Biomedical subjects

H Togari

Publications and source records attributed to H Togari.

At least 55 records · Page 3Linked to original sources

PubMed1998

Hereditary orotic aciduria heterozygotes accompanied with neurological symptoms.

We report a family with hereditary orotic aciduria heterozygotes. A 3-year-old boy who had been diagnosed as having cerebral palsy and mental retardation presented himself with an increase in excretion of urinary orotic acid. Enzymatic studies revealed that the boy and his healthy mother were hereditary orotic aciduria heterozygote carriers. We can not prove that this pyrimidine disorder caused his neurological symptoms, but his pyrimidine nucleoside supply may have been insufficient in his neonatal period.

Cerebral Palsy↗

PubMed1998

Possible prediction of adverse reactions to fluorouracil by the measurement of urinary dihydrothymine and thymine.

Dihydropyrimidine dehydrogenase (DPD) deficiency with a defect of the pyrimidine catabolic pathway has recently become the focus of considerable attention, due to the severe 5-fluorouracil (5-FU) toxicities occurring in DPD deficiency patients. Studies also suggest that 5-FU toxicities could occur in another pyrimidine metabolic disorder, dihydropyrimidinuria (DHPuria). This study shows that urinary dihydrothymine (DHT) and thymine (THY) are useful indexes for detection of DPD deficiency and DHPuria. We measured urinary DHT and THY in 276 Japanese adults to establish reference ranges. When males and females were compared, both DHT and THY levels were found to be significantly higher in females. The reference ranges (mean +/- SD with logarithmic values) for males were found to be 1.56-5.70 micromol/g of creatinine for DHT and 0.40-1.47 micromol/g of creatinine for THY. The reference ranges for females were found to be 1.89-8.33 micromol/g of creatinine for DHT and 0.58-2.30 micromol/g of creatinine for THY. In addition to this study we analyzed a DPD deficiency case and a DHPuria case. In the DPD deficiency case, the THY concentrations of all urine samples were out of the reference range. However, uracil levels in most of the samples were within the normal range. The DHPuria case excreted large amounts of DHT and dihydrouracil, both out of the normal range.

Adolescent↗

PubMed1998

Identification of novel mutations in the dihydropyrimidine dehydrogenase gene in a Japanese patient with 5-fluorouracil toxicity.

5-Fluorouracil (5-FU) is used widely in the treatment of several common neoplasms. Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-FU. Several recent studies have described a pharmacogenetic disorder in which cancer patients with decreased DPD activity develop life-threatening toxicity following exposure to 5-FU. We reported recently the first Japanese case of decreased DPD activity accompanied by severe 5-FU toxicity. The present study describes the results of molecular analysis of this patient and her family, in which three novel mutations (Arg21Gln, Val335Leu, and Glu386Ter) of the gene coding for DPD were identified. We also revealed that Arg21Gln and Glu386Ter are on the same allele and that Val335Leu is on the other allele, on the basis of analysis of the family genome. Expression analysis in Escherichia coli showed that Val335Leu and Glu386Ter led to mutant DPD protein with significant loss of enzymatic activity and no activity, respectively. The Arg21Gln mutation, however, resulted in no decrease in enzymatic activity compared with the wild type. The present data represent the first molecular genetic analysis of DPD deficiency accompanied by severe 5-FU toxicity in a Japanese patient.

Antimetabolites, Antineoplastic↗

PubMed1997

Immature teratoma producing alpha-fetoprotein without components of yolk sac tumor in the pineal region.

A case of pineal region tumor in a 9-year-old boy with a high serum alpha fetoprotein (AFP) level is reported. The serum levels of beta-human chorionic gonadotropin (HCG) and placental alkaline phosphatase (PLAP) were not elevated. The tumor was composed of radiologically different components and was removed surgically. Postoperative radiation therapy was performed and the serum level of AFP gradually declined to the normal range. The pathological diagnosis was immature teratoma, and no elements of yolk sac tumor or embryonal carcinoma were found. In the immunohistochemical study, AFP was detected in the cytoplasm of gastrointestinal-type epithelium and primitive neuroepithelial element. This is considered a rare case of intracranial immature teratoma in which AFP was detected immunohistochemically in the columnar epithelium and immature neural tissue.

Biomarkers, Tumor↗

PubMed1997

Topography of hypoxic injury proved by argyrophilia in postnatal rat brain.

The argyrophil III method, a new esterification-silver staining approach, was used to elucidate regional differences in the susceptibility of developing brain to hypoxic-ischemic (H-I) injury. We created a unilateral common carotid artery-ligation model with hypoxia (8% oxygen) in postnatal day (P) 7, P14 and P21 rats. The argyrophil (i.e., deteriorated) neurons were apparent in the ipsilateral hippocampus, cortex, and striatum in each age group. Argyrophil neurons exhibited some morphological signs of the "early phase" of injury preceding the loss of structure and/or cell death in the "late phase," as indicated by hematoxylin-eosin (H-E) staining. The argyrophil neurons were apparent as early as 12 hours after the insult, whereas the histological changes revealed by H-E staining were subtle. The early phase and late phase histological changes had a stereotyped pattern of appearance in all ages studied. However, the duration of H-I situation required to produce argyrophil cells differed according to age. The most resistive age was P14 (P14 > P7 > P21) in this observation. Therefore, argyrophil III staining is feasible for H-I brain damage model in neonates. The results suggest that both the early phase and the late phase pathological processes after H-I injury have a characteristic topographical vulnerability that does not change during development but have a differing susceptibility according to age.

Animals↗

PubMed1997

Vulnerability to cerebral hypoxic-ischemic insult in neonatal but not in adult rats is in parallel with disruption of the blood-brain barrier.

BACKGROUND AND PURPOSE: Vulnerability to cerebral hypoxic-ischemic (H-I) insult and its relation to disruption of the blood-brain barrier were investigated in postnatal rats. METHODS: Pups of postnatal day (P) 7, P14, and P21 underwent ligation of a unilateral carotid artery and were exposed to hypoxic conditions. For the detection of early-phase deterioration, brains were perfusion-fixed 24 hours after H-I insult and examined by argyrophil III method. For the detection of later infarction, animals were fixed at 72 hours after the H-I insult. RESULTS: In either case, tissue damage was detected in the striatum, parietal cortex, and hippocampus. The vulnerability of P7 and P21 rats was remarkable, as compared with P14 rats. Although the developmental status of the vasculature was not significantly different at each age, the permeability of IgG after H-I injury was prominent in P7 rats and to a lesser extent in P14 rats. In P21 rats, however, there was little IgG leakage even 24 hours after the insult. Dexamethasone pretreatment blocked the extravasation of IgG and reduced the damaged tissue in P7 and P14 rats but not in P21 rats. Percentages of reduction in infarcted areas by the dexamethasone became smaller in proportion to ages. CONCLUSIONS: The results suggest that in younger rats vulnerability to H-I insult was in parallel with permeability of the blood-brain barrier, whereas in adults in might be more dependent on cellular vulnerability.

Aging↗

PubMed1995

Alteration of ammonia and carnitine levels in short-term treatment with pivalic acid-containing prodrug.

We investigated the influence on mitochondrial functions in carnitine deficiency caused by short-term treatment of cefteram-pivoxil (CFTM-PI) which is one of pivaloyloxymethyl-esterified antibiotics in adult volunteers and diseased children. Administration of CFTM-PI caused hypocarnitinemia in all cases, and we observed a significant elevation of blood ammonia levels compared with those after its withdrawal in diseased children. A significant negative correlation was found between the levels of serum free carnitine and blood ammonia, and a positive correlation was observed between serum carnitine and blood glutamine levels in all adult samples and samples during administration in diseased children. Our data suggest that these antibiotic medications affect the mitochondrial function even in a short-term treatment and that L-carnitine supplementation would be necessary for patients treated with CFTM-PI.

Adolescent↗

PubMed1994

Sudden cerebral hypoperfusion enhances respiratory suppression in hypoxic newborn piglets.

The relationship between sudden cerebral hypoperfusion and sudden respiratory suppression was investigated in newborn piglets. A total of 11 experiments on five newborn piglets were divided into three groups: normoxic, hyperoxic and hypoxic. The sudden cerebral hypoperfusion was created by manual compression of the Arteria carotis communis and Vena jugularis interna. Respiratory suppression was calculated by measuring the duration of apnea and the percent reduction of respiratory amplitude. The means of apnea duration in normoxic and hyperoxic groups were 6.6 +/- 0.8 and 1.2 +/- 2.4 s, respectively, while two experiments on the hypoxic group showed 8.4 s and complete cessation of respiration in one of them. The per cent reductions of respiratory amplitude in the normoxic and hyperoxic groups were 23.3 +/- 8.5 and 17.6 +/- 11.7%, respectively. In the hypoxic group, one of two experiments showed a 22.7% reduction, which was equivalent to that of the normoxic group. We conclude that sudden cerebral hypoperfusion enhances respiratory suppression, especially when it coincides with hypoxia. The phenomenon may be one of the possible causes for a certain type of sudden infant death syndrome. Further study will be undertaken to elucidate the direct effects of the mechanism of cerebral hypoperfusion on respiratory suppression.

Animals↗

PubMed1994

Cerebral palsy of cystic periventricular leukomalacia in low-birth-weight infants.

We studied ultrasound findings and neurodevelopmental outcome of 24 infants weighing 2500 g or less with cystic periventricular leukomalacia. Fourteen infants had symmetrical cysts in the parietal or occipital region (group 1) and 10 had non-symmetrical cysts (group 2). Each infant was followed for more than 4 years of age (mean 5 years and 7 months). Twenty out of 24 (83.3%) children developed cerebral palsy. All of group 1 had cerebral palsy (8 diplegia and 6 ataxic diplegia), while 6 (60%) in group 2 developed cerebral palsy (4 diplegia and 2 hemiplegia). There was a significant difference in the incidence of cerebral palsy and motor ability between the two groups. The size and site of the cyst did not predict cerebral palsy. The presence of symmetrical cysts in the parietal or occipital region is a highly reliable neurosonographic finding for predicting cerebral palsy.

Cerebral Palsy↗

PubMed1994

Hypocarbia and cystic periventricular leukomalacia in premature infants.

One hundred sixty seven survivors among very low birthweight infants with a gestational age of less than 35 weeks have been studied prospectively. The purpose of this study was to clarify the relationship of severe prenatal and perinatal complications and hypocarbic alkalosis, defined as a carbon dioxide tension (PaCO2) of less than or equal to 2.67 kPa and a pH of 7.50 or greater during the first 24 hours of life, to cystic periventricular leukomalacia (PVL) depicted by serial cranial ultrasonographic examinations. Complications occurred in 16 infants, five of whom presented with PVL, while eight of 151 infants without complications had PVL. Twenty six of the infants had hypocarbic alkalosis, six with evidence of PVL, and seven of the 136 infants without hypocarbic alkalosis had PVL. These results suggest a significant relationship of complications and hypocarbic alkalosis to PVL. Mechanical ventilation should be managed carefully in premature infants to avoid PaCO2 of lower than 2.67 kPa.

Alkalosis↗

PubMed1993

Hereditary nodular heterotopia accompanied by mega cisterna magna.

This is the first report of hereditary nodular heterotopia accompanied by mega cisterna magna. Magnetic resonance imaging documented multiple bilateral subependymal nodules, which were isointense to gray matter. This disease entity is considered a dominant trait, since the mother and two daughters, half-sisters, were affected.

Adult↗

PubMed1993

A multicenter randomized trial of high frequency oscillatory ventilation as compared with conventional mechanical ventilation in preterm infants with respiratory failure.

A multicenter randomised trial was conducted in nine neonatal centers in Japan to re-evaluate the safety and the efficacy of high frequency oscillatory ventilation using the piston type oscillator (Hummingbird) in the treatment of respiratory failure in preterm infants weighing between 750 and 2000 g at birth. A total of 92 infants were enrolled in the study. Forty-six infants were allocated to high frequency oscillatory ventilation and 46 infants to conventional mechanical ventilation. There were no differences in sex, birth weight, gestation and Apgar score between groups. The study was begun 2.0 +/- 1.6 h (mean +/- S.D.) after birth in the high frequency oscillation group and 1.7 +/- 1.5 h after birth in the conventional mechanical ventilation group. The absence of intraventricular hemorrhage was confirmed by echography in all cases before beginning ventilation. Mortality was similar in high frequency oscillatory ventilation and conventional mechanical ventilation (0 and 2%). The incidence of intraventricular hemorrhage was also similar in the high frequency and conventional mechanical ventilation groups (15 and 13% overall; 4 and 2% in grades III and IV, respectively). Nine percent of the infants in high frequency oscillatory ventilation and 13% in conventional mechanical ventilation developed bronchopulmonary dysplasia, but the difference was not significant. The frequency of air leaks was also equal in both groups. Periventricular leukomalacia was detected in 9% of infants on conventional mechanical ventilation and 2% on high frequency oscillation, but the difference was not significant. Mean airway pressure was significantly higher in the high frequency oscillatory ventilation group and the infants on high frequency oscillation showed a significantly higher arterial to alveolar oxygen tension ratio after 6 h of treatment. These results suggest that high frequency oscillatory ventilation does not increase the risk of severe complications such as air leaks, intraventricular hemorrhage or periventricular leukomalacia when it is used by experienced neonatologists. Indeed high frequency oscillatory ventilation helps provide better oxygenation with higher mean airway pressure without increasing the risk of bronchopulmonary dysplasia and severe complications such as air leaks and intraventricular hemorrhage.

Bronchopulmonary Dysplasia↗

PubMed1993

Increased type III/I collagen and alpha 1(I)/alpha 2(I) chain in a bronchopulmonary dysplastic lung.

The type ratio of collagen III/I and molecule ratio of alpha 1(I)/alpha 2(I) were analysed in lungs from five infants with bronchopulmonary dysplasia (BPD) and seven control infants. All five BPD lungs showed typical characteristics, with pulmonary fibrosis and irregular cystic formation at postmortem examination. A pepsin digestion technique followed by interrupted gel electrophoresis was performed for the determination and molecular analysis of collagens III and I. The ratio of collagen types III and I were significantly increased in BPD lung (P < 0.005). The ratio of alpha 1(I) and alpha 2(I) were also significantly increased in BPD lung (P < 0.05). It is likely that collagen III is predominantly increased and that the alpha 1(I) trimer is formed in the active stage of BPD lungs.

Bronchoalveolar Lavage Fluid↗

PubMed1992

Neonatal cerebral infarction: symptoms, CT findings and prognosis.

In a retrospective multi-center study, we investigated eighteen infants with unilateral cerebral infarctions confirmed by computed tomography (CT) scans. The initial symptoms were observed in all the patients between 0 and 3 days of age. Convulsions or apneic attacks were the initial symptoms in all but one. Only 4 patients had complicated obstetric histories and none showed polycythemia or electrolyte abnormalities. All of the initial CT scans revealed unilaterally localized hypodense areas. In 10, the initial CT scans were performed within 24 hours after the clinical onset. In 16, the lesions were within the territory of the middle cerebral artery, 9 of which also involved the cortico-spinal tract (CST). In the remaining 2 patients, the lesions were located within the territory of the posterior cerebral artery. None of the 9 patients without CST involvement developed hemiplegia, whereas 5 (56%) of the 9 with CST involvement had hemiplegia, which is a fairly low incidence compared with that in adult cases. This difference was thought to be related to neonatal brain plasticity.

Cerebral Infarction↗

PubMed1992

Oxygen and reduced umbilical blood flow trigger the first breath of human neonates.

The mechanism triggering the first breath of human neonates is still unclear. In order to investigate the role of oxygen and umbilical blood flow in the onset of the first breath, a total of 20 rat and rabbit fetuses were studied. All five rat fetuses delivered in a nitrogen chamber did not commence breathing of their own accord, whereas all five rabbit fetuses delivered in oxygenated fluorocarbon fluid commenced their own breathing, suggesting that contact with oxygen rather than release from submergence is more crucial in the initiation of the first breath.

Animals↗

PubMed1992

Epidemiology of neonatal chronic lung disease in Japan.

A nationwide survey on the epidemiology of chronic lung disease (CLD) of the newborn was conducted. Questionnaires were sent to 391 level II and III neonatal centers in Japan and the registration of infants born in 1990 with chronic lung disease was requested. CLD was defined as an oxygen requirement greater than that obtainable in room air at 28 days after birth, with symptoms of persistent respiratory distress and a hazy or emphysematous and fibrous appearance on chest X-ray. A total of 301 neonatal centers (77.0%) responded and 50,290 infants at these centers were registered. Of these, 97% survived the first month and 1,135 of 48,762 neonatal survivors developed CLD. The mortality of infants with CLD was 6.2%. Survival rates at 28 days of age increased consistently with birthweight. Survival at 28 days of age in infants below 1,000 g at birth was 73.7%, but the rate was 93.9% in infants weighing 1,000-1,499 g. The incidence of CLD was inversely proportional to birthweight. Approximately one quarter of neonatal survivors with a birthweight below 1,500 g and approximately half of extremely small infants ( < 1,000 g) developed CLD. The analysis of CLD infants showed that 28.2% of them had a history of respiratory distress syndrome (RDS) and a typical fibrous appearance on chest X-ray (Type I), while 29.3% also had a history of RDS but had an atypical X-ray appearance (Type II).(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic Disease↗

PubMed1992

Effect of hypoxia on renal prostaglandin E2 production in human and rat neonates.

Effect of hypoxia on renal prostaglandin E2 (PGE2) production was shown in asphyxic newborn infants and experimental hypoxic rats. In asphyxic infants, at postnatal day 1, the urinary excretion of PGE2 in severe asphyxia (1.00 +/- 0.19 pg/kg/min, n = 10) was lower than that of the mild asphyxia (2.15 +/- 0.18 pg/kg/min, n = 10) or normal newborn infants (2.65 +/- 0.25 pg/kg/min, n = 8) (p less than 0.01). The urinary excretion of PGE2 was inversely correlated with the urinary N-acetyl-beta-D-glucosaminidase (r = -0.84, p less than 0.01). The urine volume in mild asphyxia (0.04 +/- 0.005 ml/kg/min) was higher in comparison to normal newborn infants (0.026 +/- 0.002 ml/kg/min) (p less than 0.01), but had no correlation with the urinary excretion of PGE2. In experimental hypoxic rats, the renal PGE2 concentration increased from 0.19 +/- 0.02 ng/mg protein to the maximum level of 0.59 +/- 0.03 ng/mg protein at 10 min of hypoxia. The renal PGE2 concentration then decreased to the minimum level (0.105 +/- 0.02 ng/mg protein) at 24 h after 20 min hypoxia. The renal ATP rapidly decreased during 20 min hypoxia, and gradually increased to 55.1 +/- 6.2 nmol/mg protein at 24 h after 20 min hypoxia, which recovered only about 60% of the control level. It seems likely that renal PGE2 does not play a major role in diuresis in mild birth asphyxia and that severe birth asphyxia suppresses the renal PGE2 production in early neonatal period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1991

Postnatal head growth in very premature infants with good outcome.

Postnatal head growth was examined retrospectively in 118 infants (male 60, female 58) born with a gestational age of from 24 to 29 weeks. Infants fulfilled the following criteria: (1) Those with hydrocephalus and small for dates (less than -1.5 standard deviation) were excluded. (2) Infants had normal intelligence and no cerebral palsy or epilepsy at 3 years of age or above. They were divided into four groups according to gestational ages: 24-26 wks (n = 21), 27 wks (n = 25), 28 wks (n = 41) and 29 wks (n = 31). The head circumference was measured at least twice monthly. The head growth curves in each group were obtained. After a transient decrease, head growth averaged 1.1-1.2 mm/day from day 21-30 to day 61-70 in all groups. From day 61-70 to 91-100 head growth averaged 1.2 mm/day at 24-26 wks and 0.8 mm/day at 27-29 wks, respectively.

Cephalometry↗