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A man acquired cutaneous leishmaniasis in Afghanistan. The disease involved two sites and remained active for seven months. Treatment with metronidazole was followed by resolution of the skin lesions in one month.

Actinomycin D (AMD) at concentrations that inhibit cellular RNA synthesis by 85% or more causes an acute phase of lethal cell degeneration in HeLa cultures beginning as early as 3 hr after drug exposure, resulting in the nearly complete loss of viable cells by 12 hr. The loss of cells during this acute phase of lethality is closely dose dependent. Vero, WI38, or L cells are not susceptible to this early acute cyto-intoxication by AMD, and may begin to die only after 1-2 days. Differential susceptibility to acute cyto-intoxication by AMD, or other inhibitors of RNA synthesis (daunomycin or nogalamycin), among different types of cultured cells is analogous to that observed in vivo in certain tissues and tumors, and cannot be accounted for by differences in the effect of AMD on RNA, DNA, or protein syntheses, or by the over-all loss of preformed RNA. Actinomycin D in a dose that inhibits RNA synthesis causes an equivalent loss of the prelabeled RNA in all the cell types studied. Inhibition of protein synthesis with streptovitacin A or of DNA synthesis with hydroxyurea does not cause acute lethal injury in HeLa cells as does inhibition of RNA synthesis. Furthermore, since Vero or L cells divide at about the same rate as HeLa cells, no correlation can be drawn between the rate of cell proliferation and susceptibility to the cytotoxicity of AMD. Susceptibile cells are most vulnerable to intoxication by AMD in the G(1)-S interphase or early S phase. Inhibition of protein synthesis (which protects cells against damage by other agents affecting DNA) does not protect against AMD-induced injury. Although HeLa cells bind more AMD at a given dose than Vero or L cells, the latter cell types, given higher doses, can be made to bind proportionally more AMD without succumbing to acute cyto-intoxication. It is suggested that the differential susceptibility of these cell types to acute poisoning by AMD may reflect differences among various cells in the function or stability of certain RNA species not directly involved in translation whose presence is vital to cells. In HeLa cells, these critical species of RNA are presumed to have a short half-life.

After pulse exposure to concentrations of actinomycin D (AMD) sufficient to abolish transcription, Vero cells recover RNA synthesis much more rapidly than most other cell types. This is only in part attributable to the remarkable capacity of Vero very promptly to excrete bound AMD, elimination of which, although necessary, is not a sufficient condition for resurgence of RNA synthesis. After elimination of higher concentrations of AMD from Vero, although over-all RNA synthesis resumes a normal rate within 24 hr, protein synthesis lags, and a long period of division-delay ensues. Division-delay lasting 2-3 days results from exposure of Vero to doses of AMD greater than those that suppress RNA synthesis by greater than 90% (e.g. 1 microg/ml for 2 hr) but not by lower doses, which permit almost immediate reentry into the cell cycle. In contrast, although L cells recover over-all RNA synthesis very slowly after pulse treatment with AMD, resumption of protein synthesis or cell division is not comparably delayed thereafter. These and other data suggest that the early restoration of RNA synthesis in Vero after relief of inhibition by AMD is qualitatively imperfect. The results reported herein are explainable by the hypothesis that the synthesis of those species of RNA which are involved, directly or indirectly, in reactivating the transcription of genes controlling progression in the cell cycle is relatively resistant to suppression by AMD. Decay of such RNA templates and their products, which differs in different cell types during inhibition by AMD, determines the duration of division-delay.