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M R Nejamkis

Publications and source records attributed to M R Nejamkis.

At least 55 records · Page 3Linked to original sources
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[Experimental Junin virus infection in the mouse: rototype of the disease].

As previously postulated, the pathological changes which develop in 1-4 day old mice after intracerebral inoculation of 1-1000 DL50 of Junín virus prototype strain (XJ), was designated as experimental hemorrhagic fever of the mouse EHFm. In this paper, virus distribution, hematological alterations, interferon and circulating antibody responses are described. A mortality of 93.45% occurred between 9 and 20 days post-infection (p.i.), with 81.6% of death occurring between 11 and 18 days p.i. This last period can be considered to be the critical period of the disease. The study of virus distribution shows that the brain, where the virus was inoculated, was the only place where virus could be detected 48 hs, p.i. Four days p.i., the titer in the brain increased remarkably and virus was detected in the blood. Virus, within the same values, could be isolated up to the 10th. day. Invasion of liver and spleen occurred on the 10th. and 15th. days p.i., respectively (Fig. 1). The onset of clinical symptoms coincided with widespread disemination of the virus. CF antibodies were found only 15 days p.i., with a titer of 1/64. Neutralizing antibodies remained below detection levels during the whole experiment (Fig. 1). Surviving mice (6.3%) had high circulating antibody titers 40 days p.i. This result would indicate that the morobidity of EHFm is aproximately 100% (Table 1). Poor interferon response was registered in all the organs examined, indicating a low intereron producing ability for Junin virus6. Total leukocytes and lymphocyte counts showed a slight tendecy to drop, although the values were within normal range during the first ten days (Table 2, Fig 1). On day 14 p.i., a statistically significant decrease (p less than 0.001) was found. This leuko-lymphopaenia continued until death of the animals. It is expected that the data presente here would contribute to a better understanding of the Junin virus infection in the newborn mouse, the experimental animal used.

Animals↗
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[Immunopathology induced in the rat by Junin virus].

Intra-cerebral infection of the 10-day-old rat with the XJ prototype strain of Junin virus induces an immunopathological encephalitis with 100% mortality. In contrast with previous observations, our present work with antithymocyte serum (ATS) demonstrates a pathological role for the cellular immune response in this experimental model. As regards ATS treatment, 3 schedules were employed, the most efficient being daily 0.01 ml/g weight doses from day -1 to day +9, then +12, +14 and +16, taking day 0 as the time of virus infection. Survival reached 54% and the average day of death was delayed 12 days (Table 1). No differences were recorded in brain viral titres in treated vs untreated infected controls (Table 2). Lastly, splenocyte transfer from infected 10-day-old rats, to infected 2-day-old animals, which are known to develop persistence without death, led to 40% mortality in recipients vs 0% in 2-day-old non-transferred infected controls. Therefore, it may be concluded that: a) encephalitis in the 10-day-old rat is immunological in nature and b) transfer of lymphocytes to infected 2-day-old rats, induces disease and death.

Animals↗
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[Cellular hypersensitivity in the infection of mice by Junin virus. I. Passive transfer].

The data presented confirm previous evidence of delayed hypersensitivity in mice following infection with Junin virus. Adaptive transfer of sensitized cells from adult mice which had received 5 Junin virus injections into preinfected newborn mice shortened their survival by 72 hours. It was clear, however, that the development of the immunological mechanism in adult mice occurred under certain conditions. This evidence was confirmed by the observations that the induction of cell-mediated immunity and the response of sensitized lymphocytes to viral antigens appeared to be related to multiple injections of the virus. On the other hand, the sensitized cells were present in adult mice by day 9 and vanished 60 days after the infection. These results revealed the difference between the lymphoid cells from adult mice in the early and the late stages of immunity. The implications of these results in the development of the fatal neurological disease induced by the Junin virus in newborn mice are discussed.

Animals↗
PubMedDate not supplied

[Cellular hypersensitivity in the infection of mice by Junin virus. III. Experience with Cr51 an antitheta serum].

Several aspects of the appearance and development of delayed hypersensitivity in mice infected with Junin virus are described. The results obtained showed that the development of the immunological mechanisms occurs irrespective of age. Spleen cells of donor mice inoculated with one i.p. dose of Junin virus had a poor cytotoxic activity, as demonstrated by 51Cr release and adoptive immunity procedures. Spleen cells treated with anti-theta serum and complement did not strikingly affect the development of Junin virus disease in mice. This demonstrated the capacity of T lymphocytes to influence the course of the viral infection of newborn mice adoptively transferred with immune spleen cells. No difference were detected in the virus titer in the brains of transferred and control animals, this fact suggests that immune T lymphocytes are not involved in Junín virus clearance.

Arenaviridae↗
PubMedDate not supplied

[Protection against encephalitis in rats caused by a pathogenic strain of the Junin virus, using peripheral inoculation of an attenuated strain].

Argentine Hemorrhagic Fever manifests itself in man either subclinically or in hemorrhagic or neurological forms, mortality reaching 20%. Although Candid 1 strain is undergoing pilot trials, current therapy still resorts to convalescent serum administration. A neurological model was used to evaluate protection conferred by the attenuated XJC13 Junin virus strain. Newborn rats inoculated intraperitoneally (ip) prove resistant, whereas 8-12 day-old animals infected by intracerebral route with the XJ prototype strain suffer 100% mortality with neurological signs. The aim of this study was to achieve protection in this model and attempt to elucidate the mechanisms involved in resistance. It was observed that the longer the inoculation challenge interval, the greater was the survival percentage. In protected animals, brain viral titres were 3 log lower than in challenged controls, while XJC13 infected unchallenged controls presented low CNS values throughout. Neutralizing antibody levels were not significantly different in experimental versus challenged control groups, ruling out any secondary booster effect on protected rats. Neither the transfer of immunoserum nor of endogenous or exogenous interferon altered mortality. However, when splenocytes from rats infected 10 days previously were transferred prior to XJ challenge, survival was increased to 50%, but there was no gain in protection when cells were treated with antithymocyte serum plus complement. Consequently, protection in this neurological model can be attributed to a cellular immune response.

Animals↗
PubMedDate not supplied

[Experimental infection of guinea pigs with Tacaribe virus: effect on the functioning of the immunocompetent system].

Tacaribe virus is the member most closely related to Junín virus within the Tacaribe complex. It has been demonstrated that both viruses are indistinguishable by complement-fixation, due to the high cross-reactivity. However, adult guinea pigs are highly sensitive to infection with the XJ pathogenic strain of Junín virus whereas Tacaribe virus is nonpathogenic for this species. Furthermore this last virus protects them against Junín virus. The XJ strain reduces the immune response of guinea pigs to many antigens. Both the humoral response and the hypersensitivity of the Arthus type have been reduced in infected animals. Considering that Tacaribe virus could be used as vaccine antigen, the purpose of the present study was to investigate the effect of Tacaribe infection on the immune system of guinea pigs. The data reported here supports earlier findings showing that the XJ strain of Junín virus suppresses humoral immune response as indicated by lower precipitating antibody titers to ovoalbumin (which contributed to milder Arthus cutaneous reactivity) and a significant depression of plaque-forming cells to sheep erythrocytes. In contrast, Tacaribe-infected guinea pigs did not show detectable immunosuppression employing the same models. Similar results were found when the cell-mediated immunity was investigated. Tacaribe-infected guinea pigs had a normal immune response to contact sensitivity to 2-4 dinitro-1-fluorobenzene as demonstrated by measuring ear swelling and unmodified tuberculin reaction, after injection with complete Freund's adjuvant. Our results and those of previous investigations justify the consideration of Tacaribe immunization as an approach to the prophylaxis of Argentine Hemorrhagic Fever.

Animals↗
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[Effect of cyclophosphamide on experimental infection of rats with 2 strains of the Junin virus].

The course of viral infection in rats of several ages after intracerebral inoculation with two strains of Junin virus, as well as the effect of an immunosuppressor was studied. The survival rate in 2-day-old rats was 95%, which fell to 45% in cyclophosphamide-treated infected animals (Figure 1a). However, barely 5% of these rats inoculated with the XJCl3 strain survived, while the cyclophosphamide suppressive treatment increased the rate to 36% (Figure 1b). This contrasting behaviour suggested that the XJ strain produces a subclinical infection in 2-day-old rats and the host immune mechanisms are responsible for recovery from the viral infection. Adequate immunosuppression converts sublethal experimental infections into lethal infection, accompanied by persistent viral replication in the target organ (brain) and suppression of anti-viral antibodies (Figure 2a). On the other hand, the inoculation of 2-day-old rats with the XJCl3 Junin virus may give rise to an immunopathology avoidable by CY treatment. In 10-day-old rats both strains of Junin virus caused a direct pathology, not modified by CY treatment (Table 3). This treatment failed to change susceptibility or virus concentration in the brain, but specific antibodies were considerably reduced. In the case of 26-day-old rats, there was total resistance to viral infection which remained unchanged after CY treatment.

Age Factors↗
PubMedDate not supplied

[Isolation of an Paracoccidioides brasiliensis exoantigen from solid culture media].

The goal of this work was to develop in solid medium a fast method to obtain Paracoccidioides brasiliensis (Pb) with a high yield. Four culture media were assayed: Sabouraud honey-agar, Sabouraud dextrose-agar, tomato -agar-medium (TOM) and a medium based on grape pulp. The most exhuberant growth was observed in medium based on grape pulp. Antigen was prepared in microscale at 6, 10 and 15 days incubation of solid cultures and the crude product concentrated by means of Centriplus tubes (Helena, France). Isolated antigens were subjected to polyacrylamide gel electrophoresis, followed by immunolabelling and detection of the characteristic gp45 antigen employing human and Pb-infected rat sera. Best results were observed after 10 days culture in grape medium. None of the other three media afforded comparable results.

Agar↗