Biomedical subjects
Publications and source records attributed to D M Musher.
The data presented show that spleen cells obtained from syphilitic rabbits can be used to transfer nonspecific resistance to Listeria to normal recipients. This supports the hypotheisis that infection caused by T. pallidum induces a cell-mediated immune response.
Two cases of leptospirosis diagnosed at the Texas Medical Center in a two-week period are presented. Most cases of leptospirosis go undiagnosed because the symptoms and signs are nonspecific. Leptospirosis should enter the differential diagnosis when symptoms of influenzal illness, aseptic meningitis, and viral gastroenteritis occur, especially if abnormal hepatic and renal function are shown to be present. Many, but by no means all, patients will give history of exposure to livestock or rodents. Diagnosis is best made by serologic methods; Treatment is usually not required since the disease is self-limited, and even in the more severe form, antibiotics have not been conclusively shown to be of benefit.
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In vitro testing shows nearly all strains of Proteus to be susceptible to methenamine. However, infection by urease-producing bacteria alkalinizes the urine in vivo and prevents generation of formaldehyde, the active metabolite, from methenamine. We have previously shown acetohydroxamic acid (AHA) to be an effective inhibitor of bacterial urease in vitro and in vivo. We now present data obtained by use of static and dynamic in vitro systems, which show that, by preventing urease-induced alkalinization of urine, AHA enables methenamine to exert its antibacterial effect against representative Proteus species.
Acetohydroxamic acid (AHA) is a potent inhibitor of urease which prevents alkalinization of urine and stone formation in rats in the presence of infection caused by urease-producing bacteria. Because an antibacterial effect of AHA, and synergy between kanamycin and AHA have also been described, we studied the interaction between AHA and 12 antibiotics against 14 gram-negative bacteria. Synergy, sometimes to a striking degree, was found in 17% of interactions; however, antagonism was detected in 5%. Infecting organisms would need to be studied individually before the antibacterial effect of AHA and an antibiotic could be predicted.
Tetracycline, doxycycline, and minocycline were evaluated for their antibacterial activity against methicillin-susceptible and -resistant isolates of Staphylococcus. At clinically achievable levels both doxycycline and minocycline were more active than tetracycline against methicillin-susceptible organisms. Tetracycline and doxycycline had no activity against methicillin-resistant staphylococci, whereas minocycline at 2 mug/ml inhibited six of 13 strains and, at 3 mug/ml, 10 of 13 strains.
Using an in vitro system that simulates the dynamics of the urinary tract, we have shown that concentrations of formaldehyde >/= 25 mug/ml can be achieved in urine containing >/= 0.6 mg of methenamine per ml at pH </= 5.7 or >/= 1 mg/ml at pH </= 5.85. Exposure to this concentration of formaldehyde for 2 h produced a measurable antibacterial effect. These studies suggest that an effective bacteriostatic level of formaldehyde is likely to be achieved with currently used dosages of methenamine when the urine pH is less than 5.7 to 5.85.
The response of lymphocytes from patients with syphilis and normal subjects was studied in vitro by using phytohemagglutinin (PHA), pokeweed mitogen (PWM), streptolysin O (SLO), and a preparation of Treponema refringens. Normal lymphocytes exhibited a dose-response curve to treponemes. Although lymphocytes from patients with primary and secondary syphilis responded normally to PHA and PWM, their response to SLO was suppressed and they failed to show significant stimulation by treponemes. Serum from syphilitic patients did not affect normal lymphocytes, and culturing lymphocytes from patients with syphilis in normal serum did not restore their responsiveness. Six to 10 weeks after syphilitic patients had been treated, the degree of stimulation by treponemes was the same as for normal subjects. These data give indirect support to the hypothesis that immunological suppression occurs during active infection with T. pallidum.
Several lines of evidence suggest that cell-mediated immunity (CMI) is suppressed in the early stages of infection caused by Treponema pallidum and becomes activated at the time that latency is induced. In the studies reported in this paper, rabbits were infected intravenously with T. pallidum and subsequently challenged with Listeria monocytogenes. Enhanced ability to suppress the growth of Listeria was detected in their livers between 3 and 5 weeks after infection with T. pallidum, corresponding to the onset and regression of the generalized syphilitic eruption. A second infection of T. pallidum 4 weeks after the first, at a time when suppression was beginning to wane, prolonged the listericidal activity. These observations support the hypothesis that infection by T. pallidum stimulates CMI, which, in turn, may play a role in inducing latency.
The American opossum is the only experimental animal that regularly develops bacterial endocarditis spontaneously. There was no relation between the ability of opossums to clear bacteria from the bloodstream and the subsequent development of endocarditis.
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Macrophages from mice infected with facultative intracellular organisms such as Listeria monocytogenes and BCG have been shown to resist infection by antigenically unrelated intracellular bacterial parasites. This study compares phagocytosis, bacterial growth inhibition, and oxidation of glucose by macrophages from normal mice, mice infected with listeria or BCG, or mice immunized with killed listeria in incomplete Freund's adjuvant. Macrophages from listeria- and BCG-infected mice ingested more listeria; 67 and 57%, respectively, had three or more cell-associated bacteria versus 22% of controls (P < 0.001). Peritoneal macrophages from listeria- and BCG-infected animals significantly (P < 0.001 covariance analysis) inhibited growth of listeria in suspension, whereas control macrophages had no such inhibitory effect. The rate of oxidation of glucose-1-(14)C was higher in macrophages from listeria- and BCG-infected mice than from either uninfected animals or those immunized with killed listeria. During phagocytosis of killed or live bacteria, or latex particles, the rate of glucose oxidation was increased (P < 0.01). These data suggest that the cellular immunity after infection by an intracellular organism is associated with an increase in metabolic activity of macrophages, namely, an increase in the rate of glucose oxidation resulting in enhancement of phagocytosis and killing.
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