Report on two patients with Costello syndrome and sialuria

We report on 2 unrelated patients with Costello syndrome. The first is a 5-year-old girl with “coarse” face, nasal papillomata, redundant skin of feet and hands, hyperextensible hand and finger joints, curly hair, feeding problems due to oral motor apraxia, growth and psychomotor retardation. The second is a 3-year-old boy with “coarse” face, loose skin on hands and feet, curly hair, oral motor apraxia, severe growth and psychomotor retardation. In both patients urine sialic acid levels were found to be repeatedly high. The meaning of this biochemical abnormality is discussed. © 1993 Wiley-Liss, Inc.     

Behavioral phenotyping of mice in pharmacological and toxicological research

The evaluation of behavioral effects is an important component for the in vivo screening of drugs or potentially toxic compounds in mice. Ideally, such screening should be composed of monitoring general health, sensory functions, and motor abilities, right before specific behavioral domains are tested. A rational strategy in the design and procedure of testing as well as an effective composition of different well-established and reproducible behavioral tests can minimize the risk of false positive and false negative results in drug screening. In the present review we describe such basic considerations in planning experiments, selecting strains of mice, and propose groups of behavioral tasks suitable for a reliable detection of differences in specific behavioral domains in mice. Screening of general health and neurophysiologic functions (reflexes, sensory abilities) and motor function (pole test, wire hang test, beam walking, rotarod, accelerod, and footprint) as well as specific hypothesis-guided testing in the behavioral domains of learning and memory (water maze, radial maze, conditioned fear, and avoidance tasks), emotionality (open field, hole board, elevated plus maze, and object exploration), nociception (tail flick, hot plate), psychiatric-like conditions (porsolt swim test, acoustic startle response, and prepulse inhibition), and aggression (isolation-induced aggression, spontaneous aggression, and territorial aggression) are described in further detail. This review is designed to describe a general approach, which increases reliability of behavioral screening. Furthermore, it provides an overview on a selection of specific procedures suitable for but not limited to behavioral screening in pharmacology and toxicology.     

Distribution of corticospinal neurons with collaterals to the lower brain stem reticular formation in monkey (Macaca fascicularis)

Summary An earlier retrograde double-labeling study in cat showed that up to 30% of the corticospinal neurons in the medial and anterior parts of the precruciate motor area represent branching neurons which project to both the spinal cord and the reticular formation of the lower brain stem. These neurons were found to be concentrated in the rostral portion of the motor cortex, from where axial and proximal limb movements can be elicited. In the present study the findings in the macaque monkey are reported. The fluorescent retrograde tracer DY was injected unilaterally in the spinal cord at C2 and the fluorescent tracer FB was injected ipsilaterally in the medial tegmentum of the medulla oblongata. In the contralateral hemisphere large numbers of single DY-labeled corticospinal neurons and single FBlabeled corticobulbar neurons were present. A substantial number of DY-FB double-labeled corticospinal neurons were also found, which must represent branching neurons projecting to both the spinal cord and the bulbar reticular formation. These neurons were present in: 1. The anterior portion of the cingulate corticospinal area in the lower bank of the cingulate sulcus; 2. The supplementary motor area (SMA); 3. The rostral part of precentral corticospinal area; 4. The upper portion of the precentral face representation area; 5. The caudal bank of the inferior limb of the arcuate sulcus; 6. The posterior part of the insula. In these areas 10% to 30% of the labeled neurons were double-labeled. The functional implications of the presence of branching corticospinal neurons in these areas is discussed.Abbreviations A nucleus ambiguus - AS arcuate sulcus - C cuneate nucleus - Cing. S. cingulate sulcus - corp. call. corpus callosum - CS central sulcus - Cx external cuneate nucleus - DCN dorsal column nuclei - dl dorsolateral intermediate zone - IO inferior olive - IP intraparietal sulcus - Lat. Fis. lateral fissure - LR lateral reticular nucleus - LS lunate sulcus - ML medial lemniscus - MLF medial longitudinal fascicle - mn motoneuronal pool - MRF medial reticular formation - Occ. occipital pole - P pyramid - PG pontine grey - PS principle sulcus - RB restiforme body - RF reticular formation - S solitary nucleus - SPV spinal trigeminal complex - STS superior temporal sulcus - Sup. Col. superior colliculus - TB trapezoid body - VC vestibular complex - vm ventromedial intermediate zone - III nucleus oculomotorius - VI nucleus abducens - VII nucleus, n. facialis - X motor nucleus n. vagus - XII nucleus hypoglossus Supported in part by grant 13-46-96 of FUNGO/ZWO (Dutch organisation for fundamental research in medicine)     

Cortico-cortical mediation of short-latency (lemniscal) sensory input to the motor cortex in deeply pentobitone anaesthetized cats

In pentobarbitone-anaesthetized cats, responses were recorded as surface positive potentials in the motor cortex on forelimb and brachium conjunctivum stimulation. In such a preparation, the forelimb nerve responses are mediated via the spino-cervical tract and the dorsal column-lemniscal pathway. Lesions of the sensory cortex (sparing only the depth of the coronary sulcus) abolished or reduced short-latency peripheral responses, in the motor cortex, on both skin and muscle nerve stimulation to less than 10% of control, while brachium conjunctivum responses were unchanged. Lesions of the second somatosensory area alone reduced the motor cortex responses on peripheral nerve stimulation by 10–20%. When the sensory cortex were abolished before the spreading depression reached the recording point, as judged from the brachium conjunctivum response. The depth distribution of positive and negative field potentials, constituting the early componentsof a peripheral response in the motor cortex, closely resembled that of a cortico-cortical response evoked on stimulation in area 3. It differed from that of thalamo-cortical response evoked in brachium conjunctivum stimulation. These data suggest that most, if not all, sensory input through the dorsal column and spino-cervical tract to the motor cortex is mediatd via the sensory cortex.     

Modulation of stretch-evoked reflexes in single motor units in human masseter muscle by experimental pain

The interaction between muscle pain and motor function of the jaw has been examined in recent years, but the nature of the modulation of the short-latency stretch reflex by pain is not fully understood. In this study, the reflex responses to stretch were measured in single low-threshold motor units that were kept discharging at a constant frequency, before, during and after the induction of experimental pain in one masseter muscle by controlled infusion of hypertonic saline. The probability of evoking a reflex response in individual motor units in the painful muscle at near-monosynaptic latency was reduced by a mean of about 20%. However, the overall reflex response in the surface electromyogram of both the ipsi- and contralateral masseter muscles was greater during pain. This was apparently a secondary response to the pain-induced increase in pre-stimulus activity in the motoneurone pools of both muscles, because increased motoneurone excitability may facilitate stretch reflexes. It is concluded that the most likely explanation for the reduced reflex response of low-threshold masseter motor units during experimental pain is a tonic reduction in the fusimotor drive to the masseter spindles.     

Somatotopic organization of corticospinal and corticotrigeminal neurons in the rat

The method of retrograde axonal transport of horseradish peroxidase was employed to examine the topographic organization of corticospinal and corticotrigeminal neurons in the rat. In both the first somatic sensory (SI) area and the motor (MI) area of the cortex these labeled corticofugal neurons, all of which are found in layer V, are grouped in a well organized, somatotopic pattern. Corticospinal projections which extend to lumbar levels of the spinal cord originate only from neuronal somata located in the hindlimb representation of SI and MI. Those neurons projecting to the cervical enlargement have somata mainly in the forelimb representation of SI and MI and the ventrolateral part of the trunk representation within SI. Cortical projections to the rostral cervical spinal segments appear to originate mainly from the neck and posterior head representations of SI and MI, though this conclusion is clearest for SI. Finally, neurons located exclusively within the head, muzzle, and vibrissal representation of SI project to the spinal trigeminal complex. Corticofugal neurons near the frontal pole and in an area of cortex ventrolateral to SI also project to the spinal cord. The areas involved are probably homologous to the supplementary motor (MII) and second somatic sensory (SII) areas respectively. The corticospinal and corticotrigeminal projections from these areas also appear to be organized in a somatotopic manner.It is concluded that in the rat, as in other species, the corticospinal and corticotrigeminal neurons in the sensorimotor cortex are arranged somatotopically. The somatotopic pattern found correlates remarkably well with that determined by single unit, evoked potential and cortical stimulation techniques.     

Motor and cognitive deficits in apolipoprotein E-deficient mice after closed head injury

Previous studies suggest that traumatic brain injury is associated with increased risk factor for developing Alzheimer's disease. Furthermore, the extent of the risk seems to be most pronounced in Alzheimer's disease patients who carry the ε4 allele of apolipoprotein E, suggesting a connection between susceptibility to head trauma and the apolipoprotein E genotype. Apolipoprotein E-deficient mice provide a useful model for investigating the role of this lipoprotein in neuronal maintenance and repair. In the present study apolipoprotein E-deficient mice and a closed head injury experimental paradigm were used to examine the role of apolipoprotein E in brain susceptibility to head trauma and in neuronal repair. Apolipoprotein E-deficient mice were assessed up to 40 days after closed head injury for neurological and cognitive functions, as well as for histopathological changes in the hippocampus. A neurological severity score used for clinical assessment revealed more severe motor and behavioural deficits in the apolipoprotein E-deficient mice than in the controls, the impairment persisting for at least 40 days after injury. Performance in the Morris water maze, which tests spatial memory, showed a marked learning deficit of the apolipoprotein E-deficient mice when compared with injured controls, which was apparent for at least 40 days. At this time, histopathological examination revealed overt neuronal cell death bilaterally in the hippocampus of the injured apolipoprotein E-deficient mice.

The finding that apolipoprotein E-deficient mice exhibit an impaired ability to recover from closed head injury suggests that apolipoprotein E plays an important role in neuronal repair following injury and highlights the applicability of this mouse model to the study of the cellular and molecular mechanisms involved.     

Three hands: fragmentation of human bodily awareness

We describe patient E.P. who occasionally perceives a ‘ghost' hand which copies the previous positions of the left hand with a 0.5–1 min time lag, but follows the movement patterns of the right hand. The symptoms started after an operation of a ruptured aneurysm, followed by an infarction of the right frontal lobe; E.P. also has a previously lesioned corpus callosum. Neuromagnetic recordings revealed that activity of the left secondary somatosensory cortex was strongly suppressed during the ghost arm percept, thereby providing an objective correlate for E.P.'s sensations. We conclude that simultaneous mental contents about body scheme may be based on neural information extracted at considerably different times, resulting in fragmentation of bodily awareness.     

Windows环境下步进电机匀加速的实现与计算机程序设计

本文主要介绍了奔腾计算机和步进电机的接口电路,提出了步进电机匀加速的控制算法,探讨了在 Windows 环境下以 Visual C++实现步进电机匀加速的实现途径和多任务环境下匀加速程序的设计方法。     

Differences in the abilities of individual fingers during the performance of fast,repetitive tapping movements

Using 12 healthy male subjects, the dynamic motor ability of individual fingers was investigated under four different finger tapping conditions. These were: maximum speed tapping with one finger (single-finger tapping), alternate movement of two fingers (double-finger tapping), double-finger tapping in an unsupported condition, and submaximum constant speed tapping with one finger in a passive manner. Key-contact forces for all fingers and the movement velocity of the tapping finger were monitored. With the exception of the unsupported condition, non-tapping fingers were maintained in contact with designated keys during the tapping tasks. It was found that the index finger attained the fastest cadence and greatest movement velocity, followed by the middle, little and ring fingers, respectively. Subjective assessment of rank order of "difficulty" of tapping by the subjects was highly correlated with tapping cadence. Thus dynamic motor function, as indicated by rapid, repetitive movement, differs among the individual fingers. Parallel changes were observed in the key-contact force of the neighboring non-tapping fingers during tapping. The range of the non-tapping finger forces was largest during tapping by the ring finger. A similar trend was found for passive tapping, during which the magnitude of key-contact force was less than one-third of that observed during active tapping. The lower cadence achieved by the ring finger may be attributed more to a lack of independence at the level of voluntary neuromuscular control, than to innate mechanical interaction with the other fingers. Tapping cadence of each finger was lower for the double-finger mode than for the single-finger mode. The magnitude of the observed decrease in cadence during double-finger tapping was, on the other hand, strongly dependent on finger-combination. The decrease was smallest for the index-middle finger-combination, and greatest for the ring-little finger-combination. Compatibilities with other fingers can play an essential role in the dynamic motor function of individual fingers. During the unsupported task, in which interactions were diminished by allowing all fingers to move freely, tapping cadence increased markedly. Therefore, the lower cadences observed in specific finger-combinations may be partly attributed to anatomical and neural interdigit interactions.