A 64-year-old man noticed weakness in his arms and dyspnea upon exertion. Four months later he was admitted to our hospital, where muscle atrophy and hyperactive deep tendon reflexes in the arms were observed upon examination. A needle electromyograph study revealed acute and chronic denervation in the extremities, and he was diagnosed as having amyotrophic lateral sclerosis (ALS). Seven months after onset of the disease, he died of respiratory failure. Neuropathologically, neuronal cell loss was observed in the motor cortex, hypoglossal nuclei, cervical and lumbar anterior horns and Clarke's nuclei. Some of the remaining neurons contained neurofilamentous conglomerate inclusions (CIs). A small number of Lewy body-like hyaline inclusions (LBHIs) were also observed. No the Bunina bodies, skein-like inclusions or basophilic inclusions were detectable. Tract degeneration was moderate in the dorsal and ventral spinocerebellar tracts, mild in the pyramidal tract, but not discerned in the posterior column. Immunohistochemical examinations revealed that the CIs were strongly positive for phosphorylated neurofilament and moderately positive for ubiquitin and Cu/Zn superoxide dismutase 1 (SOD1). Moreover, a number of phosphorylated tau protein-positive globose neurofibrillary tangles (NFTs) and threads were observed in the periaqueductal gray matter, oculomotor nuclei and trochlear nuclei. Although the family history was negative for neuromuscular diseases, the neuropathological findings indicated features of familial ALS with a SOD1 mutation. In fact, DNA analysis of frozen-brain tissue revealed the presence of the I113T SOD1 mutation. This case represents the first one of this mutation in a patient who showed CIs as well as LBHIs in the motor neurons at the same time, in addition to the NFTs in the mesencephalic tegmentum.

Lewy body-like inclusion (LI) is a cytoplasmic inclusion body deposited in anterior horn cells of patients with amyotrophic lateral sclerosis (ALS), in which there are phosphorylated neurofilament proteins (NFP). Since phosphorylation of NFP occurs normally in the axon, aberrant phosphorylation of NFP should take place in these cell bodies. To clarify the mechanism of LI formation it is crucial to identify the kinase responsible for the phosphorylation. We found cyclin-dependent kinase 5 (cdk5) immunoreactivity in most of LI in an ALS patient. Since cdk5 phosphorylates NFP, cdk5 is a candidate kinase for NFP in LI and might be involved in the cytoskeletal disorganization in LI-containing neurons.

A 65-year-old Japanese male consulted Ozuchi Prefectural Hospital (Iwate, Japan) on 19 January 1994 complaining of weight loss. Cecal mucosal biopsy material, which was stained with hematoxylin-eosin revealed a thick, basophilic fuzzy fringe covering the surface epithelium. Transmission and scanning electron microscopy observations demonstrated the presence of slightly wavy spirochaetes with tapered ends, which were attached to the surface epithelium of the colonic mucosa via one of these ends. The patient did not display any clinical symptoms of inflammatory bowel disease, and laboratory tests eliminated an immunodeficiency condition. Thus, in the present case, the intestinal spirochaetes appear to be harmless commensals. This paper presents the first reported case of intestinal spirochaetosis in Japan.

The results suggest that cyclin-dependent kinases (CDK)5, but no other CDKs, is involved in the formation of inclusions in IBM.

In Crohn's disease (CD), aphthous lesions are regarded as possible precursors of typical intestinal involvement. To determine the natural course of intestinal lesions in CD of aphthous type, the clinical course of 10 patients was retrospectively investigated during a period ranging from 6 to 16 years after diagnosis. The criterion for inclusion was confirmed aphthous lesions within the gastrointestinal tract with histologically verified epithelioid granuloma. The degrees of aphthous lesions in the small intestine and the colon were graded by small bowel radiography, barium enema examination and colonoscopy. Five patients developed typical CD during a period ranging from 0.8-3.3 years. The site of involvement was the ileum in three patients, the colon in one patient and both the ileum and the colon in one patient. Typical small intestinal CD occurred in four of seven patients with marked aphthous lesions of the small intestine, whereas colonic CD occurred in two of eight patients with such aphthous lesions of the colon. These findings suggest that CD of aphthous type is not necessarily a precursor of clinically overt disease. This may especially be the case for colonic aphthous lesions.