Publications

Interleukin 1 (IL-1) exerts a number of biologic actions upon cultured glomerular mesangial cells (MC). These include stimulation of cellular proliferation and induction of prostaglandin and type IV collagenase secretion. It was determined that this activity, as with other polypeptide growth factors, was associated with the activation of specific MC plasma membrane protein kinases. Plasma membranes from cycling MC were incubated with purified IL-1 and (32P) ATP in the absence of calcium and cyclic nucleotides. Macrophage IL-1 stimulated the rapid phosphorylation of several plasma membrane proteins, the most significant of which were 52-55 kd, 46 kd, and 20 kd in size. Macrophage IL-1 induced specific membrane phosphorylation in concentrations as low as 1.5 x 10(-12) M, an effect obtained with equivalent concentrations of purified MC IL-1. The 46 kd phosphoprotein, which was the most prominent, was alkali-resistant and contained phosphotyrosine when examined by phosphoamino acid analysis. The 52-55 kd and 20 kd phosphoproteins were alkali-labile and contained phosphoserine. The 46 kd phosphoprotein was the major phosphoprotein recovered from Con A-Sepharose and IL-1 affinity columns. Induction of plasma membrane-associated protein kinase activity may represent one mechanism whereby IL-1 initiates mesangial cellular activation.

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.