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Biomedical subjects

R Mizuta

Publications and source records attributed to R Mizuta.

At least 19 recordsLinked to original sources
PubMed2007

Stage-specific expression of DNasegamma during B-cell development and its role in B-cell receptor-mediated apoptosis in WEHI-231 cells.

Here, we describe the non-redundant roles of caspase-activated DNase (CAD) and DNasegamma during apoptosis in the immature B-cell line WEHI-231. These cells induce DNA-ladder formation and nuclear fragmentation by activating CAD during cytotoxic drug-induced apoptosis. Moreover, these apoptotic manifestations are accompanied by inhibitor of CAD (ICAD) cleavage and are abrogated by the constitutive expression of a caspase-resistant ICAD mutant. No such nuclear changes occur during oxidative stress-induced necrosis, indicating that neither CAD nor DNasegamma functions under necrotic conditions. Interestingly, the DNA-ladder formation and nuclear fragmentation induced by B-cell receptor ligation occur in the absence of ICAD cleavage and are not significantly affected by the ICAD mutant. Both types of nuclear changes are preceded by the upregulation of DNasegamma expression and are strongly suppressed by 4-(4,6-dichloro-[1, 3, 5]-triazin-2-ylamino)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)-benzoic acid (DR396), which is a specific inhibitor of DNasegamma. Our results suggest that DNasegamma provides an alternative mechanism for inducing nuclear changes when the working apoptotic cascade is unsuitable for CAD activation.

Animals↗
PubMed1998

The XRCC4 gene product is a target for and interacts with the DNA-dependent protein kinase.

The gene product of XRCC4 has been implicated in both V(D)J recombination and the more general process of double strand break repair (DSBR). To date its role in these processes is unknown. Here, we describe biochemical characteristics of the murine XRCC4 protein. XRCC4 expressed in insect cells exists primarily as a disulfide-linked homodimer, although it can also form large multimers. Recombinant XRCC4 is phosphorylated during expression in insect cells. XRCC4 phosphorylation in Sf9 cells occurs on serine, threonine, and tyrosine residues. We also investigated whether XRCC4 interacts with the other factor known to be requisite for both V(D)J recombination and DSBR, the DNA-dependent protein kinase. We report that XRCC4 is an efficient in vitro substrate of DNA-PK and another unidentified serine/ threonine protein kinase(s). Both DNA-PK dependent and independent phosphorylation of XRCC4 in vitro occurs only on serine and threonine residues within the COOH-terminal 130 amino acids, a region of the molecule that is not absolutely required for XRCC4's DSBR function. Finally, recombinant XRCC4 facilitates Ku binding to DNA, promoting assembly of DNA-PK and complexing with DNA-PK bound to DNA. These data are consistent with the hypothesis that XRCC4 functions as an alignment factor in the DNA-PK complex.

Animals↗
PubMed1998

Total body bone development during early childhood in very low birth weight infants without cerebral palsy and mental retardation.

Total body bone mineral density was measured by dual energy X-ray absorptiometry in 52 children who were very low birth weight (VLBW) infants without cerebral palsy and mental retardation (postconceptional age, from 10 mo to 6 y and 6 mo). VLBW infants in this study seemed to show compensatory acceleration of total body bone development, catching up with the control group during early childhood. However, in VLBW infants with at least one of the three factors such as total parenteral nutrition for 1 week or more, assisted ventilation for 1 week or more, or oxygen therapy for 28 d or more in their early stage after birth, adequate mineral supplementation might be especially important for long-term bone development.

Aging↗
PubMed1997

RAB22 and RAB163/mouse BRCA2: proteins that specifically interact with the RAD51 protein.

The human RAD51 protein is a homologue of the bacteria RecA and yeast RAD51 proteins that are involved in homologous recombination and DNA repair. RAD51 interacts with proteins involved in recombination and also with tumor suppressor proteins p53 and breast cancer susceptibility gene 1 (BRCA1). We have used the yeast two-hybrid system to clone murine cDNA sequences that encode two RAD51-associated molecules, RAB22 and RAB163. RAB163 encodes the C-terminal portion of mouse BRCA2, the homologue of the second breast cancer susceptibility gene protein in humans, demonstrating an in vitro association between RAD51 and BRCA2. RAB22 is a novel gene product that also interacts with RAD51 in vitro. To detect RAD51 interactions in vivo, we developed a transient nuclear focus assay that was used to demonstrate a complete colocalization of RAB22 with RAD51 in large nuclear foci.

Amino Acid Sequence↗
PubMed1997

An autopsy case of bathtub drowning in epilepsy.

We report an autopsy case of bathtub drowning in epilepsy. A 26-year-old female with mental retardation had been treated for refractory epilepsy. Her younger sister found her floating supine in the bathtub 45 min after starting bathing. Neuropathological examination revealed cerebral cortical dysplasia in the precentral gyrus of the left hemisphere, which had not been detected by MRI, suggesting the etiology of epilepsy. In bathtub submersion injury of an unidentified cause, neuropathological examination should be performed to reveal any lesion underlying epileptic seizures. Additionally, we present statistics on bathtub submersion injury in children aged 5 years or older in Japan based upon nationwide survey data obtained in 1991. Forty-seven percent of them had associated epilepsy or convulsive attacks and 71% died. It is necessary for epileptic patients and their families to understand that the risk of bathtub drowning can be minimized if proper precautions are taken.

Adult↗
PubMed1997

Evidence of brain ischemia in early neonatal sudden death syndrome.

Ten early neonatal sudden death victims (ENSD) were selected for neuropathological and immunohistochemical examinations. The gestational ages of the victims ranged from 36 to 42 weeks, and the postnatal ages from 8 hours to 10 days of life. In 6 of 10 patients, softening with rarefaction was observed in the subcortical or intermediate white matter, which was associated with minimal astrogliosis in the whole white matter. In 7 of the 10 ENSD victims, the number of GFAP-positive glia was significantly greater in both the deep and subcortical white matter than in controls. The brainstem showed mild gliosis in the reticular formation and vagal nuclei of the medulla oblongata in 8 of the 10 ENSD victims. In 8 of the 10 ENSD victims, the number of GFAP-positive astrocytes was greater in both the dorsal vagal nucleus and the reticular formation of the medulla oblongata than in controls. The high incidence of leukomalacia and astrogliosis in the cerebral white matter and brainstem suggests the presence of brain ischemic insults before death, which may be prenatal in some cases.

Astrocytes↗
PubMed1997

Molecular genetic characterization of XRCC4 function.

XRCC4 is a generally expressed protein of 334 amino acids that is involved in the repair of DNA double-strand breaks and in V(D)J recombination, but its function is unknown. In this study, we have used a mutational approach and the yeast two-hybrid method to perform an initial characterization of this protein. We show that the XRCC4 protein is located in the nucleus. We also demonstrate that several potential phosphorylation sites are not required for XRCC4 function in a transient V(D)J recombination assay. In addition, we show that XRCC4 forms a homodimer in vivo with the homodimerization domain being located within amino acids 115-204. Finally, we define a core domain of XRCC4 that functions in V(D)J recombination and comprises amino acids 18-204. Potential functions of XRCC4 are discussed.

Amino Acid Sequence↗
PubMed1996

Relationship of substance P and gliosis in medulla oblongata in neonatal sudden infant death syndrome.

Substance P and glial fibrillary acidic protein (GFAP) immunohistochemistry was applied to the medulla of neonatal infants who died of sudden infant death syndrome (SIDS). A quantitative analysis of cells demonstrating immunoreactivity to GFAP and substance P in 15 neonatal SIDS cases revealed increased GFAP immunoreactivity in the reticular formation, the dorsal vagal nucleus, and the solitary nucleus and an increase in substance P immunoreactivity in the spinal trigeminal nucleus and the solitary nucleus as compared with that in age-matched controls. GFAP immunopositivity suggests astrogliosis which implies a pathologic insult to neurons in the area of astrogliosis. The failure of neurons in these sites to show enhanced substance P immunopositivity may indirectly indicate altered neurons. Further study of prenatal events may be of importance in clarifying the pathogenesis of neonatal SIDS.

Chi-Square Distribution↗
PubMed1996

The V(D)J recombination defect in the xrs-6 cell line results from a point mutation in the Ku80 gene.

Defective expression of the Ku80 gene has been implicated as underlying the V(D)J recombination and DNA double-strand break repair defects in the xrs-6 Chinese hamster ovary cell line. We now show that the mutation in the Ku80 gene involves a G to A transition 15 bp upstream of exon 2. This mutation creates a new splice acceptor site which results in the generation of Ku80 transcript that cannot encode a functional product due a 13 nucleotide insertion and a resulting frameshift.

Amino Acid Sequence↗
PubMed1995

Defective DNA-dependent protein kinase activity is linked to V(D)J recombination and DNA repair defects associated with the murine scid mutation.

Murine cells homozygous for the severe combined immune deficiency mutation (scid) and V3 mutant hamster cells fall into the same complementation group and show similar defects in V(D)J recombination and DNA double-stranded break repair. Here we show that both cell types lack DNA-dependent protein kinase (DNA-PK) activity owing to defects in DNA-PKcs, the catalytic subunit of this enzyme. Furthermore, we demonstrate that yeast artificial chromosomes containing the DNA-PKcs gene complement both the DNA repair and recombination deficiencies of V3 cells, and we conclude that DNA-PKcs is encoded by the XRCC7 gene. As DNA-PK binds to DNA ends and is activated by these structures, our findings provide novel insights into V(D)J recombination and DNA repair processes.

Amino Acid Sequence↗
PubMed1994

Ku80: product of the XRCC5 gene and its role in DNA repair and V(D)J recombination.

The radiosensitive mutant xrs-6, derived from Chinese hamster ovary cells, is defective in DNA double-strand break repair and in ability to undergo V(D)J recombination. The human XRCC5 DNA repair gene, which complements this mutant, is shown here through genetic and biochemical evidence to be the 80-kilodalton subunit of the Ku protein. Ku binds to free double-stranded DNA ends and is the DNA-binding component of the DNA-dependent protein kinase. Thus, the Ku protein is involved in DNA repair and in V(D)J recombination, and these results may also indicate a role for the Ku-DNA-dependent protein kinase complex in those same processes.

Animals↗
PubMed1993

Isolation of adenovirus type 11 from the brain of a neonate with pneumonia and encephalitis.

We describe a fatal case of adenovirus pneumonia accompanied by encephalitis in a neonate who showed lethargy on the 6th day and died on the 12th day. Adenoviral particles as well as viral intranuclear inclusions were noted in pulmonary alveolar epithelium cells. Neuropathological examination revealed diffuse oedema, perivascular cuffing and gliosis in the white matter. Adenovirus type 11 was isolated from lung, hilar lymph node, and brain tissue. This is the first instance of adenovirus isolation from brain tissue in a newborn infant. The virological and neuropathological findings suggest the invasion of neural tissue by adenovirus and substantiate the significance of neurological symptoms observed in neonatal adenovirus infection.

Adenovirus Infections, Human↗
PubMed1993

Treatment of an infant with congenital sodium diarrhea by oral rehydration.

We have been following a male case of congenital sodium diarrhea (CNaD), who had a distended abdomen, passed watery stools with high sodium concentration, and showed metabolic acidosis in the first week of life. He also showed hyponatremia, low urine sodium, high serum aldosterone and high renin activity. Other possible causes of secretory diarrhea were ruled out. The initial effective treatment was oral supplements of water and electrolytes lost in the fecal fluid: with this he gained weight, and hyponatremia and metabolic acidosis were corrected. Loperamide hydrochloride was administered to increase intestinal absorption of sodium, as the serum prostaglandin was high. Watery diarrhea then improved, but as he passed acholic stools, we stopped and postponed the treatment for a while; the stools then became watery again. Although diarrhea has persisted, he has not shown any abnormalities in growth or psychomotor development for the first two years of life.

Alkalosis↗
PubMed1993

Childhood drownings and near-drownings in Japan.

In Japan, the leading cause of death for children over 1 year old is injury, and for children aged 0-14, drowning is the second leading cause of death. The purpose of the present study was to describe the epidemiological factors of drownings and near-drowning among Japanese children and to ascertain whether there are characteristic patterns for different age groups. Epidemiologic data was obtained by questionnaire. A total of 604 cases of submersion injuries were reported from 49 hospitals located in 22 Japanese prefectures. In the present paper, victims of drowning (n = 134) and near-drowning with permanent severe brain damage (n = 51) and those of near-drowning with intact survival or mild impairment (n = 419) were investigated. Preschool-aged children, especially toddlers, are at the greatest risk of drowning and near-drowning, and for children over 2 years of age, boys have three times greater risk than girls. The bathtub is the most common place of submersion injuries in Japan, especially for children under 4 years of age. The important risk factors for the victims who died or were severely impaired were associated with duration of submersion and necessity of emergency cardiopulmonary resuscitation on arrival at hospital.

Adolescent↗
PubMed1989

[Electrophysiologic effects of intravenous digoxin in infants and children with Wolff-Parkinson-White syndrome].

Electrophysiologic properties of the accessory pathway were investigated before and after the intravenous administration of digoxin (0.01-0.02 mg/kg) during electrophysiologic studies in 14 infants and children with the Wolff-Parkinson-White syndrome. Determination of electrophysiologic properties of the accessory pathway was made using transesophageal atrial pacing and/or intracardiac right atrial pacing. Maximal effect on the accessory pathway after intravenous digoxin was observed during one to six hours. Effective refractory period of the accessory pathway increased in 6 of the 14 patients, decreased in 4 and unchanged in 4. Shortest AP 1:1 conduction increased in 5 of the 12 patients, decreased in 3 and unchanged in 4. Tachycardia was not induced after digoxin in only one patient. Tachycardia cycle length, ventriculoatrial conduction time and atrioventricular conduction time were unchanged after digoxin in almost all cases. Thus, digoxin is not the first choice drug for termination and prevention of the preexcitation syndrome.

Adolescent↗
PubMed1987

[Intracranial hemorrhage in infancy due to vitamin K deficiency: report of a case with multiple intracerebral hematomas with ring-like high density figures].

It is well known that vitamin K deficiency is an important cause of the spontaneous intracranial hemorrhage in infancy. A 60-day-old male infant with spontaneous intracerebral hematomas due to vitamin K deficiency was presented. He was breast-fed. He had been medicated oral antibiotic agent for diarrhea and fever. Three days later he developed petechien, vomiting and twitching, and became drowsy. The blood studies showed anemia, and advance of ESR. He was administered of vitamin K immediately. CT scan was showed four intracerebral hematomas with niveau, which were surrounded by high-density rings. The ring-like figures were unique for this case. The reason may be next, we think. Under the states in which blood can separate easily with advance of ESR, blood clot would adhere to the wall of the hematomas. So these hematomas showed ring-like figures and had niveau in them. CT scan of this case was also interesting because there was little deviation in spite of the big hematomas. The reason of this may be that the brain of infancy is incomplete in myelination and contains much water, and that the possibility of bleeding due to vitamin K occurs slowly. We examined 84 cases of intracranial hemorrhage due to vitamin K deficiency from literatures, and they were all identified for the hemorrhage sites by CT scan. Subarachnoidal hemorrhage was in 72 cases (85.7%), subdural hemorrhage was in 41 cases (48.8%), intracerebral hematomas was in 36 cases (42.9%) and intraventricular hemorrhage was in 9 cases (10.7%). In 52 cases the CT findings were described.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗