Observations of cold-induced vasodilation in persons with spinal cord injuries.

STUDY DESIGN: Acute experimental study. OBJECTIVES: Cold-induced vasodilation is a local mechanism of protection against frostbite in non-injured persons. We assessed whether an increase in skin blood flow (SkBF) during local cooling (LC) was observed in individuals with spinal cord injuries (SCIs) and if the response patterns differed between region levels or sites. SETTING: Laboratory of Wakayama Medical University and the affiliated clinics, Japan. METHODS: A local cooler device (diameter 4 cm) was placed on the chest (sensate) and right thigh (non-sensate) in persons with cervical (SCIC; n = 9) and thoracolumbar SCIs (SCITL; n = 9). After the surface temperature under the device was controlled at 33 °C for 10 min (baseline), LC (-0.045 °C/s) was applied and the skin temperature was maintained at 15 and 8 °C for 15 min of each stage. SkBF (laser Doppler flowmetry) was monitored using a 1-mm needle-type probe inserted into its center. RESULTS: The percent change in SkBF (%ΔSkBF) on the chest remained unchanged until the end of 15 °C stage; thereafter, it increased to a level at least 70% greater than the baseline during the 8 °C stage in both groups. The %ΔSkBF on the thigh in both SCIC and SCITL notably increased from 8 and 6 min respectively, during the 8°C stage, compared to 1 min before the stage; however, it did not exceed the baseline level. CONCLUSIONS: An increase in SkBF during LC was observed both in the sensate and non-sensate areas in SCIs, although the magnitude was larger in the sensate area.

Clinical and histological evaluation of a single high energy microwave treatment for primary axillary hyperhidrosis in Asians: A prospective, randomized, controlled, split-area comparative trial.

BACKGROUND AND OBJECTIVES: Microwave treatment is an effective non-invasive treatment option for primary axillary hyperhidrosis (PAH), but the treatment parameters vary and no histopathological studies have been performed to validate clinical outcomes. This study investigated its efficacy and safety and histopathological changes after a single microwave treatment at the maximum energy level for PAH in Asians. MATERIALS AND METHODS: A prospective, clinical, and histological split-area randomized controlled trial (RCT) was performed in Japan. Twenty-six subjects underwent a single microwave treatment at the maximum energy level 5 (5.8 GHz/axilla) on the randomized side of axillae. The primary outcome was the mean difference between both sides in the improvement of modified single-underarm Hyperhidrosis Disease Severity Scale (msHDSS) scores over the course of the 12-month study period from baseline. The secondary outcomes were; the percentage of responders with at least a 2-point drop in the msHDSS score of 3 or 4 group or with a 1-point drop in the msHDSS score of 2 group; the percentage of responders with at least a 75% reduction in sweat weight over 12 months; recurrence rate; and adverse effects. We also performed a histological assessment for 13 selected subjects. RESULTS: Twenty-four subjects completed the study. There were statistically significant differences in improvement of msHDSS scores between the microwave-treated and control sides (P < 0.05) from baseline at 0.5, 1, 3, 6, and 12 months. In the msHDSS score of 3 or 4 group, the percentage of responders with at least a 2-point drop on the microwave-treated side versus control side was 72.2 versus 11.1% (P < 0.05) at 1 month, 83.3 versus 5.6% (P < 0.05) at 3 months, 61.1 versus 38.9% (P = 0.317) at 6 months and 38.9 versus 16.7% (P = 0.264) at 12 months. The percentage of responders with at least a 75% reduction in sweat weight on the microwave-treated side versus control side was 75.0 versus 37.5% at 1 month, 75.0 versus 29.2% at 3 months, 83.3 versus 50.0% at 6 months and 70.8 versus 33.3% at 12 months (all P < 0.05). Recurrence on the microwave-treated side was observed in 4.2% and 12.5% of 24 subjects at 3 and 12 months, respectively. No serious side-effects were noted. Histology showed the diameter and density of secretory eccrine glands and nerve fiber lengths around eccrine glands were significantly decreased after treatment compared to baseline (P = 0.002, 0.027, 0.003, respectively). CONCLUSIONS: A single-session microwave treatment at the maximum energy level significantly improved the PAH of Japanese patients and had minimal side effects. This technique demonstrates that diminished size of secretory eccrine glands and nerve fiber degeneration could be useful markers for predicting the efficacy of the treatment. Lasers Surg. Med. 9999:1-8, 2019. © 2019 Wiley Periodicals, Inc.

A case of alopecia as IgG4-related skin disease.

A 53-year-old man with autoimmune pancreatitis as IgG4-related disease presented alopecia. Immunostaining showed perifollicular infiltration of IgG4-positive cells and perifollicular/intrafollicular infiltration of predominantly CD4-positive cells, especially in the upper and lower parts. Alopecia areata is characterized by perifollicular/intrafollicular lymphocyte infiltration of the lower bulb and inflammation in the upper dermis. We determined the patient had IgG4-related skin disease, rather than alopecia areata. Alopecia as IgG4-related skin disease has not been reported previously.

The Clinical and Histological Effect of a Low-Fluence Q-Switched 1,064-nm Neodymium: Yttrium-Aluminum-Garnet Laser for the Treatment of Melasma and Solar Lentigenes in Asians: Prospective, Randomized, and Split-Face Comparative Study.

BACKGROUND: The low-fluence Q-switched 1,064-nm neodymium:yttrium-aluminum-garnet laser (QSNYL) is popular for melasma treatment among Asians. OBJECTIVE: This study was to evaluate the clinical and histological effects of the low-fluence QSNYL for treatment of melasma and solar lentigenes. MATERIALS AND METHODS: In this randomized split-face clinical study, 22 patients with melasma or solar lentigo received low-fluence QSNYL weekly for 10 sessions on one cheek. The treatment efficacy was determined by Mexameter skin colorimetry, physician and patient assessment, and by evaluating histological changes. RESULTS: The treated sides had statistically significant reductions in the melanin and erythema indices (EI); 50.0% of melasma and 62.5% of solar lentigo patients had >50% clearance after the final treatment. The increased EI, vascularity, and mast cell activity in patients with melasma and large-sized solar lentigo showed no improvement. The recurrence rates were 16.7% and 12.7% for melasma and solar lentigo, respectively. Postinflammatory hyperpigmentation developed in 1 patient, but no serious side effects were noted. CONCLUSION: Low-fluence QSNYL is effective in treating melasma and small type solar lentigo in Asians. The authors' study also demonstrated that lesion thickness, vascularity, and mast cell activity can be used to predict the efficacy of the treatment of these lesions.

Clinical evaluation of glycolic acid chemical peeling in patients with acne vulgaris: a randomized, double-blind, placebo-controlled, split-face comparative study.

BACKGROUND: Glycolic acid (GA) peels are frequently performed as adjuvants to the treatment of facial acne. There have been few clinical trials reported of GA peels for acne in people with darker skin. OBJECTIVES: To determine the safety and efficacy of GA peels in the treatment of moderate acne vulgaris in Asian skin. METHODS: In this prospective, randomized, double-blind, placebo-controlled, split-face clinical trial, 26 patients with moderate acne were treated with 40% GA (pH 2.0) on half of the face and placebo on the other half. The procedure was performed five times at 2-week intervals. RESULTS: The GA sides had statistically significant reductions in acne lesions at each time point from baseline values. There were statistically significant differences between the GA and placebo sides. The GA sides had better responses for noninflammatory lesions than for inflammatory lesions. In bioengineering measurements, sebum levels were statistically significantly reduced after the initiation of therapy on both sides at weeks 8 and 10, but there were no statistically significant differences between the two sides. CONCLUSION: Forty percent GA peels significantly improved moderate acne in this study. It is effective and safe in Asians.

Clinical evaluation of needle-free electronic pneumatic hyaluronic acid injection treatment for facial atrophic acne scars: A prospective, randomized comparative trial.

Acne scars are common but difficult to treat, and an effective new treatment strategy is desired. This prospective, split-face randomized controlled trial was designed to compare the safety and efficacy of needle-free electronic pneumatic hyaluronic acid injection (EPI-HA) treatment for acne scars. Thirty Japanese subjects with moderate to severe facial atrophic acne scars underwent EPI-HA treatment on a randomized side of their face. Three treatment sessions were carried out at 1-month intervals, and the subjects were followed-up for 3 months after the final treatment. Three months after the final treatment, 48.3% of treated sides met the criteria for success, compared with 0% for the control sides (P < 0.0001). Rolling type scars were much improved compared with boxcar types and icepick types. Satisfaction (or better) was reported by 55.2% of subjects at the 3-month follow-up after the final treatment, which was similar to the physicians' assessment. Three-dimensional in vivo imaging analysis detected significant difference in scar reductions between the treated and control sides in the mean scar area, scar depth, and maximum depth of the biggest scar at 1 and 3 months after the final treatment (all P < 0.05). In conclusion, EPI-HA treatment significantly improved rolling facial atrophic acne scars in our Japanese subjects, with minimal side effects.

Analysis of cytokine profiles in sera of single and multiple infantile hemangioma.

Infantile hemangiomas (IH) are benign vascular tumors that are common in infancy. They vary in growth, size, location, and depth, and although most lesions are relatively small, approximately one fifth of patients have multiple lesions. Risk factors for IH include female sex, low birth weight, multiple gestation, preterm birth, progesterone therapy, and family history, but the mechanism that causes multiple lesions is unclear. We hypothesized that blood cytokines are involved as a cause of multiple IHs, and tried to prove this using sera and membrane arrays from patients with single and multiple IHs. Serum samples were obtained from five patients with multiple lesions and four patients with a single lesion, none of which had received any treatment. Serum levels of 20 cytokines were measured using human angiogenesis antibody membrane array. Four of the 20 cytokines (bFGF, IFN-γ, IGF-I, and TGF-ß1) were higher in the patients with multiple lesions than in those with single lesion, with statistically significant difference (p < 0.05). Notably, signal for IFN-γ was evident in all cases with multiple IHs, but was absent in cases with single IH. Although not significant, there was mild correlation between IFN-γ and IGF-I (r = 0.64, p = 0.065), and between IGF-I and TGF-ß1 (r = 0.63, p = 0.066). bFGF levels were strongly and significantly correlated with the number of lesions (r = 0.88, p = 0.0020). In conclusion, blood cytokines could act as a cause of multiple IHs. This is a pilot study with a small cohort, so further large-scale studies are necessary.

Expression of collagen-related piRNA is dysregulated in cultured dermal fibroblasts derived from patients with scleroderma.

PIWI-interacting RNA (piRNA) is a class of recently discovered small non-coding RNAs. piRNAs derive from an initial transcript encompassing a piRNA cluster via a unique biosynthesis process, interact with PIWI proteins, bind to specific targets, and recruit chromatin modifiers to enable transcriptional repression. Abnormal expression of PIWI proteins and piRNAs has been reported in some human cancers, with participation of some PIWI/piRNAs complexes in tumorigenesis and association with cancer prognosis. Their expression in patients with systemic sclerosis (SSc) has not been widely elucidated. PIWI/piRNAs and their role in the pathogenesis of collagen accumulation in SSc was therefore investigated; no difference was found in the PIWIL1-4 levels between normal and cultured SSc dermal fibroblasts. Among piRNAs predicted to target SSc-related molecules, we first found significant piR-32364 up-regulation in SSc dermal fibroblasts, likely due to intrinsic TGF-ß signaling. Forced piR-32364 overexpression in normal fibroblasts significantly reduced COL1A1 expression both at mRNA and protein levels, but not COL1A2. Thus, piR-32364 overexpression in SSc fibroblasts may be the negative feedback against collagen up-regulation, which could suggest the potential of piRNAs as a therapeutic target.

The clinical significance of dupilumab-induced blood eosinophil elevation in Japanese patients with atopic dermatitis.

This study aims to clarify the clinical significance of dupilumab-induced elevation of blood eosinophil in Japanese patients with atopic dermatitis (AD). Eosinophil elevation was defined as ≥ 5% increase of eosinophil percentage within one year after dupilumab initiation. Seven patients (15.7%) were shown to have eosinophil elevation, six of whom developed dupilumab-associated conjunctivitis (DAC) and were accompanied with DAC more frequently than those without eosinophil elevation, with statistically significant difference. Eosinophil percentage resolved spontaneously in all seven patients, including the one without DAC, despite the continuation of dupilumab treatment. None of the patients with eosinophil elevation had cardiac or pulmonary complications attributable to the hypereosinophilia. The patients with eosinophil elevation were all male. Furthermore, none of four patients in whom efficacy of dupilumab was < 25% showed eosinophil elevation. Childhood onset tended to be more common in patients with the elevation of eosinophil. This study suggests that most eosinophil elevation is associated with DAC, and that the eosinophil ratio is a biomarker for DAC.

Forearm porphyrin levels evaluated by digital imaging system are increased in patients with systemic sclerosis compared with patients in pre-clinical stage.

We hypothesized that changes in skin characteristics on the forearm could be useful for early diagnosis of systemic sclerosis (SSc). We used VISIA digital imaging system to investigate this possibility for the first time. Twenty-eight Japanese patients who were diagnosed with typical or very early diagnosis of SSc (VEDOSS) were enrolled in this study, and ten age- and gender-matched patients with other disorders were included as a control group. Eight skin characteristics were analyzed. Our method of evaluating forearm skin characteristics was shown to be reproducible. The scores of WRINKLES, TEXTURE, PORES, and PORPHYRINS were higher in SSc subjects with sclerotic forearm skin (SSc forearm+; 11.004, 5.116, 3.230, and 0.084, respectively) and those without (SSc forearm-: 11.915, 4.898, 2.624, 0.0616, respectively) than in the non-SSc control subjects (10.075, 4.496, 2.459, 0.0223, respectively). Also, the scores of SPOTS, TEXTURE, PORES, UV SPOTS, BROWN SPOTS, and PORPHYRINS were elevated in SSc forearm+ (3.182, 5.116, 3.230, 5.761, 6.704, 0.084, respectively) and SSc forearm- patients (2.391, 4.898, 2.624, 9.835, 5.798, 0.0616, respectively) compared with those with VEDOSS (2.362, 4.738, 2.234, 5.999, 4.898, 0.0169, respectively). We found statistical significance in the difference in score of PORPHYRINS between SSc forearm- and VEDOSS groups (p = 0.044), and between SSc forearm+ and VEDOSS groups (p = 0.012). Therefore, they can be used to differentiate VEDOSS from early or mild SSc cases, which is sometimes clinically problematic. Our study also suggests that the porphyrin research will lead to a better understanding of SSc pathogenesis.

Dupilumab Improves Pruritus in Netherton Syndrome: A Case Study.

The patient was a 26-year-old male. He had red and scaling skin of the entire body since birth, as well as an elevated level of serum IgE. Genetic testing revealed a mutation in the SPINK5 gene, which had confirmed the diagnosis with Netherton syndrome. He has had significant pruritis since birth, and subsequently had symptoms of sleeping disorders and concentration difficulty throughout the day. Since treatment with various antihistamines were not effective, we administered dupilumab and found that it was effective in immediate elimination of pruritus and gradual reduction of the rash. Dupilumab has been administered for one year without any adverse events or recurrence of symptoms. Although studies have previously described cases who used dupilumab for Netherton syndrome, reported effects have been limited or transient. Additional studies are needed to confirm the effect of dupilumab for Netherton syndrome, which currently lack any effective treatment strategies.

Analysis of onset and clinical characteristics in Japanese patients with infantile hemangioma.

Infantile hemangioma (IH) is a common benign tumor during infancy, although the detailed mechanism behind it has not been fully elucidated. Based on previous studies, we hypothesized that formation of hemangioma might be triggered by secondary physiological events (perinatal hypoxia or mechanical stress during delivery) in patients carrying germline risk mutations. We aimed to clarify the mechanism by evaluating whether head and neck lesions were more frequent in patients in who IH appeared after birth compared with those in who it was present at birth. Clinical data of 62 lesions in 51 patients with IH were collected. All patients were analyzed for correlation of onset with gender, localization, family histories, gestational age, birth weight, and clinical subtypes. Distribution of lesions on the head and neck was slightly more frequent in the after-birth IH group, compared with those with IH present at birth, but without significant difference (47.6% vs. 40.0%, p = 0.32). On the other hand, the ratio of superficial and deep type IH at birth was significantly altered compared with that in IH after birth (19:0 vs. 26:7, p = 0.039). In addition, IHs appearing after birth tended to more commonly have multiple lesions than those with IH present at birth, with statistically significant difference (25.8% vs. 0%, p = 0.0164). There may therefore be different triggers for IHs at birth and IH after birth. Further studies with greater number of patients are necessary to validate these findings.

The clinical significance of cytokeratin 20 staining pattern in Merkel cell carcinoma.

In the present study, to identify the clinical significance of the cytokeratin (CK) 20 staining pattern in Merkel cell carcinoma (MCC), we retrospectively analyzed the major clinicopathological and immunohistochemical characteristics of 12 cases of MCC. Typical dot-like pattern was seen in eight of our patients, while four patients showed peripheral staining pattern. Interestingly, all cases of MCC with dot-like CK20 tumor cells occurred in the head and neck region, while those with peripheral CK20 pattern tended to be located in other lesions (forearm, knee, or buttock): The difference of frequency in the head and neck regions was statistically significant. Dot-like CK20 staining pattern may therefore be resulted from ultraviolet exposure. Additionally, although without significance, metastasis was more frequent in those with dot-like CK20 than in peripheral CK20 staining: All patients with peripheral CK20 pattern had complete remission by surgical excision with or without radiation therapy. CK20 staining pattern may be a novel predictor of prognosis.

Effects of low-dose Aloe sterol supplementation on skin moisture, collagen score and objective or subjective symptoms: 12-week, double-blind, randomized controlled trial.

Daily oral intake of 40 µg Aloe sterol was shown in a double-blind clinical trial to significantly increase skin barrier function, moisture and elasticity. Ultrasonographic results also suggested that the intake of Aloe sterol increases collagen content in the dermis. Here, we evaluate the effects of a much smaller dose of Aloe sterol, approximately half that used previously, on skin functions in more detail. This is a monocentric, double-blind, randomized, placebo-controlled, supplementation study of the effects of low-dose Aloe sterol on skin transepidermal water loss, hydration, collagen score, evaluation of objective or subjective symptoms, and safety after 12 weeks of daily intake. We randomly administrated either Aloe sterol or placebo to 122 healthy volunteers. Transepidermal water loss was significantly reduced and collagen score was increased in the Aloe sterol group compared with the placebo group at week 12. In the Aloe sterol group, there was significant improvement of objective skin condition (face erythema and pruritus of inner and outer arms) at week 12 compared with week 0, but not in the placebo group. Subjectively, there was significant improvement of visual analog scale of skin acne, fingernail brittleness and constipation in the Aloe sterol group. According to subgroup analysis, although not planned before the study initiation, subjects with dry skin in the Aloe sterol group had significantly increased skin hydration values at week 12 compared with the placebo group. Our results confirmed that even low-dose Aloe sterol ingestion improves skin moisture by promoting skin barrier function and dermal collagen production, which contributes to maintenance of healthy skin.

Change of serum cytokine profiles by propranolol treatment in patients with infantile hemangioma.

Infantile hemangioma is a benign cutaneous tumor, which sometimes rapidly enlarges, causes cosmetic problem, destroys normal tissue, and possibly threatens life. Dye lasers, steroid administration, and watchful waiting had been the treatment options for infantile hemangioma, but in recent years propranolol therapy has become available. The mechanism underlying the action of propranolol, however, is still unknown. We hypothesized that cytokines whose expressions change before and during the treatment are responsible for the efficacy of the drug. This study aims to prove the hypothesis using patients' sera and membrane array. In this study, the serum cytokine concentrations of five patients with infantile hemangioma were measured using membrane array of 20 angiogenic cytokines. We compared them before and during propranolol treatment to identify the cytokines responsible for the effect of propranolol. Signals for angiogenin, epidermal growth factor (EGF), platelet-derived growth factor-BB (PDGF-BB), regulated on activation, normal T-cell expressed and secreted chemokine (RANTES), tissue inhibitor of metalloproteinases 1 (TIMP-1), and tissue inhibitor of metalloproteinases 2 (TIMP-2) were evident in all five cases before treatment. Furthermore, PDGF-BB was the only cytokine of which concentration was decreased during treatment with statistically significant difference. This report is a pilot study with a small number of samples, and further detailed research with increased number of samples is necessary. Nonetheless, our results suggest that PDGF-BB may be involved in the action of propranolol. In addition, its serum concentration can be utilized as a potential marker of the therapeutic effect.

Phenol peels as a novel therapeutic approach for actinic keratosis and Bowen disease: prospective pilot trial with assessment of clinical, histologic, and immunohistochemical correlations.

BACKGROUND: Although chemical peels may be used for precancerous lesions, no histologic or immunohistochemical studies have been performed to validate clinical impressions and/or outcome. OBJECTIVE: Our purpose was to investigate the efficacy and prognostic relevance of phenol peels in Japanese patients with actinic keratosis and Bowen disease using clinical and histologic criteria. METHODS: A total of 46 patients were treated with phenol peels, and followed up for at least 1 year after treatment. Biopsy specimens were taken before and after treatment. Cases of complete response were classified by the number of treatment sessions. We evaluated parameters for epidermal thickness, proliferation, dysplasia, and apoptosis, and clinical characteristics to correlate phenol peels with assessments of efficacy, patient-selection criteria, and risk for transformation to cutaneous squamous cell carcinoma. RESULTS: There were 39 (84.8%) patients with a complete response after one to 8 treatment sessions. Statistically, differences in clinical improvement with peels and the number of treatment sessions correlated with histology, personal history of skin cancer, tumor thickness, and cyclin A expression. LIMITATIONS: This study was a prospective pilot trial. Blinded, placebo-controlled, randomized studies would be ideal. CONCLUSION: We conclude that phenol peels are very effective for treating precancerous lesions of actinic keratosis and Bowen disease. In addition, our study clearly demonstrates that tumor thickness and cyclin A could be specific and useful markers as adjunctive diagnostic tools to predict the efficacy of phenol treatment of these lesions.

Difference in distribution of malignant melanoma and melanocytic nevus in the palm and finger.

We conducted a study to try to plot the lesions of melanocytic nevus and malignant melanoma on the palm and fingers, and compared them to identify the different distribution pattern of both lesions. Data on 8 patients with melanomas (4 male and 4 female) and 26 patients with melanocytic nevus (6 male and 20 female) of palm and finger pulp who visited Wakayama Medical University Hospital between 1986 and 2018 was retrospectively collected. We found that all of the 8 lesions of melanoma were located on the finger pulps and distal to the 'distal transverse crease' of the palm, and that melanomas were not present proximal to the transverse crease. On the other hand, melanocytic nevus was present in the proximal area to the distal transverse crease of the palm more frequently than melanomas (50.0% vs. 0%), and there was statistically significant difference (p = 0.011 by Fisher's exact probability test). From these observations, our findings may reveal the contribution of mechanical stress to the cause of palmar melanoma, and may facilitate clinical differentiation between malignant melanoma and melanocytic nevus by the localization. Further studies with increased number of patients are needed to validate the finding.

Peripheral blood eosinophilia is associated with the presence of skin ulcers in patients with systemic sclerosis.

The role of eosinophil in systemic sclerosis (SSc) is still controversial. In the present study, the relationship between skin ulcers and peripheral blood eosinophilia were analyzed in patients with SSc. We retrospectively investigated the clinical records of all patients who were diagnosed with SSc on the basis of American College of Rheumatology/European League Against Rheumatism 2013 criteria, and were followed up for more than 2 years at Wakayama Medical University. As a result, maximum eosinophil counts during the 2-year follow-up period were 20-983/mm3 (median, 270), whereas maximum eosinophil percentages were 0.5-14.1% (median, 5.3%) in peripheral blood of 47 SSc patients. On the other hand, patients with skin ulcers during the 2-year follow up showed significantly increased maximum eosinophil counts compared with those without (median, 520 vs 228/mm3 ; P = 0.0001). Maximum eosinophil percentage was also significantly higher in patients with skin ulcers (median, 9.7% vs 4.6%; P = 0.00001). To note, in four of the nine patients with skin ulcers, the timing of emerging of the maximum eosinophil counts was associated with the ulcer development during the 2-year follow up. These results suggest that eosinophils are involved in the pathogenesis of vascular dysfunction of SSc. Larger studies should be performed to clarify the exact mechanism of ulcer formation caused by eosinophilia in SSc patients in the future.

Distribution analysis of infantile hemangioma or capillary malformation on the head and face in Japanese patients.

Infantile hemangioma is one of the most common tumors in infancy. Delivery may be a clue for the trigger of infantile hemangioma formation in the head and face areas. In this study, we tried to plot localization of infantile hemangioma as well as capillary malformation on the head and face, and compared them to identify their characteristics and risk factors. The distribution of 104 lesions in 100 patients with infantile hemangioma was as follows: 32 lesions on the head, 12 on the forehead, 57 on the cheek and three in the jaw area. We could not find a statistically significant correlation of the distribution with three clinical subtypes (superficial, deep and mixed), sex or size of the lesions. However, the lesions in the jaw or chin areas were significantly less frequent than other areas (P = 0.0008 or 0.03, respectively). This tendency was not found in 40 patients with capillary malformation. Mechanical stress to jaw or chin areas may be less than other areas in normal cephalic delivery. Considering the emergence after birth and age-dependent involution of infantile hemangioma, we speculate that physiological events including perinatal hypoxia or mechanical stress during delivery as the trigger of hemangioma formation. Taken together, our results may reveal the contribution of mechanical stress to the trigger of infantile hemangioma, not capillary malformation, and may facilitate clinical differentiation between the two diseases by their localization. Further studies with an increased number of patients will be necessary to validate the finding.

Aberrant expression of histo-blood group A type 3 antigens in vascular endothelial cells in inflammatory sites.

Histo-blood group ABH antigens are widely distributed in human tissues. The epitopes of ABH antigens are carried by at least four different peripheral core isotypes of internal carbohydrate backbones (type 1-4). Each type of ABH antigen is expressed tissue specifically, and aberrant expression of ABH antigens is often observed during oncogenesis. We immunohistochemically examined the expression of A type 3 antigens in wounded and diseased skin tissues (A and AB blood groups). In uninjured skin, the expression of A type 3 antigens was restricted to the eccrine sweat gland. In addition to the sweat glands, A type 3 antigens were found in vascular endothelial cells of the wound sites. The extent of A type 3 antigens expression related to postinfliction intervals. A significantly higher expression rate of A type 3 antigens in endothelial cells was also observed in diseased skin, suggesting that inflammation might induce A type 3 antigen expression in endothelial cells. Double-color immunofluorescence staining of the specimens showed that von Willebrand factor (vWF) was a core-protein of A type 3 determinants aberrantly expressed in endothelial cells in inflamed tissues, suggesting that aberrant expression of A type 3 antigens is involved in stabilization of vWF in inflammation.