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Creutzfeldt-Jakob disease (CJD) is a fatal degenerative neurological disease. Progressive dementia is its chief clinical sign, and its characteristic pathological feature is the formation of vacuoles within the degenerating brain. These vacuoles give the brain a 'spongy' appearance, and hence CJD and some similar diseases have been termed spongiform encephalopathies. Similar diseases include Kuru in man and scrapie in sheep. These diseases are often included among the so-called slow virus diseases, but the nomenclature is misleading, since the pathogenic agents responsible for the spongiform encephalopathies are unlike any known virus. In addition, Creutzfeldt-Jakob disease is unique among the spongiform encephalopathies. Unlike Kuru and scrapie, which have clearly infectious causes in nature, CJD occurs sporadically, and the majority of cases cannot be traced to any infectious transmission. Nevertheless, brain tissue from patients with CJD can be used to transmit a similar neurological disease to experimental animals. In most parts of the world, CJD affects primarily gray matter, that part of the brain where nerve cells and their interconnections predominate. In Japan, however, roughly 38 percent of cases affect the white matter of the brain as well; white matter consists of regions of the brain where long fibers insulated by their white myelin sheaths predominate. Since this form of CJD affects most areas of the brain, it has been termed 'panencephalopathic'. Japanese researchers have now shown that it is possible to isolate a pathogenic agent from panencephalopathic CJD and use it to transmit disease to laboratory animals. However, the disease caused in guinea pigs and hamsters affects specific areas of gray matter, and is not of the panencephalopathic type. There may be an interaction between the genetic characteristics of the pathogenic agent and its human host, and the panencephalopathic disease seen so commonly in Japan is likely to result from the influence of an unknown human gene or genes that occur more frequently in Japanese populations. (Consumer Summary produced by Reliance Medical Information, Inc.)

We established a clonal cell line, HAT.MC8, derived from a human pulmonary large cell carcinoma with sarcomatoid features. This cell line was successfully maintained in a protein-free medium and exhibited sarcomatoid fibroblastic features in vitro. The cells constitutively produced a large amount of interleukin 6 (IL-6) in vitro. Tumour necrosis factor alpha (TNF-alpha) not only stimulated HAT.MC8 cells to produce IL-6, but also induced a morphological change from sarcomatoid fibroblastic to epithelial features. Although this change was related to actin and zonula adherens, there was no evidence that E-cadherin participated in the change. Interleukin 1 beta (IL-1 beta) had a stimulatory effect on IL-6 production by HAT.MC8 cells, but no influence on the morphology of the cells. [ABSTRACT FROM AUTHOR]

To identify a novel regulatory factor involved in brain development or synaptic plasticity, we applied the differential display PCR method to mRNA samples from NMDA-stimulated and un-stimulated neocortical cultures. Among 64 cDNA clones isolated, eight clones were novel genes and one of them encodes a novel zinc-finger protein, HIT-4, which is 317 amino acid residues (36-38 kDa) in length and contains seven C2H2 zinc-finger motifs. Rat HIT-4 cDNA exhibits strong homology to human ZNF597 (57% amino acid identity and 72% homology) and identity to rat ZNF597 at the carboxyl region. Furthermore, genomic alignment of HIT-4 cDNA indicates that the alternative use of distinct promoters and exons produces HIT-4 and ZNF597 mRNAs. Northern blotting revealed that HIT-4 mRNA (approximately 6 kb) is expressed in various tissues such as the lung, heart, and liver, but enriched in the brain, while ZNF597 mRNA (approximately 1.5 kb) is found only in the testis. To evaluate biological roles of HIT-4/ZNF597, targeted mutagenesis of this gene was performed in mice. Homozygous (-/-) mutation was embryonic lethal, ceasing embryonic organization before cardiogenesis at embryonic day 7.5. Heterozygous (+/-) mice were able to survive but showing cell degeneration and vacuolization of the striatum, cingulate cortex, and their surrounding white matter. These results reveal novel biological and pathological roles of HIT-4 in brain development and/or maintenance.