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Biomedical subjects

E Naito

Publications and source records attributed to E Naito.

At least 73 records · Page 4Linked to original sources
PubMed1994

Vitamin D-dependent rickets type II: regulation of human osteocalcin gene expression in cells with defective vitamin D receptors by 1,25-dihydroxyvitamin D-3, retinoic acid, and triiodothyronine.

The vitamin D receptor (VDR) is a nuclear transcription factor which binds to the vitamin D response element (VDRE) of the human osteocalcin gene and regulates its expression. Humans with VDR gene mutations, ever among those with the same point mutation in their VDR gene, demonstrate clinical heterogeneity. In addition, in some patients with these mutations, rickets has not recurred following cessation of therapy during follow-up ranging from 6 to 24 years. While important, it is likely that the VDR protein is not the sole factor in the development of rickets. To try to understand these clinical findings, the complex formed between the VDRE and one or more proteins in the nuclear extracts of cultured skin fibroblasts treated with 1,25-dihydroxyvitamin D-3 (1,25(OH)2D3), retinoic acid (RA), and/or triiodothyronine (T3) was investigated since such complexes are likely to precede the transcription of the VDR gene. Complex formation in the control cells with an intact VDR was increased by treatment with either 0.1 nM, 1 nM, 10 nM 1,25(OH)2D3, 100 nM RA, or 100 nM T3; however, combinations of these compounds did not produce an additive effect. In cells of affected patients, 1,25(OH)2D3, RA, or T3 increased complex formation, while no combination had an additive effect. These results indicate that 1,25(OH)2D3, RA, and T3 play a role in the regulation of bone remodeling through modulating the formation of protein complexes on the VDRE. Therefore, the clinical observations in patients with a VDR mutation might be explained at least in part by the overlapping control of osteocalcin expression by 1,25(OH)2D3, RA and T3.

Base Sequence↗
PubMed1994

Movement-related slow potentials during motor imagery and motor suppression in humans.

Electro-encephalograms (EEGs) associated with motor imagery and motor suppression were recorded from motor-related frontal regions in humans. A negative potential was observed both during motor imagery and during NO-GO responses, as well as in movement trials. The negative potentials observed in the motor imagery trials had a similar pattern to those observed in the movement trials, although the potentials were different from those during NO-GO responses. The peak amplitude of the negative potential recorded at FCz was significantly larger than those recorded at F3, F4, C3 and C4 in the imagery task. The peak amplitude of the negative component in movement trials was larger than that in the imagery trials of all recording positions. By contrast, during the GO/NO-GO task, the peak amplitude during NO-GO responses was larger than that during the GO responses at every position. It appears, therefore, that motor imagery and motor suppression are associated with their own specific internal processes which are reflected by specific EEG patterns in motor-related frontal areas.

Adult↗
PubMed1994

Movement-related potentials associated with motor inhibition as determined by use of a stop signal paradigm in humans.

The motor inhibition process was examined in humans by monitoring reaction times, electromyograms, and movement-related potentials. Four subjects performed a simple visual Stop Signal Paradigm. The results were as follows. (1) The EEG waveform pattern was remarkably consistent among subjects. NO-GO-specific negative-positive potentials were observed under all experimental conditions. (2) The timing of the onset and the peak latency of the negative potential relative to the second stimulus, S2, were constant (about 200-210 ms and 250-260 ms for each) regardless of changes in the S2 delay. The time interval between the initial onset of the negative potential and its peak latency was constant (about 50 ms). (3) By contrast, the peak-to-peak time between the negative potential and the positive potential became smaller as the S2 delay was increased. It is suggested, therefore, that the motor inhibition process might consist of different sub-processes and that some part of the inhibition process might be of constant and specific duration.

Adult↗
PubMed1994

Molecular analysis of abnormal pyruvate dehydrogenase in a patient with thiamine-responsive congenital lactic acidemia.

A patient who responded to thiamine therapy with reduction of lactate in the blood and cerebrospinal fluid and clinical improvement was studied. Cultured lymphoblastoid cells of this patient were found to show reduced activities of pyruvate dehydrogenase complex (PDHC) and pyruvate dehydrogenase, decreased affinity of PDHC for thiamine pyrophosphate, and defective activation of PDHC by pyruvate dehydrogenase phosphatase. PDHC deficiency in fibroblasts and biopsied muscle of this patient was also due to the decreased affinity of PDHC for thiamine pyrophosphate. A mutation in the E1 alpha subunit containing the thiamine binding site and serine phosphorylation site regulating the activation/inactivation of PDHC was characterized by the polymerase chain reaction and DNA sequencing. A single A-->G transition was identified at position 131, resulting in the substitution of Arg-44 for His-44. This mutation must be a de novo mutation because it was not found in either parent's genomic DNA. In this study, we have obtained the first evidence at the molecular level for a mutation of thiamine-responsive PDHC deficiency.

Acidosis, Lactic↗
PubMed1994

Mutation of the p53 gene in gallbladder cancer.

Genetic alteration of the p53 gene was examined in tissue specimens of primary gallbladder cancer (GBC) using PCR-single strand conformation polymorphism (SSCP) and direct sequencing analyses. The p53 gene mutation was detected in five of the 16 GBC cases examined (31%). All five cases showed single point mutations; four were mutations resulting in amino acid substitution and the other was one base-pair deletion. Of the five mutations detected, four occurred at evolutionarily conserved regions and the remaining one at a well conserved region among species. Our result is similar to those of previous reports for various human cancers in mutation scattering over four of the five conserved domains.

Adult↗
PubMed1994

Controllability of motor imagery and transformation of visual imagery.

This study examined the relation between control of motor imagery and generation and transformation of visual imagery by testing 54 subjects. We used two measures of the Controllability of Motor Imagery test to evaluate the ability to control motor imagery. One was a recognition test on which the subject imagines as if one sees another's movement, and the other was a regeneration test on which one imagines as if one moves one's own body. The former test score was related to processing time of a mental rotation task and the latter one was not but would reflect sport experience. It was concluded that two meanings of the test could reflect different aspects such as observational motor imagery and body-centered motor imagery.

Adolescent↗
PubMed1994

Sex typing of forensic DNA samples using male- and female-specific probes.

Forensic DNA samples have been examined to ascertain the feasibility of a sex-typing procedure that we have recently developed. This uses two sets of primers complementary to the DXZ4 and SRY genes for polymerase chain reaction (PCR). PCR target in the DXZ4, an 80-bp sequence within the 130-bp fragment specific to females, is generated from inactive chromosome X by the DNA digestion with a methylation-sensitive restriction enzyme, HpaII. Therefore, the DXZ4 amplification and subsequent agarose gel electrophoresis detect the 80-bp fragment from female DNA. On the other hand, the SRY probe identifies a male-specific sequence on chromosome Y. Testing DNAs from fresh Turner's blood and from postmortem tissues exhibited band-signals confirming the sex identification. Degraded DNAs isolated from severely decomposed specimens were also identifiable when high-molecular-weight DNA was isolated before the assay. This demonstrates the usefulness of this method in forensic identification.

Base Sequence↗
PubMed1992

Decrease of pyruvate dehydrogenase phosphatase activity in patients with congenital lactic acidemia.

We developed an assay method for pyruvate dehydrogenase phosphatase activity using [1-14C]pyruvate and measured pyruvate dehydrogenase phosphatase activity in cultured skin fibroblasts from three patients with congenital lactic acidemia due to a defect in activation of the pyruvate dehydrogenase complex. The enzyme activity of their fibroblasts was significantly reduced to 50.7%, 64.6% and 63.1% of that of control fibroblasts. These observations suggest that the defect in activation of the pyruvate dehydrogenase complex in these patients might be due to a reduction in pyruvate dehydrogenase phosphatase activity.

Acidosis, Lactic↗
PubMed1992

Mutation of E1 alpha gene in a female patient with pyruvate dehydrogenase deficiency due to rapid degradation of E1 protein.

A mutation of an insertion of 4 bp in the gene for the alpha subunit of pyruvate dehydrogenase (E1 alpha) was found in a female with pyruvate dehydrogenase deficiency due to the rapid degradation of alpha and beta subunit proteins of pyruvate dehydrogenase. This mutation caused a frameshift that altered the amino acid sequence and created a premature stop codon. This 4-bp insertion has been found in an unrelated female patient with E1 alpha deficiency. It is rare that the same mutation is found in unrelated patients with this rare inborn error of metabolism. Furthermore, short deletions or duplications in the E1 alpha gene of patients with E1 alpha deficiency have been found only in exons 10 and 11. These exons may be hot spots for the mutations by the recombinational processes. This patient was heterozygous for the normal and a mutant allele. However, in most of the cultured skin fibroblasts from this patient, the mutant allele was expressed. These observations suggest that the X chromosome containing the normal allele was predominantly inactivated so that she developed lactic acidaemia and neurological abnormalities despite being heterozygous. The mutant alpha subunit protein failed to form a stable structure of pyruvate dehydrogenase, so that both alpha and beta subunit proteins were degraded rapidly.

Alleles↗
PubMed1992

The Rett syndrome and CSF lactic acid patterns.

We investigated both blood and cerebrospinal fluid (CSF) lactate and pyruvate levels in seven girls with the Rett syndrome (RS) and evaluated the relationship between CSF lactate and pyruvate levels and the clinical manifestations, particularly seizures, anticonvulsant medication, and breathing dysfunction including breath holding, apnea and hyperventilation. Elevated lactate and pyruvate levels in CSF with normal serum lactate were found in two RS patients. Elevated CSF lactate correlated significantly with the clinical occurrence of hyperventilation (P0 = 0.048, Fisher exact probability). We measured native and dichloroacetate (DCA)-activated pyruvate dehydrogenase (PDH) complex activities in two patients (#1 and 2) using cultured lymphoblastoid cell lines which were transformed by EB virus and the results were normal. We also analyzed CSF citric acid intermediates from 7 RS patients including citric acid, cis-aconitate, alpha-ketoglutarate, succinate, fumarate, malate and oxaloacetate. These concentrations were not significantly different from those control patients (N = 21). An elevated lactate level may be a clue to clarify the etiology of RS.

Acid-Base Equilibrium↗
PubMed1992

Ribosomal ribonucleic acid (rRNA) gene typing for species identification.

Deoxyribonucleic acid (DNA) typing of ribosomal ribonucleic acid (rRNA) genes was performed with a polymerase chain reaction (PCR) assay for species identification. A variable region of the 28S ribosomal RNA gene was amplified with primers complementary to flanking sequences phylogenetically well conserved. The products of twelve animal DNAs (human, Japanese monkey, dog, cattle, pig, cat, rabbit, mouse, rat, chicken, frog, and fish) were separated by polyacrylamide gel electrophoresis, each revealing a few bands ranging from 150 to 100 base pairs. The band patterns obtained from each DNA sample differed in number and size, which indicates the applicability of the method to species identification. Samples containing either as little as 1 pg of DNA or degraded DNA of 0.2 to 0.5 kb in length were able to give detectable bands. Postmortem human tissue DNAs were tested as an example. They showed a pattern identical to the human control one, which was distinct from those of the other animals examined.

Animals↗
PubMed1991

Screening for disorders of pyruvate metabolism by measuring the ratio of the rates of lactate production and pyruvate decarboxylation in cultured skin fibroblasts.

We assayed the rates of lactate production from [1-14C]pyruvate and decarboxylation of [1-14C]pyruvate in cultured skin fibroblasts from 8 patients with disorders of pyruvate metabolism and 16 control subjects. The disorders of pyruvate metabolism could be more readily detected by measuring the ratio between the rates of lactate production and pyruvate decarboxylation by cultured skin fibroblasts than by measuring either the rate in isolation.

Acidosis, Lactic↗
PubMed1991

Effects of deoxyadenosine on ribonucleotide reductase in adenosine deaminase-deficient lymphocytes.

To explore the relationship between ribonucleotide reductase and immunodysfunction in adenosine deaminase deficiency, the effects of deoxyadenosine on ribonucleotide reductase in ADA-deficient lymphocytes was investigated. An assay system for ribonucleotide reductase in intact permeabilized lymphocytes was developed to approximate physiological conditions. The activity of cytidine diphosphate (CDP) reductase in resting but not in proliferating lymphocytes in culture was inhibited by 1 to 10 mumol/L deoxyadenosine. The resting cells were protected from the toxicity of 1 mumol/L deoxyadenosine by 5 mmol/L nicotinamide or 30 mumol/L deoxycytidine and from that of 10 mumol/L deoxyadenosine by 30 mumol/L deoxycytidine. These findings suggest that depletion of nicotinamide adenine dinucleotide might be the principal cause of death in resting lymphocytes with ADA deficiency. It is concluded that the mechanism of deoxyadenosine toxicity on non-replicating lymphocytes, which may not be mediated by ribonucleotide reductase inhibition, is closely related to the mechanism of immunodysfunction in patients with ADA deficiency.

Adenosine Deaminase↗
PubMed1991

Therapeutic effect of sodium dichloroacetate on visual and auditory hallucinations in a patient with MELAS.

We report a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes who experienced visual and auditory hallucinations. His blood and cerebrospinal fluid lactate levels were remarkably elevated. Sodium dichloroacetate was administered orally at doses of 12.5 to 100 mg/kg/day. On normalization of the lactate levels, the hallucinations disappeared.

Acidosis, Lactic↗
PubMed1991

Diagnosis of atlantoaxial subluxation in Morquio's syndrome and spondyloepiphyseal dysplasia congenita.

Compression of the spinal cord due to atlantoaxial subluxation was diagnosed in a patient with Morquio's syndrome and in another with spondyloepiphyseal dysplasia (SED) congenita by cervical radiography and magnetic resonance imaging (MRI). The patient with Morquio's syndrome, a 15 year old boy, had no neurologic symptoms and his somatosensory evoked potential (SSEP) was normal. However, MRI demonstrated spinal cord compression at C1-C2. In contrast, the patient with SED congenita, an 11 year old girl, had neck pain, hyperreflexia and loss of vibration sense in both legs. These findings were explained by the absence of P3 and later waves in SSEP and by compression of the spinal cord observed on MRI. Both SSEP and MRI should be used for evaluating disorders in which atlantoaxial subluxation might be present.

Adolescent↗
PubMed1991

Demonstration of an unstable variant of pyruvate dehydrogenase protein (E1) in cultured fibroblasts from a patient with congenital lactic acidemia.

The deficiency of pyruvate dehydrogenase enzyme complex causes congenital lactic acidemia and devastating neurologic abnormalities in newborns and children. In the majority of cases, the basic defect appears to be in the pyruvate dehydrogenase (E1) component, which consists of two subunits, alpha and beta. Whereas some patients are deficient of a single subunit, in other patients both subunits of E1 are missing. To find out why two proteins were deficient, we investigated the cultured fibroblasts of a female patient who had missing E1-alpha and E1-beta protein bands on Western blot. Radiolabeling-immunoprecipitation studies with 35S-methionine revealed that patient fibroblasts synthesized normal sized precursor E1-alpha and E1-beta proteins, which were presumably transported into mitochondria and processed into normal sized mature proteins. However, pulse-chase analysis showed that alpha- and beta-proteins were degraded rapidly compared to normal. Our findings proved that alpha- and beta-subunits were synthesized and processed normally but failed to form a stable structure for incorporation into the pyruvate dehydrogenase complex.

Cells, Cultured↗