Quality of life before and during antihypertensive treatment: a comparative study of celiprolol and atenolol

BACKGROUND: The well-being of hypertensive patients may be adversely affected by the disease itself, its complications, and other concomitant processes such as anxiety, sedation, and side effects of the prescribed drugs. Some recently developed antihypertensive agents have been suggested to be devoid of these deleterious effects on well-being expressed as quality of life. OBJECT: We compared the effect on quality of life of a standard cardioselective beta-blocker atenolol to the effect of celiprolol as a representative of a new class of selective beta-blockers with vasodilatory properties. One-hundred-thirty-two patients with mild to moderate hypertension were eligible to enter a 28-week double-blind parallel-group study, consisting of a 4-week run-in period on placebo and a 24-week period on dosage-adjusted treatment with either atenolol or celiprolol. RESULTS: Both systolic and diastolic blood pressure were assessed, as was quality of life perception by a selected test battery including the Quality of Life Questionnaire of Bulpitt and Fletcher [1990]. During celiprolol treatment, supine blood pressure fell from 167/101 (range 120-200/95-116) to 150/92 mm Hg (p < 0.0001). This antihypertensive effect was at least as good with celiprolol as with atenolol. Quality of life perception was comparable for the 2 drugs, although some adverse effects were more frequent during atenolol than during celiprolol, particularly after prolonged treatment. Also patient compliance was better for celiprolol than for atenolol. CONCLUSIONS: Our results show that the selective beta-blocker with vasodilatory property celiprolol is at least as effective as atenolol and that it has additional advantage in terms of enhancement of some quality of life variables.     

Kv8.1, a new neuronal potassium channel subunit with specific inhibitory properties towards Shab and Shaw channels

Outward rectifier K+ channels have a characteristic structure with six transmembrane segments and one pore region. A new member of this family of transmembrane proteins has been cloned and called Kv8.1. Kv8.1 is essentially present in the brain where it is located mainly in layers II, IV and VI of the cerebral cortex, in hippocampus, in CA1-CA4 pyramidal cell layer as well in granule cells of the dentate gyrus, in the granule cell layer and in the Purkinje cell layer of the cerebellum. The Kv8.1 gene is in the 8q22.3-8q24.1 region of the human genome. Although Kv8.1 has the hallmarks of functional subunits of outward rectifier K+ channels, injection of its cRNA in Xenopus oocytes does not produce K+ currents. However Kv8.1 abolishes the functional expression of members of the Kv2 and Kv3 subfamilies, suggesting that the functional role of Kv8.1 might be to inhibit the function of a particular class of outward rectifier K+ channel types. Immunoprecipitation studies have demonstrated that inhibition occurs by formation of heteropolymeric channels, and results obtained with Kv8.1 chimeras have indicated that association of Kv8.1 with other types of subunits is via its N-terminal domain.     

The PROP1 2-base pair deletion is a common cause of combined pituitary hormone deficiency

Combined pituitary hormone deficiency (CPHD) has an incidence of approximately 1 in 8000 births. Although the proportion of familial CPHD cases is unknown, about 10% have an affected first degree relative. We have recently reported three mutations in the PROP1 gene that cause CPHD in human subjects. We report here the frequency of one of these mutations, a 301-302delAG deletion in exon 2 of PROP1, in 10 independently ascertained CPHD kindreds and 21 sporadic cases of CPHD from 8 different countries. Our results show that 55% (11 of 20) of PROP1 alleles have the 301-302delAG deletion in familial CPHD cases. Interestingly, although only 12% (5 of 42) of the PROP1 alleles of our 21 sporadic cases were 301-302delAG, the frequency of this allele (in 20 of 21 of the sporadic subjects given TRH stimulation tests) was 50% (3 of 6) and 0% (0 of 34) in the CPHD cases with pituitary and hypothalamic defects, respectively. Using whole genome radiation hybrid analysis, we localized the PROP1 gene to the distal end of chromosome 5q and identified a tightly linked polymorphic marker, D5S408, which can be used in segregation studies. Analysis of this marker in affected subjects with the 301-302delAG deletion suggests that rather than being inherited from a common founder, the 301-302delAG may be a recurring mutation.     

Characterization of genes encoding translation initiation factor eIF-2gamma in mouse and human: sex chromosome localization, escape from X-inactivation and evolution

The Delta Sxrb interval of the mouse Y chromosome is critical for spermatogenesis and expression of the male-specific minor transplantation antigen H-Y. Several genes have been mapped to this interval and each has a homologue on the X chromosome. Four, Zfy1 , Zfy2 , Ube1y and Dffry , are expressed specifically in the testis and their X homologues are not transcribed from the inactive X chromosome. A further two, Smcy and Uty , are ubiquitously expressed and their X homologues escape X-inactivation. Here we report the identification of another gene from this region of the mouse Y chromosome. It encodes the highly conserved eukaryotic translation initiation factor eIF-2gamma. In the mouse this gene is ubiquitously expressed, has an X chromosome homologue which maps close to Dmd and escapes X-inactivation. The coding regions of the X and Y genes show 86% nucleotide identity and encode putative products with 98% amino acid identity. In humans, the eIF-2gamma structural gene is located on the X chromosome at Xp21 and this also escapes X-inactivation. However, there is no evidence of a Y copy of this gene in humans. We have identified autosomal retroposons of eIF-2gamma in both humans and mice and an additional retroposon on the X chromosome in some mouse strains. Ark blot analysis of eutherian and metatherian genomic DNA indicates that X-Y homologues are present in all species tested except simian primates and kangaroo and that retroposons are common to a wide range of mammals. These results shed light on the evolution of X-Y homologous genes.     

The effects of anxiety on response times to disease detection and health promotion behaviors

It was hypothesized that increasing levels of anxiety about health issues would make response times to disease detections longer than response times to health promotion behaviors and that this effect would reverse when anxiety about health issues was decreased. In a laboratory study 82 participants recruited from undergraduates and the general community were randomly assigned to read information designed either to increase or to decrease anxiety about health. Following the anxiety manipulation participants were required to indicate their attitude about both disease detection and health promotion behaviors and response times to both types of behavior were recorded. Finally, the participants' attitudes toward all the health behaviors were measured using 9-point scales. The results supported the hypothesis.     

Job control, personal characteristics, and heart disease

A new anthropometric landmark of the face, called the maxillozygion (mz; right, left) is presented. The bilateral landmark is the most prominent point of the maxillozygomatic suture line, identified by palpation of the most anterior protruding contours on the frontal aspect of the face, located below the lateral third of the right and left bony orbits. The reliability of locating the landmark on both sides of the face by palpation is discussed. Preliminary data determining the position of the maxillozygion in the vertical, sagittal, and horizontal planes in white and Asian sample populations is presented. In general, the Asian face tends to be the same width (zygion [zy]-zy) as the white face; however, the maxillozygion is located more laterally on the Asian face compared with the white face.     

A genomic region of lactococcal temperate bacteriophage TP901-1 encoding major virion proteins

Two major structural proteins, MHP (major head protein) and MTP (major tail protein), from the lactococcal temperate phage TP901-1 were sequenced at their amino acid termini, and derived degenerate oligonucleotides were used to locate the corresponding genes in the phage genome. This genomic region was sequenced. The sequence characterized includes a total of 11 open reading frames (ORFs) showing an operon structure. Upstream of each ORF, except ORF b2 and ORF x, potential ribosome-binding sites were found, suggesting independent translation. However, coupled translation is suggested for ORF x and as a possibility for ORF b3 and ORF c2, which have ribosome-binding sites located more distant from their start codons. ORF b2 may be translationally fused with mhp at a low frequency. The mhp and mtp genes are transcribed as a 3.7-kb mRNA with at least six additional ORFs. The organization of the genomic region analyzed resembles that of other distantly related phages, providing possible roles for the uncharacterized ORFs.