PubMed Health⌕ Search

Biomedical subjects

D B Budzko

Publications and source records attributed to D B Budzko.

12 recordsLinked to original sources
PubMed1978

Enhanced resistance against Junin virus infection induced by Corynebacterium parvum.

The effects of intraperitoneal administration of Corynebacterium parvum on the course of Junin virus infection in mice were investigated. This treatment produced enhanced resistance to the virus infection, evidenced by an increase in both survival times and the proportion of survivors. The protective effect was dependent upon the dose of C. parvum, and 280 mug/g of body weight was found to be the optimal dose. In various experiments, about 80% of the infected animals receiving this dose survived, whereas survival ranged between 0 and 20% among untreated infected mice. Maximal protection was afforded by C. parvum when administered simultaneously with the virus. A smaller but significant degree of resistance was induced by C. parvum given 3 or 6 days after infection. C. parvum injected before infection was ineffective. Viral titers measured in the brains of C. parvum-treated and untreated mice at various times after infection were found to be comparable. In addition, there were no significant differences between circulating-antibody titers measured either by neutralization tests or by complement fixation. Depression of the reticuloendothelial system by treatment with silica particles also resulted in enhanced resistance to Junin virus infection, suggesting that the protective effect of C. parvum is not likely to be due merely to its capacity to stimulate macrophages. The present data, highlighting that the presence of high titers of Junin virus and disease do not necessarily correlated, suggest that in mice this disease is not the consequence of cell damage caused directly by the virus but of a still undefined indirect mechanism induced by the virus, not necessarily mediated by macrophages.

Animals↗
PubMed1977

Cytotoxic effects of normal sera on lymphoid cells. II. Requirements for inhibition of nonspecific serum cytotoxicity by agarose.

Agarose is known to inhibit nonspecifically the cytotoxic effects of normal sera on xenogeneic lymphoid cells. To find an explanation for this agarose effect we have studied its requirements using guinea pig and human sera as the source of activity and rat thymocytes as target cells. Control assays were performed using heat-inactivated (56 C, 30 min) normal rat serum. The inhibitory effect of agarose was readily reproduced with untreated sera and also when sodium ethyleneglycoltetraacetate, a selective chelator of calcium ions, was added to the sera together with excess magnesium. However, the agarose effect failed to occur in the presence of 0.01 M EDTA unless magnesium ions were restored. Abrogation of cytotoxicity in human serum by incubation with a large number of target cells instead of agarose was also found to be magnesium dependent. Titrations of human serum, performed after absorption with agarose in the presence of EDTA, which does not interfere with antigen-antibody binding, and subsequent restoration of divalent cations, revealed no significant change in its cytotoxic titer when compared with that of mock-absorbed serum not subjected to the agarose treatment. Incubation of human serum with either agarose or rat thymocytes resulted in the conversion of factor B, essential for complement activation via the alternative pathway, previously shown to provide the complement activity necessary for the cytotoxic reaction. These results suggest that the agarose effect is mainly attributable to complement consumption via the alternative pathway rather than to the absorption of "natural" antibodies.

Animals↗
PubMed1976

Depletion of complement in vivo and in vitro by extracts of Aspergillus fumigatus.

A new, nontoxic material extracted from Aspergillus fumigatus, is described with complement-depletion capacity both in vivo and in vitro. Extracts of the mycelium of A. fumigatus were found to haemolyse sheep red blood cells, to be lethal for mice and to convert C3 into its faster electrophoretic form when incubated with normal human serum. Conversion did not take place when purified C3 was used, suggesting that serum factors were required in the reaction. Adsorption of the extracts with activated carbon or heating at 100 degrees C for 30 min yielded detoxified materials devoid of both toxic and haemolytic properties but still capable of converting serum C3. In guinea pigs, administration of detoxified extracts was followed by complement depletion lasting not less than 48 h. Heating (100 degrees C for 30 min) extracts which had been previously detoxified by carbon adsorption resulted in a partial loss (40%) of their complement-inhibitory capacity indicating that part of the anticomplementarity of AFE was due to a heat-stable substance.

Animals↗
PubMed1976

Mechanisms of natural resistance to trypanosomal infection. Role of complement in avian resistance to Trypanosoma cruzi infection.

The natural resistance of chickens to Trypanosoma curzi infection and the capacity of their sera to lyse blood (trypomastigote) forms of the parasite in vitro were found to be complement-dependent phenomena. Parasites given intravenously to decomplemented chickens were detectable in their bloodstream for at least 24 h post-infection, whereas in untreated animals they became undetectable after 1 min (and destroyed flagellates were observed). One millilitre of serum had the capacity to lyse as many as 10-30 X 10(6) organisms. The lytic activity of serum in vitro was not impaired in chickens that had been immunosuppressed by four different procedures and was present in the absence of antibodies. In vitro lysis of T. cruzi by either normal or antibody-free chicken sera occurred in the absence of calcium ions but required magnesium ions, indicating that complement was activated via the alternative pathway. Administration of normal chicken serum to mice infected with T. cruzi provoked a marked decrease in their parasitaemias.

Animals↗
PubMed1975

Hemolytic, cytotoxic and complement inactivating properties of extracts of different species of Aspergillus.

Some of the biological properties of saline extracts of the mycelia of several species of the Aspergillus genus, namely, A. fumigatus, A. flavus, A. niger, A. nidulans, A. parasitucus and A. glaucus, were studied. Only the extract prepared from A. fumigatus was found to be hemolytic for sheep red blood cells. In contrast, all the extracts with the only exception of that of A. glaucus, had cytotoxic effects on Vero cells. Both, the hemolytic and cytotoxic constituents of the extracts were removable by adsorption with activated carbon. Heating of the extracts at 100 degrees C for 30 minutes also resulted in detoxification. In vivo studies, performed only with detoxified extracts of A. fumigatus, showed these were capable of depleting complement levels in guinea pigs. Complement inactivation was also found to occur in vitro and was cuased by all the extracts tested. Also triggered by the extracts was the conversion of serum C3 but not of purified C3, indicating that other serum factors are essential in the process. Despite the similarity in this respect with cobra venom factor, differences in activity after heating-negative in cobra venom factor-indicate that the complement inactivating substance/s present in the Aspergillus extracts differ from those of the snake product.

Animals↗
PubMed1975

Effects of complement depletion in experimental chagas disease: immune lysis of virulent blood forms of Trypanosoma cruzi.

In mice infected with virulent blood (trypomastigote) forms of Trypanosoma cruzi, complement depletion with cobra venom factor caused a marked exacerbation of the disease evidenced by significantly increased parasitemia levels and early mortality as compared with those of untreated infected animals. The effect was greater in mice receiving cobra venom factor on day 7 postinfection, i.e., at the time when the parasites had had time to localize and multiply in the tissues and appeared in the circulation in appreciable numbers. The possibility that complement participates in host defense against T. cruzi infection through a mechanism involving immune lysis was explored in vitro. T. cruzi trypomastigotes were found to undergo immune lysis in sera of patients with chronic Chagas' disease, in sera of immunized mice, and in solutions containing both immune mouse gamma globulin and a source of active complement. This phenomenon failed to take place either in the absence of complement or after complement inactivation by heat or utilizing complement inactivators. The lytic capacity of heated sera was restored by the addition of active complement to the system. During the immune lysis of T. cruzi blood forms, complement was activated in human sera via both the classical and the alternate pathways. In mouse sera, activation followed at least the alternate pathway.

Animals↗
PubMed1975

Immunization against experimental Chagas' disease by using culture forms of Trypanosoma cruzi killed with a solution of sodium perchlorate.

Protection against infection with virulent blood (trypomastigote) forms of Trypanosoma cruzi was accomplished in mice by immunization with culture (mainly epimastigote) forms killed by treatment with sodium perchlorate. Sodium chloride, used instead of sodium perchlorate, with all other conditions kept the same, failed to kill all the organisms, indicating that the effects of the perchlorate anion were not simply ionic or osmotic, suggesting that they might be chaotropic. A single dose of the immunogen, without adjuvants, was sufficient to significantly protect against the infection. Protection was achieved by either intraperitoneal, intramuscular, or subcutaneous immunization, though the first two routes appeared to be more effective. After challenge, parasitemias were negative in 25, 29, and 17% of the animals immunized intraperitoneally, intramuscularly, and subcutaneously, respectively.

Animals↗