Summary. The localization of chromosome 18 in human interphase nuclei is demonstrated by use of radioactive and nonradioactive in situ hybridization techniques with a DNA clone designated L1.84. This clone represents a distinct subpopulation of the repetitive human alphoid DNA family, located in the centric region of chromosome 18. Under stringent hybridization conditions hybridization of L1.84 is restricted to chromosome 18 and reflects the number of these chromosomes present in the nuclei, namely, two in normal diploid human cells and three in nuclei from cells with trisomy 18. Under conditions of low stringency, cross-hybridization with other subpopulations of the alphoid DNA family occurs in the centromeric regions of the whole chromosome complement, and numerous hybridization sites are detected over interphase nuclei. Detection of chromosome-specific target DNAs by non-radioactive in situ hybridization with appropriate DNA probes cloned from individual chromosomal subregions presents a rapid means of identifying directly numerical or even structural chromosome aberrations in the interphase nucleus. Present limitations and future applications of interphase cytogenetics are discussed.

We have isolated and characterized two human middle repetitive alphoid DNA fragments, L1.26 and L1.84, which localize to two different sets of chromosomes. In situ hybridization revealed both repeats to have major and minor binding sites on the pericentric regions of several chromosomes. Probe L1.26 maps predominantly to chromosomes 13 and 21. Probe L1.84 locates to chromosome 18. Minor hybridization sites for both probes include chromosomes 2, 8, 9, and 20; in addition, L1.26 revealed minor sites on chromosomes 18 and 22. The binding to these sites strongly depends on hybridization conditions. In Southern blot hybridizations to total human DNA, both L1.26 and L1.84 give the same ladder pattern, with a step size of 170 bp, indicating their presence as tandem repeats, but with different band intensities for each probe. The chromosome-specific nature of particular multimers was confirmed by Southern blot analyses of a human-rodent hybrid cell panel. We conclude that L1.26 and L1.84, with their related sequences, constitute subfamilies of alphoid DNA that are specific for subsets of chromosomes and, in some cases, possibly even for single chromosomes.

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Summary:Since 1963 the signal averaging technique has been applied to improve the signal to noise ratio in highly amplified EKG registrations. Based on the experiences from the literature and the authors own laboratory, the applications of the signal averaging technique in clinical cardiology are reviewed: extraction and analysis of the fetal EKG and P-wave variations, His bundle electrograms from the body surface (recovery rate 33-100% of cases), ventricular delayed depolarizations within the ST segment of the surface EKG (recovery rate, 40-90% of cases, depending on patient groups investigated), preatrial activity (sinus nodal potentials) from intracardiac (recovery rate, 80-90% of individuals), or surface EKGs (recovery rate, 60% of patients), analysis of frequency components of surface EKG-QRS complexes in patients with previous myocardial infarctions, and detection of low amplitude diastolic signals from surface phonocardiogram (recovery rate, 80% of cases). At present, advantages and limitations of the signal averaging technique may be appraised as follows: ( 1 ) sinus nodal potentials: S-A conduction times may be more reliable than those obtained by the extra-stimulus technique, since with averaging they are recorded during undisturbed sinus rhythm; direct recordings of changing S-A blocks may be impossible due to the summation process; validation of sinus nodal potentials in man necessary, (2) A-V nodal potentials: demonstration of true A-V nodal rhythm rather than His bundle rhythm; possibly direct identification of abnormal pathways in A-V nodal tachycardias; direct recordings of single A-V nodal blocks impossible due to summation process; (3) surface His bundle potentials: follow-up or screening of patients with A-V nodal and particularly His-Purkinje-system blocks; monitoring of antiarrhythmic drug therapy; atrial overlap in one-third of cases; direct identification of higher degree A-V nodal blocks impossible due to summation process (future developments may overcome this problem); (4) ventricular delayed depolarizations: possible identification of patients at high risk of sudden cardiac death; follow-up of therapeutic measures like antiarrhythmic drug therapy or cardiac surgery (bypass grafting, aneurysmectomy); validation of delayed depolarizations from body surface by direct intracardiac and/or epicardial mapping necessary.

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