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Biomedical subjects

N Allon

Publications and source records attributed to N Allon.

12 recordsLinked to original sources

Malaria circumsporozoite protein inhibits protein synthesis in mammalian cells.

Native Plasmodium circumsporozoite (CS) protein, translocated by sporozoites into the cytosol of host cells, as well as recombinant CS constructs introduced into the cytoplasm by liposome fusion or transient transfection, all lead to inhibition of protein synthesis in mammalian cells. The following findings suggest that this inhibition of translation is caused by a binding of the CS protein to ribosomes. (i) The distribution of native CS protein translocated by sporozoites into the cytoplasm as well as microinjected recombinant CS protein suggests association with ribosomes. (ii) Recombinant CS protein binds to RNase-sensitive sites on rough microsomes. (iii) Synthetic peptides representing the conserved regions I and II-plus of the P.falciparum CS protein displace recombinant CS protein from rough microsomes with dissociation constants in the nanomolar range. (iv) Synthetic peptides representing region I from the P.falciparum CS protein and region II-plus from the P.falciparum, P.berghei or P.vivax CS protein inhibit in vitro translation. We propose that Plasmodium manipulates hepatocyte protein synthesis to meet the requirements of a rapidly developing schizont. Since macrophages appear to be particularly sensitive to the presence of CS protein in the cytosol, inhibition of translation may represent a novel immune evasion mechanism of Plasmodium.

Amino Acid Sequence

Prophylaxis against soman inhalation toxicity in guinea pigs by pretreatment alone with human serum butyrylcholinesterase.

Human butyrylcholinesterase (HuBChE) has previously been shown to protect mice, rats, and monkeys against multiple lethal toxic doses of organophosphorus (OP) anticholinesterases that were challenged by i.v. bolus injections. This study examines the concept of using a cholinesterase scavenger as a prophylactic measure against inhalation toxicity, which is the more realistic simulation of exposure to volatile OPs. HuBChE-treated awake guinea pigs were exposed to controlled concentration of soman vapors ranging from 417 to 430 micrograms/liter, for 45 to 70 s. The correlation between the inhibition of circulating HuBChE and the dose of soman administered by sequential i.v. injections and by respiratory exposure indicated that the fraction of the inhaled dose of soman that reached the blood was 0.29. HuBChE to soman molar ratio of 0.11 was sufficient to prevent the manifestation of toxic signs in guinea pigs following exposure to 2.17x the inhaled LD50 dose of soman (ILD50, 101 micrograms/kg). A slight increase in HuBChE:soman ratio (0.15) produced sign-free animals after two sequential respiratory exposures with a cumulative dose of 4.5x ILD50. Protection was exceptionally high and far superior to the currently used traditional approach that consisted of pretreatment with pyridostigmine and postexposure combined administration of atropine, benactyzine, and an oxime reactivator. Quantitative analysis of the results suggests that in vivo sequestration of soman, and presumably other OPs, by exogenously administered HuBChE, is independent of the species used or the route of challenge entry. This assuring conclusion significantly expands the database of the bioscavenger strategy that now offers a dependable extrapolation from animals to human.

Animals

Spectrofluorometric method for NO determination.

A spectroscopic method for the quantitative determination of NO in aqueous solution is presented. The method is based on the uv absorbance of nitrosothiols, coupled with the inner filter effect. A threshold of 5.10(-7) M with a wide dynamic range of 5.10(-7)-10(-4) M are obtained. This method enables measurements in brain homogenates. Ultimately, since this method is immune to electrical perturbances, it will be applied at the tip of an optical fiber for in situ monitoring of NO or glutathione in brain and blood vessels.

Calibration

Functional organization of the medial geniculate body's subdivisions of the awake squirrel monkey.

The response properties of 138 cells in the medial geniculate body (MGB), of the awake squirrel monkey (Saimiri sciureus), to 7 species-specific vocalizations were studied. Cells were divided into 4 subgroups: 26 in the ventral, 24 in the medial and 46 in the lateral subdivision. Forty-two cells located on the borders between the subdivisions represent the fourth group. No significant differences were found between the subdivisions with respect to their selectivity, nor did cells in any subdivision respond preferentially to any particular vocalization. On the other hand, the response patterns of the ventral and the lateral subdivisions showed significant differences (P less than 0.001, chi 2-test) from those of the medial subdivision. Most of the cells in the medial subdivision (87.5%) responded with similar response pattern to the 7 vocalizations (mainly 'on' or 'sustain'), while most of the cells in the ventral and the lateral subdivisions (61.5% and 69.6% respectively) responded with complex, time-locked and different patterns to the various vocalizations. Cells that exhibited a response characterized as an intermediate between the two types were accumulated mainly on or close to the borders between the medial and the other subdivisions of the MGB. The possible role of each response patterns is discussed with respect to the projection of the subdivisions to the cortex.

Animals

Identification of MGB cells by Volterra kernels. I. Prediction of responses to species specific vocalizations.

The function of CNS sites is frequently explored by an analysis of its input-output relationships. However, such research are often confined to a qualitative and subjective inspection of raw data. System Identification methods can be used to formalize the stimulus--response relations, and one of them, the Volterra approach, is employed here in order to define these relations in the MGB of the squirrel monkey, natural vocalizations being the stimuli. In order to validate the formal representation of the system under study, the predictability power of the model is tested. Having the distances between responses (PSTH) and predicted response quantified, it is found that the predictions made by the model are, in general, "closer" to the actual responses then some arbitrarily chosen responses. It is concluded that there are cells in the MGB that can be characterized by their Volterra kernels, and further research on the cell's functional role can be based on these kernels.

Acoustic Stimulation

Epileptiform activity induced in single cells of the sensorimotor cortex of the cat by intracellularly applied scorpion venom.

Oscillations of 5 to 15 mV in the membrane potentials of neurons of the sensorimotor cortex of normal, awake cats were produced within 15 to 45 s after intracellular injection of Centruroides sculpturatus (c.s.) venom, but not after control injections of KCl. In every cell injected with c.s. venom, the oscillations eventually gave way to paroxysmal depolarizing shifts of appearance similar to that seen in epileptic cells. The results suggest that cortical epileptiform activity can be produced by the local action of c.s. venom, an agent known to alter the gating mechanism of sodium channels. Disruption of sodium gating may represent an intrinsic cellular mechanism involved in epileptogenesis.

Animals

Responses of single cells in the medial geniculate body of awake squirrel monkeys.

Response properties of 142 medial geniculate (MGB) cells were investigated in the awake and undrugged squirrel monkey (Saimiri sciureus). Using Jordan's (1973) parcellation of this complex nucleus, cells were assigned to 3 major subdivisions a, b and c MGB and compared for their general characteristics and response properties. b MBG cells had significantly higher rates of spontaneous firing and longer latency periods than a and c MGB cells. With regard to responsiveness to various auditory stimuli, response patterns, and tuning characteristics, cells in all 3 subdivisions were statistically similar and were thus treated as one cell population. About 95% of the cells responded to broadband white noise, steady tone bursts and frequency modulated (FM) tones. Click activated only 69% of the responding cells. Various "through-stimulus" responses comprised about 80% of the responses. Among the tone-sensitive cells, 90% responded with complex patterns, out of which 50% were frequency-dependent. About 62% of the cells (for which tuning properties were determined) were quite broadly tuned (Q10dB less than 2) and had either single or multi-peaked response areas. The other 38% were quite narrowly tuned (Q10dB greater than 2) and had single-peaked, symmetrical or "tailed" response areas. Different inhibitory and excitatory response components of individual cells had different characteristic frequencies and response thresholds. The c MGB, which is tonotopically organized in a latero-medial orientation, appears to be homologous to the cat pars lateralis of the ventral MGB. The tonotopical organization of the b MGB, which is probably homologous to the cat's medial or magnocellular subdivision, is less clear. Most of the cells which were activated by FM tones disclosed "direction sensitivity" with different degrees of pattern complexity. It is suggested that pitch resolution in the MGB is based on spatio-temporal mechanisms.

Acoustic Stimulation

Self-perceptions of the stigma of overweight in relationship to weight-losing patterns.

Preliminary, exploratory studies examine self-perceptions of the stigma of overweight in relatiopship to weight-losing patterns of female and male children of different ages. It is suggested that the concept of stigma may be a viable analytical tool in studying overweight as: an exclusive focus in interaction, related to a negative body image, overwhelming others with mixed emotions, clashing with other attributes of the person, an equivocal predictor of activities, and related to one's sense of responsibility for one's overweight. Female adolescents in the Slimnastics class in a high school and children and adolescents in an obesity clinic in a hospital were studied. Male children and female adolescents had more trouble losing weight than did female children and male adolescents. Youth who viewed overweight as both one's responsibility and as an illness that required the joint efforts of oneself and others, especially professional experts, were more successful in losing weight than those youth who believed that overweight was solely their responsibility or not at all their responsibility. Intensive focusing on one's overweight and one one's negative body image seemed to inhibit or deter weight losing for some youth.

Adolescent