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Makoto Yoneda

Publications and source records attributed to Makoto Yoneda.

14 recordsLinked to original sources
PubMed2006

Identification of mitochondrial DNA polymorphisms that alter mitochondrial matrix pH and intracellular calcium dynamics.

Mitochondrial DNA (mtDNA) is highly polymorphic, and its variations in humans may contribute to individual differences in function as well as susceptibility to various diseases such as Parkinson disease, Alzheimer disease, bipolar disorder, and cancer. However, it is unclear whether and how mtDNA polymorphisms affect intracellular function, such as calcium signaling or pH regulation. Here we searched for mtDNA polymorphisms that have intracellular functional significance using transmitochondrial hybrid cells (cybrids) carrying ratiometric Pericam (RP), a fluorescent calcium indicator, targeted to the mitochondria and nucleus. By analyzing the entire mtDNA sequence in 35 cybrid lines, we found that two closely linked nonsynonymous polymorphisms, 8701A and 10398A, increased the basal fluorescence ratio of mitochondria-targeted RP. Mitochondrial matrix pH was lower in the cybrids with 8701A/10398A than it was in those with 8701G/10398G, suggesting that the difference observed by RP was mainly caused by alterations in mitochondrial calcium levels. Cytosolic calcium response to histamine also tended to be higher in the cybrids with 8701A/10398A. It has previously been reported that 10398A is associated with an increased risk of Parkinson disease, Alzheimer disease, bipolar disorder, and cancer, whereas 10398G associates with longevity. Our findings suggest that these mtDNA polymorphisms may play a role in the pathophysiology of these complex diseases by affecting mitochondrial matrix pH and intracellular calcium dynamics.

Alzheimer Disease↗
PubMed2006

[A steroid-responsive case of severe rhabdomyolysis associated with cytomegalovirus infection].

A 31-year-old man was admitted to our hospital, complaining of muscular weakness and pain in the legs one month after a common cold. On admission, neurological examinations demonstrated moderate weakness in the arms and mild weakness in the legs with decreased or diminished deep tendon reflexes, and mild dysphagia. Weakness was gradually extended to the arm, throat and respiratory muscles, requiring artificial ventilation. Laboratory examinations demonstrated increased levels of CK (upto 24,380 IU/L) and positive anti-cytomegalovirus (CMV) -IgM antibodies in the serum, and myogloburinuria. CMV was not detected in either the blood cells or muscles by PCR. There were no antibodies against viruses including Ebstein-Barr virus and HIV, in the serum. There were no autoantibodies related to collagen diseases in the serum. Systemic PET scan did not show any evidence of malignancy. Bone marrow biopsy did not show any atypical cells. Muscle MRI demonstrated mild atrophy with high intensity signals in part. Muscle biopsy demonstrated scattered necrotic and regenerated muscle fibers without inflammatory cell infiltration. The patient was therefore diagnosed as having rhabdomyolysis associated with CMV infection. After three courses of intravenously administered high dose methylprednislone over three days, muscle weakness improved gradually, and the serum CK level was normalized in two months. The patient recovered and was removed from artificial ventilation three months after the therapy. There were no sign of renal failure. Steroid therapy should be considered for the treatment of rhabdomyolysis or myopathy associated with CMV infection in order to prevent renal failure or fatal progression of the disease.

Adolescent↗
PubMed2005

[A case of chorea-acanthocytosis onset with at age 86].

An 86-year-old woman was admitted to our hospital for orobuccolingual dyskinesia. She did not take any medication. Her relatives had no similar symptoms nor consanguineous marriage. Although orobuccolingual dyskinesia was improved by administration of haloperidol for a while, orobuccolingual dyskinesia with biting of tongue and lips, chorea and muscular atrophy in the legs, seizures and dementia appeared half a year after the onset. The decrease of cMAP suggested axonopathy in the extremities by a nerve conduction study. The serum level of CK was normal. The EEG showed generally slow wave activities. A head MRI showed mild atrophy of the bilateral caudate nuclei and frontal lobes with scattered old lacunars in the deep white matter. She was diagnosed as having chorea-acanthocytosis (ChAc) because acanthocytes (10-20%) appeared in the peripheral blood. The normal lipoprotein levels and Kell antigen expression excluded the possibilities of Bassen-Kornzweig syndrome and McLeod syndrome. In all reported cases of ChAc, she was the oldest onset patient. ChAc is warranted in a patient presenting with orobuccolingual dyskinesia with biting, in spite of elderly onset.

Age of Onset↗
PubMed2004

Mitochondrial DNA 3644T-->C mutation associated with bipolar disorder.

Mitochondrial dysfunction associated with mutant mitochondrial DNA (mtDNA) has been suggested in bipolar disorder, and comorbidity with neurodegenerative diseases was often noted. We examined the entire sequence of mtDNA in six subjects with bipolar disorder having comorbid somatic symptoms suggestive of mitochondrial disorders and found several uncharacterized homoplasmic nonsynonymous nucleotide substitutions of mtDNA. Of these, 3644C was found in 5 of 199 patients with bipolar disorder but in none of 258 controls (p = 0.015). The association was significant in the extended samples [bipolar disorder, 9/630 (1.43%); controls, 1/734 (0.14%); p = 0.007]. On the other hand, only 5 of 25 family members with this mutation developed bipolar disorder, of which 4 patients with 3644C had comorbid physical symptoms. The 3644T-->C mutation converts amino acid 113, valine, to alanine in the NADH-ubiquinone dehydrogenase subunit I, a subunit of complex I, and 113 valine is well conserved from Drosophila to 61 mammalian species. Using transmitochondrial cybrids, 3644T-->C was shown to decrease mitochondrial membrane potential and complex I activity compared with haplogroup-matched controls. According to human mitochondrial genome polymorphism databases, 3644C was not found in centenarians but was found in 3% of patients with Alzheimer disease and 2% with Parkinson disease. The result of modest functional impairment caused by 3644T-->C suggests that this mutation could increase the risk for bipolar disorder.

Adolescent↗
PubMed2004

Impact of mitochondrial DNA on radiation sensitivity of transformed human fibroblast cells: clonogenic survival, micronucleus formation and cellular ATP level.

The purpose of this study was to evaluate the impact of mitochondrial DNA (mtDNA) on the radiation sensitivity of transformed human fibroblast cells. The p+ and p0 human fibroblast cell lines were used, which carry wild-type mtDNA and no mtDNA, respectively. Clonogenic radiosensitivity was evaluated by colony formation assay and micronucleus (MN) formation assay. The ATP assay was then used to address the discrepancy between the results of the former two assays. Despite the lack of a significant difference in survival in the colony formation assay, p+ and p0 cells exhibited high and low radiosensitivities, respectively, in the MN formation assay (P < 0.003). This difference in MN formation correlated with high and low levels of cellular ATP content in p+ and p0 cells (P = 0.004). The addition of antimycin A suppressed differences in both MN formation and cellular ATP content. In the transformed human fibroblast cells we used, mtDNA played an important role in radiation-induced MN formation that was correlated with the levels of cellular ATP content. These results may imply the presence of an MN expression pathway that is dependent on the intrinsic ATP level and that may be compensated and lead to an equivalent level of clonogenic survival.

Adenosine Triphosphate↗
PubMed2004

Gastric dysmotility associated with accumulation of mitochondrial A3243G mutation in the stomach.

OBJECTIVE: We analyzed the accumulation of a mitochondrial A-to-G mutation at nucleotide position 3243 (A3243G) in the stomach and gastric motility in patients with gastric symptoms, post-prandial nausea/vomiting and epigastralgia. METHODS: Detection and quantification of A3243G mutation in mtDNA in the gastric mucosa, oral mucosa, leukocyte, and skeletal muscle were performed. Gastric motility was evaluated by gastric myoelectrical activity on electrogastrography (EGG), and gastric emptying was evaluated by measurement of plasma paracetamol concentration before and after meals. PATIENTS OR MATERIALS: Four patients with A3243G mutation in the leukocyte mtDNA and gastric symptoms were examined. RESULTS: The A3243G mutation was detected at higher percentages in the gastric body (69-94% for mutation; mean, 83%) than in the angle portion (37-82%; mean, 52%), the antrum (40-84%; mean, 57%) or leukocytes (28-52%; mean, 39%), and at slightly higher percentages than in the skeletal muscles (45-87%; mean, 70%) or oral mucosae (52-86%; mean, 69%) in the four patients examined. Abnormal EGGs were observed in the three patients examined. The pre-prandial myoelectrical activities were low in these patients (49% in patient 1, 54% in patient 2, 63% in patient 3; normal >70%). The plasma concentrations of paracetamol were low (3.6 microg/ml in patient 1, 2.4 microg/ml in patient 2, <2.0 microg/ml in patient 3; normal, 7-12 microg/ml). CONCLUSION: Accumulation of mitochondrial A3243G mutation in the stomach is a contributory factor in gastric dysmotility and gastric symptoms in patients with the mutation in their leukocytes.

Adult↗
PubMed2004

[Thiamine deficiency polyneuropathy after gastrectomy associated with high level of serum vascular endothelial growth factor (VEGF). A case report].

We report a 66-year-old man who developed vitamin B1 deficiency polyneuropathy long after a gastrectomy. After a preceding bronchial infection, the patient noticed numbness and weakness in his extremities, followed by generalized edema and exertional dyspnea. He had undergone subtotal gastrectomy due to duodenal ulcer at age 19. His daily oral intake of food was normal without any alcoholic abuse. He was admitted to our hospital with rapidly progressive gait disturbance due to muscle weakness, and sensory disturbance. Neurological examination showed peripheral polyneuropathy with distal dominant muscular weakness and sensory disturbance. Chest X-ray film showed marked cardiomegaly and pleural effusion. Nerve conduction studies showed decreases in the action potentials of both the motor and sensory nerves, with the sensory nerves being more severely affected than the motor nerves. Sural nerve biopsy demonstrated severe axonal degeneration without any inflammatory change. The blood concentration of thiamine (vitamin B1) was slightly decreased below the normal range (19 ng/ml; normal, 20-50), and the serum vascular endothelial growth factor (VEGF) was high (890 pg/ml; normal < 200 pg/ml). Intravenous administration of vitamin B1 (50 mg per day) dramatically improved his symptoms in a few days and the level of VEGF returned to nearly normal. In this gastrectomized patient many years ago, vitamin B1 deficiency neuropathy is warranted in view of a prompt response to thiamine administration. This case suggests that VEGF is involved in the pathogenesis of vitamin B1 deficiency polyneuropathy.

Aged↗
PubMed2004

[A case showing Wallerian degeneration of the bilateral middle cerebellar peduncles on MRI followed by the right pontine infarction].

We report a 63-year-old man who presented with the left facial palsy, the left hemiparesis, the left limb ataxia, and the bilateral truncal ataxia. On admission, magnetic resonance imaging (MRI) showed an abnormal high intensity lesion at the right paramedian region of the upper to middle pons on T2-weighted images (T2WI). He was diagnosed as having a pontine lacunar infarction. The contralateral cerebellar lesions were caused by involvement of the pontocerebellar fibers. On the 29th day from the onset, MRI showed the new abnormal high intensity lesions at the bilateral middle cerebellar peduncles on T2WI. These lesions were supposed to be Wallerian degeneration caused by involvement of the pontocerebellar fibers. This case suggests that Wallerian degeneration occurs followed by a unilateral infarction involving pontocerebellar fibers.

Brain Infarction↗
PubMed2003

[Adult cases of viral meningitis caused by echovirus type 13].

Adult cases of viral meningitis caused by echovirus type 13 (E13) were studied. E13 was isolated from 8 of 11 adult patients (73%) with viral meningitis between April and September 2002 in Fukui Prefecture. The mean age was 27.4 +/- 6.4 years (4 males and 4 females). The disease was prevalent among adults, especially younger adults as well as children. The symptoms and signs were as follows; headache (100%), fever (100%), nausea and/or vomiting (88%), Kernig's sign (88%), and increased deep tendon reflexes (50%). The average cell counts in cerebrospinal fluid (CSF) were 118 +/- 111/mm3. Of the 2 patients, polynuclear cells were dominant during the early phase of the disease. The prognosis was good. Since May 2002, the number of patients with viral meningitis caused by E13 has rapidly increased. Most of the reported patients were children. We should consider the possibility of E13 infection as a cause of adult viral meningitis.

Adolescent↗
PubMed2002

Gene therapy for mitochondrial disease by delivering restriction endonuclease SmaI into mitochondria.

The restriction endonuclease SmaI has been used for the diagnosis of neurogenic muscle weakness, ataxia and retinitis pigmentosa disease or Leigh's disease, caused by the Mt8993T-->G mutation which results in a Leu156Arg replacement that blocks proton translocation activity of subunit a of F(0)F(1)-ATPase. Our ultimate goal is to apply SmaI to gene therapy for this disease, because the mutant mitochondrial DNA (mtDNA) coexists with the wild-type mtDNA (heteroplasmy), and because only the mutant mtDNA, but not the wild-type mtDNA, is selectively restricted by the enzyme. For this purpose, we transiently expressed the SmaI gene fused to a mitochondrial targeting sequence in cybrids carrying the mutant mtDNA. Here, we demonstrate that mitochondria targeted by the SmaI enzyme showed specific elimination of the mutant mtDNA. This elimination was followed with repopulation by the wild-type mtDNA, resulting in restoration of both the normal intracellular ATP level and normal mitochondrial membrane potential. Furthermore, in vivo electroporation of the plasmids expressing mitochondrion-targeted EcoRI induced a decrease in cytochrome c oxidase activity in hamster skeletal muscles while causing no degenerative changes in nuclei. Delivery of restriction enzymes into mitochondria is a novel strategy for gene therapy of a special form of mitochondrial diseases.

Apoptosis↗
PubMed2002

[Luft's disease].

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Citric Acid Cycle↗
PubMed2002

[MERRF].

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DNA, Mitochondrial↗