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Biomedical subjects

Ryuji Kaji

Publications and source records attributed to Ryuji Kaji.

At least 37 records · Page 2Linked to original sources
PubMed2005

Abnormal sensory gating in basal ganglia disorders.

Basal ganglia encompass four to five distinct loops to allow parallel processing of information. Among them, the most intensively studied is the motor loop, which includes two distinct direct and indirect pathways. The direct pathway exerts facilitatory influence upon the motor cortex, whereas the indirect pathway exerts an inhibitory effect. Overall, this dual system provides a center(excitatory)-surround-(inhibitory) mechanism to focus its effect on selected cortical neurons, and several lines of evidence suggest that this center-surround mechanism is used to focus the output on a specific group of muscles required for performing a specific task. This operation is made possible through opening the sensory channel for the expected sensory feed-back afferents during movement. Thus, one of the important functions of basal ganglia seems to be the gating of sensory input for motor control. Dystonia may be caused by a mismatch between sensory input versus motor output, and parkinsonism may be viewed as a disorder of gain control of this sensorimotor integration.

Animals↗
PubMed2005

Molecular dissection and anatomical basis of dystonia: X-linked recessive dystonia-parkinsonism (DYT3).

Pathological findings in dystonia have been unclear. X-linked recessive dystonia-parkinsonism (XDP, DYT3), endemic in the Panay island, the Philippines, is characterized by the clinical onset with dystonia followed by parkinsonism. It provides a unique opportunity to explore the anatomical basis of dystonia, because it has discernible pathological changes even at its early phase of dystonia. After extensive searches for the anatomical basis in XDP, we found selective loss of striosomal neurons in the striatum in dystonic patients' brain. Because striosomal neurons inhibit nigrostriatal dopaminergic neurons via GABAergic innervation, the striosomal lesion could account for dopamine excess in the striatum, which in turn causes a hyperkinetic state or dystonia. We also identified the causative gene as one of the general transcription factor genes, TAF1. XDP has certain similarities to Huntington disease not only in pathological and clinical findings, but also the molecular mechanism, which disturbs expression of genes essential for striatal neurons, such as DRD2. Therapeutic intervention may become possible through pharmacological measures that affect gene expression.

Chromosomes, Human, X↗
PubMed2005

[Molecular and anatomical bases of dystonia: X-linked recessive dystonia-parkinsonism (DYT3)].

Pathological findings in dystonia have been unclear. X-linked recessive dystonia-parkinsonism (XDP, DYT3), endemic in the Panay island, the Philippines, is characterized by the clinical onset with dystonia followed by parkinsonism. It provides a unique opportunity to explore the anatomical basis of dystonia, because it has discernible pathological changes even at its early phase of dystonia. After extensive searches for the anatomical basis in XDP, we found selective loss of striosomal neurons in the striatum in dystonic patients' brain. Because striosomal neurons inhibit nigrostriatal dopaminergic neurons via GABAergic innervation, the striosomal lesion could account for dopamine excess in the striatum, which in turn causes a hyperkinetic state or dystonia. We also identified the causative gene as one of the general transcription factor genes, TAF1. This abnormality markedly reduced the expression of dopamine D2 receptor gene (DRD2) in neurons. XDP has certain similarities to Huntington disease not only in pathological and clinical findings, but also the molecular mechanism, which disturbs expression of genes essential for striatal neurons, such as DRD2. Therapeutic intervention may become possible through pharmacological measures that affect gene expression.

Corpus Striatum↗
PubMed2004

Subthreshold low-frequency repetitive transcranial magnetic stimulation over the premotor cortex modulates writer's cramp.

Writer's cramp, or focal hand dystonia, is characterized by involuntary coactivation of antagonist or unnecessary muscles while writing or performing other tasks. Although the mechanism underlying this muscle overactivation is unknown, recent studies of changes in cerebral blood flow during writing have demonstrated a reduction in the activation of the primary motor cortex (MC) and hyperactivity of parts of the frontal non-primary motor areas. Therefore, any measures that decrease the activities of non-primary motor areas such as the premotor cortex (PMC) and the supplementary motor area (SMA) might improve dystonic symptoms. To explore this possibility, we studied nine patients with writer's cramp and seven age-matched control subjects, using subthreshold low-frequency (0.2 Hz) repetitive transcranial magnetic stimulation (rTMS), which exerts an inhibitory action on the cortex. Previous studies have demonstrated shortened cortical silent periods in dystonia, suggesting deficient cortical inhibition in the MC. We compared the silent periods and computer-assisted ratings of handwriting before and after rTMS applied to the MC, SMA or PMC. We also used the sham coil for control runs. Stimulation of the PMC but not the MC significantly improved the rating of handwriting (mean tracking error from the target, P = 0.004; pen pressure, P = 0.01) and prolonged the silent period (P = 0.02) in the patient group. rTMS over the other sites or using a sham coil in the patient group or trials in the control group revealed no physiological or clinical changes. This increased susceptibility of the PMC in dystonia suggests that the lack of inhibition in the MC is secondary to the hyperactivity of PMC neurons. Inhibition of the PMC using rTMS could provide a therapeutic measure of writer's cramp.

Adult↗
PubMed2004

Influence of polymorphisms in the genes for cytokines and glutathione S-transferase omega on sporadic Alzheimer's disease.

We studied promoter region polymorphisms in the interleukin (IL)-1alpha, IL-1beta, IL-6, IL-10, tumor necrosis factor, and transforming growth factor (TGF)-beta1 genes in Japanese patients with Alzheimer's disease (AD) (n = 172) and normal controls (n = 163). We also examined an association of a polymorphism located in the glutathione S-transferase omega 1 (GSTO-1) gene region with AD patients. None of these genotypes or allele frequencies showed a significant difference between AD patients and controls. We also failed to detect any difference in the disease onset between each genotype of the seven polymorphisms. Although AD patients carrying high producer alleles of TGF-beta1 and IL-1beta or TGF-beta1 and IL-6 showed a tendency for an early onset of the disease, neither of these combined effects reached a significant level after multiple comparisons. Our findings suggest that genetic polymorphisms in the cytokines and GSTO do not play a major role in Japanese AD patients.

Age of Onset↗
PubMed2004

Nucling recruits Apaf-1/pro-caspase-9 complex for the induction of stress-induced apoptosis.

Nucling is a novel protein isolated from murine embryonal carcinoma cells with an up-regulated expression during cardiac muscle differentiation. We show here that Nucling was up-regulated by proapoptotic stimuli and important for the induction of apoptosis after cytotoxic stress. We further demonstrated that overexpressed Nucling was able to induce apoptosis. In Nucling-deficient cells, the expression levels of Apaf-1 and cytochrome c, which are the major components of an apoptosis-promoting complex named apoptosome, were both down-regulated under cellular stress. A deficiency of Nucling also conferred resistance to apoptotic stress on the cell. After UV irradiation, Nucling was shown to reside in an Apaf-1/pro-caspase-9 complex, suggesting that Nucling might be a key molecule for the formation and maintenance of this complex. Nucling induced translocation of Apaf-1 to the nucleus, thereby distributing the Nucling/Apaf-1/pro-caspase-9 complex to the nuclear fraction. These findings suggest that Nucling recruits and transports the apoptosome complex during stress-induced apoptosis.

Alleles↗
PubMed2004

Threshold electrotonus in chronic inflammatory demyelinating polyneuropathy: correlation with clinical profiles.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterized by multifocal demyelination along the course of the nerves, and involvement of the intermediate segments may correlate with more severe demyelination associated with breakdown of the blood-nerve barrier. Threshold electrotonus was used to study whether altered membrane properties of the median nerve at the wrist (intermediate segment) are associated with clinical profiles in 21 CIDP patients. In response to hyperpolarizing conditioning stimuli, the threshold changes were significantly greater for CIDP patients than for normal controls (n = 49). The pattern was similar to that of 11 patients with Charcot-Marie-Tooth disease type 1a, who exhibited abnormally high thresholds to hyperpolarizing currents. The abnormal threshold electrotonus was present in 48% of the CIDP patients and was associated with longer disease duration, more severe disability, poorer response to immune treatments, and slower nerve conduction velocities. Threshold electrotonus can be used to detect demyelination at the tested sites and may provide new information about pathophysiology and distribution patterns of demyelination in CIDP.

Action Potentials↗
PubMed2004

Stress control and human nutrition.

Stress is a pervasive factor in everyday life that critically affects development and functioning. Severe and prolonged stress exposure impairs homeostatic mechanisms, particularly associated with the onset of depressive illness. Brain food is aimed at preventing as well as treating a growing number of stress-related mental disorders. Some topics on the association of stress and nutrition is reviewed. (1) An increased activity of serotonergic neurons in the brain is an established consequence of stress. An increase in brain tryptophan levels on the order of that produced by eating a carbohydrate-rich/protein-poor meal causes parallel increases in the amounts of serotonin released into synapses. (2) Eating is thought to be suppressed during stress, due to anorectic effects of corticotrophin releasing hormone, and increased during recovery from stress, due to appetite stimulating effects of residual cortisol. (3) A strong inverse association between coffee intake and risk of suicide. (4) Night eating syndrome has been found to occur during periods of stress and is associated with poor results at attempts to lose weight and disturbances in the hypothalamic-pituitary-adrenal axis. (5) Dietary antioxidants present in fruits and vegetables may improve cognitive function. Therefore, it is concluded that the establishment of functional foods that correctly regulate stress response must be firmly based upon scientific knowledge and legal regulation.

Antioxidants↗
PubMed2003

Nerve excitability properties in Charcot-Marie-Tooth disease type 1A.

Charcot-Marie-Tooth disease type 1A (CMT1A) is commonly considered a prototype of a hereditary demyelinating polyneuropathy. Apart from the myelin involvement, there has been little information on axonal membrane properties in this condition. Taking advantage of the uniform nature of the disease process, we undertook the in vivo assessment of multiple axonal excitability properties at the median nerve in nine CMT1A patients with PMP22 (peripheral myelin protein 22) gene duplication and 53 controls. The thresholds of CMT1A patients were much higher than normal, and threshold electrotonus (TE) exhibited a consistent pattern of abnormalities: early steep changes (fanning out) of both hyperpolarizing and depolarizing responses were followed by increased inward rectification to hyperpolarizing currents and unusually fast accommodation to depolarizing currents. Strength-duration time constants and the shapes of recovery cycles were normal, although refractoriness and superexcitability were reduced relative to controls. The high thresholds and early fanning out of electrotonus indicated altered cable properties, such that a greater proportion than normal of applied currents reached internodal rather than nodal axolemma. The rapid accommodation to depolarizing currents suggested activation of fast K+ channels, which are normally sequestered from the nodal membrane. The excitability abnormalities are therefore consistent with a demyelinating pathology and exposure or spread of K+ channels from under the myelin. It remains to be seen whether the TE abnormalities in CMT1A, which resemble previous recordings from normal immature rats, can be distinguished from those in acquired demyelinating neuropathies.

Action Potentials↗
PubMed2003

Premovement gating of somatosensory evoked potentials after tibial nerve stimulation.

Somatosensory evoked potentials (SEPs) are attenuated or gated during movement. The mechanism for this includes both centrifugal gating of afferent input and competition with other afferents caused by the movement (peripheral gating). Using a paradigm in which the signal for triggering movement is the electric stimulus for SEPs, we studied the gating of SEPs after tibial nerve stimulation prior to foot movement, and compared it with that during counting task. Significant gating was found for P40 component, which distributed centrally and ipsilaterally to the side of the stimulation, whereas the contralateral N40 component showed no changes. Dissociated gating of P40 and N40 indicates multiple generators of these components, in contrast to the previous view of a single generator dipole projecting tangentially. Together with the previous findings in median SEPs, these gating phenomena should represent a general mechanism for sensori-motor integration in preparation for limb movement.

Adult↗
PubMed2003

Movement-related cortical potentials before jaw excursions in oromandibular dystonia.

Oromandibular dystonia is a neurological disorder characterized by involuntary contraction of masticatory and/or tongue muscles. Cortical negative shifts preceding voluntary movements called "movement-related cortical potentials" (MRCPs) reflect a central motor control process. Reduced amplitude of MRCPs has been reported in other types of dystonia. To elucidate whether the abnormality is observed also in oromandibular dystonia, we compared MRCPs associated with mandibular movements in 6 patients with this condition and in 8 normal subjects. Electroencephalograms (EEGs) were recorded from 11 electrodes, and electromyograms (EMGs) were recorded from the masseter muscle and the suprahyoid muscles. The subjects were asked to repeat mouth opening, closing, and left and right lateral mandibular excursions. MRCPs were obtained by averaging the EEG using the EMG onset as the trigger signal. In the patient group, MRCP amplitudes over central and parietal areas for mouth opening and lateral movements were significantly reduced compared to normal subjects. In normal controls, the MRCPs at mouth opening and closing were symmetrically distributed, whereas those at lateral movements showed predominance over the hemisphere ipsilateral to the direction of the movement. This laterality was lost in the patient group. These results suggest impaired cortical preparatory process for jaw movements in oromandibular dystonia.

Adult↗
PubMed2003

Influence of monocyte chemoattractant protein 1 gene polymorphism on age at onset of sporadic Parkinson's disease.

We studied polymorphisms in the genes for monocyte chemoattractant protein 1 (MCP-1) and CC chemokine receptor (CCR)-2 in 171 Parkinson's disease (PD) patients and 340 controls. Although no associations were found in alleles or genotypes, MCP-1 -2518A/G genotype affected the age-at-onset of PD patients. This effect was also detected in a second PD group, suggesting a possible involvement of MCP-1 in PD.

Adult↗