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Vacancy-type defects in Mg-implanted GaN were probed by using a monoenergetic positron beam. Mg ions were implanted into GaN to obtain 0.3-μm-deep box profiles with Mg concentrations of 1 × 10 19  cm -3 . The major defect species in an as-implanted sample was determined to be Ga-vacancy related defects such as a complex between Ga and N vacancies. The sample was annealed under a nitrogen pressure of 1 GPa in a temperature range of 1000-1480 °C without a protective capping layer. Compared with the results for Mg-implanted GaN annealed with an AlN capping layer, the defect concentration was decreased by the cap-less annealing, suggesting that the surface of the sample was an effective sink for vacancies migrating toward the surface. Depth distributions of Mg after annealing above 1300 °C were influenced by the presence of residual vacancies at this temperature. Hydrogen atoms were unintentionally incorporated into the sample during annealing, and their diffusion properties were also affected by both vacancies and Mg.

A normally-off GaN double-implanted vertical MOSFET (DMOSFET) with an atomic layer deposition (ALD)-Al₂O₃ gate dielectric film on a free-standing GaN substrate fabricated by triple ion implantation is presented. The DMOSFET was formed with Si ion implanted source regions in a Mg ion implanted p-type base with N ion implanted termination regions. A maximum drain current of 115 mA/mm, maximum transconductance of 19 mS/mm at a drain voltage of 15 V, and a threshold voltage of 3.6 V were obtained for the fabricated DMOSFET with a gate length of 0.4 μm with an estimated p-type base Mg surface concentration of 5 × 10 18 cm -3 . The difference between calculated and measured V th s could be due to the activation ratio of ion-implanted Mg as well as Fermi level pinning and the interface state density. On-resistance of 9.3 mΩ·cm² estimated from the linear region was also attained. Blocking voltage at off-state was 213 V. The fully ion implanted GaN DMOSFET is a promising candidate for future high-voltage and high-power applications.

Objective: The aim of this study was to identify a useful neuropsychological instrument for making a differential clinical diagnosis between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB)., Methods: We examined 402 AD and 38 DLB patients with neuropsychological tests that covered general cognition, frontal lobe cognitive function, non-verbal abstract reasoning, working memory and attention, and verbal memory. Discriminant analysis using a stepwise method was performed to identify the measures best able to discriminate between AD and DLB., Results: The AD patients performed significantly worse than the DLB patients on orientation to time, delayed recall subtests on the Mini-Mental State Examination, and logical memory subtests 1 and 2 of the Revised Wechsler Memory Scale. The DLB patients performed significantly worse than the AD patients on the attention, repetition, and pentagon copying subtests of the Mini-Mental State Examination, the constructional praxis subtests of the Alzheimer's Disease Assessment Scale-cognitive component-Japanese version, the Frontal Assessment Battery total score, Raven's Coloured Progressive Matrices (RCPM) sets A, AB, and B, and backward digit span. Discriminant analyses between AD and DLB established the key variables as Logical Memory 1, Logical Memory 2, backward digit span, RCPM, and delayed recall on the Mini-Mental State Examination. We inferred the AD-DLB discriminant index from the following discriminant analyses: AD-DLB discriminant index = (Backward digit span score + RCPM set B score) - (Logical Memory 1 score + Logical Memory 2 score), which offered a highly favourable value for diagnostic utility., Conclusions: The AD-DLB discriminant index, consisting of backward digit span, RCPM set B, and logical memory 1 and 2, is useful to differentiate between AD and DLB., (© 2013 The Authors. Psychogeriatrics © 2013 Japanese Psychogeriatric Society.)

Unique effects of sham-pinealectomy [intracranial surgery (IS)] which include reduced functional activity of the adrenal gland and suppressed circadian rhythms of the adrenal medulla, and which are reversed by pinealectomy, have been reported in rodents. To clarify the mechanisms, we investigated whether or what changes occur in pineal functional activity after IS. Sixty-six male rats of normal and IS groups were used at 50 days of age. The pineal gland was first examined by quantitative electron microscopy. The Sudan III-stained lipid droplet content of the pinealocytes and plasma melatonin level were then investigated using the same animals. In IS rats, the lipid droplet content of the pinealocytes decreased in both the dark and light phases 14 days after surgery. Mean volumetric ratio of nucleus, nucleolus, and mitochondria tended to increase in IS rats. The mean plasma concentration of melatonin showed apparent day-night changes, but no significant changes because of IS, 36 h and 14 days after surgery. But in the dark phase 14 days after surgery, plasma melatonin levels showed increased dispersion of values (P < 0.04). Thus, after IS the lipid content of pinealocytes showed changes not closely related to those of plasma melatonin level. From these and other results it is speculated that IS effects are dissimilar to usual stress responses, that day-night rhythms of functional activities of the pineal and adrenal medulla are differently controlled, and that pineal gland-dependent IS effects are most probably induced by changed sensitivity/states of target mechanisms to the pineal hormone melatonin.

Effects of sham-pinealectomy and pinealectomy on preganglionic nerve endings on adrenomedullary adrenaline cells were investigated electron microscopically. Adult male golden hamsters from the normal, sham-pinealectomy and pinealectomy groups maintained under 24 h light-dark cycle and constant temperature were used at 28 days after surgery. From conventional electron microscopic specimens, montage photographs made of the adrenaline cell region at a magnification of x 11,000 were used for qualitative and quantitative electron microscopic analyses in 14 animals in each experimental group. The preganglionic nerve endings were localized mainly in the following three sites: the basal lamina part, the follicular lumen-junctional intercellular part, and the adrenaline cell-invaginated part. In the latter two parts, nerve endings and fibers had no envelope frequently, and in the former two parts, nerve endings sometimes showed the invagination complex. The frequency of nerve endings was highest in the follicular lumen-intercellular part, next highest in the basal lamina part and lowest in the A cell-invaginated part. The frequency of nerve endings in the basal lamina part was lower in the pinealectomy group than in the sham-pinealectomy group (P < 0.021), and those in the other two parts showed opposite changes, more evidently in the A cell-invaginated part. Nerve ending profiles in the adrenaline cell-invaginated part--which displayed a more rounded shape--increased in size in the pinealectomy group (longer diameter: P < 0.04; shorter diameter: P < 0.05). In conclusion, preganglionic nerve endings in the adrenal medulla of the golden hamster show differential morphological changes following PX depending on the intracellular part of A cells.

Study Design: An anatomic study investigated the attachment of the nuchal muscles to the spinous process., Objective: To investigate the anatomic details of the attachment of the nuchal muscles to the spinous process, and which muscles are spared, and to what extent, when the C7 spinous process is preserved in the cervical laminoplasty., Summary of Background Data: In previous studies, it was reported that the incidence of postoperative axial pain was lower in C3-C6 laminoplasty than in C3-C7 laminoplasty, emphasizing the effectiveness of the former procedure where discission of the nuchal muscles that are attached to the C7 spinous process is avoided. However, there have been no detailed anatomic studies of the attachment of the nuchal muscles to the spinous process at the cervicothoracic junction., Methods: The anatomy of the speculum rhomboideum of the trapezius, rhomboideus minor, rhomboideus major, serratus posterior superior, splenius capitis, and splenius cervicis to the spinous processes of the cervicothoracic junction were studied using 50 cadavers., Results: The possibility of total discission of the speculum rhomboideum of the trapezius was 0% with C3-C6 laminoplasty and 18% with C3-C7 laminoplasty. More than 50% preservation of the speculum rhomboideum of the trapezius is possible in 72% in C3-C6 laminoplasty and 16% in C3-C7 laminoplasty. In C3-C7 laminoplasty, the possibility of partial preservation of the rhomboideus minor, serratus posterior superior, and splenius capitis at the spinous process was 0%, 66%, and 29%, respectively. The rhomboideus major in 16% and the splenius cervicis in 56% could be completely preserved without partial discission of the muscle attachment. On the other hand, in C3-C6 laminoplasty, the muscles that were spared without complete discission of the muscular attachment at the spinous process were the rhomboideus minor in 35%, the serratus posterior superior in 100% and the splenius capitis in 67%. The rhomboideus major in 76% and the splenius cervicis in 80% were completely spared without partial discission of the muscular attachment., Conclusion: The current study confirmed that C3-C6 laminoplasty in which the C7 spinous process is preserved reduces invasion of the nuchal muscles.

Ultrastructural features of adrenomedullary adrenaline (A) cells in golden hamsters and rats were investigated qualitatively and quantitatively with special reference to the Golgi apparatus. The A cells displayed a characteristic follicular arrangement, with each cell showing structural polarity in hamsters, but not apparently in rats. In hamsters, the Golgi apparatus of A cells was larger (t-test: P<0.001) and more frequently showed large and complexly organized structures (chi(2)-test: P<0.005) compared with that of rats. Quantitative analysis of the Golgi apparatus revealed differences in the size and numerical density of Golgi vesicles in relation to the animal species and region. Two-way analysis of variance (ANOVA) confirmed species difference in the size of coated vesicles (P<0.005) and interaction between species and region concerning the size of smooth-clear vesicles (P<0.01) and numerical density of granular vesicles (P<0.05). One-way ANOVA revealed regional differences in the size and numerical density of smooth-clear vesicles in rats and hamsters (P<0.01 approximately 0.001), and in the numerical density of coated vesicles in hamsters (P<0.05). Data were further analyzed by Tukey-Kramer's method. These and other reported results suggest that, in hamster A cells, the Golgi apparatus has different structural, molecular, and functional mechanisms which are at least partly related to the distinct cellular polarity and higher concentration of peptide hormones in secretory vesicles, and that in rat A cells, in contrast, loading secretory vesicles with A during the post-Golgi stage is predominant. In conclusion, the Golgi apparatus in hamster A cells shows markedly different ultrastructural features compared with that in rat A cells.

The present study investigates whether and how the pineal or its hormone melatonin influences female reproductive functions, namely the litter size, prenatal development of offsprings, and estrous cyclicity, especially its age-related cessation in a non-seasonal breeder, the laboratory rat. Wistar rats were maintained under a 24 h light-dark (12Lratio12D) cycle. Female rats were divided into 3 groups: non-operated (NO), sham-operated (SX), and pinealectomized (PX). Surgeries were performed in 35-40 day-old females. Starting at an age between 70 days and 7 months, female rats of all 3 groups were repeatedly mated with intact males. PX mothers more frequently delivered pups with malformations (e.g., taillessness, hydronephrosis, 7 out of 1263 pups) than control rats (0/1323; p<0.007). In the first delivery at 3 months of age, but not at later ages, PX mothers delivered more pups of lower body weight than control animals (p<0.001). Examination of vaginal smears showed that almost all female rats of the NO, SX, and PX groups had 4-day estrous cyclicity when they were young-between 60 days and 5 months of age. At an age of 17 to 18 months, most female rats of the NO and SX groups showed irregular, continuously diestrous or pseudopregnancy-like patterns, and 4-day estrous cyclicity was found in only 10% of the NO or SX animals. In contrast, about 50% of the PX rats showed 4-day estrous cyclicity at this older age (p< 0.001). Melatonin, when added to drinking water (0.4 mg/L) for 16 days during the dark phase increased the frequency of diestrous phase, except in continuously diestrous rats and very few others. This melatonin effect was strong in PX rats but relatively weak in SX rats. In conclusion, the pineal hormone appears to influence various reproductive functions and developmental processes, especially pregnancy and the timing of reproductive aging in rats. The effects of pinealectomy are more prominent at an age of 60 to 80 days (i.e., shortly after puberty) and at the beginning of the cessation of cycles in middle-aged females.

Objective: Effects of adrenomedullary hormone(s) on the induction and growth of fibrosarcoma by methylcholanthrene (MC) were examined., Methods: At 28 days of age, male Wistar rats were divided into four groups: 1) control, 2) bilateral adrenomedullectomy (Bil. AMX), 3) right AMX + left adrenomedullary autotransplantation (AMX + AMT), 4) Bil. AMX + epinephrine injection (Bil. AMX + E) groups. 14 days after surgery, MC crystals were inserted underneath the dorsal skin, and in the Bil. AMX + E group, epinephrine was injected subcutaneously, twice every week., Results: The incidence of tumor at 90 days after the MC injection was 8 per 35 cases (22.9%) in the control group, 12 per 36 cases (33.3%) in the AMX + AMT group, 8 per 28 cases (28.6%) in the Bil. AMX + E group, and each value was lower compared with that of the Bil. AMX group, 24 per 34 cases (70.6 %), (P<0.001, P<0.002, P<0.005). Such differences among groups were not seen at 165 days after the injection of MC., Discussion: The mechanisms of effects of AMX, AMT and/or epinephrine on the tumor incidence have been discussed with reference to tumor promotion, vascular neoplasia, etc. Since norepinephrine remaining in the blood of AMX rats was ineffective, at least it is likely that this inhibitory effect of epinephrine is mediated via the beta2-receptor., Conclusion: The results suggest that adrenomedullary hormone, probably epinephrine, has inhibitory effects on the induction and growth of fibrosarcoma by MC, particularly in the early stage.

To determine the characteristics of cerebral glucose metabolism in Parkinson's disease patients with visual hallucinations, group comparison studies using [18F]fluorodeoxyglucose positron emission tomography were performed. Nondemented Parkinson's disease patients in advanced stages were classified into two groups: (1) patients without visual hallucinations; (2) patients with visual hallucinations. Compared to patients without hallucinations, the relative regional cerebral glucose metabolic rate was greater in the frontal areas in patients with visual hallucinations, and the increase reached a significant level in the left superior frontal gyrus. Relative frontal hypermetabolism may be a feature of Parkinson's disease patients with visual hallucinations., (Copyright 2004 Movement Disorder Society)

Objective: Using 6-[(18)F]fluoro-L-dopa (FDOPA) and [(18)F]fluorodeoxyglucoce (FDG) positron emission tomography (PET), multiple regression analyses were performed to determine the specific brain regions that are related to cognitive and motor symptoms in nondemented patients with Parkinson's disease., Methods: Spatially normalized images of FDOPA influx rate constant (Ki) values and relative regional cerebral metabolic rates for glucose (rrCMRglc) were created. Raven's Coloured Progressive Matrices (RCPM) scores and the Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were used to determine the patients' cognitive and motor functions, respectively. Multiple correlation analyses between the FDOPA and FDG images and the cognitive and motor scores were performed for each voxel., Results: RCPM score was significantly positively correlated with the FDOPA Ki in the left hippocampus and with the rrCMRglc in the left middle frontal gyrus and right retrosplenial cortex. Motor function was significantly positively correlated with the FDOPA Ki in the bilateral striatum and with the rrCMRglc in association areas and primary visual cortex. The level of motor function was significantly inversely correlated with the FDOPA Ki in the anterior cingulate gyrus and with the rrCMRglc in bilateral primary motor cortex and right putamen., Conclusions: Changes of striatal FDOPA uptake and rrCMRglc in the primary motor cortex likely represent dysfunction in the motor system involving the corticobasal ganglia-thalamocortical loop. Change of FDOPA uptake in the anterior cingulate gyrus may be related to up-regulation of dopamine synthesis in surviving dopamine neurons. The regions where correlation with cognitive function was observed belong to a cognitive frontoparietal-hippocampal network.

The aim of the present study was to clarify whether maternal pinealectomy increases: (i) the incidence of spontaneous malformations in offspring; and (ii) litter size. More than 30 female rats in each of the control groups (normal and sham-pinealectomized) and the pinealectomized group were mated repeatedly with normal male rats and pups were autopsied mostly before weaning. No malformations were seen in offspring from the normal and sham-pinealectomized groups (n = 350 and n = 736, respectively). In contrast, in offspring from pinealectomized mothers (n = 1123), spontaneous malformations were found in five (taillessness in three and unilateral hydronephrosis or large renal cyst in the other two) or maybe six (unilateral renal hypoplasia in another) pups. This increased incidence of malformations in the latter group was statistically significant (P < 0.034 or 0.017 (Fisher's exact test), respectively). The frequency of still-born cases was not higher in pups born from pinealectomized mothers. The mean litter size was larger in the pinealectomized group compared with the control groups (P < 0.005-0.001, Student's t-test) at the first delivery (at approximately 100 days of age), but was not different at later deliveries at older ages. Our results suggest that the maternal pineal hormone suppresses: (i) the incidence of spontaneous malformations in offspring until mothers reach an old age; and (ii) litter size during the reproductively maturational phase of life.

We examined three intervention methods for their efficacy in preventing aspiration in 25 patients with Parkinson's disease (PD) and 23 patients with degenerative cerebellar ataxia (CA). On videofluoroscopic examination. 13 patients with PD (52%) and 7 patients with CA (30.4%) showed aspiration. In all PD patients and 5 patients with CA, no aspiration was observed after changing the food form. With the chin down posture and supraglottic swallow techniques, no aspiration was observed in only 1 PD patient. Among 7 patients with CA, the chin down posture and supraglottic swallow techniques resulted in the disappearance of aspiration in 4 patients. This indicates that changing the food form (ex. jelly) was effective in preventing aspiration in both PD and CA patients with a history of aspiration. In addition, the chin down posture and supraglottic swallow techniques were effective in preventing aspiration in CA patients with good sitting-position balance and cervical control.

We studied the effects of aging on middle-latency auditory evoked fields (P50m), and analyzed their interhemispheric differences. Magnetic responses following tone-burst stimuli to the right ear were measured in groups of 11 younger and 15 elderly subjects. The elderly subjects showed marked asymmetry in the P50m amplitudes. In the elderly group, the mean amplitude of the contralateral P50m was significantly larger (P<0.0005) than that of the ipsilateral P50m, while no asymmetry was shown in the younger group. The amplitude enlargement in the contralateral P50m showed significant correlation with age (R=0.60, P<0.005), while the ipsilateral P50m showed no correlation with age. These results suggest that the contralateral and ipsilateral auditory pathways are affected differently by ageing.

We investigated the relative differences in dopaminergic function through the whole brain in patients with Parkinson's disease without dementia (PD) and with dementia (PDD) using 6-[18F]fluoro-L-dopa (18F-dopa) PET and a voxel-by-voxel analysis. The 10 PD and 10 PDD patients were equivalently disabled, having mean scores of 3.2 +/- 0.6 and 3.2 +/- 0.7, respectively, on the Hoehn and Yahr rating scale. 18F-dopa influx constant (Ki) images of those patients and 15 normal age-matched subjects were transformed into standard stereotactic space. The significant differences between the groups (expressed in mean regional Ki values) were localized with statistical parametric mapping (SPM) on a voxel-by-voxel basis. Compared with the normal group, SPM localized declines of the 18F-dopa Ki bilaterally in the putamen, the right caudate nucleus and the left ventral midbrain for the PD group (P < 0.01, corrected). Compared with the normal group, the PDD group showed reduced 18F-dopa Ki bilaterally in the striatum, midbrain and anterior cingulate area (P < 0.01, corrected). A relative difference in 18F-dopa uptake between PD and PDD was the bilateral decline in the anterior cingulate area and ventral striatum and in the right caudate nucleus in the PDD group (P < 0.001, corrected). Accordingly, we conclude that dementia in PD is associated with impaired mesolimbic and caudate dopaminergic function.

We investigated the disease progression and survival in 230 Japanese patients with multiple system atrophy (MSA; 131 men, 99 women; 208 probable MSA, 22 definite; mean age at onset, 55.4 years). Cerebellar dysfunction (multiple system atrophy-cerebellar; MSA-C) predominated in 155 patients, and parkinsonism (multiple system atrophy-parkinsonian; MSA-P) in 75. The median time from initial symptom to combined motor and autonomic dysfunction was 2 years (range 1-10). Median intervals from onset to aid-requiring walking, confinement to a wheelchair, a bedridden state and death were 3, 5, 8 and 9 years, respectively. Patients manifesting combined motor and autonomic involvement within 3 years of onset had a significantly increased risk of not only developing advanced disease stage but also shorter survival (P < 0.01). MSA-P patients had more rapid functional deterioration than MSA-C patients (aid-requiring walking, P = 0.03; confinement to a wheelchair, P < 0.01; bedridden state, P < 0.01), but showed similar survival. Onset in older individuals showed increased risk of confinement to a wheelchair (P < 0.05), bedridden state (P = 0.03) and death (P < 0.01). Patients initially complaining of motor symptoms had accelerated risk of aid-requiring walking (P < 0.01) and confinement to a wheelchair (P < 0.01) compared with those initially complaining of autonomic symptoms, while the time until confinement to a bedridden state and survival were no worse. Gender was not associated with differences in worsening of function or survival. On MRI, a hyperintense rim at the lateral edge of the dorsolateral putamen was seen in 34.5% of cases, and a 'hot cross bun' sign in the pontine basis (PB) in 63.3%. These putaminal and pontine abnormalities became more prominent as MSA-P and MSA-C features advanced. The atrophy of the cerebellar vermis and PB showed a significant correlation particularly with the interval following the appearance of cerebellar symptoms in MSA-C (r = 0.71, P < 0.01, r = 0.76 and P < 0.01, respectively), but the relationship between atrophy and functional status was highly variable among the individuals, suggesting that other factors influenced the functional deterioration. Atrophy of the corpus callosum was seen in a subpopulation of MSA, suggesting hemispheric involvement in a subgroup of MSA patients. The present study suggested that many factors are involved in the progression of MSA but, most importantly, the interval from initial symptom to combined motor and autonomic dysfunction can predict functional deterioration and survival in MSA.

The treatment of dystonia is exclusively difficult. Recently botulinum toxin has been introduced into the market, but its indication is still limited. Oral administration of high dosage of anticholinergic drugs is firstly recommended for the treatment of dystonia. Effective cases usually do not show obvious side effects. Likely, diazepam is another choice, and the drug usually does not bring any adverse effect in cases with good results. Effects of other drugs such as l-dopa and antidopaminergic agents are still under discussion. In cases with myoclonus and/or tremor clonazepam can be useful for improvement of the phasic symptoms. As the prognosis of dystonia especially that of focal dystonia is not hopeless, the patients with dystonia should be informed of the facts.

This study aimed to clarify the effects of pinealectomy and sham-surgery on the area postrema (AP) by quantitative histological methods. Male, Wistar rats of normal (NO), sham-operated (SX), and pinealectomized (PX) groups were used in the late dark phase at 7 weeks of age. Consecutive frontal sections including the AP were stained with hematoxylin and eosin, and immunostained using PGP 9.5 for neurons, or GFAP or vimentin for glial cells. Consecutive sections of the AP were separated into five portions starting from the point of the central canal opening to the fourth ventricle in the caudal direction, and used for measurements. Mean cross-sectional areas of capillaries showed a lower value in the SX group than in the other two groups (vs NO, P<0.005; vs PX, P<0.03). In addition, the frequency distributions of the nuclear diameters of nerve cells showed different patterns among the three experimental groups (P<0.01), the frequency of large nuclei being higher in the SX group than in the other two groups. Possible mechanisms of the effects of sham-pinealectomy and pinealectomy and significance of the pineal-AP relation are discussed. The results of this study indicate that stuctural changes in the AP can be induced by intracranial surgery, suggesting certain pineal involvement in these changes.

The aim of this study was to define the mean regional 6-[(18)F]fluoro-l-dopa (FDOPA) uptake rate constant (K(i)) values in the striatal and extrastriatal regions of the brain of normal subjects using magnetic resonance imaging (MRI)-aided spatial normalization of the FDOPA K(i) image and using automatic region of interest (ROI) analysis. Dynamic three-dimensional FDOPA positron emission tomography (PET) and three-dimensional magnetic resonance (MR) images were acquired in 13 aged normal subjects. The FDOPA add image and the K(i) image of each subject were transformed into standard stereotactic space with the aid of individual coregistered MR image. The mean regional K(i) values of the striatal and extrastriatal regions before normalization were compared with the respective values after normalization. Then automatic ROI analysis was performed on the MRI-aided spatially normalized K(i) images of the 13 normal subjects. The K(i) values on original images and those on spatially normalized images were in good agreement, indicating that the spatial normalization technique did not change the regional K(i) values appreciably. Automatic ROI analysis of the spatially normalized FDOPA K(i) images of the normal subjects, showed high K(i) values in ventral and dorsal regions of the midbrain, amygdala, hippocampus, and medial prefrontal cortex, in addition to caudate nucleus and putamen, which correspond to the dopaminergic projections in the brain. Spatial normalization technique helped to establish a database of FDOPA K(i) images of normal subjects and high K(i) values were observed widely besides striatal regions corresponding to the dopaminergic projections in the brain., (Copyright 2000 Academic Press.)

The purpose of the present study was to determine whether swallowing training improves swallowing function in patients with Parkinson's disease. Ten patients (5 males, 5 females) who had symptoms of dysphagia and 12 healthy volunteers were studied. The initiation time of the swallowing reflex, the "premotor time" (PMT), was calculated from an electromyogram of the submental muscles before and after swallowing training. Patients with Parkinson's disease had a significantly longer PMT (p = 0.0014) than did healthy controls. There was no correlation between PMT and the duration of the disease (r = -0.146; p = 0.6867) or the patient's age (r = 0.602; p = 0.0653). After swallowing training, the patients' PMTs decreased significantly (p = 0.0051).

Positron emission tomography (PET) with [18F] 6-fluoro-L-dopa (18F-FDOPA) was performed in three South Korean patients with parkinsonism who developed after chronic manganese exposure. A 51-year-old man (patient 1) suffered from masked face, marked postural tremor of hands, dystonia in the neck and the upper extremities, severe retropulsion and lateropulsion which were typical for chronic manganese intoxication. 18F-FDOPA scan was normal. Other two patients, a 46-year-old man (patient 2) and a 47-year-old man (patient 3), showed tremor at rest and rigidity predominantly on the right side, bradykinesia, stooped posture and postural instability; all of these were typical for Parkinson's disease (PD). There was reduced uptake of 18F-FDOPA in the striatum, particularly in the posterior putamen predominant on the left side, in both patient 2 and 3. From these results, patient 1 was diagnosed as pure manganism, while patient 2 and 3 were primarily as PD, because loss of nigrostriatal fibers was obvious with asymmetry of affection in the putamen. PET with 18F-FDOPA provides valuable information for differentiation between PD and manganism, although it is not clear whether development of parkinsonian symptoms in patient 2 and 3 was modified by excessive manganese exposure.

We developed a questionnaire for the study of background factors and quality of life (QOL) in elderly patients with cerebral vascular disease (CVD) and Parkinson's disease (PD). The questionnaire covered the background factors and four sections such as physical, functional, psychological and social health sections. Each section had 15 questions and disease-specific questions for CVD or PD were included in the physical health section. We analyzed 107 patients with CVD (76 elderly patients, aged 65 or more, 31 non-elderly patients under 65) and 136 patients with PD (91 elderly, 45 non-elderly). In the background section, of a total of 243 patients with CVD and PD, the elderly patients needed the assistance of their spouse and their sons wives more frequently than non-elderly patients. With regard to rehabilitation, non-elderly CVD patients had rehabilitation more frequently than the elderly CVD patients, while a higher percentage of elderly patients with PD had rehabilitation training more frequently than the non-elderly PD patients. In the QOL section, there was no difference between elderly and non-elderly CVD patients, while elderly PD patients were statistically more significantly disabled physically and weak-minded psychologically. The physical disabilities of the elderly PD patients in this statistical investigation included slow motion, stooped posture, frozen gait, difficulty in turning and standing up, constipation and dysuria. The psychological problems of elder PD patients included forgetfulness and a feeling of aging. These patients had significantly fewer consultations by family and relatives than the non-elderly PD patients. The overall tendency of QOL in patients with CVD and PD was similar to that of PD patients.

We studied a detailed somatosensory representation map of the human primary somatosensory cortex using magnetoencephalography. Somatosensory-evoked magnetic fields following tactile stimulation of multiple points in the right hemibody (including the tongue, lips, fingers, arm, trunk, leg, and foot) were analyzed in five normal subjects. We were able to estimate equivalent current dipoles (ECDs) following stimulation of the tongue, lips, fingers, palm, forearm, elbow, upper arm, and toes in most subjects and those following the stimulation of the chest, ankle, and thigh in one subject. The ECDs were located in the postcentral gyrus and generally arranged in order along the central sulcus, which is compatible with the somatosensory "homunculus." Linear distances, averaged in five subjects, from the receptive area of the thumb to that of the tongue, little finger, forearm, upper arm, and toes were estimated to be 2.42 +/- 0.28, 1.25 +/- 0.28, 2.21 +/- 0.72, 2.75 +/- 0.63, and 5.29 +/- 0.48 cm, respectively. The moment of each ECD, which suggested the size of the cortical areas responsive to the stimulation, was also compatible with the bizarre proportion of the homunculus with a large tongue, lips, and fingers. According to these results, we were able to reproduce a large part of the somatosensory homunculus quantitatively on an individual brain MRI.

We studied 16 patients with Parkinson's disease (PD) with dysphagia and 8 young and 7 elderly normal controls videofluorographically to evaluate the nature of swallowing disorders in PD patients. In 13 patients, abnormal findings in the oral phase were residue on the tongue or residue in the anterior and lateral sulci, repeated pumping tongue motion, uncontrolled bolus or premature loss of liquid, and piecemeal deglutition. Thirteen patients showed abnormal findings in the pharyngeal phase, including vallecular residue after swallow, residue in pyriform sinuses, and delayed onset of laryngeal elevation. Ten of these patients also showed abnormal findings in both the oral and pharyngeal phases. Aspiration was seen in 9 patients. The oral transit duration was significantly longer in the patients with and without aspiration than in the control subjects. The stage transition duration, pharyngeal transit duration, duration of the upper esophageal sphincter (UES) opening, and total swallow duration were significantly longer in the patients with and without aspiration than in the young controls, but were not longer than in the elderly controls. These durational changes in the pharyngeal phase of swallowing were similar to those in the elderly controls. The findings suggest that the disturbed motility in the oral phase of swallowing may be due to bradykinesia. Although PD patients with dysphagia evince a variety of swallowing abnormalities, the duration of pharyngeal swallowing may remain within the age-related range until the symptoms worsen.

We report a patient with peripheral neuropathy caused by cisplatin for the treatment of testicular tumor. Routine studies of nerve conduction and somatosensory evoked potentials demonstrated large myelinated fiber neuropathy suggesting ganglioneuronopathy. We also performed a CO2 laser evoked potential study, and found that small myelinated fibers, which are related to pain sensation, were well preserved in this patient.

We investigated the ascending somatosensory pathway for pain in 8 patients with Machado-Joseph disease (MJD) and multiple system atrophy (MSA). Pain-related somatosensory evoked potentials (pain SEPs) by CO2 laser stimulation were examined together with conventional electrically stimulated somatosensory evoked potentials (electric SEPs). The sporadic cerebellar ataxia of patients with MSA showed a normal pattern of pain SEPs as well as electric SEPs. However, pain and electric SEPs were abnormal for the central and/or peripheral ascending pathway in MJD. These abnormalities of pain and electric SEPs in MJD were not related to the clinical severity of sensory impairment, but they indicate that MJD presents a subclinical abnormality for the ascending somatosensory pathways not only for vibratory sense but also for pain sense.

Background: The adrenal medulla is a typical paraganglion, having the same origin as the sympathetic ganglia, and contains at least two types of parenchymal cells: chromaffin cells and supporting cells. We previously reported that the extent of cellular association of chromaffin cells with supporting cells was remarkably higher in noradrenaline (NA)-than in adrenaline (A)-cell regions in the adrenal medullae of the rat and pig., Methods: Cryostat sections of adrenal medullae of nine mammalian species fixed with Zamboni fluid for 24 h were immunostained by ABC methods using antisera to S-100 protein and PNMT., Results: The distribution patterns of A and NA cells in the adrenal medullae were classified into four types. In the chipmunk and rabbit, adrenomedullary chromaffin cells consisted of A cells. S-100-immunoreactive cells were present more frequently in NA- than in A-cell regions in seven species (rat, golden hamster, cat, dog, pig, ox, and horse). These cells sent out cytoplasmic processes and formed a network by immunoreactive elements among NA cells. The cell-association patterns of S-100-positive cells with NA cell were classified into three types. In A-cell regions, only a few S-100-positive cells were seen in most of the species, although the frequency of S-100-labeled cells were exceptionally high in the horse., Conclusions: The close association of supporting cells with NA cells was commonly found in the adrenal medulla in many mammalian species, irrespective of the proportions and distribution patterns of A cells and NA cells. On the other hand, species differences existed in details of the cellular association between supporting cells and NA cells.

We report herein the cases of three patients in whom marked rapid growth of hepatocellular carcinoma (HCC) became evident after or during interferon (IFN) treatment for chronic hepatitis C. The HCC tumors were 10, 4.7, and 3.1 cm in size, and were found 7 months, 10 weeks, and 10 weeks after the initiation of IFN, respectively, in cases 1, 2, and 3. The clinical courses of these three patients suggest that the progression of HCC was more rapid during the IFN treatment period. Thus, we propose that abdominal ultrasonic (US) examination should be performed monthly in patients with chronic hepatitis who undergo IFN treatment.

Clinical phenotypes and the CAG repeat size of the androgen receptor gene were assessed in 95 Japanese patients with X-linked recessive bulbospinal neuronopathy. There was an age- and duration-dependent deterioration of muscle strength, ADL scores, and plasma creatine kinase levels. However, there was no correlation between the presence of absence of gynecomastia or diabetes mellitus and the age at onset or duration of illness. Correlations were present between the CAG repeat size and the age at onset (P < 0.0001) as well as the presence or absence of gynecomastea (P < 0.05). Muscular weakness and ADL scores were also correlated with the CAG repeat size only when they were adjusted by the age at examination not by the duration of illness. These findings suggest that CAG repeat size is one of the determinant factors of disease progression. However, extensive variation in phenotypic severity in patients with the same size of CAG repeat was present even among the siblings, suggesting that other factors than CAG repeat size influence the phenotypic manifestation. The average gain of CAG repeat size expansion was a 1.4 repeat in paternal transmission which was more unstable than that in maternal transmission, but the magnitude of the expansion in paternal transmission was much smaller than is presently known for other diseases in which CAG repeat expansion is the responsible gene defect.

Among involuntary movements, dystonia is defined as abnormal posturing produced by slow sustained muscle contractions. On the contrary, myoclonus is characterized by sudden shock-like contractions of a muscle or a group of muscles. The electromyogram (EMG) in dystonia shows continuous activity lasting 5 seconds or more. The muscles usually co-contract in the antagonists. In myoclonus the muscle bursts on EMG last usually between 10 and 50 ms. In some cases the bursts last longer, but they are 200 ms at most. Thus, the characteristics of myoclonus is quite different from those of dystonia. There are, however, unusual combination of dystonia and myoclonus. Myoclonic dystonia, in which myoclonic jerks are so severe that crucial dystonic posturing may be ignored, has been reported. Essential tremor, writing tremor and writer's cramp (writing dystonia) and myoclonic writer's cramp are sometimes seen in one family in various combination. It is suggested that there may be pathophysiological relationship between dystonia and myoclonus, although these two movement disorders have different clinical characteristics.

We examined 6 male and 10 female patients with senile tremor which started at 60 years of age or older. The patients' age on examination ranged from 66 to 82 years (mean: 73.4; SD: 5.4 years). The surface electromyogram (EMG) was recorded from the bilateral biceps brachii, triceps brachii, forearm flexor and forearm extensor muscles. The frequency of the tremor was counted and patterns of grouping discharges were analysed. The effect of mechanical perturbation to the affected muscle on tremor rhythm was also examined. The same investigations were performed in 15 male and 7 female patients with essential tremor with onset age before 60 years as control patients. The mean frequency was 6.2 Hz (SD: 1.3 Hz) in senile tremor and 7.3 Hz (SD: 1.5 Hz) in essential tremor. There was a significant difference between the two groups. The mean frequency in control patients whose age on examination was 60 years or over was, however, 6.0 Hz (SD: 0.8 Hz), and there was no difference from the mean frequency in senile tremor. The frequency in both groups was inversely correlated to the patient's age on examination. The antagonist muscles were reciprocally discharged in 15 patients in the senile tremor group and in 7 in the controls. Mechanical perturbation of the affected muscle re-set the tremor rhythm in all patients examined. Thus, senile tremor had characteristics resembling tremor in the control patients, suggesting that senile tremor may be a subtype of essential tremor.

We investigated osteoporosis and fractures in Parkinson's disease in stage II to V according to Hoehn and Yahr's disability scale. The bone mineral density (BMD) of the lumbar spine was measured in 82 patients (24 males and 58 females) and in 99 age-matched controls (28 males and 71 females) using dual energy X-ray absorptiometry, and compression fractures of the vertebrae were assessed on X-ray films. BMD decreased with age in females and was lower in females 60 years of age or over than in males at the same age. BMD in the female patients was significantly lower than in the female controls. The female patients in stage III to V had lower BMD than those in stage II. Both male and female patients with a body mass index (BMI) below 21 showed a lower BMD than those with a BMI of 21 or more. Five male (20.8%) and 37 female (63.8%) patients were diagnosed as osteoporosis. In particular 77.8% of the females aged 60 years or older had osteoporosis. Thirty-three patients (7 males and 26 females) had experienced fractures or were found to have vertebral compression fractures on X-ray films. These results suggested that osteoporosis and fractures are common in female patients with Parkinson's disease and that prevention of fractures must be important especially for patients with osteoporosis.

Clinical and videofluorographic (VF) studies of swallowing were performed in 11 patients with spinocerebellar degeneration (SCD). Eight patients had a subjective symptom of dysphagia. In VF study, seven patients represented abnormal findings in an oral phase such as residue on the tongue (2 patients), reduced tongue control (3 patients), uncontrolled bolus or premature loss of liquid (6 patients), and piecemeal deglutition (4 patients). Seven patients showed abnormality in a pharyngeal phase such as vallecular residue after swallow (5 patients), residue in pyriform sinuses after swallow (4 patients), delayed onset of laryngeal elevation (5 patients), and aspiration during swallow (5 patients). Aspiration was more obvious when barium liquid was swallowed. When the patients aspirated, techniques such as the chin down posture and the supraglottic swallow were tried in 4 of the 5 patients with the evidence of aspiration. The aspiration was prevented in 2 patients. It was suggested that in SCD the change in the form and volume of food is recommended for prevention of aspiration and that the rehabilitation techniques such as the chin down posture and the supraglottic swallow may also improve the dysphagia.

In the adrenal medulla and pineal gland, the morphological and chemical nature of supporting cells were examined immunohistochemically. In the adrenal medulla, supporting cells in noradrenaline (NA)-cell regions showed similar and intense immunoreactivities to the three glial marker proteins, S-100 protein, glial fibrillary acidic protein (GFAP) and vimentin, forming a network, while those in adrenaline (A)-cell regions were less numerous and their immunoreactivity was positive to S-100 protein but negative to GFAP and, at least in part, negative to vimentin. In the pineal gland, supporting cells in the stalk and the proximal region of the body portion formed a network and showed immunoreactivities to the three antibodies, while those in the distal region of the body portion were less numerous and their immunoreactivity was positive to S-100 protein and vimentin, but negative to GFAP. Thus, the distribution pattern and chemical nature of supporting cells showed regional differences in both glands. There were several similarities in supporting cells between those in NA-cell regions of the adrenal medulla and in the stalk and the proximal region of the body portion of the pineal gland, and also between in A-cell regions of the adrenal medulla and in the distal region of the body portion of the pineal gland, respectively. The biological and functional significances of these results are discussed.