Cleavage of platelet endothelial cell adhesion molecule-1 (PECAM-1) in platelets exposed to high shear stress.

Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) is a 130 kDa transmembrane glycoprotein that belongs to the immunoglobulin superfamily and is expressed on the surface of endothelial cells, platelets, and other blood cells. Although the importance of this adhesion molecule in various cell-cell interactions is established, its functional role in platelets remains to be elucidated. In this study, we examined whether PECAM-1 underwent changes in platelets exposed to high shear stress. Platelet PECAM-1 was cleaved under high shear stress and was released into the extracellular fluid as a fragment with an approximate molecular weight of 118 kDa. The cleavage was inhibited by an anti-VWF MoAb, but not by recombinant VWF A1 domains. These findings suggest that the GPIb-VWF interaction is involved in PECAM-1 cleavage under high shear stress, and that the cleavage is independent of GPIb clustering by VWF multimers. Furthermore, EGTA or calpeptin inhibited PECAM-1 cleavage. This finding provides evidence for the involvement of calpain in PECAM-1 cleavage. Flow-cytometric analysis revealed that PECAM-1 expression on the platelet surface was decreased under high shear stress. This reduction occurred exclusively in a specific population of platelets, which corresponded to platelet-derived microparticles (PMP). In conclusion, PECAM-1 cleavage under high shear stress is closely related to the activation of calpain and the process of PMP formation mediated by the GPIb-VWF interaction.

[A case of Sanfilippo syndrome type C: long-term clinical course and treatment].

We reported a Japanese girl with the Sanfilippo syndrome type C. She was born to healthy parents married consanguineously. She began to deteriorate and became disoriented at the age of 6 year and 8 month. She also developed sleep problems and dysphagia. Physical examination revealed short stature, slightly coarse facial features, contracture of the PIP joints and hypertrophy of the tonsils. There was neither hepatomegaly nor corneal clouding. Laboratory examination demonstrated an increase in urinary excretion of glycosaminoglycan. Electrophoresis of the urinary glycosaminoglycans indicated that heparan sulfate was the predominant component. Enzymatic assay using her skin fibroblasts demonstrated a complete deficiency of acetyl-CoA: a-glucosaminide N-acetyltransferase activity. Low dose erythromycin alleviated hypertrophy of her tonsils, thereby improving dysphagia.

[Study of appropriate expiratory velocity when measuring exhaled nitric oxide (NO) concentration].

We studied the appropriate expiratory velocity when measuring exhaled NO concentration by constant expiratory flow maneuver in relation to height and the required time for measurement, and obtained the following results. 1) There was a significant positive correlation between height and the required time. 2) There was a significant negative correlation between expiratory velocity and the required time. 3) Percent ratios of children who reached the plateau of exhaled NO concentration were significantly higher when expiratory velocity was over 2000 ml/minute. These findings suggest that expiratory velocity of over 2000 ml/minute may be appropriate when measuring exhaled NO concentration.

Role of N-acetylglutamate turnover in urea synthesis by rats treated with the thyroid hormone.

We determined whether the synthesis and degradation of N-acetylglutamate would regulate urea synthesis when the thyroid status was manipulated. Experiments were done on three groups of rats, each being given 6-propyl-2-thiouracil (PTU, a thyroid inhibitor) without a triiodothyronine (T3) treatment, treated with PTU + T3, or receiving neither PTU nor T3 (control). The plasma concentration and urinary excretion of urea, the liver concentration of N-acetylglutamate, and the liver N-acetylglutamate synthesis in rats given PTU alone were each significantly higher than in the control rats. Compared with the control rats, the liver N-acetylglutamate degradation was significantly lower in those rats given PTU without the T3 treatment. Treatment of the PTU-treated rats with T3 reversed the effects of PTU to the values of the control rats. N-Acetylglutamate synthesis in the liver was closely correlated with the excretion of urea, and inverse correlation between the liver N-acetylglutamate degradation and urea excretion was found. These results suggest that the greater synthesis and lower degradation of N-acetylglutamate in the hypothyroid (PTU alone) rats would be likely to increase the hepatic concentration of this compound and stimulate urea synthesis.

Familial neuronal migration disorder: subcortical laminar heterotopia in a mother and pachygyria in the son.

We describe clinical manifestations and magnetic resonance imaging (MRI) findings in a man and his mother who were diagnosed as having a neuronal migration disorder. The son had severe psychomotor retardation and the mother had intractable seizures and mild psychomotor retardation. MRI demonstrated moderate pachygyria in the son and subcortical heterotopia in the mother. In both patients, the frontal parts of the brain were characteristically more affected than any other areas. A dominant pattern of inheritance in the family suggests a genetic role in the underlying cause of the migration disorder. The difference in severity between the two patients also suggests an X-linked dominant inheritance. Our family fits the condition of X-linked lissencephaly.

Effect of a thyroid hormone treatment on brain protein synthesis in rats.

The effect of the thyroid hormone on the rate of brain protein synthesis in rats was studied. Experiments were conducted on three groups of rats given 6-propyl-2-thiouracil (PTU, a thyroid inhibitor) without a triiodothyronine (T3) treatment, those treated with PTU + T3, and those treated with neither PTU nor T3 (control). The fractional rates of protein synthesis in the brain, liver, and kidney of rats given PTU + T3 were significantly greater than those in rats given PTU alone. In the brain and kidney, the RNA activity [g of protein synthesized/(g of RNA.d)] were significantly correlated with the fractional rates of protein synthesis. In the liver and kidney, the RNA concentration (mg of RNA/g of protein) was related to the fractional rate of protein synthesis. These results suggest that the thyroid hormone treatment would be likely to increase the rate of protein synthesis in the brain of rats, and that the RNA activity is, at least partly, related to the fractional rate of brain protein synthesis.

Role of ornithine transport into mitochondria in urea synthesis of rats treated in thyroid hormone.

The purpose of this study was to find whether or not the ornithine transport into mitochondria regulated urea synthesis when the thyroid status is manipulated. Experiments were done on three groups of rats: given 6-propyl-2-thiouracil (PTU, a thyroid inhibitor) without triiodothyronine (T3) treatment, treated with PTU+T3 or receiving neither PTU nor T3 (control). The urinary excretion of urea, liver concentration of ornithine and ornithine transport into isolated hepatic mitochondria in rats given PTU+T3 were significantly lower than in rats given PTU alone. Ornithine transport was significantly inhibited by the addition of lysine specifically. This response was achieved well within the physiological concentration of lysine. Compared with rats given PTU without T3 treatment, the liver concentration of lysine was significantly higher in rats treated with PTU+T3 and control rats. Ornithine transport into hepatic mitochondria was closely correlated with the excretion of urea. The results suggest that the greater ornithine transport in the hypothyroid (PTU alone) rats is likely to stimulate urea synthesis. A thyroid hormone-induced increase in lysine concentration may be at least partly responsible for the changes in ornithine transport into mitochondria.

Epileptic seizures and event-related potentials (P300) in childhood partial epilepsies.

To clarify the relationship between cognitive function and clinical seizures, auditory event-related potentials (P300) were examined in 72 patients (185 trials) with partial epilepsy. Twenty-six patients (67 trials) had idiopathic partial epilepsies (IPE), and 46 (118 trials) symptomatic or cryptogenic partial epilepsies (SPE). In this study, to rule out the effects of epileptogenesis and other factors, we only examined patients with partial epilepsies undergoing carbamazepine (CBZ) monotherapy at doses of less than 16 mg/kg/day. The results were: 1) the mean age-corrected P300 latency in the patients with SPE (394 +/- 38 msec) was significantly prolonged compared with that in the patients with IPE (378 +/- 28). 2) The prolongation of the P300 latency had no relationship to the seizure frequency, seizure type or seizure duration. 3) In both epileptic groups, there was no significant correlation between the seizure-free period and the age-corrected P300 latency. Our results suggest that the effect of clinical seizures on the cognitive function may be relatively little, and that the cognitive dysfunction in partial epilepsies may mainly originate from epileptogenesis or other factors.

Event-related potentials (P300) and EEG activity in childhood partial epilepsy.

To clarify the relationship between the cognitive function and EEG activity, auditory event-related potentials (P300) were examined in 72 patients with partial epilepsy. Twenty-six patients (67 trials) had idiopathic partial epilepsies (IPE), and 46 (118 trials) symptomatic or cryptogenic partial epilepsies (SPE). For this study, patients undergoing carbamazepine monotherapy with a dose of less than 16 mg/kg/day were selected to rule out the effects of anti-epileptic drugs. The results were as follows: (1) The P300 latency tended to be prolonged in association with the EEG slowing in both epileptic groups. (2) There was no clear relationship between the frequency of paroxysmal discharges and the P300 latency. (3) The P300 latency was slightly prolonged in the patients with temporal foci compared with that in ones with extra-temporal foci. (4) There was no significant relationship between the generalization of focal paroxysmal discharges and the P300 latency. These results suggested that the influence of EEG abnormalities (particularly paroxysmal discharges) on the P300 latency is relatively little, and the cognitive dysfunction in partial epilepsies mainly originates from other factors such as the epileptogenic lesion itself.

[Trigeminal neuralgia caused by tortuous vertebrobasilar system--the clinical and imaging features].

Ten (6.8%) out of 146 patients with trigeminal neuralgia (TN) who underwent SPGR-MRI and 3D-TOF-MRA from August 1993 to October 1996, were found to have vascular compression caused by a tortuous vertebrobasilar system (TVBS). They were mostly males, demonstrated left-sided predominance, and had ipsilateral hemifacial spasm, compared with other 52 patients whose offending arteries were either superior cerebellar artery (SCA), anterior inferior cerebellar artery (AICA)or posterior inferior cerebellar artery (PICA). The patients who showed vascular compression by TVBS, presented an artery which compresses and dislocates the rootentry zone (REZ) of the trigeminal nerve, presses the brain stem at REZ and simultaneously compresses the REZ of the facial nerve. In addition, the diameters of the two branches of vertebrobasilar artery were not equal. These features indicate that the atherosclerotic change of the offending artery in TN caused by TVBS is more severe than that caused by SCA, AICA or PICA. This change causes an irregular running of artery which leads a strong compression of the trigeminal nerve REZ and of the brain stem. Consequently, the facial nerve REZ is severely affected leading to the presence of tic convulsif in TN caused by TVBS.

Distribution of referred pain from the lumbar zygapophyseal joints and dorsal rami.

OBJECTIVE: The purpose of this study was to determine the distribution of referred pain from the lumbar zygapophyseal joints (L1/2 to L5/S1) and the medial branches of the lumbar dorsal rami (Th12 to L5) in a large number of patients with chronic low back pain. SETTING: This study was conducted at the pain clinics of Kanto Teishin Hospital and Hannan Central Hospital from March 1994 to May 1996. PATIENTS AND DESIGN: Chronic low back pain patients who underwent zygapophyseal joint injection or radiofrequency facet denervation were studied. Under fluoroscopic control, the joints from L1/2 to L5/S1 were stimulated by injection of contrast medium, and the lumbar medial branches of the dorsal rami from Th12 to L5 underwent electrical stimulation during radiofrequency facet denervation. OUTCOME MEASURES: If the injection or electrical stimulation reproduced the patient's usual pain, the distribution of induced pain was determined, and the sites of induced pain were divided into six areas. RESULTS AND CONCLUSIONS: A total of 71 joints and 91 medial branches were studied in 48 patients. The distribution of referred pain from the L1/2 to L5/S1 zygapophyseal joints, and the medial branches of the dorsal rami from L1 to L5 were similar for each level stimulated, and the overlap of referred pain between each level was considerable.

[Identification of offending vessels in trigeminal neuralgia and hemifacial spasm using SPGR-MRI and 3D-TOF-MRA].

We investigated 100 consecutive patients with trigeminal neuralgia (TN) and 53 patients with hemifacial spasm (HFS) concerning the anatomical relationship between the root entry (exit) zone (REZ) of cranial nerve and the offending artery, using spoiled GRASS MRI (SPGR-MRI) and three dimensional-time of fly-MRA (MRA). In 67 of 100 (67%) patiets with TN, this new radiological method, SPGR-MRI and MRA demonstrated the relationship between the fifth cranial nerve root and offending artery causing neurovascular compression (NVC), and in 46 of 53 (87%) with HFS, demonstrated the similar relationship between seventh and eighth nerve complex and offending artery. Microvascular decompression (MVD) was performed in 10 with HFS, and NVC of the REZ of the facial nerve caused by the offending artery was exactly predicted by SPGR-MRI and MRA in 9 (90%). The combination of SPGR-MRI and MRA is very useful for demonstrating NVC as the cause of TN and HFS. On the other hand, we investigated asymptomatic 206 trigeminal and 253 facial nerves about the relationship between their REZ and the surrounding structures using the similar method. The contact of REZ of cranial nerve with surrounding artery is demonstrated in 31.6% of trigeminal nerves and in 22.5% of facial nerves. These results indicate that the contact of REZ of cranial nerve with surrounding artery is not rare in healthy subjects, though causing TN and HFS in particular patients. In this context, we discussed the difference between the contact which is asymptomatic and the compression which is symptomatic.

Withdrawal of antiepileptic drug treatment in childhood epilepsy: factors related to age.

The clinical and electroencephalographic changes with age were evaluated in 304 patients with childhood epilepsies, whose antiepileptic treatment had been discontinued after a seizure free period of more than three years. The withdrawal rate differed significantly between epileptic syndromes, being higher in idiopathic epilepsy and lower in symptomatic epilepsy. The age at withdrawal was characteristic for each epileptic syndrome, and generally showed two peaks: at preadolescence and early school age. Forty one (13.5%) of the 304 patients experienced relapses. The relapse rate differed between epileptic syndromes. Relapses occurred at a unique age in each epileptic syndrome, and were frequent in preadolescence and early adulthood. Electroencephalography that still showed paroxysmal discharges at withdrawal did not necessarily predict the occurrence of a relapse, but the changes in background activity with age, which may indicate maturation of the CNS, were significantly different between the patients with and those without relapses. The results suggest that age related to each epileptic syndrome should be considered when deciding on withdrawal of antiepileptic drugs.

Effects of antiepileptic drugs on EEG background activity in children with epilepsy: initial phase of therapy.

The effects of antiepileptic drugs (AED) on EEG background activity were evaluated in 37 newly treated children with epilepsy, compared with 46 age-matched healthy controls. Before AED therapy, the children with epilepsy, both partial (treated with carbamazepine, CBZ group) and generalized seizures (treated with valproic acid, VPA group), already exhibited significant slowing of EEG with increased delta and decreased alpha power. Following 3 to 6 months of AED therapy, this EEG slowing was enhanced in the CBZ group and reduced in the VPA group. Following 1 year of AED therapy, an increase in frequency was recognized in the CBZ group. These results suggest that 1) most children with epilepsy already exhibit slowing of the EEG at the onset of seizures, which may reflect CNS developmental deficit, 2) the short-term effects on EEG are different between CBZ and VPA, and 3) EEG development with age continues under continuous AED administration. The EEG background activity in children with epilepsy is affected by many factors, which include the underlying CNS dysfunction of the epilepsy itself and also AED therapy (type of AEDs, duration of therapy, etc).

Changes of P300 latency with age in childhood epilepsy.

Auditory event-related potentials (P300 latency; odd-ball paradigm) were examined in 129 patients with childhood epilepsies and 53 controls. The P300 latency in the patients with epilepsies (373 +/- 39.4 ms) was significantly longer than in controls (356 +/- 38.4), and the prolongation was greatest in the patients with symptomatic partial epilepsies (390 +/- 40.5), mild in those with idiopathic generalized epilepsies (370 +/- 24.3), and minimum in those with idiopathic partial epilepsies (363 +/- 28.9). Abnormal P300 latency occurred at all ages during childhood in patients with symptomatic partial epilepsies, and at older ages in patients with idiopathic generalized epilepsies. The shortening of latency with age was relatively small in patients with epilepsies compared with controls. These results suggest that the prolongation of P300 latency (i.e., existence of cognitive disturbance) displays characteristic changes with age in each epileptic syndrome.

Flunitrazepam for sleep disturbance in children with intractable epilepsy.

Add-on therapy with flunitrazepam (FNZ) was performed in 5 children with marked sleep disturbance and intractable seizures. Correction of the sleep disturbance was attained immediately after the start of FNZ administration in all patients. Furthermore, a significant decrease in the seizure frequency (3 patients) and improved quality of life (4 patients) were concomitantly observed. There was no adverse effect or interaction with conventional AEDs on long-term use.

Distribution and origins of cerebrovascular NADPH-diaphorase-containing nerve fibers in the rat.

Neuronal NADPH-diaphorase has been proved to be nitric oxide synthase itself. In this study, we investigated distribution and origins of NADPH-diaphorase-containing nerve fibers in the cerebral vessels in the rat. Adult male Sprague-Dawley rats were divided into 4 groups. Nasociliary nerves were transected bilaterally in group 1. In group 2, intracranial branches of the sphenopalatine ganglion were transected bilaterally. In group 3, both of these structures were transected. The remaining animals were served as control (group 4). Two weeks after the above procedures, they were perfused with paraformaldehyde and glutaraldehyde. The pial arteries and superior cervical, trigeminal, internal carotid, otic and sphenopalatine ganglia were dissected. All specimens were processed for NADPH-diaphorase histochemistry. Numerous NADPH-diaphorase-containing nerve fibers with varicosities forming plexuses were observed in the circle of Willis and its branches. Relatively thick nerve bundles were noted in the anterior half of the circle of Willis. They are most abundant in the internal ethmoidal artery. Approximately 5% of such fibers in anterior half of the circle of Willis disappeared in group 1, 90% in group 2, and no fibers were seen to remain in group 3. NADPH-diaphorase reaction was positive in the neurons of sphenopalatine, otic trigeminal and internal carotid ganglia. Among these ganglia, the reaction was prominent in sphenopalatine, otic and internal carotid ganglia. In summary: (1) NADPH-diaphorase-containing nerve fibers distribute to the circle of Willis and its branches.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in EEG foci with age in childhood partial epilepsies.

The age changes of epileptic foci on EEG were evaluated in 208 patients with childhood partial epilepsies, who were followed for more than 3 years. 1) The incidence of EEG foci in each region apparently differed with age. Frontal and central foci were frequent before school age and after adolescence. Temporal foci showed a peak around adolescence, and occipital foci a peak from 3 to 7 years, respectively. Parietal foci were rare at all ages. 2) The migration of EEG foci was recognized 171 times in 81 of the 208 patients (38.9%) during the clinical course. The migration was frequently seen at early school age and preadolescence, and the direction of migration was predominantly anterior to posterior at early school age, and posterior to anterior at preadolescence. These results suggest that EEG foci show characteristic changes with age during the clinical course, which may be related to maturation of the central nervous system.