Kathi C. Madison

Thrombomodulin expression by human keratinocytes. Induction of cofactor activity during epidermal differentiation.

Thrombomodulin is an endothelial cell surface glycoprotein that inhibits the procoagulant activities of thrombin and accelerates activation of the anticoagulant protein C. Because protein C deficiency is associated with cutaneous thrombosis, we investigated the expression of thrombomodulin in human skin. Thrombomodulin was detected by immunohistochemical staining both in dermal endothelial cells and in epidermal keratinocytes. Within the epidermis, thrombomodulin staining was limited to keratinocytes of the spinous layer, suggesting that thrombomodulin is induced when basal keratinocytes begin to terminally differentiate. Thrombomodulin expression also correlated with squamous differentiation in epidermal malignancies; little or no thrombomodulin staining was seen in five basal cell carcinomas, whereas strong thrombomodulin staining was observed in each of five squamous cell carcinomas. Human foreskin keratinocytes cultured in medium containing 0.07 mM calcium chloride synthesized functional thrombomodulin with cofactor activity comparable to thrombomodulin in human umbilical vein endothelial cells. Stimulation of keratinocyte differentiation with 1.4 mM calcium chloride for 48 h produced 3.5-, 3.2-, and 5.6-fold increases in thrombomodulin cofactor activity, antigen, and mRNA, respectively. These observations suggest that thrombin is regulated by keratinocyte thrombomodulin at sites of cutaneous injury, and indicate a potential role for thrombomodulin in epidermal differentiation.

Semipermeable dressings improve epidermal barrier function in premature infants.

ABSTRACT: Infants of less than 32 wk gestation have a defective epidermal barrier, with increased skin permeability and transepidermal water loss (TEWL). We studied the effect of a nonadhesive semipermeable dressing on the epidermal barrier of premature infants and on fetal skin transplanted to nude mice. Fifteen infants with a mean estimated gestational age of 27.7 wk and 16 human fetal skin grafts (estimated gestational age, 23–26 wk) transplanted to eight nude mice were studied. One lower leg (or skin graft) was treated and the other left untreated as a control. In the infants, TEWL was measured on control skin and treated skin (both through the dressing and after temporary dressing removal) on d 0, 1,2, 4, and 7. Bacterial and fungal cultures were also performed. In the mice, TEWL and skin blood flow were measured on d 0, 2, and 4. Biopsies were obtained on d 4 for a cell proliferation assay, histology, and electron microscopy. Treated infant skin showed a consistently lower bacterial number and a significantly decreased TEWL (measured through the dressing). There was also a significantly lower TEWL on the treated side, measured after temporary dressing removal, on d 1, 2, 4, and 7, documenting improved epidermal barrier function. The animal study revealed decreased TEWL and a nearly 2-fold greater d-4 keratinocytc proliferation (p = 0.01) in treated skin and decreased blood flow on d 4 in control skin (p = 0.01). There was no significant difference in the volume density of membrane coating granules or the morphology of intcrcorneocyte spaces. It is concluded that semipermeable dressings improve epidermal barrier function without increasing bacterial or fungal colonization in premature infants, and that increased cellular proliferation is associated with improved barrier function in semipermeable dressing-treated fetal skin.

Isolation of corneocyte envelopes from porcine epidermis

SummarySheets of porcine stratum corneum were dispersed into individual corneocytes after 4 h in a solution consisting of 8 mM N,N-dimethyldodecylamine oxide and 2 mM sodium dodecylsulfate in phosphate-buffered isotonic saline, at 45°C. With continued detergent treatment and moderate sonication, most of the cells lost their keratin contents and were then separated from the remaining intact cells by centrifugation in cesium chloride solution of density 1.280. Electron microscopy showed that the cell envelopes retained both the cross-linked protein envelope and its attached lipid envelope. The dry weight of envelopes was approximately 7% of the estimated dry weight of the original stratum corneum, while the corneocytes surviving intact also amounted to 7% of the starting weight. Mild alkaline hydrolysis of the corneocyte envelopes allowed the extraction of hydroxyceramides amounting to 10% of the dry weight of the envelopes. The procedure therefore provides isolated corneocyte envelopes suitable for studying both the protein and lipid components of this compound sheath.

Granulomatous mycosis fungoides. Clinicopathologic study of two cases.

Granulomatous mycosis fungoides is a rare form of mycosis fungoides with controversial histogenesis. Early reports seemed to indicate a favorable prognosis for these patients. We report two cases of granulomatous mycosis fungoides, both of which had other unusual clinical features. The cases were studied with routine light microscopy, immunohistochemistry, electron microscopy, and gene probe studies. Despite some clinical and histopathologic similarities, the results of the immunohistochemical and molecular biologic studies were diverse. These results suggest that granulomatous mycosis fungoides does not define a single subset of cases, immunophenotypically or biologically.

Ultraviolet Light Burn:A Cutaneous Complication of Visible Light Phototherapy of Neonatal Jaundice

Abstract: 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.

A survey of polar and non-polar lipids of mouse organs

Total lipid was extracted from mouse (Mus musculus) heart, kidney, lung, liver, intestine, brain, stomach, dermis and epidermis and analyzed by quantitative thin-layer chromatography. All of the tissues contained phospholipids, triglycerides, sterols and free fatty acids. All tissues except brain contained small amounts of steryl esters, and all except stomach contained some glycosylceramides. Wax diesters were found in both the dermis and epidermis. Only epidermis contained a high proportion of ceramides. Acylglucosylceramides were uniquely present in epidermis.

Erythema migrans: a spectrum of histopathologic changes.

Early cutaneous Lyme disease, erythema migrans, manifests as a gyrate erythema at the site of a tick bite. The standard histopathologic description is that of a superficial and deep perivascular lymphocytic infiltrate in which plasma cells are identified at the periphery of the lesion and eosinophils in the center. Deviation from these commonly accepted histopathologic findings may lead to an erroneous diagnosis. Herein, we describe 4 cases of erythema migrans, all biopsied at the periphery of the lesion and confirmed by serologic studies, demonstrating a variety of unconventional histopathologic patterns. These findings include eosinophils and neutrophils at the periphery of the expanding annular plaque of erythema migrans, focal interface change, spongiosis, involvement of the superficial vascular plexus alone, and an absence of plasma cells in all cases. These cases highlight the varied and nonspecific histopathologic changes that can be seen in erythema migrans, including the absence of plasma cells and the presence of focal interface change. Based on these findings, the dermatopathologist should always consider erythema migrans as a diagnostic possibility in a biopsy specimen from an expanding gyrate or annular erythema despite the presence of unusual features. In atypical clinical cases, serologic confirmation may be required for diagnosis in the presence of histopathologic findings considered unconventional for erythema migrans.