Immunogenicity of synthetic HIV-1 gp120 V3-loop peptide-conjugate immunogens.

A successful prophylactic human immunodeficiency virus type 1 (HIV-1) vaccine must elicit an immune response that will prevent establishment of the persistent viral infection. The only response shown to be effective in this regard is virus-neutralizing antibody directed against the viral gp120 hypervariable V3-loop region. Conjugate immunogens, containing cyclic peptides representing the V3 determinant covalently bound to a carrier protein, were capable of eliciting virus-neutralizing antibodies. The consistency of the response was related to peptide size. The smaller cyclic peptides, expressing relatively conserved sequences from the V3-loop apex, were poor inducers of neutralizing activity. In contrast, the largest cyclic peptides mediated neutralizing responses that were similar to those observed and previously reported for intact gp120 immunogens. A cyclic synthetic peptide expressing most of the prototypic HIV-1 MN variant V3 determinant warrants further study as a potentially effective vaccine immunogen.

Cardiovascular responses to an active coping challenge as predictors of blood pressure patterns 10 to 15 years later.

To assess the long-term predictive importance of high cardiovascular reactivity in relation to subsequent blood pressure, 51 men from a pool of 204 men originally tested at age 18 to 22 years were recruited for blood pressure assessment 10 to 15 years later. Initial testing uniformly involved monitoring of systolic pressure, diastolic pressure, and heart rate during a reaction time task involving threat of shock. In 30 of the 51 men who participated at follow-up, initial testing had also included separate visits to obtain relaxation-only baseline levels of the cardiovascular indices. At follow-up, in addition to clinic-type stethoscopic determinations, blood pressure and heart rate were assessed during work and social and leisure activities via ambulatory monitoring. Men with higher levels of systolic pressure during the task showed higher stethoscopic and ambulatory systolic pressure at follow-up. Likewise, men with higher levels of diastolic pressure during the task showed higher diastolic levels at follow-up. In the 30 men with both good task and baseline data from initial testing, those with high heart rate reactivity (task minus baseline) showed higher systolic, diastolic, and heart rate levels at follow-up than low heart rate reactors, even though their baseline blood pressures had not differed at initial testing. Similarly, men with high systolic reactivity showed higher diastolic pressure at follow-up than low systolic reactors. Multiple regression analyses also demonstrated that systolic, diastolic, and heart rate reactivity improve prediction of follow-up blood pressure when added to models incorporating the standard risk factors, baseline blood pressure, and parental history of hypertension.

Purification and characterization by fast-atom-bombardment mass spectrometry of the polymorphonuclear-leucocyte-elastase-generated A alpha (1-21) fragment of fibrinogen from human blood after incubation with calcium ionophore A23187.

The stimulation of human blood with a Ca2+ ionophore, A23187, leads to activation of polymorphonuclear leucocytes (PMN) with release of small amounts of catalyticaly active elastase, as demonstrated by the formation of a characteristic product, the N-terminal A alpha (1-21) peptide of the Aa subunit of fibrinogen. The identity of the peptide was initially established by radioimmunoassay (r.i.a.) with an antibody raised to A alpha (1-21). We now provide independent confirmation of the formation of A alpha (1-21) by fast-atom-bombardment-m.s. analysis of the fractions separated chromatographically after spiking of plasma samples with peptide labelled with [2H8]Phe at position 8. Identity of the peptides was established on the basis of their chromatographic retention time and by the distinct peaks in the mass spectra of these fractions. The relative intensities of the molecular ions of natural and labelled peptides were measured. On the basis of a comparison of the peaks of similar intensities, the concentration of the natural peptide at the time of spiking was close (79%) to the amount obtained by r.i.a. An additional peptide, des-alanyl-A alpha (2-21), was also seen. The total amount of material measured by r.i.a. could be accounted for by the sum of these two provides. The addition of label and assay by m.s. has provided an independent physical-chemical method for identifying A alpha (1-21) as a characteristic product of PMN elastase release in whole blood, but which is absent in freshly drawn blood.

Cognitive coping strategies and blood pressure responses to real-life stress in healthy young men.

Coping style is an important feature in the understanding of the relation between real-life stress and associated blood pressure (BP) responses. In this study, 10 high- and 10 low-"self-focused-coping" (SFC) male college students were tested with ambulatory BP monitoring on two typical schooldays, one of which included an examination. It was found that the high-SFC subjects, defined as those who tend to keep to themselves and/or blame themselves in stressful situations, showed higher BP responses than the low-SFC subjects, but only on the exam day. Further, the high-SFC subjects showed higher BP during the exam but also had BP elevations that were sustained during other activities throughout the same day, including evening rest. These results are discussed in terms of the relation between psychological and physiological responding.

Cardiovascular reactivity assessment: effects of choice of difficulty on laboratory task responses.

This laboratory study of cardiovascular reactivity was designed to examine how a choice of difficulty element in a mental arithmetic task would affect cardiovascular responses. 20 healthy male subjects were tested on a computer-controlled mental arithmetic task, designed to standardize performance across subjects by keeping constant the proportion of correct responses. This was achieved by automatic adjustment of problem difficulty according to ongoing performance. Subjects were led to believe that they could take either a 'difficult' or an 'easy' version of the mental arithmetic task and were asked to make a choice; in fact, all subjects were given the same task. Subjects who chose the 'difficult' mental arithmetic task (N = 10) showed significantly greater increases in myocardial contractility, cardiac output and systolic blood pressure during task performance than those who chose 'easy' (N = 10). However, subjects who chose 'difficult' were presented with more difficult problems presumably due to their exerting greater levels of effort during the task. The differences in cardiovascular responses associated with choice of difficulty were absent during testing on four subsequent tasks which did not incorporate any choice options (reaction-time, speech, mirror trace, cold pressor). These findings are interpreted as being provocative, rather than in any way conclusive. Nevertheless, they are suggestive of the possibility that choice of difficulty in laboratory tasks may be one strategy for improving the ecological validity of laboratory reactivity assessment procedures.

Hemodynamics of blood pressure responses during active and passive coping.

This laboratory study was designed to address a number of interrelated issues regarding cardiovascular reactivity to psychological stress. One objective was to extend the previous research comparing cardiovascular responses during active versus passive coping, by comparing responses to two task conditions designed to be similar in all ways except the opportunity to make a response influencing the task's outcome. A second objective was to compare responses to two different passive film tasks, which differed in outcome uncertainty and the degree of vicarious active coping achieved through identification with the role portrayed by the actors. A third objective was to evaluate whether individuals are predisposed to exhibit a particular hemodynamic pattern underlying their blood pressure adjustments, independently of the task demands imposed. Ninety healthy young adult male subjects were tested in pairs on a series of tasks that included a competitive reaction-time task, an active as well as a passive phase of a team reaction-time task, and passive viewing of two film segments. The tasks demanding active coping responses tended to raise blood pressure due primarily to an increase in cardiac output, while vascular resistance fell. During passive coping demands cardiac output increased to a lesser extent, but vascular resistance also tended to increase, thereby raising blood pressure by their synergistic effects. However, these patterns were not typical of all participating subjects. On the basis of their cardiac output and vascular resistance responses to the competitive reaction-time task, one third of the subjects were categorized as being high myocardial reactors (n = 30) and another third high vascular reactors (n = 31). Post-hoc analyses of responses to the other tasks, based on these categorizations, indicated that the hemodynamic basis of reactivity is an individual characteristic only partially modified by coping demands. The active/passive coping dimension is discussed both conceptually and in relation to the role of stress in the etiology of hypertension.