LFA-1-dependent OKT3-driven T cell clusters in common variable immunodeficiency.

The triggering of the TCR/CD3 complex by anti-CD3 (OKT3) antibody leads to the formation of T cell clusters. In cultures of T lymphocytes from most normal individuals, the peak of cluster formation occurs at 24 h, but with cells from patients with common variable immunodeficiency (CVI) it was seen earlier at 4-9 h; in addition, the clusters were larger than normal, particularly at 9 h. Cluster formation by CVI and normal cells was dependent on temperature and divalent cations, but did not require Fc receptors. Since OKT3 clustering is known to be dependent on the LFA-1/ICAM-1 adhesion system, the effect of monoclonal antibodies directed against these molecules was tested. A potent inhibitor was the antibody against the common beta chain of the integrin family (CD18), but of four MoAbs against the alpha chains (CD11), three inhibited and one stimulated T cell aggregate formation. Increased expression of LFA-1 or ICAM-1 on CVI patients' T cells could not be demonstrated. The accelerated clustering was therefore probably due to an increase in the proportion of cells carrying the activated form of LFA-1. The formation of large numbers of homotypic lymphocyte clusters might reduce the effective interaction between B and T cells, thus contributing to the depression of immunoglobulin synthesis observed in this disease.     

Comparison of three progressive exercise protocols in peripheral vascular occlusive disease.

Although claudication pain and hemodynamic responses to exercise are usually clinically assessed via graded treadmill walking, measuring these responses to other commonly performed tasks may yield a more nearly complete evaluation of peripheral vascular occlusive disease. Thus, the purpose of this study was twofold: (1) to determine the reliability of claudication and hemodynamic responses to level walking and stairclimbing and (2) to compare these responses with those obtained with graded walking at similar oxygen consumption. Ten patients with stable claudication symptoms performed graded walking, level walking, and stairclimbing progressive protocols with respective increases in grade, walking speed, and stepping rate on a modified stairclimbing device every two minutes. Similar peak oxygen consumption (13.60 to 14.18 mL/kg/min) was attained with the three protocols (P = NS). Reliability coefficients for the times to onset and to maximal claudication pain during level walking (R = 0.95 and 0.95, respectively) and during stairclimbing (R = 0.92 and 0.82, respectively) were similar to those previously obtained during graded walking. Reliability coefficients for foot transcutaneous oxygen tension during and following level walking (R = 0.78 to 0.96) and stairclimbing (R = 0.65 to 0.98) and for ankle systolic blood pressure following level walking (R = 0.95 to 0.97) and stairclimbing (R = 0.90 to 0.98) were also similar to those previously found with graded walking. Additionally, claudication and hemodynamic measurements were similar among the three exercise protocols. Thus, because graded walking, level walking, and stairclimbing progressive exercise protocols yield reliable and similar information about the hemodynamic severity of peripheral vascular occlusive disease, only one is needed for evaluation.     

Heinz Bodies Formed in Erythrocytes by Fatty Acid Ozonides and Ozone

Ozonides of the methyl esters of oleic, linoleic, linolenic and arachidonic acids were found to produce Heinz body inclusions in human and mouse erythrocytes. No simple relationships between structure and activity were noted.

Concomitant with Heinz body formation, methemoglobin and loss of cellular thiols were observed. Methyl ozonides readily oxidized glutathione and 1 mole of oxidized glutathione was formed per mole of methyl oleate ozonide. Methyl ozonides catalyzed the formation of disulfide-linked interchain polymers between hemoglobin and ovalbumin. Heinz bodies were not produced with ozone in the absence of unsaturated lipids. Heinz bodies were observed in the blood of mice exposed to ozone (0.85 ppm) for 48 hours.

These observations suggest that fatty acid ozonides could serve as a toxic chemical species formed on ozone inhalation and could explain the divergent protective effects of lipid antioxidants and thiol generating systems in vivo.     

A cross-sectional study of quality of life in an elderly population (75 years and over) with atrial fibrillation: secondary analysis of data from the Birmingham Atrial Fibrillation Treatment of the Aged study

AIMS: To compare the quality of life (QoL) of those in atrial fibrillation (AF) aged 75 years and over with that of the general population, to explore what factors affect the QoL of those with AF, and to assess the sensitivity of the EuroQol (EQ-5D) and Short-Form 12 (SF-12) generic health questionnaires in detecting differences in health status in those with AF in this age group. METHODS AND RESULTS: The study population was 1762 men and women aged 75 years and over with confirmed AF who attended a randomization clinic for the Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) study, a primary care based trial of stroke prevention. Patients self-completed the EQ-5D and SF-12 questionnaires, and a simple measure of disability (Rankin). Cardiovascular co-morbidities were collected and number of drugs used as an additional proxy for co-morbidity. Quality-of-life outcomes were compared with general population samples of the same age. On multiple regression, female gender, greater medication use, and disability were independently associated with lower QoL scores in AF. Those in AF with a Rankin score ≥2 had lower QoL scores, while those with a Rankin score <2 had higher scores than the general population. Increasing co-morbidity was associated with reduced QoL scores, with the EQ-5D and SF-12 Physical Component Score showing similar sensitivity to these associations, and the SF-12 Mental Component Score showing less sensitivity. CONCLUSION: In the absence of co-morbidity, chronic AF has little impact on generic QoL in an elderly non-acutely ill population.