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A Oka

Publications and source records attributed to A Oka.

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

[Mitochondrial DNA T to G mutation 8993 in Leigh encephalopathy and organic aciduria].

We report a 10-month-old female infant with Leigh encephalopathy caused by a T to G mutation at nucleotide 8993 of mitochondrial DNA. Initial manifestations were diarrhea and pyrexia, followed by disturbance of consciousness. Blood chemistry showed lactic acidosis, and cranial T2 weighted magnetic resonance imaging demonstrated symmetric high-intensity areas in the basal ganglia, consistent with Leigh encephalopathy. Analysis of urinary organic acids revealed a increase of alpha-ketoglutamate. Derivatives of branched chain amino acids, which accumulate in maple syrup disease, were also increased. Lipoamide dehydrogenase (E3) deficiency was initially suspected; however, normal activity of pyruvate dehydrogenase complex excluded the diagnosis. The organic aciduria disappeared after two weeks. The CNS lesions in our case were observed more prominently in the floor of the bilateral frontal lobes than in the globus pallidus and putamen. In this case, mitochondrial DNA mutation may have caused organic aciduria and the atypical imaging findings.

DNA, Mitochondrial↗
PubMed2001

Bioinformatics issues for automating the annotation of genomic sequences.

The rapid explosion in the amount of biological data being generated worldwide is surpassing efforts to manage analysis of the data. As part of an ongoing project to automate and manage bioinformatics analysis, the authors have designed and implemented a simple automated annotation system, which is described in this paper. The system is applied to existing GenBank/DDBJ/EMBL entries and compared with existing annotations to illustrate not only potential errors but also that they are generally not up-to-date, as a result of new versions of analysis tools and updates of genomic repositories. We highlight the important Bioinformatics issues of storage and management of information to ensure data and results are kept up-to-date in light of new information becoming available. Surprisingly, from just four database entries, a significant number of new features were found. We describe the results as well as identify important issues that need to be addressed in order to automate the re-analysis/re-annotation of genomic sequences within a reasonable timeframe.

Computational Biology↗
PubMed2000

Expression of DNA-dependent protein kinase catalytic subunit and Ku80 in developing human brains: implication of DNA-repair in neurogenesis.

We investigated expression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and Ku80 in developing human brain, both of which have been suggested to be involved in the repair of DNA double-strand break (DSB). Their expressions were well correlated, and the highest immunoreactivity was observed in post-mitotic immature neurons in the cerebral cortex as well as in progenitors in the periventricular germinal layer. The reactivity gradually decreased during development. Our results support the notion that DSB is generated during the ontogeny of the human central nervous system.

Adolescent↗
PubMed2000

Enhanced GAP-43 gene expression in cortical dysplasia.

Growth-associated protein GAP-43, a phosphoprotein enriched at presynaptic nerve terminals, is thought to be involved in axonal outgrowth and plasticity in synaptic connections. To explore the synaptic remodeling under the epileptic conditions, we examined GAP-43 expression in brain specimens surgically resected as epileptogenic foci from 17 patients with cortical dysplasia. In situ hybridization with GAP-43 antisense riboprobe showed significantly increased signals in the dysplastic large neurons of cortical dysplasia. Specific distribution with increased immunoreactivity for GAP-43 was not shown in the dysplastic cortex. These results suggest that GAP-43 gene expression is over-expressed in the dysplastic large neurons, reflecting activated synaptic remodeling in the epileptic condition of cortical dysplasia, although the precise site of accelerated synaptic rearrangement remains unknown.

Cerebral Cortex↗
PubMed2000

Rapid immunologic diagnosis of classic late infantile neuronal ceroid lipofuscinosis.

OBJECTIVE: To establish a new method for rapid diagnosis of late infantile neuronal ceroid lipofuscinosis (LINCL, CLN2) using specific polyclonal antibodies against the CLN2 gene product. METHODS: Cells and tissues were obtained from five patients with LINCL, two with variant type NCL, three with other lysosomal storage diseases, and eight control subjects. Two antibodies were raised against N- and C-terminal peptide fragments of the normal product of the CLN2 gene. The authors examined the possibility of diagnosis of LINCL with immunostaining and immunoblotting using specific antibodies made of the recently identified defective gene in LINCL. RESULTS: Immunoreactivity with these antibodies showed the absence or marked reduction of CLN2 immunoreactivity in the lymphocytes, lymphoblasts, and fibroblasts of all five patients with LINCL examined. CONCLUSIONS: These results indicate the usefulness of this diagnostic method based on the changes in CLN2 immunoreactivity. This relatively simple, specific, and cost-effective method is a promising diagnostic tool for this disease, although additional studies are necessary.

Aminopeptidases↗
PubMed2000

Bax and Bcl-2 protein expression following radiation therapy versus radiation plus thermoradiotherapy in stage IIIB cervical carcinoma.

BACKGROUND: The relative amounts of Bcl-2 and Bax proteins determine cell survival or death following an apoptotic stimulus. To clarify the molecular mechanism of cell death after radiotherapy or thermoradiotherapy and its relation to the response of AJCC/UICC Stage IIIB cervical carcinomas, the expression of Bax and Bcl-2 proteins was investigated both before and in the course of treatment given during this study. METHODS: Thirty-seven patients with Stage IIIB carcinoma of the uterine cervix were treated with external beam irradiation to the pelvis combined with iridium-192 high-dose-rate intracavitary brachytherapy. All patients were randomized to one of the following two groups: the radiotherapy (RT) group of 19 patients who were given radiotherapy alone, and the thermoradiotherapy (TRT) group of 18 patients who were given 3 sessions of hyperthermia in addition to RT. Specimens of the cervical tumors were obtained by punch biopsy both before and in the course of the treatment (after a total dose of 10.8 grays ¿Gy for the RT group or after 10.8 Gy plus 1 session of hyperthermia for the TRT group). The tumor sections were stained with anti-Bax and anti-Bcl-2 monoclonal antibody. On the basis of the percentage of immunopositive cells, both pretreatment and posttreatment samples were scored. Furthermore, relative changes in protein expression were determined by comparing the pretreatment scores with those in the course of treatment. In addition, treatment response was evaluated. RESULTS: A complete response was achieved in 52.6% (10 of 19) of the RT group versus 83. 3% (15 of 18) of the TRT group (P = 0.049). Better tumor control was accompanied by increased Bax expression, i.e., 10.5% (2 of 19) of the RT group versus 44.4% (8 of 18) of the TRT group (P = 0.02). The respective number of patients who partially responded (PR) or did not respond to treatment (NC) was 26.3% (5 of 19) and 21.1% (4 of 19) of the RT group versus 11.1% (2 of 18) and 5.6% (1 of 18) of the TRT group (P = 0.2 for both the PR and NC subgroups). CONCLUSIONS: TRT was found to result in better treatment responses than RT for patients with Stage IIIB cervical carcinoma. An additive or synergistic antitumor effect of TRT is likely to occur through induction of apoptosis involving one of the bax pathways.

Aged↗
PubMed2000

The developmental and aging changes of Down's syndrome cell adhesion molecule expression in normal and Down's syndrome brains.

We studied the expression of Down's syndrome cell adhesion molecule (DSCAM) in Down's syndrome (DS) and control brains, using antisera against peptide fragments of DSCAM. On Western blots of human, mouse and rat brain homogenates, the antisera recognized a product at approximately 200 kDa. In the brain of a 2-year-old patient with DS, Western blotting revealed an overexpression of DSCAM compared to an age-matched control. Immunohistochemistry demonstrated DSCAM in the cerebral and cerebellar white matter of both control and DS subjects, in accordance with the temporal and spatial sequence of myelination. In DS brains, immunoreactivity for DSCAM, compared to that for controls, was enhanced in the Purkinje cells at all ages, and in the cortical neurons during adulthood. In demented DS patients, DSCAM immunoreactivity was observed in the core and periphery of senile plaques. The pattern of DSCAM expression suggests that it may play a role as an adhesion molecule regulating myelination. The overexpression of DSCAM may also play a role in the mental retardation and the precocious dementia of DS patients, although the mechanism of neuronal dysfunction is undetermined.

Adolescent↗
PubMed2000

Communicating hydrocephalus in a patient with Gaucher's disease type 3.

The case of a 3-year-old male with type 3 Gaucher's disease, whose genotype for the beta-glucosidase gene was D409H/unknown mutation, is presented. After the onset of visceral and neurologic signs during infancy, a radiologic investigation at 3 years of age revealed communicating hydrocephalus, an unusual complication of Gaucher's disease. A ventriculoperitoneal shunt operation led to clinical and radiologic improvement. The possibility of this complication should be considered in the treatment of patients with Gaucher's disease.

Child, Preschool↗
PubMed2000

TT virus infection among renal transplant recipients.

To clarify the prevalence of TT virus (TTV) infection in renal transplant recipients and to estimate the role of TTV in patients with post-transplant liver function abnormalities, TTV-DNA of 47 renal transplant recipients was screened by polymerase chain reaction (PCR) according to a method described by Okamoto et al. before and after the renal transplantation. One of them was positive for hepatitis B surface antigen (HBsAg), one was positive for anti-hepatitis C virus (HCV) and other 45 were negative for both HBsAg and anti-HCV. TTV-DNA was detected in 22 of 47 patients before renal transplantation, and nine became positive after transplantation. All 47 patients showed a normal level of ALT before transplantation. Three of nine (33%) who became positive for TTV-DNA after transplantation and three of 16 (19%) who were negative for TTV-DNA before and after transplantation showed transient elevation of ALT. These results indicate that TTV was highly prevalent among renal transplant recipients, but a clear association between TTV and post-transplant liver function abnormality was not found.

Journal Article↗
PubMed2000

New ocular movement detector system as a communication tool in ventilator-assisted Werdnig-Hoffmann disease.

A non-contact communication system was developed for a ventilator-assisted patient with Werdnig-Hoffmann disease who had lost all voluntary movements except for those of the eye. The system detects the extraocular movements and converts them to either a 'yes' signal (produced by one lateral eyeball movement) or a 'no' signal (produced by two successive lateral eyeball movements) using a video camera placed outside the patient's visual field. The patient is thus able to concentrate on performing a task without any intrusion from the detection system. Once the setting conditions of the device have been selected, there is no need for any resetting, as the patient is unable to move his body. In addition to playing television games, the child can use the device to select television channels, compose music, and learn written Japanese and Chinese characters. This seems to broaden the patient's daily world and promote mental development.

Activities of Daily Living↗
PubMed2000

Histopathology of a human allografted kidney with clinically sufficient function.

To clarify the clinico-pathological significance of protocol biopsy and clinically silent rejection in the management of renal graft recipients, we selected a total of 139 (23%) from 604 biopsy specimens according to the following criteria: 1) less than 1.4 mg/dL of serum creatinine and 2) more than 1,500 mL/d of urine volume at time of biopsy. Clinical indications for the biopsy were classified into five categories: i) protocol biopsy (73 specimens), including 69 cases at discharge post-transplantation; ii) slight increase in serum creatinine (32); iii) proteinuria (20); iv) evaluation of pulse-therapy (13); and v) fever elevation (1). Except for the last category, the specimens were histopathologically diagnosed as being normal in 50 (68%), 6 (17%), 1 (5%), and 5 (38%) specimens, respectively. Even borderline changes, and mild acute rejection, as well as drug-induced nephropathy were included, implying the existence of clinically silent rejection or drug-induced nephropathy. Obvious diversity in the histopathological diagnosis was noted in category iii) showing proteinuria, which was mainly caused by chronic rejection, drug-induced nephropathy and glomerulonephritis. The graft survival rate was no different among the four categories, except for category v). These results indicate that biopsies obtained from functionally sufficient renal grafts could provide useful information in the management of the recipients. The clinical significance of protocol biopsy awaits further clarification by the analysis of a large number of cases.

Biopsy↗
PubMed2000

Genetic polymorphisms in the cell growth regulated gene, SC1 telomeric of the HLA-C gene and lack of association of psoriasis vulgaris.

Psoriasis vulgaris is associated with the HLA-Cw6 and Cw7 antigens. We have previously narrowed down the critical region most likely to contain the psoriasis vulgaris gene to 111 kb spanning 89 kb to 200 kb telomeric of the HLA-C locus by microsatellite mapping. This segment includes three known genes (POU5F1, SC1 and S) and four new expressed genes. Among them, SC1 (TCF19) is the cell growth regulated gene possibly with trans-activator activity. Since psoriasis vulgaris is a common skin disorder characterized by hyperproliferation of epidermal cells, it is tempting to speculate that the SCI gene is one of the strong candidate genes responsible for the development of psoriasis vulgaris. Here, we investigated genetic polymorphisms in the SC1 gene by direct DNA sequencing and polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) techniques. Three single nucleotide polymorphisms in exon 2, two of which are accompanied by amino-acid substitutions, were identified. Further, one 4-bp deletion polymorphism was detected around the acceptor site of the lariat-shaped structure necessary for RNA splicing in intron 2. No significant difference in the dimorphic or haplotypic distribution at these four polymorphic sites was observed between the patients with psoriasis vulgaris and healthy controls. This suggests that the susceptible gene for psoriasis vulgaris is not the SC1 gene itself, although a unique homozygous haplotype was identified in the patients.

Base Sequence↗
PubMed2000

New polymorphic microsatellite markers in the human MHC class II region.

The human major histocompatibility complex (MHC) class II region spans approximately 1.1 Mb and presently contains over 30 functional genes Susceptibility loci to numerous diseases, mainly of autoimmune nature are known to map to the this region, as assessed by associations with particular HLA class II alleles. However, it has been difficult to precisely localize these susceptibility loci to a single gene, for example DQB1 or DRB1, due to the tight linkage disequilibrium observed in the HLA class II region. To facilitate disease mapping within this region, we have analyzed 2 to approximately 5 bases short tandem repeats (microsatellites) in this same region. A total of 494 microsatellites were identified from the genomic sequence of the HLA class II region. These consist of 158 di-, 65 tri-, 163 tetra-, and 108 pent-nucleotide repeats, out of which four were located within the coding sequence of expressed genes (Daxx, BING1, RXRB and COL11A2). Twenty-two repeats were selected as polymorphic markers due to their high (average) number of alleles (8.9) as well as their high polymorphic content value (PIC) (0.58). These novel polymorphic microsatellites will provide useful genetic markers in HLA-related research, such as genetic mapping of HLA class II-associated diseases, transplantation matching, population genetics, identification of recombination hot spots as well as linkage disequilibrium studies.

DNA Primers↗
PubMed2000

Arabidopsis ARR1 and ARR2 response regulators operate as transcriptional activators.

The genes coding for the response regulators ARR1 and ARR2 have previously been identified by in silico screening of an expression sequence tag database and subsequent cloning from both Arabidopsis cDNA and genomic libraries. Their structures, in which the N-terminal signal receiver domain is followed by the output domain, are characteristic of typical bacterial response regulators of the two-component regulatory systems that control responses to a variety of environmental stimuli. Here we present evidence that these response regulators actually work as transcription factors. ARR1 and ARR2 were localized in the nuclei of plant cells regardless of the presence or absence of their signal receiver domain. Their middle segments, which faintly resemble the mammalian oncogene product Myb, were capable of binding double-stranded DNA in a sequence-specific manner in vitro. Their C-terminal halves functioned as transactivation domains in plant cells when combined with the DNA-binding domain of yeast GAL4. They thus possess all the essential components of a transcriptional activator. Both ARR1 and ARR2 promoted expression of a reporter gene in plant cells through their own target sequence. Truncation of their N-terminal signal receiver domain led to an increase in transactivation. An as yet unidentified phospho-relay signal may modulate the capability for transactivation and/or DNA binding through the signal receiver domain.

Arabidopsis↗
PubMed2000

Long-term ventilator support in patients with Werdnig-Hoffmann disease.

BACKGROUND: Withholding and withdrawing life-sustaining treatment for patients with Werdnig-Hoffmann disease (WHD) have been accepted as standard medical practice in most Western countries. However, a number of Japanese pediatricians are providing ventilator care for patients with this otherwise fatal disorder. We investigated the attitude of physicians in Japan who are providing ventilator care for patients with WHD. METHODS: A postal questionnaire was sent to 40 hospitals where pediatricians were taking care of 55 ventilator-assisted patients with WHD. Their views were sought on aspects of the care of these patients. RESULTS: Thirty-three pediatricians from 31 hospitals responded to the questionnaire. Mechanical ventilation was initiated as an emergency measure in one-third (12/32) of the patients before obtaining full informed consent from the parents. Two-thirds (19/32) of parents asked the physicians to start ventilator care for the patients, while only three parents asked for the life-sustaining treatment to be withheld. Although 80% (24/30) of the physicians thought that the quality of life of the ventilator-dependent patients with WHD was inadequate, about half (17/30) answered that they would start ventilator assistance if they had a new patient with WHD. DISCUSSION: Strong familial endorsement for the prolongation of a patient's life, the secure national insurance and general pro-life beliefs could have affected physicians' decisions in favor of providing life-sustaining treatments for patients with WHD.

Adult↗
PubMed2000

Fukutin protein is expressed in neurons of the normal developing human brain but is reduced in Fukuyama-type congenital muscular dystrophy brain.

Fukuyama-type congenital muscular dystrophy (FCMD) results from a mutation in a gene on chromosome 9q31, fukutin, and is characterized pathologically by micropolygyria of the cerebral and cerebellar cortices. To elucidate the physiological function of fukutin as well as its pathological role in FCMD, we raised antisera against fukutin protein and observed its expression in developing human brains with or without FCMD. Western blotting using these antibodies demonstrated a 60-kd band in the fetal but not in postnatal cerebral cortex of the controls. This band appeared negligible in the brains of FCMD fetuses. Immunohistochemistry revealed the localization of fukutin in Cajal-Retzius cells, the subpial granular layer, the neuropil of the marginal zone, the cortical plate neurons, and the ventricular neuroepithelium of the fetal cerebrum. In the fetal cerebellum, fukutin immunoreactivity was localized to the external granule cell layer, molecular layer, Purkinje cells, and some internal granular cells. The immunoreactivity in these structures was reduced markedly in postnatal normal brains, as well as in an FCMD cerebrum at 23 gestational weeks. The spatial and temporal pattern of fukutin expression is compatible with its predicted role: the regulation of neuronal migration in the fetal cerebrum and cerebellum.

Adolescent↗