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Biomedical subjects

N Sunohara

Publications and source records attributed to N Sunohara.

At least 37 records · Page 2Linked to original sources
PubMed1998

Medial nigral dopamine neurons have rich neurotrophin support in humans.

To assess the action of neurotrophin in human dopaminergic neurons, we studied the immunolocalization of neurotrophins or trks in human substantia nigra pars compacta (SNc). The neuromelanin-containing neurons in the SNc showed immunoreactivities for neurotrophins or trks, suggesting an autocrine/paracrine regulation. Quantitative analysis revealed that the percentage of those expressing NGF-like immunoreactivity (NGF-LI), BDNF-LI, NT3-LI, trkA-LI, trkB-LI, or trkC-LI was 66%, 74%, 85%, 66%, 71% or 86%, respectively. The percentage of cells expressing neurotrophins or trks was higher in the medial part than in the lateral part of the SNc. The preferential expression of neurotrophin-trk systems in the medial neurons may, at least partially, explain the differential susceptibility in Parkinson's disease.

Aged↗
PubMed1998

Neutrophin switching in spinal motoneurons of amyotrophic lateral sclerosis.

To clarify the roles of neurotrophins in the human spinal motoneurons, with special reference to amyotrophic lateral sclerosis (ALS), we studied the immunohistochemical localizations of neurotrophins and their receptors in spinal cords of patients with ALS and compared them with controls. In the controls, the majority of motoneurons showed BDNF-, NT3-, trkB- and trkC-like immunoreactivity (-LI) suggesting that the motoneurons receive an autocrine regulation by both BDNF and NT3. In ALS patients, about three-quarters of the motoneurons had degenerated and the remaining motoneurons showed significantly decreased BDNF-LI, increased NGF- and trkA-LI. These findings indicated neurotrophin-switching in the remaining spinal motoneurons of ALS patients from BDNF and NT3 responsive to NGF responsive.

Adult↗
PubMed1998

Immunohistochemical and ultrastructural characterization of ubiquitinated eosinophilic fibrillary neuronal inclusions in sporadic amyotrophic lateral sclerosis.

We found eosinophilic fibrillary neuronal inclusions (EFNI) that were argyrophilic and immunoreactive for anti-ubiquitin in the cerebral cortex of a patient with sporadic amyotrophic lateral sclerosis (ALS) and mild personality changes. Both hematoxylin and eosin and Bodian's preparations revealed the EFNI to be rod-, flame-shaped, or spherical structures existing within the swollen neuronal perinuclear region in the third, fifth, and sixth layers of the fronto-parieto-temporal cortices including the primary motor cortex. On electron microscopy, filamentous profiles aggregated and formed a single bundle or globule in the neuronal perikaryon without any limiting membrane. Most EFNI had a characteristic multiple layer arrangement. The inner core consisted of randomly oriented granule-free tubules with a fuzzy outer contour, measuring 15-20 nm in diameter. The surrounding layer was made up of granule-associated filaments, electrondense free granules, and small vesicular profiles. Large autolysosome-like membrane-bound vesicular profiles were found scattered at the periphery. Neurofilaments were usually mingled with in the surrounding cytoplasm. Many EFNI were also found in dendrites, but only a few in axons. Both granule-free tubules and granule-associated filaments expressed ubiquitin protein epitopes. Aberrant phosphorylation of neurofilament protein and induction of alphaB-crystallin were shown to exist in EFNI-bearing swollen neurons. Despite having a variety of histological appearances, our observations revealed that EFNI all have common immunocytochemical and ultrastructural characteristics, and thus we assume that EFNI represent a series of cytological alterations in the motor and extra-motor cortices of ALS patients.

Amyotrophic Lateral Sclerosis↗
PubMed1998

NACP/alpha-synuclein immunoreactivity in fibrillary components of neuronal and oligodendroglial cytoplasmic inclusions in the pontine nuclei in multiple system atrophy.

We examined neuronal cytoplasmic inclusions (NCIs) and oligodendrocytic glial cytoplasmic inclusions (GCIs) in the pontine nuclei in multiple system atrophy (MSA) using antibodies against the non-amyloid beta component of Alzheimer's disease amyloid precursor protein (NACP/alpha-synuclein). Our immunohistochemical study revealed that anti-NACP antibodies labeled both NCIs and GCIs. Immunoelectron microscopy showed that positive reaction products were localized on the 15- to 30-nm-thick filamentous components of NCIs and GCIs. The present study demonstrates that NACP is associated with cytoplasmic inclusions of MSA, and suggests a role of NACP in abnormal filament aggregation in neuronal degeneration.

Adult↗
PubMed1998

Myophosphorylase deficiency and limb-girdle muscular dystrophy in the same pedigree.

We report 2 familial patients with limb-girdle muscular dystrophy (LGD). The parents of patient 1 showed a consanguineous marriage and patient 2 was a paternal cousin of patient 1. Slowly progressive muscular weakness/wasting and dystrophic changes in the biopsied muscles were observed in both patients. However, a quantitative assay revealed a severely reduced myophosphorylase activity in patient 1 with normal activity in patient 2. A semi-ischemic exercise test disclosed no elevation of venous lactate in patient 1 with a normal increase in patient 2. A leukocytes DNA analysis in patient 1 did not show the gene deficits previously recognized in patients with McArdle's disease (McD). Patient 1 may only have abnormal myophosphorylase activity with dystrophic changes secondary to the myophosphorylase deficiency or coincidentally two genomic abnormalities for McD and LGD. LGD still has heterogenous etiologies and the responsible genes for these two disorders may be closely mapped.

Adult↗
PubMed1998

Repeated injections of nicergoline increase the nerve growth factor level in the aged rat brain.

We studied whether nicergoline, clinically active in chronic cerebrovascular insufficiency, influences nerve growth factor (NGF) levels in the rat brain. In young Fischer rats, repeated intraperitoneal injections of nicergoline (0.3 and 1.0 mg/kg body weight) did not show any effects on frontal NGF contents determined by a highly sensitive enzyme immunoassay. In aged rats, 22-month-old, however, repeated injections of nicergoline (1.0 mg/kg body weight) induced a significant increase in the NGF level in the frontal region.

Aging↗
PubMed1997

CAG repeat length and disease duration in Machado-Joseph disease: a new clinical classification.

To evaluate the clinical characteristics of Machado-Joseph disease (MJD) with reference to CAG repeat length and disease duration, we analyzed neurologic findings in 108 patients from 84 families. The majority of MJD patients presented with an ataxic gait as the initial symptom. Dysarthria and nystagmus were observed from an early stage. Bulging eyes, muscle atrophy and bradykinesia developed later. Patients with a shorter CAG repeat length or later onset had more frequent involvement of proprioceptive sensory deficit. Incidence of abnormal reflexes, tones, and proprioceptive sensation was not associated with disease duration, but with CAG repeat length. Based on these results, we propose a new clinical classification: type A (juvenile type), with hyperreflexia and dystonia, but without a proprioceptive sensory deficit; type C (adult type), with hyporeflexia and a proprioceptive sensory deficit, but without dystonia; and type B (intermediate type), the remaining patients with a mixed presentation.

Adult↗
PubMed1997

Ultrastructural characterization of the tau-immunoreactive tubules in the oligodendroglial perikarya and their inner loop processes in progressive supranuclear palsy.

Coiled bodies and interfascicular threads are conspicuous white matter abnormalities of brains of patients with progressive supranuclear palsy (PSP). Both structures are argyrophilic and immunoreactive for the microtubule-binding protein tau. This report concerns the ultrastructural localization of interfascicular threads and their relationship to coiled bodies in five PSP patients. We showed for the first time that abnormal tubules with a 13- to 15-nm diameter and fuzzy outer contours were the common structures of coiled bodies in the oligodendroglial perikarya and of interfascicular threads. Moreover, the tubules were immunolabeled by anti-tau antibodies. The abnormal tau-positive tubules of interfascicular threads were located in the inner loop of the myelin sheath. Our study further indicated that the thread-like structures in the white matter comprised, at least in part, oligodendroglial processes, and that they were also present in gray matter. We consider that the formation of coiled bodies in the perikarya and of interfascicular threads represents a common cytoskeletal abnormality of the oligodendroglia of PSP patients. Moreover, even though the white matter alterations of PSP resemble those of corticobasal degeneration, there are certain ultrastructural differences in the abnormal oligodendroglial tubules of the two diseases.

Aged↗
PubMed1997

Two cases of MND/ALS developing the syndrome of inappropriate secretion of antidiuretic hormone.

We report 2 autopsy-proven cases of motor neuron disease/amyotrophic lateral sclerosis (MND/ALS), who developed the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) prior to the respiratory failure. With respect to the underlying mechanisms of SIADH in the cases, we considered two factors; 1) dysfunction of the feedback system in ADH secretion via intrathoracic volume receptors caused by changes in intrathoracic circulation, and 2) primarily functional abnormalities in the limbic system which could influence hypothalamic osmoreceptors. It appears that SIADH can be followed by an exacerbation of respiratory dysfunction in MND/ALS.

Amyotrophic Lateral Sclerosis↗
PubMed1997

[A pedigree of autosomal dominant limb-girdle myopathy with rimmed vacuole formation].

We describe a kindred with autosomal dominant myopathy with preferential proximal limb muscle involvement. This disorder is characterized clinically by early adult onset, slow progression, normal life expectancy, weakness and atrophy of proximal limb muscles, especially in the lower limbs. Laboratory examinations showed myopathic changes mixed with neuropathic components on needle electromyography, slight elevation of serum creatine kinase, and absent cardiac involvement. In biopsied muscle findings of two patients, the presence of rimmed vacuoles was the most striking finding to explain muscle degeneration, though a few necrotic fibers were present. The pathologic and clinical findings in the present family are almost similar to those seen in "adult-onset autosomal dominant limb-girdle muscular dystrophy" reported by Chutkow et al.

Aged↗
PubMed1997

[Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy--report of an autopsied Japanese case].

We report a 75-year old Japanese man with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). His family had no consanguinous marriage and his grandfather had migraine attacks. His father showed uncontrollable emotion at the age of 59 followed by gait disturbance, disorientation, pseudobulbar palsy and died at the age of 63. The patient had migraine attacks with aura since 10 year-old and showed uncontrolableness of his emotion and gait disturbance at the age of 63 followed by disorientation, urinary incontinence and pseudobulbar palsy, and died from aspiration pneumonia at the age of 75. The postmortem examination revealed an arteriopathy in the cerebral white matter and meningeal vessels and multiple infarctions in the cerebral white matter corpus callosum, basal ganglia, middle cerebellar peduncle and pontine tegmentum. The affected arterial walls showed eosinophilic and periodic acid Schiff (PAS)-positive granules in the media, which were composed of numerous electron dense small granules in varying sizes on electron microscopic examinations. These granules showed complements (Clq, C3, C4)-like immunoreactivity but did not have IgG-, IgM-, IgA-, kappa and lambda chain-, or beta-amyloid-like immunoreactivities. The clinicopathological features in this patient were compatible with those reported as CADASIL in the European countries and this is the first case report of CADASIL in Japanese race.

Aged↗
PubMed1997

[A case of spastic tetraplegia with medullo-cervical atrophy].

A 48-year-old man, who had spastic tetraplegia and a marked atrophy of the medulla oblongata and upper cervical cord, was reported. He began to walk in spastic fashion at the age of 12 years, and was diagnosed as spastic paraplegia. His father, whose onset of the disorder was 35 years old and died of pneumonia at the age of 69 years, manifested symptoms and a course, both resembling those of the present patient. Generalized weakness progressed gradually, and the patient was confined to bed in his forties. On admission, he showed markedly increased tendon reflexes and pathological reflexes in all the extremities. Muscular weakness was severe in the neck, trunk and extremities, and mild in the facial muscles. There were neither bulbar sign, significant respiratory failure nor fasciculation of muscles. A needle EMG examination revealed no apparent neuropathic findings. MR imaging showed a marked atrophy of the medulla oblongata and upper cervical cord, which was not considered to be secondary to vascular or infectious diseases. Though sensory evoked potentials showed no response at the latencies of central nervous components, visual evoked potentials, brainstem auditory evoked response and blink reflex were normal. This case might represent an unknown hereditary degenerative disease with autosomal dominant inheritance.

Humans↗
PubMed1996

Small increase in triplet repeat length of cerebellum from patients with myotonic dystrophy.

Myotonic dystrophy (DM) is genetically characterized by abnormal expansion of an unstable CTG trinucleotide repeat, located in the 3'-untranslated region of mRNA encoding the family of serine-threonine protein kinases. DNA extracted from various organs of patients with DM was analyzed by the Southern blotting method. We identified differently expanded bands in DNAs from various tissues from patients with DM. In studying the length of the CTG repeat in different regions of the brain, we found a noticeably small increase in repeat length in the cerebellum compared with other tissues. While this phenomenon has been reported in other triplet repeat diseases such as Huntington disease, spinocerebellar ataxia type 1, and dentatorubral-pallidoluysian atrophy, we are the first to describe it in DM. Although the mechanism of expansion of the triplet repeat remains to be defined, the tissue-dependent somatic mosaicism suggests that its occurrence may depend on the differentiated state of each tissue.

Cerebellum↗
PubMed1996

Myotonia congenita with painful muscle cramps.

A sporadic Japanese case of myotonia congenita with painful muscle cramps is reported. Electromyographic examinations disclosed myotonic discharge with dive bomber sounds at insertion, and high-amplitude, high-frequency motor unit potentials during the muscle cramps. Biopsied muscle specimens and EMG findings showed non-specific mild myopathic changes. There was no abnormal expansion of CTG repeat within the myotonic dystrophy gene. This patient's disorder closely resembles Becker's myotonia congenita Type II though the family history of was non contributory.

Biopsy↗
PubMed1996

[Age-related changes in movement-related cortical potentials].

Movement-related cortical potentials (MRCP) were measured in young normal subjects (age < 40) and aged normal subjects (age > or = 60). All were right-handed. MRCPs were recorded for voluntary self-paced extension of the right middle finger or the right foot. For the middle finger extension the latency and slope of the Bereitschaftspotential (BP) and the negative slope (NS') were measured at the contralateral hand motor area, and for the foot movement they were measured from Cz. MRCPs for the finger extension were examined in 12 young subjects (5 men, 7 women, 22-38 years old, mean age 26.3 +/- 5.2 years) and 18 aged subjects (9 men, 9 women, 60-82 years old, mean age 69.4 +/- 7.2 years). BP latency and NS' latency were significantly longer in the aged subjects than in the young subjects (p < 0.001 and p < 0.05, respectively). MRCPs for the foot movement were measured in 10 young subjects (3 men, 7 women, 22-38 years old, mean age 27.1 +/- 5.4 years) and 10 aged subjects (5 men, 5 women, 60-82 years old, mean age 70.3 +/- 8.1 years). BP latency was significantly longer in the aged subjects than in the young subjects (p < 0.05), but NS' latency was not. For both finger and foot extension, neither BP slope nor NS' slope differed significantly between the groups, although both slopes were steeper in the young subjects than the aged ones. These findings suggest that the time required by the cerebrum to prepare for voluntary movement and the period of preparation for movement are longer in aged subjects than in young subjects.

Adult↗
PubMed1995

Reducing bodies in distal myopathy with rimmed vacuole formation.

A 42-year-old woman with distal myopathy with rimmed vacuoles had intracytoplasmic inclusion bodies similar to those described in reducing body myopathy. Since these inclusions were found in fibers with high acid phosphatase activity and occasional rimmed vacuoles, their formation appeared to correlate with active myofibrillar degeneration, but their origin remains unknown.

Adult↗
PubMed1995

Regional cerebral blood flow measurement using Tc-99m HMPAO SPECT in a patient with adrenoleukodystrophy.

Regional cerebral blood flow (rCBF) measurement using Tc-99m HMPAO angiography and SPECT was performed in a patient with adrenoleukodystrophy. The whole brain CBF showed great reduction to 31 ml/100 g/min as compared with an age-matched normal value of 45.9 ml/100 g/min. rCBF showed extremely decreased values of approximately 28 and 10 ml/100 g/min in bilateral frontal cortex and white matter respectively. The SPECT scan provided useful information on gray matter involvement to MRI findings of widespread white matter lesions. This quantitative nuclear medicine technique may contribute to pathophysiologic evaluation of adrenoleukodystrophy complementary with MRI.

Adrenoleukodystrophy↗