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BackgroundThe incidence of systemic lupus in children with discoid lupus is unknown.ObjectiveThis study assessed the baseline characteristics of patients with pediatric discoid lupus erythematosus (pDLE).MethodsMedical records at 17 sites were reviewed for pediatric dermatology and rheumatology patients with discoid lupus erythematosus. The inclusion criteria were clinical and/or histopathologic diagnosis of discoid lupus erythematosus with an age at onset of 1500 charts reviewed, 438 patients met the inclusion criteria. The cohort was predominantly female (72%) and racially/ethnically diverse. A diagnosis of SLE at the baseline visit (pDLE+SLE) was rendered in 162 (37%) patients using the American College of Rheumatology and in 181 (41%) patients using the Systemic Lupus International Collaborating Clinics criteria. Patients with pDLE+SLE were older at the time of rash onset (median, 12.9 vs 8.9years; P&nbsp

Psychobiological research in child psychiatry requires rigorous assessment of behavior and multiple perspectives on brain function through neurochemical, neuroendocrine, psychophysiological, and other advanced methods. The serious neuropsychiatric disorders of childhood, such as autism, attention deficit disorder, and language disorders, can be studied in complementary clinical protocols aimed at explicating patterns of behavioral and metabolic dysfunction which characterize various clinical syndromes. Clinical research with children raises sensitive ethical issues; the ethical problems can be addressed when children and families are active collaborators with the investigators and a long-term relationship is established. In this setting, participation in research can facilitate better treatment for a child. The use of novel biological strategies, such as pharmacological challenge tests, permits evaluation of the relation of specific neuronal systems to behavioral dimensions in clinical disorders. The development of a new treatment for Tourette's syndrome illustrates the integration of basic and clinical research methods.

The basis for the increased adenosine deaminase activity in deoxycoformycin-resistant rat hepatoma cells was investigated. Three variant cell lines with different levels of adenosine deaminase activity showed increases in the relative rate of synthesis of the enzyme in vivo. No difference in the rate of degradation of the enzyme was seen between the parental cell line and one variant cell line which exhibits a 180-fold increase in adenosine deaminase activity. Polysomal RNA isolated from this variant exhibited a 175-fold increase in the ability to direct the synthesis of adenosine deaminase in vitro.

Deoxycoformycin-resistant rat hepatoma cells exhibit up to 300-fold increase in adenosine deaminase activity compared to the sensitive parental cells. In order to determine the basis of the increased enzyme activity in deoxycoformycin-resistant cells, adenosine deaminase was purified from rat liver and deoxycoformycin-sensitive and -resistant cells. Physical, kinetic, and immunological properties of the purified enzymes were compared. Purified adenosine deaminase from all sources was found to be a monomer with an Mr approximately 45,000. In addition, the purified enzymes had a similar isozyme pattern in nondenaturing polyacrylamide gels. Km values for adenosine and Ki values for deoxycoformycin did not differ among the purified enzymes. By double diffusion analysis and quantitative immunoprecipitation, the purified enzymes were found to be immunologically indistinguishable. These data indicate that deoxycoformycin-resistant rat hepatoma cells produce increased amounts of adenosine deaminase protein which results in increased enzymatic activity.

Deoxycoformycin-resistant rat hepatoma cells exhibit up to a 2000-fold increase in adenosine deaminase activity compared to the sensitive parental cells. The increased enzyme activity in these cells is accompanied by similar increases in 1) the amount of adenosine deaminase protein, 2) the relative rate of adenosine deaminase synthesis in vivo, and 3) adenosine deaminase mRNA activity. To further investigate the mechanism(s) responsible for the overproduction of adenosine deaminase in these cells, we have isolated a recombinant plasmid containing a 1.4-kilobase insert complementary to at least part of the adenosine deaminase mRNA. Using this cDNA as a specific hybridization probe, all deoxycoformycin-resistant variants were shown to have increased amounts of adenosine deaminase mRNA and gene sequences. The relative increase in the level of mRNA and gene copy number was similar to the relative increase in enzyme activity for most resistant cell lines. However, the degree of adenosine deaminase gene amplification in one deoxycoformycin-resistant cell line (6-10-200) was 3-4-fold less than the relative increase in adenosine deaminase mRNA. These results indicate that the increased adenosine deaminase activity in deoxycoformycin-resistant rat hepatoma cells is due in large part, but not exclusively, to gene amplification.

We have mapped a new region of the mouse major histocompatibility complex (MHC) that contains the nuclear gene, Hmt, for the maternally transmitted antigen, Mta. The Hmt region of chromosome 17 lies between a recombinational breakpoint distal to Tla and another proximal to Tpx-1, thus including Pgk-2. A novel MHC class I gene fragment, R4B2, was cloned and mapped to this region as was another new class I gene, Thy19.4. Both lie proximal to Pgk-2, within the distal inversion in t-haplotypes. The presence of several other MHC class I genes in the Hmt region is predicted from analysis of the recombinants that define the region.