Recently, it has been shown that approximately 80% of Merkel cell carcinomas harbor a novel polyomavirus named Merkel cell polyomavirus, thought to be a carcinogenic agent. However, it is not fully elucidated whether Merkel cell carcinomas differ with regard to the presence or absence of Merkel cell polyomavirus. To address this, we investigated morphologic differences between Merkel cell polyomavirus-positive and -negative Merkel cell carcinomas by morphometry. Using polymerase chain reaction and real-time quantitative polymerase chain reaction, Merkel cell polyomavirus was detected in 20 (77%) of 26 Merkel cell carcinoma cases, including 4 Merkel cell carcinomas combined with squamous cell carcinomas. Interestingly, Merkel cell polyomavirus was detected only in ordinary (pure) Merkel cell carcinomas; none of the 4 combined Merkel cell carcinomas + squamous cell carcinomas was positive for Merkel cell polyomavirus (P = .001). Morphometric analyses revealed that Merkel cell polyomavirus-negative Merkel cell carcinomas had more irregular nuclei (P < .001) and more abundant cytoplasm (P = .001) than Merkel cell polyomavirus-positive Merkel cell carcinomas, which had uniform round nuclei and scant cytoplasm. Reliability of the morphometry was confirmed using intraobserver and interobserver reliability tests. These results demonstrated statistically significant differences in tumor cell morphology between Merkel cell polyomavirus-positive and -negative Merkel cell carcinomas and reconfirmed the absence of Merkel cell polyomavirus in combined tumors. Furthermore, the results strongly suggest fundamental biological differences between Merkel cell polyomavirus-positive and -negative Merkel cell carcinomas, supporting that Merkel cell polyomavirus plays an important role in the pathogenesis of Merkel cell polyomavirus-positive Merkel cell carcinoma.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that primarily involves the motor neuron system. Approximately 5-10% of ALS is familial. Superoxide dismutase 1 (SOD1) gene mutations are shown to be associated with about 20% of familial ALS (FALS) patients. The neuronal Lewy-body-like hyaline inclusion (LBHI) and astrocytic hyaline inclusion (Ast-HI) are morphological hallmarks of certain SOD1-linked FALS patients with SOD1 gene mutant and transgenic mice expressing human SOD1 with G85R mutation. From the detailed immunohistochemical analyses, the essential common protein of both inclusions is SOD1. Ultrastructurally, both inclusions consist of granule-coated fibrils 15-25 nm in diameter. Based on the immuno-electron microscopical finding that these abnormal granule-coated fibrils are positive for SOD1, the formation (or aggregation) of the abnormal fibrils containing SOD1 would be essential evidence in diseases caused by various SOD1 mutations. The granule-coated fibrils are also modified by advanced glycation end products (AGEs). The AGEs themselves are insoluble molecules with direct toxic effects on cells. AGE formation of SOD1 composing the granule-coated fibrils (probable AGE-modified mutant SOD1) may amplify their aggregation and produce a more marked toxicity.

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We examined the effects of repeated artificial CO(2) (1,000 ppm) bathing on tympanic temperature (T(ty)), cutaneous blood flow, and thermal sensation in six healthy males. Each subject was immersed in CO(2)-rich water at a temperature of 34 degrees C up to the level of the diaphragm for 20 min. The CO(2)-rich water was prepared using a multi-layered composite hollow-fiber membrane. The CO(2) bathing was performed consecutively for 5 days. As a control study, subjects bathed in fresh water at 34 degrees C under the same conditions. T(ty) was significantly lowered during CO(2) bathing (P < 0.05). Cutaneous blood flow in the immersed skin (right forearm) was significantly increased during CO(2) bathing compared with that during fresh-water bathing (P < 0.05), whereas cutaneous blood flow in the non-immersed skin (chest) was not different between CO(2) and fresh-water bathing. Subjects reported a "warm" sensation during the CO(2) bathing, whereas they reported a "neutral" sensation during the fresh-water bathing. The effects of the repeated CO(2) bathing were not obvious for core temperature and cutaneous blood flow, but the thermal sensation score during the CO(2) bathing was reduced sequentially by repeated CO(2) bathing (P < 0.05). These thermal effects of CO(2) bathing could be ascribed largely to the direct action of CO(2) on vascular smooth muscles and to the activity of thermoreceptors in the skin. Serial CO(2) bathing may influence the activity of thermoreceptors in the skin.