The perceived racism scale: a multidimensional assessment of the experience of white racism among African Americans.

The experience of racism is a complex, multidimensional phenomenon. At present, there are few instruments that attempt to capture the experience of racism in all of its complexity. For this study, a new instrument, the Perceived Racism Scale, has been constructed to assess the experience of racism in African Americans in a multidimensional manner. The scale not only provides a measure of the frequency of exposure to many manifestations of racism (including individual and institutional, overt and covert, attitudinal, behavioral, and cultural), but takes a step forward in more comprehensively measuring the experience of racism by assessing emotional and behavioral coping responses to racism. These responses are measured with respect to exposure to racism in three situational domains: on the job, in academic settings, and in the public realm. Measurement of responses to a fourth domain, that of exposure to racist statements, is also included. It is hoped that the Perceived Racism Scale will facilitate a more comprehensive understanding of the experience of racism among African Americans and, through its use in research and clinical settings, will ultimately move us closer to reducing the prevalence and potentially untoward effects of racism.

Interferon-gamma increases the expression of the gene encoding the beta subunit of the granulocyte-macrophage colony-stimulating factor receptor.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) activates a broad range of myeloid cells through binding to high-affinity receptors (GM-CSF-R) consisting of at least two distinct subunits, GM-CSF-R alpha and GM-CSF-R beta. The genes of these GM-CSF-R subunits have been identified recently, but little is known about the regulation of their expression. In this study, we investigated the expression of the GM-CSF-R subunit genes in normal human monocytes. Out of a panel of various cytokines and factors tested, only interferon-gamma (IFN-gamma) affected the expression of one of the GM-CSF-R subunit genes by increasing the GM-CSF-R beta mRNA expression threefold to sixfold with no effect on GM-CSF-R alpha. Maximal effects occurred 2 to 4 hours after stimulation with 500 to 5,000 U/mL IFN-gamma. Nuclear run-on assays and mRNA half-life studies showed that IFN-gamma modestly enhanced the transcription of the GM-CSF-R beta gene and stabilized the GM-CSF-R beta mRNA, with the latter mechanism predominant. Pretreatment of the monocytes with cycloheximide did not abrogate the increase of GM-CSF-R beta mRNA expression induced by IFN-gamma, indicating that de novo protein synthesis was not required for this activity. When monocytes were exposed to IFN-gamma for 6 to 24 hours, the number of GM-CSF-R per cell was increased 79% as compared with controls, whereas the receptor affinity remained unchanged. These data indicate that the GM-CSF-R expression in monocytes may be upregulated by IFN-gamma via an increased expression of the beta subunit gene, involving both transcriptional and post-transcriptional mechanisms.

Granulocyte-macrophage colony-stimulating factor and steel factor induce phosphorylation of both unique and overlapping signal transduction intermediates in a human factor-dependent hematopoietic cell line.

Steel factor (SF), the ligand for the proto-oncogene c-kit, acts synergistically with GM-CSF or IL-3 to support the growth of normal human hematopoietic progenitor cells. We examined the effects of SF on GM-CSF or IL-3 induced proliferation of a human factor-dependent cell line, MO7. SF supported MO7 cell proliferation as well as IL-3 or GM-CSF alone, and its addition dramatically enhanced (three- to sixfold) maximal GM-CSF or IL-3 stimulated proliferation. SF did not increase the number or affinity of cell surface GM-CSF receptors. We examined several early events of signal transduction in an effort to elucidate the biochemical mechanisms of synergy of these factors. Since each of these three cytokines is believed to function in part through activation of a tyrosine kinase, we examined their effects on cellular phosphotyrosine containing proteins. Each cytokine induced rapid, transient, and concentration dependent tyrosine phosphorylation of a number of substrates. For GM-CSF and IL-3, these phosphoproteins were indistinguishable (150, 125, 106, 93, 80, 79, 73, 44, 42, and 36 kDa), while SF induced major or minor tyrosine phosphorylation of 205, 140-150, 116, 106, 94, 90, 80, 79, 73, 44, 42, 39, 36, 32 kDa phosphoproteins. Two other signal transduction intermediates known to be phosphorylated and activated by GM-CSF and IL-3, the 70-75 kDa Raf-1 kinase, and p42 mitogen-activated protein kinase-2 (MAPK), were also phosphorylated by SF. Combinations of GM-CSF or IL-3 with SF did not further increase the phosphorylation of Raf-1 or p42 MAPK when compared to any of the factors alone. In contrast SF, but not GM-CSF or IL-3, induced tyrosine phosphorylation of phospholipase C-gamma (PLC-gamma). These results indicate that SF and GM-CSF/IL-3 have partially overlapping effects on early signal transducing events, as well as striking differences, such as tyrosine phosphorylation of PLC-gamma. This cell line should provide a useful model system to investigate the complicated process of hematopoietic growth factor synergy.

Human anti-murine antibody responses in ovarian cancer patients undergoing radioimmunotherapy with the murine monoclonal antibody OC-125.

Human anti-murine antibody (HAMA) responses were monitored in 23 patients with recurrent or persistent epithelial ovarian carcinoma undergoing single-dose intraperitoneal radioimmunotherapy (RIT) with the murine monoclonal antibody OC-125. Sera of patients receiving escalating doses of OC-125 F(ab')2 (10-70 mg) radiolabeled with 18 to 141 mCi of iodine-131 were assayed for HAMA by a protein A-based radioimmunoassay. Overall, 70% of patients (16/23) developed HAMA within 10 to 46 days (median = 29) postinfusion, with peak values (23 +/- 6 to 325 +/- 10 micrograms/ml) at 32 to 102 days (median = 38). HAMA was undetectable prior to infusion in all cases and persisted up to 76 weeks. Of patients receiving a dose of 123 mCi or less, 80% (16/20) developed HAMA, whereas in the 140-mCi group, none of the three patients had detectable levels. Two patients in the 140-mCi group demonstrated dose-limiting bone marrow toxicity (severe thrombocytopenia and neutropenia). It is concluded that a single intraperitoneal dose of monoclonal antibody leads to a high incidence of HAMA production. The results also suggest that the likelihood of HAMA formation in patients who either had undergone recent chemotherapy or had received the highest dose of the radioimmunoconjugate is reduced. These observations may be of significance in designing multiple-dose therapy trials as HAMA has been demonstrated to decrease antibody-to-tumor binding and may potentially increase renal, hepatic, and hematologic toxicity associated with radioimmunotherapy.

Influence of human antimurine antibody on CA 125 levels in patients with ovarian cancer undergoing radioimmunotherapy or immunoscintigraphy with murine monoclonal antibody OC 125.

Human antimurine antibody responses interfere with CA 125 antigen determinations by crosslinking the murine antiovarian carcinoma monoclonal antibody OC 125 with the second murine radiolabeled antibody used in the CA 125 radioimmunoassay. Serial CA 125 levels in 22 patients with epithelial ovarian carcinoma undergoing either radioimmunotherapy or radioimmunoscintigraphy with iodine 131-labeled F(ab')2 fragments of OC 125 were followed up for up to 96 weeks after infusion. Fourteen radioimmunoscintigraphy patients received 131I-labeled monoclonal antibody by the intraperitoneal (n = 5) or intravenous (n = 9) route: 10 of 14 had sera drawn at appropriate time points for human antimurine antibody detection; 8 of 10 had 1.3- to 363-fold increases in CA 125; 4 of 8 had detectable human antimurine antibody (18.5 to 22 and 575 to 36 micrograms/ml). Eight radioimmunotherapy patients received 131I-labeled monoclonal antibody by the intraperitoneal route: 8 of 8 displayed an apparent 4.8- to 3725-fold increase in CA 125 levels within 7 to 42 days after monoclonal antibody infusion; 6 of 8 had detectable human antimurine antibody (13 to 4 and 319 to 31 micrograms/ml). Adsorption of immunoglobulin G resulted in a 21% to 98% reduction in CA 125 antigen levels in 4 of 4 patients tested. In patients with demonstrable human antimurine antibody, CA 125 antigen levels obtained by the clinical CA 125 radioimmunoassay are spuriously elevated.