Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Complement C1 Inhibitor Protein”

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 613 records · Page 34Linked to original sources
PubMed1994

Administration of gamma interferon in human subjects decreases plasminogen activation and fibrinolysis without influencing C1 inhibitor.

Recombinant gamma interferon (rHuIFN-gamma) has been recognized to increase mRNA and protein levels of C1 inhibitor (C1 INH) in various human cells. Further, when administered to patients with colon cancer, it increased plasma C1 INH levels. A prospective trial was initiated to determine whether rHuIFN-gamma could elevate plasma C1 INH levels in six normal volunteers and two patients with type I angioedema. After 1 month of observation of plasma C1 INH levels, rHuIFN-gamma was administered subcutaneously at 25 micrograms/M2 daily for 4 consecutive days. All healthy volunteers and patients experienced local erythema, headache, myalgias, and chills during the administration of rHuIFN-gamma. C1 INH, prekallikrein, high-molecular-weight kininogen, and factor XII levels in plasma were not influenced by the rHuIFN-gamma administration. One patient with hereditary angioedema (HAE) had an attack of angioedema 3 days after completion of rHuIFN-gamma therapy. During the attack, circulating cleaved high-molecular-weight kininogen, kallikrein-alpha 2-macroglobulin complexes, and an altered 50 kd form of kallikrein were detected in the patient's plasma. Additional studies showed that rHuIFN-gamma treatment resulted in decreased total fibrinolytic activity. It was found that immediately after rHuIFN-gamma treatment, tissue plasminogen activator activity and antigen levels were not significantly decreased in volunteers. Plasminogen activator inhibitor levels rose significantly, but this activity was not due to plasminogen activator inhibitor-1 antigen, whose value significantly fell. These data suggest that rHuIFN-gamma may stimulate the expression of another plasminogen activator inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Level of plasma prekallikrein and its inhibitors in reactors and nonreactors during intravenous enhancement with contrast media.

Complex contact activation systems may play a major role in the side effects of i.v. contrast media (CM). This is why quantitative measurements of several factors (plasma prekallikrein, hematocrit (hct), alpha-2-macroglobulin, alpha-1-antitrypsin, and C1-esterase inhibitor) were determined prior to and following the injection of CM during body CT examination in 5 patient groups, each (n = 10) receiving one of 5 different CM, including ioxaglate, meglumine iodamide, metrizamide, iohexol, and meglumine diatrizoate. The initial plasma prekallikrein level was available from 45 patients and was statistically lower in reactors (mean 90.6 mumol TAMe/ml/h; n = 13) than in nonreactors (mean 107 mumol TAMe/ml/h; n = 32) (p = 0.006), but there was no statistically significant difference in the decrease of plasma prekallikrein before and at 5 min after the injection for those 2 groups. The initial plasma C1-esterase inhibitor level was lower in reactors, while the plasma alpha-2-macroglobulin level was higher in that group than in nonreactors. The results indicate that the measurement of plasma prekallikrein combined with plasma C1-esterase inhibitor and alpha-2-macroglobulin measurement could be useful when predicting which patients are prone to CM reactions.

Blood Proteins↗
PubMed2005

[Angioedema in hereditary deficiency of complement factor 1 esterase inhibitor and alpha 1-antitrypsin].

HISTORY AND CLINICAL FINDINGS: A 15-year-old girl had suffered from episodic, sometimes threatening angioedema of the face, nasopharyngeal space and distal extremities beginning at age 13. EXAMINATIONS: A C1-esterase inhibitor (C1-INH) deficiency was revealed protein-chemically and functionally. There was also an alpha (1)-antitrypsin (AAT) deficiency with heterocygotic phenotype PiMZ. The combination of C1-INH and AAT deficiency was also found in the patient's mother and brother. THERAPY AND COURSE: Under 8-month therapy with 200 mg/d danazol per os (reduction of the dosis in the last month to 100 mg/d), there was no further edema, the C1-INH concentration normalized and there was also an increase in C1-INH function. During the observation period, use of the emergency set with C1-INH concentrate was not required. CONCLUSIONS: This is the first reported case of angioedema in combination of two hereditary enzyme defects C1-INH deficiency (autosomal-dominant genetics) and AAT deficiency (autosomal-recessive). In addition to a survey of current literature, the current state of diagnostics and therapy of the hereditary angioedema is presented.

Administration, Oral↗
PubMed1988

Functional and structural similarities between protease nexin I and C1 inhibitor.

Protease nexin I is a proteinase inhibitor that is secreted by human fibroblasts and forms stable complexes with certain serine proteinases; the complexes then bind to the fibroblasts and are rapidly internalized and degraded. In this report, we show that this inhibitor, which is present in very low concentrations in plasma, has functional and structural similarities to C1 inhibitor, an abundant proteinase inhibitor in plasma. Both inhibitors complex and inactivate certain proteinases that previously were known to rapidly react only with C1 inhibitor. Kinetic inhibition studies show that protease nexin I inhibits Factor XIIa and plasma kallikrein with second-order rate constants of 2.3 x 10(3) and 2.5 x 10(5) M-1 s-1, respectively, which are similar to the rate constants for inhibition of these proteinases by C1 inhibitor. Protease nexin I inhibits C1s about one-tenth as rapidly as does C1 inhibitor. Alignment of the amino acid sequences of protease nexin I and C1 inhibitor shows that these proteins have similarity at their reactive centers (from sites P7 to P1). The remaining regions of the two proteins share much less similarity. In contrast to protease nexin I, C1 inhibitor is not secreted by human fibroblasts. Although 125I-C1s-protease nexin I complexes readily bind to human fibroblasts, binding of 125I-C1s-C1 inhibitor complexes or other 125I-proteinase-C1-inhibitor complexes to these cells is not detectable. Thus, protease nexin I and C1 inhibitor may control some common regulatory proteinases in the extravascular and vascular compartments, respectively.

Amino Acid Sequence↗
PubMed1983

Immunodiffusion assay of C1 inhibitor function in serum: prospective analysis in angioedema-urticaria.

An immunodiffusion assay for detecting C1 inhibitor function in human serum was described recently by Ziccardi and Cooper. In our present study, the applicability of this assay for C1 inhibitor deficiency or C1 inhibitor dysfunction was evaluated. Of the 39 patients evaluated, all eight patients with the common (C1 inhibitor deficiency) form of hereditary angioedema and all three patients with the variant (dysfunctional C1 inhibitor) form of hereditary angioedema were identified correctly. Treatment of patients with hereditary angioedema with stanozolol or danocrine increased their serum C1 inhibitor concentrations and normalized the immunodiffusion assay for C1 inhibitor function. In addition, the assay allowed the correct identification of three patients with the acquired form of C1 inhibitor deficiency, because the sera of these patients exhibited a distinctive pattern. The 25 samples from patients (chronic angioedema, chronic urticaria, or hypocomplementemic vasculitis) without C1 inhibitor deficiency had normal assays.

Angioedema↗
PubMed1978

[Hereditary angioneurotic edema. Clinical aspects, pathogenesis and therapy].

A family with hereditary angioedema is presented. In 4 members of the family the diagnosis was confirmed by decreased C1 esterase inhibitor levels. Clinical course and pathogenesis are described briefly. New ways of treatment are discussed, especially injection of purified C1 esterase inhibitor and stimulation of C1 esterase inhibitor synthesis by oral therapy with attenuated androgens.

Adolescent↗
PubMed1989

The effect of a bolus injection of unfractionated or low molecular weight heparin during aortobifemoral bypass grafting.

Eighteen patients undergoing aortobifemoral graft surgery for severe aortoiliac atherosclerotic disease received a bolus injection of 10,000 anti-Xa units of either unfractionated heparin (UFH) or low molecular weight heparin (LMWH) into the distal aorta as prophylaxis against thromboembolic complications related to clamping. Heparin activity was measured by factor Xa inhibition and by prolongation of the APTT. In both groups there was a delay before peak levels of heparin were observed. In the LMWH group, this amounted to 30 min. In the UFH group, APTT was prolonged by 46 s, 7 min after injection but only by 5 s at the end of the operation. In contrast, in the LMWH group, the prolongation in APTT 7 min after injection was less (34 s) but more sustained since a 12.5 s prolongation was still present at the end of the operation. During surgery, heparin activity exceeded 0.7 U/ml in the LMWH group, compared to significantly lower levels in the UFH group (less than or equal to 0.20 U/ml). By the end of the operation no heparin activity was detectable in the UFH group. Protein C antigen decreased after heparin injection and this fall was more pronounced in the UFH group. The level of C1q (a subcomponent of the first component of the complement system) was decreased in the UFH group (P less than 0.04), whereas in the LMWH group C1q levels increased. Platelet aggregation with collagen was inhibited to a significantly greater degree in the LMWH group than the UFH group (54% compared with 23%) (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed2001

C1 esterase inhibitor: new preparation. A major advance in emergency treatment of hereditary angioneurotic oedema.

(1) The reference prophylaxis of attacks of hereditary angioneurotic oedema is oral danazol, an androgenic steroid, which takes a few days to act. There was previously no curative treatment authorised in France. (2) C1 esterase inhibitor is now licensed in France as replacement therapy for patients with hereditary angioneurotic oedema due to a quantitative or qualitative deficiency in this protein. (3) The clinical evaluation file partly answers the practical questions that arise in this setting, but it does not include trials versus danazol. (4) In 36 patients with acute attacks of angioneurotic oedema, a double-blind trial showed that symptom relief was achieved in less than half an hour in 69% of attacks treated with C1 esterase inhibitor, compared to only 2% of attacks treated with placebo. (5) In the prophylactic setting, a crossover trial involving six patients refractory to conventional androgen therapy showed that injections of C1 esterase inhibitor every three days were more effective than a placebo in reducing the risk of attacks. (6) No major adverse effects have been attributed so far to C1 esterase inhibitor, but the fact that the drug is derived from human blood means that treatment carries a theoretical risk of infection by conventional infectious agents (especially nude viruses) and prions. (7) In practice, for life-threatening attacks of angioneurotic oedema, C1 esterase inhibitor is rapidly effective in two-thirds of patients and is now the reference treatment. In the absence of comparative trials, danazol remains the first-line prophylaxis when patients are scheduled for surgery a few days later, but C1 esterase inhibitor is useful when danazol is ineffective. C1 esterase inhibitor is the only available prophylaxis for patients undergoing emergency surgery (within a few hours).

Angioedema↗
PubMed1989

Molecular defects of the C1-inhibitor gene in hereditary angioedema.

Family studies of hereditary angioedema are discussed with particular emphasis on the molecular basis of the more common form of the disease (type I), characterized by quantitative C1-Inhibitor deficiencies. Results obtained in several laboratories can be interpreted in the light of the restriction maps and of the exon-intron structure of the normal C1-Inhibitor gene that have been published recently. Several partial deletions of either exon 4 or exon 7 or of larger portions of the 5' end of the gene and a duplication of exon 4 have been described. These gene alterations are essentially family-specific and they account for at least fifteen-percent of the defects in type I hereditary angioedema. Detailed sequences analyses of cloned defective genes indicate that clusters of repetitive sequences of the Alu family, located within several introns, are responsible for the relatively high frequency of gross gene alterations observed at the C1-Inhibitor locus. In contrast, most of the defects that lead to production of dysfunctional proteins appear to be point mutations within the P1 residue of the reactive site, whose codon features a hypermutable CpG dinucleotide.

Angioedema↗
PubMed1985

Elevated plasmin-alpha 2-antiplasmin complex levels in hereditary angioedema: evidence for the in vivo efficiency of the intrinsic fibrinolytic system.

The contact activation and fibrinolytic systems were assessed in 5 patients with hereditary angioedema (HAE). Reductions in F XII levels and increase in kallikrein-like activity in some patients indicated activation of the contact (intrinsic) system of coagulation. A great increase in plasmin-alpha 2-antiplasmin complex in all subjects indicated that in this disease, there is a constantly ongoing fibrinolysis. Since C1-inhibitor, the deficient protein in HAE, is a poor inhibitor of the well-known extrinsic (tissue-type) plasminogen activator, but the major inhibitor of the contact activation system and a related in vitro phenomenon termed intrinsic fibrinolysis, our data show that this fibrinolytic system is also sometimes operating efficiently in vivo. Furthermore, the known clinical data on HAE are compatible with a role of intrinsic fibrinolysis in the pathophysiology of this disease.

Angioedema↗
PubMed1998

C1-esterase inhibitor blocks T lymphocyte proliferation and cytotoxic T lymphocyte generation in vitro.

We have previously shown that activated C1s complement and activated T cells cleave beta2-microglobulin (beta2m) in vitro leading to the formation of desLys58 beta2m. This process can specifically be inhibited by C1-esterase inhibitor (C1-inh). Furthermore we showed that exogenously added desLys58 beta2m in nanomolar amounts to a one-way allogenic mixed lymphocyte culture (MLC) increased the endogenous production of IL-2 and the generation of allo-specific cytotoxic T lymphocytes. C1-inh was purified from fresh human plasma and added to human or murine MLC and mitogen-stimulated lymphocyte cultures grown in the presence of complement-inactivated serum. Read-outs were cell proliferation, lymphokine production and development of T cell-mediated cytotoxicity. We found that addition of C1-inh to MLC and mitogen-exposed murine and human lymphocyte cultures inhibited proliferation, the development of allospecific cytotoxic activity, and changed the endogenous production of IL-2, IL-4, IL-10, IL-12 and IFN-gamma. These data clearly demonstrate a regulatory function of C1-inh on T cell-mediated immune functions.

Animals↗
PubMed1984

Antibody-independent C1 activation by E. coli.

Antibody-independent interactions of C1 with several E. coli strains were examined. Purified C1 was directly activated by the semi-rough mutant E. coli J-5, its parental wild-type strain, E. coli 0111:B4, and two clinical isolates, E. coli (P) and E. coli (A), in the absence of C1 inhibitor. E. coli J-5 activated C1 about 10-fold more rapidly and bound approximately threefold more C1 than the other strains. E. coli J-5, but not the other strains, also bound C1s2, provided that the subcomponent was offered to the bacteria in the presence of C1q and calcium; such binding was thus independent of the presence or absence of C1r2. After C1 activation in the absence of C1 inhibitor, activated C1s spontaneously dissociated from E. coli 0111:B4, (P), and (A), but remained associated with E. coli J-5. The regulatory protein C1 inhibitor prevented C1 activation by the weaker activators, E. coli strains 0111:B4, (P), and (A), but had no effect on C1 activation by E. coli J-5. Although C1 inhibitor thus failed to modulate C1 activation by E. coli J-5, it did block the enzymatic activity of activated C1 bound to this strain. Analyses of the molecular processes involved revealed differences with other systems. In the presence of C1 inhibitor, the C1s subunit of C1 activated by E. coli J-5 underwent further cleavage with the release into the supernatant of C1s fragments and complexes of C1 inhibitor with light chain fragments. Such fragments were not disulfide-linked to the remainder of the C1s molecule. The bulk of the heavy chain remained adherent to the surface of E. coli J-5. This finding documents the presence of a binding site for activated C1s on the surface of E. coli J-5 and localizes this site to the heavy chain. These studies thus indicate that several E. coli strains are direct C1 activators. Furthermore, E. coli J-5 provides another example of a direct C1 activator having binding sites not only for C1q but also for dimeric C1s. The studies also show that there are multiple properties of particles which determine the ability to activate C1, the rate of activation, the possibility of regulation of the activation process by C1 inhibitor, and the fate of activated C1.

Antibodies, Bacterial↗
PubMed2000

Control of the classical and the MBL pathway of complement activation.

The activation of complement via the mannan-binding lectin (MBL) pathway is initiated by the MBL complex consisting of the carbohydrate binding molecule, MBL, two associated serine proteases, MASP-1 and MASP-2, and a third protein, MAp19. In the present report we used an assay of complement activation specifically reflecting the physiological activity of the MBL complex to identify biological and synthetic inhibitors. Inhibitor activity towards the MBL complex was compared to the inhibition of the classical pathway C1 complex and to a complex of MBL and recombinant MASP-2. A number of synthetic inhibitors were found to differ in their activities towards complement activation via the MBL pathway and the classical pathway. C1 inhibitor inhibited both pathways whereas alpha2-macroglobulin (alpha2M) inhibited neither. C1 inhibitor and alpha2M were found to be associated with the MBL complex. Upon incubation at 37 degrees C in physiological buffer, the associated inhibitors as well as MASP-1, MASP-2, and MAp19 dissociated from MBL, whereas only little dissociation of the complex occurred in buffer with high ionic strength (1 M NaCl). The difference in sensitivity to various inhibitors and the influence of high ionic strength on the complexes indicate that the activation and control of the MBL pathway differ from that of the classical pathway. MBL deficiency is linked to various clinical manifestations such as recurrent infections, severe diarrhoea, and recurrent miscarriage. On the other hand, impaired control of complement activation may lead to severe and often chronically disabling diseases. The results in the present report suggests the possibility of specifically inhibiting of the MBL pathway of complement activation.

Animals↗