Publications

Glomerular mesangial cell (MC)--derived IL-1 may be an important factor in the development of the hypercellularity and sclerosis characteristic of many forms of glomerulonephritis. To define the regulation of IL-1 synthesis by human MC, Northern blot analyses were performed using specific probes for monocytic IL-1 alpha and beta mRNA. Proliferating MC expressed mRNA for both IL-1 alpha and beta, whereas nonproliferating MC contained no detectable IL-1 mRNA. Synchronized MC expressed IL-1 alpha and beta mRNA within 2 h of stimulation with serum. This serum effect could be reproduced with platelet-derived growth factor and epidermal growth factor. Immune precipitations of 35S-methionine-labeled cells indicate that the mesangial IL-1 is synthesized as a 33-kD precursor protein with a pI of 7.2. Extracellular mesangial IL-1 has a pI of 7.0 and molecular weight of 17 kD, consistent with its identification as IL-1 beta. Cellular proliferation in glomerular disease may be driven in part by peptide growth factor-mediated induction of mesangial IL-1 gene expression and protein synthesis.

Naturally occurring fogs are usually hypoosmolar with respect to body fluids and can be quite acidic. Because both hypoosmolarity and acidity can cause bronchoconstriction, we studied whether there was a positive interaction between these stimuli in 12 subjects with asthma. We administered the following aerosols: hypoosmolar saline (30 mOsm) at pH 5.5, 3 hypoosmolar acids (0.005 M H2SO4, 0.01 M HNO3 and a 1:1 mixture of 0.005 M H2SO4 and 0.01 M HNO3, all 30 mOsm) at pH 2, and isoosmolar 0.005 M H2SO4 (300 mOsm) at pH 2. Each aerosol was administered on a separate day and was inhaled through a mouthpiece during tidal breathing. Specific airway resistance (SRaw) was measured before and after the subjects inhaled aerosols delivered at as much as 5 doubling nebulizer outputs. For each aerosol challenge, an output-response curve was generated, and the nebulizer output required to increase SRaw by 100% above baseline (PO100) was calculated. Mean values of PO100 were significantly lower for each of the hypoosmolar acids than for hypoosmolar saline (1.65 + 0.43 g/min [mean + SEM] for saline compared with 0.95 + 0.11, 1.05 + 0.20, and 0.90 + 0.14 for H2SO4, HNO3, and a 1:1 mixture of the two; all p values less than 0.025). Mean values of PO100 did not differ among the 3 acids studied. For 7 of 12 subjects, all 3 acids caused a leftward shift in the output-response curve from the curve generated for hypoosmolar saline aerosol. Isoosmolar H2SO4 did not increase SRaw by 100% in any subjects, even at the maximal nebulizer output that delivered a concentration of H2SO4 in excess of 40 mg/m3.(ABSTRACT TRUNCATED AT 250 WORDS)

Digital and palmar dermatoglyphics were examined in 29 men and 27 women with dementia of the Alzheimer type (DAT) and 112 age-, sex-, and racial group-matched controls. Female patients had significantly (p less than 0.05) more accessory triradii and complete Sydney creases than controls; no dermatoglyphic differences were detected in the males. Separating the patients by age of onset prior to or after age 65 years did not help differentiate patients from controls by dermatoglyphic profile. This study failed to confirm either the previously reported dermatoglyphic differences between DAT patients and controls or the reported similarity of the dermatoglyphic pattern of DAT to that of Down syndrome patients.

Both the interleukin-2 receptor-alpha (Tac, p55, IL-2R alpha) gene and the long terminal repeat (LTR) of type 1 HIV are activated by various T cell mitogens. We now demonstrate that an inducible 86 kd nuclear protein termed HIVEN86A specifically binds to both the enhancer element of the HIV-1 LTR and a closely related 12 bp sequence present in the 5' regulatory region (-267 to -256) of the IL-2R alpha gene. The interaction of these binding sites with HIVEN86A and perhaps other cellular proteins such as NF-kappa B appears importantly involved in mitogen activation since the isolated IL-2R alpha promoter binding site or single elements of the normally duplicated HIV-1 enhancer alone are sufficient to confer mitogen inducibility on an unresponsive heterologous promoter. Together these findings suggest that the normal action of an inducible nuclear DNA binding protein(s) involved in the regulation of IL-2R alpha gene expression can be subverted by the HIV-1 provirus to promote activation of retroviral gene transcription.