Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Mediator Complex”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,531 records · Page 85Linked to original sources
PubMedDate not supplied

Type III mixed cryoglobulinemia associated with digital necrotic ulcer successfully treated with intermittent intravenous pulse cyclophosphamide--a case report.

Cryoglobulinemic vasculitis is an immune complex-mediated vasculitis predominantly affecting small vessels. The authors report an 18-year-old woman with painful digital necrotic ulcer due to type III cryoglobulinemic vasculitis on the basis of systemic lupus erythematosus. Serum protein electrophoresis and immunoelectrophoresis demonstrated a polyclonal peak of the immunoglobulin Glambda (IgGlambda) and IgMlambda type. The patient was successfully treated with intermittent intravenous pulse cyclophosphamide.

Adolescent↗
PubMed1990

Is there an allergic synovitis?

Nine patients had attacks of joint pain and sometimes swelling precipitated by certain foods or associated with allergic manifestations. All were atopic subjects--three having strong evidence of Type I (immediate) allergy and three 'urticarial arthralgia', in which attacks of severe urticaria and joint pain occurred coincidentally. Food allergy appeared to be responsible for the joint symptoms in three patients and in one it was possible to precipitate swelling of a knee due to synovitis with effusion by drinking milk a few hours beforehand, the synovial fluid having mildly inflammatory features and a relatively high eosinophil count. It seems that allergy is an occasional cause of episodic rheumatic pain or synovitis in certain atopic patients, whether or not they have an underlying arthritis. These are usually Type I hypersensitivity reactions, though it is thought that some food-allergic reactions are immune complex-mediated.

Adult↗
PubMed1982

An epizootic of diffuse glomerulonephritis in white perch (Roccus americanus) from a heavily polluted industrial basin in Lake Ontario.

Examination of 43 white perch from a heavily polluted water basin showed all had severe diffuse glomerulonephritis. There were fibrinoid necrosis of tuft vessels, especially the afferent and efferent arterioles, and thickened basement membranes which ultrastructurally contained dense deposits in a subendothelial location. None of these lesions was found in white bass, a closely related species, from the same source nor in white perch from other relatively nonpolluted sites in Lake Ontario or Lake Erie. This is a dramatic example of a rare lesion in fish and possible represents an immune-complex mediated response to an environmental pollutant.

Animals↗
PubMed1994

Acute interstitial pneumonia in mink kits inoculated with defined isolates of Aleutian mink disease parvovirus.

The present study addressed the causal role of Aleutian mink disease parvovirus (ADV) in acute interstitial pneumonia in mink kits. All the examined isolates of ADV caused interstitial pneumonia in newborn kits, although the severity of disease and the mortality varied. These findings indicate that ADV is the direct causal agent of this disease in mink kits and that cofactors, which could have been present in the original ADV-K isolate, do not play a role. Acute interstitial pneumonia characterized by hypertrophy and hyperplasia of alveolar type II cells, intranuclear viral inclusions, interstitial edema, and hyaline membrane formation was experimentally reproduced in mink kits infected as newborns with five different isolates of ADV. Four hundred forty-nine newborn mink kits were included in the study, of which 247 were necropsied. The lesions caused by the different isolates were indistinguishable by histopathologic examination, but the incidence (50-100%) and severity (mortality of 30-100%, n = 218) of disease among the mink kits varied. Also, the content of ADV antigens in the lungs of infected kits varied among the groups. According to these features, the examined isolates could be placed in groups of high and low virulence. ADV-K, ADV-Utah I, and ADV-DK were in a highly virulent group producing a mortality of 90-100% (n = 110) in mink inoculated as newborns. ADV-GL and ADV-Pullman belonged to a group of low virulence, with an incidence of clinical disease of 50-70% and a mortality of approximately 30-50% (n = 118) in kits inoculated as newborns. The mortality in the control group receiving a mock inoculum was around 12% (n = 34). The period from infection to development of fatal disease varied from approximately 12 days for the highly virulent isolates up to around 20 days for the isolates of low virulence. The 107 mink kits that survived inoculation with ADV as newborns developed lesions typical of classical Aleutian disease irrespective of the ADV isolate used. The lesions consisted of chronic immune complex-mediated glomerulonephritis and infiltrations with mononuclear cells, including plasma cells in lung, liver, spleen, kidney, mesenteric lymph node, and intestine. Surviving kits also had hypertrophy of the bronchus-associated lymphoid tissue and focal subpleural, intraalveolar accumulations of large cells with foamy cytoplasm, so-called lipid pneumonia.

Acute Disease↗
PubMed1994

Autoimmunity and heavy metals.

This brief review is focused on those heavy metals (cadmium, gold and mercury) that have strong associations with autoimmunity. Cadmium treatment of rats and mice results in autoimmune responses that vary with species and inbred strain of animals. However, there is no solid evidence demonstrating that the renal pathology observed in humans exposed to cadmium has an autoimmune pathogenesis. More clear-cut are the autoimmune effects of preparations containing gold salts, that have been widely used in the treatment of rheumatoid arthritis. Gold may cause autoimmune thrombocytopenia, immune complex-mediated glomerulonephritis and other autoimmune disorders. Similarly, there is solid evidence that mercury can induce autoimmune disease both in humans and experimental animals. The lessons to be derived from metal-induced autoimmunity relate to structure-activity relationship, pathogenesis, etiology and genetics. They probably apply to xenobiotic-induced autoimmune disease in general.

Animals↗
PubMed1996

Primary antiphospholipid syndrome evolving into systemic lupus erythematosus.

A young woman had a history of spontaneous venous thromboembolic disease which recurred on several occasions after cessation of treatment with oral anticoagulants. The presence of antiphospholipid antibodies (lupus anticoagulant and a high titre of lgG class anticardiolipin antibodies) in the absence of other clinical and serological features of systemic lupus erythematosus (SLE) confirmed a diagnosis of primary antiphospholipid syndrome (PAPS). Antinuclear antibodies (ANA) were positive (1:1280; speckled pattern). Twelve years after the first thrombotic episode she fulfilled criteria for the classification of SLE (antinuclear antibodies, platelet count < 100 x 10(9)/l, anti-dsDNA antibodies, Coombs' positive haemolytic anaemia). She suffered a myocardial infarction while adequately anticoagulated and developed polyarthritis and immune complex-mediated nephritis over the next 3 years. This case history supports suggestions made by others that a strongly positive ANA test in a patient diagnosed with PAPS may be a harbinger for the development of SLE. Such evolution can take place over more than 10 years.

Adult↗
PubMed2003

Functional phenotype of phosphoinositide 3-kinase p85alpha-null platelets characterized by an impaired response to GP VI stimulation.

Phosphoinositide 3-kinases (PI3Ks), a family of lipid kinases comprising 3 classes with multiple isoforms, have been shown to participate in different phases of platelet signaling. To investigate the roles that enzymes play in platelet function in vivo and determine which isoforms are important for particular signaling events, we analyzed platelet function of gene knockout mice deficient in the p85alpha regulatory subunit of heterodimeric class IA PI3K. The kinase activity of p85alpha-/- platelets was only 5% of the activity of platelets from wild-type littermates. Platelet aggregation induced by adenosine diphosphate (ADP), thrombin, U46619, phorbol 12-myristate 13-acetate (PMA), or botrocetin was not defective in p85alpha-/- mice, compared with wild-type animals. In contrast, aggregation induced by collagen and collagen-related peptide (CRP) was partially but readily impaired in p85alpha-/- mice. Both P-selectin expression and fibrinogen binding in response to CRP were also decreased to a similar extent in p85alpha-/- platelets. Platelets from p85alpha-/- mice appeared to spread poorly over a CRP-coated surface with intact filopodial protrusions. Significant attenuation of CRP-induced tyrosine phosphorylation in known PI3K effectors such as Btk, Tec, PKB/Akt, and phospholipase Cgamma2 were observed with p85alpha-/- platelets, whereas no alteration was noted in upstream molecules of Syk, LAT, and SLP-76. Considered as a whole, these results provide the first genetic evidence that PI3K p85alpha plays a significant role in platelet function, almost exclusively in the glycoprotein (GP) VI/Fc receptor gamma chain complex-mediated signaling pathway.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2006

Abulia following penetrating brain injury during endoscopic sinus surgery with disruption of the anterior cingulate circuit: case report.

BACKGROUND: It is common knowledge that the frontal lobes mediate complex human behavior and that damage to these regions can cause executive dysfunction, apathy, disinhibition and personality changes. However, it is less well known that subcortical structures such as the caudate and thalamus are part of functionally segregated fronto-subcortical circuits, that can also alter behavior after injury. CASE PRESENTATION We present a 57 year old woman who suffered penetrating brain injury during endoscopic sinus surgery causing right basal ganglia injury which resulted in an abulic syndrome. CONCLUSION: Abulia does not result solely from cortical injury but can occur after disruption anywhere in the anterior cingulate circuit--in the case of our patient, most prominently at the right caudate.

Akinetic Mutism↗
PubMed2000

IFN-gamma transgenic mice: clues to the pathogenesis of systemic lupus erythematosus?

Transgenic mice overexpressing IFN-gamma in the epidermis develop an inflammatory skin disease resembling cutaneous lupus erythematosus shortly after birth. By 3 months of age, most female transgenics develop a lupus-like syndrome characterised by production of IgG anti-dsDNA, antihistone and antinucleosome autoantibodies. The autoantibodies are nephritogenic, with one-third of females developing a severe immune complex mediated glomerulonephritis. Analysis of these transgenics suggests that pathogenic autoantibodies arise via an antigen-driven T-cell-dependent mechanism with apoptotic keratinocytes acting as a potential source of autoantigen. The mechanism of autoantibody production in IFN-gamma transgenics may be relevant to human lupus and is consistent with a central role for cutaneous T cells in the pathogenesis of systemic lupus erythematosus in man.

Animals↗
PubMed2003

CEACAM1 is a potent regulator of B cell receptor complex-induced activation.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1, CD66a) is a member of the immunoglobulin (Ig) superfamily, previously characterized as an adhesion and signaling molecule in epithelial, endothelial, and hematopoietic cells. Here, we show that the CEACAM1 isoform expression pattern is different in nonactivated and activated primary mouse B lymphocytes and that CEACAM1 influences B cell receptor complex-mediated activation. A CEACAM1-specific monoclonal antibody strongly triggered proliferation of mouse B cells when combined with surface IgM cross-linking. However, anti-CEACAM1 was not mitogenic when added alone. The proliferation was more pronounced and lasted longer as compared with other activators of B cells, such as anti-IgM in the presence of interleukin-4 or lipopolysaccharide. A similar, costimulatory effect was exerted by CEACAM1-expressing fibroblasts, indicating that homophilic CEACAM1-CEACAM1 cell-mediated binding is the physiological stimulus for CEACAM1-triggered B cell signaling. The anti-CEACAM1/anti-IgM-activated cells aggregated in a lymphocyte function-associated antigen-1-dependent manner. Furthermore, cells that were activated by anti-CEACAM1/anti-IgM secreted Ig but did not go through Ig class-switching. Anti-CEACAM1 induced phosphorylation of c-Jun N-terminal kinase (stress-activated protein kinase) but did not activate the extracellular signal-regulated kinase or p38 mitogen-activated protein kinases.

Animals↗
PubMed2004

Tumour necrosis factor and other proinflammatory cytokines in systemic lupus erythematosus: a rationale for therapeutic intervention.

Systemic lupus erythematosus (SLE) is an autoantibody and immune complex mediated disease. However, it is the ensuing inflammatory process that leads to irreversible organ damage. In fact several murine models of SLE suggest that this inflammatory organ damage can be prevented even in the presence of autoantibodies. Given data from experimental models as well as from patients, proinflammatory cytokines including tumour necrosis factor (TNF) alpha apparently play a significant role in the inflammatory process, but may have immunoregulatory functions at the same time. Therefore, anti-TNF alpha therapy may constitute an interesting candidate approach for treating SLE inflammatory organ disease, but potentially at the cost of increased autoantibody formation. Clinical trials will be required to answer whether TNF alpha blockade fulfils this hope with an acceptable safety profile. Interferon (IFN)-gamma, interleukin (IL)-18, IL-6 and possibly IL-1 are increased in SLE and likewise involved in the inflammatory process. Specific therapeutic agents for blocking these cytokines should be available in the near future.

Animals↗
PubMed2004

Hypocomplementemia in systemic lupus erythematosus and primary antiphospholipid syndrome: prevalence and clinical significance in 667 patients.

The objective of the study was to analyse the prevalence and clinical significance of hypocomplementemia in a large series of patients diagnosed either with systemic lupus erythematosus (SLE) or with primary antiphospholipid syndrome (APS) and its association with the main clinical, hematological and immunological features of these diseases. Between 1992 and 2003, complement determinations (C3 and C4 levels, CH50 activity) were performed in 597 consecutive patients diagnosed with SLE (530 women and 67 men, mean age 32.6 years) and 70 with primary APS (57 women and 13 men, mean age 38.7) visited in our department. Complement determinations are routinely made at the first visit of patients and yearly during the follow-up. SLE and primary APS were diagnosed according to current classification criteria. Hypocomplementemia was detected in 371 (62%) of SLE patients. Compared with patients with normal complement values, those with hypocomplementemia showed a higher prevalence of female gender (P < 0.001), fever (P = 0.021), nephropathy (P < 0.001), cutaneous vasculitis (P = 0.023), positive anti-dsDNA antibodies (P = 0.012) and cryoglobulinemia (P < 0.001). In addition, patients with hypocomplementemia showed a higher prevalence of APS-related features such as hemolytic anemia (P = 0.001) and antiphospholipid antibodies (P < 0.001). Hypocomplementemia was prospectively related to accumulated hospitalization in SLE patients but not with the accumulated number of lupus flares or with the survival after follow-up of five years. In contrast, 33 (47%) patients with primary APS presented low complement values, which were associated with a higher prevalence of livedo reticularis (P = 0.022), thrombocytopenia (P = 0.004), lupus anticoagulant (P = 0.013), positive IgM-aCL (P = 0.039), positive ANA (P = 0.002) and anti-dsDNA (P = 0.046). The diagnostic value of hypocomplementemia in patients with SLE is based on the association with disease activity, immune-complex mediated manifestations (glomerulonephritis, cryoglobulinemia) and APS-related features (livedo reticularis, hemolytic anemia and aPL). Hypocomplementemia was found in nearly half of patients with primary APS, and was associated with some APS features (livedo reticularis, thrombocytopenia, aPL) but also with SLE-related immunological markers (ANA and anti-dsDNA), identifying a subset of patients with primary APS with a higher risk of evolving to SLE. These results clearly support the routine determination of complement factors in the clinical follow-up of patients with SLE and primary APS.

Adult↗
PubMed2004

Review of ACR renal criteria in systemic lupus erythematosus.

The American College of Rheumatology renal criteria require re-evaluation to incorporate recent advances in the classification of glomerulonephritidies. Renal biopsy is now common and safely performed by experienced nephrologists in community as well as academic settings. The optimal criterion is renal histopathology findings of an immune complex mediated glomerulonephritis as interpreted by an experienced pathologist employing accepted criteria. Renal biopsies should be analysed by routine histopathology, immunofluorescent and electron microscopy. Rating of activity and chronicity should be noted. Secondary criteria for patients unable to undergo renal biopsy includes a combination of findings. These include proteinuria, hypocomplementemia, elevated anti-dsDNA antibodies and an active urine sediment. Proteinuria is a nonspecific finding and, most importantly, can be associated with a number of comorbidities including diabetes, hypertension and atherosclerotic disease. Persistent proteinuria > 0.5 g per day or a spot protein to creatine ratio of > 0.5 should be accompanied by an additional feature supporting active lupus such as positive serologies (hypocomplementemia and/or elevated anti-dsDNA antibodies) and/or active urinary sediment. Similarly, active urinary sediment should be accompanied by the additional criterion of proteinuria to meet renal criteria. Decline in renal function is not a reliable criterion given the numerous medications, comorbidities and other clinical circumstances which may result in this feature.

Humans↗
PubMed2005

Relapse with transformation of lupus nephritis in a transplant kidney.

Lupus nephritis is a constellation of different renal histologies, characterized by an immune complex mediated glomerular disease. Histological transformation in lupus nephritis usually occurs from a mild mesangial proliferative glomerulonephritis to a more aggressive diffuse proliferative lesion. We present a case of relapsed systemic lupus erythematosus (SLE) in a renal transplant recipient in which there was a histological transformation from the original diffuse proliferative lupus nephritis in the native kidneys to a membranous lupus nephritis in the renal transplant.

Adult↗
PubMed2006

The renin-angiotensin system in lupus: physiology, genes and practice, in animals and humans.

Although multiple studies suggest a potential role for angiotensin II in inflammation, most were performed either in vitro or in animals with non-immune-complex-mediated diseases. Extrapolation of these findings to humans, particularly patients with lupus, which involves multiple immunoregulatory pathways, is unclear. In autoimmune-prone MRL/lpr mice, angiotensin-converting-enzyme (ACE) inhibition improved survival although to a lesser degree than cyclophosphamide and diminished the glomerular histopathologic damage, proteinuria, lymphoid hyperplasia, dermatitis, and hypergammaglobulinemia, with a reduction in TGF-beta1 and beta 2 expression in the kidneys and renal chemokine mRNA expression. Spleen levels of IL-4 and IL-10 were also reduced. Uncontrolled studies in patients with treatment-refractory lupus nephritis showed a significant reduction in proteinuria with ACE-inhibitors and Angiotensin receptor blockers treatment. The 'masking' effect of ACE-inhibitors should be taken into consideration, as an exacerbation of lupus nephritis may be missed when estimated by the magnitude of proteinuria, which is decreased by these treatments. No single ACE genotype was consistently associated with subsets of SLE patients. In retrospective analyses, ACE-inhibitor use predicted a favourable outcome in 94 cases of pauci-immune vasculitis. The attenuating effect of angiotensin II inhibitors on the progression of chronic renal disease is well recognized. The data on the role of this intervention in lupus is limited.

Angiotensin II↗
PubMed2004

Hormonal regulation of metastasis-associated protein 3 transcription in breast cancer cells.

Metastasis-associated protein 3 (MTA3) is a cell type-specific subunit of the Mi-2/NuRD transcriptional corepressor complex. In breast cancer cells, MTA3 and the Mi-2/NuRD complex mediate repression of Snail, a transcription factor that promotes epithelial to mesenchymal transitions. Thus, MTA3 functions to maintain a differentiated, epithelial status in breast cancer. Interestingly, in mammary epithelial cells, MTA3 biosynthesis requires both functional estrogen receptor (ER) and estradiol. Here we have investigated the molecular basis for estrogen and ER-dependent expression of MTA3 in breast cancer cells. Molecular dissection of the MTA3 promoter using transient transfection assays identified a composite element required for high-level transcription consisting of an SP1 site in close proximity to a consensus estrogen response element half-site. Depletion of either SP1 or ER-alpha by RNA interference led to loss of MTA3 transcript in multiple breast cancer cell lines, indicating a requirement for both transcription factors in expression of endogenous MTA3. The MTA3 gene thus joins a growing list of loci regulated by both SP1 and ER.

Base Sequence↗
PubMed1997

Dynamics of connexins, E-cadherin and alpha-catenin on cell membranes during gap junction formation.

We examined the dynamics of connexins, E-cadherin and alpha-catenin during gap-junction disassembly and assembly in regeneration hepatocytes by immunofluorescence microscopy, and immunogold-electron microscopy using SDS-digested freeze-replicas. The present findings suggest that during the disappearance of gap junctions most of the gap junction plaques are broken up into smaller aggregates, and then the gap junction proteins may be removed from the cell membrane, but some of the connexons or connexins remain dispersed in the plane of membrane as pure morphologically indistinguishable intramembrane proteins. Double-immunogold electron microscopy using a polyclonal antibody for connexins and a monoclonal antibody for E-cadherin or alpha-catenin revealed co-localization of these molecules at cell-to-cell contact sites during the reappearance of gap junction plaques. This implies that, at least in regenerating hepatocytes, the cadherin-catenin complex-mediated cell-to-cell contact sites act as foci for gap junction formation. In addition, connexin-immunoreactivity was also observed along tight junctional strands, suggesting that the gap junction may also form along the tight junctions.

Animals↗
PubMed1999

Mechanism of extracellular domain-deleted dominant negative cadherins.

The cadherin/catenin complex mediates Ca2+-dependent cell-cell interactions that are essential for normal developmental processes. It has been proposed that sorting of cells during embryonic development is due, at least in part, to expression of different cadherin family members or to expression of differing levels of a single family member. Expression of dominant-negative cadherins has been used experimentally to decrease cell-cell interactions in whole organisms and in cultured cells. In this study, we elucidated the mechanism of action of extracellular domain-deleted dominant-negative cadherin, showing that it is not cadherin isotype-specific, and that it must be membrane-associated but the orientation within the membrane does not matter. In addition, membrane-targeted cytoplasmic domain cadherin with the catenin-binding domain deleted does not function as a dominant-negative cadherin. Expression of extracellular domain-deleted dominant-negative cadherin results in down-regulation of endogenous cadherins which presumably contributes to the non-adhesive phenotype.

Cadherins↗