A surprisingly high association between an HLA-DR locus antigen and narcolepsy was revealed in the Japanese. All 40 Japanese patients with narcolepsy (22 males and 18 females) were confirmed to be DR2 positive. However, the DR2 of the patients was found to associate negatively with Bw52, whereas Bw52-DR2 is the commonest haplotype in normal Japanese population. These data suggested that a "disease" allele predisposing to narcolepsy was inherited with relatively rare haplotypes with DR2 in the Japanese.

We investigated the mechanism of phenotypic plasticity of hepatocytes in a three-dimensional organoid culture system, in which hepatocytic spheroids were embedded within a collagen gel matrix. Hepatocytes expressed several bile duct markers including cytokeratin (CK) 19 soon after culture and underwent branching morphogenesis within the matrix in the presence of insulin and epidermal growth factor. Cultured hepatocytes did not express Delta-like, a specific marker for oval cells and hepatoblasts. Furthermore, hepatocytes isolated from c-kit mutant rats (Ws/Ws), which are defective in proliferation of oval cells, showed essentially the same phenotypic changes as those isolated from control rats. The bile duct-like differentiation of hepatocytes was associated with increased expression of Jagged1, Jagged2, Notch1, and several Notch target genes. CK19 expression and branching morphogenesis were inhibited by dexamethasone, a mitogen-activated protein kinase kinase 1 (MEK1) inhibitor (PD98059), and a phosphatidyl inositol 3-kinase inhibitor (LY294002). After being cultured for more than 3 weeks within the gels, hepatocytes transformed into ductular structures surrounded by basement membranes. Our results suggest that hepatocytes might have the potential to transdifferentiate into bile duct-like cells without acquiring a stem-like phenotype and that this is mediated through specific protein tyrosine phosphorylation pathways.

Development of preprogrammable conductive nanowires is a requisite for the future fabrication of nanoscale electronics based on molecular assembly. Here, we report the synthesis of conductive metal nanowires from nucleoprotein filaments, complexes of single- or double-stranded DNA and RecA protein. A genetically engineered RecA derivative possessing a reactive and surface accessible cysteine residue was reacted with functionalized gold particles, resulting in nucleoprotein filaments with gold particles attached. The template-based gold particles were enlarged by chemical deposition to form uniformly metallized nanowires. The programming information can be encoded in DNA sequences so that an intricate electrical circuit can be constructed through self-assembly of each component. As the RecA filament has higher degree of stiffness than double-stranded DNA, it provides a robust scaffold that allows us to fabricate more reliable and well-organized electrical circuitry at the nanoscale. Furthermore, the function of homologous pairing provides sequence-specific junction formation as well as sequence-specific patterning metallization.

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Summary: Forty-eight narcoleptic patients were randomly selected from a group of 197 narcoleptic outpatients, and a SO-g oral glucose tolerance test (OGTT) was performed. Blood glucose levels were determined by oximetry before and 30, 60, and 120 min after the glucose administration. Serum insulin concentrations (IRI) were determined by enzyme immunoassay, and an insulinogenic index (II) was calculated. (II = the ratio of IRI increment to blood glucose increment in 30 min following glucose load.) From the results of the OGTT, six patients with definite diabetes mellitus (DM) were identified (12.5%, 4 men and 2 women) according to World Heath Organization criteria (1980). The II of the DM patients was significantly low, with an average of 0.13 ± 0.03. From recent data in the literature on the prevalence of DM in the general Japanese adult population (1.75-5.5%), it was concluded that the frequency of DM among our randomly selected narcoleptic patients was significantly increased. The positive results for diabetes in our six narcoleptic patients could not be attributed to obesity, because there was no difference between the obesity indices of DM and nonDM narcoleptic patients, nor was there a difference between the frequency of DM in obese and nonobese patients. Key Words: Narcolepsy-Non-insulin-dependent diabetes mellitus--Oral glucose tolerance test-Obesity-Insulinogenic index.During the past 30 years, as we have treated and followed up several hundred narcoleptic patients at the Department of Neuropsychiatry, Tokyo University Hospital, we have had the impression that there were many diabetic patients among those with narcolepsy.With regard to the relationship between narcolepsy and diabetes mellitus (OM), only the reports by Roberts in 1964 0), 1965 (2), and 1967 (3) are available, to our knowledge. Roberts reported that 183 of 252 narcoleptic patients (72.6%) were diabetic. However, his diagnostic criteria for narcolepsy was ambiguous and not operational. More than half of his patients lacked cataplexy, and 50 had paroxysmal discharges on electroencephalogram. It may be that his patients had various disorders that would not meet today's criteria for the diagnosis of narcolepsy. Furthermore, his criteria of blood glucose levels for the di-

Our findings suggest that increased magnesium intake was a significant protective factor for the incidence of Type 2 diabetes in the general Japanese population, especially among subjects with insulin resistance, low-grade inflammation and a drinking habit.

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