Septicemia from infected caval 'umbrella'.
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Biomedical subjects
Publications and source records attributed to C L Anderson.
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Many factors will influence the tissue response to catecholamine stimulation. Isolated human granulocytes (PMNs) release the lysosomal enzyme beta-glucuronidase following incubation with complement-activated zymosan particles. Isoproterenol, histamine, and prostaglandin E1 (PGE1) inhibit this PMN release of beta-glucuronidase. The effect of exercise on this in vitro granulocyte response was studied in two groups: highly conditioned marathon runners (n = 6) and unconditioned subjects (n = 7). A 13-km run did not produce leukocytosis in the highly conditioned marathon runners and the granulocyte response to isoproterenol was unchanged in cells obtained immediately following the run. In contrast, the seven unconditioned subjects exercised to a maximal response on the treadmill. Following exercise there was an increase in plasma catecholamines, a significant leukocytosis, and granulocytes from the immediate postexercise period responded less well to isoproterenol.
A case of subacute bacterial endocarditis presenting with hemoptysis and late onset of cardiac murmurs, in the absence of pyrexia, was reported. The causative agent was a fastidious, slow-growing, unclassified, gram-negative bacterium, DF-2 (decarboxylase fermenter-2), apparently transmitted by a dog bite. The absence of classic signs of bacterial endocarditis poses a diagnostic challenge and stresses the need for an awareness of atypical presentations of subacute bacterial endocarditis.
Rhinovirus respiratory infections have been frequently associated with the precipitation of an asthma attack. As an explanation for virus-provoked asthma, it has been proposed that viruses or their products may alter beta-adrenergic responsiveness. Isolated human granulocytes have provided an in vitro study model for this problem. Granulocyte release of the lysosomal enzyme beta-glucuronidase (BG) occurred after incubation with complement-activated zymosan particles, and this release was inhibited by isoproterenol (ISO), histamine (HIS) acting via its H2 receptor, and prostaglandin E1 (PGE1). In asthma, the granulocyte response to HIS and ISO was impaired, and the ISO impairment was accentuated during virus-provoked asthma. After an in vitro incubation of polymorphonuclear leukocytes (PMN) with rhinovirus 16, the granulocyte response to ISO, HIS, and PGE1 was significantly reduced. This change in agonist response was proportional to the virus dosage, maximal at 37 degrees C and after a 60-min incubation period, and occurred with heat or UV-inactivated virus. It is possible that impaired beta-adrenergic responsiveness may also develop in other tissues, such as the airway smooth muscle, and thus explain, in part, wheezing during viral respiratory infections.
We asked whether binding of human immunoglobulin (Ig)G antibody reacting with Raji cells could be distinguished from binding of IgG immune complexes. Using a standard Raji assay employing 125I-IgG goat anti-human Fc gamma, we found that digestion of Raji cells with pronase reduced by 95% their ability to bind complement-fixed aggregated human gamma globulin and complement-fixed tetanus toxoid-antitetanus toxin complexes. However, binding at 37 degrees C of IgG from the sera of 16 patients with systemic lupus erythematosus (SLE) to pronase-digested Raji cells was reduced much less consistently and extensively (9-100% reduction; mean reduction of 51%). In more detailed studies of two SLE sera, sucrose density gradient centrifugation showed that greater than 50% of the IgG binding to undigested Raji cells sedimented in the 7S region. Pepsin digestion of immunoglobulin fractions from four SLE sera caused a reduction in SLE IgG binding to undigested Raji cells when detected with 125I anti-Fc gamma, but an increase when binding was detected with 125I-anti-Fab, suggesting that substantial SLE IgG can bind through F(ab')2 regions. Binding of IgG from SLE sera was not directed at neoantigenic sites induced by pronase digestion because binding activity was adsorbed with undigested cells as readily as with digested cells. Moreover, sera from 10 SLE patients that had negative Raji assays contained no IgG that bound to pronase-digested Raji cells. We conclude that much of the IgG bound at 37 degrees C to Raji cells from the sera of many patients with SLE does not represent immune complexes but is probably antibody directed toward sites on the Raji cell.
Since the U937 cell line expresses many characteristics of normal human monocytes and macrophages, we studied in detail its receptors for IgG by measuring direct binding and inhibition of binding of 16 radioiodinated human myeloma proteins representative of the 4 subclasses. As with normal monocytes, IgG1 and IgG3 bound most efficiently (17.3 and 15.7% bound), IgG4 less readily (7.1% bound), and IgG2 least readily (0.6% bound). Scatchard plots of IgG1 binding showed approximately 18,000 binding sites/cell with Ka approximately 10(8) liter/mol. IgG1 binding was inhibited equally well by IgG1 and IgG3 (50% inhibition with 0.26 +/- 0.03 and 0.26 +/- 0.09 microgram, respectively). IgG4 inhibited less readily (0.68 +/- 0.12 microgram). Three IgG2 proteins were not inhibitory (115 +/- 59) but one IgG2 myeloma inhibited well (0.89 +/- 0.47). IgG Fc fragments inhibited IgG1 binding 1000-fold more efficiently than Fab fragments, IgM, and IgA. Reciprocal inhibition experiments gave no indication of multiple receptor sites of differing specificities. In situ, the IgG1 receptor was resistant to proteases. The data suggest that the U937 Fc receptor may be a useful model of human macrophage structure and function.
The plasma membrane Fc receptor for IgG2b on P388D1 cells, solubilized by detergent, was inactivated by incubation with phospholipase C. Soluble Fc receptor activity could be restored by the addition of liposomes of either phosphatidylethanolamine or phosphatidylinositol. The reconstituted Fc receptor was trypsin sensitive. These data indicate that Fc receptor binding of IgG2b results from the concerted action of membrane lipid and protein.
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Early removal of the optic cup of the chick embryo prevents innervation of the contralateral optic lobe. This reduces the rate of development od citrate synthetase. The posthatch increase of the level of this enzyme related to oxidative metabolism is not impaired by denervation of the chick optic lobe.
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The effectiveness of intraaortic balloon counterpulsation is reduced frequently by arterial insufficiency following balloon insertion and occasionally by inability to pass the balloon centrally from a peripheral site. From a series of patients undergoing cardiac catheterization, a subgroup with increased likelihood of needing balloon counterpulsation can be selected. Patients so chosen have received one aortoiliac injection of contrast material at the time of cardiac catheterization. Impressive degrees of vessel irregularity and stenosis on an atherosclerotic basis and of tortuosity of normal lumen size have been noted. Such information, gathered at little additional risk or irradiation, is considered to be important in the subsequent choice of sides for transfemoral insertion and may rule out attempted passage of the balloon by this route, directing the surgeon to a deliberate, prompt, transabdominal or thoracic aortic insertion if necessary.
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By using radiolabeled myeloma proteins specific for each of two distinct Fc receptor activities on macrophage-like murine cell lines ("aggregated IgG FcR" activity and "monomer IgG2a FcR" activity), we have been able to detect solubilized FcR of both types in detergent lysates of these cells. The two solubilized Fc receptors can be distinguished and physically separated from one another by means of affinity chromatography and by sucrose gradient centrifugation. They also differ in their sensitivity to phospholipase C. The detergent solubilized monomer IgG2a FcR can be removed from solution with a Sepharose IgG2a column, has an S value of 4 to 5 and is resistant to phospholipase C. The solubilized aggregated IgG FcR does not bind to insolubilized IgG2a, has an S value of greater than 19, and is sensitive to phospholipase C treatment. We conclude from these studies that two different cell membrane macromolecules are responsible for the Fc receptor activities observed in macrophage-like cell lines.
To evaluate subclass specificity and aggregate size requirements of IgG receptors on mouse cells, we measured binding of radiolabeled monomeric and BDB-aggregated mouse myeloma proteins fractionated into various sizes by means of gel filtration. Monomers, tetramers, and high molecular weight (approximately 10(7) daltons) aggregates were used. The various cells and cell lines studied could be segregated into three patterns of reactivity: (a) Macrophage and macrophage-like cell lines bound monomer IgG2a preferentially; high molecular weight IgG aggregates bound as follows: IgG1 = IgG2b = IgG2a. (b) Lymphoid lines D2N and S49 showed no capacity to bind monomer IgG2a; high molecular weight aggregates bound as follows: IgG1 = IgG2b less than IgG2a. (c) Other Thy-1-positive lymphoid cell lines (EL4 and L5178) and normal T and B cells showed no capacity to bind monomer IgG; high molecular weight IgG aggregates bound to a lesser extent than to cells of the first two categories in the following manner: IgG1 less than IgG2b greater than or equal to IgG2a. The variable pattern of reactivity of the macrophage-like cell lines with monomer and aggregated IgG suggested that two distinct receptors for IgG were present: one capable of binding IgG2a and another capable of binding all aggregates. Further evidence for this hypothesis was obtained by analysis of the inhibitory capacity of different IgG subclasses on the binding of aggregated IgG and monomer IgG2a to P388 cells. Inhibition of monomer IgG2a binding was effected only by monomer or aggregated IgG2a, whereas inhibition of binding of aggregated IgG1 or IgG2b was noted with aggregates of all three subclasses with some preferential inhibition by monomer IgG2b being observed. Furthermore, monomer IgG2b binding was preferentially inhibitable by monomer IgG2b. It is postulated from these data that two receptor sites are present on this macrophage-like cell line, one reactive with aggregates of all three subclasses as well as monomer IgG2b, and another receptor specific for monomer IgG2a which also binds aggregated IgG2a. Support of this concept was obtained by trypsinization experiments in which the binding of monomer IgG2a was markedly decreased by trypsin treatment of cells, whereas the binding of aggregated IgG2b was unaffected by this treatment.
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The medical literature has emphasized repeatedly the association of alpha1-antitrypsin deficiency with panacinar emphysema and cirrhosis of the liver. Previous reports have linked bronchiectasis with alpha1-antitrypsin deficiency. The present case confirms this association and adds the presence of an hepatic abnormality characteristics of alpha1-antitrypsin deficiency to complete the syndrome. The patient's phenotype was found to be MDuarteZ. It has been suggested that patients with diffuse bronchiectasis should be screened for alpha1-antitrypsin deficiency. We would add that a complete assessment of hepatic function, including liver biopsy, should be carried out in those individuals with reduced levels of alpha1-antitrypsin.
We assayed detergent cell lysates and culture supernatant fluid of mouse cells for the presence of soluble FcR by means of a radioligand bioassay. Strict correlation was found between the amount of FcR present in soluble form and that found on intact cells. The soluble FcR of all cells tested, except mouse macrophages, behaved as lipoprotein by buoyant density centrifugation analysis and enzyme treatment. In the absence of detergent, soluble FcR sedimented as a 20S macromolecule; in detergent the material was 7 to 9S. It was readily bound by insolubilized IgG but not by insolubilized BSA or F(ab')2 fragments of IgG.
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