We have determined the DNA sequence of the long unique region (UL) in the genome of herpes simplex virus type 1 (HSV-1) strain 17. The UL sequence contained 107943 residues and had a base composition of 66-9~ G+C. Together with our previous work, this completes the sequence of HSV-1 DNA, giving a total genome length of 152260 residues of base composition 68.3~ G+C. Genes in the UL region were located by the use of published mapping analyses, transcript structures and sequence data, and by examination of DNA sequence characteristics. Fifty-six genes were identified, accounting for most of the sequence. Some 28 of these are at present of unknown function. The gene layout for UL was found to be very similar to that for the corresponding part of the genome of varicella-zoster virus, the only other completely sequenced alphaherpesvirus, and the amino acid sequences of equivalent proteins showed a range of similarities. In the whole genome of HSV-1 we now recognize 72 genes which encode 70 distinct proteins. INTRODUCTION In the last decade, the study of animal viruses has been revolutionized by the application of nucleic acid sequencing techniques to viral genomes. Many smaller virus genomes have been completely sequenced, and the sequences interpreted to give high resolution views of the genetic organization and the nature of the encoded proteins, while comparisons of sequences have enhanced our understanding of relationships between viruses. For larger virus genomes, total determination of nucleotide sequence remains a formidable undertaking, and only two complete sequences of virus genomes larger than 105 residues have been published. These are for the gammaherpesvirus Epstein-Barr virus (EBV) of 172282 residues (Baer et al., 1984) and the alphaherpesvirus varicella-zoster virus (VZV) of 124884 residues (Davison & Scott, 1986a). In this paper we report a third complete herpesvirus genome sequence, that of herpes simplex virus type 1 (HSV-1), which comprises 152260 residues. The molecular biology and genetics of HSV types 1 and 2 have been widely investigated such that overall they are the most extensively characterized of the family Herpesviridae. A decade ago, studies on the structure of HSV DNA showed it to be a linear molecule which could be viewed as consisting of two covalently linked segments, designated long (L) and short (S). Each segment contains a unique sequence flanked by a pair of inverted repeat sequences, as shown in Fig. 1. The long repeat (RL) and short repeat (Rs) sequences are distinct. The molecule also

SUMMARYThe entire DNA sequence of varicella-zoster virus (VZV) was determined using the M13-dideoxynucleotide technology. The genome is variable in size, but the sequence which was obtained comprises 124 884 bp. Analysis of the sequence indicated that the genome contains 70 genes distributed about equally between the two DNA strands. The genes are organized compactlyl but regions of overlap between protein-coding regions are not extensive. Many of the genes are arranged in T-coterminal families, and at least one is spliced. The discerned organization of VZV genes and that deduced for herpes simplex virus type 1 (HSV-I) from published transcript mapping data indicate that these two members of the Alphaherpesvirinae are very similar in gene layout. Comparisons of the predicted amino acid sequences of VZV proteins with those available for HSV-1 proteins generally suggest evolution from an ancestral genome, and allow the functions of several VZV genes to be deduced, although limited regions where the genomes differ in functional organization were also identified.

The Na+/Ca2+ exchanger plays a prominent role in regulating intracellular Ca2+ levels in cardiac myocytes and can serve as both a Ca2+ influx and efflux pathway. A novel inhibitor, KB-R7943, has been reported to selectively inhibit the reverse mode (i.e., Ca2+ entry) of Na+/Ca2+ exchange transport, although many aspects of its inhibitory properties remain controversial. We evaluated the inhibitory effects of KB-R7943 on Na+/Ca2+ exchange currents using the giant excised patch-clamp technique. Membrane patches were obtained from Xenopus laevis oocytes expressing the cloned cardiac Na+/Ca2+ exchanger NCX1.1, and outward, inward, and combined inward-outward currents were studied. KB-R7943 preferentially inhibited outward (i.e., reverse) Na+/Ca2+ exchange currents. The inhibitory mechanism consists of direct effects on the transport machinery of the exchanger, with additional influences on ionic regulatory properties. Competitive interactions between KB-R7943 and the transported ions were not observed. The antiarrhythmic effects of KB-R7943 were then evaluated in an ischemia-reperfusion model of cardiac injury in Langendorff-perfused whole rabbit hearts using electrocardiography and measurements of left ventricular pressure. When 3 microM KB-R7943 was applied for 10 min before a 30-min global ischemic period, ventricular arrhythmias (tachycardia and fibrillation) associated with both ischemia and reperfusion were almost completely suppressed. The observed electrophysiological profile of KB-R7943 and its protective effects on ischemia-reperfusion-induced ventricular arrhythmias support the notion of a prominent role of Ca2+ entry via reverse Na+/Ca2+ exchange in this process.

Pancreozymin in man as in animals appears to act as a specific enzyme stimulant. The preparations of pancreozymin used in these experiments also contain cholecystokinin, which causes the gall bladder to contract, and a smooth muscle stimulant, possibly substance P.The (Lagerlof, 1939(Lagerlof, , 1942 Diamond, Siegel, Gall, and Karlen, 1939;Diamond andSiegel, 1940, 1941;Comfort and Osterberg, 1940;Pratt, Brugsch, and Rostler, 1940;Pollard, Miller, and Brewer, 1942;Lake, 1947;Dornberger, Comfort, Wollaeger, and Power, 1948;Dreiling and Hollander, 1948, 1950;Friedman and Snape, 1950;Dreiling, 1950Dreiling, , 1951Dreiling, , 1953Dreiling, , 1955 Dreiling and Janowitz, 1957;Wenger and Raskin, 1958).In anaesthetized animals secretin produced a large volume of pancreatic juice of constant alkalinity and low enzyme content. Harper and Raper (1943) isolated from the small intestine a second material, other than secretin, which increased the enzyme output by the pancreas without affecting the volume of juice. This material they named pancreozymin. Crick, Harper, and Raper (1949) later published a revised method of preparing secretin and pancreozymin and preliminary experiments showed that pancreozymin had the same effect on man as in animals