This study confirms the beneficial effect of weight reduction on hyperinsulinemia in obese individuals. Participation in supervised exercise did not result in additional improvement in weight loss or insulin sensitivity. We also observed a marked increase in insulin levels with only partial weight regain. Determining the amount of sustained weight loss necessary for continued improvement in insulin sensitivity will require further study.

Objective. To evaluate the correlation between the presence of antibodies to an endogenous retroviral element-encoded nuclear protein autoantigen, HRES-1, and the presence of other antinuclear antibodies and HLA class I1 alleles in patients with systemic lupus erythematosus (SLE) and overlap syndromes.Methods. Antibody reactivities to native and recombinant proteins and synthetic peptides were assessed by counterimmunoelectrophoresis, enzyme-linked immunosorbent assay, and Western blotting. HLA class I1 alleles were determined by oligonucleotide typing.Results. significant association between anti-HRES-1 and anti-RNP and an inverse correlation between HRES-1 and RolLa autoantibodies in patients with SLE or overlap syndromes. Antigenic epitopes of HRES-1 and the retroviral gag-related region of the 70-kd protein component of U1 small nuclear RNP, which share 3 consecutive highly charged amino acids (Arg-Arg-Glu), an additional Arg, and functionally similar ArgILys residues, represent cross-reactive epitopes between the two proteins. Selective removal of HRES-1 antibodies from sera of HRES-l-seropositive/RNP-seropositive patients by absorption on recombinant HRES-l/glutathione-Stransferase-conjugated agarose beads had no effect on anti-RNP reactivities. A comparative multivariate analysis of HLA class I1 genes revealed a differential segregation of DQBl alleles in HRES-l-seropositive versus HRES-1-seronegative patients (P = 0.04). While a relative increase of DQB1*0402 among HRES-1-seropositive patients was noted across ethnic groups (P = 0.02), a decrease of DQB1*0201 and DQB1*0301 was found in white HRES-l-seropositive patients (P = 0.04).Conclusion. Autoantibodies to HRES-1 are detectable in a distinct subset of patients with autoimmune disease, primarily in those who do not have antibodies to Ro and La. Anti-HRES-1 and anti-RNP reactivities are mediated by cross-reactive but separate antibody molecules. HLA-DQB genes, rather than HLA-DRB or DQA genes, may have a more significant influence on generation of these antinuclear autoantibodies.A hallmark of the destructive autoimmune process in patients with systemic lupus erythematosus

The effects of MK-801 upon motor activity and memory were assessed in a novel use of open-field behavior testing. In this study, rats were treated with different doses of MK-801 (0.025, 0.05, 0.1 and 0.2 mg/kg) and given a brief 10-min exposure to an open-field in which locomotor activity and within-session habituation were measured. Doses of MK-801 < or =0.1 mg/kg had no effect upon locomotor activity or within-session habituation. MK-801 0.2 mg/kg produced a marked hyperlocomotion and completely prevented within-session habituation. One day later, the animals were tested for their retention of habituation to evaluate the effects of MK-801 on memory processes. In that animals treated with 0.2 mg/kg MK-801 failed to habituate to the novel environment under the influence of 0.2 mg/kg MK-801, it was not surprising that these animals were impaired on the retention test for the novel environment. Importantly, however, the 0.1 mg/kg MK-801 treatment, which did not affect locomotor activity or within-session habitation to the novel environment, severely interfered with retention of the novel environment. Additional experiments indicated that this result could not be accounted for by drug conditioning or drug state-dependent effects. Thus, the results indicated that MK-801 can produce profound effects upon motor activity and memory and that these two effects can be disassociated.

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