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L F Fries

Publications and source records attributed to L F Fries.

44 records · Page 3Linked to original sources

C3b covalently bound to IgG demonstrates a reduced rate of inactivation by factors H and I.

We have prepared C3b covalently linked to IgG via a hydroxylamine-sensitive bond between the C3b alpha' chain and sites predominantly, but not exclusively, located in the IgG heavy chain. This C3b species displays relative resistance to inactivation by factors H and I when compared with free C3b. This resistance appears to be due entirely to reduced affinity of C3b-IgG for factor H. Resistance to inactivation is not conferred on C3b by binding to another serum glycoprotein of similar size, ceruloplasmin, and may be a special property of IgG. C3b-IgG demonstrates an enhanced capacity to consume serum C3 relative to C3b. These alterations of the behavior of C3b when bound to IgG may in part explain the augmentation of alternative pathway activity by IgG. In addition, IgG-induced protection of C3b might influence both complement-mediated killing and phagocytosis of bacteria, as well as modify the in vivo handling of IgG-containing soluble immune complexes.

Ceruloplasmin↗

Monocyte receptors for the Fc portion of IgG are increased in systemic lupus erythematosus.

Defective clearance of IgG-sensitized particles has been documented in systemic lupus erythematosus (SLE). This defect may be of pathogenetic significance because it allows the prolonged circulation of endogenous immune complexes with subsequent tissue deposition. To assess the possible contribution of a genetically determined defect in phagocyte Fc-IgG receptor expression or immune complex saturation of Fc-IgG receptors to impaired clearance, we used a well-characterized monomer binding assay to quantitate monocyte Fc-IgG receptors in normal controls and in 26 patients with SLE. Mean monocyte Fc-IgG receptor numbers were increased in both male and female SLE patients relative to normal controls. Increasing receptor numbers correlated positively with increasing clinical disease activity and increasing titers of antibody to native, double-stranded DNA. No significant correlation was found between any single disease symptom, organ system involvement, drug therapy, antigenic C3 levels, or immune complex levels and receptor number. A negative correlation was noted between Fc-IgG receptor binding affinity constants in SLE patients and clinical disease activity, but none of the observed affinity constants fell outside the 95% confidence normal range, and the mean affinity constants for patients both with and without active disease were not significantly different from controls. Our results are inconsistent with a genetically determined defect in Fc-IgG receptor elaboration by mononuclear phagocytes, and suggest that simple immune complex saturation does not underlie abnormal Fc-IgG-mediated clearance in SLE.

Adult↗

Plasma fibronectin enhances phagocytosis of opsonized particles by human peripheral blood monocytes.

We have investigated the effect of plasma fibronectin (Fn) on binding and phagocytosis of sheep erythrocytes (E) by human peripheral blood monocytes. Unopsonized E were not phagocytosed in the absence or presence of Fn, but Fn enhanced the phagocytosis of E bearing IgG. Sheep erythrocytes sensitized with IgM and C3b were ingested only when monocytes were exposed to Fn. The Fn enhancement of phagocytosis occurred for both fluid-phase and glass-adherent monocytes. Experiments in which Fn was washed out before mixing monocytes with opsonized E demonstrated that the Fn effect occurred because of interaction with the monocytes and not the opsonized particles. Chromatography of the Fn on Biogel A 1.5m showed that the phagocytosis-enhancing activity exactly co-chromatographed with the Fn protein. Fn did not increase the number of monocyte membrane receptors for the Fc fragment of monomeric IgG. We conclude that Fn enhances monocyte phagocytosis, not by binding to particles as a conventional opsonin, but by stimulating monocytes to ingest already opsonized particles more avidly.

Erythrocytes↗

Monocyte receptors for the Fc portion of IgG increase in number in autoimmune hemolytic anemia and other hemolytic states and are decreased by glucocorticoid therapy.

Peripheral blood monocyte receptors for the Fc portion of IgG were quantitatively studied in 43 normal subjects, in 14 patients with warm antibody autoimmune hemolysis (AIHA), and in nine individuals with nonantibody-mediated hemolysis. Monocytes of normal females expressed significantly greater numbers of Fc gamma receptors than did similar cells from male subjects, with no difference in affinity for the IgG1 probe. Monocyte Fc gamma receptor number was increased in patients of both sexes with AIHA; a similar, but smaller, increase in monocyte Fc gamma receptor number was noted in patients with nonantibody-mediated hemolysis. Glucocorticoid administration was associated with a dose-dependent decrease in monocyte Fc gamma receptor number in normal volunteers and patients. Possible etiologic mechanisms and pathogenetic consequences of enhanced monocyte Fc gamma binding in AIHA are discussed.

Adolescent↗

Monocyte receptors for the Fc portion of IgG studies with monomeric human IgG1: normal in vitro expression of Fc gamma receptors in HLA-B8/Drw3 subjects with defective Fc gamma-mediated in vivo clearance.

The Fc gamma receptors of reticuloendothelial cells are presumed to play an important role in the clearance of circulating particles opsonized with IgG. In order to quantify these receptors and assess their contribution to the clearance phenomenon in man, Scatchard analysis has been applied to 125I-IgG1 myeloma protein binding by a model mononuclear phagocyte, the peripheral blood monocyte. Close compliance to the criteria for linear Scatchard plots has been obtained. The kinetics of binding at 37 degrees C were consistent with a simple, reversible, bimolecular reaction. A saturable, single class of high-affinity binding sites was discerned with a Ka of 2.61 +/- 0.13 x 10(8) M-1 and a mean of 35,500 +/- 1700 receptors per monocyte. These receptors expressed approximately equal affinities for IgG subclasses 1 and 3, with progressively lower affinities for IgG subclasses 4 and 2, respectively. Parameters of IgG1 binding to monocytes of patients with dermatitis herpetiformis and normal individuals of HLA-B8/Drw3 haplotype were not significantly different from controls, despite the previous demonstration of retarded IgG-mediated clearance in one-half of such subjects. Receptor number and affinity failed to correlate with T 1/2 for sensitized erythrocyte clearance in vivo. Functional defects in in vivo clearance, even in the absence of circulating immune complexes, are not necessarily related to abnormal expression of Fc gamma receptors by phagocytes.

Antigen-Antibody Complex↗

Inheritance of mixed cryoglobulinemia.

This paper describes a family in which 10 members of 3 generations have IgM-IgG cryoglobulinemia. Their pedigree is characteristic of autosomal dominant inheritance. No underlying disease that could account for the cryoglobulinemia has been identified in any patient, and no linkage of the cryoglobulinemia to HLA-A and -B locus haplotypes, blood group antigens, or immunoglobulin Gm allotypes has been detected. The rheumatoid factors of this kindred react with some, but not all, human IgG; however, their rheumatoid factors are not antibodies to any known human Gm or Km allotype. This family demonstrates that "essential" mixed cryoglobulinemia can be inherited, and that the clinical manifestations of an inherited cryoglobulinemia may vary among family members.

ABO Blood-Group System↗

Accuracy of screening for pulmonary embolism in the emergency room.

Pertinent historical, clinical, and laboratory findings were recorded for 37 consecutive patients who presented to the emergency room complaining of shortness of breath and chest pain but without evidence of coronary insufficiency, pneumonia, or musculoskeletal injury. 13 had pulmonary embolism suggested by lung scan with or without pulmonary angiogram, or, in 2 cases, by right heart catheterization. As a group, these patients in whom embolism was judged probable approached fairly closely the profiles of previous studies of patients with documented pulmonary emboli. Nonetheless, they differed very little, and in no clinically useful way short of lung scans and invasive studies, from the remaining 24 patients in whom embolism was judged unlikely. In the population served by this emergency room, which has a high morbidity from chest diseases and putative predisposing conditions to pulmonary embolism, screening patients for high and low probability groups for this diagnosis cannot be done on clinical grounds alone. Six-projection ventilation-perfusion lung scanning may be the only acceptable screening examination, and should be available directly from the emergency room in hospitals with an active emergency service.

Emergency Service, Hospital↗

Cunninghamella bertholletiae infection associated with deferoxamine therapy.

Cunninghamella bertholletiae, an uncommon cause of human infection, has been reported with increasing frequency in recent years. C. bertholletiae belongs to the order Mucorales and produces infections similar to those produced by the other agents of mucormycosis. Infections with this group of organisms have typically been seen either in patients with diabetes mellitus or in those receiving chemotherapy. Recent reports of mucormycosis in dialysis patients receiving deferoxamine for iron or aluminum overload have raised the possibility that deferoxamine therapy is a risk factor for mucormycosis. A case of C. bertholletiae infection in a patient receiving deferoxamine for iron overload unrelated to hemodialysis was investigated in detail, and possible explanations for this patient's infection were assessed.

Deferoxamine↗