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Biomedical subjects

M Majer

Publications and source records attributed to M Majer.

At least 37 records · Page 2Linked to original sources

Intramuscular and/or intralumbar postexposure treatment of rabies virus-infected cynomolgus monkeys with human interferon.

From 9 to 10 of 10 cynomolgus monkeys infected with rabies street virus died of rabies about 20 days postinfection (pI). Symptoms of illness appeared 1 to 4 days before death. In an attempt to protect infected animals from the disease, human leukocyte interferon (HIF) was administered intramuscularly (i.m.) near the site of infection or into the cerebrospinal fluid between the first and second lumbar vertebrae (i.e., intralumbarly [i.l.]). Multiple HIF doses given over a period of several days proved more effective than a single HIF dose. In every experiment, i.m. HIF treatment was started 1 day pI. The best result obtained was a survival rate of 7 of 10 monkeys. The i.l. HIF administration schedules, consisting of multiple doses given over a period of at least 8 days, were started on day 3, 7, or 11 pI. Here the best result noted was the protection of 5 of 10 treated monkeys. The latest successful postexposure i.l. HIF treatment began on day 11 pI. The highest protection rate, 8 survivors of 10 treated monkeys, was achieved by a combined i.m. and i.l. HIF treatment. From these results we conclude that human patients severely bitten by rabid animals should in addition to an active immunization be i.m. and i.l. treated with HIF. Particularly, i.l. HIF administration could be effective, even when given several days pI. Whether an HIF administration starting after the appearance of clinical symptoms of rabies can help cannot be decided upon from the studies made in this monkey model. The most obvious difference between rabies in humans and cynomolgus monkeys is the duration of illness between the outbreak of the disease and death (1 to 4 days only in this animal model). It might have been due to this short period of illness that i.l. and i.m. HIF treatment at the appearance of clinical symptoms failed to help any of the monkeys treated.

Animals↗

[A purified rabies vaccine from human diploid cell cultures (author's transl)].

In order to improve the tolerance of rabies vaccine from human diploid cell cultures, the rabies virus antigen is purified in the sucrose density gradient by means of a flow ultracentrifuge. The purified virus has a specific infectiosity of 10(9) LD50 and a speicific activity of 250 units "relative activity" per 1 mg protein. The purified vaccine has been shown to be well tolerated, effective and stable.

Animals↗

[The importance of interferon for rabies prophylaxis (author's transl)].

The importance of interferon for the prophylaxis of rabies is not yet fully understood. About 50% of cynomolgus monkeys infected with rabies virus could be protected from the disease with human interferon which was administered at a total dose of 1--10 million units per animal either intramuscularly 24 hours after infection or by intralumbar injection up to 11 days after. The clinical relevance of the findings is discussed.

Animals↗

Diarrhea in newborn cynomologus monkeys infected with human rotavirus.

Of six newborn cynomolgus monkeys (Macaca fascicularis) naturally delivered and normally nursed five developed diarrhea after oral administration of human rotavirus. Virus excretion was observed in the stool of four animals. This virus was transmitted to four out of six other monkeys causing diarrhea in only one animal.

Animals↗

Rabies vaccine HDC: toxicological studies in laboratory animals.

A purified rabies vaccine prepared in human diploid cell cultures (Wistar 38 adapted Pitman-Moore strain) was tested in several animal species with single and repeated administration. Acute toxicity studies were performed in mice, rats, and guinea pigs with s.c. or i.m. injections of at least 1 human dose/animal. The results gave no evidence of toxic effects. Studies on local compatibility were carried out in white rabbits (i.c. and s.c.) and albino guinea pigs (i.m.). During the observation period of 1 or 2 weeks after inoculation no adverse reactions were seen. Pyrogen tests in rabbits with 6 lots of vaccines showed that rabies vaccine is pyrogenfree. Long-term studies with 4 injections into rats and dogs and observation over a 4-month period gave no alterations of hematological parameters and of the urinalysis. The behaviour of the animals was not altered. Short- and long-term experiments in animals showed the innocuity of this type of rabies vaccine.

Animals↗

A purified human diploid cell rabies vaccine.

Continuous-flow isopycnic banding of rabies virus in sucrose gradient was used to purify the antigen for the preparation of a human diploid cell rabies vaccine. Prior to the addition of the stabilizer, the average specific potency of several vaccine batches was 234 antigenic values per 1.0 mg of protein. Further data regarding potency and stability of this vaccine are presented.

Antigens, Viral↗

Antigenicity of low concentrated HDCS vaccine with and without adjuvant as compared to the standard fluid formulation.

It can be shown that 0.1% aluminum hydroxide is able to compensate a 90% difference in antigen content of a human diploid cell strain rabies vaccine in man. This conclusion, however, is drawn only from the formation of neutralizing antibodies (kinetics and antibody concentration). Further experiments should be performed to compare also the protective capacity of HDCS vaccines varying in antigen content and adjuvant. A sole reduction of viral antigen is reflected by a corresponding reduction in antibody formation provided the different doses fall within the logarithmic part of the dose-response curve.

Adjuvants, Immunologic↗

Administration of human interferon to rabies virus-infected monkeys after exposure.

The treatment of rabies-infected cynomolgus monkeys (Macaca fascicularis) with human interferon after exposure was studied. The monkeys were infected with rabies street virus by the intramuscular route; larger than or equal to 24 hr after infection, human interferon was administered intramuscularly or by lumbar spinal injection into the cerebrospinal fluid. Whereas 90% of the infected untreated monkeys died, 40%-80% of animals treated with interferon survived. No or only low levels of neutralizing antibody to rabies virus were found in the sera of monkeys that survived after a single intramuscular injection of human interferon. Distinctly higher antibody titers, however, were detected in the sera of surviving monkeys that had been given six consecutive intralumbar doses of interferon beginning three days after infections. Therefore, we conclude that in these monkeys rabies virus propagated until it spread into the central nervous system, where further viral replication was inhibited by the human interferon administered by the intralumbar route.

Animals↗

[Seroepidemiological Investigations on the epidemiology of human rotavirus infections (author's transl)].

263 sera of infants and children up to 10 years of age were tested for antibodies (CF-test) against Nebraska calf diarrhoea virus (NCDV) which is antigenically related to the rotavirus of man; in addition the mean antibody titers in different age groups were investigated. Antibodies of maternal origin were eliminated during the first year of life. Most of the infections occurred during the second year of life and at the end of this year 40-50% of the investigated children demonstrated antibodies against NCDV; this frequency persists during the rest of the investigated life period.

Antibodies, Viral↗

[Immunosuppression and endogenic viral reinfection (author's transl)].

The consequence of nonspecific immunosuppressive therapy is a more frequent appearance of virus infections in the patients. They are largely caused by herpes and papova viruses. In addition to primary and recurrent exogenous infections, endogenous reinfections also have great importance. Clinically there is a broad palette from severe to inapparent types of infection. The use of live virus vaccines is contraindicated during immunosuppressive therapy.

Herpesviridae Infections↗

Immunity after infections with Myxoviruses.

Influenza, parainfluenza and respiratory syncytial viruses cause respiratory infections in man with consequent transient and sometimes imperfect against reinfection. Humoral immunity and probably cell-mediated immunity contribute to resistance. Whereas circulating antibodies are more important for influenza viruses, secretory antibody are relatively speaking more important for parainfluenza and respiratory syncytial virsues. Measles and mumps induced longlasting immunity which can be correlated with circulating neutralizing antibodies. Certain immune responses against measles and respiratory syncytial virus cause pathological reactions after infection with the same virus.

Animals↗