Malaria and Artificial Fever in the Treatment of Paresis

O’leary, Paul A.; Bruetsch, Walter L.; Ebaugh, Franklin G.; Simpson, Walter M.; Solomon, Harry C.; Warren, Stafford L.; Vonderlehr, R. A.; Usilton, Lida J.; Sollins, I. V.

doi:10.1001/jama.1940.02810350021006

Cited by 17 publications

(8 citation statements)

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“…Furthermore, it is well-known that elevation of the body temperature of infected humans or experimentally infected rabbits frequently results in the amelioration of syphilitic infection (25,28). Fever therapy induced by iatrogenic infection with Borrelia or Plasmodium species or by hypertherm cabinets was used before the advent of antibiotics as a treatment for human syphilis (2,5,23). In contrast to the results obtained with T. pallidum, for each of the other spirochetes analyzed we were able to detect a subset of proteins that were synthesized at a distinctly higher level following the temperature shift.…”

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confidence: 60%

Heat shock response of spirochetes

et al. 1991

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We examined the heat shock response of the pathogenic spirochetes Treponema pallidum, Borrelia burgdorferi, and Leptospira interrogans and certain saprophytic spirochetes. Cellular proteins synthesized after shifts to higher temperatures were [35S]methionine labeled and analyzed by gel electrophoresis and fluorography. Only T. pallidum failed to exhibit an obvious heat shock response. GroEL and DnaK homologs were identified in the various species, although these proteins were not thermoinducible in T. pallidum or Treponema denticola. DNA hybridization studies indicate that spirochetal groEL and dnaK genes are highly conserved.

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confidence: 60%

Heat shock response of spirochetes

et al. 1991

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“…As early as 1539, Rodrigo Ruy de Isla observed the beneficial effects of fever on the course of the disease among the sailors of Columbus's crew (37). Furthermore, fever therapy induced by iatrogenic infection with Borrelia or Plasmodium species or by hypertherm cabinets was used as a treatment for human syphilis before the advent of antibiotics (1,2,27). It has also been shown that an increase in body temperature of infected humans or experimentally infected rabbits could result in the amelioration of syphilitic infection (30,36).…”

Section: Discussionmentioning

confidence: 99%

Treponema pallidum 3-Phosphoglycerate Mutase Is a Heat-Labile Enzyme That May Limit the Maximum Growth Temperature for the Spirochete

et al. 2001

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In the causative agent of syphilis, Treponema pallidum, the gene encoding 3-phosphoglycerate mutase, gpm, is part of a six-gene operon (tro operon) that is regulated by the Mn-dependent repressor TroR. Since substrate-level phosphorylation via the Embden-Meyerhof pathway is the principal way to generate ATP in T. pallidum and Gpm is a key enzyme in this pathway, Mn could exert a regulatory effect on central metabolism in this bacterium. To study this, T. pallidum gpm was cloned, Gpm was purified from Escherichia coli, and antiserum against the recombinant protein was raised. Immunoblots indicated that Gpm was expressed in freshly extracted infective T. pallidum. Enzyme assays indicated that Gpm did not require Mn 2؉ while 2,3-diphosphoglycerate (DPG) was required for maximum activity. Consistent with these observations, Mn did not copurify with Gpm. The purified Gpm was stable for more than 4 h at 25°C, retained only 50% activity after incubation for 20 min at 34°C or 10 min at 37°C, and was completely inactive after 10 min at 42°C. The temperature effect was attenuated when 1 mM DPG was added to the assay mixture. The recombinant Gpm from pSLB2 complemented E. coli strain PL225 (gpm) and restored growth on minimal glucose medium in a temperature-dependent manner. Increasing the temperature of cultures of E. coli PL225 harboring pSLB2 from 34 to 42°C resulted in a 7-to 11-h period in which no growth occurred (compared to wild-type E. coli). These data suggest that biochemical properties of Gpm could be one contributing factor to the heat sensitivity of T. pallidum.Syphilis, a sexually transmitted disease caused by the spirochete Treponema pallidum, remains a major public health problem in the world. T. pallidum cannot be cultivated in vitro, making it difficult to assess the role of genes in physiology, survival in the host, and pathogenesis. One approach to studying the functions of T. pallidum genes is to clone and overexpress these genes in Escherichia coli and then characterize the recombinant proteins in vitro. This approach was taken recently to characterize the TroR regulatory protein from T. pallidum (28). In the presence of Mn 2ϩ , TroR binds the operator of the transport-related operon (tro) and represses transcription. The tro operon contains six genes (14). The first four genes encode a putative ABC metal transport system (troA to -D), the fifth gene encodes TroR (troR), and the last gene encodes a glycolytic enzyme, 3-phosphoglycerate mutase (gpm, referred to as pgm in the T. pallidum genome database), which converts 3-phosphoglycerate (3-PGA) to 2-phosphoglycerate (2-PGA) (8, 11). Since T. pallidum can only generate ATP via glycolysis, 3-phosphoglycerate mutase is a key enzyme for the spirochete.Bacterial phosphoglycerate mutases are divided into two classes, based on their requirement for the cofactor 2,3-diphosphoglycerate (DPG) (10). Phosphoglycerate mutases from spore-forming Bacillus species, such as Bacillus megaterium, Bacillus subtilis, and Bacillus stearothermophilus, are DPG independent b...

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“…They concluded that the response was similar for mild or intermediate paresis, but ''artificial fever'' was more effective in severe paresis. 35 The crude death rate, defined in the study as death from any cause within 3 months of treatment, was 8% for ''artificial fever'' therapy and 13% for malaria therapy.…”

Section: Induced Fever By Other Methodsmentioning

confidence: 99%

“…34 The Cooperative Clinical Group, which combined clinical data from major hospitals across the USA, compared the results of 1100 patients treated with malaria and 320 treated with “artificial fever.” They concluded that the response was similar for mild or intermediate paresis, but “artificial fever” was more effective in severe paresis. 35 The crude death rate, defined in the study as death from any cause within 3 months of treatment, was 8% for “artificial fever” therapy and 13% for malaria therapy.…”

Section: Induced Fever By Other Methodsmentioning

confidence: 99%

Fever therapy for general paresis

Albert

1999

Int J Dermatology

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Malaria and Artificial Fever in the Treatment of Paresis

Cited by 17 publications

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Heat shock response of spirochetes

Heat shock response of spirochetes

Treponema pallidum 3-Phosphoglycerate Mutase Is a Heat-Labile Enzyme That May Limit the Maximum Growth Temperature for the Spirochete

Fever therapy for general paresis

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