Molecular cloning and nucleotide sequence of rat brain argininosuccinate lyase cDNA with an extremely long 5'-untranslated sequence: evidence for the identity of the brain and liver enzymes.

Argininosuccinate lyase (EC 4.3.2.1) is an enzyme present in the brain of ureotelic animals. Using as a probe rat liver argininosuccinate lyase cDNA, already isolated and sequenced (Amaya, Y., Matsubasa, T., Takiguchi, M., Kobayashi, K., Saheki, T., Kawamoto, S. and Mori, M., J. Biochem., 103 (1988) 177-181), we screened a rat brain cDNA library constructed in the lambda gt11 expression vector and obtained a single cDNA clone. This cDNA clone contained an open reading frame encoding a polypeptide of 461 amino acid residues (predicted Mr = 51,390), a 5'-untranslated sequence of 967 bp and a 3'-untranslated sequence of 74 bp. The length of the 5'-non-coding region of the cDNA seems to be one of the longest among the cDNAs heretofore isolated. A comparison of the brain cDNA sequence (2424 bp) with the corresponding region of the liver cDNA (1574 bp) revealed differences in 5 nucleotides. The brain clone contained A----G and C----G base differences from the hepatic sequence, resulting in amino acid changes from Tyr and Arg in the liver clone, to Cys and Gly in the brain clone, respectively. The other 3 nucleotide differences are silent with respect to the amino acid sequence of the protein. Therefore, the amino acid sequence of the brain argininosuccinate lyase, as deduced from the nucleotide sequence of its cDNA clone, was identical with that of the liver protein, except for two amino acid residues. These minor changes may reflect a microheterogeneity of the argininosuccinate lyase gene. The brain and liver enzymes seem to be encoded by the same structural gene.

Study on congenital complete heart block in children by 24-hour ambulatory electrocardiographic monitoring.

Ambulatory electrocardiographic monitoring was performed in 18 children with a congenital complete heart block (CCHB). They had no cardiac structural anomalies. These patients could be divided into 3 groups according to the pattern of fluctuations in beat-to-beat ventricular rates. Type 1 patients showed rapid and transient fluctuations and demonstrated a high correlation between atrial and ventricular rates. Type 3 patients showed a constant ventricular rate and little variation through the 24 hour period and there was no appreciable correlation between atrial and ventricular rates. Twelve of 18 patients had additional arrhythmias. A few sporadic ventricular premature contractions (VPCs) were found in 9 patients, and bigeminy of VPCs or ventricular tachycardias were seen in 2 patients during exercise. Frequent and sudden prolongation of RR intervals was found during sleep in 3 patients. The longest intervals of ventricular asystoles were 7.2, 3.2 and 3.2 sec, respectively. The mechanism of this phenomenon appeared to be not only an exit block, but also arrest or a lack of automaticity of a subsidiary pacemaker. One of these patients developed frequent Stokes-Adams attacks. Type 3 patients with sudden prolongation of RR intervals and/or frequent ventricular arrhythmias should be under careful observation. Ambulatory electrocardiographic monitoring is recommended for children with CCHB for evaluation of potential risk factors for Stokes-Adams attacks.

Cardiac arrhythmias in healthy children revealed by 24-hour ambulatory ECG monitoring.

Ambulatory electrocardiographic monitoring was performed on 360 healthy children, from newborn infants to junior high school students. They were divided into five groups by age: group A, 63 newborn infants on the first day of life; group B, 50 infants aged 1-11 months; group C, 53 kindergarten pupils aged 4-6 years; group D, 97 primary school pupils aged 9-12 years; and group E, 97 junior high school students aged 13-15 years. The maximal and minimal heart rates were significantly greater in infants than in older children. Sinus arrhythmia was recorded in every child. One boy in group E had an episode of sinus arrest for three seconds without any symptoms. First-degree and Wenckebach type second-degree atrioventricular blocks were not detected in group A and group B, but were most frequent in group E, especially during sleep. Supraventricular premature contractions (SVPCs) were the most common type of arrhythmia detected in this study. More than half of the children had at least one SVPC per 24-h monitoring period, and there were many children with frequent SVPCs in group E. The incidence of ventricular premature contractions (VPCs) in children of groups A and E was rather higher than in the other groups. Ventricular tachycardia was not recorded in any child except one newborn infant who had a couplet of VPCs without symptoms. Each group had different types and incidences of arrhythmias. There was a rising incidence of arrhythmias with advancing age, except in the neonatal period.