Hirohiko Sueki

Effects of α-hydroxy acids on photoaged skin: Apilot clinical, histologic, and ultrastructural study

Background : α-Hydroxy acids (AHAs) have been reported to improve aging skin. The mechanisms of action of AHAs on epidermal and dermal compartments need clarification. Objective : Our purpose was to determine the effects of AHAs on photoaged human skin by clinical and microanalytic means. Methods : Patients applied a lotion containing 25% glycolic, lactic, or citric acid to one forearmand a placebo lotion to the opposite forearm for an average of 6 months. Thickness of forearm skin was measured throughout the study. Biopsy specimens from both forearms were processed for analysis at the end of the study. Results : Treatment with AHAs caused an approximate 25% increase in skin thickness. The epidermis was thicker and papillary dermal changes included increased thickness, increased acid mucopolysaccharides, improved quality of elastic fibers, and increased density of collagen. No inflammation was evident. Conclusion : Treatment with AHAs produced significant reversal of epidermal and dermalmarkers of photoaging.

Pigmented malignant pilomatrixoma: report of a case and review of the literature.

An unusual variant of malignant pilomatrixoma displaying melanization of epithelial elements is described. Melanization is a rare event even in the benign form of this adnexal neoplasm. Previously reported cases of malignant pilomatrixoma are re‐viewd; none containing pigment have been previously reported to our knowledge. Possible etiologies for lack of pigment in most benign and malignant pilomatrixoma are discussed .

Eccrine syringofibroadenoma (Mascaro): an ultrastructural study

To confirm the eccrine acrosyringeal differentiation of eccrine syringofibroadenoma (ESFA) and to elucidate the histogenesis of its angiofibrotic stroma, a case of ESFA from a 45‐year‐old man was examined by light and electron microscopy. Histologically, the parenchyma featured anastomosing, slender epithelial cords containing small cuboidal cells and occasional duct‐like structures. The stroma had increased numbers of mast cells, increased capillaries with swollen endothelial cells, and prominent fibrosis. Ultrastructurally, the following findings were characteristic of ESFA: a) abundant glycogen particles in epithelial cells, b) numerous intracytoplasmic and extracellular spaces lined with microvilli, c) intraepithelial duct formation, consisting of microvilli, vesicles, rod‐shaped dense bodies, multivesicular dense bodies, and peripheral network of tonofilaments, and d) large numbers of mast cells, closely associated with fibroblasts, surrounding increased numbers of capillaries containing swollen endothelial cells. These ultrastructural features support the acrosyringeal differentiation of ESFA. We hypothesize that mast cell hyperplasia and degranulation may play an important role in the formation of the angiofibrolic stroma.

Increased factor XIIIa transglutaminase expression indermal dendrocytes after treatment with α-hydroxy acids: Potential physiologic significance

BACKGROUND Topical alpha-hydroxy acids (AHAs) have been shown to improve photoaging in human skin. OBJECTIVE We studied factor XIIIa transglutaminase expression in dermal dendrocytes (DDs) and mast cell degranulation after treatment of the skin with AHAs. METHODS Skin biopsy specimens obtained from patients after 4 to 8 months of treatment with lotions containing 25% AHAs were evaluated for factor XIIIa transglutaminase expression with immunoperoxidase and electron microscopy. Immunoperoxidase-stained sections were studied by means of semiquantitative methods and image analysis. Mast cell degranulation was studied by image analysis. RESULTS Increased factor XIIIa transglutaminase expression was seen after treatment with AHAs. All treated sites had increased scores compared with control sites by semiquantitative methods. Seventy-five percent of treated sites showed an increased mean area over control sites of factor XIIIa transglutaminase positivity with image analysis. These results correlated with an increased level of mast cell degranulation in treated sites and with activation of DDs as seen by electron microscopy. CONCLUSION Treatment of the skin with AHAs leads to mast cell degranulation and increased expression of factor XIIIa transglutaminase by activated DDs. Mast cell degranulation may lead to activation of DDs and increased factor XIIIa transglutaminase expression, via the action of tumor necrosis factor-alpha. We speculate that clinical and histologic improvement in photoaged skin after treatment with AHAs may be somehow related to this process.

Structural diversity of mast cell granules in black and white skin

Background  There are conflicting reports of structural differences between black and white skin, other than pigmentary differences.

Quantitative and ultrastructural analysis of inflammatory infiltrates in male pattern alopecia

In order to determine whether lymphocytic inflammation around the lower infundibula in male pattern alopecia is incidental or a general phenomenon, we performed morphometric and ultrastructural analysis of inflammatory infiltrates in the transitional zones of the vertex and occipital hairy scalps of 19 patients with male pattern alopecia. Six normal subjects served as controls. The number of inflammatory infiltrates around the follicular infundibula of the alopecic vertices and non-alopecic occiputs of male pattern alopecia patients was significantly greater than the corresponding control value. The number of mast cells in the widened fibrous tracts in the vertices of male pattern alopecia patients was significantly greater than those in the adventitial fibrotic sheaths of control subjects and the non-alopecic occiputs of male pattern alopecia patients. These data support the idea that the inflammatory process may be, at least in part, responsible for the development of male pattern alopecia.

Immunolocalization of aquaporin‐5 in normal human skin and hypohidrotic skin diseases

Aquaporin (AQP)‐5 has been shown to be expressed in the secretory parts of mouse, rat and horse sweat glands. However, the precise localization of AQP‐5 in normal and diseased human skin has not been fully determined. The aim of the present study was to further clarify the immunolocalization of AQP‐5 in normal human skin and hypohidrotic skin diseases. Normal human scalp skin and biopsies from skin affected by hypohidrotic diseases were analyzed for AQP‐5 and/or dermcidin expression by immunohistochemistry, immunofluorescence and/or immunoelectronmicroscopy. AQP‐5 was expressed on the apical and basolateral plasma membranes of the clear cells in eccrine sweat coils, but not in ductal components or apocrine glands. Numbers of AQP‐5‐positive coils in the secretory part of eccrine sweat glands were decreased in Sjögren’s syndrome, but not in skin affected by idiopathic segmental anhidrosis or idiopathic pure sudomotor failure. AQP‐5 was mostly localized to the plasma membranes of clear cells in the secretory coils of eccrine sweat glands, suggesting that it plays a role in producing the primary sweat fluid.

Immunohistochemical and ultrastructural characterization of tonofilament and hemidesmosome abnormalities in a case of epidermolysis bullosa herpetiformis (Dowling-Meara)

BACKGROUND A neonate with epidermolysis bullosa herpetiformis (EBH) (Dowling-Meara) had an undescribed ultrastructural and immunohistochemical abnormality. OBJECTIVE The objective was to clarify the ultrastructural and immunohistochemical abnormalities in EBH to gain further insight into the pathogenesis of this disorder. METHODS Tissue from the patient was studied with routine histochemistry, electron microscopy, and immunohistochemistry. RESULTS Excessive clumping of tonofilaments on electron microscopic examination, anomalous hemidesmosomes, and immunohistochemical evidence of aberrant keratin expression by basal epidermal cells was found. CONCLUSION This case of EBH provides further evidence for primary abnormalities involving cytoskeletal-membrane attachment plaque formation in this rare disorder.

Cutaneous toxicity of chemical irritants on hairless Guinea pigs.

To evaluate the toxicity of irritant chemicals on animal skin, investigators have frequently had to apply high concentrations, owing to the fact that its susceptibility is less than that of human skin. High concentrations are so damaging to tissue that specific effects are obscured on the various layers. The aim of the present study was to elucidate the effects of a variety of irritating chemicals on the skin of hairless guinea pigs. Graded concentrations of these irritating substances were applied to the back for varying periods. Histologic changes were analyzed by light and electron microscopy. The structural alterations varied greatly among the chemicals, reflecting quite different mechanisms of action. Hairless guinea pigs are quite susceptible to chemical injury, especially to their hair follicles and dermal components. The hairless guinea pig appears to be an advantageous model to assess the acute and chronic effects of chemical irritants.

Vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK 222584 inhibits both the induction and elicitation phases of contact hypersensitivity.

Vascular endothelial growth factor (VEGF) and its endothelial cell receptors (VEGFR) have been shown to be involved in the pathogenesis of the contact hypersensitivity (CHS) reaction. Previous studies have demonstrated that anti‐VEGFR‐2 antibody significantly suppresses the elicitation phase of CHS but does not affect the induction phase. PTK787/ZK 222584 (1‐[4‐chloroanilino]‐4‐[4‐pyridylmethyl] phthalazine succinate; PTK/ZK) is a potent inhibitor of VEGFR tyrosine kinases. To test the effect of PTK/ZK on the induction and elicitation phases of CHS separately, we used an established method of CHS assay‐sensitization and challenge in BALB/c mice. Either 50 mg/kg/day PTK/ZK or vehicle serving as a control was administered orally in the induction or elicitation phases separately. In the afferent phase, flow cytometry of skin‐draining lymph node cells revealed that the migration of Langerhans cells was suppressed in the mice treated with PTK/ZK at sensitization. The degrees of ear swelling at 24 and 48 h were significantly diminished in mice treated with PTK/ZK at sensitization (P < 0.05). In the efferent phase, the degrees of ear swelling at 24 h (P < 0.01) and 48 h (P < 0.05), ear blood flow at 24 and 48 h (P < 0.01), and production of VEGF in the epidermis at 24 h (P < 0.05) were significantly suppressed in mice treated with PTK/ZK at elicitation. These findings and previous demonstrations suggest that both VEGF R‐1 and VEGF R‐2 are needed during the induction phase, and that VEGFR‐2 has a pivotal role in the elicitation phase of the CHS reaction.