Showing papers by "Myron S. Cohen published in 1987"

Role of extracellular iron in the action of the quinone antibiotic streptonigrin: mechanisms of killing and resistance of Neisseria gonorrhoeae.

Abstract: The quinone antibiotic streptonigrin is believed to kill bacteria by promoting formation of oxygen radicals. This antibiotic has also been used to select resistant bacterial mutants, some of which vary in iron utilization. We examined the effects of streptonigrin on Neisseria gonorrhoeae and several types of gonococcal mutants. Streptonigrin (0.025 microgram/ml) efficiently killed gonococcal strain FA1090, and this effect depended on iron. Streptonigrin-resistant mutant FA6271 had normal iron uptake but was moderately deficient in total iron. Resistance most likely resulted from failure of FA6271 to divert electrons to streptonigrin, as demonstrated by a reduction in KCN-insensitive respiration (a hallmark of the action of quinones) and superoxide formation. Other mutants selected for inability to use human iron-binding proteins (strains FA6273 and FA6275) had no increase in streptonigrin MIC and no decrease in KCN-insensitive respiration. Mutants did not demonstrate an increase in superoxide dismutase or catalase. Streptonigrin killing of gonococci depended on a reaction(s) in which extracellular iron was important, presumably because iron was required for catalysis of hydroxyl radical. The results suggest that a membrane component may be a target for the actions of streptonigrin.

Cefoperazone and prothrombin time

Abstract: Excerpt To the editor: In their article on the relationship between beta-lactam antibiotics and coagulopathy, Sattler and colleagues (1) cited our results (2) from a multicenter trial of cefoperazo...

17β-Estradiol Inhibits the Oxidative Metabolism of U937 Cells Indirectly via Lymphocytes

Abstract: The effect of 17β-estradiol (E) on the oxidative metabolism of U937 cells was studied. E had no direct effect on the proliferation, surface adherence, or luminol-enhanced luminescence (LEL) of the U937 cells. Exposure of U937 cells to lymphocyte-conditioned medium (LCM) and 1,25-dihydroxyvitamin D3 allowed a maximal LEL response by cells stimulated with phorbol myristate acetate. In contrast, LCM from lymphocytes exposed to E (LCM-E) did not stimulate LEL to the same extent as did an equal volume of LCM. Increasing the E concentration in the lymphocyte medium was associated with a dosedependent reduction in the LEL response of the U937 cells. Mixing equal quantities of LCM and LCM-E significantly decreased LEL levels. LEL stimulated by LCM, γ-interferon, or differentiation-inducing factor was reduced by the presence of LCM-E. The inhibitory action of LCM-E was reversible and metabolite specific. 17α-E produced an effect that was only one tenth the magnitude of the E effect. These findings indicate that E ...

Metabolic responses of Neisseria gonorrhoeae to human serum and myeloid cells. Adaptation to host defenses

Abstract: The interaction of gonococci with host defenses including serum and phagocytic cells has been extensively studied. We have shown that a small molecular weight factor in serum stimulates gonococcal metabolism. This factor has now been isolated by column chromatography and may be released from mammalian cells including phagocytes. Exposure of gonococci to serum decreases membrane fluidity as demonstrated by EPR, seems to reduce OMP shedding, and reduces uptake by PMNS. Serum stimulated gonococci consume O2 to an extent adequate to interfere with PMN formation of reactive oxygen intermediates. We propose that all of these responses are adaptive and favor survival of this pathogen.

Outpatient antibiotic therapy for osteomyelitis.

Abstract: To the Editor.— The March 28, 1986, issue ofJAMAcontained an article offering an economic analysis of outpatient therapy for osteomyelitis.1This article is now being distributed by representatives of the Smith Klein & French pharmaceutical company for the purpose of encouraging the use of the cephalosporin antibiotic cefonicid (Monocid) in this setting. In their introduction, the authors justify their analysis by noting that "a new... cephalosporin antibiotic, cefonicid sodium, has been shown to be effective in treating osteomyelitis in the outpatient setting." This statement is supported by reference to a clinical trial published in a supplement toReviews of Infectious Diseasesunderwritten by Smith Klein & French.2This clinical trial examined (in an uncontrolled fashion) cefonicid therapy for osteomyelitis in 15 patients, 12 of whom completed therapy. The investigators in this clinical trial appropriately noted the limitations of their study: small numbers, no comparison group, lack