In a postmortem study of a patient with adult-onset acid maltase deficiency (AMD), morphological abnormalities were confined to skeletal muscle and consisted of a vacuolar myopathy. Acid maltase activity, however, was approximately 6% of normal in muscle, liver, and brain, and 3% of normal in heart. Kinetic characteristics, and inhibition by antibodies and Zn++, showed that the residual activity was "authentic" acid maltase. Neutral maltase activity was normal in muscle and liver, but decreased in brain (55% of normal) and heart (19% of normal). Although the relative decrease of acid maltase was similar in different tissues, absolute residual activity was lowest in skeletal muscle: this may explain the selective involvement of this tissue in late-onset AMD.

Adult↗

PubMedDate not supplied

Chlorotrifluoroethylene nephrotoxicity in rats: a subacute study.

Male Fischer-344 rats were exposed via inhalation to a sublethal concentration (395 ppm +/- 33 ppm; 1882 mg/m3) of the nephrotoxin chlorotrifluoroethylene (CTFE) for 4 h per day for 5 consecutive days. Within 1 day after the first exposure, rats exhibited diuresis, increased water intake, decreased urine osmolality, increased urinary lactic dehydrogenase activity and increased plasma creatinine and urea nitrogen. When animals were exposed repeatedly, values for these parameters declined or returned to control levels during the exposure sequence in a manner comparable to rats receiving the single exposure. By the third day post exposure, coagulative necrosis involving primarily the pars recta, but extending to the pars convoluta, of the proximal tubule was present. Regeneration was apparent by the third day of exposure, and additional necrosis was minimal despite further exposures. Daily levels of urinary inorganic fluoride, an index of CTFE metabolism, were increased to 3-6 mu moles/24 h/rat during the exposure sequence which coincided with a brief elevation in serum fluoride at the end of each exposure. Adaptation to CTFE is evident either through changes in the metabolism or disposition of CTFE or from a refractive property of the regenerating tissue to CTFE.

Animals↗

PubMedDate not supplied

Interleukin-1beta-induced promatrilysin expression is mediated by NFkappaB-regulated synthesis of interleukin-6 in the prostate carcinoma cell line, LNCaP.

Previously, our laboratory showed that interleukin-1beta (IL-1beta) secreted by lipopolysaccharide-activated monocytes induces promatrilysin expression in the prostate carcinoma cell line, LNCaP. We now demonstrate that IL-1beta-induced promatrilysin expression is mediated by an indirect mechanism that requires nuclear factor Kappa B (NFkappaB)-dependent synthesis of IL-6. Inhibition of protein synthesis with cycloheximide blocked IL-1beta-mediated induction of matrilysin mRNA suggesting that synthesis of one or more additional factors is required for IL-1beta-induced promatrilysin protein expression. Blockage of NFkappaB transactivation activity abrogated IL-1beta-induced promatrilysin expression to baseline levels suggesting that NFkappaB transactivation activity is necessary. Inhibition of IL-6 activity attenuated IL-1beta-induced promatrilysin, but not NFkappaB transactivation activity indicating that IL-6 acts downstream of NFkappaB in potentiation of IL-1beta-mediated promatrilysin expression. Inhibition of protein synthesis with cycloheximide did not alter IL-6-induced induction of matrilysin mRNA indicating that, contrary to the mechanism by which IL-1beta regulates promatrilysin expression, IL-6-mediated matrilysin mRNA expression does not require new protein synthesis. Transient transfection with dominant negative STAT3 inhibited IL-1beta- and IL-6-induced promatrilysin. These data provide evidence that NFkappaB-mediated IL-6 synthesis is required for IL-1beta-induced promatrilysin expression, and IL-6 signaling through STAT3 plays a role in IL-1beta-induced promatrilysin expression.

Adenocarcinoma↗