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PubMed1979

Hereditary angioedema controlled with danazol. Report of a case.

Hereditary angioedema is a condition which should be approached with caution and concern for the patient. The fact that the disease can be fatal cannot be overemphasized. The routine medical history should include questions aimed at identifying these patients. If the angioedema patient is to be treated, provisions must be made for maintenance of an adequate airway. This should include intubation if deemed necessary, and the practitioner should be prepared for a tracheostomy. Close observation following extubation is indicated. A case report in which the patient was controlled with danazol, a synthetic androgen, has been presented. The primary advantage of this drug is a decrease in the various side effects which have been associated with other therapeutic agents used previously in the treatment of hereditary angioedema.

Adult↗

PubMedDate not supplied

Epsilon-amino-caproic acid in the treatment of Osler's hereditary angioneurotic edema.

This clinical entity described for the first time by Osler in 1888 presented a great therapeutic problem during many decades because of its severity. Landerman and later on Donaldson and Evans established the pathogenic mechanisms of this disease finding a deficiency in the inhibitor of the first activated component of complement, an alpha 2 aminoglycoprotein, to be the mechanism responsible of the same. More concretely, alterations in the plasmin, kinin and kallikrein systems are those that will lead to a change in vascular permeability with resultant tissue alterations. Four cases of hereditary angioneurotic edema are studied in female patients aged between 15 and 50 years and with family history consistent with angioneurotic familiar edema in which there were six cases of death due to edema of the glottis. Once the diagnosis had been made the patients were subjected to treatment with EACA at doses of 2.5 gm every 6 hours. The determinations of complement were similar in the four cases, with marked decreases in C4 and C1 inhibitor with a decrease in total complement in three cases. Regarding secondary effects, vomiting was found only in one cases, which as the dose was reduced did not necessitate termination of treatment. In summary, considering the results obtained in the cases above, we believe that due to its good tolerance and moderate cost, epsilon-amino-caproic acid at the abovementioned dosage is an excellent pharmacological agent in the treatment of Osler's hereditary angioneurotic edema.

Adolescent↗

PubMed1988

Clinical safety of intravenous immune globulin and freedom from transmission of viral disease.

Although rare, side-effects have been associated with the administration of iv immune globulins (IVIG). While the clinical presentation may be similar, several different mechanisms account for these adverse reactions. There are those effects in the hypogammaglobulinaemic patient which are probably due to antigen-antibody interaction (so-called inflammatory reactions), those due to spontaneous activation of the complement system (possibly caused by IgG aggregates), those due to true hypersensitivity (for example, hypersensitivity to IgA), and those due to possible contaminants or even stabilizers or preservatives which might have been used. The incidence and nature of clinical side-effects seen in 37 patients who were treated with a native IVIG is shown. In addition, data are provided which support the absence of transmission of human immune deficiency virus in idiopathic thrombocytopenia (ITP) patients, and the agents of non-A, non-B hepatitis in 41 immune-deficient patients having periods of follow-up ranging up to 18 months. Finally, evidence of the inactivation of human immunodeficiency virus during the manufacturing procedure is provided.

Antibodies, Viral↗

PubMed1995

Papulacandin B resistance in budding and fission yeasts: isolation and characterization of a gene involved in (1,3)beta-D-glucan synthesis in Saccharomyces cerevisiae.

Papulacandin B, an antifungal agent that interferes with the synthesis of yeast cell wall (1,3)beta-D-glucan, was used to isolate resistant mutants in Schizosaccharomyces pombe and Saccharomyces cerevisiae. The resistance to papulacandin B always segregated as a recessive character that defines a single complementation group in both yeasts (pbr1+ and PBR1, respectively). Determination of several kinetic parameters of (1,3)beta-D-glucan synthase activity revealed no differences between S. pombe wild-type and pbr1 mutant strains except in the 50% inhibitory concentration for papulacandin B of the synthases (about a 50-fold increase in mutant activity). Inactivation of the synthase activity of both yeasts after in vivo treatment with the antifungal agent showed that mutant synthases were more resistant than the corresponding wild-type ones. Detergent dissociation of the S. pombe synthase into soluble and particulate fractions and subsequent reconstitution indicated that the resistance character of pbr1 mutants resides in the particulate fraction of the enzyme. Cloning and sequencing of PBR1 from S. cerevisiae revealed a gene identical to others recently reported (FKS1, ETG1, CWH53, and CND1). Its disruption leads to reduced levels of both (1,3)beta-D-glucan synthase activity and the alkali-insoluble cell wall fraction. Transformants containing the PBR1 gene reverse the defect in (1,3)beta-D-glucan synthase. It is concluded that Pbr1p is probably part of the (1,3)beta-D-glucan synthase complex.

Aminoglycosides↗

PubMed1975

Interaction of collagen with serum complement: inhibition of complement-mediated hemolysis.

Collagens from various vertebrate tissues were tested for their ability to consume complement (C) activity upon incubation in human serum or with isolated components of complement. 10 of 12 collagens tested had anticomplementary activity. The heat-denatured form of collagen, gelatin, was found weakly anticomplementary, but elastin was found inactive in the interaction with C. Inactivation of C is a reaction which is dependent on the time of incubation and the collagen concentration and partially dependent on the temperature of incubation. Most collagens depleted C from human serum in presence of cation chelators, EDTA and EGTA, whereas the large part of anticomplementary activity of soluble collagens obtained from rat skin was abolished in presence of EDTA. Evidence is presented that two different principles in collagens play a role in inactivation of C. A factor, contained in insoluble collagens and inhibitable by mild oxidation with periodate, inactivates C1 directly even in presence of chelating agents. Another principle, contained in soluble and insoluble collagen and resistant to periodate treatment, depletes C in serum by utilization of C via the alternate pathway (the C3 shunt).

Animals↗

PubMed1990

[Accessory use of protease-inhibiting agents for disease remission in a patient with autoimmune hemolytic anemia associated with B-CLL].

Protease inhibiting agents, which have inhibitory effects on complement system, were used to treat a patient with autoimmune hemolytic anemia (AIHA) associated with B cell chronic lymphocytic leukemia (B-CLL). Although this patient had failed to respond thoroughly to prednisolone, the additional use of protease inhibitors induced a disease remission of hemolytic anemia. The result suggests that complement components are of importance in the pathogenesis of hemolysis in AIHA, and supports the accessory use of protease inhibiting agents in autoimmune hematologic diseases associated with the complement activation and hypersplenism.

Aged↗

PubMed1983

The effect of a novel C5 inhibitor (K-76 COONa) on tumor cell chemotaxis.

Walker carcinosarcoma cells were cultured as an ascitic tumor in the rat. These cells were studied for their response to human chemotactic factors derived from complement. Complement activation for tumor chemotaxis was performed by reaction of serum with a tumor extract. An anticomplementary agent, K-76 sodium monocarboxylic acid (K-76 COONa), was tested in these systems. It was found to be effective in blocking the formation of a chemotactic factor for tumor cells from human complement at a concentration of 300 micrograms/ml. Addition of K-76 COONa after complement activation had no effect. No effect on random migration of tumor cells was found at concentrations of 500 micrograms/ml. No effect on tumor cell viability was found up to 500 micrograms/ml. At 1000 micrograms/ml there was a 15% decrease in viability (p less than 0.05). Since chemotactic mechanisms (probably from activated complement) may play a role in the movement of tumor cells, this apparently low toxic anticomplementary agent (K-76 COONa) may be of value in the prevention of tumor metastases.

Animals↗

PubMed1994

Roles of antibodies and complement in phagocytic killing of enterococci.

The contributions of complement and antibodies to polymorphonuclear leukocyte (PMN)-mediated killing of enterococci were investigated with pooled normal human serum (PNHS) or immune human sera (IHS) from patients with serious enterococcal infections. Each IHS containing antienterococcal antibodies demonstrated by enzyme-linked immunosorbent assay and Western blotting (immunoblotting) was examined with the enterococcus strain isolated from the same patient. PNHS promoted PMN-mediated killing of enterococci similar to that for IHS. PMN-mediated killing was consistently abrogated after preopsonization with heat-inactivated PNHS, but some heat-inactivated IHS supported neutrophil bactericidal activity. Inhibition of the classical pathway of complement by chelation of either PNHS or IHS with Mg-EGTA [Mg-ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] did not alter PMN-mediated killing, suggesting that activation of the alternative pathway of complement is sufficient to promote killing of enterococci by PMNs. PMN-mediated killing assays were also performed with normal rabbit serum and immune rabbit serum against enterococci. Preopsonization with heat-inactivated immune rabbit serum resulted in PMN-mediated killing of enterococci, which was ablated after adsorption of the serum with the same isolate used for immunization. The influence of different phenotypic enterococcal traits on neutrophil-mediated killing was also investigated. Similar kinetics of killing were observed for derivatives of Enterococcus faecalis strains regardless of resistance to antimicrobial agents or production of beta-lactamase, hemolysin, gelatinase, or surface proteins involved in the aggregative response to pheromones. In summary, PMN-mediated killing of enterococci appears to depend primarily on complement activation by either the classical or the alternative pathway. Human antienterococcal antibodies generated during infection variably promoted neutrophil bactericidal activity, while antibody raised in a rabbit supported PMN-mediated killing of the organism examined. Finally, the different phenotypic properties of E. faecalis examined did not influence the neutrophil-mediated killing of these organisms.

Adult↗

PubMed1992

[Functional determination of C1-inhibitors in human blood].

The author describes the method of assessment of the C1-inhibitor, the principle being activation of plasma prekallikrein by Hageman factor fragment (HFf) to the active enzyme kallikrein which splits the specific chromogenic substrate NO-Pro-Phe-Arg-pNA. In the presence of acetone the influence of C1-INH is eliminated and the assessed amount of kallikrein corresponds to the prekallikrein plasma level. In a parallel estimation without acetone after formation of the C1-INH complex the residual amount of kallikrein is assessed. The difference between the two levels is proportional to the formed enzyme-inhibitor complex. The method was tested on plasma of healthy donors and the results were compared with assessment of C1-INH by a modification of Schapira's method (6) (correlation coefficient r = 0.88) and with Cullmann's method (8) (r = 0.61). The advantage of the proposed method is that it does not require commercially unavailable enzyme preparations, that it uses as activating agent HFf concentrate, prepared in the laboratory and that along with the C1-INH level also the plasma level of prekallikrein is assessed.

Complement C1 Inactivator Proteins↗

PubMed1978

Inhibition of the classical and alternative pathways by amino acids and their derivatives.

Effects of various aminoacids and their derivatives on the classical pathway and alternative pathway of the complement were studied. Leupeptin, acetyl-leucyl-leucyl-arginal, inhibited CH50 and Cl-esterase, but did not inhibit the alternative pathway. When aminoacids of carbon chains of the order of seven were used, arginine and lysine had stronger effects than trans-aminomethyl cyclohexane carboxylic acid (t-AMCHA), cis-aminomethyl cyclohexane carboxylic acid (cis-AMCHA) and epsilon aminocaproic acid (EACA). SH-compounds, cysteine, homocysteine and glutathione, had the strongest inhibitory effects among these aminoacids on both classical and alternative pathways. When effects on Cl esterase were compared, arginine, lysine, t-AMCHA, cis-AMCHA and EACA had weak inhibition while SH-compounds showed strong inhibition. Poly-L-lysine, which had extremely strong inhibition of CH50, had no inhibition of Cl esterase. The inhibitory effects of antifibrinolytic agents, EACA and t-AMCHA, were weak but when effects on early parts of the classical pathway, C(1,4,2)H50 were tested, some inhibitory activities were recognized. Thus inhibitory effects of these agents were due to their activities on the early parts of the classical pathway.

Amino Acids↗

PubMed1985

Cold promoted activation and factor XII, prekallikrein and C1-inhibitor.

During incubation of plasma in the cold an amidolytic activity due to the kallikrein-alpha 2-macroglobulin complex appears in the plasma of about 40% of the women under hormonal contraception. The factor XII and prekallikrein activity are significantly increased 151.9% and 112.4% respectively in the cold promoted activation positive plasmas (CPA pos) whereas the activity of C1-inhibitor is decreased, 76%. The quotient of the product of the C1-inhibitor and alpha 2-macroglobulin values divided by the product of the FXII and prekallikrein values is significantly lower in the CPA pos plasma 0.49 than in CPA neg plasma 0.96 (p less than 0.05). These results alone do not explain the cold promoted activation, since a patient with a C1-inhibitor as low as 9% showed no increase of the amidolytic activity after a 24 hr incubation at 4 degrees C. However, the addition of purified C1-inhibitor to a CPA pos. plasma inhibits the cold activation. Heparin at a concentration of 0.5 IU/ml delays the appearance of the amidolytic activity.

Adolescent↗

PubMed1990

Construction of an Azospirillum brasilense Sp7 recA mutant.

Cosmid clones encoding the recA gene of Azospirillum brasilense were isolated by intergeneric complementation of an Escherichia coli recA mutant. Site-directed Tn5 mutagenesis and subcloning of one complementing cosmid clone allowed us to localize the A. brasilense recA gene on a 1.2 kb DNA fragment. One Tn5 insertion that inactivates the cloned recA gene was crossed into the chromosome of A. brasilense by marker exchange. The resulting A. brasilense recA mutant showed increased sensitivity to the DNA methylating agent methyl methanesulfonate and to ultraviolet light and had at least one hundredfold reduced recombinational activity compared to the parent strain.

Azospirillum brasilense↗

PubMed1989

Mechanism of ranitidine associated anemia.

Ranitidine, an H2 receptor antagonist, has been associated with hematotoxicity. The mechanism(s) underlying the toxicity is not well understood. The authors studied the mechanism of anemia in a patient with ranitidine associated anemia and thrombocytopenia. Clinical evaluation suggested drug-induced Coombs' positive reticulocytopenic hemolysis. In vitro, with the patient off ranitidine, the authors were able to induce Coombs' positivity by incubating patient's red cells with ranitidine and his serum. This process was inhibited by prior exposure of his red cells to histamine. In vitro studies using clonal assays for hematopoietic progenitors revealed that while the patient's serum or ranitidine alone did not affect the patient's or normal bone marrow hematopoiesis, the simultaneous presence of both agents significantly suppressed both patient's and normal erythroid progenitor (BFU-E) colony development. This suppressive effect was prevented by the prior exposure of marrow to histamine and was not observed when the patient's serum was heat inactivated. These studies suggest that the anemia may have resulted from complement-dependent autoimmune destruction/inhibition of progenitor/mature erythroid cells by a process critically dependent on the presence of ranitidine and possibly acting at or near the histamine receptor.

Anemia↗

PubMed1991

Beta-lactam antibiotics potentiate magainin 2 antimicrobial activity in vitro and in vivo.

The ability of magainin 2 to augment antibiotic therapy was examined. Susceptibility to magainin 2 was determined on Escherichia coli incubated in the presence and absence of sublethal concentrations of antibiotics both in vitro and in vivo. Experiments in buffer and normal human serum revealed that E. coli exposed to sublethal amounts of cefepime, a beta-lactam antibiotic, was significantly more susceptible to the antimicrobial activity of magainin 2. Bacteria incubated with subinhibitory concentrations of other beta-lactam type antibiotics, but not amikacin (an aminoglycoside) or ciprofloxacin (a quinolone), were also more susceptible to magainin 2 in normal human serum. Bacteria were less susceptible to magainin 2 when they were examined in heat-inactivated serum. Complement was shown to be required for magainin 2 activity in serum by using C8-deficient sera. The combination of magainin 2 and cefepime was shown to be more antimicrobial in normal human serum for a variety of bacterial strains. Magainin 2 was completely inactive as a therapeutic agent when it was administered alone (2 mg per mouse) but significantly increased the survival of mice when it was administered with a low level of cefepime.

Animals↗

PubMed1980

Detoxication disturbances and uncoupling effects in vitro of some chlorinated guaiacols, catechols and benzoquinones.

The effects of chlorinated guaiacols, catechols and benzoquinones - earlier identified in discharges from pulp and paper mills -- on oxidative phosphorylation in mitochondria and on detoxication mechanisms in microsomes have been investigated. The same biological systems have been used in testing outgoing water from a sulphite plant. Trichlorocatechol and tetrachlorocatechol and the corresponding guaiacols increase N oxygenation of N,N-dimethylaniline, while C-oxygenation decreases, indicating disturbances in microsomal detoxication. The substances tested have in general an uncoupling effect on mitochondrial oxidative phosphorylation. However, tetrachloroguaiacol seems to differ in having a specific effect on the succinate dehydrogenase part of the respiratory chain. Extracts from waste water from a sulphite plant have a considerable effect on the mitochondrial system such as to produce an increase in basal respiration and a loss of respiratory control. N- and C-oxygenation and phosphorylation have been extensively used in this and other laboratories for evaluating the toxicity of chemicals. The application on water extract described here is rapid and easily handled and thus provides a valuable complement to other water quality tests.

Animals↗

PubMed1982

Characterization of a coronavirus isolated from rats with sialoadenitis.

A causative agent, provisionally designated as CARS, was isolated from the enlarged submaxillary gland of rat which was characterized as a sialoadenitis, using mouse-derived Balb/c3T3 clone A31 (3T3) cell culture. The virus could be propagated in 3T3 cell culture where it produced multinucleated giant cells and formed clear plaques. It was identified as a member of the coronavirus group from the following results: RNA content was suggested by the lack of the effect of cytosine arabinoside, the infectivity was sensitive to lipid solvents and inactivated at 56 degrees C for 5 minutes, the viral particle showed typical coronavirus morphology which was approximately 100 nm in diameter. Serologically, although CARS and sialodacryoadenitis virus (SDAV) actually belonged to the rat-coronavirus group, some antigenic variations existed between these two agents in the results of both neutralization and complement-fixation tests using monovalent antisera. When inoculated intranasally into susceptible rats, CARS caused clinically and histologically overt sialoadenitis as observed in the natural outbreak, and retained its virulence for rats in several passages of mouse brain and even when cell culture was used, while rats which were inoculated with SDAV were asymptomatic.

Animals↗

PubMed1974

Interrelationship between serum beta-lysin, lysozyme, and the antibody-complement system in killing Escherichia coli.

The effects of different serum components alone and in conjunction with each other on Escherichia coli B were investigated. In general, the viability, turbidity, and electron microscope results were compatible with the following conclusions. The most efficient killing and destruction of E. coli B occurred when beta-lysin, lysozyme, and the antibody-complement system functioned in cooperation with each other at the serum concentration in isotonic solutions. The addition of sucrose protected the bacteria from the lethal and lytic action of these agents. Elimination of lysozyme from serum had the least effect on bactericidal activity, even though lysozyme treatment caused the cell wall to separate from the cytoplasmic membrane and caused clear areas to appear in the inner granular layer of the cell wall. Beta-lysin removal had an intermediate effect on the serum bactericidal activity. Beta-lysin treatment caused cell walls to collapse, allowed cytoplasmic contents to leak out of the cells, and stopped the separation of cell wall and cytoplasmic membrane, which normally takes place in 0.5 M sucrose solution. Inactivation of the complement eliminated the serum bactericidal activity against E. coli B. After treatment with antibody and complement, the cell walls became thick and indistinct, a portion of the cytoplasmic contents escaped, and patches of the middle layer of the cell wall appeared in freeze-etch preparations. Beta-lysin damaged the cytoplasmic membrane, lysozyme damaged the inner peptidoglycan layer of the cell wall, and the antibody-complement system damaged both the middle lipopolysaccharide layer of the cell wall and the cytoplasmic membrane.

Animals↗

PubMed1981

Nerve growth factor and an anticomplimentary protease in mouse saliva elicited by nerve stimulation.

1. Three substances previously identified in mouse saliva ((1) biologically active nerve growth factor (NGF), (2) a material immunologically identical to the alpha-subunit of 7S-NGF and (3) an anticomplementary protease) were quantified in both mandibular gland saliva and mixed salivary secretions elicited by stimulation of either the sympathetic or parasympathetic nerves to the salivary glands. 2. The concentrations and specific activities of all three substances in pure mandibular saliva equalled or exceeded those found in mixed secretions from all salivary glands. 3. All three substances were found to be primarily secreted as a result of sympathetic rather than parasympathetic nerve stimulation as their concentrations and specific activities were much greater in sympathetic than in parasympathetic mixed salivary secretions. 4. Bioactive NGF, alpha-subunit-like material, and an anticomplementary protease were demonstrated to be released selectively through activation of alpha-adrenergic receptors as the concentrations and specific activities of all three substances were markedly reduced by pre-treatment with an alpha-adrenergic blocker (phenoxybenzamine) but not by pre-treatment with either a muscarinic or a beta-adrenergic blocker (atropine or propranolol, respectively). 5. Measurement of total protein in saliva elicited by sympathetic nerve stimulation following pre-treatment with an alpha-adrenergic, beta-adrenergic, or muscarinic blocking agent demonstrated that proteins other than those examined in the present study must be released by activation of beta-adrenergic receptors.

Animals↗