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Biomedical subjects

B P Murphy

Publications and source records attributed to B P Murphy.

At least 19 recordsLinked to original sources

Electrophysiological measurements of spectral mechanisms in the retinas of two cervids: white-tailed deer (Odocoileus virginianus) and fallow deer (Dama dama).

Electroretinogram (ERG) flicker photometry was used to study the spectral mechanisms in the retinas of white-tailed deer (Odocoileus virginianus) and fallow deer (Dama dama). In addition to having a rod pigment with maximum sensitivity (lambda max) of about 497 nm, both species appear to have two classes of photopic receptors. They share in common a short-wavelength-sensitive cone mechanism having lambda max in the region of 450-460 nm. Each also has a cone having peak sensitivity in the middle wavelengths, but these differ slightly for the two species. In white-tailed deer the lambda max of this cone is about 537 nm; for the fallow deer the average lambda max value for this mechanism was 542 nm. Deer resemble other ungulates and many other types of mammal in having two classes of cone pigment and, thus, the requisite retinal basis for dichromatic color vision.

Animals

N-(phenylacetyl)glycyl-D-aziridine-2-carboxylate, an acyclic amide substrate of beta-lactamases: importance of the shape of the substrate in beta-lactamase evolution.

Certain acyclic depsipeptides, but not peptides, are substrates of typical beta-lactamases [Pratt, R.F., & Govardhan, C.P. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 1302]. This may reflect either the greater chemical reactivity of depsipeptides (and of beta-lactams, the natural substrates) than peptides or the greater ease of distortion of the depsipeptide (ester) than the peptide (amide) group into a penicillin-like conformation. The latter explanation has been shown to be more likely by employment of a novel beta-lactamase substrate. N-(phenylacetyl)glycyl-D-aziridine-2-carboxylate, which combines a high chemical reactivity with a close to tetrahedral amide nitrogen atom. Although this substrate was better (higher kcat/KM) than a comparable depsipeptide for beta-lactamases, it was poorer than the depsipeptide for the Streptomyces R61 D-alanyl-D-alanine peptidase (which catalyzes specific peptide hydrolysis). It therefore seems likely that one vital feature of the putative evolution of a DD-peptidase into a beta-lactamase would have been modification of the active site to, on one hand, accommodate bicyclic beta-lactams and, on the other, exclude productive binding of planar acyclic amides. Certain serine beta-lactamases and the R61 DD-peptidase also catalyze methanolysis and aminolysis by D-phenylalanine of the N-acylaziridine. The latter reaction, the first amide aminolysis shown to be catalyzed by a beta-lactamase, is a very close analogue of the transpeptidase reaction of DD-peptidases. The methanolysis reaction appeared to proceed by way of the same acyl-enzyme intermediate as formed from depsipeptides possessing the same acyl moiety as the aziridine. The kinetics of methanolysis were employed to determine whether acylation or deacylation was rate limiting to the hydrolysis reaction under saturating substrate concentrations. The kinetics of the aminolysis reaction, catalyzed by the Enterobacter cloacae P99 beta-lactamase, showed the characteristics of, and were interpreted in terms of, a sequential mechanism previously deduced for depsipeptides and this enzyme [Pazhanisamy, S., & Pratt, R. F. (1989) Biochemistry 28, 6875-6882]. This mechanism features two separate binding sites, only one of which is productive. Strikingly, the binding of the N-acylaziridine to the nonproductive site was very tight, such that essentially all hydrolysis at substrate concentrations above 0.1Km proceeded via the ternary complex; this could also be true of penicillins.

Aziridines

A thiono-beta-lactam substrate for the beta-lactamase II of Bacillus cereus. Evidence for direct interaction between the essential metal ion and substrate.

An 8-thionocephalosporin was shown to be a substrate of the beta-lactamase II of Bacillus cereus, a zinc metalloenzyme. Although it is a poorer substrate, as judged by the Kcat./Km parameter, than the corresponding 8-oxocephalosporin, the discrimination against sulphur decreased when the bivalent metal ion in the enzyme active site was varied in the order Mn2+ (the manganese enzyme catalysed the hydrolysis of the oxo compound but not that of the thiono compound), Zn2+, Co2+ and Cd2+. This result is taken as evidence for kinetically significant direct contact between the active-site metal ion of beta-lactamase II and the beta-lactam carbonyl heteroatom. No evidence was obtained, however, for accumulation of an intermediate with such co-ordination present.

Bacillus cereus

Evidence for an oxyanion hole in serine beta-lactamases and DD-peptidases.

A thionocephalosporin is shown to be a much poorer substrate of representative serine beta-lactamases of class A (RTEM-2) and class C (Enterobacter cloacae P99) and a much poorer inhibitor of the Streptomyces R61 DD-peptidase than is the analogous oxo beta-lactam. These results provide kinetic evidence for the existence of a catalytic oxyanion hole in these enzymes.

Carboxypeptidases

Cerebral air embolism resulting from invasive medical procedures. Treatment with hyperbaric oxygen.

The introduction of air into the venous or arterial circulation can cause cerebral air embolism, leading to severe neurological deficit or death. Air injected into the arterial circulation may have direct access to the cerebral circulation. A patent foramen ovale provides a right-to-left shunt for venous air to embolize to the cerebral arteries. The ability of the pulmonary vasculature to filter air may be exceeded by bolus injections of large amounts of air. Sixteen patients underwent hyperbaric oxygen therapy for cerebral air embolism. Neurological symptoms included focal motor deficit, changes in sensorium, and visual and sensory deficits. Eight patients (50%) had complete relief of symptoms as a result of hyperbaric treatment, five (31%) had partial relief, and three patients (19%) had no benefit, two of whom died. The treatment of cerebral air embolism with hyperbaric oxygen is based upon mechanical compression of air bubbles to a much smaller size and the delivery of high doses of oxygen to ischemic brain tissue.

Adolescent

Ability of the inflatable penile prosthesis to withstand rapid changes in altitude.

Small air bubbles unavoidably included in the fluid of the inflatable penile prosthesis will expand upon exposure to increased altitude. Three prostheses with predetermined amounts of air underwent decompressions in an altitude chamber. The device was able to contain the expanded air bubbles with no extravasation of fluid or air or damage to the system.

Altitude

Factitious decompression sickness.

The diagnosis of decompression sickness is made largely by history; there are few physical findings and no radiographic or laboratory tests to support the diagnosis. We present three cases of factitious decompression sickness in which patients fabricated an appropriate history and underwent compression therapy. Due to the potential severity of decompression sickness and the relative safety of compression therapy, the initiation of therapy must not be delayed in a case of decompression sickness. Once therapy is begun, investigation into the particulars of a suspicious case can be made.

Adult

Alcohol consumption and cigarette smoking in Busselton, 1966-1978.

In Busselton, mass health examination (MHE) questionnaires about alcohol consumption indicate that more people are drinking wine and fewer people are drinking beer. The evidence suggests an increase in the number of women consuming alcohol. The proportion of drinkers was higher among patients attending doctors with interests in wineries and/or vineyards compared with those patients attending doctors without such interests. More patients of doctors who smoked were smokers compared with those patient of doctors who were non-smokers. Smoking in Busselton appears to be declining at the rate of 0.5% to 1% of the population per annum; this decline is more marked in people who had attended one or more MHEs than in newcomers to MHEs. These trends have encouraged a more active approach to the prevention of smoking in school children.

Adult

Drug usage in a western Australian rural community.

Drug usage in two agricultural shires, Kondinin and Kulin, was surveyed by questionnaire. Both prescription and over the counter (OTC) drugs were recorded together with age, sex, forced expiratory volume in one second (FEV1), systolic blood pressure (SBP) and body weight, and 1284 people, or 55.8% of the eligible population over six years of age, participated. Approximately 35%, 53% and 12% of people said they were taking no drugs, one to two drugs and three or more drugs respectively, a result very similar to that found in an earlier urban study (Traralgon). The interaction of all five factors on drug consumption was studied jointly by multivariate analysis; FEV1, SBP and weight were normalised using standard tables. Prescription drug usage was directly related to obesity, respiratory impairment and sex (P less than 0.01) but not to age or SBP. People taking either OTC drugs or none at all differed only in sex, with females taking more than males (P less than 0.01). There were no differences in the factors studied between prescription only and prescription plus OTC drug users.

Adolescent

The effects of zero population growth on the incidence of cleft lip and palate in Western Australia.

A total of 613 cases of cleft lip, cleft palate, and combinations of both (CLP(P)) has been ascertained in the period from 1958 to 1975 in Western Australia. Near-total ascertainment of cases during this period was obtained from multiple sources. There has been a significant decline in the total incidence and the cleft lip and palate (CLP) incidence in males. The hypothesis is presented that these changes are linked to the changing fertility pattern throughout Australia (as technological improvements are made in the simplicity and efficacy of birth control), and abortion (as social attitudes change); and as the birthrate drops towards zero population growth (ZPG). The paper presents two critical observations: (i) the link between CLP(P) incidence, and demographic changes; (ii) in differing behaviour of cleft lip (CL) and CLP, which were previously regarded as linked conditions.

Australia

Serum IgE levels in patients with liver disease.

IgE (reaginic antibody) levels have been estimated on 160 occasions in 120 patients with liver disease. IgE levels were significantly raised in patients with untreated active chronic hepatitis, and returned towards normal with steroid or immunosuppressive therapy. They were also increased in patients with liver disease associated with alcoholism. There were no significant alterations in IgE levels in other types of acute or chronic liver disease. There were no significant correlations between IgE levels and the age or sex of the patients and the results of other laboratory tests carried out.

Acute Disease

Prevalence of cardiovascular risk factors including fasting serum triglyceride levels in the Cunderdin health survey of 1971.

In a mass health examination conducted in the Shires of Cunderdin and Tammin, 83% of subjects on the electoral rolls attended for screening of cardiovascular risk factors including fasting blood lipid measurements. Fasting serum triglyceride levels are presented. Other factors measured showed quite close similarities to those in the Busselton 1972 Health Survey. On conventional criteria of percentage of desirable weight, fasting serum cholesterol level and fasting serum triglyceride level, a very large proportion of the survey population was found to be eligible for preventive dietary advice--for example, 50% of males and females aged 40 to 59 years. The effective education and after-care of subjects found to be at risk requires further development of resources.

Adult