The murine local lymph node assay (LLNA) is a well-established alternative to the guinea pig maximization test (GPMT) or Buehler test (BT) for the assessment of the skin sensitizing ability of a drug, cosmetic material, pesticide or industrial chemical. Instead of radioisotope using in this method, Takeyoshi M. et al. (2001) has developed a modified LLNA based on the 5-bromo-2'-deoxyuridine (BrdU) incorporation (LLNA:BrdU-ELISA). The LLNA:BrdU-ELISA is practically identical to the LLNA methodology excluding the use of BrdU, for which a single intraperitoneal injection of BrdU is made on day 4, and colorimetric detection of cell turnover. We conducted the validation study to evaluate the reliability and relevance of LLNA:BrdU-ELISA. The experiment involved 7 laboratories, wherein 10 chemicals were examined under blinded conditions. In this study, 3 chemicals were examined in all laboratories and the remaining 7 were examined in 3 laboratories. The data were expressed as the BrdU incorporation using an ELISA method for each group, and the stimulation index (SI) for each chemical-treated group was determined as the increase in the BrdU incorporation relative to the concurrent vehicle control group. An SI of 2 was set as the cut-off value for exhibiting skin sensitization activity. The results obtained in the experiments conducted for all 10 chemicals were sufficiently consistent with small variations in their SI values. The sensitivity, specificity, and accuracy of LLNA:BrdU-ELISA against those of GPMT/BT were 7/7 (100%), 3/3 (100%), and 10/10 (100%), respectively.
S UM MARY Two patients are described with distinctive clinical features including an insidious onset, slow progression, bilateral ptosis, weakness of facial muscles, dysphagia, muscle atrophy, and weakness with a distal distribution in the extremities, and cardiomyopathy with conduction system disorders. Electromyographic studies and muscle biopsy showed features highly suggestive of a myopathic disorder. One case is considered to be sporadic. The other seems to be a familial disorder, because of the presence of a mild atrioventricular block and right incomplete bundle branch block in the patient's son and the presence of eyelid ptosis in his sister. This may be a variant of oculopharyngeal myopathy with distal and cardiomyopathy. It will be necessary to perform long-term follow-up studies in these families.A syndrome which included ptosis, external ophthalmoplegia, dysphagia or muscle atrophy or both, and weakness in the extremities has been reported by many authors (
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