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M A MELLY

Publications and source records attributed to M A MELLY.

11 recordsLinked to original sources
PubMed1965

THE DYNAMICS OF RETICULOENDOTHELIAL BLOCKADE.

The dynamics of "reticuloendothelial blockade" were studied in living rabbits and isolated, perfused rabbit livers utilizing gelatin as a blockading agent and Au(198) stabilized in gelatin as a tracer. Employing the above experimental model, the following observations were made. (a) RES blockade was specific and dependent on the surface properties of the particle under study. (b) RES blockade was not caused by saturation of hepatic removal mechanisms. (c) RES blockade was not caused by depletion of demonstrable serum opsonins. (d) RES blockade appeared to correlate with high circulating levels of the blockading agent, per se. Thus, under the conditions employed, the term "reticuloendothelial blockade" was a misnomer. Although specificity of liver macrophage-particle interaction was evident and deserves further study, the data suggest that blockade as usually studied is a laboratory phenomenon induced by the continuing circulation of the blockading agent.

Animals↗
PubMed1962

Factors relating to the virulence of Staphylococci. II. Observations on four mouse-pathogenic strains.

Four clumping factor-negative strains of Staphylococcus aureus were found to closely resemble the diffuse colonial variant of the Smith strain. All produced fatal intraperitoneal infections in mice, all grew in diffuse, streaming colonies in plasma or serum soft agar, and all behaved like encapsulated microorganisms in in vitro opsonic systems. These staphylococci were resistant to phagocytosis in the peritoneal cavities of normal mice. When mice were immunized with heat-killed vaccines prepared from the Smith diffuse variant these strains were rapidly ingested by peritoneal leukocytes and the animals survived. This observation suggests that these strains share the same or a similar phagocytosis-retarding antigen. While most pathogenic staphylococci isolated from human material do not behave like these unusual mouse-virulent strains, indirect evidence is cited to support the suggestion that other staphylococci may acquire similar phagocytosis-resisting characteristics during in vivo multiplication. Studies to support or refute this thesis are in progress.

Animals↗
PubMed1962

Factors relating to the virulence of Staphylococci. III. Antibacterial versus antioxic immunity.

Antitoxic and antibacterial immunity have been clearly differentiated in the experimental mouse infection produced by the diffuse colonial variant of the Smith strain of Staphylococcus aureus. Immunization with crude toxoid protected mice from otherwise lethal doses of alpha hemolysin, but did not alter mortality following intraperitoneal infection with living staphylococci. Conversely, animals immunized with heat killed vaccines were readily killed by culture supernates containing alpha hemolysin, but were strikingly protected from otherwise fatal intraperitoneal infection with viable staphylococci. Protection was directly related to the ability of the immunizing substance to promote early intraperitoneal phagocytosis of the infecting inoculum. In these studies with the Smith diffuse variant, rapid intraperitoneal phagocytosis was induced by vaccination with whole cell bacterial vaccines but not by alpha hemolysin toxoid.

Animals↗
PubMed1960

Fate of staphylococci within human leukocytes.

Direct observations by phase microscopy have demonstrated that small numbers of pathogenic staphylococci survive prolonged periods of time within living human polymorphonuclear leukocytes. Non-pathogenic microorganisms are rapidly destroyed in similar preparations. Leukocytes in which staphylococci remained viable often appeared less vigorous after ingesting microorganisms, but intracellular survival could not be correlated with obvious leukocyte damage with any consistency. Both pathogenic and non-pathogenic cocci were seen to divide within living granulocytes during the first few minutes after ingestion. Occasionally pathogenic staphylococci multiplied in dying cells after long periods of intracellular residence. Phagocytosis of more than one pair of staphylococci by a single leukocyte appeared to act as a stimulus to bacterial destruction. Multiple ingestions of pathogenic staphylococci reduced the incidence of survival of the total microbiol population contained within the cell.

Granulocytes↗
PubMed1960

Further observations on the behavior of staphylococci within human leukocytes.

A specific serum factor was required for rapid phagocytosis of pathogenic staphylococci by human polymorphonuclear leukocytes when the ingestion process was studied in siliconed glass systems and the concentrations of staphylococci were maintained at low levels. In contrast to certain other microbes, the resistance to phagocytosis which characterized pathogenic staphylococci was relative, and phagocytosis was readily accomplished when large populations of staphylococci were present in the test system. A factor promoting phagocytosis was present in eight of eight normal adult sera. In contrast, the sera of twenty-eight of thirty normal rabbits did not promote phagocytosis. Serum obtained from 2 rabbits maintained in the rabbit colony for several months acquired the ability to opsonize pathogenic staphylococci. The phagocytosis-promoting factor was almost completely removed by prior absorption of test sera with the homologous strain. The factor was incompletely removed by absorption with heterologous strains of pathogenic staphylococci and was not significantly reduced by absorption with coagulase-negative staphylococci or unrelated microorganisms. Present evidence suggests that the factor promoting phagocytosis is a thermostable opsonin. While the activity of heated serum could not be restored by the addition of small amounts of fresh serum or complement, the addition of large amounts of complement partially restored opsonic activity. Incubation of staphylococci in fresh serum prior to heat inactivation did not reduce subsequent phagocytosis, further suggesting the heat stability of the phagocytosis-promoting factor. Preliminary studies correlating the presence of antistaphylococcal hemagglutinins and phagocytosis-promoting factor in certain sera suggest that the two factors were not necessarily related. The phagocytosis of staphylococci in fresh human serum was inhibited by the addition of fresh or inactivated rabbit serum. Further studies on the nature of such inhibition are in progress. Once ingestion was accomplished, coagulase-positive staphylococci consistently survived in significant numbers within the cytoplasm of human granulocytes. Coagulase-negative staphylococci appeared to be destroyed within the leukocyte and could not be recultured from the cytoplasm following 3 to 4 hours of intracellular residence.

Adult↗
PubMed1958

Studies on bacteriemia. IV. Alterations in rabbit mortality associated with aging of a culture of Escherichia coli.

Rabbits given an intravenous injection of an 18 to 24 hour broth culture of E. coli commonly died within 28 hours. The injection of a 4 hour broth culture of the same strain of E. coli containing equal numbers of living bacilli produced only an occasional death. Initial clearance rates and subsequent bacteriemias were similar in animals receiving either culture. Study of changes in circulating leukocytes or the temperature response to washed bacterial cells or culture filtrates failed to reveal obvious differences in host response to young or old cultures. It was found that both living bacterial cells and some substance or substances present in culture filtrates were required to produce subsequent death. The injection of whole old cultures containing both these factors produced hypothermia instead of the endotoxin type fever response which followed the injection of whole young cultures. Subsequent experiments revealed that this hypothermia appeared to be secondary to a period of transient but profound shock which occurred soon after the injection in rabbits receiving old cultures. No significant alterations in arterial pressure accompanied injections of young cultures. Evidence is presented which suggests that this period of hypotension rendered animals more likely to die with a persisting bacteriemia tolerated without event by non-shocked animals. The mechanisms which operate to increase mortality during the post shock period are as yet unclarified.

Aging↗
PubMed1957

Studies on bacteriemia. III. The blood stream clearance of Escherichia coli in rabbits.

Large numbers of E. coli were rapidly removed from the blood stream of rabbits at rates which initially paralleled the removal of similar numbers of staphylococci. Splanchnic tissues removed approximately two-thirds of the circulating bacilli in transit through the liver and spleen. In contrast to the cessation of splanchnic trapping noted 20 to 40 minutes following the injection of staphylococci, splanchnic trapping of E. coli continued unchanged for 3 to 5 hours unless the splanchnic tissues were dearly reseeding the blood stream. This resulted in the continued disappearance of E. coli over a 60 to 90 minute period, and differed from the constant bacteriemia maintained beyond 20 minutes after the injection of staphylococci. Some of the differences in the initial clearance of these two microorganisms appeared to relate to differences in host leukocyte-bacterium relationships. In vitro studies indicated that E. coli were rapidly killed following ingestion by rabbit polymorphonuclear leukocytes. Staphylococci survive such ingestion. The injection of E. coli was followed by a prolonged granulocytopenia with evidence of sequestration of granulocytes within the pulmonary vascular bed. The injection of staphylococci was followed by a transient leukopenia, with rapid return of granulocytes to the circulation (15). It appears probable that E. coli ingested by sequestered leukocytes are destroyed within the cell, and that leukocytes do not reenter the circulation containing living E. coli. Such intraleukocytic residence in the blood stream has been shown to be of possible importance in the maintenance of staphylococcal bacteriemia (14). An increasing E. coli bacteriemia occurred rapidly after the initial clearance period, indicating that many sequestered bacilli remained viable. Increasing bacteriemia also occurs 3 to 5 hours after the injection of staphylococci. The bacterial or host cell mechanisms which allow this secondary resurgence of bacterial populations are currently under investigation.

Animals↗
PubMed1957

Studies on bacteriemia. II. Further observations on the granulocytopenia induced by the intravenous injection of Staphylococci.

Intravenous injection of staphylococci produced a marked, transient granulocytopenia inrabbits. Leukopenia was rapidly followed by return of polymorphonuclear leukocytes to the peripheral blood, and normal circulating granulocyte levels were reestablished within 20 to 40 minutes. Differential arterio-venous leukocyte studies showed that polymorphonuclear leukocytes were trapped within the pulmonary vascular bed and, less constantly, in the splanchnic viscera during the initial 10 to 20 minutes following the injection of staphylococci. Granulocytes were subsequently found in larger numbers in blood leaving the lungs and splanchnic tissues, suggesting that entrapped polymorphonuclear leukocytes rapidly reentered the blood stream. This sequence of changes in circulating granulocytes was not significantly altered by splenectomy or the administration of cortisone. It has previously been shown that virtually all staphylococci in the blood stream are found within circulating polymorphonuclear leukocytes 10 to 40 minutes after the injection of culture (9). It is during this period that granulocytes return to the blood stream in large numbers. These observations suggest that staphylococci are phagocyted by polymorphonuclear leucocytes temporarily sequestered in the lungs and splanchnic viscera. It appears probable that some sequestered granulocytes containing living staphylococci subsequently return to the circulation. Such intraleukocytic staphylococci are believed to play a role in the maintenance of bacteriemia.

Agranulocytosis↗