flow velocity waveform variables of alterations in left ventricular preload, afterload, and inotropy using pharmacologic and physiologic maneuvers. SETTING: Medical school laboratory. SUBJECTS: Healthy volunteers. INTERVENTIONS: Increasing infusion rates of dobutamine (1.25 to 5 micrograms/kg.min), esmolol (1.25 to 5 mg/min), phentolamine (1.25 to 5 mg/min), methoxamine (1.25 to 5 mg/min), metaraminol (1.25 to 5 mg/min), and placebo (1.25 to 5 mL of 0.9% saline/min) and increasing plasma removal (0.5 to 1 L) in awake, rested, supine subjects. MEASUREMENTS AND MAIN RESULTS: Ascending aortic blood flow was measured by the suprasternal Doppler approach allowing calculation of waveform variables of stroke distance and minute distance (linear measures of stroke volume and cardiac output), peak velocity, mean acceleration and flow time corrected for heart rate. An index of systemic vascular resistance was obtained by dividing mean systemic BP by the minute distance. Inotropic changes predominantly affected peak velocity and mean acceleration. Changes in preload mainly affected the flow time corrected for heart rate, whereas afterload changes had an intermediate effect. Unsuspected but subsequently confirmed hemodynamic effects were seen with esmolol and metaraminol. CONCLUSIONS: Aortic blood flow velocity waveform variables measured by Doppler ultrasound can be used to noninvasively follow changes in left ventricular preload, afterload, and inotropy.

Adrenergic beta-Antagonists↗
PubMed1991

Assay for beta-glucuronidase in species of the genus Escherichia and its applications for drinking-water analysis.

Recently, Escherichia species other than Escherichia coli have been isolated from potable water. Environmental isolates as well as clinical isolates of E. adecarboxylata, E. blattae, E. fergusonii, E. hermannii, and E. vulneris were assayed for the enzyme beta-glucuronidase by using EC MUG medium and the Colilert system. None of the isolates were positive for the enzyme by either method.

Escherichia↗
PubMed1991

Rapid in-line blood warming using microwave energy: preliminary studies.

The management of massive blood loss resulting from trauma or surgery necessitates rapid transfusion capability. Hypothermia secondary to shock, transfusion, and prolonged surgical procedures significantly increases morbidity and mortality in these patients. Transfusion at high flow rates frequently exceeds the warming capacity of conventional blood-warming devices, whose inherent resistance also limits the maximal flow rates. Microwave ovens are capable of blood warming, but have been associated with unacceptable hemolysis. We have investigated the possibility of using microwave energy to provide rapid in-line blood warming. Fresh blood from 10 human subjects was warmed from an average of 18 degrees C to temperatures ranging from 37 to 39 degrees C at flow rates from 250 to 500 mL/min. Laboratory analysis of free plasma hemoglobin, haptoglobin, hematocrit, hemoglobin, and electrolytes showed no difference between heated and control samples. LDH was elevated in those samples warmed repeatedly, but remained within the normal range. These data indicate the potential for further investigation utilizing properly controlled microwave energy for in-line blood and fluid warming.

Blood Transfusion↗
PubMed1991

Scanning tunneling microscope images of adenine and thymine at atomic resolution.

The scanning tunneling microscope has been used to obtain images of DNA that reveal its major and minor grooves and the direction of helical coiling, but sufficient resolution has not yet been achieved to identify its bases. To determine if this technology is capable of identifying individual DNA bases, we have examined the molecular arrangements of adenine and thymine attached to the basal plane of highly oriented pyrolytic graphite. Both molecules form highly organized lattices following deposition on heated graphite. Lattice dimensions, structural periodicities, and the epitaxy of adenine and thymine molecules with respect to the basal plane of graphite have been determined. Images of these molecules at atomic resolution reveal that the aromatic regions are strongly detected in both molecules while the various side-groups are not well-resolved. These studies provide the first evidence that tunneling microscopy can be used to discriminate between purines and pyramidines.

Adenine↗
PubMed1991

Deaths following trauma: an audit of performance.

The TRISS methodology was applied to identify preventable trauma deaths in a retrospective audit of 267 (M = 0.908) patients admitted to a teaching hospital through the resuscitation room of its accident and emergency department during a 1-year period. No unexpected survivors were identified; of the 44 deaths (Z = 5.35), 25 (56.8%) were judged preventable by the TRISS method. Those deaths deemed preventable were subjected to peer review by a panel of six consultants. The findings are discussed in respect of recommendations made for UK trauma centre provision by the Working Party Report of the Royal College of Surgeons of England on the management of patients with major injuries.

Adolescent↗