Neoplasms among A-bomb survivors in Hiroshima: first report of the Research Committee on Tumor Statistics, Hiroshima City Medical Association, Hiroshima, Japan.
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In April 1993, a phytoplankton dinoflagellate was isolated from Hiroshima Bay, Hiroshima Prefecture, Japan, and unambiguously identified as Alexandrium tamarense on the basis of the morphological characteristics. The dinoflagellates, cultures in modified SW-2 medium at 15 degrees C for 15 days, showed a specific toxicity of 30.7 x 10-6 MU/cell. HPLC analysis demonstrated that the toxin was composed mainly of gonyautoxin-4 (GTX4) and protogonyautoxin-2 (PX2 or GTX8)(27.6 and 37.0 mole%, respectively). Total toxin concentration of this strain was 39.5 fmole/cell. Short-necked clams, mussels, and oysters contaminated by the dinoflagellate showed a more complicated composition, with GTX1 as the major component (61.8 mole% for short-necked clams, 60.5 mole% for mussels, 42.5 mole% for oysters), and PX2 was only present in trace amounts.
Paralytic toxicity of ribbon worms ("himomushi" in Japanese), identified as undescribed species of the genus Cephalothrix, found on the surface of the shells of cultured oysters in Hiroshima Bay, Hiroshima Prefecture was examined between April 1998 and December 2001. The toxicity study showed that all of specimens were found to contain toxins with strong paralytic action in mice; the highest toxicity (as tetrodotoxin, TTX) was 25,590 mouse units (MU) per gram for whole body throughout the monitoring period. The main toxic component of this himomushi toxin (HMT) was isolated from a pooled specimen (390 g; total toxicity 2,897,000MU) by a method that consisted of treatment with activated charcoal, chromatography on Bio-Gel P-2 and Bio-Rex 70 (H+ form), and finally crystallization from an acidified methanolic solution. The recrystallized toxin showed a specific toxicity of 3520MU/mg. This toxin showed (M+H)+ and (M+H-H(2)O)+ ion peaks at m/z 320 and 302, respectively, by electrospray ionization-mass spectrometry (ESI-MS). The absorption band at 3353, 3235, 1666, 1612 and 1076 cm(-1) were observed in infrared spectrum of this toxin. This spectrum was indistinguishable from that of TTX. The 1H-NMR spectrum for the recrystallized toxin was the same as that for TTX. The pair of doublets centered at 2.33 (J=10.0Hz) and 5.48 ppm (J=10.0Hz) which are characteristic of TTX, were shown to be coupled by double irradiation. Furthermore, by gas chromatography-mass spectrometry (GC-MS) of the alkali-hydrolyzate of this toxin indicated the presence of quinazoline skeleton (C9-base) specific to TTX.
In 1998, during the surveillance of the toxicity of various marine fouling organisms in Hiroshima Bay, Hiroshima Prefecture, Japan, specimens of the ribbon worm, "himomushi" Cephalothrix sp. (Nemertean) adherent to the shells of cultured oysters hanging onto floating culture rafts were found to contain toxins which showed strong paralytic action in mice throughout the survey period, February to May. The maximum toxicity (as tetrodotoxin, TTX) was 14,734 MU/g whole body. Attempts were made to identify the paralytic toxins in this worm. The "himomushi" toxin (HMT) was extracted from the worm with 80% methanol acidified with acetic acid and the extract defatted with dichloromethane. The aqueous layer was chromatographed on activated charcoal and the unbound and bound toxic fractions were analyzed by high-performance liquid chromatography and gas chromatography-mass spectrometry. It was rather unexpectedly revealed from these results that HMT was comprised of TTX, 4-epiTTX, anhydroTTX and three unidentified toxins. To our knowledge, this is the first report of the occurrence of toxic organisms, containing a high concentration of TTX, adherent to cultured bivalves such as oysters.
An examination of registered cases of parathyroid tumor in Hiroshima Prefecture between 1974 and 1987 revealed 23 cases. An epidemiological study showed that the incidence of parathyroid tumors in Hiroshima Prefecture was significantly higher in the total exposed, especially among the proximally exposed (within 2,000 m from the hypocenter), than in the control nonexposed group (P less than 0.001). A similar trend was seen for parathyroid tumor associated with primary hyperparathyroidism.
To assess levels of shellfish intoxication by the paralytic shellfish poison (PSP)-producing dinoflagellate Alexandrium tamarense, potential health risks to human shellfish consumers and the possible need for regulatory intervention, yearly variations of maximum cell density of this species were examined from 1993 to 2004 in Kure Bay and Kaita Bay, which are located within Hiroshima Bay, Hiroshima Prefecture, Japan. The seawater temperature was determined concomitantly. In Kure Bay, maximum concentrations of 1,400 and 1,300 cells/mL at 0 and 5 m depths were observed on 21 and 24 April 1997. In Kaita Bay, remarkably high concentrations above 1,000 cells/mL of A. tamarense were observed in two out of three years investigated. These facts suggest that the environment in both bays is favorable for the propagation of A. tamarense. The temperature range at which the natural population of A. tamarense blooms was generally from 12 to 16 degrees C. Four strains (ATKR-94, -95, -97 and -01) from Kure Bay and one strain (ATKT-97) from Kaita Bay were established. The strain ATKR-94, cultured in modified SW-2 medium at 15 degrees C for 15 days, showed a specific toxicity of 33.8 x 10(-6) MU/cell. The toxins in all five strains exist almost exclusively as beta-epimers (C2 (PX2 or GTX8), GTX3, dcGTX3 and GTX4), which accounted for 54.9 to 73.0 mol% of the total. The corresponding a-epimers (C1 (PX1 or epi-GTX8), GTX2, dcGTX2 and GTX1) accounted for 6.0 to 28.9 mol%. The toxin profiles of ATKR-97 and ATKT-97 were characterized by unusually high proportions of low-potency sulfocarbamoyl toxin, which comprised 62.4 and 68.2 mol%, respectively, of total toxins. In the toxic bivalves, the low-toxicity sulfocarbamoyl components, major components of A. tamarense, were present in amounts of only a few percent, suggesting that in vivo conversion of PSP occurs after ingestion. A comparison of the toxin profiles of the causative dinoflagellate and contaminated bivalves showed that PSP components exist in the bivalves in the form of alpha-epimers, presumably owing to accumulation or storage of the toxins.
In this study, we investigated 31 foreign patients who had been diagnosed as having pulmonary tuberculosis at the National Hiroshima Hospital or Hiroshima Anti-Tuberculosis Association between 1982 to 1995. Their age ranged from 17 to 63 years, and all of them had been in Japan for less than five years. Twelve of the patients came from South America, 18 from Asia, and one from Egypt. Seven Peruvians had been infected in a tuberculosis outbreak. The reasons of their immigration were job-seeking (14 out of 31), education (8 out of 31), and marriage to Japanese men (6 out of 31). None of them were illegal immigrants. In four women who had married Japanese men, various symptoms such as cough, sputum, and slight fever came on during pregnancy, however, none of them had been diagnosed as having tuberculosis, and consequently they had received no medication during pregnancy. In 6 out of the 8 patients who were college students, their sputa were negative for tubercle bacilli, and they could be treated by chemotherapy as outpatients. In provincial cities, every effort should be made to detect tuberculosis among members of the foreign community who are living under different environments and conditions.
During surveillance on the toxicity of invertebrates such as bivalves inhabiting the coasts of Hiroshima Bay in 2001 and 2002, the carnivorous gastropod rapa whelk Rapana venosa collected in the estuary of Nikoh River, was found to contain toxins which showed paralytic actions in mice; the maximum toxicities (as paralytic shellfish poison, PSP) were 4.2 MU/g (May 2001) and 11.4 MU/g (April 2002). Their total toxicities were 224 and 206 MU/viscera of one specimen throughout the monitoring period. Attempts were made to identify the toxic principle in the gastropod. The viscera were extracted with 80% ethanol acidified with acetic acid, followed by defatting with dichloromethane. The aqueous layer obtained was treated with activated charcoal and then applied to a Sep-Pak C18 cartridge. The unbound toxic fraction was analyzed by high-performance liquid chromatography techniques. The gastropod toxin was rather unexpectedly identified as PSP. It was comprised of high toxic component (gonyautoxin-3; GTX3, GTX2, saxitoxin; STX) as the major components, which accounted for approximately 91 mol% of all components along with C1 and C2, which are N-sulfocarbamoyl derivatives. Judging from their toxin patterns, it is suggested that the PSP toxification mechanism of the gastropod that PSP toxins produced by phytoplankton such as Alexandrium tamarense, are transferred to and accumulated in plankton feeders such as the short-necked clam, and then transferred to this carnivorous rapa whelk R. venosa through predation.
The paper is an analytical overview of the main results presented at the 3rd Dosimetry Workshop in Hiroshima(9-11 of March 2005), where different aspects of the dose reconstruction around the Semipalatinsk nuclear test site(SNTS) were discussed and summarized. The results of the international intercomparison of the retrospective luminescence dosimetry(RLD) method for Dolon' village(Kazakhstan) were presented at the Workshop and good concurrence between dose estimations by different laboratories from 6 countries (Japan, Russia, USA, Germany, Finland and UK) was pointed out. The accumulated dose values in brick for a common depth of 10mm depth obtained independently by all participating laboratories were in good agreement for all four brick samples from Dolon' village, Kazakhstan, with the average value of the local gamma dose due to fallout (near the sampling locations) being about 220 mGy(background dose has been subtracted).Furthermore, using a conversion factor of about 2 to obtain the free-in-air dose, a value of local dose approximately 440 mGy is obtained, which supports the results of external dose calculations for Dolon': recently published soil contamination data, archive information and new models were used for refining dose calculations and the external dose in air for Dolon village was estimated to be about 500 mGy. The results of electron spin resonance(ESR) dosimetry with tooth enamel have demonstrated the notable progress in application of ESR dosimetry to the problems of dose reconstruction around the Semipalatinsk nuclear test site. At the present moment, dose estimates by the ESR method have become more consistent with calculated values and with retrospective luminescence dosimetry data, but differences between ESR dose estimates and RLD/calculation data were noted. For example mean ESR dose for eligible tooth samples from Dolon' village was estimated to be about 140 mGy(above background dose), which is less than dose values obtained by RLD and calculations. A possible explanation of the differences between ESR and RLD/calculations doses is the following: for interpretation of ESR data the "shielding and behaviour" factors for investigated persons should be taken into account. The "upper level" of the combination of "shielding and behaviour" factors of dose reduction for inhabitants of Dolon' village of about 0.28 was obtained by comparing the individual ESR tooth enamel dose estimates with the calculated mean dose for this settlement. The biological dosimetry data related to the settlements near SNTS were presented at the Workshop. A higher incidence of unstable chromosome aberrations, micronucleus in lymphocytes, nuclear abnormalities of thyroid follicular cells, T-cell receptor mutations in peripheral blood were found for exposed areas (Dolon', Sarjal) in comparison with unexposed ones(Kokpekty). The significant greater frequency of stable translocations (results of analyses of chromosome aberrations in lymphocytes by the FISH technique) was demonstrated for Dolon' village in comparison with Chekoman(unexposed village). The elevated level of stable translocations in Dolon' corresponds to a dose of about 180 mSv, which is close to the results of ESR dosimetry for this village. The importance of investigating specific morphological types of thyroid nodules for thyroid dosimetry studies was pointed out. In general the 3rd Dosimetry Workshop has demonstrated remarkable progress in developing an international level of common approaches for retrospective dose estimations around the SNTS and in understanding the tasks for the future joint work in this direction. In the framework of a special session the problems of developing a database and registry in order to support epidemiological studies around SNTS were discussed. The results of investigation of psychological consequences of nuclear tests, which are expressed in the form of verbal behaviour, were presented at this session as well.
To evaluate the resistance for major oral antimicrobial agents, mainly new quinolones, we carried out a drug susceptibility surveillance of 3,050 strains of 11 microbial species clinically isolated at 8 institutions such as general hospitals and examination centers in Hiroshima city. 10 antimicrobial agents were used: 3 new quinolone drugs, 5 beta-lactam drugs, minocycline and clarithromycin. Among Gram-positive bacteria, methicillin resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis showed low susceptibility to the new quinolone drugs, while methicillin susceptible Staphylococcus aureus (MSSA) and Streptococcus pneumoniae were highly sensitive to these drugs. Among Gram-negative bacteria, Pseudomonas aeruginosa showed high resistance for the new quinolone drugs, but enteric bacteria and Haemophilus influenzae did not show marked resistance, maintaining almost good sensitivity to these drugs. To reduce the appearance of resistant bacteria, appropriate antimicrobial agents should be selected. Drug susceptibility surveillance in the community will be also important in the future.
During the period 1978-84 a total of 34,422 cases with malignant tumors were accessed by the Hiroshima Tumor Tissue Registry. Of these, 3,136 (9.1%) were classified as having multiple primary cancers (MPC). A detailed review was conducted on 1,148 cases selected from the latter group, and 330 (29%) were found to have been falsely registered as having MPC. "False" MPC cases were classified into six major categories according to the type of error: Category I--invasions or metastases occurring at the same or adjacent site within three months of the primary tumor, misclassified as separate primaries; Category II--invasions or metastases occurring at the same or adjacent site more than three months of the primary tumor, misclassified as separate primaries; Category III--metastases to distant sites, misclassified as separate primaries; Category IV--tumors lacking a clear description of location, resulting in registrations as "false" MPC; Category V--tumors with revisions or corrections in their pathological diagnoses resulting in false MPC; Category VI--tumors with errors in coding and other operational procedures resulting in false MPC. The cases in Categories I, II and III together comprised 52% of all false MPC cases (18%, 23% and 11%, respectively). In many of these cases, it was difficult to reject the possibility of one tumor being a metastasis of the other. This suggests that specific criteria may help reduce the number of false MPC cases of these types. Cases in Categories IV, V and VI represented 24%, 14% and 9%, respectively, of all false MPC cases. Errors encountered in these cases may be prevented by the concentrated efforts of clinicians and hospital pathologists as well as by an improvement in the operation of the registry.
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