Acute immune complex disease in rabbits. The role of complement and of a leukocyte-dependent release of vasoactive amines from platelets.
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By depletion of C3 from rabbits undergoing acute experimental immune complex disease with an anticomplementary factor in cobra venom, it has been possible to demonstrate that deposition of the complexes in arteries and glomeruli does not require the complement components reacting after C2. Immunological reactions, in which platelets release their vasoactive amines, have been examined in rabbits undergoing immune complex disease. A correlation was obtained between the presence of a complement-independent reaction which required blood leukocytes, antigen and platelets, the deposition of immune complexes, and the induction of glomerulonephritis. C3 depletion did, however, have a marked alleviating effect on the severity of the arterial lesions. Neutrophil accumulation and the subsequent necrotizing arteritis were prevented. In contrast, the character and severity of the glomerulonephritis was not altered by depletion of later-acting complement components. (+info)
Uveoscleral aqueous outflow in the rhesus monkey: importance of uveal reabsorption.
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The uveal absorption of aqueous humor at two different intraocular pressures was measured in rhesus monkeys by sampling vortex vein blood during anterior chamber perfusion of Ringer's solution containing both fluorescein and 125I albumin. At 20 mm. Hg, an excess of fluorescein equivalent in amount to 0.45 microliter/min. of anterior chamber perfusate and an excess of 125I albumin equivalent to 0.18 microliter/min. of perfusate was found in the vortex vein blood compared to systemic blood. At 32 mm. Hg, an excess of 0.86 microliter/min. of fluorescein and 0.26 microliter/min. of 125I albumin was measured. The increase in fluorescein absorption at the higher intraocular pressure was significant (0.025 less than p less than 0.05), with a uveal outflow facility of 0.034 microliter/min./mm. Hg. At an intraocular pressure of 20 mm. Hg, uveal aqueous outflow is less than 10% of total aqueous outflow. The pressure dependence of the uveal uptake of fluorescein implies an aqueous reabsorption into the uveal vessels by ultrafiltration. Uveoscleral aqueous "outflow" appears to consist of intraocular uveal reabsorption of water and small molecules from the aqueous, with only larger molecules like albumin actually leaving the eye through posterior scleral vessel perforations. This reabsorption plays a minor role in intraocular pressure regulation under normal conditions. (+info)
Simultaneous measurement of thyroxine and triiodothyronine peripheral turnover kinetics in man.
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Serum triiodothyronine (T(3)) kinetics in man have been difficult to define presumably due to the interference of iodoproteins generated during the peripheral metabolism of T(3). The use, in the present study, of an anion-column chromatographic method for separation of serum T(3) as well as thyroxine (T(4)) from these iodoproteins has overcome this technical handicap. Simultaneous measurement of serum (125)I-T(3) and (131)I-T(4) kinetics were performed in 31 subjects from the clinical categories of euthyroid, primary hypothyroid, thyrotoxic and posttreatment hypothyroid Graves' disease, factitial thyrotoxic, and idiopathically high and low thyroxinebinding globulin states. The normal mean T(3) fractional turnover rate (kT(3)) was 0.68 (half-life = 1.0 days), increased in toxic Graves' disease patients to 1.10 (half-life = 0.63 days), and decreased in primary hypothyroid patients to 0.50 (half-life = 1.38 days). The mean T(3) equilibration time averaged 22 hr except in hypothyroid and high thyroxine-binding globulin (TBG) patients where the equilibration period was delayed by 10 hr. The mean T(3) distribution space in normal subjects was 38.4 liters. This was reduced in subjects with high TBG levels (26 liters) and increased in patients with low TBG and in all hyperthyroid states (53-55 liters). The normal serum T(3) concentration was estimated by radioimmunoassay to be 0.106 mug/100 ml. Combined with the mean T(3) clearance value of 26.1 liters/day, the calculated T(3) production rate was 27.6 mug/day. The mean T(3) production rate increased to 201 mug/day in thyrotoxic Graves' disease patients and was reduced to 7.6 mug/day in primary hypothyroid subjects. T(3) production rate was normal in subjects with altered TBG states. The ratio of T(3) to T(4) production rate in normal subjects was 0.31 and was unchanged in patients with altered TBG values. This ratio was increased in all Graves' disease patients with the highest value being 0.81 in the posttreatment hypothyroid Graves' disease group. This apparent preferential production of T(3) may have been responsible for the retention of rapid turnover kinetics for T(3) and T(4) observed in treated Graves' disease patients. The finding that factitial thyrotoxic patients also displayed similar rapid T(3) and T(4) turnover kinetics indicates that these alterations are not a unique feature of Graves' disease per se. When comparing the peripheral turnover values for T(3) and T(4) in man, it is apparent that alterations in metabolic status and serum TBG concentration influence both hormones in a parallel manner; however, changes in metabolic status seem to have a greater influence on T(3) kinetics while alterations in TBG concentrations have a greater effect on T(4). These observations probably relate to the differences in TBG binding affinity and peripheral tissue distribution of these two hormones. (+info)
A comparison of Coomassie blue dye with radioiodinated albumin as an indicator for plasma volume estimation in human subjects.
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Plasma volume has been estimated in 10 human subjects using Coomassie blue and (131)I radioiodinated human serum albumin dilution methods simultaneously. Three different methods of correction used by previous workers to overcome the error due to early dye loss were applied. Satisfactory agreement with the established radioiodinated albumin method was only obtained by extrapolation of the semilogarithmic plot of Coomassie blue plasma dye concentration between five and 10 minutes to the time of injection. The significance of the controversial Evans blue ;mixing curve' is discussed. An analogous phase in the Coomassie blue disappearance slope is considered to be due to initial rapid loss of dye from the circulation rather than to the process of mixing. It is shown that Coomassie blue fulfils the criteria listed in the discussion for plasma volume estimation. (+info)
Cells as antigen carriers and as immunoglobulin producers. Synthesis of antibody and allogeneic immunoglobulin after transfer of antigen-treated cells to newborn rabbits.
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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. (+info)
Experimental chronic glomerulitis.
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Three of 16 rabbits injected (intravenously) daily with crystalline bovine serum albumin (BSA) for periods in excess of 10 wk developed chronic glomerulonephritis. In vivo, animals with chronic proteinuria formed variable quantities of soluble complex after injection of antigen while animals without proteinuria exhibited rapid removal of the injected BSA. In vitro studies demonstrated that a major part of the antibodies produced by rabbits with chronic nephritis lacked precipitating properties. Interpretations of these observations were presented in the discussion. It is suggested that, in addition to quantity, quality of antibody plays an important role in the development of chronic serum sickness. Complexes formed with nonprecipitating antibody, which are less rapidly removed from circulation, would have a greater opportunity to deposit in glomeruli and induce inflammation. (+info)
On the mechanisms of maternofetal transfer of human albumin and gamma-G globulin in the mouse.
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Human serum albumin and human gammaG globulin were labeled with (131)I, and the labeled proteins were then mixed with different amounts of the respective unlabeled protein. These mixtures were injected intravenously into pregnant mice near term, and the amounts of protein-bound radioactivity present in the fetuses and in maternal serum 24 hr later were determined. The concentration of human albumin found in the fetus was proportional to the maternal serum concentration of this protein over the maternal range studied, from 0.03 to 935 mg/100 ml. On the other hand, the fetal concentration of human gammaG first increased rapidly as the maternal concentration increased to approximately 200 mg/100 ml and then decreased as the maternal concentration continued to increase above this level; however, as the maternal human gammaG level increased above approximately 1100 mg/100 ml, the fetal concentration again increased and became proportional to the maternal concentration. The data suggest that maternofetal transfer of human gammaG in the mouse may be mediated by two processess; one of these, as with the transfer of human albumin, appears to be first order in relation to the maternal serum concentration, and the other appears to be consistent with a carrier or enzymatic process that is directly or indirectly inhibited at high maternal serum levels. (+info)
Heterogeneity of antibody-forming cells. An electron microscopic analysis.
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Cell suspensions from draining lymph nodes of immune and nonimmune rats were reacted in vitro with (125)I-labeled antigens. In light microscopic radioautographs of smears, 17% of the immunized cells were tagged by specific antigen; 2.0% of control cells were positive. In electron microscopic radioautographs, 90% of the labeled elements from immune donors were lymphocytes, blast and plasma cells; 10% were monocytes-macrophages or other elements, including naked nuclei. 15% of the labeled cells from control materials were lymphocytes and plasma cells, while 85% were monocytes-macrophages and naked nuclei. Within cell suspensions derived from immunized animals there were almost twice as many lymphocytes marked by isotope as plasma cells, and the lymphocytes ranged in morphology from mature monoribosomal elements to immature polyribosomal cells. Antibody-forming cells fixed labeled antigen at their surfaces. The monocyte-macrophage class was distinguished by a high mean grain count and by distribution of grains within cytoplasmic vacuoles and lysosomes. (+info)