SAPK/JNK plays a role in transforming growth factor-beta-induced VEGF synthesis in osteoblasts.

We previously reported that transforming growth factor-beta (TGF-beta) activates p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase, resulting in the stimulation of vascular endothelial growth factor (VEGF) synthesis in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the involvement of stress-activated protein kinase/c- Jun N-terminal kinase (SAPK/JNK), another member of the MAP kinase superfamily, in TGF-beta-induced VEGF synthesis in these cells. TGF-beta markedly induced SAPK/JNK phosphorylation. SP600125, a specific inhibitor of SAPK/JNK, markedly reduced TGF-beta-induced VEGF synthesis. SP600125 suppressed TGF-beta-induced SAPK/JNK phosphorylation. PD98059, an inhibitor of upstream kinase of p44/p42 MAP kinase and SB203580, an inhibitor of p38 MAP kinase, each failed to reduce TGF-beta-induced SAPK/JNK phosphorylation. A combination of SP600125 and PD98059 or SP600125 and SB203580 suppressed TGF-beta-stimulated VEGF synthesis in an additive manner. These results strongly suggest that TGF-beta activates SAPK/JNK in osteoblasts, and that SAPK/JNK plays a role in addition to p42/p44 MAP kinase and p38 MAP kinase in TGF-beta-induced VEGF synthesis.

Involvement of SAPK/JNK in prostaglandin E(1)-induced VEGF synthesis in osteoblast-like cells.

We previously reported that prostaglandin E(1) (PGE(1)) activates both p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase via cAMP-dependent protein kinase in osteoblast-like MC3T3-E1 cells, and that p38 MAP kinase but not p42/p44 MAP kinase is involved in PGE(1)-induced synthesis of vascular endothelial growth factor (VEGF). In the present study, we investigated the involvement of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in the PGE(1)-induced VEGF synthesis in MC3T3-E1 cells. PGE(1) induced the phosphorylation of SAPK/JNK. SP600125, a specific inhibitor of SAPK/JNK, markedly reduced the PGE(1)-induced VEGF synthesis. Forskolin, a direct activator of adenylyl cyclase, elicited the phosphorylation of SAPK/JNK, and 8bromo-cAMP, a plasma membrane-permeable cAMP analogue-stimulated VEGF synthesis was significantly reduced by SP600125. SP600125 suppressed the PGE(1)-induced phosphorylation of SAPK/JNK without affecting the phosphorylation of p38 MAP kinase induced by PGE(1). The phosphorylation of c-Jun induced by PGE(1) was also inhibited by SP600125. SB203580, a p38 MAP kinase inhibitor, failed to reduce the PGE(1) induced phosphorylation of SAPK/JNK. A combination of SP600125 and SB203580 suppressed the PGE(1)-stimulated VEGF synthesis in an additive manner. These results strongly suggest that PGE(1) activates SAPK/JNK in osteoblasts, and that SAPK/JNK plays a part in PGE(1)-induced VEGF synthesis.

Contingent negative variation in children with orthostatic dysregulation.

BACKGROUND: Children with orthostatic dysregulation (OD) appear to have hypodynamia, as well as the symptoms described in the OD criteira. Hypodynamia, which is greatly influenced by motivation, volition and concentration, is unexceptionally recognized in their everyday life. It has been suggested that the symptoms and hypodynamia aggravate considerably the quality of life (QOL) of children with OD. The purpose of this study was to distinguish the characteristics of contingent negative variation (CNV) and post imperative negative variation, which may reflect the level of attention and motivation in children with OD. METHODS: Twelve patients with OD aged 10-15 years and 23 age-matched healthy children were included. The CNV was recorded from Fz, Cz and Pz linked to earlobes during 30 trials consisting of a warning stimulus and an imperative stimulus with an interstimulus interval (ISI) of 2 s and an intertrial interval (ITI) of 10 s. The imperative stimulus of each trial required a button to be pressed. RESULTS: The untreated children with OD did not have a significantly smaller CNV amplitude than healthy children. Children with OD treated with midodrine and autonomic training had a significantly larger CNV amplitude than the untreated children, in the area of early, late and total CNV at the three sites. CONCLUSION: The present study confirms that children with OD have diminished motivation and deterioration of concentration, which cause hypodynamia in everyday life. Treatment for OD improves the symptoms, diminished motivation and deterioration of concentration, consequently restoring dynamia. Treatment for OD should be recommended to ameliorate QOL of children with OD.

Identification of Tetrahymena hsp60 as a 14-nm filament protein/citrate synthase-binding protein and its possible involvement in the oral apparatus formation.

BACKGROUND: Tetrahymena 14-nm filament protein (14FP) is bifunctional, with roles as a citrate synthase in mitochondria and as a cytoskeletal protein in nuclear events during fertilization and in oral morphogenesis. In this study, to further our understanding of the bifunctional property of 14FP, we attempted to screen 14FP-binding proteins using affinity column chromatography. RESULTS: Through the screening of 14FP-binding proteins using 14FP-affinity chromatography, we detected 65 kDa and 70 kDa proteins that bound to 14FP in an ATP dependent manner. From the N-terminal amino acid sequence, these proteins were identified as the Tetrahymena mitochondrial chaperones, hsp60 and mthsp70, respectively. Tetrahymena hsp60 was recognized with a monoclonal antibody raised against human hsp60. Immunofluorescence and immunoelectron microscopy using the monoclonal antibody showed that Tetrahymena hsp60 was localized to mitochondria. Moreover, Tetrahymena hsp60 was also present at extramitochondrial sites including basal bodies of cilia and oral apparatus, and particularly at the developing oral apparatus during cell division. CONCLUSION: These results suggest that Tetrahymena hsp60 is localized in basal bodies and is involved in cortical patterning such as the formation of the oral apparatus as well as having a role in the folding of mitochondrial proteins in mitochondria.

Determination of division plane and organization of contractile ring in Tetrahymena.

In the molecular mechanism of division plane determination and contractile ring formation, Tetrahymena 85kDa protein (p85) is localized to the presumptive division plane before the formation of the contractile ring. p85 directly interacts with Tetrahymena calmodulin (CaM) in a Ca2+-dependent manner, and p85 and CaM colocalize in the division furrow. A Ca2+/CaM inhibitor N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide HCI (W7) inhibits the direct interaction between p85 and Ca2+/CaM. W7 also inhibits the localization of p85 and CaM to the division plane, and the formation of the contractile ring and division furrow. In addition, p85 binds to G-actin in a Ca2+/CaM dependent manner, but does not bind F-actin. Tetrahymena profilin is localized to division furrow and binds Tetrahymena elongation factor-1alpha (EF-1alpha). EF-1alpha, which induces bundling of Tetrahymena F-actin, is also localized to the division furrow during cytokinesis. The evidence also indicates that Ca2+/CaM inhibits the F-actin-bundling activity of EF-1alpha, and that EF-1alpha and CaM colocalize in the division furrow. In this review, we propose that the Ca2+/CaM signal and its target protein p85 cooperatively regulate the determination of the division plane and the initiation of the contractile ring formation, and that profilin and a Ca2+/CaM-sensitive actin-bundling protein, EF-1alpha, play pivotal roles in regulating the organization of the contractile ring microfilaments.

Calmodulin and Ca2+/calmodulin-binding proteins are involved in Tetrahymena thermophila phagocytosis.

The ciliated protist, Tetrahymena thermophila, possesses one oral apparatus for phagocytosis, one of the most important cell functions, in the anterior cell cortex. The apparatus comprises four membrane structures which consist of ciliated and unciliated basal bodies, a cytostome where food is collected by oral ciliary motility, and a cytopharynx where food vacuoles are formed. The food vacuole is thought to be transported into the cytoplasm by a deep fiber which connects with the oral apparatus. Although a large number of studies have been done on the structure of the oral apparatus, the molecular mechanisms of phagocytosis in Tetrahymena thermophila are not well understood. In this study, using indirect immunofluorescence, we demonstrated that the deep fiber consisted of actin, CaM, and Ca2+/CaM-binding proteins, p85 and EF-1alpha, which are closely involved in cytokinesis. Moreover, we showed that CaM, p85, and EF-1alpha are colocalized in the cytostome and the cytopharynx of the oral apparatus. Next, we examined whether Ca2+/CaM signal regulates Tetrahymena thermophila phagocytosis, using Ca2+/CaM inhibitors chlorpromazine, trifluoperazine, N-(6-aminohexyl)-1-naphthalenesulfonamide, and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide HCI. In Tetrahymena, it is known that Ca2+/CaM signal is closely involved in ciliary motility and cytokinesis. The results showed that one of the inhibitors, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide HCl, inhibited the food vacuole formation rather than the ciliary motility, while the other three inhibitors effectively prevented the ciliary motility. Considering the colocalization of CaM, p85, and EF-1alpha to the cytopharynx, these results suggest that the Ca2+/CaM signal plays a pivotal role in Tetrahymena thermophila food vacuole formation.

Complete paternal uniparental isodisomy for chromosome 1 revealed by mutation analyses of the TRKA (NTRK1) gene encoding a receptor tyrosine kinase for nerve growth factor in a patient with congenital insensitivity to pain with anhidrosis.

Uniparental disomy (UPD) is defined as the presence of a chromosome pair that derives from only one parent in a diploid individual. The human TRKA gene on chromosome 1q21-q22 encodes a receptor tyrosine kinase for nerve growth factor and is responsible for an autosomal recessive genetic disorder: congenital insensitivity to pain with anhidrosis (CIPA). We report here the second case of paternal UPD for chromosome 1 in a male patient with CIPA who developed normally at term and did not show overt dysmorphisms or malformations. He had only the usual features of CIPA with a homozygous mutation at the TRKA locus and a normal karyotype with no visible deletions or evidence of monosomy 1. Haplotype analysis of the TRKA locus and allelotype analyses of whole chromosome 1 revealed that the chromosome pair was exclusively derived from his father. Non-maternity was excluded by analyses of autosomes other than chromosome 1. Thus, we have identified a complete paternal isodisomy for chromosome 1 as the cause of reduction to homozygosity of the TRKA gene mutation, leading to CIPA. Our findings further support the idea that there are no paternally imprinted genes on chromosome 1 with a major effect on phenotype. UPD must be considered as a rare but possible cause of autosomal recessive disorders when conducting genetic testing.

Infant case with a malignant form of Brugada syndrome.

We report a 6-month-old Japanese infant with a malignant form of Brugada syndrome, who had frequent episodes of ventricular fibrillation (VF) and nonsustained polymorphic ventricular tachycardia (VT). To the best of our knowledge, this infant is the youngest patient reported to have Brugada syndrome. Continuous infusion of a beta-adrenergic agonist and intravenous injection of a parasympathetic antagonist suppressed the electrical storm of polymorphic VT and VF. Combined oral administration of a beta1-adrenergic agonist, a parasympathetic antagonist, and quinidine has successfully suppressed recurrences of VT or VF for 6 months, and the combination may have the potential to decrease the incidence of VT or VF as an adjunctive therapy with prophylactic placement of an implantable cardioverter defibrillator.

Reorganization of microtubules in the amitotically dividing macronucleus of tetrahymena.

We developed a modified immunofluorescence protocol that permitted visualization of microtubules inside the macronucleus of the ciliate Tetrahymena. Although the amitotically dividing macronucleus lacks a spindle, an elaborate system of microtubules is assembled inside the macronucleus and between the macronucleus and the cortex. Microtubules could not be detected inside the interphase macronuclei. The early stage of macronuclear division was associated with the assembly of short macronuclear microtubules that localized randomly. The intramacronuclear microtubules were subsequently organized in a radial manner. During elongation of the macronucleus, the distribution of macronuclear microtubules changed from radial to parallel. During constriction of the macronucleus, dense and tangled macronuclear microtubules were detected at the region of nuclear constriction. In the cytosol, microtubules were linking the macronucleus and cell cortex. During recovery after drug-induced depolymerization, microtubules reassembled at multiple foci inside the macronucleus in close proximity to the chromatin. We propose that these microtubules play roles in chromatin partitioning, macronuclear constriction, and positioning of the macronucleus in relation to the cell cortex.

Cytokinesis in Tetrahymena: determination of division plane and organization of contractile ring.

A protein, Tetrahymena p85, is localized to the presumptive division plane before the formation of the contractile ring. p85 directly interacts with Tetrahymena calmodulin (CaM) in a Ca(2+)-dependent manner, and p85 and CaM colocalize in the division furrow. A Ca(2+)/CaM inhibitor N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide HCl (W7) inhibits the direct interaction between p85 and Ca(2+)/CaM. W7 also inhibits the localization of p85 and CaM to the division plane, and the formation of the contractile ring and division furrow. Tetrahymena fimbrin and elongation factor-1a (EF-1alpha), which induce bundling of Tetrahymena F-actin, are also localized to the division furrow during cytokinesis. The Tetrahymena fimbrin has two actin-binding domains, but lacks the EF-hand Ca(2+)-binding motif, suggesting that Tetrahymena fimbrin probably cross-links actin filaments in a Ca(2+)- insensitive manner during cytokinesis. The evidence also indicates that Ca(2+)/CaM inhibits the F-actin-bundling activity of EF-1alpha; and EF-1alpha and CaM colocalize in the division furrow. In this review, we propose that the Ca(2+)/CaM signal and its target protein p85 cooperatively regulate the determination of the division plane, and that a Ca(2+)-insensitive actin-bundling protein, Tetrahymena fimbrin, and a Ca(2+)/CaM-sensitive actin-bundling protein, EF-1alpha, play pivotal roles in regulating the organization of the contractile ring microfilaments.

Influence of emission from rice straw burning on bronchial asthma in children.

BACKGROUND: Emission from rice straw burning (ERSB) is observed everywhere after harvest of rice in Niigata Prefecture every year. Pediatricians and many guardians in this district have had the impression that ERSB may induce asthma attack. Recent studies have suggested that particulate air pollution plays a role in the exacerbation of asthma. The authors investigated relationship of ERSB to asthma attack in children. METHODS: A questionnaire on rice straw burning (RSB) was circulated to guardians and pediatric institutions. Change in the monthly number of children with asthma attack (CAA) for 5 years from January 1994 to December 1998 was investigated. In addition, change in the number of CAA from the meteorologic conditions and RSB was investigated from the fourth week of August to the third week of September in 1996, 1997 and 1998. Challenge test exposure to ERSB was tried on a volunteer adult with chronic asthma. The situation of air pollution was examined by measuring suspended particulate matter (PM10). The relationship between PM10 and the number of CAA was studied. RESULTS: A majority of the guardians had the impression that ERSB induces asthma attack. Pediatricians replied similarly to the questionnaire. The number of CAA visiting our emergency room and admitted to our ward increased in the season of RSB. The PM10 had a significant correlation with the number of CAA. It was suggested that the increase in CAA may be not due to the meteorologic conditions, but to the influence of ERSB. CONCLUSION: The ERSB has made an issue of air pollution. Furthermore, the possibility that ERSB induces or exacerbates asthma attack has become clear in the present study. Therefore, it is recommended that RSB should be abolished for the health of inhabitants, especially children with asthma.

Tetrahymena elongation factor-1 alpha is localized with calmodulin in the division furrow.

Translation elongation factor 1 alpha (EF-1 alpha) catalyzes the GTP-dependent binding of amino-acyl-tRNA to ribosomes. We previously reported that Tetrahymena EF-1 alpha induced the formation of bundles of rabbit skeletal muscle filamentous actin (F-actin) as well as Tetrahymena F-actin [Kurasawa et al. (1996) Zool. Sci. (Tokyo) 13, 371-375], and that Ca(2+)/calmodulin (CaM) regulated the F-actin-bundling activity of EF-1 alpha [Kurasawa et al. (1996) J. Biochem. 119, 791-798]. In the present study, we investigated the binding between Tetrahymena EF-1 alpha and CaM using a Tetrahymena EF-1 alpha affinity column, and the localization of EF-1 alpha and CaM by indirect immunofluorescence. Only CaM in the Tetrahymena cell extract bound to Tetrahymena EF-1 alpha in a Ca(2+)-dependent manner. In interphase Tetrahymena cells, EF-1 alpha and CaM are colocalized in the crescent structure of the oral apparatus and the apical ring, while in dividing cells, they are colocalized in the division furrow. This is the first report describing the coexistence of EF-1 alpha and CaM in the division furrow, suggesting that EF-1 alpha and CaM are involved in the organization of contractile ring microfilaments during cytokinesis.

Cloning and sequencing of the gene for a Tetrahymena fimbrin-like protein.

Tetrahymena F-actin-binding protein, which induces bundling of Tetrahymena F-actin, was localized to a division furrow during cytokinesis. We report here the cloning and characterization of the gene and cDNA of a Tetrahymena F-actin-binding protein. The cDNA encodes a protein comprising 579 deduced amino acids with a calculated molecular mass of 65.9 kDa. The predicted amino acid sequence shares 37.7, 41.8, and 39% identity with the sequences of yeast fimbrin, Arabidopsis thaliana fimbrin, and Dictyostelium discoideum plastin, respectively. The Tetrahymena F-actin-binding protein also shares two actin-binding domains previously identified in the fimbrin/plastin family, but lacks the EF-hand Ca2+-binding motif, suggesting that this protein is a novel-fimbrin-like protein in Tetrahymena. Moreover, we cloned a genomic DNA encoding the Tetrahymena fimbrin-like protein and performed Southern and Northern hybridizations. The results indicate that the genomic DNA possesses 9 introns and that both the gene and transcript of Tetrahymena fimbrin-like protein are single. Thus, we suggest that Tetrahymena fimbrin-like protein localizes to the division furrow and probably cross-links actin filaments in a Ca(2+)-insensitive manner during cytokinesis.

Molecular cloning of the gene for p85 that regulates the initiation of cytokinesis in Tetrahymena.

Tetrahymena p85 is localized to the presumptive division plane before division furrow formation; its molecular weight in SDS-polyacrylamide gel electrophoresis differs in wild-type and temperature-sensitive cell-division-arrest mutant cdaA1 cells. At the restrictive temperature, p85 localization and division furrow formation are not observed in cdaA1 cells. In this study, we purified p85 and cloned a wild-type p85 cDNA. The deduced amino acid sequence of p85 was composed mainly of two kinds of repeat sequences. One of these contained regions homologous to a calmodulin-binding site and a part of actin, and the other contained a region homologous to a part of a cdc2 kinase homologue. Moreover, we cloned a cDNA encoding the cdaA1 p85. There was no difference in the predicted amino acid sequences of wild-type and cdaA1 p85, suggesting that the difference in molecular weight between p85 in wild-type and mutant cells is caused by a disorder of posttranslational-modification mechanisms of p85 in the cdaA1 cell.

Ca(2+)/calmodulin and p85 cooperatively regulate an initiation of cytokinesis in Tetrahymena.

Tetrahymena p85 differs in mobility in two-dimensional SDS-polyacrylamide gel electrophoresis between wild-type and temperature-sensitive cell-division-arrest mutant cdaA1 cell extracts, and is localized to the presumptive division plane before the formation of the division furrow. The p85 contained three identical sequences which show homology to the calmodulin binding site of Ca(2+)/calmodulin dependent protein kinase Type II in Saccharomyces cerevisiae. We found the p85 directly interacts with Tetrahymena calmodulin in a Ca(2+)-dependent manner, using a co-sedimentation assay. We next examined the localization of p85 and calmodulin during cytokinesis using indirect immunofluorescence. The results showed that both proteins colocalize in the division furrow. This is the first observation that calmodulin is localized in the division furrow. Moreover, the direct interaction between p85 and Ca(2+)/calmodulin was inhibited by Ca(2+)/calmodulin inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide HCl. When the cells were treated with the drug just before the beginning of cytokinesis, the drug also inhibited the localization of p85 and calmodulin to the division plane, and the formation of the contractile ring and division furrow. Therefore, we propose that the Ca(2+)/calmodulin signal and its target protein p85 cooperatively regulate an initiation of cytokinesis and may be also concerned with the progression of cytokinesis in Tetrahymena.

Molecular cloning and cell-cycle-dependent expression of the acetyl-CoA synthetase gene in Tetrahymena cells.

To identify transcriptionally regulated mediators associated with the cell cycle, we adopted the differential mRNA display technique for cell cultures of Tetrahymena pyriformis synchronized by cyclic heat treatment. One cDNA fragment that was expressed differently during synchronous cell division had a greatly decreased expression at 30 min after the end of heat treatment (EHT). Using this fragment as a probe, we isolated the full-length cDNA for T. pyriformis acetyl-CoA synthetase (TpAcs) which encodes a 651 amino acid polypeptide with a predicted molecular mass of 72.8 kDa. The deduced amino acid sequence of T. pyriformis ACS shows 42% sequence identity compared with that of Lysobacter sp. acetyl-CoA synthetase (ACS), an enzyme which catalyses the formation of acetyl-CoA from acetate via an acetyl-adenylate intermediate. The deduced sequence is also 41% and 40% identical compared with those of Pseudomonas putida and Coprinus cinereus ACS, respectively. The deduced sequence of T. pyriformis ACS also shares similar characteristics of the conserved motifs I and II in the ACS family. To further investigate the actions of the gene encoding this enzyme, mRNA expression was determined during the course of synchronized cell division in T. pyriformis. Northern blot results show that the mRNA level was dramatically decreased at 30 min after EHT prior to entering synchronous cell division (which occurs 75 min after EHT), suggesting that mRNA expression of the TpAcs was associated with the cell cycle and that the down-regulated expression of TpAcs at 30 min after EHT would be required for the initiation of the oncoming synchronous cell division in T. pyriformis.

Contingent negative variation in children with anorexia nervosa.

BACKGROUND: Central catecholamines, particularly dopaminergic and noradrenergic systems, have affected the appetitive behavior in patients with anorexia nervosa (AN). The purpose of this study is to distinguish the characteristics of contingent negative variation (CNV) and postimperative negative variation (PINV), which may reflect the level of catecholamine in children with AN. METHODS: Eight children with AN aged 10 to 15 years and 23 age-matched healthy children were recruited. Contingent negative variation was recorded from the frontal midline (Fz), central midline (Cz) and parietal midline (Pz) referenced to linked earlobes during 30 trials consisting of a warning stimulus and an imperative stimulus with an interstimulus interval of 2 s and an intertrial interval of 10 s. The imperative stimulus of each trial required a button press. RESULTS: Children with AN had a diminished amplitude of the CNV. They had a significantly more attenuated early CNV and late CNV amplitude at Cz than normal children. No significant differences were observed between AN children and normal children in the amplitude of PINV at all three electrode sites. No difference could be found between the two groups in the frequencies of normal and abnormal duration of PINV. CONCLUSION: These findings suggest that early CNV may be diminished by norepinephrine deficiency and late CNV may be attenuated by dopaminergic deficiency in children with AN. Reduced CNV may represent impaired cognitive processes which reflect impaired appetitive behavior in AN children.

Ratio of eosinophil cationic protein/eosinophil count as a new marker in children with acute asthma.

BACKGROUND: It is a matter of concern whether serum eosinophil cationic protein (ECP) can be considered as a disease marker in children with acute asthma being treated without corticosteroids. METHODS: Fourteen children (nine male, five female, aged 6-12 years) with acute asthmatic exacerbation, administered the appropriate drugs, with the exception of systemic or inhaled corticosteroids, were examined. They were all free from apparent asthmatic attacks during a follow-up period of 1 month. Serum ECP, eosinophil count and forced expiratory volume in 1 s (FEV1) were measured at referral, on the day of discharge, 1 week and 4 weeks after discharge, respectively. RESULTS: The ratio of ECP/eosinophil count (ECP:Eo ratio), expressed as micrograms of ECP (microgram/L)/the number of eosinophil (/microL) x 1000, was also evaluated as a marker of eosinophil activation. Compared with the value at referral, FEV1 (% predicted) significantly increased on the day of discharge (P < 0.05), 1 week after (P < 0.05) and 4 weeks after discharge (P < 0.05). However, serum ECP concentrations showed no significant changes during the follow-up period. Eosinophil count showed no significant changes on the day of discharge or 1 week after discharge, but significantly increased 4 weeks after discharge (P < 0.05). In contrast, the ECP:Eo ratio significantly decreased on the day of discharge (P < 0.05), 1 week after (P < 0.05) and 4 weeks after discharge (P < 0.05). CONCLUSION: These data suggest that serum ECP is a poor disease marker in asthmatic children with acute exacerbation who receive no corticosteroid therapy, probably due to marked changes in the eosinophil count. However, the ECP:Eo ratio might be a better marker than serum ECP in such patients.

Sympathetic skin response in diabetic children: do diabetic children have diabetic neuropathy?

BACKGROUND: Abnormal sympathetic skin response (SSR) has been reported in adult patients with diabetic neuropathy. In addition, other studies have revealed abnormal SSR in diabetic patients not having autonomic symptoms and autonomic dysfunctions. These findings have been only obtained from adult patients. There have been few reports on the autonomic functions in diabetic children. Accordingly, it is not clear whether the autonomic neuropathy occurs in diabetic children. The aim of the present study is to clear autonomic function in children with insulin-dependent diabetes mellitus by SSR. METHODS: The SSR was measured in 28 normal healthy children and in eight patients with IDDM not having symptoms of dysautonomia. The SSR was elicited using 10 stimuli on programmed Nihonkoden Neuropack Sigma model machine. Following a single electrical stimulation, four SSR were recorded in both the palms and the soles simultaneously. RESULTS: The SSR were simultaneously obtained in 100% of the two groups. The amplitudes in the palms and soles were not significantly different between the two groups. The mean and shortest latency in the soles were significantly longer in the IDDM group than in the control group (P < 0.01). None of the measurements of SSR revealed correlation with duration of diabetes and onset of illness. CONCLUSIONS: Diabetic neuropathy may not have occurred in young patients having shorter duration of illness. Conversely, assuming that prolonged latency is abnormal, it may even have occurred in them. Follow up on these patients with prolonged latencies would be required.