Biomedical subjects

H Ujike

Publications and source records attributed to H Ujike.

At least 37 records · Page 2Linked to original sources

PubMed2001

Prevalence of homozygous deletions of the parkin gene in a cohort of patients with sporadic and familial Parkinson's disease.

Mutation of the parkin gene is a cause of familial Parkinson's disease of the autosomal recessive form; however, its significance in all Parkinson's disease cases is unclear. Deletions in the parkin gene were found in only 2.2% of 184 Japanese patients with Parkinson's disease. However, deletions were present in 25.0% and 40.0% of the patients with juvenile-onset (< 40 y) and with familiality, respectively. On the other hand, deletions were not found in any adult-onset cases (> 40 y). Half of the patients with parkin gene-related Parkinson's disease lacked both heredity and consanguinity.

Age of Onset↗

PubMed2001

Depth thresholds of motion parallax as a function of head movement velocity.

The lower parallactic depth threshold is determined by (a) the ratio of relative image velocity to head velocity when the head moves fast (>13 cm/s) and (b) the motion threshold when the head moves slow (<13 cm/s). These two results are explained by a single system that codes the ratio of relative image velocity to head velocity, using the same image velocity signal as that used for motion perception. In this explanation, ratios coded from low relative image velocities, which are slightly higher than the motion threshold, produce a perception of depth only when the head moves slowly.

Depth Perception↗

PubMed2001

Two kinds of mitogen-activated protein kinase phosphatases, MKP-1 and MKP-3, are differentially activated by acute and chronic methamphetamine treatment in the rat brain.

Two functionally different MAP kinase phosphatases (MKPs) were investigated to clarify their roles in behavioral sensitization to methamphetamine (METH). MKP-1 mRNA levels increased substantially by about 60-300% in a range of brain regions, including several cortices, the striatum and thalamus 0.5-1 h after acute METH administration. After chronic METH administration its increase was less pronounced, but a more than 50% increase was still seen in the frontal cortex. MKP-1 protein levels also increased 3 h after acute or chronic METH administration. MKP-3 mRNA levels increased by about 30-50% in several cortices, the striatum and hippocampus 1 h after acute METH administration, but only in the hippocampus CA1 after chronic METH administration. Pre-treatment with the D(1) dopamine receptor antagonist, SCH23390, attenuated the METH-induced increase of MKP-1 and MKP-3 mRNA in every brain region, while pre-treatment with the NMDA receptor antagonist, MK-801, attenuated it in some regions. These findings suggest that in METH-induced sensitization, MKP-1 and MKP-3 play important roles in the neural plastic modification in widespread brain regions in the earlier induction process, but in the later maintenance process, they do so only in restricted brain regions such as MKP-1 in the frontal cortices and MKP-3 in the hippocampus.

Acute Disease↗

PubMed2001

[Advanced findings on the molecular mechanisms for behavioral sensitization to psychostimulants].

Repeated administration of psychostimulants like methamphetamine and cocaine induce behavioral sensitization, which is recognized as an animal model for dependence and psychoses. Many previous studies have proved two major cascades play a crucial roles for molecular mechanisms underling sensitization. The first one is activation of D1 dopamine receptors by robust increase of dopamine release, followed by activation of adenylyl cyclase, increase of cyclic AMP, activation of protein kinase A (PKA) and phosphorylation of proteins by PKA. The second one is activation of NMDA receptor by enhanced release of glutamine, followed by increased intracellular Ca2+ concentration, formation of Ca2+/calmodulin complex, and phosphorylation of several proteins such as calcineurin, CaM-K II and nitric oxide synthase. Recent advanced findings on sensitization mechanisms were reviewed from three different aspects: 1) Studies using knockout mice offered quite amazing findings that D1DA-receptor-lacking mice or dopamine-transporter-lacking mice can develop sensitization and dependence, which were not consistent with the previously established hypotheses based on behavioral pharmacology. In addition, those data showed the important roles of vesicular monoamine transporter 2, 5HT1B receptors and delta FosB. 2) Research on neural-plasticity-related sensitization revealed the involvement of several molecules such as tissue plasminogen activator, arc (activity-regulated, cytoskeleton-associated), synaptophysin and stathmin. Increased expression of these genes may participate in the rearrangement of neural networks with synaptogenesis and expansion of dendrites 3) Trials to discover novel-genes-involved sensitization phenomenon using differential display or subtraction cloning found some candidate genes, mrt-1, NAC-1 and CART. Although in these areas are still in progress, accumulating findings will elucidate the details of the molecular mechanism of behavioral sensitization and dependence.

Animals↗

PubMed2001

[A case of spinocerebellar ataxia type 6 with hypochondriasis and severe parkinsonism].

We report a case of 68-year-old woman who was diagnosed spinocerebellar ataxia type 6 (SCA 6) by genomic testing. She presented hypochondriasis, parkinsonism, and ataxia. Since the age of 60, she noted difficulty in walking due to dizziness, and MRI showed minimal cerebellar atrophy. She became unable to walk without assistance at the age 67. She was referred to us when she was 68 years old. She had no family history of cerebellar ataxia, and her general physical examination was normal. Her speech was fluent, with neither slurring nor scanning, and she complained of much anxiety regarding her physical condition and was diagnosed as having hypochondriasis. Neurological examination revealed parkinsonism consisting of small steppage gait, mask-like face, akinesia, rigidity of neck and limbs, and postural instability. She also showed cerebellar signs such as saccadic smooth pursuit, ataxia of upper and lower limbs, and increased tendon reflexes. Her parkinsonism had developed slowly and symmetrically yet she showed a lack of response to levodopa. Our results suggest that the genomic testing is useful for differential diagnosis for the diseases presenting ataxia and parkinsonism, even if the family history is negative.

Aged↗

PubMed2000

Transformation of the visual-line value in binocular vision: stimuli on corresponding points can be seen in two different directions.

We examined Wheatstone's (1838 Philosophical Transactions of the Royal Society of London 128 371-394) claim that images falling on retinally corresponding points can be seen in two different directions, in violation of Hering's law of identical visual direction. Our analyses showed that random-dot stereograms contain stimulus elements that are conceptually equivalent to the line stimuli in the stereogram from which Wheatstone made his claim. Our experiment demonstrated that two lines embedded in a random-dot stereogram appeared in two different directions when they stimulated retinally corresponding points, if the disparity gradient value of the lines was infinity relative to adjacent elements. To ensure that the two lines stimulated corresponding points, observers made vergence eye movements while maintaining the perception of the two lines in two different directions.

Convergence, Ocular↗

PubMed1999

Subjective staircase: a multiple wallpaper illusion.

When observers binocularly fixate on an inclined sheet of paper with equally spaced dots, an apparent "staircase" is seen. We varied the inclination of the sheet, the spacing among the dots, and the viewing distance. The results indicate that (1) as the space and the inclination decreased, the number of apparent steps increased and the height of apparent steps decreased, and (2) as the distance and the inclination increased, the number of apparent steps decreased, and eventually the illusion disappeared. The nearest-neighbor rule and the extent of the vertical horopter inclination explain the characteristics of the illusion.

Adult↗

PubMed1999

[Is there solid evidence for reorganization of the neural network associated with development of behavioral sensitization to psychostimulants?].

Behavioral sensitization or reverse tolerance induced by repeated treatment of psychostimulants, such as amphetamine and cocaine, has been widely used as an animal model for schizophrenia. This phenomenon may result from almost eternally lasting plastic functional adaptation in the brain. Such long-lasting plasticity must accompany anatomical and morphological neural changes. Histological studies revealed that chronic treatment of psychostimulants induced thickness, elongation and an increased branch number of neurites and dendrites in cortices and accumbens, and an increased spine density. These changes may seem a positive adaptation for neural transmission, however, similar histological changes were seen after toxicity of methamphetamine as deafferation compensation. Therefore, further studies are needed to establish the significance of these morphological changes induced by chronic psychostimulants. On the other hand, neuromolecular studies showed increased phosphorylation of neuromodulin, increased expression of tissue-type plasminogen activator, synaptotagmin IV and arc, which are assumed to play roles in neural outgrowth and synaptogenesis. Although all of these histological and neuromolecular findings may suggest reorganization of the neural network should grow along with behavioral sensitization, more solid evidence is indispensable to confirm it.

Adaptation, Physiological↗

PubMed1999

[Two cases of sporadic juvenile Parkinson's disease caused by homozygous deletion of Parkin gene].

Parkin gene, which is one of the causes of familial Parkinson's disease, was cloned in 1998, and it was found that mutations of this gene induces familial Parkinson's disease of autosomal recessive form (AR-JP). Clinical studies have revealed that almost cases of AR-JP are consanguineous or hereditary. However, AR-JP may also be caused by marriage between two carriers. We therefore investigated the existence of a homozygous deletion in the parkin gene in 10 patients with juvenile Parkinson's disease with the onset of age younger than 40 years without consanguinity or heredity. A large delection of the gene was found in 2 of the 10 patients with sporadic Parkinson's disease, and both of these deletion were exon 4. The present study clearly suggests that juvenile Parkinson's disease in Japan may be caused by abnormalities in parkin gene regardless of family history or consanguinity.

Age of Onset↗

PubMed1998

A novel Arg362Ser mutation in the sterol 27-hydroxylase gene (CYP27): its effects on pre-mRNA splicing and enzyme activity.

A novel C to A mutation in the sterol 27-hydroxylase gene (CYP27) was identified by sequencing amplified CYP27 gene products from a patient with cerebrotendinous xanthomatosis (CTX). The mutation changed the adrenodoxin cofactor binding residue 362Arg to 362Ser (CGT 362Arg to AGT 362Ser), and was responsible for deficiency in the sterol 27-hydroxylase activity, as confirmed by expression of mutant cDNA into COS-1 cells. Quantitative analysis showed that the expression of CYP27 gene mRNA in the patient represented 52.5% of the normal level. As the mutation occurred at the penultimate nucleotide of exon 6 (-2 position of exon 6-intron 6 splice site) of the gene, we hypothesized that the mutation may partially affect the normal splicing efficiency in exon 6 and cause alternative splicing elsewhere, which resulted in decreased transcript in the patient. Transfection of constructed minigenes, with or without the mutation, into COS-1 cells confirmed that the mutant minigene was responsible for a mRNA species alternatively spliced at an activated cryptic 5' splice site 88 bp upstream from the 3' end of exon 6. Our data suggest that the C to A mutation at the penultimate nucleotide of exon 6 of the CYP27 gene not only causes the deficiency in the sterol 27-hydroxylase activity, but also partially leads to alternative pre-mRNA splicing of the gene. To our knowledge, this is the first report regarding effects on pre-mRNA splicing of a mutation at the -2 position of a 5' splice site.

Alternative Splicing↗

PubMed1998

A robust increase in expression of arc gene, an effector immediate early gene, in the rat brain after acute and chronic methamphetamine administration.

The effect of acute and chronic administration of methamphetamine (METH) on the levels of activity-regulated cytoskeleton-associated protein (arc), an effector-immediate early gene, mRNA has been investigated in rat brain using in situ hybridization. Levels of arc mRNAs in the brain regions examined increased significantly from 0.5-1 h after an acute METH (4 mg/kg) administration compared with basal levels. The increase in arc mRNA continued by 3 h, and then subsided to basal levels by 6 h. The degree of increase in arc mRNA and the peak time after METH administration varied according to brain area. Arc mRNA in cerebral cortices showed robust increase 1 h after METH administration. In the striatum and hippocampus, it showed earlier and later increase, respectively, and its degree of both was less than in the cortices. Microscopic examination revealed that the METH-induced arc mRNAs in the parietal cortex were enriched in layers IV and VI, and those in the striatum existed mainly in the medium-sized neuron. Pretreatment with either 0.5 mg/kg SCH23390 or 0.25 mg/kg MK-801 almost completely blocked the enhanced striatal arc mRNA levels induced by acute METH administration, whereas such pretreatments only partially reduced the effect of METH in the cerebral cortical regions. In the chronic treatment experiment, the arc mRNA levels of the group that received chronic treatment with METH followed by a METH challenge showed an increase like seen after acute METH administration. Since previous studies proposed that arc is one of cytoskeleton-associated proteins and is selectively localized in neural dendrites, the results of the present study suggested that arc may play an important role in the synaptic plasticity underlying METH-induced adaptational changes including behavioral sensitization.

Animals↗

PubMed1998

Schizophrenic psychoses and the CNTF null mutation.

Genetic susceptibility plays an important role in the development of schizophrenic psychoses, and the neural maldevelopment hypothesis is suggested by neuropathological and neuroimaging findings. We investigated the association between a null mutation in the ciliary neurotrophic factor (CNTF) gene and functional psychoses including schizophrenia and schizoaffective disorder. The frequency of mutant allele was significantly increased in patients with schizoaffective disorder, but not in those with schizophrenia in comparison with controls. The CNTF null mutation resulting in CNTF deficiency may confer potential susceptibility to schizoaffective disorder.

Adult↗

PubMed1998

Effect of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline on methamphetamine- and cocaine-induced behavioral sensitization.

The present study investigated the effect of pretreatment with 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, on behavioral sensitization induced by methamphetamine (METH) and cocaine at doses that are transitional relative to the induction of an acute response of locomotion and interrupting episodes of sniffing and head movement. Male Sprague-Dawley rats were randomly assigned to four groups that received daily either 20 mg/kg NBQX + 3 mg/kg METH, 40 mg/kg NBQX + 3 mg/kg METH, vehicle + 3 mg/kg METH, or vehicle + saline daily for 10 days. In another experiment, rats of four groups received daily either 20 mg/kg NBQX + 15 mg/kg cocaine, 40 mg/kg NBQX + 15 mg/kg cocaine, vehicle + 15 mg/kg cocaine, or vehicle + saline daily for 10 days. NBQX did not attenuate activity/stereotypy induced by acute administration of either psychostimulant. Pretreatment with NBQX did not affect augmentation of activity/stereotypy scores by repeated administration of METH or cocaine. There was no significant difference in the intensity of activity/stereotypy between the NBQX + METH and vehicle + METH groups and between the NBQX + cocaine and vehicle + cocaine groups following a challenge injection with 2 mg/kg METH alone or 15 mg/kg cocaine alone, respectively, given 7 days after the last dose of repeated treatment session. Pretreatment with NBQX alone for 10 days (20 mg/kg for 5 days and 40 mg/kg for subsequent 5 days) did not affect the intensity of activity/stereotypy induced by a challenge injection with 2 mg/kg METH given 7 days after the last dose of repeated injection session. NBQX at 40 mg/kg had no apparent effect on acute METH (3 mg/kg)-induced dopamine release in the striatum. These results suggest tht AMPA receptors are unlikely to be involved in induction of behavioral sensitization that is manifested as augmented activity/stereotypy following repeated administration of METH or cocaine.

Animals↗

PubMed1998

Apparent depth with retinal image motion of expansion and contraction yoked to head movement.

The two main questions addressed in this study were (a) what effect does yoking the relative expansion and contraction (EC) of retinal images to forward and backward head movements have on the resultant magnitude and stability of perceived depth, and (b) how does this relative EC image motion interact with the depth cues of motion parallax? Relative EC image motion was produced by moving a small CCD camera toward and away from the stimulus, two random-dot surfaces separated in depth, in synchrony with the observers' forward and backward head movements. Observers viewed the stimuli monocularly, on a helmet-mounted display, while moving their heads at various velocities, including zero velocity. The results showed that (a) the magnitude of perceived depth was smaller with smaller head velocities (< 10 cm s-1), including the zero-head-velocity condition, than with a larger velocity (10 cm s-1), and (b) perceived depth, when motion parallax and the EC image motion cues were simultaneously presented, is equal to the greater of the two possible perceived depths produced from either of these two cues alone. The results suggested the role of nonvisual information of self-motion on perceiving depth.

Adult↗

PubMed1997

VMAT2 knockout mice: heterozygotes display reduced amphetamine-conditioned reward, enhanced amphetamine locomotion, and enhanced MPTP toxicity.

The brain vesicular monoamine transporter (VMAT2) pumps monoamine neurotransmitters and Parkinsonism-inducing dopamine neurotoxins such as 1-methyl-4-phenyl-phenypyridinium (MPP+) from neuronal cytoplasm into synaptic vesicles, from which amphetamines cause their release. Amphetamines and MPP+ each also act at nonvesicular sites, providing current uncertainties about the contributions of vesicular actions to their in vivo effects. To assess vesicular contributions to amphetamine-induced locomotion, amphetamine-induced reward, and sequestration and resistance to dopaminergic neurotoxins, we have constructed transgenic VMAT2 knockout mice. Heterozygous VMAT2 knockouts are viable into adult life and display VMAT2 levels one-half that of wild-type values, accompanied by smaller changes in monoaminergic markers, heart rate, and blood pressure. Weight gain, fertility, habituation, passive avoidance, and locomotor activities are similar to wild-type littermates. In these heterozygotes, amphetamine produces enhanced locomotion but diminished behavioral reward, as measured by conditioned place preference. Administration of the MPP+ precursor N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to heterozygotes produces more than twice the dopamine cell losses found in wild-type mice. These mice provide novel information about the contributions of synaptic vesicular actions of monoaminergic drugs and neurotoxins and suggest that intact synaptic vesicle function may contribute more to amphetamine-conditioned reward than to amphetamine-induced locomotion.

Amphetamine↗

PubMed1997

rGbeta1: a psychostimulant-regulated gene essential for establishing cocaine sensitization.

Repeated doses of cocaine or amphetamine lead to long-lasting behavioral manifestations that include enhanced responses termed sensitization. Although biochemical mechanisms that underlie these manifestations currently remain largely unknown, new protein synthesis has been implicated in several of these neuroadaptive processes. To seek candidate biochemical mechanisms for these drug-induced neuroplastic behavioral responses, we have used an approach termed subtracted differential display (SDD) to identify genes whose expression is regulated by these psychostimulants. rGbeta1 is one of the SDD products that encodes a rat G-protein beta subunit. rGbeta1 expression is upregulated by cocaine or amphetamine treatments in neurons of the nucleus accumbens shell region, a major center for psychostimulant effects in locomotor control and behavioral reward. Antisense oligonucleotide treatments that attenuate rGbeta1 expression in regions including the nucleus accumbens abolish the development of behavioral sensitization when they are administrated during the repeated cocaine exposures that establish sensitization. These treatments fail to alter acute behavioral responses to cocaine, and they do not block the expression of cocaine sensitization when it is established before oligonucleotide administrations. Full, regulated rGbeta1 expression is a biochemical component essential to the establishment of a key consequence of repeated cocaine administrations, sensitization.

Amino Acid Sequence↗

PubMed1997

Opiate receptor knockout mice define mu receptor roles in endogenous nociceptive responses and morphine-induced analgesia.

Morphine produces analgesia at opiate receptors expressed in nociceptive circuits. mu, delta, and kappa opiate receptor subtypes are expressed in circuits that can modulate nociception and receive inputs from endogenous opioid neuropeptide ligands. The roles played by each receptor subtype in nociceptive processing in drug-free and morphine-treated states have not been clear, however. We produced homologous, recombinant mu, opiate receptor, heterozygous and homozygous knockout animals that displayed approximately 54% and 0% of wild-type levels of mu receptor expression, respectively. These mice expressed kappa receptors and delta receptors at near wild-type levels. Untreated knockout mice displayed shorter latencies on tail flick and hot plate tests for spinal and supraspinal nociceptive responses than wild-type mice. These findings support a significant role for endogenous opioid-peptide interactions with mu opiate receptors in normal nociceptive processing. Morphine failed to significantly reduce nociceptive responses in hot plate or tail flick tests of homozygous mu receptor knockout mice, and heterozygote mice displayed right and downward shifts in morphine analgesia dose-effect relationships. These results implicate endogenous opioid-peptide actions at mu opiate receptors in several tests of nociceptive responsiveness and support mu receptor mediation of morphine-induced analgesia in tests of spinal and supraspinal analgesia.

Analgesia↗

PubMed1997

AMPA receptors modulate dopamine release in the striatum, as measured by brain microdialysis.

The effect of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f) quinoxaline (NBQX), a potent and selective antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors, on the release of dopamine from the striatum was investigated in freely moving rats using an in vivo microdialysis technique. Perfusion with 1.0 mM AMPA increased the concentration of striatal extracellular dopamine. After systemic administration of NBQX (40 mg/kg, i.p.), dopamine levels in the striatal perfusate decreased. The AMPA-induced increase in dopamine levels was suppressed significantly by the systemic administration of NBQX (40 mg/kg, i.p.). Perfusion with tetrodotoxin (TTX, 5 microM) alone reduced the basal level of dopamine by 80%. Perfusion with 1.0 mM AMPA together with TTX produced a 3.9-fold increase in dopamine efflux from the TTX reduced basal level. However, the maximum dopamine level obtained thereby was close to the basal level of dopamine seen prior to perfusion with TTX. The present results demonstrate that AMPA receptors participate in tonic facilitative modulation of striatal extracellular level of dopamine. In addition, the results support the view that glutamatergic neurons modulate the release of dopamine via subtypes of excitatory amino acid receptors in the central nervous system.

3,4-Dihydroxyphenylacetic Acid↗