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H Togari

Publications and source records attributed to H Togari.

At least 19 recordsLinked to original sources
PubMed2002

Study to increase the frequency of autopsies performed for cases of infant deaths--proposed revision of the law on postmortem examination and corpse preservation and other related regulations.

By definition, sudden infant death syndrome (SIDS) requires diagnosis through exclusion by conducting an autopsy. To obtain a reliable diagnosis of this disease, an autopsy is essential. However, the frequency with which autopsies are conducted in Japan is not sufficient to meet the need associated with the diagnosis of SIDS. To improve this frequency, various public policies, such as nationwide implementation of the administrative autopsy system (medical examiner system), the application of the practice of autopsy approved by families, and legally required autopsies, are being considered; but none has been put into practice. On the other hand, attention has been called to the fact that the Law on postmortem examination and corpse preservation, which was instituted at the end of the Second World War, requires updating. In the current report, it is proposed that the following be added to Article 8, item 3 of this Law: "the Metropolitan or Prefectural Governor must insist that an autopsy be conducted on all cases of a sudden and unexpected death of an infant to investigate the cause of this death." At present, the annual incidence of SIDS in Japan is reported to be 500. To put the above-recommended legal requirement into practice, the estimated annual addition to the budget, if conducted as approved or an administrative autopsy, will be in the order of 150,000-500,000 dollar, which is within the prescribed limits for an appropriation.

Autopsy↗
PubMed2001

Neonatal-onset hereditary coproporphyria with male pseudohermaphrodism.

The appearance of hereditary coproporphyria (HCP) before puberty is very rare, and all reported cases of early-onset HCP have been in the homozygous or the compound heterozygous state. Some have been identified as harderoporphyria, which is a rare erythropoietic variant form of HCP. These conditions can be differentiated by molecular analysis because the gene abnormality responsible for harderoporphyria seems to be unique (K404E). Early-onset HCP, not harderoporphyria, is reported with a gene mutation in the heterozygous state and male pseudohermaphrodism. It was shown that adrenal gland hypofunction resulted in male pseudohermaphrodism. This case demonstrates the possibility that abnormalities of steroid metabolism influence porphyria.

Adrenal Insufficiency↗
PubMed2001

Exhaled nitric oxide decreases during exercise-induced bronchoconstriction in children with asthma.

Nitric oxide (NO) produced in the airways can be either detrimental or protective to the host. To investigate the role of NO in the pathogenesis of exercise-induced bronchoconstriction (EIB), we measured exhaled NO (ENO) after exercise challenge in 39 asthmatic and six normal children. FEV(1) and ENO were measured before and at 0, 5, 10, and 15 min after exercise performed on a treadmill for 6 min. EIB was defined as a decrease in FEV(1) of more than 15% after the exercise. Normal children (control group) did not have EIB. Twenty-one patients with asthma had EIB (EIB group) whereas the remaining 18 patients did not (non-EIB group). The baseline ENO value was significantly higher in the asthmatic children than in the normal children, and there was a positive correlation between the maximal percent decrease in FEV(1) and the baseline ENO value (r = 0.501, p = 0.012). At the end of the exercise, ENO had decreased in all the subjects. In the non-EIB and control groups, ENO rebounded to above the baseline at 5 min after the exercise and thereafter. In contrast, ENO remained at a decreased level in the EIB group. The change in ENO did not correlate with the change in minute ventilation, and beta-agonist inhalation at the peak of EIB that accelerated the recovery of FEV(1) did not affect the depressed level of ENO, demonstrating that the reduction of ENO is not a simple consequence of increased ventilation nor airway obstruction. Among the EIB group, steroid-treated patients showed sooner recovery in ENO after the exercise than steroid-naive patients. Our study suggests that NO production in response to exercise may be impaired in patients with EIB, and that ENO represents not only airway inflammation but also a protective function of NO in EIB.

Administration, Inhalation↗
PubMed2001

Developmental characteristics of apnea in infants who succumb to sudden infant death syndrome.

We compared the breathing characteristics of 40 infants who subsequently died of sudden infant death syndrome (SIDS) with those of 607 healthy infants matched for sex and age. The infants were between 2 and 19 wk old at the time of recording. Compared with the control group, the infants who died of SIDS experienced significantly more frequent episodes of obstructive and mixed sleep apnea. The duration of the apneic episodes did not exceed 15 s. Moreover, the SIDS group had a greater proportion of infants with obstructive and mixed apneic episodes than did the control group. In both groups, the frequency of episodes among male infants with apnea was greater than that among female infants. After the age of 9 wk, the proportion of male infants with episodes of obstructive apnea was greater in the SIDS group than in the control group. The frequency of apneic episodes decreased with age. The rate of decrease was significantly greater in the control subjects than in the SIDS group. This finding was made mainly in male infants. The present study provides further indirect evidence for a slower maturation of respiratory control in some infants who ultimately die of SIDS.

Female↗
PubMed2001

Human neuroblastomas with unfavorable biologies express high levels of brain-derived neurotrophic factor mRNA and a variety of its variants.

The expression of human brain-derived neurotrophic factor (BDNF) was investigated in 16 primary human neuroblastomas with favorable biologies, 15 with unfavorable biologies, and in human neuroblastoma cell lines. We demonstrated higher expressions of human BDNF mRNA in neuroblastomas with unfavorable biologies and with N-myc amplification than in those with favorable biologies. For the first time we revealed the composition of splice variants of human BDNF mRNA and analyzed their expression in neuroblastomas by reverse transcription polymerase chain reaction (RT-PCR). Interestingly, human BDNF mRNA consisted of at least six isoforms, four isoforms resembling those of rat BDNF mRNA, a human-specific isoform and a new isoform. The expression of four isoforms were more prominent in tumors with unfavorable biologies than in those with favorable biologies (P<0.05). As previously we had reported, over 80% of the primary tumors expressed either the full-length form of BDNF receptor, TRKB, or a truncated form of TRKB lacking the tyrosine kinase domain. The full-length TRKB was predominantly detected in tumors with unfavorable biologies, and the truncated one in those with favorable biologies. These results suggest that an autocrine and/or paracrine mechanism involving BDNF may stimulate signal transduction via TRKB receptors rich in neuroblastomas with unfavorable biologies, resulting in an aberrant survival of tumor cells.

Age Factors↗
PubMed2001

Optical imaging reveals cation--Cl(-) cotransporter-mediated transient rapid decrease in intracellular Cl(-) concentration induced by oxygen--glucose deprivation in rat neocortical slices.

In brain slices from young (postnatal day (P) 10--15) rat somatosensory cortex, real-time neuronal intracellular Cl(-) concentration ([Cl(-)](i)) recordings were made by an optical technique measuring 6-methoxy-N-ethlquinolinium iodide (MEQ) fluorescence. Oxygen--glucose deprivation (in vitro model of ischemia) induced a long-lasting [Cl(-)](i) increase preceded by a rapid, transient [Cl(-)](i) decrease that could not be inhibited by blockers of Cl(-) pumps, Cl(-) channels, or Cl(-) antiporters, but was sensitive to cation-Cl(-) cotransporter inhibitors (bumetanide and furosemide). Use of low external Na(+) or high external K(+) revealed that the Na(+),K(+)-2Cl(-) cotransporter was inhibited by bumetanide and furosemide, whereas the K(+)-Cl(-) cotransporter was preferentially inhibited by furosemide under our experimental conditions. With a reduced inward driving force for Na(+) (reducing Na(+),K(+)-2Cl(-) cotransport), the transient [Cl(-)](i) decrease was only rarely induced by oxygen-glucose deprivation. In contrast, with a reduced outward driving force for K(+) (reducing K(+)-Cl(-) cotransport), the transient [Cl(-)](i) decrease still occurred. These results suggest that the transient [Cl(-)](i) decrease was primarily mediated by a rapid inhibition of the inwardly directed Na(+),K(+)-2Cl(-) cotransporter. Reverse transcriptase-polymerase chain reaction (RT-PCR) experiments suggested that the isoform involved is NKCC1. We hypothesize that the initial rapid Cl(-) efflux might effectively delay the irreversible Cl(-) influx that mediates neuronal injury.

Animals↗
PubMed2001

Interleukin-1beta induces the expression of lipocortin 1 mRNA in cultured rat cortical astrocytes.

Lipocortin 1 (LC1) has been shown to increase in neuronal damage and act as a neuroprotectant and a neurotrophic factor. IL-1beta acts as a mediator of inflammation and has been reported as a potent inducer of various neurotrophic factors including nerve growth factor and fibroblast growth factor. In this study, we investigated the relationship between LC1 and IL-1beta in cultured rat astrocytes. Time-and dose-dependent experiments of IL-1beta on rat cortical astrocytes in culture revealed that the expression of LC1 mRNA was significantly augmented by IL-1beta at 8 h, 10 ng/ml. In addition, IL-1beta evoked an extracellular secretion of LC1 without its cytotoxic effects. The effect of IL-1beta was completely abolished when we treated cells with inhibitor of mitogen-activated protein kinases (MAPKs) (PD98059) (25 microM), phospholipase A(2) inhibitor mepacrine (30 microM) and protein synthesis inhibitor cycloheximide (CHX) (10 microg/ml). This suggests that induction of LC1 by IL-1beta is through a MAPKs and phospholipaseA(2) pathway and requires protein synthesis. These results indicate that IL-1beta released in the central nervous system (CNS) injury can stimulate the transcription of the LC1 gene. Subsequent synthesis and release of LC1 may provide trophic support to neurons and modulate the action of IL-1beta in brain damage.

Animals↗
PubMed2001

A prospective clinical study on inhaled nitric oxide therapy for neonates in Japan.

BACKGROUND: This is the first report about a prospective clinical investigation to study the efficacy and safety of nitric oxide (NO) inhalation in infants with persistent pulmonary hypertension of the newborn (PPHN) in Japan. METHODS: Patients in the present study had to meet the following entry criteria: (i) they had to be younger than 7 days of age; (ii) they had to have evidence of PPHN as defined by echocardiograph; (iii) they had to have severe systemic hypoxemia under mechanical ventilation at 100% oxygen supplementation; and (iv) they had to have a failure to respond to conventional therapies. Patients were excluded from this trial if they had any of the following: hypoplastic lung, structural cardiac lesions or severe multiple anomalies. RESULTS: Nitric oxide inhalation therapy was performed in 68 infants who had severe PPHN at 18 hospitals between May 1995 and May 1997. At birth, 21 of 68 infants (31%) weighed less than 1,500 g and 39 infants weighed more than 2,500 g. The diagnoses associated with PPHN were as follows: 27 infants had meconium aspiration syndrome, 15 infants had dry lung syndrome, nine infants had congenital diaphragmatic hernia, six infants had respiratory distress syndrome, three infants had pneumonia and eight infants had other diagnoses. The mean oxygenation index (OI) before NO inhalation therapy in 68 infants was 43.2; 55 infants (81%) had good responses. CONCLUSIONS: These results may be valuable for further randomized controlled and double-blind trials in Japan to evaluate whether NO inhalation therapy is more effective than conventional therapy in infants with severe PPHN.

Administration, Inhalation↗
PubMed2001

Nitric oxide inhalation and nitric oxide synthase inhibitor supplement for endotoxin-induced hypotension.

BACKGROUND: This study was performed to determine whether a combined therapy of nitric oxide (NO) inhalation and nitric oxide synthase (NOS) inhibitor is effective in experimental animals with endotoxin-induced refractive hypotension accompanied by pulmonary hypertension. METHODS: Escherichia coli lipopolysaccharide (1 mg/kg) was administered to 10 newborn piglets to induce endotoxemia. The experiment then began 60 min later, when the systemic arterial pressure dropped. The inhalation of 20 p.p.m. NO at 60 and 120 min of endotoxemia created a control group. Another group was also administered N w-nitro-L-arginine (L-NNA; 5 mg) after the first NO inhalation at 60 min of endotoxemia (the L-NNA group). Pulmonary arterial pressure, systemic arterial pressure and cardiac output were measured and compared among the groups. RESULTS: Three of the 5 piglets in the control group died of hypotensive shock, while in the L-NNA group the systemic arterial pressure recovered to pre-endotoxin administration levels. The L-NNA group produced a further increase in pulmonary arterial pressure against which NO inhalation was effective. CONCLUSION: Nitric oxide inhalation alone carries a potential risk of further lowering systemic arterial pressure in a piglet with hypotension induced by endotoxin, whereas the combined therapy resulted in the recovery of the blood pressure to pre-endotoxin levels. The combined therapy was simultaneously effective against pulmonary hypertension.

Animals↗
PubMed2000

Frequency of obstructive and mixed sleep apneas in 1,023 infants.

STUDY OBJECTIVES: To collect normative data on the frequency of obstructive and mixed sleep apneas in healthy infants. STUDY DESIGN: 1100 infants were recorded during one night in a sleep laboratory. SETTING: the recordings were performed in an infant sleep laboratory. PATIENTS: The recordings of 1023 infants were used for analysis, the data of 77 infants being excluded because of poor recording quality. The infants were born full-term, were healthy at the time of study, had no history of apnea and were aged between 2 and 28 weeks. The polysomnographic recordings were analyzed visually and were subdivided according to the age of the subjects into 2-7 weeks, 8-11 weeks, 12-15 weeks, 16-19 weeks and 20-27 weeks of life. INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: At 2-7 weeks of life, obstructive apneas (p=.013) and mixed apneas (p=.004) were significantly more frequent than at any other age group. At 8 to 11 weeks of life, obstructive apneas were significantly more frequent in boys than girls (p=.016). CONCLUSIONS: The present findings add to our knowledge of infants' respiratory characteristics during sleep.

Female↗
PubMed2000

The healthy human infant tends to sleep in the prone rather than the supine position.

There are few reports about developmental behavior relating to roll over among healthy infants. We assessed the relationship between the placed position on sleeping and altered sleeping position the next morning by roll over among healthy infants. A health check-up clinic distributed a total of 1626 questionnaires to parents whose infant's ages are 1.5 years (or 18 months) old. The age at the first roll over and the change in sleeping position the next morning after they started to roll over, were investigated. The mean age of roll over from the supine to the prone among infants who were placed mainly in the prone sleeping position, at least in the first week of life, was 4.0 months (S.D., 1.1). The mean age of roll over from the supine to the prone among infants who were placed mainly in the supine sleeping position during early neonatal life and thereafter was 4.4 months (S.D., 1.2). The age of the first roll over from supine to prone was significantly younger in infants who were placed mainly in the prone sleeping position during early neonatal life. Among 651 infants who had been placed supine, 34.7% were found prone by roll over the next morning. Among 211 infants who had been placed prone, 14.2% were found supine by roll over the next morning. The number of infants who rolled over from supine to prone position was statistically greater than those from prone to supine. It is likely that the healthy human infant tends to sleep in the prone rather than the supine position. The finding is especially important for the correct assessment of the position in which SIDS cases were found dead.

Humans↗
PubMed2000

Urinary pyrimidine analysis in healthy newborns, infants, children, adults and patients with congenital metabolic diseases.

BACKGROUND: In previous reports, the reference range for urinary pyrimidine was determined on the basis of a small number of samples, with data for only a few patients being reported. In the present study, we measured urinary pyrimidine compounds in 25 healthy newborns, 33 healthy infants, 130 healthy children and 166 healthy adults. In addition, we also analyzed urinary pyrimidine compounds in various patients with abnormal pyrimidine metabolism, such as congenital pyrimidine metabolism disorders and urea cycle disorders. METHODS: We analyzed urines by high-performance liquid chromatography with column switching. Analyses were performed with both a reverse-phase column and an anion-exchange column. The columns were connected by a column switch, with all systems being controlled automatically by a computerized system controller. RESULTS: The excretion of pyrimidine compounds in patients with abnormal pyrimidine metabolism (containing heterozygotes) was out of our reference ranges. CONCLUSIONS: These results suggest that urinary pyrimidine analysis is a useful index for the diagnosis of pyrimidine metabolism disorders, urea cycle disorders and these heterozygotes. Based on this large-group analysis of healthy individuals, we were able to determine the reference ranges of urinary orotic acid, dihydrouracil and uracil for each age group.

Adolescent↗
PubMed2000

During neonatal mechanical ventilatory support, the delivered nitric oxide concentration is affected by the ventilatory setting.

OBJECTIVE: To assess whether the delivered nitric oxide (NO) concentration is affected by a change in the ventilatory setting during neonatal mechanical ventilatory support. DESIGN: Prospective, experimental study. SETTING: Laboratory at Nagoya City University Medical School. INTERVENTIONS: This study was performed by using a pressure-limited, time-cycled, ventilatory support with a neonatal circuit and a 50-mL silicone test lung. NO in N2 gas was administrated into the inspiratory limb at a distance of 4 cm, 80 cm, or 160 cm from the Y piece connected to the adapter of an endotracheal tube. The NO concentration was measured every 0.5 sec by a chemiluminescence analyzer at the Y piece. MEASUREMENT AND MAIN RESULTS: NO concentrations were compared with each of the ventilatory settings of peak inspiratory pressure (PIP) (10-30 cm H2O), positive end-expiratory pressure (0-10 cm H2O), ventilatory flow (10, 20, 30 L/min), and ventilatory rate (30, 40, 50, 60, 70 breaths/min), respectively. The NO concentration was significantly lower when NO was added at 4 cm than at 80 cm or 160 cm from Y piece at the same ventilatory setting of PIP, positive end-expiratory pressure and ventilatory flow, respectively, (p < .01). Although the NO concentration was increased as the settled PIP level was increased (p < .01 or p < .05), it was not changed when the settled positive end-expiratory pressure level was increased. A decrease was seen in the NO concentration as the settled ventilatory flow was increased (p < .01). Lastly, the NO concentration fluctuated greatly in association with the settled ventilatory rate. CONCLUSION: The NO concentration delivered to patients is influenced by the ventilatory setting during neonatal mechanical ventilatory support.

Female↗
PubMed2000

Urinary orotic acid levels in normal pregnancy and pregnancy-induced hypertension.

Our objective was to study the urinary levels of orotic acid in normal pregnancy and in pregnancy-induced hypertension. Such levels were measured using high-performance liquid chromatography with column-switching. The levels of urinary orotic acid (micromol/g creatinine) in normal pregnancy (n = 14) were 6.9 +/- 2.3 (first trimester), 10.1 +/- 2.4 (20 weeks) and 12.0 +/- 3.7 (30 weeks). In pregnancy-induced hypertension (n = 14), the corresponding levels were 6.5 +/- 1.7, 7.8 +/- 2.7 and 7.6 +/- 2.3, respectively. Normal pregnant subjects individually showed a significant elevation at 20 and 30 weeks of gestation as compared with those in the first trimester (p < 0.01). A high consumption of arginine in nitric oxide production during normal pregnancy may cause a physiological elevation of urinary orotic acid. The absence of an elevation in pregnancy-induced hypertension may be associated with a decrease in nitric oxide production.

Arginine↗
PubMed2000

Screening for pyrimidine metabolism disorders using dried filter-paper urine samples: method development and a pilot study in Nagoya City, Japan.

A screening system for pyrimidine metabolism disorders by measurement with high-performance liquid chromatography using dried filter-paper urine samples is presented. This system permits the simultaneous determination of dihydrouracil, uracil, orotic acid and pseudouridine. The coefficient of variations for the four compounds on the filter-paper urine samples were 0.010 approximately 0.069 and the recoveries were 98.5 approximately 107.1%. The detection limits of the four compounds were 2 approximately 20 micromol/liter. The correlation between the filter-paper urine samples and liquid urine samples was excellent (0.938-0.988). We supeculated that this method could be used to detect pyrimidine metabolism disorders, such as dihydropyrimidinuria, dihydropyrimidine dehydrogenase deficiency and hereditary orotic aciduria. As a pilot study, we have analyzed dried filter-paper urine samples from 34, 200 healthy Japanese, and found three cases of dihydropyrimidinuria without clinical symptoms.

Drug Stability↗
PubMed2000

Unique electroencephalographic change of acute encephalopathy in glutaric aciduria type 1.

We report the peculiar serial electroencephalographic (EEG) findings in a 7-year-old boy with glutaric aciduria type 1 during an episode of acute encephalopathy. The patient developed Reye-like syndrome triggered by cellulitis. Cranial magnetic resonance imaging demonstrated diffuse softening of cerebral hemisphere. The EEG on the day following onset of acute encephalopathy showed suppression burst pattern including continuous 14-15 Hz rhythmic waves at first. Then, periodic synchronous discharge appeared and lasted for about 40 minutes. Periodic synchronous discharge finally disappeared and nearly total electrocerebral silence continued. There have been no reports indicating such a change of EEG in a short period. The serial EEG changes probably reflect the process of electrical death of neurons in cerebral hemispheres.

Acute Disease↗
PubMed2000

Decreased fluorouracil cytotoxic effect on EB-virus transformed lymphocytes from hereditary orotic aciduria.

5-Fluorouracil (5-FU), used widely for malignancies, phosphorylate mostly by uracil phosphoribosyl transferase (UPRT). Patients with hereditary orotic aciduria lack the orotate phosphoribosyl transferase (OPRT) activity. In the cancer cells, the OPRT activity is paralleled with the UPRT activity. This study shows that the UPRT activity of the hereditary orotic aciduria homozygote decreased about 40% of normal controls. Moreover, we investigated the 5-FU cytotoxic effects on hereditary orotic aciduria (one homozygote, 4 heterozygotes and 7 normal controls), using EB-virus transformed lymphocytes (EB-LC). 5-FU was addded to the culture medium at concentrations ranging from 0 to 10.0 micromol/l. The 5-FU cytotoxic effects on the homozygote were milder than those on controls at each 5-FU concentration. The 5-FU cytotoxic effects in the heterozygotes were at intermediate levels between the homozygote and controls. We speculate that 5-FU cytotoxic effects, both anti-tumor effects and adverse reactions, would be weak when a patient with hereditary orotic aciduria was treated with 5-FU.

Antimetabolites↗