Spinal cord atrophy and reorganization of motoneuron connections following long-standing limb loss in primates.
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Primates with long-standing therapeutic amputations of a limb at a young age were used to investigate the possibility that deefferented motor nerves sprout to new muscle targets. Injections of anatomical tracers into the muscles proximal to the amputated stump labeled a larger extent of motoneurons than matched injections on the intact side or in normal animals, including motoneurons that would normally supply only the missing limb muscles. Although the total numbers of distal limb motoneurons remained normal, some distal limb motoneurons on the amputated side were smaller in size and simpler in form. These results suggest that deprived motoneurons survive and retain function by reinnervating new muscle targets. The sprouted motor efferents may account for some of the reorganization of primary motor cortex that follows long-standing amputation. (+info)
The cortical representation of shadows cast by retinal blood vessels.
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PURPOSE: We inquired whether the representation of angioscotomas could be detected in the primary (striate) visual cortex. METHODS: In 12 normal squirrel monkeys, the ocular fundi were photographed and retinal vascular landmarks were projected onto a tangent screen for calibration. Each animal then underwent monocular enucleation under general anesthesia. Animals were perfused after 8 to 10 days, and flat-mounted sections of striate cortex were processed for the metabolic enzyme cytochrome oxidase (CO). RESULTS: In each animal, the cortical region corresponding to the blind spot appeared as a 3 x 2 mm oval in the CO staining pattern. It stood out because it received input from only 1 eye. In 9 of 12 animals, the representation of the major retinal vessels was also visible, for the same reason. In our best examples, CO sections showed about 10 thin lines radiating from the blind spot representation. Some could be traced for 15 mm, all the way to the vertical meridian. Vessels only 12 minutes of arc in diameter were represented in the cortex. Each angioscotoma representation in the cortex could be matched with its corresponding retinal vessel in the fundus. CONCLUSIONS: Our findings show that (1) the visual field map in layer IVc is more precise than indicated by physiological studies, and (2) visual experience must refine the final pattern of geniculocortical projections, given that the retinal vessels can produce a shadow only after birth. (+info)
Efficacy of vaccines containing rhoptry-associated proteins RAP1 and RAP2 of Plasmodium falciparum in Saimiri boliviensis monkeys.
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A vaccine trial was conducted with rhoptry-associated proteins 1 and 2 (RAP1 and RAP2) of Plasmodium falciparum in Saimiri boliviensis monkeys to compare the ability of parasite-derived (PfRAP1 and 2) and recombinant proteins (rRAP1 and 2) to induce protective immune responses and to find adjuvants suitable for use in humans. Eight groups of 6 monkeys each were immunized with parasite-derived or recombinant RAP1 and 2 with Freund's complete adjuvant (FCA) followed by Freund's incomplete adjuvant (FIA), Montanide ISA720 adjuvant, or CRL1005 adjuvant. Recombinant RAP1 and RAP2 were also administered separately, with Montanide ISA720. After 3 immunizations, monkeys were challenged by iv inoculation of 50,000 parasites of the Uganda Palo Alto strain of P. falciparum. Of the animals vaccinated using FCA/FIA, 1 of 6 control monkeys, 3 of 6 immunized with PfRAP1 and 2, and 2 of 6 with rRAP1 and 2 did not require drug treatment. Of the monkeys vaccinated with Montanide ISA720 adjuvant, 0 of the 6 control monkeys, 2 of 6 immunized with RAP1 and 2, 1 of 6 immunized with rRAP1, and 4 of 6 immunized with RAP2 did not require drug treatment. Two of 6 monkeys immunized with PfRAP1 and 2 with CRL1005 did not require treatment. All groups receiving RAP1, RAP2, or both had a significant decrease in initial parasite multiplication rates and there was a significant negative correlation between anti-RAP2 antibody and multiplication rates. Animals were rechallenged with the homologous parasite 126 days after the first challenge. Of the monkeys that did not require drug treatment after the first challenge, none developed detectable parasitemia following rechallenge. (+info)
Adaptation of a chloroquine-resistant strain of Plasmodium vivax from Indonesia to New World monkeys.
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The spread of chloroquine-resistant Plasmodium vivax from Papua New Guinea and Indonesia poses a serious health threat to areas of Southeast Asia where this species of malaria parasite is endemic. A strain of P. vivax from Indonesia was adapted to develop in splenectomized Aotus lemurinus griseimembra, Aotus vociferans, Aotus nancymai, and Saimiri boliviensis monkeys. Transmission to splenectomized Saimiri monkeys was obtained via sporozoites. Chemotherapeutic studies indicated that the strain was resistant to chloroquine and amodiaquine while sensitive to mefloquine. Infections of chloroquine-resistant P.vivax in New World monkeys should be useful for the development of alternative treatments. (+info)
Enadoline discrimination in squirrel monkeys: effects of opioid agonists and antagonists.
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Squirrel monkeys were trained to discriminate i.m. injections of the kappa-opioid receptor agonist enadoline (0.0017 mg/kg) from saline in a two-lever drug-discrimination procedure. Enadoline produced a reliable discriminative stimulus that was reproduced by the kappa-selective agonists PD 117302, U 50,488, GR 89686A, (-)-spiradoline, ICI 204448, and EMD 61753, and by the mixed-action kappa/mu-agonists bremazocine and ethylketocyclazocine. The discriminative stimulus effects of enadoline were not reproduced by the mu-selective agonist morphine, the delta-selective agonist BW373U86, the mixed-action opioids nalbuphine and nalorphine, or by the less active enantiomers of enadoline and spiradoline PD 129829 and (+)-spiradoline, respectively. The selective mu-opioid antagonist beta-funaltrexamine (10.0 mg/kg) did not appreciably alter the dose-effect function for enadoline in any subject. However, the nonselective and kappa-selective opioid antagonists quadazocine (0.03-3.0 mg/kg) and nor-BNI (3-10 mg/kg), and the mixed-action opioid nalbuphine (0.3-30 mg/kg) served to surmountably antagonize enadoline's discriminative stimulus effects. The antagonist effects of nor-BNI were long-lasting and did not distinguish between drugs purported to act at different kappa-receptor subtypes. The present results bolster the view that common discriminative stimulus effects of enadoline and other opioids are mediated by kappa-agonist actions that are surmountably antagonized by nor-BNI in a long-lasting manner. The enadoline-antagonist effects of nalbuphine support the idea that it acts with low efficacy at kappa-opioid receptors. (+info)
Assessment of the efficiency of protein utilization in young squirrel and macaque monkeys.
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The efficiency of protein utilization was assessed in three groups of infant squirrel monkeys fed diets containing restricted amounts of lactalbumin, casein, and soy protein isolate as the sole nitrogen source for 3-week periods. Lactalbumin was fed in similar conditions to a group of macaques for comparison. The regression of weight gain on protein intake was calculated for each dietary protein yielding an estimate of protein needs for weight maintenance and an estimate of the efficiency of utilization of protein for growth (slope X percentage protein in tissue). Mean requirements for weight maintenance of infant squirrel monkeys for lactalbumin, casein and soy protein isolate were 3.43, 3.63, and 7.96 g/kg per day and growth was accomplished with an efficiency of 27.8, 32.1, and 22.2%, respectively. In contrast, the macaques utilized lactalbumin with an efficiency of 65%, similar to that of the infant cebus monkey and adult man. The low efficiency found in young squirrel monkeys was altered neither when the habitual feeding schedule was prolonged from 16 to 24 hr per day in a group of casein-fed animals nor when sulfur amino acids were added to casein. (+info)
Functional organization of squirrel monkey primary auditory cortex: responses to pure tones.
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The spatial organization of response parameters in squirrel monkey primary auditory cortex (AI) accessible on the temporal gyrus was determined with the excitatory receptive field to pure tone stimuli. Dense, microelectrode mapping of the temporal gyrus in four animals revealed that characteristic frequency (CF) had a smooth, monotonic gradient that systematically changed from lower values (0.5 kHz) in the caudoventral quadrant to higher values (5--6 kHz) in the rostrodorsal quadrant. The extent of AI on the temporal gyrus was approximately 4 mm in the rostrocaudal axis and 2--3 mm in the dorsoventral axis. The entire length of isofrequency contours below 6 kHz was accessible for study. Several independent, spatially organized functional response parameters were demonstrated for the squirrel monkey AI. Latency, the asymptotic minimum arrival time for spikes with increasing sound pressure levels at CF, was topographically organized as a monotonic gradient across AI nearly orthogonal to the CF gradient. Rostral AI had longer latencies (range = 4 ms). Threshold and bandwidth co-varied with the CF. Factoring out the contribution of the CF on threshold variance, residual threshold showed a monotonic gradient across AI that had higher values (range = 10 dB) caudally. The orientation of the threshold gradient was significantly different from the CF gradient. CF-corrected bandwidth, residual Q10, was spatially organized in local patches of coherent values whose loci were specific for each monkey. These data support the existence of multiple, overlying receptive field gradients within AI and form the basis to develop a conceptual framework to understand simple and complex sound coding in mammals. (+info)
Seasonal fluctuation of antibody levels to Plasmodium falciparum parasitized red blood cell-associated antigens in two Senegalese villages with different transmission conditions.
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The recombinant R23, PfEB200, and GST-5 antigens derive from conserved antigens associated with the Plasmodium falciparum-infected erythrocyte membrane. They were identified as targets of protective antibodies in the Saimiri sciureus model. We have assessed here the humoral response to these antigens in humans. Cross-sectional surveys were conducted in two Senegalese villages with different levels of endemicity. The prevalence of specific IgG and IgM was similar and influenced by age in both localities. The anti-R23 antibodies decreased after the rainy season, particularly in the children less than ten years old. The anti-PfEB200 response did not show significant seasonal variation. The anti-GST-5 response increased in both the less-than 10-year-old and the greater-than 10-year-old groups after the rainy season in Dielmo, but only in the Ndiop villagers who were more than 10-years-old. Thus, antigen-specific seasonal variations of antibody levels were influenced differently by age in both villages. The isotype distribution was antigen-specific and differed for both seasons. (+info)