Allergic rhinitis: not just a runny nose.
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Biomedical subjects
Publications and source records attributed to G Roberts.
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The major sperm protein (MSP) of Ascaris suum mediates amoeboid motility by forming an extensive intermeshed system of cytoskeletal filaments analogous to that formed by actin in many other amoeboid cells. MSP is a dimeric molecule that polymerizes to form non-polar filaments constructed from two helical subfilaments that wind round one another. Moreover, MSP filaments can interact with one another to form higher-order assemblies without requiring the range of accessory proteins usually employed in actin-based systems. A knowledge of how MSP polymerizes and forms the hierarchical series of helical MSP macromolecular assemblies is fundamental to understanding locomotion in these cells. Here we describe the solution structure of MSP dimers determined by NMR spectroscopy under conditions where MSP does not polymerize to form filaments. The solution structure is indistinguishable from that observed in putative MSP subfilament helices by X-ray crystallography, indicating that MSP polymerization is not accompanied by a major conformational change. We also show that the rate of MSP polymerization associated with movement of vesicles in an in vitro motility assay is enhanced by the presence of magnesium and manganese ions and use NMR to show that the primary residues that bind these ions are 24-25 and 83-86. These residues are distant from the interface formed between MSP dimers in subfilament helices, and so are probably not involved in this level of polymerization. Instead the manganese and magnesium ion binding appears to be associated with the assembly of subfilaments into filaments and their subsequent aggregation into bundles.
Reciprocal altruism can become established among selfish, unrelated individuals if they use responsive strategies such as 'tit-for-tat. This result raises the fundamental question: how altruistic should one be? The problem is difficult to solve using current 'prisoner's dilemma' based models because they allow only the discrete choice of cooperating or defecting. In reality, however, cooperation is rarely all-or-nothing. Furthermore, if cooperative investment is variable, a new and more subtle kind of cheating becomes possible: individuals may invest slightly less than their partner. A concern is that this 'short-changing' will erode cooperative ventures. Here we show that cooperation can thrive despite variable investment through the new strategy of 'raise-the-stakes'. This strategy offers a small amount on first meeting and then, if matched, raises its investment, something that no strategy in the discrete model can do. We show that such behaviour can readily invade a population of non-altruists and cannot be effectively exploited. The practice of 'testing the water' rather than making sudden cooperative 'leaps of faith' powerfully reinforces the stability and effectiveness of reciprocity.
In this paper we present a resource-explicit Donor-Receiver model for reciprocally altruistic interactions that obeys the defining inequalities of the Prisoner's Dilemma. In our model, individuals vary in the quantity of resource they invest when cooperating (termed "generosity") and they have the freedom to opt out of interactions with potential partners on the basis of their past experiences with these players (termed "choosiness"). Dynamic optimal solutions were found using a genetic algorithm in which the decision rules (cooperate or defect), generosity when cooperating, and choosiness exhibited by individuals when deciding to opt out, were all coded on genes held on two separate chromosomes. Through this genetic algorithm, individuals that had alleles which resulted in greatest success at playing our modified Prisoner's Dilemma left more offspring. When the benefit of receiving a unit resource exceeded the cost of giving, then generous cooperative behaviour tended to emerge within the population, even when the alleles of all the individuals in the starting population were set to defect. When the probability of individuals re-encountering one another was increased, individuals not only cooperated more, but they developed greater generosity. However, as the ratio of the benefits received to costs expended increased above 1, individuals in this model remained highly cooperative but their median generosity decreased significantly. In contrast to earlier studies using genetic algorithms, the extra potential for cheating afforded by asymmetrical degrees of generosity meant that genuinely cooperative behaviour did not emerge in the equivalent round-robin tournament in which individuals were not able to exercise partner preference.
OBJECTIVE: To report a case of a 3-year-old child with an extraordinarily massive lead concentration, 26.4 micromol/L (550 microg/dL), following environmental exposure to lead paint in the home. LITERATURE REVIEW: The relevant literature concerning the treatment of lead encephalopathy was reviewed during the treatment of this child and preparation of the manuscript. To our knowledge, the landmark article written by Julian Chisolm in 1968 is the only recent article that reported similarly high levels of lead concentration. This case, however, is the first in which 3 chelating agents were used for the treatment of lead encephalopathy. We also reviewed the literature on the use of whole bowel irrigation in heavy metal intoxications. CONCLUSIONS: In this case, aggressive gut decontamination with whole bowel irrigation and triple chelation therapy with British anti-Lewisite, EDTA, and oral succimer was well tolerated and seemed effective for rapidly deleading the child. The extent to which her lead concentration increased while being treated with oral succimer alone necessitated further chelation with EDTA. Further evaluation is necessary to determine if triple chelation therapy is an appropriate method for severe lead intoxication, and if the use of whole bowel irrigation should be considered in heavy metal intoxication.
This study used multi-group path analysis to test the hypothesis that disability's total effect on self-rated health differs for different-aged persons with multiple sclerosis (MS). Data (n=806) collected as part of a larger study examining quality of life for persons with MS were used to construct and compare models of health appraisal for three age groups, 18 to 45 (n=347), 46 to 60 (n=339), and 61 to 78 (n=120). The results suggest that while the same general model describes health appraisal in each age group, disability's total effect on self-rated health is less in the older and middle-aged groups than in the youngest group. Further, disability's direct effect, rather than the hypothesized indirect effects, accounts for the group differences. The findings support the other work in this area suggesting that age may moderate the effect of "objective" health status on self-rated health. The generally surprising finding was the "break point" for this effect -- contrary to other research that suggests older persons may differ from other-aged individuals, in this sample of persons with MS, the youngest group differed from the others. These results are discussed in terms of MS specifically and health appraisal more generally.
OBJECTIVE: To determine the factors that predict the effectiveness of desmopressin in the treatment of childhood nocturnal enuresis. PATIENTS AND METHOD: Sixty-six children with monosymptomatic nocturnal enuresis were treated with intranasal or oral desmopressin for a 4-week period. starting with a standard dose of 20 microg (0.2 mg oral) and increasing after 2 weeks where no progress was apparent to 40 microg (0.4 mg oral). Before treatment a range of variables (demographic, situational, enuretic history, physiological, parental attitude and child) were recorded. Three parameters of success acted as dependent variables, with stepwise linear regression models used to determine pretreatment predictors of success with desmopressin. RESULT: Each outcome variable produced a very similar model of predictors. Success, as assessed by the most dry nights over a 14-night period, was associated with less severe enuresis before treatment, a parental belief that the child's enuresis was unstable and higher birthweight. CONCLUSION: From the analysis, a model of arginine vasopressin release is proposed and the clinical implications of the findings addressed.
A patient with basilar artery rupture caused by a septic embolus originating from a mitral valve vegetation is reported. The pathogenesis, investigation and management of infected cerebral aneurysms are reviewed.
We systematically reviewed studies of the prevalence of domestic violence. Selected overseas community studies were compared with all Australian prevalence studies found to be published. Twelve-month prevalence estimates of partner abuse in Australia varied from 2.1 per cent to 28.0 per cent, depending mainly on the definition of domestic violence used in each study. Implications of the lack of a precise definition result in varying operationalised definitions of partner abuse, from all types of violence in relationships (including a single minor violent incident), through to only those violent incidents that are classified as a crime. Recommendations for any future prevalence studies in this field include the need to collect frequency data which reflected the fact that partner abuse against women is a complex behavioural phenomenon involving emotional, physical and sexual abuse against a partner, not just simply physical incidents.
The ability to identify yeast isolates by the new enzymatic RapID Yeast Plus System was compared to the ability to identify yeast isolates by the API 20C system. A total of 447 yeast isolates representing Blastoschizomyces capitatus, 17 Candida spp., 5 Cryptococcus spp., Geotrichum spp., 2 Hanseniaspora spp., Hansenula anomala, Hansenula wingei, 3 Rhodotorula spp., Saccharomyces cerevisiae, Sporobolomyces salmonicolor, Trichosporon beigelii, and 2 Prototheca spp. were evaluated. Also, five quality control strains (Candida spp. and Cryptococcus laurentii) with well-documented reactivities by the RapID Yeast Plus System were used. Each isolate was evaluated by both methods with a 48-h culture grown at 30 degrees C on Sabouraud dextrose agar (Emmons modification) by following the recommendations of the manufacturers. The RapID Yeast Plus System enzymatic reactions were read after 4 h of incubation, and the API 20C carbohydrate assimilation identification profiles were obtained after 72 h of incubation. There was good (95.7%) agreement between the identifications obtained by the two methods with the eight common Candida spp. and with Cryptococcus neoformans. The agreement was lower when the emerging Candida spp. and other yeast-like pathogens were tested (79.1 and 75.2%, respectively). These preliminary data suggest the potential utility of the RapID Yeast Plus System for use in the clinical laboratory for the rapid identification of common yeast pathogens as well as certain new and emerging species.
A 30-year-old woman presented with a progressive neurologic disorder characterized by seizures, buccolingual dyskinesias, orofacial tics, choreiform movements, atrophy, and areflexia. Investigations revealed normal lipid profile except for aprebetalipoproteinemia. Phase-contrast and electron microscopy showed 35 to 40% acanthocytes. MRI and 18fluorodeoxyglucose-PET studies showed caudate atrophy and hypometabolism. The phenotype of this patient is neuroacanthocytosis and its association with aprebetalipoproteinemia may represent a new subentity of the disorder.
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The complex ATP-activation kinetics of plant H+-ATPase requires two ATP effects on the enzyme. They may result from the simultaneous existence of two ATP sites or a single site that consecutively changes its properties. We describe here three main models for ATP binding to the plant H+-ATPase. Considering the experimental data there are some restrictions in their application. A system with two simultaneous catalytic sites with cooperative binding is possible provided the substrate exerts regulatory properties, and when ES (or SE) leads to a slower velocity path than SES (v1 < v2). In other words, simple cooperativity does not work. A system with two substrate sites, one of which is catalytic and the other is always and only regulatory (i.e. it affects the overall reaction rate), offers two alternatives: one with potential cooperative binding (the system does not discriminate between binding to the catalytic and regulatory sites; and the other with intrinsically different affinities of catalytic and regulatory sites (i.e. the system discriminates between binding to the two binding sites). Here it is also obligatory that ES (or SE) leads to a slower-velocity path than SES (v1 < v2). Thirdly, a system is possible with single ATP domain that is consecutively catalytic and regulatory as the cycle proceeds. These three mechanisms give rise to equivalent rate equations. Therefore, there is no way to distinguish between them on the basis of kinetic studies. Another conclusion drawn from modeling these schemes is that the form of the plots might resemble but not correspond to certain cooperativity type. For instance, for two substrate sites, a true negative cooperativity for substrate binding can mimic positive cooperativity if the v1 velocity pathway is much slower than the v2 one.
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Flights from foraging flocks of sanderlings, Calidris alba were observed at Redcar, northeast England, in order to investigate how individual decisions to fly related to the behaviour of other flock members. Flights of sanderlings tended to be either of all birds in the flock on the ground, or of single birds or groups representing only a small proportion of the foraging flock. The latter accounted for the majority of movement events but after weighting by flock size the former accounted for the majority of bird movements. As flock size increased, the number of birds that flew without the whole flock taking flight increased. Thus, as flock size increased, it took more individual departures before the whole flock took flight. When flocks were disturbed by people or dogs, they were more cohesive, with more departures being of whole flocks.Copyright 1997 The Association for the Study of Animal BehaviourCopyright 1997The Association for the Study of Animal Behaviour.
Fungi represent the etiologic agent in a large number of patients with chronic sinusitis. Despite this, no study has examined the effects of fungi on ciliated epithelium. This study evaluates the effects of cultures and filtrates of Aspergillus fumigatus and Alternaria alternata on ciliary beat frequency (CBF) in vitro. CBF was recorded after exposure to either a control or experimental solution. A statistical comparison of control and experimental values was performed to determine significance at P < 0.05. A statistically significant inhibition of CBF in cultures and filtrates of A fumigatus and A alternata was demonstrated. We conclude that a soluble metabolite produced by clinical isolates of both A fumigatus and A alternata causes inhibition of CBF and may represent one virulence factor involved in the development of fungal sinusitis.
OBJECTIVE: The diagnosis and treatment of intracranial aneurysms (IAs) prior to rupture reduces the high morbidity and mortality associated with their occurrence. Elevated serum lipoprotein (a) [Lp(a)] level, an independent risk factor for atherogenesis, has been demonstrated in sporadic IA disease (1). The purpose of this study was to assess the degree of correlation between elevated Lp(a) levels and the occurrence of IAs in asymptomatic first degree relatives of index cases from three families exhibiting a familial tendency towards IA development. METHODS: 25 family members and 41 healthy controls were screened by random serum Lp(a) sampling. All family members received 4-vessel cerebral angiography. RESULTS: Eleven family members were found on angiography to harbour asymptomatic aneurysms and all were successfully treated by surgery. Of these 11, ten had significantly raised serum Lp(a) levels (> 30 mg%). Fourteen family members had negative angiograms. Eight of this latter group, mean age 43.6 +/- 3.8 years, had serum Lp(a) levels above the normal range. Mean Lp(a) levels were 53.7 +/- 1.2 mg% in subjects with aneurysms compared with 22.1 +/- 1.45 mg% in subjects without demonstrable aneurysms and 10.5 +/- 0.48 mg% in the control population. CONCLUSION: The prevalence of elevated Lp(a) levels in these families and the high degree of association of raised Lp(a) levels with the presence of IAs in several family members warrants follow up of angiographically negative young subjects. We require a case-control study to establish whether particular polymorphisms at the apoprotein (a) gene level are associated with the occurrence of IAs in these families.
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