Research Article
Abstract
Actively metabolizing human erythrocytes catalyze the extracellular reduction of ferricyanide to ferrocyanide. Because neither of these anions can enter the cell, reducing equivalents generated in the course of glycolysis must in some manner be transferred across the cell membrane, thereby resulting in ferricyanide reduction. Work described in this paper suggests that the transmembrane reduction is effected by ascorbic acid. This compound in its oxidized form (dehydroascorbate) rapidly enters the cell. Here it obtains reducing equivalents which appear to come from NADH made available at the level of glyceraldehyde 3-phosphate dehydrogenase. Once reduced, it leaves the cell as ascorbic acid and accomplishes the non-enzymatic reduction of ferricyanide.
Authors
E P Orringer, M E Roer
Abstract
We have carried out perfusion studies on hydropenic and bicarbonate-loaded rats to provide direct in vivo observations on bicarbonate accumulation in the short loops of Henle. Analysis of early distal tubular fluid was made during bicarbonate-free saline perfusion from the end proximal to the early distal site, documenting accumulation of "new" bicarbonate. During perfusion in hydropenic rats, steady-state bicarbonate concentrations were suggested by early distal values of approximately equal to mM, which were independent of perfusion rate and virtually indistinguishable from bicarbonate concentration measured during free flow when filtered bicarbonate was allowed to enter the loop. Thus, loop bicarconate accumulation was apparently sufficient to allow new bicarbonate to enter at a rate comparable to that delivered to the early distal site during free flow, recognizing of course that free-flow delivery rates are the result of complex components of filtration and bidirectional fluxes. In bicarbonate-loaded rats, however, bicarbonate accumulation rates although higher than in hydropenia, were much lower than free-flow delivery rates. Furthermore, early distal bicarbonate concentrations during bicarbonate loading fell as perfusion rate increased, presumably because of a limitation to increasing ionic bicarbonate entry.
Authors
D Z Levine, M K Byers, R A McLeod, J A Luisello, S Raman
Abstract
Using the isolated rat kidney perfused with an artificial medium containing glucose as the sole fuel, we studied the renal handling of immunoreactive arginine vasopressin (AVP) and determined the effect of various factors on the ability of the kidney to remove AVP.
Authors
Ralph Rabkin, Leonard Share, Paul A. Payne, Judy Young, Joan Crofton
Abstract
The effect of the microtubule inhibitor colchicine on the metabolism of 125I-low density lipoprotein (LDL) by cultured human skin fibroblasts and aortic medial cells was studied in vitro. Colchicine did not alter the binding of LDL to cell surface receptors. However, the rate of LDL endocytosis was reduced to 58% of that expected. Despite diminished endocytosis, LDL was found to accumulate within the cells to 165% of that expected, whereas the release of LDL protein degradation products into the medium was reduced to 34% of control, findings consistent with a reduced rate of intracellular LDL breakdown. Colchicine did not alter cell content of the acid protease which degrades LDL, nor did [3H]colchicine accumulate in lysosomal fractions. However, colchicine did alter the intracellular distribution of both fibroblast lysosomes and endosomes. After colchicine, lysosomes tended to accumulate in the perinuclear region, whereas endosomes were found at the cell periphery. These findings are consistent with the hypothesis that ingested LDL is less available to lysosomal enzymes in the presence of colchicine. The actions of colchicine appear to be a result of destruction of cell microtubules. Lumicolchicine, a mixture of colchicine isomers which (unlike the parent compound) does not bind to the subunit of microtubules, was without effect.
Authors
Richard E. Ostlund Jr., Barbara Pfleger, Gustav Schonfeld
Abstract
The crystal-induced chemotactic factor, a cell-derived chemoattractant for neutrophils, binds specifically to a site on human neutrophils but not to erythrocytes or lymphocytes, suggesting a relationship between the presence of specific binding sites on the neutrophils and the ability to be chemotactically activated. The Scatchard analysis revealed an equilibrium dissociation constant at 37 degrees C of 0.446 micrometer and the presence of approximately equal to 6.44 x 10(5) binding sites for 125I-crystal-induced chemotactic factor per cell. Binding was not displaced by the synthetic chemotactic factors F-Met-Leu-Phe and Gly-His-Gly or by complement-activated plasma providing evidence of the specificity of the receptor.
Authors
I Spilberg, J Mehta
Abstract
Although numerous interventions have been shown to exert a salutary effect on the ischemic myocardium, the severity of ischemia generally has been measured by indirect techniques. In the present investigation the effect of ischemia on intramural carbon dioxide tension (PmCO2) was measured directly in the open-chest, anesthetized dog with a mass spectrometer during repetitive 10-min coronary artery occlusions separated by 45-min periods of reflow; simultaneously, regional myocardial blood flow in the ischemic area was measured by 127Xenon washout. In all dogs the increase in PmCO2 from before to 10 min after the first occlusion (ΔPmCO2) exceeded that during subsequent occlusions. In those dogs not receiving an intervention (controls), ΔPmCO2 during the third occlusion was similar to that during the second occlusion. When propranolol, hyaluronidase, and nitroglycerin were administered to different groups of dogs before the third occlusion, each caused significantly smaller elevations in ΔPmCO2 than those occurring during the control second occlusion, and the combination of all three interventions induced the smallest increase in ΔPmCO2. Regional myocardial blood flow rose with hyaluronidase and was unchanged with propranolol, nitroglycerin, and the three drugs in combination. In contrast to these beneficial interventions, isoproterenol infused with the third occlusion caused a higher ΔPmCO2 than during the control second occlusion. It is concluded, first, that interventions that modify the severity of ischemia can be evaluated by measuring intramural carbon dioxide tension; second, that propranolol, hyaluronidase, and nitroglycerin reduce ischemic injury, whereas isoproterenol increases it; and third, that the combination of propranolol, hyaluronidase, and nitroglycerin exerts an additive beneficial effect on ischemia.
Authors
L. David Hillis, Shukri F. Khuri, Eugene Braunwald, Robert A. Kloner, Donald Tow, Ernest Barsamian, Peter R. Maroko
Abstract
The effect of the antigen-induced, immunoglobulin (Ig)E-dependent release of mediators from human lung tissue was analyzed for coincident changes in the tissue levels of cyclic nucleotides. Simultaneously with the appearance of mediators, lung cyclic guanosine 3′,5′-monophosphate (GMP) increased from 0.9±0.2 to 12.63±4.5 pmol/mg protein and cyclic AMP increased threefold from the initial levels of 5.1±1.4 pmol/mg protein. The release of histamine and prostaglandin (PG)F2α, as well as the associated increases in cyclic nucleotides, peaked within 10 min of anaphylaxis. Antagonists of histamine's H-1 receptor prevented anaphylaxis-associated increases in cyclic GMP, whereas H-2 antagonists prevented the cyclic AMP response. Neither of these antagonists influenced the pattern or quantity of histamine or slow-reacting substance of anaphylaxis release. Prevention of PGF2α synthesis with acetylsalicylic acid failed to influence histamine or slow-reacting substance of anaphylaxis release or the concomitant increases in cyclic nucleotides. Histamine, added exogenously, produced a prompt increase in the cyclic AMP and cyclic GMP levels of human lung. As was seen after anaphylaxis, H-1 anatagonists prevented the cyclic GMP response to histamine, whereas H-2 antagonists prevented the cyclic AMP response.
Authors
Leslie F. Platshon, Michael Kaliner
Abstract
In this study two groups of patients with acute Chagas' disease were identified. Group one consisted of five patients with apparent acute Chagas' disease. These patients showed symptoms and signals of an acute illness, such as high fever and enlarged spleen. One of these patients developed severe myocarditis and heart failure. Group two consisted of seven patients with inapparent acute Chagas' disease. This was a nonclinical entity, not perceived by the patient who did not seek medical care. The diagnosis was made by the shift of a serologic test which indicates the presence of immunoglobulin M antibodies to Trypanosoma cruzi.
Authors
Antonio R. L. Teixeira, Glória Teixeira, Vanize Macêdo, Aluizio Prata
Abstract
Booster immunization of normal individuals with soluble tetanus toxoid resulted in the ability of the individuals' peripheral blood lymphocytes to synthesize immunoglobulin (Ig)G antitetanus toxoid antibody in vitro when stimulated by pokeweed mitogen. The capacity for this in vitro antitetanus toxoid antibody response developed within 14 days after booster immunization, reached a peak between days 36--50, and disappeared by day 60. The inability of pokeweed mitogen to stimulate antitetanus toxoid antibody synthesis in vitro before booster immunization was not due to excess suppression by thymus-derived (T) lymphocytes but reflected insufficient numbers of functionally specific helper T lymphocytes and bone marrow-derived (B) lymphocytes. Antigen-specific T-lymphocyte suppression and decreased B-lymphocyte function were associated with the observed reduction of in vitro synthesis of antitetanus toxoid antibody from 20--60 days post-immunization. The in vitro kinetics of antitetanus toxoid antibody synthesis paralleled the synthesis of total IgG in that stimulation by pokeweed mitogen was required and that antibody secretion into the medium initiated by day 4 and increased through day 9.
Authors
R H Stevens, A Saxon
Abstract
Gonococci are capable of attaching to the surface of polymorphonuclear leukocytes (PMN). In this location they resist phagocytosis and are not killed by PMN. To delineate the factors involved in the survival of these gonococci, we investigated the interaction of virulent gonococci, which adhere to cells and resist phagocytosis, and avirulent gonococci, which are phagocytized and killed by PMN. In the presence of serum, both virulent and avirulent gonococci associate equally well with PMN and stimulate increases in oxidative metabolism. In the absence of serum virulent gonococci attached to PMN and stimulated PMN oxidative metabolism to a greater extent than avirulent gonococci which did not attach to PMN (P = 0.0009). Therefore, the survival of virulent gonococci attached to the PMN surface is not a result of failure to activate oxidative and bactericidal mechanisms. Both virulent and avirulent gonococci stimulated equivalent PMN specific granule release as measured by the appearance of lactoferrin in the media. Phagocytosis of avirulent gonococci stimulated significantly greater beta-glucuronidase release (P = 0.01) and myeloperoxidase-mediated iodination of protein (P = 0.001) by PMN than attachment of virulent gonococci. In the absence of serum neither type of gonococci stimulated beta-glocuronidase release or protein iodination by PMN. Thus, virulent gonococci fail to stimulate primary granule release by PMN. To further assess the role of attachment versus ingestion on the survival of gonococci, PMN were treated with cytochalasin B to block ingestion. Cytochalasin B-treated PMN were unable to kill either virulent or avirulent gonococci despite normal degranulation stimulated by the latter. The failure of PMN to kill surface-attached gonococci appears to be a consequence of the failure of PMN to enclose the virulent gonococci within a phagosome. The phagocytic vacuole thus plays a critical role in normal PMN bactericidal activity by providing a closed space in which the proper concentration of substances may be achieved to generate microbicidal activity.
Authors
P Densen, G L Mandell
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