Walter H. Johnson

Clinical, Genetic, and Biophysical Characterization of a Homozygous HERG Mutation Causing Severe Neonatal Long QT Syndrome

Previous studies have identified mutations in five ion channel genes as a cause of long QT syndrome, a heterogeneous disorder characterized by prolongation of the QT interval, multiform ventricular tachycardia (torsades de pointes), seizures, syncope, and sudden death. However, in these studies, the average age of initial symptoms is in the third decade of life or later, and few reports have described the genetic causes of long QT syndrome presenting in the prenatal or neonatal period. We used a candidate gene approach to identify the genetic cause of long QT syndrome in an infant whose initial manifestations were detected in utero. Direct bidirectional sequencing of long QT syndrome genes identified a previously unreported HERG missense mutation (R752Q). Three asymptomatic family members were heterozygous for R752Q, and the proband, who manifested ventricular tachycardia in utero, was homozygous. R752Q was not found in 100 normal unrelated chromosomes. Paternal DNA was unavailable for testing. Transient transfection of HERG generated robust IKr, but no current was observed for the mutant HERG. The HERG mutant, R752Q, is associated with a mild phenotype, inasmuch as family members with a heterozygous mutation appear unaffected. The homozygous mutation results in absence of functional IKr, causing a profound loss of HERG channel function, creating the equivalent of a “HERG knockout” and leading to a severe phenotype.

Association of atrial flutter with orthodromic reciprocating fetal tachycardia.

Abstract Mechanisms of fetal tachycardia may be difficult to determine in utero. Selection of optimal antiarrhythmic therapy may also be difficult. We report a case of fetal tachycardia with varying heart rate, which converted in utero to a gestational-age appropriate heart rate after maternal administration of quinidine sulfate.

Recent Minnesota Mass Results

I wish to report on several features of the work of the Mass Measuring group at the University of Minnesota that have occurred since the 1967 Winnipeg conference. The main efforts recently have been in three areas; (a) the measurements of U235 U238, and Th232 (b) a study of the feasibility of mass measurements of short half-life radioactive isotopes, and (c) development of a new technique for peak matching which may be used with only partially resolved doublets.

Recent Mass Doublet Results from the University of Minnesota

This paper will describe some of the recent mass doublet measurements made at the University of Minnesota during the period since AMCO 5. I will discuss two Ph.D. thesis experiments. The first, submitted by Dr. Justin Halverson in June 1977 involves doublet measurements of some isotopes of erbium, hafnium and osmium and also a remeasurement of the 13C – 12C mass difference. The second thesis, by Ronald Smith, was submitted in December 1977 and involved our first attempt at doublet measurements of short half-life unstable isotopes with conventional doublet techniques.

Mass spectrometric calibration of the /sup 1/3C single neutron separation energy

A 41 cm double focusing mass spectrometer has been used to measure three closely spaced doublets /sup 1/2C/sub 6/ /sup 2/H/sub 6/- /sup 1/3C/sub 6/ /sup 1/H/sub 6/, /sup 1/2C/sub 6/ /sup 1/H/sub 1/2-/sup 1/2C/sub 6/ /sup 2/H/sub 6/, and /sup 1/2C/sub 6/ /sup 1/H/sub 1/2-/sup 1/3C/sub 6/ /sup 1/H/sub 6/ in order to determine precisely the mass and the neutron separation energy of /sup 1/3C. The redetermination of the deuterium mass is included to allow a comparison with earlier work in this laboratory. The neutron separation energy for /sup 1/3C is then employed to calculate the ground-state ..gamma..-ray energy for the reaction /sup 1/2C(n,..gamma..)/sup 1/3C.

Recent Doublet Results and Measurement Technique Development at the University of Minnesota

This paper will describe some recent doublet results and describe further peak matching technique development which has occurred as part of the continuing program of atomic mass measurements at the University of Minnesota. At AMCO 4, David Kayser presented a brief review of a technique we have named generalized peak matching (1). This technique is particularly useful in circumstances in which the two members of the doublet to be measured are not completely resolved. Dr. Kayser has developed the general theory of this process which deals with the determination of the mass differences for a multi-component spectrum. In order to be brief in this part of the presentation, the technique will be illustrated only with a mass doublet. Suppose that we assume a two component spectrum with individual peak shapes f(t). The two component spectrum may be written g(t) = f(t) + A f(t−b) in which b is the spacing and A is the amplitude ratio between the peaks. We may use Laplace transform theory to transform this equation to g(s) =(1+Ae-bs)f(s). This process isolates the quantities A and b from the function f(s).

Some Atomic Masses in the Region from Gallium Through Molybdenum

In 1961, operational difficulties in the 16-inch double focusing mass spectrometer at the University of Minnesota became progressively more apparent, especially in measurements of heavier isotopes where maximum resolution is required. These difficulties necessitated the movement and reconstruction of the instrument. Some of the modifications made at that time will be discussed in this report. This improved spectrometer was then employed to measure a number of mass doublets in the region from gallium through xenon. Some of the atomic masses of the stable isotopes between A = 69 and A = 100 will be reported in this paper, while some masses between A = 100 and A = 130 will be reported in the following paper. These mass results are compared with other mass spectroscopic results and with nuclear reaction results wherever possible, and in addition, a partial mass table of radioactive atoms has also been calculated for this region by combining the stable mass results with available disintegration energies. Finally, one can then use these mass values to study the nuclear binding energy systematics in the region around the neutron shell closure at N = 50, as well as the proposed sub-shell at N = 40 and Z = 40.