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Biomedical subjects

P M Cossio

Publications and source records attributed to P M Cossio.

At least 19 recordsLinked to original sources
PubMed1986

Experimental infection of Akodon molinae (Rodentia, Cricetidae) with Junín virus.

Experimental infection with the XJ-Clone 3 strain of Junín virus in laboratory bred Akodon molinae, a cricetid rodent inhabiting the borders of endemic Argentine hemorrhagic fever areas, was studied. Suckling animals inoculated intracerebrally proved sensitive and became chronically infected. Sixty percent of the rodents showed neurologic involvement, with mortality reaching 60%. Virus was recovered from the brain at 7, 15, 21, 37, and 57 days postinfection (pi). By immunofluorescence (IF), viral antigens were observed up to 182 days pi in cells of the central nervous system (CNS). Concurrently, immunoglobulin deposits were detected in infected CNS cells from 21 up to 182 days pi. These deposits increased with the progression of the immune response as measured by IF antibodies. The detection of immune complexes in brain cells of apparently healthy animals suggests that neither viral replication nor the development of a humoral immune response are necessary requisites for neurovirulence in this host. Infection of adult rodents by different routes failed to induce disease or mortality and virus could not be recovered from oral swabs, blood, or organs. Our data suggest that Akodon molinae could play a role in nature as an alternative reservoir of Junín virus in addition to the main reservoir, Calomys musculinus.

Animals↗
PubMed1985

Cryostat sections with tissue amastigotes of Trypanosoma cruzi as a substrate for Chagas' disease serology.

Sera from 30 chronic chagasic patients together with 52 control samples (34 with other pathological conditions and 18 from normal individuals) were titrated by the indirect immunofluorescent technique (IFA) on Trypanosoma cruzi amastigotes. Acetone-fixed cryostat sections of skeletal muscle of Rockland mice 10 days post-infection with the RA isolate of T. cruzi were used as substrate. Results were compared with titres obtained by conventional IFA on epimastigotes. All 52 control sera had amastigote titres less than or equal to 2 double dilutions (dd) as compared with epimastigote values. Out of the 30 chagasic samples, differences were greater than or equal to 4 dd (less than or equal to 1 log) for 22, 3 dd for 5 and less than or equal to 2 dd for the remaining 3, when comparing amastigote and epimastigote titres. These results show that the use of amastigotes in cryostat sections of infected tissue for performing Chagas' serology in a simple, adequate and sensitive method.

Antibodies↗
PubMed1984

Experimental myocarditis induced in Swiss mice by homologous heart immunization resembles chronic experimental Chagas' heart disease.

The Swiss mouse is considered a satisfactory model for experimental chronic chagasic myocarditis and there is some evidence of an immunopathologic mechanism in the development of this disease. To further support this conjecture, 45-day-old albino Swiss mice (40 animals) were immunized with homologous heart in complete Freund's adjuvant. As controls, 20 animals were likewise inoculated with allogeneic testis, as "non-related" antigen. Three mice from the former group died suddenly at 19-21 days postinoculation while the survivors were sacrificed at 60 days for serum samples, and histologic analysis of the heart and skeletal muscle. Electrocardiographic records were taken at Days 0, 30, and 60 postinoculation. Of myocardium-inoculated animals and testis-inoculated mice 33/37 (89%) and 1/20 (5%), respectively, exhibited myocarditis (P less than 0.001). Histologic lesions were highly reminiscent of those observed in chronic experimental Chagas' disease of Swiss mice. Antimuscle antibodies were seen, by indirect immunofluorescence employing cryostat sections, in 30/33 (91%) of the former group and in 3/20 (15%) of the latter (P less than 0.001), some of which recognized a surface antigen of primary cultured fetal rat myocardiocytes. Mice inoculated with myocardium also exhibited electrocardiographic abnormalities consisting in QRS interval widening. Results show that following an autoimmune experimental design the main features of chronic chagasic myocarditis may be reproduced in the Swiss mouse. This agrees with the likely role of an immunopathologic mechanism in heart damage due to Trypanosoma cruzi infection.

Animals↗
PubMed1984

The guinea pig model for Argentine hemorrhagic fever.

Guinea pigs infected by the peripheral route with the XJ pathogenic strain of Junin virus showed viscerotropism mainly in reticulo-phagocytic rich organs. By immunofluorescence, heavy infection of reticular-phagocytic cells was demonstrated, supporting the leading role of these cell types. Absence of neurotropism was demonstrated by the inability to recover infectious virus, as well as the absence of antigens, immunoglobulins, or 3rd component of complement deposits, in cells, vessels, or meninges. The correlation between infectivity and antigen expression observed in organs, and the absence of evidence of immunopathologic mechanisms, strongly suggest a direct viral effect in these experimental conditions. The results show that infection of guinea pigs by the peripheral route is an adequate model for human Argentine hemorrhagic fever with the exception of central nervous system involvement. Comparisons are made with infections produced in guinea pigs by attenuated strains, as well as with the disease in primates and humans.

Adrenal Glands↗
PubMed1983

Heterophil nature of EVI antibody in Trypanosoma cruzi infection.

Previous findings implying the autoreactive capability of circulating complement-fixing (EVI) antibodies in patients with Chagas' disease (American trypanosomiasis), under both in vitro and in vivo conditions have been irreproducible. The presence of the tissue antigens involved in the reactivity with EVI antibodies is exclusively confined to nonhuman substrates, suggesting the heterophil nature of these antibodies which, on the other hand, have also been described in human sera collected in areas free from Chagas' disease. This would preclude any direct pathogenic effect of EVI antibodies when present in the circulation, though they may be useful immunological markers of unsuspected Trypanosoma cruzi infection in endemic areas.

Animals↗
PubMed1982

Side effects of immunization with liver attenuated Trypanosoma cruzi in mice and rabbits.

Immunity against lethal, bloodstream forms of Trypanosoma cruzi was achieved in mice by preinoculation of approximately equal to 10(5) culture epimastigotes of an attenuated T. cruzi strain (TCC). The risks of TCC inoculation in terms of pathogenicity or eventual increase in virulence of TCC progeny were evaluated. No pathogenic parasites could be selected from TCC progeny by either mouse, triatome, or culture passages. Immunizing doses of live TCC did not induce in adult mice alterations resembling chronic Chagas' disease, as judged by patterns of mortality, tissue damage, autoantibodies, or parasite recovery. On the basis of the same criteria, However, a remarkable similarity could be established between the disease caused in mice by inoculation of low numbers (10(2)) of pathogenic trypomastigotes and human chronic Chagas' disease. Although patent parasitemias were never revealed in fresh blood mounts obtained from TCC-inoculated mice, a few hemocultures and xenodiagnoses gave positive results, particularly soon after inoculations at birth. The parasites recovered by either method remained in the attenuated, epimastigote stage. In rabbits, no local lesions, fever, weight loss, or histopathological alterations were detected after subcutaneous inoculation of 10(7) TCC organisms, although one fifth of the animals yielded positive hemocultures of epimastigotes. The contrasting host response to cultured epimastigotes as compared with blood trypomastigotes indicates that, in experimental Chagas' disease, immunoprotection is not necessarily associated with immunopathology.

Animals↗
PubMed1981

Junin virus infection of guinea pigs: immunohistochemical and ultrastructural studies of hemopoietic tissue.

An association between viral antigens, cytopathic effect (CPE) and viral titers in blood and lymphoid tissues suggests a direct CPE of Junin virus on the lymphopoietic organs of guinea pigs infected with 10(3) 50% lethal doses of the XJ prototype strain. After seven days of infection, all lymphoreticular organs had infectivity titers higher than those for blood. Virus was recovered from bone marrow and lymph nodes at day 5 after infection; peak titers were obtained from bone marrow, spleen, and lymph nodes after day 10. Granular specific fluorescence was detected in the cytoplasm of reticular monocytes after day 7; megakaryocytes showed positive fluorescence, but specific staining of other lymphoid cells was not observed. Necrosis of bone marrow, lymph nodes, and spleen was observed after day 9. CPE consisted of overdevelopment of reticuloendoplasmic cisterne of reticulomonocytes and myeloblasts. Typical Junin virus particles were observed. Reticular cells were gradually destroyed, and simultaneous necrosis of surrounding lymphoid cells was observed.

Animals↗
PubMed1981

Calcium ions and the influence of chagasic sera on the effects of ouabain on isolated rat atria.

The effects of chagasic sera containing an antibody (EVI antibody) on "non toxic" and "toxic" actions of ouabain on isolated rat atria suspended in different media, were explored. Ouabain failed to evoke any significantly positive contractile effect on atria beating in EVI Positive Human Sera (EVI(+)S), and only produced "toxic" actions (arrhythmias, contracture enhanced frequency, reduced inotropism). On the contrary, atria beating in Krebs-Ringer-Bicarbonate (KRB) or in Normal Human Sera (NHS) reacted to added ouabain with a classical dose-dependent positive inotropic effect. The threshold concentration of ouabain required to elicit the onset of "toxic" effects was higher in KRB than in EVI(+)S. Decreasing the extracellular Ca2+ concentration or treating the auricles with verapamil, facilitated positive inotropic influence of ouabain and attenuated the "toxic" effects observed on atria beating in EVI(+)S. In addition, the combination of (--)-propranolol plus verapamil enhanced the facilitatory influence of verapamil induced on the positive inotropic effect of ouabain and reduced the "toxic" influences evoked on atria exposed to EVI(+)S. These findings support the notion that the overall "toxic" responses to ouabain on cardiac tissue immersed in an EVI(+)S containing solution may be related to a combined effect of the EVI antibody activating beta-adrenoceptors as well as to a rise in the tissue Ca2+ content.

Animals↗
PubMed1980

Description of a BHK/21 cell line persistently infected with Junin virus: its use in diagnostic procedures.

A BHK/21 cell line persistently infected by an arenavirus is described. During four consecutive passages, 30-45% of the cells showed granular cytoplasmic antigen by indirect immunofluorescence, employing both Argentine hemorrhagic fever convalescent sera and sera from animals immunized with Junin virus. Virus isolated from the cells killed suckling mice but not adult mice and protected guinea pigs against further challenge with the virulent prototype strain of Junin virus. Neutralization tests showed that the virus isolated from the cells was neutralized by anti-Junin virus antisera. The usefulness of this cell line in rapid immunofluorescent serological procedures is described.

Animals↗
PubMed1980

Lymphatic tissue in Argentine hemorrhagic fever. Pathologic features.

Spleen and lymph nodes from seven fatal cases of Argentine hemorrhagic fever were studied by light and electron microscopy and by immunofluorescent techniques. In addition, Junin virus infectivity was determined. Destruction of splenic white pulp and of lymph node cortex was observed. The ultrastructural study showed a characteristic cytopathic effect on the macrophages with presence of intracisternal virus-like particles and occasional virions budding from the plasma membrane. The immunofluorescent techniques indicated the presence of Junin virus antigenic determinants in the cytoplasm of macrophages in the examined organs. Junin virus titers were three times higher than in peripheral blood. These results suggest that lymphatic tissue is one of the main sites of viral replication and that the macrophages are the targets of Junin virus.

Antigens, Viral↗