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We investigated the crystal structure of an HLA-A"2402-restricted CTL epitope in the HIV-1 nef gene (Nef134-10) before (pHLA) or after TCR docking. The wild type epitope and two escape mutants were included in the study. Y135F was an early-appearing major mutation, while F139L was a late-appearing mutation which was selected in the patients without Y135F. F139 was an eminent feature of the Nef134-10 epitope. Wild type-specific TCR was less fit to F139L mutant suggesting that F139L is an escape from the CTL against the wild type epitope. Although Y135F mutation disrupted the hydrogen bond to HLA-A"2402 His70, newly formed hydrogen bond between T138 and His70 kept the conformation of the epitope in the reconstituted pMHC. TCR from Y135F- or dually-specific CTL had unique mode of binding to the mutant epitope. Y135F has been reported as a processing mutant but CTL carrying structurally adequate TCR can be found in the patients. [ABSTRACT FROM AUTHOR]

The outbreak of severe acute respiratory syndrome (SARS) has drawn enormous attention and caused fear worldwide since early 2003. The disease appears to be under control now; however, the possible return of SARS must be emphasized. Although many clinical experiments have been reported, the treatment of SARS is largely anecdotal, and so far no treatment consensus has been reached. We summarize 14 clinical reports and attempt to assess the effectiveness of various treatment regimens. A combination treatment of steroids and ribavirin was widely used empirically from the outset of the epidemic. In general, the use of steroids for SARS seemed beneficial, but the optimal timing, dosage, and duration of treatment have not yet been determined. On the other hand, ribavirin administration apparently reduced neither the rate of intratracheal intubation nor that of mortality. Moreover, significant toxicity, such as hemolytic anemia, has been attributed to ribavirin. A few preliminary trials and in vitro data suggest the possibility of treating SARS with interferon. Other agents, including the HIV protease inhibitor glycyrrhizin and convalescent plasma, remain to be evaluated. [ABSTRACT FROM AUTHOR]

Although mefloquine is the only drug licensed for malaria chemoprophylaxis in Japan, there have been few reports describing the effects of and adverse events in the prophylactic usage of mefloquine in a Japanese population. We therefore performed a questionnaire-based study in 21 travelers who were prescribed mefloquine for malaria chemoprophylaxis between October 2001 and December 2003. The study revealed that only 8 out of 21 (38.1%) of the travelers could complete the prophylaxis schedules. Another 8 travelers (38.1%) with incomplete adherence stated that they did not take mefloquine because of either actually experienced or anticipated adverse events. Twelve of the 16 travelers (75.0%) who took mefloquine complained of at least one adverse event probably related to mefloquine. As an overall impression about mefloquine chemoprophylaxis, 14 of the 21 travelers stated that they would take mefloquine again for the next travel to malaria-endemic areas, although 5 of them were concerned about adverse events. These results suggest that, although mefloquine is an indispensable drug for malaria prevention, other effective and well-tolerated chemoprophylactic antimalarials should be available for Japanese travelers who do not tolerate mefloquine. [ABSTRACT FROM AUTHOR]

A 24-year-old Japanese man showed neurological disturbances 2 weeks after complete recovery from Plasmodium vivax infection. Magnetic resonance (MR) images of the brain showed multiple high-intensity spotty lesions in the left cerebral cortex and subcortex. Cerebrospinal fluid examination, including polymerase chain reaction analysis for viruses, revealed no sign of active infection. Repeated blood smears were negative for malaria. We diagnosed acute disseminated encephalomyelitis (ADEM) following Plasmodium vivax malaria from the clinical course and MR images. ADEM should be regarded as one of the neurological complications after malarial infection. [ABSTRACT FROM AUTHOR]