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Background/Aims: Several physical agents such as low‐energy lasers have been used in the treatment of chronic skin ulcers. This study was performed to investigate potential effects of a newly‐developed, specific near‐infrared light source on wound repair.

• BACKGROUND.— Amyloidosis cutis dyschromica, a special type of primary cutaneous amyloidosis, is assumed to be a congenital disorder and sun exposure is thought to be the major causal factor. Herein we report a case of this rare disease and DNA repair characteristics of UV damages in the fibroblasts derived from the patient. OBSERVATIONS.— A 24-year-old Japanese woman showed hyperpigmented and hypopigmented xerotic lesions in sun-exposed skin since she was 10 years old; deposits of amyloid material were detected in the papillary dermis. The fibroblasts were hypersensitive to UV-B, but not so sensitive to UV-C. Unscheduled DNA synthesis of the patient's cells after UV-C exposure was lower than that of normal cells at 3 hours and both reached the same level at 6 hours. After UV-B exposure, unscheduled DNA synthesis of the patient's cells was lower than that of normal cells at least until 6 hours after UV exposure. CONCLUSION.— Although the origin of amyloidosis cutis dyschromica is unknown, hypersensitivity to UV-B with possible DNA repair defects is suggested to be the cause of this disease.(Arch Dermatol. 1992;128:966-970)

The Ca2+‐dependent cell‐cell adhesion molecules, termed cadherins, are subdivided into several subclasses. E (epithelial)‐ and P (placental)‐cadherins are involved in the selective adhesion of epidermal cells.

Some three‐dimensional culture models of the skin were reviewed including our systems using a collagen dermal substitute and a matrix dermal substitute. No obvious junctional structures, such as hemidesmosomes and the lamina densa, were formed between the basal keratinocytes and the dermal substitutes, when the cytoplasmic membrane of the basal keratinocytes directly faced the collagenous materials. On the other hand, when the cytoplasmic membrane of the basal keratinocytes faced the preformed basement membrane, the type IV collagen film, or the extracellular matrix gel, an organized interaction occurred between the basal keratinocytes and the dermal substitute through hemidesmosomes and a rudimentary lamina densa. Keratinocyte differentiation in the suprabasal layers seemed to be closely related to such a basal cell differentiation. Our preliminary examination of the experimental amyloid production by the epidermal sheet from the lesional skin of patients with primary localized cutaneous amyloidosis suggested that the basal cells in the transplanted lesional epidermis produced amyloid fibrils in our in vitro culture model. This is another use of the three‐dimensional culture models of the skin in addition to the application of the systems to wound treatment. Microsc. Res. Tech. 38:387–393, 1997.© 1997 Wiley‐Liss, Inc.

Some three-dimensional culture models of the skin were reviewed including our systems using a collagen dermal substitute and a matrix dermal substitute. No obvious junctional structures, such as hemidesmosomes and the lamina densa, were formed between the basal keratinocytes and the dermal substitutes, when the cytoplasmic membrane of the basal keratinocytes directly faced the collagenous materials. On the other hand, when the cytoplasmic membrane of the basal keratinocytes faced the preformed basement membrane, the type IV collagen film, or the extracellular matrix gel, an organized interaction occurred between the basal keratinocytes and the dermal substitute through hemidesmosomes and a rudimentary lamina densa. Keratinocyte differentiation in the suprabasal layers seemed to be closely related to such a basal cell differentiation. Our preliminary examination of the experimental amyloid production by the epidermal sheet from the lesional skin of patients with primary localized cutaneous amyloidosis suggested that the basal cells in the transplanted lesional epidermis produced amyloid fibrils in our in vitro culture model. This is another use of the three-dimensional culture models of the skin in addition to the application of the systems to wound treatment. Microsc. Res. Tech. 38:387–393, 1997. © 1997 Wiley-Liss, Inc.

The Ca²⁺-dependent cell-cell adhesion molecules, termed cadherins, are subdivided into several subclasses. E (epithelial)- and P (placental)-cadherins are involved in the selective adhesion of epidermal cells. E-cadherin is expressed on the cell surfaces of all epidermal layers and P-cadherin is expressed only on the surfaces of basal cells. Ultrastructural studies have shown that E-cadherin is distributed on the plasma membranes of keratinocytes with a condensation in the intercellular space of the desmosomes. During human skin development P-cadherin expression is spatiotemporally controlled and closely related to the segregation of basal layers as well as to the arrangement of epidermal cells into eccrine ducts. In human skin diseases E-cadherin expression is markedly reduced on the acantholytic cells of tissues in pemphigus and Darier's disease. Cell adhesion molecules are now considered to play a significant role in the cellular connections of cancer and metastatic cells. Reduced expression of E-cadherin on invasive neoplastic cells has been demonstrated for cancers of the stomach, liver, breast, and several other organs. This reduced or unstable expression of E- and P-cadherin is observed in squamous cell carcinoma, malignant melanoma, and Paget's disease, but cadherin expression is conserved in basal cell carcinoma. Keratinocytes cultured in high calcium produce much more intense immunofluorescence of intercellular E- and P-cadherin than those cells grown in low calcium. E-cadherins on the plasma membrane of the keratinocytes are shifted to desmosomes under physiological conditions, and therein may express an adhesion function in association with other desmosomal cadherins. Soluble E-cadherins in sera are elevated in various skin diseases including bullous pemphigoid, pemphigus vulgaris, and psoriasis, but not in patients with burns. Markedly high levels in soluble E-cadherin are demonstrated in patients with metastatic cancers. Microsc. Res. Tech. 38:343–352, 1997. © 1997 Wiley-Liss, Inc.

Granulation‐like, flesh colored tumors developed in the verrucous plaques of a 70‐year‐old man and a 86‐year‐old man. The verrucous plaques, which had appeared more than 15 or 20 years earlier, were found to be a common type of seborrheic keratosis. The newly appearing tumors histologically consisted of large, glycogen‐rich, clear epidermal cells and surrounding basaloid cells, resulting in multilobular architecture. Dyskeratotic cells and parakeratotic plugs showing trichilemmal keratinization were present in both cases. Bowenoid changes were seen in a part of the plaque from one case, and many mitotic cells and an invading figure in the tumorous cells of the other. These cases demonstrate the rare possibility of trichilemmal neoplasms developing in a common type of seborrheic keratosis.

A 72‐year‐old Japanese woman developed small, asymptomatic, subepidermal vesicles on the limbs, back, chest and abdomen. Immunoperoxidase staining of the lesional skin showed linear deposition of IgG, IgA and C3along the basement membrane zone (BMZ), and indirect immunofluorescence studies revealed IgG and IgA class circulating anti‐BMZ auto‐antibodies in the patient's serum. Ultrastructurally, the vesicles were caused by dermo‐epidermal separation at the lamina lucida, and the immune deposits were located just beneath the basal lamina in a band‐like pattern. Immunoelectron microscopic observation of normal human skin incubated with the patient's serum using an organ culture system revealed that the anti‐BMZ antibodies reacted with the anchoring fibrils. Administration of dapson was not effective, but betamethasone was. This case of subepidermal bullous disease is unique and cannot be classified into any existing category of bullous dermatoses.

Electron microscopy of the skin lesions of a patient with the classical type of dermatitis herpetiformis (DH), showing granular IgA deposits beneath the epidermis and gluten‐sensitive enteropathy, revealed that the initial changes of the vesicular or blister formation are neutrophilic invasion above the basal lamina and consequent degeneration of the basal cells. Retrospective electron microscopic studies using the refixation‐reembedding method performed on four previous cases of classical DH revealed the coexistence of degeneration of the basal cells and dermal vacuolization in two cases, blister formation above the basal lamina in one case, and blister formation in the uppermost dermis with basal lamina remaining along the blister roof in one case. The infiltrating inflammatory cells in the skin of classical type of DH seem to injure the epidermal‐dermal junction, including the basal cells and the uppermost dermis, to initiate the blister or vesicular formation.

Keratinocytes freshly isolated from unwounded skin could not attach and spread on fibronectin (FN)-coated culture dishes and could not bind and phagocytose FN-coated beads. These adhesive functions were activated, however, in Keratinocytes that were isolated from healing wounds. Moreover, adhesiveness of basal Keratinocytes to FN substrata was activated during epidermal cell or explant culture. Activation was specific for attachment to FN compared to other adhesion ligands, and occurred even when epidermal cells were cultured on collagen, basement membrane matrix, or lectin-coated substrata. Biochemical studies showed that Keratinocytes have a 140× 103Mr FN receptor analogous to the fibroblast receptor for FN, and that this receptor is expressed in activated Keratinocytes but not in Keratinocytes freshly isolated from unwounded skin. The absence of FN receptors from Keratinocytes in unwounded skin is not surprising since the basal Keratinocytes of the epidermis are attached to a basement membrane containing laminin and type IV collagen. During wound repair, however, these cells migrate over or through a FN-coated matrix. Consequently, expression of FN receptors may be an essential feature of healing. Believing that FN is the required substratum for keratinocyte migration during wound healing, we have initiated clinical studies to determine if topical application of FN is useful as a therapy for non-healing cutaneous ulcers.

Hemangiomatous tumors were induced in Balb/c nude mice by inoculating F‐2 cells (5 times 106) from a novel tumorigenic murine endothelial cell line which had been established and maintained in our laboratories. These tumors were morphologically investigated in the course of development. Subcutaneous hemorrhage was observed at the inoculation site within 12 hours after the injection of F‐2 cells, followed by development of skin tumors of various sizes at the same sites. They were dome‐shaped, glossy surfaced, black, soft tumors. Mice finally died of massive blood loss due to internal and/or external hemorrhage (on day 10–77). Light microscopically, F‐2 cells formed aggregates immediately after inoculation and then branched into a network of channels and cysts containing erythrocytes. Thereafter, spongiform structures composed of various sizes of cysts appeared with subsequent formation of a single large blood‐filled cyst lined by one or two layers of thin cells. Under an electron microscope, F‐2 cells, possessing large amounts of cytoplasm, formed narrow spaces which were occasionally incomplete with ambiguous basal lamina at the early stages. However, later, in large cysts, they became attenuated, tightly connected, and produced complete lumen surrounded by a basal lamina. Immuno‐histological demonstration of H‐2 K, D antigen showed that tumors induced by F‐2 cells mainly consisted of the inoculated F‐2 cells. These results indicate that F‐2 presents a good experimental system for investigation of vascular endothelial cell tumorigenesis and differentiation.

Flowcytometry demonstrated that murine endothelial cell line F‐2 expresses MHC class I antigen, FcR II, Mac‐1 and vascular cell adhesion molecule‐1 (VCAM‐1), but not intercellular adhesion molecule‐1 (ICAM‐1) and class II antigen. However, co‐culturing with TNF‐α for 24 hr resulted in the increased expression of ICAM‐1, and the decreased expression of VCAM‐1. IL‐1α and IFN‐γ exerted this regulatory effect on VCAM‐1 but not on ICAM‐1. T (Con A blast) and B (LPS blast) cells adhered to F‐2 cells at almost equal levels, and the adhesion was enhanced 20 to 50% when the cells were precultured with TNF‐α for 24 hr. The inhibition assay using either (anti‐ICAM‐1 + anti‐LFA‐1, lymphocyte function‐associated antigen‐1) or (anti‐VCAM‐1 + anti‐VLA‐4, very late antigen‐4) mAbs demonstrated that the ICAM‐1 system was utilized more preferentially by T than B blasts when F‐2 cells were stimulated with TNF‐α, and the VCAM‐1 system was vice versa under the unstimulated and stimulated conditions. Granulocytes also adhered to F‐2 cells, but no mAbs could inhibit the adhesion. Although F‐2 cells produced a considerable amount of IL‐6, GM‐CSF and neutrophil chemotactic activity, a 24 hr incubation with TNF‐α resulted in an increase of 12 fold in IL‐6 and 3 fold in neutrophil chemotactic activity production.