Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelial cell products, plasminogen activator inhibitor (PAI) and von Willebrand factor (vWF), were assayed in 25 patients with newly-diagnosed and untreated polymyalgia rheumatica (PMR), before and after three and 12 months of corticosteroid treatment. The mean values of PAI and vWF, and also the levels of acute phase reactants (erythrocyte sedimentation rate, fibrinogen, haptoglobin, orosomucoid, C-reactive protein) and platelet counts, were elevated in the active untreated disease. In contrast to the acute phase proteins, both PAI and vWF remained increased after three and 12 months of glucocorticoid treatment. This suggested an active vasculitis, despite a clinically-inactive disease. Particularly high levels of vWF both before and after glucocorticoid therapy were found in two patients who subsequently developed vascular complications during the follow-up period.
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PMID:Plasminogen activator inhibitor and von Willebrand factor in polymyalgia rheumatica. 161 95

One of our 7 patients (14%) with chronic cluster headache had an abnormal orbital phlebogram; this was significantly less than the 61% encountered in our 13 patients with active episodic cluster headache who had this test done. There were no pathologically increased values for serum haptoglobin or orosomucoid in our 9 patients with chronic cluster headache, again significantly less than in our 43 patients with active episodic cluster headache, 51 percent of whom had pathologically increased values of haptoglobin or orosomucoid. These inflammatory signs decreased after the episodic cluster headache was over. Episodic cluster headache we suggest to be due to temporary sympathicoplegia caused by venous vasculitis in the cavernous sinus region; chronic cluster headache we attribute to permanent post-inflammatory sympathicoplegia in the middle fossa.
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PMID:Orbital phlebography and signs of inflammation in episodic and chronic cluster headache. 1170 87

Interleukin 6 (IL-6) has manifold biological functions involved in the immune or inflammatory responses of the host to various stimuli. Here we asked whether IL-6 might be responsible for manifestations of Kawasaki disease (KD), such as immunoglobulin hypersecretion, lymphocyte activation and systemic vasculitis. IL-6 activity in the serum was determined by a sensitive colorimetric assay using an IL-6-dependent murine hybridoma clone. Usually sera from healthy or afebrile donors contained only negligible levels of IL-6 activity below the detection threshold of the assay. Importantly it was found that serum IL-6 was markedly elevated in all patients with acute KD. Serum levels of IL-6 activity gradually diminished during the course of the disease and reached undetectable or lower levels at the convalescent phase. However, such elevated levels of serum IL-6 activity were also observed in the majority of other febrile diseases, such as bacterial or viral infections, indicating that the appearance of IL-6 in the serum could generally occur in febrile or inflammatory disease conditions. Serum IL-6 activity correlated with serum concentrations of some acute phase proteins (APP), such as C-reactive protein, haptoglobin and alpha 1-acid glycoprotein, implying its role for modulating induction of APP in vivo. IL-6 is well known to be secreted by a variety of cell types. Further studies, including immunohistochemical analysis using anti-IL-6 antibody, will be necessary to examine whether the source of serum IL-6 in KD might be different from that seen in other diseases.
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PMID:The acute phase nature of interleukin 6: studies in Kawasaki disease and other febrile illnesses. 247 58

Angiogenesis is an important process in chronic inflammatory diseases. We observed that sera from patients with systemic vasculitis stimulated angiogenesis in an in vitro model using human umbilical vein endothelial cells cultured on a basement membrane (Matrigel) substrate. After 40% ammonium sulfate precipitation, angiogenic activity remained in the low molecular weight fraction and could be inactivated by heat. SDS-page of serum FPLC fractions exhibiting maximal angiogenic activity demonstrated two prominent species of 45 and 16-20 kD in patients' sera. These bands were much less apparent in sera obtained from control subjects. Amino-terminal sequencing of the 45-kD protein demonstrated that it was haptoglobin. Purified haptoglobin stimulated angiogenesis in a dose-dependent manner. The angiogenic activity of vasculitis patients' sera was partially inhibited by an antihaptoglobin antibody. Furthermore, serum haptoglobin levels in vasculitis patients correlated both with disease and angiogenic activity. Haptoglobin angiogenic activity was confirmed in two in vivo models using an implanted disc and a subcutaneous injection of basement membrane. Stimulation of angiogenesis is a newly recognized biological function of haptoglobin. The increased levels of haptoglobin found in chronic inflammatory conditions may play an important role in tissue repair. In systemic vasculitis, haptoglobin might also compensate for ischemia by promoting development of collateral vessels.
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PMID:Identification of haptoglobin as an angiogenic factor in sera from patients with systemic vasculitis. 768 Jun 72

Iron-derived reactive oxygen species are implicated in the pathogenesis of various vascular disorders including atherosclerosis, vasculitis, and reperfusion injury. The present studies examine whether heme, when liganded to physiologically relevant proteins as in hemoglobin, can provide potentially damaging iron to intact endothelium. We demonstrate that reduced ferrohemoglobin, while relatively innocuous to cultured endothelial cells, when oxidized to ferrihemoglobin (methemoglobin), greatly amplifies oxidant (H2O2)-mediated endothelial-cell injury. Drawing upon our previous observation that free heme similarly primes endothelium for oxidant damage, we posited that methemoglobin, but not ferrohemoglobin, releases its hemes that can then be incorporated into endothelial cells. In support, cultured endothelial cells exposed to methemoglobin--in contrast to exposure to ferrohemoglobin, cytochrome c, or metmyoglobin--rapidly increased their heme oxygenase mRNA and enzyme activity, thereby supporting heme uptake; ferritin production was also markedly increased after such exposure, thus attesting to eventual incorporation of Fe. These cellular methemoglobin effects were inhibited by the heme-scavenging protein hemopexin and by haptoglobin or cyanide, agents that strengthen the liganding between heme and globin. If the endothelium is exposed to methemoglobin for a more prolonged period (16 hr), it accumulates large amounts of ferritin; concomitantly, and presumably associated with iron sequestration by this protein, the endothelium converts from hypersusceptible to hyperresistant to oxidative damage. We conclude that when oxidation of hemoglobin facilitates release of its heme groups, catalytically active iron is provided to neighboring tissue environments. The effect of this relinquished heme on the vasculature is determined both by extracellular factors--i.e., plasma proteins, such as haptoglobin and hemopexin--as well as intracellular factors, including heme oxygenase and ferritin. Acutely, if both extra- and intracellular defenses are overwhelmed, cellular toxicity arises; chronically, when ferritin is induced, resistance to oxidative injury may supervene.
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PMID:Endothelial-cell heme uptake from heme proteins: induction of sensitization and desensitization to oxidant damage. 841 93

We describe a patient with allergic granulomatous angitis who developed autoimmune hemolytic anemia (AIHA). A 44-year-old male had been suffering from bronchial asthma. On admission, laboratory tests revealed the presence of severe eosinophilia (21,500/microliters), elevation of total immunoglobulin E (IgE), high lactic dehydrogenase (LDH) and low haptoglobin levels, in addition to moderate reticulocytosis. During admission, the patient showed almost simultaneous occurrence of vasculitis in the extremities, severe hemolysis and exacerbation of asthma in relation to the progression of eosinophilia. Both IgM and IgG autoantibodies were considered to be responsible for hemolysis. Interestingly, serum levels of interleukin-4 (IL-4) and IL-5 were increased in association with eosinophilia and increased IgE production. These findings suggest that the AIHA in this patient is mediated or enhanced at least partly by high IL-4 and IL-5 production. Although AIHA in this syndrome is very rare, it should be considered as a clinical manifestation.
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PMID:Autoimmune hemolytic anemia in allergic granulomatous angitis (Churg-Strauss syndrome). 886 25

The primary toxicity associated with repeated oral administration of the PDE4 inhibitor IC542 to the rat is an inflammatory response leading to tissue damage primarily in the gastrointestinal tract and mesentery. Although necrotizing vasculitis is frequently seen with other PDE4 inhibitors, blood vessel injury was rare following IC542 administration and was always associated with inflammation in the surrounding tissue. The incidence and severity of the histologic changes in these studies correlated with elevated peripheral blood leukocytes, serum IL-6, haptoglobin, and fibrinogen, and with decreased serum albumin. By monitoring haptoglobin, fibrinogen and serum albumin changes in IC542-treated rats, it was possible to identify rats with early histologic changes that were reversible. Since PDE4 inhibition is generally associated with anti-inflammatory activity, extensive inflammation in multiple tissues was unexpected with IC542. Co-administration of dexamethasone completely blocked IC542-induced clinical and histologic changes in the rat, confirming the toxicity resulted from inflammatory response. In addition, IC542 augmented release of the proinflammatory cytokine IL-6 in LPS-activated whole blood from rats but not monkeys or humans. The effect of IC542 on IL-6 release from rat leukocytes in vitro is consistent with the proinflammatory response observed in vivo and demonstrates species differences to PDE4 inhibition.
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PMID:Characterization of the inflammatory response to a highly selective PDE4 inhibitor in the rat and the identification of biomarkers that correlate with toxicity. 1650 43

In the present study plasma samples from 15 systemic lupus erythematosus (SLE) patients and 16 healthy controls of initially unknown haptoglobin (Hp) phenotype were separated by 2-DE, and tryptic digests of the excised Hpalpha polypeptide chain spots were analyzed by MALDI-TOF-MS. Selected tryptic peptides were sequenced by nano-(n)ESI-IT MS/MS. The six major Hp phenotypes were present, although with distinct frequencies in controls and SLE patients. Thus, there were an increased proportion of SLE patients with Hp 2-2, or Hp 2-1S phenotypes. The Hp phenotype distribution resulted in allele frequencies of 0 625 (Hp(2)), 0.281 (Hp(1S)), and 0.093 (Hp(1F)) in healthy controls, correlating fairly well with the allele frequencies of European populations. In contrast, the Hp allele frequencies of the SLE patients were 0.733 (Hp(2)), 0.233 (Hp(1S)), and 0.033 (Hp1(1F)), which clearly indicated an increased frequency of Hp(2), a similar proportion of Hp(1S) and a diminished proportion of Hp(1F) in SLE patients compared with that in healthy controls. Preferential Hpalpha2 expression in SLE patients may contribute to some of the clinical manifestations of the disease such as hypergammaglobulinemia, systemic vasculitis, and cardiovascular disorders.
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PMID:Proteomic analysis of plasma from patients with systemic lupus erythematosus: increased presence of haptoglobin alpha2 polypeptide chains over the alpha1 isoforms. 1654 81

A 60-year-old male who had been treated for polymyalgia rheumatica (PMR) with Raynaud's phenomenon was admitted to our hospital with acrocyanosis and rapid progressive anemia. Hemolytic anemia with reduction of haptoglobin and cold agglutinin was detected, and the patient had a negative Donath-Landsteiner test. A skin biopsy from his toe revealed microthromboembolism without vasculitis, resulting in the diagnosis of cold agglutinin disease (CAD). This is a first case report of CAD complicated with PMR.
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PMID:A case of cold agglutinin disease in the course of treatment for polymyalgia rheumatica. 1934 Mar 95