The platelet-derived growth factor-inducible gene JE has been widely used as a molecular marker for the cellular response to growth factors, antimitogenic agents, and other biological response modifiers; however, the structure of the JE gene and the nature of its encoded protein have not been previously described. We present here structural and regulatory features of the JE gene and its product that link it to a family of cytokines, including macrophage colony-stimulating factor, interferon a, interleukin 6 (also known as interferon I2, B-cell-stimulatory factor 2, 26-kDa protein, and hybridoma/ plasmacytoma growth factor), and interleukin 2. Just as T lymphocytes secrete interleukins as a component of their response to mitogens, it appears that fibroblasts secrete cytokines as a component of their response to platelet-derived growth factor.In confluent growth-arrested BALB/c 3T3 cells, plateletderived growth factor (PDGF) stimulates expression of a family of single-copy genes. The protooncogenes c-myc and c-fos are members of this gene family (1-5). However the PDGF-inducible genes detected and characterized as such were the "competence" genes, JE, KC, and JB. Partial cDNA clones for these three genes were isolated by differential screening of a cDNA library from PDGF-treated fibroblasts (6). The c-myc (7-12) and c-fos (13,14) bovine calf serum and antibiotics. Confluent density-arrested monolayer cell cultures were prepared as previously described (20) and then transferred to fresh DMEM supplemented with 5% platelet-poor plasma, which is free of PDGF (21). Cells were kept in platelet-poor plasma for 16 hr prior to analysis.Due to growing safety concerns about processing thousands of units of clinically outdated human platelets each year, our laboratory now uses medium conditioned by v-sis-transformed NRK (normal rat kidney) cells (sisconditioned medium) as the routine source of PDGF (B chain homodimer). All experimental results generated with sisconditioned medium have been confirmed with either homogeneous PDGF from human platelets or recombinant v-sis protein (Amgen Biologicals, Thousand Oaks, CA). Recombinant human interleukin la (IL-la) was obtained from Genzyme (Norwalk, CT).Gene and cDNA Cloning. For the isolation of JE genomic DNA, 106 plaques from the BALB/c germ line DNA library of Davis et al. (22) were transferred to nitrocellulose and probed as described (23). The probe was the 750-base-pair (bp) Pst I fragment of pBC-JE (6) nick-translated to 108 cpm/pg. Four hybridizing clones (AJE-1, AJE-2, AJE-3, and AJE-4) were identified and subcloned in pGEM-1 (Promega Biotec, Madison, WI) for sequence analysis. For the isolation of JE cDNA, poly(A)-selected RNA was prepared from BALB/c 3T3 cells that had been treated with PDGF (v-sis conditioned medium) for 2 hr. cDNA was synthesized by the RNase H method (24) and cloned in AgtlO. About 106 plaques were screened as above. Seventy-eight hybridizing plaques were identified, three of which (cJE-1, cJE-2, and cJE-3) were subcloned in pGEM-1. Sequence ...

Patients with hemochromatosis and serum ferritin levels less than 1000 microg/L are unlikely to have cirrhosis. Liver biopsy to screen for cirrhosis may be unnecessary in such patients, regardless of age or serum liver enzyme levels.

Objective-There are limited data comparing hepatic phenotype among hemochromatosis patients with different HFE genotypes. The goal of this study was to compare hepatic histopathologic features and hepatic iron concentration (HIC) among patients with phenotypic hemochromatosis and different HFE genotypes.Methods-We studied 182 U.S. patients with phenotypic hemochromatosis. Degree of hepatic fibrosis, pattern of iron deposition, presence of steatosis or necroinflammation, and HIC were compared among different HFE genotypes.Results-C282Y/H63D compound heterozygotes and patients with HFE genotypes other than C282Y/C282Y were more likely to have stainable Kupffer cell iron (31.1% vs 9.5%; p=0.02), portal or lobular inflammation (28.9% vs 15.6%; p=0.03) and steatosis (33.3% vs 10.2%; p<0.01) on liver biopsy than C282Y homozygotes. Mean log 10 HIC (p<0.05) and log 10 ferritin (p<0.05) were higher among C282Y homozygotes than in patients with other HFE genotypes. In a logistic regression analysis using age, gender, HFE genotype, log 10 ferritin, and log 10 HIC as independent variables, log 10 SF (p = 0.0008), male sex (p = 0.0086), and log 10 HIC (p=0.047), but not HFE genotype (p = 0.0554) were independently associated with presence or absence of advanced hepatic fibrosis. Conclusions-C282Y/H63Dcompound heterozygotes and other non-C282Y homozygotes who express the hepatic hemochromatosis phenotype frequently have evidence of steatosis or chronic hepatitis and lower body iron stores than C282Y homozygotes. These data suggest that presence of concomitant liver disease may explain expression of the hemochromatosis phenotype among non-C282Y homozygotes. Increased age, HIC and ferritin are associated with advanced hepatic fibrosis, regardless of HFE genotype.

Increased global SLE disease activity is associated with concurrent NP events attributed to SLE, particularly for diffuse NP and CNS NP events. The findings have diagnostic and therapeutic implications for SLE patients with NP events and inform pathogenetic mechanisms underlying NPSLE.

In density-arrested monolayer cultures of Balb/c 3T3 cells, platelet-derived growth factor (PDGF) stimulates expression of the c-myc and c-fos proto-oncogenes, as well as the functionally uncharacterized genes, JE, KC, and JB. These genes are not coordinately regulated. Under ordinary conditions, c-fos, JE, KC, and JB respond to PDGF only when the cells are in a state of G0 growth arrest at the time of PDGF addition. The c-myc gene is regulated in opposition to the other genes, responding best to PDGF in cycling cultures.