Masakazu Saito

Urinary leukotriene E4 after exercise challenge in children with asthma

To assess the role of sulfidopeptide leukotrienes in the pathogenesis of exercise-induced asthma (EIA), the urinary levels of leukotriene E4 (LTE4), a metabolite of LTC4 and LTD4, were measured by RIA before and after exercise in 13 children with EIA and 10 healthy children. Mass spectrometry was used to confirm the presence of LTE4 in urine and the specificity of the RIA. There was no significant difference in the urinary LTE4 levels before exercise between the children with asthma and healthy children (109 [21 to 265] versus 122 [45 to 156] pg/mg of creatinine; median and range). Urinary LTE4 levels increased significantly after exercise in the children with EIA (from 109 [21 to 265] to 196 [40 to 655] pg/mg of creatinine; median and range; p less than 0.05) but not in the healthy children. The children with asthma demonstrated no significant correlation between the LTE4 level after exercise and the degree of bronchoconstriction, as revealed by the maximal percent fall in the peak expiratory flow rate. Taken together with a recent study that pretreatment with a potent and selective LTD4 antagonist markedly attenuated EIA, our findings suggest that sulfidopeptide leukotrienes may play some role in the pathogenesis of this type of asthma with other factors also being involved in determining the overall airway response.

Evaluation of variability of proteinuria indices

We compared several indices of proteinuria, namely protein concentration, hourly protein excretion rate (Up/h) and protein/creatinine ratio (Up/Ucr) in single voided urine samples as well as 24 h-urinary protein excretion (24 h-Up), in 44 children, aged 4–16 years, with varying degrees of urinary protein excretion. We found an excellent correlation between Up/h and Up/Ucr in early morning samples. These two indices in early morning samples had excellent correlation with 24 h-Up, comparable to those in any other urine sample of the day. Among daytime samples, Up/h varied widely, in contrast to Up/Ucr, which had significantly less variability. We analysed six early morning and six bedtime samples from 39 of these subjects, and found smaller coefficients of variation for individual patients indices in morning samples. Up/h was more variable than Up/Ucr, especially in bedtime samples. Urinary protein concentration had a poorer correlation with 24 h-Up and was more variable than any other index. We conclude that the Up/Ucr in early morning samples, which has the advantages both of simplicity and low day-to-day variability in a given patient, is a superior index of proteinuria.

Exercise-induced urinary excretion of leukotriene E4 in children with atopic asthma

ABSTRACT: Urinary levels of leukotriene (LT) E4, a stable end-product of LTC4 and LTD4, were measured before and after exercise in 10 children with severe asthma and seven children with moderate asthma using HPLC and RIA to clarify the relationship of LT to the severity of asthma and to the degree of bronchospasm in exercise-induced asthma. The urinary LTE4 level significantly increased after exercise in the severe asthma group, but not in the moderate asthma group (14.3 ± 14.5 to 24.3 ± 20.6 versus 19.6 ± 12.3 to 17.6 ± 10.8 ng/mmol creatinine, p < 0.05). The urinary LTE4 level increased in 10 patients (eight with severe asthma), and it decreased in seven patients (five with moderate asthma). A significant difference in the degree of bronchospasm after exercise (as shown by the maximal % fall in the peak expiratory flow rate), was seen when patients with increased urinary LTE4 excretion were compared with those with decreased excretion (60.4 ± 17.3 versus 24.1 ± 14.3%, p < 0.01). Our findings suggest that exercise-induced asthma, or at least a subtype of exercise-induced asthma, may partly develop through the release of LTC4.

Urinaryα1 as an index of proximal tubular function in early infancy

Urinary α1-microglobulin (U-A1M) was measured in healthy term infants on days 1, 4, 7, 14, 28, 90 and 180 of life. U-A1M was high until day 14 and declined thereafter. It was significantly correlated with urinary β2-microglobulin (U-B2M) throughout the study, but not with serum A1M on days 1 or 7. Similar to U-B2M, U-A1M in the clinically stable term infants with intrauterine growth retardation (n=4–7) was not elevated on days 1–7. In the sick infants who needed immediate resuscitatio at birth (n=4–8), U-A1M as well as U-B2M was high on days 1–7 and then decreased to normal levels, suggesting that U-A1M can be used as a sensitive marker of acute proximal tubular damage and its recovery. These observations indicate that U-A1M is a useful index of proximal tubular function in early infancy.

Assessment of tubular function in neonates using urinary β2-microglobulin

Renal proximal tubular function was assessed in neonates by measuring urinary β2-microglobulin (β2M) concentrations on days 1, 4, 7, 14 and 28. Values were elevated in stable preterm low-birthweight (LBW) neonates but not in stable term LBW neonates, suggesting that proximal tubular maturation is related to gestational age rather than birthweight. The urinary β2M was significantly increased on day 1 in neonates with the meconium aspiration syndrome but was not significantly different from normal subsequently. This indicated that although the proximal tubular cells may be susceptible to perinatal hypoxia, they maintain a remarkable capacity to recover in a relatively short period. Neonates with transient tachypnoea of the newborn had normal urinary levels of β2M indicating their renal tubular function was not impaired.

Methylenetetrahydrofolate reductase polymorphism in Kawasaki disease

Abstract Background: A genetic aberration in the 5,10‐methylenetetrahydrofolate reductase (MTHFR) gene (677 C to T substitution) has been shown to result in reduced enzyme activity. The hypothesis tested in the present study was that a higher proportion of Kawasaki disease (KD) patients with coronary artery lesions (CAL) would have the T677 allele compared with patients without CAL and healthy subjects.

MRI assessment of myelination patterns in high-risk infants

Magnetic resonance imaging (MRI) was used in high-risk infants to assess the myelination process and its relationship with neurologic outcome. The time period when delayed myelination is best detected by MRI was also studied. MRI was performed in 39 high-risk infants (i.e., preterm infants, infants with respiratory distress syndrome, or with neonatal convulsions and asphyxia). In 10 of 11 infants with normal development, MRI revealed a normal myelination pattern before 2 months of age, and in 11 of 13 infants after 2 months of age. Conversely, in infants with poor outcomes, MRI demonstrated delayed myelination patterns in only 1 of 4 infants before 2 months of age but in 9 of 11 infants after 2 months of age. In patients with poor outcomes, delayed myelination was found more frequently after rather than before 2 months of age. These findings demonstrate that delayed myelination detected by MRI is useful in predicting the neurologic outcome of high-risk infants, especially after 2 months of age.

Effects of ACTH on brain midline structures in infants with infantile spasms

Changes of the midline structures of the brain, including the pons, cerebellar vermis, and corpus callosum, induced by adrenocorticotropic hormone (ACTH) therapy in 7 infants with infantile spasms were investigated using magnetic resonance imaging. Decreased volume of these parts of the brain was induced in almost all infants. Decreased volume of the pons was thought to be closely related to sleep disturbance during ACTH therapy. These results may demonstrate that the cessation of convulsive episodes in infants with infantile spasms treated with ACTH is due to its direct action on the brainstem.

Corpus callosum in developmentally retarded infants

The development of the corpus callosum was examined by magnetic resonance imaging in developmentally retarded infants ranging in age from 1-13 months. Results were compared with those of normal infants. Eighteen magnetic resonance imaging studies were performed on 18 developmentally retarded infants. Fifty-four magnetic resonance imaging studies were performed on 38 normally developed infants. The thickness of the corpus callosum was measured at a point one-third of the length of the entire corpus callosum from the most anterior aspect of the genu. The development of the corpus callosum was related to aging in both groups. There was significant difference in the thickening of the corpus callosum between normal and developmentally retarded infants.

Pathophysiologic study on methylmalonic aciduria : decrease in liver high-energy phosphate after propionate loading in rats

ABSTRACT: Methylmalonate or propionate was i.v. infused into B12-deprived and control rats. In the B12-deprived rats, the plasma and liver concentrations of B12 decreased to 8 and 13%, respectively, of those of the control rats. The propionate loading produced a disproportionate increase in liver propionate levels; the mean ratio of methylmalonate to propionate in the liver was approximately 1.0 after methylmalonate loading, whereas it was 0.1 to 0.2 after propionate loading. The liver propionate and methylmalonate levels in the B12-deprived rats were twice as high as those in the control rats. The mean ratio of β-ATP to inorganic phosphate in the liver, measured with 31P-magnetic resonance spectroscopy, decreased from 0.60 to 0.48 in the B12-deprived rats and from 0.78 to 0.63 in the control rats after methylmalonate loading; the ratio decreased from 0.57 to 0.37 in the B12-deprived rats and from 0.76 to 0.56 in the controls after propionate loading. Statistical analysis showed that propionate loading caused a more marked decrease in ATP than did methylmalonate loading (F = 26.33, degree of freedom 1 and 15; p < 0.001), while B12-deprivation caused a more marked decrease in ATP than did the control diet (F = 92.26, df 1 and 15; p < 0.001). The concentrations of tricarboxylic acid cycle intermediates and related organic acids in the livers of the rats suggested that propionate inhibited NAD+-dependent enzymes in the cycle. These results indicate that propionate, which accumulates during crises in methylmalonic aciduria, contributes to the decrease in ATP levels to a greater extent than does methylmalonate, and thus impairs the ATP-dependent carboxylation of propionate itself to methylmalonate.