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Biomedical subjects

M M Stevenson

Publications and source records attributed to M M Stevenson.

At least 73 records · Page 4Linked to original sources
PubMed1989

Human recombinant tumor necrosis factor alpha protects susceptible A/J mice against lethal Plasmodium chabaudi AS infection.

The effect of intravenous treatment with human recombinant tumor necrosis factor alpha (rTNF-alpha) on infection of susceptible A/J and resistant C57BL/6 mice with Plasmodium chabaudi AS was examined. Treatment of A/J mice with 10(3) or 10(5) U of rTNF-alpha on days 0, 3, 5, 7, and 9 after intraperitoneal infection with 10(6) parasitized erythrocytes resulted in 80% survival and a significant decrease in the peak parasitemia level. Treatment of susceptible A/J hosts with 10(5) but not 10(3) U of rTNF-alpha resulted in increased survival but did not alter the peak parasitemia level following infection with 10(7) parasitized erythrocytes. Moreover, all surviving A/J mice completely eliminated the parasite by approximately 4 weeks and were fully protected against a secondary infection. Except at a dose of 5 x 10(5) U of rTNF-alpha, which resulted in 100% mortality of infected animals, rTNF-alpha did not alter the course or outcome of infection with P. chabaudi AS in resistant C57BL/6 mice.

Animals↗
PubMed1987

Development of inflammation and augmented chemotactic responsiveness of murine peritoneal macrophages following treatment with Entamoeba histolytica trophozoites.

The accumulation of inflammatory cells in the peritoneal cavity of C57BL/6 mice was examined following intraperitoneal injection of Entamoeba histolytica trophozoites. Two different strains of E. histolytica were used: a virulent strain (IP:0682:1) and a non-virulent strain (DKB). Injection of 10(6) trophozoites of either strain resulted in significant increases in the numbers of total peritoneal cells, macrophages and polymorphonuclear cells as compared to either saline-injected control mice or mice injected with 10-fold lower doses of trophozoites. The in vitro chemotactic response of macrophages from amoebae-induced exudates was also examined. Macrophages from mice treated with strain IP:0682:1 or DKB strain trophozoites were more responsive to complement-derived chemotactic factors than macrophages from saline-injected mice. This increase was significant on day 2 and persisted at enhanced levels until day 20 when the experiment was terminated. In addition, it was found that trophozoites activated normal mouse serum resulting in the production of serum-derived chemotactic activity.

Amebiasis↗
PubMed1986

Macrophage chemotactic response in mice is controlled by two genetic loci.

The level of the in vitro chemotactic responsiveness of murine inflammatory peritoneal macrophages is dependent upon the genetic background of the host. A survey of the responses of macrophages from various inbred strains showed three categories of response (high, intermediate, and low), indicating that genetic control is multigenic. Among the high responder strains were those derived from the C57BL (B) background, while mice of the A/J (A) strain exhibited the lowest response. In order to determine the number of genes controlling the level of macrophage chemotactic responses, segregation analysis of backcross mice derived from high responder B and low responder A parental mice was performed. The results of analysis of the data by the maximum likelihood modeling, a computerized method, showed that the difference in macrophage chemotactic responsiveness in the strain combination of B and A mice is due to the effects of two autosomal genetic loci.

Animals↗
PubMed1986

Modulation of primary antibody responses to sheep erythrocytes in Plasmodium chabaudi-infected resistant and susceptible mouse strains.

The in vivo primary antibody response to sheep erythrocytes (SRBC) was determined in genetically resistant C57BL/6 and susceptible A/J mice during the course of infection with Plasmodium chabaudi. Spleen cells from both strains of mice, immunized with SRBC and infected on the same day, showed significant increases in the number of direct plaque-forming cells. The response of malaria-infected C57BL/6 mice was significantly enhanced in comparison with the responses of both normal C57BL/6 and malaria-infected A/J mice. When mice were immunized at later times in the infection, the level of the response declined in both strains until it was less than 50% of the response of normal mice. Thus, suppression of the primary antibody response to SRBC does not correlate with the outcome of P. chaubaudi infection in genetically resistant and susceptible hosts.

Animals↗
PubMed1986

Cytotoxicity of commercial peritoneal dialysis solutions towards peritoneal cells of chronically uremic mice.

A gradual loss of cell viability was observed during in vitro incubation of peritoneal cells from chronically uremic mice in commercial peritoneal dialysis solutions. The magnitude of this cytotoxicity toward peritoneal cells harvested from uremic mice and controls was comparable. Resident peritoneal cells were always found to be more susceptible than thioglycolate-elicited peritoneal populations of either macrophages or polymorphonuclear cells. In order to elucidate the factors contributing to this phenomenon, resident peritoneal cells recovered from normal mice were incubated in vitro for 1 h in various solutions of known pH and osmolarity consisting of buffered and unbuffered commercial peritoneal dialysis solutions. The results clearly show that the major part of the cytotoxicity is attributable to the low pH of the solutions. Once pH was corrected, the hyperosmolarity of these solutions had no effect on cell viability; however, a small but significant cytotoxicity remained. Factors other than those addressed in this study probably account for the observed residual cytotoxicity.

Animals↗
PubMed1985

Correlation between chemoattractant-induced leukocyte adherence inhibition, macrophage chemotaxis, and macrophage inflammatory responses in vivo.

Variations in the magnitude of inflammatory macrophage response in vivo and macrophage chemotaxis in vitro, observed among inbred mouse strains, suggest that these traits are genetically-regulated. The development of an A X B series of recombinant inbred (RI) strains of mice derived from the C57BL/6J (B, high responder) and A/J (A, low responder) resulted in the availability of a large number of new inbred strains which express a spectrum of variations in the magnitude of these traits. These strains were used in the present study as a tool to examine the possible correlation between the phenomenon of leukocyte adherence inhibition (LAI) and those of macrophage inflammatory response in vivo and macrophage chemotaxis in vitro under the assumption the LAI requires the same cellular events as chemotaxis and that LAI resembles, grossly, the accumulation of nonadherent inflammatory cells in vivo. The typing of A X B RI strains for the traits of LAI, macrophage accumulation in vitro, and macrophage inflammatory response in vivo resulted in a correlation between the magnitude of response of those three phenomena in the total of 19 inbred strains tested, thus suggesting that the chemoattractant-induced LAI is biologically related to the events that mediate macrophage chemotaxis in vitro and the macrophage inflammatory response to sterile irritants in vivo.

Animals↗
PubMed1985

Murine malaria: resistance of AXB/BXA recombinant inbred mice to Plasmodium chabaudi.

The level of resistance to infection with Plasmodium chabaudi is genetically controlled. We have previously reported that a single dominant gene is responsible for the variation in host resistance to malaria between susceptible A/J- and resistant C57BL-derived mice. In the present study, recombinant inbred strain analysis was performed with AXB/BXA recombinant inbred strains derived from A/J and C57BL/6 progenitors. Typing of 17 AXB/BXA recombinant inbred strains confirmed the unigenic control of inheritance in this particular strain combination and allowed us to demonstrate genetic linkage between the traits of resistance (defined as a prolonged survival and a low peak parasitemia) and the magnitude of splenomegaly. The influence of sex on the course of infection, which we previously reported in the examination of segregating populations (Stevenson et al., Infect. Immun. 38:80-88, 1982), was again demonstrated in the survey of RI strains.

Animals↗
PubMed1984

Macrophage activity in mice undergoing chronic graft-versus-host reactions.

The functional state of the mononuclear phagocyte system has been investigated in mice undergoing chronic graft-versus-host (GVH) reactions (GVHR), initiated by the injection of parental DBA/2 lymphoid cells into (DBA/2 X C57BL/6)F1 hybrid mice. Macrophage function was assessed in vivo by the ability to develop host resistance to infection with Listeria monocytogenes and found to be normal in GVH mice, as measured by the development of resistance during the early phase of natural (macrophage-mediated) resistance to the infection. During the later phase of acquired immunity to listerial infection, GVH mice had lowered resistance, but this was attributed to impaired T cell immunity rather than to defective macrophage function. The inflammatory response to a phlogistic agent, thioglycolate, was also found to be normal in GVH mice, as measured by the accumulation of inflammatory macrophages in the peritoneal cavity. In an in vitro assessment of macrophage function, phagocytosis was found to be enhanced initially (2 weeks following GVHR induction) but it subsequently became depressed for the duration of the study (12 weeks after GVHR induction). Macrophage chemotactic activity was initially normal, then became depressed and remained so for the duration of the study. Thus, despite the profound suppression of specific immunity induced by the GVH reaction and the functional defects of GVH macrophages apparent in vitro, the response of the mononuclear phagocyte system to in vivo stimuli, such as infection or inflammation, is unimpaired in GVH mice.

Animals↗
PubMed1984

Natural resistance to listeriosis: role of host inflammatory responsiveness.

The accumulation of inflammatory macrophages at the infective foci appears to represent the major host defense mechanism during the early or innate phase of resistance to infection with Listeria monocytogenes. Certain inbred strains of mice, such as A/J [A] have genetically-determined defects in macrophage mobilization in vivo in response to intraperitoneal (IP) treatment with the nonspecific inflammatory stimulus, thioglycollate. These strains of mice are also genetically-susceptible to infection with Listeria. In contrast, other strains (C57BL/6J or B10.A/SgSn [B]) are high responders for both genetically-determined traits. Linkage analysis of the two traits in backcross progeny showed that the trait of a high macrophage inflammatory response segregates with the trait of resistance to Listeria. These observations suggested that the gene(s) controlling the level of the macrophage inflammatory response is identical with or linked to the gene(s) controlling resistance to Listeria. We have found additional evidence to support this hypothesis by analyzing the expression of the two traits in 12 AXB/BXA recombinant inbred [RI] mouse strains derived from progenitor B (high macrophage response, Listeria-resistant) and A (low macrophage response, Listeria-susceptible) mice. Furthermore, those AXB/BXA strains, which like progenitor A mice, are susceptible to infection with Listeria exhibit a defect in the number of polymorphonuclear leukocytes recovered from peritoneal exudates 18 h after IP injection with thioglycollate. The strain distribution pattern of both the resistance/susceptibility to Listeria and the leukocyte inflammatory response in RI strains is concordant with that of Hc allele coding for effective/defective levels of C5 complement protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Enhancement of resistance to Listeria monocytogenes infection in mice by pyrimidine analogs.

The modulation of murine host resistance to infection with Listeria monocytogenes by the substituted pyrimidine anti-viral compounds, 2-amino-5-bromo-6-methyl-4-pyrimidinol (ABMP), 2-amino-5-bromo-6-phenyl-4-pyrimidinol (ABPP) and 2-amino-5-iodo-6-phenyl-4-pyrimidinol (AIPP) was investigated. BAF1 mice given three daily injections of ABMP, ABPP (as well as of the interferon-inducer poly I:C) demonstrated enhanced anti-listerial resistance, as measured by a 100-fold increase in the median lethal dose of Listeria compared to vehicle-treated control mice. This enhancement was also detectable as a decrease (up to 100-fold) in the number of viable Listeria recoverable from the livers and spleens of mice during the non-immune phase of natural resistance (24-72 h following infection) to this pathogen. In contrast, AIPP did not enhance anti-listerial resistance. Since each of the effective agents have been shown to induce the production of interferon, the role of interferon in the mechanism of natural resistance to Listeria was evaluated. The serum of untreated B10.A mice infected with Listeria was shown to contain high levels of interferon. Treatment of these mice with a potent anti-mouse interferon antibody preparation completely neutralized circulating interferon activity; however, such treatment had no apparent effect on the growth of Listeria. In addition, mice which received injections of both ABMP and anti-interferon demonstrated a level of resistance identical to that seen in mice given ABMP and normal serum. Based on these results, we propose that although interferon is produced in response to listerial infection, interferon is not a critically important mediator in the mechanism of natural resistance to this pathogen. Furthermore, it appears that the immunomodulating activity of these experimental compounds does not involve interferon.

Animals↗
PubMed1983

Murine malaria: dissociation of natural killer (NK) cell activity and resistance to Plasmodium chabaudi.

Striking differences in the resistance to P. chabaudi infection among different inbred mouse strains have previously been correlated with the level of both the spontaneous and the infection-induced enhanced level of NK cell activity. We have examined this putative correlation in individual animals of backcross progeny derived from A/J (malaria-susceptible, low NK cell activity) and B10.A (malaria-resistant, high NK cell activity) progenitors. We have found that NK cell activity and resistance to malaria segregated independently. Furthermore, C57BL/6-bg/bg mice which are deficient in NK cell activity were found to be as resistant to malaria as their heterozygous C57BL/6-bg/+siblings. We conclude that low NK cell activity, characteristic of A/J strain mice, is not a sufficient determinant of the exquisite susceptibility of these animals to infection with Plasmodium chabaudi.

Animals↗
PubMed1983

Blood transfusion reaction in a patient with immunoglobulin A deficiency.

Selective deficiency of serum IgA is the most common immunodeficiency in humans; when immunodeficient individuals receive blood transfusions a severe anaphylactoid reaction can develop. The present report describes such a patient. After the transfusion reaction a hemagglutination inhibition assay revealed that her blood contained less than 1.0 micrograms/ml of IgA and an anti-IgA antibody that reacted with the 2 IgA proteins, isotypes IgA1 and IgA2. Immediately after the reaction the patient's serum anti-IgA antibody titer was 1:16,384, and when reevaluated 5 weeks later it was 1:8000. All 3 of her children were shown to be IgA deficient, and 2 of them had antibodies against IgA2. This type of anaphylactoid reaction can be avoided by transfusing blood from IgA-deficient donors, frozen deglycerolized red cells, or red cells that have been washed several times to extract all IgA proteins.

Adult↗