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K Ikeguchi

Publications and source records attributed to K Ikeguchi.

At least 19 recordsLinked to original sources
PubMed2002

Early-onset ataxia with ocular motor apraxia and hypoalbuminemia: the aprataxin gene mutations.

BACKGROUND: Early-onset ataxia with hypoalbuminemia is regarded as a variant form of Friedreich ataxia in Japan. Early-onset ataxia with hypoalbuminemia and ataxia with ocular motor apraxia have been considered as the same clinical entity because of the recent identification of a common mutation in the aprataxin gene. A new clinical entity named early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH) has been proposed to explain these two diseases. OBJECTIVE: To disclose the clinical features of EAOH and to identify the mutations in the aprataxin gene in six patients in four Japanese families with EAOH. METHODS: The clinical features, laboratory findings, sural nerve biopsy results, and brain MRI or CT findings for these patients were evaluated, and molecular analysis was performed, which involved sequencing of the aprataxin gene directly or use of the subcloning method. RESULTS: Cerebellar ataxia and peripheral neuropathy were noted in all six patients. Ocular motor apraxia was observed in five patients; two of these patients had obvious head thrust. Choreiform movements of the limbs and mental deterioration were observed in five patients. Although foot deformity was noted in five patients, kyphoscoliosis was noted only in one patient. In all patients, hypoalbuminemia and hypercholesterolemia were evident, and brain MRI or CT showed marked cerebellar atrophy. Nerve biopsy revealed depletion of large myelinated fibers in three of the five patients examined. Molecular analysis of the aprataxin gene revealed an insertion mutation (insT at nt167) and two missense mutations (A-to-G transition at nt80 and C-to-T transition at nt95, the former being novel). CONCLUSION: We found clinical heterogeneity in the patients with EAOH in this study. With the disease course, the choreiform movements tended to reduce in degree, and hypoalbuminemia became evident. Molecular analysis identified one insertion and two missense mutations including a novel missense one, which was located at a highly conserved amino acid residue in the aprataxin gene product.

Adult↗
PubMed2002

A Japanese SPG4 family with a novel missense mutation of the SPG4 gene: intrafamilial variability in age at onset and clinical severity.

OBJECTIVES: We report the results of clinical and genetic studies on a Japanese SPG4 family. MATERIAL AND METHODS: Family N included eight patients in four generations with autosomal dominant transmission. We performed neurological and molecular analyses on the SPG4 gene in the family members comprising three patients, 12 at-risk individuals, and three normal spouses. RESULTS: The three patients showed pure spastic paraplegia, two of them exhibiting a decrease in vibration sense. There was marked intrafamilial variability in age at onset and clinical severity in the present family. On molecular analysis, a novel missense mutation (nt1579 C-->T) in exon 12 of the SPG4 gene was found in the three patients, three probably affected, and an asymptomatic carrier. CONCLUSION: The present SPG4 family, which was shown to have a novel SPG4 mutation, exhibited marked variability in the clinical features, indicating the participation of additional factors in the phenotypic appearance of this family.

Adenosine Triphosphatases↗
PubMed2002

Delayed delivery of AAV-GDNF prevents nigral neurodegeneration and promotes functional recovery in a rat model of Parkinson's disease.

Glial cell line-derived neurotrophic factor (GDNF) is a strong candidate agent in the neuroprotective treatment of Parkinson's disease (PD). We investigated whether adeno-associated viral (AAV) vector-mediated delivery of a GDNF gene in a delayed manner could prevent progressive degeneration of dopaminergic (DA) neurons, while preserving a functional nigrostriatal pathway. Four weeks after a unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA), rats received injection of AAV vectors expressing GDNF tagged with FLAG peptide (AAV-GDNFflag) or beta-galactosidase (AAV-LacZ) into the lesioned striatum. Immunostaining for FLAG demonstrated retrograde transport of GDNFflag to the substantia nigra (SN). The density of tyrosine hydroxylase (TH)-positive DA fibers in the striatum and the number of TH-positive or cholera toxin subunit B (CTB, neuronal tracer)-labeled neurons in the SN were significantly greater in the AAV-GDNFflag group than in the AAV-LacZ group. Dopamine levels and those of its metabolites in the striatum were remarkably higher in the AAV-GDNFflag group compared with the control group. Consistent with anatomical and biochemical changes, significant behavioral recovery was observed from 4-20 weeks following AAV-GDNFflag injection. These data indicate that a delayed delivery of GDNF gene using AAV vector is efficacious even 4 weeks after the onset of progressive degeneration in a rat model of PD.

Animals↗
PubMed2001

Intravenous immunoglobulin therapy for diabetic amyotrophy.

A 49-year-old woman with diabetes mellitus developed progressive weakness and atrophy of both thighs rendering her wheelchair-bound within two months. The neurological findings and electrophysiological test results were compatible with diabetic amyotrophy (DA). Immediately after intravenous immunoglobulin (IVIg) therapy (20 g x 3 days), she became able to walk with a cane. After the next course of the therapy, she could walk without assistance. This dramatic effect of IVIg therapy together with the recent observation of vasculitic neuropathy in DA indicates an inflammatory process in this condition, and gives support to this treatment for DA.

Diabetic Neuropathies↗
PubMed2000

Triple transduction with adeno-associated virus vectors expressing tyrosine hydroxylase, aromatic-L-amino-acid decarboxylase, and GTP cyclohydrolase I for gene therapy of Parkinson's disease.

Parkinson's disease (PD), a neurological disease suited to gene therapy, is biochemically characterized by a severe decrease in the dopamine content of the striatum. One current strategy for gene therapy of PD involves local production of dopamine in the striatum achieved by inducing the expression of enzymes involved in the biosynthetic pathway for dopamine. We previously showed that the coexpression of tyrosine hydroxylase (TH) and aromatic-L-amino-acid decarboxylase (AADC), using two separate adeno-associated virus (AAV) vectors, resulted in more effective dopamine production and more remarkable behavioral recovery in 6-hydroxydopamine-lesioned parkinsonian rats, compared with the expression of TH alone. Not only levels of TH and AADC but also levels of tetrahydrobiopterin (BH4), a cofactor of TH, and GTP cyclohydrolase I (GCH), a rate-limiting enzymes for BH4 biosynthesis, are reduced in parkinsonian striatum. In the present study, we investigated whether transduction with separate AAV vectors expressing TH, AADC, and GCH was effective for gene therapy of PD. In vitro experiments showed that triple transduction with AAV-TH, AAV-AADC, and AAV-GCH resulted in greater dopamine production than double transduction with AAV-TH and AAV-AADC in 293 cells. Furthermore, triple transduction enhanced BH4 and dopamine production in denervated striatum of parkinsonian rats and improved the rotational behavior of the rats more efficiently than did double transduction. Behavioral recovery persisted for at least 12 months after stereotaxic intrastriatal injection. These results suggest that GCH, in addition to TH and AADC, is important for effective gene therapy of PD.

Animals↗
PubMed2000

Gene therapy of Parkinson's disease using adeno-associated virus (AAV) vectors.

Parkinson's disease (PD) is characterized by the progressive loss of the dopaminergic neurons in the substantia nigra and a severe decrease in dopamine in the striatum. A promising approach to the gene therapy of PD is intrastriatal expression of dopamine-synthesizing enzymes [tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC)]. The most appropriate gene-delivery vehicles for neurons are adeno-associated virus (AAV) vectors, which are derived from non-pathogenic virus. Therefore, TH and AADC genes were introduced into the striatum in the lesioned side using separate AAV vectors in parkinsonian rats, and the coexpression of TH and AADC resulted in better behavioral recovery compared with TH alone. Another strategy for gene therapy of PD is the protection of dopaminergic neurons in the substantia nigra using an AAV vector containing a glial cell line-derived neurotrophic factor (GDNF) gene. Combination of dopamine-supplement gene therapy and GDNF gene therapy would be a logical approach to the treatment of PD.

Animals↗
PubMed2000

Determination of medullasin levels for the diagnosis of multiple sclerosis.

OBJECTIVES: To obtain a simple and reliable clinical parameter for the diagnosis of multiple sclerosis among patients with neurological diseases. PATIENTS AND METHODS: Heparinized peripheral blood was obtained from patients with multiple sclerosis and those with non-inflammatory neurological diseases and healthy volunteers. A new enzyme immunoassay method determining medullasin levels in human granulocytes was developed by using mouse monoclonal antibody against medullasin. RESULTS: A newly developed enzyme immunoassay method for medullasin can detect as little as 1 ng/ml medullasin and results can be obtained within 2 h. Eighty-five out of 112 patients with multiple sclerosis (75.8%) showed positive results (above means of normals + 2 SD) in the medullasin test, while 15.4% (12/78) of patients with non-inflammatory neurological disease had positive results. CONCLUSION: This newly developed enzyme immunoassay method for medullasin is considered to be a useful paraclinical test for the diagnosis of multiple sclerosis.

Adolescent↗
PubMed2000

An autopsy case of Alzheimer's disease with a progressive supranuclear palsy overlap.

A 74-year-old man developed abnormal forgetfulness, soon followed by unstable speech content and marked disorientation. At 77 years of age, the patient started to occasionally fall, an aspect of progressive supranuclear palsy. He then became bedridden. The patient eventually died of pneumonia at 79 years of age. Neuropathological examination revealed profiles of both progressive supranuclear palsy and Alzheimer's disease. Although the two conditions both belong to tauopathy, their pathologically proven combination was rare. Furthermore, the case had the possibility of being a subgroup of tauopathy.

Aged↗
PubMed2000

[Diabetic coma].

Explore the source record for details and available documents.

Acidosis, Lactic↗
PubMed1998

Behavioral recovery in 6-hydroxydopamine-lesioned rats by cotransduction of striatum with tyrosine hydroxylase and aromatic L-amino acid decarboxylase genes using two separate adeno-associated virus vectors.

Parkinson's disease (PD) is characterized by the progressive loss of the dopaminergic neurons in the substantia nigra and a severe decrease in dopamine in the striatum. A promising approach to the gene therapy of PD is intrastriatal expression of enzymes in the biosynthetic pathway for dopamine. Tyrosine hydroxylase (TH) catalyzes the synthesis of L-dopa, which must be converted to dopamine by aromatic L-amino acid decarboxylase (AADC). Since the endogenous AADC activity in the striatum is considered to be low, coexpression of both TH and AADC in the same striatal cells would increase the dopamine production and thereby augment the therapeutic effects. In the present study, the TH gene and also the AADC gene were simultaneously transduced into rat striatal cells, using two separate adeno-associated virus (AAV) vectors, AAV-TH and AAV-AADC. Immunostaining showed that TH and AADC were coexpressed efficiently in the same striatal cells in vitro and in vivo. Moreover, cotransduction with these two AAV vectors resulted in more effective dopamine production and more remarkable behavioral recovery in 6-hydroxydopamine (6-OHDA)-lesioned rats, compared with rats receiving AAV-TH alone (p < 0.01). These findings suggest an alternative strategy for gene therapy of PD and indicate that the simultaneous transduction with two AAV vectors can extend their utility for potential gene therapy applications.

Animals↗
PubMed1998

Effects of repeated systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mice on interleukin-1beta and nerve growth factor in the striatum.

Interleukin (IL)-1beta and nerve growth factor (NGF) were measured for the first time in the brain (caudate nucleus and putamen, and frontal cortex) from control mice and mice treated with a parkinsonism-inducing neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), by highly-sensitive sandwich enzyme-linked immunosorbent assays (ELISAs) The concentrations of interleukin (IL)-1beta in the striatal regions were significantly higher in MPTP-treated mice than those in control mice treated with saline (P < 0.005), whereas those in the frontal cortex did not show significant differences between MPTP-treated and control mice. The present results agreed with our previous data on increased IL-1beta in the postmortem striatum from patients with Parkinson's disease (PD). In contrast, the concentrations of nerve growth factor (NGF) in the striatal regions were significantly lower in MPTP-treated mice, down to a 54% level of control mice (P < 0.05), but those in the frontal cortex did not show significant differences between MPTP-treated and control mice. Since NGF may play important roles as neurotrophic factors in the brain, the present results suggest that both the elevation of pro-inflammatory cytokine IL-1beta and the decrease of NGF in the dopaminergic striatal region of MPTP- treated mice may be related to neuronal cell death.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1998

Prevention of dopaminergic neuron death by adeno-associated virus vector-mediated GDNF gene transfer in rat mesencephalic cells in vitro.

Glial cell line-derived neurotrophic factor (GDNF) is known as a potent neurotrophic factor for dopaminergic neurons. Since adeno-associated virus (AAV) vector is a suitable vehicle for gene transfer into neurons, rat E14 mesencephalic cells were transduced with an AAV vector expressing GDNF. When compared with mock transduction, a larger number of dopaminergic neurons survived in AAV-GDNF-transduced cultures (234% and 325% of controls at 1 and 2 weeks, respectively; P < 0.01). Furthermore, the dopaminergic neurons in the latter cultures grew more prominent neurites than those in the former. These findings suggest that AAV vector-mediated GDNF gene transfer may prevent dopaminergic neuron death, and is therefore a logical approach for the treatment of Parkinson's disease.

Animals↗
PubMed1997

[A case report of tongue cancer presenting with SSD type brain embolism induced by chemotherapy with CBDCA and 5-FU].

We report a case of tongue cancer presenting with SSD type brain embolism induced by chemotherapy with CBDCA and 5-FU (CF Therapy) A 35-year-old woman underwent CF therapy for squamous cell carcinoma of the tongue. Immediately after CF therapy, aphasia and serious exercise paralysis appeared. However, symptoms disappeared 2 days later and no abnormality was found by brain CT. We report that SSD type brain embolism is one of the noteworthy side effects of CF therapy.

Adult↗
PubMed1997

[Usefulness of transcranial magnetic stimulation in the objective assessment of therapy for adrenoleukodystrophy].

Adrenoleukodystrophy (ALD) is a hitherto untreatable, X-linked recessive disorder of the central nervous system characterized by the systemic accumulation of very-long-chain fatty acids. Although various treatments have been proposed, objective evidence of their efficacy is insufficient. This is partly due to the absence of an appropriate method for evaluating the functions of the central nervous system (CNS). In this study, we took up the central motor conduction time (CMCT) as an index of the CNS functions, and measured it in two patients with ALD under steroid pulse therapy to know if this parameter is useful in assessing the effects of therapy. The right and the left motor cortex was stimulated separately with a MAGSTIM 200 magnetic stimulator, using a round coil of 9cm mean diameter to stimulate the hand area or a double cone coil to stimulate the leg area. CMCT, the time an impulse takes to travel from the motor cortex to the anterior horn cells in the corresponding region, was measured by a combination of transcranial magnetic stimulation (TMS) and F wave technique. Before treatment, CMCT to the cervical cord was prolonged slightly in both patients; CMCT to the lumbar cord was prolonged slightly in one and moderately in the other. After repeated steroid pulse therapy, a definite improvement, although partial and transient, was observed in either case. TMS thus seems to be useful not only for detecting functional derangement of the pyramidal tract but for evaluating the efficacy of therapy for this disease.

Adrenoleukodystrophy↗
PubMed1995

Mianserin treatment of patients with psychosis induced by antiparkinsonian drugs.

We evaluated the effects of mianserin, a relatively selective 5-HT2 receptor antagonist, on symptoms related to drug-induced psychosis in patients with Parkinson's disease (PD). A total of 12 patients with PD who had developed drug-induced psychosis showed delirium (DSM-III-R criteria; n = 10) and pure visual hallucinations (n = 2). The antiparkinsonian drugs involved in the drug-induced psychosis were L-DOPA/carbidopa, bromocriptine, trihexyphenidyl, and amantadine. They received mianserin (mean 36.7 mg, range 20-60 mg) given orally for 8 weeks. Complete relief or marked improvement in psychotic symptoms was noted in 8 patients, moderate improvement in 2 patients, and no effect in 2 patients. The parkinsonian disability also decreased slightly in 8 patients. These results suggest that serotonin antagonism at 5-HT2 receptors may not only play an important role in the treatment of drug-induced psychosis in PD, but may also ameliorate the symptoms of parkinsonism.

Administration, Oral↗