Induction of ceramide glucosyltransferase activity in cultured human keratinocytes. Correlation with culture differentiation.

Ceramides are the major component of the extracellular lipids that comprise the epidermal permeability barrier. They are derived from glucosylceramides (GlcCer) upon their extrusion from lamellar granules into the extracellular space in the upper layers of the epidermis. To better understand the regulation of the unique pathway for ceramide production in epidermis, we have studied the activity of the enzyme responsible for GlcCer synthesis, ceramide glucosyltransferase (CerGlc transferase), during keratinocyte culture differentiation. Human keratinocyte cultures were expanded in low calcium keratinocyte growth medium (KGM) and then switched to either normal calcium KGM (nKGM) or "complete" Dulbecco's modified Eagle's medium/Ham's F-12 (3:1) supplemented with 10% fetal bovine serum (cDMEM). At 7 and 10 days after the medium switch, electron microscopy revealed that cDMEM cultures were more fully differentiated morphologically and contained numerous lamellar granules. The GlcCer/DNA content of cDMEM cultures increased to 6 times that of day 0 cultures and was nearly 4 times greater than that of nKGM cultures, whereas the total lipid/DNA content of cDMEM cultures increased to only 1.8 times that of day 0 cultures and was approximately 1.2 times that of nKGM cultures. CerGlc transferase activity/DNA increased 6 times in cDMEM cultures but <1.5 times in nKGM cultures. By contrast, beta-glucocerebrosidase activity, which is responsible for the conversion of GlcCer to ceramide, increased to a similar extent in both differentiating culture systems. Treatment of cultures with the reversible CerGlc transferase inhibitor, DL-threo-1-phenyl-2-(palmitoylamino)-3-morpholino-1-propanol, prevented the increase of GlcCer in cDMEM cultures, and blocked conversion of exogenously added ceramide to GlcCer. A low level of CerGlc transferase activity, relative to that in differentiated keratinocytes, was detected in cultures of other human cell types. These results indicate that CerGlc transferase activity is induced during epidermal differentiation and that regulation of this enzyme may be an important determinant of the specialized production and compartmentalization of epidermal sphingolipids.

Ultraviolet light burn: a cutaneous complication of visible light phototherapy of neonatal jaundice.

Visible light phototherapy is an easily administered and effective treatment for neonatal indirect hyperbilirubinemia. Reported cutaneous side effects include transient rashes and the uncommon bronze baby syndrome. A more hazardous side effect is ultraviolet burn. Two premature infants developed phototherapy-induced erythema, one associated with a second-degree burn, after exposure to fluorescent daylight bulbs inadvertently used without Plexiglass shields, thus allowing prolonged ultraviolet A (UVA) exposure. Premature infants, especially during the first two weeks of life, may be significantly susceptible to UVA-induced erythema. Plexiglass shields should always be in place during visible light phototherapy, and nursery staff should be made aware of their purpose.

Early skeletal hyperostoses secondary to 13-cis-retinoic acid.

Prolonged therapy with retinoid drugs (chemically similar to vitamin A) often results in skeletal hyperostoses, similar to those seen in idiopathic skeletal hyperostosis. Eight patients, aged 5-26 years, with dermatologic disorders were treated with 13-cis-retinoic acid. Skeletal surveys were obtained before and during treatment. In 1 year, six of the eight patients had developed such skeletal hyperostoses in both axial and appendicular regions. The cervical spine was the most common site of involvement. None of the children demonstrated accelerated skeletal maturation. Two of the patients had mild musculoskeletal discomfort during this period. The findings indicate that high-dose 13-cis-retinoic acid therapy may cause skeletal hyperostoses, requiring radiographic monitoring during prolonged periods of treatment. An implication of these observations, relating to the etiology of idiopathic skeletal hyperostosis, is discussed.