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Biomedical subjects

Y Eto

Publications and source records attributed to Y Eto.

At least 37 records · Page 2Linked to original sources
PubMed2001

Magnetic resonance imaging in three children with kernicterus.

The incidence of kernicterus has been greatly reduced by effective monitoring and treatment for hyperbilirubinemia. Findings on magnetic resonance imaging (MRI) in patients with kernicterus are characteristic. This study presents three cases of possible kernicterus without typical symptoms but with MRI features consistent with kernicterus. These cases suggest that kernicterus can develop, especially in preterm infants, in the presence of relatively low levels of bilirubin and the absence of obvious acute symptoms. Therefore assessing the risk of kernicterus may be difficult in the neonatal period. In addition, MRI findings at the posteromedial border of the globus pallidus in patients with athetotic cerebral palsy are strong evidence of brain damage caused by kernicterus.

Brain↗
PubMed2001

Frontal lobe dementia with abnormal cholesterol metabolism and heterozygous mutation in sterol 27-hydroxylase gene (CYP27).

Of the primary dementing disorders that cause frontotemporal dementia, the best-known is Pick disease. We report on a 44-year-old woman with progressive frontal lobe dementia and spastic paraplegia. Examination revealed increased serum levels of cholestanol with abnormal cholesterol metabolism and a heterozygous mutation of the sterol 27-hydroxylase gene (CYP27). Biochemical findings were compatible with cerebrotendinous xanthomatosis (CTX); however, the clinical manifestations were very dissimilar. To our knowledge, a symptomatic carrier of this mutation among CTX patients has not been reported. We speculate that the present patient has a previously undescribed neurodegenerative disease related to abnormal cholesterol metabolism with this heterozygous mutation.

Adult↗
PubMed2001

Efficient and cancer-selective gene transfer to hepatocellular carcinoma in a rat using adenovirus vector with iodized oil esters.

Gene therapy for cancer requires efficient, selective gene transfer to cancer cells. In gene therapy for hepatocellular carcinoma (HCC), gene transfer is efficient for small tumors, but not for large tumors. The delivery of anticancer agents and of iodized oil esters as embolic agents through tumor-feeding arteries is known as transarterial embolization. We speculate that genes may be efficiently and selectively transferred for HCC using iodized oil esters because these esters may remain together with a genetic vector within HCC selectively. Hence, we have studied the effect of iodized oil esters on adenovirus vector-mediated gene transfer for HCC in vivo. A rat model of HCC induced with diethylnitrosamine and phenobarbital was injected with either AxCALacZ, which expresses the beta-galactosidase of Escherichia coli, or AxCALacZ and iodized oil esters into the hepatic artery. Histological comparisons revealed that the beta-galactosidase expression in the rats with HCC injected with AxCALacZ and iodized oil esters was greater (P<.0001) in small tumors (P=.0046) and large tumors (P=.0023), and more selective (P=.0229) than in only AxCALacZ-injected rats. These results suggest that iodized oil esters are injected into hepatic artery together with adenovirus vector, and that genes may be efficiently and cancer-selectively transferred to HCC.

Adenoviridae↗
PubMed2001

Intraventricular administration of recombinant adenovirus to neonatal twitcher mouse leads to clinicopathological improvements.

Twitcher mouse is a murine model of human globoid cell leukodystrophy (Krabbe disease), which is characterized by a genetic deficiency in galactocerebrosidase (GALC) activity. The nervous system is affected early and severely by demyelination in the white matter. So far, there is no effective treatment for Krabbe disease except bone marrow transplantation (BMT). However, BMT has inherent limitations such as unavailability of donors and graft-versus-host disease. In this study, we injected recombinant adenovirus encoding GALC into the lateral ventricle of twitcher mice at postnatal day 0 (PND 0) and the therapeutic effects were evaluated. Our results showed slight, but significant improvements in motor functions, body weight and twitching and a prolonged life span. In brain, GALC activity was increased to 15% that of normal littermates and psychosine concentration was decreased to 55% that of untreated twitcher mice at PND 15. The number of PAS-positive globoid cells in brain stem was also reduced significantly at PND 35. In contrast, when adenoviruses were injected to the twitcher mice at PND 15, almost no improvements were observed. These results demonstrate that the timing of treatment may be of great importance in Krabbe disease.

Adenoviridae↗
PubMed2001

Interleukin-1 beta enhances and interferon-gamma suppresses activin A actions by reciprocally regulating activin A and follistatin secretion from bone marrow stromal fibroblasts.

Activin A is a multi-functional cytokine with a potent stimulation on erythroid cell differentiation in the bone marrow. The actions of activin A are determined by a balance of the levels of activin A and its inhibitor, follistatin (FS). However, the regulation of its actions in the bone marrow has been unclear. Here we show that bone marrow-derived stromal fibroblasts are the major source of activin A and FS in the bone marrow, and that the production of activin A is enhanced by interleukin-1beta (IL-1beta) and lipopolysaccharide (LPS), whereas interferon-gamma (IFN-gamma) inhibits the secretion of activin A by stromal fibroblasts. Concomitantly, IL-1beta as well as LPS inhibits and IFN-gamma stimulates FS secretion from stromal fibroblasts. Thus, these cytokines potently regulate activin A actions by reciprocal modulation of activin A and FS secretion from stromal fibroblasts. Because activin A exhibits anti-inflammatory effects in various tissues, up-regulation of activin A actions by IL-1beta and endotoxin in the bone marrow may play a protective role against inflammatory processes as well as anaemia. The present results also suggest that the inhibitory effect of IFN-gamma on erythropoiesis is mediated at least in part by a suppression of activin A actions in bone marrow.

Activins↗
PubMed2001

Establishment and characterization of immortalized Schwann cells from murine model of Niemann-Pick disease type C (spm/spm).

Niemann-Pick disease type C (NPC) is characterized by an accumulation of unesterified cholesterol in the endosomal/lysosomal (E/L) system, resulting in progressive neurodegeneration and death during early childhood. To investigate the cellular pathomechanism of nervous system involvement in NPC, continuous neural cell lines are desirable. In this study, we obtained neuronal and Schwann cell cultures and established spontaneously immortalized Schwann cell lines from dorsal root ganglia and peripheral nerves of NPC model mouse (spm/spm). One of the cell lines, designated SPMS9, had distinct Schwann cell phenotypes and was maintained over 10 months without phenotypic alterations. The level of Npc1 mRNA was markedly decreased, and NPC1 protein was not detectable in SPMS9 cells. These cells contained intracytoplasmic granules positive for filipin cholesterol staining and immunoreactive for GM2 ganglioside. Electron-microscopically, intracytoplasmic polymorphous membranous inclusions and vacuoles were demonstrated in SPMS9 cells. The treatment with an inhibitor of ceramide-specific glucosyltransferase, N-butyldeoxynojirimysin (NB-DNJ) markedly reduced the intracytoplasmic granular immunofluorescence for GM2 ganglioside in SPMS9 cells, whereas the amount of filipin-positive granules remained unchanged. The SPMS9 cells retained vesicular fluorescence of cationic dye acriflavine 16-24 hours after loading, indicating the defect of transmembrane efflux pump activity of NPC1 in the E/L compartment in these cells. These immortalized Schwann cells can be useful in studies on the nervous system lesions in NPC.

Animals↗
PubMed2001

OARE-1, a Ty1-copia retrotransposon in oat activated by abiotic and biotic stresses.

Transcriptionally active Ty1-copia LTR-retrotransposons were found in oat using RT-PCR for amplifying the reverse transcriptase domain. Sequence analysis of the RT-PCR clones suggested that oat LTR-retrotransposons consist of at least seven groups, which were tentatively designated as Oatrt1 to Oatrt7. A full length copy of Oatrt1 was isolated from an oat genomic library, and was designated OARE-1. OARE-1 was 8,665 bp long and a member of the BARE-1 subgroup. The oat genome carried it in multiple copies (at least 10,000 copies / a hexaploid genome). The expression of OARE-1 was intensively induced by wounding, UV light, jasmonic acid and salicylic acid, and its pattern was very similar to that of the PAL (phenylalanin ammonia lyase) gene. Furthermore, OARE-1 was highly activated by infection with an incompatible race of the crown rust fungus, Puccinia coronata. These results suggest that OARE-1 is highly sensitive to various abiotic and biotic stimuli leading to plant defense responses.

Amino Acid Sequence↗
PubMed2001

In vivo gene transfer of dominant-negative rho-kinase induces regression of coronary arteriosclerosis in pigs.

Small GTPase Rho and its target Rho-kinase play an important role in various cellular functions that may be involved in the pathogenesis of arteriosclerosis. Here we show that adenovirus-mediated transfer of dominant-negative Rho-kinase (AdDNRhoK) induces a regression of coronary constrictive remodeling and abolishes coronary vasospastic activity in vivo. Porcine coronary segments were chronically treated with interleukin-1,beta which resulted in the development of constrictive remodeling and vasospastic responses to serotonin in vivo. AdDNRhoK, but not that of beta-galactosidase, into the interleukin-1beta-treated coronary segment caused regression of constrictive remodeling and abolished vasospastic activity in 3 weeks. The unregulated phosphorylation of the target proteins of Rho-kinase at the coronary lesion was significantly suppressed by AdDNRhoK. These results indicate that Rho-kinase is substantially involved in the mechanism of coronary arteriosclerosis, which can be reversed by selective inhibition of the molecule in our porcine model in vivo.

Animals↗
PubMed2001

Adenovirus-mediated transfer of dominant-negative rho-kinase induces a regression of coronary arteriosclerosis in pigs in vivo.

Small GTPase Rho and its target Rho-kinase/ROK/ROCK play an important role in various cellular functions, including smooth muscle contraction, actin cytoskeleton organization, and cell adhesion and migration, all of which may be involved in the pathogenesis of arteriosclerosis. Here, we show that adenovirus-mediated transfer of dominant-negative Rho-kinase (DNRhoK) induces a marked regression of coronary constrictive remodeling and abolishes coronary vasospastic activity in vivo. Porcine coronary segments were chronically treated with interleukin-1beta, which resulted in the development of constrictive remodeling and vasospastic responses to serotonin, as previously reported. Adenovirus-mediated transfer of DNRhoK, but not that of beta-galactosidase, into the interleukin-1beta-treated coronary segment caused a marked regression of the constrictive remodeling and abolished the vasospastic activity in 3 weeks. Western blot analysis showed that the phosphorylation of adducin and the ezrin/radixin/moesin family, the target proteins of Rho-kinase, were upregulated at the coronary lesions and were significantly suppressed by the transfer of DNRHOK: These results indicate that Rho-kinase is substantially involved in coronary constrictive remodeling and vasospastic responses, both of which can be reversed by the selective inhibition of the molecule in our porcine model in vivo.

Adenoviridae↗
PubMed2001

Adenoviral gene transfer of glial cell line-derived neurotrophic factor to injured adult motoneurons.

Glial cell line-derived neurotrophic factor (GDNF) strongly supports the survival of injured neonatal motoneurons, suggesting its potential uses in the treatment of motoneuron injury and motor neuron diseases. We examined neuroprotective effects of an adenoviral vector encoding GDNF (AxCAhGDNF) on the survival of lesioned adult rat facial and spinal motoneurons. The facial nerve or the seventh cervical segment (C7) ventral and dorsal roots of 3 month-old Fischer 344 male rats were avulsed and removed from the stylomastoid or vertebral foramen, respectively, and AxCALacZ (adenovirus containing beta-galactosidase gene), AxCAhGDNF, or PBS was inoculated in the lesioned foramen. One week after the avulsion and treatment with AxCALacZ, the animal showed expression of beta-galactosidase activity in lesioned facial and spinal motoneurons. Animals avulsed and treated with AxCAhGDNF showed intense immunolabeling for GDNF in lesioned facial and spinal motoneurons and expression of virus-induced human GDNF mRNA transcripts in the lesioned brain stem and spinal cord tissues. The treatment with AxCAhGDNF after avulsion significantly prevented the loss of lesioned facial and C7 spinal motoneurons, ameliorated choline acetyltransferase immunoreactivity, and suppressed the activity of nitric oxide synthase in these neurons. These results indicate that the adenovirus-mediated gene transfer of GDNF may prevent the degeneration of motoneurons in adult humans with motoneuron injury and motor neuron diseases.

Adenoviridae↗
PubMed2001

[Investigation to sequelae of acute encephalopathy].

We investigated 22 children with sequelae of acute encephalopathy. The patients were divided into 4 groups; group I with almost complete recovery (2 cases), group II with mild mental deterioration (4 cases), group III with severe mental deterioration (8 cases) and group IV with severe mental deterioration and severe physical disabilities (8 cases). There was no difference between 4 groups with regard to the past history, and status at the onset. The period of rehabilitation in hospital was different, being 0.4 month in group I, 2.6 months in group II, 3.0 months in group III and 3.6 months in group IV. The rehabilitation approach consisted mainly of medical therapy and range of motion exercise in the early stage followed trainings for walking and cognition. Family support was essential during the entire course. Evaluation with the functional independence measure was very useful for the rehabilitation.

Activities of Daily Living↗
PubMed2000

Rescue of ischemic brain injury by adenoviral gene transfer of glial cell line-derived neurotrophic factor after transient global ischemia in gerbils.

Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor (TGF)-beta superfamily, is one of the most potent neurotrophic factors and promotes survival of many populations of cells. We examined neuroprotective effect of an adenoviral vector encoding glial cell line-derived neurotrophic factor (AxCAhGDNF) on the transient global ischemia. Gerbils received administration of AxCAhGDNF or an adenoviral vector encoding bacterial beta-galactosidase gene (AxCALacZ) through the lateral ventricle. Two days later, occluding bilateral common carotid arteries for 5 min using aneurysm clips produced the transient global forebrain ischemia. Animals showed intense immunolabeling for GDNF in ependymal cells on 2, 4 and 7 days after the operation. The exogenous gene transducted by adenovirus in the same cells was detected by in situ hybridization. The treatment with AxCAhGDNF significantly prevented the loss of hippocampal CA1 pyramidal neurons 2 to 7 days after the operation, as compared to AxCALacZ treatment. Also terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) staining was markedly reduced in the case with AxCAhGDNF treatment at 7 days after the operation. These results indicated that the adenovirus-mediated gene transfer of GDNF might prevent the delayed neuronal death of stroke and other disorders of the cerebral vasculature.

Adenoviridae↗
PubMed2000

Adenoviral vector-mediated GDNF gene transfer prevents death of adult facial motoneurons.

We examined neuroprotective effects of an adenoviral vector encoding glial cell line-derived neurotrophic factor (AxCAhGDNF) on the lesioned adult rat facial motoneurons. After facial nerve avulsion, animals locally injected into the facial canal with AxCALacZ (adenovirus encoding beta-galactosidase gene) or AxCAhGDNF showed expression of beta-galactosidase activity or intense immunolabeling for GDNF in lesioned facial motoneurons, respectively. The treatment with AxCAhGDNF after avulsion significantly prevented the loss of lesioned facial motoneurons, ameliorated choline acetyltransferase immunoreactivity, and suppressed the activity of nitric oxide synthase in these neurons. These results indicate that the adenovirus-mediated gene transfer of GDNF may prevent the degeneration of motoneurons in adult humans with peripheral nerve injury and motor neuron diseases.

Adenoviridae↗
PubMed2000

Reduction of lysosomal storage in murine mucopolysaccharidosis type VII by transplantation of normal and genetically modified macrophages.

This study examined the ability of macrophages to serve as target cells of gene therapy for mucopolysaccharidosis (MPS) type VII using a murine model. Bone marrow cells were harvested from syngeneic normal mice and differentiated to macrophages. These cells were given to nonmyeloablated MPS VII mice. After transplantation, donor cells populated the liver and spleen. The pathologic improvement at day 38 after transplantation was significant and glycosaminoglycan storage was reduced. To develop gene therapy using this system, a retroviral vector expressing human beta-glucuronidase (HBG) was used to infect macrophages cultivated from MPS VII mice and given to nonmyeloablated MPS VII mice. At 38 days after transplantation, HBG-positive cells were still observed histochemically and pathologic improvement was significant. These observations suggest that macrophage transplantation is a promising method for treatment of murine MPS VII without myeloablation, and macrophages may be good target cells for ex vivo gene therapy for MPS VII.

Animals↗
PubMed2000

Rescue of lesioned adult rat spinal motoneurons by adenoviral gene transfer of glial cell line-derived neurotrophic factor.

Glial cell line-derived neurotrophic factor (GDNF) has been shown to protect cranial and spinal motoneurons, that suggests potential uses of GDNF in the treatment of spinal cord injury and motor neuron diseases. We examined neuroprotective effect of human GDNF encoded by an adenovirus vector (AxCAhGDNF) on the death of lesioned adult rat spinal motoneurons. The seventh cervical segment (C7) ventral and dorsal roots and dorsal root ganglia of adult Fisher 344 rats were avulsed, and AxCAhGDNF, AxCALacZ (adenovirus encoding beta-galactosidase gene) or PBS was inoculated in C7 vertebral foramen. One week after the avulsion and treatment with AxCALacZ, the animals showed expression of beta-galactosidase activity in lesioned spinal motoneurons. Animals avulsed and treated with AxCAhGDNF showed intense immunolabeling for GDNF in lesioned spinal motoneurons and expression of virus-induced human GDNF mRNA transcripts in the lesioned spinal cord tissue. Nissl-stained cell counts revealed that the treatment with AxCAhGDNF significantly prevented the loss of lesioned ventral horn motoneurons 2 to 8 weeks after avulsion, as compared to AxCALacZ or PBS treatment. Furthermore, the AxCAhGDNF treatment ameliorated choline acetyltransferase immunoreactivity in the lesioned motoneurons after avulsion. These results indicate that the adenovirus-mediated gene transfer of GDNF may prevent the degeneration of motoneurons in adult humans with spinal cord injury and motor neuron diseases.

Adenoviridae↗