Biomedical subjects
E A Murphy
Publications and source records attributed to E A Murphy.
Antineutrophil cytoplasmic antibody titres in patients with recent infection.
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Sulphoxidation status in rheumatoid arthritis.
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Two sisters with ANCA positive vasculitis.
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Effectiveness of flushing on reducing lead and copper levels in school drinking water.
Samples from drinking water fountains in 50 schools in New Jersey were collected at specific times during a typical school day and analyzed for lead, copper, pH, alkalinity, and hardness. First-draw lead and copper levels (medians 0.010 mg/l and 0.26 mg/l, respectively) decreased significantly after 10 min of flushing in the morning (medians 0.005 mg/l lead and 0.068 mg/l copper), but levels increased significantly by lunchtime (medians 0.007 mg/l lead and 0.12 mg/l copper) after normal use of fountains in the morning by students. Corrosive water, as defined by the aggressive index, contained significantly higher levels of lead and copper (medians 0.012 mg/l and 0.605 mg/l, respectively) than noncorrosive water (medians 0.005 mg/l and 0.03 mg/l, respectively).
Cyclosporine A induced colitis and acquired selective IgA deficiency in a patient with juvenile chronic arthritis.
A 12-year-old girl with juvenile chronic arthritis was treated with cyclosporine A for recurrent uveitis. Two years later she presented with weight loss and diarrhea. Investigations suggested drug induced colitis. She improved after withdrawal of cyclosporine and her nonsteroidal antiinflammatory drug. Symptoms recurred on rechallenge with cyclosporine. She has developed a progressive selective IgA deficiency which persists despite cessation of cyclosporine.
Twin studies of Alzheimer disease: II. Some predictions under a genetic model.
The twin method for investigating genetic and environmental causes of disease has been applied mostly in early-onset illnesses. Analysis of late-onset disorders requires reexamination of common assumptions about the relation between genetic causes and the degree of concordance expected. This paper considers Alzheimer disease (AD) as an example of a late-onset disorder with putative genetic factors. For argument it employs the strong hypothesis that AD is an autosomal dominant trait with age-dependent expression, as described by a previously published parametric model. That model encompasses 2 principal variants of disease: a rare form with onset in middle life, and a more common late-onset type which is nonetheless eventually fully penetrant. The present work then specifies the probability that, when a given member of a twin pair (the proband) is affected, an identical or fraternal co-twin also shows the disease. Such probability is expressed as a function of the age at onset of the proband and the current age of the pair. Even under strong working assumptions regarding genetic influence, the expected proportion of identical co-twins actually affected with AD will not exceed 40% until the subjects are about 80 years old. Therefore, except in very old subjects, modest twin concordance is a feeble argument against genetic causes, or in favor of exclusively environmental ones. In this sense the interpretation of results of twin studies in AD and other late-onset disorders differs substantially from studies of diseases with early onset.
Threshold model in the genetics of age-dependent disease in twins: I. General principles as applied to Alzheimer disease.
In the context of the etiology and pathogenesis of Alzheimer disease (AD), we discuss assumptions under which categorical data on the phenotypes of twin pairs may be used to estimate standardized characteristics (correlation and the critical threshold) for an age-dependent multinomial process. Important topics include Erlangian, gamma, and Poisson processes, tetrachoric and trichoric functions, and degrees of freedom and how they relate to estimation from both an abstract and a practical standpoint. Under plausible assumptions about the age-dependence of a heritable trait, it is possible to generate sufficient degrees of freedom to test the genetic model and to explore age-dependence and the impact of environmental factors that may influence it systematically. Though general in scope, the model is focused on data from twin pairs. The statistical strategy is briefly outlined, but its properties are not examined in detail.
Reassessment of lead exposure in New Jersey using GIS technology.
In order to prevent children's exposure to lead, a variety of sources must be controlled. The New Jersey Department of Environmental Protection and Energy (NJDEPE) is using its Geographic Information System to identify areas within Newark, East Orange, and Irvington, New Jersey, where there may be greater environmental exposure to lead. Sensitive populations are identified through the U.S. Bureau of the Census information. Blood screening data provided by the New Jersey Department of Health (NJDOH) provide reported patterns of elevated blood lead in the study area. Comparisons of these spatial patterns will assist the NJDEPE in its soil sampling activities and lead exposure research, will provide information for public education, and will provide valuable information on sections of the study area where further screening and public education may be needed.
Angular homeostasis. VIII. Pursuit of a slowly moving target in a plane: relevance to lateralization in cardiovascular ontogeny.
We explore the pursuit in a plane of a target moving at constant slow speed in a straight line. Two models of the pursuit are given. In the continuous case, the pursuer is moving at constant speed and is subject to proportionate angular homeostasis with correction constant b. In the discrete version movement occurs at a constant speed in a sequence of straight line segments of constant length (called the step size, s) the end of the segments being called the vertices. The pattern considered is not the absolute position of the pursuer, but its distance and orientation relative to the target. Both the transients and the asymptotic orbit are addressed. A key quantity is r, the speed of the target expressed as a fraction of that of the pursuer. If the speed of the pursuer is defined as unity, r is also the ratio of the speeds. There exists a critical speed fraction, R(b,s), a function of b and s, that defines what the term slow designates. R(b,s), which has to be found numerically, has the following property. For r less than R(b,s), the asymptotic path is a simple closed curve. In the discrete case the vertices converge to a simple closed curve. The larger r, the more the path (or in the discrete analogue its set of vertices) departs from a circle, and the more eccentric the target is with respect to it. Interest centers on two issues. First we address the transient patterns of the path, notably whether or not the sense of any particular path (clockwise or counterclockwise) is the same throughout, or changes at some stage.(ABSTRACT TRUNCATED AT 250 WORDS)
Rhodopsin and the retinal G-protein distinguish among G-protein beta gamma subunit forms.
The beta gamma subunits of G-proteins are composed of closely related beta 35 and beta 36 subunits tightly associated with diverse 6-10 kDa gamma subunits. We have developed a reconstitution assay using rhodopsin-catalyzed guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) binding to resolved alpha subunit of the retinal G-protein transducin (Gt alpha) to quantitate the activity of beta gamma proteins. Rhodopsin facilitates the exchange of GTP gamma S for GDP bound to Gt alpha beta gamma with a 60-fold higher apparent affinity than for Gt alpha alone. At limiting rhodopsin, G-protein-derived beta gamma subunits catalytically enhance the rate of GTP gamma S binding to resolved Gt alpha. The isolated beta gamma subunit of retinal G-protein (beta 1, gamma 1 genes) facilitates rhodopsin-catalyzed GTP gamma S exchange on Gt alpha in a concentration-dependent manner (K0.5 = 254 +/- 21 nM). Purified human placental beta 35 gamma, composed of beta 2 gene product and gamma-placenta protein (Evans, T., Fawzi, A., Fraser, E.D., Brown, L.M., and Northup, J.K. (1987) J. Biol. Chem. 262, 176-181), substitutes for Gt beta gamma reconstitution of rhodopsin with Gt alpha. However, human placental beta 35 gamma facilitates rhodopsin-catalyzed GTP gamma S exchange on Gt alpha with a higher apparent affinity than Gt beta gamma (K0.5 = 76 +/- 54 nM). As an alternative assay for these interactions, we have examined pertussis toxin-catalyzed ADP-ribosylation of the Gt alpha subunit which is markedly enhanced in rate by beta gamma subunits. Quantitative analyses of rates of pertussis modification reveal no differences in apparent affinity between Gt beta gamma and human placental beta 35 gamma (K0.5 values of 49 +/- 29 and 70 +/- 24 nM, respectively). Thus, the Gt alpha subunit alone does not distinguish among the beta gamma subunit forms. These results clearly show a high degree of functional homology among the beta 35 and beta 36 subunits of G-proteins for interaction with Gt alpha and rhodopsin, and establish a simple functional assay for the beta gamma subunits of G-proteins. Our data also suggest a specificity of recognition of beta gamma subunit forms which is dependent both on Gt alpha and rhodopsin. These results may indicate that the recently uncovered diversity in the expression of beta gamma subunit forms may complement the diversity of G alpha subunits in providing for specific receptor recognition of G-proteins.
Angular homeostasis VII: non-monotonic correction systems.
We extend our model of angular homeostasis to correction functions that have a single maximum at a discrepant angle less than pi radians. We find that there are stable, and asymptotically stable, solutions that in general consist of self-intersecting curves. We investigate conditions for these curves to be periodic, and describe their symmetries. One typical pattern of such a closed curve involves a finite number of loops, each having a reflection axis of symmetry, with the complete curve having a cyclic rotation group. These bear a close resemblance to patterns found in lobulated biological structures (such as the petals of a flower or the primitive fetal hand). We further discuss implications for morphogenesis.
Case-control studies of environmental influences in diseases with genetic determinants, with an application to Alzheimer's disease.
Many diseases have both genetic and environmental determinants. Some require both, and the disease phenotype then appears only when a vulnerable genotype is expressed after interaction with environmental factors. The detection of such environmental factors has received little prior consideration in diseases with genetic causes. In particular, case-control studies of such diseases may compare exposures among cases, who have the susceptible genotype, and controls who mostly lack it. The authors explored the likely results of such studies, using the example of Alzheimer's disease as an illness where environmental factors may interact with a necessary susceptible genotype to accelerate disease expression. They found that case-control studies of environmental factors in complex genetic diseases will usually produce an odds ratio that differs little from the relative risk among susceptible individuals. In rare situations, however, the discrepancy may be gross. The statistical power of such studies also agrees well with familiar published estimates, suggesting that little power is lost even though the controls are mostly not susceptible. Power may be increased, however, in studies of common illnesses with genetic determinants when the case-control method is applied among discordant monozygotic twins.
Effect of added reactive aluminum on aldicarb adsorption by a high organic soil.
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Assessment of genetic risk in congenital heart disease.
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Antibodies to Proteus in rheumatoid arthritis.
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Sarcoidosis and acute myeloid leukaemia.
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Rheumatoid arthritis: workload and outcome over 10 years.
Rheumatoid arthritis remains a chronic disabling disorder in which medical and surgical intervention may provide amelioration but not cure. In this study a cohort of 123 rheumatoid patients were followed for a period of 10 years from the time of prescription of their initial second-line agent. The workload involved in managing articular, extra-articular and intercurrent disease in these patients has been documented and outcome in relation to continued use of 'disease modifying' therapy evaluated. At 10 years 24 patients (20 per cent) had died and 7 (5 per cent) were not traced; of the 92 (75 per cent) who were assessed, three had become wheelchairbound, two for reasons other than rheumatoid arthritis. Seventy-one per cent of patients required joint surgery, 36 per cent management of peptic ulcer and 45 per cent experienced major episodes of sepsis. Analysis of the results in the 92 patients who were evaluated at 10 years showed significant improvement in Ritchie articular index, pain score, morning stiffness, haemoglobin, platelets, ESR, total globulins, IgG and IgM. Grip strength and Lee functional index showed a trend towards deterioration which did not reach significance. Sixty-seven (73 per cent) of the 92 patients remained on a second- or third-line agent at 10 years (median duration of treatment 107 months); 25 (27 per cent) were not receiving such therapy (median duration of second- and third-line therapy 13 months). The group remaining on treatment showed significant improvement similar to that of the total study group. Those not on treatment improved only for articular index; Lee functional index deteriorated significantly. There was a correlation between area under the curve for ESR over 10 years and radiological progression of disease in hands (r = 0.29, p = 0.026) and in knees and hips (r = 0.3748, p = 0.012) over the 10 year period. Radiographic score correlated well with Lee functional index at the outset and at 10 years and also with the change in the radiographic score over the 10-year period. Unlike the results of previous studies, there was no morbidity from vertebral collapse; this may be related to the low dose of corticosteroids in this cohort (seven patients received systemic corticosteroids). Thus while the aim of treating patients for prolonged periods with second- or third-line therapy was achieved in the majority with no overt evidence of cumulative toxicity, sustained medical and surgical intervention was and will be needed in order to minimize disability in these and other patients with rheumatoid arthritis.