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Nobuyoshi Fukuhara

Publications and source records attributed to Nobuyoshi Fukuhara.

9 recordsLinked to original sources
PubMed2006

[A suspected case of alcoholic pellagra encephalopathy with marked response to niacin showing myoclonus and ataxia as chief complaints].

We report a 47-year-old alcoholic man with alcoholic pellagra encephalopathy (APE) showing myoclonus and ataxia as chief complaints. He had been a heavy drinker for 30 years. He had noticed appetite loss and subsequently showed a subacutely progressive gait disturbance. He had no history of diarrhea, dementia, or dermatitis. On admission, he showed severe alcoholic liver cirrhosis with a large amount of ascites, limbs and truncal ataxia, myoclonus of the limbs and areflexia, although his consciousness was alert and there were no sign of dermatitis. Though the plasma level of ammonia was normal, we started administration of amino acids suspecting hepatic encephalopathy. Symptoms showed no improvement, and subsequent administration of thiamine was also ineffective. A decreased serum level of niacin was demonstrated. After administration of nicotinamide, the symptoms improved gradually. This patient received a diagnosis of APE. Endemic pellagra, characterized by the classical triad of dermatitis, diarrhea and dementia, is known to be caused by a dietary deficiency of the niacin, and has now become very rare in developed countries. At present, pellagra is encountered most often in patients with chronic alcoholism, which is called APE. APE patients often show only disturbance of consciousness. Although several reports has described ataxia and myoclonus in patients with APE, APE patients with myoclonus and ataxia as chief complaints have not previously been reported. On autopsy cases, central chromatolysis of neurons in the dentate nucleus of the cerebellum, gracile and cuneate nuclei, and the Clarke's column has been demonstrated. The APE patients would show myoclonus and ataxia as their first symptoms. In conclusion, we would like to emphasize that administration of niacin should be started for the treatment of chronic alcoholic patients showing myoclonus and ataxia even without the classical triads found in endemic pellagra patients.

Alcoholism↗
PubMed2006

[Transient elevation of the number of microembolic signal in a patient with primary antiphospholipid antibody syndrome].

We report a 55-year-old man complaining of monoparesis of the right arm and dementia. Brain magnetic resonance imaging (MRI) demonstrated multiple foci of fresh cerebral embolism. The serum lupus anticoagulant was positive, however, the serum anticardiolipin antibody and other autoantibodies indicating connective tissue diseases were negative. This patient received a diagnosis of primary antiphospholipid antibody syndrome. Transcranial Doppler(TCD) monitoring of the middle cerebral artery showed the presence of microembolic signal (MES). We initiated anticoagulant therapy with intravenous heparin administration, and three days later we added oral warfarin administration. We used both warfarin and heparin together for only three days. The number of MES increased transiently after initiating of warfarin administration, then decreased by warfarin therapy with production of an international normalized ratio (INR) of prothrombin time over 2. His neurological symptoms normalized except for monoparesis of the right arm. There were no foci of fresh cerebral infarct disclosed on brain MRI performed two months after admission. The treatment strategy for antiphospholipid antibody (APS) patients has not yet been established. Some reports and guideline recommended that the stroke patients with APS should be treated with long-term oral anticoagulant therapy, target INR 2.5 (optimal range 2.0 to 3.0). In this patient, we confirmed a decrease in the number of MES by warfarin therapy with production of INR over 2. In APS patients, detection of MES by TCD is a useful device for adjustment of the warfarin dose. Concerning the course of MES and warfarin therapy, transient elevation of the number of MES after initiation of warfarin therapy would suggest the hypercoagulability due to an acute decrease in serum protein C level. Using the TCD technique, we detected such hypercoagulability for the first time.

Anticoagulants↗
PubMed2005

Wobble modification deficiency in mutant tRNAs in patients with mitochondrial diseases.

Point mutations in mitochondrial (mt) tRNA genes are associated with a variety of human mitochondrial diseases. We have shown previously that mt tRNA(Leu(UUR)) with a MELAS A3243G mutation and mt tRNA(Lys) with a MERRF A8344G mutation derived from HeLa background cybrid cells are deficient in normal taurine-containing modifications [taum(5)(s(2))U; 5-taurinomethyl-(2-thio)uridine] at the anticodon wobble position in both cases. The wobble modification deficiency results in defective translation. We report here wobble modification deficiencies of mutant mt tRNAs from cybrid cells with different nuclear backgrounds, as well as from patient tissues. These findings demonstrate the generality of the wobble modification deficiency in mutant tRNAs in MELAS and MERRF.

Base Sequence↗
PubMed2004

Aprataxin, the causative protein for EAOH is a nuclear protein with a potential role as a DNA repair protein.

Early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH) is an autosomal recessive neurodegenerative disorder characterized by early-onset ataxia, ocular motor apraxia, and hypoalbuminemia. Recently, the causative gene for EAOH, APTX, has been identified. Of the two splicing variants of APTX mRNA, the short and the long forms, long-form APTX mRNA was found to be the major isoform. Aprataxin is mainly located in the nucleus, and, furthermore, the first nuclear localization signal located near the amino terminus of the long-form aprataxin is essential for its nuclear localization. We found, based on the yeast two-hybrid and coimmunoprecipitation experiments, that the long-form but not the short-form aprataxin interacts with XRCC1 (x-ray repair cross-complementing group 1). Interestingly the amino terminus of the long-form aprataxin is homologous with polynucleotidekinase-3'-phosphatase, which has been demonstrated to be involved in base excision repair, a subtype of single-strand DNA break repair, through interaction with XRCC1, DNA polymerase beta, and DNA ligase III. These results strongly support the possibility that aprataxin and XRCC1 constitute a multiprotein complex and are involved in single-strand DNA break repair, and furthermore, that accumulation of unrepaired damaged DNA underlies the pathophysiological mechanisms of EAOH.

Alternative Splicing↗
PubMed2003

[A quantitative evaluation of spinocerebellar degeneration by an acoustic analysis--the effect of taltirelin hydrate on patients with Machado-Joseph disease].

A clinical evaluation of 10 patients with Machado-Joseph disease (MJD) was performed by using an acoustic analysis soft (SoundScope, GW Instruments Inc) before and on 4 weeks of treatment of taltirelin hydrate (TH). A rapid repetitive monosyllable/ka/was recorded as the samples were analyzed in a computer. The repetition period (ms) and the maximum intensity (volt) was measured from the sound spectrogram and the amplitude envelope for each speech wave. Three acoustic parameters, which were mean of period (ms) (m-P), coefficient of variation of period (%) (CV-P), and coefficient of variation of amplitude (%) (CV-A), were calculated according to Ishida's acoustic analysis method. The average age in this study group was 52.4 +/- 11.4 years (32-73 years), the mean scores of International Cooperative Ataxia Rating Scale (ICARS) was 35.0 +/- 18.6. Significant correlation was shown between CV-A and ICARS scores before therapy (p < 0.05). CV-P was decreased significantly (p < 0.05) from 10.9 +/- 0.12% to 9.2 +/- 0.26% after TH, and its degree of decrement correlated with ICARS scores (p < 0.05), which means a greater effect of TH is expected in patients with milder symptoms. ICARS scores did not change with a statistical significance. TH was shown to be effective on the ataxic speech of patients with MJD by quantitative methods. The acoustic analysis used in this study is a sensitive and objective evaluation method for following up the clinical severity of MJD and judging effectiveness of a drug.

Adult↗
PubMed2002

A novel mutation in the GNE gene and a linkage disequilibrium in Japanese pedigrees.

Distal myopathy with rimmed vacuoles (DMRV) is an autosomal recessive muscular disorder characterized by weakness of the anterior compartment of the lower limbs with onset in early adulthood and sparing of the quadricep muscles. The UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) gene was recently identified as the causative gene for hereditary inclusion body myopathy (HIBM). To investigate whether DMRV and HIBM are allelic diseases, we conducted mutational analysis of the GNE gene of six Japanese DMRV pedigrees and found that all the pedigrees share a homozygous mutation (V572L) associated with a strong linkage disequilibrium, suggesting a strong founder effect in Japanese DMRV pedigrees.

Carbohydrate Epimerases↗
PubMed2002

[Statistic rCBF study of extrapyramidal disorders].

We studied regional cerebral blood flow (rCBF) in 16 patients with Parkinson's disease (PD), 2 patients with dementia with Lewy bodies (DLB), 2 patients with progressive supranuclear palsy (PSP), 2 patients with striatonigral degeneration, and 16 normal volunteers, using Three-dimensional stereotactic surface projections (3 D-SSP). Decreased rCBF in PD patients was shown in the posterior parietal and occipital cortex. Decreased rCBF in DLB was shown in the frontal, parietal and occipital cortex with relative sparing of the sensorimotor cortex. Decreased rCBF in PSP was shown in the frontal cortex. Decreased rCBF in SND was shown in the frontal cortex and cerebellum. Statistic rCBF analysis using 3 D-SSP was a useful measure for the early differential diagnosis of extrapyramidal disorders.

Aged↗
PubMedDate not supplied

Human cerebellar activation in relation to saccadic eye movements: a functional magnetic resonance imaging study.

PURPOSE: The functional organization of the human cerebellum involved in saccadic eye movements was investigated using functional magnetic resonance imaging (fMRI). METHODS: The subjects were 7 normal volunteers aged 18-34 years. Visual stimuli were back-projected onto a screen placed at the subjects' feet. The stimulation period of 30 s consisted of a saccade target jumping back and forth horizontally by 20 degrees once per second. The control period of 30 s consisted of a fixed target. The stimulation and control periods were alternated 10 times during the presentation. Functional images were collected with a 1.5-tesla clinical MRI scanner. The significance of activation was determined by Statistical Parametric Mapping (SPM 99) at a threshold of p < 0.001 (uncorrected), and significantly activated areas were superimposed on the T(1)-weighted images. RESULTS: Significantly activated areas related to visually guided saccades were observed in the cerebellar vermis (declive and folium), in the bilateral cerebellar hemispheres (mainly the superior semilunar lobule) of the cerebellum, in the frontal eye field, in the supplementary eye field and in parts of the parietal lobule of the cerebrum. CONCLUSION: Our results suggest that the cerebellar posterior vermis and bilateral hemispheres are related to saccades in humans. These results are consistent with neurophysiological data obtained in primates.

Adolescent↗