Alterations in Plasmodium falciparum genotypes during sequential infections suggest the presence of strain specific immunity

Many of the asexual stage Plasmodium falciparum proteins that are the targets of host protective responses are markedly polymorphic. The full repertoire of diversity is not defined for any antigen. Most studies have focused on the genes encoding merozoite surface proteins 1 and 2 (MSP1, MSP2). We explored the extent of diversity of some of the less studied merozoite surface antigens and analyzed the degree of complexity of malaria field isolates by deriving nucleotide sequences of several antigens. We have determined the genotype of apical membrane antigen 1 (AMA1) in a group of 30 field samples, collected over 29 months, from individuals living in an area of intense malaria transmission in Irian Jaya, identifying 14 different alleles. AMA1 genotyping was combined with previously determined MSP2 typing. AMA1 had the greatest power in distinguishing between isolates but methodological problems, especially when mixed infections are present, suggest it is not an ideal typing target. MSP1, MSP3, and glutamate-rich protein genotypes were also determined from a smaller group of samples, and all results were combined to derive an extended antigenic haplotype. Within this subset of 10 patients, nine different genotypes could be discerned; however, five patients were all infected with the same strain. This strain was present in individuals from two separate villages and was still present 12 months later. This strain was predominant at the first time point but had disappeared at the fourth time point. This significant change in malaria genotypes could be due to strain-specific immunity developing in this population.

Ocular scanning and perceptual size distortion in hemispatial neglect: effects of prism adaptation and sequential stimulus presentation

When asked to compare two lateralized shapes for horizontal size, neglect patients often indicate the left stimulus to be smaller. Gainotti and Tiacci (1971) hypothesized that this phenomenon might be related to a rightward bias in the patients' gaze. This study aimed to assess the relation between this size underestimation and oculomotor asymmetries. Eye movements were recorded while three neglect patients judged the horizontal extent of two rectangles. Two experimental manipulations were performed to increase the likelihood of symmetrical scanning of the stimulus display. The first manipulation entailed a sequential, rather than simultaneous presentation of the two rectangles. The second required adaptation to rightward displacing prisms, which is known to reduce many manifestations of neglect. All patients consistently underestimated the left rectangle, but the pattern of verbal responses and eye movements suggested different underlying causes. These include a distortion of space perception without ocular asymmetry, a failure to view the full leftward extent of the left stimulus, and a high-level response bias. Sequential presentation of the rectangles and prism adaptation reduced ocular asymmetries without affecting size underestimation. Overall, the results suggest that leftward size underestimation in neglect can arise for a number of different reasons. Incomplete leftward scanning may perhaps be sufficient to induce perceptual size distortion, but it is not a necessary prerequisite.

Coronary flow responses to exercise training: further evidence of the benefit of an underutilized therapeutic modality

Inactivity is associated with endothelial dysfunction and the development of cardiovascular disease. Exercise training has a favourable effect in the management of hypertension, heart failure and ischaemic heart disease. These beneficial effects are probably mediated through improvements of vascular function and, in this issue of Clinical Science, Hagg and co-authors propose a coronary artery effect. The use of a Doppler technique for non-invasive assessment of coronary flow reserve in a small animal model is an exciting aspect of this study. If feasible in the hands of other investigators, the availability of sequential coronary flow measurements in animal models may help improve our understanding of the mechanisms of disorders of the coronary circulation.

Respiratory and cardiovascular responses to hypoxia in the Australian lungfish

Simultaneous measurements of pulmonary blood flow (qPA), coeliacomesenteric blood flow (qCoA), dorsal aortic blood pressure (PDA), heart rate (fH) and branchial ventilation frequency (fv) were made in the Australian lungfish, /Neoceratodus forsteri, /during air breathing and aquatic hypoxia. The cho­linergic and adrenergic influences on the cardiovascular system were investigated during normoxia using pharmacological agents, and the presence of catecholamines and serotonin in different tissues was investi­gated using histochemistry. Air breathing rarely occurred during normoxia but when it did, it was always associated with increased pulmonary blood flow. The pulmonary vasculature is influenced by both a cho­linergic and adrenergic tonus whereas the coeliacomesenteric vasculature is influenced by a β-adrenergic vasodilator mechanism. No adrenergic nerve fibers could be demonstrated in /Neoceratodus /but catecholamine-containing endothelial cells were found in the atrium of the heart. In addition, serotonin-­immunoreactive cells were demonstrated in the pulmonary epithelium. The most prominent response to aquatic hypoxia was an increase in gill breathing frequency followed by an increased number of air breaths together with increased pulmonary blood flow. It is clear from the present investigation that /Neoceratodus /is able to match cardiovascular performance to meet the changes in respiration during hypoxia.

Asset Price Instability and Policy Responses: The Legacy of Liberalisation

The debate about the dynamics and potential policy responses to asset inflation has intensified in recent years. Some analysts, notably Borio and Lowe, have called for 'subtle' changes to existing monetary targeting frameworks to try to deal with the problems of asset inflation and have attempted to developed indicators of financial vulnerability to aid this process. In contrast, this paper argues that the uncertainties involved in understanding financial market developments and their potential impact on the real economy are likely to remain too high to embolden policy makers. The political and institutional risks associated with policy errors are also significant. The fundamental premise that a liberalised financial system is based on 'efficient' market allocation cannot be overlooked. The corollary is that any serious attempt to stabilize financial market outcomes must involve at least a partial reversal of deregulation.

Antibody responses and protective immunity to recombinant vaccinia virus-expressed bluetongue virus antigens

The role of individual viral proteins in the immune response to bluetongue virus (BTV) is not clearly understood. To investigate the contributions of the outer capsid proteins, VP2 and VP5, and possible interactions between them, these proteins were expressed from recombinant vaccinia viruses either as individual proteins or together in double recombinants, or with the core protein VP7 in a triple recombinant. Comparison of the immunogenicity of the vaccinia expressed proteins with BTV expressed proteins was carried out by inoculation of rabbits and sheep. Each of the recombinants was capable of stimulating an anti-BTV antibody response, although there was a wide range in the level of response between animals and species. Vaccinia-expressed VP2 was poorly immunogenic, particularly in rabbits. VP5, on the whole, stimulated higher ELISA titers in rabbits and sheep and in some animals in both species was able to stimulate virus neutralizing antibodies. When the protective efficacy of VP2 and VP5 was tested in sheep, vaccinia-expressed VP2, VP5 and VP2 + VP5 were protective, with the most consistent protection being in groups immunized with both proteins. (C) 1997 Elsevier Science B.V.

Analysis of tissue responses to fin tagging in Australian carcharhinids

Tissue responses to the application of Rototags and Jumbo Rototags in the first dorsal fin of Carcharhinus melanopterus, C. obscurus and C. plumbeus were examined. The acute response included tissue tearing and haemorrhage and was present by 5 days post-tagging. The intermediate response had begun by 20 days post-tagging and continued beyond 207 days. This response involved decreased red blood cell activity as the inflammatory response commenced. The chronic response had begun by 301 days and was complete by 553 days with a layer of fibrous connective tissue walling off the tag. External damage to the fin was caused by continued abrasion by the tag. Repair scales were observed at 242 days using scanning electron microscopy and were confirmed histologically in 61- and 553-day samples. Repair scales were not seen in areas of continuous abrasion. No infection was observed in tissues surrounding the wound. Disruption of the fin surface was observed due to abrasion by the tag, but did not appear to cause a severe tissue reaction. The tissue responses observed were consistent with a normal, but relatively slow, healing in the vicinity of the tag wound. Use of Rototags or Jumbo Rototags appears to be an efficient way of marking elasmobranchs with minimal damage to the shark. (C) 1998 The Fisheries Society of the British Isles.

Adjustment to a low-control situation: Reexamining the role of coping responses

The aim of the study was to test a revised conceptualization of the role of coping in adjustment to a low-control stressor-women's adjustment to a failed in vitro fertilization (NF) attempt. Data were collected prior to the IVF treatment (Time I) and twice after the failed NF attempt (1 to 2 weeks after finding out the results, n = 171, and fi weeks later, n = 139). Initial adjustment was assessed at Time I, whereas measures of coping and both self-report and partner ratings of adjustment were obtained at Times ? and 3. As predicted, escapist strategies and problem-management strategies (mainly at Time ?) were associated with poor adjustment, whereas problem-appraisal coping was associated with better adjustment., There was also support for the proposed positive relationship between adjustment and emotional approach coping (on self-report adjustment).

Vaccine-induced Th1-type responses are dominant over Th2-type responses in the short term whereas pre-existing Th2 responses are dominant in the longer term

The effect of adjuvant on induction of human papillomavirus type 16 E7 protein-specific cytotoxic T lymphocytes (CTL) and immunoglobulin G (IgG)(2a) antibody was studied in C57BL/6 J mice immunized with various adjuvants and E7 protein. Quil-A adjuvant, but not complete Freund's adjuvant (CFA) or Algammulin, induced a T-helper 1 (Th1)-type response to E7, which was characterized by CTL activity against a tumour cell line transfected with E7 protein and by E7-specific IgG(2a). All tested adjuvants elicited comparable levels of E7-specific IgG(1). The longest duration and greatest magnitude of CTL response was seen following two immunizations with the highest dose of E7 and Quil-A. Simultaneous immunization with a Th1 and a T helper 2 (Th2)-promoting adjuvant gave a Th1-type response. However, E7 and Quil-A were unable to induce a Th1-type response (as measured by the inability to generate anti-E7 IgG(2a) antibody) in animals with a pre-existing Th2-type response to E7. These results suggest that saponin adjuvants may be suitable for immunotherapy in humans where a Th1-type response is sought, provided that there is no pre existing Th2-type response to the antigen.

Effects of stimulus modality and task condition on blink startle modification and on electrodermal responses

Participants in Experiments 1 and 2 performed a discrimination and counting task to assess the effect of lead stimulus modality on attentional modification of the acoustic startle reflex. Modality of the discrimination stimuli was changed across subjects. Electrodermal responses were larger during task-relevant stimuli than during task-irrelevant stimuli in all conditions. Larger blink magnitude facilitation was found during auditory and visual task-relevant stimuli, but not for tactile stimuli. Experiment 3 used acoustic, visual, and tactile conditioned stimuli (CSs) in differential conditioning with an aversive unconditioned stimulus (US). Startle magnitude facilitation and electrodermal responses were larger during a CS that preceded the US than during a CS that was presented alone regardless of lead stimulus modality. Although not unequivocal, the present data pose problems for attentional accounts of blink modification that emphasize the importance of lead stimulus modality.

Likelihood-based estimation of the regression model with scrambled responses

A significant problem in the collection of responses to potentially sensitive questions, such as relating to illegal, immoral or embarrassing activities, is non-sampling error due to refusal to respond or false responses. Eichhorn & Hayre (1983) suggested the use of scrambled responses to reduce this form of bias. This paper considers a linear regression model in which the dependent variable is unobserved but for which the sum or product with a scrambling random variable of known distribution, is known. The performance of two likelihood-based estimators is investigated, namely of a Bayesian estimator achieved through a Markov chain Monte Carlo (MCMC) sampling scheme, and a classical maximum-likelihood estimator. These two estimators and an estimator suggested by Singh, Joarder & King (1996) are compared. Monte Carlo results show that the Bayesian estimator outperforms the classical estimators in almost all cases, and the relative performance of the Bayesian estimator improves as the responses become more scrambled.

Exploring sequential data: Commentary on Bowers, Jentsch, Salas, and Braun (1998)

In an investigation intended to determine training needs of night crews, Bowers et al. (1998, this issue) report two studies showing that the patterning of communication is a better discriminator of good and poor crews than is the content of communication. Bowers et al. characterize their studies as intended to generate hypotheses for training needs and draw connections with Exploratory Sequential Data Analysis (ESDA). Although applauding the intentions of Bowers ct al., we point out some concerns with their characterization and implementation of ESDA. Our principal concern is that the Bowers et al. exploration of the data does not convincingly lead them back to a better fundamental understanding of the original phenomena they are investigating.