PubMed Health⌕ Search

Biomedical subjects

M R Nejamkis

Publications and source records attributed to M R Nejamkis.

At least 19 recordsLinked to original sources
PubMed1993

[Evaluation of alternative hemoculture tests for the diagnosis of early neonatal sepsis].

In order to evaluate the diagnostic usefulness of coadjuvant tests such as external auditory canal swab culture and cultures from nasopharyngeal and gastric aspirates, and to determine the incidence and etiology of early neonatal sepsis (ENS) at our Unit, 90 newborn cases whose mothers experienced premature rupture of the membranes (PRM) were studied prospectively. Although a firm diagnosis requires positive blood cultures, the difficulty in recovering microorganisms and the trauma induced by sample collection in the baby justify the search for alternative diagnostic tests. Out of 2293 childbirths during 1991, 90 mothers (4%) had PRM more than 24 hours pre-partum, while 6.9/1000 (16/2293) developed ENS. In newborns from PMR mothers, ENS percentage was 3.3%, but increased to 5.5% in association with chorionamnionitis and reached 8.8% in premature cases. Among etiological ENS agents, Gram-positive microorganisms predominated (Table 1), particularly Staphylococcus aureus. Despite the finding that none of the coadjuvant assays (Table 2) had sufficient sensitivity or positive predictive value to identify all septic cases, they may prove useful to pinpoint newborns at high risk due to amniotic fluid exposure to infection or to chorioamnionitis.

Argentina↗
PubMed1988

Ribavirin effect on experimental Junin virus-induced encephalitis.

Junin virus, the etiological agent of Argentine hemorrhagic fever, produces in man a disease mainly characterized by hemorrhagic alterations, commonly accompanied by neurological symptoms, and leading to 10% mortality. Intracerebral inoculation in 10-day-old rats or intraperitoneal inoculation in 2-day-old rats leads to high mortality due to severe encephalitis. Here, the effect of Ribavirin on these experimental models was tested in order to evaluate the degree of protection achieved against neuropathological manifestations. In intracerebrally infected 10-day-old rats the drug was administered 2 hr before virus inoculation. Doses ranged from 30 to 90 mg/kg body weight. Protection reached 40% for the 60 and 90 mg doses. Intraperitoneally infected 2-day-old rats received the drug in five 30-mg daily doses, starting the same day as virus inoculation. Survival was 73%. Viral replication within peritoneal macrophages dropped markedly, leading to much lower CNS viral titres. Together with results reported in primates, our findings support further studies on Ribavirin, with a view to eventual trials in humans.

Animals↗
PubMed1987

Macrophages are involved in age-dependent resistance of rats to Junin virus infection.

We attempted to correlate rat age with resistance to intraperitoneal infection with the XJ strain of Junin virus. Accordingly, mortality, viral replication in macrophages and brain, as well as neutralizing antibody (NA) levels were recorded in animals inoculated at 2, 5, 10 and 26 days of life. Two-day-old animals demonstrated both the greatest mortality (86%) and viral replication in macrophages, allowing virus to reach the brain where high titers were detected. This age group also had the highest NA titers. Mortality, viral multiplication and NA titers diminished with increasing age of the animals. The ability of peritoneal macrophages to support viral replication, therefore, seems to determine rat susceptibility to intraperitoneal infection with Junin virus.

Aging↗
PubMed1986

Junin virus access to CNS by extraneural rat inoculation.

This study was carried out to determine the pathways along which two strains of Junin virus (JV), the pathogenic XJV and the attenuated XJC13V, reach the CNS following IP inoculation of 2-day-old rats. A sequential study of infectivity and antigen distribution in peritoneal macrophages, spleen, and brain was performed. Mortality was 85% with the former strain, but only 15% with the latter. At 4-7 days PI, XJV-infected animals had viral antigen in 10% of peritoneal macrophages. Viremia and spleen virus lasted for 10-15 days. Low brain titers were detected at day 7, with a peak at day 15. Brain antigen correlated with virus titers. In contrast, XJC13V-infected rats, macrophage antigen appeared later and to a lesser degree (1% of cells). Viremia and spleen virus were transient, while both the titer of brain virus and the viral antigen proved lower. Antibody titers were over twofold higher for XJ-infected animals. It is suggested that the different replication rate at the inoculation site could account for the greater ability of the XJV strain to reach the CNS. A greater antigen mass and/or more numerous antigenic determinants presented by the macrophage could explain the higher antibody titers found in XJ-injected rats, which were unable, however, to prevent viral spread.

Animals↗
PubMed1986

Brain inflammatory exudate in Junin virus-infected rats: its characterization by the immunoperoxidase (PAP) technique.

Morphologic changes in cyclophosphamide (CY)-suppressed vs. control non-suppressed new-born rats infected i.c. with XJC13 strain of Junin virus were compared and the cells involved in CNS lesions were identified by the PAP technique. Fifty per cent of the control rats exhibited widespread cerebral necrosis vs. only 15% of the immunosuppressed animals. The first cells to reach Junin virus-infected CNS in controls were T lymphocytes, which destroyed viral antigen-laden target neurons and astrocytes. B lymphocytes and macrophages, presumably attracted by viral antigen and/or by lymphokines, made their appearance a day or two later. Activated macrophages phagocytosed necrotic cells and perhaps exerted a cytotoxic effect upon target neural cells, whereas the actual role of B lymphocytes requires further explanation. In CY-treated rats, cerebral lesions were smaller and the cellular exudate, though similar, proved much scantier than in controls. A similar extent of cerebellar necrosis was observed in both groups.

Animals↗
PubMed1986

Macrophage maturity and modulation of response to Junín virus in infected rats.

Replication of Junín virus in peritoneal macrophages from newborn rats was greater for prototype strain XJ than for strain XJC13, whereas in cells from adult animals viral multiplication proved minimal. Transfer of peritoneal adherent cells from normal adult to strain XJ-infected newborn rats lowered mortality significantly. Silica blockade of macrophages protected two-day-old strain XJ-infected animals and depressed brain titers of virus significantly, whereas treatment had no effect on strain XJC13-infected rats. Macrophages from infected two-day-old rats caused illness and death in recipient animals. Silica blockade rendered macrophage-mature 11-day-old rats partially susceptible to infection with Junín virus. Thus pathogenicity of strain XJ in the two-day-old rat by the intraperitoneal route depends on the ability to replicate in peritoneal macrophages, whereas strain XJC13 is nonlethal because it fails to multiply efficiently in these cells. Macrophage maturity seems essential to inhibit viral replication and thus confer protection on the adult host.

Age Factors↗
PubMed1986

[Protection conferred by a hyperimmune serum and its fractions on rats infected with the Junin virus].

Suckling rats infected by ic route with 10(3)LD50 of the XJC13 strain of JV were passively immunized with homologous hyperimmune serum (HIS). Animals treated at 2 days pi with HIS showed a significant increase in survival vs. non-treated infected controls (82% vs 5%). However, at 4 days pi, transfer failed to modify survival. By means of DEAE Sephadex A25 column chromatography, the presence of neutralizing immunoglobulin closely correlated with protective antibodies, but were not restricted to the IgG-containing fraction. Employing Sephadex G200, chromatography demonstrated the absence of neutralizing and protective activity in the high molecular weight protein fraction. Results show that the success of HIS treatment depends on early administration. Besides, it was found that fractions capable of conferring protection exhibited high neutralizing antibody titers.

Animals↗
PubMed1985

[Role of macrophages in the dissemination of the Junin virus in the rat].

The 2-day-old rat is known to be susceptible to infection by ip route with the XJ strain of Junin virus but resists inoculation with XJC13 strain (85% vs 15% mortality). In order to determine whether peritoneal macrophages play a role in modulating the course of infection, viral replication in adherent peritoneal cells infected with either strain was studied. XJ was found to replicate 30-fold as regards XJC13 at day 3 pi. Besides, silica blockage of peritoneal macrophages was also evaluated. Following silica treatment, 60% survival was recorded for XJ-infected animals vs 15% for untreated infected controls. No significant differences were recorded for silica-treated XJC13-infected rats vs untreated infected controls. These preliminary findings indicate that, upon replication within the host's macrophages at the peritoneal inoculation site, virus spreads readily to reach the target organs. Effective silica blockage lends support to this pathway, as shown by significantly greater survival in XJ-infected rats.

Animals↗
PubMed1985

Attenuation parameters for Junin virus in the newborn rat.

To characterize a virus strain as attenuated, both biologic and biochemical criteria are necessary. In the case of Junin virus, the 2-day-old rat has proved to be a biologic attenuation marker as regards mortality. Here we studied the behaviour of the prototype XJ vs the attenuated XJC13 strain inoculated by either ic or ip route to determine differential hematologic and splenic parameters. Humoral immune response against SRBC was also investigated. By either route XJ caused significant leucocytosis, while the other hematologic parameters remained unchanged. No alterations were found following XJC13 infection. XJ produced significant splenomegaly whereas XJC13 had no effect. Similarly PFC anti-SRBC count was decreased during XJ infection but not after XJC13 infection. These differences between the pathogenic XJ and the attenuated XJC13 strain may be attributed to the former's greater spread. The drop in PFC could be due to spleen dysfunction and/or viral effects on the cell subpopulation involved.

Animals↗
PubMed1984

Protection conferred against Junin virus infection in rats.

2-day-old Wistar rats intracerebrally infected with the XJC13 strain of virus exhibited a 5% survival rate which rose to 71% after immune serum treatment. Brain viral titers were relatively unaffected by this treatment. Histologic studies showed necrosis in the cerebellum and brain cortex with mononuclear cell infiltration in both treated and nontreated groups. Beginning on day 16 postinfection, however, intracerebral perivascular gliosis foci and mild meningeal congestion were minimal in the treated animals. These findings imply that passively transferred humoral immunity leads to prompt recovery in this experimental model.

Animals↗
PubMed1984

[Differentiation among strains of Junín virus by intraperitoneal infection in the rat].

The 2-day-old rat is known to resist intracerebral infection with the XJ prototype strain of Junin virus, but 95-100% mortality results when infected with the attenuated XJC13 strain. When this animal was inoculated by intraperitoneal route, behaviour was diametrically opposite: the XJ strain proved lethal, while de XJC13 led to low mortality. Studies on mortality, virus titer in different organs, and anti-viral humoral response in 2-day-old rats infected with Junin virus strains were carried out in order to use this system as a new attenuation marker. Mortality rates recorded for rats inoculated with either strain, were markedly different, being 84% in the XJ-infected group and barely reaching 17% in the XJC13 group. Brain viral titers were higher in the former group than the latter (10(5.26) PFU/ml vs. 10(3) PFU/ml at day 17 pi). For this reason, viral replication may be used as a virulence marker in this experimental model. Antibody levels were also higher in the XJ group most likely due to greater viral replication. The above findings support the use of the 2-day-old rat as a biologic attenuation marker since susceptibility to infection is strain-dependent.

Animals↗
PubMed1983

[Infection in rats by the intraperitoneal route with Junín virus].

The susceptibility of the rat, infected at various ages by intraperitoneal route with the XJ prototype strain of Junin virus was studied two day-old animals showed maximum mortality, being the most suitable dose 10(3) LD50. Antiviral humoral response at 35 days pi was tested in survivors of all ages. Highest neutralizing antibody titers were found in those infected up to 4 days of age. This host behaves quite differently when infected by intracerebral route with the same XJ strain.

Age Factors↗
PubMed1983

Action of antithymocyte serum on Junin virus infection in rats.

Two-day-old rats resistant to intracerebral (i.c.) infection with XJ strain of Junin virus (JV), were rendered sensitive to JV by treatment with antithymocyte serum (ATS). The mortality reached 80%, the virus titres in brain were higher and the serum neutralizing antibodies dropped but brain lesions were absent throughout. The same host was susceptible to XJCl3 strain infection, which induced lethal encephalitis manifested by severe necrotic foci in cerebellum. ATS treatment conferred significant protection against this strain; the mortality was 63%, viral titres in brain remained unchanged but the lesions were mild as compared with non-treated animals. It seems likely that the XJ strain allowed the 2-day-old rat to develop serum antibodies against JV, while the XJCl3 strain unleashed an immunopathologic response.

Animals↗
PubMed1982

New attenuation marker for junin virus based on immunologic responses of guinea pigs.

A new attenuation marker to distinguish a virulent strain (XJJV) from an attenuated strain (XJC13JV or XJOJV) of Junin virus by means of the humoral and cellular responses to unrelated antigens was studied in guinea pigs. Strain XJJV suppressed the humoral immune response, as shown by the lower titers of precipitating antibody to ovalbumin. The concomitant decrease in serum complement level contributed to a milder Arthus cutaneous reactivity. In contrast, the attenuated strains did not decrease the humoral response. The pathogenic strain suppressed cell-mediated immunity, as demonstrated by decreased contact sensitivity to 2,4-dinitro-1-fluorobenzene and by depression of delayed skin reactions to tuberculin purified protein derivative. When attenuated strains were used, such suppressive effects were not observed. For virulent strain XJJV, virus replication in lymphoid organs and immunosuppressive effects were correlated. These findings provide a further means to differentiate between virulent and attenuated strains of Junin virus for the purpose of vaccine control of Argentine hemorrhagic fever.

Animals↗