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Y Mizuno

Publications and source records attributed to Y Mizuno.

At least 37 records · Page 2Linked to original sources
PubMed2004

PARK6-linked autosomal recessive early-onset parkinsonism in Asian populations.

The authors performed linkage analysis in 39 families with autosomal recessive early-onset PD (AR-EOPD) negative for parkin and DJ-1 mutations. Eight families including three Japanese, two Taiwanese, one Turkish, one Israeli, and one Philippine showed evidence of linkage with PARK6 with multipoint log of the odds (lod) score of 9.88 at D1S2732. The results indicate worldwide distribution of PARK6-linked parkinsonism.

Age of Onset↗
PubMed2004

Neurogenesis in olfactory bulb identified by retroviral labeling in normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated adult mice.

Neurogenesis occurs during development and in the normal adult brain. Recent studies identified areas exhibiting postlesional selective neurogenesis and neuronal repair. In the olfactory bulb (OB), one of the most studied regions of the brain for neurogenesis, seizures and strong odor exposure are known to enhance neurogenesis. Here, we report enhanced neurogenesis in OB after dopaminergic neuronal loss induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a selective toxin for dopaminergic neurons. The neurogenesis has been previously confirmed mainly by the uptake of 5-bromodeoxyuridine (BrdU), a marker of proliferating cells, but methodological problems related to BrdU labeling might result in inaccurate findings with respect to specificity, toxicity and incorporation into normal/lesioned brain. For a better identification of neurogenesis, we used a retroviral vector. First, we investigated the population dynamics of newly formed neurons in different regions of OB including the glomerular layer, the most superficial layer of OB. Quantification of neurogenesis in OB revealed by our retroviral vector was substantially similar to that by BrdU-based method. One week after MPTP application and dopaminergic neuronal loss in OB, neurogenesis of dopaminergic neurons in OB increased by three-fold, but no such process was noted in non-dopaminergic neurons. Our results indicate selective dopaminergic neurogenesis in OB in response to neuronal damage/loss.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2004

Th1 and Th2 cytokine production is suppressed at the level of transcriptional regulation in Kawasaki disease.

To clarify the functional state of T cells in Kawasaki disease, we analysed mRNA expression levels of Th1/Th2 cytokines (IFN-gamma and IL-4) along with Th1/Th2-inducing transcription factors, T-bet and GATA-3, which play pivotal roles in the development of Th1 and Th2 cells, respectively. By real-time PCR, IFN-gamma mRNA levels in peripheral blood mononuclear cells (PBMNC) were significantly decreased in Kawasaki disease patients compared with those with measles, and tended to be lower than those in healthy controls. T-bet mRNA levels were significantly decreased in patients with Kawasaki disease compared with healthy controls. In addition, IL-4 and GATA-3 mRNA levels were significantly decreased in Kawasaki disease compared with healthy controls. Regulatory cytokine mRNA levels (TGF-beta and IL-10) were also decreased in Kawasaki disease. The mRNA levels of IFN-gamma showed a significant positive correlation with those of T-bet in Kawasaki disease. These results suggest that the suppressed function of Th1 and Th2, associated with the suppression of both T-bet and GATA-3 gene expression, may be one of the immunological characteristics of Kawasaki disease.

Child↗
PubMed2004

In vitro characterization of the relationship between the Q-angle and the lateral component of the quadriceps force.

Although the Q-angle is routinely measured, the relationship between the Q-angle and the lateral component of the quadriceps force acting on the patella is unknown. Five cadaver knees were flexed on a knee simulator with a normal Q-angle, and flexed after increasing and decreasing the Q-angle by shifting the quadriceps origin laterally and medially, respectively. The motion of the femur, tibia and patella was tracked from 20 to 90 degrees of flexion using electromagnetic sensors. The motion of landmarks used to quantify the Q-angle was tracked to determine the 'dynamic Q-angle' during flexion. The lateral component of the force applied by the actuator secured to the quadriceps tendon was also quantified throughout flexion. Increasing the initial Q-angle significantly (p < 0.05) increased the dynamic Q-angle and the lateral force exerted through the quadriceps tendon throughout flexion. Decreasing the initial Q-angle significantly decreased the dynamic Q-angle at 90 degrees of flexion and significantly decreased the lateral force exerted through the quadriceps tendon from 20 to 40 degrees of flexion. Even though the dynamic Q-angle changes during flexion, an abnormally large initial Q-angle can be an indicator of an abnormally large lateral force acting on the patella during flexion.

Aged↗
PubMed2003

New parkin mutations and atypical phenotypes in families with autosomal recessive parkinsonism.

The frequency of parkin mutations was evaluated in 30 families of highly diverse geographic origin with early-onset autosomal recessive parkinsonism. Twelve different mutations, six of which were new, were found in 10 families from Europe and Brazil. Patients with parkin mutations had significantly longer disease duration than patients without the mutation but with similar severity of disease, suggesting a slower disease course. Two patients with parkin mutations had atypical clinical presentation at onset, with predominant tremor when standing.

Adult↗
PubMed2003

Gene therapy for Parkinson's disease.

We review recent progress in gene therapy utilizing experimental parkinsonian models including our data. Investigation of ex vivo gene therapy for Parkinson's disease (PD) is to provide L-dopa by transplantation of genetically modified cells into the striatum. Recently, neuronal progenitor cells (NPC) are recognized as the most appropriate target population for such genetic and cellular therapy of PD. We have developed modified pseudo-typed retrovirus production system. Using this gene transfer system, it is easy and efficient to introduce the gene into NPC because high titer virus vector is easily obtained. For the in vivo gene therapy, adeno-associated virus (AAV) vector is best virus vector because it is easy to introduce gene into neurons without inflammatory reaction. We established in vivo models of the inhibition of the caspase-cascade by overexpression of apoptotic protease activating factor-1-dominant negative inhibitor (Apaf-1-DN) using AAV vector. We showed that Apaf-1-DN delivery using an AAV vector system could prevent nigrostriatal degeneration in MPTP mice, suggesting that it might be an anti-mitochondrial apoptotic gene therapy for PD.

Animals↗
PubMed2003

Migration of enhanced green fluorescent protein expressing bone marrow-derived microglia/macrophage into the mouse brain following permanent focal ischemia.

Brain ischemia induces a marked response of resident microglia and hematopoietic cells including monocytes/macrophages. The present study was designed to assess the distribution of microglia/macrophages in cerebral ischemia using bone marrow chimera mice known to express enhanced green fluorescent protein (EGFP). At 24 h after middle cerebral artery occlusion (MCAO), many round-shaped EGFP-positive cells migrated to the ischemic core and peri-infarct area. At 48-72 h after MCAO, irregular round- or oval-shaped EGFP/ionized calcium-binding adapter molecule 1 (Iba 1)-positive cells increased in the transition zone, while many amoeboid-shaped or large-cell-body EGFP/Iba 1-positive cells were increased in number in the innermost area of ischemia. At 7 days after MCAO, many process-bearing ramified shaped EGFP/Iba 1-positive cells were detected in the transition to the peri-infarct area, while phagocytic cells were distributed in the transition to the core area of the infarction. The distribution of these morphologically variable EGFP/Iba 1-positive cells was similar up to 14 days from MCAO. The present study directly showed the migration and distribution of bone marrow-derived monocytes/macrophages and the relationship between resident microglia and infiltrated hematogenous element in ischemic mouse brain. It is important to study the distribution of intrinsic and extrinsic microglia/macrophage in ischemic brain, since such findings may allow the design of appropriate gene-delivery system using exogenous microglia/macrophages to the ischemic brain area.

Animals↗
PubMed2003

Cervical dystonia in dentatorubral-pallidoluysian atrophy.

Hereditary dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal-dominant neurodegenerative disease characterized by variable clinical phenotypes. Its characteristic clinical manifestations include ataxia, choreoathetotic movements, seizures, myoclonus and dementia, but cervical dystonia has been rarely reported. Here we report a family with DRPLA who presented with cervical dystonia. The proband was a 66-year-old woman. Cervical dystonia was the initial and the most prominent symptom, and mild cerebellar signs and choreic movements were also observed. DNA analysis revealed expanded trinucleotide repeats within the DRPLA gene. The daughter of the proband, a 29-year-old woman, also had cervical dystonia for 3 years. Cranial magnetic resonance imaging showed a mild atrophy of the brainstem and the cerebellum in both of these patients. DRPLA should be considered in the differential diagnosis of patients presenting with cervical dystonia.

Adult↗
PubMed2003

Th1 and Th1-inducing cytokines in Salmonella infection.

Thl and Thl-inducing cytokines and T cell responses were investigated in human salmonellosis. Serum IFN-gamma, IL-12 and IL-18 levels were increased significantly in patients with salmonellosis. The increase in serum IL-15 and IL-18 levels was more significant and prolonged in patients with the systemic form of salmonellosis than in those with the gastroenteric form. The serum IFN-gamma level was correlated significantly with IL-12 and IL18 levels, and the IL-15 level was correlated significantly with IL-18. Upon stimulation with Salmonella in vitro, mononuclear cells from salmonellosis patients produced significantly higher amounts of IFN-gamma and IL-12 compared with those from healthy controls. Anti-IL-12 moAb or anti-IL18 MoAb significantly inhibited Salmonella-induced IFN-gamma production in vitro. gamma delta T cells expressed significantly higher levels of IFN-gamma mRNA in salmonellosis patients than in healthy controls. The results suggest that Th1-inducing cytokines appear to be involved in the in vivo response against Salmonella infection, promoting IFN-gamma production by alpha beta and gamma delta T cells which plays a protective role against Salmonella.

Adolescent↗
PubMed2003

Increased serum levels of interferon-gamma-inducible protein 10 and monokine induced by gamma interferon in patients with haemophagocytic lymphohistiocytosis.

We measured serum interferon-gamma-inducible protein 10 (IP-10) and monokine induced by gamma interferon (MIG) levels to investigate the role of these molecules in the pathophysiology of haemophagocytic lymphohistiocytosis (HLH). Serum IP-10 and MIG levels were significantly increased in patients with active HLH compared with those of healthy controls. Serum MIG levels decreased gradually during the course of disease in a patient who recovered without therapy. On the other hand, rapid reduction of MIG and IP-10 levels was observed after chemotherapy in a patient with severe HLH. IP-10 and MIG mRNA expression was enhanced in liver and spleen, and IP-10 mRNA expression was enhanced in bone marrow in the patients, suggesting activated macrophages that infiltrated in these organs as one of the main producers of these cytokines. Serum IP-10 and MIG levels showed a significant correlation with serum IFN-gamma levels. In addition, these chemokines had a significant correlation with fever and serum LDH levels, which are clinical indicators of disease activity of HLH. These results suggest that IP-10 and MIG which are produced by activated macrophages by the stimulation of IFN-gamma, play an important role in the pathophysiology of HLH, by recruitment of activated Th1 cells into the tissues or organs.

Acute Disease↗
PubMed2003

Correlates of depressive symptoms among HIV-positive injection drug users: the role of social support.

Using cross-sectional data from an ethnically diverse sample of HIV-positive injection drug users (IDUs), we sought to identify correlates of depressive symptoms. We were particularly interested in whether perceived social support was associated with depression among HIV-positive IDUs and whether social support buffered adverse effects of other correlates. Data were collected from a sample of HIV-positive IDUs recruited from a variety of venues in the New York City and San Francisco metropolitan areas in the USA. Multiple regression analysis identified four significant correlates of depressive symptoms. Perceived social support and having a regular place for HIV medical care were significantly associated with lower levels of depressive symptoms, while history of mental health problems and non-injection polydrug use were significantly associated with higher levels of depressive symptoms. Moreover, a significant interaction effect was found between social support and non-injection polydrug use, indicating that social support buffers the association between non-injection polydrug use and depression. These results suggest that increasing social support might be a useful tool for HIV-positive IDUs in reducing depression and the adverse effect of non-injection polydrug use.

Adult↗
PubMed2003

In-vitro uptake of vitamin A by Plasmodium falciparum.

The vitamin-A uptake of Plasmodium falciparum was investigated by culturing a standard isolate of the parasite (FCR-3) with (3)H-labelled vitamin A, at concentrations of the vitamin corresponding to those normally present in human serum. The (3)H-labelled vitamin A accumulated in the parasites from each culture in a parasitaemia-dependent manner. The radioactivity detected in the parasites increased with parasite maturation from the ring to the late-trophozoite stage. In addition, most of the radioactivity incorporated into the parasite cells was in the cytoplasm. The accumulation of vitamin A in the cytoplasm of late trophozoites indicates that P. falciparum may use vitamin A, from its human host, as an antioxidant, to protect itself from oxidative stress while intra-erythrocytic. The amount of the vitamin taken up by the parasite in vitro is small compared with the deficit that sometimes causes severe hypovitaminosis A in malaria cases. Consumption of vitamin A by the parasites together with the systemic decreases in non-enzymatic antioxidants that are seen in malaria may together cause this characteristic hypovitaminosis.

Animals↗
PubMed2002

Clinical and genetic studies of families with the tau N279K mutation (FTDP-17).

The tau N279K mutation was identified in four separately ascertained families in the United States, Japan, and France and in another recently discovered affected individual in Japan. The authors analyzed genealogical and clinical records and DNA samples. Average age at onset was 43 years; survival time was 7 years. All families exhibited similar clinical features, with parkinsonism, dementia, and supranuclear palsy uniformly seen. A founder effect indicated by a shared disease haplotype was seen only in two Japanese families. The N279K mutation can develop independently in different parts of the world.

Adult↗
PubMed2002

Enlargements of somatosensory-evoked potentials in progressive supranuclear palsy.

OBJECTIVE: To evaluate the usefulness of the somatosensory-evoked potential (SEP) in differentiating progressive supranuclear palsy (PSP) from other movement disorders. MATERIALS AND METHODS: The median nerve SEPs were studied in patients with PSP, Parkinson's disease and essential tremor, and in healthy controls. RESULTS: The amplitudes of the median nerve SEPs were enlarged only in patients with PSP. In four of the 10 patients with PSP, giant SEPs were elicited either unilaterally or bilaterally. CONCLUSIONS: The enlargement of the SEP in PSP may be useful for early differentiation of PSP, and this enlargement suggest a disease-specific dysfunction in the sensory processing mechanism of PSP which distinguishes it from other movement disorders.

Adult↗