Huntington's disease (HD) is one of 10 known diseases caused by a (CAG)(n) trinucleotide repeat expansion that is translated into an abnormally long polyglutamine tract. We have developed stable inducible neuronal (PC12) cell lines that express huntingtin exon 1 with varying CAG repeat lengths under doxycycline (dox) control. The expression of expanded repeats is associated with aggregate formation, caspase-dependent cell death and decreased neurite outgrowth. Post-mitotic cells expressing mutant alleles were more prone to cell death compared with identical cycling cells. To determine early metabolic changes induced by this mutation in cell models, we studied changes in gene expression after 18 h dox induction, using Affymetrix arrays, cDNA filters and adapter-tagged competitive PCR (ATAC-PCR). At this time point there were low rates of inclusion formation, no evidence of mitochondrial compromise and no excess cell death in the lines expressing expanded compared with wild-type repeats. The expression profiles suggest novel targets for the HD mutation and were compatible with impaired cAMP response element (CRE)-mediated transcription, which we confirmed using CRE-luciferase reporter assays. Reduced CRE-mediated transcription may contribute to the loss of neurite outgrowth and cell death in polyglutamine diseases, as these phenotypes were partially rescued by treating cells with cAMP or forskolin.

In addition to the three commonly recognized classes of human immunoglobulins (IgG, IgA, and IgM), a fourth immunoglobulin class was recently identified and designated IgD (yD) (1, 2). Serum values in normal subjects ranged from less than 3 ug to greater than 100 /Ag IgD per ml of serum (2). The median serum IgD concentration was 30 Mg per ml, about 1/, o of the serum IgG concentration. IgD is the least plentiful member of the immunoglobulin family.The immunoglobulin system is interesting from a metabolic standpoint. The biological half-life of normal IgG is about 23 days and its synthetic rate 40 mg per kg per day (3, 4). In contrast, the half-lives of IgA and IgM are about the same (4 to 5 days), but the synthetic rate of 20 mg per kg per day for IgA compared to 4 mg per kg per day for IgM explains in part the higher serum level of IgA (5-7).Nothing was known, however, about the metabolic behavior of immunoglobulin D. We therefore undertook this study using radioactive iodinelabeled IgD hoping to elucidate reasons for the relatively low serum concentration and to determine whether the metabolism of IgD is related to that of the other immunoglobulin classes.The metabolism of labeled IgD was investigated in 28 patients selected so as to cover a wide range of immunoglobulin disorders. These included patients with a) increased synthesis of specific immunoglobulins, b) deficient immunoglobulin synthesis, c) increased catabolism of certain immunoglobulins, and d) no discernible abnormalities of the immunoglobulin system. The results of these studies indicate that the synthetic rate is the major factor controlling the serum IgD concen-

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Review of 31 computed tomographic (CT) scans in 15 neonates with herpes simplex encephalitis (HSE) type 2 revealed the most characteristic early findings to be patchy and widespread areas of low attenuation, primarily in white matter, with minimal contrast material enhancement in a meningeal pattern. The low-attenuation lesions increased rapidly in size and prominence during the course of the disease. This was usually accompanied by increased attenuation of cortical gray matter that persisted for weeks to months. Atrophic changes appeared rapidly, being evident in the 3d week. Late findings consisted of very extensive, diffuse, low attenuation of white matter with cortical atrophy. Calcification assumed a variety of distributions, from punctate to an extensive gyral pattern. The cerebellum was involved in nine patients. Early CT findings were not good predictors of outcome, but later serial CT scans showing progression or stability of findings were more accurate in prognosis. CT serves primarily to confirm the diagnosis of neonatal HSE.