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The beta-globin gene cluster of Wistar rat was extensively cloned and the embryonic genes were mapped and sequenced. Four overlapping lambda Dash recombinant clones cover about 31 kb and contain four nonadult beta-globin genes, 5'-epsilon1-gamma1-gamma2-psigamma3-3'. The epsilon1 and gamma2 are active genes, since their protein products were detected in the fetal stage of the rat (Iwahara et al., J Biochem 119:360-366, 1996). The gamma1 locus might be a pseudogene, since the ATA box in the promoter region is mutated to GTA; however, no other defect is observed. The psigamma3 locus is a truncated pseudogene because a 19-base deletion, which causes a shift of the reading frame, is observed between the second nucleotide of the putative codon 68 and codon 76. A sequence comparison suggests that the psigamma3 might be produced by a gene conversion event of the proto-gamma-globin gene set. Possible histories of the evolution of rat nonadult beta-globin genes are discussed.

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In order to clarify the molecular basis of the heterogeneity of rat hemoglobins, two DNA clones containing the genes for adult type beta-globins were isolated from a rat genomic DNA library. The results obtained in the present experiments are summarized as follows. 1) Clone lambda Rg beta 59 contained the gene for an adult rat beta-major globin, II beta, while clone lambda Rg beta 45 contained the genes for two adult rat beta-minor globins, III beta, and O beta, respectively. 2) The entire nucleotide sequences of these genes were determined, indicating that the genes are all composed of 3 exons and 2 introns, and code for 146 amino acid residues. The genes exhibited structural features typical to known expressed beta-like globin genes, implying that they are all functional. 3) The predicted amino acid sequences completely agreed with the amino acid sequences of II beta, III beta and O beta globins, respectively, which we isolated in a separate experiment. 4) Sequence comparisons of three rat globin genes with one another and with the known mouse beta-major and beta-minor globin genes showed the occurrence of interesting homologies between two species from evolutional aspects. 5) Southern hybridization analysis of the genomic DNA implies that a number of beta-like globin genes other than the present ones exist in the rat genome.

SUMMARYThe purpose of the present study was to clarify the characteristics of myocardial ischemic attacks in patients with exertional angina (EA, 56 cases), exertional and rest angina (ERA, 28 cases), rest angina (RA, 4 cases), and variant angina (VA, 39 cases). The Holter electrocardiographic findings were compared among the four types of angina pectoris. The frequency of symptomatic ischemic attacks in descending order was 46.0% in EA, 29.0% in ERA, 28.1% in RA, and 21.6% in VA, while the frequency of asymptomatic ischemic attacks was in the reverse order. The maximal heart rates during symptomatic ischemic attacks were in descending order, EA, ERA, RA, and VA. The maximal heart rate during ischemic attacks was significantly lower in patients with spontaneous angina than in those with exercise-induced ischemia for all types of angina (p<0.05, respectively). Further, the difference in maximal heart rate during ischemic attacks between the ambulatory electrocardiogram and exercise test was greater in patients with RA and VA than in those with EA. Therefore, this suggests that increased coronary vascular tone is a cause of spontaneous ischemic attacks in each type of angina pectoris.