Biomedical subjects
Publications and source records attributed to H Stickl.
Newborn babies have been vaccinated orally on five consecutive days, with 5 droplets of a vaccine containing 10(11) killed Bordetella pertussis. Eight out of twelve subjects showed antibody titres varying between 1:20 and 1:80.
A case of generalized progressive vaccinia with lethal outcome after smallpox vaccination observed in an 8 months old girl during 1968 is reported. This complication was the first sign of an underlying immune deficiency in this child. The most conspicious findings suggesting a humoral immune defect were an absent serum IgM in combination with decreased IgA and IgG levels. An additional cellular defect was suggested by a generalized hypoplasia of the thymus and the entire lymphatic system as shown during autopsy. Vaccinia virus could be found not only in skin eruptions intra vitam but also in lung, liver and brain tissue in post mortem studies.
The oral administration of appropriate antigens causes a decrease in sensitization as shown by the models of tuberculin allergy in guinea pigs and of the sensitization of guinea pigs and rabbits to corynebacterium acnes antigens.
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In chromosomes of peripheral lymphocytes of 35 patients with multiple sclerosis treated with azathioprine, antilymphocytic globulin or thoracic-duct drainage structural aberrations (breaks and gaps) were found at a significantly high rate. The aberration rates were increased in another ten untreated patients as well, but less so. Patients previously treated had a high aberration rate, too. The B- and C-chromosomes of patients treated with azathioprine were more frequently involved than those of control subjects. The terminal segment of the long arm of chromosome 1 was mostly affected in these patients, while in all groups there was an increase of aberrations in the centre of the long arm of the C-chromosome. The clinical significance of these chromosomal aberrations is not yet clear.
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The attenuated MVA strain of vaccinia virus was previously shown to be innocuous and immunogenic at intracutaneous injection. It was therefore suggested for clinical trial. Preliminary results in human vaccinees are promising. The present experiments were initiated to study the intramuscular injection of the vaccine as a preferable route of administration. Histological examination was done in rabbits and monkeys. At the site of injection there were but minor inflammatory reactions considerably less pronounced than after the injection of commercial tetanus vaccine which was used for comparison. Intramuscular immunization with strain MVA repeated twice protected rabbits against an intravenous challenge with vaccinia strain Elstree; monkeys were protected against experimental smallpox. Intramuscular immunization with attenuated smallpox vaccine is suggested for clinical trial.
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The anti-inflammatory activity of FL 70, a derivative of 2,5-dihydroxy-benzoic acid, was examined in a number of conventional experimental models. In addition, FL-70 was tested for its inhibitory action on enzymes. The results were as follows: 1. The induction of a local inflammatory reaction and the subsequent i.v. injection of trypan blue showed that FL 70 reduces the capillary permeability. 2, FL-70 significantly suppresses exudation in the formalin-induced peritonitis of the rat. 3. A slight inhibition of an edema in the footpad of the rat induced by formalin-dextran was not shown to be statistically significant. 4. Local swelling could be markedly inhibited in the turpentine-oil induced inflammatory reaction of the rabbit. 5. Exudation and formation of granulomatous tissue was inhibited in Selye's granuloma. 6. FL-70 markedly inhibited the local inflammatory reaction accompanying the cutaneous reaction in experimental vaccinia infection of the rabbit skin. The size of the infiltration after intracutaneous infection of the virus was not reduced. 7. FL-70 could not prevent the onset of clinical signs, if administered in experimental allergic encephalitis. 8. The activity of acid phosphatase was inhibited by FL-70. Alcaline phosphatase, cholinesterase, leucin aminopeptidase, glucose-6- phosphatase-dehydrogenase (G-6-PDH), trypsin and chymotrypsin were unaffe-ted. FL-70 inhibits the following, G-6-PDH activated reduction process: glucose-6-phosphate (see article).
Vaccinia virus infection was performed by scarification of the shaved skin (5 times 5 cm2) on the back of Pirbright guinea pigs. The macrophage migration inhibition test was performed with peritonealexudate cells 7, 11, 14 and 21 days after infection. Macrophage migration inhibition occurred after exposure of the cells to whole brain tissue antigen on the 7th, 11th, 14th day after infection (s. table 1). Lymphocyte transformation responses were examined by 14C-2-Thymidin uptake using blood cultures and basic encephalitogenic protein and whole brain tissue extract as antigens. A positive transformation response could be demonstrated from one to 8 weeks after infection (s. table 2). The specificity of the transformation response to brain antigen was established using control cultures stimulated with PHA or PPD. In no case stimulation occured with PPD. Stimulation with PHA was not altered. On the other hand the spontaneous lymphocyte transformation was enhanced at one week after infection and lymphocyte cultures exposed to heat inactivated vaccinia virus showed transformation from the 3th week after infection until the end of the observation period (i.e. 8 weeks) (s. table 2). The reason why cell mediated hypersensitivity to brain antigen is induced following vaccinia infection remains unknown. The most probable among several possible mechanisms seem a) the induction of virus-specific antigens on the surface of infected cells or b) the release of brain specific antigen through virus infection.
29 guinea pigs, strain Pirbright, were infected with vaccinia virus, strain Elstree, by the dermal route. The observation period was 14 days. Thereafter, the animals were killed and their central nervous systems (CNS) histologically and immunohistologically, the blood fluorescence-serologically examined. Histological examination revealed meningitis, ependymitis or disseminated meningoencephalitis with slight perivascular cuffing in 72% of the animals. The viral antigen was found in 3 animals (10%). It was present most often in the cytoplasma of the arachnoidal and/or ependymal cells, as well as in the cells of the vessel walls and less often in the glial and/or nerve cells. The infected cells showed no severe degenerative changes. The blood-brain-barrier displayed localized disturbances. The examination of the myelin sheaths revealed disseminated foci of disappearance of myelin fluorescence in the perivascular, paraventricular and subcortical regions. Antibodies directed against myelin sheaths, or nerve cells could be detected in the sera of 48% of the animals. The results give evidence that the vaccinia infection is capable to induce a potentially pathogenic autoimmune reaction directed against brain. Such an immunomechanism can be triggered without any signs of acute lytic infection of the CNS. The mechanism and significance of this reaction are discussed.
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