赤松 浩彦

Previous studies have demonstrated that the numbers of interfollicular epidermal stem cells (IFE-SCs) and dermal stem cells (DSCs) decrease with age and that this decrease is attributed to the age-related deterioration of skin homeostatic functions and the delay in wound healing. Meanwhile, functional decline in the stem cells is also considered to be responsible for the deteriorated skin homeostatic functions and the delayed wound healing associated with aging. In the present study, we focused on epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) signaling and fibroblast growth factor-2/fibroblast growth factor receptor (FGF2/FGFR) signaling to analyze the age-related changes. Immunohistological analysis revealed that the expressions of EGFR and FGFR1 declined in IFE-SCs and DSCs with age, respectively. Additionally, IFE-SCs and DSCs isolated from the skin samples of elderly subjects exhibited lowered responsiveness to EGF and FGF2, respectively. These results suggest that the lowered responsiveness of the skin stem cells to growth factors may be a factor involved in the age-related deterioration of skin regenerative functions during wound healing and skin homeostatic functions. We hope that homeostatic and wound healing functions in the skin could be maintained if the decreased expressions of EGFR and FGFR1 in IFE-SCs and DSCs, respectively, can be suppressed.

BACKGROUND: Age-related thinning and reduced cell proliferation in the human epidermis are associated with the accumulation of senescent cells and decreases in the number and function of epidermal stem cells. OBJECTIVE: This study examined the expression of INHBA/Activin-A in human epidermis and expression differences with age, and the effect of Activin-A on epidermal stem/progenitor cells. METHODS: Immunohistochemical staining was used to analyze age-related changes in the expression of INHBA/Activin-A in the epidermal tissue of young and old subjects. Epidermal INHBA/Activin-A expression levels, epidermal morphology, and the number of epidermal stem/progenitor cells or proliferating cells were investigated using older abdominal skin samples. The effects of Activin-A on the development of a three-dimensional (3D) reconstructed epidermis and cell proliferation were also assessed. RESULTS: INHBA/Activin-A expression levels in the human epidermis increased with age, although they varied among individuals. In the epidermis of older abdominal skin samples, INHBA/Activin-A expression levels negatively correlated with epidermal thickness, the rete ridge depth and the interdigitation index. The proportion of epidermal stem/progenitor cells and proliferating cells decreased with increases in INHBA/Activin-A expression levels. Activin-A had no effect on the differentiation of keratinocytes in the 3D-reconstructed epidermis; however, thinning of the 3D epidermis was noted. Moreover, the addition of Activin-A inhibited the proliferation of epidermal stem/progenitor cells in a concentration-dependent manner. CONCLUSIONS: Age-related increased in INHBA/Activin-A expression levels were observed in the human epidermis, and may contribute to epidermal thinning and decreases in the number of epidermal stem/progenitor cells and proliferative activity.

AIMS: Although skin manifestations are common in diabetic patients, its characteristics are poorly identified. This study explored the differentiation process of keratinocytes in type 2 diabetes mellitus (T2DM) in vivo. METHODS: Back skin of T2DM model KKAy/TaJcl mice (KKAy) and C57BL/6JJcl mice (control) aged 8 and 12 weeks was used. The mRNA expression of differentiation markers of keratinocytes was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of each marker in situ was examined immunohistochemically. RESULTS: KKAy mice showed hyperglycemia versus control mice. The histological findings showed increased thickness and structural impairment of epidermal tissue in KKAy mice. The qRT-PCR revealed that the expression of integrin beta 1 and keratin 14 in KKAy and control mice was identical. However, the expression of involucrin at 8 weeks, keratin 10 at 12 weeks, and filaggrin and loricrin at 8 and 12 weeks was decreased in KKAy mice. Immunohistochemical findings showed that filaggrin was markedly decreased in KKAy mice, though Ki-67 remained unchanged. CONCLUSION: The terminal differentiation process was impaired in the diabetic skin, while keratinocyte proliferation was preserved. Damaged terminal differentiation of keratinocytes may contribute to impairment of the skin barrier function in diabetic dermatoses.

BACKGROUND: Capillary structural abnormalities cause skin disorders. Mottled redness, i.e., skin redness unevenness, may appear on the sun-exposed skin, suggesting capillary structural abnormalities, although its mechanism remains unclear. OBJECTIVE: To observe the capillary structures in the sun-exposed skin where skin redness unevenness is likely to occur, and clarify the mechanism of capillary structural abnormalities. METHODS: The tissue structures in the skin with skin redness unevenness were observed by LC-OCT. Subsequently, immunostaining of the sun-exposed skin where skin redness unevenness is often observed, was performed. Vascular endothelial cells were UV-irradiated to analyze the expression and functions of genes involved in the capillary structures and morphogenesis. RESULTS: The skin with skin redness unevenness exhibited scattering of dilated tubular tissue and disturbance of distribution uniformity. Immunostaining of the sun-exposed skin that were more likely to be exposed to UV rays also revealed similarly disorder of capillary structures. In addition, UVA-irradiated vascular endothelial cells exhibited increased expression of ETBR, involved in telangiectasia, decreased expression of BMPR2, involved in the morphogenesis and maintenance of the blood vessels, and reduced migration of the capillaries. CONCLUSION: UV rays alter ETBR and BMPR2 expression in the skin capillaries, and cause partial dilation and decreased migration, resulting in capillary structural abnormalities and causing skin redness unevenness.

The self-duplication and differentiation of dermal stem cells are essential for the maintenance of dermal homeostasis. Fibroblasts are derived from dermal stem cells and produce components of connective tissue, such as collagen, which maintains the structure of the dermis. Cell-cell communication is required for the maintenance of tissue homeostasis, and the role of exosomes in this process has recently been attracting increasing attention. Dermal stem cells and fibroblasts have been suggested to communicate with each other in the dermis; however, the underlying mechanisms remain unclear. In the present study, we investigated communication between dermal stem/progenitor cells (DSPCs) and fibroblasts via exosomes. We collected exosomes from DSPCs and added them to a culture of fibroblasts. With the exosomes, COL1A1 mRNA expression was up-regulated and dependent on the Akt phosphorylation. Exosomes collected from fibroblasts did not show the significant up-regulation of COL1A1 mRNA expression. We then performed a proteomic analysis and detected 74 proteins specific to DSPC-derived exosomes, including ANP32B related to Akt phosphorylation. We added exosomes in which ANP32B was knocked down to a fibroblast culture and observed neither Akt phosphorylation nor enhanced type I collagen synthesis. Additionally, an immunohistochemical analysis of skin tissues revealed that ANP32B expression levels in CD271-positive dermal stem cells were lower in old subjects than in young subjects. These results suggest that DSPCs promote type I collagen synthesis in fibroblasts by secreting exosomes containing ANP32B, which may contribute to the maintenance of skin homeostasis; however, this function of DSPCs may decrease with aging.

Emerging evidence has pointed to the noxious effects of senescent cells in various tissues, and senescent cells in the epidermis are known to accumulate with age. We hypothesized that there is a mechanism by which senescent cells in the epidermis are preferentially removed and that the function of such removal mechanism declines as age increases. In this study, we investigated whether Notch signalling is involved in such senescent cell removal. We found that Notch1 receptor was expressed more highly in p16INK4a-positive senescent cells than in surrounding cells in human epidermis both in young and old subjects. On the other hand, the expression of its ligand JAG1 was decreased in the epidermis of aged subjects. When normal epidermal cells and UVB-irradiated senescent cells were mixed and three-dimensional reconstructed epidermis was developed in vitro, the senescent cells were preferentially removed from the basal layer and located in the upper layer. We also found that the depletion of senescent cells from the basal layer was suppressed by JAG1 knockdown in normal cells or using a Notch signalling inhibitor. From these results, Notch signalling may be involved in senescent cell removal in the epidermis and the age-related decrease of JAG1 expression in the basal layer may lead to accumulation of senescent cells owing to reduced activation of Notch signalling.

Currently, human-skin derived cell culture is a basic technique essential for dermatological research, cellular engineering research, drug development, and cosmetic development. But the number of donors is limited, and primary cell function reduces through cell passage. In particular, since adult stem cells are present in a small amount in living tissues, it has been difficult to obtain a large amount of stem cells and to stably culture them. In this study, skin derived cells were isolated from the epidermis, dermis, and adipose tissue collected from single donor, and immortalization was induced through gene transfer. Subsequently, cell lines that could be used as stem cell models were selected using the differentiation potential and the expression of stem cell markers as indices, and it was confirmed that these could be stably cultured. The immortalized cell lines established in this study have the potential to be applied not only to basic dermatological research but also to a wide range of fields such as drug screening and cell engineering.

INTRODUCTION: The skin is comprised of various kinds of cells and has three layers, the epidermis, dermis and subcutaneous adipose tissue. Stem cells in each tissue duplicate themselves and differentiate to supply new cells that function in the tissue, and thereby maintain the tissue homeostasis. In contrast, senescent cells accumulate with age and secrete senescence-associated secretory phenotype (SASP) factors that impair surrounding cells and tissues, which lowers the capacity to maintain homeostasis in each tissue. Previously, we found Gremlin 2 (GREM2) as a novel SASP factor in the skin and reported that GREM2 suppressed the differentiation of adipose-derived stromal/stem cells. In the present study, we investigated the effects of GREM2 on stem cells in the epidermis and dermis. METHODS: To examine whether GREM2 expression and the differentiation levels in the epidermis and dermis are correlated, the expressions of GREM2, stem cell markers, an epidermal differentiation marker Keratin 10 (KRT10) and a dermal differentiation marker type 3 procollagen were examined in the skin samples (n = 14) randomly chosen from the elderly where GREM2 expression level is high and the individual differences of its expression are prominent. Next, to test whether GREM2 affects the differentiation of skin stem cells, cells from two established lines (an epidermal and a dermal stem/progenitor cell model) were cultured and induced to differentiate, and recombinant GREM2 protein was added. RESULTS: In the human skin, the expression levels of GREM2 varied among individuals both in the epidermis and dermis. The expression level of GREM2 was not correlated with the number of stem cells, but negatively correlated with those of both an epidermal and a dermal differentiation markers. The expression levels of epidermal differentiation markers were significantly suppressed by the addition of GREM2 in the three-dimensional (3D) epidermis generated with an epidermal stem/progenitor cell model. In addition, by differentiation induction, the expressions of dermal differentiation markers were induced in cells from a dermal stem/progenitor cell model, and the addition of GREM2 significantly suppressed the expressions of the dermal differentiation markers. CONCLUSIONS: GREM2 expression level did not affect the numbers of stem cells in the epidermis and dermis but affects the differentiation and maturation levels of the tissues, and GREM2 suppressed the differentiation of stem/progenitor cells in vitro. These findings suggest that GREM2 may contribute to the age-related reduction in the capacity to maintain skin homeostasis by suppressing the differentiation of epidermal and dermal stem/progenitor cells.

Introduction: Adipose-derived stromal/stem cells (ASCs) have attracted attention as a promising material for regenerative medicine. Previously, we reported an age-related decrease in the adipogenic potential of ASCs from human subjects and found that the individual difference in this potential increased with age, although the mechanisms remain unclear. Recently, other groups demonstrated that a secreted antagonist of bone morphogenetic protein (BMP) signaling, Gremlin 2 (GREM2), inhibits the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) into osteoblasts and the adipogenesis of 3T3-L1 cell. Here, we examined the effects of GREM2 on the differentiation of ASCs into adipocytes. Methods: To examine changes in GREM2 expression levels with age, immunohistochemistry was performed on subcutaneous adipose tissues from subjects 12-97 years of age. Next, GREM2 gene expression levels in ASCs collected from subjects 5-90 years of age were examined by RT-PCR, and the change with age and correlation between the expression level and the adipogenic potential of ASCs were analyzed. In addition, to assess whether GREM2 affects adipogenesis, ASCs (purchased from a vendor) were cultured to induce adipogenesis with recombinant GREM2 protein, and siRNA-induced GREM2 knockdown experiment was also performed using aged ASCs. Results: In adipose tissues, GREM2 expression was observed in cells, including ASCs, but not in mature adipocytes, and the expression level per cell increased with age. GREM2 expression levels in ASCs cultured in vitro also increased with age, and the individual differences in the level increased with age. Of note, partial correlation analysis controlled for age revealed that the adipogenic potential of ASCs and the GREM2 gene expression level were negatively correlated. Furthermore, based on a GREM2 addition experiment, GREM2 has inhibitory effects on the adipogenesis of ASCs through activation of Wnt/β-catenin signaling. On the other hand, GREM2 knockdown in aged ASCs promoted adipogenesis. Conclusions: The GREM2 expression level was confirmed to play a role in the age-related decrease in adipogenic potential observed in ASCs isolated from adipose tissues as well as in the enhancement of the individual difference, which increased with age. GREM2 in adipose tissues increased with age, which suggested that GREM2 functions as an inhibitory factor of adipogenesis in ASCs.

Melanocyte stem cells (McSCs) are localized in the bulge region of hair follicles and supply melanocytes, which determine hair color by synthesizing melanin. Ectopic differentiation of McSCs, which are usually undifferentiated in the bulge region, causes depletion of McSCs and results in hair graying. Therefore, to prevent hair graying, it is essential to maintain McSCs in the bulge region, but the mechanism of McSC maintenance remains unclear. To address this issue, we investigated the role of CXCL12, a chemokine which was previously suggested to induce migration of melanocyte lineage cells, as a niche component of McSCs. Immunohistological analysis revealed that CXCL12 was highly expressed in the bulge region of human hair follicles. CXCL12 mRNA expression level was significantly lower in white hairs plucked from human scalps than in black hairs. CXCL12 attracted the migration of early-passage normal human epidermal melanocytes (eNHEMs), an in vitro model of McSCs, which had characteristics of immature melanocyte precursors. We also found that CXCL12 suppressed their differentiation. These results suggest that CXCL12 regulates differentiation of McSCs as well as their proper localization, and maintaining McSCs by regulating CXCL12 expression level in the bulge region may be a key to preventing hair graying.

Hair follicle stem cells (HFSC) are localized in the bulge region of the hair follicle and play a role in producing hair. Recently, it has been shown that the number of HFSC decreases with age, which is thought to be a cause of senile alopecia. Therefore, maintaining HFSC may be key for the prevention of age-related hair loss, but the regulatory mechanisms of HFSC and the effects of aging on them are largely unknown. In general, stem cells are known to require regulatory factors in the pericellular microenvironment, termed the stem cell niche, to maintain their cell function. In this study, we focused on the extracellular matrix proteoglycan decorin (DCN) as a candidate factor for maintaining the human HFSC niche. Gene expression analysis showed that DCN was highly expressed in the bulge region. We observed decreases in DCN expression as well as the number of KRT15-positive HFSC with age. In vitro experiments with human plucked hair-derived HFSC revealed that HFSC lost their undifferentiated state with increasing passages, and prior to this change a decrease in DCN expression was observed. Furthermore, knockdown of DCN promoted HFSC differentiation. In contrast, when HFSC were cultured on DCN-coated plates, they showed an even more undifferentiated state. From these results, as a novel mechanism for maintaining HFSC, it was suggested that DCN functions as a stem cell niche component, and that the deficit of HFSC maintenance caused by a reduction in DCN expression could be a cause of age-related hair loss.

The Guidelines for the Treatment of Acne Vulgaris of the Japanese Dermatological Association was first published in Japanese in 2008 and revised in 2016 and 2017. These guidelines (GL) indicate the standard acne treatments in Japan and address pharmaceutical drugs and treatments applicable or in use in Japan. In these GL, the strength of the recommendation is based on clinical evidences as well as availability in Japanese medical institutions. In the 2016 and 2017 GL, some of the clinical questions were revised, and other questions were added in accordance with approval of topical medicines containing benzoyl peroxide (BPO). Rather than monotherapies of antibiotics, the 2017 GL more strongly recommend combination therapies, especially fixed-dose combination gels including BPO in the aspects of pharmacological actions and compliance in the acute inflammatory phase to achieve earlier and better improvements. The 2017 GL also indicate to limit the antimicrobial treatments for the acute inflammatory phase up to approximately 3 months and recommend BPO, adapalene, and a fixed-dose combination gel of 0.1% adapalene and 2.5% BPO for the maintenance phase to avoid the emergence of antimicrobial-resistant Propionibacterium acnes. The 2017 GL also discuss rosacea, which requires discrimination from acne and a different treatment plan.

Interfollicular epidermal stem cells (IFE-SCs) have self-renewal and differentiation potentials, and maintain epidermal homeostasis. Stem cells in vivo are regulated by the surrounding environment called niche to function properly, however, IFE-SC niche components are not fully understood. In order to elucidate the mechanisms of keeping epidermal homeostasis and of skin aging, and also to develop new therapeutic technologies for skin diseases, we searched for niche factors that regulate IFE-SCs. We found that laminin-332, a basement membrane component, was highly expressed at the tips of the dermal papillae, where IFE-SCs are localized, and that the stem cells by themselves expressed laminin-332. Knockdown of laminin-332 during the culture of IFE-SC-model cells to construct 3-dimensional epidermis in vitro resulted in failure to form proper structure, although no significant change was observed in either cell growth or apoptosis. Pre-coating of the culture insert with laminin-332 restored the normal formation of 3-dimensional epidermis. From these results, it was shown that laminin-332 is an essential niche component for the proper differentiation of IFE-SCs.

According to recent studies, stem cells are found in various tissues in our bodies. It has been reported that stem cells can reside in the skin tissues, including the epidermis, dermis, hair follicles and subcutaneous tissues. Homeostasis of the skin is maintained because these stem cells collaborate with each other to form new cells. We previously identified the CD271(p75NTR)(+) cell as a stem cell that was present in the epidermis, dermis and subcutaneous tissue, and further investigated the role of stem cells in wound healing and their association with skin disease. In this study, we investigated the localization of CD271(+) cells in human skin (epidermis and dermis) and its age-related changes in stem cells using CD271(+) cells. The study revealed that the number of CD271(+) cells in the epidermis and dermis decreased with aging. It is possible that such an age-related decrease in stem cells causes impaired regenerative ability and is associated with various skin diseases. If the relationship between stem cells and skin aging and diseases can be elucidated by investigations such as this study, it may lead to the development of novel anti-aging technologies and medical treatments for skin diseases in the future.

During aging, increases in the number of senescent cells are seen in various tissues. On the other hand, stem cells play crucial roles in tissue repair and homeostasis. Therefore, it is likely that stem cells give rise to new cells that replace senescent cells. However, how stem cells contribute to homeostasis in the dermis has not been elucidated. Here, we investigated the effects of factors secreted from senescent fibroblasts on stem cells. We found that senescent human dermal fibroblast (HDF) conditioned medium (CM) significantly enhanced stem cell migration compared with young HDF CM. The senescent HDF CM strongly secreted chemokine ligand 2 (CCL2). Furthermore, CCL2 was found to enhance stem cell migration, and the inhibition of CCR2, a receptor for CCL2, reduced stem cell migration. These results suggest that senescent fibroblasts recruit stem cells by secreting various factors and that the CCL2/CCR2 axis is one of the mechanisms underlying this phenomenon.

To clarify the influence of the fatty acid composition of sebum in acne vulgaris, we investigated the amounts and fatty acid compositions of triglycerides (TG) and free fatty acids (FFA), and the amounts of cutaneous superficial Propionibacterium acnes in acne patients and healthy subjects. The foreheads of 18 female patients, 10 male patients, 10 healthy females and 10 healthy males were studied in a Japanese population. There were significant differences in the amounts of sebum, TG and cutaneous superficial P.acnes, as well as the fatty acid compositions of TG and FFA between acne patients and healthy subjects in females. Their fatty acid compositions were correlated with the amount of TG with or without acne. It was clarified that the fatty acid compositions of TG and FFA depended on the amount of TG, and there were no differences in the fatty acid composition in the presence and absence of acne.

When bacteria are isolated from acne lesions, P. Acnes, Propionibacterium granulosum, and Staphylococcus epidermidis are typically detected. In many cases, P. Acnes alone or a mixture of P. Acnes and S. epidermidis is detected. Among these bacterial species, P. Acnes plays the most important role in the onset of acne. In this article, we focus on acne and P. Acnes.

It has been reported that the abnormal regulation of melanocyte stem cells (McSCs) causes hair greying; however, little is known about the role of McSCs in skin hyperpigmentation such as solar lentigines (SLs). To investigate the involvement of McSCs in SLs, the canonical Wnt signalling pathway that triggers the differentiation of McSCs was analysed in UVB-induced delayed hyperpigmented maculae in mice and human SL lesions. After inducing hyperpigmented maculae on dorsal skin of F1 mice of HR-1x HR/De, which was formed long after repeated UVB irradiation, the epidermal Wnt1 expression and the number of nuclear -catenin-positive McSCs were increased as compared to non-irradiated control mice. Furthermore, the expression of dopachrome tautomerase (Dct), a downstream target of -catenin, was significantly upregulated in McSCs of UVB-irradiated mice. The Wnt1 expression and the number of nuclear -catenin-positive McSCs were also higher in human SL lesions than in normal skin. Recombinant Wnt1 protein induced melanocyte-related genes including Dct in early-passage normal human melanocytes (NHEMs), an in vitro McSC model. These results demonstrate that the canonical Wnt signalling pathway is activated in SL lesions and strongly suggest that the accelerated differentiation of McSCs is involved in SL pathogenesis.

Background Monopolar radiofrequency (mRF) devices have been shown to be clinically effective for treating aging skin, but there are few histologic studies about the mechanisms. Objective To histologically analyze chronologic and quantitative change in collagens after mRF treatment to determine the mechanisms of the antiaging effect. Methods Five patients were enrolled in this study. Skin specimens were taken before and 1 and 3months after treatment. Immunostaining was performed to determine change in type I and III collagen levels and stem and other cell counts in skin layers. Results In all cases, both types of collagen significantly increased after irradiation in the dermis (p<.05), and their changes were noticed uniformly in all layers. No significant change was noticed in stem and other cell counts. Conclusions This study histologically demonstrated that type I and III collagen increased significantly in the dermis after mRF treatment. The amount of stem cells did not affect the increase in collagens.

Objectives: We investigated the facial skin microbiota of Japanese acne patients. Methods: Skin swab samples were obtained from 100 acne patients and 28 healthy controls to evaluate Propionibacterium and Staphylococcus spp. using a culture method. Malassezia spp. were evaluated using a non-culture method. Antibiotic resistance of Propionibacterium spp. was also examined. Results: Acne patients and controls did not show significant differences in Propionibacterium and Staphylococcus spp. populations. However, the number of Malassezia globosa from patients was greater than that from controls. Moreover, the number of Propionibacterium spp. from patients carrying antibiotic-resistant strains was significantly greater than that from patients not carrying them. Conclusions: The present study characterized the facial skin microbiota of Japanese acne patients, suggesting a correlation between acne and quantitative differences in Malassezia microbiota. It was also found that the antibiotic resistance of Propionibacterium spp. may affect its abundance in the skin. (C) 2013 S. Karger AG, Basel

In healthy individuals, skin integrity is maintained by epidermal stem cells which self-renew and generate daughter cells that undergo terminal differentiation. Despite accumulation of senescence markers in aged skin, epidermal stem cells are maintained at normal levels throughout life. Therefore, skin ageing is induced by impaired stem cell mobilisation or reduced number of stem cells able to respond to proliferative signals. In the skin, existence of several distinct stem cell populations has been reported. Genetic labelling studies detected multipotent stem cells of the hair follicle bulge to support regeneration of hair follicles but not been responsible for maintaining interfollicular epidermis, which exhibits a distinct stem cell population. Hair follicle epithelial stem cells have at least a dual function: hair follicle remodelling in daily life and epidermal regeneration whenever skin integrity is severely compromised, e.g. after burns. Bulge cells, the first adult stem cells of the hair follicle been identified, are capable of forming hair follicles, interfollicular epidermis and sebaceous glands. In addition, - at least in murine hair follicles - they can also give rise to non-epithelial cells, indicating a lineage-independent pluripotent character. Multipotent cells (skin-derived precursor cells) are present in human dermis; dermal stem cells represent 0.3% among human dermal foreskin fibroblasts. A resident pool of progenitor cells exists within the sebaceous gland, which is able to differentiate into both sebocytes and interfollicular epidermis. The self-renewal and multi-lineage differentiation of skin stem cells make these cells attractive for ageing process studies but also for regenerative medicine, tissue repair, gene therapy and cell-based therapy with autologous adult stem cells not only in dermatology. In addition, they provide in vitro models to study epidermal lineage selection and its role in the ageing process. (c) 2008 Elsevier Inc. All rights reserved.

For the epidemiological surveys and evaluations of therapy, it is essential to evaluate the severity of diseases. There are several reported methods of assessment for acne severity including lesion counting, comparison of the patient's to a photographic standard and comparison of the patient's to a text description. But all of these are based on opinions of specialists. In this study, we attempted to make an evidence-based grading criteria for acne severity, which was expected to yield consents from most dermatologists. The dermatologists consulted classified the global severity of acne patients without any standard and then counted the numbers of eruptions. Three independent expert dermatologists graded the photographs of these patients. We compared the verdicts of the consulted dermatologist and three experienced dermatologists, and analyzed the relationships between these classifications and numbers of eruptions. Our results showed that most of the dermatologists have similar latent recognitions of acne severity. We selected representative photographs as standards, which would contribute to making adjustments for judgments. Global classifications of dermatologists correlated with numbers of inflammatory eruptions (papules plus pustules), but did not with numbers of comedones. The appropriate divisions of inflammatory eruptions of half of the face to decide classifications were: 0-5, "mild"; 6-20, "moderate"; 21-50, "severe"; and more than 50, "very severe".

Recently, we established an acne severity classification that is based on scientific evidence. Our classification allows three different methods for grading, which include general impression of consulted dermatologist, photograph-based estimation by independent experts, and grading by lesion counting. In our classification, we proposed standard photographs for the estimation of general severity to adjust the basis of judgments. In this study, we evaluated the validity of our classification. We made questionnaires of acne severity using acne patients' photographs, which were selected from the collection of representative photographs of our classification. Participants answered these questionnaires before and after our presentations about our classification of acne severity. We identified the conformity rate with our consensus decision. The results revealed that average conformity rates were raised from 67.0% to 88.9% among Japanese dermatologists and from 68.0% to 79.8% among Korean ones. These data show the adequacy of both our grading system itself and its presentation. We believe our classification will be one of the most effective and reasonable grading systems to classify acne severity.

皮膚科専門医療機関を初診したざ瘡患者346名を対象にアンケート調査を実施した.ざ瘡の初発年齢は平均15.1歳,ざ瘡での初診年齢は平均19.8歳,医療機関以外で初めて対処した年齢は平均16.5歳であった.約90%の患者が医療機関の受診前にざ瘡への何らかの対処を行っていた.今回の調査により,ざ瘡を発症してもすぐに医療機関を受診せず,薬局などで薬剤を購入し自己判断で対処している患者が多いことが確認された.DLQI日本語版によるQOL評価では,特に症状・感情面においてざ瘡患者のQOLの低下が認められた.ざ瘡の悪化時期・誘因について,身体的・精神的ストレスがかかるときや食事との関係を挙げる患者が多かった.また調査協力施設の皮膚科医に対するアンケート結果では,現行のざ瘡治療に対する満足度は,内服抗菌薬と軽症例に対する外用抗菌薬以外では低く,本邦のざ瘡治療への満足度が全体的に低いことが示された.(著者抄録)

急性期の脳神経外科的処置後の患者における頭痛の有無や頭蓋内圧(Intracranial Pressure:ICP)の変動に対する精神性発汗量と温熱性発汗量の推移について調査した.測定結果から,まず,ICPおよび血圧の変動と精神性発汗量の変動は相関することがわかった.次に,頭痛があり,収縮期血圧がやや高くICPの亢進が推測される状態では,精神性発汗量が温熱性発汗量よりも有意に多く検出された.対照として同一症例で頭痛がなく,収縮期血圧がほぼ正常の状態では精神性発汗と温熱性発汗はほとんど検出されなかった.一方,ICPが亢進している場合のみならず,薬剤を用いてICPを降下させた場合においても精神性発汗量が温熱性発汗量よりも有意に多く検出された.急性期の脳神経外科的処置後の患者に対する看護では,ICP亢進の早期発見は非常に重要である.今回の結果から,精神性発汗量を測定することでICPの推移を間接的であるが,非侵襲的および簡易的に連続モニタリングすることができる可能性があることが示唆された(著者抄録)

Fexofenadine, a histamine H1-receptor antagonist, is approved for the treatment of pruritus associated with atopic dermatitis. The effects of fexofenadine on scratching behaviour, and plasma levels of histamine and eotaxin were assessed in a new model of atopic dermatitis. Mice fed a diet low in M92+and Zn2+(special diet S) were compared with mice on a normal diet (N) or diet S plus fexofenadine HCl for weeks 0 - 10 (S + F0-10), 0 - 5 (S + F0-5) or 6 - 10 (S + F6-10) (seven mice per group). Compared with group N, group S mice showed significantly greater scratching frequency, and plasma histamine and eotaxin concentrations; these three variables were significantly lower in group S + F0-10than in group S. Scratching frequency increased when fexofenadine was discontinued. Fexofenadine significantly reduced mast cell and eosinophil numbers. Histamine may be important in the pathological changes seen in this model of atopic dermatitis, suggesting that it might aid future development of antihistamines for the treatment of atopic dermatitis. Copyright © 2006 Cambridge Medical Publications.

74歳，女性。2003年1月当院産婦人科で子宮脱の手術を施行した際，外陰部の黒色結節を指摘された。その後経過観察するも皮疹が残存するため当科を受診。初診時，左大陰唇に2×2cmの黒色結節を認めた。自覚症状はなく，鼠径リンパ節は触知しなかった。臨床所見から脂漏性角化症を疑い，皮膚生検を行ったところ，基底細胞癌の所見であったため切除した。自験例を含め最近10年間の当科における基底細胞癌84例と全国アンケ-トを検討した結果，基底細胞癌は主に顔面にみられ，外陰部に関しては男性が1例，女性が自験例の1例と，全国アンケート同様発症頻度は少なかった。

尋常性痤瘡（以下痤瘡と略す）は日常よく遭遇する皮膚疾患であるが，その発症機序は複雑であり，いまだ不明な点も多い．毛包内常在菌であるPropionibacterium acnes（以下P. acnesと略す）は，痤瘡の発症に関与する最も重要な因子の一つであり，P. acnesの菌数の増加が痤瘡の発症の原因となるため，治療においてはP. acnesの菌数を減少させることを目的として抗菌剤がしばしば用いられる．また痤瘡治療で汎用されるその他の薬剤としては，補助的な治療剤として種々のビタミン剤が用いられているが，その奏効機序は明らかではなく，P. acnesに対する直接的な影響もいまだ十分に検討されていない．そこで今回われわれは，各種ビタミンのP. acnesに対する影響をin vitroで検討した．各種ビタミンをP. acnesを接種した液体培地に添加，培養し，濁度およびリパーゼ活性を測定した．その結果，ビタミンB₂，K₃，K₅についてはP. acnesの増殖を抑制することが，またビタミンB₅は増殖に影響することなく，ビタミンK₃，K₅は増殖抑制効果に並行してリパーゼ活性を抑制することが判明した．これらの事実は，痤瘡治療においてビタミンB₂，B₅，K₃，K₅を用いる根拠となるかもしれない．

46歳男.右中指外傷後,指先の黒色斑,続いて右腋窩に巨大なしこりを認めた.右腋窩には70×80×80mmの弾性硬で下床との可動性を欠く巨大な皮下腫瘤を認めた.腫瘤は悪性黒色腫と診断されたが,原発巣である右中指および爪縁下の黒褐色病変は部分的に自然退縮をきたしていた.DAV-Feron療法には抵抗性で,現在,DAC-Tam療法,インターフェロンβ局注,放射線治療の併用により右腋窩リンパ節は縮小傾向にある

ラテックスアレルギーに関する国内初の大規模な意識・実態調査を,藤田保健衛生大学病院の全医療従事者(1512名)を対象に実施した.まず,ラテックスアレルギーについての知識や,天然ゴム製品を使用した際に臨床症状を経験したことがあるかどうかをアンケートで尋ねた.その結果,約85%の人がラテックスアレルギーについて知っていることがわかった.一方,臨床症状を経験したと答えた人は,全体の約19%であった.臨床症状を訴えた人を対象として皮膚テストを行った結果,44人(全体の3.3%)がラテックスアレルギーであると確定診断された.また,ラテックスアレルギーと診断された人は,アトピー性皮膚炎や手湿疹を有する傾向があることがわかった.さらに,天然ゴム製品に曝露される機会が多い環境の職員ほど,ラテックスアレルギーの有病率が高いことが明らかとなった.ラテックスアレルギーの診断に関しては,抗原特異lgE抗体検出試験は感度が低く効果的ではないものの,プリックテストや使用テストが有効であることが確認された.