Cells as antigen carriers and as immunoglobulin producers. Synthesis of antibody and allogeneic immunoglobulin after transfer of antigen-treated cells to newborn rabbits.

The injection into newborn rabbits of a small quantity of human albumin, associated with red blood corpuscles or nucleated rabbit cells, induces an antibody response in the majority of animals, whereas the same quantity of antigen in solution fails to stimulate antibody formation or induces tolerance. The promoting capacity of the cells depends on attachment of antigen to them. The antibody produced after the injection of albumin, associated with nucleated cells, is of recipient origin. However, immunoglobulin carrying the marker of donor cells can be demonstrated in the recipient animals, and may reach serum concentrations similar to those normally present in animals which are heterozygous with respect to the marker. It appears that the antibody-promoting function and the synthetic capacity for allotype are quite distinct and that the period required for allotype formation is very short with mononuclear peritoneal exudate cells and is very much longer with cells from the thymus. The capacity of cells from lymph nodes for sustained allotype formation is less than that of thymus cells but greater than that of mononuclear peritoneal exudate cells.

Augmentation of intrapericardial nitric oxide level by a prolonged-release nitric oxide donor reduces luminal narrowing after porcine coronary angioplasty.

BACKGROUND: Nitric oxide (NO) is a potent vasodilator and antiplatelet agent that suppresses vascular smooth muscle cell proliferation. Hypothesizing that generating NO in the pericardial space would reduce luminal narrowing after coronary angioplasty without affecting systemic hemodynamics, we have determined the effect of a novel NO donor on vascular healing after balloon overstretch. METHODS AND RESULTS: Diazeniumdiolated bovine serum albumin (D-BSA; molecular weight 74 kDa, half-life for NO release 20 days) was radioiodinated and found by intravital gamma-imaging to have a longer residence time in pig pericardium than a low-molecular-weight (0.5 kDa) analogue (22 versus 4.6 hours, respectively). Intrapericardial injection of D-BSA immediately before 30% overstretch of normal left anterior descending and left circumflex coronary arteries dose dependently reduced the intimal/medial area ratio by up to 50% relative to controls treated with underivatized albumin when measured 2 weeks after intervention. Positive remodeling was also noted, which increased luminal area relative to control. CONCLUSIONS: Perivascular exposure of coronary arteries to NO via intrapericardial D-BSA administration reduced flow-restricting lesion development after angioplasty in pigs without causing significant systemic effects. The data suggest that intrapericardial delivery of NO donors for which NO release rates and pericardial residence times are matched and optimized might be a beneficial adjunct to coronary angioplasty.

Changes in albumin/platelet interaction with an artificial surface--due to a antibiotics, pyridoxal phosphate, and lymphocytes.

Protein adsorption and platelet adhesion are two important biological processes arising at the blood prosthetic interface. The effect of certain antibiotics, namely, neomycin, gentamicin, ampicillin, penicillin-G, and streptomycin to modulate the albumin polycarbonate surface interaction was investigated using 125I albumin from a protein mixture in the presence and absence of isolated calf lymphocytes. This study also demonstrated the changes in platelet-surface adhesion with these antibiotics. The effect of pyridoxal phosphate to modulate the red blood cell-mediated platelet-surface attachment was also attempted. It appears from pyridoxal phosphate studies that pyridoxal 5'-phosphate (PLP) could modify the surface-platelet attachment. It also inhibited the fibrinogen-induced platelet adhesion. It seems, the addition of antibiotics to the polymerprotein system increased the level of surface-bound albumin variably whereas lymphocytes incubated in the medium did not affect the surface-albumin concentration with time course. These antibiotics also inhibited the surface-induced platelet adhesion to variable degrees. Our earlier studies have indicated that certain antibiotics or antiplatelet drugs can inhibit the fibrinogen binding to an artificial surface. Therefore, it may be possible that the enhanced albumin-surface concentration or reduced fibrinogen-surface binding, in the presence of these antibiotics, may itself be one of the parameter for a reduced platelet-surface attachment, which may also improve the blood compatibility of the substrate. A better understanding of the mechanism of antibiotics is needed in in vivo conditions to correlate these findings.

Effect of serum albumin on dynamic force-area curve of dipalmitoyl lecithin.

In line with previous findings at 25 degrees C, solutions of serum albumin in the subphase stabilized the surface activity of DPL spread films at 25 degrees C as well as 37 degrees C. In contrast, films adsorbed from mixtures of DPL and albumin exhibitied a marked inhibitory action of the albumin on DPL activity. The inhibitory effect increased with the relative protein concentration but, with albumin/DPL ratios smaller than 2, the DPL activity was regained gradually with cycling. With larger albumin/DPE negative effect of albumin was counteracted by higher temperatures (37 degrees C vs 25 degress C) and modest cholesterol concentrations; with greater cholesterol concentrations the known inhibitory effect of cholesterol prevailed. The inhibitory effect of albumin was potentiated by humidity; saturation of the atmosphere with water vapor at 37 degrees C abolished the DPL character of DPL-RSA mixtures and prevented its return (zero surface tension) upon reversal of the atmosphere from saturated water vapor to dry air. The data are important in the interpretation of the surface activity of pulmonary washings and other pulmonary extracts.

Effect of circulating FFA on lactate production by skeletal muscle during stimulation.

The present experiments were undertaken to study the effects of FFA on lactate production by skeletal muscle during stimulation. In the first group, dogs were anesthetized with sodium pentobarbital and given no anticoagulant. The second group was also anesthetized with sodium pentobarbital but in addition given heparin and a fat-albumin infusion to elevate FFA. Stimulating the nerves to a group of skeletal muscles in the hindlimb (1.5/s) increased muscle blood flow 2.4-fold in both groups. In the first group stimulation did not alter the arteriovenous difference of lactate across the muscles. The difference was close to zero before and during stimulation. However in the second group, in which FFA were elevated, stimulation produced a large increase in muscle lactate production. In both groups there were no differences in the L/P ratio of muscle venous blood during stimulation. These results indicate that an increase in lactate production following muscle stimulation is not necessarily related to a state of tissue hypoxia.

The use of radioisotope methods in pharmacologic and toxicologic studies.

By the use of radioisotopes, some pharmacologic studies can be carried out with less perturbation of physiologic processes than with other methods. Some isotope methods used at the Chair of Pharmacology of the Medical Academy in Lódz include determination of capillary circulation in the heart and skeletal muscle, minute output and stroke volume of the heart, renal clearance of 125J hippurate, and levels of some hormones and enzymes.

[Scintigraphic studies on the influence of coronary-effective drugs on myocardial perfusion during rest]. / Szintigraphische Untersuchungen über den Einfluss koronarwirksamer Substanzen auf die Myokardperfusion in Ruhe

A hemodynamically effective coronary stenosis causes in the myocardial scintigram a maldistribution of the albumin particles within the corresponding myocardial regions. During exercise or after medicamental vasodilatation the differences in regional myocardial perfusion are amplified. Various scintigraphic pictures can be shown in a double-scintigram investigation using particles labelled by different radionuclides before and after vasodilatation. According to the method of double-scintigraphy the influence of coronary active media (dipyridamol, nitroglycerin, nifedipine) on regional myocardial perfusion is investigated. Because of its long-acting vasodilatation dipyridamol leads to a malperfusion in poststenotic myocardial areas. A similar vasodilatation effect combined with reduced activity in the second perfusion scintigram can be noticed after injection of contrast medium. In contrast to the drugs described above comparable scintigraphic changes after nitroglycerin and nifedipine are due to a different myocardial perfusion pattern, which is only showing a relative malperfusion in the poststenotic regions. At rest neither nitroglycerin nor nifedipine is able to normalize the regional myocardial perfusion.