Thy28 protects against anti-CD3-mediated thymic cell death in vivo.

Apoptotic cell death plays a pivotal role in the development and/or maintenance of several tissues including thymus. Deregulated thymic cell death is associated with autoimmune diseases including experimental autoimmune encephalomyelitis (EAE), a prototype murine model for analysis of human multiple sclerosis. Because Thy28 expression is modulated during thymocyte development, we tested whether Thy28 affects induction of EAE as effectively as antigen-induced thymocyte deletion using Thy28 transgenic (TG) mice. Thy28 TG mice showed partial resistance to anti-CD3 monoclonal antibody (mAb)-induced thymic cell death in vivo, as assessed by annexin V-expression and loss of mitochondrial membrane potential. The resistance to anti-CD3 mAb-induced cell death in Thy28 TG mice appeared to correlate with a decreased c-Jun N-terminal kinase phosphorylation and reduced down-regulation of Bcl-xL. Moreover, thymic hyperplasia was detected in Thy28 TG mice, although thymocyte development was unaltered. Development of peripheral lymphoid tissues including spleen and lymph nodes was also unaltered. Thy28 TG spleen T cells showed an increased production of IFN-γ, but not IL-17, in response to both anti-CD3 and anti-CD28 mAbs. Finally, Thy28 TG mice displayed accelerated induction of EAE as assessed by disease incidence, clinical score, and pathology following immunization with myelin oligodendrocyte glycoprotein compared with control WT mice. These findings suggest that modulation of Thy28 expression plays a crucial role in the determination of thymic cell fate, which may contribute to the development of EAE through proinflammatory cytokine production.

Distribution of cerebellar cortical lesions in multiple system atrophy: a topographic neuropathological study of three autopsy cases in Japan.

We investigated neuropathologically the distribution of the cerebellar cortical lesions in three Japanese autopsy cases of multiple system atrophy (MSA) using hemisphere specimens. The lesions were classified as mild, moderate or severe. The distribution of cerebellar cortical lesions in all three cases were uniform: the cerebellar cortical lesions were more conspicuous in the vermis than in the hemisphere. These neuropathological findings differ from the established theory that cerebellar lesions of MSA are more pronounced in the hemisphere than in the vermis. The degree of cerebellar cortical lesions in our cases increased in relation to the duration of the disease. Our pathological data may contribute to the morphological differential diagnosis in various neurodegenerative disorders including late cortical cerebellar atrophy. Our neuropathological findings may also make a contribution to the neuroradiological progress in the differential diagnosis of spinocerebellar disease.

Characterization of new inbred strains of Dahl-Iwai salt-sensitive and salt-resistant rats.

Dahl-Iwai salt-sensitive (S) and salt-resistant (R) rat strains were newly established as inbred strains. To characterize the strains, the Dahl-Iwai S and R rats were fed low-salt (0.3% NaCl) and high-salt (8.0% NaCl) diets from 5 weeks after birth, and systolic blood pressure and pathologic findings were examined at intervals. The distributions of alleles at 19 biochemical and immunologic loci also were examined in the aforementioned strains, together with those for the inbred SS/Sea and SR/Sea strains, which were derived from inbred SS/Jr and SR/Jr strains, respectively. The Dahl-Iwai S rats were hypertensive after 3 weeks of consuming the 8.0% NaCl diet and died from 6 to 10 weeks after the diet was initiated. Renal lesions developed after 4 weeks' consumption of the high-salt diet. The Dahl-Iwai S rats were not hypertensive until at least the age of 21 weeks while they consumed the 0.3% NaCl diet, whereas it was reported that the SS/Jr rats became hypertensive at about 20 weeks of age when they consumed the low-salt diet. The Dahl-Iwai R rats were normotensive whether fed the 0.3 or 8.0% NaCl diet. Hydronephrosis was not observed in the Dahl-Iwai R rats, though it develops in SR/Jr rats with high frequency. Different distributions were detected for kidney alkaline phosphatase-1 (Akp-1) and amylase-1 (Amy-1) alleles between the Dahl-Iwai S and SS/Sea strains, and for esterase-14 (Es-14) and seminal vesicle protein-1 (Svp-1) alleles between the Dahl-Iwai R and SR/Sea strains. The phenotypic differences between the substrains of inbred Dahl rats could be ascribed to different genetic backgrounds.