We studied the effects on saccades of ablation of the dorsal cerebellar vermis (lesions centered on lobules VI and VII) in three monkeys in which the deep cerebellar nuclei were spared. One animal, with a symmetrical lesion, showed bilateral hypometric horizontal saccades. Two animals, with asymmetrical lesions, showed hypometric ipsilateral saccades, and saccades to vertically positioned targets were misdirected, usually deviating away from the side to which horizontal saccades were hypometric. Postlesion, all animals showed an increase (2- to 5-fold) in trial-to-trial variability of saccade amplitude. They also showed a change in the ratio of the amplitudes of centripetal to centrifugal saccades (orbital-position effect); usually centrifugal saccades became smaller. In the two animals with asymmetrical lesions, for saccades in the hypometric direction, latencies were markedly increased (up to approximately 500 ms). There was also an absence of express and anticipatory saccades in the hypometric direction. When overall saccade latency was increased, centrifugal saccades became relatively more delayed than centripetal saccades. The dynamic characteristics of saccades were affected to some extent in all monkeys with changes in peak velocity, eye acceleration, and especially eye deceleration. There was relatively little effect of orbital position on saccade dynamics, however, with the exception of one animal that showed an orbital position effect for eye acceleration. In a double-step adaptation paradigm, animals showed an impaired ability to adaptively adjust saccade amplitude, though increased amplitude variability postlesion may have played a role in this deficit. During a single training session, however, the latency to corrective saccades-which had been increased postlesion-gradually decreased and so enabled the animal to reach the final position of the target more quickly. Overall, both in the early postlesion period and during recovery, changes in saccade amplitude and latency tended to vary together but not with changes in saccade dynamics or adaptive capability, both of which behaved relatively independently. These findings suggest that the cerebellum can adjust saccade amplitude and saccade dynamics independently. Our results implicate the cerebellar vermis directly in every aspect of the on-line control of saccades: initiation (latency), accuracy (amplitude and direction), and dynamics (velocity and acceleration) and also in the acquisition of adaptive ocular motor behavior.

We generated interleukin-5 receptor alpha chain (IL-5R alpha)-deficient (IL-5R alpha-/-) mice by gene targeting. The IL-5R alpha-/- mice showed decreased numbers of B-1 cells concomitant with low serum concentrations of IgM and IgG3. They showed no IL-5-induced enhancement of B cell responses to T-independent antigens. The number of alpha beta T cell receptor-positive thymocytes tended to decrease in 3-week-old IL-5R alpha-/- mice, returning to normal by 6 weeks of age. The IL-5R alpha-/- mice produced basal levels of eosinophils, while their bone marrow cells failed to form eosinophilic colonies in response to IL-5. Impaired eosinophilopoiesis in IL-5R alpha-/-mice enhanced the survival of Angiostrongylus cantonensis. These results indicate that IL-5-induced eosinophils serve as potent effector cells in the killing of Angiostrongylus cantonensis in mice.

BackgroundHereditary short stature syndromes are clinically and genetically heterogeneous disorders and the cause have not been fully identified. Yakuts are a population isolated in Asia; they live in the far east of the Russian Federation and have a high prevalence of hereditary short stature syndrome including 3-M syndrome. A novel short stature syndrome in Yakuts is reported here, which is characterised by autosomal recessive inheritance, severe postnatal growth retardation, facial dysmorphism with senile face, small hands and feet, normal intelligence, Pelger-Huët anomaly of leucocytes, and optic atrophy with loss of visual acuity and colour vision. This new syndrome is designated as short stature with optic atrophy and Pelger-Huët anomaly (SOPH) syndrome.AimsTo identify a causative gene for SOPH syndrome.MethodsGenomewide homozygosity mapping was conducted in 33 patients in 30 families.ResultsThe disease locus was mapped to the 1.1 Mb region on chromosome 2p24.3, including the neuroblastoma amplified sequence (NBAS) gene. Subsequently, 33 of 34 patients were identified with SOPH syndrome and had a 5741G/A nucleotide substitution (resulting in the amino acid substitution R1914H) in the NBAS gene in the homozygous state. None of the 203 normal Yakuts individuals had this substitution in the homozygous state. Immunohistochemical analysis revealed that the NBAS protein is well expressed in retinal ganglion cells, epidermal skin cells, and leucocyte cytoplasm in controls as well as a patient with SOPH syndrome.ConclusionThese findings suggest that function of NBAS may associate with the pathogenesis of short stature syndrome as well as optic atrophy and Pelger-Huët anomaly.

We studied the effects on smooth pursuit eye movements of ablation of the dorsal cerebellar vermis (lesions centered on lobules VI and VII) in three monkeys in which the cerebellar nuclei were spared. Following the lesion the latencies to pursuit initiation were unchanged. Monkeys showed a small decrease (up to 15%) in gain during triangular-wave tracking. More striking were changes in the dynamic properties of pursuit as determined in the open-loop period (the 1st 100 ms) of smooth tracking. Changes included a decrease in peak eye acceleration (e.g., in one monkey from approximately 650 degrees /s(2), prelesion to approximately 220-380 degrees /s(2), postlesion) and a decrease in the velocity at the end of the open-loop period [e.g., in another monkey from a gain (eye velocity/target velocity at 100 ms of tracking) of 0.93, prelesion to 0.53, postlesion]. In individual monkeys, the pattern of deficits in the open-loop period of pursuit was usually comparable to that of saccades, especially when comparing the changes in the acceleration of pursuit to the changes in the velocity of saccades. These findings support the hypothesis that saccades and the open-loop period of pursuit are controlled by the cerebellar vermis in an analogous way. Saccades could be generated by eye velocity commands to bring the eyes to a certain position and pursuit by eye acceleration commands to bring the eyes toward a certain velocity. On the other hand, changes in gain during triangular-wave tracking did not correlate with either the saccade or the open-loop pursuit deficits, implying different contributions of the oculomotor vermis to the open loop and to the sustained portions of pursuit tracking. Finally, in a pursuit adaptation paradigm (x0.5 or x2, calling for a halving or doubling of eye velocity, respectively) intact animals could adaptively adjust eye acceleration in the open-loop period. The main pattern of change was a decrease in peak acceleration for x0.5 training and an increase in the duration of peak acceleration for x2 training. Following the lesion in the oculomotor vermis, this adaptive capability was impaired. In conclusion, as for saccades, the oculomotor vermis plays a critical role both in the immediate on-line and in the short-term adaptive control of pursuit.