Bowen disease of the palm associated with human papillomavirus 52.

Human papillomavirus (HPV) is a well-known risk factor for many human cancers, especially cervical cancers. Among the nonmelanoma skin cancers, Bowen disease (BD) of the genitalia and fingers has also been shown to be closely associated with the high-risk types of HPV, especially HPV16. We report a case of BD of the palm, which is a very rare location for BD. In addition to its rare location, HPV52, which is classified as a mucous high-risk HPV type, was detected in the lesion by PCR restriction fragment length polymorphism analysis. To our knowledge, this is the first reported case of BD associated with HPV52.


Generalized malignant acanthosis nigricans with "deck-chair sign".


Drug-induced skin damage by intravenous administration of Nifekalant hydrochloride

塩酸ニフェカラントによる皮膚障害の1例


A clinicopathological study of primary cutaneous invasive squamous cell carcinoma: relationship between a new clinicopathological classification and program

皮膚原発浸潤性有棘細胞癌(Primary Cutaneous Invasive Squamous Cell Carcinoma)の臨床病理学的検討:臨床病理学的新分類と予後の関係

We performed a clinicopathological analysis of 305 cases of primary cutaneous invasive squamous cell carcinoma (SCC) diagnosed in Tokushima University hospital in the past 25 years. We proposed a new clinicopathological classification of SCC based on epidemiological factors and divided it into nine categories; actinic keratosis type, bowen type, keratoacanthomatous type, cystic type, genital type, cicatricial type, radiodermatitis type, xeroderma pigmentosa type, and miscellaneous type. We examined the clinicopathological characteristics in each category such as favorite locations and prognosis. Among the clinical characteristics of those cases, such as sex ratio and age at the time of the excision, the favorite sites were similar to those in former reports in Japan. The actinic keratosis type is a significant type with little metastasis, but the radiodermatitis type and the genital type showed high metastatic rates. The case that occurred on the face showed little metastasis, but the cases on the lower limbs and genitalia had high metastatic rates. Cases with a tumor thickness of less than 4 mm showed lower metastatic rates than those with a tumor thickness of more than 4 mm. We divided those 25 years into five year segments as investigation periods and examined the numbers of cases, sex ratios, and the frequencies of the actinic keratosis type, the Bowen disease type, and the other types and found that these factors were essentially equal.

1983年から2007年の25年間で，徳島大学病院皮膚科および形成外科で経験した皮膚原発浸潤性有棘細胞癌305例について，特に発症要因を重要視した臨床病理学的新分類法を用いて分類し，日光角化症型，Bowen病型，ケラトアカントーマ型，嚢腫型，外陰部型，瘢痕型，放射線皮膚炎型，色素性乾皮症型，その他，の9型に分類した．各型に関して好発部位や転移の有無/予後の違いなどの臨床病理学的検討を行った．その結果，症例全体の臨床的特徴は，男性に多く発生していること，切除時年齢，発生部位の割合など，本邦における以前の報告とほぼ同様であった．さらに病型では，日光角化症型は転移を起こしにくく，外陰部型・放射性皮膚炎型は転移を起こしやすかった．次に発生部位では顔面に生じたものは転移を起こしにくく，下肢・外陰部に生じたものは転移を起こしやすかった．腫瘍の厚さでは4 mm未満の症例は転移を起こしにくく，4 mm以上の症例は転移を起こしやすかった．調査した25年間を5年毎に区切り，各年代における日光角化症型，Bowen病型，それ以外のタイプの4群の症例数の推移と男女比を調査したが，その構成に大きな変化はなかった．


Relapsing polychondritis associated with psoriasis vulgaris and alopecia areata.


Ichthyosis hystrix, Curth-Macklin type: a new sporadic case with a novel mutation of keratin 1.


Generalized hypopigmented macules after bone-marrow transplantation.


Clinical case reports: Coexistence of low-grade sebaceous carcinoma and basal cell carcinoma in a nevus sebaceous

症例 低悪性度脂腺癌および基底細胞癌を併発した脂腺母斑

A 60-year-old Japanese man visited our outpatient clinic complaining of a black protruding tumor on his left cheek with a 3-year history. The tumor arose in a pre-existing skin-colored plaque that had been noticed since his childhood. We suspected a basal cell carcinoma (BCC) arising in a nevus sebaceus (NS), and excised the lesion including the NS. A histopathological examination of the whole specimen demonstrated the coexistence of a low-grade sebaceous carcinoma (low-grade SC) and BCC in an NS. An NS is classified into three progression stages, and various types of epithelial tumors occur secondarily in the lesion at the third stage, especially when patients are more than 50 years old. Among those secondary malignant tumors, BCC is the most common, and SC is rather rare. We reviewed the literature and summarized 31 cases of malignant sebaceous tumors arising in an NS, focusing on clinical characteristics. Surprisingly, seven cases had other malignant tumors, most of which were BCC as in our case. Only one patient with SC in an NS died from metastasis, and another 30 cases were cured after appropriate treatments. Therefore, we suggest that SC in an NS is curable by careful extirpation, although the prognosis of common SC is rather poor. But seen on the background of this case the concept of `low-grade SC' should be kept in mind.

60歳，男性．幼少時より左耳前部に正常皮膚色局面があった．初診の3年前より病変内に黒色腫瘤が出現し，徐々に増大したため当科を受診した．脂腺母斑から発生した基底細胞癌と考え，脂腺母斑を含めて切除した．摘出標本では，脂腺母斑内の離れた場所に基底細胞癌と低悪性度脂腺癌が独立して認められた．脂腺母斑に続発する悪性腫瘍では基底細胞癌が最も多く，脂腺癌の報告はまれである．脂腺母斑に続発した悪性脂腺腫瘍の症例を検討し，臨床的特徴について若干の考察を加え報告する．


Paraneoplastic pemphigus associated with non-Hodgkin's lymphoma.


Coexistence of giant blue nevus of the scalp with hair loss and alopecia areata.

A 43-year-old Japanese man presented with a 13-year history of a grayish macule measuring 7 cm in diameter with sparse hairs on the vertex. Histopathological examination demonstrated two types of melanocytes, spindle-shaped and ovoid cells, with abundant melanin aggregated around the upper part of the pilosebaceous apparatus. Fibrous, thick collagen bundles were also seen surrounding the upper part of the small hair follicles. There was no infiltration of melanocytes or lymphocytes in the lower dermis or adipose tissue. Based on these findings, a diagnosis of blue nevus, cellular type, was made. Giant cellular blue nevi on the scalp are rare, and 11 cases reported in the published work have shown characteristic features such as hair loss and cranial invasion of nevus cells. It should be noted that melanocytes of giant blue nevi have a high potential to damage other organs such as underlying bone and hair follicles. The patient also showed a typical lesion of alopecia areata on the left temporal which was successfully treated with topical corticosteroid.


Scalp angiosarcoma successfully treated with weekly docetaxel and linac electron beam

電子線照射とWeeklyドセタキセル療法が奏効した頭部血管肉腫の1例


Basal cell carcinoma arising on the palm.


Diltiazem-associated photodistributed hyperpigmentation: report of two Japanese cases and published work review.

Scherschum et al. proposed diltiazem-associated photodistributed hyperpigmentation as a novel type of drug-induced photosensitive lichenoid eruption. The characteristic clinical features were slate-gray reticulated hyperpigmentation on sun-exposed areas, while lichenoid dermatitis with prominent pigmentary incontinence was noted histologically. Although the clinical and histological features were similar to those of lichen planus pigmentosus, the histological features did not show either compact hyperkeratosis or wedge-shaped hypergranulosis, which are typical histological features of lichen planus. We describe two Japanese cases of diltiazem-associated photodistributed hyperpigmentation, who were successfully treated with topical tacrolimus, and review the published work.


嚥下障害を伴った皮膚筋炎に対し免疫グロブリン大量療法(IVIG)が奏効した2例

嚥下障害を伴った皮膚筋炎に対し免疫グロブリン大量療法(IVIG)が奏効した2例


Resin splint as a new conservative treatment for ingrown toenails.

Several conservative as well as surgical methods are used for the treatment of ingrown toenails until date. The conservative methods are either based on nail splinting or on orthonyxia, but no methods employing both principles have been reported thus far. Moreover, surgical methods usually involve postoperative pain, prolonged wound healing and restricted activities of daily living. Therefore, considering the need of a simplified, non-invasive method, in this study, we applied a novel splint to treat patients with ingrown toenails and estimated the clinical efficacy as well as rate of recurrence following treatment. The splint is a plate made of resin that is attached to the lateral edge of the nail using a bandage. We studied 61 patients (19 men and 42 women; mean age 36 years), with an average application duration of 9.3 months and an average follow-up period of 10 months in all patients. All patients experienced pain relief within a week of splint application and a decrease in the degree of nail deformity. Moreover, follow-up revealed a recurrence rate of 8.2%. Therefore, we believe that this new device is an excellent conservative treatment method for patients with ingrown toenails.

The Journal of Medical Investigation : JMI


【肉芽腫症】 右環指の腫脹を契機に診断したサルコイドーシスの1例

【肉芽腫症】 右環指の腫脹を契機に診断したサルコイドーシスの1例


硫酸クロピドグレルによる薬剤性過敏症症候群の1例

硫酸クロピドグレルによる薬剤性過敏症症候群の1例


60年以上続くリンパ浮腫肢に生じた脈管肉腫の1例

60年以上続くリンパ浮腫肢に生じた脈管肉腫の1例


Isaacs症候群を合併し難治であったびまん性筋膜炎の1例

Isaacs症候群を合併し難治であったびまん性筋膜炎の1例


Clinicopathological Study of Drug-induced Hypersensitivity Syndrome (DIHS)


【血管炎・血行障害】 片側の指端壊死で発症した混合性結合組織病続発の抗リン脂質抗体症候群


Prevention of pressure ulcers in home care patients

きず・きずあと(創傷)治療:最近の進歩床ずれの在宅ケア

A large proportion of home care patients are at risk of pressure ulcer. The occurrence rate of pressure ulcer is higher in home care patients than that in the patients of hospitals and welfare facilities. The home care patients need long-term conservative treatment because of the depth of the pressure ulcers.Treatment of the pressure ulcers at home results in increase of caregivers burden. Therefore,prevention and early detection of pressure ulcers are important in home nursing. In early stage of pressure ulcers，``deep tissue injury''should be taken into consideration because of its progressive nature. It is a new concept which presents deep tissue damage remaining superficial skin intact.One of clinical features in this condition is induration in a deep layer.The past decade has seen a huge growth in the application of pressure relieving mattresses,absorbent products for urinary and faecal incontinence, and skin barrier products to prevention of the pressure ulcers. Economical, physical, and psychological burden of nursing at home should be decreased with an accumulation of these information and utilization of the products. Therefore, it is important for caregivers to consult with their care managers and acquire new knowledge and information.


Centrifugal lipodystrophy of the scalp presenting with an arch-form alopecia: a 10-year follow-up observation.

We describe a 10-year follow-up observation of progressive arch-form alopecia caused by centrifugal lipodystrophy (CLD) in a Japanese boy. A 2.5-year-old boy developed a slightly depressed lesion demarcated by a horseshoe-shaped erythematous border on his right neck, which then extended to the scalp. Four years later, arch-form alopecia became apparent in the right temporal region along with an erythematous border. The arch-form alopecia gradually expanded centrifugally, leaving a slight residual depression, but hair regrowth was seen within the area of alopecia. Histological examination of the erythematous border revealed non-specific inflammatory changes in the subcutaneous fat. Magnetic resonance imaging findings revealed a loss of subcutaneous fat inside the lesion. The alopecia continuously extended until he was 12 years old, but, thereafter, expansion ceased and hair regrowth gradually occurred in the arch-form alopecia. A linear non-hairy lesion 5 cm in length still remained when he was 13 years old. CLD might involve the scalp and cause linear, arch-form alopecia.


Real-time in vivo imaging of p16Ink4a reveals cross-talk with p53

Expression of the p16(Ink4a) tumor suppressor gene, a sensor of oncogenic stress, is up-regulated by a variety of potentially oncogenic stimuli in cultured primary cells. However, because p16(Ink4a) expression is also induced by tissue culture stress, physiological mechanisms regulating p16(Ink4a) expression remain unclear. To eliminate any potential problems arising from tissue culture-imposed stress, we used bioluminescence imaging for noninvasive and real-time analysis of p16(Ink4a) expression under various physiological conditions in living mice. In this study, we show that oncogenic insults such as ras activation provoke epigenetic derepression of p16(Ink4a) expression through reduction of DNMT1 (DNA methyl transferase 1) levels as a DNA damage response in vivo. This pathway is accelerated in the absence of p53, indicating that p53 normally holds the p16(Ink4a) response in check. These results unveil a backup tumor suppressor role for p16(Ink4a) in the event of p53 inactivation, expanding our understanding of how p16(Ink4a) expression is regulated in vivo.


Brunsting-Perry type localized bullous pemphigoid, possibly induced by furosemide administration and sun exposure.

A 56-year-old male visited our hospital complaining of irregular-shaped atrophic erythematous plaques with blood crust, erosion, pigmentation, and depigmentation, localized on his forehead, bilateral cheeks, and ear lobes, for over one year. He has been receiving peritoneal dialysis and furosemide administration due to chronic renal failure for four years. Direct immunofluorescence examination exhibited linear depositions of IgG and C3 in the basement membrane zone. Antibodies against the recombinant NC16a-domain of BP180 were negative by enzyme-linked immunosorbent assays (ELISA), though BP230 ELISA was positive. Immunoblotting using extracts of normal human epidermis demonstrated that the patient's serum reacted with BP180 and BP230. IgG class autoantibodies to recombinant proteins of the C-terminal domain of BP180 were also detected by immunoblotting. This case was diagnosed as localized bullous pemphigoid (LBP). Oral administration of prednisolone 10 mg daily was started and furosemide administration was ceased. The eruptions disappeared thereafter with superficial scars. This is the second reported case of Brunsting-Perry type LBP associated with IgG class autoantibodies to the C-terminal domain of BP180. Furthermore, photosensitivity caused by furosemide administration may contribute to the induction and exacerbation of the lesions.


Primary dermal melanoma: A case report and molecular characterization.

Swetter et al. proposed primary dermal melanoma (PDM) as a distinct entity based on an excellent prognosis. The histopathological features of PDM are extremely similar to those of metastatic melanoma or clear cell sarcoma (CCS). We describe a 38-year-old woman with a subcutaneous tumor in her left thigh. Physical and imaging examinations showed no evidence of metastatic melanoma. The lesion showed obvious strong expression of KIT by immunohistochemistry, but no EWS-ATF1 fusion transcript specific for CCS was detected by reverse transcription polymerase chain reaction. In further analyses of KIT expression in other tumors, three of four primary melanomas (75%) and six of 12 metastatic melanomas (50%) were moderately or strongly positive, however, both the primary and metastatic lesions of CCS tested negative. We believe this to be a case of PDM, and emphasize the distinctiveness of PDM.


Pemphigoid nodularis : the importance of ELISA for diagnosis


Malignant acanthosis nigricans with enhanced expression of fibroblast growth factor receptor 3.


Identification of ultraviolet B-sensitive genes in human peripheral blood cells.

Ultraviolet B (UVB) is a serious irritant for the skin and increases a risk for skin cancer. To identify UVB-sensitive genes in peripheral blood, 11 healthy male volunteers were exposed to 0.3 J/cm(2) of narrow-band (NB)-UVB, about half of minimal erythema dose (MED) in Japanese, and gene expression in blood was analyzed at 4 h, 24 h, 4 d and 7 d after the irradiation using microarray carrying oligonucleotide probes for 2,000 stress-responsive genes. RNA prepared before the irradiation was used as a reference control. Microarray analysis identified 21 genes as UVB-responsive genes with a peak at 24 h in 6 subjects, and real-time PCR validated the significant down-regulation of 9 (ABCB10, ATF1, ABCD3, TANK, FAS, SLC30A9, CHUK, CASP1, and ABCE1) out of the 21 genes in 11 subjects. Considering sensitive and characteristic features of 9 marker genes, they may be useful indicators for monitoring systemic response to UVB irradiation.

The Journal of Medical Investigation : JMI


Targeted deletion of the murine corneodesmosin gene delineates its essential role in skin and hair physiology

Controlled proteolytic degradation of specialized junctional structures, corneodesmosomes, by epidermal proteases is an essential process for physiological desquamation of the skin. Corneodesmosin (CDSN) is an extracellular component of corneodesmosomes and, although considerable debate still exists, genetic studies have suggested that the CDSN gene in the major psoriasis-susceptibility locus (PSORS1) may be responsible for susceptibility to psoriasis, a human skin disorder characterized by excessive growth and aberrant differentiation of keratinocytes. CDSN is also expressed in the inner root sheath of hair follicles, and a heterozygous nonsense mutation of the CDSN gene in humans is associated with scalp-specific hair loss of poorly defined etiology. Here, we have investigated the pathogenetic roles of CDSN loss of function in the development of skin diseases by generating a mouse strain with targeted deletion of the Cdsn gene. Cdsn-deficient mouse skin showed detachment of the stratum corneum from the underlying granular layer and/or detachment within the upper granular layers due to the disrupted integrity of the corneodesmosomes. When grafted onto immunodeficient mice, Cdsn-deficient skin showed rapid hair loss together with epidermal abnormalities resembling psoriasis. These results underscore the essential roles of CDSN in hair physiology and suggest functional relevance of CDSN gene polymorphisms to psoriasis susceptibility.

Proceedings of the National Academy of Sciences of the United States of America


The Interaction of JRAB/MICAL-L2 with Rab8 and Rab13 Coordinates the Assembly of Tight Junctions and Adherens Junctions.

The assembly of tight junctions (TJs) and adherens junctions (AJs) is regulated by the transport of integral TJ and AJ proteins to and/or from the plasma membrane (PM) and it is tightly coordinated in epithelial cells. We previously reported that Rab13 and a junctional Rab13-binding protein (JRAB)/molecule interacting with CasL-like 2 (MICAL-L2) mediated the endocytic recycling of an integral TJ protein occludin and the formation of functional TJs. Here, we investigated the role of Rab13 and JRAB/MICAL-L2 in the transport of other integral TJ and AJ proteins claudin-1 and E-cadherin to the PM by using a Ca(2+)-switch model. Although knockdown of Rab13 specifically suppressed claudin-1 and occludin but not E-cadherin transport, knockdown of JRAB/MICAL-L2 and expression of its Rab13-binding domain (JRAB/MICAL-L2-C) inhibited claudin-1, occludin, and E-cadherin transport. We then identified Rab8 as another JRAB/MICAL-L2-C-binding protein. Knockdown of Rab8 inhibited the Rab13-independent transport of E-cadherin to the PM. Rab8 and Rab13 competed with each other for the binding to JRAB/MICAL-L2 and functionally associated with JRAB/MICAL-L2 at the perinuclear recycling/storage compartments and PM, respectively. These results suggest that the interaction of JRAB/MICAL-L2 with Rab8 and Rab13 coordinates the assembly of AJs and TJs.


Severe radiation-induced injury after cardiac catheter ablation:a case requiring free anterolateral thigh flap and vastus lateralis muscle flap reconstruction on the upper arm

Although cases of radiation-induced skin injury after fluoroscopically-guided procedures have been reported since 1996, diagnosis and treatment of such injury remain difficult. We present the case of a patient who complained of two ulcers, one on his right arm and one on his back, and limited motion of the right elbow joint after repeated cardiac radiofrequency catheter ablations. After resection of the skin ulcer on the patient's arm and of degenerated tissue in the distal part of the triceps brachii muscle, a combined free flap incorporating an anterolateral thigh flap and vastus lateralis muscle flap was transplanted. In the present case, this combined flap was very useful for simultaneous reconstruction of the muscle and skin defects under and over the tendon because the muscle flap and skin flap could be arranged separately.

Journal of Plastic, Reconstructive & Aesthetic Surgery: JPRAS


Visualizing the dynamics of p21 (Wafl/Cip1)cyclin-dependent kinase inhibitor expression in living animals.

Although the role of p21(Waf1/Cip1) gene expression is well documented in various cell culture studies, its in vivo roles are poorly understood. To gain further insight into the role of p21(Waf1/Cip1) gene expression in vivo, we attempted to visualize the dynamics of p21(Waf1/Cip1) gene expression in living animals. In this study, we established a transgenic mice line (p21-p-luc) expressing the firefly luciferase under the control of the p21(Waf1/Cip1) gene promoter. In conjunction with a noninvasive bioluminescent imaging technique, p21-p-luc mice enabled us to monitor the endogenous p21(Waf1/Cip1) gene expression in vivo. By monitoring and quantifying the p21(Waf1/Cip1) gene expression repeatedly in the same mouse throughout its entire lifespan, we were able to unveil the dynamics of p21(Waf1/Cip1) gene expression in the aging process. We also applied this system to chemically induced skin carcinogenesis and found that the levels of p21(Waf1/Cip1) gene expression rise dramatically in benign skin papillomas, suggesting that p21(Waf1/Cip1) plays a preventative role(s) in skin tumor formation. Surprisingly, moreover, we found that the level of p21(Waf1/Cip1) expression strikingly increased in the hair bulb and oscillated with a 3-week period correlating with hair follicle cycle progression. Notably, this was accompanied by the expression of p63 but not p53. This approach, together with the analysis of p21(Waf1/Cip1) knockout mice, has uncovered a novel role for the p21(Waf1/Cip1) gene in hair development. These data illustrate the unique utility of bioluminescence imaging in advancing our understanding of the timing and, hence, likely roles of specific gene expression in higher eukaryotes.


Analysis of the absorbance spectra of skin lesions as a helpful tool for detection of major pathophysiological changes

Although reflectance spectrophotometry is often applied to measurement of skin color, raw data of reflectance spectra of normal and lesional skin are difficult to analyze. The purpose of this pilot study was to determine whether measurement of spectral difference in absorbance (SDA) between various skin lesions and normal skin adjacent to them could yield useful information for clinics in dermatology. We studied spectral reflectance of a total of 173 various skin lesions. After converting obtained reflectance into apparent absorbance A (=log(10)(1/reflectance)), we examined the profile of SDA, that is, A(lesion)-A(normal skin) in the range of 400-700 nm, and compared them with the absorbance spectra of melanin and hemoglobin. SDA of epidermal pigmentary disorders was similar to the absorption spectrum of melanin in vitro, but the cases with intradermal melanin deposition showed a different pattern, reflecting the scattering effect of the dermis. SDA of erythematous lesions was similar to the spectra of either oxygenated or reduced hemoglobin, and varied according to the oxygenated level of cutaneous blood. SDA of lesions with a combination of factors appeared as a simple summation of spectra corresponding to each of the factors. Our method may offer easy and quick detection of major pathophysiological changes in skin lesions.


Difference between intrafollicular microorganism profiles in perioral and seborrhoeic dermatitis

Although often associated with overuse of topical corticosteroids, perioral dermatitis seems to develop seldom in patients with typical seborrhoeic dermatitis in spite of long-term application of corticosteroids. In order to compare the profiles of intrafollicular microorganisms in the lesions of perioral and seborrhoeic dermatitis, tape-stripped samples were obtained from eight lesions of perioral dermatitis, 10 lesions of seborrhoeic dermatitis, and the perioral skin of 31 normal subjects. After staining with Toluidine blue, resident microorganisms on plucked hair roots were evaluated microscopically. In all patients with perioral dermatitis and two normal subjects, 20-70% of sample hairs were positive for fusiform bacteria regarded as fusobacteria. Malassezia-positive hairs were rarely seen in these cases. Seborrhoeic dermatitis showed the opposite results. Perioral dermatitis may tend to develop under fusiform-bacteria-rich conditions, rather than Malassezia-rich conditions as in the case of seborrhoeic dermatitis.


Malignant Melanoma of Soft Parts (Clear Cell Sarcoma) --- A Case Report

A subcutaneous tumor localized on the sole of the foot of a 25-year-old Japanese man was diagnosed as a malignant melanoma of the soft parts. We performed a wide local excision, elective lymph node dissection, and chemotherapy. Eight years after treatment, the patient is alive without local recurrence or metastasis.


Molecular carcinogenesis of squamous cell carcinomas of the skin.

Squamous cell carcinomas (SCCs) of the skin were suggested to develop through a multistep process that involves activation of proto-oncogenes and/or inactivation of tumor suppressor genes in the human skin keratinocytes. Exposure to ultra-violet (UV), especially UV-B, radiation is the most common cause for these genetic abnormalities in cells. We review causation of SCCs and genetic abnormalities in human SCCs with the current work. To elucidate the multistep process, we developed a method for examining the combinatorial function in vivo of plural genes in human keratinocytes. Using high efficiency retroviral transductions, we could express plural genes serially in normal human primary keratinocytes and use these cells to regenerate human skin on SCID mice. A combinatorial transduction of H-RasV12 and cyclin dependent kinase 4 (CDK4) produced human epidermal neoplasia resembling SCC. These findings were consistent with our previous results of mutation analysis in SCCs, one of which had both mutations of H-Ras gene and the INK4a locus. Therefore, it is suggested that a combination of these genetic abnormalities might be crucial to the carcinogenesis at least in a subset of SCCs.

The Journal of Medical Investigation : JMI


足底に難治性潰瘍を伴ったWerner症候群の3例 --- WRN遺伝子変異の検討


Skin reflectance-spectra and colour-value dependency on measuring-head aperture area in ordinary reflectance spectrophotometry and tristimulus colourimetry

Measurement of skin colour has become increasingly popular in the study of dermatology with the increased availability of portable instruments. However, different instruments have been reported as giving different results from measurement of the same skin region. The aim of this study was to examine the effects of differences in measuring-head aperture area on skin reflectance spectra and colour values. We measured both reflectance spectra and CIE-L*a*b* values of the skin in five different anatomical regions on 10 subjects using two MINOLTA reflectance spectrometers that were identical apart from the aperture area of the measuring heads (diameters: 5 and 11 mm). For comparison, data were also obtained from a skin-coloured tile. Skin reflectance values measured with the wider-aperture instrument were higher than those measured with the other, irrespective of anatomical location. The differences between the two were near zero at an incident light wavelength of 400 nm, but increased to around 10% of the reflectance value at 700 nm, increasing exponentially with incident light of increasing wavelength. Skin colour was observed to be brighter, redder and yellower, in CIE-L*a*b* expression, when measured with the wider-aperture instrument. The differences between measurements obtained from the skin-coloured tile were much smaller. Skin reflectance and colour values measured with reflectance instruments are not absolute data but depend on the aperture area of the measuring head. This is probably due to variations in the proportion of longer-wavelength light reflected from the skin and collected by the instrument.


Minoxidil-Induced hair growth is mediated by adenosine in cultured dermal papilla cells: possible involvement of sulfonylurea receptor 2B as a target of minoxidil

The mechanism by which minoxidil, an adenosine-triphosphate-sensitive potassium channel opener, induces hypertrichosis remains to be elucidated. Minoxidil has been reported to stimulate the production of vascular endothelial growth factor, a possible promoter of hair growth, in cultured dermal papilla cells. The mechanism of production of vascular endothelial growth factor remains unclear, however. We hypothesize that adenosine serves as a mediator of vascular endothelial growth factor production. Minoxidil-induced increases in levels of intracellular Ca(2+) and vascular endothelial growth factor production in cultured dermal papilla cells were found to be inhibited by 8-sulfophenyl theophylline, a specific antagonist for adenosine receptors, suggesting that dermal papilla cells possess adenosine receptors and sulfonylurea receptors, the latter of which is a well-known target receptor for adenosine-triphosphate-sensitive potassium channel openers. The expression of sulfonylurea receptor 2B and of the adenosine A1, A2A, and A2B receptors was detected in dermal papilla cells by means of reverse transcription polymerase chain reaction analysis. In order to determine which of the adenosine receptor subtypes contribute to minoxidil-induced hair growth, the effects of subtype-specific antagonists for adenosine receptors were investigated. Significant inhibition in increase in intracellular calcium level by minoxidil or adenosine was observed as the result of pretreatment with 8-cyclopentyl-1,3-dipropylxanthine, an antagonist for adenosine A1 receptor, but not by 3,7-dimethyl-1-propargyl-xanthine, an antagonist for adenosine A2 receptor, whereas vascular endothelial growth factor production was blocked by both adenosine A1 and A2 receptor antagonists. These results indicate that the effect of minoxidil is mediated by adenosine, which triggers intracellular signal transduction via both adenosine A1 and A2 receptors, and that the expression of sulfonylurea receptor 2B in dermal papilla cells might play a role in the production of adenosine.

The Journal of Investigative Dermatology


Common disease among elderly people:Bullous disorders

高齢者によくみられる皮膚疾患:水疱性疾患


A novel PTEN mutation in a Japanese patient with Cowden disease.

Cowden disease (CD) is an autosomal dominant syndrome characterized by multiple hamartomatous lesions and an increased risk for malignancies. Recent evidence has indicated that the PTEN gene, encoding a protein tyrosine phosphatase, is the CD susceptibility gene. However, another line of evidence has suggested that CD might be genetically heterogeneous. Clinical features of CD are variable, and there are interfamilial differences in the expression of skin lesions. Therefore, information on PTEN mutations in CD patients should be accumulated to clarify the genotype-phenotype correlation. In the present study, we found heterozygous germline mutations of PTEN in all of three Japanese patients with CD examined, indicating no genetic heterogeneity among our patients. The mutations included two non-sense mutations of R335X and R130X, and a mis-sense mutation of C136R. To the best of our knowledge, the C136R mutation has not previously been reported in CD patients. This novel mutation was located outside the core motif of the phosphatase domain of PTEN protein, where most of the missense mutations previously reported in CD patients were clustered. Mucocutaneous manifestations were far fewer in the patient with this mutation than in the patients with nonsense mutations. Whether the phenotypic difference in mucocutaneous features was due to the different mutations remains unclear.


Lack of somatic mutation in the PTEN gene in squamous cell carcinomas of human skin.

The tumor suppressor gene PTEN is deleted and/or mutated in a variety of tumors and the susceptibility gene for Cowden disease. Loss of heterozygosity of chromosome 10q23, where PTEN resides, in squamous cell carcinomas (SCCs) of human skin and the association of SCC with Cowden disease were reported previously. In the present study, we screened for mutations of PTEN in SCCs by polymerase chain reaction single strand conformation polymorphism analysis to examine whether PTEN is involved in the carcinogenesis of SCC. None of 21 SCCs showed somatic mutations in the coding regions of PTEM. Instead the same allelic variation was detected in two cases without any clinical features of Cowden disease. Our results indicate that inactivation of PTEN does not play an important role in the carcinogenesis of SCC.


Cerebriform intradermal nevus:A case of scalp expansion on the galea.


Cerebriform Intradermal Nevus --- A Case of Scalp Expansion on the Gales


Lack of mutation in the INK4a locus in basal cell carcinomas.


Mutation of the fibrobrast growth factor receptor2 gene in Japanese patients with Apert syndrome


Mutations of the INK4a locus in squamous cell carcinomas of human skin.

Biochemical and Biophysical Research Communications


p53 Gene Mutation Analysis in Porokeratosis and Porokeratosis-associated Squamous Cell Carcinoma.

In this and previous studies, we have shown p53 overexpression immunohistochemically in 14 of 17 porokeratotic specimens obtained from 14 lesions of nine cases, and in all six specimens of squamous cell carcinoma (SCC) arising on porokeratotic lesions of two cases. We screened mutations in exons 5 to 10 of the p53 gene in all these specimens by polymerase chain reaction-single strand conformation polymorphism analysis. Mutations of the p53 gene were detected in two of the six SCCs but not in any of the 17 porokeratotic specimens. These two mutations were C to T transitions at codons 146 and 175 in exon 5, which were a nonsense mutation at a dipyrimidine site and a missense mutation at a CG site, respectively. To our knowledge, neither of these mutations has been identified in skin cancers before. Our observations indicate that mutations of the p53 gene are not the major molecular etiology for porokeratosis, but are related to its skin carcinogenesis, and that p53 overexpression in porokeratosis is not due to p53 gene mutations.


胸鎖関節部に発生したDermoid Cystの1例

胸鎖関節部に発生したDermoid Cystの1例


単純性血管腫上に生じた基底細胞癌

単純性血管腫上に生じた基底細胞癌


広範囲皮膚潰瘍の植皮術にリドカインクリームを使用した1例

広範囲皮膚潰瘍の植皮術にリドカインクリームを使用した1例


精神分裂病患者に発症したBuffalo humpの1例

精神分裂病患者に発症したBuffalo humpの1例


カラーアトラス―爪床の有棘細胞癌―

カラーアトラス―爪床の有棘細胞癌―


A Case of Dermatomyositis Complicated by Thrombotic Thrombocytopenic Purpura


Prolonged nuclear accumulation of p35 in xeroderma pigmentosum complementation group A cell after ultraviolet irradiation


Linear porokeratosis with multiple squamous cell carcinomas Study of p53 expression in porokeratosis and squamous cell carcinoma


骨外性粘液型軟骨肉腫に対する遊離植皮術後に発症した肺塞栓の1例

骨外性粘液型軟骨肉腫に対する遊離植皮術後に発症した肺塞栓の1例


悪性リンパ腫を合併した基底細胞癌の2例

悪性リンパ腫を合併した基底細胞癌の2例


3世代にわたって発症した軸前性多合趾症の1例

3世代にわたって発症した軸前性多合趾症の1例


7%リドカインクリームと60%リドカインテープの効果比較―リドカインクリームの採皮における使用経験も含めて―


Serial Cultivation of Human Nail Matrix Cells under Serum-free Conditions

We have established serial cultures of human nail matrix cells (NMCs) under serum-free conditions. We cultured NMCs using two different methods depending upon the volume of nail matrix obtained. When a sufficient amount of nail matrix was obtained, they were minced and treated with 0.25% trypsin and 0.03% EDTA. The NMCs were transferred directly as a dispersed cell culture into KGM medium. Because a sufficient amount of matrix was rarely obtained, we developed a method by which NMCs were cultured primarily as implanted small matrices in Eagle's MEM (high Ca+ medium) supplemented with 15% fetal bovine serum for the first 4 to 5 days; during this time, the NMCs expanded from the matrices and formed colonies around them. NMCs then were cultured with KGM. In both methods, KGM medium supported the growth of NMCs without a biological feeder layer. These cells could be cultivated serially for at least seven passages. Half of the cells were positively stained with a monoclonal antibody against hair (hard) keratin which is expressed in nail matrix in vivo, indicating that the cells originated from the nail matrix. These methods will now permit investigations of nail matrix cells that previously were unfeasible because of the relative lack of cells and difficulties with propagation.


Frequent p53 Accumulation in the Chronically Sun-Exposed Epidermis and Clonal Expansion of p53 Mutant Cells in the Epidermis Adjacent to Basal Cell Carcinoma.

The Journal of Investigative Dermatology


被虐待児症候群にみられた重症熱傷の2例

被虐待児症候群にみられた重症熱傷の2例


Malignant Melanoma Developing in an Area of Palmoplantar Keratoderma (Greithers Disease)


Effect of deferoxamine on thrombusm formation in a Rabbit Ear Chamber of an ischemic flap

Scientific papers of x I th international conferderation for Plastic Surgery


p53 Gene Mutations in Human Skin Cancers and Precancerous Lesions: Comparison with Immunohistochemical Analysis.


第1鰓裂由来の瘻孔および嚢腫の3例

第1鰓裂由来の瘻孔および嚢腫の3例


皮膚潰瘍に対するSNK-863軟膏の臨床評価

皮膚潰瘍に対するSNK-863軟膏の臨床評価

Japanese Journal of Medicine and Pharmaceutical Science


小範囲熱傷に対するアロアスクDⓇとバラマイシンⓇ軟膏との臨床効果の比較

小範囲熱傷に対するアロアスクDⓇとバラマイシンⓇ軟膏との臨床効果の比較


先天性外鼻軟骨欠損を伴ったBinder症候群の1例

先天性外鼻軟骨欠損を伴ったBinder症候群の1例


輪ゴムによる頚部仮性絞扼症の1例

輪ゴムによる頚部仮性絞扼症の1例


皮膚科領域感染症に対するS-1108の臨床的検討

皮膚科領域感染症に対するS-1108の臨床的検討


下腿潰瘍と深部血栓性静脈炎，肺血流低下を伴ったベーチェット病

下腿潰瘍と深部血栓性静脈炎，肺血流低下を伴ったベーチェット病


シクロスポリンが奏効した尋常性天疱瘡の1例

シクロスポリンが奏効した尋常性天疱瘡の1例


Immunohistological analysis of P53 expression in human skin tumors

The p53 expression in various skin tumors was immunohistologically evaluated using two mouse monoclonal anti-p53 antibodies, PAb421 and PAb1801. The p53 expression was not detected in the normal epidermal cells. Nuclear staining suggested that the p53 expression was observed in 10 of 26 squamous cell carcinomas (SCCs) from 24 patients, in one undifferentiated carcinoma, one proliferating trichilemmal cyst, one malignant proliferating trichilemmal tumor and in one metastatic carcinoma of breast cancer. None off four cases of Bowen's disease (SCC in situ) showed nuclear staining. In the SCCs, five of 20 primary lesions, three of four recurrent lesions and both of two metastatic lesions had positive nuclei. There was one case of SCC in which a primary lesion was negative but a recurrent lesion was positive. Thus, p53 expression was more frequently observed in SCCs at more clinically advanced stages. This may suggest that p53 has some relevance to progression of SCC. Nuclear staining was not detected in any of the following cases: two cases of seborrheic keratosis, one eccrine poroma, one keratoacanthoma, 11 basal cell epitheliomas, two mammary Paget's disease, three genital Paget's disease, one sebaceous carcinoma, four malignant melanomas, six lymphomas, two leukemia cutis and two angiosarcomas.


プロスタグランジンE1の皮膚微小循環に及ぼす影響―生体顕微鏡法による検討―

プロスタグランジンE1の皮膚微小循環に及ぼす影響―生体顕微鏡法による検討―


培養ヒト成長期毛包および外毛根鞘細胞に対するMinoxidil Sulfateの影響


皮膚科領域におけるグランダキシン○Rの臨床的検討

皮膚科領域におけるグランダキシン○Rの臨床的検討


家族内発生をみた石灰化上皮種

家族内発生をみた石灰化上皮種


VASODILATORY EFFECTS OF PROSTAGLANDIN E1(PGE1)ON MICROCIRCULATION OBSERVED IN THE RABBIT EAR CHAMBER

International confederation for plastic and reconstructive surgery


The influence of cutaneous factors on the transcutaneous PO2 and PCO2 at various body sites

The transcutaneous partial pressures of oxygen (tcpO2) and carbon dioxide (tcpCO2) were measured at eight different sites in 10 adult male subjects with an electrode at a temperature of 44 degrees C. The mean tcpO2 values (mmHg) were significantly lower on the face (forehead 26.6, cheek 29.6) and the palm (26.4) than at other sites (60.6-69.6). The tcpCO2 values (mmHg) were only slightly higher on the face. Removal of the stratum corneum produced an average increase of the tcpO2 on the palm of 37.6 mmHg and on the forehead of 19.6 mmHg. However, in 10 children with an age range of 3-9 years, the difference in the mean pO2 between the cheek and forearm was very small. There was no significant difference in the cutaneous blood flow at 44 degrees C between the cheek, palm and forearm.


The effect of 1, 25-dihydroxyvitamin D3 on the growth and differentiation of cultured human outer root sheath cells from normal subjects and patients with Vitamin D-dependent rickets type with alopecia

We examined the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the growth and differentiation of cultured human hair outer root sheath cells (ORSC) from normal subjects and patients with vitamin D-dependent rickets type II (DDR-II) with alopecia. 1,25(OH)2D3 dose-dependently suppressed the plating efficiency, clonal growth, and DNA synthesis of normal ORSC. It enhanced the cornified envelope formation and caused morphological changes in the cells. All results indicated the existence of specific receptors for 1,25(OH)2D3 in the ORSC, and suggest that 1,25(OH)2D3 is a potent inhibitor of proliferation of ORSC as well as a stimulator of terminal differentiation. However, the cells from DDR-II patients with alopecia did not respond to 1,25(OH)2D3, suggesting a lack of the specific receptors in the cells. The differences in the cellular response to the hormone between the normal ORSC and those from the patients were apparent and easily distinguishable, therefore this experiment may be a rapid and simple diagnostic test for DDR-II patients with alopecia. Large number of hairs were difficult to obtain from patients with alopecia, and we developed a new culture method to accomplish these studies from a few plucked hair follicles. Our system may be useful in the culture of ORSC from limited number of follicles, and could be utilized to analyse the cellular characteristics of ORSC in patients with hair diseases.


Transcutaneous PO2 and PCO2 Measurements in Various Skin Lesions

Low tcPO2 levels were observed in various skin lesions, indicating that most pathological changes in the skin induce such a reduction. In contrast, the tcPCO2 changed less, with the exception of marked elevations in bullous or prenecrotic lesions. This procedure may have practical applications in clinical dermatology, particularly in quantitating the response to therapy and in predicting a necrotic change.


Culture of human outer root sheath cells from plucked hair follicles in serum-free conditions

We succeeded in culturing human outer root sheath cells (ORSC) in serum-free conditions without a biological feeder layer. The combination of collagen type IV substrate and modified MCDB 153 medium supplemented with bovine pituitary gland extract (K-GM medium) could support the growth of ORSC. These cells can be serially cultivated for at least 4 passages and stored in liquid nitrogen with good recovery. Thus, a large series of experiments using ORSC may be run simultaneously.


手術により得た爪母より，explant culture，dispersed cell culture，およびゲル内での三次元的なexplant cultureの3方法でヒト爪母細胞を培養した．Explant cultureではⅣ型コラーゲンをコートしたシャーレ上でも無処理シャレー上でも初期には細胞は同様に増殖したが，無処理シャーレでは細胞が早期より角化(細胞の大型化と脱核)した．Dispersed cell cultureではⅣ型コラーゲンをコートしたシャーレとⅣ型コラーゲンをコートしたⅠ型コラーゲン膜上でともに細胞は増殖したが，plating efficiencyは前者では約0.2%，後者では約0.5%であった．また前者では角化が早く始った．無処理シャーレ上でも細胞は接着したが増殖しなかった．培養経過中にコロニー内で細胞が積み重なり，程度の差はあれ，ドーム状に盛り上る現象が，explant culture，dispersed cell cultureでみられた．コラーゲンゲル内での三次元的なexplant cultureでは全方向に向かって細胞が出現し，樹枝状に増殖した．電顕所見ではケラトヒアリン顆粒はみられず，コラーゲン膜と細胞間に基底模様構造もみられなかった．培養細胞の抗毛ケラチンモノクローナル抗体を含む各種抗ケラチン抗体に対する反応は，組織爪母細胞と同様で，表皮基底細胞，表皮有棘細胞，培養表皮細胞のいずれとも異っていた．爪母細胞は表皮細胞や外毛根鞘細胞とほぼ同じ条件でよく増殖し，表皮細胞とは異った性質を有することがわかった．


クレゾールによる自傷性皮膚腫瘍を呈したMünchausen症候群の1例

クレゾールによる自傷性皮膚腫瘍を呈したMünchausen症候群の1例


唇・顎裂を合併した高度短合指症例の経験

唇・顎裂を合併した高度短合指症例の経験


Treacher collins症候群の治療経験 ―側頭筋頭蓋骨移植―

Treacher collins症候群の治療経験 ―側頭筋頭蓋骨移植―


Malignant proliferating trichilemmal tumorの2例


卵黄腸管(臍腸管)遺残の2例 ―臍形成について―

卵黄腸管(臍腸管)遺残の2例 ―臍形成について―


Japanese Journal of Clinical Dermatology


Eosinophilic Polymyositis Induced by Tranilast

A 38-year-old man with asthma developed eosinophilic polymyositis following the administration of Tranilast, an antiasthmatic agent. Low grade fever, erythematous rashes on the entire body, dysphagia, blood eosinophilia, elevations of serum creatine phosphokinase and myoglobin levels, and inverted T waves in the electrocardiogram were noted. A muscle biopsy showed focal degeneration of muscle fibers with an infiltrate of eosinophils and lymphocytes. A rechallenge with Tranilast resulted in erythema formation, blood eosinophilia, and elevations of some serum muscle enzymes and myoglobin levels. Tranilast was considered to be the causative agent. This is the first reported case of Tranilast-induced eosinophilic polymyositis.


ヒト抜去毛包のコラーゲンゲル内培養

ヒト抜去毛包のコラーゲンゲル内培養

肉眼的に外毛根鞘を付着するヒト抜去毛包をⅠ型コラーゲンゲル内で培養した．培養3∼4日目より毛包が肥大し，また外毛根鞘部よりゲル内に上皮系の細胞も出現し，以後4週間にわたり突起を形成しながら3次元に増殖した．毛球部を取り除いた細切毛包の培養でも同様の細胞増殖がみられた事より，増殖した上皮細胞は外毛根鞘由来と考えた．突起の数，径，性状は個々の毛包で異なっていた．肥大毛包部では最外層にDNA合成細胞が局在し，突起部でも外側縁にDNA合成細胞がみられた．本実験系は各種条件下での外毛根鞘細胞の3次元増殖を観察するのに適した系と思われる．また外毛根鞘細胞と他器官の細胞との相互作用の探究にも役立つであろう．


外傷後に生じた鼻部囊腫の1例

外傷後に生じた鼻部囊腫の1例


術後性上顎骨嚢胞が疑われた1例

A 33-year-old man, who had received an operation for paranasal sinusitis at the age 16, developed an asymptomatic mass in the right cheek. Our examination showed a cyst destroying the maxillary bone. The cyst was surgically removed and ultimately considered to be a postoperative maxillary cyst. The resulting defect in the maxillary bone was filled with iliac bone chips with satisfactory results. Though most cases of such cysts tend to occur under the supraorbital nerve and vessels, this case was found to overlie them. We reviewed previously reported cases and briefly discussed the cause, differential diagnosis, and treatment of this disorder.

術後16年を経て出現した術後性上顎骨嚢胞と思われる症例を, 腸骨を用いて再建し, 再発も無く整容的にも満足しえたので報告した．また本例も含め, 上顎骨周囲に発生する疾患について若干の文献的考察を加えた．


ビタミンD依存性クル病Ⅱ型患者毛包細胞に及ぼす1，25-dihydroxyvitamin D3の影響


Liquid-holding recovery of sister chromatid exchanges in UV-irradiated normal and xeroderma pigmentosum complementation groups A and F fibroblasts.


CULTURE OF DISPERSED HAIR FOLLICLE CELLS FROM PLUCKED OUT HAIRS WITHOUT A FEEDER LAYER

Dispersed hair follicle cells from plucked out hairs have been successfully grown on collagen type IV without a biological feeder layer. The optimal calcium concentration for the culture of these cells was also studied and decided to be 0.3-0.5 mM. In this calcium range and on collagen type IV, colony formation and colony growth were best and big colonies with a paving stone-like cell arrangement were formed. The availability of such cultured cells for the treatment of missing skin is proposed instead of cultured epidermal keratinocytes which have been commonly used for wound dressing.

The Tokushima Journal of Experimental Medicine


痔瘻と交通した臀部慢性膿皮症の1例

痔瘻と交通した臀部慢性膿皮症の1例


耳介部ケロイドの治療経験

耳介部ケロイドの治療経験


円形脱毛症における毛球部浸潤リンパ球の免疫組識化学的解析

円形脱毛症における毛球部浸潤リンパ球の免疫組識化学的解析


Follicular atrophoderma with multiple basal cell carcinomas. An abortive form of bazex syndrome.:-An Abortive Form of Bazex Syndrome-

Follicular Atrophodermaを持つ中年男子にみられた多発性基底細胞癌 ―Bazex症候群の不完全型か―

Multiple basal cell carcinomas developed predominantly on the sun exposed areas in a 52-year-old Japanese man. He also had follicular atrophoderma on the extensor aspect of the extremities. Five other siblings were free from symptoms, but his mother suffered from follicular atrophoderma. These findings were consistent with the syndrome described by Bazex et al. However, because the patient lacked other cardinal skin synptoms such as abnormalities of scalp hair and sweating, a diagnosis of an abortive form of Bazex syndrome was made. Numerous basal cell carcinomas were also observed on the trunk, a non-exposed area, previously irradiated with X-rays. We would like to emphasize that radiation therapy should be avoided in patients with Bazex syndrome. Here we report the first case of this rare inherited syndrome in Japan.

四肢伸側に毛孔性皮膚萎縮を持つ中年男子に基底細胞癌が多発した．他の5人兄弟には皮疹をみなかつたが, 母親にも同様の毛孔性皮膚萎縮をみたことよりBazex症候群が疑われた．毛孔性皮膚萎縮は幼児期より前腕, 下腿の伸側ではつきりしており, ほとんどに体毛を伴つたが一部では脱落していた．基底細胞癌は42才時より顔面に初発し, 以後, 頭頸部や限界線照射の既往がある躯幹にも多発した．以上の臨床所見と, 頭髪, 発汗の異常はみられなかつたことを考えあわせ不完全型のBazex症候群と考えた．なお患者は22才時, 尋常性乾癬のため躯幹に限界線照射を受けたが, 両部にも多数の基底細胞癌が出現したことより, Bazex症候群患者には放射線治療は禁忌と考えた．


先天性上口唇正中瘻孔の1例

先天性上口唇正中瘻孔の1例


Postconfluent Hair Follicle Cellsに対するMinoxidilの影響


1.25-Dihydroxyvitamin D3のHair Follicle Cellに与える影響


Effect of Minoxidil on Cultured Human Hair Follicle Cells

Minoxidil (MX), whether applied topically or taken orally, has been said to increase the thickness and length of hairs. Knowing the functions of MX on the scalp hairs, we investigated the effect of MX on preconfluent human hair follicle cells in culture. The hair follicle cells used were derived from plucked scalp hair follicles according to the culture methods previously reported by us. Both plating efficiency and colony growth were supressed by MX at all the drug concentrations tested: 1, 10 and 100 <I>μ</I>g/ml. Cell morphology was not so affected by MX. Terminal differentiations such as stratification of cells and appearance of large denucleated cells were seen at all MX levels, as in the control. We found no evidence that MX activates the proliferation, or modulates the differentiation of HFC in vitro.

培養hair follicle cellsに対するminoxidilの影響について検討した．その結果, hair follicle cellsの増殖はテストしたすべてのminoxidil濃度(1, 10, 100<I>μ</I>g/ml)において抑制された．しかし, hair follicle cellsの形態的変化はみられず, 細胞の大型化, 核の消失, 重層化などの分化過程がコントロールとほぼ同様に観察された．


Xeroderma Pigmentosum with Diabetes Mellitus.:-A Report of 2 Cases plus Clinical and Biological Studies of 8 Cases of Xeroderma Pigmentosum Occurring in Tokushima-

糖尿病と尋常性乾癬の合併をみた色素性乾皮症 ―色素性乾皮症と内部臓器の老化について考察―

Two brothers with XP were found to be suffering from diabetes mellitus. The elder brother also had psoriasis vulgaris. XP is an autosomal recessive disease with an extensive heterogeneity in clinical features, and is characterized by cellular DNA repair deficiency. On the other hand, both ataxia telangiectasia and Fanconi's anemia are also autosomal recessive syndromes characterized by certain DNA repair defects. And it has been well known that patients (homozygotes) with these syndromes frequently develop diabetes mellitus. These observations led us to suppose that XP patients may also be predisposed to DM. Clinical and biological studies of 8 patients with XP in Tokushima have been carried out. Three patients of rather an old age (older than 48) had diabetes mellitus, and one had a hyperlipemia. The number of patients analyzed was very small, but it should be noted that the frequency of DM in XP patients might be high. We also report the first case of XP occurring together with DM and psoriasis vulgaris in Japan.

糖尿病(DM)を合併する色素性乾皮症(XP)の兄弟例を経験した．兄には尋常性乾癬も合併していた．XPはDNA損傷の修復に異常があるため, 皮膚に早期より老化症状が出現すると考えられる．一方Fanconi貧血やataxia telangiectasiaのような, DNA修復に異常がみられる疾患には糖尿病の合併がよく知られている．また早老症の代表であるWerner症候群は糖尿病の合併が普通である．これらのことより, 1985∼1987年に経験した8例のXP患者の内部臓器の異常について調べたところ, 3例にDMが, 1例に高脂血症がみつかつた．XPでは皮膚のみならず, 内部臓器にも, 早期より老化現象が出現する可能性があることを強調した．


脱毛を合併するビタミンD依存性クル病Ⅱ型の5症例

脱毛を合併するビタミンD依存性クル病Ⅱ型の5症例

紫外線照射により皮膚で合成されたり，または食物として摂取されたビタミンDは，肝臓と腎臓で水酸化を受け，ビタミンD作用(カルシウム代謝の調節など)を実際に発揮する1.25-dihydroxyvitaminD3(1.25(OH)2D3と略記)に変換される．1.25(OH)2D3は標的臓器細胞中の特異レセプターと結合し，DNAに働き，蛋白合成を介してホルモン効果を発揮する．この一連の機序のどこかに障害があるとカルシウム代謝異常症が出現する．1978年，Brooksらは，1.25(OH)2D3の合成，代謝は正常であるが，それに対する標的細胞内のレセプター異常の結果発症するクル病をビタミンD依存性クル病Ⅱ型(Vitamin D Dependent Reckets type II，以下DDR2と略記)として報告した．以後30例近く報告されているが，注目すべきことに大半の患者に脱毛がみられる．本邦でも6症例の報告を見るが，いずれも小児科，内科医により発表され，皮膚医にとってなじみの少ない疾患と思われる．しかし乳幼児，小児における脱毛の診察にあたっては，鑑別疾患の1つにあげねばなるまい．今回我々は脱毛を伴うDDR2の5症例を経験したので，主に脱毛についての考察を加えて報告する．


Duo DERMの採皮創に対する臨床経験 ―細菌検査を中心に―

Duo DERMの採皮創に対する臨床経験 ―細菌検査を中心に―


A Method for Culturing Human Hair Follicle Cells (III):-Determination of optimal culture conditions: The effects of substrates and Ca<SUP>++</SUP> concentrations-

Hair Follicle Cellsの培養法(Ⅲ) ―至適培養条件の決定，とくに培養基質，Caイオン濃度の影響について―

The effects of substrates and medium ionic calcium concentrations on the growth and differentiation of human hair follicle cells in dispersed cell culture were investigated. Compared to other extracellular matrices such as collagen type I, fibronectin and laminin, a substrate of collagen type IV increased colony formation 3-7 fold. Colony growth of human hair follicle cells was doubled at medium ionic calcium concentrations of 0.3 mM compared to higher or lower levels, and terminal differentiation of human hair follicle cells was suppressed with lower calcium levels over the range 0.1∼0.9 mM.

各種培養基質および培地中Ca++濃度が抜去毛毛包由来hair follicle cellの増殖, 分化におよぼす影響について, dispersed cell cultureにて検討した．その結果, I型コラーゲン, フィブロネクチン, ラミニンに比較し, IV型コラーゲンを培養基質とした場合に最も有効にhair follicle cellのコロニーが得られた．また, 培地中Ca++濃度が0.3mMのとき, hair follicle cellは最もよくコロニーを形成した．Ca++濃度0.1∼0.9mMの範囲内でhair follicle cellの分化(角化, 重層化, cornified envelope形成など)は, Ca++濃度が低下するにつれて抑制された．


A Method for Culturing Human Hair Follicle Cells (II):-Plucked Human Hair Follicles-

Hair Follicle cellsの培養法(Ⅱ) ―抜去毛より採取した毛包の培養法―

We performed an explant culture and a dispersed cell culture of plucked hair follicles and could obtain hair follicle cell colonies without contamination of fibroblasts by both culture methods. To determine the optimal culture condition, MMC treated 3T3 cells, collagen type I membrane (undcr surface: 3T3 cells without MMC treatment) and collagen type IV were used as feeder layers or substrate. The hair follicle cell growth could be constantly viewed only on the collagen type IV coated dishes. Therefore, it is suggested that collagen type IV, a component of the basement membrane, is essential for the growth of hair follicle cells from plucked human hair follicles.

真皮成分の付着していない抜去毛毛包のexplant cultureおよびdispersed cell cultureを試み, 線維芽細胞の混在しないhair follicle cellのみのコロニーを得ることができた．マイトマイシンC処理した3T3細胞, 裏面に3T3細胞を培養したI型コラーゲン膜をfeeder layerとした場合に比較し, 基底膜の構成成分であるIV型コラーゲンを培養基質としたときに最も有効にhair follicle cellのコロニーが得られた．


A Method for Culturing Human Hair Follicle Cells (I):-A Method for Culturing Hair Follicles Obtained from Surgically Resected Scalp-

Hair Follicle Cellsの培養法(Ⅰ) ―手術摘出頭皮より採取した毛包の培養法―

We cultured human hair follicle cells from follicles of the surgically resected scalp skin. In the presence of calcium (1.96 mM), a physiological concentration, the cells piled up, keratinized and rapidly displayed a terminal differentiation, as seen in skin epidermal cells. Only when they were cultured from the start with a physiological calcium concentration medium and then with a low calcium concentration one (0.43 mM) did monolayered, polygonal and large nucleated basal cell-like cells appear, and were retained for about 20 days. To remove the fibroblasts which grow rapidly and surround hair follicle cell colonies in the course of culture, we scraped them off with a rubber policeman and the growth was suppressed to some extent.

手術時に摘出した頭皮より採取した毛包を材料として, 外毛根鞘由来の上皮系細胞であるhair follicle cells(HFC)の培養を試みた．通常Ca++培地では皮膚表皮細胞と同様に重層化·角化などの分化過程がみられた．次に通常Ca++培地にて培養を開始し, 7日目からHFCの分化を抑制する目的で低Ca++培地を使用したところ, 基底細胞と思われる細胞の単層のコロニーを約20日間にわたり維持観察できた．また, 培養経過中に優位となり, HFCを駆逐する線維芽細胞の抑制にはrubber policemanによる物理的削除を行い, 一定の効果をおさめた．


EFFECTS OF SIX TOPLCAL CORTLCOSTEROIDS ON DNA SYNTHESIS OF NORMAL HUMAN SKIN FIBROBLASTS

The Tokushima Journal of Experimental Medicine


Japanese Journal of Clinical Dermatology


Treatment of Patients with Darier's Disease with Topical Application of Solbase (a Mixture of Polyethylene Glycol 400 & 4000) Plus Occlusion

ダリエ病に対するポリエチレングリコールODT療法

Topical application of Solbase (a mixture of polyethylene glycol 400 & 4000) plus occlusion improved the eruptions of 2 patients with Darier's disease. To determine the mechanism of action, the effect of polyethelene glycol 400 on the rat epidermal DNA synthesis was investigated using autoradiography and doing 14C-thymidine incorporation studies. Seven days' topical application of polyethylene glycol 400 activated epidermal DNA synthesis nearly double the value seen in the control. This therapy should be considered for patients with Darier's disease and especially for whom retinoids cannot be prescribed.

2人のダリエ病患者にソルベース(ポリエチレングリコール400, 4000の合剤)のODTを行い皮疹の改善をみた．作用機序を知る目的で, ポリエチレングリコール400(PEG400)をラット皮膚に塗布し, 表皮DNA合成について14C-チミジンの取り込みとin vitroオートラジオグラフィー法でみたところ, PEG400塗布は表皮DNA合成を亢進させる結果を得た．この結果とPEGの持つ薬理学的性質を考えあわせ, ダリエ病に対する作用機序について考察した．また, ソルベースODT療法は, レチノイド内服が不可能なダリエ病患者に対して有効であることを述べた．


特異な瘢痕浸潤を示したサルコイドーシス

特異な瘢痕浸潤を示したサルコイドーシス


Sarcoidosis successfully treated with allopurinol

【肉芽腫症】 アロプリノールが有効であったサルコイドーシスの1例


Angiostatic effects of corticosteroid on wound healing of rabbit ear

Wound healing is a complex biologic process with initial inflammation, granulation tissue formation, and matrix remodeling. We observed the relation between angiostatic effects and corticosteroid administration time in the rabbit ear chamber. Angiogenesis in the chamber was studied using a microscope-television system. Two experiments were undertaken to represent the systemic and the topical administration of steroids. In experiment 1, 10 mg of triamcinolone acetonide was injected three times intramuscularly (on the day of implantation of the chamber, and the 7th and 14th day after implantation). Vascularization in this group was significantly delayed at the 7th, 14th, and 21st days but no difference from controls was observed in the size and density of vessels after its completion. In experiment 2, 3 mg of triamcinolone acetonide was injected once into the skin adjacent to the chamber on the 10th day after installment of chambers or on the day of installment. In the former group, new vascular growth was delayed until the 21st day after installment. The hemorrhagic zone had narrowed and vascular dilation was observed. In the latter group, endothelial budding was delayed and vascular constriction occurred. New vascular growth was severely delayed and granulation filling of the chamber was not completed. These results suggest not only that the topical administration had the stronger inhibitory effect on neovascularization than the systemic administration but that the effect differed depending on the stage of wound healing. In view of this effect of this steroid, we should pay careful attention to the time when steroids are administered to patients.

The Journal of Medical Investigation : JMI


Woolly hair nevus: neonatal alopecia can be an initial manifestation.


Verrucous extramammary Pagets disease accompanying human papillomavirus 40-associated condyloma acuminatum: importance of multiple skin biopsies


Multiple pilosebaceous cysts induced by topical steroid therapy


Lack of association between extramammary Pagets disease and human papillomavirus infection