Tokyo subway attack

Fidder and coworkers (50) developed a versatile procedure that identifies phosphylated butyrylcholi-nesterase. Adducted butyrylcholinesterase is isolated from plasma by affinity chromatography (procainamide column), digested with pepsin, and a nonapep-tide containing the phosphylated active-site serine residue detected using LC/ESI/MS/MS (quadrupole-TOF hybrid instrument). A C18 150 x 0.3-mm LC column was used, eluted with a gradient of water-acetonitrile-0.2 % formic acid. The method was applied successfully to casualties of sarin poisoning from the Tokyo subway attack (see Chapter 17). 

Application of the fluoride-reactivation method to serum samples of victims from the Tokyo subway attack, and of the Matsumoto incident, yielded, sarin concentrations in the range of 0.2-4.1ng/ml serum (44). Evidently, these casualties had been exposed to an organophosphate with the formula i-PrO(CH3)P(0)X, presumably with X = F (sarin). 

The hydrolytic displacement method was applied to four victims killed in the Tokyo subway attack (two died immediately and two later in hospital). Isopropyl methylphosphonic acid was identified at levels sufficient for full scan mass spectra to be obtained using a benchtop quadmpole mass spectrometer (46). Methylphosphonic acid was also identified. Some two years later, methylphosphonic acid... 

Finally, mass spectrometric determination of the phosphonylated peptic nonapeptide from butyrylcholinesterase allowed the positive identification of sarin-inhibited enzyme in serum samples from several Japanese victims of the Tokyo subway attack (see Figure 10). 

Murata, K., S. Araki, K. Yokoyama, T. Okumura, S. Ishimatsu, N. Takasu, and R.F. White. 1997. Asymptomatic sequelae to acute sarin poisoning in the central and autonomic nervous system 6 months after the Tokyo subway attack. J. Neurol. 244 601-606. 

Tsuchihashi, H., Katagi, M., Tatsuno, M., Miki, A., Nishikawa, M. (2005). Identification of VX metabolites and proof of VX use in the victim s serum. International Symposium on NBC Terrorism Defense in Commemoration of the 10th Anniversary of the Tokyo Subway Attack (2005 Symposium). Choshi City, Chiba, Japan, June 16-19, 2005, Book of Abstracts, p. 6. 

In the Tokyo subway attack, 640 victims were seen within hours of the incident. Five were critically injured and... 

Ohtani, T., Iwanami, A., Kasa, K., Yamasue, H., Kato, T., Sasaki, T., Kato, N. (2004). Post-traumatic stress disorder symptoms in victims of Tokyo subway attack a 5-year follow-up study. Psychiatry Clin. Neurosci. 58(6) 624-9. 

Fidder et al. introduced an electrospray-ionization tandem mass spectrometry method for diagnosing OP exposure by measuring the mass of the OP-labeled active site peptide of human butyrylcholinesterase (Fidder et al, 2002). His starting material was 0.5 ml of human plasma from a victim of the Tokyo subway attack. The mass of the active site peptide was higher by 120 atomic mass units, compared to the mass of the unlabeled active site peptide. This added mass was exactly the added mass expected from sarin. The peptide s MS-MS fragmentation spectrum yielded the sequence of the peptide, and verified that the OP label was on serine 198, the active site serine. Examples of the MS-MS spectra from tryptic peptides of pure, OP-labeled human butyrylcholinesterase are shown in Figure 56.1. 

Yokoyama, K., Ogura, Y., Kishimoto, M., Hinoshita, F., Hara, S., Yamada, A., Mimura, N., Seki, A., Sakai, O. (1995). Blood purification for severe sarin poisoning after the Tokyo subway attack. J. Am. Med. Assoc. 274 379. 

Respiratory alkalosis >60% of cases in 1995 Tokyo subway attack... 

Tissue sample collection is obviously the most invasive and usually limited to a deceased casualty. Consequently, tissue collection is not normally used for diagnosis to medically respond but for forensic analysis, such as the formalin-fixed brain tissues from the Tokyo subway attack victims, to verify GB as the agent employed (Matsuda et al., 1998). 

Although the police investigation collected enough evidence to prove that sarin was used by AUM Shinrikyo terrorists in Tokyo, the final scientific proof came this summer, when two laboratories independently determined sarin metabolites in blood and urine samples drawn from Tokyo subway attack victims. The Holland group of investigators liberated them from plasma butyrylcholineste-rases [14], while the Japanese group used urine instead [30],... 

Yokoyama K, Yamada A, MimuraN. Clinical profiles of patients with sarin poisoning after the Tokyo subway attack. Am J Med 1996 May 100(5) 586. 

Yokoyama K, Ogura Y, Kishimoto M et al. (1995). Blood purification for severe sarin poisoning after the Tokyo subway attack. JAMA, 274, 379. 

The Matsumoto sarin attack occurred on June 27, 1994, one year before the Tokyo subway sarin attack, and although the group responsible for the Matsumoto attack was not known at the time of the Tokyo subway attack, emergency doctors in Japan knew that the diagnosis and treatment of sarin poisoning should follow that of accidental organophosphorus poisoning. 

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