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S Ishimatsu

Publications and source records attributed to S Ishimatsu.

At least 19 recordsLinked to original sources

The Tokyo subway sarin attack--lessons learned.

The sarin gas attack in the Tokyo subway system is reviewed from a clinical toxicology perspective. Based on the lessons learned from this attack, the following areas should be addressed on a global scale. First, an adequate supply of protective equipment is required, including level B protective equipment with a pressure demand breathing apparatus. In addition, a system should be established that enables a possible cause to be determined based on symptoms, physical findings, general laboratory tests, and a simple qualitative analysis for poisonous substances. If an antidote is needed, the system should enable it to be administered to the victims as quickly as possible. Preparation for a large-scale chemical attack by terrorists requires the prior establishment of a detailed decontamination plan that utilizes not only mass decontamination facilities but also public facilities in the area. A system should be established for summarizing, evaluating, and disseminating information on poisonous substances. Finally, a large-scale scientific investigation of the Tokyo sarin attack should be conducted to examine its long-term and subclinical effects and the effects of exposure to asymptomatic low levels of sarin.

Antidotes↗

Angiotensin II augmented migration and invasion of choriocarcinoma cells involves PI3K activation through the AT1 receptor.

While angiotensin II (Ang II) has been shown to inhibit migration of extravillous trophoblasts via plasminogen activator inhibitor-1 (PAI-1) activation, it has remained unclear whether it stimulates or inhibits malignant behavior of choriocarcinoma cells. Since we previously found an involvement of the renin-angiotensin system (RAS) in the proliferative potential in choriocarcinoma cells (BeWo), mediated via the Ang II type 1 receptor (AT1R), in the present study we investigated the effects of Ang II on choriocarcinoma cell migration/invasion in vitro using Transwell cell culture chambers. Ang II (10(-8)M) promoted migration and invasion by a choriocarcinoma cell line and augmented random cell mobility on checkerboard analysis. Immunoblotting showed Ang II to activate the phosphorylation of FAK and Akt in BeWo cells. Furthermore Ang II effects on cell migration were abolished by a selective AT1R antagonist and a phosphatidylinositol 3-kinase (PI3K) inhibitor. The present results suggest that Ang II-induced migration and invasion of choriocarcinoma cells probably involves PI3K following binding to the AT1R.

Angiotensin II↗

Comparison of gene expression of cytokines mRNA in lungs of rats induced by intratracheal instillation and inhalation of mineral fibers.

To investigate whether the results of intratracheal instillation studies on mineral fibers reflect the findings obtained by long-term inhalation data on mineral fibers, we have examined gene expression of cytokines and pathological features in lungs induced by intratracheal instillation and inhalation of mineral fibers. Male Wistar rats were given a single intratracheal instillation of 2 mg alumina silicate refractory fiber (RF1) or potassium octatitanate whisker (PT1), and were sacrificed 4 wk after the fiber instillation. Long-term inhalation studies were also performed. In these, animals were exposed to fiber aerosol of RF1 or PT1 for 5 days/wk for 1 yr, and sacrificed after 1 yr of inhalation. Expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and transforming growth factor-beta1 (TGF-beta1) from lungs was observed by reverse-transcription polymerase chain reaction (RT-PCR). The expression of TNF-alpha, IL-6, and TGF-beta1 mRNA in PT1-exposed lung was significantly higher than for those exposed to RF1 in both intratracheal instillation and inhalation studies. Pathological findings revealed that mild pulmonary fibrosis was seen in the lungs after intratracheal instillation and inhalation of PT1 but not RF1. Similarities were observed not only in gene expression of cytokines but in pathological features between both studies. These data suggested that the results of intratracheal instillation reflect the findings obtained from long-term inhalation data.

Aluminum Silicates↗

Sampling and detection of Legionella pneumophila aerosols generated from an industrial cooling tower.

Cooling tower water has frequently been cited as a source of infection in outbreaks of Legionnaires' disease. However, there have been few reports on the presence of legionellae in aerosols from cooling towers. This paper describes our use of an impinger or a six-stage microbial impactor for detecting legionellae in air around a cooling tower contaminated with L. pneumophila (1.2+/-0.3x10(5) CFU/100 ml). Phosphate-buffered saline, Page's saline, 2% yeast extract solution and buffered yeast extract (BYE) broth were tested to evaluate their collection efficiency. These solutions were compared in laboratory experiments using an aerosol of L. pneumophila serogroup (SG) 1. Because BYE broth was the most efficient and storable collecting fluid among them, it was used for outdoor air sampling. In the outdoor air sampling, aerosolized L. pneumophila SG 6 was detected in the air around the cooling tower by the impinger (0.09 CFU/l. air). No legionellae were detected by the impactor with Legionella-selective agar plates (WYOalpha) because the plates were overgrown with fungi. Repetitive element PCR (rep-PCR) and arbitrarily primed PCR (AP-PCR) were employed to assess the epidemiological relationship among Legionella isolates from the air sample and the cooling tower water samples. L. pneumophila SG 6 isolated from the aerosols produced rep-PCR and AP-PCR fingerprints identical to those of L. pneumophila SG 6 strains from the cooling tower water, suggesting that the bacterium was aerosolized from the cooling tower.

Aerosols↗

Psycho-physiological effects of the terrorist sarin attack on the Tokyo subway system.

The investigation describes the follow-up of the victims of the 1995 Tokyo sarin attack who were followed by a team at the St. Luke's International Hospital. A symptom questionnaire ("St. Luke's Questionnaire") was developed and given 2, 3, and 5 years following the sarin attack. Somatic and psychological symptoms have continued for 5 years after the incident. New post-traumatic stress disorder diagnostic criteria, which include physical symptoms, were developed and applied for assessment of the outcomes. The St. Luke's cohort was also compared with other Japanese sarin attack cohorts. Interventions, including counseling, medical treatments, and support group activities, were associated with fewer symptoms among the victims.

Adult↗

Effect of repeated exposure to methanol and toluene vapor on the metabolism of rats.

Wistar male rats were repeatedly exposed to methanol and toluene vapors individually and simultaneously by inhalation 6 hours a day, five days a week for 4 weeks. Blood was obtained from the tail of the rats up to 23 hours after the end of 4-week exposure and the methanol and toluene concentrations were measured. Major metabolites of methanol and toluene, that is, formic acid and hippuric acid in urine were measured up to 6 days after the end of 4-week exposure. The biological half time of toluene in blood in the simultaneous exposure group was shorter than that in the toluene exposure group. This tendency was almost the same as that for one-day exposure, although the biological half time of solvents in the rat blood was prolonged. The half times of methanol were also longer than those for one-day exposure.

Animals↗

A clearance model of inhaled man-made fibers in rat lungs.

A clearance model of inhaled man-made fibers (MMFs) was developed, and the calculated fiber numbers and dimensions were compared with the experimental ones using a glass fiber (GF), ceramic fiber (RF1) and two potassium octatitanate whiskers (PT1, TW). If the translocation rate by macrophages is constant and the effect of dissolution and disintegration can be ignored, the fiber number is expected to decrease exponentially with time. In the experimental study, however, the fiber number did not always decrease exponentially. In the case of RF1, the fiber number decreased almost exponentially and the diameter decreased linearly with the time. The clearance rate constant of GF during 3 to 6 months after the end of one-month exposure was greater than that during 1 to 3 months. On the contrary, the clearance rate constants of PT1 and TW during 1 to 6 months were greater than next six months. The diameter and the length of GF did not change significantly. The fiber length of PT1 tends to become longer with time although the diameter did not change significantly. Our theoretical model gives a satisfactory fit to these experimental results.

Administration, Inhalation↗

A new digestion method for recovery of MMMFs from lungs.

A new tissue digestion method is proposed to recover man-made mineral fibers (MMMFs) from lungs, which is an improved Kjeldahl method using microwaves. Tissue digestion is carried out under five different conditions in this experiment, and the most suitable condition is found as follows; dried rat lung (0.5 g of wet weight) is put into a flask with 0.1 ml of H2SO4 and 2.0 ml of HNO3, and treated by microwaves for 5 min. After the treatment, 1.0 ml of H2O2 is added immediately and the sample is treated again under the same condition. Pure samples of glass fibers and refractory ceramic fibers are treated by this proposed method. Numbers and sizes of the fibers are measured before and after the treatment on enlarged photos taking by a scanning electron microscope. As no significant changes are observed in fiber dimensions and numbers, the proposed method is shown to be applicable to recover these MMMFs from lungs.

Acids↗

A preliminary study on delayed vestibulo-cerebellar effects of Tokyo Subway Sarin Poisoning in relation to gender difference: frequency analysis of postural sway.

To evaluate delayed (long-term) effects of acute sarin poisoning on postural balance, nine male and nine female victims of the Tokyo Subway Sarin Poisoning in Japan (sarin cases) were examined by computerized posturography 6-8 months after the poisoning. Their plasma cholinesterase activities (ChE) on the day of the poisoning (March 20, 1995) were 13-95 (mean 68.2) IU/l for females and 19-131 (mean 75.9) IU/l for males, which were not significantly different between the two sexes. In females, the postural sway of low frequency (0-1 Hz) in the anterior-posterior direction and area of sway with eyes open was significantly larger in the cases than in the controls. Romberg quotients for the low-frequency sway in the anterior-posterior direction for females and low-frequency sway and length of sway in the medio-lateral direction for males were significantly related to log ChE. It is suggested that a delayed effect on the vestibulo-cerebellar system was induced by acute sarin poisoning; females might be more sensitive than males.

Adult↗

The Tokyo subway sarin attack: disaster management, Part 1: Community emergency response.

The Tokyo subway sarin attack was the second documented incident of nerve gas poisoning in Japan. Prior to the Tokyo subway sarin attack, there had never been such a large-scale disaster caused by nerve gas in peacetime history. This article provides details related to how the community emergency medical services (EMS) system responded from the viewpoint of disaster management, the problems encountered, and how they were addressed. The authors' assessment was that if EMTs, under Japanese law, had been allowed to maintain an airway with an endotracheal tube or use a laryngeal mask airway without physician oversight, more patients might have been saved during this chemical exposure disaster. Given current legal restrictions, advanced airway control at the scene will require that doctors become more actively involved in out-of-hospital treatment. Other recommendations are: 1) that integration and cooperation of concerned organizations be established through disaster drills; 2) that poison information centers act as regional mediators of all toxicologic information; 3) that a real-time, multidirectional communication system be established; 4) that multiple channels of communication be available for disaster care; 5) that public organizations have access to mobile decontamination facilities; and 6) that respiratory protection and chemical-resistant suits with gloves and boots be available for out-of-hospital providers during chemical disasters.

Disaster Planning↗

The Tokyo subway sarin attack: disaster management, Part 2: Hospital response.

The Tokyo subway sarin attack was the second documented incident of nerve gas poisoning in Japan. The authors report how St. Luke's Hospital dealt with this disaster from the viewpoint of disaster management. Recommendations derived from the experience include the following: Each hospital in Japan should prepare an emergent decontamination area and have available chemical-resistant suits and masks. Ventilation in the ED and main treatment areas should be well planned at the time a hospital is designed. Hospital disaster planning must include guidance in mass casualties, an emergency staff call-up system, and an efficient emergency medical chart system. Hospitals should establish an information network during routine practice so that it can be called upon at the time of a disaster. The long-term effects of sarin should be monitored, with such investigation ideally organized and integrated by the Japanese government.

Disaster Planning↗

The Tokyo subway sarin attack: disaster management, Part 3: National and international responses.

The authors report the national and international responses to the disaster produced by the Tokyo subway sarin attack. From a worldwide historical perspective, there had never been such a large-scale disaster caused by nerve gas during peacetime. Therefore, this event should be studied from various viewpoints in cooperation with members of the international community. To this end, the Japanese government should help coordinate a large-scale and detailed investigation of the Tokyo subway sarin attack, including the long-term effects of sarin. The authors also recommend that the Japanese Self Defense Forces should be used more effectively in large-scale disasters. The system of direct control of disaster management by the Japanese government could be useful in a large-scale disaster.

Disaster Planning↗

Asymptomatic sequelae to acute sarin poisoning in the central and autonomic nervous system 6 months after the Tokyo subway attack.

Six to eight months after the Tokyo subway attack in March 1995, the neurophysiological effects of acute sarin poisoning were investigated in 18 passengers exposed to sarin (sarin cases) in the subways to ascertain the focal or functional brain deficits induced by sarin. The event-related and visual evoked potentials (P300 and VEP), brainstem auditory evoked potential, and electrocardiographic R-R interval variability (CVRR), together with the score on the posttraumatic stress disorder (PTSD) checklist, were measured in the sarin cases and the same number of control subjects matched for sex and age. None of the sarin cases had any obvious clinical abnormalities at the time of testing. The P300 and VEP (P100) latencies in the sarin cases were significantly prolonged compared with the matched controls. In the sarin cases, the CVRR was significantly related to serum cholinesterase (ChE) levels determined immediately after exposure; the PTSD score was not significantly associated with any neurophysiological data despite the high PTSD score in the sarin cases. These findings suggest that asymptomatic sequelae to sarin exposure, rather than PTSD, persist in the higher and visual nervous systems beyond the turnover period of ChE; sarin may have neurotoxic actions in addition to the inhibitory action on brain ChE.

Acute Disease↗

Distribution of various nickel compounds in rat organs after oral administration.

In this study, eight kinds of nickel (Ni) compounds were orally administered to Wistar male rats and the distribution of each compound was investigated 24 h after the administration. The Ni compounds used in this experiment were nickel metal [Ni-M], nickel oxide (green) [NiO(G)], nickel oxide (black) [NiO(B)], nickel subsulfide [Ni3S2], nickel sulfide [NiS], nickel sulfate [NiSO4], nickel chloride [NiCl2], and nickel nitrate [Ni(NO3)2]. The solubilities of the nickel compounds in saline solution were in the following order; [Ni(NO3)2 > NiCl2 > NiSO4] >> [NiS > Ni3S2] > [NiO(B) > Ni-M > NiO(G)]. The Ni level in the visceral organs was higher in the rats given soluble Ni compounds; Ni(NO3)2, NiCl2, NiSO4, than that in the rats receiving other compounds. In the rats to which soluble Ni compounds were administered, 80-90% of the recovered Ni amounts in the examined organs was detected in the kidneys. On the other hand, the Ni concentration in organs administered scarcely soluble Ni compounds; NiO(B), NiO(G), and Ni-M were very low. The estimated absorbed fraction of each Ni compounds was increased with the increase of the solubility. These results suggest that the kinetic behavior of Ni compounds administered orally is closely related with the solubility of Ni compounds, and that the solubility of Ni compounds is one of the important factors for determining the health effect of Ni compounds.

Absorption↗

Biological effects of inhaled magnesium sulphate whiskers in rats.

Male Wistar rats were exposed to two types of magnesium sulphate whiskers by inhalation for six hours a day, five days a week, for four weeks (sub-chronic study), or for one year (chronic study) to clarify the biological effects of the whiskers. There were few whiskers detected in the rat lungs even at one day after the exposure, suggesting that they are dissolved and eliminated rapidly from the lungs. To measure the clearance rate of the whiskers from the lungs, an intratracheal instillation was performed in golden hamsters. The half life of the whiskers in the lung was determined as 17.6 minutes by temporally measuring the magnesium concentration up to 80 minutes after the instillation. A histopathological examination indicated a frequent occurrence of adenoma and carcinoma in the year after chronic exposure, but it was not significantly different between exposed and control rats.

Animals↗

Pulmonary deposition and clearance of glass fiber in rat lungs after long-term inhalation.

In this study Wistar male rats were exposed to glass fiber obtained by the disintegration of a binderless glass fiber filter, for 6 hr/day, 5 days/week for 12 months. The mass median aerodynamic diameter (MMAD) of the fiber, determined with an Andersen sampler, was 2.6 microns. The count median diameter and length of the fibers measured by scanning electron microscopy (SEM) were 0.51 and 5.5 microns, respectively. The daily average exposure fiber concentration was 2.2 +/- 0.6 mg/m3. Some rats were sacrificed 24 hr after removal from the exposure chamber following the 12 months' exposure. Others were sacrificed 12 months after the end of exposure. The wet organ weights were recorded at the time of death and the silicon content of the lungs was determined by absorption spectrophotometry. After 12 months' exposure, the amount of glass fiber retained in the rat lungs was 1.49 mg, and after 12 months' clearance it was 0.61 mg. The biological half-life in a single exponential model was to be 8.7 months, much longer than the predicted value of 1.5 months obtained in a previous experiment in which rats were exposed for 4 weeks to the same glass fiber.

Administration, Inhalation↗

Effect of aggressive haemoperfusion on the clinical course of patients with paraquat poisoning.

The effect of aggressive haemoperfusion; i.e. haemoperfusion of 10 h or more during the first 24 h after ingestion, on the clinical course of paraquat poisoning was studied. Among 40 patients admitted within 15 h after ingestion of paraquat with an SIPP of less than 100 (h x micrograms ml-1), 21 received aggressive haemoperfusion and 19 received conventional haemoperfusion; i.e. haemoperfusion of less than 10 h during the same period. Survival rates of patients with severity between an SIPP of 100 and Proudfoot's curve in the two groups were compared by the log-rank test. Aggressive haemoperfusion did not improve the outcome but did improve the survival rates; that is, the number of patients surviving at particular points in time (P < 0.05). The length of haemoperfusion for the aggressive haemoperfusion group was longer than that for the conventional group on the first day (P < 0.001), but the difference was insignificant during the following two days. Neither the time from ingestion to haemoperfusion, urine volume from the first to third day, nor initial plasma-paraquat concentrations and SIPP were significant between groups. These findings imply that aggressive haemoperfusion reduces the severity of paraquat poisoning and elongates survival time. We, therefore, propose that the efficacy of more aggressive haemoperfusion, such as the 'continuous haemoperfusion' proposed by Okonek et al., should be further studied.

Adolescent↗