Deficits in spatial coding and feature binding following damage to spatiotopic maps in the human pulvinar.

We report a patient with unilateral damage to the rostral part of the pulvinar who was impaired in localizing stimuli in the inferior visual field contralateral to the lesion and who made errors in the binding of shape and color in that quadrant. The findings demonstrate the importance of the pulvinar in spatial coding and provide support for the function of the thalamus in binding of features. They also provide evidence for a homology between the visual field maps of the inferior and lateral subdivisions of the pulvinar in monkeys and in humans, such that the inferior visual field is represented in the rostral part of the nucleus.     

Neuronal activity in the globus pallidus of multiple system atrophy patients.

The pathophysiological changes in neural activity that characterize multiple system atrophy (MSA) are largely unknown. We recorded the activity of pallidal neurons in 3 patients with clinical and radiological features of MSA who underwent unilateral microelectrode-guided pallidotomy for disabling parkinsonism. Findings in these patients were compared with 4 control patients with a clinical diagnosis of Parkinson's disease (PD). The position, firing rates, and firing patterns of single neurons in the pallidal complex were analyzed in both MSA and PD patients. The mean spontaneous firing rate of neurons in the internal segment of the globus pallidus internus (GPii) was significantly lower in MSA than in PD patients. There were no significant differences between MSA and PD patients, however, in firing rates of neurons in the external globus pallidus (GPe) or in the external segment of GPi (GPie). In addition, no significant differences in firing pattern were found between MSA and PD patients. In conclusion, this study has shown that firing rates of neurons in GPii but not in GPie and GPe are different in MSA patients compared with that in PD patients, a finding that may reflect the poor clinical results of pallidotomy reported in patients with MSA.     

Use of the microorganism Bacillus stearothermophilus as a model to evaluate toxicity of the lipophilic environmental pollutant endosulfan

Microorganisms are very powerful tools for the supply of information about the toxic effects of lipophilic compounds, since an impairment of cell growth usually occurs as a result of perturbations related, in most cases, with the partition of toxicants in membranes. The thermophilic eubacterium Bacillus stearothermophilus has been used as a model system to identify α- and β-endosulfan interactions with the membrane possibly related with the insecticide toxicity. Two approaches have been pursued: (a) bacterial growth is followed and the effects of endosulfan isomers determined; (b) biophysical studies with the fluorescent fluidity probe 1,6-diphenyl-1,3,5-hexatriene (DPH) were performed to assess the effects of α- and β-endosulfan on the organization of the membrane lipid bilayer. The effects on growth were quantitatively evaluated by determination of growth parameters, namely the lag phase, the specific growth rate and the cell density reached by cultures in the stationary phase. Growth inhibition by α and β-endosulfan dependent on the concentration is diminished or removed by the addition of 2.5 m Ca²⁺ to bacterial cultures. Fluorescence DPH polarization consistently showed opposite effects of Ca²⁺ and α- and β-endosulfan on the physical state of bacterial polar lipid dispersions.     

What can natural infection of African monkeys with simian immunodeficiency virus tell us about the pathogenesis of AIDS?

The simian immunodeficiency viruses are a diverse group of viruses that naturally infect a wide range of African primates, including chimpanzees, African green monkeys (AGM) and sooty mangabey monkeys (SM). Although natural infection is widespread in feral populations of AGMs and SMs, this infection does not result in immunodeficiency. However, experimental inoculation of Asian macaque species results in an immunodeficiency syndrome that is remarkably similar in pathogenesis to human AIDS. Thus, SIVsm infection of macaques results in AIDS, and similarly experimental inoculation of pigtailed macaques with at least one SIVagm isolate, SIVIhoest or SIVsun, results in AIDS. The extent of plasma viremia in pathogenic infection is an excellent prognostic indicator of clinical course, with higher viral load being predictive of shorter survival and low viremia being predictive of long-term non-progression. Based upon this paradigm, one would have expected naturally infected animals to exhibit low levels of viremia. In reality, AGMs, SMs, mandrills and chimpanzees infected naturally with their own unique viruses display moderate to high levels of plasma viremia. A significant reduction in CD4+ T-cells in infected versus uninfected SMs suggests that the virus may be cytopathic to some degree. These infected animals still maintain adequate CD4+ T-cells over their entire life in captivity. A distinct characteristic of natural infection is the lack of immunopathology as demonstrated by normal lymph node morphology, lower expression of activation and proliferation markers on CD4+ T-cells, and a generally muted immune response to the virus. Naturally infected SMs and AGMs clearly mount antiviral cellular and humoral immune responses. Therefore, models suggesting immune tolerance to SIV are far too simplistic to explain the lack of disease in these animals. It is probable that a unique balance between T-cell renewal and proliferation and loss through activation-induced apoptosis, and virus-induced cell death has been achieved in SMs and AGMs. The study of the dynamics of T-cell production, proliferation and cell death in asymptomatic natural infection should, therefore, yield insights into the pathogenesis of AIDS.     

Towards cellular receptors for prions

Transmissible spongiform encephalopathies (TSE) are attributed to the conversion of the cellular prion protein (PrP(c)) into an abnormal isoform (PrP(sc)). This can be caused by the invasion of living organisms by infectious particles, or be inherited due to mutations on the PrP(c) gene. One of the most intriguing problems of prion biology is the inability to generate the infectious agent in vitro. This argues strongly that other cellular proteins besides those added in test tubes or found in cellular preparations are necessary for infection. Despite recent progress in the understanding of prion pathology, the subcellular compartments in which the interaction and conversion of PrP(c) into PrP(sc) take place are still controversial. PrP(c) interacts with various macromolecules at the cell membrane, in endocytic compartments and in the secretory pathway, all of which may play specific roles in the internalisation of PrP(sc) and conversion of PrP(c). A specific interacting protein required for the propagation of prions was originally proposed as a prion receptor, and later referred to as a ligand, a cofactor, protein X, or a partner. However, current studies indicate that PrP(c) associates with multi-molecular complexes, which mediate a variety of functions in distinct cellular compartments. It is proposed that a deeper understanding of the mechanics of such interactions, coupled to a better knowledge of the corresponding signalling pathways and ensuing cellular responses, will have a major impact on the prevention and treatment of TSE.     

Local and systemic antibody class responses to an infectious laryngotracheitis virus vaccine strain

Chickens infected with infectious laryngotracheitis virus (ILTV) responded by producing virus-specific IgG in their sera, which increased steadily in concentration, but with slight fluctuations, until peak titres were reached 40 days post-inoculation (pi), immediately prior to the second challenge. Thereafter, following an initial lag, concentrations continued to increase for 21 days before falling slightly at the end of the experiment. In contrast, peak concentrations of ILTV-specific IgM were reached 6 days pi falling to their lowest levels by day 16, before increasing to a second peak and trough on days 26 and 32, respectively. This cyclical production of ILTV-specific IgM was confirmed in a second experiment. The pattern of production of ILTV-specific IgG, IgM and IgA, detected in tracheal washings, occurred in the same cyclical manner. IgM was produced first, peak concentrations being detected 5 days pi, whereas IgG and IgA did not peak until 10 days pi, with second peaks of each class being detected 25-30 days pi. The possibility that the cyclical antibody class response to ILTV infection is related to the previously reported intermittent pattern of re-excretion of the virus is discussed.     

DADOS-Survey: an open-source application for CHERRIES-compliant Web surveys

Background  

The Internet has been increasingly utilized in biomedical research. From online searching for literature to data sharing, the Internet has emerged as a primary means of research for many physicians and scientists. As a result, Web-based surveys have been employed as an alternative to traditional, paper-based surveys. We describe DADOS-Survey, an open-source Web-survey application developed at our institution that, to the best of our knowledge, is the first to be compliant with the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). DADOS-Survey was designed with usability as a priority, allowing investigators to design and execute their own studies with minimal technical difficulties in doing so.     

Interaction of toxic venoms with the complement system

Thirty-nine venoms from various vertebrate and invertebrate species were tested for their ability to consume haemolytic complement (C) activity upon incubation in fresh guinea-pig serum. Nineteen had `anti-complementary' activity, and these were provisionally sorted into the following groups: Pattern I—exemplified by the Naja haje (Egyptian cobra) and six other Elapidae species (all cobras), which induced selective consumption of C3—C9, and led to formation of a stable C3—C9-consuming intermediate; Pattern II—exemplified by the Agkistrodon rhodostoma (Malayan pit viper), Bitis arietans (puff adder), Bothrops jararaca (South American pit viper), Bothrops atrox (Fer de Lance) and three other species, which induced marked consumption of C4 and C2, as well as C3—C9, but did not form a stable C3—C9-consuming intermediate; and individual animals, e.g. the Lachesis muta (bushmaster), which induced other patterns (III—VI) of complement component consumption. Active fractions of representative venoms were partially purified by ion exchange and gel filtration chromatography and their interactions with the complement system characterized further. It is anticipated that these enzymes, with a capacity to activate the complement system in unique ways, will prove to be of further experimental usefulness.