To clarify the clinical, neuropathological, and molecular characteristics of spinocerebellar ataxia type 6 (SCA6), two unrelated Japanese families with SCA6 were studied. A clinical feature of the two families was late onset "pure" cerebellar ataxia. Pathologically, three SCA6 brains consistently showed Purkinje cell dominant cortical cerebellar degeneration. Morphometric analysis showed that loss of the cerebellar granule cells and inferior olivary neurons were very mild compared with the severity of Purkinje cell loss. There was no obvious ubiquitin immunoreactive nuclear inclusions. All aVected patients had identical expanded alleles, and the expansion was also homogeneously distributed throughout the brain without mosaicism. The present study showed that SCA6 is characterised by Purkinje cell dominant cortical cerebellar degeneration, highly stable transmission of the CAG repeat expansion, and lack of ubiquitin immunoreactive nuclear inclusions. (J Neurol Neurosurg Psychiatry 1999;67:86-89)

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Small cell lung cancer (SCLC) and neuroblastoma (NB), the most aggressive adult and infant neuroendocrine cancers, respectively, are immunologically characterized by a severe reduction in major histocompatibility complex (MHC) that is indispensable for anti-tumor immunity. We had reported that the severe reduction of MHC in SCLC was caused by a deficient interferon ( Small cell lung cancer (SCLC) and neuroblastoma (NB) are the most aggressive adult and infant neuroendocrine neoplasms, respectively.

An autopsy case of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is reported. It presented with generalized muscle atrophy, stroke-like episodes, schizophrenia-like mental disorder and progressive dementia. Serum lactate and pyruvate levels were high. In the biopsied muscles, ragged-red fibers were observed by light microscopy and aggregation of abnormal mitochondria with paracrystaline formation by electron microscopy. The most characteristic neuropathological findings were infarct-like lesions widespread in the cerebral cortex. In addition, this case showed some unusual pathological features: (1) diffuse moderate fibrillary gliosis in the whole cerebral and cerebellar white matter, which might have been due to metabolic disturbances; (2) several focal lesions with demyelination and numerous spheroids in the pontocerebellar fibers; and (3) marked degeneration of the posterior columns and spinocerebellar tracts. Electron microscopic examination revealed that abnormal mitochondria were markedly aggregated in smooth muscle cells and endothelium of the cerebral and cerebellar blood vessels. These fine structural findings suggest a "mitochondrial angiopathy".

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In this study, the significance of lymphocytic infiltration in juvenile thyroid carcinoma is clarified. We examined nine patients younger than 20 years of age. Histopathologically, there was good correlation between lymphocytic infiltration and the development and spread of carcinoma. It is believed that lymphocytic infiltration around the tumor is an immunologic reaction induced by antigens from the carcinoma itself, and also that the reaction may progress according to tumor development. Immunocytochemically, we determined what type of inflammatory cells infiltrated the thyroid and demonstrated HLA-DR expression in the cancer cells. These findings are similar to autoimmune thyroiditis in which antibody-dependent cellular cytotoxicity (ADCC) works as a main immunomechanism.

An unusual benign lung neoplasm, a papillary adenoma of type II pneumocytes, was resected from a 26-year-old man who showed no clinical symptoms. The tumor was 2.0 cm in diameter and was localized in the subpleural region of S7 of the right lung; the cut surface showed a spherical medullary mass encapsulated by a thin layer of connective tissue. Histologically, there were cuboidal to columnar epithelial cells with a little nuclear atypia showing a monotonous papillary pattern with a delicate stroma in most parts of the tumor. There was neither capsular invasion nor metastasis of tumor cells. Nuclear DNA analysis of the tumor cells showed a diploid pattern and a low S-phase fraction. The immunohistochemical study revealed that most tumor cells contained a large amount of surfactant apoprotein in the cytoplasm. Osmiophilic lamellar bodies characteristic of type II pneumocytes were frequently found by electron microscopy. These findings indicate that this was a benign adenoma of the lung arising from type II pneumocytes.

The nuclear DNA content of paraffin-embedded parathyroid tumors from 49 patients with proven primary hyperparathyroidism was determined by flow cytometric analysis. The lesions included 14 primary and 11 locally recurrent or metastatic lesions from 16 carcinoma patients, 28 single adenomas from 28 patients, and 15 hyperplastic glands from five patients with familial multiple endocrine neoplasia type 1. No abnormal DNA stemline was found in any of the hyperplastic glands. One (3.6%) of the adenomas was aneuploid. There was no difference in ploidy patterns between the primary and recurrent lesions of the carcinomas and five (31%) of the carcinomas expressed aneuploidy. Four of the five patients with aneuploid carcinoma had recurrences including pulmonary metastases. One of them died of this disease 12 years after the initial operation, and all except one of the others are hypercalcemic even after removal of the successive recurrent or metastatic tumors. Of the 11 patients with diploid carcinoma, four had either local recurrence or pulmonary metastasis. Two of them are living with normocalcemia 3 and 6 years, respectively, after removal of the recurrent tumors and the others are alive with mild hypercalcemia. The remaining seven patients with diploid carcinoma, however, have no recurrence 2 to 5 years after the initial operation. Thus aneuploid parathyroid carcinomas are likely to show more malignant behavior than those with a diploid DNA pattern. All of the patients with adenoma and hyperplasia have been normocalcemic after a mean follow-up interval of 37 months. This study indicates that flow cytometric analysis of nuclear DNA content is a valuable adjunct to histologic examination in the diagnosis of parathyroid carcinoma and the prediction of the clinical outcome.