Publications

To evaluate partner notification of opposite-sex sexual partners of AIDS patients as a means of limiting sexual and vertical transmission of human immunodeficiency virus (HIV), the authors examined the first 27 months of their experience with partner notification. Overall, of 145 AIDS patients eligible to participate, 51 (35%) were interviewed and identified 135 opposite-sex sexual partners. Of the 135 partners, 59 (44%) were interviewed and 34 (25%) were tested, resulting in the diagnosis of 7 (5%) HIV-infected partners. Refusal rates for index patients and partners were low (9% and 12%, respectively). Costs for the program were $454 per partner interviewed and $2,203 per seropositive partners identified. The authors conclude that although partner notification is more expensive than more widely targeted AIDS prevention and education efforts, its ability to target case finding, education, and counseling to women at highest risk of infection makes it potentially cost-effective for prevention of vertically transmitted HIV infection.

The IL-2 and the IL-2-R alpha genes are both expressed transiently in normal T lymphocytes after Ag or mitogen activation. In contrast, the human T cell line, IARC 301, expresses these two genes constitutively and we have previously demonstrated that its growth depends on the autocrine production of this T cell growth factor and high affinity IL-2R. To dissect the molecular basis for the unusual persistent expression of the IL-2 and IL-2-R alpha genes in these IARC 301 T cells, we have analyzed the interactions of constitutively expressed nuclear proteins with the 5' flanking regions of the IL-2 and IL-2-R alpha genes using both DNase I footprinting and gel retardation techniques. We have found that a region in both genes (-276 to -250 for IL-2-R alpha and -203 to -183 for IL-2), which corresponds to a kappa B enhancer element, is specifically protected by nuclear proteins from IARC 301. In agreement with this finding, both the IL-2 and IL-2-R alpha promoters are active in transient transfection assays in IARC 301 cells. In contrast, mutation of the kappa B enhancer results in markedly attenuated activities of both promoters. Two proteins binding the kappa B sequence, NF-kappa B and KBF1, are constitutively expressed in IARC 301 nuclei and induced by PMA and PHA in Jurkat. They bind to the kappa B motifs with different relative affinities that may reflect their different contribution in the expression of various promoters.

HIVEN86A is an inducible member of a set of cellular proteins that specifically bind to the kappa B enhancer (Franza et al., 1987; Franza, 1988; Franza, 1990; Ballard et al., 1989; Bohnlein et al., 1988). This enhancer motif has been detected in numerous cellular and viral transcription control domains (Boshart et al., 1985; Sen & Baltimore, 1986; Nabel & Baltimore, 1987). Recently, cDNAs have been cloned (Kieran et al., 1990; Baldwin & Sharp, 1987) that encode the 50 kD DNA binding subunit of murine NF-kappa B (for review: Leonardo & Baltimore, 1989) and the closely related human kappa binding factor (KBF-1) (Kimura et al., 1986; Baldwin & Sharp, 1987). A 350 amino acid domain at the N-terminus of these proteins was found to be homologous with the v-rel oncogene from the avian reticuloendotheliosis virus, strain T (REV-T), as well as a maternal effect gene, dorsal (Kieran et al., 1990; Ghosh et al., 1990). Dorsal is known to activate transcription of certain Drosophila genes (Rushlow et al., 1987). The v-Rel oncoprotein has been identified as a transcriptional activator (Gelinas & Temin, 1988; Hannink & Temin, 1989; Bull et al., 1990) in certain assay systems and shown to be induced by the tumor promoter, phorbol 12-myristate 13-acetate (PMA) in avian cells (for review: Rice & Gilden, 1988). HIVEN86A is also inducible by PMA (Franza et al., 1987; Franza, 1988; Franza, 1990). We now demonstrate that the protein product of the human c-rel proto-oncogene is structurally identical to HIVEN86A.

Sulfuric acid (H2SO4) is the most common acid air pollutant in the United States and is thought to have adverse respiratory effects. Sulfuric acid exists in polluted air as a dissolved solute in both small (haze) and large (fog) particles. Previous work in our laboratory has failed to demonstrate bronchoconstriction after near ambient, large-particle H2SO4 exposure in subjects with asthma. However, other investigators have found slight but significant changes in lung function following inhalation of small-particle or small-particle, low-relative-humidity (RH) H2SO4 aerosols, leading us to hypothesize that particle size and/or RH may be important variables in acid aerosol exposure. We initially studied the effects of resting inhalation of large-particle (volume median diameter, VMD, approximately equal to 6 microns) and small-particle (VMD approximately equal to 0.4 microns) aerosols with an H2SO4 concentration of 3 mg/m3 through a mouthpiece and found no effect on specific airway resistance (SRaw) or symptom scores. In a second mouthpiece study designed to compare high-RH (100%), large-particle (VMD approximately equal to 6 microns) and low-RH (less than 10%), small-particle (VMD approximately equal to 0.3 microns) aerosols with an H2SO4 concentration of 3 mg/m3, we again found no effect of either aerosol. We then examined the effects of small-particle aerosols inhaled in dry air during moderate exercise. Although breathing low-RH air during exercise provoked increases in SRaw in almost all subjects, this could not be attributed to H2SO4 since low-RH saline aerosol produced a similar result.(ABSTRACT TRUNCATED AT 250 WORDS)

In reticulocytes, the enzyme 15-lipoxygenase (15-LO) is believed to contribute to cellular differentiation, and in leukocytes and airway cells 15-LO generates inflammatory mediators. The recent availability of antibodies to 15-LO now allows us to determine which specific cells contain the enzyme, to characterize its subcellular localization, and to determine its expression at the translational level. A polyclonal antibody to recombinant human reticulocyte 15-LO was used with a standard immunofluorescent technique. In rabbit red blood cells, fluorescence appeared during the course of anemia. Early reticulocytes did not fluoresce, but more mature reticulocytes showed increased fluorescent intensity. Late reticulocytes contained little fluorescence. Among human leukocytes, only eosinophils fluoresced. In human trachea, 15-LO immunofluorescence was localized to epithelial cells, and both basal and ciliated cells fluoresced. In all cells studied, fluorescence was localized to the cytoplasm and was variable in degree among cells in each preparation. We conclude that the 15-LO of airway cells and eosinophils is immunologically related to the reticulocyte 15-LO. Furthermore, the variable fluorescence among cells (e.g., in epithelium) and during development (e.g., reticulocytes) suggests a role of 15-LO in cell growth and development.