RESUMEN
In 1854, Dr. John Snow identified the Broad Street pump as the source of an intense cholera outbreak by plotting the location of cholera deaths on a dot-map. He had the pump handle removed and the outbreak ended...or so one version of the story goes. In medical geography, the story of Snow and the Broad Street cholera outbreak is a common example of the discipline in action. While authors in other health-related disciplines focus on Snow's "shoe-leather epidemiology", his development of a water-borne theory of cholera transmission, and/or his pioneering role in anaesthesia, it is the dot-map that makes him a hero in medical geography. The story forms part of our disciplinary identity. Geographers have helped to shape the Snow narrative: the map has become part of the myth. Many of the published accounts of Snow are accompanied by versions of the map, but which map did Snow use? What happens to the meaning of our story when the determinative use of the map is challenged? In his book On the Mode of Communication of Cholera (2nd ed., John Churchill, London, 1855), Snow did not write that he used a map to identify the source of the outbreak. The map that accompanies his text shows cholera deaths in Golden Square (the subdistrict of London's Soho district where the outbreak occurred) from August 19 to September 30, a period much longer than the intense outbreak. What happens to the meaning of the myth when the causal connection between the pump's disengagement and the end of the outbreak is examined? Snow's data and text do not support this link but show that the number of cholera deaths was abating before the handle was removed. With the drama of the pump handle being questioned and the map, our artifact, occupying a more illustrative than central role, what is our sense of Snow?
Asunto(s)
Cólera/historia , Brotes de Enfermedades/historia , Epidemiología/historia , Geografía/historia , Cólera/epidemiología , Inglaterra/epidemiología , Historia del Siglo XIX , Humanos , Mapas como Asunto , Mitología , Salud Pública/historiaRESUMEN
Glycosylation variants of the virulent Leishmania major clone V121 were generated by mutagenesis with N-methyl-N-nitroso-N-nitroguanidine and selected using the galactose-specific lectin Ricinus communis II (RCA II). Three mutants, 4B9, 1D1 and 1C12, which failed to bind RCA II, were found to have an altered expression of lipophosphoglycan (LPG), a molecule implicated in the attachment to host macrophages and survival within the phagolysosome. There were differences in the antigenicity, molecular weight and localization of LPG from mutant parasites as compared to V121. Expression of gp63, a surface molecule also implicated in attachment to macrophages, was unaltered. All 3 mutants caused disease when injected into genetically susceptible BALB/c mice but lesions developed at a much slower rate than those caused by the virulent V121 clone. This slow rate of lesion development did not correlate with promastigotes' ability to invade macrophages in vitro. Karyotype analysis showed that there was a reduction in the size of chromosome band number 2 in all 3 mutants. The differences in LPG and chromosome band 2 were retained by mutant clones following passage through mice, suggesting that these phenotypes are stable. Although the mutant parasites were infective and caused lesions, the changed structure of the LPG appeared to influence the virulence of the parasites.
Asunto(s)
Glicoesfingolípidos/biosíntesis , Leishmania major/patogenicidad , Leishmaniasis Cutánea/parasitología , Ricina/farmacología , Aglutinación , Animales , Western Blotting , Células Cultivadas , Resistencia a Medicamentos/genética , Femenino , Técnica del Anticuerpo Fluorescente , Regulación de la Expresión Génica , Glicoesfingolípidos/genética , Cariotipificación , Leishmania major/efectos de los fármacos , Leishmania major/genética , Ratones , Ratones Endogámicos BALB C , Mutagénesis , Bazo/parasitología , Virulencia/genéticaRESUMEN
For murine cutaneous leishmaniasis, data to date suggest a correlation between the presence of gamma interferon (IFN-gamma) and resistance in C57BL/6 mice and the presence of interleukin-4 (IL-4) and disease in BALB/c mice. In this study, 13 inbred strains of mice covering the range of susceptibility to disease were infected with Leishmania major to determine whether the subsequent expression of IFN-gamma or IL-4 is a reliable indicator of cure or progressive disease. The presence of IL-4 and IFN-gamma mRNAs in the draining lymph nodes was examined 9 weeks after infection, when differences in disease severity became obvious. There were large differences in the levels of IL-4 mRNA among the different strains, whereas IFN-gamma mRNA was detected at similar levels in all strains. The levels of IL-4 mRNA correlated with lesion score, with susceptible and intermediate strains containing up to 100-fold more than any of the resistant strains. Differences in the levels of IFN-gamma mRNA were within only a fourfold range, with significant overlap among susceptible, intermediate, and resistant strains. Similarly, the levels of IFN-gamma secreted in vitro by lymph node cells from infected mice in response to L. major antigens were within a 10-fold range for most strains, and there was no correlation with lesion score. Analysis of Leishmania-specific antibody levels revealed a correlation between immunoglobulin G1 (IgG1) titers and lesion score, consistent with the role of IL-4 as a switch factor for IgG1. In contrast, there was no correlation between IgG2a titers and lesion score, supporting the notion that IFN-gamma synthesis (which promotes IgG2a production) is not correlated with disease state. These data suggest that along the spectrum of murine cutaneous leishmaniasis, IL-4 is a reliable indicator of disease, but IFN-gamma is not prognostic for resistance.
Asunto(s)
Interferón gamma/biosíntesis , Interleucina-4/biosíntesis , Leishmania tropica , Leishmaniasis Cutánea/inmunología , Animales , Anticuerpos Antiprotozoarios/sangre , Secuencia de Bases , Femenino , Interferón gamma/genética , Interleucina-4/genética , Leishmania tropica/inmunología , Leishmaniasis Cutánea/genética , Ratones , Ratones Endogámicos , Datos de Secuencia Molecular , ARN Mensajero/análisisRESUMEN
Several attempts have been made to induce resistance in mice to Schistosoma japonicum (Philippines) or Schistosoma mansoni by exposure to living male and/or female adult worms, their antigens or irradiated cercariae. No resistance was demonstrated in the following cases: re-exposure of mice to cercariae following praziquantel (PZQ) treatment of existing infection; re-exposure of mice following cyclosporin A (CsA) treatment at the time of first cercarial exposure; subcutaneous or intraperitoneal deposition of living male or female worms; repeated intranasal administration of crude worm homogenates plus Bordetella pertussis vaccine (BPV) as adjuvant. Homologous 60Co-irradiated cercariae were very effective at inducing resistance to infection with S. mansoni but not to infection with S. japonicum (Philippines) in a limited series of experiments. A regime of infection, immunization with homologous Escherichia coli-derived glutathione-S-transferases (GST), then PZQ treatment followed by homologous re-exposure did not result in significant resistance in either the S. mansoni or the S. japonicum (Philippines) systems. Mice given irradiated cercariae plus GST were not more resistant to subsequent S. mansoni infection than mice given irradiated cercariae alone. The results generally confirm and extend those reported by others with the conclusion that resistance to schistosomes in mice is difficult to achieve by exposure to adult worm antigens alone. Moreover, additional immunization with the GST available to date as cloned gene products, and injected in Freund's complete adjuvant, does not influence the outcome of exposure to crude worm antigens including any additive effects of protective irradiated cercariae.