Further analysis of pemphigus autoantibodies and their use in studies on the heterogeneity, structure, and function of desmosomes.

Pemphigus is an autoimmune disease that causes blistering of human epidermis. We have recently shown that autoantibodies in the serum of three pemphigus patients bind to desmosomes (Jones, J. C. R., J. Arnn, L. A. Staehelin, and R. D. Goldman, 1984, Proc. Natl. Acad. Sci. USA., 81:2781-2785), and we suggested that pemphigus blisters form, at least in part, from a specific antibody-induced disruption of desmosomes in the epidermis. In this paper, experiments are described that extend our initial observations. 13 pemphigus serum samples, which include four known pemphigus vulgaris (Pv) and four known pemphigus foliaceus (Pf) serum samples, have been analyzed by both immunofluorescence and by immunoblotting using cell-free desmosome preparations. Tissue sections of mouse skin processed for double indirect immunofluorescence using each of the pemphigus serum samples and a rabbit antiserum directed against a component of the desmosomal plaque (desmoplakin) show similar punctate cell surface staining patterns. This suggests that all 13 pemphigus serum samples contain autoantibodies that recognize desmosomes. These autoantibodies appear specific for stratified squamous epithelial cell desmosomes and do not recognize desmosomes of other tissues (e.g., mouse heart and mouse intestine). Cultured mouse keratinocytes, which possess well-defined desmosomes, were processed for indirect immunofluorescence using the pemphigus serum samples. Eight of the 13 sera (including the four known Pv samples but not the known Pf sera) stain desmosomes in these preparations. By double indirect immunofluorescence the desmoplakin antiserum stains a double fluorescent line along the contacting edges of cultured keratinocytes, whereas the positive pemphigus serum samples stain a single fluorescent line along this same border. We believe that these pemphigus autoantibodies recognize extracellular antigens located somewhere within the region between the two apposing membranes that comprise the desmosome. The pemphigus sera exhibit positive immunoblotting reactions with desmosome-enriched fractions obtained from bovine tongue epithelium. Three serum samples (including two of the four known Pf serum samples) react with 160- and 165-kD desmosome-associated polypeptides (Koulu, L., A. Kusimi, M. S. Steinberg, V. Klaus-Kovtun, and J. R. Stanley, 1984, J. Exp. Med., 160:1509-1518). Another eight serum samples (including the four known Pv sera) recognize a 140-kD desmosome-associated polypeptide. We propose that the antigens recognized by these human autoantibodies may play important roles in the adhesion of cells within the epidermis.(ABSTRACT TRUNCATED AT 400 WORDS)

Craniofacial gliomas.

Ten patients with gliomas were treated between 1977 and 1993. Three of the lesions (30 percent) exhibited intracranial extension. Fifty percent (2 of 4) of the intranasal lesions exhibited intracranial extension. Effective removal of the lesion required manipulation of nasal bones in intranasal lesions and extranasal lesions with intranasal extension. Gliomas with an intracranial component were best addressed through a combined intracranial and extracranial approach.

In pursuit of optimal periorbital rejuvenation: laser resurfacing with or without blepharoplasty and brow lift.

LEARNING OBJECTIVES: The reader is presumed to have a broad understanding of plastic surgical procedures and concepts. After studying this article, the participant should be able to: Physicians may earn 1 hour of Category 1 CME credit by successfully completing the examination based on material covered in this article. The examination begins on page 333. Although blepharoplasty and coronal foreheadplasty have been the traditional methods for improving the periorbital region, in our opinion these techniques together can address only three of the 11 major signs of periorbital aging. We found no improvement with skin-muscle flap type blepharoplasty and coronal lift in the wrinkling and pigmentation changes in the infrabrow, crow's-foot, lower lid, and malar regions, and no improvement in malar bags, "dark circles" under the eyes, or the apparent lengthening of the vertical height of the lower lid and its associated sharp transition between cheek and lid skin. CO(2) laser resurfacing can improve these signs of periorbital aging and permits the laser transconjunctival approach if blepharoplasty is necessary, thus eliminating a visible lower lid incision. When brow ptosis is present, we prefer endoscopic brow lift to minimize dysesthesia and incision size. We evaluated 174 patients and contrasted the results of the traditional approach versus laser resurfacing with or without laser blepharoplasty and endoscopic brow lift. The mean time to evaluation was 9 months, ranging up to 2 (1/2) years. We found that the laser approach can address almost all of the 11 major signs of periorbital aging at one procedure. It is minimally invasive, technically simple and fast, offers lasting improvements, and yields high patient satisfaction and better results with fewer persistent problems than the traditional surgical approach.

Release of acquired syndactylies in Kindler syndrome.

Kindler syndrome is a rare, blistering skin disease characterized by acral bullae, poikiloderma, and diffuse cutaneous atrophy. Kindler syndrome has been established as a separate entity from epidermolysis bullosa; however, controversy still remains as to whether Kindler syndrome can be differentiated from Weary's hereditary acrokeratotic poikiloderma. Fusion of the digits secondary to blistering and scarring, "pseudosyndactyly," has been reported in several patients with Kindler syndrome; however, surgical correction of the syndactylies in these patients has not been described. In this report, a patient with Kindler syndrome underwent surgical treatment of acquired syndactylies. Treatment included a tailored approach to preparation of the patient for surgery, surgical separation of fused tissues, selection of donor site for skin-graft harvest, postoperative dressings, splinting, and therapy. Results in our patient 2 years after correction demonstrate that syndactyly release in Kindler syndrome can be accomplished effectively, with improvement in both function and appearance.

Is the hemidesmosome a half desmosome? An immunological comparison of mammalian desmosomes and hemidesmosomes.

Although the mammalian epidermal basal cell hemidesmosome bears some superficial resemblance to one half of a desmosome at the ultrastructural level, examination of the structure of the electron-dense submembranous plaques of the hemidesmosome and desmosome reveals that they differ with respect to their overall morphology and dimensions. Based on these findings, we wondered whether components of the desmosome are present in the hemidesmosome. In order to determine this we prepared a number of stratified squamous epithelial tissues for indirect immunofluorescence using antibody preparations directed against known desmosome components including desmoplakin and certain glycoproteins. These antibody preparations do not show reaction with hemidesmosomes by indirect immunofluorescence criteria. We have also utilized bullous pemphigoid (BP) autoantibodies that have been shown to recognize hemidesmosomes in mammalian skin cells [Mutasim et al., J. Invest. Derm., 84:47-53, 1985]. Double label indirect immunofluorescence observations of neonatal mouse skin prepared using desmoplakin antibodies and BP autoantibodies reveal that hemidesmosomes that are stained by the BP autoantibodies are not recognized by the desmoplakin antibodies. We confirmed these findings at the ultrastructural level by indirect immunogold localization of desmoplakin antibodies and BP autoantibodies. Therefore, the hemidesmosome does not appear to be one half of a desmosome and may possess a very different molecular organization relative to the desmosome. We raise the possibility that the variability between the hemidesmosome and desmosome that we detect at the morphological and immunological level may reflect the functional differences of these two types of junctions.

A cell surface desmosome-associated component: identification of tissue-specific cell adhesion molecule.

Autoantibodies in the serum of patients suffering the blistering skin disease pemphigus vulgaris recognize a 140-kDa glycoprotein (GP) present in enriched fractions of bovine tongue epidermal desmosomes. Immunofluorescence observations of cryostat sections of bovine tongue epidermis reveal that affinity-purified rabbit antibodies to the 140-kDa GP generate a punctate intercellular stain that is similar to that generated by antibodies directed against a desmosome plaque component (desmoplakin). In cultured mouse keratinocytes, the antibodies against 140-kDa GP recognize desmosomes along areas of cell-cell contact. Double immunofluorescence of cultured keratinocytes with these antibodies and a desmoplakin antiserum reveals that the antibodies against the 140-kDa GP stain a single fluorescent line along areas of cell-cell contact. This single fluorescent line lies between double fluorescent lines generated by the desmoplakin antiserum. Immunogold ultrastructural localization reveals that the 140-kDa antigen is localized not only along the intercellular area of the desmosome but also is found along the whole epidermal cell surface. The antibodies to the 140-kDa GP are able to induce a disruption of cell-cell contact in cultured keratinocytes that possess desmosomes. We propose that the 140-kDa GP is a cell adhesion molecule (CAM). Furthermore we discuss the heterogeneity of desmosomes in the light of our findings that antibodies against the 140-kDa GP recognize specific stratified squamous epithelial tissues.

Aesthetic CO(2) laser surgery: evaluation of 907 patients.

Resurfacing the skin to improve skin quality is an important concept in aesthetic plasticsurgery. Although time-honored methods (e.g., dermabrasion and chemical peel) are available for this purpose, they have several disadvantages. A newer method with a highenergy pulsed carbon dioxide laser provides a more controllable and more predictable method of resurfacing facial skin. In our study of 907 patients, monitored up to 2 years 868 laser resurfacing procedures were done for facial wrinkles. Eight hundred two of 868 (92.4%) achieved very good to excellent results (>75% removal of wrinkles in 92.4% of cases). Forty-six of 61 (75.4%) patients with acne scars also obtained very good to excellent results. Most patients with selected skin lesions (rhinophyma, actinic cheilitis, epidermal nevi, seborrheic keratoses, syringomas, xanthelasmas, and postsurgical scars) achieved good to excellent results, although these are admittedly more difficult to quantify. Major complications were uncommon. One hundred one of 907 (11.1%) patients had development of temporary hyperpigmentation, which resolved in an average of 2.6 weeks. Thirty-four of 907 (3.8%) patients had development of mild permanent hypopigmentation. Eight of 908 (0.9%) patients had development of some induration that resolved with use of intralesional steroids. Most of these (5 of 8) were in the perioral area. Three of 907 (0.3%) patients had development of a small persistent scar. Seven of 316 (2%) patients undergoing periorbital resurfacing had development of some mild scleral show. Early in our experience one patient developed ectropion that required surgical correction. We conclude that the new generation high-energy pulsed carbon dioxide laser is safe andeffective for resurfacing facial skin. However, this procedure is very technique dependent and requires a combination of didactic and hands-on training, conservative surgical judgment, and diligent patient follow-up to obtain optimal results with minimal complications.

Peripheral vascular disease in spinal cord injury patients: a difficult diagnosis.

The timely detection of peripheral vascular disease (PVD) in spinal cord injury (SCI) patients is difficult because the usual symptoms of claudication and rest pain are absent. In fact, the initial manifestation of PVD in SCI patients is often advanced gangrene, so that healing, primarily or following major amputation, is either difficult and prolonged or impossible. In addition, sacral and ischial pressure sores common among SCI patients may be exacerbated and reconstruction made more difficult by PVD. Five SCI patients presented with lower extremity gangrene as the initial recognized manifestation of PVD at our institution between January 1992 and January 1994. All 5 patients had risk factors for PVD. Four out of ten limbs in these patients required amputation, either above the knee or below the knee. Three patients required concurrent vascular reconstruction of the aortoiliac segments, including an aortobiprofunda femoral bypass, an iliac embolectomy with femoral-femoral bypass, and iliac angioplasty. Three patients had ischial and/or sacral pressure sores that had recurred following multiple musculocutaneous flap reconstructions before vascular disease was recognized. The timely diagnosis of PVD involving the iliac segment in the SCI patient is sometimes overlooked and is often necessary to optimize the treatment of both lower extremity ulcers and sacral/ ischial pressure sores common among these patients.