Caprine beta-mannosidosis: clinical and pathological features.

Beta-mannosidosis, an inherited defect of glycoprotein catabolism associated with deficiency of tissue beta-mannosidase and accumulation of Man(beta 1-4)GlcNAc and Man(beta 1-4)GlcNAc(beta 1-4)GlcNAc, appeared in four of 13 offspring of a single pair of clinically normal, related Nubian goats. Neurological examinations revealed that all four affected goats were unable to rise or walk. All had facial dysmorphism, dome-shaped skulls, small palpebral fissures, carpal contractures, hyperextension of the pastern joints, proximal muscle atrophy, intermittent ocular oscillations resembling pendular nystagmus, marked intention tremor, and deafness. With intensive care, three affected kids were hand-reared and then killed at 1, 7, and 21 days of age. Macroscopically, there were paucity of myelin in the cerebral and cerebellar hemispheres and ventricular dilatation. Microscopically, the extent and distribution of cytoplasmic vacuolation, myelin paucity, axonal spheroids, and filamentous expansions were evaluated in the cerebrum, cerebellum, brainstem, spinal cord, and peripheral nerves of the four affected kids and two age-matched, clinically normal kids. Widespread cytoplasmic vacuolation correlated with the previously reported accumulation of oligosaccharides in the brain and kidney and the deficiency of tissue beta-mannosidase. beta-Mannosidosis, not yet identified in man or other species, is characterized by distinctive neonatal clinical, pathological and biochemical features which differentiate it from the alpha-mannosidosis and other inherited diseases of glycoprotein catabolism.

Children's decoding of emotion in expressive body movement: the development of cue attunement.

Little research has focused on children's decoding of emotional meaning in expressive body movement: none has considered which movement cues children use to detect emotional meaning. The current study investigated the general ability to decode happiness, sadness, anger, and fear in dance forms of expressive body movement and the specific ability to detect differences in the intensity of anger and happiness when the relative amount of movement cue specifying each emotion was systematically varied. Four-year-olds (n = 25), 5-year-olds (n = 25), 8-year-olds (n = 29), and adults (n = 24) completed an emotion contrast task and 2 emotion intensity tasks. Decoding ability exceeding chance levels was demonstrated for sadness by 4-year-olds; for sadness, fear, and happiness by 5-year-olds: and for all emotions by 8-year-olds and adults. Children as young as 5 years were shown to rely on emotion-specific movement cues in their decoding of anger and happiness intensity. The theoretical significance of these effects across development is discussed.

Influence of phentolamine and propranolol on the length of tonus and clonus in pentylenetetrazol-induced seizures in dogs.

The goal of this study was to test the hypothesis that phentolamine and propranolol premedication would affect tonus differently than clonus in pentylenetetrazol (PTZ)-induced tonic-clonic seizures in dogs. Tonic-clonic seizures were induced with IV infusion of PTZ, given as an initial 300-mg bolus and then 100-mg boluses every 10 S until a seizure began. Premedication with phentolamine (2 mg/kg of body weight) significantly shortened clonus (P less than 0.05), whereas propranolol (1 mg/kg) significantly lengthened clonus (P less than 0.05). Neither phentolamine nor propranolol significantly altered the length of tonus or the dose of PTZ required to induce seizures (P greater than 0.05). This indicates that tonus and clonus may have different neural mechanisms and that adrenergic receptors may be involved in the neural mechanisms of clonus.

Clinical evaluation of the new compound diphenylsilanediol for ani-epileptic efficacy and toxicity.

A controlled clinical trial of the anti-epileptic efficacy and toxic side effects of diphenylsilanediol was conducted on 24 client-owned epileptic dogs. Data obtained from an abbreviated procedural treatment program indicated that diphenylsilanediol compared favorably with primidone as an anti-epileptic compound, but had limiting toxic side effects to the liver, pancreas, and possibly to other tissues. There was a mean reduction of 60.7% in seizure frequency in 15 epileptic dogs treated with diphenylsilanediol when compared with their pretreatment frequency. There was a mean reduction of 55.6% in seizure frequency in 9 spileptic control dogs treated with primidone. Samples of blood obtained from the dogs in the program on the 4th, 8th, 12th, 24th, and 36th weeks of treatment were examined for complete blood cell count, blood urea nitrogen, liver function, and pancreatic function. Toxic side effects were not seen among the primidone-treated control dogs, with the exception of occasional dose-related drowsiness. Among the diphenylsilanediol-treated dogs, 3 developed liver disease, 2 developed definite pancreatic changes, and 2 showed evidence of bone marrow suppression. Four dogs died during treatment with diphenylsilanediol, whereas no deaths occurred during the same interval of primidone therapy.

Therapeutic serum concentrations of primidone and its metabolites, phenobarbital and phenylethylmalonamide in epileptic dogs.

Fifteen dogs with idiopathic epilepsy were included in a 9-month clinical trial to determine the therapeutic serum concentrations of primidone and its active metabolites, phenobarbital and phenylethylmalonamide. Dogs with a seizure frequency greater than 1/mo or with a record of multiple seizures greater than 1/day were chosen for the study. Each dog was given primidone 3 times daily at dosages intended to maximize seizure control and to minimize undesired side effects. Maintenance period blood samples were taken from fasted dogs 7 hours after dosing in the 3rd, 5th, 7th, and 9th months of the trial to determine therapeutic serum concentrations of primidone and its metabolites. Two blood samples also were taken from all dogs 7 hours after dosing, during an enforced drowsy period, to establish upper limits of desirable serum concentrations of the drug. Seizure frequencies during the trial were controlled in 13 dogs, 7 of which had no seizures during the 9-month trial. The mean percentage reduction in seizure frequency from pretrial frequency was 85%. Two dogs appeared refractory to primidone therapy. Serum phenobarbital was the best metabolite of primidone to use to assess therapeutic serum concentrations. The therapeutic antiepileptic serum concentration of phenobarbital was found to be between 25 and 40 micrograms/ml of serum. Serum phenobarbital concentrations greater than 40 micrograms/ml resulted in side effects in most dogs.

Vaccine-induced rabies in four cats.

Vaccine-induced rabies in 4 cats was characterized by rigid posterior paralysis. In 3 cats, paralysis began in 1 hindlimb and rapidly spread to the other hindlimb. Later, forelimb and cranial nerve deficits were noticed. Onset of clinical signs was 13 to 17 days after IM vaccination with an ERA-strain modified live-virus rabies vaccine approved for use in cats. Each cat eventually was euthanatized. In each case, brain tissue was found to contain rabies virus on fluorescent antibody and mouse inoculation studies. An antibody titer and mouse inoculation studies. An antibody titer against rabies virus was found in the CSF of 1 cat. In each case, viral isolates were shown to be of an ERA strain rather than natural ("street") rabies.

Caprine beta-mannosidosis: phenotypic features.

The clinical features of caprine beta-mannosidosis were evaluated in 10 newborn goats, one stillborn goat and one goat fetus. The phenotypic abnormalities observed in all 10 live affected animals included an inability to rise from a recumbent position, moderate to marked intention tremor, eye movements resembling pendular nystagmus, clinical deafness, bilateral Horner's syndrome, carpal contractures, pastern joint hyperextension, thickened skin and to a varying degree, a dome-shaped skull. Subjective evaluation suggested that most animals had a decreased muscle mass. Together, these characteristics represent a common phenotype which is expressed at birth in caprine beta-mannosidosis.

The role of perceptual salience in the development of analysis and synthesis processes.

The ability of 6- and 11-year-old children to solve problems requiring the analysis or the synthesis of salience-assessed stimulus relations was investigated. The relative salience of the relations of form, color, and position was assessed and a salience hierachy determined for each child. Following salience assessment, children were given a recall problem in which the salience of the relations and the type of evaluation required for solution were varied. In analysis problems, the relative salience of the irrelevant relation was either higher or lower than that of the relevant relation. In synthesis problems, the two relations to be evaluated were either more or less salient. Both younger and older children were able to solve problems requiring the analysis or the synthesis of relations, but the rate of solution varied as a function of the salience of the relations involved. There was no evidence that either analysis or synthesis preceded the other in the course of development.

Young children's knowledge of their memory span: effects of task and experience.

This study investigated the hypothesis that young children have knowledge about their memory that they may be unable to articulate, but are able to reflect on and use in problem-solving. Forty-eight kindergarteners made one of two types of judgments about their memory span for words. Half of the children made prospective verbal predictions about the number of words they thought they could recall from a list of 10. The other half made concurrent, nonverbal predictions by listening to words on a tape and manually stopping the tape when they heard as many words as they thought they could recall. Children's actual recall for words was then assessed. All children participated in multiple trials to assess the effect of task experience on their predictions. Analyses revealed that predictions made in the concurrent task were significantly more accurate than those made in the prospective task. All children lowered their predictions across trials, although only in the concurrent task were children's final-trial predictions not significantly greater than their actual recall. No meaningful effects or interactions were associated with actual recall scores. These results revealed that young children manifested greater memory knowledge when this knowledge was assessed through their concurrent problem-solving behavior rather than through their prospective verbal predictions.

Effects of perceptual salience on the matrix task performance of four- and six-year-old children.

The effects of salience on 4- and 6-year-old children's ability to classify multiplicatively was investigated. A rank-ordered salience hierachy consisting of 3 dimensions was first assessed for each S. Several weeks later half the Ss of each age group were presented with a series of 9 3 times 3 matrix problems consisting of values from 2 dimensions ranked high in salience. The remaining half received identically structured matrices consisting of values from 1 highly salient dimension and of others from a dimension ranked low in salience. The goal in each problem was to select that compound stimulus from a set of alternatives that appropriately filled an empty cell in the matrix. Prior to the matrix problems, half the Ss in each matrix condition received sensitization training designed to increase the salience of the relevant dimensions in the matrix problems. The results showed that the pre-assessed salience of the relevant dimensions affected matrix solution in that more accurate performance was associated with those problems with both relevant dimensions relatively high in salience than those with one high and one low. Although the older Ss solved more problems, the evidence for coordination in the younger Ss was clear. No effects of sensitization training were found.

The cytoplasmic domain of the alpha-subunit of glycoprotein (GP) Ib mediates attachment of the entire GP Ib-IX complex to the cytoskeleton and regulates von Willebrand factor-induced changes in cell morphology.

The glycoprotein (GP) Ib-IX complex is one of the major platelet membrane glycoproteins. Its extracellular domain binds von Willebrand factor at a site of injury, an interaction that leads to activation of intracellular pathways. Its intracellular domain associates tightly with the platelet cytoskeleton through actin-binding protein. The goal of the present study was to investigate the role of the cytoplasmic domain of the GP Ib-IX complex and its interaction with the cytoskeleton. Cultured cells were transfected with the cDNAs coding for GP Ib(beta), GP IX, and full-length or truncated forms of GP Ib(alpha). Western blots of detergent-insoluble fractions of Triton X-100-lysed cells showed that deletion of amino acids Trp-570 to Ser-590 from the cytoplasmic domain of GP IB(alpha) abolished the interaction of the entire GP Ib-IX complex with the cytoskeleton. Truncated GP Ib(alpha) that was unable to associate with the cytoskeleton retained its ability to associate with GP Ib(beta), to be inserted into the membrane, and to bind von Willebrand factor. Cells expressing GP Ib(alpha) changed their shape following adhesion to immobilized von Willebrand factor. Cells expressing truncated GP Ib(alpha) also changed their shape following adhesion but showed a very different morphology as compared to cells expressing full-length GP Ib(alpha). These results show that GP Ib-IX-von Willebrand factor interactions lead to cytoskeletal reorganizations, that the cytoplasmic domain of GP Ib(alpha) regulates these reorganizations, and that the cytoplasmic domain of GP Ib(alpha) is absolutely required for attachment of the GP Ib-IX complex to the cytoskeleton.

Comparative evaluation of a new inhalation anesthetic, BAX-3224, and halothane in Macaca speciosa.

Two groups of 8 monkeys were anesthetized with either BAX-3224, a new fluorinated methyl-propyl ether, or with halothane, 3 hours daily for a total of 30 hours. Vomiting incidence was 12.5 percent with BAX-3224 during both induction and recovery, compared with 3.7 percent for halothane during induction and 7 percent for halothane during recovery. Induction time did not change during the course of study with either agent. Respiration was spontaneous and cardiopulmonary function was stable. Electroretinographic (ERG) responses were consistent, flicker-light responses similar, but visual evoked responses (VER) were not present during BAX-3224 anesthesia. A 33 percent incidence of electroencephalographic (EEG) silence occurred with BAX-3224, which was consistent with absence of VER. Hematologic and serum chemistry values were similar for both agents. Serum fluoride ion concentrations, measured before exposure and 4 times during the 10-day study, did not change after administration of either agent. This finding was significant for BAX-3224, a fluorinated ether. No cardiac arrhythmias were observed during BAX-3224 anesthesia, compared with a 17 percent incidence during halothane induction. Recovery time was 32 minutes following BAX-3224 and 14 minutes after halothane. BAX-3224 produced anesthesia similar to that of halothane, did not induce changes incompatible with recovery from anesthesia, and showed great potential as a new volatile liquid anesthetic agent with excellent biologic stability.