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Biomedical subjects

S Tsuji

Publications and source records attributed to S Tsuji.

At least 415 records · Page 23Linked to original sources
PubMed1997

Molecular genetics of triplet repeats: unstable expansion of triplet repeats as a new mechanism for neurodegenerative diseases.

Expansion of trinucleotide repeats has been identified as a common mechanism of hereditary neurodegenerative diseases including spinal and bulbar muscular atrophy (SBMA), Huntington's disease, dentatorubral-pallidoluysian atrophy (DRPLA), Machado-Joseph disease (MJD), fragile X syndrome, myotonic dystrophy and Friedreich's ataxia. These diseases share unique features, which are difficult to explain based on Mendelian inheritance. These unique clinical genetic features include genetic anticipation and a broad spectrum of clinical presentations, which have been shown to be associated with the instability of the trinucleotide repeats. Recent studies suggest that gene products with expanded polyglutamine tracts may be toxic to neuronal cells, and the mechanisms of neurotoxicity should be thoroughly investigated. To develop therapeutic measures, creation of animal models or cell culture systems for the investigation of neurotoxicity will be indispensable.

Age of Onset↗
PubMed1997

Cerebellar ataxia and peripheral neuropathy due to chronic bromvalerylurea poisoning.

A patient with chronic bromvalerylurea poisoning showed cerebellar ataxia and peripheral neuropathy. The patient was a 42-year-old Japanese man who developed consciousness disturbance, diplopia, slurred speech, ataxia and gait disturbance after having taken bromvalerylurea for ten years. Magnetic resonance imaging revealed atrophy of the cerebellum and pontine tegmentum. An electrophysiological study revealed decreased motor nerve conduction velocity and amplitude of compound muscle action potentials of the right tibial nerve. Histological findings of the left sural nerve indicated a slightly decreased large myelinated fiber diameter, which suggested chronic axonal damage.

Adult↗
PubMed1997

[Clinical characteristics and linkage analysis of autosomal recessive form of juvenile parkinsonism(AR-JP)].

We present the clinical characteristics of autosomal recessive form of juvenile parkinsonism(AR-JP) (MIM 600116) and the result of the linkage analysis using 11 markers on the long arm of chromosome 6. We examined 25 patients of 13 Japanese AR-JP families. They showed female predominance, mean age at onset at 24.4 +/- 10.3 years, slow progression, good response to levodopa and frequent occurrence of wearing-off phenomenon and dopa-induced dyskinesia. Compared to Parkinson's disease(PD), the parkinsonian triad(tremor, rigidity and bradykinesia) were mild, but dystonic posture, postural instability and hyperreflexia were more prominent compared to PD. By the linkage analysis, we obtained a strong evidence for linkage of the AR-JP gene to a 17 cM region of chromosome 6q25.2-27 including the Mn-superoxide dismutase gene(SOD2) with a maximal cumulative multipoint lod score of 9.44 at 0.9 cM telomeric to D6S253.

Adolescent↗
PubMed1997

Localization of a gene for an autosomal recessive form of juvenile Parkinsonism to chromosome 6q25.2-27.

An autosomal recessive form of juvenile Parkinsonism (AR-JP) (MIM 600116) is a levodopa-responsive Parkinsonism whose pathological finding is a highly selective degeneration of dopaminergic neurons in the zona compacta of the substantia nigra. By linkage analysis of diallelic polymorphism of the Mn-superoxide dismutase gene (SOD2), we found a family with AR-JP showing perfect segregation of the disease with the SOD2 locus. By extending the linkage analysis to 13 families with AR-JP, we discovered strong evidence for the localization of the AR-JP gene at chromosome 6q25.2-27, including the SOD2 locus, with the maximal cumulative pairwise LOD scores of 7.26 and 7.71 at D6S305 (theta = .03) and D6S253 (theta = .02), respectively. Observation of obligate recombination events, as well as multipoint linkage analysis, placed the AR-JP gene in a 17-cM interval between D6S437 and D6S264. Delineation of the AR-JP gene will be an important step toward our understanding of the molecular mechanism underlying selective degeneration of the nigral neurons.

Adolescent↗
PubMed1997

[The diagnosis of amyotrophic lateral sclerosis supported by motor evoked potential and brain MRI studies].

A 57-year-old man developed severe muscle weakness and atrophy of the upper extremities within a five-month period. Neurological examination revealed severe weakness and atrophy in the scapular muscles and proximal and distal muscles of the upper extremities. Fasciculations were also observed in the various muscles of the upper extremities. There was neither muscle weakness, atrophy nor fasciculation in either his face, neck muscles or lower extremities. He had no pseudobulbar or bulbar signs. Tendon reflexes were mildly hyperactive in the jaw and lower extremities, and normal in the upper extremities. There were no pathological reflexes, spasticity or sensory disturbances. The needle EMG study revealed denervation potentials in all muscles of the upper extremities examined. The nerve conduction study revealed no findings of the conduction block. Cervical spine X-rays revealed the narrowing of the spinal foramens at the left C3/C4 and bilateral C4/C5, C5/C6, and C6/C7 intervertebral levels. In addition, magnetic resonance imaging (MRI) revealed compressions of the cervical cord at C4/C5 and C5/C6 intervertebral levels. These clinical and neuroradiological findings resembled those of the cervical spondylotic amyotrophy (CSA). However, the motor evoked potential (MEP) study revealed the pyramidal tract dysfunction above the levels of the pyramidal decussation. Furthermore, brain MRI revealed abnormal foci in both internal capsules which were characterized by hyperintense relative to cortical gray matter on T2-weighted images and still hyperintense to white matter on proton-density-weighted images. In addition, T2-weighted images demonstrated a low signal within the motor cortex and hyperintense lesions in the white matter of the precentral gyri. These MRI findings indicated the degeneration of the pyramidal tract and corresponded to those found in the patients with amyotrophic lateral sclerosis (ALS) which have been recently reported. It has been difficult to distinguish ALS from CSA. However, MEP and brain MRI studies were useful for distinguishing these two diseases in this patient. In addition, this patient showed typical MRI findings suggesting the degeneration of the pyramidal tract, although this patient had a relatively short course of illness and did not show obvious physical findings suggesting pyramidal tract dysfunction.

Amyotrophic Lateral Sclerosis↗
PubMed1997

Endothelin-1 in the gastric mucosa in stress ulcers of critically ill patients.

OBJECTIVE: Gastric microcirculatory disturbances are involved in the pathogenesis of stress ulcers; however, vasomodulators causing this process are not fully understood. This study was conducted to investigate the role of endothelin 1 (ET-1), a potent vasoconstrictive peptide, in stress ulcers in critically ill patients. METHODS: Using sandwich enzyme immunoassay, we measured ET-1 content in plasma and the gastric mucosa of 16 critically ill patients with traumatic head injury on admission and of 11 healthy subjects. Gastric mucosal samples were obtained endoscopically. When gastric drainage contained occult blood, endoscopic examination was performed again, and ET-1 concentrations in injured and adjacent normal mucosa were compared. RESULTS: Plasma and mucosal ET-1 concentrations were significantly higher in critically ill patients on admission (6.1 +/- 0.6 pg/ml and 13.8 +/- 1.6 ng/g, respectively) compared with values in control subjects (2.7 +/- 0.4 pg/ml and 8.2 +/- 0.5 ng/g, respectively) (p < 0.01). The mucosal ET-1 concentration tended to be elevated in patients who had experienced hypoxia compared with those who had not (p = 0.07). In five patients who were again examined endoscopically, the ET-1 concentration in the injured mucosa was significantly higher than that in adjacent mucosa (19.2 +/- 3.2 and 10.1 +/- 1.6 ng/g, respectively; p < 0.05). CONCLUSIONS: These results suggest that endogenous ET-1 plays an important role in the local pathogenesis of stress ulcers, especially those caused by hypoxia.

Adult↗
PubMed1997

[Posterior cortical atrophy with incomplete Bálint's syndrome].

We report a patient of posterior cortical atrophy (PCA) with progressive memory disturbance and incomplete Bálint's syndrome consisting of optic ataxie (ataxie optique type) and visual inattention without psychic paralysis of fixation of gaze. The patients is a 58-year-old woman who noticed memory disturbance at 53 years old. Neurological deficit at 54 years old was detected only in the domain of memory, and mild diffuse brain atrophy was revealed on MRI. Memory disturbance progressed gradually, and at the age of 58 she was noticed to have visual disorder. Neuropsychological examination revealed severe memory disorder, incomplete Bálint's syndrome, transcortical sensory aphasia, mild ideational apraxia, and severe constructional apraxia. Visual inattention was too severe to evaluate visual acuity and visual field. MRI showed moderate dilatation of bilateral lateral ventricles, especially in their posterior horns, with atrophy of bilateral temporo-parieto-occipital lobes and hippocampus. IMP-SPECT revealed a diffuse decrease of cerebral blood flow in the bilateral temporo-parieto-occipital region, predominantly in the parietal regions. We believe that she is still in the early phase of PCA, and that psychic paralysis of fixation of gaze, visual agnosia will be noted in several years. Our patient represents an example of early stage PCA from neuropsychological and MRI findings.

Ataxia↗
PubMed1997

[Clinical significance of 123I-MIBG myocardial scintigraphy in patients with hypertrophic cardiomyopathy].

We studied the abnormality of myocardial sympathetic nervous system in patients with hypertrophic cardiomyopathy using 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in comparison with the parameters of other clinical examinations. In 50 patients with HCM, the heart to mediastinum 123I-MIBG uptake ratio (H/M) was significantly low and washout rate (WR) of 123I-MIBG was significantly high respectively compared with normal subjects (n = 8). H/M was negatively correlated with serum norepinephrine level, wall thickness of left ventricle, left ventricular mass index, left ventricular end diastolic pressure respectively, and WR was positively correlated with those parameters respectively. On the other hand, LF/HF calculated by spectral analysis in holter electrocardiogram was positively correlated with H/M, and negatively correlated with WR. In HCM, H/M in patients with subjective symptoms was significantly lower than that without subjective symptoms, and WR in patients with paroxysmal atrial fibrillation was significantly higher than that without paroxysmal atrial fibrillation. This study revealed that H/M and WR reflected the severity and the difference of disease type in HCM. In conclusion, 123I-MIBG contributes to evaluating more details in diagnosis and pathophysiology of HCM.

3-Iodobenzylguanidine↗
PubMed1997

[An adult case of bacterial meningitis caused by penicillin-resistant Streptococcus pneumoniae with gene mutations of penicillin binding proteins].

A 62-year-old Japanese male developed acute bacterial meningitis. Administration of ABPC, CDZM, INH, and RFP was started. The causative bacteria was identified as penicillin-resistant Streptococcus pneumoniae (PRSP) 3 days later. We changed ABPC to PAPM/BP and the bacterial meningitis improved dramatically. Measurement of minimum inhibitory concentration (MIC) of the bacterial strain from CSF and blood showed that it is susceptible to PAPM/BP and RFP. Mechanism of drug resistance is considered to be gene mutations of penicillin binding protein (PBP) that decreases drug affinity to PBP. Recently penicillin resistance of Streptococcus pneumoniae has been found to be associated with mutations of pbp-2b, 1a genes and the cefem resistance of that is with those of pbp-2x, and 1a genes. By PCR (polymerase chain reaction) analysis we identified the mutations of pbp-1a, 2x, and 2b genes of the isolated strain of Streptococcus pneumoniae. We emphasize the importance of detection of pbp gene mutations for the diagnosis of PRSP infections.

Acute Disease↗
PubMed1997

[A case of lumbosacral lipoma-associated adult onset tethered cord syndrome with initial symptoms of sensory disturbance and intractable foot ulcers].

A 63-year-woman who complained of sensorimotor disturbance of the lower extremities and urinary disturbance was presented. She noted loss of superficial sensation in both feet and foot ulcers at the age of 20 years. Her illness was initially diagnosed as hereditary sensory neuropathy type 1 (HSN1). The foot ulcers were so intractable that she had to have her right leg amputated at the age of 48 years. She had a severely impaired superficial sensation in the lower extremities and buttock, distal weakness of the left leg, and dysuria at the age of 60 years. The neurological examination revealed that she had segmental sensorimotor disturbance below the levels of the 5th lumbar segment. MRI demonstrated tethered cord with a lumbosacral lipoma. Adult onset tethered cord syndrome (TCS) that presents with HSN 1-like symptoms as initial clinical features has not yet been reported. Foot ulcers are often seen in child onset TCS in which the degree of tethered cord is severer than adult onset cases. It is reported that release of the tethered cord promotes healing of the foot ulcers. We recommend MRI for the study of the lumbosacral cord of patients with HSN 1-like symptoms, because there is a possibility that such patients may have TCS and early surgical treatment is effective for TCS.

Charcot-Marie-Tooth Disease↗
PubMed1997

[Distal myopathy with rimmed vacuoles(DMRV)].

Distal myopathy with rimmed vacuoles (DMRV) is an autosomal recessive muscular disorder that has been predominantly reported to occur in Japanese population. This disease is characterized clinically by weakness of the distal muscles in the lower limbs in early adulthood, most typically in the tibialis anterior muscle presenting with footdrop. Recently, the gene locus for familial vacuolar myopathy sparing quadriceps muscle with autosomal recessive inheritance (hereditary inclusion body myopathy, HIBM), which was reported to occur in Jews of Persian origin, was mapped to chromosome 9. Since DMRV and HIBM share similar clinical, genetic, and histopathological features, we performed linkage analysis on seven DMRV families. Detection of obligate recombination events as well as pairwise and multipoint linkage analyses revealed that the most likely location of the DMRV gene is in a 23.3 cM interval defined by D9S319 and D9S276 on chromosome 9, which overlap the critical region for HIBM locus. The results raise the possibility that DMRV and HIBM are allelic disease. Identification of the gene(s) for DMRV and HIBM using positional cloning strategy will lead to clarification of the genetic homogeniety for these diseases as well as the understanding in common pathways causing muscle degeneration with vacuolar formation.

Chromosome Mapping↗
PubMed1997

[Effect of maternal paternal transmissions on clinical manifestations of CTG repeat on myotonic dystrophy].

The increasing size of the CTG repeat in successive generations is considered to the molecular basis for anticipation in DM. Maternal offspring show severe clinical manifestation than paternal transmitted offspring. The intergenerational amplification of this repeat is influenced by the sex of the parent transmitting mutant allele, in that a greater average intergenerational amplification is seen on maternal transmission. Also in the severest form of CDM almost exclusively transmitted maternal allele, the number of repeats is generally higher than that seen in non-CDM. But whether the unknown another maternal factor influence defined children having large mutant allele from mother is important question. The parental bias based on the different methylation patterns, mitochondria genome or different expressions of mRNA species are unlikely. The maternal effect might be explained the differences of the expressions of mRNA according to alternating splicing. And intrauterine effect, chromosomal imprinting or other unknown maternal factors have been expected to be involved in the pathophysiology.

Alleles↗
PubMed1997

[The correlation of the heteroplasmy of mtDNA and clinicopathological findings in the patients with mitochondrial encephalomyopathies].

In most cases of the mitochondrial encephalomyopathies, the mutations of mtDNA usually appear in heteroplasmic states. The degree of mtDNA heteroplasmy has been suggested to play an important role in determining the clinical phenotype and the organ-specific defects. We had devised a novel method for quantitative analysis of heteroplasmy using PCR-SSCP, this method is useful to accurately quantitate heteroplasmy of very small amount of samples. Using this method, we analyzed the heteroplasmy of skeletal muscle or leucocyte from 12 cases of MERRF and 5 cases of MELAS. And we analyzed autopsied cases (2 MERRF and 2 MELAS patients), and the cellular or organellar distributions of heteroplasmy of CNS in MERRF patients, and discussed the correlation of heteroplasmy of mtDNA and clinicopathological findings.

Adolescent↗
PubMed1997

[The diagnosis and follow-up evaluation of acute cerebellar ataxia supported by a cerebellar stimulation study].

A 70-year-old woman who has been suffering from diabetes mellitus since 67 years of age rapidly developed severe truncal ataxia. Neurological examination showed severe truncal ataxia, incoordination and decreased deep sensations in the bilateral lower extremities. A CSF study revealed a moderately elevated total protein (125 mg/dl) without any elevation of the cell count. A nerve conduction study supported the diagnosis of polyneuropathy. Lumbar MRI revealed spinal canal stenosis at the L3/L4-L5/S1 intervertebral levels due to disk herniations and ossification of the yellow ligaments. We examined cerebellar stimulation in order to determine whether the ataxia was due to dysfunction of the cerebellum or peripheral nervous system. Conditioning electrical stimulation over the cerebellum did not change the size of motor potentials evoked by magnetic cortical stimulation in the right first dorsal interosseous muscle. Her clinical course was good, and the limb and truncal ataxia became very mild about 4 months after the onset, although there was little change in the decreased deep sensations. The cerebellar stimulation in the second study was normal. We diagnosed her as having acute cerebellar ataxia and thought that the decreased deep sensations were due to diabetic polyneuropathy and lumbosacral radiculopathies. A cerebellar stimulation study was useful for the diagnosis and follow-up evaluation of acute cerebellar ataxia in this patient.

Acute Disease↗
PubMed1997

[A case of cortical reflex positive-negative myoclonus--electrophysiological study].

An 11-year-old girl who had the positive-negative myoclonus and the history of the generalized tonic clonic seizure was electrophysiologically studied. She had no siblings with either myoclonus or epilepsy, and her intellectual level was normal. She had no other neurological deficits including ataxia, pyramidal and extrapyramidal signs. Surface EMG showed a brief increase in the EMG activity followed by the silent period associated with positive and negative myoclonus during sustained wrist extension. Giant SEP and C reflex (38.6 ms) following electric stimulation of the median nerve at the wrist were obtained in the resting condition and the silent period (about 180 ms) following C reflex was obtained during voluntary contraction. Jerk-locked back averaging of the EEG time-locked to the onset of the myoclonic discharge recorded from the right biceps muscle showed a cortical spike at the left central region preceding the myoclonus onset by 12.6 ms. The latency of C reflex in this case was very short compared with that of previously reported cortical reflex myoclonus. The estimated cortical delay between the arrival of the somatosensory volley and the motor cortex discharge responsible for the C reflex was -1.0 ms and this value was shorter than that in patients with typical cortical reflex myoclonus (mean 3.7 +/- 1.1 ms). Conditioning stimuli (C) of the right median nerve at the wrist started to facilitate the amplitude of the motor evoked potential recorded from the right abductor pollicis brevis muscle after magnetic test stimuli (T) of the left motor cortex at 20 ms of the C-T interval. This C-T interval was shorter than that (24.6 +/- 1.6 ms) in patients with the typical cortical myoclonus. These electrophysiological findings suggested the shorter reflex pathway of the cortical reflex myoclonus in this case than in typical cortical reflex myoclonus. We speculated that the myoclonus was based upon the direct sensory projection from the thalamus to the motor cortex in this case.

Child↗
PubMed1997

[Electrophysiological study of a case of clinically diagnosed corticobasal degeneration with rhythmic myoclonus].

A 66-year-old man with clinically diagnosed corticobasal degeneration was studied electrophysiologically. The patient had bilateral forced grasping, rigidity, bradykinesia and hyperreflexia which were predominant on the right side, motor aphasia, constructional apraxia, forced laughing, dysequilibrium and myoclonus of the right upper extremity. Several anti-parkinsonism drugs were ineffective. Brain MRI revealed cortical atrophy of the fronto-temporo-parietal lobes with left predominance. On single photon emission computed tomography, cerebral blood perfusion was decreased, especially on the left side in the fronto-temporal lobes, basal ganglia and thalamus. Myoclonus was distal dominant, worse on action or posture, and was rhythmic, mimicking a tremor. On surface EMG recording of the myoclonus, agonist and antagonist muscle pairs were activated simultaneously and rhythmic activities with frequencies ranging from 7 to 8 Hz were seen. The patient had an enhanced C reflex with a relatively short latency (41.0 ms) after median nerve stimulation only at the right wrist. Additionally, during voluntary contraction, the time-constant EMG silence lasting for about 80-90 ms followed the C reflexes. On somatosensory evoked potentials (SEPs) to the median nerve stimulation, N20 latencies were normal and P25 and N33 amplitudes were not giant. There was no premovement corticat spike when a jerk-locked averaging method was used. Regarding motor evoked potentials (MEPs) elicited by magnetic brain stimulation, central motor conduction times were normal. The estimated cortical delay between the arrival of a somatosensory volley and the motor cortical discharge responsible for C reflex was 1.0 ms, which was shorter than those (3.1 +/- 0.9 ms) estimated in five patients with typical cortical reflex myoclonus. A conditioning stimulation (C) of the right median nerve produced marked facilitation of MEPs following magnetic stimulation of the left motor cortex, at conditioning-test intervals (C-T intervals) of 20-22 ms, whereas a conditioning stimulation of the left median nerve did not produce the same effect. These C-T intervals were thought to be very short, considering that N20 latency was 19.6 ms in this patient. The duration of the EMG silence following the C reflex corresponded to that of the EMG silence between muscle activities during his rhythmic myoclonus, and also the myoclonus was reset by occurrence of the C reflex. These electrophysiological findings indicate that his myoclonus was based upon the enhancement of direct sensory input from the thalamus to the motor cortex. Moreover, it is suggested that the existence of the time-constant EMG silence following the C reflex was related to the myoclonal rhythm.

Aged↗