The biosynthesis of cytidine nucleotides and the level of cytochrome P-450 in rat liver after administration of alpha-hexachlorocyclohexane.
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Biomedical subjects
Publications and source records attributed to J Seifert.
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Incompatibility reactions due to hydroxyethyl starch (HES) were observed during 8 out of 10,273 infusions of 500 ml 6% HES (Plasmasteril). The clinical symptoms ranged from skin reactions to tachycardia, hypotension and shock. In 3 of the 8 patients with incompatibility serum immunoglobulin concentrations were reduced after the anaphylactoid reaction. Specific antibodies against HES were, however, not detected. Serum IgE levels stayed within their normal limits. Positive reactions of the immediate type to intradermal skin tests with different dilutions of Plasmasteril were obtained in five patients.
Sheep red blood cells were stabilized with sulfosalicylic acid and sensitized with purified horse-IgG by the action of glutardialdehyde. The cells were used in an indirect microhemmagglutination test with serum samples from 12 rabbits immunized with horse-IgG and complete Freund's adjuvant as well as from 10 control animals. 32 human serum samples were examined, 6 of them from patients with established horse protein allergy. The results were compared to those of a standard method of indirect hemagglutination using fresh human erythrocytes (group O Rh-), an active hemagglutination test against horse erythrocytes, Ouchterlony's immunodiffusion and skin tests with horse-IgG. The method proved to be very sensitive. The results correlated well with those of the other immunological techniques. The stable sensitized cells did not lose sensitivity after 1 year of storage at 4 degrees C.
Horse anti-human lymphocyte globulin (ALG) solutions contain, like human gamma-globulin preparations, a varying amount of IgG aggregates, which increase during longer periods of storage. Aggregate formation does not impair the immunosuppressive potency of ALG, as has been shown by prolongation of skin allograft survival time in primates. Deaggregated ALG, which can be obtained by ultracentrifugation at 100,000 g over 2 h, is less immunogenic than aggregate containing ALG. The clinical compatibility of ALG was significantly improved by ultracentrifugal deaggregation.
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Anticomplementary activity, aggregate content, and elimination of i.v. human gamma globulin (HGG). During storage of HGG globulin aggregate formation increases leading to anticomplementary activity. Seventeen patients suffering from postoperative sepsis showed significantly faster elimination rates of HGG than 6 healthy controls, while there was no difference in albumin elimination.
Twenty patients with multiple sclerosis, in whom treatment with azathioprine and steroids had not altered the progression of the disease, were given additional treatment with either antilymphocyte globulin (ALG) (seven patients), thoracic duct drainage (TDD) (five patients) or a combination of both (eight patients). Four of the seven patients treated with the addition of ALG showed remarkable improvement which has lasted little improvement. In the eight patients receiving both had severe allergic reactions to ALG which prevented adequate dosage. TDD alone was performed in patients sensitive to ALG. These five patients showed little improvement. In the eight patients receiving both ALG and TDD there was marked improvement in four patients which has again lasted several years. The main side effect of ALG therapy is allergic reactions. Major infections or tumour formation did not occur in any patients.
With isotopic and immunological methods it could be demonstrated that: 1. Rabbit- and horse-proteins can be absorbed from the gut into blood and lymph of rats and dogs in highmolecular form. 2. The highmolecular part after the passage of the intestinal wall was calculated between 5 and 20%. 3. The increase of the lymphocytotoxicity in the lymph of rats from 1:2 to 1:16 after enteral application of horse-antihuman-lymphocyte-gammaglobulin indicates the biological activity of the protein after the penetration through the gut. Furthermore the immunosuppressive effect of ALS after oral application could be demonstrated on the survival time of allogeneic skin transplants. A significant lymphopenia could be induced in dogs after the oral application of horse-antidog-gammaglobulin. From these findings far reaching consequences must be drawn concerning nutritional and immunological aspects. By the enteral absorption of proteins for example a natural tolerance must be induced which is broken in food allergies. Furthermore it is conceivable that the immunocompetent cells of the gastro-intestinal tract can be manipulated for the purpose of immunization or desensibilization within therapeutical programs of prophylactic medicine.
ALG is mainly used for immunosuppressive treatment following organ transplants. Controlled clinical trials demonstrated the efficacy of ALG in kidney, bone marrow and skin transplantation. Pilot studies describe a therapeutic effect in human autoaggression. A possible therapeutic effect, however, depends upon the strict observation of the following criteria: 1. Adequate dosage (20 mg/kg and more). 2. Intravenous application. 3. Suppression of sensitization against xenogeneic globulin by induction of immunological unresponsiveness before ALG-treatment (prevention of allergic complications and increase of ALG efficacy). Previously published negative results with ALG can be explained by failure to comply with the above criteria.
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The uptake and distribution of glucose, galactose, fructose and inulin in dogs was investigated in the lymph of the thoracic duct and in different blood vessels after enteral and parenteral administration. Whereas inulin could be detected neither in the lymph nor in portal venous blood after enteral administration, all other sugars were found in different concentrations in blood and lymph. Although the concentration of different sugars in the lymph after enteral and parenteral application can be compared to that in serum, the amount of sugars transported via the lymphatics is so small that it can be neglected.
Already few hours after artificial occlusion of the thoracic duct of dogs different communications appear between the lymphatic and the venous system: 1. Lymphovenous communications in the cervical area leading to the right venous angle. 2. Lymphovenous communications at heart level leading to the right venous angle. These lymphovenous communications seem to be preformed anastomoses, which are opened by an increase of the intralymphatic pressure.
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