Potential of the Panama strain of Plasmodium vivax for the testing of malarial vaccines in Aotus nancymai monkeys.
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Aotus monkeys were infected with a strain of Plasmodium vivax from Panama to determine its potential for the testing of malarial vaccines. After sporozoite inoculation, 3 splenectomized Aotus nancymai that had been infected previously with Plasmodium falciparum and P. vivax had prepatent periods of 13, 15, and 15 days with maximum parasite counts of 12,726/microl, 5,310/microl, and 9,180/microl. Three other A. nancymai previously infected with P. falciparum only had prepatent periods of 17, 15, and 15 days with maximum parasite counts of 44,460/microl, 31,500/microl, and 42,660/microl. One monkey with no previous history of infection had a prepatent period of 14 days after sporozoite inoculation, and a maximum parasite count of 100,000/microl; detectable parasitemia persisted for almost 500 days with 13 recognizable peaks in the parasite count. Anopheles dirus, Anopheles freeborni, Anopheles stephensi, and Anopheles quadrimaculatus mosquitoes were readily infected with the Panama strain. (+info)
Sensory representation abnormalities that parallel focal hand dystonia in a primate model.
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In our hypothesis of focal dystonia, attended repetitive behaviors generate aberrant sensory representations. Those aberrant representations interfere with motor control. Abnormal motor control strengthens sensory abnormalities. The positive feedback loop reinforces the dystonic condition. Previous studies of primates with focal hand dystonia have demonstrated multi-digit or hairy-glabrous responses at single sites in area 3b, receptive fields that average ten times larger than normal, and high receptive field overlap as a function of horizontal distance. In this study, we strengthen and elaborate these findings. One animal was implanted with an array of microelectrodes that spanned the border between the face and digits. After the animal developed hand dystonia, responses in the initial hand representation increasingly responded to low threshold stimulation of the face in a columnar substitution. The hand-face border that is normally sharp became patchy and smeared over 1 mm of cortex within 6 weeks. Two more trained animals developed a focal hand dystonia variable in severity across the hand. Receptive field size, presence of multi-digit or hairy-glabrous receptive fields, and columnar overlap covaried with the animal's ability to use specific digits. A fourth animal performed the same behaviors without developing dystonia. Many of its physiological measures were similar to the dystonic animals, but receptive field overlap functions were minimally abnormal, and no sites shared response properties that are normally segregated such as hairy-glabrous combined fields, or multi-digit fields. Thalamic mapping demonstrated proportionate levels of abnormality in thalamic representations as were found in cortical representations. (+info)
Responses of neurons in the middle temporal visual area after long-standing lesions of the primary visual cortex in adult new world monkeys.
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The retinotopic organization of the middle temporal visual area (MT) was determined in six adult owl monkeys and one adult marmoset 69 d to 10 months after lesions of the dorsolateral primary visual cortex (V1). The lesions removed were limited to extensive parts of the representation of the lower visual quadrant in V1. Microelectrodes were used to record from neurons at numerous sites in MT to determine whether parts of MT normally devoted to the lower visual quadrant (1) were unresponsive to visual stimuli, (2) acquired responsiveness to inputs from intact portions of V1, or (3) became responsive to some other visually driven input such as a relay from the superior colliculus via the pulvinar to MT. All monkeys (n = 6) with moderate to moderately large lesions had unresponsive portions of MT even after 10 months of recovery. These unresponsive regions were retinotopically equivalent to the removed parts of V1 in normal animals. Thus, there was no evidence for an alternative source of activation. In addition, these results indicate that any retinotopic reorganization of MT based on inputs from intact portions of V1 was not extensive, yet neurons near the margins of responsive cortex may have acquired new receptive fields, and the smallest 5 degrees lesion of V1 failed to produce an unresponsive zone. Deprived portions of MT were not remarkably changed in histological appearance in cytochrome oxidase, Nissl, and Wisteria floribunda agglutinin preparations. Nevertheless, some reduction in myelin staining and other histological changes were suggested. We conclude that MT is highly dependent on V1 for activation in these monkeys, and alternative sources do not become effective over months when normal activation is absent. Additionally, remaining V1 inputs have only a limited capacity to expand their activation territory into deprived portions of MT. (+info)
Severe anemia affects both splenectomized and non-splenectomized Plasmodium falciparum-infected Aotus infulatus monkeys.
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Severe anemia is the earliest and a frequently fatal complication of Plasmodium falciparum infection. Here we describe Aotus infulatus as a primate model suitable to study this malaria complication. Both non-splenectomized and splenectomized monkeys receiving different inocula of P. falciparum FVO strain presented large (> 50%) decreases in hematocrit values during infection. Non-splenectomized animals were able to control parasite growth (parasitemia did not exceed 4%), but they had to be treated because of severe anemia. Three of 4 splenectomized monkeys did not control parasitemia and were treated, but developed severe anemia after treatment when presenting a negative blood film. Destruction of parasitized red blood cells alone cannot account for the degree of anemia. Non-splenectomized monkeys repeatedly infected with homologous parasites became rapidly and progressively resistant to reinfection and to the development of severe anemia. The data presented here point to A. infulatus as a suitable model for studying the pathogenesis of severe malarial infection. (+info)
Primary structure of the herpesvirus saimiri genome.
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This report describes the complete nucleotide sequence of the genome of herpesvirus saimiri, the prototype of gammaherpesvirus subgroup 2 (rhadinoviruses). The unique low-G + C-content DNA region has 112,930 bp with an average base composition of 34.5% G + C and is flanked by about 35 noncoding high-G + C-content DNA repeats of 1,444 bp (70.8% G + C) in tandem orientation. We identified 76 major open reading frames and a set of seven U-RNA genes for a total of 83 potential genes. The genes are closely arranged, with only a few regions of sizable noncoding sequences. For 60 of the predicted proteins, homologous sequences are found in other herpesviruses. Genes conserved between herpesvirus saimiri and Epstein-Barr virus (gammaherpesvirus subgroup 1) show that their genomes are generally collinear, although conserved gene blocks are separated by unique genes that appear to determine the particular phenotype of these viruses. Several deduced protein sequences of herpesvirus saimiri without counterparts in most of the other sequenced herpesviruses exhibited significant homology with cellular proteins of known function. These include thymidylate synthase, dihydrofolate reductase, complement control proteins, the cell surface antigen CD59, cyclins, and G protein-coupled receptors. Searching for functional protein motifs revealed that the virus may encode a cytosine-specific methylase and a tyrosine-specific protein kinase. Several herpesvirus saimiri genes are potential candidates to cooperate with the gene for saimiri transformation-associated protein of subgroup A (STP-A) in T-lymphocyte growth stimulation. (+info)
Modified merozoite surface protein-1 peptides with short alpha helical regions are associated with inducing protection against malaria.
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The merozoite surface protein-1 represents a prime candidate for development of a malaria vaccine. Merozoite surface protein-1 has been shown to demonstrate high-activity peptide binding to human red blood cells. One of the high-activity binding peptides, named 5501, located in the N-terminus (amino acid sequence MLNISQHQCVKKQCPQNS) of the 19-kDa molecular mass fragment of merozoite surface protein-1, is conserved, nonimmunogenic and nonprotective. Its critical binding residues were identified and replaced with amino acids of similar mass but different charge, in order to modify their immunogenic and protective characteristics. Three analogues with positive or negative immunological results were studied by nuclear magnetic resonance to correlate their three-dimensional structure with their biological functions. The studied peptides presented alpha-helical fragments, but in different peptide regions and extensions, except for randomly structured 5501. We show that altering a few amino acids induced immunogenicity and protectivity against experimental malaria and changed the peptide three-dimensional structure, suggesting a better fit with immune-system molecules. (+info)
Needle-free Biojector injection of a dengue virus type 1 DNA vaccine with human immunostimulatory sequences and the GM-CSF gene increases immunogenicity and protection from virus challenge in Aotus monkeys.
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A dengue-1 DNA vaccine containing sequences encoding premembrane and envelope proteins (DIME) was previously shown to elicit virus neutralizing antibodies in rhesus and Aotus monkeys, and the primates were partially protected from viremia upon challenge. To increase the neutralizing antibody levels and subsequent protection from virus challenge, four strategies were evaluated: (a) coimmunization with a plasmid expressing Aotus GM-CSF gene; (b) coimmunization with a plasmid containing human immunostimulatory sequences (ISS); (c) coimmunization with both the GM-CSF gene and ISS; and (d) delivery of vaccine using the needle-free Biojector system. Vaccination with the mixed formulation containing DIME, GM-CSF gene, and ISS, by either needle injection or Biojector, led to neutralizing antibody titers that were stable for up to 6 months after vaccination. Furthermore, 6 of 7 monkeys (85%), and 7 of 8 monkeys (87%) receiving this formulation were completely protected from viremia when challenged 1 and 6 months after vaccination, respectively. This is a significant improvement compared to our previous study in which one of three monkeys (33%) receiving just the DIME vaccine was completely protected from viremia at 6 months after immunization. (+info)
Adaptation of a strain of Plasmodium falciparum from Ghana to Aotus lemurinus griseimembra, A. nancymai, and A. vociferans monkeys.
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A strain of Plasmodium falciparum from Ghana was adapted to Aotus lemurinus griseimembra, A. nancymai, and A. vociferans monkeys. Gametocytes in splenectomized A. nancymai were infective to Anopheles freeborni mosquitoes. Sporozoite transmission was accomplished in two splenectomized A. nancymai with prepatent periods of 22 and 25 days. The Ghana III/CDC strain of P. falciparum is susceptible to treatment with chloroquine and mefloquine. (+info)