Solution structure of the cytoplasmic domain of the human immunodeficiency virus type 1 encoded virus protein U (Vpu)

The HIV-1-specific Vpu protein is an 81 amino acid class I integral membrane phosphoprotein that induces degradation of the virus receptor CD4 in the endoplasmic reticulum and enhances the release of virus particles from infected cells. Vpu is of amphipathic nature and consists of a hydrophobic N-terminal membrane anchor proximal to a polar C-terminal cytoplasmic domain. In our recent work, focussed on the structural analysis of the cytoplasmic tail, we established an α-helix-flexible-α-helix-turn model. Now we present the experimental solution structure of the Vpu cytoplasmic domain which has been elucidated in aqueous 50% trifluoroethanol solution by 2D ¹H NMR spectroscopy, and restrained molecular dynamics and energy minimization calculations. Under these conditions the peptide, Vpu^32-81, is predominantly monomeric and adopts a well defined helix-interconnection-helix-turn conformation, in which the four regions are bounded by residues 37-51, 52-56, 57-72 and 73-78. The presence of the cis isomer of Pro-75 manifests itself as a doubling of cross peaks of neighbouring residues in the 2D spectra. A related variant peptide, Vpum^32-81, in which the Vpu-phosphoacceptor sites Ser⁵² and Ser⁵⁶ were exchanged for Asn, adopts a very similar structure and, taken together, provides evidence that the second helix and the turn form a comparatively rigid region. Both helices are amphipathic in character, but show different charge distributions. In general the cytoplasmic region is N-terminally positively charged, passes through a region of alternating charges in helix 1 and then becomes negatively charged. The flexibility of the interconnection permits orientational freedom of the two helices. The motif found here is the first experimentally refined solution structure of the cytoplasmic domain of Vpu, and it is conceivable that these α-helices are important for a previously defined physical interaction with an α-helical Vpu-responsive element located within the cytoplasmic tail of CD4. © Munksgaard 1996.     

Long-term Outcomes of Drinking: a 20-year longitudinal study of men

This paper examines long-term changes in drinking, with regard to: (a) the degree to which overall patterns of drinking have shifted or remained across a 20-year period; (b) whether these patterns vary on the basis of age; and (c) the degree to which distinct patterns of drinking may be differentially subject to mortality and/or nonresponse. Data for this investigation are from a 20-year prospective follow-up study of two general population surveys. The first of these was originally interviewed in 1964 and consists of interviews with 405 males aged 23 and older; the second, originally interviewed in 1967, consists of interviews with 786 males aged 21–59. The results indicate that while consumption was modestly associated with mortality from all causes, no significant relationship was observed between consumption and non-response. The results also indicate that as respondents aged 20 years, mean levels of alcohol consumption remained stable. This was true despite the fact that when individual respondents did change their drinking, they were more likely to decrease their consumption than increase it. These results do not support conclusion drawn from cross-sectional studies that aging modifies consumption patterns.     

Effects of methotrexate in vitro on epidermal cell proliferation

Epidermal cell migratory activity and epidermal cell proliferation are clearly dissociable in explant culture. Epidermal cell migration requires a non-dialysable, 65,000 mol.wt factor which is destroyed at 100 C but is stable at 80 C for at least 30 min. In the presence of dialysed serum or heated serum (80° C for 30 min) or DNA synthesis inhibitors (methotrexate or hydroxyurea), cells will migrate from the explant but will not proliferate. At least two factors are required for normal proliferation under these restricted conditions—an adequate supply of DNA precursers, i.e. nucleosides, and a heat labile (80° C) non-dialysable serum component. Methotrexate in concentrations of 1.0 μg/ml or greater added to cultures in normal fetal calf serum significantly inhibited mitoses; however, when added to serum dialysed to remove thymidine, mitotic inhibition occurred at a concentration of 0.1 μg/ml of methotrexate and when added to dialysed serum and kept in dialysed serum, inhibition occurred with 0.01 μg/ml of methotrexate. Methotrexate did not inhibit outgrowth. Hydroxyurea also inhibited mitoses but did not effect outgrowth.     

Notation System and Overlay Diagrams for the Analysis of Paced Electrocardiograms

With the advent of adaptive dual-chamber pacing, the interaction between the pacemaker and the heart is becoming increasingly complex and the interpretation of paced electrocardiograms more difficult. We have developed a set of notation conventions for use in teaching and rhythm-atrip analysis. Easily-drawn symbols delineate successful, unsuccessful, and inhibited pacing and sensing events as well as refractory and blanking periods. Another application is to generate movable transparent overlays after programming a pacemaker, to be used in interpreting subsequent rhythm strips.     

PLASMA ANDROGENIC ACTIVITY IN WOMEN WITH ACNE VULGARIS AND IN HEALTHY GIRLS BEFORE, DURING AND AFTER PUBERTY

The possible relationship between plasma androgenic activity and acne vulgaris was investigated. Plasma testosterone and sex hormone binding globulin (SHBG) levels were determined in healthy girls during different stages of puberty, in healthy adult women and in women with acne vulgaris. Testosterone increase during puberty, whereas SHBG decreased during the early stages before it increased and stabilized plasma concentrations of testosterone and SHBG. Women with severe acne vulgaris had testosterone levels in the same range but the SHBG levels were significantly lower than those of healthy women and women with mild acne. These results show a high androgenic activity in the intermediate stages of puberty, when acne vulgaris is a common complaint and an increased androgenic activity in adult women with severe acne vulgaris.     

Pseudomalfunctions of Dual-Chamber Pacemakers

La prolifération de la stimulation auriculoventriculaire a crée de nombreux cas de "pseudo-dysfonctionnemenl" du stimulateur. En ce qui concerne ľinterpretation electrocardiographique, il est devenu parfois impossible de faire la distinction entre normal et anormal. La classification et les critères de ces phénomenes sont décrits. Il semble que seule la connaissance parfaite du fonctionnement de cheque stimulateur préviendra la fausse interprétation des tracés éléctrocardiographiques.
The proliferation of dual-chamber pacemakers has created a host of electrocardiography problems relating to interpretation. The term "pseudomalfunction" identifies an electrocardiographic finding that looks like pacemaker malfunction but is not. Several different models of dual-chamber pacemakers, which are either presently available or in clinical evaluation, produce different types of pseudomalfunc-tions. These are classified and described. Intimate knowledge of individual pacemaker characteristics is required for proper evaluation of these units.     

Is the Automatic Atrial Defibrillator a Promising Approach?

Automatic Atrial Defibrillator. Atrial fibrillation is a common arrhythmia, accounting for more consumption of medical resources than any other arrhythmia. The impact of the disease results from the combination of a loss of atrial contraction, and atrial control over cardiac rate. Studies in animals demonstrated the basic feasibility of atrial defibrillation using electrodes passed intravenously. Subsequent studies in patients confirmed that low-energy shocks were effective in converting atrial fibrillation and were safe if delivered synchronous to the R wave in the absence of a short preceding RR interval. Preliminary experience suggests that a small implanted device might provide beneficial therapy for patients with recurring episodes of persistent, drug-refractory, atrial fibrillation.