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Biomedical subjects

Kenji Nakashima

Publications and source records attributed to Kenji Nakashima.

At least 73 records · Page 4Linked to original sources
PubMed2004

[An update on the familial headache syndromes].

Migraine is a common form of the chronic headache syndromes. Although the pathogenesis of migraine still remains enigmatic, there have been remarkable progress in headache research. Point mutations of P/Q-type Ca2+ channel alpha 1 subunit (CACNA1A) gene have been identified in familial hemiplegic migraine (FHM), which linked to chromosome 19 (FHM-1, OMIM 141500). Na-K ATPase alpha2 gene has been identified as the causative gene for FHM linked to 1q21-23 (FHM-2, OMIM 602481). Common forms of migraine (i.e. migraine with and without aura) seems to be caused from multifactorial genetic factors and environmental factors. An association study of allelic variation at Codon 23 (Cys or Ser) of 5HT2C-R gene in Japanese samples revealed that the Ser allele frequency in migraine with aura was significantly higher than that in the non-headache controls. However, negative association of this polymorphism have been reported in Caucasian migrainures. The C677T allelic variation of 5,10-methylenetetrahydrofolate reductase (MTHFR) are focused on in association with the coronary heart diseases and the cerebrovascular diseases. The T allelic frequency in migraine sufferers was significantly higher than that in controls. The C677T mutation of MTHFR is one of the genetic risk factors for migraine. These observations are confirmed in Turkish, Australian and Spanish samples. Positive associations of angiotensin converting enzyme (ACE) gene, endotheline receptor-A (ET-A) gene, and insulin receptor gene have been reported. Using the genomewide screen technology, significant linkage between the migraine with aura and a marker on 4q24 has been reported in Finnish families. The genome wide screen analysis will be one of the powerful strategies on exploring migraine gene. Genetic study of migraine headache is a promised and fruitful field and will provide deep understanding to migraine headache. Discovery of new responsible or susceptible genes to migraine will also open an avenue to develop new therapeutic strategy of migraine.

Headache Disorders↗
PubMed2003

PI3K is a key molecule in the Nrf2-mediated regulation of antioxidative proteins by hemin in human neuroblastoma cells.

Oxidative stress and ferrous metabolism are important in the pathogenesis in Parkinson's disease. In dopaminergic neurons, several stress proteins are upregulated under oxidative stress. To clarify this mechanism, we investigated hemin-related signal transduction and the induction of oxidative stress-related proteins in SH-SY5Y cells. We identified phosphatidylinositol 3-kinase (PI3K) and Nrf2 as important molecules in the induction of heme oxygenase-1, thioredoxin, and peroxiredoxin-I. PI3K-related signal controlled Nrf2 activation, and consequently, PI3K inhibitors blocked the nuclear translocation of Nrf2 and induction of stress proteins. These observations suggest that PI3K and Nrf2 are key molecules in maintaining suitable conditions under oxidative stress and ferrous metabolism.

DNA-Binding Proteins↗
PubMed2003

Hypertrophy of IMC of carotid artery in Parkinson's disease is associated with L-DOPA, homocysteine, and MTHFR genotype.

In recent years, an intense interest has developed in the association between Parkinson's disease (PD) and hyperhomocysteinemia. Homocysteine (Hcy) is a neuronal excitotoxic amino acid, and is well known as a risk factor for vascular diseases. Some reports suggest that the administration of L-DOPA may promote hyperhomocysteinemia and idiopathic atherosclerosis. In this study, we report that a mild hypertrophy of the intima-media complex (IMC) of the carotid artery, which has been established as a marker for systemic atherosclerosis, is observed in PD patients compared with normal subjects. PD patients that were treated with L-DOPA for long durations showed a hypertrophic IMC, while the patients that were not treated with L-DOPA did not show any hypertrophic changes in the IMC. These hypertrophic changes were observed primarily in patients with a Hoehn-Yahr stage of 3-5. PD patients with hypertrophic IMC of the carotid artery also exhibited elevated plasma levels of Hcy associated with the C677T genotype of 5,10-methylenetetrahydrofolate reductase (MTHFR). Moreover, a prolonged duration of treatment with L-DOPA in patients with MTHFR T/T genotype enhanced the hypertrophy of IMC, compared with patients with the C/C or C/T genotype. These results suggest that hyperhomocysteinemia promoted by the C677T genotype of MTHFR and prolonged treatment with L-DOPA enhances atherosclerosis in PD patients and affects their general condition.

Aged↗
PubMed2003

Visual hallucinations as REM sleep behavior disorders in patients with Parkinson's disease.

To clarify whether visual hallucinations in patients with Parkinson's disease (PD) are related to rapid eye movement (REM) sleep, nocturnal polysomnographic variables were compared between a group with hallucinations (hallucinators, n = 14) and a group without hallucinations (nonhallucinators, n = 8). A multiple sleep latency test (MSLT) was performed on 3 hallucinators, and the content of dreams during daytime REM sleep was investigated. The efficacy of clonazepam, a standard treatment choice for REM sleep behavior disorders, was investigated in 8 hallucinators. Nocturnal polysomnograms of the hallucinators showed a higher amount of stage 1-REM sleep with tonic electromyogram (stage 1-REM) than the nonhallucinators, and the reported occurrences of nocturnal hallucinations corresponded with the periods of stage REM or stage 1-REM in most hallucinators. The frequency of sleep onset REM periods (SOREMP) on the MSLT were pathologically high in the hallucinators, and the content of the dreams during the MSLT period was quite similar to their hallucinations. During clonazepam treatment, the frequency of hallucinatory symptoms decreased in 5 of 8 hallucinators. These results indicate that visual hallucinations in PD are likely to be related to a REM sleep disorder manifested as the appearance of both stage 1-REM during the night and SOREMP in the daytime.

Aged↗
PubMed2003

Development of computerized Kana Pick-out Test for the neuropsychological examination.

The Kana Pick-out Test, which was developed in Japan and done with paper and pencil, is said to be suitable for inspecting higher-order brain function and to be a good method for screening persons with mild or slight dementia. We have developed a computerized version of the Kana Pick-out Test, which runs on a stand-alone computer, intended to be utilized for mass screening and self-administration. The program was developed with Microsoft Visual Basic 6.0 and runs under the Windows operating system on any IBM PC compatible computer. In this study, all subjects could use the system by interacting with the computer and it was found that the system seemed to have the capability of detecting cognitive status equal to the paper-based Kana Pick-out Test. Besides this, we developed a network-based Kana Pick-out game software which was intended to attract user's notice. The game program was written in JAVA language and runs on a web-browser supporting JAVA on any operating system. The program, a so called applet, is located on our web site (http://environ.med.tottori-u.ac.jp) and anyone can use the applet by accessing our homepage.

Adult↗
PubMed2003

Vertical ophthalmoplegia in a demented patient with striatopallidodentate calcification.

A case is presented here of a 73-year-old man who showed signs of dementia, supranuclear vertical ophthalmoplegia, pseudobulbar palsy, axial dystonia, mild rigidity, and parkinsonian gait. Computed tomography of the head revealed symmetrical calcification in the striatum, globus pallidus and dentate nucleus to an extraordinary degree. No metabolic conditions were observed that could explain the intracranial calcification. Oral administration of levodopa improved the patient's motor symptoms to some extent. Ophthalmoplegia, parkinsonism and dementia combined are typically seen in patients with progressive supranuclear palsy. However, the present case and a few others that have been reported would seem to indicate that these unique symptoms might also be found in patients with intracranial calcification.

Aged↗
PubMed2003

Demyelinating and axonal features of Charcot-Marie-Tooth disease with mutations of myelin-related proteins (PMP22, MPZ and Cx32): a clinicopathological study of 205 Japanese patients.

Three genes commonly causing Charcot-Marie-Tooth disease (CMT) encode myelin-related proteins: peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ) and connexin 32 (Cx32). Demyelinating versus axonal phenotypes are major issues in CMT associated with mutations of these genes. We electrophysiologically, pathologically and genetically evaluated demyelinating and axonal features of 205 Japanese patients with PMP22 duplication, MPZ mutations or Cx32 mutations. PMP22 duplication caused mainly demyelinating phenotypes with slowed motor nerve conduction velocity (MCV) and demyelinating histopathology, while axonal features were variably present. Two distinctive phenotypic subgroups were present in patients with MPZ mutations: one showed preserved MCV and exclusively axonal pathological features, while the other was exclusively demyelinating. These axonal and demyelinating phenotypes were well concordant among siblings in individual families, and MPZ mutations did not overlap among these two subgroups, suggesting that the nature and position of the MPZ mutations mainly determine the axonal and demyelinating phenotypes. Patients with Cx32 mutations showed intermediate slowing of MCV, predominantly axonal features and relatively mild demyelinating pathology. These axonal and demyelinating features were present concomitantly in individual patients to a variable extent. The relative severity of axonal and demyelinating features was not associated with particular Cx32 mutations. Median nerve MCV and overall histopathological phenotype changed little with disease advancement. Axonal features of diminished amplitudes of compound muscle action potentials (CMAPs), axonal loss, axonal sprouting and neuropathic muscle wasting all changed as disease advanced, especially in PMP22 duplication and Cx32 mutations. Median nerve MCVs were well maintained independently of age, disease duration and the severity of clinical and pathological abnormalities, confirming that median nerve MCV is an excellent marker for the genetically determined neuropathic phenotypes. Amplitude of CMAPs was correlated significantly with distal muscle strength in PMP22 duplication, MPZ mutations and Cx32 mutations, while MCV slowing was not, indicating that clinical weakness results from reduced numbers of functional large axons, not from demyelination. Thus, the three major myelin-related protein mutations induced varied degrees of axonal and demyelinating phenotypic features according to the specific gene mutation as well as the stage of disease advancement, while clinically evident muscle wasting was attributable to loss of functioning large axons.

Action Potentials↗
PubMed2003

The antiplatelet aggregation effects of aspirin suppositories.

To confirm that aspirin suppositories are an effective treatment for acute ischemic stroke, we examined the suppressive effects of 200-mg aspirin suppositories on platelet aggregation. Aspirin suppositories suppressed platelet aggregation induced by ADP or collagen, and the suppression continued for 24 h. There was no significant difference in suppression of platelet aggregation between aspirin administered by suppository and orally given aspirin. These results suggest that aspirin suppositories are a useful treatment for acute ischemic stroke.

Adenosine Diphosphate↗
PubMed2003

Steroid-responsive limbic encephalitis.

A 71-year-old man presented with gradually progressing cognitive decline following acute febrile exanthematous disorder. The MRI showed an abnormality in the bilateral limbic systems. An elevation of cerebrospinal fluid (CSF) protein with lymphocyte pleocytosis was noted. Immunoblot of the CSF revealed the presence of anti-white matter antibodies that mainly recognized astrocytes. Intravenous steroid followed by oral steroid reduced the symptoms to a remarkable degree. The patient has now been successfully sustained with steroid for more than two years. We considered that this case is classified as non-paraneoplastic limbic encephalitis, and acquired autoimmunity played a major role in the pathogenesis of this case.

Aged↗
PubMed2003

Brainstem infarction presenting with neurogenic stuttering.

We reported a sixty-year-old man who developed acquired stuttering after a brainstem infarction. Infarctions were detected in the midbrain and upper pons. Neurogenic stuttering of this patients indicated that the midbrain and upper pons could be lesion sites responsible for acquired stuttering. We speculated that the reticular network extending from the brainstem to the frontal cortices, and the periaqueductal gray matter could be closely related regions generating neurogenic stuttering.

Brain Stem Infarctions↗
PubMed2003

[The measurement of phosphorylated tau in human cerebrospinal fluid as a diagnostic marker for Alzheimer's disease].

We examined total 570 cerebrospinal fluid (CSF) samples from a variety of diseases, including Alzheimer's disease (AD; n = 236), non-AD-demented and nondemented diseases (n = 239), and normal controls (n = 95) to quantitate levels of tau protein phosphorylated at serine 199 (CSF/p-tau199) by a recently established sandwich ELISA. The CSF/p-tau199 levels in the AD group were significantly elevated compared to those in all the other non-AD groups. Receiver operating characteristics curves showed that the diagnostic sensitivity and specificity for the AD group vs all the other non-AD group using the CSF/p-tau199 were 85. 2% and 85.0%, respectively. Although there was a significant positive correlation between CSF/p-tau199 and CSF total tau (CSF/t-tau) levels in the AD group, CSF/p-tau199 classifies patients with AD and other disorders more accurately than the CSF/t-tau. Our study suggests that CSF/p-tau199 testing will help in supporting antemortem diagnosis of AD and in conducting emerging therapies that should be based on an accurate detection of AD while patients are alive.

Adult↗
PubMed2003

[A case report of syphilitic meningitis with right oculomotor nerve palsy].

A 63-year-old man presented with acute-onset right ptosis and diplopia. The patient reported having engaged in unspecified sexual activities during his third decade and was found to have positive syphilitic serological findings at the age of 56 years. No clinical symptoms were noted at this time. On admission, he showed only right oculomotor nerve palsy. The patient's intelligence, gait and sensory functions were normal. Laboratory analysis revealed positive syphilitic serological findings and examination of the cerebrospinal fluid (CSF) further revealed pleocytosis, a higher IgG index and positive syphilitic reactions. A computed tomographic scan and other imaging studies were diagnostically nonspecific. We made a diagnosis of right oculomotor nerve palsy due to syphilitic meningitis. We treated the syphilitic meningitis with intravenous injections of penicillin G (24 million units per day for 21 days). Jarisch-Herxheimer reaction and other side effects were not apparent. We first made a thorough examination of the CSF to rule out diagnosis of meningitis, and pursued methylprednisolone pulse therapy (MPP, 1 g/day for 3 days) to treat the oculomotor nerve palsy. The ptosis and diplopia showed signs of improvement following the second MPP therapy session. The present case suggests that neurosyphilis is an important differential diagnosis for presentations of unspecific oculomotor nerve palsy and that MPP therapy may prove an effective treatment for it, even where there has been the long clinical onset.

Humans↗
PubMed2003

[A case of acute cholinergic adverse effects induced by donepezil overdose: a follow-up of clinical course and plasma concentration of donepezil].

A 79-year-old woman with Alzheimer's disease was admitted due to acute cholinergic symptoms induced by overdose (45 mg) of donepezil (DPZ). Physical examination showed bradycardia, sinus arrhythmia, vomiting and respiratory insufficiency. She was treated with atropine intravenously and her cholinergic symptoms subsided in the next evening. After 5 days she was discharged from the hospital and DPZ was withholded for about 4 weeks. The plasma concentration of DPZ was 54.6 ng/ml on admission and gradually decreased to the normal limits in about 90 hours. The calculative half-life of DPZ was about 55 hours. Since the half-life of DPZ is long and differs between individuals, hospitalization and treatment with atropine is recommended for cholinergic side effects induced by overdose of DPZ. It is important to prevent dosing errors in cooperation with medical providers, patients and families.

Aged↗
PubMed2002

Double-blind crossover study of branched-chain amino acid therapy in patients with spinocerebellar degeneration.

To determine whether treatment with branched-chain amino acids (BCAA) can improve the condition of patients with ataxia, a double-blind crossover study of BCAA therapy was performed in 16 patients with spinocerebellar degeneration (SCD). The patients were treated with BCAA in oral doses of 1.5, 3.0, or 6.0 g or with placebo daily for 4 weeks in each study phase. The order of treatment phases (placebo or BCAA) was assigned randomly. An International Cooperative Ataxia Rating Scale (ICARS) was used to quantify the severity of symptoms of SCD. The mean ICARS score improved significantly with BCAA treatment compared with the mean pretreatment score (p<0.01). In addition, the improvement in the mean global ICARS score was significant in the middle-dose group compared with that in the placebo group (p<0.02). The estimated improvement in kinetic functions compared with pretreatment (p<0.01) was significant after treatment with BCAA, 1.5 and 3.0 g. All of the responders manifested predominantly cerebellar symptoms, especially those with spinocerebellar ataxia type 6 (SCA6). Thus, treatment with BCAA may be effective in patients with the cerebellar form of SCD.

Aged↗
PubMed2002

Non-linear dynamics applied to human respiratory movement during sleep.

We investigated the relationship between approximate entropy (ApEn) and correlation dimension (D2) in respiratory movement to reveal the non-linear dynamics in respiration during sleep. Seven healthy volunteers participated in this study. We recorded respiratory movement during sleep at night. We estimated the values of D2 and ApEn in respiratory movement. A significant relationship was observed between ApEn and D2 during sleep (r = 0.67, P < 0.001). Surrogate data analysis revealed that the respiratory movements had significant non-linear property. This evidence suggests that ApEn and D2 may become new indices to evaluate non-linear respiratory dynamics during sleep.

Adult↗
PubMed2002

Static stabilometry in patients with migraine and tension-type headache during a headache-free period.

The vestibulospinal system was evaluated using a stabilometric method in patients with migraine and episodic tension-type headache during headache-free periods. Migraine patients often complain of dizziness or vertigo during headache attacks and some exhibit these symptoms between attacks. Computerized static stabilometry is a reliable and non-invasive technique to evaluate the equilibrium function in various diseases. The subjects consisted of 21 patients with migraine, 12 patients with episodic tension-type headache and, age- and sex-matched controls. We performed two sets of static stabilometric measurements with eyes open (EO) and eyes closed (EC) for 30 s. The averages of two sessions of the following six stabilometric parameters were used for the analysis: locus length (LNG), environmental area (ENV-AREA), rectangle area (REC-AREA), locus length per second, locus length per environ area (L/E), and root mean square area. Romberg quotients (EC/EO) of these six parameters were also analyzed. The mean values of LNG, ENV-AREA and REC-AREA in the EC session in the migraine group were significantly greater than those in the controls (P < 0.05, Mann-Whitney rank sum test). Romberg quotients of all stabilometric parameters except the L/E in the migraine group were significantly greater than in the controls. Patients with episodic tension-type headache did not show any differences in the stabilometric study from the controls. The present findings suggest that patients with migraine show a significant increase of the body sway during the EC session, which indicates an underlying dysfunction in the vestibulospinal system.

Adolescent↗