Human polymorphonuclear leukocytes contain synexin, a calcium-binding protein that mediates membrane fusion.
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Annexin A7↗
Biomedical subjects
J D Ernst
Publications and source records attributed to J D Ernst.
Complement (C5)-derived chemotactic activity accounts for accumulation of polymorphonuclear leukocytes in cerebrospinal fluid of rabbits with pneumococcal meningitis.
Experiments were performed to identify the chemoattractant for polymorphonuclear leukocytes that appears in the cerebrospinal fluid of rabbits with experimental pneumococcal meningitis. Meningitis was induced in anesthetized New Zealand white rabbits by injecting 10(4) cells of stationary-phase Streptococcus pneumoniae type III intracisternally. Before bacteria were injected, cerebrospinal fluid contained neither polymorphonuclear leukocytes nor chemotactic activity. Significant chemotactic activity for rabbit polymorphonuclear leukocytes was detected 12 h after inoculation with bacteria and was maximal after 18 to 20 h. Chemotactic activity appeared in cerebrospinal fluid while concentrations of pneumococci and total protein were increasing but before there was any accumulation of polymorphonuclear leukocytes. The chemotactic activity in cerebrospinal fluid was heat stable (56 degrees C for 30 min), eluted from Sephadex G-75 with a profile identical to that of the chemotactic activity in zymosan-activated rabbit serum, and was inhibited by treatment with antibodies to native human C5. In addition, preincubation of polymorphonuclear leukocytes with partially purified rabbit C5a selectively inhibited their subsequent chemotactic responses to cerebrospinal fluid. These data indicate that complement (C5)-derived chemotactic activity appears in cerebrospinal fluid during the course of experimental pneumococcal meningitis in rabbits and suggest that this activity accounts for the accumulation of polymorphonuclear leukocytes observed in this infection.
Animals↗
Inhibition of isolation of Escherichia coli in blood cultures by trimethoprim-sulfamethoxazole.
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Blood↗
Correlation of in vitro time-kill curves and kinetics of bacterial killing in cerebrospinal fluid during ceftriaxone therapy of experimental Escherichia coli meningitis.
Ceftriaxone was highly active in eliminating Escherichia coli from the cerebrospinal fluid of rabbits infected with experimental meningitis. However, concentrations equal to or greater than 10 times the minimal bactericidal concentration had to be achieved to ensure optimal efficacy (rate of kill, 1.5 log10 CFU/ml per h). In contrast to other beta-lactams studied in this model, ceftriaxone concentrations in cerebrospinal fluid progressively increased, whereas serum steady state was obtained by constant infusion. The percent penetration was 2.1% after 1 h of therapy, in contrast to 8.9% after 7 h (P less than 0.001). In vitro time-kill curves done in cerebrospinal fluid or broth more closely predicted the drug concentrations required for a maximum cidal effect in vivo than that predicted by determinations of minimal inhibitory or bactericidal concentrations.
Animals↗
Experimental pneumococcal meningitis: role of leukocytes in pathogenesis.
Two groups of rabbits with experimental meningitis induced by direct intracisternal inoculation of Streptococcus pneumoniae cells were studied. One group was rendered profoundly leukopenic by nitrogen mustard, and the other had normal leukocyte counts. The two groups had comparable bacterial growth rates (mean generation time, 60 versus 67 min) and ultimate bacterial populations in the cerebrospinal fluid (CSF) (mean log10 CFU, 9.1 versus 8.7); therefore leukocytes did not effectively slow or limit the growth of pneumococci in the CSF in vivo. Increased CSF protein, decreased CSF glucose, and increased CSF lactate levels were similar in both groups, suggesting that leukocytes are not essential for these changes to occur. Quantitative blood cultures revealed identical levels of pneumococcal bacteremia until 13 to 14 h after the initiation of infection, when the leukopenic rabbits showed a larger number of pneumococci in the blood, ultimately exceeding the number reached in nonleukopenic rabbits by 100-fold. Leukocytes therefore limit the extent of pneumococcal bacteremia after infection of the CSF despite their lack of effect on the course or the CSF manifestations of experimental meningitis.
Animals↗
Acquired aortic stenosis in systemic lupus erythematosus.
Two patients with systemic lupus erythematosus had aortic valvular stenosis resulting from massive thrombotic deposits on the valve. This condition has not been described previously, but a similar process has been reported to have caused mitral stenosis in a patient.
Adult↗
Antibiotic combinations in experimental infections in animals.
The study of experimental infections has afforded the opportunity to examine the response to antimicrobial therapy in the complex milieu of living animals. This review summarizes the information gained from studies of combination antibiotic therapy for experimental endocarditis, meningitis, and other infections in which host defenses are unable to participate in effecting cure. The studies cited suggest that antibiotic combinations that yield rapid microbial killing are more effective in the treatment of these selected infections than are those combinations that do not give enhanced killing. In addition, the relevance of various methods of demonstrating antimicrobial synergy is examined, and in light of the results of treatment of experimental infections, suggestions for the applications of these methods to the evaluation of the efficacy of antibiotic combinations on infections in humans are given.
Animals↗
Combination antifungal chemotherapy for experimental disseminated candidiasis: lack of correlation between in vitro and in vivo observations with amphotericin B and rifampin.
Disseminated candidiasis was established in guinea pigs immunosuppressed with high-dose cortisone acetate. After the disease had been characterized by histopathologic study and quantitative culture of selected organs, guinea pigs were given amphotericin B alone or in combination with rifampin. The addition of rifampin to the regimen enhanced the in vitro rate of killing of the strain of Candida albicans used in the studies but was not noticeably beneficial in treatment of the disease in guinea pigs. Thus, the demonstration of an enhanced rate of killing in vitro was not a reliable basis for prediction of the response to the drug in vivo.
Amphotericin B↗