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At least 973 records · Page 54Linked to original sources
PubMed1995

A case of Henoch-Schönlein purpura in disseminated tuberculosis.

Tuberculosis is still a common disease, even in some parts of developing countries. Although its major impact is pulmonary, the tuberculosis is actually a disseminated disease. An unusual form of renal involvement of tuberculosis is glomerulonephritis, as a part of systemic vasculitis, Henoch-Schoenlein Purpura (HSP). A 41-year-old man, being treated with antituberculous agents for pulmonary tuberculosis, was transferred to our hospital because of newly developed generalized purpura and pretibial edema. Renal manifestations were proteinuria and hematuria. Renal biopsy disclosed interstitial chronic granulomatous inflammation with caseous necrosis and strong nodular mesangial Ig A deposit, along with trace granular Ig G deposition and perivascular C3 deposit. Skin lesions were non-thrombocytopenic palpable purpurae, proved leukocytoclastic vasculitis by skin biopsy. All clinical symptoms and signs were relieved by antituberculous medication. We concluded that disseminated tuberculosis might be a cause of HSP, an immune complex mediated disease.

Adult↗
PubMed1988

Early signal transduction by the antigen receptor without commitment to T cell activation.

The T lymphocyte antigen-receptor complex mediates antigen-specific cell activation, at least in part, through the production of inositolphospholipid-derived second messengers. Little is known about how second messenger events, typically measured within minutes of ligand binding, eventually lead to distal biologic responses such as expression of lymphokine genes. Several monoclonal antibodies directed against the receptor complex were tested for their ability to elicit transmembrane signaling in the parental Jurkat line and in a somatic mutant (J.CaM1) with a deficient receptor function. One antibody elicited substantial early Ca2+ mobilization responses in both cells but was unable to promote expression of the interleukin-2 gene in J.CaM1. In J.CaM1 there was a diminished production of phosphatidylinositol second messengers, and the elevation in intracellular free Ca2+ was transient. Thus, short-term Ca2+ mobilization does not always indicate complete signal transmission and lead to a full cellular response.

Calcium↗
PubMed2005

Assays for proteasome assembly and maturation.

The 20S proteasome is a complex multisubunit protease that is present in all phylae of life. Eukaryotic 26S proteasomes, which are composed of 20S proteasomes and 19S activator complexes, mediate the degradation of ubiquitylated proteins. Biogenesis of proteasomes involves a coordinated expression of proteasome genes as well as numerous assembly and maturation steps. Activation of proteolytic sites occurs via autocatalytic processing of the N-terminal propeptides of beta subunits. This process is coupled to the dimerization of half-proteasome precursor complexes and, in eukaryotes, requires the presence of the Ump1 maturation factor to occur efficiently. After activation of proteolytic sites the encased Ump1 is degraded rapidly. Here we describe methods that track assembly and maturation of proteasomes in bacteria and eukaryotic cells. Assembly intermediates and mature forms of the proteasome present in cells at steady state are analyzed by gel filtration and immunoblotting after sodium dodecyl sulfate (SDS)- and native polyacrylamide gel electrophoresis (PAGE). The kinetics of proteasome assembly is followed by pulse chase detection of beta subunit maturation or of Ump1 degradation.

Adenosine Triphosphatases↗
PubMed1991

Differential effects of oestrogen in murine lupus: acceleration of glomerulonephritis and amelioration of T cell-mediated lesions.

Oestrogen is known to accelerate glomerulonephritis and autoantibody production in human and murine systemic lupus erythematosus (SLE). In this study we demonstrate that treatment of castrated autoimmune MRL +/+ mice with physiological doses of oestrogen results in enhanced immunoglobulin and autoantibody production as well as increased deposition of IgG in renal glomeruli. Accelerated development of glomerulonephritis was also evident from the increase of albuminuria. Interestingly, in contrast to these deteriorative effects of oestrogen on immune complex-mediated disease we now show that the lymphocytic infiltrations in the submandibular glands and perivascular lesions in the kidneys were significantly diminished after exposure to oestrogen. This remarkable impact of physiological oestrogen levels on the outcome of SLE in MRL +/+ mice is postulated to be the result of a differential effect on T and B cell-mediated immune responses.

Animals↗
PubMed1999

H-transfer rates in ion-neutral complexes versus those in intact aliphatic ions

The relative rates of H-transfer between partners in ion-neutral complexes were compared with those in intramolecular rearrangements using results of first differential photoionization mass spectrometry measurements. Complex-mediated H-transfers are inferred to have rates of the same order as those for intramolecular hydrogen rearrangements, suggesting a similar range of motion of the reactive sites in both types of reactions. It is also concluded that at their fastest H-transfers take place between the partners in ion-neutral complexes within at most the time of several rotations of the partners in the complexes. Copyright 1999 John Wiley & Sons, Ltd.

Journal Article↗
PubMed1990

Role of circulating immune complexes in the immunopathogenesis of silicosis.

The sera of 19 silica-dust-exposed subjects and of an equal number of age-, sex- and socioeconomic-strata-matched controls were analysed for antinuclear factor, rheumatoid factor, C-reactive protein, immunoglobulins G, M, A, and complement C3 and C4. Circulating immune complexes were also precipitated in all subjects and their immunoglobulin and complement C3 and C4 were estimated. Silica-exposed subjects were divided into two groups depending upon the radiological findings and it is suggested that IgA plays an important role in the immunopathogenesis of the disease and that lung changes could be due to the immune-complex-mediated mechanisms utilizing an alternative complement pathway.

Adolescent↗
PubMed1995

Streptococcus-mutans-induced nephritis in rabbits: rheumatoid factors and nephritogenicity.

The pathogenesis of streptococcus-induced nephritides (SIN) involves immune complex-mediated inflammation; however, specific mechanisms are still poorly understood. Using preparations of two strains of Streptococcus mutans (SM) in attempts to induce SIN in rabbits, one preparation was strongly and the other virtually not nephritogenic. The non-nephritogenic preparation provided a negative control for our studies. Streptococcal components were present in circulating immune complexes (CIC) as well as in tissue-bound immune complexes (TIC), especially early in the disease. CIC and TIC also contained rheumatoid factors (RF), which tended to predominate in late stages of the disease. The nephritogenic and the non-nephritogenic preparations of SM shared the same major tissue-binding components and induced similar titers of antimicrobial antibodies, but differed significantly in their ability to induce CIC and RF. It is proposed that kidney-binding microbial components, antimicrobial antibodies and high serum concentration of RF are necessary and sufficient determinants for the pathogenesis of SIN in this rabbit model.

Animals↗
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↗
PubMed1984

Estrogen immunosuppression is regulated through estrogenic responses in the thymus.

Previous studies have clearly established that physiologic and pharmacologic levels of estrogens modulate immunologic responses that result in simultaneous activation of the reticuloendothelial system and depression of cell-mediated immunity. The mechanisms of estrogen immunoregulation were examined in adult female mice administered pharmacologic levels of exogenous estrogens. Evaluation of steroidal and nonsteroidal compounds with varying degrees of estrogenicity (i.e., uterotrophic activity) provided evidence that their immunotoxicity, for the most part, correlates with estrogenicity. The mechanisms responsible for these effects appear to be complex, mediated through a direct chemical interaction with lymphoid target cells, as well as with nonlymphoid tissue, resulting in the release of soluble immunoregulatory factors. The latter phenomenon was examined in detail and it appears to constitute a regulatory factor(s) produced by thymic epithelium in response to an estrogen stimulus. This response is not only estrogen specific but may involve specific binding to estrogen receptors or receptor-like structures present in cytosol preparations from thymic epithelial cells.

Animals↗
PubMed1997

Design, synthesis, and characterization of a cationic peptide that binds to nucleic acids and permeabilizes bilayers.

We have designed a cationic amphipathic peptide, KALA (WEAKLAKALAKALAKHLAKALAKALKACEA), that binds to DNA, destabilizes membranes, and mediates DNA transfection. KALA undergoes a pH-dependent random coil to amphipathic alpha-helical conformational change as the pH is increased from 5.0 to 7.5. One face displays hydrophobic leucine residues, and the opposite face displays hydrophilic lysine residues. KALA-mediated release of entrapped aqueous contents from neutral and negatively charged liposomes increases with increasing helical content. KALA binds to oligonucleotides or plasmid DNA and retards their migration in gel electrophoresis. It displaces 50% of ethidium bromide from DNA at a charge ratio (+/-) of 0.9/1. In cultured cells, KALA assists oligonucleotide nuclear delivery when complexes are prepared at a 10/1 (+/-) charge ratio. KALA/DNA (10/1)(+/-) complexes mediate transfection of a variety of cell lines. The KALA sequence provides a starting point for a family of peptides that incorporate other functions to improve DNA delivery systems.

Amino Acid Sequence↗
PubMed1986

Focal cerebral vasculitis associated with circulating immune complexes and brain irradiation.

In this report we describe a patient with a benign glioma treated with surgery and radiation. After a period of stability he developed subacute bacterial endocarditis, and deteriorated neurologically. Computed tomographic scans did not show recurrent tumor. An angiogram showed vasculitis restricted to the previously irradiated area. Secondary to subacute bacterial endocarditis was the presence of high levels of circulating immune complexes. His neurological status was unchanged after antibiotics, but improved after treatment with dexamethasone. We interpret the clinical course as an immune-complex-mediated vasculitis superimposed on a subclinical radiation vasculitis. This case supports the hypothesis that immune mechanisms may be involved in delayed radiation injury to the nervous system.

Adult↗
PubMed1997

Liver inflammation and acute respiratory distress syndrome in a patient receiving hepatitis B vaccine: a possible relationship?

We describe a patient in whom clinical evidence of liver and lung dysfunction developed after he received the second dose of recombinant hepatitis B vaccine, despite no serologic evidence of viral hepatitis. However, liver biopsy specimens demonstrated both surface antigens and core antigens, possibly indicating silent hepatitis B virus infection. A search for an infective etiology for the patient's subsequent clinical deterioration in lung function did not yield pathogens: postmortem examination revealed evidence of immune complex-mediated organ injury in the liver, lungs, and kidneys.

Antigen-Antibody Complex↗
PubMed1986

Bleeding time in hemophilia A: potential mechanisms for prolongation.

Prolongation of bleeding time has been previously observed in hemophilia, although no cause has been elucidated. We measured bleeding time, platelet aggregation, nucleotide release, and thromboxane B2 (TXB2), plasma 6-keto-PGF 1 alpha, platelet-associated IgG (PAIgG), and circulating immune complexes in 31 unselected patients with severe hemophilia A and in 17 controls. In 85% of patients with hemophilia A, the bleeding time was greater than 2 SD above the control level (greater than 8 minutes). Sixty-six percent of patients with hemophilia A had circulating immune complexes, and there was a striking relationship between the presence of these complexes and prolonged bleeding time. Plasma 6-keto-PGF 1 alpha levels were significantly elevated in the patient group, and correlated with bleeding time changes. Platelet aggregation and nucleotide release were normal in the patients with hemophilia, although reduced platelet TXB2 biosynthesis was noted in 26%. No correlation was demonstrated between bleeding time and impairment of platelet TXB2 formation. Seventy-two percent of the patients with hemophilia A had elevated levels of PAIgG, and an inverse relationship between PAIgG and platelet count was observed. No relationship was noted between platelet count and bleeding time. This study indicates that the majority of patients with hemophilia A have prolonged bleeding times. The close correlation between bleeding time, plasma 6-keto-PGF 1 alpha levels, and the presence of circulating immune complexes suggests a role for immune complex-mediated defects in vascular function as the basis for bleeding time prolongation.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Immune complex induced glomerular lesions in C5 sufficient and deficient mice.

The role in the pathogenesis of immune complex-mediated glomerulonephritis of C5 or some terminal complement component dependent upon C5 for activation was explored in a congenic strain of C5 sufficient (NSN) and C5 deficient (OSN) mice. When these mice were given daily injections of heterologous protein, horse apoferritin (HAF), there were profound differences between the strains in the development of glomerulonephritis and renal dysfunction. When NSN and OSN mice produced low levels of anti-HAF, NSN mice developed extensive glomerular deposits of HAF and immune reactants and a mild proliferative glomerulonephritis. In contrast, comparable OSN mice developed only trace mesangial localization of HAF and no glomerular lesions by light microscopy. When NSN and OSN mice produced high levels of anti-HAF, both strains had equivalent glomerular immune deposits; however, NSN mice developed a severe necrotizing and crescentic glomerulonephritis, while OSN mice had much less glomerular injury. Compared to OSN mice, these NSN mice also had much more severe tubulointerstitial injury, and significantly higher serum creatinine levels. Thus, in this experimental model, the absence of C5 resulted in reduced glomerular immune complex localization when there were small amounts of circulating immune reactants; and in markedly reduced glomerular leukocyte influx, necrosis and crescent formation, when large amounts of immune reactants have localized in glomeruli. These effects could be mediated by C5 (such as C5a) or by some terminal complement component(s) dependent upon C5 for activation.

Age Factors↗
PubMed1990

IgG subclass antibody production in human serum sickness.

The role of IgG-subclass antibodies in the spectrum of immunologic disorders has not yet been fully defined. In an attempt to understand its role in an immune complex-mediated disease, we studied patients who developed serum sickness (SSX) after treatment with an equine-derived immunoglobulin, antithymocyte globulin (ATG), for bone marrow failure. The predominant IgG subclass produced was IgG1, representing nearly 80% of all IgG anti-ATG activity present. The appearance of IgG anti-ATG antibodies and C1q-containing immune complexes was closely correlated with symptoms of SSX. Although other antibody isotypes were present and may have contributed to the patients' symptoms, it is evident that IgG1 is the predominant IgG subclass produced in human SSX caused by a heterologous protein.

Adolescent↗
PubMed2000

The RAG proteins and V(D)J recombination: complexes, ends, and transposition.

V(D)J recombination proceeds through a series of protein:DNA complexes mediated in part by the RAG1 and RAG2 proteins. These proteins are responsible for sequence-specific DNA recognition and DNA cleavage, and they appear to perform multiple postcleavage roles in the reaction as well. Here we review the interaction of the RAG proteins with DNA, the chemistry of the cleavage reaction, and the higher order complexes in which these events take place. We also discuss postcleavage functions of the RAG proteins, including recent evidence indicating that they initiate the process of coding end processing by nicking hairpin DNA termini. Finally, we discuss the evolutionary and functional implications of the finding that RAG1 and RAG2 constitute a transposase, and we consider RAG protein biochemistry in the context of several bacterial transposition systems. This suggests a model of the RAG protein active site in which two divalent metal ions serve alternating and opposite roles as activators of attacking hydroxyl groups and stabilizers of oxyanion leaving groups.

Animals↗
PubMed1998

Bilateral anterior ischemic optic neuropathy following influenza vaccination.

Optic neuritis is an occasional complication of vaccination. Visual loss can be unilateral or bilateral, and most patients recover substantially without treatment. The presumptive mechanism is an immune-mediated demyelinating injury of the optic nerve. We report two patients who had permanent visual loss following influenza vaccination. Their pattern of visual loss, segmental optic disc changes, and failure of visual recovery were atypical for demyelinating optic neuritis and reminiscent of a primary ischemic injury to the optic nerve. We speculate that an immune complex-mediated vasculopathy following vaccination can cause anterior ischemic optic neuropathy. Clinicians should be aware of this entity because of the less favorable prognosis for visual recovery in these cases.

Blindness↗
PubMed1999

Elongator, a multisubunit component of a novel RNA polymerase II holoenzyme for transcriptional elongation.

The form of RNA polymerase II (RNAPII) engaged in transcriptional elongation was isolated. Elongating RNAPII was associated with a novel multisubunit complex, termed elongator, whose stable interaction was dependent on a hyperphosphorylated state of the RNAPII carboxy-terminal domain (CTD). A free form of elongator was also isolated, demonstrating the discrete nature of the complex, and free elongator could bind directly to RNAPII. The gene encoding the largest subunit of elongator, ELP1, was cloned. Phenotypes of yeast elp1 delta cells demonstrated an involvement of elongator in transcriptional elongation as well as activation in vivo. Our data indicate that the transition from transcriptional initiation to elongation involves an exchange of the multiprotein mediator complex for elongator in a reaction coupled to CTD hyperphosphorylation.

Cell Division↗