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PubMed1979

Detection of immune complexes by a new assay, the polyethylene glycol precipitation-complement consumption test (PEG-CC).

A new assay for the detection of circulating immune complexes, the polyethylene glycol precipitation-complement consumption assay (PEG-CC), is described. The test is both simple and sensitive, and exhibits a high degree of specificity. Immune complexes are first isolated from serum by precipitation in 2.5% polyethylene glycol (PEG) and concentrated. They are then assayed functionally by measuring their ability to fix complement using a sensitive kinetic assay for total haemolytic complement. The test can detect aggregated IgG in serum at concentrations around 6.0 micrograms/ml (about 2.0 micrograms absolute. Using DNA-anti-DNA and ovalbumin-anti-ovalbumin immune complexes prepared in vitro, antigen concentrations less than 0.5 micrograms/ml can be detected. Interference by endogenous complement, polyanions and other factors in test sera has been virtually eliminted by the design of the assay. The increased specificity of the PEG-CC test for immune complexes, should prove useful in the diagnosis and monitoring of immune complex-mediated diseases.

Animals↗
PubMed1978

Merocyanine 540 as a fluorescent probe of membranes: staining of electrically excitable cells.

With the exception of certain blood cells considered in the accompanying paper (Valinsky, Easton and Reich, 1978), merocyanine 540 (MC 540), a fluorescent membrane probe, selectively strains the membranes of a wide variety of electrically excitable cells, but not those of nonexcitable cells. This reaction is Ca2+-dependent when staining is performed in buffered iso-osmotic sucrose, Ca2+-independent when staining proceeds at high ionic strength, inhibited by La3+ and sodium Suramin, enhanced by controlled, low level photosensitization of cell-associated dye and essentially irreversible. These characteristics of the staining reaction depend upon the maintenance of both cell viability and a normal unperturbed membrane structure. Although the mechanisms involved in the staining specificity remain unknown, observation of MC 540 partitioning between benzene and water in model reactions indicates that dye transport into hydrophobic solvents is accompanied by the formation of stoichiometric complexes with cations and phospholipids. These results may suggest the existence of specific, possibly phospholipid-rich membrane domains that mediate complex formation with MC 540 in excitable cells; comparable domains either would not exist, or would be inaccessible at the external surfaces of nonexcitable cells.

Benzoxazoles↗
PubMed1978

Pulmonary hemorrhage in systemic lupus erythematosus.

The clinicopathological features of four patients with systemic lupus erythematosus and pulmonary hemorrhage are described. Our study confirms that pulmonary hemorrhage may be a dominant clinical expression of lung involvement in this disease. Its clinical manifestations are usually quite characteristic. However, hemoptysis may be absent. Radiographically, bilateral alveolar infiltrates resembling pulmonary edema or infection may be seen. Pulmonary hemorrhage was a major contributing factor to the death of three of our patients. The possible pathogenetic mechanisms responsible for pulmonary hemorrhage in our patients and other patients previously recorded in the literature are reviewed. Evidence supporting an immune complex pathogenesis is presented. Our immunopathological and ultrastructural studies demonstrate deposition of immune aggregates in the lungs in the alveolar septa, large blood vessels, and bronchioles in a manner similar to that which has been observed in the experimental serum sickness model of immune complex mediated pulmonary injury. The histological abnormalities, although nonspecific, are consistent with this interpretation, and collectively show diffuse alveolar lining cell and endothelial cell injury. However, an immune complex pathogenesis may not completely explain the occurrence of pulmonary hemorrhage in SLE. Other factors, including bleeding disorders, pulmonary infection, oxygen toxicity, and the "shock lung" syndrome, may also have contributed to lung hemorrhage in some of these patients.

Adolescent↗
PubMed1979

Quantitation and characterization of soluble immune complexes precipitated from sera by polyethylene glycol (PEG).

Polyethylene glycol (PEG) was used to isolate immune complexes from sera. Complexes were then quantified and partially characterized by a variety of immunological techniques. Complexes were detected in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Felty's syndrome and vasculitis, but not in polymyositis, scleroderma or Behçets syndrome. The level of immune complexes correlated with disease activity in SLE and RA patients. Rheumatoid factors and anti-DNA antibodies were enriched by PEG precipitation of RA and SLE sera, respectively, thus these antibodies appeared to be present in the form of soluble immune complexes. Immune complexes usually contained all three immunoglobulin classes, IgG, IgM and IgA. Complexes from RA patients were generally larger and often contained Clq, while C3 was found almost exclusively in SLE complexes which also tended to be smaller. Such compositional differences may one day explain the differences in clinical manifestations of various immune complex-mediated diseases.

Antibodies, Antinuclear↗
PubMed2026

Phosphatase-mediated mitigation of rare earth element toxicity to Pseudomonas putida.

Anthropogenic activities are driving an increasing flux of rare earth elements (REE) into environmental compartments, raising concerns about their biological impact, particularly on microorganisms that sustain ecosystem functioning. Here, we provide a systematic assessment of the toxicity of all 16 REE toward Pseudomonas putida KT2440, a soil bacterium that can use these metals as enzyme cofactors. Dose-response growth inhibition assays revealed high sensitivity to light REE. Toxicity correlated strongly with ionic radius, with IC50 values ranging from 0.3 µM for lanthanum to 10 µM for scandium. Serial propagation of P. putida under gradually increasing REE stress yielded resistant populations, from which two stably resistant strains were isolated. Genome resequencing showed that both strains carried a single mutation in uxpB, encoding an alkaline phosphatase. Gene deletion and overexpression experiments, together with phosphatase activity measurements, confirmed the involvement of uxpB in REE resistance. Our findings reveal a previously unrecognized mechanism of tolerance to REE, suggesting that mutations enhancing phosphatase activity promote phosphate release from organic phosphorus compounds, thereby reducing REE bioavailability through phosphate-mediated complexation and/or immobilization.

Alkaline phosphatase↗
PubMed1979

Ferritin- and apoferritin-induced immune complex glomerulonephritis in mice.

In order to study the effects of the protein moiety independent of the protein-iron complex in the development of ferritin-induced glomerulonephritis, we compared the effects of ferritin, equimolar amounts of apoferritin, and equimolar amounts of iron dextran in Swiss albino mice. The results were compared to both saline-injected and non-injected controls. Ferritin resulted in a glomerulonephritis associated with predominantly mesangial deposition of immune complexes. Tubulo-interstitial changes occurred as well. Iron dextran resulted in similar but less severe tubulo-interstitial changes and evoked no glomerular alterations. Apoferritin resulted in an immune complex glomerulonephritis usually associated with membranous deposits. No tubular or interstitial changes occurred. Proteinuria developed in animals receiving apoferritin. Since the protein-iron complex caused tubular and interstitial damage, apoferritin may provide a more suitable model of immune-complex-mediated glomerulonephritis.

Animals↗
PubMedDate not supplied

Chronic serous otitis media: an immune complex disease.

In characterizing the immunochemical and biochemical nature of middle ear effusions (MEE) of chronic serous otitis media (SOM), we have previously shown that MEE contain all major immunoglobulin classes, increased levels of several lysosomal enzymes, decreased total complement, but increased levels of C3. This report extends these observations by showing that MEE also contains C3 proactivator (C3PA) that can be activated by those organisms involved in acute otitis media, which confirms a functional alternate complement pathway. Furthermore, we have demonstrated the presence of soluble immune complexes in MEE using the Raji cell test. These data further support an immune complex mediated etiopathogenesis for chronic SOM.

Adolescent↗
PubMed1978

Acute massive pulmonary hemorrhage in systemic lupus erythematosus.

Acute massive pulmonary hemorrhage is described as part of the clinical picture of SLE. Seven patients had sudden onset of high fever, dyspnea, tachycardia, and cough with blood-tinged sputum that within hours progressed to massive hemoptysis and death. There were no vasculitis or other inflammatory lung changes found at autopsy. Only one of the seven reported cases survived when treated with 2 g of intravenous hydrocortisone daily. The mechanism of this pulmonary bleeding is unknown but seems to be an immune complex mediated phenomenon.

Adolescent↗
PubMed1978

Suppression of rat adjuvant disease by cyclophosphamide pretreatment: evidence for an antibody mediated component in the pathogenesis of the disease.

Cyclophosphamide (Cy), given intraperitoneally at a dose of 100 mg per kg body weight 3 days before adjuvant, was found to abolish the development of adjuvant disease in the PVG/c rat. This treatment, however, enhanced the delayed hypersensitivity responses to purified protein derivative of tuberculin (PPD) developed by these animals. Lower doses of Cy caused a partial inhibition of arthritis which was dose-related. When the time between giving Cy and the injection of adjuvant was increased, a gradual time-dependent recovery of the response was observed. The arthritic response was restored by the passive transfer of 7.6 x 10(7) to 1.5 x 10(8) normal syngeneic spleen cells, although the development of secondary lesions was delayed by 7-14 days. The response could also be restored by the transfer of small amounts of serum from arthritic, but not normal, rats. Large amounts of serum failed to restore the response. Additional evidence that pretreatment with Cy preferentially depleted the B lymphocytes was obtained by the histological examination of the lymphoid tissue. It was also shown that the primary antibody response to sheep erythrocytes was abolished by Cy, but that skin allograft rejection was unaffected. A partial inhibition of the acute inflammatory reaction to carrageenan was observed 3 days after giving Cy. It is suggested that the pathogenesis of adjuvant arthritis involves an immune complex-mediated phase, whihc initiates the joint lesions. Once these lesions have formed, cell-mediated immune mechanisms predominate in the development of the disease. It is not known whether the persistence of immune complexes is necessary to maintain the lesions.

Animals↗
PubMed1979

Diabetes mellitus with immune complex glomerulonephritis.

The present study describes 3 patients with the simultaneous occurrence of diabetic nephropathy and immune-complex mediated glomerulonephritis. Renal manifestation included proteinuria and hematuria which were preceded by or co-existent with an infectious process. Renal manifestation included proteinuria and hematuria which were preceded by or co-existent with an infectious process. Renal histology showed the characteristic change of diabetic nephropathy along with those of immune complex glomerulonephritis. Immunofluorescence studies showed a linear pattern with a superimposed granular pattern of IgG and C3 deposits. Renal function and urinary findings improved in the 2 patients who were followed up.

Adult↗
PubMed1979

Degenerative vascular disease and myocardial infarction in mice with lupus-like syndrome.

The pathogenesis of the degenerative vascular disease and myocardial infarction that develop in mice with lupus-like disease was studied by immunofluorescence, light microscopy, and electron microscopy. Medium and small coronary arteries and arterioles of both infarcted and noninfarcted hearts had focal degenerative lesions consisting of deposits of periodic-acid--Schiff (PAS)-positive or eosinophilic material in the intima and to a lesser extent in the media, degenerative changes in the media without accompanying cellular inflammation, and occasional proliferation or swelling of intimal cells. These lesions often narrowed and, together with platelet aggregation, occasionally occluded the vascular lumens. Granular deposits of mouse immunoglobulin, C3, and occasionally gp70 were present in the walls of medium and small arteries, arterioles, and venules of both infarcted and noninfarcted myocardium. Dense deposits of foreign material were found by electron microscopy in areas corresponding to the immune deposits. These findings are consistent with the interpretation that these noninflammatory vascular lesions are caused by local deposition of antigen--antibody complexes. The immune-complex--mediated injury appears to lead to thrombotic and/or obliterative vascular changes that contribute to decrease of the coronary blood flow and to the development of myocardial infarction.

Animals↗
PubMed1979

Electron spin resonance study of the role of NO . catalase in the activation of guanylate cyclase by NaN3 and NH2OH. Modulation of enzyme responses by heme proteins and their nitrosyl derivatives.

The role of NO . catalase in the activation of partially purified soluble guanylate cyclase of rat liver by NaN3 and NH2OH was examined by electron spin resonance (ESR) spectroscopy. Equilibration of bovine liver catalase with NO resulted in formation of a paramagnetic species exhibiting a three-line ESR spectrum similar to that of NO . catalase. This paramagnetic complex produced concentration-dependent stimulation of preparations of partially purified guanylate cyclase that were devoid of detectable endogenous heme content. The stimulation of partially purified guanylate cyclase by NO . catalase was similar to that obtained with NO . hemoglobin and with NO . cytochrome P-420 prepared by reaction of hepatic microsomes of phenobarbital-treated rats with NO. By contrast, these same enzyme preparations did not respond to NO or catalase alone. Addition of hematin or hemoglobin plus a reducing agent to purified guanylate cyclase restored enzyme responsiveness to NO and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), but not to NaN3 or NH2OH. Responses to the latter agents were restored by catalase and potentiated by a H2O2-generating system. Formation of the NO . catalase complex was evident by ESR spectroscopy in test solutions containing NaN3 or nh2oh, catalase, and a glucose-glucose oxidase, H2O2-generating system. The presence of NO . catalase correlated well with the ability of test solutions to activate purified guanylate cyclase. These results provide evidence for catalase-dependent NO generation from NaN3 and NH2OH under conditions leading to guanylate cyclase activation. Preformed NO . hemoglobin or NO . cytochrome P-420 also activated heme-deficient partially purified guanylate cyclase. The ability of several preformed NO . heme protein complexes, but not NO, to stimulate heme-deficient guanylate cyclase supports the concept that formation of the paramagnetic nitrosyl . heme complex, mediated by either enzymatic or nonenzymatic reactions, is a common and essential step in the process by which NO or NO-forming compounds activate guanylate cyclase. In the absence of the NO ligand, both hemoglobin and catalase suppress the stimulatory effects of the corresponding NO . heme proteins on guanylate cyclase. Release of each heme protein from the NO . heme protein complex occurs more rapidly under aerobic compared to anaerobic conditions. However, hemoglobin is approximately 2000 times more effective as an inhibitor of NO . hemoglobin stimulation of guanylate cyclase than is catalase as an inhibitor of NO . catalase action. This finding may explain the more pronounced decline in the rate of cGMP generation in air in the presence of NO . hemoglobin compared to NO . catalase. The results imply that guanylate cyclase responses to activators that can form NO are determined by both the stimulatory activity of the endogenous heme acceptors of NO and the relative inhibitory effects of the unliganded heme proteins present.

Anaerobiosis↗
PubMed1977

Penicillin-induced immunohemolytic anemia associated with circulating immune complexes.

Eleven days after administration of multiple penicillin analogs, a 55-year-old female developed a Coombs-positive hemolytic anemia. The patient's erythrocytes were coated with IgG, complement components (C4/C3) and her serum contained elevated 125I-Clq binding activity (a measure of the presence of immune complexes). Her serum, in the presence of fresh complement and penicillin, induced complement sensitization of normal erythrocytes. Immune complex-mediated complement activation and the haptene type of erythrocyte sensitization accounted for accelerated red blood cell destruction in this patient.

ABO Blood-Group System↗
PubMed1978

De novo development of membranous nephropathy in cadaver renal allografts.

Glomerulonephritis in transplant recipients often reflects recurrence of the immunopathogenetic mechanism causing the original renal disease. Membranous nephropathy (MN), a progressive immune complex mediated glomerular disease and the commonest cause of idiopathic nephrotic syndrome in adults, has been virtually unreported in transplant recipients. Two cases are reported here of typical MN (by clinical, light, immunofluorescent and electron microscopic criteria) developing de novo in the transplants of patients whose original diseases were anti-GBM nephritis and focal glomerular sclerosis. NM developed following episodes of viral hepatitis and renal infarction respectively. Possible mechanisms by which this lesion might develop in these patients are investigated and discussed. Chronic immune complex nephropathy (MN) can develop de novo in immunosuppressed transplant recipients apparently initiated by events in the post-transplant period.

Adolescent↗
PubMed2026

rRNA expansion segments mediate ribosome dimerization as a conserved stress response.

Inhibition of messenger RNA translation is a common feature in proteostatic stress cellular responses. Puromycin, a widely used compound for studying translation, disrupts protein synthesis by mimicking the 3' end of aminoacyl-transfer RNAs. Despite its extensive use as a research tool to probe the connection between translation activity and various physiological and pathological states, the cellular response associated with puromycin-induced translation stress remains incompletely understood. Here, we used electron tomography and topology analysis to define the effects of puromycin on the translation machinery in situ. We show that puromycin-treated neuronal cells exhibit an accumulation of eIF5A-bound ribosomes in a translationally inactive "idle" state, and thereby defining a broader role of eIF5A in ribosome homeostasis. Additionally, the idle ribosomes formed dimeric complexes mediated by ribosomal RNA expansion segments, suggesting an evolved mechanism involving these regions in translational hibernating and protecting idle ribosomes. We further show that the hibernating disome formation is not unique to puromycin administration but represents a conserved mechanism as a response to different cellular stressors including endoplasmic reticulum stress and amino acid depletion. Collectively, our findings illuminate distinct states of mammalian ribosome hibernation and dimerization, providing new insights into the relationship of cellular stress and the dynamic regulation of ribosomal activity.

Ribosomes↗
PubMed1979

Membranous glomerulonephritis in congenital syphilis.

The glomerulonephritis of congenital syphilis is thought to be immune-complex mediated. We describe a case of C. S. in whom the only manifestation was a glomerulonephritis. Immunopathogenic studies allowed the identification of treponemal antigen in glomeruli. The elution of immunoglobulins from renal tissue showed that glomerular deposits contained antitreponemal antibodies. Cryoglobulins with antitreponemal activity were also isolated from the patient's serum.

Antibodies, Bacterial↗
PubMedDate not supplied

Pharmacological aspects of immune reactions.

"Immunopharmacology" evolved as a field of research in its own right when it was appreciated that pharmacological methods can contribute to the understanding of immune mechanisms on the one hand or can be used to influence or even control immune reactions at all stages and levels. The best studied subjects of immunopharmacology are release and effects of the chemical mediator substances which are responsible for the reactions of effector cells thus causing the clinical symptoms in allergic or inflammatory diseases. In the type I allergic (anaphylactic) reactions the primary target cells are tissue mast cells or basophil granulocytes which discharge their granular contents upon interaction of immunoglobulin E fixed to their surface with the specific antigen or--in the anaphylactoid reaction--upon stimulation with an appropriate chemical substance (so-called histamine-liberator). In both cases the stimulus leads to an influx or intracellular shift from one compartment to another of calcium ions, which in turn trigger membrane fusion and degranulation. This process can vary from a physiological secretion (in the case of IgE-antigen-interaction) to a pathological cytolysis (in the case of high concentrations of activated complement components or other chemical histamine releasers). As long as it is secretory it is subject to vegetative and hormonal modulation and regulation, mainly by catecholamines and other substances which increase cellular cAMP levels or inhibit calcium fluxes. Although cholinergic stimuli under certain circumstances induce mast cell degranulation and histamine release no definite role has yet been established for cholinergic mechanisms in type I allergies. Type II (Cytotoxic) and type III (immune complex mediated) allergies share the complement requirement. As far as mast cells and basophils are involved in such reactions their sensitivity towards pharmacological modulators is comparable to reactions induced by chemical histamine releasers. Otherwise these types of allergic reactions are dominated by phenomena of general inflammation. In those mainly cytotoxic effects of lipases and hydrolases are involved. cAMP active agents have, therefore, only limited modulating effects and steroid hormones are more effective in inhibiting the acute lesions in type II and III allergies. Only during the last decade the involvement of chemical mediators in type IV (cellular immunity) allergic reactions has been appreciated. 26 different factors called lymphokines have been discovered and classified as mediators of cellular immune reactions. However, rather little is yet known about their chemical nature and about the influence of drugs on their production or action.

Allergens↗
PubMed1979

A Golgi and electron microscopic study of a dysplastic gangliocytoma of the cerebellum.

The fine structure of a dysplastic gangliocytoma of the cerebellum is studied by means of the Golgi method and electron microscopic examination. Thick proximally unbranched dendrites with terminal arborizations and varicose inflorescences in the form of a basket are stained with the Golgi method. Axons are always descendant to the inner myelinated layer of the redistributed cerebellar cortex, while ascendant collaterals are observed at the level of the outer myelinated layer. Clear and dense-core vesicles and synapses are common in the cellular profiles under electron microscopic examination. From these data and because of the lack of putative connections through the white matter, an organized, self-regulated, catecholamine-mediated complex may be postulated.

Axons↗