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Biomedical subjects

W Brendel

Publications and source records attributed to W Brendel.

At least 127 records · Page 7Linked to original sources

Anaphylactoid reactions to infusions of plasma protein and human serum albumin. Role of aggregated proteins and of stabilizers added during production.

Six patients suffering from anaphylactoid reactions after infusion of pasteurized plasma (PP) or human serum albumin (HSA) were investigated. Clinical symptoms ranged from urticaria and hypotension to cardiac arrest. Immunoglobulin levels, especially of IgA, were normal, as were concentrations of complement factors C3, C4 and factor B. In skin and lymphocyte transformation tests patients, with the exception of one severely allergic to protein, did not react to the monomeric pure HSA. Five out of six patients reacted against HSA aggregates and three patients to the HSA modified by caprylate added as stabilizer during commercial HSA production. It is concluded that the anaphylactoid reactions developing after PP or HSA infusion result from a non-specific reaction to protein aggregates and in some cases possibly from a specific immune response to the caprylate-modified HSA.

Anaphylaxis↗

[Absorption of a proteolytic enzyme originating from plants out of the gastro-intestinal tract into blood and lymph of rats (author's transl)].

The absorption of the proteolytic enzyme bromelain was investigated in adult rats. Bromelain was labelled radioactively with 125-Iodine and intraduodenally applied. During the observation time of 6 hours blood- and lymphsamples were collected and their radioactivity measured. By radiochromatography high molecular protein could be separated from low molecular protein fragments. By means of a rabbit-anti-bromelainserum bromelain could be identified in the agar-double diffusion technique. Results show that adult rats can absorb bromelain up to 40% in a high molecular form. This observation explains the increased proteolytic activity in serum after oral application as well as the clinical effect concerning the treatment of edema or hematoma.

Animals↗

Mitigation of hyperacute rejection by antilymphocyte globulin (ALG).

In HR, primarily humoral immunologic factors trigger a sequence of events that finally destroys the transplanted organ. Unspecific trapping of WBC diminishes the RBF, especially in the first compartment--the cortex. Pretreatment with ALG is able to suppress this cellular participation partially, thus postponing the stop of RBF without preventing the influence of humoral factors on the graft. As shown by pathologic and functional criteria recorded for 8 hr, an exclusive measurement of total RBF does not reflect an inhibition of the course of HR.

Acute Disease↗

[Prolonged survival time of xenogeneic kidney transplants following intravenous application of concanavalin A].

Concanavalin A is used as a mitogen for the stimulation of lymphocytes in vitro. It increases the proliferation of different populations of lymphocytes and activates the function of regulator lymphocytes. This effect appears to be modified in vivo in such a way that daily IV application prolongs survival times of allogeneic and xenogeneic kidney grafts significantly. The reason seems to be an influence on behavior, which is reflected in a pronounced peripheral lymphopenia. To support and investigate this mechanism, further combinations of antilymphocyte globulin, fox red blood cells, and Concanavalin A pretreatment were used in pilot studies.

Animals↗

[Absorption and distribution of cytoplasmic organ lysates (conjunctisan A eye drops) following intraconjunctival application (author's transl)].

The absorption and transport pathways of Conjunctisan A were determined, and its mode of action clarified, by means of radioactive labeling. A dose of 0.5 ml of this drug, labeled with I131, was applied to the conjunctival sacs of rats and rabbits. After six hours there was highly significant enrichment in the ocular tissues. The highest degree of enrichment was found in the uvea, i.e., the ciliary body, choroid and retina. However, there was also moderate enrichment in the lens and the vitreous. It was proved immunologically that the radioactivity was identical with the original Conjunctisan A molecule. In particular, it as demonstrated that the enriched Conjunctisan A in the aqueous humor precipitates with the specific antibody.

Absorption↗

Elimination and organ distribution of intravenously administered allogeneic and xenogeneic IgG modifications. (Standard IgG, F (ab)2-fragments and beta-propiolactone treated IgG) in dogs.

Dog IgG was produced by fractionation procedures used for the production of clinically used i.v. gammaglobulins. Chemical modification of dog IgG was done by pepsin or beta-propiolactone treatment. The intravascular half-life of beta-propiolactone IgG was 8.5 +/- 2.1 days compared to 4.5 +/- 1.6 days of pepsin treated IgG. Tissue concentrations of radioactive labelled beta-propiolactone IgG were generally higher than of pepsin digested IgG. Pepsin treated Igg was degraded to a significantly higher extent (26% of the administered radioactivity was bound to fragments smaller than 6000 MW after three days) than beta-propiolactone IgG (9% fragments after the same interval, P less than 0.001). It is concluded that the short intravascular half-life of pepsin IgG cannot be explained by increased extravascular filling, but is due to rapid degradation and excretion via the kidneys. There was no obvious difference in elimination and organ distribution between standard and beta-propiolactone IgG.

Animals↗

[Antigen-elimination technic. An in vivo method for studies of the human immune response against horse gamma globulin].

In 20 patients treated with antilymphocyte horse gamma-globulin (ALG) the immune response was tested by means of the antigen elimination technique before, during and after ALG-therapy. The comparison of this method with agargel diffusion test, indirect hemagglutination and skin tests showed that immunization of patients against horse protein is indicated earlier and more reliable with the antigen elimination. Therefore this technique should be utilized during a therapy with foreign proteins especially when the results of other immunological test methods are insufficient.

Animals↗

Quantitation of passive cutaneous anaphylaxis (PCA) by using radiolabelled antigen.

The major problem of detecting reaginic antibody by passive cutaneous anaphylaxis (PCA) is the quantitation of the dye reaction. Radiolabelled antigen was used in an attempt to quantitate the PCA reaction (Radio-PCA). Antisera containing reaginic antibody against human serum albumin (HSA) were produced in rabbits. These antisera were injected into normal rabbit skin in different dilutions. Twenty-four hours later HSA was injected intravenously either with Evans Blue or as 125-I-HSA. Radioactivity found in antibody-containing skin was significantly higher than in control specimens containing saline or normal rabbit serum, as low as antiserum dilutions of 1:1,000. Compared with the Evans Blue technique Radio-PCA was able to distinguish quantitatively between different antiserum dilutions at a higher level of statistical significance.

Animals↗

[Concentration of intravenously administered gammaglobulin preparations in dog skin (author's transl)].

Chemical modification of standard gammaglobulin with enzyme treatment (pepsin) or stabilization (beta-propiolactone) is able to influence elimination, fragmentation and organ distribution of intravenously administered gammaglobulins as shown in 36 dogs after i.v. application of allogenic and xenogenic gammaglobulin preparations. Pepsin-gammaglobulin was eliminated and fragmented most rapidly. Gammaglobulin concentrations of all preparations in the skin showed as slower decrease than comparable blood concentrations. The highest skin concentrations 10 days after i.v. application were found for beta-propiolactone gammaglobulin with 6.2 +/- 1.6 microgram/g compared to a blood level of 7.9 +/- 0.9 microgram/ml.

Animals↗

Preparation and properties of trypsin and chymotrysin coupled covalently to poly (N-vinylpyrrolidone).

Water-soluble poly(N-vinylpyrrolidone) of molecular weight 10 000 was modified by hydrolysis of 5% of the gamma-lactam rings, and formation of the N-hydroxysuccinimidester. This activated polymer was bound covalently to trypsin (EC 3.4.21.4) and chymotrypsin (EC 3.4.21.1) to complexes of a molecular weight of about 150 000. The bound enzymes showed an increase in stability towards autolysis. Towards small molecular weight substrates the trypsin-poly (N-vinylpyrrolidone) conjugate showed an increase in specific activity of 1: 1.6, whereas the activity towards larger substrate was found to be only 20%. Chymotrypsin-poly(N-vinylpyrrolidone) showed decreased activity against small (50%) and large (7%) molecular weight substrates.

Chemical Phenomena↗

[Long-term therapy using horse anti-dog lymphocyte globulin without sensitization against horse protein].

Eight mongrel dogs received a standard daily i.v. infusion of 20 mg/kg b.w. deaggregated horse-anti-dog-lymphocyte-globulin (ALG) and additional prednisolone (1 mg/kg b.w. daily i.v.) over a maximum period of 82 days following pretreatment with deaggregated normal horse IgG. No sensitization against horse protein was observed during therapy of afterwards as proved by lack of humoral antibodies against horse antigens, maintained lymphopenia, good compatibility, longterm prolongation of xenogeneic skin graft survival (85.6+/-20.6 days, n=8' untreated controls 12.5+/-1.3 days, n=4) and longterm suppression of cytotoxic antibodies against donor lymphocytes. The level of preformed agglutinating antibodies against horse erythrocytes was significantly reduced, while preformed antibodies against other species remained normal. The immune response to a challenge injection of anti-lymphocyte-serum (ALS) 6-11 weeks after termination of treatment was significantly lower in the ALG treated animals as compared to the control group. These results suggest the involvement of a specific mechanism of unresponsiveness against ALG other than immunosuppression only. It is concluded, that by the described method sensitization against ALG can be prevented during longterm treatment.

Animals↗

High incidence of horse serum protein allergy in various autoimmune disorders.

In 186 persons (68 patients suffering from different so-called autoimmune diseases, 30 kidney recipients, 38 control patients from a surgical ward, and 50 healthy volunteers) the immune response to horse IgG was examined. The lowest rate of sensitization was found in kidney transplant recipients (3%) and the highest in autoimmune patients (33%). After excluding 39 patient who had received horse serum treatment prior to the examination, it was found that without previous injection of horse serum, 27% of the patients with autoimmune disease were sensitized to horse IgG. Compared to the other groups (kidney transplant recipients, 4%: surgical controls, 0%; healthy volunteers, 3%), this difference was statistically significant (p is less than 0.01).

Allergens↗